# PAPER

TITLE:
Co-administration of live measles and yellow fever vaccines and inactivated pentavalent vaccines is associated with increased mortality compared with measles and yellow fever vaccines only. An observational study from Guinea-Bissau.

AUTHORS:
Ane Baerent Fisker, Henrik Ravn, Amabelia Rodrigues, Marie Drivsholm Ostergaard, Garlito Bale, Christine Stabell Benn, Peter Aaby


TITLE:
In one study on rubella vaccination in 19 pregnant women, 9 aborted, 8 induced and 1 spontaneously.

ABSTRACT:
Experience with the vaccine can be summarized as follows: There were minimal problems with neuralgia and neuropathy as a result of the vaccine; vaccinated children were not a significant source of infection to the pregnant woman; the duration of immunity is similar to that obtained with natural rubella virus, but with lower antibody levels; and reinfection is more common with vaccination, but apparently no viremia develops. Several studies were reported regarding inadvertent vaccination in women who were pregnant at the time of vaccination. In one series [7], 19 pregnant women who were vaccinated were studied. Ten went to term and delivered normal babies and 9 aborted, 8 induced and 1 spontaneously. In one induced abortion, virus was demonstrable in fetal tissue including, notably, in the eye. Another case of CRS was diagnosed in utero amniocentesis [12], and the fetus was aborted at 12 weeks' gestation. Another evaluation of reinfection during pregnancy [1] confirmed that this was of little risk to the fetus, as there was no apparent viremia. In summary, then, in one ophthalmological generation, from Gregg until the present time, we have experienced the recognition, the observation, and, essentially, the conquest of the congenital rubella syndrome. However, if vaccination programs are not assiduously continued, we can expect a renewed upsurge of this difficult problem.


TITLE:
During the first five years of rubella immunizations in adults concerns emerged about the possibility that the vaccines do harm to the fetus in pregnant women.

ABSTRACT:
Despite extensive use of atttenuated rubella vaccine during the past five years, the degree of fetal risk in susceptible women inoculated early in pregnancy is still an unresolved issue. Although there is considerable evidence of chronic vaccine virus infection of the products of gestation in aborted fetuses, congenital defects have not yet been reported in the newborn infants of susceptible vaccinated pregnant women. The normal findings in the newborn infant can be misleading with respect to the safety of the vaccines in early pregnancy, because they represent only a small selected group of reported cases. The immediate need is for more complete reporting of all relevant cases wherever they occur in order to determine without many more years of delay whether the fetal risk has public health significance or is so low as to be of negligible importance.


TITLE:
This study found evidence of a causal relation between the RA 27/3 rubella vaccine strain and chronic arthritis in adult women.

AUTHORS:
C P Howson, M Katz, R B Johnston, H V Fineberg

ABSTRACT:
In August 1991 the Institute of Medicine released a report entitled "Adverse Effects of Pertussis and Rubella Vaccines" that examined, among other relations, the relation between immunization with the RA 27/3 rubella vaccine strain and chronic arthritis. The committee spent 20 months reviewing a wide range of information sources including case series and individual case reports published in peer-reviewed journals and reported by vaccine manufacturers; unpublished case reports from physicians, parents, and other concerned persons; epidemiological studies; and laboratory studies. There were no animal studies available. The committee found that the evidence is consistent with a causal relation between the RA 27/3 rubella vaccine strain and chronic arthritis in adult women, although the evidence is limited in scope. Proving that rubella vaccination can cause chronic arthritis will require a better understanding of pathogenetic mechanisms and additional well-designed studies. We briefly describe the committee's evaluative methods and present the evidence underlying its conclusion.


TITLE:
Vaccine-associated paralytic poliomyelitis (VAPP) has emerged as the predominant form of the disease in the United States since 1980.

AUTHORS:
P M Strebel, Roland W Sutter, S L Cochi, R J Biellik, E W Brink, Olen M Kew, M A Pallansch, W A Orenstein, A R Hinman

ABSTRACT:
Poliomyelitis caused by wild poliovirus has been virtually nonexistent in the United States since 1980, and vaccine-associated paralytic poliomyelitis (VAPP) has emerged as the predominant form of the disease. We reviewed national surveillance data on poliomyelitis for 1960-1989 to assess the changing risks of wild-virus, vaccine-associated, and imported paralytic disease; we also sought to characterize the epidemiology of poliomyelitis for the period 1980-1989. The risk of VAPP has remained exceedingly low but stable since the mid-1960s, with approximately 1 case occurring per 2.5 million doses of oral poliovirus vaccine (OPV) distributed during 1980-1989. Since 1980 no indigenous cases of wild-virus disease, 80 cases of VAPP, and five cases of imported disease have been reported in the United States. Three distinct groups are at risk of vaccine-associated disease: recipients of OPV (usually infants receiving their first dose), persons in contact with OPV recipients (mostly unvaccinated or inadequately vaccinated adults), and immunologically abnormal individuals. Overall, 93% of cases in OPV recipients and 76% of vaccine-associated cases have been related to administration of the first or second dose of OPV. Our findings suggest that adoption of a sequential vaccination schedule (inactivated poliovirus vaccine followed by OPV) would be effective in decreasing the risk of VAPP while retaining the proven public health benefits of OPV.


TITLE:
Severe tetanus has been reported in immunized patients with high anti-tetanus titers.

ABSTRACT:
Severe (grade III) tetanus occurred in three immunized patients who had high serum levels of anti-tetanus antibody. The disease was fatal in one patient. One patient had been hyperimmunized to produce commercial tetanus immune globulin. Two patients had received immunizations 1 year before presentation. Anti-tetanus antibody titers on admission were 25 IU/ml to 0.15 IU/ml by hemagglutination and ELISA assays; greater than 0.01 IU/ml is considered protective. Even though one patient had seemingly adequate anti-tetanus titers by in vitro measurement (0.20 IU), in vivo mouse protection bioassays showed a titer less than 0.01 IU/ml, implying that there may have been a hole in her immune repertoire to tetanus neurotoxin but not to toxoid. This is the first report of grade III tetanus with protective levels of antibody in the United States. The diagnosis of tetanus, nevertheless, should not be discarded solely on the basis of seemingly protective anti-tetanus titers.


TITLE:
Outbreak of paralytic poliomyelitis in Oman: evidence for widespread transmission among fully vaccinated children.

AUTHORS:
Roland W Sutter, P A Patriarca, S Brogan, P G Malankar, M A Pallansch, Olen M Kew, A G Bass, S L Cochi, J P Alexander, D B Hall

ABSTRACT:
From January, 1988, to March, 1989, a widespread outbreak (118 cases) of poliomyelitis type 1 occurred in Oman. Incidence of paralytic disease was highest in children younger than 2 years (87/100,000) despite an immunisation programme that recently had raised coverage with 3 doses of oral poliovirus vaccine (OPV) among 12-month-old children from 67% to 87%. We did a case-control study (70 case-patients, 692 age-matched controls) to estimate the clinical efficacy of OPV, assessed the immunogenicity of OPV and extent of poliovirus spread by serology, retrospectively evaluated the cold chain and vaccine potency, and sought the origin of the outbreak strain by genomic sequencing. 3 doses of OPV reduced the risk of paralysis by 91%; vaccine failures could not be explained by failures in the cold chain nor on suboptimum vaccine potency. Cases and controls had virtually identical type 1 neutralising antibody profiles, suggesting that poliovirus type 1 circulation was widespread. Genomic sequencing indicated that the outbreak strain had been recently imported from South Asia and was distinguishable from isolates indigenous to the Middle East. Accumulation of enough children to sustain the outbreak seems to have been due to previous success of the immunisation programme in reducing spread of endemic strains, suboptimum efficacy of OPV, and delay in completing the primary immunisation series until 7 months of age. Additionally, the estimated attack rate of infection among children aged 9-23 months exceeded 25% in some regions, suggesting that a substantial proportion of fully vaccinated children had been involved in the chain of transmission.


TITLE:
Underestimation of central nervous system complications after pertussis immunization appears to be prevalent.

ABSTRACT:
Bias in the evaluation of CNS complications following pertussis immunization are the following: 1) Notifications of postimmunization adverse events, 2) Publications by vaccine producers on the frequency of adverse reactions, 3) Comparison of permanent brain damage after DPT and DT immunization, 4) Pro-immunization, 5) Immunization associated viral encephalitis, 6) Accuracy of statistics, 7) Personal. A review of these points indicates an underestimation of CNS complications after pertussis immunization.


TITLE:
Neonatal tetanus despite protective serum antitoxin concentration.

AUTHORS:
S Y Maselle, R Matre, R Mbise, T Hofstad

ABSTRACT:
Using the ELISA technique to estimate serum antibodies against tetanus toxin, seven neonates with clinical tetanus were found to have antibody levels 4-13 times higher than the presumed minimum protective level of 0.01 IU/ml. All but one of their mothers had been vaccinated with tetanus toxoid in pregnancy. In two other neonates, whose mothers had received multiple booster doses of toxoid during pregnancy, the anti-toxin concentrations were 100- and 400-times the presumed protective level. Therefore the toxin dose may overwhelm the pre-existing anti-toxin level and produce disease. Furthermore, multiple booster injections of tetanus toxoid may not only enhance serum anti-toxin titres, but could also lead to an ineffective immune response.


TITLE:
A major measles epidemic occurred in 1989 in the region of Quebec despite a 99% vaccine coverage.

AUTHORS:
Nicole Boulianne, Gaston De Serres, B Duval, J R Joly, F Meyer, P DÃ©ry, M Alary, D Le HÃ©naff, N ThÃ©riault

ABSTRACT:
The 1989 measles outbreak in the province of Quebec has been largely attributed to an incomplete vaccination coverage. In the Quebec City area (pop. 600,000) 1,363 confirmed cases of measles did occur. A case-control study conducted to evaluate risk factors for measles allowed us to estimate vaccination coverage. It was measured in classes where cases did occur during the outbreak. This population included 8,931 students aged 5 to 19 years old. The 563 cases and a random sample of two controls per case selected in the case's class were kept for analysis. The vaccination coverage among cases was at least 84.5%. Vaccination coverage for the total population was 99.0%. Incomplete vaccination coverage is not a valid explanation for the Quebec City measles outbreak.


TITLE:
Pregnant cows vaccinated against a Brucella strain experienced an abortion rate of 58%.

AUTHORS:
D S Davis, J W Templeton, T A Ficht, J D Huber, R D Angus, L G Adams

ABSTRACT:
Protection against Brucella abortus induced abortion and infection provided by strain 19 (S19) vaccination was evaluated in American bison (Bison bison). Forty-eight pregnant bison were manually inoculated (MI) with S19 vaccine, 44 were ballistically inoculated (BI) with an absorbable hollow pellet containing lyophilized S19, and 46 were manually injected with buffered saline as non-vaccinated controls (NVC). All bison were Brucella spp. seronegative prior to the experiment, in the second trimester of pregnancy, and were randomly assigned to experimental groups. Approximately 60 days post-vaccination, abortions were observed in the vaccinated bison. Brucella abortus strain 19 was recovered from a bison that had recently aborted, her fetus, and from 11 of 12 other aborted fetuses. Fifty-eight percent (53 of 92) of vaccinated bison aborted, and no abortions were observed in the NVC bison. One cow aborted during her second post-vaccinal pregnancy and S19 was identified from the dam and fetus indicating that chronic S19 infections can occur in bison. Positive antibody titers were present 10 mo post-vaccination in 73% (66 of 91) of the bison. Thirteen mo post-vaccination, 30 MI vaccinates, 27 BI vaccinates, and 30 NVC bison were challenged during the second trimester of pregnancy with 1 x 10(7) CFU of B. abortus strain 2308 via bilateral conjunctival inoculation. Protection against abortion was 67% (P less than or equal to 0.0001) for vaccinated bison compared to 4% in NVC. Protection against B. abortus infection was determined to be 39% (P greater than or equal to 0.001) for vaccinates and 0% (zero of 30) for NCV. Persistent antibody titers, vaccine induced abortions, and chronic S19 infections indicate that the S19 vaccine doses used in this study are not suitable for pregnant bison.


TITLE:
A measles outbreak at a college with a prematriculation immunization requirement.

AUTHORS:
B S Hersh, Lauri E Markowitz, R E Hoffman, D R Hoff, Mj Doran, J C Fleishman, S R Preblud, W A Orenstein

ABSTRACT:
In early 1988 an outbreak of 84 measles cases occurred at a college in Colorado in which over 98 percent of students had documentation of adequate measles immunity (physician diagnosed measles, receipt of live measles vaccine on or after the first birthday, or serologic evidence of immunity) due to an immunization requirement in effect since 1986.


TITLE:
Vaccination of pregnant monkeys resulted in abortions in 2 out of 25.

ABSTRACT:
We studied Aotus lemurinus, Panamanian night monkeys, for susceptibility to Toxoplasma infection and for their capacity to develop immunity using either sufadiazine prophylaxis or the non-persistent ts-4 vaccine. The animals were highly susceptible to infection with a mouse pathogenic (T265) and a mouse nonpathogenic (T163) Toxoplasma isolate. A calculated single bradyzoite by mouth gave rise to infection which was fatal in nine to 12 days. Chemoprophylaxis with 60-300 of sulfadiazine mg per day for up to 40 days protected the animals; however this was followed by fatal reactivation of infection between 11 and 70 days after treatment was stopped. Vaccination was carried out in two or three doses subcutaneously. Challenge was performed in 26 animals using both Toxoplasma isolates. Five monkeys (19%) survived for over a year, 10 died after a prolonged illness, and 11 died as rapidly as the seven controls. Safety tests showed the vaccine to be nonpathogenic in 111 adults except for slight fever and local inflammation, although one of four juveniles died from disseminated infection. Vaccination of 25 pregnant monkeys was non-pathogenic; however two of 25 fetuses were aborted, one of which was infected and one newborn had microphthalmia, retinitis and a cataract; four of the offspring were not tested. When six lactating monkeys were vaccinated, Toxoplasma was not transmitted to the infants. The high susceptibility to Toxoplasma and the low immunizability was circumstantially attributed to absence of exposure and lack of selection by Toxoplasma of these arboreal monkeys even though about 50% of terrestrial animals from the same area were infected.(ABSTRACT TRUNCATED AT 250 WORDS).


TITLE:
Even though 95% of the children had measles antibodies after vaccination, vaccine efficacy was not more than 68%.

AUTHORS:
Peter Aaby, K Knudsen, T G Jensen, J Tharup, A Poulsen, Morten Sodemann, M C da Silva, Hilton C Whittle

ABSTRACT:
Measles incidence, vaccine efficacy, and mortality were examined prospectively in two districts in Bissau where vaccine coverage for children aged 12-23 months was 81% (Bandim 1) and 61% (Bandim 2). There was little difference in cumulative measles incidence before 9 months of age (6.1% and 7.6%, respectively). Between 9 months and 2 years of age, however, 6.1% contracted measles in Bandim 1 and 13.7% in Bandim 2. Even adjusting for vaccination status, incidence was significantly higher in Bandim 2 (relative risk 1.6, P = .04). Even though 95% of the children had measles antibodies after vaccination, vaccine efficacy was not more than 68% (95% confidence interval [CI] 39%-84%) and was unrelated to age at vaccination. Unvaccinated children had a mortality hazard ratio of 3.0 compared with vaccinated children (P = .002), indicating a protective efficacy against death of 66% (CI 32%-83%) of measles vaccination. These data suggest that it will be necessary to vaccinate before age 9 months to control measles in hyperendemic urban African areas.


TITLE:
The occurrence of secondary vaccine failure and vaccine-modified measles in the United States may lead to underreporting of measles cases and result in overestimation of vaccine efficacy in h

AUTHORS:
M B Edmonson, D G Addiss, J T McPherson, J L Berg, S R Circo, J P Davis

ABSTRACT:
A prolonged school-based outbreak of measles provided an opportunity to study "vaccine-modified" mild measles and secondary vaccine failure. Thirty-six (97%) of 37 unvaccinated patients had rash illnesses that met the Centers for Disease Control clinical case definition of measles, but 29 (15%) of 198 vaccinated patients did not, primarily because of low-grade or absent fever. Of 122 patients with seroconfirmed measles, 10 patients (all previously vaccinated) had no detectable measles-specific IgM and significantly milder illness than either vaccinated or unvaccinated patients with IgM-positive serum. Of 108 vaccinated patients with seroconfirmed measles, 17 patients (16%) had IgM-negative serology or rash illnesses that failed to meet the clinical case definition; their mean age (13 years), age at the time of vaccination, and time since vaccination did not differ from those of other vaccinated patients. The occurrence of secondary vaccine failure and vaccine-modified measles does not appear to be a major impediment to measles control in the United States but may lead to underreporting of measles cases and result in overestimation of vaccine efficacy in highly vaccinated populations.


TITLE:
Post-infection rabies vaccination increases mortality in mice.

ABSTRACT:
When mice infected 1 or 2 days before by an IM inoculation after high passage of the virus in the species ("challenge virus standard" strain) received an injection of live (Flury) or inactivated virus, their mortality was increased in comparison with unvaccinated controls. In the case of the inactivated virus vaccine, mortality was proportional to the dose of vaccine received. Conversely, when vaccination was carried out in mice recently infected with the same doses of a heterologous strain adapted to foxes, this phenomenon could not be demonstrated. The consequences of these observations on failures of treatment in animals infected with a homologous strain, cases of rabies occurring after vaccination or quality control of vaccines are discussed.


TITLE:
A history of prior vaccination is not always associated with immunity nor with the presence of specific antibodies.

AUTHORS:
L Sekla, W Stackiw, G Eibisch, I Johnson

ABSTRACT:
During an epidemic of measles in a vaccinated community, five serodiagnostic tests were performed on 67 persons on whom clinical and epidemiological data were available. The test found most suitable for a rapid diagnosis of measles infection was an Enzyme Linked Immuno Sorbent Assay for the detection of specific IgM antibodies. Only one false negative IgM was recorded. In a group of 45 persons who fulfilled the clinical definition of measles, specific IgM antibodies were detected in the acute phase serum of only 30 (66.6%), of whom 17 were vaccinated. When the convalescent sera were tested, specific IgM antibodies were detected in 25 of the 28 (89.2%) vaccinated, and in 17 of the 17 (100%) non vaccinated clinical cases. A convalescent blood should be tested in persons with a rash illness and no IgM antibodies in the acute phase serum. There were individual variations in the time of appearance of IgM. On the day of onset of rash, IgM antibodies were detected in 7 of the 12 (58.3%). A history of prior vaccination is not always associated with immunity nor with the presence of specific antibodies.


TITLE:
Between May 1985 and September 1987, 228 reports of disease due to Haemophilus Influenzae in vaccinated children were submitted to the FDA.

ABSTRACT:
Haemophilus b polysaccharide vaccine was first licensed in the United States in April 1985. Between May 1985 and September 1987, 228 reports of disease due to Haemophilus influenzae in vaccinated children were submitted to the Food and Drug Administration, of which 216 were accepted for analysis. We compared the relative frequencies of the different disease entities caused by H. influenzae type b reported in vaccinated children with those reported in unvaccinated children (greater than 1000 cases that occurred between 1973 and 1984, as reported in the literature). Over 90% of the vaccinated children were greater than or equal to 24 mo of age. A higher proportion of cases was reported to have occurred within the first two months after vaccination, with 10 cases occurring within 72 h of vaccination. Vaccination did not alter the expected frequencies of the different clinical entities associated with invasive H. influenzae disease. No estimates of clinical efficacy are possible based on the adverse events submitted to the Food and Drug Administration.


TITLE:
A Haemophilus b polysaccharide vaccine resulted in minus 58 percent efficacy in children in Minnesota in August 1985.

AUTHORS:
Michael T Osterholm, J H Rambeck, K E White, J L Jacobs, L M Pierson, J D Neaton, C W Hedberg, K L MacDonald, D M Granoff

ABSTRACT:
We evaluated the efficacy of Haemophilus b polysaccharide vaccine in children in Minnesota using a case-control study. The vaccine became available in Minnesota in August 1985. During the subsequent 28 months, 88 cases of invasive H influenzae type b disease were identified in children 24 to 71 months of age, the group targeted for vaccination. Of the 88 cases, 36 (41%) occurred in vaccinated children. Fifty-eight (33%) of 176 controls were vaccinated during a similar period. The vaccine's protective efficacy for children with any history of vaccination was -58% (95% confidence interval = -204% to 18%). The vaccine's protective efficacy for children who were most likely to be protected by vaccination was -55% (95% confidence interval = -238% to 29%). Our results indicate that vaccination with Haemophilus b polysaccharide vaccine had no effect in preventing H influenzae type b disease in Minnesota children.


TITLE:
Sudden Infant Death syndrome mortality rate in the period zero to three days following DTP was found to be 7.3 times higher than in the period 30 days after immunization.

AUTHORS:
A M Walker, Hershel Jick, D R Perera, R S Thompson, T A Knauss

ABSTRACT:
We compared the recency of diphtheria-tetanus-pertussis (DTP) immunization in healthy children with birthweights greater than 2500 gms who died of sudden infant death syndrome (SIDS) to that of age-matched reference children, using a modified case-control analysis. Focusing on very narrow time intervals following immunization, we found the SIDS mortality rate in the period zero to three days following DTP to be 7.3 times that in the period beginning 30 days after immunization (95 per cent confidence interval, 1.7 to 31). The mortality rate of non-immunized infants was 6.5 times that of immunized infants of the same age (95 per cent CI, 2.2 to 19). The latter result and to some extent the former appear to be ascribable to known risk factors for SIDS. Although the mortality ratios for SIDS following DTP, as estimated from this study, are high the period of apparently elevated risk was very short, so that only a small proportion of SIDS cases in infants with birthweights greater than 2500 gms could be associated with DTP.


TITLE:
In 1985 twin boys simultaneously succumbed to sudden unexpected deaths two to three hours after vaccination with diphtheria, tetanus, and pertussis vaccine (DTP).

ABSTRACT:
In 1985 twin boys simultaneously succumbed to sudden unexpected deaths two to three hours after vaccination with diphtheria, tetanus, and pertussis vaccine (DTP). This occurrence again raises the question of whether an association of sudden infant death (SID) with vaccination is other than temporal. Taking the incidence of SID in conjunction with rates of infant vaccination in the United Kingdom, nine infants would be expected to die, each year by chance alone, suddenly within 24 hours of (and within each 24 hour period succeeding) vaccination with DTP. Twins are at a greater risk of SID than single born infants and occasionally are found dead together. A number of studies into DTP vaccination as a risk factor in SID have shown that SID is less common in vaccinated than in unvaccinated infants.


TITLE:
Provocation by vaccine injections can increase the risk of paralytic poliomyelitis by up to 25 fold.

ABSTRACT:
Provocation by injections can increase the risk of paralytic poliomyelitis by up to 25 fold. In England and Wales the risk of provocation paralysis from DPT given with oral poliovirus is 1 to 2 cases per million children immunized. Cases in India following immunization with oral poliovaccine and DPT are likely to be caused by wild rather than vaccine virus. Most cases of poliomyelitis in the Third World probably follow provocation by unsterile and unnecessary injections. There should normally be very few cases due to immunization. Injections should be sterile and only given when necessary.


TITLE:
A measles outbreak in Montana in 1985 indicates vaccine failure.

AUTHORS:
R M Davis, E D Whitman, W A Orenstein, S R Preblud, Lauri E Markowitz, A R Hinman

ABSTRACT:
From January 4 to May 13, 1985, an outbreak of 137 cases of measles occurred in Montana and persisted for 12 generations of spread. A total of 114 cases occurred on the Blackfeet Indian reservation in northwest Montana. Of the 137 cases, 82 (59.9%) were in school-aged children (aged 5-19 years). Of the 114 cases on the reservation, 108 (94.7%) were classified as programmatically nonpreventable. A total of 64 (82.1%) of the 78 patients on the reservation who were born after 1956 and were above the recommended age at vaccination had a history of adequate measles vaccination. Additionally, an audit of immunization records at the schools in Browning, Montana, where most of the cases occurred, showed that 98.7% of students were appropriately vaccinated. A retrospective cohort study in the Browning schools failed to identify age at vaccination or time since vaccination as significant risk factors for vaccine failure. Overall vaccine efficacy was 96.9% (95% confidence interval = 89.5-98.2%). None of 80 Browning students who were vaccinated at less than 12 months of age and revaccinated at 15 months of age or older became infected. A case-control study showed a significant association between attendance at Browning basketball games and infection early in the outbreak. This outbreak suggests that measles transmission may persist in some settings despite appropriate implementation of the current measles elimination strategy.


TITLE:
Lactobacillus bulgaricus contains a substance which may improve immunogenicity and reduce the toxicity of pertussis vaccination (whooping cough vaccine).

AUTHORS:
I B Shepeleva, N S Zakharova, T N Remova, I G Bazhanova, M V Britsina

ABSTRACT:
The influence of blastolysin, the cell-wall glycopeptide of Lactobacillus bulgaricus, on the main immunobiological properties of pertussis vaccine, its immunogenicity and toxicity, has been studied. The use of blastolysin, introduced as a stimulating agent in definite doses and following definite administration schedules, has been shown to permit achieving not only an increase in the immunogenicity of the corpuscular pertussis vaccine, but also a considerable decrease in its toxicity and histamine-sensitizing activity.


TITLE:
Measles outbreak in a fully immunized secondary-school population with up to 99 percent vaccination.

AUTHORS:
T L Gustafson, A W Lievens, P A Brunell, R G Moellenberg, C M Buttery, L M Sehulster

ABSTRACT:
An outbreak of measles occurred among adolescents in Corpus Christi, Texas, in the spring of 1985, even though vaccination requirements for school attendance had been thoroughly enforced. Serum samples from 1806 students at two secondary schools were obtained eight days after the onset of the first case. Only 4.1 percent of these students (74 of 1806) lacked detectable antibody to measles according to enzyme-linked immunosorbent assay, and more than 99 percent had records of vaccination with live measles vaccine. Stratified analysis showed that the number of doses of vaccine received was the most important predictor of antibody response. Ninety-five percent confidence intervals of seronegative rates were 0 to 3.3 percent for students who had received two prior doses of vaccine, as compared with 3.6 to 6.8 percent for students who had received only a single dose. After the survey, none of the 1732 seropositive students contracted measles. Fourteen of 74 seronegative students, all of whom had been vaccinated, contracted measles. In addition, three seronegative students seroconverted without experiencing any symptoms. We conclude that outbreaks of measles can occur in secondary schools, even when more than 99 percent of the students have been vaccinated and more than 95 percent are immune.


TITLE:
An outbreak of measles occurred in a high school with a documented vaccination level of 98 per cent.

AUTHORS:
B M Nkowane, S W Bart, W A Orenstein, M Baltier

ABSTRACT:
An outbreak of measles occurred in a high school with a documented vaccination level of 98 per cent. Nineteen (70 per cent) of the cases were students who had histories of measles vaccination at 12 months of age or older and are therefore considered vaccine failures. Persons who were unimmunized or immunized at less than 12 months of age had substantially higher attack rates compared to those immunized on or after 12 months of age. Vaccine failures among apparently adequately vaccinated individuals were sources of infection for at least 48 per cent of the cases in the outbreak. There was no evidence to suggest that waning immunity was a contributing factor among the vaccine failures. Close contact with cases of measles in the high school, source or provider of vaccine, sharing common activities or classes with cases, and verification of the vaccination history were not significant risk factors in the outbreak. The outbreak subsided spontaneously after four generations of illness in the school and demonstrates that when measles is introduced in a highly vaccinated population, vaccine failures may play some role in transmission but that such transmission is not usually sustained.


TITLE:
The risk of adverse events from the pertussis outweighed the risk of pertussis infection during the period of 1970-83 in children living in non-deprived circumstances in Britain.

ABSTRACT:
Since 1975, acceptance of pertussis vaccine has fallen from over 70% to 50% or less in most parts of Britain. This permits evaluation of a continuing natural experiment in which the frequency and severity of whooping cough can be compared those of adverse events following injections of pertussis vaccine. National data show an increase in notifications of whooping cough in most parts of Britain since 1975. Hospital admissions show considerable variation between areas with relatively high rates in some areas of deprivation but very low rates in more affluent areas even where vaccine-acceptance is around 50%. Deaths of infants with whooping cough have decreased steadily since 1900, the rate since 1975 being the lowest ever. Active epidemiological surveillance in Glasgow, with a population of 216,000 children and 13,000 births annually, shows that outbreaks and severe cases requiring admission to hospital were concentrated consistently in a few areas of deprivation. There is a significant correlation between vaccine-acceptance and hospital admission by district of residence but analysis of variance shows this effect to be less than that of overcrowding in households and other deprivation variables. In each of three outbreaks studied prospectively (1974-5, 78-78 and 82) about 30% of cases occurred in children who had received three doses of pertussis vaccine. Such vaccination had a significant protective effect in children aged 1-4 years but not in older children. There was no evidence of a herd immunity sufficient to protect infants below age for vaccination. Admissions to hospital decreased during the period 1970-83. There were no deaths attributable to proven or suspected infections with Bordetella pertussis during the period 1972-1983. No cases of encephalopathy, permanent brain damage or lung damage were detected in a follow up of all cases notified, surveyed or admitted to hospital between 1975 and 1982. Collectively, these national and local data provided estimates of the frequency of infection, complications of infection, admission to hospital and death in children with whooping cough for comparison with local, national and published estimates of the frequency and severity of adverse reactions, encephalopathy, permanent brain damage and death after injections of pertussis vaccine. It is concluded that, in children living in non-deprived circumstances in Britain, the risk of pertussis vaccine during the period 1970-83 exceeded those of whooping cough. In some deprived sectors, the risks from whooping cough might have been marginally higher but there was no evidence that this was associated with any increase in deaths or permanent disabilities.


TITLE:
DPT vaccines have been associated with recurrent seizures.

ABSTRACT:
Twenty-two patients with recurrent seizures that started less than 24 hours after immunization with diphtheria, tetanus, and pertussis (DTP) vaccine were retrospectively studied. The initial seizure generally occurred after one of the first three DTP vaccine immunizations, and followed that immunization by less than 12 hours. Two of the 22 patients were siblings. Eight patients had additional immunizations with DTP vaccine and four had immediate worsening of their seizures. Of the 22 patients, only one was seizure free and stopped taking anticonvulsants. Three patients exhibited normal development, and 11 had severe developmental delays. Based on these observations, we reviewed current contraindications for immunization with pertussis vaccine.


TITLE:
Sudden infant death syndrome and DTP vaccine timing may be linked.

ABSTRACT:
Because diphtheria and tetanus toxoids pertussis (DTP) vaccine is routinely given during the period of highest incidence of sudden infant death syndrome (SIDS), this study was undertaken to determine if there is a temporal association between DTP immunization and SIDS. Parents of 145 SIDS victims who died in Los Angeles County between January 1, 1979, and August 23, 1980, were contacted and interviewed regarding their child's recent immunization history. Fifty-three had received a DTP immunization. Of these 53, 27 had received a DTP immunization within 28 days of death. Six SIDS deaths occurred within 24 hours and 17 occurred within 1 week of DTP immunization. These SIDS deaths were significantly more than expected were there no association between DTP immunization and SIDS. An additional 46 infants had a physician/clinic visit without DTP immunization prior to death. Forty of these infants died within 28 days of this visit, seven on the third day and 22 within the first week following the visit. These deaths were also significantly more than expected. These data suggest a temporal association between DTP immunization, physician visits without DTP immunization and SIDS.


TITLE:
Congenital malformation is a possible consequence of rubella vaccination during pregnancy.

AUTHORS:
S R Preblud, H C Stetler, J A Frank, W L Greaves, A R Hinman, K L Herrmann

ABSTRACT:
Ninety-four susceptible women received either Cendehill or HPV-77 rubella vaccine. All gave birth to healthy infants. Seventeen susceptible women received the RA 27/3 vaccine. All their infants were free of abnormalities compatible with congenital rubella, as were 54 born to mothers of unknown immune status at the time of RA 27/3 vaccination and those later found to be immune. An additional susceptible woman received an unknown strain of vaccine; she also had a healthy infant. The risk of severe congenital malformations after rubella vaccination is low. In our 112 cases, the maximum risk was approximately 3%. Concern about the potential adverse effects of rubella vaccine on the fetus should not interfere with vaccination of women of childbearing age. However, since the actual risk may not be zero, women known to be pregnant should not be vaccinated, and conception should be avoided for three months after vaccination.


TITLE:
There is evidence that measles vaccine recipients can shed measles vaccine.

AUTHORS:
Paul A Rota, AS Khan, E Durigon, T Yuran, Y S Villamarzo, William J Bellini

ABSTRACT:
Analysis of urine specimens by using reverse transcriptase-PCR was evaluated as a rapid assay to identify individuals infected with measles virus. For the study, daily urine samples were obtained from either 15-month-old children or young adults following measles immunization. Overall, measles virus RNA was detected in 10 of 12 children during the 2-week sampling period. In some cases, measles virus RNA was detected as early as 1 day or as late as 14 days after vaccination. Measles virus RNA was also detected in the urine samples from all four of the young adults between 1 and 13 days after vaccination. This assay will enable continued studies of the shedding and transmission of measles virus and, it is hoped, will provide a rapid means to identify measles infection, especially in mild or asymptomatic cases.


TITLE:
Vaccination in infants less than 3 months is associated with an increased risk of sudden infant death syndrome.

ABSTRACT:
Because diphtheria, tetanus, pertussis and poliomyelitis vaccine is routinely given during the period of highest incidence of sudden infant death syndrome (SIDS), we carried out a retrospective case-control study to assess whether such vaccination increased the risk of SIDS. The vaccination status of 118 SIDS and 332 control children, matched for sex, date of birth and age of the victims at death, was compared: the victims of SIDS were not significantly more often vaccinated than control children, the odds ratio was estimated at 1.9 with a 95% confidence interval from 0.9 to 3.9. There was a statistical difference between vaccination status of SIDS cases and controls aged less than three months. Nine percent of SIDS cases under 3 months had been vaccinated whereas the matched controls had not. In our study DTCP vaccination was not a risk factor for SIDS; although more of the SIDS infants less than 3 months of age had been vaccinated. This result however, concerns only one subgroup of the population studied and needs to be confirmed with another study of only SIDS infants less than 3 months of age, because DTCP vaccination was not a risk factor for SIDS when considering the total sample of the study.


TITLE:
Primary and secondary vaccine failure may explain the 1992 measles epidemic in Cape Town.

AUTHORS:
N Coetzee, G D Hussey, G Visser, P Barron, A Keen

ABSTRACT:
Over the last 6 years there has been a decline in the incidence of measles in Cape Town. However, during August 1992 an outbreak occurred, with cases reported at many schools in children presumably immunised. The objectives of this study were to characterise the epidemic in Cape Town and to determine possible reasons for the outbreak. The investigation consisted of two components--a description of the epidemic and an investigation of an outbreak at one primary school. Results indicate that during the last 4 months of the year, 757 cases were notified in Cape Town, compared with 144 in the first 8 months. The epidemic affected mainly white and coloured children over 5 years of age (P < 0.001). In contrast, during the period before the epidemic most cases occurred in black children and in those aged less than 1 year (P < 0.001). There was no significant increase in hospitalised cases. Investigation of the outbreak at one school revealed that the attack rate was 7.6% (25/329 children). Immunisation coverage (at least one dose of any measles vaccine) was 91% and vaccine efficacy was estimated to be 79% (95% CI 55-90); it was highest for monovalent measles (100%) and lowest for measles-mumps-rubella (74%). The epidemiology of measles in Cape Town has thus changed as evinced in this epidemic, with an increase in the number of cases occurring in older, previously vaccinated children. The possible reasons for this include both primary and secondary vaccine failure.(ABSTRACT TRUNCATED AT 250 WORDS).


TITLE:
Measles, mumps, and rubella catch up immunisation in a measles epidemic did not appear to confer protection and was associated with a variety of new side effects of the vaccine.

AUTHORS:
R J Roberts, Q D Sandifer, M R Evans, M Z Nolan-Farrell, P M Davis

ABSTRACT:
To investigate the reasons for poor uptake of immunisation (non-immunisation) and the possible side effects of measles, mumps, and rubella vaccine in a catch up immunisation campaign during a community outbreak of measles.


TITLE:
A 1993 outbreak of measles in a highly immunised Australian population.

ABSTRACT:
An outbreak of 18 cases of measles in a primary school in the Australian Capital Territory in August and September 1993 provided the opportunity to study measles immunisation status and measles vaccine efficacy. Parents of 384 (78 per cent) of 491 children answered a questionnaire on recent illness consistent with measles and measles immunisation. Parents transcribed details of measles immunisation from the personal health record of the child to the questionnaire. Thirty-three per cent of cases and 3.4 per cent of the other children had not been immunised. Overall, 95 per cent of children had been immunised. The efficacy for all measles vaccines was estimated to be 90 per cent (95 per cent confidence interval (CI) 75 to 96) and for measles-mumps vaccine 87 per cent (CI 70 to 95). All of the immunised cases had received measles-mumps vaccine. There was no increased risk of measles infection in those who had been immunised at under 15 months of age compared with those immunised at 15 months or older, or in those who could not provide a date of immunisation compared with those who could. None of the children who had received two doses of vaccine caught measles. The date of immunisation was provided by 65 per cent of the respondents who said their children had been immunised. Asking parents to provide this date instead of viewing the health record is a less expensive way of assessing immunisation status but this method needs to be evaluated. Measles outbreaks still occur in highly immunised populations when vaccine efficacy appears to be acceptable.


ABSTRACT:
Vaccination for birth control has several advantages over currently available methods of family planning and should prove an attractive addition to the contraceptive armamentarium both in developing countries and in a developed country such as Australia. Concerns have been voiced by consumer health advocates that vaccines, like other long acting contraceptive methods, may be abused by health authorities in developing countries and by their use in vulnerable groups such as aborigines in our own country. These concerns need to be recognised and addressed. More difficult to accommodate are the anxieties expressed by feminist groups about the 'loss of control' and 'lack of body awareness' inherent in a method, such as a vaccine, that is relatively easily administered and has no overt side effects. There is no evidence that these concerns are shared by women in general. The antifertility vaccine that will most likely be applied first in family planning programmes is one directed against the pregnancy hormone hCG. A WHO vaccine directed against the C-terminal peptide of beta-hCG provokes a specific and safe immune response and will enter Phase 2 trials in Sweden this year. Subsequent developments with this vaccine will include the replacement of the current emulsion vehicle by a delivery system based on biodegradeable microspheres which will give a more sustained antigen release and duration of effectiveness.


TITLE:
Acute posterior multifocal placoid pigment epitheliopathy after hepatitis B vaccine has been reported.

AUTHORS:
A P BrÃ©zin, P Massin-Korobelnik, M Boudin, A Gaudric, P LeHoang

ABSTRACT:
To report two cases of acute posterior multifocal placoid pigment epitheliopathy after immunization with a recombinant hepatitis B virus vaccine.


TITLE:
Pertussis vaccination and asthma: is there a link?


TITLE:
The Institute of Medicine determined that routine childhood vaccines are linked to a number of serious adverse reactions.

ABSTRACT:
In September 1993, the Institute of Medicine released a report entitled Adverse Events Associated With Childhood Vaccines: Evidence Bearing on Causality. The report examined putative serious adverse consequences associated with administration of diphtheria and tetanus toxoids; measles, mumps, and measles-mumps-rubella vaccines; oral polio vaccine and inactivated polio vaccine; hepatitis B vaccines; and Haemophilus influenzae type b (Hib) vaccines. The committee spent 18 months reviewing all available scientific and medical data, from individual case reports (published and unpublished) to controlled clinical trials. The committee found that the evidence favored the rejection of a causal relation between diphtheria and tetanus toxoids and encephalopathy, infantile spasms, and sudden infant death syndrome, and between conjugate Hib vaccines and susceptibility to Hib disease. The committee found that the evidence favored acceptance of a causal relation between diphtheria and tetanus toxoids and Guillain-Barré syndrome and brachial neuritis, between measles vaccine and anaphylaxis, between oral polio vaccine and Guillain-Barré syndrome, and between unconjugated Hib vaccine and susceptibility to Hib disease. The committee found that the evidence established causality between diphtheria and tetanus toxoids and anaphylaxis, between measles vaccine and death from measles vaccine-strain viral infection, between measles-mumps-rubella vaccine and thrombocytopenia and anaphylaxis, between oral polio vaccine and poliomyelitis and death from polio vaccine-strain viral infection, and between hepatitis B vaccine and anaphylaxis. For five vaccine-related adverse events, there was no evidence identified. For the remaining 33 vaccine-related adverse events, the evidence was inadequate to accept or reject a causal relation.


TITLE:
Since the 1993 pertussis epidemic in Cincinnati occurred primarily among children who had been appropriately immunized, it is clear that the whole-cell pertussis vaccine failed to give full protection against the disease.

AUTHORS:
C D Christie, M L Marx, C D Marchant, S F Reising

ABSTRACT:
In 1993 there was a resurgence of pertussis in the United States. Altogether, 6335 cases were reported, the most in 26 years.


TITLE:
Measles vaccination in developing countries has resulted in higher infant mortality rates.


TITLE:
Lack of correlation between serum rotavirus antibody titers and protection following vaccination with reassortant RRV vaccines.

ABSTRACT:
In a large placebo-controlled efficacy trial of the rhesus tetravalent (RRV-TV) and serotype 1 monovalent (RRV-S1) rotavirus vaccines in multiple sites throughout the United States, protection against rotavirus disease over a 2-year period was found to be 57 and 40%, respectively (Bernstein et al., J. Am. Med. Assoc., 1995, 273, 1191-1196). Sera collected from a subset of subjects during this trial were used to determine possible correlations between rotavirus antibody responses after vaccination and protection. Between 82% (RRV-S1) and 92% (RRV-TV) of the vaccinees seroconverted by at least one of the six antibody assays performed (i.e. rotavirus IgA and neutralizing antibody to RRV and serotype 1-4 human rotaviruses). Rises in neutralizing antibody were due primarily to RRV. The seroconversion rate was only 18-22% to each of the four human rotavirus serotypes following RRV-TV vaccination and was only 43% to serotype 1 human rotavirus after RRV-S1 administration. Furthermore, no correlate of immunity against rotavirus infection or disease was identifiable based on seroconversion to any of the antibodies measured. Likewise, no consistent relationship was found between the titers of any of these six antibodies following vaccination and protection against rotavirus, thus suggesting that serum antibody titers will not be useful markers of protection with these reassortant RRV vaccines. In addition, vaccinated subjects did not develop higher titers of neutralizing antibody to human rotaviruses following a subsequent natural rotavirus illness, a further indication that only weak immune responses to human rotaviruses were stimulated by vaccination with the RRV reassortants.(ABSTRACT TRUNCATED AT 250 WORDS).


TITLE:
In a measles outbreak from March 1991 to April 1992 in Rio de Janeiro 76.4% of those suspected to be infected had received measles vaccine before their first birthday.

AUTHORS:
S A de Oliveira, W N Soares, M O Dalston, M T de Almeida, AJ Costa

ABSTRACT:
From March 1991 to April 1992, 250 measles suspected cases were studied in the Municipality of Niterói, State of Rio de Janeiro. The median age found was 11 years and 76.0% of the cases were in school age children. Exposure histories were present in 149 patients and schools were the most frequent sites of transmission (45.0%). Vaccination status was known for 127 studied cases and 76.4% of them had received measles vaccine before their first birthday. One or more complications were reported for 68 cases and in 8.9% of the studied cases hospitalization was required. Frequency of complications varied according to each age group studied and were more commonly encountered among children < 1 year of age (55.6%). The history of previous vaccination did not diminish the number of complications of the cases studied. The results of this work show changes in age distribution of measles leading to sizeable outbreaks among teenagers and young adults.


TITLE:
High titre measles vaccination increases female mortality in those receiving immunization in West Africa.

AUTHORS:
K M Knudsen, Peter Aaby, Hilton C Whittle, M Rowe, B Samb, Francois Simondon, J Sterne, P Fine

ABSTRACT:
The World Health Organization (WHO) recommended the use of high titre measles vaccine in 1989. Subsequent long term follow-up of several trials yielded results suggesting higher mortality among children inoculated with medium and high titre vaccines compared to standard titre vaccines, although none of the individual trials found significant differences in mortality.


