No evidence of an association between MMR vaccine and gait disturbance. Timing of routine immunisations and subsequent hay fever risk. Vaccinations, infections and antibacterials in the first grass pollen season of life and risk of later hayfever. Combined trivalent and bivalent measles, mumps and rubella virus vaccination. A controlled trial. Joint and limb symptoms in children after immunisation with measles, mumps, and rubella vaccine. Statistical analysis of MMR vaccine adverse events on aseptic meningitis using the case cross-over design. Neurologic disorders after measles-mumps-rubella vaccination. Risks of convulsion and aseptic meningitis following measles-mumps-rubella vaccination in the United Kingdom. MMR vaccination and pervasive developmental disorders: a case-control study. Surveillance of symptoms following MMR vaccine in children. An evaluation of measles, mumps and rubella vaccine in a population of Yorkshire infants. Frequency of true adverse reactions to measles-mumps-rubella vaccine. A double-blind placebo-controlled trial in twins. Trivalent combined measles-mumps-rubella vaccine. Findings in clinical-laboratory studies. Comparative efficacy of three mumps vaccines during disease outbreak in Eastern Switzerland: cohort study. Clinical and laboratory studies of combined live measles, mumps, and rubella vaccines using the RA 27/3 rubella virus. Vaccination history and risk of childhood leukaemia. Lack of association between measles-mumps-rubella vaccination and autism in children: a case-control study. Encephalopathy after whole-cell pertussis or measles vaccination: lack of evidence for a causal association in a retrospective case-control study. A new combined trivalent live measles (AIK-C strain), mumps (Hoshino strain), and rubella (Takahashi strain) vaccine. Findings in clinical and laboratory studies. Comparative efficacy of Rubini, Jeryl-Lynn and Urabe mumps vaccine in an Asian population. A population-based study of measles, mumps, and rubella vaccination and autism. Childhood vaccination and type 1 diabetes. Clinical and serologic evaluation of measles, mumps, and rubella (HPV-77:DE-5 and RA 27/3) virus vaccines, singly and in combination. Evaluation of a trivalent measles, mumps, rubella vaccine in children. Thrombocytopenic purpura after measles, mumps and rubella vaccination: a retrospective survey by the French regional pharmacovigilance centres and pasteur-mérieux sérums et vaccins. Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association. No evidence of an increase of bacterial and viral infections following Measles, Mumps and Rubella vaccine. Mumps in a boarding school: description of an outbreak and control measures. Vaccination and allergic disease: a birth cohort study. No demonstrable association between the Leningrad-Zagreb mumps vaccine strain and aseptic meningitis in a large clinical trial in Egypt. The effectiveness of the mumps component of the MMR vaccine: a case control study. Outbreak of aseptic meningitis associated with mass vaccination with a urabe-containing measles-mumps-rubella vaccine: implications for immunization programs. Immunogenicity and efficacy of one dose measles-mumps-rubella (MMR) vaccine at twelve months of age as compared to monovalent measles vaccination at nine months followed by MMR revaccination at fifteen months of age. Pervasive developmental disorders in Montreal, Quebec, Canada: prevalence and links with immunizations. [Estimation of the efficacy of three strains of mumps vaccines during an epidemic of mumps in the Geneva canton (Switzerland)]. No effect of MMR withdrawal on the incidence of autism: a total population study. No evidence for a new variant of measles-mumps-rubella-induced autism. [An epidemic outbreak of mumps. A study of vaccinal efficacy]. Multiple sclerosis incidence in the era of measles-mumps-rubella mass vaccinations. A population-based case-control study on viral infections and vaccinations and subsequent multiple sclerosis risk. Outbreak of aseptic meningitis and mumps after mass vaccination with MMR vaccine using the Leningrad-Zagreb mumps strain. Illness after measles-mumps-rubella vaccination. Effectiveness of Jeryl Lynn-containing vaccine in Spanish children. Clinical evaluation of a new measles-mumps-rubella trivalent vaccine. Measles transmission and vaccine effectiveness during a large outbreak on a densely populated island: implications for vaccination policy. MMR vaccine and idiopathic thrombocytopaenic purpura. Risk of serious neurologic disease after immunization of young children in Britain and Ireland. Measles-mumps-rubella vaccination and asthma-like disease in early childhood. Age at first measles-mumps-rubella vaccination in children with autism and school-matched control subjects: a population-based study in metropolitan atlanta. Risk of immune thrombocytopenic purpura after measles-mumps-rubella immunization in children. Childhood vaccinations and risk of asthma. Association between drug and vaccine use and acute immune thrombocytopenia in childhood: a case-control study in Italy. Outbreak of mumps associated with poor vaccine efficacy - Oporto Portugal 1996. A randomised single blind trial of a combined mumps measles rubella vaccine to evaluate serological response and reactions in the UK population. Mumps vaccine L-Zagreb, prepared in chick fibroblasts. I. Production and field trials. Risk of hospitalization because of aseptic meningitis after measles-mumps-rubella vaccination in one- to two-year-old children: an analysis of the Vaccine Safety Datalink (VSD) Project. MMR vaccination and febrile seizures: evaluation of susceptible subgroups and long-term prognosis. MMR vaccine and Crohn's disease: ecological study of hospital admissions in England, 1991 to 2002. MMR-vaccine and regression in autism spectrum disorders: negative results presented from Japan. Outbreak of measles in primary school students with high first dose MMR vaccination coverage.
MMR vaccine has been reported to cause gait disturbance, and this possible association has been claimed to support the MMR-causes-autism theory.
                To determine whether any association between gait disturbance and MMR vaccination exceeds the age related background rate of gait disturbance, using record linkage and self control case series analyses.
                MMR vaccination records were linked to hospital admission and general practitioner attendance data. An increased rate of gait problems with onset in various intervals in the 60 day period after MMR vaccination was looked for in children aged 12 to <24 months.
                No evidence of an increased rate of hospital admission or general practice consultations for gait disturbance was found in the putative post-vaccination risk periods.
                This study provides no evidence for a causal association between MMR and gait disturbance. Suggestions that immunisation influences allergic disease risk, either positively (pertussis) or negatively (BCG) are of concern for vaccination policy.
                To determine whether DTP, MMR, and BCG vaccination in infancy influenced hay fever risk.
                Case-control study of 7098 hay fever cases and controls, within two primary care databases. One control per case was matched for practice, age, and sex. Odds ratios (OR) were derived using conditional logistic regression.
                Compared to those completing in month 5 (base group) (39.3%), DTP unvaccinated children (4.3%) had a similar risk of hay fever (OR = 0.94, 95% CI 0.73 to 1.23). However, those completing after 12 months (4.2%) had a reduced risk (OR = 0.60, 95% CI 0.45 to 0.76) compared to the base group. Compared to those vaccinated in month 14 (base group) (29.5%), MMR unvaccinated children (2.3%) had an OR of 0.79 (95% CI 0.58 to 1.08). Completion of MMR after two years was associated with reduced hay fever risk (OR = 0.62, 95% CI 0.48 to 0.80) compared to the base group. The effects of late immunisation with DTP and MMR were independent. Those vaccinated with BCG by age 2 (2.4%) had an odds ratio of 1.28 (95% CI 0.96 to 1.70). Adjustment for consulting behaviour, social factors, or sibship size did not alter these associations.
                Immunisation against DTP or MMR does not increase the risk of hay fever. The lower confidence limit for BCG vaccination contradicts the hypothesised protective effect. The reduced risk of hay fever among children immunised late may be explained by a third factor causing both postponement and reduced risk such as intercurrent febrile illnesses. It has been hypothesized that early-life exposure to vaccinations, infections or antibacterials influence allergic disease development. Concurrent exposure to grass pollens may alter any effect.
                To test the hypothesis that exposure to antibacterials, vaccinations (DTP or MMR) or specific infections during the first grass pollen seasons of life influences the risk of hayfever more than at any other time of the year.
                Nested case-control studies were based on birth cohorts within two large databases of computerized patient records from UK general practices: the General Practice Research Database (GPRD) and Doctors' Independent Network (DIN). Seven thousand ninety-eight hayfever cases, diagnosed after age 2, were matched to controls for practice, age, sex and follow-up of control to case ascertainment date. Conditional logistic regression was used to compare exposure by age 1 (age 2 for MMR) inside vs. outside the grass pollen season (May, June, July). Odds ratios (ORs) were pooled across databases.
                There were no associations in either database between MMR during vs. outside the grass pollen season and later hayfever. Of 23 infections studied, none were statistically significant; although analyses for the less common conditions were limited by low statistical power. The pooled OR for hayfever comparing exposure to antibacterials only in the grass pollen season with only outside it was 1.20 (95% CI 0.98-1.47) and for DTP was 0.84 (95% CI 0.72-0.98).
