Post-vaccination Adverse Events Research Articles

The effect of prophylactic antipyretic administration on post-vaccination adverse reactions and antibody response in children: a systematic review.

BackgroundProphylactic antipyretic administration decreases the post-vaccination adverse reactions. Recent study finds that they may also decrease the antibody responses to several vaccine antigens. This systematic review aimed to assess the evidence for a relationship between prophylactic antipyretic administration, post-vaccination adverse events, and antibody response in children.MethodsA systematic search of major databases including MEDLINE and EMBASE was carried out till March 2014. Randomized controlled trials (RCTs) comparing prophylactic antipyretic treatment versus placebo post-vaccination in children ≤6 years of age were included. Two reviewers independently applied eligibility criteria, assessed the studies for methodological quality, and extracted data [PROSPERO registration: CRD42014009717].ResultsOf 2579 citations retrieved, a total of 13 RCTs including 5077 children were included in the review. Prophylactic antipyretic administration significantly reduced the febrile reactions (≥38.0°C) after primary and booster vaccinations. Though there were statistically significant differences in the antibody responses between the two groups, the prophylactic PCM group had what would be considered protective levels of antibodies to all of the antigens given after the primary and booster vaccinations. No significant difference in the nasopharyngeal carriage rates (short-term and long-term) of H. influenzae or S. pneumoniae serotypes was found between the prophylactic and no prophylactic PCM group. There was a significant reduction in the local and systemic symptoms after primary, but not booster vaccinations.ConclusionsThough prophylactic antipyretic administration leads to relief of the local and systemic symptoms after primary vaccinations, there is a reduction in antibody responses to some vaccine antigens without any effect on the nasopharyngeal carriage rates of S. pneumoniae & H. influenza serotypes. Future trials and surveillance programs should also aim at assessing the effectiveness of programs where prophylactic administration of PCM is given. The timing of administration of antipyretics should be discussed with the parents after explaining the benefits & risks.

Rationally respond to post-vaccination adverse events

Rationally respond to post-vaccination adverse events

Antibody response to the non‐adjuvanted and adjuvanted influenza A H1N1/09 monovalent vaccines in renal transplant recipients

The 2009 pandemic influenza A (H1N1) virus spread rapidly throughout Brazil. Non-adjuvanted and the adjuvanted influenza A H1N1/09 monovalent vaccine were recommended as a single dose to persons at risk including renal transplant recipients (RTR). We analyzed the safety and the immune response of 2 influenza A H1N1/09 monovalent vaccines in RTR, and identified factors influencing the immune response. A total of 78 RTR received a single dose of either influenza A H1N1 2009 monovalent AS03-adjuvanted vaccine or a non-adjuvanted vaccine, and 58 healthy controls received a single dose of non-adjuvanted vaccine. Antibody responses to influenza A H1N1 were measured by hemagglutination inhibition assay and were compared between groups on the day of vaccination and 21-30days thereafter, using geometric mean titer (GMT), and seroprotection (SP) and seroconversion (SC) rates. Among RTR, after adjuvanted and non-adjuvanted H1N1 vaccination, the SP rate increased from 16.7% to 61.7% (P<0.001) and to 50% (P<0.001), and SC rates were 61.7% and 50%, respectively. For healthy controls, SP rate increased from 25.8% to 89.7% (P<0.001), and SC rate was 87.9% after vaccination. Pre-vaccination GMT for the adjuvanted and non-adjuvanted RTR vaccine groups and healthy controls was 9.7 (95% confidence interval [CI] 7.3-13.1), 8.9 (95% CI 5.4-14.7), and 12.5 (95% CI8.7-18.2), and significantly increased to 49.8 (95% CI 31.3-79.4, P<0.001), 43.2 (95% CI 16.3-114.4, P<0.001), and 323.8 (95% CI 213.9-490.2, P<0.001), respectively. Deceased-donor type transplant significantly reduced SP (odds ratio [OR]=4.62, 95% CI 1.36-15.69, P=0.014) and SC (OR=6.29, 95% CI 1.89-20.98, P=0.003) rates, and younger age positively affected SP (OR=0.11; 95% CI 0.03-0.04, P=0.001). Adverse events were mild, and renal function showed no change post vaccination. RTR vaccinated with either an adjuvanted or non-adjuvanted monovalent influenza vaccine presented poor response compared with healthy controls. Post-vaccination adverse events were mild, and no rejection episode or renal dysfunction was observed.