TITLE:
The vaccination of pregnant sheep resulted in abortions and hydranencephaly.

ABSTRACT:
A cell culture attenuated Australian bluetongue virus serotype 23 (BLU23) prototype vaccine was assessed for its effects on pregnant Merino sheep. Seventy-six ewes were vaccinated at 5 different stages of gestation, and the failure to lamb at term was as follows: 35 to 43 days of gestation, 20/36 (56%); 57 to 64 days of gestation, 3/10 (30%); 81 to 88 days of gestation, 3/10 (30%); 109 to 116 days of gestation, 0/10 (0%); 130 to 137 days of gestation, 0/10 (0%). Of 30 ewes vaccinated with a cell culture supernatant fluid control between 35 and 43 days of gestation, 6.7% (2/30) failed to lamb at term. Two ewes vaccinated with BLU23 vaccine between 35 and 43 days of gestation had lambs with hydranencephaly. All other lambs born were clinically normal. Three ewes vaccinated with BLU23 aborted. Two of these were vaccinated between 35 and 43 days of gestation, the 3rd between 81 and 88 days of gestation. Five lambs were born with BLU group antibody. Four of these were from ewes vaccinated between 35 and 43 days of gestation, and 2 of these had hydranencephaly. The fifth was from a ewe vaccinated between 57 and 64 days of gestation. The vaccine did not produce disease in adult sheep, but was a potent cause of early foetal death and to a much lesser extent foetal malformation.


TITLE:
Acute transverse myelitis after influenza vaccination has been reported.

ABSTRACT:
Descriptions in the literature of magnetic resonance imaging (MRI) findings in post-vaccination myelitis are scarce. Described here is a case of acute transverse myelitis that occurred after administration of an influenza vaccination. T1-weighted MRIs showed diffuse, fusiform spinal cord enlargement, extending from C-3 to rostral thoracic levels. Intramedullary lesions containing increased T2 signal were found in the areas of cord enlargement. The involvement on MRI was profound, extending far rostral to the level of the discrete clinical myelopathy. The lesions did not enhance after contrast administration. The patient had a complete long-term recovery of neurological function. This represents the first report of MRI findings in acute transverse myelitis after influenza vaccination.


TITLE:
A vaccine developed for bison resulted in inducing placentitis and abortion in pregnant cows.

AUTHORS:
M V Palmer, S C Olsen, M J Gilsdorf, L M Philo, P R Clarke, N F Cheville

ABSTRACT:
To determine the ability of Brucella abortus strain RB51 to induce placentitis and abortion in bison after SC vaccination.


TITLE:
Live attenuated virus Vaccines produced on chicken-derived cells contain low levels of particle-associated reverse transcriptase (RT).

ABSTRACT:
We have recently shown that live attenuated virus vaccines produced on chicken-derived cells contain low levels of particle-associated reverse transcriptase (RT). In both virus and corresponding control harvests produced on chicken embryo fibroblasts, these activities were present at significantly higher concentrations than in the vaccines. In order to identify the putative retrovirus sequence responsible for this activity, a novel method for the selective PCR amplification of particle-associated retrovirus RNA that uses DNA primers complementary to the primer binding sites of the known exogenous retroviruses in combination with an anchor primer was applied. A product of the endogenous avian retrovirus family EAV-0, termed EAV-0(B1), was reproducibly generated with a tRNA(Trp)-derived primer from the RT peak fraction of a sucrose density gradient run with a harvest of a live attenuated measles vaccine. In contrast, no products were detected with primers derived from tRNA(Pro), tRNA(Lys)1,2 or tRNA(Lys)3. In the same fraction, genomic RNA of EAV-0(B1) was demonstrated by long PCR. Analysis of several sucrose density gradients from different harvests of various manufacturers demonstrated accumulation of, and colocalization with, RT activity for the EAV-0(B1) RNA but not for a chicken cellular mRNA. Synthesis of cDNA from EAV-0(B1) RNA was shown by endogenous RT reaction. Furthermore, complexes of naturally primed EAV-0(B1) RNA with RT were demonstrated. Taken together, these data strongly suggest that EAV-0 is able to produce virus-like particles with an active RT.


TITLE:
The use of post-mortem tissues in the production of biologicals, vaccines and feedstuffs may be contributing to transmissible encephalopathies.

ABSTRACT:
The use of post-mortem tissues as sources for the production of biologicals, vaccines and feedstuffs has led to the transmission or generation of transmissible encephalopathies in some recipients. For example, the use of pituitary-derived human growth hormone and gonadotropins has resulted in the transmission of Creutzfeldt-Jakob disease to other humans [1], the use of formalin-inactivated sheep brain as a source for louping ill vaccine led to the transmission of scrapie to over 1,000 sheep from one vaccine lot [2], and the use of rendered products from ruminant carcasses in the domestic animal food chain led to the emergence and epizootic of bovine spongifrom encephalopathy in the United Kingdom [3]. Infection with transmissible encephalopathies by iatrogenic or other mechanisms is difficult to predict or control. The characteristics of these pathogens do not permit easy detection, clearance, or inactivation in routine biopharmaceutical production environments.


TITLE:
Passive immunity against measles is superior in infants of mothers who experienced naturally acquired measles infection versus those who were vaccinated.

AUTHORS:
Gaston De Serres, J R Joly, M Fauvel, F Meyer, B Masse, Nicole Boulianne

ABSTRACT:
Neutralizing antibody titers of 47 infants whose mothers sustained measles (measles group) and 70 whose mothers were vaccinated (vaccine group) were compared at birth, 4 and 8 months of age. All children had antibodies at birth and 88% at 4 months. At 8 months, 49% had antibodies in the measles group and 15% in the vaccine group (P < 0.001). The geometric mean titers were significantly lower in the vaccine group than in the measles group and the difference corresponded to the antibody loss occurring in only 1.5 months of life. This small difference may reflect past exposure to wild virus of many vaccinated mothers.


TITLE:
Varicella vaccine virus can be contagious and infect others.

AUTHORS:
M B Salzman, R G Sharrar, S Steinberg, P LaRussa

ABSTRACT:
A 12-month-old healthy boy had approximately 30 vesicular skin lesions 24 days after receiving varicella vaccine. Sixteen days later his pregnant mother had 100 lesions. Varicella-vaccine virus was identified by polymerase chain reaction in the vesicular lesions of the mother. After an elective abortion, no virus was detected in the fetal tissue. This case documents transmission of varicella-vaccine virus from a healthy 12-month-old infant to his pregnant mother.


TITLE:
Varicella vaccine virus can be contagious and infect others - Article 2.

AUTHORS:
P LaRussa, S Steinberg, F Meurice, A Gershon

ABSTRACT:
Twelve days after receiving an investigational Oka strain live attenuated varicella vaccine, a 38-year-old healthy white woman developed a rash consisting of 30 scattered lesions. Sixteen days later, her 2 children also developed rash. Swabs obtained from the skin lesions of the vaccinee and her children demonstrated the presence of varicella-zoster virus (VZV) DNA by a polymerase chain reaction (PCR) assay. Restriction endonuclease polymorphisms present in wild and vaccine type VZV were examined, and the amplified VZV DNA was determined to be vaccine type. This case documents transmission of varicella vaccine type virus from a healthy vaccinee to susceptible household contacts. Since vaccine-associated rashes are uncommon and mild, it is likely that transmission of vaccine virus will also be uncommon. With widespread immunization beginning in the United States, ongoing studies will define the frequency of this transmission.


TITLE:
38,787 adverse events including infant death (highest in 1-3 month olds) after vaccination were reported between 1991-1994. (The authors speciously claim SIDS and not vaccination caused these deaths).

ABSTRACT:
To provide an overview of the data, function, and performance of the Vaccine Adverse Event Reporting System.


TITLE:
Cutaneous lupus erythematosus and buccal aphthosis after hepatitis B vaccination has been reported in a 6-year-old child

AUTHORS:
P GrÃ©zard, M Chefai, V Philippot, H Perrot, M Faisant

ABSTRACT:
Although the hepatitis B vaccination tolerance is generally good, adverse effects, which are specially neurologic and cutaneous, have been observed and some cases of induced diseases with immunological disorders have been reported.


TITLE:
Vaccines produced in chick embryo cells had significant reverse transcriptase activity.

ABSTRACT:
A recent publication reporting the presence of low levels of reverse transcriptase (RT) activity in certain vaccines for human use necessitated that regulatory agencies address the issue of whether this RT activity presented a risk to humans. Detection of low levels of RT activity corresponding to fewer than ten virions became possible with the development of highly-sensitive polymerase chain reaction (PCR)-based RT (PBRT) assays. Variations of the PBRT assay were developed in three laboratories. These assays were reported as being at least one million-fold more sensitive than conventional RT assays.


TITLE:
Despite a high coverage with measles vaccines in parts of west Africa, epidemics of measles occur with reduced severity in an increasing proportion of older children who have been vaccinated.

AUTHORS:
Hilton C Whittle, Peter Aaby, B Samb, Henrik Jensen, J Bennett, Francois Simondon

ABSTRACT:
Despite a high coverage with measles vaccines in parts of west Africa, epidemics of measles occur with reduced severity in an increasing proportion of older children who have been vaccinated. We examined the effect of exposure to natural measles on immunity in vaccinated children.


TITLE:
Hepatitis B vaccine is associated with an increased risk of liver problems in U.S. children less than 6 years old, 1993 and 1994.

ABSTRACT:
Data to assess the benefits and risks of hepatitis B vaccine for the general population of U.S. children are sparse. This study addressed the problem of external validity found in previous studies of high risk populations by evaluating the benefit of hepatitis B vaccination for the general population of American children. We calculated the risk of liver problems among hepatitis B vaccinated and non-hepatitis B vaccinated children using logistic regression. Hepatitis B vaccinated children had an unadjusted odds ratio of 2.94 and age-adjusted odds ratio of 2.35 for liver problems compared with non-hepatitis B vaccinated children in the 1993 National Health Interview Survey. Hepatitis B vaccinated children had an unadjusted odds ratio of 2.57 and age-adjusted odds ratio of 1.53 for liver problems compared with non-hepatitis B vaccinated children in the 1994 National Health Interview Survey dataset.


TITLE:
Coriandrum sativum has antioxidant activity.

ABSTRACT:
The antiperoxidative effect of coriander seeds (Coriandrum sativum) was studied in rats administered high fat diet. Significant decrease in the levels of lipid peroxides, free fatty acids and glutathione was observed when compared to control group whereas the activity of antioxidant enzymes showed increase.


TITLE:
Vaccination can precipitate lupus erythematosus.

AUTHORS:
S A Older, D F Battafarano, RJ Enzenauer, A M Krieg

ABSTRACT:
To report a series of five patients who developed systemic lupus erythematosus (SLE) after immunization and review the literature on vaccine-associated connective tissue diseases and the theoretical mechanisms that could explain such an association.


TITLE:
Symptomatic Gulf War Syndrome is strongly associated with the presence of autoantibodies to squalene, an adjuvant used in vaccines.

ABSTRACT:
Gulf War Syndrome (GWS) is a multisystemic illness afflicting many Gulf War-era veterans. The molecular pathological basis for GWS has not been established. We sought to determine whether the presence of antibodies to squalene correlates with the presence of signs and symptoms of GWS. Participants in this blinded cohort study were individuals immunized for service in Desert Shield/Desert Storm during 1990-1991. They included 144 Gulf War-era veterans or military employees (58 in the blinded study), 48 blood donors, 40 systemic lupus erythematosus patients, 34 silicone breast implant recipients, and 30 chronic fatigue syndrome patients. Serum antibodies to squalene were measured. In our small cohort, the substantial majority (95%) of overtly ill deployed GWS patients had antibodies to squalene. All (100%) GWS patients immunized for service in Desert Shield/Desert Storm who did not deploy, but had the same signs and symptoms as those who did deploy, had antibodies to squalene. In contrast, none (0%) of the deployed Persian Gulf veterans not showing signs and symptoms of GWS have antibodies to squalene. Neither patients with idiopathic autoimmune disease nor healthy controls had detectable serum antibodies to squalene. The majority of symptomatic GWS patients had serum antibodies to squalene.


TITLE:
Vaccination may be contributing to autoimmune disease.

ABSTRACT:
The question of a connection between vaccination and autoimmune illness (or phenomena) is surrounded by controversy. A heated debate is going on regarding the causality between vaccines, such as measles and anti-hepatitis B virus (HBV), and multiple sclerosis (MS). Brain antibodies as well as clinical symptoms have been found in patients vaccinated against those diseases. Other autoimmune illnesses have been associated with vaccinations. Tetanus toxoid, influenza vaccines, polio vaccine, and others, have been related to phenomena ranging from autoantibodies production to full-blown illness (such as rheumatoid arthritis (RA)). Conflicting data exists regarding also the connection between autism and vaccination with measles vaccine. So far only one controlled study of an experimental animal model has been published, in which the possible causal relation between vaccines and autoimmune findings has been examined: in healthy puppies immunized with a variety of commonly given vaccines, a variety of autoantibodies have been documented but no frank autoimmune illness was recorded. The findings could also represent a polyclonal activation (adjuvant reaction). The mechanism (or mechanisms) of autoimmune reactions following immunization has not yet been elucidated. One of the possibilities is molecular mimicry; when a structural similarity exists between some viral antigen (or other component of the vaccine) and a self-antigen. This similarity may be the trigger to the autoimmune reaction. Other possible mechanisms are discussed. Even though the data regarding the relation between vaccination and autoimmune disease is conflicting, it seems that some autoimmune phenomena are clearly related to immunization (e.g. Guillain-Barre syndrome). The issue of the risk of vaccination remains a philosophical one, since to date the advantages of this policy have not been refuted, while the risk for autoimmune disease has not been irrevocably proved. We discuss the pros and cons of this issue (although the temporal relationship (i.e. always 2-3 months following immunization) is impressive).


TITLE:
DTP or tetanus vaccination increases the risk of allergies and related respiratory symptoms in children and adolescents.

ABSTRACT:
Findings from animal and human studies confirm that diphtheria and tetanus toxoids and pertussis (DTP) and tetanus vaccinations induce allergic responses; associations between childhood vaccinations and subsequent allergies have been reported recently.


TITLE:
Measles virus DNA from the MMR vaccine has been found in peripheral mononuclear cells in patients with ulcerative colitis and children with autism, indicating its possible role in the pathogenesis of these disorders.

AUTHORS:
H Kawashima, T Mori, Y Kashiwagi, K Takekuma, A Hoshika, A Wakefield

ABSTRACT:
It has been reported that measles virus may be present in the intestine of patients with Crohn's disease. Additionally, a new syndrome has been reported in children with autism who exhibited developmental regression and gastrointestinal symptoms (autistic enterocolitis), in some cases soon after MMR vaccine. It is not known whether the virus, if confirmed to be present in these patients, derives from either wild strains or vaccine strains. In order to characterize the strains that may be present, we have carried out the detection of measles genomic RNA in peripheral mononuclear cells (PBMC) in eight patients with Crohn's disease, three patients with ulcerative colitis, and nine children with autistic enterocolitis. As controls, we examined healthy children and patients with SSPE, SLE, HIV-1 (a total of eight cases). RNA was purified from PBMC by Ficoll-paque, followed by reverse transcription using AMV; cDNAs were subjected to nested PCR for detection of specific regions of the hemagglutinin (H) and fusion (F) gene regions. Positive samples were sequenced directly, in nucleotides 8393-8676 (H region) or 5325-5465 (from noncoding F to coding F region). One of eight patients with Crohn disease, one of three patients with ulcerative colitis, and three of nine children with autism, were positive. Controls were all negative. The sequences obtained from the patients with Crohn's disease shared the characteristics with wild-strain virus. The sequences obtained from the patients with ulcerative colitis and children with autism were consistent with being vaccine strains. The results were concordant with the exposure history of the patients. Persistence of measles virus was confirmed in PBMC in some patients with chronic intestinal inflammation.


TITLE:
Hepatitis B vaccination is associated with potentially neurotoxic mercury exposure in infants.

AUTHORS:
G V Stajich, G P Lopez, S W Harry, W R Sexson

ABSTRACT:
Thimerosal, a derivative of mercury, is used as a preservative in hepatitis B vaccines. We measured total mercury levels before and after the administration of this vaccine in 15 preterm and 5 term infants. Comparison of pre- and post-vaccination mercury levels showed a significant increase in both preterm and term infants after vaccination. Additionally, post-vaccination mercury levels were significantly higher in preterm infants as compared with term infants. Because mercury is known to be a potential neurotoxin to infants, further study of its pharmacodynamics is warranted.


TITLE:
Influenza vaccine has been reported to be a possible trigger of rhabdomyolysis induced acute renal failure in those taking statin drugs.

AUTHORS:
E Plotkin, J Bernheim, S Ben-Chetrit, A Mor, Z Korzets


TITLE:
At the present time, the only poliovirus-caused poliomyelitis cases reported in Brazil and other countries of the Americas are of vaccine etiology.

ABSTRACT:
At the present time, the only poliovirus-caused poliomyelitis cases reported in Brazil and other countries of the Americas are of vaccine etiology. It is important for epidemiological surveillance and immunization programs to evaluate the epidemiological profile of cases of vaccine-associated paralytic poliomyelitis (VAPP) in order to establish criteria for case definition and vaccination strategies. To research VAPP in Brazil, 30 cases diagnosed and classified as such by the Ministry of Health between 1989 and 1995 were submitted to a descriptive study of clinical, laboratory, and epidemiological data. In addition, the risk of occurrence of VAPP was estimated in relation to determinants based on a cohort of 3,656 persons with acute flaccid paralysis. Among individuals who had received oral polio vaccine (OPV) from 4 to 40 days before the onset of paralysis, we found a relative risk of 8.88 (95% CI: 4.37-18.03) for VAPP as compared with persons who had not been vaccinated during the same time interval. For individuals who developed VAPP in the period following national vaccination days, the estimated relative risk was 2.94 (95% CI: 1.44-6.00). For the first dose of OPV administered to the general population the estimated risk was 1 case of VAPP for every 2.39 million doses; for total doses of OPV the risk was 1 case in 13.03 million doses. A major share of VAPP cases were related to children affected by prodromes (fever and gastrointestinal signs and/or symptoms), isolation of vaccine poliovirus type 2, paralysis of the lower limbs, and a mean age of 1 year.


TITLE:
Vaccinated children and adults may serve as reservoirs for silent pertussis infection and become potential transmitters to unprotected infants.

AUTHORS:
I Srugo, D Benilevi, R Madeb, S Shapiro, T Shohat, E Somekh, Y Rimmar, V Gershtein, R Gershtein, E Marva, N Lahat

ABSTRACT:
We tested 46 fully vaccinated children in two day-care centers in Israel who were exposed to a fatal case of pertussis infection. Only two of five children who tested positive for Bordetella pertussis met the World Health Organization's case definition for pertussis. Vaccinated children may be asymptomatic reservoirs for infection.


TITLE:
Hepatitis B vaccine is positively associated with adverse health outcomes in the general population of US children.

AUTHORS:
M A Fisher, S A Eklund, S A James, X Lin

ABSTRACT:
This study evaluated infrequent adverse reactions to hepatitis B vaccine by investigating the association of this vaccine with adverse health outcomes for U.S. children less than six years of age. The evaluation of the association between hepatitis B vaccine and chronic arthritis provides needed data, relevant to the Institute of Medicine's Report that there are inadequate data available to assess the causal relationship of hepatitis B vaccine to arthritis risk.


TITLE:
Differential diagnosis of acute flaccid paralysis and its role in poliomyelitis surveillance.


TITLE:
The administration of meningitis C vaccination 1 week before the onset of HSP suggests that it can be added to the list of potential triggering agents.


TITLE:
Rotavirus vaccinations have a history of causing adverse effects such as intussusception.

AUTHORS:
Lynn R Zanardi, Penina Haber, Gina T Mootrey, M T Niu, Melinda Wharton

ABSTRACT:
Rotavirus vaccine was licensed on August 31, 1998, and subsequently recommended for routine use among infants. To assess rare adverse events, postlicensure surveillance was conducted.


TITLE:
HIV-1/AIDS may have been caused by contaminated polio vaccines grown in SIV infected chimpanzee kidney cells during the late 1950's.

ABSTRACT:
The simian immunodeficiency virus (SIV) of the common chimpanzee is widely acknowledged as the direct ancestor of HIV-1. There is increasing historical evidence that during the late 1950s, kidneys were routinely excised from central African chimpanzees by scientists who were collaborating with the polio vaccine research of Dr Hilary Koprowski, and sent - inter alia - to vaccine-making laboratories in the USA and Africa, and to unspecified destinations in Belgium. While there is no direct evidence that cells from these kidneys were used as a substrate for growing Dr Koprowski's oral polio vaccines, there is a startling coincidence between places in Africa where his CHAT vaccine was fed, and the first appearances in the world of HIV-1 group M and group-M-related AIDS. Because of the enormous implications of the hypothesis that AIDS may be an unintended iatrogenic (physician-caused) disease, it is almost inevitable that this theory will engender heated opposition from many of those in the scientific establishment, and those with vested interests.


TITLE:
A case of lethal inflammatory polyradiculoneuropathy with spinal cord involvement after hepatitis B vaccination.

AUTHORS:
E Sindern, J M Schroder, M Krismann, J P Malin

ABSTRACT:
We report on a 36-year-old man who developed an inflammatory polyradiculoneuropathy similar to Guillain-Barré syndrome 9 days after hepatitis B vaccination. Extensive immunotherapy including immunoglobulins, steroids, plasmapheresis, cyclophosphamide and methotrexate did not stop the progressive course of the disease and the patient died 4 months later due to multiorgan failure with septic shock symptoms and adult respiratory distress syndrome (ARDS).The neuropathological investigation showed severe axonal loss with mild demyelination of peripheral nerves and mononuclear cell infiltrates, predominantly T-lymphocytes, in nerve roots and spinal ganglia. In addition, there were unusual, perivascular and parenchymal lymphocytic cell infiltrates in the grey matter, especially the anterior horns of the spinal cord. The temporal relationship to hepatitis B vaccination, the strong increase of HBs-antibodies within 3 weeks after vaccination, and the presumptive immune mediated pathology of this disorder suggest a possible etiologic link with hepatitis B vaccine.


TITLE:
Viruses (wild-type or recombinant vaccine-type) can silently prime for and trigger central nervous system autoimmune disease.

AUTHORS:
D J Theil, I Tsunoda, F Rodriguez, J L Whitton, Robert S Fujinami

ABSTRACT:
Although many viruses have been isolated from patients with multiple sclerosis (MS), as yet, no one agent has been demonstrated to cause MS. In contrast, epidemiological data indicate that viral infections are associated with exacerbations of MS. Here, we present data showing that virus infections can subclinically prime animals for central nervous system (CNS) autoimmune disease; long after the original infection has been eradicated, a nonspecific challenge/infection can trigger an exacerbation. The priming infectious agent must show molecular mimicry with self-CNS antigens such as glial fibrillary acidic protein (GFAP), myelin associated glycoprotein (MAG) or myelin proteolipid protein (PLP). The subsequent challenge, however, may be nonspecific; complete Freund's adjuvant (CFA), or infection with a recombinant vaccinia virus encoding an irrelevant protein, could trigger CNS disease. In the CNS, we could detect a mononuclear cell infiltration, but no demyelination was found. However, if the pathogenesis of MS is similar to that of this novel animal model for CNS autoimmune disease, our findings could help explain why exacerbations of MS are often associated with a variety of different viral infections.


TITLE:
In the present study, intracytoplasmic inclusions were constantly detected in macrophages of the MMF lesions and were shown to contain aluminium by three different methods.

AUTHORS:
Romain Kroum Gherardi, M Coquet, P Cherin, L Belec, P Moretto, P A Dreyfus, J F Pellissier, P Chariot, F J Authier

ABSTRACT:
Macrophagic myofasciitis (MMF) is an emerging condition of unknown cause, detected in patients with diffuse arthromyalgias and fatigue, and characterized by muscle infiltration by granular periodic acid-Schiff's reagent-positive macrophages and lymphocytes. Intracytoplasmic inclusions have been observed in macrophages of some patients. To assess their significance, electron microscopy was performed in 40 consecutive cases and chemical analysis was done by microanalysis and atomic absorption spectrometry. Inclusions were constantly detected and corresponded to aluminium hydroxide, an immunostimulatory compound frequently used as a vaccine adjuvant. A lymphocytic component was constantly observed in MMF lesions. Serological tests were compatible with exposure to aluminium hydroxide-containing vaccines. History analysis revealed that 50 out of 50 patients had received vaccines against hepatitis B virus (86%), hepatitis A virus (19%) or tetanus toxoid (58%), 3-96 months (median 36 months) before biopsy. Diffuse myalgias were more frequent in patients with than without an MMF lesion at deltoid muscle biopsy (P < 0.0001). Myalgia onset was subsequent to the vaccination (median 11 months) in 94% of patients. MMF lesion was experimentally reproduced in rats. We conclude that the MMF lesion is secondary to intramuscular injection of aluminium hydroxide-containing vaccines, shows both long-term persistence of aluminium hydroxide and an ongoing local immune reaction, and is detected in patients with systemic symptoms which appeared subsequently to vaccination.


TITLE:
Antibodies formed to rubella virus induce demyelination in rat brain cells, indicating that infection with and/or vaccination against rubella may induce autoimmune demyelination.

AUTHORS:
C Besson Duvanel, P Honegger, J M Matthieu

ABSTRACT:
To link the presence of intrathecal virus-specific oligoclonal immunoglobulin G (IgG) in multiple sclerosis patients to a demyelinating activity, aggregating rat brain cell cultures were treated with antibodies directed against two viruses, namely, rubella (RV) and hepatitis B (HB). Anti-RV antibodies in the presence of complement decreased myelin basic protein concentrations in a dose-dependent manner, whereas anti-HB antibodies had no effect. A similar but less pronounced effect was observed on the enzymatic activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase, which is enriched in noncompact membranes of oligodendrocytes. These effects were comparable to those in cultures treated with antibodies directed against myelin oligodendrocyte glycoprotein (MOG), previously found to be myelinotoxic both in vitro and in vivo. Sequence homologies were found between structural glycoprotein E(2) of RV and MOG, suggesting that demyelination was due to molecular mimicry. To support the hypothesis that demyelination was caused by anti-RV IgG that recognized an MOG epitope, we found that anti-RV antibodies depleted MOG in a dose-dependent manner. Further evidence came from the demonstration that anti-RV and anti-MOG IgG colocalized on oligodendrocyte processes and that both revealed by Western blot a 28 kDa protein in CNS myelin, a molecular weight corresponding to MOG. These findings suggest that a virus such as RV exhibiting molecular mimicry with MOG can trigger an autoimmune demyelination.


TITLE:
Smallpox vaccine caused iatrogenic vaccinia in children in Russia.

AUTHORS:
G G Onishchenko, V I Markov, V N Ustiushin, S V Borisevich, G I Kuznetsova, S la Loginova, A M Berezhnoi, N T Vasil'ev, V A Maksimov, A A Makhlai

ABSTRACT:
The comparative study of the specimens of the morphological elements of exanthema obtained from 8 children with the clinical diagnosis of secondary exogenic vaccinia, dried smallpox vaccine and the cultures of other orthopoxviruses (rabbit pox, monkey pox and buffalo pox viruses) was made. The isolation and identification of the causative agents from the specimens was carried out with the use of modern virological, electron microscopic and molecular methods. The study proved the fact that 8 children had orthopoxvirus infection with its causative agent identified as vaccinia virus.


TITLE:
Over 600 cases of sudden infant death syndrome following vaccination were reported from 1990-1997.

AUTHORS:
L E Silvers, S S Ellenberg, Robert P Wise, F E Varricchio, Gina T Mootrey, M E Salive

ABSTRACT:
To examine the fatalities reported to the federally administered Vaccine Adverse Event Reporting System (VAERS), a passive surveillance system, in its first 7 years.


TITLE:
Transmissable spongiform encephalopathies may be passed iatrogenically through vaccines.

ABSTRACT:
The recent emergence of bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob Disease (vCJD) suggests that transmissible spongiform encephalopathies (TSEs) pose an ongoing threat to human and animal health. To avoid iatrogenic transmission of TSEs in vaccines, strategies must be developed to obviate TSE agent infectivity in cellular substrates, cell culture media components and enzymes, and excipients, and to validate the safety of these components and field vaccines efficiently.


TITLE:
Hepatitis B vaccine may induce myelitis in susceptible individuals.

AUTHORS:
F Karaali-Savrun, A Altintas, S Saip, A Siva

ABSTRACT:
We present four incidental cases that developed partial myelitis following the administration of hepatitis B vaccine in 1998. The first two cases, a 33-year-old man and a 42-year-old woman developed progressive sensory symptoms without motor involvement within 4 weeks following the vaccination. Their magnetic resonance imaging (MRI) disclosed similar lesions consistent with myelitis at their cervical spinal cord. A comparable inflammatory lesion was seen at the T9-T10 levels of the spinal cord in the third case, who was a 40-year-old woman presenting with numbness in her legs and urinary retention following the vaccination. The fourth case who was a 42-year-old woman, presented with sensory symptoms in her left extremities, which developed 3 months after the vaccination. Her MRI showed a hyperintense lesion at C6. She also had two tiny lesions in her cranial MRI. In all cases, there was no history of preceding infections and no clinical evidence suggestive of any other disorders that may cause myelopathy. All patients recovered completely within 3 months with the exception of the third patient who developed new neurological symptoms after 12 months. Similar clinical and imaging presentation of myelitis following hepatitis B vaccination within a 1 year period with no other demonstrable clinical and laboratory evidence for any other disorder raise the probability of a causal link between these two events.


TITLE:
Pertussis vaccine has been linked to hypotonic-hyporesponsive episodes (HHE) in infants and children.

ABSTRACT:
Vaccine safety has become a major community concern and of particular importance for parents, vaccine recipients and vaccine providers. A hypotonic-hyporesponsive episode (HHE) is a sudden and unexpected episode of loss of tone, unresponsiveness and colour change which uncommonly affects infants and children after vaccination. Although any vaccine may be associated with this adverse event, HHE usually follows administration of a pertussis containing vaccine. There has been renewed interest in this adverse event in the light of community concerns regarding vaccine safety. The focus of this interest has been to formulate an acceptable case definition, to document possible risk factors and to better define the outcome of HHE. In addition, studies have documented the outcome of revaccination of children who have had an HHE. Although much remains to be learnt about HHE it would appear that there are no long-term sequelae and that children who have had an HHE can be revaccinated. Parents should be provided with the available information such that they can make an assessment of the risks and benefits of pertussis vaccination. The benefits of pertussis vaccination still outweigh the risk and universal childhood pertussis vaccination should continue to be advocated.


TITLE:
Breastfeeding attenuates reductions in energy intake induced by a mild immunologic stimulus represented by DPTH immunization.

AUTHORS:
Mardya Lopez-Alarcon, Cutberto Garza, Jean-Pierre Habicht, Lourdes Martinez, Virginia Pegueros, Salvador Villalpando

ABSTRACT:
An attenuated severity of infections is among the well-documented benefits of breast-feeding. The degree to which this attenuated severity extends to the amelioration of anorexia is understood incompletely, and possible underlying mechanisms have received limited evaluation. This study was designed to test whether breast-feeding attenuates reductions in energy intake associated with a mild immunologic stimulus and to assess poststimulus relationships among putative reductions in energy intake and serum interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha and leptin concentrations. A quasi-experimental, hospital-based study was conducted in 23 healthy fully breast- (BF) and formula-fed (FF) infants who received the quadruple diphtheria, pertussis, tetanus and hemophilus influenza (DPTH) immunization as an immunologic challenge. Only FF infants had decreased energy intakes (12 +/- 2%, P = 0.001) after immunization. Leptin concentrations increased after immunization only in FF infants (30 +/- 7%, P = 0.03). Correlations between postimmunization increases in IL-beta and reductions in energy intake were of borderline significance (r = -0.56, P = 0.08). These findings support the view that breast-feeding protects against anorectic responses to mild immunologic stimuli. Increases in leptin are associated with reductions in energy consumption in the postimmunization period in FF infants and postimmunization changes in IL-1beta concentrations likely are related to reductions in energy intake in response to immunologic stimuli.


TITLE:
Neurological adverse events associated with vaccination.

ABSTRACT:
Public tolerance to adverse reactions is minimal. Several reporting systems have been established to monitor adverse events following immunization. The present review summarizes data on neurologic complications following vaccination, and provides evidence that indicates whether they were directly associated with the vaccines. These complications include autism (measles vaccine), multiple sclerosis (hepatitis B vaccine), meningoencephalitis (Japanese encephalitis vaccine), Guillain-Barré syndrome and giant cell arteritis (influenza vaccine), and reactions after exposure to animal rabies vaccine. Seizures and hypotonic/hyporesponsive episodes following pertussis vaccination and potential risks associated with varicella vaccination, as well as vaccine-associated paralytic poliomyelitis following oral poliovirus vaccination, are also described. In addition, claims that complications are caused by adjuvants, preservatives and contaminants [i.e. macrophagic myofasciitis (aluminium), neurotoxicity (thimerosal), and new variant Creutzfeldt-Jakob disease (bovine-derived materials)] are discussed.


TITLE:
Anthrax vaccination contributes to joint related adverse reactions.

ABSTRACT:
The purpose of this analysis was to evaluate anthrax vaccine (AVA) and joint related adverse reactions based upon analysis of the VAERS database in light of the current possibility of the use of anthrax as a biological warfare agent.


TITLE:
Review: based on currently available research pneumoccal vaccination should not be recommended for large scale use in ear infection prone populations.

AUTHORS:
M Straetemans, E A Sanders, Reinier H Veenhoven, A G Schilder, R A Damoiseaux, G A Zielhuis

ABSTRACT:
Acute otitis media (AOM) is one of the most common diseases in early infancy and childhood. Long term effects of recurrent episodes of otitis media, rapid emergence of drug resistant bacteria associated with AOM worldwide and huge estimated direct and indirect annual costs associated with otitis media have emphasized the need for an effective vaccination program to prevent episodes of AOM.


TITLE:
The vaccine adjuvant squalene in anthrax vaccines given to soldiers in the Gulf War resulted in the formation of antibodies to squalene which are associated with Gulf War Syndrome.

AUTHORS:
Pamela B Asa, Russell B Wilson, Robert F Garry

ABSTRACT:
We previously reported that antibodies to squalene, an experimental vaccine adjuvant, are present in persons with symptoms consistent with Gulf War Syndrome (GWS) (P. B. Asa et al., Exp. Mol. Pathol 68, 196-197, 2000). The United States Department of Defense initiated the Anthrax Vaccine Immunization Program (AVIP) in 1997 to immunize 2.4 million military personnel. Because adverse reactions in vaccinated personnel were similar to symptoms of GWS, we tested AVIP participants for anti-squalene antibodies (ASA). In a pilot study, 6 of 6 vaccine recipients with GWS-like symptoms were positive for ASA. In a larger blinded study, only 32% (8/25) of AVIP personnel compared to 15.7% (3/19) of controls were positive (P > 0.05). Further analysis revealed that ASA were associated with specific lots of vaccine. The incidence of ASA in personnel in the blinded study receiving these lots was 47% (8/17) compared to an incidence of 0% (0/8; P < 0.025) of the AVIP participants receiving other lots of vaccine. Analysis of additional personnel revealed that in all but one case (19/20; 95%), ASA were restricted to personnel immunized with lots of vaccine known to contain squalene. Except for one symptomatic individual, positive clinical findings in 17 ASA-negative personnel were restricted to 4 individuals receiving vaccine from lots containing squalene. ASA were not present prior to vaccination in preimmunization sera available from 4 AVIP personnel. Three of these individuals became ASA positive after vaccination. These results suggest that the production of ASA in GWS patients is linked to the presence of squalene in certain lots of anthrax vaccine.


TITLE:
The measles-mumps-rubella vaccine causes autoantibodies to be formed against myelin basic protein (the protective coating of the nerves) contributing to the pathogenesis of autism.

AUTHORS:
Vijendra K Singh, Sheren X Lin, Elizabeth Newell, Courtney Nelson

ABSTRACT:
Autoimmunity to the central nervous system (CNS), especially to myelin basic protein (MBP), may play a causal role in autism, a neurodevelopmental disorder. Because many autistic children harbor elevated levels of measles antibodies, we conducted a serological study of measles-mumps-rubella (MMR) and MBP autoantibodies. Using serum samples of 125 autistic children and 92 control children, antibodies were assayed by ELISA or immunoblotting methods. ELISA analysis showed a significant increase in the level of MMR antibodies in autistic children. Immunoblotting analysis revealed the presence of an unusual MMR antibody in 75 of 125 (60%) autistic sera but not in control sera. This antibody specifically detected a protein of 73-75 kD of MMR. This protein band, as analyzed with monoclonal antibodies, was immunopositive for measles hemagglutinin (HA) protein but not for measles nucleoprotein and rubella or mumps viral proteins. Thus the MMR antibody in autistic sera detected measles HA protein, which is unique to the measles subunit of the vaccine. Furthermore, over 90% of MMR antibody-positive autistic sera were also positive for MBP autoantibodies, suggesting a strong association between MMR and CNS autoimmunity in autism. Stemming from this evidence, we suggest that an inappropriate antibody response to MMR, specifically the measles component thereof, might be related to pathogenesis of autism.


TITLE:
This report provides further documentation for a causal association linking the HBV vaccine with lichen planus.

AUTHORS:
N G Stavrianeas, A C Katoulis, A Kanelleas, E Hatziolou, S Georgala

ABSTRACT:
Immunization with the hepatitis B virus (HBV) is effective and safe with an estimated incidence of adverse reactions, either local or systemic, of less than 0.1%. Cutaneous side effects are rare and include lichen planus (LP) and lichenoid reactions. We report the case of a 21-year-old female, in whom a persistent, papulonodular lesion developed at the site of the injection, 6 weeks after the second dose of the HBV. Histological examination revealed lichenoid and pseudolymphomatous features. In addition, sensitization to thiomersal, a vaccine constituent, was documented by patch testing. The association of LP with chronic liver disease is well established. Furthermore, less than 20 cases of lichen or lichenoid reactions, following HBV vaccination, have been reported. Although several arguments have been presented, it is still debated whether there is a causal association or the occurrence of LP following HBV vaccination is a simple coincidence. It has been speculated that a T-cell-mediated, graft-versus-host-like reaction, triggered by a sensitizing protein, is directed against keratinocytes expressing an epitope of hepatitis B surface antigen or a similar epitope. Our case may represent a localized lichenoid reaction to HBV vaccination, a local reactive hyperplasia or a persisting delayed hypersensitivity reaction to a vaccine constituent. This is the first case of a local lichenoid reaction at the injection site of the HBV vaccine, providing further documentation for a causal association linking the HBV vaccine with LP.


TITLE:
Tetanus vaccine given to Phillipino women of reproductive age may have been designed to induce an anti-fertility action.


TITLE:
Hepatitis B vaccination has been linked to autoimmune inflammatory polyneuropathy (PN).

AUTHORS:
Claude Vital, Anne Vital, Georges Gbikpi-Benissan, MaitÃ© Longy-Boursier, Marie-ThÃ©rÃ©se Climas, Yves Castaing, Marie-HÃ©lÃ©ne Canron, Michel Le Bras, Klaus Petry

ABSTRACT:
Autoimmune inflammatory polyneuropathy (PN) can be triggered by vaccination. We report 3 such cases. A 36-year-old female nurse presented 15 days after a hepatitis B vaccination (HBV) with acute sensory disturbances in the lower limbs. She had severe ataxia but no weakness. Cerebrospinal fluid (CSF) protein level was 84 mg/100 mL, with 3 lymphocytes. A 66-year-old man presented 21 days after HBV with severe motor and sensory PN involving all 4 limbs. A 66-year-old man presented 15 days after a yellow fever vaccination with progressive motor and sensory PN involving all 4 limbs and bilateral facial paralysis. CSF protein level was 300 mg/100 mL, with 5 lymphocytes. Six weeks later, a tracheostomy was performed. In these 3 patients, the nerve deficits lasted for months. In each case, peripheral nerve biopsy showed KP1-positive histiocytes but no T-lymphocytes in the endoneurium. On ultrastructural examination, there was axonal degeneration in the first 2 cases; in case 2, a few myelinated fibers exhibited an intra-axonal macrophage but the myelin sheath was preserved. There was only 1 example of macrophage-associated demyelination in case 2, but these were numerous in case 3. It is likely that in the first 2 cases, an autoimmune reaction against some axonal or neuronal components was triggered by HBV. It induced an acute sensory ataxic PN in case 1 and an acute motor and sensory axonal neuropathy (AMSAN) in case 2. The third patient had a chronic inflammatory demyelinating PN, likely triggered by yellow fever vaccination.


TITLE:
Hepatitis B vaccination was statistically associated with gastrointestinal reactions including: hepatitis, gastrointestinal disease and liver function test abnormalities.

ABSTRACT:
Hepatitis B is the most important infectious cause of acute and chronic liver disease. Hepatitis B vaccine, a highly purified, genetically engineered, single antigen vaccine, has generally been accepted as a safe vaccine. In 2000, the Institute of Medicine noted that few vaccines for any disease have been actively monitored for adverse effects over long periods and encouraged evaluation of active long-term monitoring studies of large populations to further evaluate the relative safety of vaccines. The aim of this study was to accept the charge of the 2000 Institute of Medicine Report and extend our own work to determine the frequency of gastrointestinal adverse reactions after hepatitis B vaccination and determine if this frequency was increased over the background rate of gastrointestinal conditions in the U.S. adult population.


TITLE:
Experimental in utero inoculation of late-term swine fetuses with porcine circovirus type 2 results in a high rate of reproductive abnormalities, including mummification and stillbirth.

AUTHORS:
Charles S Johnson, Han S Joo, Kochakorn Direksin, Kyoung-Jin Yoon, Young K Choi

ABSTRACT:
All 37 fetuses of 3 laparotomized pregnant sows at 86, 92, and 93 days of gestation were inoculated intramuscularly through the uterine wall with porcine circovirus type 2 (PCV-2). The sows were allowed to farrow, and blood and tissue samples were collected from their piglets before and after suckling colostrum. Thirteen fetuses from 2 sows at 90 and 103 days of gestation were used as controls. Of the 37 PCV-2 inoculated fetuses, 24 were grossly normal and 13 were mummified, stillborn, or weak-born at farrowing. Infection with PCV-2 was demonstrated in various tissues of grossly normal and abnormal fetuses by virus isolation, polymerase chain reaction, and immunohistochemical methods. Antibodies specific to PCV-2 were also detected from the sera or thoracic fluids of abnormal fetuses and unsuckled normal pigs. No evidence of PCV-2 infection was found in any control fetuses. The present results confirm previous findings that PCV-2 can infect late-term swine fetuses and may cause reproductive abnormalities.


TITLE:
Adverse events associated with 17D-derived yellow fever vaccination--United States, 2001-2002.

ABSTRACT:
In June 2001, seven cases of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) (previously called multiple organ system failure) in recipients of 17D-derived yellow fever vaccine (YEL) were reported to the Advisory Committee on Immunization Practices (ACIP). ACIP reviewed the cases, recommended enhanced surveillance for adverse events, and updated the ACIP statement on YEL. This report summarizes the preliminary surveillance findings, including two new suspected cases of YEL-AVD and four suspected cases of YEL-associated neurotropic disease (YEL-AND) (previously called postvaccinal encephalitis). Although YEL remains essential for travelers to areas in which yellow fever (YF) is endemic (Figure), these findings underscore the need for continued enhanced surveillance and timely clinical assessment of YEL-associated disease.


TITLE:
Exposure to HiB immunization is associated with an increased risk of insulin dependent diabetes.

ABSTRACT:
The hemophilus vaccine has been linked to the development of autoimmune type 1 diabetes, insulin dependent diabetes (IDDM) in ecological studies.