                Although an interaction between early exposure to microbial agents and concurrent grass pollen exposure on hayfever risk seemed plausible, there was little evidence to support it across a range of analyses. However, the effect of DTP though weak deserves further study. nan To assess whether the combined measles, mumps, and rubella vaccine increases the incidence of joint and limb symptoms in young children.
                Comparison of six week recalled incidence of symptoms in two groups of children: children who had been immunised at the start of the six weeks, and children eligible for immunisation but who had not received it.
                South Manchester Health Authority.
                2658 children immunised during July 1989-February 1990 and 2359 not yet immunised. Questionnaires were returned for 1846 immunised children and 1075 not immunised.
                Recalled rate of joint and limb episodes determined by postal questionnaire and later by clinical follow up.
                Compared with non-immunised children the immunised group had an increased incidence of new episodes (relative risk 1.6 (95% confidence interval (1.2 to 2.1)) and first ever episodes, though this was not significant (1.7 (0.3 to 3.5)). The risk of first episodes was increased in girls (3.5 (1.1 to 12.2)) but not in boys (1.0 (0.4 to 2.6)). Similarly, an increased risk was seen in children aged under 5 (12.0 (1.6 to 92.3)) but not in older children (0.7 (0.3 to 1.5)). Most episodes were mild and self limiting, but three immunised children required hospital referral.
                Measles, mumps, and rubella vaccine is associated with an increased risk of episodes of joint and limb symptoms, especially in girls and children under 5. The risk of frank arthritis is substantially less than after wild rubella infection. Vaccination is quite effective in reducing the incidence of disease. However, it may cause some adverse events. For example, one of the adverse events of measles-mumps-rubella(MMR) vaccination is the occurrence of aseptic meningitis. Since the vaccination rate is usually quite high, it is not plausible to use popular study designs such as cohort or case-control studies. We considered a case cross-over design to investigate the association between MMR vaccination and aseptic meningitis in Korean children. We used the Cochran-Mantel-Haenszel(CMH) approach, and obtained a Mantel-Haenszel odds ratio estimator as a measure of association. However, the validity of case cross-over design or the CMH approach in vaccine adverse studies has not been fully investigated. In this paper, through Monte Carlo simulation studies, we show the appropriateness of the case cross-over design and the CMH approach. We also discuss alternative approaches such as Poisson regression using offset and a simple uniformity test. In conclusion, the case cross-over design seems useful to investigate the association between vaccination and occurrence of acute adverse events.
                Copyright 2004 John Wiley & Sons, Ltd. The possibility of adverse neurologic events has fueled much concern about the safety of measles-mumps-rubella (MMR) vaccinations. The available evidence concerning several of the postulated complications is controversial. The aim of this study was to assess whether an association prevails between MMR vaccination and encephalitis, aseptic meningitis, and autism.
                A retrospective study based on linkage of individual MMR vaccination data with a hospital discharge register was conducted among 535 544 1- to 7-year-old children who were vaccinated between November 1982 and June 1986 in Finland. For encephalitis and aseptic meningitis, the numbers of events observed within a 3-month risk interval after vaccination were compared with the expected numbers estimated on the basis of occurrence of encephalitis and aseptic meningitis during the subsequent 3-month intervals. Changes in the overall number of hospitalizations for autism after vaccination throughout the study period were searched for. In addition, hospitalizations because of inflammatory bowel diseases were checked for the children with autism.
                Of the 535 544 children who were vaccinated, 199 were hospitalized for encephalitis, 161 for aseptic meningitis, and 352 for autistic disorders. In 9 children with encephalitis and 10 with meningitis, the disease developed within 3 months of vaccination, revealing no increased occurrence within this designated risk period. We detected no clustering of hospitalizations for autism after vaccination. None of the autistic children made hospital visits for inflammatory bowel diseases.
                We did not identify any association between MMR vaccination and encephalitis, aseptic meningitis, or autism. Measles-mumps-rubella (MMR) vaccines containing the Urabe strain of mumps were withdrawn in the United Kingdom in 1992 following demonstration of an increased risk of aseptic meningitis 15-35 days after vaccination. Following introduction of a replacement MMR vaccine (Priorix; GlaxoSmithKline, London, United Kingdom) in 1998, active surveillance of aseptic meningitis and convulsion was established to evaluate the risk associated with the new vaccine. No laboratory-confirmed cases of mumps meningitis were detected among children aged 12-23 months after administration of 1.6 million doses of Priorix (upper 95% confidence limit of risk: 1:437,000) in England and Wales. The upper 95% confidence limit excluded the risk found for mumps meningitis with Urabe vaccines (1:143,000 doses). No cases of aseptic meningitis were detected among children aged 12-23 months, who had received over 99,000 doses of Priorix (upper 95% confidence limit of risk: 1:27,000), in a regional database of hospital-admitted cases. This compares with an observed risk of 1:12,400 for Urabe vaccines. An elevated relative incidence of convulsion was found in the 6- to 11-day period after receipt of Priorix (relative incidence = 6.26, 95% confidence interval: 3.85, 10.18)-consistent with the known effects of the measles component of MMR vaccine-but not in the 15- to 35-day period (relative incidence = 1.48, 95% confidence interval: 0.88, 2.50) as occurred with Urabe-containing vaccines. This study demonstrates the power of active postmarketing surveillance to identify or exclude events too rare to be detected in prelicensure trials. Concern that measles-mumps-rubella (MMR) vaccination might cause autism has led to a fall in vaccine coverage. We investigated whether MMR vaccination is associated with an increased risk of autism or other pervasive developmental disorders.
                We did a matched case-control study using the UK General Practice Research Database. Cases were people born in 1973 or later who had first recorded diagnosis of pervasive developmental disorder while registered with a contributing general practice between 1987 and 2001. Controls were matched on age, sex, and general practice.
                1294 cases and 4469 controls were included. 1010 cases (78.1%) had MMR vaccination recorded before diagnosis, compared with 3671 controls (82.1%) before the age at which their matched case was diagnosed. After adjustment for age at joining the database, the odds ratio for association between MMR and pervasive developmental disorder was 0.86 (95% CI 0.68-1.09). Findings were similar when restricted to children with a diagnosis of autism, to those vaccinated with MMR before the third birthday, or to the period before media coverage of the hypothesis linking MMR with autism.
                Our findings suggest that MMR vaccination is not associated with an increased risk of pervasive developmental disorders. nan In October 1988 combined measles, mumps and rubella (MMR) vaccination replaced monocomponent measles as part of the routine childhood vaccination programme in the United Kingdom. Prior to this policy change a study was undertaken in 335 children aged 15 months, to evaluate the clinical reactions and immunogenicity of the new combined MMR vaccine (Trimovax, Immravax, Merieux), in comparison with an established monocomponent measles vaccine (Rouvax, Merieux). Parents were asked to select whether their child should receive MMR vaccine or measles monocomponent; over 95% chose MMR. Children who were given the MMR vaccine had seroconversion rates of 96% for measles, 97% for mumps and 100% for rubella, whilst those who received monocomponent measles vaccine had a seroconversion rate of 100%. The number of side effects reported was similar with both vaccines; all were mild and self-limiting. The results from this study confirm the efficacy and low reactogenicity of MMR vaccine and support its use as part of the routine childhood immunisation programme in the United Kingdom. The vast majority of adverse reactions following immunisation of children with live measles-mumps-rubella (MMR) vaccine were shown in a double-blind, placebo-controlled, cross-over study in 581 twin pairs to be only temporally but not causally related to the vaccination. The true frequency of side-effects caused by MMR vaccine, estimated from the discordance rates of individual signs and symptoms between MMR vaccinees and their placebo-injected twins, was between 0.5 and 4.0%. Moreover, respiratory symptoms, nausea, and vomiting were observed more frequently in the placebo-injected group than in the MMR vaccinated group. nan nan nan Previous studies on vaccination and childhood leukaemia generated inconsistent results.
                In the Northern California Childhood Leukaemia Study, a case-control study with incident cases and matched birth certificate controls, detailed written vaccination records were collected. A total of 323 cases aged 0-14 years at diagnosis and 409 controls were included in this analysis. All vaccinations were censored on the reference date (date of diagnosis for cases and the corresponding date for matched controls). Conditional logistic regression analysis was conducted, adjusting for potential confounding factors. A primary variable of interest is the number of administrations (doses) of various types of vaccines.
