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Background: Probiotics have been shown to be immunomodulatory and can affect antibody responses following vaccination. Several immunisations are associated with suboptimal seroconversion rates leaving a substantial part of the population exposed to infection., Objectives: To evaluate the influence of probiotic supplementation on the immune response of infants following mumps, measles, rubella and varicella vaccination., Methods: A randomised, placebo-controlled, double blinded prospective trial was performed in a cohort of healthy infants. Study subjects were randomly assigned to receive probiotics or placebo for a total of 5 months, starting 2 months prior to vaccination. Antibody levels against vaccine components were measured 3 months after immunisation. Treatment-related and vaccine-related adverse events were recorded., Findings: 47 infants completed the study, 25 in the probiotic group and 22 in the placebo group. There was no statistically significant difference in the number of infants failing to reach protective antibody titres against the different vaccine components (three infants in the placebo group against one in the treatment group for rubella, two each for mumps, four children vs two for measles). When combining all results in both groups, a larger percentage of failures to seroconvert occurred in the placebo group (17% vs 8%, p=0.052), a result of borderline significance. The number of infants needed to treat in order to prevent one failed vaccine component was 12. There was no difference in the rate of treatment related adverse effects between the two groups. There was a significant trend toward fewer vaccine related adverse effects in the treatment group., Conclusions: Oral probiotics given to infants during the period of immunisation do not interfere with the immune response to mumps, measles, rubella and varicella vaccine, and may improve seroconversion rates.

Concern exists about measles, mumps and rubella (MMR) vaccine in egg-allergic children, although this has been shown to be safe. Guidelines from the Royal College of Paediatrics and Child Health (RCPCH) and British Society of Allergy and Clinical Immunology (BSACI) suggesting which children should be referred to hospital for MMR, were published in 2000. We audited referrals to hospital for MMR against these guidelines. One hundred and ten children were referred for MMR to Birmingham Heartlands Hospital (2002-2004) and Alder Hey Children's Hospital (2006-2009). Eighty-two (75%) children did not meet the published criteria. Only 13 children (12%) had severe egg allergy. The first dose of MMR vaccine was delayed by >30 days in 81% of children. All children were given MMR, none had a significant reaction. Children with egg allergy do not need to be given MMR in hospital, but MMR is often delayed by unnecessary hospital referral. New BSACI guidelines encouraging MMR vaccination of egg-allergic children in primary care need to be disseminated.

Objective: To examine how journals and magazines disseminate research evidence and guidance on best practice to health professionals by aligning commentaries on measles, mumps, and rubella vaccine (MMR) evidence in journals with key events in the MMR controversy., Design: Content analysis., Data Sources: Comment articles in six commonly read UK publications., Main Outcome Measures: Number of comment pieces by publication, year and article type; trends in the focus, tone and inclusion of recommendations on MMR., Results: 860 articles met the inclusion criteria (BMJ n = 104, Community Practitioner n = 45, Health Visitor n = 24, Practice Nurse n = 61, Nursing Standard n = 61 and Pulse n = 565). Of these 860 comment pieces, 264 made some reference to evidence endorsing the safety of MMR. Around one in 10 were rated as negative (10.9%, n = 29) or neutral (11.3%, n = 30) in relation to MMR safety, and nearly a quarter (22.7%, n = 60) were rated as mixed. Following the publication of Wakefield et al's 1998 paper there was a period of neutrality. In 2000, despite growing public concerns and widespread media coverage, fewer than 20 comment pieces were published. Less than a quarter of comment pieces (n = 196, 22.7%) included recommendations., Conclusion: While a period of neutrality may reflect a professional response to uncertainty by holding back until consensus emerges, it may also represent a missed opportunity to promote evidence-based practice.

Objective: To study the immunogenicity and reactogenicity of a combined Haemophilus influenzae type b and Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) when administered as a booster dose in combination with a measles, mumps and rubella vaccine (MMR)., Design: A phase 3 open randomised controlled trial., Setting: One centre in Oxford, UK and nine centres in Poland., Subjects: 12-15-month-old healthy children., Interventions: In the primary stage of the study 500 healthy 6-12-week-old infants were randomised in a 3:1 ratio to receive Hib-MenC-TT+DTPa-IPV or MenC-CRM197 vaccine+DTPa-IPV-Hib. In the booster stage, 476 participants (190 in the UK and 286 in Poland) were vaccinated with Hib-MenC-TT and MMR., Main Outcome Measures: The proportion of children with protective serum antibody levels against MenC and Hib 6 weeks following a Hib-MenC-TT booster dose., Results: The co-primary objectives were met: the Hib-MenC-TT booster dose induced protective antibody titres in children vaccinated with Hib-MenC-TT+DTPa-IPV or MenC-CRM197+DTPa-IPV-Hib at 2, 3 and 4 months of age. 94.8% (lower limit of (LL) 95% CI 92.4) of participants had rSBA-MenC >or=1:128 and 100% (LL 95% CI 99.2) achieved anti-PRP concentrations >or=1.0 microg/ml. The percentage of toddlers with a post boost rSBA-MenC of 1:128 was significantly higher after priming with Hib-MenC-TT (97.7%) than after MenC-CRM197 (86%) (difference: 11.7%; 95% CI 6.2 to 19.4)., Conclusion: The waning antibody titres against Hib and MenC following primary immunisation can be boosted to protective levels by administering the Hib-MenC-TT vaccine at 12-15 months of age, supporting the recent introduction of this vaccine in the UK immunisation schedule to sustain protection of children against Hib and MenC disease., Trial Registration Number: NCT00258700. Study ID: 103974 (http://clinicaltrials.gov).