TITLE:
Adult rubella and adult hepatitis B vaccines were statistically associated with chronic arthritis which persisted for at least one year.

ABSTRACT:
This analysis examined the incidence rate of chronic arthritis adverse reactions reported following adult rubella and hepatitis B vaccinations. In this analysis, etiologic mechanisms for chronic arthritis following adult rubella and hepatitis B vaccines were also explored.


TITLE:
MMR vaccination is associated with an increased risk for idiopathic thrombocytopaenic purpura.

ABSTRACT:
To estimate the relationship between idiopathic thrombocytopaenic purpura (ITP) and the measles, mumps and rubella (MMR) vaccination in children; calculating the relative risk estimate for ITP with in 6 weeks after MMR vaccination and the attributable risk of ITP within 6 weeks after MMR vaccination.


TITLE:
Review: possible adverse effects that are associated with smallpox vaccination.

AUTHORS:
Joanne Cono, Christine G Casey, David M Bell

ABSTRACT:
The guidance in this report is for evaluation and treatment of patients with complications from smallpox vaccination in the preoutbreak setting. Information is also included related to reporting adverse events and seeking specialized consultation and therapies for these events. The frequencies of smallpox vaccine-associated adverse events were identified in studies of the 1960s. Because of the unknown prevalence of risk factors among today's population, precise predictions of adverse reaction rates after smallpox vaccination are unavailable. The majority of adverse events are minor, but the less-frequent serious adverse reactions require immediate evaluation for diagnosis and treatment. Agents for treatment of certain vaccine-associated severe adverse reactions are vaccinia immune globulin (VIG), the first-line therapy, and cidofovir, the second-line therapy. These agents will be available under Investigational New Drug (IND) protocols from CDC and the U.S. Department of Defense (DoD). Smallpox vaccination in the preoutbreak setting is contraindicated for persons who have the following conditions or have a close contact with the following conditions: 1) a history of atopic dermatitis (commonly referred to as eczema), irrespective of disease severity or activity; 2) active acute, chronic, or exfoliative skin conditions that disrupt the epidermis; 3) pregnant women or women who desire to become pregnant in the 28 days after vaccination; and 4) persons who are immunocompromised as a result of human immunodeficiency virus or acquired immunodeficiency syndrome, autoimmune conditions, cancer, radiation treatment, immunosuppressive medications, or other immunodeficiencies. Additional contraindications that apply only to vaccination candidates but do not include their close contacts are persons with smallpox vaccine-component allergies, women who are breastfeeding, those taking topical ocular steroid medications, those with moderate-to-severe intercurrent illness, and persons aged < 18 years. In addition, history of Darier disease is a contraindication in a potential vaccinee and a contraindication if a household contact has active disease. In the event of a smallpox outbreak, outbreak-specific guidance will be disseminated by CDC regarding populations to be vaccinated and specific contraindications to vaccination. Vaccinia can be transmitted from a vaccinee's unhealed vaccination site to other persons by close contact and can lead to the same adverse events as in the vaccinee. To avoid transmission of vaccinia virus (found in the smallpox vaccine) from vaccinees to their close contacts, vaccinees should wash their hands with warm soapy water or hand rubs containing > or = 60% alcohol immediately after they touch their vaccination site or change their vaccination site bandages. Used bandages should be placed in sealed plastic bags and can be disposed of in household trash. Smallpox vaccine adverse reactions are diagnosed on the basis of clinical examination and history, and certain reactions can be managed by observation and supportive care. Adverse reactions that are usually self-limited include fever, headache, fatigue, myalgia, chills, local skin reactions, nonspecific rashes, erythema multiforme, lymphadenopathy, and pain at the vaccination site. Other reactions are most often diagnosed through a complete history and physical and might require additional therapies (e.g., VIG, a first-line therapy and cidofovir, a second-line therapy). Adverse reactions that might require further evaluation or therapy include inadvertent inoculation, generalized vaccinia (GV), eczema vaccinatum (EV), progressive vaccinia (PV), postvaccinial central nervous system disease, and fetal vaccinia. Inadvertent inoculation occurs when vaccinia virus is transferred from a vaccination site to a second location on the vaccinee or to a close contact. Usually, this condition is self-limited and no additional care is needed. Inoculations of the eye and eyelid require evaluation by an ophthalmologist and might require therapy with topical antiviral or antibacterial medications, VIG, or topical steroids. GV is characterized by a disseminated maculopapular or vesicular rash, frequently on an erythematous base, which usually occurs 6-9 days after first-time vaccination. This condition is usually self-limited and benign, although treatment with VIG might be required when the patient is systemically ill or found to have an underlying immunocompromising condition. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. EV occurs among persons with a history of atopic dermatitis (eczema), irrespective of disease severity or activity, and is a localized or generalized papular, vesicular, or pustular rash, which can occur anywhere on the body, with a predilection for areas of previous atopic dermatitis lesions. Patients with EV are often systemically ill and usually require VIG. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. PV is a rare, severe, and often fatal complication among persons with immunodeficiencies, characterized by painless progressive necrosis at the vaccination site with or without metastases to distant sites (e.g., skin, bones, and other viscera). This disease carries a high mortality rate, and management of PV should include aggressive therapy with VIG, intensive monitoring, and tertiary-level supportive care. Anecdotal experience suggests that, despite treatment with VIG, persons with cell-mediated immune deficits have a poorer prognosis than those with humoral deficits. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. Central nervous system disease, which includes postvaccinial encephalopathy (PVE) and postvaccinial encephalomyelitis (or encephalitis) (PVEM), occur after smallpox vaccination. PVE is most common among infants aged < 12 months. Clinical symptoms of central nervous system disease indicate cerebral or cerebellar dysfunction with headache, fever, vomiting, altered mental status, lethargy, seizures, and coma. PVE and PVEM are not believed to be a result of replicating vaccinia virus and are diagnoses of exclusion. Although no specific therapy exists for PVE or PVEM, supportive care, anticonvulsants, and intensive care might be required. Fetal vaccinia, resulting from vaccinial transmission from mother to fetus, is a rare, but serious, complication of smallpox vaccination during pregnancy or shortly before conception. It is manifested by skin lesions and organ involvement, and often results in fetal or neonatal death. No known reliable intrauterine diagnostic test is available to confirm fetal infection. Given the rarity of congenital vaccinia among live-born infants, vaccination during pregnancy should not ordinarily be a reason to consider termination of pregnancy. No known indication exists for routine, prophylactic use of VIG in an unintentionally vaccinated pregnant woman; however, VIG should not be withheld if a pregnant woman develops a condition where VIG is needed. Other less-common adverse events after smallpox vaccination have been reported to occur in temporal association with smallpox vaccination, but causality has not been established. Prophylactic treatment with VIG is not recommended for persons or close contacts with contraindications to smallpox vaccination who are inadvertently inoculated or exposed. These persons should be followed closely for early recognition of adverse reactions that might develop, and clinicians are encouraged to enroll these persons in the CDC registry by calling the Clinician Information Line at 877-554-4625. To request clinical consultation and IND therapies for vaccinia-related adverse reactions for civilians, contact your state health department or CDC's Clinician Information Line (877-554-4625). Clinical evaluation tools are available at http.//www.bt.cdc.gov/agent/smallpox/vaccination/clineval. Clinical specimen-collection guidance is available at http://www.bt.cdc.gov/agent/smallpox/vaccination/vaccinia-specimen-collection.asp. Physicians at military medical facilities can request VIG or cidofovir by calling the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) at 301-619-2257 or 888-USA-RIID.


TITLE:
Hepatitis C prevalence in Southern Italy may be due to iatrogenic transmission through the Salk Polio vaccine 1956-1965.

AUTHORS:
Maurizio Montella, Anna Crispo, Maria Grimaldi, Vincenzo Tridente, Mario Fusco

ABSTRACT:
Since the first studies on hepatitis C virus (HCV) prevalence were published, it has been evident that southern Italy is an area of hyperendemicity. A recent study conducted in southern Italy suggested that the high prevalence of HCV infection might be the result of past iatrogenic transmission. Polio vaccination with the parenteral Salk vaccine between 1956 and 1965 by multiple use of unsafe glass syringes may have been one of the major causes of the spread of HCV infection among southern Italian adults who are now older than 40 years of age. Persons born between the 1940s and early 1960s have a nearly 3-fold increased risk of HCV seropositivity than the younger age group. The findings are consistent with a cohort effect of exposure to the Salk parenteral vaccination.


TITLE:
Vaccine-induced scrapie has been reported in animals.

AUTHORS:
Gianluigi Zanusso, Cristina Casalone, Pierluigi Acutis, Elena Bozzetta, Alessia Farinazzo, Matteo Gelati, Michele Fiorini, Gianluigi Forloni, Man Sun Sy, Salvatore Monaco, Maria Caramelli

ABSTRACT:
An accidental intra- and interspecies transmission of scrapie occurred in Italy in 1997 and 1998 following exposure to a vaccine against Mycoplasma agalactiae. PrP(Sc) in affected sheep and goats, collected from a single flock exposed to vaccination 2 years earlier, was molecularly typed. In five animals with iatrogenic scrapie, a PrP(Sc) type with a 20 kDa core fragment was found in all areas of the brain investigated. In three sheep and one goat, this isoform co-occurred with a fully glycosylated isoform that had a protease-resistant backbone of 17 kDa, whereas in two sheep and four goats, the two PrP(Sc) types were detected in different regions of the brain. In sheep with natural field scrapie, a PrP(Sc) type with physico-chemical properties indistinguishable from the 20 kDa isoform was found. The present results suggest the co-presence of two prion strains in mammary gland and brain homogenates used for vaccination.


TITLE:
MMR vaccine may induce autoantibody formation against the gut (secretin or its receptor) and/or the brain, contributing to the pathogenesis of autism-spectrum disorder.

ABSTRACT:
In a subgroup of children with autism-spectrum like conditions symptoms seem to appear as a 'regression' (in normal development). It has been postulated that the onset of such autistic symptoms may involve an autoimmune response against the central nervous system and that the antigenic determinant could possibly be gastrointestinal in origin. It has been suggested that the presence of the measles virus and 'autistic enterocolitis' demonstrates the possibility that the MMR triple vaccine may be mediating the inflammation with possible production of antibodies against the virus containing vaccine. Such an antibody may share antigenic determinant to molecules found in the gut. We propose that this may be secretin or its receptor, found in the gut as well as in the central nervous system. The antibody response to the gut may also conceivably occur in the brain at a critical time in development. The modulation of development by secretin may be a static event possibly occurring at a specific time in early childhood development and if it involves an autoimmune response then a disruption in development may result. These hypothesized events can only occur if the MMR vaccine shares antigenic determinants that resemble secretin or any of its receptor types and remains to be studied.


TITLE:
Distinct rises in the incidence of T1DM occurred 2-4 years following the introduction of the MMR and pertussis vaccines.

ABSTRACT:
We previously analyzed data from a hemophilus vaccine trial and identified clusters of extra cases of type 1 diabetes mellitus (T1DM) caused by the vaccine that occurred between 36 and 48 months after immunization. Published reports indicate clustering of cases of T1DM occurring approximately 2-4 years after mumps infection. Others have reported a 2-4 year delay between the onset of autoantibodies and the development of T1DM. We attempted to determine whether similar clustering of cases of T1DM occurred after immunization with vaccines other than hemophilus.


TITLE:
Among US military personnel vaccinated against smallpox, myopericarditis occurred at a rate of 1 per 12,819 primary vaccinees, and 3.6 fold higher in those without previous vaccinia vaccination.

AUTHORS:
Jeffrey S Halsell, James R Riddle, ] Edwin Atwood, Pierce Gardner, Robert Shope, Gregory A Poland, Gregory C Gray, Stephen Ostroff, Robert E Eckart, Duane R Hospenthal, Roger L Gibson, John D Grabenstein, Mark K Arness, David N Tornberg,

ABSTRACT:
In the United States, the annual incidence of myocarditis is estimated at 1 to 10 per 100,000 population. As many as 1% to 5% of patients with acute viral infections involve the myocardium. Although many viruses have been reported to cause myopericarditis, it has been a rare or unrecognized event after vaccination with the currently used strain of vaccinia virus (New York City Board of Health).


TITLE:
Pneumococcal conjugate vaccine is not effective to prevent ear infections in previously unvaccinated toddlers and children with a history of recurrent ear infections.

AUTHORS:
Reinier H Veenhoven, Debby Bogaert, Cuno Uiterwaal, Carole Brouwer, Herma Kiezebrink, Jacob Bruin, Ed Ijzerman, Peter Hermans, Ronald de Groot, Ben Zegers, Wietse Kuis, Ger Rijkers, Anne Schilder, Elisabeth Sanders

ABSTRACT:
Pneumococcal conjugate vaccine prevents recurrent acute otitis media (AOM) in infants immunised at 2, 4, 6, and 12-15 months of age. We aimed to find out whether this vaccine also prevents AOM in older children who have had previous episodes of AOM.


TITLE:
Autistic children have elevated levels of measles antibodies indicating that measles vaccination may be causing autoimmunity in these children.

ABSTRACT:
Virus-induced autoimmunity may play a causal role in autism. To examine the etiologic link of viruses in this brain disorder, we conducted a serologic study of measles virus, mumps virus, and rubella virus. Viral antibodies were measured by enzyme-linked immunosorbent assay in the serum of autistic children, normal children, and siblings of autistic children. The level of measles antibody, but not mumps or rubella antibodies, was significantly higher in autistic children as compared with normal children (P = 0.003) or siblings of autistic children (P <or= 0.0001). Furthermore, immunoblotting of measles vaccine virus revealed that the antibody was directed against a protein of approximately 74 kd molecular weight. The antibody to this antigen was found in 83% of autistic children but not in normal children or siblings of autistic children. Thus autistic children have a hyperimmune response to measles virus, which in the absence of a wild type of measles infection might be a sign of an abnormal immune reaction to the vaccine strain or virus reactivation.


TITLE:
Measles vaccine and glyphosate-induced parkinsonism has been reported.

AUTHORS:
Maria do Desterro Leiros da Costa, Lilian Regina Goncalves, Egberto Reis Barbosa, Luiz Alberto Bacheschi

ABSTRACT:
We report the brain magnetic resonance (MR) imaging abnormalities observed at the basal ganglia system of 5 patients (2 female and 3 male), who fulfilled the criteria of parkinsonism. The onset of parkinsonian syndrome ranged from 5 to 52 years old. All patients underwent MR exams with a 1.5T MR equipment. High field T2-weighted sequences disclosed hypersignal bilateral and symmetrically located exclusively at substantia nigra (3 cases), exclusively at globus pallidus (1case) and simultaneously at substantia nigra, globus pallidus and nigro-strital interconnections (1case). For three patients, the diagnose of secondary parkinsonism was supported by clinical data: the first had the onset of the symptoms after the exposure to an herbicide (glyphosate); the second after vaccination against measles; the third after coma due to encephalitis. For the other two patients, the onset of PS was progressive, resembling a typical idiopathic Parkinson's disease (PD) but the findings at the MR dimissed this initial diagnose. In this study, the contribution of neuroimaging was crucial to recognize secondary parkinsonism though the ethiological agents could not be determined in these patients.


TITLE:
Administration of varicella vaccine before the age of 15 months, and the prescription of oral steroids, may be associated with a slightly increased risk of breakthrough disease.

AUTHORS:
Thomas Verstraeten, Aisha O Jumaan, John P Mullooly, Jane F Seward, Hector S Izurieta, Frank DeStefano, Steven B Black, Robert T Chen

ABSTRACT:
Varicella breakthrough, the occurrence of varicella disease >42 days after vaccination, is indicative of vaccination failure. A sevenfold increased risk of breakthrough among vaccinated children with asthma was observed in a 1996 varicella outbreak in a child care center. More recent outbreak investigations have also identified age at vaccination as a potential risk factor for breakthrough. We assessed the association of varicella breakthrough with asthma, steroids, age at varicella vaccination, and timing of measles-mumps-rubella (MMR) vaccination.


TITLE:
High-titer measles vaccination before 9 months of age has been linked to increased female mortality.

AUTHORS:
Peter Aaby, Henrik Jensen, Francois Simondon, Hilton C Whittle

ABSTRACT:
In 1989, high-titer (HT) Edmonston-Zagreb measles vaccine with a titer more than 10(4.7) plaque-forming-units was recommended by the World Health Organization for use in areas with a high incidence of measles in children younger than 9 months. In 1992, the recommendation was rescinded following reports from Guinea-Bissau, Senegal, and Haiti showing an increased incidence of female mortality occurring after administration of HT Edmonston-Zagreb vaccination. We reviewed 9 studies of HT measles vaccines that reported data on mortality. These reports included 4 randomized trials comparing HT vaccine administered to children younger than 9 months with standard-titer (ST) vaccines (10(3.0) to 10(4.0) plaque-forming-units) given at 9 months of age. Five studies from Zaire, Haiti, Senegal, Rwanda, and Zaire had no control group receiving ST vaccine at 9 months of age, but investigators were able to examine the female-to-male mortality ratio within these HT studies. Investigators have hypothesized that HT vaccine had caused immune suppression similar to that of measles infection. The present review suggests first that the HT vaccine itself is unlikely to be the cause because the effect was not found in all studies. Second, the increased mortality started only after 9 to 10 months of age when controls received ST measles vaccine, and HT groups received the "control vaccine." It was not found in the studies that provided another measles vaccine instead of control vaccine. Third, because the HT studies with excess mortality rates showed increased female mortality rates, we need to find environmental or contextual conditions associated with increased female mortality rates in some studies to explain the problem associated with HT measles vaccination.


TITLE:
Varicella vaccine has been reported to cause chronic, acyclovir-resistant herpes zoster infection in an immunosuppressed child.

AUTHORS:
Myron J Levin, Karen M Dahl, Adriana Weinberg, Roger Giller, Amita Patel, Philip R Krause

ABSTRACT:
A 1-year-old boy was vaccinated with the Oka strain of varicella just prior to the discovery of a tumor that required intensive antitumor therapy. Three months later he developed herpes zoster, which developed into chronic verrucous lesions that were refractory to treatment with acyclovir and which subsequently disseminated. DNA from a biopsy specimen of a chronic herpes-zoster lesion indicated that the Oka vaccine strain of the the virus caused this severe complication. Analysis of this viral DNA demonstrated a mutation in the viral thymidine kinase gene. Plasmids containing this altered gene were unable to produce functional thymidine kinase in an in vitro translation system. The presence of this mutation would explain the clinical resistance to acyclovir. This is the first report of Oka-strain varicella virus causing severe disease after reactivation and of resistance to acyclovir during an infection caused by this virus.


TITLE:
Pneumococcal vaccines do not appear to reduce the risk of death from pneumonia in adult populations.

ABSTRACT:
Diseases caused by Streptococcus pneumoniae (S. pneumoniae) continue to cause substantial morbidity and mortality throughout the world. Polysaccharide pneumococcal vaccines have been developed for over 50 years and may have the potential to prevent disease and death.


TITLE:
Passive acquired immunity against measles in infants born to naturally infected and vaccinated mothers.

AUTHORS:
Leszek Szenborn, Annedore Tischer, Jerzy Pejcz, Zbigniew Rudkowski, Marta Wojcik

ABSTRACT:
Currently, the majority of newborns in Poland are born to mothers who have been immunized against measles. The aim of this study was to compare the maternal measles antibody titers of infants born to mothers who had been infected by measles wild virus (group I) with those born to mothers who had been vaccinated (group II).


TITLE:
Primary infections with either B. pertussis or Bordetella parapertussis stimulated a vigorous antibody response to ACT. In contrast, patients in whom DTP and DTaP vaccines failed had minimal ACT antibody responses.

AUTHORS:
James D Cherry, Dorothy X L Xing, Penny Newland, Kashmira Patel, Ulrich Heininger, Michael J Corbel

ABSTRACT:
Presence of antibody to adenylate cyclase toxin (ACT) has been noted following Bordetella pertussis infection. Because ACT is not presently in any acellular pertussis vaccines, it has been considered as a possible antigen to use in B. pertussis diagnostic enzyme-linked immunosorbent assay (ELISA) studies. We determined antibody to B. pertussis ACT by ELISA and Western blot tests in serum samples obtained from unvaccinated children, from children vaccinated with several diphtheria and tetanus toxoid vaccines (DTP vaccines), from children vaccinated with vaccines containing acellular pertussis components in combination with diphtheria and tetanus toxoids (DTaP vaccines), and from children and adults with pertussis. Primary infections with either B. pertussis or Bordetella parapertussis stimulated a vigorous antibody response to ACT. In contrast, patients in whom DTP and DTaP vaccines failed had minimal ACT antibody responses. The lack of a significant ACT antibody response in children in whom the vaccine failed is of interest but would seem to preclude the use of ACT in diagnostic tests.


TITLE:
The psychic reactions following injections of bacterial vaccines.


TITLE:
Allergy to viral and rickettsial vaccines; review of the literature.


TITLE:
Thimerosal-containing vaccines are associated with autism prevalence and measles-containing vaccines are associated with serious neurological disorders.

ABSTRACT:
The purpose of the study was to evaluate the effects of MMR immunization and mercury from thimerosal-containing childhood vaccines on the prevalence of autism.


TITLE:
A chickenpox outbreak occurred in a school in which 97% of students without a prior history of chickenpox were vaccinated.

AUTHORS:
Barna D Tugwell, Lore E Lee, Hilary Gillette, Eileen M Lorber, Katrina Hedberg, Paul R Cieslak

ABSTRACT:
We investigated a chickenpox outbreak that started in an Oregon elementary school in October 2001, after public schools began phasing in a varicella vaccination requirement for enrollment. We sought to determine the rate of varicella vaccination and effectiveness and risk factors for breakthrough disease.


TITLE:
Rotavirus vaccination has been associated with increased risk for gastroenteritis and intussusception.

AUTHORS:
Penina Haber, Robert T Chen, Lynn R Zanardi, Gina T Mootrey, Roseanne English, M Miles Braun

ABSTRACT:
The rhesus-human rotavirus reassortant-tetravalent vaccine (RRV-TV) was licensed on August, 31, 1998, and subsequently recommended for routine infant immunizations in the United States. After approximately 1 million doses had been administered, an increase in acute risk of intussusception in vaccinees led to the suspension of the use of RRV-TV and its withdrawal from the market. These postmarketing safety studies focused on a single adverse event (intussusception) and, to minimize the risk of a false-positive finding, accepted only cases that met a strict case definition. Safer rotavirus vaccines are needed to prevent the substantial global morbidity and mortality caused by rotavirus infections; their development and future use may benefit from a better understanding of the postmarketing safety profile of RRV-TV beyond intussusception.


TITLE:
Diphtheria-tetanus-pertussis vaccines increase child mortality in rural Guinea-Bissau.

AUTHORS:
Peter Aaby, Henrik Jensen, Joaquim Gomes, Manual Fernandes, Ida Maria Lisse

ABSTRACT:
and objective Previous studies from areas with high mortality in West Africa have not found diphtheria-tetanus-pertussis (DTP) vaccine to be associated with the expected reduction in mortality, a few studies suggesting increased mortality. We therefore examined mortality when DTP was first introduced in rural areas of Guinea-Bissau in 1984-1987. Setting Twenty villages in four regions have been followed with bi-annual examinations since 1979.


TITLE:
Case report: failure to clear persistent vaccine-derived neurovirulent poliovirus infection in an immunodeficient man.

AUTHORS:
Calman MacLennan, Glynis Dunn, Aarnoud P Huissoon, Dinakantha S Kumararatne, Javier Martin, Paula O'Leary, Ronald A Thompson, Husam Osman, Philip Wood, Philip Minor, J Wood, Deenan Pillay

ABSTRACT:
Individuals who chronically excrete neurovirulent poliovirus of vaccine-origin are of considerable concern to the Global Polio Eradication programme. Chronic infection with such polioviruses is a recognised complication of hypogammaglobulinaemia.


TITLE:
The anthrax vaccine is one of the most reactogenic vaccines reported in the Vaccine Adverse Events Reporting System (VAERS) database.

ABSTRACT:
The Institute of Medicine (IOM) of the United States Academy of Sciences in 2000 encouraged the evaluation of active long-term monitoring studies of large populations to further evaluate the relative safety of anthrax vaccine. Anthrax is a deadly bacterial infectious disease that currently has been engineered as a biological warfare agent. The vaccine produced against anthrax is a cell-free crude culture of the various toxin components of the natural disease. The U.S. military current goal is to vaccinate its entire personnel by 2003. The purpose of this study was to evaluate anthrax vaccination and its association with arthritic, immunological and gastrointestinal adverse reactions based upon analysis of the Vaccine Adverse Events Reporting System (VAERS) database.


TITLE:
Whole cell pertussis vaccines may have been causing serious neurological disorders.

ABSTRACT:
Serious neurological disorders reported following whole-cell pertussis in comparison to acellular pertussis vaccines were evaluated. The Vaccine Adverse Events Reporting System (VAERS) was analyzed for Emergency Department (ED) visits, life-threatening reactions, hospitalizations, disabilities, deaths, seizures, infantile spasms, encephalitis/encephalopathy, autism, Sudden Infant Death Syndrome (SIDS) and speech disorders reported with an initial onset of symptoms within 3 days following whole-cell pertussis and acellular pertussis vaccines among those residing in the US from 1997 to 1999. Controls were employed to evaluate potential biases in VAERS. Evaluations as to whether whole-cell and acellular vaccines were administered to populations of similar age and sex were undertaken because these factors might influence the study's results. Statistical increases were observed for all events examined following whole-cell pertussis vaccination in comparison to acellular pertussis vaccination, excepting cerebellar ataxia. Reporting biases were minimal in VAERS, and whole-cell and acellular pertussis vaccines were administered to populations of similar age and sex. Biologic mechanisms for the increased reactogenicity of whole-cell pertussis vaccines may stem from the fact that whole-cell pertussis vaccines contain 3,000 different proteins, whereas DTaP contains two to five proteins. Whole-cell pertussis vaccine contains known neurotoxins including: endotoxin, pertussis toxin and adenylate cyclase. Our results, and conclusions by the US Institute of Medicine, suggest an association between serious neurological disorders and whole-cell pertussis immunization. In light of the presence of a safer and at least equally efficacious acellular pertussis vaccine alternative, the Japanese and US switch to using acellular pertussis vaccine seems well justified. Other countries using whole-cell pertussis-containing vaccines should consider following suite in the near future.


TITLE:
Undernutrition as an underlying cause of child deaths associated with diarrhea, pneumonia, malaria, and measles.

AUTHORS:
Laura E Caulfield, Mercedes de Onis, Monika Blossner, Robert E Black

ABSTRACT:
Previous analyses derived the relative risk (RR) of dying as a result of low weight-for-age and calculated the proportion of child deaths worldwide attributable to underweight.


TITLE:
Influenza vaccination does not appear to be effective during pregnancy in preventing hospitalizations and outpatient visits for respiratory illness in pregnant women and their infants.

AUTHORS:
Steven B Black, Henry R Shinefield, Eric K France, Bruce H Fireman, Sharon T Platt, David Shay,

ABSTRACT:
The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommends influenza vaccination for women who will be in the second or third trimester of pregnancy during the influenza season. We analyzed hospital admissions with principal diagnoses of influenza or pneumonia and influenza-like illness (ILI) outpatient visits to study the effectiveness of influenza vaccine during pregnancy in protecting women and infants from influenza-related morbidity. Estimates of influenza vaccine effectiveness across five flu seasons (Fall 1997 to Spring 2002) were calculated using Cox proportional hazards models for women and infant study populations in Kaiser Permanente Northern California. Outpatient utilization outcomes included physician visits with a diagnosis of upper respiratory infection, pharyngitis, otitis media, asthma, bronchial asthma, viral infection, pneumonia, fever, cough, or wheezing associated with respiratory illness. Inpatient outcomes included hospitalizations with principal diagnoses of influenza or pneumonia. Women who received influenza vaccine during pregnancy had the same risk for ILI visits compared with unvaccinated women, adjusting for women's age and week of delivery. When asthma visits were excluded from the outcome measure, we also found no difference in the risk of outpatient visits for vaccinated and unvaccinated women. Hospital admissions for influenza or pneumonia for women in the study population were quite rare and no women died of respiratory illness during pregnancy. Infants born to women who received influenza vaccination had the same risks for influenza or pneumonia admissions compared with infants born to unvaccinated women, adjusting for infant's gender, gestational age, week of birth, and birth facility. Maternal influenza vaccination was also not a significant determinant of risk of ILI (excluding otitis media) outpatient visits for infants, nor did it significantly affect the risk of otitis media visits. Influenza vaccination during pregnancy did not significantly affect the risk of cesarean section, adjusting for the woman's age. It also did not affect the risk of preterm delivery. Although the immunogenicity of influenza vaccination in pregnancy in mother and infant has been well documented, in this study, we were unable to demonstrate the effectiveness of influenza vaccination with data for hospital admissions and physician visits. One possible interpretation of these findings is that typical influenza surveillance measures based on utilization data are not reliable in distinguishing influenza from other respiratory illness. Hospitalizations for respiratory illness were uncommon in both vaccinees and nonvaccinees.


TITLE:
DTP vaccination may contribute to urinary tract disease and sudden infant death syndrome.

ABSTRACT:
Prophylactic vaccinations may sometimes shorten the incubation period of some illnesses and/or convert a latent infection/inflammation into a clinically apparent disease. Cytokines play a major role in mediating the inflammatory process in various clinical entities and represent a potential source of tissue damage if their production is not sufficiently well controlled. It seems that irregularities in production of proinflammatory cytokines may be responsible for the abnormalities associated with full-blown clinical symptoms of various urinary tract diseases observed after DTP vaccination in 13 infants and young children hospitalized over the past 24 years. On admission, upper respiratory tract diseases, atopic dermatitis, and/or latent urinary tract infection/inflammation were found in these children. It is suggested that the whole-cell pertussis present in DTP vaccine, acting as an excessive stimulus in these patients, produced symptoms reminiscent of biologic responses to circulating proinflammatory monokines such as IL-1beta, TNF-alpha, and IL-6 because earlier it was reported that in vitro the whole-cell vaccine induced significantly more such cytokine production than did the acellular pertussis or diphtheria-tetanus-only vaccine. Analysis of the cellular immune disturbances previously reported in urinary tract infection/inflammation (increased serum and/or urinary IL-1alpha, IL-1 receptor antagonist, IL-6 and IL-8), steroid-sensitive nephrotic syndrome (increased IL-2, IFN-gamma, TNF-alpha, and decreased or increased IL-4, depending on the cells studied), and atopic dermatitis (decreased IFN-gamma and increased IL-4 production), may suggest that similar subclinical chronic cytokine-mediated abnormalities produced in the course of latent diseases revealed in our patients, combined with those caused by DTP vaccination stimulus, were responsible for the pathomechanism of these clinical entities. This speculation is in agreement with the reports on the long-lasting induction of cytokine release and down-regulation of hepatic cytochrome P-450 isoenzyme activities after administration of DTP vaccine to mice and may be supported by the fact that TH1 phenotype is associated with the up-regulation of intercellular adhesion molecule-1 and RANTES, whereas TH2 phenotype is associated with the up-regulation of the vascular cell adhesion molecule and P-selectin, which are key players in the migration into inflamed tissues and localization of lymphocytes and other allergic effector and inflammatory cells. Because several inflammatory cytokines down-regulate gene expression of major cytochrome P-450 and/or other enzymes with the specific effects on mRNA levels, protein expression, and enzyme activity, thus affecting the metabolism of several endogenous lipophilic substances such as steroids, lipid-soluble vitamins, prostaglandins, leukotrienes, thromboxanes, and exogenous substances, their irregularities in the body may eventually lead to the flare of latent diseases in some predisposed subjects. Also, interleukin genetic polymorphisms, especially the constellation of TNF-alpha and IL-6 genetic variants, might predispose some infants with infection to a more than usually intense inflammatory response in the kidneys after vaccination. It seems that the aforementioned pathomechanism may also be responsible for some cases of sudden infant death syndrome, which is often preceded by infection/inflammation.


TITLE:
Hepatitis B vaccine is associated with an increased risk of multiple sclerosis.

AUTHORS:
Miguel A Hernan, Susan S Jick, Michael J Olek, Hershel Jick

ABSTRACT:
A potential link between the recombinant hepatitis B vaccine and an increased risk of multiple sclerosis (MS) has been evaluated in several studies, but some of them have substantial methodologic limitations.


TITLE:
Pneumococcal vaccines are ineffective in children with a history of recurrent acute ear infections.

AUTHORS:
Reinier H Veenhoven, Debby Bogaert, Anne G M Schilder, Ger T Rijkers, Cuno S P M Uiterwaal, Herma H Kiezebrink, Muriel J P van Kempen, Ingeborg J Dhooge, Jacob Bruin, Ed P F Ijzerman, Ronald de Groot, Wietse Kuis, Peter W M Hermans, Elisabeth A M Sanders

ABSTRACT:
We recently showed that vaccination with a 7-valent pneumococcal conjugate vaccine (PCV7) followed by a 23-valent pneumococcal polysaccharide vaccine (PPSV23) failed to prevent new episodes of acute otitis media (AOM) in previously unvaccinated toddlers and children with a history of recurrent AOM. We describe in detail the impact of pneumococcal vaccinations on nasopharyngeal carriage of S. pneumoniae in this study population.


TITLE:
The use of misoprostol for early pregnancy failure after failed expectant management is less costly than curettage.

AUTHORS:
G C M Graziosi, J W van der Steeg, P H W Reuwer, A P Drogtrop, H W Bruinse, B WJ Mol

ABSTRACT:
The increased pressure on health care expenses implies that physicians should consider economic aspects as part of the clinical decision-making process. Direct and indirect costs of a strategy starting with misoprostol in treatment of early pregnancy failure as compared to curettage is therefore performed.


TITLE:
Hepatitis B vaccination is associated with a wide range of autoimmune diseases.

ABSTRACT:
Adverse events and positive re-challenge of symptoms reported in the scientific literature and to the Vaccine Adverse Event Reporting System (VAERS) following hepatitis B vaccination (HBV) were examined.


TITLE:
Guillain-Barre syndrome following hepatitis B vaccination has been reported.

AUTHORS:
M Khamaisi, Yehuda Shoenfeld, Hedi Orbach

ABSTRACT:
A 52-year-old woman developed Guillain-Barré syndrome 10 weeks after immunization with recombinant hepatitis B vaccine. Common infectious causes of GBS were ruled out. The temporal relationship between GBS and hepatitis B virus (HBV) vaccination was suggestive of a vaccine-induced cause. The possible mechanisms of this very, rare complication are discussed.


TITLE:
Widening influenza vaccine coverage is not correlated with declining mortality rates in any age group. The benefits of vaccination are substantially overestimated.

AUTHORS:
Lone Simonsen, Thomas A Reichert, CÃ©cile Viboud, William C Blackwelder, Robert J Taylor, Mark A Miller

ABSTRACT:
Observational studies report that influenza vaccination reduces winter mortality risk from any cause by 50% among the elderly. Influenza vaccination coverage among elderly persons (> or =65 years) in the United States increased from between 15% and 20% before 1980 to 65% in 2001. Unexpectedly, estimates of influenza-related mortality in this age group also increased during this period. We tried to reconcile these conflicting findings by adjusting excess mortality estimates for aging and increased circulation of influenza A(H3N2) viruses.


TITLE:
Hepatitis B vaccinations is associated with autoimmune hazards.

ABSTRACT:
According to Hippocratic tradition, the safety level of a preventive medicine must be very high, as it is aimed at protecting people against diseases that they may not contract. This paper points out that information on the safety of hepatitis B vaccine (HBV) is biased as compared to classical requirements of evidence-based medicine (EBM), as exemplified by a documented selectivity in the presentation or even publication of available clinical or epidemiological data. Then, a review is made of data suggesting that HBV is remarkable by the frequency, the severity and the variety of its complications, some of them probably related to a mechanism of molecular mimicry leading to demyelinating diseases, and the others reproducing the spectrum of non-hepatic manifestations of natural hepatitis B. To be explained, this unusual spectrum of toxicity requires additional investigations based upon complete release of available data.


TITLE:
The intranasal innoculation of pregnant sows with porcine circovirus 2 results in abortion and reproductive failure.

AUTHORS:
J-S Park, J Kim, Y Ha, K Jung, C Choi, J-K Lim, S-H Kim, C Chae

ABSTRACT:
Six pregnant sows were inoculated intranasally at 3 weeks before the expected farrowing date with porcine circovirus 2 (PCV2). The PCV2-inoculated sows showed abortion and premature farrowing, whereas two uninfected negative control sows remained clinically healthy and farrowed normally. PCV2 antigen and DNA were detected by immunohistochemistry and in-situ hybridization, respectively, in lymph node, spleen, thymus, lung, tonsil and liver from both stillborn and liveborn piglets. Simultaneous detection of viral protein and DNA provided molecular evidence of PCV2 infection and replication. The experiment suggested that PCV2 is capable of crossing the placenta, replicating primarily in lymphoid tissues, and inducing reproductive failure.


TITLE:
Biological assays lend support to the association between measles virus or MMR and autism.

AUTHORS:
Jane E Libbey, Thayne L Sweeten, William M McMahon, Robert S Fujinami

ABSTRACT:
Autistic disorder (autism) is a behaviorally defined developmental disorder with a wide range of behaviors. Although the etiology of autism is unknown, data suggest that autism results from multiple etiologies with both genetic and environmental contributions, which may explain the spectrum of behaviors seen in this disorder. One proposed etiology for autism is viral infection very early in development. The mechanism, by which viral infection may lead to autism, be it through direct infection of the central nervous system (CNS), through infection elsewhere in the body acting as a trigger for disease in the CNS, through alteration of the immune response of the mother or offspring, or through a combination of these, is not yet known. Animal models in which early viral infection results in behavioral changes later in life include the influenza virus model in pregnant mice and the Borna disease virus model in newborn Lewis rats. Many studies over the years have presented evidence both for and against the association of autism with various viral infections. The best association to date has been made between congenital rubella and autism; however, members of the herpes virus family may also have a role in autism. Recently, controversy has arisen as to the involvement of measles virus and/or the measles, mumps, rubella (MMR) vaccine in the development of autism. Biological assays lend support to the association between measles virus or MMR and autism whereas epidemiologic studies show no association between MMR and autism. Further research is needed to clarify both the mechanisms whereby viral infection early in development may lead to autism and the possible involvement of the MMR vaccine in the development of autism.


TITLE:
The mercury containing vaccine adjuvant known as thimerosal has immunosuppressive and autoimmune effects in mice.

AUTHORS:
S Havarinasab, B Haggavist, E Bjorn, K M Pollard, P Hultman

ABSTRACT:
The possible health effects of the organic mercury compound thimerosal (ethylmercurithiosalicylate), which is rapidly metabolized to ethylmercury (EtHg), have recently been much debated and the effect of this compound on the immune system is largely unknown. We therefore studied the effect of thimerosal by treating A.SW (H-2s) mice, susceptible to induction of autoimmunity by heavy metals, with 10 mg thimerosal/L drinking water (internal dose ca 590 microg Hg/kg body weight/day) for up to 30 days. The lymph node expression of IL-2 and IL-15 mRNA was increased after 2 days, and of IL-4 and IFN-gamma mRNA after 6 and 14 days. During the first 14 days treatment, the number of splenocytes, including T and B cells as well as Ig-secreting cells decreased. A strong immunostimulation superseded after 30 days treatment with increase in splenic weight, number of splenocytes including T and B cells and Ig-secreting cells, and Th2- as well as Th-1-dependent serum immunoglobulins. Antinucleolar antibodies (ANoA) targeting the 34-kDa nucleolar protein fibrillarin, and systemic immune-complex deposits developed. The H-2s strains SJL and B10.S also responded to thimerosal treatment with ANoA. The A.TL and B10.TL strain, sharing background genes with the A.SW and B10.S strain, respectively, but with a different H-2 haplotype (t1), did not develop ANoA, linking the susceptibility to H-2. Thimerosal-treated H-2s mice homozygous for the nu mutation (SJL-nu/nu), or lacking the T-cell co-stimulatory molecule CD28 (B10.S-CD28-/-), did not develop ANoA, which showed that the autoimmune response is T-cell dependent. Using H-2s strains with targeted mutations, we found that IFN-gamma and IL-6, but not IL-4, is important for induction of ANoA by thimerosal. The maximum added renal concentration of thimerosal (EtHg) and inorganic mercury occurred after 14 days treatment and was 81 microg Hg/g. EtHg made up 59% and inorganic mercury 41% of the renal mercury. In conclusion, the organic mercury compound thimerosal (EtHg) has initial immunosuppressive effects similar to those of MeHg. However, in contrast to MeHg, thimerosal treatment leads in genetically susceptible mice to a second phase with strong immunostimulation and autoimmunity, which is T-cell dependent, H-2 linked and may at least partly be due to the inorganic mercury derived from the metabolism of ethyl mercury.


TITLE:
Despite high coverage rates for primary immunization in. infants and children pertussis incidence rates are increasing.

AUTHORS:
Tina Tan, Evelinda Trindade, Danuta Skowronski

ABSTRACT:
The World Health Organization recommended that a pertussis incidence of <1 case per 100,000 population be achieved in Europe by 2000. Available data indicate that this goal has generally not been achieved, and the incidence is actually rising in some countries. Understanding the reasons for this increased incidence may lead to better global control of pertussis. In the majority of countries where pertussis is a notifiable disease, a case-based national surveillance system is in place. However, different case definitions, methods of diagnosis and reporting and surveillance systems make direct intercountry comparisons difficult, and pertussis is not a statutory notifiable disease in every country. Nevertheless the general consensus is that reported incidences are probably considerably lower than the actual incidence of pertussis; underreporting is common. Prolonged cough may be the only clinical feature in adolescents or adults, who may present for diagnosis late (precluding laboratory confirmation) or not at all. When they do present, their condition is often misdiagnosed because, in part, clinicians continue to perceive pertussis as a childhood disease. Despite underreporting, an increased incidence of infant, adolescent and adult pertussis has been observed worldwide since the introduction of widespread vaccination. This is of concern because adolescents and adults have been identified as a source of transmission of pertussis to very young infants who are unimmunized or partially immunized and thus more vulnerable to disease-related complications and higher mortality. In recent years, acellular pertussis vaccines have been incorporated into the immunization schedules of many developed countries, gradually replacing whole cell vaccines. Dosing schedules vary between countries, although primary immunization with 3 doses of the pertussis vaccine within the first 6 months of life exists in most countries. Only Australia, Austria, Canada, France and Germany have incorporated an adolescent booster dose into their current immunization schedules, in recognition of the rising incidence of pertussis in adolescents and adults. Despite high coverage rates for primary immunization in infants and children, pertussis continues to be a global concern, with increased incidence widely noted. This global epidemiologic summary highlights differences worldwide in pertussis reporting, incidence and approaches to prevention. It underscores a general shift in the age distribution of pertussis toward older groups. Understanding the link between these observations may lead to better informed global control strategies, especially those pertaining to immunization schedules and use of pertussis vaccine.


TITLE:
The demyelinating effect of hepatitis B vaccination could be due to the contamination of the vaccine by partial hepatitis B virus polymerase.

ABSTRACT:
Reports of multiple sclerosis developing after hepatitis B vaccination have led to the concern that this vaccine might be a cause of multiple sclerosis in previously healthy subjects. Some articles evidenced that minor Hepatitis B virus (HBV) polymerase proteins could be produced by alternative transcriptional or translational strategies. Their detection is very difficult because they are in minute concentration and probably enzymatically inactive, however, it was shown that they could be exposed on the outside of the virus particles and also be immunogenic. In addition, HBV polymerase shares significant amino acid similarities with the human myelin basic protein. We hypothesise that some of the apparent adverse reactions to the vaccine could be due to a process called of molecular mimicry, the HBV polymerase, which could be a contaminant in the recombinant or plasma-derived vaccines, could act as autoantigens and induce autoimmune demyelinating diseases such as multiple sclerosis.


TITLE:
Timing of routine immunisations (earlier = increased) and subsequent hay fever risk.