                Vaccinations against diphtheria, pertussis, tetanus, poliomyelitis, measles, mumps, and rubella were not associated with the risk of leukaemia. The odds ratio for each dose of Haemophilus influenzae type b (Hib) vaccine was 0.81 (95% CI 0.68-0.96). Compared with children who received two or fewer doses of Hib vaccine, those who received three or more doses had a significantly reduced risk of childhood leukaemia (odds ratio = 0.55, 95% confidence interval 0.32-0.94). The number of doses of hepatitis B vaccine received was not associated with leukaemia risk.
                Hib vaccination is associated with a reduced risk of childhood leukaemia. Future studies with detailed exposure assessment and large sample sizes are needed to further address the role of vaccinations in the etiology of childhood leukaemia. The first objective of the study was to determine whether there is a relationship between the measles-mumps-rubella (MMR) vaccination and autism in children. The second objective was to examine whether the risk of autism differs between use of MMR and the single measles vaccine.
                Case-control study.
                The 96 cases with childhood or atypical autism, aged 2 to 15, were included into the study group. Controls consisted of 192 children individually matched to cases by year of birth, sex, and general practitioners.
                Data on autism diagnosis and vaccination history were from physicians. Data on the other probable autism risk factors were collected from mothers. Logistic conditional regression was used to assess the risk of autism resulting from vaccination. Assessment was made for children vaccinated (1) Before diagnosis of autism, and (2) Before first symptoms of autism onset. Odds ratios were adjusted to mother's age, medication during pregnancy, gestation time, perinatal injury and Apgar score.
                For children vaccinated before diagnosis, autism risk was lower in children vaccinated with MMR than in the nonvaccinated (OR: 0.17, 95% CI: 0.06-0.52) as well as to vaccinated with single measles vaccine (OR: 0.44, 95% CI: 0.22-0.91). The risk for vaccinated versus nonvaccinated (independent of vaccine type) was 0.28 (95% CI: 0.10-0.76). The risk connected with being vaccinated before onset of first symptoms was significantly lower only for MMR versus single vaccine (OR: 0.47, 95% CI: 0.22-0.99).
                The study provides evidence against the association of autism with either MMR or a single measles vaccine. Whole-cell pertussis (wP) and measles vaccines are effective in preventing disease but have also been suspected of increasing the risk of encephalopathy or encephalitis. Although many countries now use acellular pertussis vaccines, wP vaccine is still widely used in the developing world. It is therefore important to evaluate whether wP vaccine increases the risk of neurologic disorders.
                A retrospective case-control study was performed at 4 health maintenance organizations. Records from January 1, 1981, through December 31, 1995, were examined to identify children aged 0 to 6 years old hospitalized with encephalopathy or related conditions. The cause of the encephalopathy was categorized as known, unknown or suspected but unconfirmed. Up to 3 controls were matched to each case. Conditional logistic regression was used to analyze the relative risk of encephalopathy after vaccination with diphtheria-tetanus-pertussis (DTP) or measles-mumps-rubella (MMR) vaccines in the 90 days before disease onset as defined by chart review compared with an equivalent period among controls indexed by matching on case onset date.
                Four-hundred fifty-two cases were identified. Cases were no more likely than controls to have received either vaccine during the 90 days before disease onset. When encephalopathies of known etiology were excluded, the odds ratio for case children having received DTP within 7 days before onset of disease was 1.22 (95% confidence interval [CI] = 0.45-3.31, P = 0.693) compared with control children. For MMR in the 90 days before onset of encephalopathy, the odds ratio was 1.23 (95% confidence interval = 0.51-2.98, P = 0.647).
                In this study of more than 2 million children, DTP and MMR vaccines were not associated with an increased risk of encephalopathy after vaccination. Trivalent virus vaccine, containing measles AIK-C strain, mumps Hoshino strain, and rubella Takahashi strain, was administered to a total of 1369 healthy children, 8 months to 18 years of age. For comparative study, monovalent vaccines of AIK-C strain and Hoshino strain were administered to 147 and 122 initially seronegative children, respectively. The clinical and serological responses following vaccination were analyzed. Among the recipients of the trivalent vaccine, 893 were initially seronegative to all three viruses. Inoculation induced sufficient serological responses: 99.7% for measles and rubella viruses and 96.3% for mumps virus. The incidence of febrile reaction (greater than or equal to 37.5 degrees C axillary temperature) was low, 15.9%, and a temperature of 39.0 degrees C or higher occurred in only 1.3% of the subjects. The seroconversion rate, magnitude of antibody titers, and incidence of clinical reactions following the trivalent vaccination were similar to those occurring after the monovalent measles vaccination. The comparative efficacy of the three mumps vaccine strains (Jeryl-Lynn, Urabe and Rubini) was conducted in an Asian population from data arising from an epidemiological investigation of seven institutional outbreaks of mumps in Singapore.
                Demographic information (gender, age, ethnic group), clinical presentation and vaccination history (date and place of mumps vaccination, type of mumps vaccine received) of all children who attended the six childcare centres and one primary school where outbreaks of 20 or more cases of mumps occurred in 1999 were collected. The attack rate of the unvaccinated group and the attack rates of the vaccine groups (for each vaccine strain) were determined and the vaccine efficacy of the three vaccines calculated.
                The vaccine efficacy of the Jeryl-Lynn strain, Urabe strain and Rubini strain mumps vaccine were 80.7, 54.4 and -55.3%, respectively.
                Rubini strain mumps vaccine conferred no protection and has since been deregistered in Singapore. It has been suggested that vaccination against measles, mumps, and rubella (MMR) is a cause of autism.
                We conducted a retrospective cohort study of all children born in Denmark from January 1991 through December 1998. The cohort was selected on the basis of data from the Danish Civil Registration System, which assigns a unique identification number to every live-born infant and new resident in Denmark. MMR-vaccination status was obtained from the Danish National Board of Health. Information on the children's autism status was obtained from the Danish Psychiatric Central Register, which contains information on all diagnoses received by patients in psychiatric hospitals and outpatient clinics in Denmark. We obtained information on potential confounders from the Danish Medical Birth Registry, the National Hospital Registry, and Statistics Denmark.
                Of the 537,303 children in the cohort (representing 2,129,864 person-years), 440,655 (82.0 percent) had received the MMR vaccine. We identified 316 children with a diagnosis of autistic disorder and 422 with a diagnosis of other autistic-spectrum disorders. After adjustment for potential confounders, the relative risk of autistic disorder in the group of vaccinated children, as compared with the unvaccinated group, was 0.92 (95 percent confidence interval, 0.68 to 1.24), and the relative risk of another autistic-spectrum disorder was 0.83 (95 percent confidence interval, 0.65 to 1.07). There was no association between the age at the time of vaccination, the time since vaccination, or the date of vaccination and the development of autistic disorder.
                This study provides strong evidence against the hypothesis that MMR vaccination causes autism.
                Copyright 2002 Massachusetts Medical Society A link between childhood vaccinations and the development of type 1 diabetes has been proposed.
                We evaluated a cohort comprising all children born in Denmark from January 1, 1990, through December 31, 2000, for whom detailed information on vaccinations and type 1 diabetes was available. Using Poisson regression models, we estimated rate ratios according to vaccination status, including the trend associated with the number of doses, among all children and in a subgroup of children who had siblings with type 1 diabetes. Given recent claims of clustering of cases of diabetes two to four years after vaccination, we also estimated rate ratios during the period after vaccination.
                Type 1 diabetes was diagnosed in 681 children during 4,720,517 person-years of follow-up. The rate ratio for type 1 diabetes among children who received at least one dose of vaccine, as compared with unvaccinated children, was 0.91 (95 percent confidence interval, 0.74 to 1.12) for Haemophilus influenzae type b vaccine; 1.02 (95 percent confidence interval, 0.75 to 1.37) for diphtheria, tetanus, and inactivated poliovirus vaccine; 0.96 (95 percent confidence interval, 0.71 to 1.30) for diphtheria, tetanus, acellular pertussis, and inactivated poliovirus vaccine; 1.06 (95 percent confidence interval, 0.80 to 1.40) for whole-cell pertussis vaccine; 1.14 (95 percent confidence interval, 0.90 to 1.45) for measles, mumps, and rubella vaccine; and 1.08 (95 percent confidence interval, 0.74 to 1.57) for oral poliovirus vaccine. The development of type 1 diabetes in genetically predisposed children (defined as those who had siblings with type 1 diabetes) was not significantly associated with vaccination. Furthermore, there was no evidence of any clustering of cases two to four years after vaccination with any vaccine.
                These results do not support a causal relation between childhood vaccination and type 1 diabetes.