Objective: To test the hypothesis that measles vaccination was involved in the pathogenesis of autism spectrum disorders (ASD) as evidenced by signs of a persistent measles infection or abnormally persistent immune response shown by circulating measles virus or raised antibody titres in children with ASD who had been vaccinated against measles, mumps and rubella (MMR) compared with controls., Design: Case-control study, community based., Methods: A community sample of vaccinated children aged 10-12 years in the UK with ASD (n = 98) and two control groups of similar age, one with special educational needs but no ASD (n = 52) and one typically developing group (n = 90), were tested for measles virus and antibody response to measles in the serum., Results: No difference was found between cases and controls for measles antibody response. There was no dose-response relationship between autism symptoms and antibody concentrations. Measles virus nucleic acid was amplified by reverse transcriptase-PCR in peripheral blood mononuclear cells from one patient with autism and two typically developing children. There was no evidence of a differential response to measles virus or the measles component of the MMR in children with ASD, with or without regression, and controls who had either one or two doses of MMR. Only one child from the control group had clinical symptoms of possible enterocolitis., Conclusion: No association between measles vaccination and ASD was shown.

We report a case of pneumonia in a 13 month old male child with partial DiGeorge syndrome who died after inadvertently receiving live viral vaccines. Although live viral vaccines have been used safely in some children with DiGeorge syndrome, there are insufficient data to recommend their routine use in those with severe immunodeficiency.

Objective: To explore how the measles, mumps, and rubella (MMR) vaccine controversy impacted on the lives of parents caring for children with autism., Design: Qualitative focus group study., Setting: United Kingdom., Patients: A purposively selected sample of 38 parents took part in 10 focus group discussions between March 2003 and May 2005., Results: Many parents felt that the MMR vaccine could be too potent for children who are susceptible to developing autism. Of the parents whose children received the MMR vaccine, many felt guilty that they may have caused or contributed to their child's autism. Some parents felt frustrated by health professionals' lack of understanding of the negative impact the MMR controversy has had on them. Some parents were anxious about subsequent MMR decision-making for their children., Conclusions: The controversy has had a negative impact on some parents of children with autism. This has implications for health professionals, who need to be particularly aware of the issues these parents face in future MMR decision-making for their affected child and younger siblings. It is anticipated that these findings will raise awareness among health professionals of the difficulties faced by such parents. More generally, there is a need to promote a greater awareness of the important role health visitors can play in parental decision-making and for research examining whether health professionals feel they receive sufficient training in communication skills. It is also essential that the latest scientific research findings are disseminated quickly to these parents and to those health professionals advising parents on matters of vaccine safety.

Background: Suggestions that immunisation influences allergic disease risk, either positively (pertussis) or negatively (BCG) are of concern for vaccination policy., Aims: To determine whether DTP, MMR, and BCG vaccination in infancy influenced hay fever risk., Methods: 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., Results: 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., Conclusions: 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.

Background: MMR vaccine has been reported to cause gait disturbance, and this possible association has been claimed to support the MMR-causes-autism theory., Aims: 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., Methods: 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., Results: 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., Conclusions: This study provides no evidence for a causal association between MMR and gait disturbance.

Background: The recorded prevalence of autistic spectrum disorders has risen over recent decades. Measles, mumps and rubella (MMR) vaccine has been blamed, by causing a "new variant" form of "regressive autism" associated with "autistic enterocolitis"., Aims: To estimate the prevalence of autism and to assess any changes in parental perception regarding the onset or causes of autism., Methods and Results: A total of 567 children with autistic spectrum disorder in five districts in north east London were identified, born 1979-98. Reported autism, excluding the 94 cases of Asperger's syndrome, increased by year of birth until 1992, since when prevalence has plateaued. This flattening off persisted after allowing for expected delay in diagnosis in more recent birth cohorts. The age at diagnosis of autistic spectrum disorder was estimated to have decreased per five year period since 1983, by 8.7% for childhood autism and by 11.0% for atypical autism. There was some evidence that MMR was more likely to be mentioned as a trigger after August 1997 than before., Conclusions: The prevalence of autism, which was apparently rising from 1979 to 1992, reached a plateau from 1992 to 1996 at a rate of some 2.6 per 1000 live births. This levelling off, together with the reducing age at diagnosis, suggests that the earlier recorded rise in prevalence was not a real increase but was likely due to factors such as increased recognition, a greater willingness on the part of educationalists and families to accept the diagnostic label, and better recording systems. The proportion of parents attributing their child's autism to MMR appears to have increased since August 1997.

Combined measles, mumps, and rubella (MMR) vaccine did not increase the risk of hospitalisation with invasive bacterial infection in the three months after vaccination; rather there was a protective effect. These results provide no support for the concept of "immunological overload" induced by multiple antigen vaccinations, nor calls for single antigen vaccines.

Parents of autistic children with regressive symptoms who were diagnosed after the publicity alleging a link with measles, mumps, and rubella (MMR) vaccine tended to recall the onset as shortly after MMR more often than parents of similar children who were diagnosed prior to the publicity. This is consistent with the recall bias expected under such circumstances.

A CAUSAL ASSOCIATION BETWEEN MEASLES: mumps-rubella (MMR) vaccine and idiopathic thrombocytopenic purpura (ITP) was confirmed using immunisation/hospital admission record linkage. The absolute risk within six weeks of immunisation was 1 in 22 300 doses, with two of every three cases occurring in the six week post-immunisation period being caused by MMR. Children with ITP before MMR had no vaccine associated recurrences.