AUTHORS:
S A Bremner, I M Carey, S DeWilde, N Richards, W C Maier, S R Hilton, D P Strachan, D G Cook

ABSTRACT:
Suggestions that immunisation influences allergic disease risk, either positively (pertussis) or negatively (BCG) are of concern for vaccination policy.


TITLE:
Fifty-one percent of cases of patients in a 1998/1999 mumps outbreak had at least one MMR vaccination, indicating their effectiveness may be overestimated.

AUTHORS:
Richard Harling, Joanne M White, Mary E Ramsay, Karen F Macsween, Corry van den Bosch

ABSTRACT:
In 1998/1999, an outbreak of mumps occurred among children of a religious community in North East London. A case control study was conducted to assess the effectiveness of the mumps component of the MMR vaccine. One hundred and sixty-one cases of mumps were identified and 192 controls were selected. Fifty-one percent of cases and 77% of controls had a history at least one MMR vaccination. The observed effectiveness of any MMR vaccination adjusted for age, sex and general practice was 69% (95% CI: 41-84%). This is consistent with the results of other observational studies of mumps containing vaccines, but lower than the immunogenicity of mumps vaccines reported by clinical trials. This discrepancy is because observational studies tend to underestimate vaccine effectiveness, and because immunogenicity is not necessarily an accurate biological marker of vaccine effectiveness. Two doses of vaccine were more effective (88% (95% CI: 62-96%)) than a single dose (64% (95% CI: 40-78%)). The current two-dose vaccination programme remains the best method for controlling mumps infection in the community.


TITLE:
Fatal adverse pulmonary reaction in calves after inadvertent intravenous vaccination has been reported.

ABSTRACT:
Fatal adverse reactions to vaccination are uncommon and poorly documented. To our knowledge, this is the first case report of fatal adverse reaction to an inadvertent intravenous vaccination in three calves vaccinated against respiratory (Somnustar Ph) and clostridial (Tasvax 8) diseases. All three calves had severe acute interstitial pneumonia with multifocal pulmonary hemorrhages that resulted in fatal respiratory failure. Qualitatively, the pulmonary lesions in these calves were similar to those in septicemic/endotoxemic calves; however, the severity and extensity of pulmonary hemorrhages were of a higher degree than those usually observed in clinical septicemia/endotoxemia. In addition, approximately 30% of the arterioles and small arteries were surrounded by hemorrhages, which occasionally extended around adjacent bronchioles. A unilateral peri-jugular hematoma with recent transmural perforation of jugular vein found in all three calves was believed to have been caused by the injection needle during vaccination, and the fatal pulmonary changes were believed to have been secondary to the intravenous injection of vaccine.


TITLE:
Infection and vaccines are triggers for autoimmune disease.

ABSTRACT:
The etiology of autoimmune diseases is still not clear but genetic, immunological, hormonal and environmental factors are considered to be important triggers. Most often autoimmunity is not followed by clinical symptoms unless an additional event such as an environmental factor favors an overt expression. Many environmental factors are known to affect the immune system and may play a role as triggers of the autoimmune mosaic.Infections: bacterial, viral and parasitic infections are known to induce and exacerbate autoimmune diseases, mainly by the mechanism of molecular mimicry. This was studied for some syndromes as for the association between SLE and EBV infection, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection and more. Vaccines, in several reports were found to be temporally followed by a new onset of autoimmune diseases. The same mechanisms that act in infectious invasion of the host, apply equally to the host response to vaccination. It has been accepted for diphtheria and tetanus toxoid, polio and measles vaccines and GBS. Also this theory has been accepted for MMR vaccination and development of autoimmune thrombocytopenia, MS has been associated with HBV vaccination. Occupational and other chemical exposures are considered as triggers for autoimmunity. A debate still exists about the role of silicone implants in induction of scleroderma like disease.Not only foreign chemicals and agents have been associated with induction of autoimmunity, but also an intrinsic hormonal exposure, such as estrogens. This might explain the sexual dimorphism in autoimmunity.Better understanding of these environmental risk factors will likely lead to explanation of the mechanisms of onset and progression of autoimmune diseases and may lead to effective preventive involvement in specific high-risk groups. So by diagnosing a new patient with autoimmune disease a wide anamnesis work should be done.


TITLE:
Hepatitis B vaccination has the potential to induce central demyelinating disorders such as multiple sclerosis.

ABSTRACT:
In spite of a huge number of reports of severe hazards after injection of hepatitis B vaccine (HBV), the issue is regularly raised that no mechanism is available for the development of central demyelinating disorders such as multiple sclerosis (MS). A number of convergent facts, however, suggests that the manufacturing process could introduce HBV polymerase as a contaminant, and then trigger an auto-immune process against myelin in some vaccinated subjects. Of great significance, this hypothesis is likely to give the missing link to account for the considerable body of clinical and epidemiological evidence documenting that, for a drug used with a preventive purpose, HBV has an unusual potential to induce central neurological disorders amongst others unwanted side-effects.


TITLE:
Among female infants, those who receive both BCG and DTP vaccines experience higher mortality than those who receive only one of the two vaccines.

AUTHORS:
Lawrence H Moulton, Lakshmi Rahmathullah, Neal A Halsey, R D Thulasiraj, Joanne Katz, James M Tielsch

ABSTRACT:
The aim of this study was to assess the relationship between receipt of routine childhood immunizations and infant mortality before 6 months of age.


TITLE:
A case of influenza vaccine induced have necrotizing glomerulonephritis in decursu vasculitis has been reported.

AUTHORS:
Lidia Hyla-Klekot, Grazyna Kucharska, Witold Cieslak

ABSTRACT:
Vaccinations against influenza are common, acceptable way of prevention of influenza, which develops as epidemic on huge areas of Europe. We described 17 years old girl, who has developed vasculitis after vaccination against influenza vaccine Vaxigrip produced by Aventis Pasteur. Aggressive immunosuppressive treatments caused regression majority of clinical symptoms and normalization of renal function tests.


TITLE:
Hepatitis B vaccination significantly increases the risk of a wide range of autoimmune diseases.

ABSTRACT:
Hepatitis B infection is one of the most important causes of acute and chronic liver disease. During the 1980s, genetically engineered hepatitis B vaccines (HBVs) were introduced in the United States. A large-series of serious autoimmune conditions have been reported following HBVs, despite the fact that HBVs have been reported to be "generally well-tolerated." A case-control epidemiological study was conducted to evaluate serious autoimmune adverse events prospectively reported to the vaccine adverse events reporting system (VAERS) database following HBVs, in comparison to an age, sex, and vaccine year matched unexposed tetanus-containing vaccine (TCV) group for conditions that have been previously identified on an a priori basis from case-reports. Adults receiving HBV had significantly increased odds ratios (OR) for multiple sclerosis (OR = 5.2, p < 0.0003, 95% Confidence Interval (CI) = 1.9 - 20), optic neuritis (OR = 14, p < 0.0002, 95% CI = 2.3 - 560), vasculitis (OR = 2.6, p < 0.04, 95% CI = 1.03 - 8.7), arthritis (OR = 2.01, p < 0.0003, 95% CI = 1.3 - 3.1), alopecia (OR = 7.2, p < 0.0001, 95% CI = 3.2 - 20), lupus erythematosus (OR = 9.1, p < 0.0001, 95% CI = 2.3 - 76), rheumatoid arthritis (OR = 18, p < 0.0001, 95% CI = 3.1 - 740), and thrombocytopenia (OR = 2.3, p < 0.04, 95% CI = 1.02 - 6.2) in comparison to the TCV group. Minimal confounding or systematic error was observed. Despite the negative findings of the present study regarding the rare serious adverse effects of HBVs, it is clear that HBV does, indeed, offer significant benefits, but it is also clear that chances of exposure to hepatitis B virus in adults is largely life-style dependent. Adults should make an informed consent decision, weighing the risks and benefits of HBV, as to whether or not to be immunized.


TITLE:
Sudden infant death syndrome (SIDS) shortly after hexavalent vaccination has been reported.

AUTHORS:
Giulia Ottaviani, Anna Maria Lavezzi, Luigi Matturri

ABSTRACT:
Experts from panels of the European Agency for the Evaluation of Medical Products have investigated whether there might be a link between hexavalent vaccines and some cases of deaths that occurred. Participants included pathologists with experience in the field of vaccines and sudden infant death syndrome who conducted autopsies. However, to the best of our knowledge, little, if any, attention was paid to examination of the brainstem and the cardiac conduction systems on serial sections, nor was the possibility of a triggering role of the vaccine in these deaths considered. Herein we report the case of a 3-month-old female infant dying suddenly and unexpectedly shortly after being given a hexavalent vaccination. Examination of the brainstem on serial sections revealed bilateral hypoplasia of the arcuate nucleus. The cardiac conduction system presented persistent fetal dispersion and resorptive degeneration. This case offers a unique insight into the possible role of hexavalent vaccine in triggering a lethal outcome in a vulnerable baby. Any case of sudden unexpected death occurring perinatally and in infancy, especially soon after a vaccination, should always undergo a full necropsy study according to our guidelines.


TITLE:
When polled 5% of nonpediatricians would not use Haemophilus Influenzae type b vaccine if they had a child born in 2004.

AUTHORS:
Klara M Posfay-Barbe, Ulrich Heininger, Christoph Aebi, Daniel Desgrandchamps, Bernard Vaudaux, Claire-Anne Siegrist

ABSTRACT:
Immunization has an essential impact on public health worldwide. Numerous studies have shown the efficacy of different vaccines to protect individuals from various diseases. However, some parents choose not to vaccinate their children for reasons such as, among others, doubts regarding their usefulness, concerns over safety or efficacy, etc. Physicians are known to exert a direct influence on immunization rates by answering questions and clarifying misconceptions. Yet, it is unknown how they immunize their own children.


TITLE:
Some oral poliovirus vaccines were contaminated with infectious SV40 after 1961.

AUTHORS:
Rochelle Cutrone, John Lednicky, Glynis Dunn, Paola Rizzo, Maurizio Bocchetta, Konstantin Chumakov, Philip Minor, Michele Carbone

ABSTRACT:
Some polio vaccines prepared from 1954 to 1961 were contaminated with infectious SV40. It has been assumed that all polio vaccines were SV40 free in the United States after 1961 and in other countries after 1962. Following a WHO requirement that was prompted by the detection of SV40 in some human tumors, we conducted a multilaboratory study to test for SV40 polio vaccines prepared after 1961. Vaccine samples from 13 countries and the WHO seed were initially tested by PCR. The possible presence of intact and/or infectious SV40 DNA in PCR-positive samples was tested by transfection and infection of permissive CV-1 cells. All results were verified by immunohistochemistry, cloning, and sequencing. All the vaccines were SV40 free, except for vaccines from a major eastern European manufacturer that contained infectious SV40. We determined that the procedure used by this manufacturer to inactivate SV40 in oral poliovirus vaccine seed stocks based on heat inactivation in the presence of MgCl2 did not completely inactivate SV40. These SV40-contaminated vaccines were produced from early 1960s to about 1978 and were used throughout the world. Our findings underscore the potential risks of using primary monkey cells for preparing poliovirus vaccines, because of the possible contamination with SV40 or other monkey viruses, and emphasize the importance of using well-characterized cell substrates that are free from adventitious agents. Moreover, our results indicate possible geographic differences in SV40 exposure and offer a possible explanation for the different percentage of SV40-positive tumors detected in some laboratories.


TITLE:
Hepatitis B vaccination may contribute to autoimmune demyelinating complications due to immunological cross-reactivity between Hepatitis B virus surface antigen and myelin basic protein.

AUTHORS:
Dimitrios-Petrou Bogdanos, Heather Smith, Yun Ma, Harold Baum, Giorgina Mieli-Vergani, Diego Vergani

ABSTRACT:
On the basis of the reported association between hepatitis B vaccination (HBvacc) and autoimmune demyelinating complications such as multiple sclerosis (MS), we have looked for aminoacid similarities between the small hepatitis B virus surface antigen (SHBsAg), and the MS-autoantigens myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) that could serve as targets of immunological cross-reactivity. Twenty-mer peptides spanning 4 SHBsAg/MOG and 1 SHBsAg/MBP mimicking pairs, were constructed and tested by ELISA as targets of cross-reactive responses. A total of 147 samples from 58 adults were collected before HBvacc (58/58), and post-HBvacc (48/58 before the second and 41/58 before the third boost). Eighty-seven sera from anti-SHBsAg antibody negative patients with various diseases were tested as pathological controls. Reactivity to at least one of the SHBsAg peptides was found in 8 (14%) pre-HBvacc subjects; amongst the remaining 50, reactivity to at least one of the SHBsAg peptides appeared in 47 (94%) post-HBvacc. Reactivity to at least one of the MOG mimics was present in 4 (8%) pre-HBvacc and in 30 (60%) post-HBvacc (p < 0.001). Overall 30/50 (60%) vaccinees had SHBsAg/MOG double reactivity on at least one occasion compared to none before-vaccination and in 2 (2%) of the pathological controls (p < 0.001 for both). SHBsAg/MOG double reactivity was cross-reactive as confirmed by inhibition studies. At 6 months post-vaccination, 3 of the 4 anti-MOG reactive cases before vaccination and 7 of the 24 (29%) of the anti-MOG reactive cases at 3 months post-vaccination had lost their reactivity to MOG5-24. There was no reactivity to the SHBsAg/MBP mimics. None of the vaccinees reported symptoms of demyelinating disorders. In view of the observed SHBsAg/MOG cross-reactivity, the vaccine's possible role as an immunomodulator of viral/self cross-reactivity must be further investigated.


TITLE:
Acute hepatitis B can occur in those who are vaccinated against it and who are exposured through unprotected sexual contact and iatrogenically.

AUTHORS:
G Rosner, Y Lurie, L Blendis, Z Halpern, R Oren

ABSTRACT:
Since the adoption of a universal hepatitis B immunisation strategy, the reported incidence of acute hepatitis B has declined dramatically worldwide including in Israel. However, new cases of acute hepatitis B still occur. The aim of this study was to describe the incidence of acute hepatitis B in a referral area, routes of transmission, and outcome.


TITLE:
Pregnant cows vaccinated with live attenuated Smithburn Rift Valley virus had a high rate of abortions which were associated with elevations in IgG and IgM antibodies.

AUTHORS:
Boulos Botros, Adel Omar, Khairat Elian, Gihan Mohamed, Atef Soliman, Adel Salib, Diaa Salman, Magdi Saad, Kenneth Earhart

ABSTRACT:
Three hundred eighteen European cows and 115 buffaloes were vaccinated with locally prepared Smithburn vaccine, of which, 100 cows and 20 buffaloes were pregnant. Twenty-eight cows aborted within 72 days post-vaccination, buffaloes did not abort. Blood samples collected 77 days post-vaccination from aborted cows, 17 pregnant cows, 5 pregnant buffaloes, and 32 non-pregnant cows. Sera were tested by ELISA for anti-RVF IgM and IgG. All aborted cows were strongly positive for IgG. Five of 17 cows and two of five buffaloes that did not abort were IgG positive. The percentage of IgM positives in aborted cows was 25% and 0% in non-aborted cows. The percentage of IgG positives in pregnant non-aborted cows was lower than in non-pregnant cows. The percentage of IgG positives of non-pregnant cows was lower than pregnant aborted cows. Virus was isolated from one aborted fetus. The nucleotide sequence of fetus virus was compared to Smithburn of Onderstepoort, local Smithburn and virus isolates from 1993 to 1994 and 1977 RVF outbreaks. The nucleotide sequences of Onderstepoort and Egyptian Smithburn vaccines were almost identical. The sequences of 1993-1994 isolates were identical to 1977 outbreak virus. Virus from the fetus had two mutations; it is apparently a variant that is genetically distant from local Smithburn and Onderstepoort vaccines. Fetus virus was genetically distant from virus of 1993/1994 and 1977 outbreaks. In conclusion, antibody response to vaccination with local Smithburn had occurred in some, but not all the cows and buffaloes. Virus isolation from the fetus suggests in utero transmission of used vaccine virus, which resulted in high abortions in European cows.


TITLE:
Near complete vaccination coverage for varicella does not prevent outbreaks in those treated.

AUTHORS:
Adriana S Lopez, Dalya Guris, Laura Zimmerman, Linda Gladden, Tamara Moore, Dirk T Haselow, Vladimir N Loparev, D Scott Schmid, Aisha O Jumaan, Sandra L Snow

ABSTRACT:
The implementation of a routine childhood varicella vaccination program in the United States in 1995 has resulted in a dramatic decline in varicella morbidity and mortality. Although disease incidence has decreased, outbreaks of varicella continue to be reported, increasingly in highly vaccinated populations. In 2000, a varicella vaccination requirement was introduced for kindergarten entry in Arkansas. In October 2003, large numbers of varicella cases were reported in a school with high vaccination coverage. We investigated this outbreak to examine transmission patterns of varicella in this highly vaccinated population, to estimate the effectiveness of 1 dose of varicella vaccine, to identify risk factors for vaccine failure, and to implement outbreak control measures.


TITLE:
Feline injection site-associated sarcoma is a serious problem associated with malignancy.

ABSTRACT:
Feline injection site-associated sarcoma (FISAS) or vaccination-associated sarcoma is a serious problem in cats because of the ethical and therapeutic consequences associated with the disease. The exact aetiology of FISAS is unclear; therefore, instituting preventative measures such as delaying or discontinuing vaccination schedules is questionable. This paper will give insights into the disease process, will attempt to answer the question, "what causes FISAS?", and will discuss preventative measures to decrease the chance of occurrence. Tumours are in general uncommon in the cat, however, malignant tumours, such as sarcomas, occur relatively frequently. FISAS have stimulated interest because of their reported linkage to certain types of vaccine. FISASs are reported to have an incidence of 1-10 per 10,000 cats and often appear in conjunction with a traumatic incident (such as a vaccination). The tumour displays an extreme malignant biological behaviour, both being locally aggressive and metastasising in 25-70% of the cases. Although the pathology still remains unclear, an exaggerated inflammatory/granulomatous response seems to be the predisposing factor in the transformation to FISAS. A multi-step carcinogenesis model, including genetic, iatrogenic and local factors seems to be the most plausible explanation for the occurrence of the tumour. Multi-modal therapy, based on aggressive surgical removal of the tumour in combination with radiation and/or chemotherapy, is usually recommended but randomised clinical studies have not yet been performed to prove the efficacy of any of the modalities. The question of whether FISAS can be prevented by not injecting irritant products remains unanswered. No specific brands of vaccine, manufacturers or factors associated with vaccine administration have been significantly associated with FISAS in a multi-institutional and epidemiological study. Control and evaluation measures as recommended by the US-based taskforce include determination of risk groups, extending re-vaccination intervals, the use of single component products and the use of consistent, predetermined sites for vaccination.


TITLE:
Influenza-related mortality is not prevented with increasing vaccination coverage.

AUTHORS:
Caterina Rizzo, CÃ©cile Viboud, Emanuele Montomoli, Lone Simonsen, Mark A Miller

ABSTRACT:
We investigated trends in influenza-related mortality among the elderly population in Italy associated with increased vaccination coverage. Using Italian vital statistics data, we studied monthly death rates for pneumonia and influenza and all-cause for persons >/=65 years of age by 5-year age groups for 1970-2001. Using a classic seasonal regression modelling approach, we estimated the age-specific seasonal excess mortality rates among Italian elderly as a measure of influenza-related deaths. We studied trends in excess mortality after adjusting for population aging and analyzing separately seasons dominated by the severe A/H3N2 subtype and those dominated by other circulating influenza subtypes. After the late 1980s, no decline in age-adjusted excess mortality was associated with increasing influenza vaccination distribution primarily targeted for the elderly. These findings suggest that either the vaccine failed to protect the elderly against mortality (possibly due to immune senescence), and/or the vaccination efforts did not adequately target the frailest elderly. As in the US, our study challenges current strategies to best protect the elderly against mortality, warranting the need for better controlled trials with alternative vaccination strategies.


TITLE:
Deep morphea after vaccination in two young children has been reported.

AUTHORS:
Antonio Torrelo, JosÃ© Suarez, Isabel Colmenero, Daniel Azorin, Antonio Perera, Antonio Zambrano

ABSTRACT:
A number of dermatoses have been reported to appear in close temporal or spatial relationship to the intramuscular injection of vaccines. We describe two young children who had morphea consistent with the deep morphea type (morphea profunda) that appeared at the site of a previous vaccination. Trauma has been implicated as an important trigger of morphea, both in children and in adults. Furthermore, vaccines might induce an immune response, which could lead to morphea in predisposed individuals.


TITLE:
Vaccination-associated adverse events occur in approximately 1 of every 6 toddlers receiving measles-mumps-rubella vaccine dose 1, with high fever occurring in 1 of 20

AUTHORS:
Charles W LeBaron, Daoling Bi, Bradley J Sullivan, Carol Beck, Paul Gargiullo

ABSTRACT:
In 1989, the American Academy of Pediatrics and the Advisory Committee on Immunization Practices recommended that school children receive 2 doses of measles-mumps-rubella vaccine. With measles and rubella eliminated from the United States, measles-mumps-rubella vaccine adverse events have come under scrutiny, but no study has compared the reactogenicity of the first (measles-mumps-rubella vaccine dose 1) and second (measles-mumps-rubella vaccine dose 2) doses at the most common ages of administration in the United States.


TITLE:
Diphtheria immunisation is weakly associated with an increased risk of asthma by age 7 years.

AUTHORS:
Kazunori Nakajima, Shyamali C Dharmage, John B Carlin, Cathryn L Wharton, Mark A Jenkins, Graham G Giles, Michael J Abramson, E Haydn Walters, John L Hopper

ABSTRACT:
There is ongoing conjecture over whether childhood immunisation leads to an increased risk of developing atopic diseases.


TITLE:
Vaccination is associated with thrombocytopenic purpura in children.

AUTHORS:
J Rajantie, B Zeller, I Treutiger, S Rosthoj,

ABSTRACT:
Patients who presented with purpura and blood platelets <30x10(9)/l within 1 month after vaccination were collected from a population based material of 506 consecutive pediatric patients with newly diagnosed ITP. Of the 35 such patients, 24 had thrombocytopenia after MMR vaccination giving an estimated ITP risk of approximately 1 in 30,000 MMR inoculations. Symptoms of the 35 patients were nearly always acute. Thrombocytopenia disappeared within a month in 74% of the study patients and lasted longer than 6 months in only 10%. Bleeding episodes were uncommon during the follow-up period. We conclude that the incidence of symptomatic thrombocytopenia after vaccinations is much lower than that after respective natural infections and that the outcome in most cases is excellent.


TITLE:
Maternal influenza vaccination during pregnancy does not reduce the incidence of acute respiratory illness visits among infants.

AUTHORS:
Eric K France, Renae Smith-Ray, David McClure, Simon Hambidge, Stanley Xu, Kristi Yamasaki, David Shay, Eric Weintraub, Alicia M Fry, Steven B Black, Henry R Shinefield, John P Mullooly, Lisa A Jackson

ABSTRACT:
To determine whether influenza vaccination of pregnant women prevents visits for respiratory illness in their infants born during the influenza season.


TITLE:
Evidence exists demonstrating that diptheria-tetanus-pertussis (DTP) vaccines increase mortality in children.

AUTHORS:
Peter Aaby, Christine Stabell Benn, Jens Nielsen, Ida Maria Lisse, Amabelia Rodrigues, Henrik Jensen

ABSTRACT:
Observational studies of diphtheria-tetanus-pertussis (DTP) vaccine from longitudinal study sites have reported divergent effects on child survival, ranging from 10-fold reduction to threefold increased mortality. None of these studies had complete information on DTP vaccinations from both survivors and children who died. We reviewed the data analysis methodology to assess whether methodological differences could explain the divergent results.


TITLE:
Hair mercury in breast-fed infants exposed to thimerosal-preserved vaccines indicates significant levels of exposure.

AUTHORS:
Rejane C Marques, JosÃ© G Dorea, Marlon F Fonseca, Wanderley R Bastos, Olaf Malm

ABSTRACT:
Because of uncertainties associated with a possible rise in neuro-developmental deficits among vaccinated children, thimerosal-preserved vaccines have not been used since 2004 in the USA (with the exception of thimerosal-containing influenza vaccines which are routinely recommended for administration to pregnant women and children), and the EU but are widely produced and used in other countries. We investigated the impact of thimerosal on the total Hg in hair of 82 breast-fed infants during the first 6 months of life. The infants received three doses of the hepatitis-B vaccine (at birth, 1 and 6 months) and three DTP (diphtheria, tetanus, and pertussis) doses at 2, 4 and 6 months, according to the immunization schedule recommended by the Ministry of Health of Brazil. The thimerosal in vaccines provided an ethylmercury (EtHg) exposure of 25 microgHg at birth, 30, 60 and 120 days, and 50 microgHg at 180 days. The exposure to vaccine-EtHg represents 80% of that expected from total breast milk-Hg in the first month but only 40% of the expected exposure integrated in the 6 months of breastfeeding. However, the Hg exposure corrected for body weight at the day of immunization was much higher from thimerosal- EtHg (5.7 to 11.3 microgHg/kg b.w.) than from breastfeeding (0.266 microgHg/kg b.w.). While mothers showed a relative decrease (-57%) in total hair-Hg during the 6 months lactation there was substantial increase in the infant's hair-Hg (446%). We speculate that dose and parenteral mode of thimerosal-EtHg exposure modulated the relative increase in hair-Hg of breast-fed infants at 6 months of age.


TITLE:
Injection site reactions occur in 28% of those who receive the anthrax vaccine, with women having twice the incidence of reaction versus men.

AUTHORS:
Michael M McNeil, I-Shan Chiang, John T Wheeling, Yujia Zhang

ABSTRACT:
In the 1960s, the Centers for Disease Control and Prevention (CDC) held the investigational new drug (IND) application for the anthrax vaccine and collected short-term safety data from approximately 16,000 doses administered to almost 7000 individuals. While some recent anthrax vaccine safety studies have suggested that women experience more injection site reactions (ISRs), to our knowledge the IND safety data were not previously examined for a gender-specific difference.


TITLE:
Incidence of adverse reactions to vaccines in pediatric populations are under-reported and may be as high as 43.4% for certain vaccine combinations.

AUTHORS:
Pilar Carrasco-Garrido, Carmen Gallardo-Pino, Rodrigo JimÃ©nez-Garcia, Miguel A Tapias, Angel Gil de Miguel

ABSTRACT:
To detect the appearance and specify the types of adverse reactions to vaccines registered in a paediatric population.


TITLE:
The hepatitis B vaccine may induce autoimmune demyelinating disease through the molecular mimicry that exists between the vaccine antigen, Epstein-Barr virus and human myelin.

ABSTRACT:
Acquired autoimmunity syndromes occur after viral vaccinations. Molecular mimicry is involved in these phenomena as is the necessity for the presence of two chemically complimentary antigens and an immunologic adjuvant. The HLA pattern of the host is also an important factor. The example used to explain these phenomena is demyelinating disease that follows hepatitis B vaccination. The somatic antigen of the hepatitis B virus in the vaccine has chemical complimentarity with the Epstein-Barr virus antigen in the vaccine recipient. The Epstein-Barr virus shows molecular mimicry with human myelin. The immunologic adjuvant is either present in the vaccine or muramyl peptides in the individual who is vaccinated. Why more than one type of autoimmune disease occurs is explained by the fact that specific autoimmune T-cells have been shown to develop clones that attack multiple human tissues.


TITLE:
CRP level in infants is elevated in the 48 hours following immunization.

AUTHORS:
Massroor Pourcyrous, Sheldon B Korones, Kristopher L Arheart, Henrietta S Bada

ABSTRACT:
To determine the incidence of cardiorespiratory events and abnormal C-reactive protein (CRP) level associated with administration of a single vaccine or multiple separate vaccines simultaneously.


TITLE:
Simultaneous sudden infant death syndrome has been reported in twins two days after receiving multiple vaccinations.

AUTHORS:
Yasemin Balci, Mehmet Tok, B Kenan Kocaturk, Cinar Yenilmez, Coskun Yirulmaz

ABSTRACT:
The simultaneous sudden deaths of twins rarely occur and therefore it has received limited attention in the medical literature. When the deaths of the twins meet the defined criteria for sudden infant death syndrome (SIDS) independently and take place within the same 24 h range it can be called as simultaneous SIDS (SSIDS). The case(s): Twin girls (3.5-month-old) were found dead by their mother in their crib, both in supine position. The infants were identical twins and delivered at a hospital by cesarean section. Both infants were healthy and did not have any serious medical history. Two days prior to the incident, the twins had received the second dose of oral polio, DPT and the first dose of hepatitis B vaccines and they had fever on the first day of the vaccination and been given teaspoonful of acetaminophen. Death scene investigation, judicial investigation, parental assessment, macroscopic and microscopic autopsy findings and the toxicological analysis did not yield any specific cause of death. The case(s) were referred to a supreme board composed of multidisciplinary medical professionals at the Institute of Forensic Medicine, Ministry of Justice, in Istanbul. The Board decided that the available data was consistent with SIDS. These SIDS case(s) are presented because twin SIDS are rare and this is the first time that a simultaneous twin SIDS have been reported in Turkey. Simultaneous SIDS cases have many implications regarding definition, diagnosis and medico-legal approach.


TITLE:
HPV vaccination does not have a therapeutic effect in young women with pre-existing human papillomavirus infection.

AUTHORS:
Allan Hildesheim, Rolando Herrero, Sholom Wacholder, Ana Cecilia Rodriguez, Diane Solomon, M Concepcion Bratti, John T Schiller, Paula Gonzalez, Gary Dubin, Carolina Porras, Silvia E Jimenez, Douglas R Lowy

ABSTRACT:
Viruslike particle human papillomavirus (HPV) vaccines were designed to prevent HPV infection and development of cervical precancers and cancer. Women with oncogenic HPV infections might consider vaccination as therapy.


TITLE:
It is hypothesized, in the present review, that Alisa potential factor for induction or maintaining the inflammation in Crohn's disease.

ABSTRACT:
Aluminum (Al) is a common environmental compound with immune-adjuvant activity and granulomatous inflammation inducer. Al exposure in food, additives, air, pharmaceuticals, and water pollution is ubiquitous in Western culture. Crohn's disease (CD) is a chronic relapsing intestinal inflammation in genetically susceptible individuals and is influenced by yet unidentified environmental factors. It is hypothesized, in the present review, that Al is a potential factor for induction or maintaining the inflammation in CD. Epidemiologically, CD incidence is higher in urban areas, where microparticle pollution is prevalent. Al immune activities share many characteristics with the immune pathology of CD: increased antigen presentation and APCs activation, many luminal bacterial or dietary compounds can be adsorbed to the metal and induce Th1 profile activity, promotion of humoral and cellular immune responses, proinflammatory, apoptotic, oxidative activity, and stress-related molecule expression enhancement, affecting intestinal bacterial composition and virulence, granuloma formation, colitis induction in an animal model of CD, and terminal ileum uptake. The Al-bacterial interaction, the microparticles homing the intestine together with the extensive immune activity, put Al as a potential environmental candidate for CD induction and maintenance.


TITLE:
Hepatitis B vaccine associated with dermatomyositis has been reported.

AUTHORS:
Arie Altman, Martine Szyper-Kravitz, Yehuda Shoenfeld

ABSTRACT:
The etiology of dermatomyositis is unknown, but immune mechanisms play an important role. Several dermatological manifestations have been reported among carriers of hepatitis B surface antigen, and after vaccination with the HBV vaccine. Almost all the skin reactions described were peculiar skin eruptions suggestive of an immune complex reaction. Some authors described the occurrence of dermatomyositis after BCG and influenza vaccination. We report a case of a 6-year-old child, who was vaccinated for hepatitis B virus and developed a flu-like disease accompanied by a skin rash, which had the typical features of dermatomyositis. The association of vaccination with autoimmunity is discussed.


TITLE:
A case of extensive ulcerating vasculitis following a BCG vaccination has been reported.

AUTHORS:
A Ghattaura, K A Eley, E Molenaar, G Smith

ABSTRACT:
Adverse reactions following BCG vaccination are uncommon, with an estimated prevalance of 0.4 per 1000 vaccines [Lotte A, Wasz-Hockert O, Poisson N, et al. Second IUATLD study on complications induced by intradermal BCG vaccination. Bull Int Union Tuber 1988;63:47-59]. Complications include erythema, blistering, abscess formation, regional lymphadenitis and keloid formation. The onset of cutaneous tuberculosis (TB) has also been reported. We describe the case of 12-year-old girl who developed extensive primary ulceration involving most of her left upper arm at the site of a BCG vaccination. A skin graft to the arm failed to take at the periphery and the ulcerated area increased to involve most of the upper lateral arm. Over a period of 18 months, secondary lesions developed on her forehead prompting further investigation of a systemic disease process. Following extensive immunological and microbiological examination, a diagnosis of vaccine-induced granulomatous vasculitis was made and the patient responded to a combination of antituberculous therapy and steroids. Once the disease process was under control, skin grafting of the ulcerated area was successful in achieving wound closure. Non-healing ulceration may be referred to the plastic surgeon and a diagnosis of vasculitis should be considered in difficult cases. A multidisciplinary team approach involving immunologists, dermatologists and plastic surgeons provides the best opportunity for a successful long-term outcome in terms of disease control as well as immediate skin cover.


TITLE:
Delay in diphtheria, pertussis, tetanus vaccination is associated with a reduced risk of childhood asthma.

AUTHORS:
Kara L McDonald, Shamima I Huq, Lisa M Lix, Allan B Becker, Anita L Kozyrskyj

ABSTRACT:
Early childhood immunizations have been viewed as promoters of asthma development by stimulating a T(H)2-type immune response or decreasing microbial pressure, which shifts the balance between T(H)1 and T(H)2 immunity.


TITLE:
An economic analysis of mass smallpox vaccination reveals that cardiovascular adverse events would be sizeable and costly.

AUTHORS:
Ismael R Ortega-Sanchez, Mercedes M Sniadack, Gina T Mootrey

ABSTRACT:
Of >39,000 civilian public health responders vaccinated against smallpox in 2003, 203 reported cardiovascular adverse events (CAEs). An association exists between the US vaccinia strain and myocarditis and/or pericarditis ("myo/pericarditis" [MP]). Other associations are inconclusive. We used surveillance and follow-up survey data of CAE case patients to estimate the resources used during the 2003 smallpox vaccination program and used a probabilistic model to estimate the potential costs of CAEs in a mass vaccination campaign. For every million adult vaccinees, 3001 CAEs (including 351 MP cases) would occur, with >92% in revaccinees. CAEs would require a median of 5934 outpatient visits, 1786 emergency department visits, 533 days in general wards, 132 days in intensive care units, 5484 cardiac enzymes tests, 3504 electrocardiograms, 3049 chemistry tests, 2828 complete blood counts, and 1444 transthoracic echocardiograms, among other procedures. CAEs would reduce productivity (15,969 work days lost) and cost $11 per vaccinee. In a mass vaccination campaign, the care of a sizable number of CAEs would be resource intensive.


TITLE:
Myocarditis and pericarditis have been reported following smallpox vaccination in Europe, Australia and the United States.

AUTHORS:
Juliette Morgan, Martha H Roper, Laurence Sperling, Richard A Schieber, James D Heffelfinger, Christine G Casey, Jacqueline W Miller, Scott Santibanez, Barbara Herwaldt, Paige Hightower, Pedro L Moro, Beth F Hibbs, Nancy H Levine, Louisa E Chapman, John Iskander, J Michael Lane, Melinda Wharton, Gina T Mootrey, David L Swerdlow

ABSTRACT:
Myocarditis was reported after smallpox vaccination in Europe and Australia, but no association had been reported with the US vaccine. We conducted surveillance to describe and determine the frequency of myocarditis and/or pericarditis (myo/pericarditis) among civilians vaccinated during the US smallpox vaccination program between January and October 2003. We developed surveillance case definitions for myocarditis, pericarditis, and dilated cardiomyopathy after smallpox vaccination. We identified 21 myo/pericarditis cases among 37,901 vaccinees (5.5 per 10,000); 18 (86%) were revacinees, 14 (67%) were women, and the median age was 48 years (range, 25-70 years). The median time from vaccination to onset of symptoms was 11 days (range, 2-42 days). Myo/pericarditis severity was mild, with no fatalities, although 9 patients (43%) were hospitalized. Three additional vaccinees were found to have dilated cardiomyopathy, recognized within 3 months after vaccination. We describe an association between smallpox vaccination, using the US vaccinia strain, and myo/pericarditis among civilians.


TITLE:
Measles-mumps-rubella vaccine that is given in the second year of life is associated with an increased risk of immune thrombocytopenia purpura.

AUTHORS:
Eric K France, Jason Glanz, Stanley Xu, Simon Hambidge, Kristi Yamasaki, Steven B Black, Michael Marcy, John P Mullooly, Lisa A Jackson, James Nordin, Edward A Belongia, K Hohman, Robert T Chen, Robert Davis

ABSTRACT:
The measles-mumps-rubella vaccine has been associated with immune thrombocytopenia purpura in 2 small studies.


TITLE:
The oral polio vaccine is unlikely to be able to eradicate polio from India.

ABSTRACT:
Polio eradication programme was launched in India in 1995, and polio eradication was expected to occur by 2000. Remarkable decline in polio incidence occurred, but, polio was not eradicated. Majority of polio cases are occurring in two states viz., Uttar Pradesh and Bihar. It is also being observed that majority of polio cases had received many doses of polio vaccine. In 2005 monovalent OPV1 (mOPV1) and monovalent OPV3 (mOPV3) were also introduced in Uttar Pradesh and Bihar, but, number of polio cases increased 10-fold in 2006. In 2007 number of vaccination rounds were increased to one round every month, but in 2007 number of polio cases increased further. In 2005 there were 66 polio cases whereas in 2006 and 2007 number of polio cases increased to 676 and 863, respectively. Some genetic factors in children from Uttar Pradesh and Bihar appear to be responsible for poor antibody generation by OPV. Some mutations in polio viruses may be responsible for development of resistance to antibodies generated by OPV and a reason for the recent steep rise in polio incidence since 2006. Because of these two factors, OPV cannot eradicate polio from India.


TITLE:
The number of elective abortions following vaccination during pregnancy may be under-reported and could be substantial.

ABSTRACT:
Generally, live-virus vaccines are contraindicated for pregnant women because of the theoretical risk of transmission of the vaccine virus to the fetus. Advisory groups recommend avoiding pregnancy in the immediate period after administration of such contraindicated vaccines (CVs) and stress benefit-to-risk evaluation for live or inactivated vaccines regarding pregnancy. Given the limited available data and theoretical risks associated particularly with live-virus vaccines, inadvertent immunization with CVs may lead to elective termination of pregnancy (ETP), despite advisory group statements that "vaccination is not ordinarily an indication to terminate the pregnancy." The Vaccine Adverse Event Reporting System (VAERS), a national passive surveillance system managed by the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC), accepts reports of adverse events after vaccination. The objectives of this review were to describe reports of ETP in VAERS and characterize the circumstances of inadvertent administration of vaccines to pregnant women among ETP reports. We reviewed VAERS reports of ETP submitted from 1990 to 2006. Reports of ETP for reasons other than vaccination during or shortly before pregnancy, such as fetal abnormalities or deaths, were excluded. Of 80 ETP reports, 62 (78%) originated from the US; 79 (99%) were reported by manufacturers. Median age of vaccinees was 26 years (range: 13-43 years; 67 reports). Seventy-three vaccinees (91%) received a single vaccine; 65 (81%) received at least one live-virus vaccine. In 48 (60%) ETP reports, vaccinees were unaware of pregnancy at time of immunization. In 15 (19%) reports, vaccinees became pregnant within 3 months of vaccination; in 13 (16%) reports, vaccinees might have been pregnant before vaccination; in 4 (5%) reports, information was missing. All 80 reports of ETP involved vaccines for which possible effects on fetal development are unknown. However, no cases of vaccine-associated congenital rubella or varicella syndromes have been reported in the medical literature. Also, these syndromes have not been reported to varicella or rubella vaccine pregnancy registries. VAERS has the limitations of passive surveillance systems. Under-reporting of ETP in VAERS could be substantial. More attention may be needed to assess the likelihood of pregnancy when administering vaccines to women with child-bearing potential, and to inform women who learn they are pregnant shortly after being immunized of current information on risks. Quantifying the frequency of ETP related to CVs and the risk (if any) to the fetus of such vaccines can help to inform policy, practice, and individual decision making. Good quality information may be obtained from controlled observational studies.


TITLE:
Approximately 1 in every 5 children who receives 1 dose of varicella vaccine may develop varicella disease, also known as breakthrough disease, if exposed to varicella-zoster virus.

AUTHORS:
Sujit lyer, Manoj K Mittal, Richard L Hodinka

ABSTRACT:
Approximately 1 in every 5 children who receives 1 dose of varicella vaccine may develop varicella disease, also known as breakthrough disease, if exposed to varicella-zoster virus. Currently, in communities with high vaccination coverage, varicella cases mostly occur in vaccinated individuals. We report on the first population-based description of the clinical and epidemiological characteristics of varicella in populations with increasing vaccine coverage between 1997 and 2005. In vaccinated children 1-14 years of age, varicella was most often mild and modified; the atypical disease presentation may result in diagnostic challenges to health care providers. However, despite the generally mild nature of these cases, approximately 25% caused >50 lesions, and some resulted in serious complications similar to those occurring in unvaccinated individuals. Continued surveillance of the risk and characteristics of breakthrough disease will be needed, to monitor the effect of the new 2-dose vaccine recommendation for children.


TITLE:
Between 1995 and 2005 25,306 adverse events were reported from varicella vaccine.

AUTHORS:
Sandra S Chaves, Penina Haber, Kimp Walton, Robert P Wise, Hector S Izurieta, D Scott Schmid, Jane F Seward

ABSTRACT:
Widespread use of varicella vaccine in the United States could enable detection of rare adverse events not identified previously. We reviewed data from 1995 to 2005 from the Vaccine Adverse Event Reporting System, including data from laboratory analyses, to distinguish adverse events associated with wild-type varicella-zoster virus (VZV) versus those associated with vaccine strain. Almost 48 million doses of varicella vaccine were distributed between 1995 and 2005. There were 25,306 adverse events reported (52.7/100,000 doses distributed); 5.0% were classified as serious (2.6/100,000 doses distributed). Adverse events associated with evidence of vaccine-strain VZV included meningitis in patients with concurrent herpes zoster. Patients with genetic predispositions may rarely have disease triggered by receipt of varicella vaccine. Overall, serious adverse events reported after varicella vaccination continue to be rare and must be considered relative to the substantial benefits of varicella vaccination. Ongoing safety surveillance and further studies may shed light on some of the hypothesized associations.


TITLE:
Inactivated flu vaccines have not been proven to be effective or safe in preventing influenza in healthy children under two.

AUTHORS:
Tom Jefferson, Alessandro Rivetti, Anthony Harnden, Carlo Di Pietrantonj, Vittorio Demicheli

ABSTRACT:
The consequences of influenza in children and adults are mainly absenteeism from school and work. However, the risk of complications is greatest in children and people over 65 years old.


TITLE:
Swine and influenza vaccines induce anti-ganglioside antibodies associated with autoimmune neuropathies such as Guillain-Barre syndrome.

AUTHORS:
Irving Nachamkin, Sean V Shadomy, Anthony P Moran, Nancy Cox, Collette Fitzgerald, Huong Ung, Adrian T Corcoran, John K Iskander, Lawrence B Schonberger, Robert T Chen

ABSTRACT:
Receipt of an A/NJ/1976/H1N1 "swine flu" vaccine in 1976, unlike receipt of influenza vaccines used in subsequent years, was strongly associated with the development of the neurologic disorder Guillain-Barré syndrome (GBS). Anti-ganglioside antibodies (e.g., anti-GM(1)) are associated with the development of GBS, and we hypothesized that the swine flu vaccine contained contaminating moieties (such as Campylobacter jejuni antigens that mimic human gangliosides or other vaccine components) that elicited an anti-GM(1) antibody response in susceptible recipients.


TITLE:
A case of sudden infant death associated with hexavalent immunization has been reported.