                Copyright 2004 Massachusetts Medical Society A double-blind, placebo-controlled comparison of single component and combination measles, mumps, and rubella (HPV-77:DE-5 and RA 27/3) virus vaccines involving 502 young children was conducted. The rubella antibody response was similar with RA 27/3 rubella and measles-mumps-rubella (RA 27/3) vaccines, but was diminished with the combination vaccine that incorporated HPV-77:DE-5 rubella. There was no evidence of enhanced clinical reactivity with either of the measles-mumps-rubella vaccines. nan Thrombocytopenic purpura (TP) after vaccination with measles, mumps and rubella has occasionally been reported.
                To evaluate the incidence and characteristics of thrombocytopenic purpura reported in France after measles, mumps or rubella vaccination with monovalent or multivalent vaccines.
                A retrospective epidemiologic survey was conducted. All confirmed cases of TP reported spontaneously either to the French Regional Pharmacovigilance Centres or to the manufacturer (Pasteur-Mérieux Sérums et Vaccins) between 1984 and June 30, 1992, were reviewed.
                Sixty cases of TP in children between 1 and 11 years of age occurred 2 to 45 days after administration of 1 of 7 vaccines. The reported incidence of TP varied from 0.17 and 0.23/100,000 doses of measles or rubella vaccines, respectively, given alone to 0.87/100,000 doses of combined measles-rubella vaccines and 0.95/100,000 doses of the measles-mumps-rubella vaccine. The mean platelet count was 8000 +/- 6000/mm3 and was lower than 10,000/mm3 in 58% of cases. The immediate outcome was favorable in 89.5% of cases.
                According to the clinical course and biologic findings, vaccine-associated TP appears to be similar to that occurring after natural measles or rubella infections and is not distinguishable from acute childhood idiopathic thrombocytopenic purpura not associated with vaccination. Such observations, combined with a clear temporal relationship between measles-mumps-rubella vaccination and the occurrence of TP, make a causal relationship highly plausible. Nevertheless the incidence of these events remains relatively low with a favorable immediate outcome. We undertook an epidemiological study to investigate whether measles, mumps, and rubella (MMR) vaccine may be causally associated with autism.
                Children with autism born since 1979 were identified from special needs/disability registers and special schools in eight North Thames health districts, UK. Information from clinical records was linked to immunisation data held on the child health computing system. We looked for evidence of a change in trend in incidence or age at diagnosis associated with the introduction of MMR vaccination to the UK in 1988. Clustering of onsets within defined postvaccination periods was investigated by the case-series method.
                We identified 498 cases of autism (261 of core autism, 166 of atypical autism, and 71 of Asperger's syndrome). In 293 cases the diagnosis could be confirmed by the criteria of the International Classification of Diseases, tenth revision (ICD10: 214 [82%] core autism, 52 [31%] atypical autism, 27 [38%] Asperger's syndrome). There was a steady increase in cases by year of birth with no sudden "step-up" or change in the trend line after the introduction of MMR vaccination. There was no difference in age at diagnosis between the cases vaccinated before or after 18 months of age and those never vaccinated. There was no temporal association between onset of autism within 1 or 2 years after vaccination with MMR (relative incidence compared with control period 0.94 [95% CI 0.60-1.47] and 1.09 [0.79-1.52]). Developmental regression was not clustered in the months after vaccination (relative incidence within 2 months and 4 months after MMR vaccination 0.92 [0.38-2.21] and 1.00 [0.52-1.95]). No significant temporal clustering for age at onset of parental concern was seen for cases of core autism or atypical autism with the exception of a single interval within 6 months of MMR vaccination. This appeared to be an artifact related to the difficulty of defining precisely the onset of symptoms in this disorder.
                Our analyses do not support a causal association between MMR vaccine and autism. If such an association occurs, it is so rare that it could not be identified in this large regional sample. The suggestion that multi-antigen vaccines might overload the immune system has led to calls for single antigen vaccines. In 2003 we showed that rather than an increase there appeared to be a reduced risk of severe bacterial infection in the three months following Measles, Mumps and Rubella vaccine (MMR). The present analysis of illnesses in a general population is based on an additional 10 years of data for bacterial infections and also includes admissions with viral infections. Analyses were carried out using the self-controlled case-series method and separately for bacterial and viral infection cases, using risk periods of 0-30 days, 31-60 days and 61-90 days post MMR vaccine. An analysis was also carried out for those cases which were given MMR and Meningococcal serogroup C (MCC) vaccines concomitantly. A reduced risk was seen in the 0-30-day period for both bacterial infection (relative incidence=0.68, 95% CI 0.54-0.86) and viral infections (relative incidence=0.68, 95% CI 0.49-0.93). There was no increased risk in any period when looking at combined viral or bacterial infections or for individual infections with the single exception of an increased risk in the 31-60 days post vaccination period for herpes infections (relative incidence=1.69, 95% CI 1.06-2.70). For the children given Meningococcal group C vaccines concomitantly no significantly increased risk was seen in either the bacterial (relative incidence=0.54, 95% CI 0.26-1.13) or viral cases (relative incidence=0.46, 95% CI 0.11-1.93). Our study confirms that the MMR vaccine does not increase the risk of invasive bacterial or viral infection in the 90 days after the vaccination and does not support the hypothesis that there is an induced immune deficiency due to overload from multi-antigen vaccines. The number of cases of mumps in the UK has increased during 2004-2005. Understanding why some people are more susceptible to mumps infection will help target vaccination and other control measures in the future. This paper describes a mumps outbreak in a boarding school in Scotland (October to November 2004).
                To describe the characteristics of cases in a mumps outbreak; and to conduct a case-control study looking at the effect of previous measles-mumps-rubella (MMR) vaccination.
                Descriptive epidemiology.
                Clinical, laboratory and surveillance data.
                A private school with 600 boarding and day pupils.
                Fifty cases were notified to the public health department as having mumps. Twenty of the cases (40%) were confirmed virologically, all born between 1987-1991. A matched case-control study was conducted to explore the effect of prior MMR vaccination. Compared to no vaccine, MMR protected against mumps (odds ratio = 0.7), two doses offering best protection (odds ratio = 0.5), but the study was not large enough to detect a statistically significant difference.
                Some children and young people in the UK are currently incompletely vaccinated. This outbreak illustrates the potential of a mumps outbreak to disrupt the medical, educational and social life of a school. All children should be vaccinated with two doses of MMR vaccine before school entry. Children and young people born between 1979-1991 should be given the necessary additional dose(s) of MMR vaccine. We examined the effect of vaccination for diphtheria; polio; pertussis and tetanus; or measles, mumps, and rubella on the incidence of physician-diagnosed asthma and eczema.
                We used a previously established birth cohort in the West Midlands General Practice research database.
                We found an association between vaccination and the development of allergic disease; however, this association was present only among children with the fewest physician visits and can be explained by this factor.
                Our data suggest that currently recommended routine vaccinations are not a risk factor for asthma or eczema. To address the claim that the Leningrad-Zagreb (L-Z) mumps vaccine strain is causally associated with aseptic meningitis, a prospective, post-marketing safety study was conducted with a measles-mumps-rubella vaccine (MMR) (TRESIVAC(R); Serum Institute of India Ltd., Pune, India), which uses the L-Z strain as its mumps component in Egypt. In all, 453 119 children (65 423 children aged 16-24 months and 329 211 children aged 5-7 years) received MMR. The control groups which, as a result of local health regulations, were slightly younger than vaccinees, comprised 12 253 and 46 232 children, respectively. Using questionnaires, the parents recorded solicited local, systemic and neurological adverse events for up to 42 days post-vaccination. All data were analysed externally on an intention-to-treat basis by individuals not participating in the study. Local and/or systemic reactions were reported in a small percentage of participants, with pain, fever and parotitis being the most common signs among vaccinees in both age groups. No case of aseptic meningitis, encephalitis, anaphylaxis or convulsions was observed in any participant. Thus, in this series of more than 450 000 Egyptian children, the L-Z mumps vaccine strain in this vaccine did not cause aseptic meningitis. The vaccine is considerably cheaper than Western competitors and a valid alternative to other MMR vaccines. 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. A mass immunization campaign with a Urabe-containing measles-mumps-rubella vaccine was carried out in 1997 in the city of Salvador, northeastern Brazil, with a target population of children aged 1-11 years. There was an outbreak of aseptic meningitis following the mass campaign. Cases of aseptic meningitis were ascertained through data collected from the records of children admitted to the local referral hospital for infectious diseases between March and October of 1997, using previously defined eligibility criteria. Vaccination histories were obtained through home visits or telephone calls. Eighty-seven cases fulfilled the study criteria. Of those, 58 cases were diagnosed after the vaccination campaign. An elevated risk of aseptic meningitis was observed 3 weeks after Brazil's national vaccination day compared with the risk in the prevaccination period (relative risk = 14.3; 95% confidence interval: 7.9, 25.7). This result was confirmed by a case series analysis (relative risk = 30.4; 95% confidence interval: 11.5, 80.8). The estimated risk of aseptic meningitis was 1 in 14,000 doses. This study confirms a link between measles-mumps-rubella vaccination and aseptic meningitis. The authors discuss the implications of this for the organization and planning of mass immunization campaigns. measles is a common cause of morbidity and mortality in developing countries. Although the measles-mumps-rubella vaccine (MMR) is currently in use in developed countries, monovalent measles vaccine (MV) is routinely recommended by World Health Organization (WHO) at 9 months of age in Turkey, as in many other developing countries. In this study, 442 Turkish children received MV at 9 months of age and were revaccinated with MMR vaccine at 15 months of age. In the second group 495 children received MMR at 12 months of age with no earlier measles vaccination. Antibodies were measured before the first vaccination and 6 weeks after the MMR. All children had been followed for occurrence of measles infection for 60 months. Two vaccination schedules were compared for immunogenicity and protection rates.