AUTHORS:
Stefano D'Errico, Margherita Neri, Irene Riezzo, Giuseppina Rossi, Cristoforo Pomara, Emanuela Turillazzi, Vittorio Fineschi

ABSTRACT:
The association between sudden infant death syndrome and immunization is frequently discussed. Serious adverse events following vaccination have generally been defined as those adverse events that result in permanent disability, hospitalization or prolongation of hospitalization, life threatening illness, congenital anomaly or death. They are generally referred to the inherent properties of the vaccine (vaccine reaction) or some error in the immunization process (programme error). The event could also be totally unrelated but only temporally linked to immunization (coincidental event). A fatal case of a 3-month-old female infant, who died within 24 h of vaccination with hexavalent vaccine is presented. Clinical data, post-mortem findings (acute pulmonary oedema, acute pulmonary emphysema), quali-quantitative data collected from immunohistochemical staining (degranulating mast cells) and laboratory analysis with a high level of beta-tryptase in serum, 43.3 microg/l, allows us to conclude that acute respiratory failure likely due to post hexavalent immunization-related shock was the cause of death.


TITLE:
A case of lethal status epilepticus and lymphocytic pneumonitis has been reported.

AUTHORS:
JozÃ©lio Freire de Carvalho, Yehuda Shoenfeld

ABSTRACT:
The case reported refers to a patient who developed status epilepticus in the day of her third dose of hepatitis B vaccination and we review the literature on this subject. A 12 year-old girl, without a relevant previous history, taking no drugs, developed a seizure attack followed by unconsciousness, and eventually died after three days of her third dose of hepatitis B (HB) vaccination. Autopsy study revealed cerebral edema with congestion and herniation and diffuse interstitial type pneumonitis. There seem to be a straight forward time relationship between the third HB vaccine, the event of convulsion and the sudden death of the patient. We suggest that, in some cases, vaccination may be the triggering factor for autoimmune and neurological disturbances in genetically predisposed individuals and physicians should be aware of this possible association.


TITLE:
Influenza vaccines may induce hepatitis-B virus-related vasculitis and severe neuropathy.

AUTHORS:
Yuko Wada, Chie Yanagihara, Yo Nishimura, Nobuyuki Oka

ABSTRACT:
We report the case of a 68-year-old man who developed hepatitis B virus (HBV)-related vasculitis, manifesting as mononeuritis multiplex, 8 days after influenza vaccination. The patient was a carrier of wild-type HBV, and had never received influenza vaccination. Histologic examination of the left sural nerve revealed necrotising vasculitis predominantly involving small blood vessels. HbsAg deposits were observed at a high density around the epineurial blood vessels of the sural nerve. He was treated with prednisone and Lamivudine. His condition improved gradually. However, seroconversion of HBs and HBe Ag was not detected. At the last follow-up 2 years later, his vascilitis did not recur. On the basis of the time of onset of vasculitis, the presumptive immune-mediated pathology of this disorder suggests a possible etiologic link with influenza vaccine. To our knowledge, our case is the first to show vasculitis of peripheral nerves proven pathologically after influenza vaccination.


TITLE:
Vacccination for DPT, Hepatitis B and influenza has been reported to be associated with the development of erythema multiforme in an infant.

ABSTRACT:
Erythema multiforme is a cutaneous reaction pattern precipitated by varied agents, notably herpes simplex and drugs. It predominantly occurs in adolescents and young adults but may be seen at other ages also. While vaccination is rarely a precipitating factor for erythema multiforme, it may occasionally be seen in infants and children. We report here a case of a two month-old infant with lesions of erythema multiforme minor appearing after two weeks following vaccination for DPT, Hepatitis B and influenza.


TITLE:
Influenza vaccination may increase the risk of Guillain-Barre Syndrome.

AUTHORS:
C I Blanco-Marchite, L Buznego-Suarez, M A Fagundez-Vargas, M MÃ©ndez-Llatas, P Pozo-Martos

ABSTRACT:
Miller Fisher Syndrome (MFS) is the most frequent variant of the Guillain-Barré Syndrome. It is characterised by the classic triad of ophthalmoplegia, ataxia and areflexia. We present a case of a patient who developed these clinical findings 5 days after flu vaccination.


TITLE:
Birth defects are more common in pregnant women who received the anthrax vaccine during their first trimester versus later in pregnancy.

AUTHORS:
Margaret A K Ryan, Tyler C Smith, Carter J Sevick, William K Honner, Rosha A Loach, Cynthia A Moore, J David Erickson

ABSTRACT:
In response to bioterrorism threats, anthrax vaccine has been used by the US military and considered for civilian use. Concerns exist about the potential for adverse reproductive health effects among vaccine recipients. This retrospective cohort evaluated birth defects, in relation to maternal anthrax vaccination, among all infants born to US military service women between 1998 and 2004. Department of Defense databases defined maternal vaccination and infant diagnoses; multivariable regression models described potential associations between anthrax vaccination and birth defects in liveborn infants. Among 115,169 infants born to military women during this period, 37,140 were born to women ever vaccinated against anthrax, and 3,465 were born to women vaccinated in the first trimester of pregnancy. Birth defects were slightly more common in first trimester-exposed infants (odds ratio = 1.18, 95% confidence interval: 0.997, 1.41) when compared with infants of women vaccinated outside of the first trimester, but this association was statistically significant only when alternative referent groups were used. Although the small observed association may be unlikely to represent a causal relation between vaccination in early pregnancy and birth defects, this information should be considered when making decisions about administering anthrax vaccine to pregnant women.


TITLE:
Chronic fatigue syndrome may be associated with silicone implants and/or vaccinations.

ABSTRACT:
Chronic fatigue syndrome (CFS) that defines by prolonged fatigue and other manifestations, was recently integrated into a spectrum of central sensitivity syndromes including several diseases as fibromylagia. CFS etiology is multi-factorial commonly triggered by infectious agents. Vaccines, induce an immune response similarly to infections, and may trigger just like infections autoimmune diseases, CFS and fibromyalgia. Furthermore vaccines contain an adjuvant which enhances their immune stimulation.


TITLE:
Influenza vaccination does not prevent ischemic stroke and it does not reduce the rate of acute previous infections in stroke patients.

AUTHORS:
G Pifol-Ripoll, I de la Puerta, S Santos, F Purroy, E Mostacero

ABSTRACT:
Acute and chronic infections may play a role in promoting complications of atherosclerotic disease. We evaluated the importance of acute infections and chronic bronchitis (CB; as a chronic inflammatory state) in several subtypes of ischemic stroke, and we investigated whether the influenza vaccination was independently associated with a reduced likelihood of stroke.


TITLE:
A gender-selective toxicity of thimerosal was observed; this finding is relevant to autism spectrum diagnosis prevalence among males and females.

ABSTRACT:
A recent report shows a correlation of the historical use of thimerosal in therapeutic immunizations with the subsequent development of autism; however, this association remains controversial. Autism occurs approximately four times more frequently in males compared to females; thus, studies of thimerosal toxicity should take into consideration gender-selective effects. The present study was originally undertaken to determine the maximum tolerated dose (MTD) of thimersosal in male and female CD1 mice. However, during the limited MTD studies, it became apparent that thimerosal has a differential MTD that depends on whether the mouse is male or female. At doses of 38.4-76.8mg/kg using 10% DMSO as diluent, seven of seven male mice compared to zero of seven female mice tested succumbed to thimerosal. Although the thimerosal levels used were very high, as we were originally only trying to determine MTD, it was completely unexpected to observe a difference of the MTD between male and female mice. Thus, our studies, although not directly addressing the controversy surrounding thimerosal and autism, and still preliminary due to small numbers of mice examined, provide, nevertheless, the first report of gender-selective toxicity of thimerosal and indicate that any future studies of thimerosal toxicity should take into consideration gender-specific differences.


TITLE:
Human Papilloma Virus (HPV) vaccine is associated with demyelinating events.

AUTHORS:
I Sutton, R Lahoria, Il Tan, P Clouston, Mh Barnett

ABSTRACT:
Vaccination is generally considered safe in patients with multiple sclerosis (MS). We report five patients who presented with multifocal or atypical demyelinating syndromes within 21 days of immunization with the quadrivalent human papilloma virus (HPV) vaccine, Gardasil. Although the target population for vaccination, young females, has an inherently high risk for MS, the temporal association with demyelinating events in these cases may be explained by the potent immuno-stimulatory properties of HPV virus-like particles which comprise the vaccine. A prospective case-control study of patients with MS or clinically isolated demyelinating syndromes receiving the Gardasil vaccine may provide relevant safety data in this population.


TITLE:
Varicella vaccine has been reported to cause herpes zoster skin lesions and meningitis in a previously healthy boy.

AUTHORS:
Myron J Levin, Roberta L DeBiasi, Vanda Bostik, D Scott Schmid

ABSTRACT:
A previously healthy boy who had received varicella vaccine developed herpes zoster with meningitis. The vaccine strain recovered from scabs of 3 skin lesions had the wild-type allele at position 108111, a vaccine marker never previously associated with vaccine-associated adverse events. The vaccine strain from cerebrospinal fluid also contained mutations never previously observed at vaccine-associated single nucleotide polymorphisms that would alter amino acid sequences in ORF54 and ORF59. The presence of distinct strains in skin lesions and cerebrospinal fluid indicate that >1 variant strain may reactivate to cause herpes zoster.


TITLE:
Influenza vaccines were not shown to be effective among children 6 to 59 months of age during 2 influenza seasons.

AUTHORS:
Peter G Szilagyi, Gerry Fairbrother, Marie R Griffin, Richard W Hornung, Stephanie Donauer, Ardythe Morrow, Mekibib Altaye, Yuwei Zhu, Sandra Ambrose, Kathryn M Edwards, Katherine A Poehling, Geraldine Lofthus, Michol Holloway, Lyn Finelli, Marika Iwane, Mary Allen Staat

ABSTRACT:
To measure vaccine effectiveness (VE) in preventing influenza-related health care visits among children aged 6 to 59 months during 2 consecutive influenza seasons.


TITLE:
Hepatitis B vaccination is associated with an increased risk of CNS inflammatory demyelination after 3 years of age.

AUTHORS:
Yann Mikaeloff, Guillaume Caridade, Samy Suissa, Marc Tardieu

ABSTRACT:
The risk of CNS inflammatory demyelination associated with hepatitis B (HB) vaccine is debated, with studies reporting conflicting findings.


TITLE:
There has been a five-fold increase in pediatric parapneumonic empyema since introduction of pneumococcal conjugate vaccine.

AUTHORS:
Debra J Hendrickson, Dean A Blumberg, Jesse P Joad, Sanjay Jhawar, Ruth J McDonald

ABSTRACT:
A retrospective review of medical records for all pediatric parapneumonic empyema (PPE) patients admitted to our hospital from 1996 to 2006 revealed that PPE increased 5-fold in the post-heptavalent pneumococcal conjugate vaccine (PCV7) period (2001-2005) relative to the pre-PCV7 period (1996-2000), from 13 cases to 65. Most of this increase was associated with culture-negative empyema, which accounted for 61% of all post-2000 cases; 19% was culture-positive pneumococcal empyema. Our analysis indicates that non-PCV7 serotypes became more prevalent at our institution after introduction of the vaccine.


TITLE:
Vaccine-derived poliovirus infection is estimated to have infected many thousands of people.

AUTHORS:
Alison Wringe, Paul E M Fine, Roland W Sutter, Olen M Kew

ABSTRACT:
Eight outbreaks of paralytic polio attributable to circulating vaccine-derived poliovirus (cVDPV) have highlighted the risks associated with oral poliovirus vaccine (OPV) use in areas of low vaccination coverage and poor hygiene. As the Polio Eradication Initiative enters its final stages, it is important to consider the extent to which these viruses spread under different conditions, so that appropriate strategies can be devised to prevent or respond to future cVDPV outbreaks.


TITLE:
Acute disseminated encephalomyelitis (ADEM) may be caused by vaccination.

AUTHORS:
William Huynh, Dennis J Cordato, Elias Kehdi, Lynette T Masters, Chris Dedousis

ABSTRACT:
Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system that is usually considered a monophasic disease. ADEM forms one of several categories of primary inflammatory demyelinating disorders of the central nervous system including multiple sclerosis, optic neuropathy, acute transverse myelitis, and neuromyelitis optica (Devic's disease). Post-infectious and post-immunisation encephalomyelitis make up about three-quarters of cases, where the timing of a febrile event is associated with the onset of neurological disease. Post-vaccination ADEM has been associated with several vaccines such as rabies, diphtheria-tetanus-polio, smallpox, measles, mumps, rubella, Japanese B encephalitis, pertussis, influenza, hepatitis B, and the Hog vaccine. We review ADEM with particular emphasis on vaccination as the precipitating factor. We performed a literature search using Medline (1976-2007) with search terms including "ADEM", "acute disseminated encephalomyelitis", "encephalomyelitis", "vaccination", and "immunisation". A patient presenting with bilateral optic neuropathies within 3 weeks of "inactivated" influenza vaccination followed by delayed onset of ADEM 3 months post-vaccination is described.


TITLE:
Aluminium-containing adjuvants in vaccines may be causing autoimmune conditions such as chronic fatigue syndrome and the inflammatory myopathy known as macrophagic myofasciitis.

AUTHORS:
Christopher Exley, Louise Swarbrick, Romain Kroum Gherardi, FranÃ§ois-JÃ©rÃ´me Authier

ABSTRACT:
Macrophagic myofasciitis and chronic fatigue syndrome are severely disabling conditions which may be caused by adverse reactions to aluminium-containing adjuvants in vaccines. While a little is known of disease aetiology both conditions are characterised by an aberrant immune response, have a number of prominent symptoms in common and are coincident in many individuals. Herein, we have described a case of vaccine-associated chronic fatigue syndrome and macrophagic myofasciitis in an individual demonstrating aluminium overload. This is the first report linking the latter with either of these two conditions and the possibility is considered that the coincident aluminium overload contributed significantly to the severity of these conditions in this individual. This case has highlighted potential dangers associated with aluminium-containing adjuvants and we have elucidated a possible mechanism whereby vaccination involving aluminium-containing adjuvants could trigger the cascade of immunological events which are associated with autoimmune conditions including chronic fatigue syndrome and macrophagic myofasciitis.


TITLE:
Varicella vaccine has been reported to viral meningitis in an immunocompetent child.

ABSTRACT:
Herpes zoster complicated by meningitis has been mainly reported in immunocompromised patients after reactivation of wild-type varicella-zoster virus. We present one of the first cases of aseptic meningitis after herpes zoster caused by reactivation of vaccine-type varicella-zoster virus in an immunocompetent child. We also highlight the increasing role of both wild-type and vaccine strains of varicella-zoster virus as a cause of viral meningoencephalitis and the use of appropriate laboratory tools to rapidly and accurately identify the virus in order to provide prompt patient care and management.


TITLE:
Autism spectrum disorders are associated with vaccination, heavy metal toxicity and excitotoxicity.

ABSTRACT:
The autism spectrum disorders (ASD) are a group of related neurodevelopmental disorders that have been increasing in incidence since the 1980s. Despite a considerable amount of data being collected from cases, a central mechanism has not been offered. A careful review of ASD cases discloses a number of events that adhere to an immunoexcitotoxic mechanism. This mechanism explains the link between excessive vaccination, use of aluminum and ethylmercury as vaccine adjuvants, food allergies, gut dysbiosis, and abnormal formation of the developing brain. It has now been shown that chronic microglial activation is present in autistic brains from age 5 years to age 44 years. A considerable amount of evidence, both experimental and clinical, indicates that repeated microglial activation can initiate priming of the microglia and that subsequent stimulation can produce an exaggerated microglial response that can be prolonged. It is also known that one phenotypic form of microglia activation can result in an outpouring of neurotoxic levels of the excitotoxins, glutamate and quinolinic acid. Studies have shown that careful control of brain glutamate levels is essential to brain pathway development and that excesses can result in arrest of neural migration, as well as dendritic and synaptic loss. It has also been shown that certain cytokines, such as TNF-alpha, can, via its receptor, interact with glutamate receptors to enhance the neurotoxic reaction. To describe this interaction I have coined the term immunoexcitotoxicity, which is described in this article.


TITLE:
The epidemic of autism may be linked to both vaccinations and mitochondrial diseases.

ABSTRACT:
Autism has been characterized as a behavioral disorder since it was first described by Leo Kanner in 1943. The number of autistic children has increased over the last decade. The incidence of autism was 1 in 10000 before the 1970s and has steadily increased to 1 in 150 in 2008 with a male:female predominance of 4:1. The cause of this epidemic has remained unknown, but several hypotheses have been studied. Many of these suggest an environmental trigger, such as the ethyl mercury contained in the preservative thimerosal, which has been used in vaccines since 1931. Other possible triggers associated with vaccinations are chemical toxins and live viruses. James has published studies suggesting a genetic predisposition in the families of autistic children, exposing them to a deficiency in glutathione and an inability to detoxify heavy metals. Vargas has shown autism to encompass ongoing inflammation in the brains of autistic children. The Hannah Poling vaccine decision was a landmark case. Poling's family was awarded funds for ongoing medical care of an autistic child who was found to have mitochondrial dysfunction exacerbated by vaccines that left her with autistic behavior and seizures. Several studies have emerged supporting the fact that a significant number of autistic children do have mitochondrial dysfunction. The impact that the Poling case will have on the ability of parents of autistic children to gain access to funds to enable them to properly care for their children remains to be seen.


TITLE:
Vaccines and flu shots containing mercury may contribute to severe neurological diseases and/or death in children.

ABSTRACT:
Cadmium, arsenic, lead, and mercury have been linked to autism, attention deficit disorder, mental retardation and death of children. Mercury in thimerosal found in many vaccines and flu shots contributes significantly to these problems. Decomposition of the thimerosal can produce more toxic compounds, either methylethylmercury or diethylmercury, in the body. These compounds have a toxicity level similar to dimethylmercury. Within the human body, a mitochondrial disorder may release the more toxic form of mercury internally. Young children and pregnant women must minimize internal exposure to the vaccines and flu shots containing mercury.


TITLE:
Neonate exposure to thimerosal mercury from hepatitis B vaccines may be a significant problem.

AUTHORS:
JosÃ© G Dorea, Rejane C Marques, Katiane G Brandao

ABSTRACT:
Infant exposure to ethylmercury (EtHg) has not only increased but is starting earlier as a result of the current immunization schedule that uses thimerosal-containing vaccines (TCVs). Although vaccination schedule varies considerably between countries, infants in less-developed countries continue to be exposed to EtHg derived from more affordable TCVs. We studied the exposure of newborns to EtHg from hepatitis B vaccines; hospital records (21,685) were summarized for the years 2001 to 2005 regarding date of birth, vaccination date, and birth weight. Most of the vaccinations occurred in the first 24 hours postdelivery; over the 5 years, there was an increase in vaccinations within hours of birth (same day), from 7.4% (2001) to 87.8% (2005). Nearly 94.6% of infants are now being vaccinated within the first 24 hours. Range of mercury exposure spread from 4.2 to 21.1 microg mercury/kg body weight for those receiving TCVs with the highest thimerosal concentration; these exposure levels are conservative for 2% of children receiving vaccines within 2 to 3 postnatal days, when they are still going through physiological postnatal weight loss. Because of the particular timing (transitioning from in utero to ex utero metabolism) and specific aspects of exposure (i.e., parenteral mode, bypassing gastroenteric barriers) and dose (related to vaccine manufacturer and with variation in birth weight), this study reveals critical issues that can modulate toxicokinetics and toxicodynamics of organomercurials in neonates.


TITLE:
Porcine circovirus type 2 (PCV2) vaccination of pregnant pigs may result in vertical transmission of PCV2 to the offspring.

AUTHORS:
D M Madson, A R Patterson, S Ramamoorthy, N Pal, Xiang-Jin Meng, T Opriessnig

ABSTRACT:
The aims of this study were to determine if porcine circovirus type 2 (PCV2) vaccination of the dam is effective in preventing fetal PCV2 infection and reproductive failure. Twelve pregnant, PCV2-naïve sows were randomly divided into four groups, with three sows in each group. Group 1 sows served as noninoculated, nonvaccinated negative controls, group 2 sows were vaccinated with a commercially available PCV2 vaccine at 28 days of gestation and were not inoculated, group 3 sows were vaccinated at 28 days of gestation and inoculated with PCV2b at 56 days of gestation, and group 4 sows were inoculated with PCV2b but were not vaccinated. Serum samples from all sows were collected weekly throughout the gestation period, and sows were allowed to farrow naturally. At parturition, sow colostrum samples, presuckle serum samples, and tissues from the piglets were collected. Reproductive failure was not observed under the study conditions. PCV2 vaccination induced PCV2-specific immunoglobulin G and serum neutralizing antibodies in sows from groups 2 and 3 and prevented detectable PCV2 viremia in the dams after challenge. In group 3, PCV2 DNA was detected in colostrum samples, fetuses, and live-born pigs; however, microscopic lesions and PCV2-specific antigen were not present in any of the fetuses in this group. The results from this study indicate that vertical transmission of PCV2 can occur in PCV2-vaccinated dams.


TITLE:
The vaccine adjuvant thimerosal induces adverse changes in the cerebellum of mice, lending plausibility to the association between autism and low-dose mercury exposure.

AUTHORS:
Takeshi Minami, Eriko Miyata, Yamato Sakamoto, Hideo Yamazaki, Seiji Ichida

ABSTRACT:
Thimerosal, an ethyl mercury compound, is used worldwide as a vaccine preservative. We previously observed that the mercury concentration in mouse brains did not increase with the clinical dose of thimerosal injection, but the concentration increased in the brain after the injection of thimerosal with lipopolysaccharide, even if a low dose of thimerosal was administered. Thimerosal may penetrate the brain, but is undetectable when a clinical dose of thimerosal is injected; therefore, the induction of metallothionein (MT) messenger RNA (mRNA) and protein was observed in the cerebellum and cerebrum of mice after thimerosal injection, as MT is an inducible protein. MT-1 mRNA was expressed at 6 and 9 h in both the cerebrum and cerebellum, but MT-1 mRNA expression in the cerebellum was three times higher than that in the cerebrum after the injection of 12 microg/kg thimerosal. MT-2 mRNA was not expressed until 24 h in both organs. MT-3 mRNA was expressed in the cerebellum from 6 to 15 h after the injection, but not in the cerebrum until 24 h. MT-1 and MT-3 mRNAs were expressed in the cerebellum in a dose-dependent manner. Furthermore, MT-1 protein was detected from 6 to 72 h in the cerebellum after 12 microg/kg of thimerosal was injected and peaked at 10 h. MT-2 was detected in the cerebellum only at 10 h. In the cerebrum, little MT-1 protein was detected at 10 and 24 h, and there were no peaks of MT-2 protein in the cerebrum. In conclusion, MT-1 and MT-3 mRNAs but not MT-2 mRNA are easily expressed in the cerebellum rather than in the cerebrum by the injection of low-dose thimerosal. It is thought that the cerebellum is a sensitive organ against thimerosal. As a result of the present findings, in combination with the brain pathology observed in patients diagnosed with autism, the present study helps to support the possible biological plausibility for how low-dose exposure to mercury from thimerosal-containing vaccines may be associated with autism.


TITLE:
Varicella vaccine has been associated with viremia and streptococcal toxic shock syndrome.

AUTHORS:
Claire M Italiano, Cheryl S Toi, Simon P Chan, Dominic E Dwyer

ABSTRACT:
A 49-year-old health care worker received varicella vaccine in accordance with current Australian guidelines. She developed streptococcal toxic shock syndrome, complicated by acute atraumatic dislocation of the right wrist secondary to poststreptococcal reactive arthritis - to our knowledge, the first report of spontaneous wrist dislocation as a complication in this condition. Vaccination was accompanied by prolonged viraemia with the varicella vaccine strain - also, we believe, the first report of this in an immunocompetent patient.


TITLE:
Typhoid but not placebo injection produced an inflammatory response indexed by increased circulating interleukin-6 and significant mood reduction at 3 hours.

AUTHORS:
Neil A Harrison, Lena Brydon, Cicely Walker, Marcus A Gray, Andrew Steptoe, Hugo D Critchley

ABSTRACT:
Inflammatory cytokines are implicated in the pathophysiology of depression. In rodents, systemically administered inflammatory cytokines induce depression-like behavior. Similarly in humans, therapeutic interferon-alpha induces clinical depression in a third of patients. Conversely, patients with depression also show elevated pro-inflammatory cytokines.


TITLE:
Smallpox vaccination has been associated with cardiac complications such as myopericarditis.

AUTHORS:
Luis F Mora, Akbar H Khan, Laurence S Sperling

ABSTRACT:
In 2002, the US Federal government initiated a campaign to vaccinate military personnel and members of the civilian population against smallpox to counter a possible bioterrorism attack. More than 1,200,000 military personnel and approximately 40,000 civilians have been vaccinated since that time. The incidence of myopericarditis in these vaccinees has clearly exceeded calculated background rates and has prompted discussion about cardiac inflammation and other potential vaccine-associated cardiac complications such as dilated cardiomyopathy (DCM) and myocardial ischemia. Although it seems reasonable to predict that some cases of smallpox-associated myopericarditis will progress to DCM, only small numbers have been documented so far, and a causal relationship is difficult to ascertain. With regard to myocardial ischemia, both historical and current data do not suggest a causal association with the vaccine. We describe a case report of myopericarditis following smallpox immunization and provide a review of all cardiac complications associated with vaccination.


TITLE:
Pneumococcal conjugate vaccination is associated with higher levels of serious adverse respiratory events and nonrespiratory events in infants 6 weeks to 6 months of age.

AUTHORS:
Marilla G Lucero, Hanna Nohynek, Gail Williams, Veronica Tallo, Eric A F Simoes, Socorro Lupisan, Diozele Sanvictores, Simon Forsyth, Taneli Puumalainen, Juanita Ugpo, Marites Lechago, Margaret de Campo, Erma Abucejo-Ladesma, Lydia Sombrero, Antti Nissinen, Anu Soininen, Petri Ruutu, lan Riley, Helen P Makela

ABSTRACT:
Pneumococcus is a leading cause of childhood pneumonia worldwide. Pneumococcal conjugate vaccines (PCV) have demonstrated efficacy against childhood invasive pneumococcal disease (IPD) and pneumonia in the United States and Africa. No information is available from Asia on the impact of PCV on childhood pneumonia.


TITLE:
Combined MMR and varicella live vaccine is associated with higher rates of febrile convulsion than giving the vaccines separately.

AUTHORS:
Steven J Jacobsen, Bradley K Ackerson, Lina S Sy, Trung N Tran, Tonia L Jones, Janis F Yao, Fagen Xie, T Craig Cheetham, Patricia Saddier

ABSTRACT:
A combined measles, mumps, rubella, varicella live vaccine (MMRV, Merck and Co., Inc., US) was recently licensed in the US. Pre-licensure clinical trial data showed a significant increase in fever in days 5-12 following MMRV vaccination as compared to the vaccines given separately (MMR+V). This post-licensure retrospective cohort study was undertaken to assess the incidence of febrile convulsion following MMRV.


TITLE:
Vaccine-induced, simian immunodeficiency virus-specific CD8+ T cells reduce virus replication but do not protect from simian immunodeficiency virus disease progression.

AUTHORS:
Jessica C Engram, Richard M Dunham, George Makedonas, Thomas H Vanderford, Beth Sumpter, Nichole R Klatt, Sarah J Ratcliffe, Seema Garg, Mirko Paiardini, Monica McQuoid, John D Altman, Silvija I Staprans, Michael R Betts, David A Garber, Mark B Feinberg, Guido Silvestri

ABSTRACT:
Our limited understanding of the interaction between primate lentiviruses and the host immune system complicates the design of an effective HIV/AIDS vaccine. To identify immunological correlates of protection from SIV disease progression, we immunized two groups of five rhesus macaques (RMs) with either modified vaccinia Ankara (MVA) or MVADeltaudg vectors that expressed SIVmac239 Gag and Tat. Both vectors raised a SIV-specific CD8(+) T cell response, with a magnitude that was greater in mucosal tissues than in peripheral blood. After challenge with SIVmac239, all vaccinated RMs showed mucosal and systemic CD8(+) T cell recall responses that appeared faster and were of greater magnitude than those in five unvaccinated control animals. All vaccinated RMs showed a approximately 1-log lower peak and early set-point SIV viral load than the unvaccinated animals, and then, by 8 wk postchallenge, exhibited levels of viremia similar to the controls. We observed a significant direct correlation between the magnitude of postchallenge SIV-specific CD8(+) T cell responses and SIV viral load. However, vaccinated RMs showed no protection from either systemic or mucosal CD4(+) T cell depletion and no improved survival. The observation that vaccine-induced, SIV-specific CD8(+) T cells that partially control SIVmac239 virus replication fail to protect from immunological or clinical progression of SIV infection underscores both the complexity of AIDS pathogenesis and the challenges of properly assessing the efficacy of candidate AIDS vaccines.


TITLE:
Vaccine-induced immunity in pregnant pigs is not effective in preventing viremia in offspring.

ABSTRACT:
The objectives of this study were to determine if vaccination against porcine circovirus type 2 (PCV2) or previous PCV2 infection of the dam are sufficient to prevent fetal infection when dams are artificially inseminated with PCV2-spiked semen. Nine sows (Sus domestica) were allocated into three groups of three dams each: The PCV2 naïve negative control Group 1 was artificially inseminated with extended PCV2 DNA negative semen during estrus, whereas the extended semen used in the vaccinated Group 2 (PCV2 vaccine was given 8 wk before insemination) and PCV2-exposed Group 3 (infected with PCV2 12 wk before insemination) was spiked with 5 mL of PCV2 inoculum with a titer of 10(4.2) tissue culture infectious dose (TCID(50)) per milliliter at each breeding. The dams in the vaccinated and PCV2-exposed groups were positive for PCV2 antibody but negative for PCV2 DNA in serum at the time of insemination. Three negative control dams, two vaccinated dams, and three dams with previous PCV2 exposure became pregnant and maintained pregnancy to term. After artificial insemination, viremia was detected in one of three vaccinated dams and in two of three dams with previous PCV2 exposure. At farrowing, PCV2 infection was not detected in any piglets or fetuses expelled from the negative control dams or from dams with previous PCV2 exposure. In litters of the vaccinated dams, 15 of 24 live-born piglets were PCV2 viremic at birth, with 6 of 26 fetuses having detectable PCV2 antigen in tissues. In conclusion, vaccine-induced immunity did not prevent fetal infection in this sow model using semen spiked with PCV2.


TITLE:
Rift Valley fever vaccine in goats cause severe deleterious pathological changes in liver especially in kids and causing abortion in pregnant does.

ABSTRACT:
RVF live attenuated vaccine (Smithburn strain) was evaluated by using goats as experimental animal. The results indicate that this vaccine cause severe deleterious pathological changes in liver especially in kids and causing abortion in pregnant does. The virus was seen to be propagated inside hepatic cells forming intranuclear inclusions which was also seen by E.M. Viral antigens were detected in hepatic cells, gall bladder, endothelial lining of blood vessels, leukocytes, kidneys and heart by using immunoflourescent technique. It could be concluded that the use of live attenuated vaccine of RVF (Smithburn strain) for immunization of live stock is not safe in Egypt as it considered an endemic area.


TITLE:
Varicella outbreaks occur in vaccinated populations, even when receiving 2 doses.

AUTHORS:
Philip L Gould, Jessica Leung, Connie Scott, D Scott Schmid, Helen Deng, Adriana Lopez, Sandra S Chaves, Meredith Reynolds, Linda Gladden, Rafael Harpaz, Sandra Snow

ABSTRACT:
In June 2006, the Advisory Committee on Immunization Practices (ACIP) expanded its June 2005 recommendation for a second dose of varicella vaccine during outbreaks to a recommendation for routine school entry second dose varicella vaccination. In October 2006, the Arkansas Department of Health was notified of a varicella outbreak among students where some received a second dose during an outbreak-related vaccination campaign in February 2006.


TITLE:
Varicella vaccine may be associated with aplastic anemia in children.

AUTHORS:
Paola Angelini, Fotini Kavadas, Navneet Sharma, Susan E Richardson, Graham Tipples, Chaim Roifman, Yigal Dror, Yehuda Nofech-Mozes

ABSTRACT:
Varicella zoster vaccine is a safe vaccine that is rarely associated with life-threatening complications. We describe an immunocompetent child who developed transient severe aplastic anemia concomitant with a typical clinical and laboratory-proven chickenpox syndrome 3 weeks after immunization. A causative association between the vaccine and the hematologic disease is possible, and pediatricians should be aware of this severe although rare adverse event.


TITLE:
Children vaccinated with MMR before age 10 are at significantly higher risk of multiple sclerosis.

AUTHORS:
Cecilia Ahigren, Kjell TorÃ©n, Anders OdÃ©n, Oluf Andersen

ABSTRACT:
Viral infections are probably involved in the pathogenesis of multiple sclerosis (MS). A recent cohort study in the Gothenburg population revealed no change in MS incidence associated with the introduction of the Swedish measles, mumps and rubella vaccination programmes. The aim of the present study was to clarify whether these infections or vaccinations, and two other infections, varicella and infectious mononucleosis, influence MS risk. We performed a population-based case-control study in Gothenburg that included 509 MS cases and 2,067 controls, born 1959-1986. Data on infections and vaccinations were obtained from questionnaires and from child health and school health records. We found no significant associations between measles, mumps, rubella or varicella and MS risk. These results were consistent between the two source materials. Infectious mononucleosis was associated with significantly higher MS risk (odds ratio 2.03, 95% CI 1.52-2.73). Overall, there was no significant association between measles-mumps-rubella (MMR) vaccination and MS risk, while those MMR vaccinated before age ten only were at significantly higher MS risk (odds ratio 4.92, 95% CI 1.97-12.20). Those MMR vaccinated both before and after age ten had intermediate MS risk. Infection with measles, mumps, rubella and varicella did not influence MS risk in contrast to infectious mononucleosis which conferred doubled MS risk. The association with 'early' MMR vaccination only was an isolated finding, limited by a small number of subjects and multiple testing. Most likely this was a chance finding. Future studies could investigate it on an a priori basis.


TITLE:
Serious adverse events associated with whole cell pertussis vaccine, e.g. sudden infant death syndrome and encephalopathy, may have occurred in metabolically vulnerable children.

AUTHORS:
Kumanan Wilson, Beth Potter, Douglas Manuel, Jennifer Keelan, Pranesh Chakraborty

ABSTRACT:
In the early 1980's concerns about the safety of the whole cell pertussis vaccine in the United States resulted in declining vaccination rates and the withdrawal of multiple vaccine providers from the market. While the possibility of inflammation and febrile reactions to the vaccine were acknowledged by public health authorities, parents also claimed the vaccine was associated with sudden infant death syndrome and encephalopathy. Epidemiological studies examining this question, however, consistently failed to identify an association. We argue that these reactions may have occurred in metabolically vulnerable children, specifically those with defects in fatty acid oxidation. In these children the combination of anorexia and fever that could be caused by the vaccine may have resulted in hypoglycemic episodes and possibly death. We believe that this association was not detected because these conditions were not recognized at the time and because these conditions are uncommon. Nevertheless, at a population level, enough events could have occurred to cause concern amongst parents.


TITLE:
Postlicensure safety survelliance has revealed a disproportionate reporting of syncope and venous thromboembolic events following quadrivalent HPV vaccination.

AUTHORS:
Barbara A Slade, Laura Leidel, Claudia Vellozzi, Emily Jane Woo, Wei Hua, Andrea Sutherland, Hector S Izurieta, Robert Ball, Nancy Miller, M Miles Braun, Lauri E Markowitz, John Iskander

ABSTRACT:
In June 2006, the Food and Drug Administration licensed the quadrivalent human papillomavirus (types 6, 11, 16, and 18) recombinant vaccine (qHPV) in the United States for use in females aged 9 to 26 years; the Advisory Committee on Immunization Practices then recommended qHPV for routine vaccination of girls aged 11 to 12 years.


TITLE:
Hepatitis B vaccination coverage has fallen to beneath 30% in France due to concerns over safety.

ABSTRACT:
In 1998, official concerns were first voiced over a possible association between hepatitis B virus (HBV) vaccination and multiple sclerosis (MS). Despite a number of studies that have demonstrated no such association, ten years on the French population's confidence in the vaccine remains shaken and immunization rates of infants have stagnated beneath 30%. With a chronic carriage of the virus estimated at 0.68%, it seems unlikely that France will be able to control the circulation of the virus. This article analyses attitudes towards HBV vaccination based on recent surveys: not only the public but also the vast majority of "vaccinators" (88%) questions the safety of the vaccine. Physicians opposed to vaccinating infants cite the possibility of adverse events occurring later in life and their lack of trust in the health authorities and the pharmaceutical industry. Both the general public and physicians feel more inclined to vaccinate adolescents and adults, even though it was for these age groups (especially the latter) that neurological adverse events were notified. It appears that above all, the usefulness of the vaccine and its safety profile for young children should be explained in understandable language by all those involved in public health, including the media. However, when opting for public health policies on the basis of statistical estimations, the importance of individual cases (e.g. MS in the family) should not be overlooked both for biological and ethical reasons.


TITLE:
In the US the highest number of cases of Guillain-Barre syndrome are associated with influenza and hepatitis B vaccines.

AUTHORS:
Nizar Souayah, Abu Nasar, M Fareed K Suri, Adnan I Qureshi

ABSTRACT:
There are isolated reports of Guillain-Barré syndrome (GBS) after receiving vaccination.


TITLE:
A case of hypersensitivity reaction, myelodysplastic syndrome and pancytopenia, which developed after an thimerosal-containing tetanus vaccine.

AUTHORS:
Hasan Karsen, Hayrettin Akdeniz, Mustafa H Karahocagil, Ali I Baran, Remzi Erten

ABSTRACT:
A case of hypersensitivity reaction, myelodysplastic syndrome and pancytopenia, which developed after an administration of thimerosal-containing tetanus vaccine, is presented and discussed.


TITLE:
Influenza vaccines may be causing vasculitis.

AUTHORS:
Rainer Birck, Isabelle Kaelsch, Peter Schnuelle, Luis Felipe Flores-Suarez, Rainer Nowack

ABSTRACT:
Whether autoimmune or rheumatic disease may be precipitated after vaccination is controversially discussed among experts. Here we describe 4 cases of new onset or relapsing antineutrophil cytoplasmic antibodies associated vasculitis occurring in timely association with influenza vaccination. In the literature different subtypes of vasculitis have been repeatedly reported after influenza vaccination. Several trials in patients with preexisting auto-immune disease failed to indicate an increased risk for disease recurrence after influenza vaccination but these investigations might be underpowered to detect this very rare but relevant side effect. Although our report does not prove a causal association between vaccination and vasculitis, it seems possible that in rare cases vaccination might induce vasculitic disease.


TITLE:
Long-term persistence of vaccine-derived aluminum hydroxide within the body assessed by MMF is associated with cognitive dysfunction.

AUTHORS:
Maryline Couette, Marie-Francoise Boisse, Patrick Maison, Pierre Brugieres, Pierre Cesaro, Xavier Chevalier, Romain Kroum Gherardi, Anne-Catherine Bachoud-Levi, FranÃ§ois-JÃ©rÃ´me Authier

ABSTRACT:
Macrophagic myofasciitis (MMF) is an emerging condition, characterized by specific muscle lesions assessing long-term persistence of aluminum hydroxide within macrophages at the site of previous immunization. Affected patients mainly complain of arthromyalgias, chronic fatigue, and cognitive difficulties. We designed a comprehensive battery of neuropsychological tests to prospectively delineate MMF-associated cognitive dysfunction (MACD). Compared to control patients with arthritis and chronic pain, MMF patients had pronounced and specific cognitive impairment. MACD mainly affected (i) both visual and verbal memory; (ii) executive functions, including attention, working memory, and planning; and (iii) left ear extinction at dichotic listening test. Cognitive deficits did not correlate with pain, fatigue, depression, or disease duration. Pathophysiological mechanisms underlying MACD remain to be determined. In conclusion, long-term persistence of vaccine-derived aluminum hydroxide within the body assessed by MMF is associated with cognitive dysfunction, not solely due to chronic pain, fatigue and depression.


TITLE:
Autoimmune autistic disorder, a major subset of autism, is associated with autoantibody formation caused by viral (wild and vaccine-induced) infection.

ABSTRACT:
Autism causes incapacitating neurologic problems in children that last a lifetime. The author of this article previously hypothesized that autism may be caused by autoimmunity to the brain, possibly triggered by a viral infection. This article is a summary of laboratory findings to date plus new data in support of an autoimmune pathogenesis for autism.


TITLE:
Vaccination is associated with an increased risk for hemolytic anemia.

AUTHORS:
Allison L Naleway, Edward A Belongia, James G Donahue, Burney A Kieke, Jason M Glanz,

ABSTRACT:
Several case reports have described immune hemolytic anemia (IHA) following vaccination in children. We examined the risk of IHA in the 42 days following vaccination exposure using a self-controlled case series study design. In our population-based cohort of nearly 4.5 million children in the Vaccine Safety Datalink, we identified 55 confirmed cases of new-onset IHA from 1991 through 2000. We found no association between IHA and diphtheria-pertussis-tetanus vaccination (incidence rate ratio (IRR)=0.65, 95% CI: 0.19-2.24), hepatitis B vaccination (IRR=1.73, 95% CI: 0.59-5.01), or any vaccination (IRR=1.04, 95% CI: 0.46-2.32).


TITLE:
The development of human vaccines for anthrax has suffered from a number of technical challenges.

ABSTRACT:
Anthrax is caused by a Gram-positive aerobic spore-forming bacillus called Bacillus anthracis. Although primarily a disease of animals, it can also infect man, sometimes with fatal consequences. As a result of concerns over the illicit use of this organism, considerable effort is focused on the development of therapies capable of conferring protection against anthrax. while effective concerns over the toxicity of the current vaccines have driven the development of second-generation products. Recombinant Protective Antigen (rPA), the nontoxic cell-binding component of anthrax lethal toxin, is the principal immunogen of the vaccines currently undergoing human clinical trials. While these new vaccines are likely to show reduced side effects they will still require multiple needle based dosing and the inclusion of the adjuvant alum which will make them expensive to administer and stockpile. To address these issues, researchers are seeking to develop vaccine formulations capable of stimulating rapid protection following needle-free injection which are stable at room temperature to facilitate stockpiling and mass vaccination programs. Recent concerns over the potential use of molecular biology to engineer vaccine resistant strains has prompted investigators to identify additional vaccine targets with which to extend the spectrum of protection conferred by rPA. While the injection of research dollars has seen a dramatic expansion of the anthrax vaccine field it is sobering to remember that work to develop the current second generation vaccines began around the time of the first gulf war. Almost two decades and millions of dollars later we still do not have a replacement vaccine and even when we do some argue that the spectrum of protection that it confers will not be as broad as the vaccine it replaces. If we are to respond effectively to emerging biological threats we need to develop processes that generate protective vaccines in a meaningful time frame and yield products in months not decades!


TITLE:
Vaccination for rabies, varicella or Lyme disease may result in acute or subacute post-vaccination small fiber neuropathy.

AUTHORS:
Nizar Souayah, Senda Ajroud-Driss, Howard W Sander, Thomas H Brannagan, Arthur P Hays, Russell L Chin

ABSTRACT:
Neuropathy following vaccination has been reported; however, biopsy-confirmed small fiber neuropathy has not been described. We report five patients who developed paresthesias within one day to two months following vaccination for rabies, varicella zoster, or Lyme disease. On examination, there was mild sensory loss in distal extremities, preserved strength, normal or minimally abnormal electrodiagnostic findings, and decreased epidermal nerve fiber densities per skin biopsy. Empiric immunomodulatory therapy was tried in two patients and was ineffective. All patients' symptoms have improved, but persist. We conclude that an acute or subacute, post-vaccination small fiber neuropathy may occur and follow a chronic course.


TITLE:
Rates of intussusception associated with rotavirus vaccines may be significantly underestimated.

AUTHORS:
Margaret M Cortese, Mary Allen Staat, Geoffrey A Weinberg, Kathryn Edwards, Marilyn A Rice, Peter G Szilagyi, Caroline B Hall, Daniel C Payne, Umesh D Parashar

ABSTRACT:
Because a previous rotavirus vaccine was associated with intussusception, new rotavirus vaccines are monitored postlicensure for any such association. Accurate background intussusception rates are needed to determine whether the number of cases observed after vaccination exceeds that expected by chance. Previously, intussusception rates were obtained from inpatient discharge databases. We sought to determine the rate of intussusception among infants managed only with short-stay or emergency department care.


TITLE:
There is currently no evidence from randomised studies that influenza vaccine given to people with CF is of benefit to them.

ABSTRACT:
Viral respiratory tract infections in people with cystic fibrosis (CF) have a deteriorating effect on their lung function and disease progression. Annual influenza vaccination is therefore commonly recommended for people with CF.


TITLE:
The HPV16 vaccine carries with it significant cross-reactivity risk due to the homologies that exist between the HPV and human proteome.

ABSTRACT:
The potential adverse events associated with vaccination for infectious diseases underscore the need for effective analysis and definition of possible vaccine side effects. Using the HPV16 proteome as a model, we quantified the actual and theoretical risks of anti-HPV16 vaccination, and defined the potential disease spectrum derived from concomitant cross-reactions with the human organism.


TITLE:
Vaccination against novel H1N1 may accelerate atherogenesis (heart disease).

AUTHORS:
Sucharit Bhakdi, Karl Lackner, Hans-Wilhelm Doerr

ABSTRACT:
Programs for vaccination against the new influenza A/H1N1 targeting many hundred million citizens in Europe and the USA are to be launched in the fall of this year. The USA is planning to employ a non-adjuvanted vaccine, whereas European nations are opting for inclusion of MF59, the adjuvant contained in an alternative seasonal flu vaccine, or the related adjuvant AS03 that is contained in a recently developed H5N1 vaccine. We draw attention to unappreciated hazards of using adjuvanted vaccine in Europe. Evidence from animal experiments in conjunction with clinical epidemiological data indicates that, quite irrespective of cause, stimulation of the immune system may accelerate atherogenesis. Application of adjuvanted flu vaccines to individuals at risk may therefore aggravate the course of underlying atherosclerotic vessel disease with all the clinical consequences. The same may hold true for other widespread diseases that are propelled by deregulated immune mechanisms. Safety trials conducted to date have not specifically taken these possible side effects into account, and unexpected serious adverse effects thus may follow in the wake of a general vaccination program. A prudent consequence would be to establish careful survey systems alongside with mass application of new adjuvanted vaccines, or to hold mass vaccination in reserve for use only in situations of true need, such as would arise with the emergence of a more virulent new H1N1 virus strain, or to use non-adjuvanted vaccines in individuals who are potentially at risk for adverse side effects.


TITLE:
Systemic lupus erythematosus related to hepatitis B vaccine has been reported.

AUTHORS:
Nancy Agmon-Levin, Yaron Zafrir, Z Paz, T Shilton, Gisele Zandman-Goddard, Yehuda Shoenfeld

ABSTRACT:
The objective of this article is to identify common and atypical features of systemic lupus erythematosus diagnosed following hepatitis B vaccination. We analyzed retrospectively the medical records of 10 systemic lupus erythematosus patients from different centers, who developed the disease following hepatitis B vaccination and determined the prevalence of different manifestations and the time association to vaccination. In this case series, 80% of the patients were female, mean age 35 +/- 9 years, of which 20% received one inoculation, 20% received two doses and 60% received all three inoculations. The mean latency period from the first hepatitis B virus immunization and onset of autoimmune symptoms was 56.3 days. All patients were diagnosed with systemic lupus erythematosus, according to the American College of Rheumatology revised criteria within 1 year. The prevalence of some systemic lupus erythematosus manifestations was typical and included involvement of the joints (100%), skin (80%), muscles (60%) and photosensitivity (30%). Other symptoms differed in this unique group of systemic lupus erythematosus patients such as low rate of kidney and hematologic involvement, and a relatively high rate of hepatitis (20%). Neurological (80%) and pulmonary (70%) symptoms were also common in this group. Data from this case-series, and previously documented cases in the literature could only show a temporal relation between hepatitis B vaccination and the appearance of systemic lupus erythematosus. Systemic lupus erythematosus related to vaccine may differ from idiopathic systemic lupus erythematosus in its clinical presentation and may resemble drug-induced systemic lupus erythematosus. Thus, physicians should be alerted to this potential association, its possible long latency period and unique presentations, and be encouraged to report and analyze these cases.


TITLE:
Vaccination is associated with a rare autoimmune neurological condition transverse myelitis.

AUTHORS:
Nancy Agmon-Levin, Shaye Kivity, Martine Szyper-Kravitz, Yehuda Shoenfeld

ABSTRACT:
Transverse myelitis is a rare clinical syndrome in which an immune-mediated process causes neural injury to the spinal cord. The pathogenesis of transverse myelitis is mostly of an autoimmune nature, triggered by various environmental factors, including vaccination. Our aim here was to search for and analyze reported cases of transverse myelitis following vaccination. A systematic review of PubMed, EMBASE and DynaMed for all English-language journals published between 1970 and 2009 was preformed, utilizing the key words transverse myelitis, myelitis, vaccines, post-vaccination, vaccination and autoimmunity. We have disclosed 37 reported cases of transverse myelitis associated with different vaccines including those against hepatitis B virus, measles-mumps-rubella, diphtheria-tetanus-pertussis and others, given to infants, children and adults. In most of these reported cases the temporal association was between several days and 3 months, although a longer time frame of up to several years was also suggested. Although vaccines harbor a major contribution to public health in the modern era, in rare cases they may be associated with autoimmune phenomena such as transverse myelitis. The associations of different vaccines with a single autoimmune phenomenon allude to the idea that a common denominator of these vaccines, such as an adjuvant, might trigger this syndrome.


TITLE:
Erythema multiforme has been reported as a possible side effect of vaccination for human papillomavirus.

AUTHORS:
A C Katoulis, A Liakou, E Bozi, M Theodorakis, A Alevizou, A Zafeiraki, M Mistidou, N G Stavrianeas

ABSTRACT:
Erythema multiforme (EM) is an acute self-limited immune-mediated reaction manifested by target skin lesions with mucous membrane involvement. The most common causes are infections and drugs. Vaccinations have been reported as a triggering factor, and they may be a frequent cause of EM in childhood. A 19-year-old female developed several target lesions of the hands and feet 10 days after the second dose of human papillomavirus (HPV) vaccine. Clinico-histologically, a diagnosis of EM minor was made. Treatment with topical corticosteroids and oral antihistamines resulted in complete clearance of the rash. Four months later, she received the last booster dose of the vaccine. A few subtle lesions appeared and disappeared spontaneously after a few days. Gardasil is a non-infectious vaccine, developed for the prevention of cervical cancer, precancerous genital lesions and genital warts. It delivers the major capsid (L1) protein of HPV types 6, 11, 16 and 18. Mild local reactions are the main adverse events. The only serious events are very rare cases of anaphylaxis. In our patient, the temporal relationship between the development of EM and the vaccination suggests that the HPV vaccine probably was the causal agent. This is the first published case of EM following HPV vaccination.


TITLE:
Bell's palsy is a possible complication of hepatitis B vaccination in children.

ABSTRACT:
Bell's Palsy is the sudden onset of unilateral temporary paralysis of facial muscles resulting from seventh cranial nerve dysfunction. Presented here is a two-year old female patient with right peripheral facial palsy following hepatitis B vaccination. Readers' attention is drawn to an uncommon cause of Bell's Palsy, as a rare complication of hepatitis B vaccination.


TITLE:
Rabies vaccine may be ineffective during symptomatic rabies and may contribute to "early death."

ABSTRACT:
Administration of rabies vaccine or rabies immune globulin (RIG) during symptomatic rabies is ineffective, and there are concerns about the phenomenon of "early death" reported in animals that develop rabies after receipt of rabies vaccine or immune globulin. Survival analyses of the original animal data confirm these findings in two species, whereas analyses of human case reports and the Milwaukee Protocol registry suggest lower risk of "early death" in humans. There may be a deleterious interaction of rabies vaccine and RIG with bat rabies in humans. Animal studies of bat rabies virus with bat-origin vaccines and RIG are urgently needed.


TITLE:
Hepatitis B vaccine may have a possible association with the development of uveitis in some patients.

AUTHORS:
Frederick W Fraunfelder, Eric B Suhler, Frederick T Fraunfelder

ABSTRACT:
To report a possible association between hepatitis B vaccine and uveitis.


TITLE:
Optic neuritis following hepatitis B vaccination has been reported.

AUTHORS:
Muferet Erguven, Sirin Guven, Umit Akyuz, Olcay Bilgic, Fuat Laloglu

ABSTRACT:
Hepatitis B vaccination can prevent hepatitis B virus infection and its serious consequences, including liver cancer and cirrhosis. Serious side effects reported after receiving hepatitis B vaccination are very uncommon. A majority of the ophthalmological complications seen following hepatitis B vaccination consist of vision loss, optic neuritis, papillary edema, uveitis, acute placoid pigment epitheliopathy and central vein occlusion. We present a 9-year-old girl who was referred to our hospital with decrease in vision and pain in the left eye a week after hepatitis B vaccination. A diagnosis of vaccine-induced optic neuritis was made. The clinical picture improved after systemic corticosteroid treatment. Acute optic neuritis might be a rare complication of hepatitis B vaccination. Parents should be aware of the potential serious side effects of the vaccine.


TITLE:
MMR vaccination is associated with an increased risk of developing acute immune thrombocytopenia in childhood.

AUTHORS:
Federica Bertuola, Carla Morando, Francesca Menniti-Ippolito, Roberto Da Cas, Annalisa Capuano, Giorgio Perilongo, Liviana Da Dalt

ABSTRACT:
Immune thrombocytopenic purpura (ITP) is an immunomediated disease characterized by a decrease in platelet count and, in its more severe forms, by bleeding symptoms. Many drugs have been implicated in the pathogenesis of drug-induced thrombocytopenia in adults; only limited data on drug-related ITP in children have been published. Our study was set up to evaluate the consistency of the association between drug and vaccine use and ITP in children. This study is part of an Italian multicentre study on adverse drug reactions in children, coordinated by the Italian National Institute of Health, which was started in November 1999 and is ongoing. The study was conducted by enrolling all children aged more than 1 month who were hospitalized through the paediatric emergency department for the following conditions: thrombocytopenia (platelet count <100 x 103/L); acute neurological disorders; non-infectious mucocutaneous diseases and vasculitis; and endoscopically confirmed gastroduodenal lesions and/or clinically defined haematemesis and melaena. Children with chronic pathologies or concomitant diagnoses of cancer or immunodeficiency were not included in our study. During hospital admission, a physician interviewed parents using a structured questionnaire. The main aim of the interview was to collect information on drug exposure in a time period of 3 weeks and vaccine exposure in a period of 6 weeks preceding hospitalization. Using a case-control study design, exposure of children with thrombocytopenia (cases) to drugs and vaccines was compared with similar exposure of children with gastroduodenal lesions and neurological disorders (controls); this allowed us to estimate the odds ratios (ORs) of the occurrence of thrombocytopenia associated with the use of drugs or vaccines. Up to December 2007, the study population included 387 cases of thrombocytopenia and 1924 controls. Despite the low platelet count, ITP was generally a mild disease, without serious bleeding in the majority of cases and associated with a short length of hospital stay. After adjusting for concurrent use of other drugs, use of the antibacterials was associated with a more than 2-fold increase in the risk of developing ITP (OR 2.4; 95% CI 1.8, 3.1). Mucolytics and NSAIDs were associated with an OR of 1.9; 95% CI 1.2, 2.9 and 1.5; 95% CI 1.0, 2.1 respectively, while paracetamol (acetaminophen) was associated with an OR of 1.5; 95% CI 1.2, 2.0. MMR vaccination was associated with an increased risk of developing ITP (OR 2.4; 95% CI 1.2, 4.7). The results of this study provide evidence for an association between ITP and exposure to selected antibacterials, NSAIDs, paracetamol, mucolytics and MMR vaccination.


TITLE:
Hepatitis B vaccination has been linked to anaphylactic shock and death in infants.

ABSTRACT:
To evaluate the safety of Hepatitis B vaccine by analyzing the 10 infants death after Hepatitis B vaccination.


TITLE:
Acute necrotizing encephalopathy secondary to diphtheria, tetanus toxoid and whole-cell pertussis vaccination has been reported.

AUTHORS:
Hale Aydin, Esra Ozgul, Anmet Muhtesem Agildere

ABSTRACT:
We present a previously healthy 6-month-old boy who was admitted to our hospital with lethargy, hypotonia and focal clonic seizures 6 days following diptheria, tetanus toxoid and whole-cell pertussis vaccination. A diagnosis of acute necrotising encephalopathy was made with the aid of MRI, including diffusion-weighted imaging and proton MR spectroscopy.


TITLE:
Anthrax vaccine development suffers from a wide range of potentially insurmountable problems.

AUTHORS:
Dorota Zakowska, Janusz Kocik, Michat Bartoszcze

ABSTRACT:
The threat of bioterrorism with B. anthracis against civilian population is one of major concern. After successful bioterroristic attack in 2001 in US renewed research interest has prompted in the development of new and more effective vaccine against anthrax. There are two licensed vaccines against anthrax--AVA-Bio-Thrax US and UK--sterile culture filtrate prepared by alum precipitation. Both vaccines are based on PA antigen. There are several concerns regarding PA based vaccines. They require six sc injections and yearly booster, high rates of local reaction after vaccination is observed, the immunity is not long lasting, vaccination do not protect animals against different strains of B. anthracis. New strategies in the development of anthrax vaccines have been presented (recombinant PA, subunits vaccine, mutants, conjugated). Using proteomic approaches new antigens have been also identified as candidates for future vaccines. More effective and easy to perform methods of vaccination have been reviewed.


TITLE:
Immunization of mothers with pneumococcal capsular polysaccharide vaccine during pregnancy is ineffective for infants.

AUTHORS:
Claudia R C Lopes, Eitan N Berezin, Ting Hui Ching, Jaildo de Souza Canuto, Vanilda Oliveira da Costa, Erika Monteiro Klering

ABSTRACT:
Pneumococcal (Pnc) carriage is associated with pneumococcal diseases. Breast feeding and maternal vaccination may be a useful approach to prevent pneumococcal infection in young infants. We examined the risk of Pnc carriage by infants at six months of age after pneumococcal polysaccharide vaccination of pregnant women. We selected 139 pregnant woman. The woman were randomly allocated to receive 23-valent polysaccharide vaccines during pregnancy (Group 1) after pregnancy (Group 2) or not receive any vaccine (Group 3). Nasopharyngeal swabs were collected from the infants at three and six months of age. The infants were evaluated monthly during the first six months. We included 47 mothers in Group 1, 45 mothers in Group 2 and 47 mothers in Group 3. Forty-seven percent of the babies were exclusively breast fed until six months, 26% received both breast feeding and artificial feeding and 13% received only artificial feeding. Among those patients, 26% were colonized by Pnc at six months (12 from Group 1, 13 from Group 2, and 12 from Group 3). There was no significant difference in colonization between the three groups. Thirty percent of the children were colonized by a non-susceptible strain. We concluded that young infants (three months old) are already susceptible to pneumococcal carriage. Vaccination during pregnancy with a polysaccharide vaccine did not decrease Pnc colonization.


TITLE:
There is no solid evidence available supporting the belief that vaccines are effective in preventing influenza in the elderly.

AUTHORS:
Tom Jefferson, Carlo Di Pietrantonj, Lubna A Al-Ansary, Eliana Ferroni, Sarah Thorning, Roger E Thomas

ABSTRACT:
Vaccines have been the main global weapon to minimise the impact of influenza in the elderly for the last four decades and are recommended worldwide for individuals aged 65 years or older. The primary goal of influenza vaccination in the elderly is to reduce the risk of complications among persons who are most vulnerable.


TITLE:
Influenza vaccination for healthcare workers who work with the elderly has no effect on laboratory-proven influenza, pneumonia or deaths from pneumonia.

AUTHORS:
Roger E Thomas, Tom Jefferson, Toby J Lasserson

ABSTRACT:
Healthcare workers' (HCWs) influenza rates are unknown, but may be similar to the general public and they may transmit influenza to patients.


TITLE:
Swine flu vaccine adjuvants may cause harm in patients with autoimmune diseases such as multiple sclerosis.

ABSTRACT:
Vaccines are generally considered a simple compound and clinicians are sometimes unaware of the possible dangers related to the new adjuvanted vaccine approach. Due to their cost effectiveness and in order to obtain stronger response with a lower antigen dose, adjuvanted vaccines are preferred during pandemics. Adjuvants are strong immunostimulants and may be harmful in some special patient groups, such as in multiple sclerosis. There is a significant need for the effort among clinicians to heighten the awareness of the potential harms. In patient groups like multiple sclerosis, it is very important to advise vaccination with non-adjuvanted vaccines. Pure vaccine (without adjuvant) must be obtained for these groups.


TITLE:
HPV vaccination has been linked to demyelination.

AUTHORS:
Francis J DiMario, Mirna Hajjar, Thomas Ciesielski

ABSTRACT:
We report the course of a 16-year-old girl who presented with near complete visual loss associated with chiasmal neuritis and a biopsy proven tumefactive demyelinating lesion on magnetic resonance imaging (MRI) in association with a recent immunization against human papilloma virus.


TITLE:
Vaccination may contribute to causing a wide variety of autoimmune disorders.

AUTHORS:
Hedi Orbach, Nancy Agmon-Levin, Gisele Zandman-Goddard

ABSTRACT:
Infectious agents contribute to the environmental factors involved in the development of autoimmune diseases possibly through molecular mimicry mechanisms. Hence, it is feasible that vaccinations may also contribute to the mosaic of autoimmunity. Evidence for the association of vaccinations and the development of these diseases is presented in this review. Infrequently reported post-vaccination autoimmune diseases include systemic lupus erythematosus, rheumatoid arthritis, inflammatory myopathies, multiple sclerosis, Guillain-Barré syndrome, and vasculitis. In addition, we will discuss macrophagic myofasciitis, aluminum containing vaccines, and the recent evidence for autoimmunity following the use of human papillomavirus vaccine.


TITLE:
Varicella-zoster vaccine has been linked to herpes zoster opthalmicus and encephalitis as possible, though rare side effects.

AUTHORS:
Giorgos Chouliaras, Vana Spoulou, Mark Quinlivan, Judith Breuer, Maria Theodoridou

ABSTRACT:
Varicella-zoster virus vaccine has diminished the consequences of chicken pox in terms of health and economical burden. The increasing number of doses administered worldwide has revealed rare but important adverse effects that had not occurred during clinical trials. We report here the case of an immunocompetent 3(1/2)-year-old girl who developed encephalitis and herpes zoster opthalmicus 20 months after her immunization with varicella-zoster virus vaccine. Molecular analysis confirmed the vaccine strain as the causative agent. After an intravenous course with acyclovir, the child made a full recovery with no neurologic sequelae.


TITLE:
The risk of miscarriage increases following HPV vaccination.

AUTHORS:
Sholom Wacholder, Bingshu Eric Chen, Allen Wilcox, George Macones, Paula Gonzalez, Brian Befano, Allan Hildesheim, Ana Cecilia Rodriguez, Diane Solomon, Rolando Herrero, Mark Schiffman,

ABSTRACT:
To assess whether vaccination against human papillomavirus (HPV) increases the risk of miscarriage.


TITLE:
Vaccination as a probable cause of incontinentia pigmenti reactivation has been reported.

AUTHORS:
Ali Alikhan, Andrew D Lee, Donald Swing, Christie Carroll, Gil Yosipovitch

ABSTRACT:
We report a female infant with recurrent biopsy-proven vesicobullous incontinentia pigmenti occurring after her 12-month and 18-month immunizations. To our knowledge, incontinentia pigmenti vesicobullous recurrence following immunizations has not been reported. We propose that vaccinations may serve as triggers for incontinentia pigmenti reactivation.


TITLE:
Hepatitis B vaccines have a potential to occasionally trigger the onset of immune diseases in individuals with an underlying genetic or immunological susceptibility.

ABSTRACT:
The hepatitis B virus (HBV) is an important infectious cause of acute and chronic liver disease throughout the world. Recombinant hepatitis B vaccines have been developed to combat morbidity and mortality associated with HBV infection. These vaccines have been associated with autoimmune diseases mostly among adult vaccine recipients. Epidemiological surveys have not established unequivocal causality between the hepatitis B vaccine and the development of various autoimmune neuromuscular disorders. However, case histories and series hint at a temporal association between hepatitis B vaccines and the development of various neuropathy syndromes, polyarteritis nodosa complicated by vasculitic neuropathy, myasthenia gravis and dermatomyositis. Conceivably, the hepatitis B vaccines have a potential to occasionally trigger the onset of immune diseases in individuals with an underlying genetic or immunological susceptibility.


TITLE:
BCG revaccination may raise mortality in young children.

AUTHORS:
Adam Edvin Roth, Christine Stabell Benn, Henrik Ravn, Amabelia Rodrigues, Ida Maria Lisse, Maria Yazdanbakhsh, Hilton C Whittle, Peter Aaby

ABSTRACT:
To determine whether BCG revaccination at 19 months of age reduces overall child mortality.


TITLE:
A measles outbreak was reported in a highly vaccinated population, San Diego, 2008

AUTHORS:
David E Sugerman, Albert E Barskey, Maryann G Delea, Ismael R Ortega-Sanchez, Daoling Bi, Kimberly J Ralston, Paul A Rota, Karen Waters-Montijo, Charles W Lebaron

ABSTRACT:
In January 2008, an intentionally unvaccinated 7-year-old boy who was unknowingly infected with measles returned from Switzerland, resulting in the largest outbreak in San Diego, California, since 1991. We investigated the outbreak with the objective of understanding the effect of intentional undervaccination on measles transmission and its potential threat to measles elimination.


TITLE:
Viral nucleic acids in live-attenuated vaccines: detection of minority variants and an adventitious virus.

AUTHORS:
Joseph G Victoria, Chunlin Wang, Morris S Jones, Crystal Jaing, Kevin McLoughlin, Shea Gardner, Eric L Delwart

ABSTRACT:
Metagenomics and a panmicrobial microarray were used to examine eight live-attenuated viral vaccines. Viral nucleic acids in trivalent oral poliovirus (OPV), rubella, measles, yellow fever, varicella-zoster, multivalent measles/mumps/rubella, and two rotavirus live vaccines were partially purified, randomly amplified, and pyrosequenced. Over half a million sequence reads were generated covering from 20 to 99% of the attenuated viral genomes at depths reaching up to 8,000 reads per nucleotides. Mutations and minority variants, relative to vaccine strains, not known to affect attenuation were detected in OPV, mumps virus, and varicella-zoster virus. The anticipated detection of endogenous retroviral sequences from the producer avian and primate cells was confirmed. Avian leukosis virus (ALV), previously shown to be noninfectious for humans, was present as RNA in viral particles, while simian retrovirus (SRV) was present as genetically defective DNA. Rotarix, an orally administered rotavirus vaccine, contained porcine circovirus-1 (PCV1), a highly prevalent nonpathogenic pig virus, which has not been shown to be infectious in humans. Hybridization of vaccine nucleic acids to a panmicrobial microarray confirmed the presence of endogenous retroviral and PCV1 nucleic acids. Deep sequencing and microarrays can therefore detect attenuated virus sequence changes, minority variants, and adventitious viruses and help maintain the current safety record of live-attenuated viral vaccines.


TITLE:
The use of animal cells in the production of vaccines may cause infection by endogenous retroviruses associated with chronic fatigue and prostate cancer.

ABSTRACT:
Retroviruses are classified as exogenous or endogenous according to their mode of transmission. Generally, endogenous retroviruses (ERVs) are not pathogenic in their original hosts; however, some ERVs induce diseases. In humans, a novel gammaretrovirus was discovered in patients with prostate cancer or chronic fatigue syndrome. This virus was closely related to xenotropic murine leukemia virus (X-MLV) and designated as xenotropic murine leukemia virus-related virus (XMRV). The origin and transmission route of XMRV are still unknown at present; however, XMRV may be derived from ERVs of rodents because X-MLVs are ERVs of inbred and wild mice. Many live attenuated vaccines for animals are manufactured by using cell lines from animals, which are known to produce infectious ERVs; however, the risks of infection by ERVs from xenospecies through vaccination have been ignored. This brief review gives an overview of ERVs in cats, the potential risks of ERV infection by vaccination, the biological characteristics of RD-114 virus (a feline ERV), which possibly contaminates vaccines for companion animals, and the methods for detection of infectious RD-114 virus.


TITLE:
Prior receipt of seasonal flu vaccine (2008-09)was associated with increased risk of medically attended pandemic H1N1 illness (2008-09).

AUTHORS:
Danuta M Skowronski, Gaston De Serres, Natasha S Crowcroft, Naveed Z Janjua, Nicole Boulianne, Travis S Hottes, Laura C Rosella, James A Dickinson, Rodica Gilca, Pam Sethi, Najwa Ouhoummane, Donald J Willison, Isabelle Rouleau, Martin Petric, Kevin Fonseca, Steven J Drews, Anuradha Rebbapragada, Hugues Charest, Marie-Eve Hamelin, Guy Boivin, Jennifer L Gardy, Yan Li, Trijntje L Kwindt, David M Patrick, Robert C Brunham,

ABSTRACT:
In late spring 2009, concern was raised in Canada that prior vaccination with the 2008-09 trivalent inactivated influenza vaccine (TIV) was associated with increased risk of pandemic influenza A (H1N1) (pH1N1) illness. Several epidemiologic investigations were conducted through the summer to assess this putative association.


TITLE:
Vaccination proponents have suggested that breastfeeding should be delayed in order to prevent immune factors within breast milk from inactivating vaccine-associated antibody titer elevations and vaccine potency.

AUTHORS:
Sung-Sil Moon, Yuhuan Wang, Andi L Shane, Trang Nguyen, Pratima Ray, Penelope Dennehy, Luck Ju Baek, Umesh Parashar, Roger I Glass, Baoming Jiang

ABSTRACT:
Live oral rotavirus vaccines have been less immunogenic and efficacious among children in poor developing countries compared with middle income and industrialized countries for reasons that are not yet completely understood. We assessed whether the neutralizing activity of breast milk could lower the titer of vaccine virus and explain this difference in vitro.


TITLE:
Pertussis vaccination may activate a genetic predisposition for encephalopathy in susceptible individuals.

AUTHORS:
Anne M Mcintosh, Jacinta McMahon, Leanne M Dibbens, Xenia Iona, John C Mulley, Ingrid E Scheffer, Samuel F Berkovic

ABSTRACT:
Pertussis vaccination has been alleged to cause an encephalopathy that involves seizures and subsequent intellectual disability. In a previous retrospective study, 11 of 14 patients with so-called vaccine encephalopathy had Dravet syndrome that was associated with de-novo mutations of the sodium channel gene SCN1A. In this study, we aimed to establish whether the apparent association of Dravet syndrome with vaccination was caused by recall bias and, if not, whether vaccination affected the onset or outcome of the disorder.


TITLE:
Breastfeeding is associated with a decreased incidence of fever after immunizations.

AUTHORS:
Alfredo Pisacane, Paola Continisio, Orsola Palma, Stefania Cataldo, Fabiola De Michele, Ugo Vairo

ABSTRACT:
The objective of this study was to evaluate the effects of breastfeeding on the risk for fever after routine immunizations.


TITLE:
Guillain-Barre syndrome following H1N1 immunization in a pediatric patient has been reported.

AUTHORS:
Marie-Eve Tremblay, AurÃ©lie Closon, Guy D'Anjou, Jean-Francois BussiÃ©res

ABSTRACT:
To report a case of Guillain-Barré syndrome (GBS) following a dose of influenza A (H1N1) vaccine (Arepanrix).


TITLE:
An animal vaccine was identified as a possible cause of a series of lamb abortions.

AUTHORS:
Nicholas Wheelhouse, Kevin Aitchison, Karine Laroucau, Jill Thomson, David Longbottom

ABSTRACT:
Chlamydophila abortus, the agent of ovine enzootic abortion (OEA), is a major cause of lamb mortality worldwide. Disease can be controlled through the use of vaccines based on the 1B temperature-sensitive mutant strain of C. abortus. This study investigated suspected OEA cases across Scotland for the presence of the 1B strain by analysis of recently identified unique point mutations (9). Thirty-five cases were C. abortus-positive and 14 came from vaccinated flocks. Analysis of single nucleotide polymorphisms by PCR-RFLP and sequence analysis revealed the presence of point mutations consistent with the presence of the 1B vaccine strain in 5 of these 14 samples. Quantitative real-time PCR revealed comparable numbers of genome copies of the 1B strain in infected placentas to those present following wild-type infection. This study is the first to demonstrate the presence of the 1B vaccine strain in the placentas of OEA cases and suggests a probable causal role in the disease.


TITLE:
Adverse events following smallpox vaccination with ACAM2000 in a military population have been reported.

AUTHORS:
Thomas M Beachkofsky, Scott C Carrizales, Jeffrey J Bidinger, David E Hrncir, Darren E Whittemore, Chad M Hivnor

ABSTRACT:
Generalized vaccinia and benign exanthems are 2 adverse events that have been associated with the smallpox vaccination. Accurate incidence and prevalence rates of each are not readily available, but these events are thought to be uncommon. To our knowledge, this is the first case series to provide clinical as well as pathologic descriptions of multiple papulovesicular eruptions occurring after receiving the second-generation smallpox vaccine, ACAM2000 (Acambis, Canton, Massachusetts), among a vaccinia-naïve military population. In addition, we report the first confirmed case, to our knowledge, of generalized vaccinia following administration of the ACAM2000 vaccine.


TITLE:
There is little evidence supporting the belief that vaccines are effective in preventing influenza in healthy adults.

AUTHORS:
Tom Jefferson, Carlo Di Pietrantonj, Alessandro Rivetti, Ghada A Bawazeer, Lubna A Al-Ansary, Eliana Ferroni

ABSTRACT:
Different types of influenza vaccines are currently produced worldwide. Healthy adults are presently targeted mainly in North America.


TITLE:
Maturational changes in amygdala volume and the binding capacity of an opioid antagonist in the amygdala was significantly altered in infant macaques receiving the vaccine schedule.

AUTHORS:
Laura Hewitson, Brian J Lopresti, Carol Stott, N Scott Mason, Jaime Tomko

ABSTRACT:
This longitudinal, case-control pilot study examined amygdala growth in rhesus macaque infants receiving the complete US childhood vaccine schedule (1994-1999). Longitudinal structural and functional neuroimaging was undertaken to examine central effects of the vaccine regimen on the developing brain. Vaccine-exposed and saline-injected control infants underwent MRI and PET imaging at approximately 4 and 6 months of age, representing two specific timeframes within the vaccination schedule. Volumetric analyses showed that exposed animals did not undergo the maturational changes over time in amygdala volume that was observed in unexposed animals. After controlling for left amygdala volume, the binding of the opioid antagonist [(11)C]diprenorphine (DPN) in exposed animals remained relatively constant over time, compared with unexposed animals, in which a significant decrease in [(11)C]DPN binding occurred. These results suggest that maturational changes in amygdala volume and the binding capacity of [(11)C]DPN in the amygdala was significantly altered in infant macaques receiving the vaccine schedule. The macaque infant is a relevant animal model in which to investigate specific environmental exposures and structural/functional neuroimaging during neurodevelopment.


TITLE:
Systemic lupus erythematosus has been triggered by hepatitis B vaccine.

AUTHORS:
D Santoro, G Vita, R Vita, A Mallamace, V Savica, G Bellinghieri, S Benvenga, S Gangemi

ABSTRACT:
Find an association between hepatitis B vaccine-related systemic lupus erythematosus and HLA.


TITLE:
Increasing varicella vaccine coverage in Australia between 1998-2009 corresponds with increased levels of herpes zoster (shingles) cases managed in the same time period.

AUTHORS:
Mark R Nelson, Helena C Britt, Christopher M Harrison

ABSTRACT:
To assess whether the management rate of herpes zoster (HZ) in Australian general practice has changed since varicella vaccines became available; and to ascertain the mean age of patients attending general practice for HZ management, to assist with planning of vaccination to prevent HZ in older Australians.


TITLE:
Transverse myelitis has been reported in association with a nasal attenuated novel influenza A(H1N1) vaccine.

AUTHORS:
Wafa Akkad, Bassel Salem, Jerome W Freeman, Mark K Huntington

ABSTRACT:
Transverse myelitis has been reported in association with vaccination, including influenza vaccination.


TITLE:
Newborn primates receiving mercury-containing hepatitis B vaccines exhibit neurodevelopmental delays.

AUTHORS:
Laura Hewitson, Lisa A Houser, Carol Stott, Gene Sackett, Jaime L Tomko, David Atwood, Lisa Blue, E Railey White

ABSTRACT:
This study examined whether acquisition of neonatal reflexes in newborn rhesus macaques was influenced by receipt of a single neonatal dose of hepatitis B vaccine containing the preservative thimerosal (Th). Hepatitis B vaccine containing a weight-adjusted Th dose was administered to male macaques within 24 h of birth (n = 13). Unexposed animals received saline placebo (n = 4) or no injection (n = 3). Infants were tested daily for acquisition of nine survival, motor, and sensorimotor reflexes. In exposed animals there was a significant delay in the acquisition of root, snout, and suck reflexes, compared with unexposed animals. No neonatal responses were significantly delayed in unexposed animals. Gestational age (GA) and birth weight (BW) were not significantly correlated. Cox regression models were used to evaluate main effects and interactions of exposure with BW and GA as independent predictors and time-invariant covariates. Significant main effects remained for exposure on root and suck when controlling for GA and BW, such that exposed animals were relatively delayed in time-to-criterion. Interaction models indicated there were various interactions between exposure, GA, and BW and that inclusion of the relevant interaction terms significantly improved model fit. This, in turn, indicated that lower BW and/or lower GA exacerbated the adverse effects following vaccine exposure. This primate model provides a possible means of assessing adverse neurodevelopmental outcomes from neonatal Th-containing hepatitis B vaccine exposure, particularly in infants of lower GA or BW. The mechanisms underlying these effects and the requirements for Th requires further study.


TITLE:
Exposure to thimerosal during early postnatal life produces lasting alterations in the densities of brain opioid receptors along with other neuropathological changes, which may disturb brain development.

AUTHORS:
Mieszko Olczak, Michalina Duszczyk, Pawel Mierzejewski, Teresa Bobrowicz, Maria Dorota Majewska

ABSTRACT:
Thimerosal added to some pediatric vaccines is suspected in pathogenesis of several neurodevelopmental disorders. Our previous study showed that thimerosal administered to suckling rats causes persistent, endogenous opioid-mediated hypoalgesia. Here we examined, using immunohistochemical staining technique, the density of ?-opioid receptors (MORs) in the brains of rats, which in the second postnatal week received four i.m. injections of thimerosal at doses 12, 240, 1,440 or 3,000 ?g Hg/kg. The periaqueductal gray, caudate putamen and hippocampus were examined. Thimerosal administration caused dose-dependent statistically significant increase in MOR densities in the periaqueductal gray and caudate putamen, but decrease in the dentate gyrus, where it was accompanied by the presence of degenerating neurons and loss of synaptic vesicle marker (synaptophysin). These data document that exposure to thimerosal during early postnatal life produces lasting alterations in the densities of brain opioid receptors along with other neuropathological changes, which may disturb brain development.


TITLE:
The way that the effectiveness of HPV vaccines are framed influences whether or not respondents believe they are effective and their acceptance level of vaccine mandate policies.

AUTHORS:
Cabral A Bigman, Joseph N Cappella, Robert C Hornik

ABSTRACT:
To experimentally test whether presenting logically equivalent, but differently valenced effectiveness information (i.e. attribute framing) affects perceived effectiveness of the human papillomavirus (HPV) vaccine, vaccine-related intentions and policy opinions.


TITLE:
There were 69 reports of Guillain-Barre Syndrome (GBS) after Gardasil vaccination that occurred in the United States between 2006 and 2009.

AUTHORS:
Nizar Souayah, P A Michas-Martin, Abu Nasar, Nataliya Krivitskaya, Hussam A Yacoub, Hafiz Khan, Adnan I Qureshi

ABSTRACT:
Using data from Vaccine Adverse Event Reporting System, we identified 69 reports of Guillain-Barré Syndrome (GBS) after Gardasil vaccination that occurred in the United States between 2006 and 2009. The onset of symptoms was within 6 weeks after vaccination in 70% of the patients in whom the date of vaccination was known. The estimated weekly reporting rate of post-Gardasil GBS within the first 6 weeks (6.6 per 10,000,000) was higher than that of the general population, and higher than post-Menactra and post-influenza vaccinations. Further prospective active surveillance for accurate ascertainment and identification of high-risk groups of GBS after Gardasil vaccination is warranted.


TITLE:
Seasonal influenza vaccine (2008-2009) is associated with an increased risk of influenza-like illness from pandemic H1N1 infection.

AUTHORS:
Naveed Z Janjua, Danuta M Skowronski, Travis S Hottes, William Osei, Evan Adams, Martin Petric, Suzana Sabaiduc, Tracy Chan, Annie Mak, Marcus Lem, Patrick Tang, David M Patrick, Gaston De Serres, David Bowering

ABSTRACT:
In April 2009, an elementary school outbreak of pandemic H1N1 (pH1N1) influenza was reported in a community in northern British Columbia, Canada--an area that includes both non-Aboriginal and Aboriginal residents living on or off a reserve. During the outbreak investigation, we explored the relationship between prior receipt of trivalent inactivated influenza vaccine (TIV) and pH1N1-related illness.


TITLE:
Influenza A vaccination containing adjuvant causes cardiac autonomic dysfunction and inflammation which may transiently increase the risk of cardiovascular events.

AUTHORS:
Gaetano A Lanza, Lucy Barone, Giancarla Scalone, Dario Pitocco, Gregory A Sgueglia, Roberto Mollo, Roberto Nerla, Francesco Zaccardi, Giovanni Ghirlanda, Filippo Crea

ABSTRACT:
Inflammation, platelet reactivity and cardiac autonomic dysfunction increase the risk of cardiovascular events, but the relationships between these prognostic markers are poorly defined. In this study, we investigated the effect of an inflammatory stimulus (influenza A vaccine) on platelet activation and cardiac autonomic function.


TITLE:
A case of Leukemia Cutis arising at the site of injection of a Tetanus Booster has been reported.

AUTHORS:
R M Guinovart, J M Carrascosa, C Ferrandiz


TITLE:
Male newborns vaccinated with hepatitis B prior to 1999 had a 3-fold higher risk for parentally reported autism.

ABSTRACT:
Universal hepatitis B vaccination was recommended for U.S. newborns in 1991; however, safety findings are mixed. The association between hepatitis B vaccination of male neonates and parental report of autism diagnosis was determined. This cross-sectional study used weighted probability samples obtained from National Health Interview Survey 1997-2002 data sets. Vaccination status was determined from the vaccination record. Logistic regression was used to estimate the odds for autism diagnosis associated with neonatal hepatitis B vaccination among boys age 3-17 years, born before 1999, adjusted for race, maternal education, and two-parent household. Boys vaccinated as neonates had threefold greater odds for autism diagnosis compared to boys never vaccinated or vaccinated after the first month of life. Non-Hispanic white boys were 64% less likely to have autism diagnosis relative to nonwhite boys. Findings suggest that U.S. male neonates vaccinated with the hepatitis B vaccine prior to 1999 (from vaccination record) had a threefold higher risk for parental report of autism diagnosis compared to boys not vaccinated as neonates during that same time period. Nonwhite boys bore a greater risk.


TITLE:
Diphtheria-tetanus-pertussis vaccine administered simultaneously with measles vaccine is associated with increased morbidity and poor growth in girls.

AUTHORS:
J Agergaard, E Nante, G Poulstrup, Jens Nielsen, K L Flanagan, L Ostergaard, Christine Stabell Benn, Peter Aaby

ABSTRACT:
Combined vaccination with diphtheria-tetanus-pertussis (DTP) and measles vaccine (MV) has been associated with increased mortality in observational studies. Among children missing MV and a dose of DTP and oral polio vaccine (OPV), we conducted a randomised trial of providing MV+DTP+OPV simultaneously, as currently recommended, or MV+OPV only, and examined the effect on morbidity and growth. We hypothesised that the MV+OPV group would experience less morbidity and grow better. Due to previous observations of sex differences in the non-specific effects of vaccinations, we analysed all data stratified by sex.


TITLE:
Over 1,000 confirmed cases of vaccine-induced thrombocytopenia were reported between 1990-2008.

AUTHORS:
Emily Jane Woo, Robert P Wise, David Menschik, Sean V Shadomy, John Iskander, Judy Beeler, Frederick Varricchio, Robert Ball

ABSTRACT:
We reviewed thrombocytopenia (TP) reports to the US Vaccine Adverse Event Reporting System (VAERS). We examined TP patterns for differences in single versus multiple immunization reports, presence of a live viral vaccine, seriousness, age, and interval to symptom onset. We found 1510 reports of possible TP and after exclusions evaluated 1440 for possible causes. Most (1078; 75%) met the regulatory definition of a serious adverse event. TP was reported after inactivated and live viral vaccines. Platelet counts <10×10(9)/L were reported. Identified vaccines could be prioritized for hypothesis-testing studies.


TITLE:
Thrombocytopenic purpura following vaccination in early childhood has been reported.

ABSTRACT:
The etiology of thrombocytopenia during infancy and early childhood may be different from that of older children, because young children frequently receive vaccines. The following study was performed to understand whether there was a causal relationship between vaccinations and thrombocytopenia.


TITLE:
Noticeable adverse reactions to the HPV vaccine occurred in 22% of those polled.

AUTHORS:
M Amparo Torrecilla Rojas, Miguel Pedregal Gonzalez, Fermin Garcfa Rodriguez, Josefa Ruiz Fernandez

ABSTRACT:
To describe the most frequent adverse reactions produced by the human papillomavirus (HPV) vaccine.


TITLE:
Delayed focal lipoatrophy after AS03-adjuvanted influenza A (H1N1) 2009 vaccine has been reported.

AUTHORS:
Emilie Javelle, Benjamin Soulier, Christian Brosset, SolÃ©ne Lorcy, Fabrice Simon

ABSTRACT:
Intramuscular vaccination may lead to loss of subcutaneous fat resulting in skin depression at the site of injection. We report for the first time a delayed lipoatrophy after with AS03-adjuvanted influenza A (H1N1) 2009 vaccine. Inadequate administration into the adipose tissue may be causative. During next pandemic, education to optimal intramuscular administration and prolonged monitoring of adverse effects could be proposed.


TITLE:
H1N1 vaccination has been linked to possible new-onset seizure.


TITLE:
Autoimmune hemolytic anemia following MF59-adjuvanted influenza vaccine has been reported.

AUTHORS:
Sabrina Montagnani, Marco Tuccori, Giuseppe Lombardo, Arianna Testi, Stefania Mantarro, Elisa Ruggiero, Corrado Blandizzi

ABSTRACT:
To describe 2 cases of autoimmune hemolytic anemia (AIHA) following the administration of MF59-adjuvanted influenza vaccine.


TITLE:
Mycoplasma testing of cell substrates and biologics is often not performed due to the long turn around.