                seroconversion and clinical protection rates were significantly higher in children who received only MMR at 12 months of age than in children revaccinated at 15 months of age. Seroconversion rate for measles was 69.9% in children who received MMR at 12 months of age and 90.3% in children revaccinated at 15 months of age (P=0.0003). While there was no measles case in children who were revaccinated, 12 (2.7%) children in the first group acquired measles during the follow-up period. Vaccination at 12 months of age appeared to be better than the current national standard. The late elimination of maternal antibodies and the inhibitory effect of a weak antibody response after the first dose of vaccine at 9 months may explain the better immunogenicity and efficacy of the MMR vaccine given at 12 months of age. The prevalence of pervasive developmental disorders has increased in recent years. Links with the measles component of the measles-mumps-rubella vaccine and the cumulative exposure to thimerosal through other vaccines have been postulated.
                The purpose of this work was to estimate the pervasive developmental disorder prevalence in Montreal, Canada, in cohorts born from 1987 to 1998 and evaluate the relationship of trends in pervasive developmental disorder rates with: (1) changes in cumulative exposure to ethylmercury (thimerosal) occurring through modifications in the immunization schedule of young children and (2) trends in measles-mumps-rubella vaccination use rates and the introduction of a 2-measles-mumps-rubella dosing schedule during the study period.
                We surveyed 27749 children born from 1987 to 1998 attending 55 schools from the largest Anglophone school board. Children with pervasive developmental disorders were identified by a special needs team. The cumulative exposure by age 2 years to thimerosal was calculated for 1987-1998 birth cohorts. Ethylmercury exposure ranged from medium (100-125 microg) from 1987 to 1991 to high (200-225 microg) from 1992 to 1995 to nil from 1996 onwards when thimerosal was entirely discontinued. Measles-mumps-rubella coverage for each birth cohort was estimated through surveys of vaccination rates. The immunization schedule included a measles-mumps-rubella single dose at 12 months of age up to 1995, and a second measles-mumps-rubella dose at 18 months of age was added on after 1996.
                We found 180 children (82.8% males) with a pervasive developmental disorder diagnosis who attended the surveyed schools, yielding a prevalence for pervasive developmental disorder of 64.9 per 10000. The prevalence for specific pervasive developmental disorder subtypes were, for autistic disorder: 21.6 of 10000; for pervasive developmental disorder not otherwise specified: 32.8 of 10000; and for Asperger syndrome: 10.1 of 10000. A statistically significant linear increase in pervasive developmental disorder prevalence was noted during the study period. The prevalence of pervasive developmental disorder in thimerosal-free birth cohorts was significantly higher than that in thimerosal-exposed cohorts (82.7 of 10000 vs 59.5 of 10000). Using logistic regression models of the prevalence data, we found no significant effect of thimerosal exposure used either as a continuous or a categorical variable. Thus, thimerosal exposure was unrelated to the increasing trend in pervasive developmental disorder prevalence. These results were robust when additional analyses were performed to address possible limitations because of the ecological nature of the data and to evaluate potential effects of misclassification on exposure or diagnosis. Measles-mumps-rubella vaccination coverage averaged 93% during the study interval with a statistically significant decreasing trend from 96.1% in the older birth cohorts (1988-89) to approximately 92.4% in younger birth cohorts (1996-1998). Thus, pervasive developmental disorder rates significantly increased when measles-mumps-rubella vaccination uptake rates significantly decreased. In addition, pervasive developmental disorder prevalence increased at the same rate before and after the introduction in 1996 of the second measles-mumps-rubella dose, suggesting no increased risk of pervasive developmental disorder associated with a 2-measles-mumps-rubella dosing schedule before age 2 years. Results held true when additional analyses were performed to test for the potential effects of misclassification on exposure or diagnostic status. Thus, no relationship was found between pervasive developmental disorder rates and 1- or 2-dose measles-mumps-rubella immunization schedule.
                The prevalence of pervasive developmental disorder in Montreal was high, increasing in recent birth cohorts as found in most countries. Factors accounting for the increase include a broadening of diagnostic concepts and criteria, increased awareness and, therefore, better identification of children with pervasive developmental disorders in communities and epidemiologic surveys, and improved access to services. The findings ruled out an association between pervasive developmental disorder and either high levels of ethylmercury exposure comparable with those experienced in the United States in the 1990s or 1- or 2-dose measles-mumps-rubella vaccinations. The number of mumps cases reported in Switzerland markedly increased from 1993 to 1995 although vaccination coverage against mumps had risen steadily since the national MMR immunization program was launched in 1987. In 1991, an estimated 80% of children 27 to 36 month-old were immunized against mumps. The purpose of the present study was to assess the hypothesis that the epidemic was the consequence of a low vaccine efficacy of the Rubini strain--a mumps vaccine strain that has been widely used in Switzerland.
                Vaccine efficacy was assessed by measuring secondary attack rates among immunized and nonimmunized children 16 year-old or younger who wre family contacts of cases.
                From February 1993 to April 1996, Geneva pediatricians reported 283 primary cases of mumps and 63 secondary cases. Estimate of vaccine efficacy was equal to 6.3% (95% CI: -45.9; 39.8) for the Rubini strain, as compared to 73.1% (95% CI: 41.8; 87.6) for the Urabe Am 9 strain, and 61.6% (95% CI: 0.0; 85.4) for the Jeryl Lynn strain, two vaccine strains of mumps that had also been used in Geneva.
                Our study supports the hypothesis that the Rubini vaccine strain of mumps does not confer sufficient long-lasting protection against mumps. A causal relationship between the measles, mumps, and rubella (MMR) vaccine and occurrence of autism spectrum disorders (ASD) has been claimed, based on an increase in ASD in the USA and the UK after introduction of the MMR vaccine. However, the possibility that this increase is coincidental has not been eliminated. The unique circumstances of a Japanese MMR vaccination program provide an opportunity for comparison of ASD incidence before and after termination of the program.
                This study examined cumulative incidence of ASD up to age seven for children born from 1988 to 1996 in Kohoku Ward (population approximately 300,000), Yokohama, Japan. ASD cases included all cases of pervasive developmental disorders according to ICD-10 guidelines.
                The MMR vaccination rate in the city of Yokohama declined significantly in the birth cohorts of years 1988 through 1992, and not a single vaccination was administered in 1993 or thereafter. In contrast, cumulative incidence of ASD up to age seven increased significantly in the birth cohorts of years 1988 through 1996 and most notably rose dramatically beginning with the birth cohort of 1993.
                The significance of this finding is that MMR vaccination is most unlikely to be a main cause of ASD, that it cannot explain the rise over time in the incidence of ASD, and that withdrawal of MMR in countries where it is still being used cannot be expected to lead to a reduction in the incidence of ASD. A link has been postulated between measles-mumps-rubella (MMR) vaccine and a form of autism that is a combination of developmental regression and gastrointestinal symptoms that occur shortly after immunization. This hypothesis has involved 3 separate claims: 1) that there is new phenotype of autism involving regression and gastrointestinal symptoms, 2) that this new variant is responsible for the alleged rise of autism rates, and 3) that this phenotype is associated with biological findings suggestive of the persistence of measles infection. We tested the first of these claims. If this new "autistic enterocolitis" syndrome had some validity, then 1 or several of the following 6 predictions should be supported by empirical data: 1) childhood disintegrative disorder has become more frequent, 2) the mean age of first parental concern for autistic children who are exposed to MMR is closer to the mean immunization age than in children who are not exposed to MMR, 3) regression in the development of children with autism has become more common in MMR-vaccinated children, 4) the age of onset for autistic children with regression clusters around the MMR immunization date and is different from that of autistic children without regression, 5) children with regressive autism have distinct symptom and severity profiles, and 6) regressive autism is associated with gastrointestinal symptoms and/or inflammatory bowel disorder.
                Three samples were used. Epidemiologic data on 96 children (95 immunized with MMR at a median age of 13.5 months) who were born between 1992 and 1995 and had a pervasive developmental disorder diagnosis as reported in a recent UK survey (post-MMR sample) were compared with data from 2 previous clinical samples (1 pre-MMR [n = 98] and 1 post-MMR [n = 68]) of autistic patients. All patients were assessed with the standardized Autism Diagnostic Interview (ADI), allowing rigorous comparison of age at first parental concerns and rates of regression across samples. Reliability was excellent on ADI scores, age of parental concern, and developmental regression. Furthermore, data on bowel symptoms and disorders were available in the epidemiologic survey from both pediatric and parental sources, and immunization dates were obtained from computerized records.
                The prevalence of childhood disintegrative disorder was 0.6/10 000 (95% confidence interval: 0.02-3.6/10 000); this very low rate is consistent with previous estimates and is not suggestive of an increased frequency of this form of pervasive developmental disorder in samples of children who are immunized with MMR. There was no difference in the mean age at first parental concern between the 2 samples exposed to MMR (19.3 and 19.2 months) and the pre-MMR sample (19.5 months). Thus, MMR immunization was not associated with a shift toward an earlier age for first parental concerns. Similarly, the rate of developmental regression reported in the post-MMR sample (15.6%) was not different from that in the pre-MMR sample (18.4%); therefore, there was no suggestion that regression in the developmental course of autism had increased in frequency since MMR was introduced. In the epidemiologic sample, the subset of autistic children with regression had no other developmental or clinical characteristics, which would have argued for a specific, etiologically distinct phenotype. Parents of autistic children with developmental regression detected the first symptoms at a very similar age (19.8 months) to those of autistic children without regression (19.3 months). Moreover, the mean intervals from MMR immunization to parental recognition of autistic symptoms were comparable in autistic children with or without regression (248 vs 272 days; not significant). In the epidemiologic sample, gastrointestinal symptoms were reported in 18.8% of children. Constipation was the most common symptom (9.4%), and no inflammatory bowel disorder was reported. Furthermore, there was no association between developmental regression and gastrointestinal symptoms (odds ratio: 0.63; 95% confidence interval: 0.06-3.2; not significant), and only 2.1% of the sample experienced both problems, a rate that did not exceed chance expectations.
                No evidence was found to support a distinct syndrome of MMR-induced autism or of "autistic enterocolitis." These results add to the recent accumulation of large-scale epidemiologic studies that all failed to support an association between MMR and autism at population level. When combined, the current findings do not argue for changes in current immunization programs and recommendations. Description of an outbreak of mumps in an urban area. Study of the effectiveness of the mumps component of the triple virus (TV) vaccination.
                Cross sectional descriptive study of the outbreak. The cases were obtained from the Andalusian Register of Infectious Diseases (SVEA in Spanish). The effectiveness of the vaccine was studied through a retrospective cohort design, with the cohorts defined according to their vaccination history.
                Urban area of low social class and income and young population pyramid. The outbreak occurred between March and November 1997. The effectiveness of vaccination at one school was studied. PATIENTS AND OTHER PARTICIPANTS, RESIDENTS IN THE AREA: The source of the population was the 1996 municipal census.
                The declared cases of mumps were taken from the SVEA. The state of vaccination was documented through a review of the school registration records, vaccination cards and the health centre register of names.
                A total of 283 cases of mumps were declared. There were more cases in the 0-10 age group than at older ages. 79% of cases were vaccinated (95% CI, 74.3-73.7). Effectiveness of a dose of the mumps component of the vaccine was low (46%; CI, 0-84), though the effectiveness of a second dose was higher (87%; CI, 27-99).
                The low effectiveness of the mumps component of the TV vaccination was confirmed. It is proposed that the age for the second dose should be brought forward to school-starting age (primary, first year). Ensuring school vaccination is recommended. Viral childhood infections may be involved in the multiple sclerosis (MS) pathogenesis. Following national Swedish vaccination programs, measles sharply declined in the 1970s, and measles, mumps, and rubella were virtually eliminated in cohorts born from 1981.
                To examine whether the vaccination induced reduction in these infections influences the MS incidence. In addition, the public health aspect justified an early evaluation of beneficial as well as harmful effects of mass vaccinations.
                From an incidence material of 534 MS patients, born 1959-1990, we selected one unvaccinated cohort and four cohorts, each corresponding to a vaccination program (MS patients = 251).
                With the ability to detect a decrease by 30-35%, and an increase by 37-48% in the MS incidence in the first three cohorts, we found no vaccination related MS incidence changes. The background MS incidence showed a significant gradual age dependent increase.
                While the present follow-up provided limited power in the last cohort, there is no evidence as yet that the radical decline in three viral infections influenced the MS incidence. However, the increasing background MS incidence of unknown cause may have concealed a reduction in MS risk associated with mass vaccinations. 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. Data from routine surveillance during two mass immunisation campaigns (MIC) with Measles-mumps-rubella (MMR)vaccine using Leningrad-Zagreb mumps strain in two states in Brazil were analysed to estimate the risk of vaccine-related meningitis and mumps. Increase in the incidence of the two diseases was observed in both states, 3 weeks after the vaccination campaigns. The estimated number of doses applied per one case of vaccine-related meningitis ranged from 6199 (95% CI: 4854-8058) to 19,247 (95% CI: 12,648-29,513) depending on the diagnostic criteria used and state. It was 300 doses (95% CI: 286-317) for each case of mumps. The implications for vaccination policy are discussed. To provide accurate information on the common sequelae of measles-mumps-rubella (MMR) vaccination and to compare post-vaccine symptoms in children vaccinated at 13 and 15 months.
                Prospective cluster randomized controlled trial.
                Twenty-two family practices in southwestern Ontario.
                All 376 infants who were due to receive MMR vaccine in the next year, 253 (67.3%) successfully completed the study.
                MMR vaccine administered at 13 months by half of the family physicians and at 15 months by the remaining half.
                Family physician's physical findings in children 7 days and 30 days after vaccine; reported illnesses by mothers in a daily diary in the month before and after vaccination and medical records of visits to family physicians and hospital admissions in the month before and after vaccination.
                Compared with the incidence rates in the corresponding weeks before vaccination, the rates of lymphadenopathy (23.8%) and fever (16.8%) were higher 1 week afterward and the rate of rash (26.9%) was higher 7 to 14 days afterward. Fewer health problems were reported in the third and fourth weeks after vaccination than in the corresponding weeks beforehand. Hospital admissions after vaccination were no more frequent than those before once cause and time of admission were taken into account. The two age groups did not differ in any of the outcomes.
                Mothers should be informed about the possibility of increased physical findings in the weeks after MMR vaccination, especially lymphadenopathy, nasal discharge and rash. Since the occurrence of sequelae does not seem to differ significantly between 13-month-old recipients and 15-month-old recipients, it should not influence the decision of when to administer the vaccine. We evaluated the effectiveness of the Jeryl Lynn strain vaccine in a large outbreak of mumps in Navarre, Spain, 2006-2008. Each of the 241 cases of mumps occurring in children over 15 months of age born between 1998 and 2005 was compared with 5 controls individually matched by sex, birth date, district of residence and paediatrician. Vaccination history was obtained blindly from clinical records. Conditional logistic regression was used to obtain the matched odds ratios (ORs), and effectiveness was calculated as 1-OR. Some 70% of cases had received one dose of measles-mumps-rubella vaccine, and 24% had received two doses. Overall vaccine effectiveness was 72% (95% CI, 39-87%). Two doses were more effective (83%; 54-94%) than a single dose (66%; 25-85%). Among vaccinated children, risk was higher in those who had received the first dose after 36 months of age (OR=3.1; 1.2-8.4) and those who had received the second dose 3 or more years before study enrolment (OR=10.2; 1.5-70.7). Early waning of immunity in children after the second dose may contribute to reduced vaccine effectiveness for mumps prevention. In a series of clinical studies of a combined measles (Schwarz strain), mumps (Jeryl Lynn strain), and rubella (Cendehill strain) vaccine, 1,481 children received the vaccine or a placebo. The vaccine did not cause any significant reactions. The frequencies of mild, transient fever or rash or both in triple-susceptible vaccinees were similar to those that follow use of Schwarz strain measles vaccine alone. Measles, mumps, and rubella seroconversion rates in triple-susceptible vaccinees ranged from 95% to 100%. Geometric mean antibody titers were as high as those that usually result from use of these same virus strains as monovalent vaccines. The Republic of the Marshall Islands (RMI) is a South Pacific nation freely associated with the United States. In 2003, the RMI experienced the largest measles outbreak within the United States or its associated areas for more than a decade, although the reported coverage of 1-dose measles-mumps-rubella (MMR) vaccine was 80%-93%. The outbreak ended only after vaccination of >35,000 persons among a population of 51,000. Of outbreak cases, 41% were reported to have been previously vaccinated. We studied measles attack rates in RMI households to assess vaccine effectiveness and patterns of disease transmission.