AUTHORS:
Dmitriy V Volokhov, Laurie J Graham, Kurt A Brorson, Viadimir E Chizhikov

ABSTRACT:
Mycoplasmas, particularly species of the genera Mycoplasma and Acholeplasma, are known to be occasional microbial contaminants of cell cultures that produce biologics. This presents a serious concern regarding the risk of mycoplasma contamination for research laboratories and commercial facilities developing and manufacturing cell-derived biological and biopharmaceutical products for therapeutic use. Potential undetected contamination of these products or process intermediates with mycoplasmas represents a potential safety risk for patients and a business risk for producers of biopharmaceuticals. To minimize these risks, monitoring for adventitious agents, such as viruses and mycoplasmas, is performed during the manufacture of biologics produced in cell culture substrates. The "gold standard" microbiological assay, currently recommended by the USP, EP, JP and the US FDA, for the mycoplasma testing of biologics, involves the culture of viable mycoplasmas in broth, agar plates and indicator cells. Although the procedure enables highly efficient mycoplasma detection in cell substrates and cell-derived products, the overall testing strategy is time consuming (a minimum of 28 days) and requires skilled interpretation of the results. The long time period required for these conventional assays does not permit their use for products with short shelf-lives or for timely 'go/no-go' decisions during routine in-process testing. PCR methodology has existed for decades, however PCR based and other alternative methods for mycoplasma detection have only recently been considered for application to biologics manufacture. The application of alternative nucleic acid-based, enzyme-based and/or recombinant cell-culture methods, particularly in combination with efficient sample preparation procedures, could provide advantages over conventional microbiological methods in terms of analytical throughput, simplicity, and turnaround time. However, a challenge to the application of alternative methods for detection of mycoplasmas remains whether these alternative methods can provide a limit of detection comparable or superior to those of the culture methods. An additional challenge is that nucleic acid amplification technique (NAT) methods do not allow for accurate discrimination between viable and non-viable mycoplasma contaminants, which might lead to false-positive results (e.g. from inactivated raw materials, etc.). Our review provides an overview of these alternative methods and discusses the pros and cons of their application for the testing of mycoplasmas in biologics and cell substrates.


TITLE:
A modified self-controlled case series method links multidose vaccinations to sudden unexpected death.

AUTHORS:
Ronny Kuhnert, Hartmut Hecker, Christina Poethko-Muller, Martin Schlaud, Mechtild Vennemann, Heather J Whitaker, C Paddy Farrington

ABSTRACT:
The self-controlled case series method (SCCS) was developed to analyze the association between a time-varying exposure and an outcome event. We consider penta- or hexavalent vaccination as the exposure and unexplained sudden unexpected death (uSUD) as the event. The special situation of multiple exposures and a terminal event requires adaptation of the standard SCCS method. This paper proposes a new adaptation, in which observation periods are truncated according to the vaccination schedule. The new method exploits known minimum spacings between successive vaccine doses. Its advantage is that it is very much simpler to apply than the method for censored, perturbed or curtailed post-event exposures recently introduced. This paper presents a comparison of these two SCCS methods by simulation studies and an application to a real data set. In the simulation studies, the age distribution and the assumed vaccination schedule were based on real data. Only small differences between the two SCCS methods were observed, although 50 per cent of cases could not be included in the analysis with the SCCS method with truncated observation periods. By means of a study including 300 uSUD, a 16-fold risk increase after the 4th dose could be detected with a power of at least 90 per cent. A general 2-fold risk increase after vaccination could be detected with a power of 80 per cent. Reanalysis of data from cases of the German case-control study on sudden infant death (GeSID) resulted in slightly higher point estimates using the SCCS methods than the odds ratio obtained by the case-control analysis.


TITLE:
Killed cholera vaccination generates an inferior immune response in comparison to patients with naturally acquired cholera.

AUTHORS:
Mohammad Murshid Alam, M Asrafuzzaman Riyadh, Kaniz Fatema, Mohammad Arif Rahman, Nayeema Akhtar, Tanvir Ahmed, Mohiul Islam Chowdhury, Fahima Chowdhury, Stephen B Calderwood, jason B Harris, Edward T Ryan, Firdausi Qadri

ABSTRACT:
The mediators of protective immunity against cholera are currently unknown, but memory B-cell responses may play a central role in facilitating long-term and anamnestic responses against Vibrio cholerae, the cause of cholera. We compared memory B-cell responses in adults with natural cholera in Bangladesh (n = 70) to responses in Bangladeshi adults after one-dose (n = 30) or two-dose (n = 30) administration of an oral killed cholera vaccine, WC-rBS (Dukoral; Crucell), assessing the responses at the acute stage of disease or prevaccination and then on days 3, 30, 90, 180, 270, and 360. Individuals with natural cholera developed prominent vibriocidal and plasma anti-cholera toxin B subunit (CtxB) and lipopolysaccharide (LPS) IgG and IgA responses, but these responses returned to baseline by 1 year of follow-up. Vaccinees developed plasma anti-CtxB and anti-LPS IgG and IgA responses that were generally comparable to those in individuals recovering from natural disease, but vibriocidal responses were lower in vaccinees than in infected patients. Individuals recovering from natural disease developed memory B-cell IgG and IgA anti-CtxB and anti-LPS responses by day 30, and these responses were detectable through at least days 180 to 360. In contrast, we detected no IgA or IgG memory B-cell responses to LPS in vaccinees; anti-CtxB IgA responses were only detectable on day 30, and anti-CtxB IgG responses were detectable until days 90 to 180, compared to days 270 to 360 in patients. These findings may explain in part the relatively short-term protection afforded by oral cholera vaccination compared to natural disease.


TITLE:
Thimerosal at concentrations relevant for infants exposure in vaccines is toxic to cultured human brain cells and to laboratory animals.

ABSTRACT:
There is a need to interpret neurotoxic studies to help deal with uncertainties surrounding pregnant mothers, newborns and young children who must receive repeated doses of Thimerosal-containing vaccines (TCVs). This review integrates information derived from emerging experimental studies (in vitro and in vivo) of low-dose Thimerosal (sodium ethyl mercury thiosalicylate). Major databases (PubMed and Web-of-science) were searched for in vitro and in vivo experimental studies that addressed the effects of low-dose Thimerosal (or ethylmercury) on neural tissues and animal behaviour. Information extracted from studies indicates that: (a) activity of low doses of Thimerosal against isolated human and animal brain cells was found in all studies and is consistent with Hg neurotoxicity; (b) the neurotoxic effect of ethylmercury has not been studied with co-occurring adjuvant-Al in TCVs; (c) animal studies have shown that exposure to Thimerosal-Hg can lead to accumulation of inorganic Hg in brain, and that (d) doses relevant to TCV exposure possess the potential to affect human neuro-development. Thimerosal at concentrations relevant for infants' exposure (in vaccines) is toxic to cultured human-brain cells and to laboratory animals. The persisting use of TCV (in developing countries) is counterintuitive to global efforts to lower Hg exposure and to ban Hg in medical products; its continued use in TCV requires evaluation of a sufficiently nontoxic level of ethylmercury compatible with repeated exposure (co-occurring with adjuvant-Al) during early life.


TITLE:
Adverse effects of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine in 6- to 7-year-old children.

AUTHORS:
Sung-Hsi Wei, Yen-Nan Chao, Song-En Huang, Tsuey-Feng Lee, Luan-Yin Chang

ABSTRACT:
Although the safety profile of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines in adolescents and adults has been documented, few data have reported about their adverse events in children. Healthy 6- to 7-year-old children who were immunized with Tdap vaccine were evaluated for adverse events on Days 1, 2, 4, and 7 postimmunization. Information of sex, body mass index (BMI), and previous diphtheria-pertussis-tetanus (DPT) immunization history was obtained and evaluated for the association with the adverse events. A total of 243 6- to 7-year-old children were immunized with Tdap. Among the 243 children immunized, remarkable adverse events included redness more than or equal to 10 mm in 47 (19%) children, induration more than or equal to 10 mm in 57 (23%), tenderness in 130 (53%), and fever in 12 (5%). Redness and induration resolved in 7 days and fever resolved on Day 4. The adverse events were not associated with gender, BMI above the mean value, or the type of fourth DPT immunization. Adverse events after Tdap vaccination were mild and dissolved within 7 days in 6- to 7-year-old children.


TITLE:
Vaccinia Virus infections can be transmissible and can cause severe complications in those with weakened immune systems.

AUTHORS:
Christine M Hughes, David Blythe, Yu Li, Ramani Reddy, Carol Jordan, Cindy Edwards, Celia Adams, Holly Conners, Catherine Rasa, Sue Wilby, Jamaal Russell, Kelly S Russo, Patricia Somsel, Danny L Wiedbrauk, Cindy Dougherty, Christopher Allen, Mike Frace, Ginny Emerson, Victoria A Olson, Scott K Smith, Zachary Braden, Jason Abel, Whitni Davidson, Mary Reynolds, Inger K Damon

ABSTRACT:
Vaccinia virus is an orthopoxvirus used in the live vaccine against smallpox. Vaccinia virus infections can be transmissible and can cause severe complications in those with weakened immune systems. We report on a cluster of 4 cases of vaccinia virus infection in Maryland, USA, likely acquired at a martial arts gym.


TITLE:
There are 76 factors (cytokines/chemokines/growth-factors/others) that have been identified that are involved in various steps of the establishment of pregnancy and which could become targets/liabilities for vaccine-induced abortion/contraception.

ABSTRACT:
Current methods of contraception lack specificity and are accompanied with serious side effects. A more specific method of contraception is needed. Contraceptive vaccines can provide most, if not all, the desired characteristics of an ideal contraceptive. This article reviews several factors involved in the establishment of pregnancy, focusing on those that are essential for successful implantation. Factors that are both essential and pregnancy-specific can provide potential targets for contraception. Using database search, 76 factors (cytokines/chemokines/growth factors/others) were identified that are involved in various steps of the establishment of pregnancy. Among these factors, three, namely chorionic gonadotropin (CG), leukemia inhibitory factor (LIF), and pre-implantation factor (PIF), are found to be unique and exciting molecules. Human CG is a well-known pregnancy-specific protein that has undergone phase I and phase II clinical trials, in women, as a contraceptive vaccine with encouraging results. LIF and PIF are pregnancy-specific and essential for successful implantation. These molecules are intriguing and may provide viable targets for immunocontraception. A multiepitope vaccine combining factors/antigens involved in various steps of the fertilization cascade and pregnancy establishment may provide a highly immunogenic and efficacious modality for contraception in humans.


TITLE:
Live attenuated influenza vaccines may cause shedding of the virus in children 6-59 months.

AUTHORS:
Raburn M Mallory, Tingting Yi, Christopher S Ambrose

ABSTRACT:
A trivalent, Ann Arbor strain, live attenuated influenza vaccine (LAIV) is approved for use in children 24 months of age and older in a number of countries. The incidence, duration, and other parameters of viral shedding after vaccination with LAIV have not been fully described in children ? 5 years of age.


TITLE:
Zinc supplementation has a beneficial effect on malaise, one of the influenza vaccine associated adverse events, and decrease serum TNF-a levels.

AUTHORS:
S Songul Yalcin, Defne Engur-Karasimav, Dursun Alehan, Kadriye Yurdak6Ã©k, Suheyla Ozkutlu, Turgay Coskun

ABSTRACT:
To investigate whether zinc supplementation could affect serum tumor necrosis factor-alpha (TNF-?) levels in congenital and acquired cardiac patients attending for an influenza vaccine.


TITLE:
There is a highly statistically significant correlation between increasing number of vaccine doses and increasing infant mortality rates.

ABSTRACT:
The infant mortality rate (IMR) is one of the most important indicators of the socio-economic well-being and public health conditions of a country. The US childhood immunization schedule specifies 26 vaccine doses for infants aged less than 1 year--the most in the world--yet 33 nations have lower IMRs. Using linear regression, the immunization schedules of these 34 nations were examined and a correlation coefficient of r = 0.70 (p < 0.0001) was found between IMRs and the number of vaccine doses routinely given to infants. Nations were also grouped into five different vaccine dose ranges: 12-14, 15-17, 18-20, 21-23, and 24-26. The mean IMRs of all nations within each group were then calculated. Linear regression analysis of unweighted mean IMRs showed a high statistically significant correlation between increasing number of vaccine doses and increasing infant mortality rates, with r = 0.992 (p = 0.0009). Using the Tukey-Kramer test, statistically significant differences in mean IMRs were found between nations giving 12-14 vaccine doses and those giving 21-23, and 24-26 doses. A closer inspection of correlations between vaccine doses, biochemical or synergistic toxicity, and IMRs is essential.


TITLE:
VAERS had significantly higher ORs than autism following thimerosal containing DTaP vaccines in comparison to thimerosal free DTaP vaccines.

AUTHORS:
Mieszko Olczak, Michalina Duszczyk, Pawel Mierzejewski, Ksenia Meyza, Maria Dorota Majewska

ABSTRACT:
The neurotoxic organomercurial thimerosal (THIM), used for decades as vaccine preservative, is a suspected factor in the pathogenesis of some neurodevelopmental disorders. Previously we showed that neonatal administration of THIM at doses equivalent to those used in infant vaccines or higher, causes lasting alterations in the brain opioid system in rats. Here we investigated neonatal treatment with THIM (at doses 12, 240, 1440 and 3000 ?g Hg/kg) on behaviors, which are characteristically altered in autism, such as locomotor activity, anxiety, social interactions, spatial learning, and on the brain dopaminergic system in Wistar rats of both sexes. Adult male and female rats, which were exposed to the entire range of THIM doses during the early postnatal life, manifested impairments of locomotor activity and increased anxiety/neophobia in the open field test. In animals of both sexes treated with the highest THIM dose, the frequency of prosocial interactions was reduced, while the frequency of asocial/antisocial interactions was increased in males, but decreased in females. Neonatal THIM treatment did not significantly affect spatial learning and memory. THIM-exposed rats also manifested reduced haloperidol-induced catalepsy, accompanied by a marked decline in the density of striatal D? receptors, measured by immunohistochemical staining, suggesting alterations to the brain dopaminergic system. Males were more sensitive than females to some neurodisruptive/neurotoxic actions of THIM. These data document that early postnatal THIM administration causes lasting neurobehavioral impairments and neurochemical alterations in the brain, dependent on dose and sex. If similar changes occur in THIM/mercurial-exposed children, they could contribute do neurodevelopmental disorders.


TITLE:
There is evidence that a DNA vaccine exhibits anti-fertility properties.

AUTHORS:
Meng-Fei Yu, Wen-Ning Fang, Gao-Feng Xiong, Ying Yang, Jing-Pian Peng

ABSTRACT:
Previously we have found that DNA vaccine, pCMV4-rZPC' can generate specific antibodies against rabbit ZPC (amino acid 263-415, rZPC'), which binds to ovarian ZP and leads to a significant reduction of fertility in vivo. The purpose of this study was to evaluate the effect of antisera from pCMV4-rZPC(')-immunized mice on sperm-oocyte interaction in vitro. The effect of antisera from DNA vaccine-immunized mice on fertilization and early embryonic development was studied using an in vitro fertilization system. The results showed that the antisera supplemented in fertilization medium (10%, v/v) significantly decreased the rate of fertilization compared to that of control groups (P<0.05); whereas the antisera showed no significant effect on the rate of fertilization when ZP-free eggs were used. Moreover, the antisera pre-neutralized with mouse soluble zona pellucida lost the capacity to inhibit fertilization when compared with that of control groups. In addition, the antisera showed no detrimental effect on early developmental potential of mouse embryos in vitro. Taken together, our study provided herein direct evidence showing that antisera generated by DNA vaccine can block sperm-egg recognition during fertilization via targeting the oocyte ZP proteins.


TITLE:
There is a positive association between autism prevalence and childhood vaccination uptake across the U.S. population.

ABSTRACT:
The reason for the rapid rise of autism in the United States that began in the 1990s is a mystery. Although individuals probably have a genetic predisposition to develop autism, researchers suspect that one or more environmental triggers are also needed. One of those triggers might be the battery of vaccinations that young children receive. Using regression analysis and controlling for family income and ethnicity, the relationship between the proportion of children who received the recommended vaccines by age 2 years and the prevalence of autism (AUT) or speech or language impairment (SLI) in each U.S. state from 2001 and 2007 was determined. A positive and statistically significant relationship was found: The higher the proportion of children receiving recommended vaccinations, the higher was the prevalence of AUT or SLI. A 1% increase in vaccination was associated with an additional 680 children having AUT or SLI. Neither parental behavior nor access to care affected the results, since vaccination proportions were not significantly related (statistically) to any other disability or to the number of pediatricians in a U.S. state. The results suggest that although mercury has been removed from many vaccines, other culprits may link vaccines to autism. Further study into the relationship between vaccines and autism is warranted.


TITLE:
Yellow fever vaccination and increased relapse rate in travelers with multiple sclerosis.

ABSTRACT:
To investigate the effect of yellow fever (YF) immunization on the subsequent multiple sclerosis (MS) relapse risk.


TITLE:
Paralytic poliomyelitis associated with bivalent oral polio vaccines occurs at a rate over up to 70-fold higher than monovalent oral polio vaccine in Hungary.

AUTHORS:
Concepcion F Estivariz, Zsuzsanna Molnar, Linda Venczel, Beatrix Kapusinszky, James A Zingeser, Galina Y Lipskaya, Olen M Kew, Gyorgy Berencsi, Agnes Csohan

ABSTRACT:
Historical records of patients with vaccine-associated paralytic poliomyelitis (VAPP) in Hungary during 1961-1981 were reviewed to assess the risk of VAPP after oral polio vaccine (OPV) administration. A confirmed VAPP case was defined as a diagnosis of paralytic poliomyelitis and residual paralysis at 60 days in a patient with an epidemiologic link to the vaccine. Archived poliovirus isolates were retested using polymerase chain reaction and sequencing of the viral protein 1 capsid region. This review confirmed 46 of 47 cases previously reported as VAPP. Three cases originally linked to monovalent OPV (mOPV) 3 and one case linked to mOPV1 presented after administration of bivalent OPV 1 + 3 (bOPV). The adjusted VAPP risk per million doses administered was 0.18 for mOPV1 (2 cases/11.13 million doses), 2.96 for mOPV3 (32 cases/10.81 million doses), and 12.82 for bOPV (5 cases/390,000 doses). Absence of protection from immunization with inactivated poliovirus vaccine or exposure to OPV virus from routine immunization and recent injections could explain the higher relative risk of VAPP in Hungarian children. In polio-endemic areas in which mOPV3 and bOPV are needed to achieve eradication, the higher risk of VAPP would be offset by the high risk of paralysis due to wild poliovirus and higher per-dose efficacy of mOPV3 and bOPV compared with trivalent OPV.


TITLE:
Hepatitis B vaccine alters the expression of 144 genes in 7 the mouse liver within 1 day of vaccination, 7 of which are related to inflammation and metabolism.

AUTHORS:
Heyam Hamza, Jianhua Cao, Xinyun Li, Shuhong Zhao

ABSTRACT:
Pharmaceutical companies usually perform safety testing of vaccines, but all requirements of the World Health Organization and drug pharmacopoeias depend on general toxicity testing, and the gene expression study of hepatitis B vaccine is not done routinely to test vaccine quality. In this study, we applied a new technique of gene expression analysis to detect the inflammation and metabolism genes that might be affected by hepatitis B vaccine in mouse liver. Mice were used and divided into three groups: the first and second groups were treated with one or two human doses of vaccine, respectively, and the third group was used as a control. A microarray test showed that expression of 144 genes in the liver was significantly changed after 1 day of vaccination. Seven of these genes, which were related to inflammation and metabolism, were chosen and confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) at 1, 4 and 7 days. The expression level of these genes can be considered as a biomarker for the effects of the vaccine.


TITLE:
In Kings County Washington, between 2002-2007, of the 176 confirmed cases of pertussis in infants under age 1 seventy-seven percent were age-appropriately vaccinated.

AUTHORS:
Matthew P Hanson, Tao S Kwan-Gett, Atar Baer, Krista Rietberg, Mara Ohrt, Jeffrey S Duchin

ABSTRACT:
To describe the epidemiology of infant pertussis in King County, Washington, and to better understand the implications for tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination among older children, adolescents, and adults.


TITLE:
The association with DTwP vaccines and increased infant mortality in females may be due to vaccine adjuvants and Th2 polarizing effects.

ABSTRACT:
A number of mainly observational studies suggest that many African females below the age of one year die each year from the nonspecific effects of vaccination with diphtheria-tetanus toxoids and killed (whole-cell) Bordetella pertussis (DTwP). In contrast, similar studies suggest that many African females and males may have their lives saved each year by the nonspecific immunological benefits of Bacillus Calmette-Guerin (BCG) vaccination. From an immunological point of view, we hypothesise that the adverse effects of DTwP vaccine may occur because of the Th2-polarising effect of the aluminium phosphate adjuvant in the vaccine and because intramuscular administration of the vaccine may cause chronic inflammation at the site of injection. However, the Th1-polarising effect of BCG is likely to be beneficial. Sexual dimorphism affecting immune functions and vitamin A supplementation may influence both the deleterious and beneficial nonspecific effects of immunisation.


TITLE:
Aluminium based adjuvants caused cell death and the subsequent release of host cell DNA, which acts as a potent endogenous immunostimulatory signal mediating alum adjuvant activity.

AUTHORS:
Thomas Marichal, Keiichi Onata, Denis Bedoret, Claire Mesnil, Catherine Sabatel, Kouji Kobiyama, Pierre Lekeux, Cevayir Coban, Shizuo Akira, Ken J Ishii, Fabrice Bureau, Christophe J Desmet

ABSTRACT:
Aluminum-based adjuvants (aluminum salts or alum) are widely used in human vaccination, although their mechanisms of action are poorly understood. Here we report that, in mice, alum causes cell death and the subsequent release of host cell DNA, which acts as a potent endogenous immunostimulatory signal mediating alum adjuvant activity. Furthermore, we propose that host DNA signaling differentially regulates IgE and IgG1 production after alum-adjuvanted immunization. We suggest that, on the one hand, host DNA induces primary B cell responses, including IgG1 production, through interferon response factor 3 (Irf3)-independent mechanisms. On the other hand, we suggest that host DNA also stimulates 'canonical' T helper type 2 (T(H)2) responses, associated with IgE isotype switching and peripheral effector responses, through Irf3-dependent mechanisms. The finding that host DNA released from dying cells acts as a damage-associated molecular pattern that mediates alum adjuvant activity may increase our understanding of the mechanisms of action of current vaccines and help in the design of new adjuvants.


TITLE:
Development of fulminant Type 1 diabetes with thrombocytopenia after influenza vaccination has been observed.

AUTHORS:
H Yasuda, M Nagata, H Moriyama, H Kobayashi, T Akisaki, H Ueda, K Hara, K Yokono

ABSTRACT:
Fulminant Type 1 diabetes was originally reported as idiopathic Type 1 diabetes. Involvement of viral infections in the pathogenesis of fulminant T1D has been suggested, but the development of fulminant Type 1 diabetes after influenza vaccination has not been reported.


TITLE:
Adjuvants in vaccines may trigger innate cells response by toll-like receptors, thus eliciting a possible non-IgE mediated allergy phenomenon or causing B-cell activation and autoimmunity.

ABSTRACT:
Diagnosis of adverse effects caused by vaccines mainly includes investigative approaches based on skin tests, histamine, tryptase and serum IgE levels which should allow to diagnose an IgE-mediated allergy reaction, most caused by additive components. Incidence of vaccine-related allergy and anaphylaxis due to vaccination are very poorly represented among population, based on the latest epidemiological and safety reports. Notwithstanding, routinely allergy diagnostic tools show many pitfalls and contradictory results when used to highlight an allergy onset or a clinical manifestation recalling an hypersensitivity reaction. Furthermore, adjuvants in vaccines may trigger innate cells response by toll-like receptors, thus eliciting a possible non-IgE mediated allergy phenomenon or causing B-cell activation and autoimmunity. A cellular test, such as a basophil activation test, or more widely a flow cytometry analysis of immune cells, might add new insights to the comprehension of allergy due to vaccination , thus ameliorating the diagnostic endowment in the hand of physicians.


TITLE:
Annual influenza vaccination hampers the development of virus-specific CD8(+) T cell responses necessary to protect against influenza infection.

AUTHORS:
Rogier Bodewes, Pieter L A Fraaij, Martina M Geelhoed-Mieras, Carel A van Baalen, Harm A W M Tiddens, Annemarie M C van Rossum, Fiona R van der Klis, Ron A M Fouchier, Albert D ME Osterhaus, Guus F Rimmelzwaan

ABSTRACT:
Infection with seasonal influenza A viruses induces immunity to potentially pandemic influenza A viruses of other subtypes (heterosubtypic immunity). We recently demonstrated that vaccination against seasonal influenza prevented the induction of heterosubtypic immunity against influenza A/H5N1 virus induced by infection with seasonal influenza in animal models, which correlated with the absence of virus-specific CD8(+) T cell responses. Annual vaccination of all healthy children against influenza has been recommended, but the impact of vaccination on the development of the virus-specific CD8(+) T cell immunity in children is currently unknown. Here we compared the virus-specific CD8(+) T cell immunity in children vaccinated annually with that in unvaccinated children. In the present study, we compared influenza A virus-specific cellular and humoral responses of unvaccinated healthy control children with those of children with cystic fibrosis (CF) who were vaccinated annually. Similar virus-specific CD4(+) T cell and antibody responses were observed, while an age-dependent increase of the virus-specific CD8(+) T cell response that was absent in vaccinated CF children was observed in unvaccinated healthy control children. Our results indicate that annual influenza vaccination is effective against seasonal influenza but hampers the development of virus-specific CD8(+) T cell responses. The consequences of these findings are discussed in the light of the development of protective immunity to seasonal and future pandemic influenza viruses.


TITLE:
Flu vaccination causes measurable increases in inflammation in pregnant women which may increase the risk of preeclempsia and adverse outcomes such as preterm birth.

AUTHORS:
Lisa M Christian, Jay D Iams, Kyle Porter, Ronald Glaser

ABSTRACT:
In the U.S., seasonal trivalent influenza virus vaccine (TIV) is currently universally recommended for all pregnant women. However, data on the maternal inflammatory response to vaccination is lacking and would better delineate the safety and clinical utility of immunization. In addition, for research purposes, vaccination has been used as a mild immune trigger to examine in vivo inflammatory responses in nonpregnant adults. The utility of such a model in pregnancy is unknown. Given the clinical and empirical justifications, the current study examined the magnitude, time course, and variance in inflammatory responses following seasonal influenza virus vaccination among pregnant women.


TITLE:
Influenza vaccination has been reported to cause Miller Fisher syndrome.

AUTHORS:
Ashkan Shoamanesh, Kristine Chapman, Anthony Traboulsee

ABSTRACT:
Although postvaccination Guillain-Barré syndrome is commonly reported, there have only been 2 previously reported cases of postvaccination Miller Fisher syndrome, and none in association with the novel influenza A(H1N1) vaccine.


TITLE:
Conjugate vaccines may predispose children to autism spectrum disorders.

ABSTRACT:
The first conjugate vaccine was approved for use in the US in 1988 to protect infants and young children against the capsular bacteria Haemophilus influenzae type b (Hib). Since its introduction in the US, this vaccine has been approved in most developed countries, including Denmark and Israel where the vaccine was added to their national vaccine programs in 1993 and 1994, respectively. There have been marked increases in the reported prevalence of autism spectrum disorders (ASDs) among children in the US beginning with birth cohorts in the late 1980s and in Denmark and Israel starting approximately 4-5 years later. Although these increases may partly reflect ascertainment biases, an exogenous trigger could explain a significant portion of the reported increases in ASDs. It is hypothesized here that the introduction of the Hib conjugate vaccine in the US in 1988 and its subsequent introduction in Denmark and Israel could explain a substantial portion of the initial increases in ASDs in those countries. The continuation of the trend toward increased rates of ASDs could be further explained by increased usage of the vaccine, a change in 1990 in the recommended age of vaccination in the US from 15 to 2 months, increased immunogenicity of the vaccine through changes in its carrier protein, and the subsequent introduction of the conjugate vaccine for Streptococcus pneumoniae. Although conjugate vaccines have been highly effective in protecting infants and young children from the significant morbidity and mortality caused by Hib and S. pneumoniae, the potential effects of conjugate vaccines on neural development merit close examination. Conjugate vaccines fundamentally change the manner in which the immune systems of infants and young children function by deviating their immune responses to the targeted carbohydrate antigens from a state of hypo-responsiveness to a robust B2 B cell mediated response. This period of hypo-responsiveness to carbohydrate antigens coincides with the intense myelination process in infants and young children, and conjugate vaccines may have disrupted evolutionary forces that favored early brain development over the need to protect infants and young children from capsular bacteria.


TITLE:
There is a lack of evidence for the effectiveness of influenza vaccines in adults aged 65 years or older.

AUTHORS:
Michael T Osterholm, Nicholas S Kelley, Alfred Sommer, Edward A Belongia

ABSTRACT:
No published meta-analyses have assessed efficacy and effectiveness of licensed influenza vaccines in the USA with sensitive and highly specific diagnostic tests to confirm influenza.


TITLE:
Despite the CDC's current recommendation to vaccinate postpartum women before hospital discharge with the tetanus and diphtheria toxoids and acellular pertussis (Tdap) vaccine in order to prevent pertussis infection in their offspring, it does not reduce

AUTHORS:
Luis A Castagnini, C Mary Healy, Marcia A Rench, Susan H Wootton, Flor M Munoz, Carol J Baker

ABSTRACT:
Mothers often are the source of pertussis illness in young infants. The Centers for Disease Control and Prevention recommend tetanus and diphtheria toxoids and acellular pertussis (Tdap) vaccine for postpartum women before hospital discharge. In January 2008, this recommendation was implemented in a predominantly Hispanic, medically underserved population at Ben Taub General Hospital (BTGH) in Houston (hereafter the intervention population).


TITLE:
Aluminium hydroxide-induced macrophagic myofasciitis (MMF) associated with vaccination has been reported.

AUTHORS:
Elodie Passeri, Chiara Villa, Maryline Couette, Emmanuel Itti, Pierre Brugieres, Pierre Cesaro, Romain Kroum Gherardi, Anne-Catherine Bachoud-Levi, FranÃ§ois-JÃ©rÃ´me Authier

ABSTRACT:
Macrophagic myofasciitis (MMF) is characterized by specific muscle lesions assessing long-term persistence of aluminum hydroxide within macrophages at the site of previous immunization. Affected patients are middle-aged adults, mainly presenting with diffuse arthromyalgias, chronic fatigue, and cognitive dysfunction. Representative features of MMF-associated cognitive dysfunction (MACD) include (i) dysexecutive syndrome; (i) visual memory; (iii) left ear extinction at dichotic listening test. In present study we retrospectively evaluated the progression of MACD in 30 MMF patients. Most patients fulfilled criteria for non-amnestic/dysexecutive mild cognitive impairment, even if some cognitive deficits seemed unusually severe. MACD remained stable over time, although dysexecutive syndrome tended to worsen. Long-term follow-up of a subset of patients with 3 or 4 consecutive neuropsychological evaluations confirmed the stability of MACD with time, despite marked fluctuations.


TITLE:
Aluminium vaccine adjuvants appear to contribute to the rising prevalence of autism.

ABSTRACT:
Autism spectrum disorders (ASD) are serious multisystem developmental disorders and an urgent global public health concern. Dysfunctional immunity and impaired brain function are core deficits in ASD. Aluminum (Al), the most commonly used vaccine adjuvant, is a demonstrated neurotoxin and a strong immune stimulator. Hence, adjuvant Al has the potential to induce neuroimmune disorders. When assessing adjuvant toxicity in children, two key points ought to be considered: (i) children should not be viewed as "small adults" as their unique physiology makes them much more vulnerable to toxic insults; and (ii) if exposure to Al from only few vaccines can lead to cognitive impairment and autoimmunity in adults, is it unreasonable to question whether the current pediatric schedules, often containing 18 Al adjuvanted vaccines, are safe for children? By applying Hill's criteria for establishing causality between exposure and outcome we investigated whether exposure to Al from vaccines could be contributing to the rise in ASD prevalence in the Western world. Our results show that: (i) children from countries with the highest ASD prevalence appear to have the highest exposure to Al from vaccines; (ii) the increase in exposure to Al adjuvants significantly correlates with the increase in ASD prevalence in the United States observed over the last two decades (Pearson r=0.92, p<0.0001); and (iii) a significant correlation exists between the amounts of Al administered to preschool children and the current prevalence of ASD in seven Western countries, particularly at 3-4 months of age (Pearson r=0.89-0.94, p=0.0018-0.0248). The application of the Hill's criteria to these data indicates that the correlation between Al in vaccines and ASD may be causal. Because children represent a fraction of the population most at risk for complications following exposure to Al, a more rigorous evaluation of Al adjuvant safety seems warranted.


TITLE:
PCV2 infection is now widespread worldwide, and increasing numbers of disease conditions have been linked to PCV2 infection in pigs.

ABSTRACT:
The discovery of porcine circovirus type 2 (PCV2) in 1998 initiated intensive research on arguably the most economically important pathogen facing the global swine industry today. PCV2 infection is now widespread worldwide, and increasing numbers of disease conditions have been linked to PCV2 infection in pigs. In this special issue of Virus Research, leading experts in the field review the history, epidemiology, transmission, clinical and pathological features, immunology, pathogenesis, molecular biology and vaccine development of PCV2 and porcine circovirus associated disease (PCVAD). In addition, circovirus-like DNA sequences recently identified from humans and other animal species and their biological significances are also reviewed. The articles in this special issue identify gaps in current PCV2 research and offer insights for the direction of future research.


TITLE:
Autoimmunity following hepatitis B vaccine has been reported.

AUTHORS:
Yaron Zafrir, Nancy Agmon-Levin, Z Paz, T Shilton, Yehuda Shoenfeld

ABSTRACT:
In this study we analyzed the clinical and demographic manifestations among patients diagnosed with immune/autoimmune-mediated diseases post-hepatitis B vaccination. We aimed to find common denominators for all patients, regardless of different diagnosed diseases, as well as the correlation to the criteria of Autoimmune (Auto-inflammatory) Syndrome induced by Adjuvants (ASIA).


TITLE:
Possible systemic lupus erythematosus following HPV immunization has been reported.

ABSTRACT:
The link between autoimmunity and infectious agents has been strongly suggested by reports of lupus or lupus-like syndromes following immunization. This report describes three patients with either newly diagnosed systemic lupus erythematosus (SLE) or SLE flare, following vaccination for human papilloma virus (HPV). CASE 1: A 17-year-old female completed two doses of HPV vaccine uneventfully. Two months later, she developed arthralgias with pruritic rashes on both lower extremities, later accompanied by livedo reticularis, bipedal edema with proteinuria, anemia, leucopenia, hypocomplementemia and high titers of anti-nuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA). Kidney biopsy showed International Society of Nephrology/Renal Pathology Society Class III lupus nephritis. She was started on high dose steroids followed by pulse cyclophosphamide therapy protocol for lupus nephritis, and subsequently went into remission. CASE 2: A 45-year-old housewife, previously managed for 11 years as having rheumatoid arthritis, had been in clinical remission for a year when she received two doses of HPV immunization. Four months later, she developed fever accompanied by arthritis, malar rash, oral ulcers, recurrent ascites with intestinal pseudo-obstruction, and behavioral changes. Cranial MRI showed vasculitic lesions on the frontal and parietal lobes. Laboratory tests showed anemia with leucopenia, hypocomplementemia, proteinuria, ANA positive at 1:320, and antibodies against dsDNA, Ro/SSA, La/SSB and histone. She improved following pulse methylprednisolone with subsequent oral prednisone combined with hydroxychloroquine. CASE 3: A 58-year-old housewife diagnosed with SLE had been in clinical remission for 8 years when she received two doses of HPV immunization. Three months later, she was admitted to emergency because of a 1-week history of fever, malar rash, easy fatigability, cervical lymph nodes, gross hematuria and pallor. Laboratory exams showed severe anemia, thrombocytopenia, active urine sediments, and hypocomplementemia. Despite pulse steroid therapy, blood transfusions, intravenous immunoglobulin and aggressive resuscitative measures, she expired a day after hospital admission.


TITLE:
Mechanisms of aluminum adjuvant toxicity and autoimmunity in pediatric populations.

ABSTRACT:
Immune challenges during early development, including those vaccine-induced, can lead to permanent detrimental alterations of the brain and immune function. Experimental evidence also shows that simultaneous administration of as little as two to three immune adjuvants can overcome genetic resistance to autoimmunity. In some developed countries, by the time children are 4 to 6 years old, they will have received a total of 126 antigenic compounds along with high amounts of aluminum (Al) adjuvants through routine vaccinations. According to the US Food and Drug Administration, safety assessments for vaccines have often not included appropriate toxicity studies because vaccines have not been viewed as inherently toxic. Taken together, these observations raise plausible concerns about the overall safety of current childhood vaccination programs. When assessing adjuvant toxicity in children, several key points ought to be considered: (i) infants and children should not be viewed as "small adults" with regard to toxicological risk as their unique physiology makes them much more vulnerable to toxic insults; (ii) in adult humans Al vaccine adjuvants have been linked to a variety of serious autoimmune and inflammatory conditions (i.e., "ASIA"), yet children are regularly exposed to much higher amounts of Al from vaccines than adults; (iii) it is often assumed that peripheral immune responses do not affect brain function. However, it is now clearly established that there is a bidirectional neuro-immune cross-talk that plays crucial roles in immunoregulation as well as brain function. In turn, perturbations of the neuro-immune axis have been demonstrated in many autoimmune diseases encompassed in "ASIA" and are thought to be driven by a hyperactive immune response; and (iv) the same components of the neuro-immune axis that play key roles in brain development and immune function are heavily targeted by Al adjuvants. In summary, research evidence shows that increasing concerns about current vaccination practices may indeed be warranted. Because children may be most at risk of vaccine-induced complications, a rigorous evaluation of the vaccine-related adverse health impacts in the pediatric population is urgently needed.


TITLE:
Hepatitis B vaccine induces cell death in liver cells and mouse liver.

AUTHORS:
Heyam Hamza, Jianhua Cao, Xinyun Li, Changchun Li, Mengjin Zhu, Shuhong Zhao

ABSTRACT:
Vaccines can have adverse side-effects, and these are predominantly associated with the inclusion of chemical additives such as aluminum hydroxide adjuvant. The objective of this study was to establish an in vitro model system amenable to mechanistic investigations of cytotoxicity induced by hepatitis B vaccine, and to investigate the mechanisms of vaccine-induced cell death. The mouse liver hepatoma cell line Hepa1-6 was treated with two doses of adjuvanted (aluminium hydroxide) hepatitis B vaccine (0.5 and 1 ?g protein per ml) and cell integrity was measured after 24, 48 and 72 h. Hepatitis B vaccine exposure increased cell apoptosis as detected by flow cytometry and TUNEL assay. Vaccine exposure was accompanied by significant increases in the levels of activated caspase 3, a key effector caspase in the apoptosis cascade. Early transcriptional events were detected by qRT-PCR. We report that hepatitis B vaccine exposure resulted in significant upregulation of the key genes encoding caspase 7, caspase 9, Inhibitor caspase-activated DNase (ICAD), Rho-associated coiled-coil containing protein kinase 1 (ROCK-1), and Apoptotic protease activating factor 1 (Apaf-1). Upregulation of cleaved caspase 3,7 were detected by western blot in addition to Apaf-1 and caspase 9 expressions argues that cell death takes place via the intrinsic apoptotic pathway in which release of cytochrome c from the mitochondria triggers the assembly of a caspase activation complex. We conclude that exposure of Hepa1-6 cells to a low dose of adjuvanted hepatitis B vaccine leads to loss of mitochondrial integrity, apoptosis induction, and cell death, apoptosis effect was observed also in C2C12 mouse myoblast cell line after treated with low dose of vaccine (0.3, 0.1, 0.05 ?g/ml). In addition In vivo apoptotic effect of hepatitis B vaccine was observed in mouse liver.


TITLE:
The design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate.

AUTHORS:
Vittorio Demicheli, Alessandro Rivetti, Maria Grazia Debalini, Carlo Di Pietrantonj

ABSTRACT:
Mumps, measles and rubella (MMR) are serious diseases that can lead to potentially fatal illness, disability and death. However, public debate over the safety of the trivalent MMR vaccine and the resultant drop in vaccination coverage in several countries persists, despite its almost universal use and accepted effectiveness.


TITLE:
Rotavirus vaccines have been found contaminated with porcine circovirus.

AUTHORS:
Sarah M Gilliland, Lindsay Forrest, Heather Carre, Adrian Jenkins, Neil Berry, Javier Martin, Philip Minor, Silke Schepelmann

ABSTRACT:
DNA from porcine circovirus type 1 (PCV1) and 2 (PCV2) has recently been detected in two vaccines against rotaviral gastroenteritis from manufacturers A and B. We investigated if PCV1 sequences are present in other viral vaccines. We screened seeds, bulks and final vaccine preparations from ten manufacturers using qRT-PCR. We detected 3.8 × 10³ to 1.9 × 10? PCV1 DNA copies/milliliter in live poliovirus seeds for inactivated polio vaccine (IPV) from manufacturer A, however, following inactivation and purification, the finished IPV was PCV1-negative. PCV1 DNA was not detectable in live polio preparations from other vaccine producers. There was no detectable PCV1 DNA in the measles, mumps, rubella and influenza vaccines analysed including material supplied by manufacturer A. We confirmed that the PCV1 genome in the rotavirus vaccine from manufacturer A is near full-length. It contains two mutations in the PCV cap gene, which may result from viral adaptation to Vero cells. Bulks of this vaccine contained 9.8 × 10¹? to 1.8 × 10¹¹ PCV1 DNA copies/millilitre and between 4.1 × 10? and 5.5 × 10? DNA copies were in the final doses. We found traces of PCV1 and PCV2 DNA in the rotavirus vaccine from manufacturer B. This highlights the issue of vaccine contamination and may impact on vaccine quality control.


TITLE:
Increased risk (4.4 fold) of noninfluenza respiratory virus infections associated with receipt of inactivated influenza vaccine.

AUTHORS:
Benjamin J Cowling, Vicky J Fang, Hiroshi Nishiura, Kwok-Hung Chan, Sophia Ng, Dennis K M Ip, Susan S Chiu, Gabriel M Leung, J S Malik Peiris

ABSTRACT:
We randomized 115 children to trivalent inactivated influenza vaccine (TIV) or placebo. Over the following 9 months, TIV recipients had an increased risk of virologically-confirmed non-influenza infections (relative risk: 4.40; 95% confidence interval: 1.31-14.8). Being protected against influenza, TIV recipients may lack temporary non-specific immunity that protected against other respiratory viruses.


TITLE:
The pathogenic role of aluminium hydroxide is now recognized by the presence of chronic fatigue syndrome, macrophagic myofasciitis and subcutaneous pseudolymphoma, linked to intramuscular injection of aluminium hydroxide-containing vaccines.

AUTHORS:
Olivier Guillard, Bernard Fauconneau, Alain Pineau, Annie Marrauld, Jean-Pierre Bellocq, Marie-Pierre Chenard

ABSTRACT:
Aluminium hydroxide is used as an effective adjuvant in a wide range of vaccines for enhancing immune response to the antigen. The pathogenic role of aluminium hydroxide is now recognized by the presence of chronic fatigue syndrome, macrophagic myofasciitis and subcutaneous pseudolymphoma, linked to intramuscular injection of aluminium hydroxide-containing vaccines. The aim of this study is to verify if the subcutaneous pseudolymphoma observed in this patient in the site of vaccine injection is linked to an aluminium overload. Many years after vaccination, a subcutaneous nodule was discovered in a 45-year-old woman with subcutaneous pseudolymphoma. In skin biopsy at the injection site for vaccines, aluminium (Al) deposits are assessed by Morin stain and quantification of Al is performed by Zeeman Electrothermal Atomic Absorption Spectrophotometry. Morin stain shows Al deposits in the macrophages, and Al assays (in ?g/g, dry weight) were 768.10±18 for the patient compared with the two control patients, 5.61±0.59 and 9.13±0.057. Given the pathology of this patient and the high Al concentration in skin biopsy, the authors wish to draw attention when using the Al salts known to be particularly effective as adjuvants in single or repeated vaccinations. The possible release of Al may induce other pathologies ascribed to the well-known toxicity of this metal.


TITLE:
Over 40,000 cases of AFP are reported annually since 2007 regardless of the number of actual polio cases.

AUTHORS:
Rie R Yotsu, Katharine Abba, Helen Smith, Abhijit Das

ABSTRACT:
Cases of polio in India declined after the implementation of the polio eradication programme especially in these recent years. The programme includes surveillance of acute flaccid paralysis (AFP) to detect and diagnose cases of polio at early stage. Under this surveillance, over 40,000 cases of AFP are reported annually since 2007 regardless of the number of actual polio cases. Yet, not much is known about these children. We conducted a qualitative research to explore care and support for children with AFP after their diagnosis.


TITLE:
Vaccine-derived poliovirus may become pathogenic in complex viral ecosystems, through frequent recombination events and mutations.

AUTHORS:
Marie-Line Joffret, Sophie JÃ©gouic, MaÃ©l Bessaud, Jean Balanant, Coralie Tran, Valerie Caro, Barbara Holmblat, Richter Razafindratsimandresy, Jean-Marc Reynes, Mala Rakoto-Andrianarivelo, Francis Delpeyroux

ABSTRACT:
Five cases of poliomyelitis due to type 2 or 3 recombinant vaccine-derived polioviruses (VDPVs) were reported in the Toliara province of Madagascar in 2005.


TITLE:
We consider it likely that pandemrix vaccination contributed to the increased incidence of narcolepsy in Finland in 2010 in HLA DQB1*0602 positive children.

AUTHORS:
Markku Partinen, Outi Saarenpad-Heikkila, Ismo Ilveskoski, Christer Hublin, Miika Linna, Paivi OlsÃ©n, Pekka Nokelainen, Reija AlÃ©n, Tiina Wallden, Merimaaria Espo, Harri Rusanen, Jan Olme, Heli Satila, Harri Arikka, Pekka Kaipainen, Ilkka Julkunen, Turkka Kirjavainen

ABSTRACT:
Narcolepsy is a rare neurological sleep disorder especially in children who are younger than 10 years. In the beginning of 2010, an exceptionally large number of Finnish children suffered from an abrupt onset of excessive daytime sleepiness (EDS) and cataplexy. Therefore, we carried out a systematic analysis of the incidence of narcolepsy in Finland between the years 2002-2010.


TITLE:
Immune-mediated myelitis following hepatitis B vaccination has been reported.

ABSTRACT:
The hepatitis B virus (HBV) is an important international cause of infectious acute and chronic liver diseases. HBV vaccines were developed to combat the potential life-threatening effects of HBV infection. Published case histories, retrospective reviews and analyses of epidemiological data report on the onset of immune-mediated myelitis after recombinant HBV vaccination, mostly in adults with a presumed genetic/immunologic predisposition. However, HBV vaccination has not borne out to be a significant trigger of serious autoimmune events, including acute myelitis, in populations at large over prolonged observation periods after immunization. Published study methods lack the sensitivity to categorically establish a causal relationship between exposure to HBV vaccine components and immune mediated myelitis, but in practice the faint possibility of such a link should not be totally rejected.


TITLE:
Thirty-five percent of children with juvenile idiopathic arthritis experienced flare of the disease after vaccination.

AUTHORS:
Natasa Toplak, Vesna Subelj, Tanja Kveder, Sasa Cucnik, Katarina Prosenc, Alenka Trampus-Bakija, Ljupco Todorovski, Tadej Avcin

ABSTRACT:
Influenza vaccination in children with rheumatic diseases is often recommended, but not frequently performed. Our aim was to assess the safety and efficacy of annual influenza vaccination in a longitudinal follow-up study of an unselected group of children with juvenile idiopathic arthritis (JIA).


TITLE:
From 1990 to the present, the number of cases (n = 31) and deaths (n = 12) from the yellow fever vaccine in travelers has exceeded the reports of YF (n = 6) acquired by natural infection.

ABSTRACT:
The live, attenuated yellow fever (YF) 17D vaccine provides highly effective and durable immunity and is widely used for travelers to and residents of endemic areas of South America and Africa. Neurotropic and viscerotropic serious adverse events associated with these vaccines occur rarely, but YF 17D vaccine-associated viscerotropic disease (YEL-AVD) is notable for its lethality. There appear to be two distinct patterns of risk for YEL-AVD: the first in younger persons, particularly women, with defects in innate immunity, in whom the case-fatality rate is higher; and the second in elderly persons, particularly men with age-related immune senescence and a lower case-fatality rate. From 1990 to the present, the number of cases (n = 31) and deaths (n = 12) from YEL-AVD in travelers has exceeded the reports of YF (n = 6) acquired by natural infection, raising the question whether the risk of vaccination exceeds the benefit in travelers. To provide some guidance on this point, the rate of vaccine-related injury is compared with the rate of naturally acquired disease in a new analysis that estimates the immunologically susceptible denominator population in YF endemic and epidemic areas. For many years, the risk of vaccine-related illness and death was similar to the risk of illness and death from natural infection with YF in South America. Africa posed a substantially higher estimated risk of wild-type YF than vaccine-related injury. Multiple factors should be considered in making decisions about YF vaccination, including specific destination, season of the year, local evidence for YF transmission, likelihood of exposure to vector mosquitoes and individual risk factors for YEL-AVD, with the goal of increasing vaccine coverage for travel to high-risk areas and reducing unnecessary vaccination. Prospects for future, safer vaccines are also described.


TITLE:
Mumps outbreak among vaccinated university students associated with a large party, the Netherlands, 2010.

AUTHORS:
Katie Greenland, Jane Whelan, Ewout Fanoy, Marjon Borgert, Koen Hulshof, Kioe-Bing Yap, Corien Swaan, Tjibbe Donker, Rob van Binnendijk, Hester de Melker, Susan HahneÃ©

ABSTRACT:
We investigated a mumps outbreak within a highly vaccinated university student population in the Netherlands by conducting a retrospective cohort study among members of university societies in Delft, Leiden and Utrecht. We used an online questionnaire asking for demographic information, potential behavioural risk factors for mumps and the occurrence of mumps. Vaccine status from the national vaccination register was used. Overall, 989 students participated (20% response rate). Registered vaccination status was available for 776 individuals, of whom 760 (98%) had been vaccinated at least once and 729 (94%) at least twice. The mumps attack rate (AR) was 13.2% (95%CI 11.1-15.5%). Attending a large student party, being unvaccinated and living with more than 15 housemates were independently associated with mumps ((RR 42 (95%CI 10.1-172.4); 3.1 (95%CI 1.7-5.6) and 1.8 (95%CI 1.1-3.1), respectively). The adjusted VE estimate for two doses of MMR was 68% (95%CI 41-82%). We did not identify additional risk factors for mumps among party attendees. The most likely cause of this outbreak was intense social mixing during the party and the dense communal living environment of the students. High coverage of MMR vaccination in childhood did not prevent an outbreak of mumps in this student population.


TITLE:
In 2011, there were an extra 47,500 new cases of non-polio acute flaccid paralysis (NPAFP); Clinically indistinguishable from polio paralysis but twice as deadly, the incidence of NPAFP was directly proportional to doses of oral polio received.

ABSTRACT:
It was hoped that following polio eradication, immunisation could be stopped. However the synthesis of polio virus in 2002, made eradication impossible. It is argued that getting poor countries to expend their scarce resources on an impossible dream over the last 10 years was unethical. Furthermore, while India has been polio-free for a year, there has been a huge increase in non-polio acute flaccid paralysis (NPAFP). In 2011, there were an extra 47,500 new cases of NPAFP. Clinically indistinguishable from polio paralysis but twice as deadly, the incidence of NPAFP was directly proportional to doses of oral polio received. Though this data was collected within the polio surveillance system, it was not investigated. The principle of primum-non-nocere was violated. The authors suggest that the huge bill of US$ 8 billion spent on the programme, is a small sum to pay if the world learns to be wary of such vertical programmes in the future.


TITLE:
Neutralizing antibodies, elicited by the mouse brain-derived and formalin-inactivated JEV Nakayama vaccine among a limited number of vaccinees, have reduced neutralizing capacity against circulating GI virus.

AUTHORS:
Yi-Chin Fan, Jo-Mei Chen, Hsien-Chung Chiu, Yi-Ying Chen, Jen-Wei Lin, Chen-Chang Shih, Chih-Ming Chen, Chao-Chin Chang, Gwong-Jen J Chang, Shyan-Song Chiou

ABSTRACT:
Genotype I (GI) Japanese encephalitis virus (JEV) that replaced GIII virus has become the dominant circulating virus in Asia. Currently, all registered live and inactivated JEV vaccines are derived from genotype III viruses. In Taiwan, the compulsory JEV vaccination policy recommends that children receives four doses of formalin-inactivated Nakayama (GIII) JEV vaccine.


TITLE:
Case report: a shoulder injury related to vaccine administration.

AUTHORS:
Matthew G Barnes, Christopher Ledford, Karen Hogan

ABSTRACT:
A 22-year-old woman with no significant medical history developed acute left shoulder pain and severe restrictions in range of motion after a seasonal influenza vaccine injection. Imaging by MRI, approximately 8 weeks after the injection, and by ultrasound, approximately 9.5 weeks after the injection demonstrated contusions on the humerus, injury of the supraspinatus, and effusion in the subacromial bursa. Her reaction was reported to the Vaccine Adverse Event Reporting System as a case of shoulder injury related to vaccine administration, likely due to injection of the influenza vaccine into the subacromial bursa. This case serves as a catalyst for discussion regarding vaccination technique and the potential to prevent complications arising from vaccine overpenetration.


TITLE:
Reactivation of Herpes Zoster Keratitis in an Adult After Varicella Zoster Vaccination.

AUTHORS:
Charles W Hwang, Walter A Steigleman, Erika Saucedo-Sanchez, Sonal S Tuli

ABSTRACT:
In this study, the case of a patient who presented with reactivation of herpes zoster (HZ) keratitis and worsening of neurotrophic keratopathy, keratouveitis, and keratoconjunctivitis sicca after vaccination with live attenuated HZ vaccine (Zostavax) is described.


TITLE:
Mumps orchitis occurs vaccinated postpubertal males.

AUTHORS:
Bum Sik Tae, Byeong Kuk Ham, Jae Heon Kim, Jae Young Park, Jae Hyun Bae

ABSTRACT:
Although the measles-mumps-rubella vaccination covers most children against mumps in Korea, the development of mumps has been reported. However, the clinical manifestations of mumps orchitis in postpubertal vaccinated patients have never been investigated. Herein we report the clinical features of mumps orchitis in postpubertal vaccinated patients.


TITLE:
C-reactive protein (CRP) elevation occur in infants without sepsis after hepatitis B vaccination.

AUTHORS:
Istemi Han Celik, Gamze Demirel, Fuat Emre Canpolat, Omer Erdeve, Ugur Dilmen

ABSTRACT:
Hepatitis B virus (HBV) infection continues to be a serious global health problem. During the course of HBV vaccination, we observed C-reactive protein (CRP) elevation in term infants without sepsis. Therefore, we prospectively studied interleukin-6 (IL-6) and CRP responses to HBV immunization. In 70 healthy term infants without signs and symptoms of sepsis and sepsis risk factors, IL-6, CRP, and white blood cell count levels were determined before and 24 h after immunization. Significant increases in CRP levels were seen 24 h after vaccination (p?<?0.001). Although CRP levels of 22 infants at second evaluation were above the cutoff level for sepsis (4.82 mg/L), they had no clinical signs and symptoms of sepsis. After 48-72 h, CRP levels of these infants returned to normal levels with no blood culture positivity.


TITLE:
Acute optic neuritis is a rare complication of MR vaccination and may occur early after immunization.

ABSTRACT:
To report two cases of optic neuritis with onset less than 24 hours following measles-rubella (MR) vaccination.


TITLE:
Risk of Guillain-Barre syndrome after 2010-2011 influenza vaccination.

AUTHORS:
Francesca Galeotti, Marco Massari, Roberto D'Alessandro, Ettore Beghi, Adriano Chio, Giancarlo Logroscino, Graziella Filippini, Maria Donata Benedetti, Maura Pugliatti, Carmela Santuccio, Roberto Raschetti,

ABSTRACT:
Influenza vaccination has been implicated in Guillain Barré Syndrome (GBS) although the evidence for this link is controversial. A case-control study was conducted between October 2010 and May 2011 in seven Italian Regions to explore the relation between influenza vaccination and GBS. The study included 176 GBS incident cases aged ?18 years from 86 neurological centers. Controls were selected among patients admitted for acute conditions to the Emergency Department of the same hospital as cases. Each control was matched to a case by sex, age, Region and admission date. Two different analyses were conducted: a matched case-control analysis and a self-controlled case series analysis (SCCS). Case-control analysis included 140 cases matched to 308 controls. The adjusted matched odds ratio (OR) for GBS occurrence within 6 weeks after influenza vaccination was 3.8 (95 % CI: 1.3, 10.5). A much stronger association with gastrointestinal infections (OR = 23.8; 95 % CI 7.3, 77.6) and influenza-like illness or upper respiratory tract infections (OR = 11.5; 95 % CI 5.6, 23.5) was highlighted. The SCCS analysis included all 176 GBS cases. Influenza vaccination was associated with GBS, with a relative risk of 2.1 (95 % CI 1.1, 3.9). According to these results the attributable risk in adults ranges from two to five GBS cases per 1,000,000 vaccinations.


TITLE:
Chart-confirmed Guillain-Barre syndrome after 2009 H1N1 influenza vaccination among the Medicare population, 2009-2010.

AUTHORS:
Laura L Polakowski, Sukhminder K Sandhu, David B Martin, Robert Ball, Thomas E Macurdy, Riley L Franks, Jonathan M Gibbs, Garner F Kropp, Armen Avagyan, Jeffrey A Kelman, Christopher M Worrall, Guoying Sun, Rebecca E Kliman, Dale R Burwen

ABSTRACT:
Given the increased risk of Guillain-Barré Syndrome (GBS) found with the 1976 swine influenza vaccine, both active surveillance and end-of-season analyses on chart-confirmed cases were performed across multiple US vaccine safety monitoring systems, including the Medicare system, to evaluate the association of GBS after 2009 monovalent H1N1 influenza vaccination. Medically reviewed cases consisted of H1N1-vaccinated Medicare beneficiaries who were hospitalized for GBS. These cases were then classified by using Brighton Collaboration diagnostic criteria. Thirty-one persons had Brighton level 1, 2, or 3 GBS or Fisher Syndrome, with symptom onset 1-119 days after vaccination. Self-controlled risk interval analyses estimated GBS risk within the 6-week period immediately following H1N1 vaccination compared with a later control period, with additional adjustment for seasonality. Our results showed an elevated risk of GBS with 2009 monovalent H1N1 vaccination (incidence rate ratio = 2.41, 95% confidence interval: 1.14, 5.11; attributable risk = 2.84 per million doses administered, 95% confidence interval: 0.21, 5.48). This observed risk was slightly higher than that seen with previous seasonal influenza vaccines; however, additional results that used a stricter case definition (Brighton level 1 or 2) were not statistically significant, and our ability to account for preceding respiratory/gastrointestinal illness was limited. Furthermore, the observed risk was substantially lower than that seen with the 1976 swine influenza vaccine.


TITLE:
An Italian study found that 61% of women experienced an adverse event after the administration of the first dose of HPV vaccine.

AUTHORS:
Stefania Spila-Alegiani, Roberto Da Cas, Cristina Giambi, Roberto Raschetti, Stefania Salmaso

ABSTRACT:
We carried out an active surveillance of common adverse events occurring among women (9 to 26 years old) receiving human papillomavirus vaccine (Gardasil® and Cervarix®) in 9 Italian Regions.


TITLE:
Acute immune thrombocytopenic purpura as adverse reaction to oral polio vaccine (OPV).

AUTHORS:
Cheng-Qiang Jin, Hai-Xin Dong, Zhuo-Xiang Sun, Jian-Wei Zhou, Cui-Yun Dou, Shu-Hua Lu, Rui-Rui Yang

ABSTRACT:
A case of acute immune thrombocytopenic purpura following oral polio vaccine (OPV) is reported. An 82-d-old infant developed purpura at the same day after the second dose of oral polio vaccine. Until the time of hospital admission, the male infant had been in good health and had not received any drugs, and the possible causes of this condition were excluded. His platelet count was 13×10(9)/L. Platelet-associated IgG was elevated, but the amount of megakaryocytes in bone marrow aspirates was within the normal range, suggesting immune mechanism-associated thrombocytopenia. The infant recovered with the proper treatment within 30 d. Attention should be paid to OPV-associated thrombocytopenia, though it seems to be less frequent than after natural infections.


TITLE:
Human papilloma virus vaccine and primary ovarian failure: another facet of the autoimmune/inflammatory syndrome induced by adjuvants.

AUTHORS:
Serena Colafrancesco, Carlo Perricone, Lucija Tomijenovic, Yenuda Shoenfeld

ABSTRACT:
Post-vaccination autoimmune phenomena are a major facet of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) and different vaccines, including HPV, have been identified as possible causes.


TITLE:
Repetitive administration of aluminium to neonatal mice in amounts comparable to those to children receive via routine vaccinations result in neurodisruptive effects.

AUTHORS:
Christopher A Shaw, Y Li, Lucija Tomljenovic

ABSTRACT:
Our previous ecological studies of autism spectrum disorder (ASD) has demonstrated a correlation between increasing ASD rates and aluminium (Al) adjuvants in common use in paediatric vaccines in several Western countries. The correlation between ASD rate and Al adjuvant amounts appears to be dose-dependent and satisfies 8 of 9 Hill criteria for causality. We have now sought to provide an animal model to explore potential behavioural phenotypes and central nervous system (CNS) alterations using s.c. injections of Al hydroxide in early postnatal CD-1 mice of both sexes. Injections of a "high" and "low" Al adjuvant levels were designed to correlate to either the U.S. or Scandinavian paediatric vaccine schedules vs. control saline-injected mice. Both male and female mice in the "high Al" group showed significant weight gains following treatment up to sacrifice at 6 months of age. Male mice in the "high Al" group showed significant changes in light-dark box tests and in various measures of behaviour in an open field. Female mice showed significant changes in the light-dark box at both doses, but no significant changes in open field behaviours. These current data implicate Al injected in early postnatal life in some CNS alterations that may be relevant for a better understanding of the aetiology of ASD.


TITLE:
Vaccine-induced anti-HA2 antibodies promote virus fusion and enhance influenza virus respiratory disease.

AUTHORS:
Surender Khurana, Crystal L Loving, Jody Manischewitz, Lisa R King, Phillip C Gauger, Jamie Henningson, Amy L Vincent, Hana Golding

ABSTRACT:
Vaccine-induced disease enhancement has been described in connection with several viral vaccines in animal models and in humans. We investigated a swine model to evaluate mismatched influenza vaccine-associated enhanced respiratory disease (VAERD) after pH1N1 infection. Vaccinating pigs with whole inactivated H1N2 (human-like) virus vaccine (WIV-H1N2) resulted in enhanced pneumonia and disease after pH1N1 infection. WIV-H1N2 immune sera contained high titers of cross-reactive anti-pH1N1 hemagglutinin (HA) antibodies that bound exclusively to the HA2 domain but not to the HA1 globular head. No hemagglutination inhibition titers against pH1N1 (challenge virus) were measured. Epitope mapping using phage display library identified the immunodominant epitope recognized by WIV-H1N2 immune sera as amino acids 32 to 77 of pH1N1-HA2 domain, close to the fusion peptide. These cross-reactive anti-HA2 antibodies enhanced pH1N1 infection of Madin-Darby canine kidney cells by promoting virus membrane fusion activity. The enhanced fusion activity correlated with lung pathology in pigs. This study suggests a role for fusion-enhancing anti-HA2 antibodies in VAERD, in the absence of receptor-blocking virus-neutralizing antibodies. These findings should be considered during the evaluation of universal influenza vaccines designed to elicit HA2 stem-targeting antibodies.


TITLE:
Influenza vaccination did not reduce the risk of subsequent hospital admission among patients with vaccine failure. These findings do not support the hypothesis that vaccination mitigates influenza illness severity.

AUTHORS:
Huong Q McLean, Jennifer K Meece, Edward A Belongia

ABSTRACT:
Influenza vaccine is moderately effective for preventing influenza illness. It is not known if vaccination reduces the risk of subsequent hospital admission among patients with vaccine failure and laboratory confirmed influenza illness.


TITLE:
There is evidence supporting an association between increasing organic-Hg exposure from Thimerosal-containing childhood vaccines and the subsequent risk of an ASD.

AUTHORS:
David A Geier, Brian S Hooker, Janet K Kern, Paul G King, Lisa K Sykes, Mark R Geier

ABSTRACT:
Autism spectrum disorder (ASD) is defined by standardized criteria of qualitative impairments in social interaction, qualitative impairments in communication, and restricted and stereotyped patterns of behavior, interests, and activities. A significant number of children diagnosed with ASD suffer a loss of previously-acquired skills, which is suggestive of neurodegeneration or a type of progressive encephalopathy with an etiological pathogenic basis occurring after birth. To date, the etiology of ASD remains under debate, however, many studies suggest toxicity, especially from mercury (Hg), in individuals diagnosed with an ASD. The present study evaluated concerns about the toxic effects of organic-Hg exposure from Thimerosal (49.55% Hg by weight) in childhood vaccines by conducting a two-phased (hypothesis generating/hypothesis testing) study with documented exposure to varying levels of Thimerosal from vaccinations.


TITLE:
This review found evidence of a causal relationship between HPV vaccine and autoimmune diseases in a few cases in the examined studies, and the risk vs. benefit of vaccination is still to be solved.

AUTHORS:
Paolo Pellegrino, Carla Carnovale, Marco Pozzi, Stefania Antoniazzi, Valentina Perrone, Dionigi Salvati, Marta Gentili, Tatiana Brusadelli, Emilio Clementi, Sonia Radice

ABSTRACT:
The human papilloma virus (HPV) vaccines were introduced to reduce the incidence of cervical cancer. The bivalent vaccine is effective against HPV-16, -18, -31, -33 and -45 while the quadrivalent vaccine is effective against HPV-16, 18, 31, 6 and 11 types. The immunisation, recommended for adolescent females, has led to high vaccine coverage in many countries. Along with the introduction of the HPV vaccines, several cases of onset or exacerbations of autoimmune diseases following the vaccine shot have been reported in the literature and pharmacovigilance databases, triggering concerns about its safety. This vaccination programme, however, has been introduced in a population that is at high risk for the onset of autoimmune diseases, making it difficult to assess the role of HPV vaccine in these cases and no conclusive studies have been reported thus far. We have thus analysed and reviewed comprehensively all case reports and studies dealing with either the onset of an autoimmune disease in vaccinated subject or the safety in patients with autoimmune diseases to define the role of the HPV vaccines in these diseases and hence its safety. A solid evidence of causal relationship was provided in few cases in the examined studies, and the risk vs. benefit of vaccination is still to be solved. The on-going vigilance for the safety of this vaccine remains thus of paramount importance.


TITLE:
Case report: an outbreak of measles among persons with prior evidence of immunity, New York City, 2011.

AUTHORS:
Jennifer B Rosen, Jennifer S Rota, Carole J Hickman, Sun B Sowers, Sara Mercader, Paul A Rota, William J Bellini, Ada J Huang, Margaret K Doll, Jane R Zucker, Christopher M Zimmerman

ABSTRACT:
Measles was eliminated in the United States through high vaccination coverage and a public health system able to rapidly respond to measles. Measles may occur among vaccinated individuals, but secondary transmission from such individuals has not been documented.


TITLE:
Difficulties in eliminating measles and controlling rubella and mumps in a 99% measles vaccine compliant population.

AUTHORS:
Zhifang Wang, Rui Yan, Hanging He, Qian Li, Guohua Chen, Shengxu Yang, Enfu Chen

ABSTRACT:
The reported coverage of the measles-rubella (MR) or measles-mumps-rubella (MMR) vaccine is greater than 99.0% in Zhejiang province. However, the incidence of measles, mumps, and rubella remains high. In this study, we assessed MMR seropositivity and disease distribution by age on the basis of the current vaccination program, wherein the first dose of MR is administered at 8 months and the second dose of MMR is administered at 18-24 months.


TITLE:
Thimerosal had a proapoptotic effect on primary human lymphocytes at concentrations 100 times less to those contained in the multidose vaccine.

AUTHORS:
Emily Loison, BÃ©atrice Poirier-Beaudouin, ValÃ©rie Seffer, Audrey Paoletti, Vered Abitbol, Eric Tartour, Odile Launay, Marie-Lise Gougeon

ABSTRACT:
Thimerosal is a preservative used widely in vaccine formulations to prevent bacterial and fungal contamination in multidose vials of vaccine. Thimerosal was included in the multidose non-adjuvanted pandemic 2009 H1N1 vaccine Panenza. In the context of the analysis of the ex-vivo T cell responses directed against influenza vaccine, we discovered the in vitro toxicity Panenza, due to its content in thimerosal. Because thimerosal may skew the immune response to vaccines, we investigated in detail the ex-vivo effects of thimerosal on the fate and functions of T cells in response to TCR ligation. We report that ex-vivo exposure of quiescent or TCR-activated primary human T cells to thimerosal induced a dose-dependent apoptotic cell death associated with depolarization of mitochondrial membrane, generation of reactive oxygen species, cytochrome c release from the mitochondria and caspase-3 activation. Moreover, exposure to non-toxic concentrations of thimerosal induced cell cycle arrest in G0/G1 phase of TCR-activated T cells, and inhibition of the release of proinflammatory cytokines such as IFN gamma, IL-1 beta, TNF alpha, IL-2, as well as the chemokine MCP1. No shift towards Th2 or Th17 cells was detected. Overall these results underline the proapoptotic effect of thimerosal on primary human lymphocytes at concentrations 100 times less to those contained in the multidose vaccine, and they reveal the inhibitory effect of this preservative on T-cell proliferation and functions at nanomolar concentrations.


TITLE:
In this animal study measles vaccine did not prevent infection or disease against wild type MeV.

AUTHORS:
Wen-Hsuan W Lin, Chien-Hsiung Pan, Robert J Adams, Beth L Laube, Diane E Griffin

ABSTRACT:
Infection with wild-type measles virus (MeV) induces lifelong protection from reinfection, and parenteral delivery of the live attenuated measles vaccine (LAV) also provides protection from measles. The level of neutralizing antibody is a good indicator of protection, but the independent roles of MeV-specific antibody and T cells have not been identified. In this study, macaques immunized with LAV through a nebulizer and a mouthpiece developed MeV-specific T-cell responses but not neutralizing antibodies. Upon challenge with wild-type MeV, these animals developed rashes and viremias similar to those in naive animals but cleared viral RNA from blood 25 to 40 days faster. The nebulizer-immunized animals also had more robust MeV-specific CD4(+) and CD8(+) T-cell responses than the naive animals after challenge, characterized by a higher number and better durability of gamma interferon (IFN-?)-producing cells. Induction of MeV-specific circulating CD4(+) and CD8(+) T cells capable of producing multiple cytokines correlated with clearance of viral RNA in the nebulizer-immunized macaques. These studies demonstrated that MeV-specific T-cell immunity alone did not prevent measles, but T-cell priming enhanced the magnitude, durability, and polyfunctionality of MeV-specific T cells after challenge infection and correlated with more rapid clearance of MeV RNA. IMPORTANCE The components of vaccine-induced immunity necessary for protection from infection and disease have not been clearly identified for most vaccines. Vaccine development usually focuses on induction of antibody, but T-cell-based vaccines are also under development. The live attenuated measles vaccine (LAV) given subcutaneously induces both T cells and neutralizing antibody and provides solid protection from infection. LAV delivered to the upper respiratory tract through a nebulizer and mouthpiece induced a T-cell response but no neutralizing antibody. These T-cell-primed macaques demonstrated no protection from rash or viremia when challenged with wild-type MeV, but viral RNA was cleared more rapidly than in unimmunized animals. Thus, T-cell immunity did not protect from infection or acute disease but facilitated virus clearance during recovery. These studies demonstrate the importance and independent roles of T cells and antibody in protection and recovery from measles.


TITLE:
An association between Pandemrix vaccination and narcolepsy has been observed in Finland and Sweden

AUTHORS:
D O'Flanagan, A S Barret, M Foley, S Cotter, C Bonner, C Crowe, B Lynch, B Sweeney, H Johnson, B McCoy, E Purcell

ABSTRACT:
In 2011, the Irish Medicines Board received reports of onset of narcolepsy following vaccination against influenza A(H1N1)pdm09 with Pandemrix. A national steering committee was convened to examine the association between narcolepsy and pandemic vaccination. We conducted a retrospective population-based cohort study. Narcolepsy cases with onset from 1 April 2009 to 31 December 2010 were identified through active case finding. Narcolepsy history was gathered from medical records. Pandemic vaccination status was obtained from vaccination databases. Two independent experts classified cases using the Brighton case definition. Date of onset was defined as date of first healthcare contact for narcolepsy symptoms. Incidence of narcolepsy in vaccinated and non-vaccinated individuals was compared. Of 32 narcolepsy cases identified, 28 occurred in children/adolescents and for 24 first healthcare contact was between April 2009 and December 2010. Narcolepsy incidence was 5.7 (95% confidence interval (CI): 3.4–8.9) per 100,000 children/adolescents vaccinated with Pandemrix and 0.4 (95% CI: 0.1–1.0) per 100,000 unvaccinated children/adolescents (relative risk: 13.9; absolute attributable risk: 5.3 cases per 100,000 vaccinated children/adolescents). This study confirms the crude association between Pandemrix vaccination and narcolepsy as observed in Finland and Sweden. The vaccine is no longer in use in Ireland. Further studies are needed to explore the immunogenetic mechanism of narcolepsy.


TITLE:
High antibody titres against predicted Mycoplasma surface proteins do not prevent sequestration in infected lung tissue in the course of experimental contagious bovine pleuropneumonia.

AUTHORS:
Elise Schieck, Anne Liljander, Carl Hamsten, Nimmo Gicheru, Massimo Scacchia, Flavio Sacchini, Martin Heller, Christiane Schnee, Anja Sterner-Kock, Andreas Hlinak, Jan Naessens, Jane Poole, Anja Persson, Joerg Jores

ABSTRACT:
Contagious bovine pleuropneumonia (CBPP), a severe respiratory disease of cattle caused by Mycoplasma mycoides subsp. mycoides (Mmm) is endemic in many African countries due to fragmented veterinary services and the lack of an efficient vaccine and sensitive diagnostics. More efficient tools to control the disease are needed, but to develop the tools, a better understanding of host-pathogen interactions is necessary. The aim of this study was to characterize the kinetics of the humoral immune response against 65 Mmm surface antigens for an extended period in cattle that survived a primary infection with Mmm. We describe clinical and haematological outcomes, and dissect the humoral immune response over time, to specific antigens and compared the antibody responses between different pathomorphological outcomes. No antigen-specific antibodies correlating with protection were identified. Interestingly we found that animals that developed Mycoplasma-containing sequestra had significantly higher antibody levels against proteins comprising the surface proteome than the animals that cleared Mycoplasma from their lungs. Based on these data we suggest that high antibody titres might play a role in the establishment of pathomorphological changes, such as vasculitis, which should be investigated in future studies. Beneficial antibody specificities and cellular immune responses need to be identified in order to foster the development of an improved vaccine in the future.


TITLE:
Vaccines with Thimerosal led to more adverse events in this study.

AUTHORS:
Nguyen Trong Hieu, Michal Sarnecki, Jeroen Tolboom

ABSTRACT:
To evaluate the safety and immunogenicity of the thiomersal-free (TF) and thiomersal-containing (TC) formulations of Hepavax-Gene in healthy Vietnamese neonates.


TITLE:
A post vaccine case report involving an adverse event and the presence of a microdeletion of chromosome 22 linked to the DiGeorge syndrome.

AUTHORS:
Mariella Valenzise, Antonio Cascio, Malgorzata Wasniewska, Giuseppina Zirilli, Maria Ausilia Catena, Stefania Arasi

ABSTRACT:
We describe a case of a 15-month-old female child admitted to our hospital because of fever, rash, neurological signs (oscillation between states of irritability and drowsiness), palpebral edema and drooping eyelid, appeared 10 days after the vaccination for measles, mumps and rubella. Brain MRI images showed multiple bilateral hyperintense lesions in the white matter typical of acute disseminated encephalomyelitis (ADEM), an autoimmune demyelinating disorder with inflammatory lesions of the central nervous system, due to viral antigens or vaccines. In the mean time, because of patient's vague phenotypic manifestations, suggestive of a genetic defect, array comparative genomic hybridization was carried out which showed the presence of a microdeletion 22q11.21, linked to the DiGeorge syndrome. Our case suggests that pediatric cases of post-vaccination ADEM, in which neurological signs persist, should be investigated for genetic phenotypical features, in order to exclude the presence of a genetic syndrome or disease.


TITLE:
Vaccination of any type was associated with an increased risk of CNS ADS onset within the first 30 days after vaccination only in younger (<50 years) individuals (OR, 2.32; 95% Cl, 1.18-4.57).

AUTHORS:
Annette Langer-Gould, Lei Qian, Sara Y Tartof, Sonu M Brara, Steven J Jacobsen, Brandon E Beaber, Lina S Sy, Chun Chao, Rulin Hechter, Hung Fu Tseng

ABSTRACT:
Because vaccinations are common, even a small increased risk of multiple sclerosis (MS) or other acquired central nervous system demyelinating syndromes (CNS ADS) could have a significant effect on public health.


TITLE:
Increasing organic Hg exposure from Thimerosal-containing vaccines increased the subsequent risk of pervasive developmental disorder diagnosis.

AUTHORS:
David A Geier, Janet K Kern, Paul G King, Lisa K Sykes, Mark R Geier

ABSTRACT:
Thimerosal is an organic mercury (Hg)-containing compound (49.55 % Hg by weight) historically added to many multi-dose vials of vaccine as a preservative. A hypothesis testing case-control study evaluated automated medical records in the Vaccine Safety Datalink (VSD) for organic Hg exposure from Thimerosal in Haemophilus influenzae type b (Hib)-containing vaccines administered at specific times within the first 15 months of life among subjects diagnosed with pervasive developmental disorder (PDD) (n?=?534) in comparison to controls. The generally accepted biologically non-plausible linkage between Thimerosal exposure and subsequent diagnosis of febrile seizure (n?=?5886) was examined as a control outcome. Cases diagnosed with PDD received significantly more organic Hg within the first 6 months of life (odds ratio (OR)?=?1.97, p?<?0.001) and first 15 months of life (OR?=?3.94, p?<?0.0001) than controls, whereas cases diagnosed with febrile seizure were no more likely than controls to have received increased organic Hg. On a per microgram of organic Hg basis, cases diagnosed with a PDD in comparison to controls were at significantly greater odds (OR?=?1.0197, p?<?0.0001) of receiving increasing organic Hg exposure within the first 15 months of life, whereas cases diagnosed febrile seizure were no more likely than controls (OR?=?0.999, p?>?0.20) to have received increasing organic Hg exposure within the first 15 months of life. Routine childhood vaccination is an important public health tool to reduce the morbidity and mortality associated with infectious diseases, but the present study provides new epidemiological evidence of a significant relationship between increasing organic Hg exposure from Thimerosal-containing vaccines and the subsequent risk of PDD diagnosis in males and females.


TITLE:
This study suggests that in some cases chronic fatigue and fibromyalgia can be temporally related to immunization, as part of ASIA syndrome.

AUTHORS:
Nancy Agmon-Levin, Yaron Zafrir, Shaye Kivity, Ari Balofsky, Howard Amital, Yehuda Shoenfeld

ABSTRACT:
The objectives of this study were to gather information regarding demographic and clinical characteristics of patients diagnosed with either fibromyalgia (FM) or chronic fatigue (CFS) following hepatitis B vaccination (HBVv) and furthermore to apply the recently suggested criteria of autoimmune (auto-inflammatory) syndromes induced by adjuvants (ASIA), in the aim of identifying common characteristics that may suggest an association between fibromyalgia, chronic fatigue and HBV vaccination. Medical records of 19 patients with CFS and/or fibromyalgia following HBVv immunization were analyzed. All of which were immunized during 1990-2008 in different centers in the USA. All medical records were evaluated for demographics, medical history, the number of vaccine doses, as well as immediate and long term post-immunization adverse events and clinical manifestations. In addition, available blood tests, imaging results, treatments and outcomes were analyzed. ASIA criteria were applied to all patients. The mean age of patients was 28.6 ± 11 years, of which 68.4 % were females. 21.05 % had either personal or familial background of autoimmune disease. The mean latency period from the last dose of HBVv to onset of symptoms was 38.6 ± 79.4 days, ranging from days to a year. Eight (42.1 %) patients continued with the immunization program despite experiencing adverse events. Manifestations that were commonly reported included neurological manifestations (84.2 %), musculoskeletal (78.9 %), psychiatric (63.1 %), fatigue (63.1 %), gastrointestinal complains (58 %) and mucocutaneous manifestations (36.8 %). Autoantibodies were detected in 71 % of patients tested. All patients fulfilled the ASIA criteria. This study suggests that in some cases CFS and FM can be temporally related to immunization, as part of ASIA syndrome. The appearance of adverse event during immunization, the presence of autoimmune susceptibility and higher titers of autoantibodies all can be suggested as risk factors. ASIA criteria were fulfilled in all patients eluding the plausible link between ASIA and CFS/FM.


TITLE:
This study supports an association between increasing exposure from thimerosal containing childhood vaccines and the subsequent risk of specific delays in development among males and females.

AUTHORS:
David A Geier, Janet K Kern, Brian S Hooker, Paul G King, Lisa K Sykes, Mark R Geier

ABSTRACT:
Within the first 3 years of life, the brain develops rapidly. Its development is characterized by critical developmental periods for speech, vision, hearing, language, balance, etc.; and alteration in any of the processes occurring in those critical periods can lead to specific delays in development.


TITLE:
This review concludes that chronic adjuvant stimulation may lead to lymphoma.

ABSTRACT:
The emerging epidemic of Hodgkin and non-Hodgkin lymphomas worldwide continues to defy our understanding and forces the search for the causative factors. Adjuvants are known to act as triggers of immune and inflammatory responses. Animal experiments have demonstrated that long-term inflammation is related to aggravation of the immune network resulting in cellular and humoral responses leading to autoimmunity and lymphoma development. Chronic stimulation of the immune system is thought to be the key mechanism through which infectious diseases as well as autoimmune diseases can lead to lymphomagenesis. Many adjuvants can act similarly perturbing immune system's function, inducing a state of prolonged immune activation related to chronic lymphatic drainage. Several mechanisms were proposed by which adjuvants induce inflammation, and they are discussed herein. Some of them are triggering inflammasome; others bind DNA, lipid moieties in cells, induce uric acid production or act as lipophilic and/or hydrophobic substances. The sustained inflammation increases the risk of genetic aberrations, where the initial polyclonal activation ends in monoclonality. The latter is the hallmark of malignant lymphoma. Thus, chronic adjuvant stimulation may lead to lymphoma.


TITLE:
Rabies encephalitis in a child: a failure of rabies post exposure prophylaxis?

AUTHORS:
Faten Tinsa, Aida Borgi, Imen Jahouat, Khadija Boussetta

ABSTRACT:
Rabies remains a serious public health problem in many developing countries. The diagnosis is easy when a non-immunised patient presents with hydrophobia and hypersalivation after a bite by a known rabid animal but more difficult when a patient presents atypical symptoms after having received rabies postexposure prophylaxis. Rabies postexposure prophylaxis failure is rare. We report a case of a 6-year-old boy who presented febrile seizure with agitation and cerebellar signs, without hydrophobia or hypersalivation, 17 days after a dog bite. Despite four doses of rabies vaccine and immunoglobulin, he died. Diagnostic confirmation of rabies encephalitis was made in post mortem on brain biopsies by fluorescent antibody technique.


TITLE:
Brain translocation of aluminum particles is linked to a troJan horse mechanism previously described for infectious particles.

AUTHORS:
Romain Kroum Gherardi, Housam Eidi, Guillemette CrÃ©peaux, FranÃ§ois-JÃ©rÃ´me Authier, Josette Cadusseau

ABSTRACT:
Aluminum oxyhydroxide (alum) is a crystalline compound widely used as an immunological adjuvant of vaccines. Concerns linked to the use of alum particles emerged following recognition of their causative role in the so-called macrophagic myofasciitis (MMF) lesion detected in patients with myalgic encephalomyelitis/chronic fatigue/syndrome. MMF revealed an unexpectedly long-lasting biopersistence of alum within immune cells in presumably susceptible individuals, stressing the previous fundamental misconception of its biodisposition. We previously showed that poorly biodegradable aluminum-coated particles injected into muscle are promptly phagocytosed in muscle and the draining lymph nodes, and can disseminate within phagocytic cells throughout the body and slowly accumulate in brain. This strongly suggests that long-term adjuvant biopersistence within phagocytic cells is a prerequisite for slow brain translocation and delayed neurotoxicity. The understanding of basic mechanisms of particle biopersistence and brain translocation represents a major health challenge, since it could help to define susceptibility factors to develop chronic neurotoxic damage. Biopersistence of alum may be linked to its lysosome-destabilizing effect, which is likely due to direct crystal-induced rupture of phagolysosomal membranes. Macrophages that continuously perceive foreign particles in their cytosol will likely reiterate, with variable interindividual efficiency, a dedicated form of autophagy (xenophagy) until they dispose of alien materials. Successful compartmentalization of particles within double membrane autophagosomes and subsequent fusion with repaired and re-acidified lysosomes will expose alum to lysosomal acidic pH, the sole factor that can solubilize alum particles. Brain translocation of alum particles is linked to a Trojan horse mechanism previously described for infectious particles (HIV, HCV), that obeys to CCL2, signaling the major inflammatory monocyte chemoattractant.


TITLE:
This was a case study in which 3 patients with autoimmune/auto-inflammatory syndrome induced by adjuvants (ASIA) after quadrivalent human papillomavirus vaccination (HPV).

AUTHORS:
Juan-Manuel Anaya, Benjamin Reyes, Ana M Perdomo-Arciniegas, Bernardo Camacho-Rodriguez, Adriana Rojas-Villarraga

ABSTRACT:
This was a case study in which 3 patients with autoimmune/auto-inflammatory syndrome induced by adjuvants (ASIA) after quadrivalent human papillomavirus vaccination (HPV) were evaluated and described. All the patients were women. Diagnosis consisted of HLA-B27 enthesitis related arthritis, rheumatoid arthritis and systemic lupus erythematous, respectively. Our results highlight the risk of developing ASIA after HPV vaccination and may serve to increase the awareness of such a complication. Factors that are predictive of developing autoimmune diseases should be examined at the population level in order to establish preventive measures in at-risk individuals for whom healthcare should be personalized and participatory.


TITLE:
This study found an increase in adverse events after the routine immunization of extremely low-birth-weight infants in the NICU.

AUTHORS:
Stephen D DeMeo, Sudha R Raman, Christoph P Hornik, Catherine C Wilson, Reese Clark, P Brian Smith

ABSTRACT:
Immunization of extremely low-birth-weight (ELBW) infants in the neonatal intensive care unit (NICU) is associated with adverse events, including fever and apnea or bradycardia, in the immediate postimmunization period. These adverse events present a diagnostic dilemma for physicians, leading to the potential for immunization delay and sepsis evaluations.


TITLE:
The Wakefield scare created a natural experiment that may demonstrate a causal relationship between fetal cell line manufactured vaccines and ASD prevalence.

AUTHORS:
Theresa A Deisher, Ngoc V Doan, Kumiko Koyama, Sarah Bwabye

ABSTRACT:
To assess the public health consequences of fetal cell line manufactured vaccines that contain residual human fetal DNA fragments utilizing laboratory and ecological approaches including statistics, molecular biology and genomics.


TITLE:
Asymptomatic transmission is the most parsimonious explanation for many of the observations surrounding the resurgence of B. pertussis in the US and UK.

ABSTRACT:
The recent increase in whooping cough incidence (primarily caused by Bordetella pertussis) presents a challenge to both public health practitioners and scientists trying to understand the mechanisms behind its resurgence. Three main hypotheses have been proposed to explain the resurgence: 1) waning of protective immunity from vaccination or natural infection over time, 2) evolution of B. pertussis to escape protective immunity, and 3) low vaccine coverage. Recent studies have suggested a fourth mechanism: asymptomatic transmission from individuals vaccinated with the currently used acellular B. pertussis vaccines.