                For the household secondary attack rate study, households were selected by convenience sampling of outbreak measles cases. The primary case was defined as the first person with measles in a household. Secondary cases were household members with measles onset 7-18 days after the primary case's rash onset. Vaccine effectiveness analysis was limited to children aged 6 months to 14 years, with vaccination status verified against written records.
                Seventy-two households were included in the study. The median household size was 11 persons, and the median number of persons per room was 5.5. Secondary cases were more likely than primary cases to be infants (46% vs. 13%; P=.03). MMR vaccine effectiveness was 92% (95% confidence interval [CI], 67%-98%) for 1 dose and 95% (95% CI, 82%-98%) for 2 doses.
                Measles vaccine effectiveness was high; thus, diminished effectiveness was not the main cause of the outbreak. In communities with high population density and household crowding, very high population immunity is needed to prevent measles outbreaks and to protect infants below the age of vaccination. This may require excellent implementation of a routine 2-dose measles vaccination strategy. 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.
                Using the General Practice Research Database we identified children with a first-time diagnosis of ITP from a base population of children aged less than 6 years between January 1988 and December 1999. After describing the characteristics of all the children identified with ITP, we focused on cases aged 13-24 months to perform a population-based, case-control analysis to estimate the relative risk of developing ITP within 6 weeks after MMR vaccination. We also calculated the risk of ITP attributable to the MMR vaccination.
                Sixty-three children with a first time diagnosis of ITP were identified; 23 cases were between 13 and 24 months old. The relative risk estimate for ITP within 6 weeks after MMR vaccination, compared to the combined group of unvaccinated children and children vaccinated with MMR more than 26 weeks previously was 6.3 (95% CI 1.3-30.1). The attributable risk of developing ITP within 6 weeks after MMR vaccination was estimated to be 1 in 25,000 vaccinations (95% confidence interval 21,300, 89,400).
                This study confirms the increased risk of ITP within 6 weeks after MMR vaccination. However, the attributable risk of ITP within 6 weeks after MMR vaccination is low. We sought to investigate the risk of serious neurologic disease after immunization in early childhood.
                The results of a 3-year prospective study of children (2-35 months old) in Britain and Ireland with encephalitis and/or severe illness with convulsions and fever were linked to each child's vaccine history. Cases were reported via the British Paediatric Surveillance Unit's network. The self-controlled case-series method was used to investigate associations between immunization and acute potential adverse events. The risk periods investigated were 0 to 3 and 0 to 7 days post-diphtheria, tetanus, whole cell pertussis, Haemophilus influenzae type b or meningococcal C conjugate vaccine and 6 to 11 and 15 to 35 days post-measles, mumps, rubella vaccine.
                A total of 157 disease episodes from 155 children met the analytical case definition. There were 11 cases of herpes simplex encephalitis and 23 cases of primary human herpesvirus 6 and/or 7 infection. There was no evidence of a raised relative incidence of serious neurologic disease in any of the specified risk periods with the exception of a raised relative incidence of 5.68 in the 6-11 days after measles, mumps, rubella vaccine. Based on this relative incidence, between 3 and 6 of the 6 cases in this period were estimated to be attributable to the vaccine with a best estimate of 5. The 6 cases all had fever with convulsions lasting >30 minutes; in all but 1, there was complete recovery by discharge from hospital. Of the 5 patients who recovered, 1 had a concurrent primary human herpesvirus 6 infection and one a primary human herpesvirus 7.
                Six to 11 days after measles, mumps, rubella vaccine there is an increased risk of fever and convulsions lasting >30 minutes. All 6 of the episodes temporally related to immunization met the criteria for complex febrile convulsions. The estimated attributable risk of serious neurological disease was similar to that previously found for measles vaccine. The authors evaluated the association between receipt of measles-mumps-rubella (MMR) vaccine and asthma-like disease in early childhood in a Danish nationwide cohort study (N = 871,234). Two outcomes were included: hospitalizations with asthma diagnoses and use of anti-asthma medications (for a subset of the cohort only). Poisson regression was used to estimate rate ratios according to vaccination status. MMR-vaccinated children were less often hospitalized with an asthma diagnosis (rate ratio (RR) = 0.75, 95% confidence interval (CI): 0.73, 0.78) and used fewer courses of anti-asthma medication (RR = 0.92, 95% CI: 0.91, 0.92) than unvaccinated children. This "protective" effect of MMR vaccine was more pronounced for hospitalizations with severe asthma diagnoses (status asthmaticus: RR = 0.63, 95% CI: 0.49, 0.82) and use of medication that was highly specific for asthma (long-acting beta2-agonist inhalant: RR = 0.68, 95% CI: 0.63, 0.73). MMR vaccine was not negatively associated with anti-asthma medications often used for wheezing illnesses in early childhood (systemic beta2-agonist: RR = 1.02, 95% CI: 1.01, 1.02). These results are compatible not with an increased risk of asthma following MMR vaccination but rather with the hypothesis that MMR vaccination is associated with a reduced risk of asthma-like disease in young children. To compare ages at first measles-mumps-rubella (MMR) vaccination between children with autism and children who did not have autism in the total population and in selected subgroups, including children with regression in development.
                A case-control study was conducted in metropolitan Atlanta. Case children (N = 624) were identified from multiple sources and matched to control children (N = 1824) on age, gender, and school. Vaccination data were abstracted from immunization forms required for school entry. Records of children who were born in Georgia were linked to Georgia birth certificates for information on maternal and birth factors. Conditional logistic regression was used to estimate odds ratios (ORs).
                The overall distribution of ages at MMR vaccination among children with autism was similar to that of matched control children; most case (70.5%) and control children (67.5%) were vaccinated between 12 and 17 months of age. Similar proportions of case and control children had been vaccinated before 18 or before 24 months. No significant associations for either of these age cutoffs were found for specific case subgroups, including those with evidence of developmental regression. More case (93.4%) than control children (90.6%) were vaccinated before 36 months (OR: 1.49; 95% confidence interval: 1.04-2.14 in the total sample; OR: 1.23; 95% confidence interval: 0.64-2.36 in the birth certificate sample). This association was strongest in the 3- to 5-year age group.
                Similar proportions of case and control children were vaccinated by the recommended age or shortly after (ie, before 18 months) and before the age by which atypical development is usually recognized in children with autism (ie, 24 months). Vaccination before 36 months was more common among case children than control children, especially among children 3 to 5 years of age, likely reflecting immunization requirements for enrollment in early intervention programs. The measles-mumps-rubella vaccine has been associated with immune thrombocytopenia purpura in 2 small studies.
                By using the Vaccine Safety Datalink, we identified measles-mumps-rubella-vaccinated children aged 1 to 18. A case of immune thrombocytopenia purpura was defined as a patient with a platelet count of < or = 50,000/microL with clinical bleeding and normal red and white blood cell indices. The immune thrombocytopenia purpura incidence rates during exposed (42 days after vaccination) and unexposed time periods were determined. A retrospective cohort of vaccinated children was used to determine incident rate ratios for children aged 1 to 18 years, 12 to 23 months, and 12 to 15 months.
                A total of 1,036,689 children received 1,107,814 measles-mumps-rubella vaccinations; there were 259 confirmed patients with immune thrombocytopenia purpura. Because only 5 exposed cases occurred after age 2, analyses were limited to children aged 12 to 23 months. Exposed patients aged 12 to 23 months had lower median platelet counts than those who were unexposed and had similar median duration of illness (11 vs 10 days). The incident rate ratio was highest for children aged 12 to 15 months at 7.10. The incident rate ratio for boys aged 12 to 15 months was 14.59, and the incident rate ratio for girls in the same age group was 3.22. Seventy-six percent of immune thrombocytopenia purpura cases in children aged 12 to 23 months were attributable to measles-mumps-rubella vaccination. This vaccine causes 1 case of immune thrombocytopenia purpura per every 40,000 doses.
                Measles-mumps-rubella vaccine that is given in the second year of life is associated with an increased risk of immune thrombocytopenia purpura. A few previous studies have suggested that childhood vaccines, particularly whole cell pertussis vaccine, may increase the risk of asthma. We evaluated the suggested association between childhood vaccinations and risk of asthma.
                Cohort study involving 167,240 children who were enrolled in 4 large health maintenance organizations during 1991 to 1997, with follow-up from birth until at least 18 months to a maximum of 6 years of age. Vaccinations were ascertained through computerized immunization tracking systems, and onset of asthma was identified through computerized data on medical care encounters and medication dispensings.
                In the study 18,407 children (11.0%) developed asthma, with a median age at onset of 11 months. The relative risks (95% confidence intervals) of asthma were: 0.92 (0.83 to 1.02) for diphtheria, tetanus and whole cell pertussis vaccine; 1.09 (0.9 to 1.23) for oral polio vaccine; 0.97 (0.91 to 1.04) for measles, mumps and rubella (MMR) vaccine; 1.18 (1.02 to 1.36) for Haemophilus influenzae type b (Hib); and 1.20 (1.13 to 1.27) for hepatitis B vaccine. The Hib result was not consistent across health maintenance organizations. In a subanalysis restricted to children who had at least 2 medical care encounters during their first year, the relative risks decreased to 1.07 (0.71 to 1.60) for Hib and 1.09 (0.88 to 1.34) for hepatitis B vaccine.
                There is no association between diphtheria, tetanus and whole cell pertussis vaccine, oral polio vaccine or measles, mumps and rubella vaccine and the risk of asthma. The weak associations for Hib and hepatitis B vaccines seem to be at least partially accounted for by health care utilization or information bias. 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. Vaccination against mumps in Portugal began in 1987, with the introduction of the combined measles, mumps, and rubella vaccine (MMR) in the national vaccination programme (Programa Nacional de Vacinacao: PNV) for both sexes at 15 months. In November 1990, Four hundred and twenty children were randomly assigned to receive either mumps measles rubella (MMR) vaccine (207) or measles vaccine (213) in a single blind study, to investigate the reactogenicity and serology of the MMR vaccine. There was no significant difference between the number of children developing symptoms after MMR vaccination to those developing symptoms after measles vaccination. Both vaccines are associated with a rash, temperature and restlessness five to thirteen days after vaccination. The serological response to measles vaccine was similar in both groups with 92-6% seroconverting with MMR, and 96-8% with measles. Seroconvertion against mumps and rubella with the MMR vaccine was 88% and 96% respectively. This study confirms the safety and efficacy of the MMR vaccine in a UK population. Leningrad-L3 Mumps Vaccine virus has been further attenuated by adaptation and passage on SPF chick embryo fibroblast cell cultures. This new mumps strain has been designated L-Zagreb and has been used to prepare mumps vaccines which meet the WHO requirements. Observations during both the field trial period prior to registration and during the later use of the vaccine showed that the few reactions observed were mild and that seroconversion was obtained in 88-98% of vaccines. The morbidity of mumps in Croatia declined more than tenfold after the introduction of the new vaccine. During a mumps epidemic, vaccine efficiency was calculated to be 97-100%. To assess the level of increased risk, if any, of hospitalizations for aseptic meningitis after Jeryl-Lynn mumps strain measles-mumps-rubella (MMR) vaccine in the Vaccine Safety Datalink population.
                A possible increased risk of aseptic meningitis 8 to 14 days after receipt of MMR was observed in a preliminary screening analysis of automated data from the Vaccine Safety Datalink (VSD) project Year 2 analysis. To further evaluate this association a retrospective 10-year matched case-control study was undertaken in the four health maintenance organizations (HMOs) in the VSD project. Cases ascertained from a broad scan of the automated data were validated against a standard case definition. Two controls matched on age, sex, HMO and HMO membership were assigned per case.
                The VSD project involves the cooperative collection of automated vaccination and medical outcome data from four large HMOs that currently have 500,000 children younger than 7 years of age under surveillance. Review of automated screening results from the first 2 years of data revealed a possible increased risk of aseptic meningitis 0 to 14 days after MMR with a relative risk of 3.61 (95% confidence interval, 1.0 to 13.1) although the total number of cases was small. Although the automated data had suggested a possible association of aseptic meningitis with MMR containing the Jeryl-Lynn strain of mumps, review of validated hospitalized cases during the observation period did not reveal evidence of an increased risk of aseptic meningitis after MMR containing the Jeryl-Lynn strain of mumps (odds ratio < 1.0 for all analyses).
                Although it is recognized that hospitalized cases represent a minority of the total cases of aseptic meningitis, it is reassuring that in this evaluation no increased risk of aseptic meningitis after MMR vaccine was found. The rate of febrile seizures increases following measles, mumps, and rubella (MMR) vaccination but it is unknown whether the rate varies according to personal or family history of seizures, perinatal factors, or socioeconomic status. Furthermore, little is known about the long-term outcome of febrile seizures following vaccination.
                To estimate incidence rate ratios (RRs) and risk differences of febrile seizures following MMR vaccination within subgroups of children and to evaluate the clinical outcome of febrile seizures following vaccination.
                A population-based cohort study of all children born in Denmark between January 1, 1991, and December 31, 1998, who were alive at 3 months; 537,171 children were followed up until December 31, 1999, by using data from the Danish Civil Registration System and 4 other national registries.
                Incidence of first febrile seizure, recurrent febrile seizures, and subsequent epilepsy.
                A total of 439,251 children (82%) received MMR vaccination and 17,986 children developed febrile seizures at least once; 973 of these febrile seizures occurred within 2 weeks of MMR vaccination. The RR of febrile seizures increased during the 2 weeks following MMR vaccination (2.75; 95% confidence interval [CI], 2.55-2.97), and thereafter was close to the observed RR for nonvaccinated children. The RR did not vary significantly in the subgroups of children that had been defined by their family history of seizures, perinatal factors, or socioeconomic status. At 15 to 17 months, the risk difference of febrile seizures within 2 weeks following MMR vaccination was 1.56 per 1000 children overall (95% CI, 1.44-1.68), 3.97 per 1000 (95% CI, 2.90-5.40) for siblings of children with a history of febrile seizures, and 19.47 per 1000 (95% CI, 16.05-23.55) for children with a personal history of febrile seizures. Children with febrile seizures following MMR vaccinations had a slightly increased rate of recurrent febrile seizures (RR, 1.19; 95% CI, 1.01-1.41) but no increased rate of epilepsy (RR, 0.70; 95% CI, 0.33-1.50) compared with children who were nonvaccinated at the time of their first febrile seizure.
                MMR vaccination was associated with a transient increased rate of febrile seizures but the risk difference was small even in high-risk children. The long-term rate of epilepsy was not increased in children who had febrile seizures following vaccination compared with children who had febrile seizures of a different etiology. nan It has been suggested that the measles, mumps, and rubella vaccine (MMR) is a cause of regressive autism. As MMR was used in Japan only between 1989 and 1993, this time period affords a natural experiment to examine this hypothesis. Data on 904 patients with autism spectrum disorders (ASD) were analyzed. During the period of MMR usage no significant difference was found in the incidence of regression between MMR-vaccinated children and non-vaccinated children. Among the proportion and incidence of regression across the three MMR-program-related periods (before, during and after MMR usage), no significant difference was found between those who had received MMR and those who had not. Moreover, the incidence of regression did not change significantly across the three periods. Indigenous cases of measles continue to occur in Singapore despite the implementation of a two-dose mumps, measles and rubella (MMR) vaccination policy in 1998. We investigated a measles outbreak that took place in a primary school from April 17 to May 6, 2004 to identify all cases, evaluate vaccine efficacy (VE) and implement outbreak control measures.
                A case of measles was defined as anyone having generalised rash and fever with or without cough, coryza or conjunctivitis during the outbreak period, and who had either laboratory-confirmed acute measles infection or was epidemiologically linked to a patient with laboratory-confirmed measles infection. Vaccination status was obtained from the studentos health booklet and confirmed with the National Immunisation Registry. Attack rates in unvaccinated (ARU) and vaccinated (ARV) students were calculated and VE was evaluated using the formula: VE (percent) = [(ARU-ARV) / ARU] x 100 percent.
                Nine students, aged between eight and 14 years, from five classes in primary three and primary six, were epidemiologically linked to have measles. None of them had received the second dose of the MMR vaccine. 93 percent of students in the affected classes (n = 184) had prior documented evidence of receiving at least one dose of MMR vaccination, as compared to 96.5 percent for the entire school enrolment (n = 1,309). The attack rate was 1.2 percent in the vaccinated group and 53.8 percent in the unvaccinated group. The VE for the primary dose of MMR in the affected classes was 97.8 percent.
                It is important to achieve a high coverage for the primary dose of MMR vaccine in order to prevent any potential outbreaks prior to receiving the booster dose.
The design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate. The evidence of adverse events following immunisation with the MMR vaccine cannot be separated from its role in preventing the target diseases.