Ontology-based time information representation of vaccine adverse events in VAERS for temporal analysis.

BackgroundThe U.S. FDA/CDC Vaccine Adverse Event Reporting System (VAERS) provides a valuable data source for post-vaccination adverse event analyses. The structured data in the system has been widely used, but the information in the write-up narratives is rarely included in these kinds of analyses. In fact, the unstructured nature of the narratives makes the data embedded in them difficult to be used for any further studies.ResultsWe developed an ontology-based approach to represent the data in the narratives in a “machine-understandable” way, so that it can be easily queried and further analyzed. Our focus is the time aspect in the data for time trending analysis. The Time Event Ontology (TEO), Ontology of Adverse Events (OAE), and Vaccine Ontology (VO) are leveraged for the semantic representation of this purpose. A VAERS case report is presented as a use case for the ontological representations. The advantages of using our ontology-based Semantic web representation and data analysis are emphasized.ConclusionsWe believe that representing both the structured data and the data from write-up narratives in an integrated, unified, and “machine-understandable” way can improve research for vaccine safety analyses, causality assessments, and retrospective studies.

A prática da enfermagem frente aos eventos adversos pós-vacinação

Este artigo tem como objetivos identificar eventos adversos pós-vacinação, foco da prática da enfermagem, em base de dados do Sistema de Informação de Eventos Adversos Pós-Vacinação e discutir a atuação do enfermeiro na sua vigilância. Utilizaram-se dados secundários referentes às vacinas aplicadas na rede pública de saúde brasileira, no período de 1999 a 2008, totalizando 65.442 registros, sendo 59.899 confirmados e 1.403 associados com outra vacina. Os 16 eventos de atuação da enfermagem perfizeram 21.727 registros. Embora representem 35,4% dos registros, os dados não refletem a realidade, pois sua fidedignidade depende da rede de conhecimento que engloba diagnóstico, notificação e inclusão no sistema. Discutiram-se as intervenções para os eventos de maior prevalência: febre e eventos locais. A maioria das intervenções estabelecidas no manual de eventos adversos estava de acordo com a literatura, porém verificaram-se diferenças de conteúdo entre as condutas para um mesmo evento decorrente de vacinas diferentes.

Evaluation of Immunization Rates and Safety Among Children With Inborn Errors of Metabolism

Children with inherited metabolic disorders are a potential high-risk group for vaccine-preventable diseases, yet information regarding immunization rates and vaccine safety within this population is limited. Using Northern California Kaiser Permanente's electronic medical record, we identified children with inborn errors of metabolism from 1990 to 2007. We assessed immunization rates among infants with inborn errors of metabolism born at Northern California Kaiser Permanente matched to healthy infants (1 to 20), comparing both vaccines received by 2 years of age and age at vaccination. We assessed postvaccination adverse events among children up to 18 years old with inborn errors of metabolism, separately comparing emergency-department visits and hospitalizations during postvaccine days 0 to 30 (primary) and days 0 to 14 (secondary). Comparing infants with inborn errors of metabolism (n = 77) versus matched control subjects (n = 1540), similar proportions were up to date for vaccines at 2 years of age, and there was no evidence of delay in receipt of recommended vaccines during the first year. Vaccination of children with inborn errors of metabolism (n = 271) was not associated with any significant increase in emergency-department visits or hospitalizations during the 30 days after vaccination. Secondary analyses suggested that there may be increased rates of hospitalizations 2 weeks after vaccination for the sickest 1- to 4-year-old children. Children with inborn errors of metabolism at Northern California Kaiser Permanente received vaccines on the same immunization schedule as healthy infants. Immunization was not associated with increased risk for serious adverse events during the month after vaccination, providing overall reassurance that routine vaccination of children with inborn errors of metabolism does not result in adverse effects.

Influenza Vaccination in Healthy Working Adults in Russia

All age groups are affected by influenza infection, resulting in significant medical and economic burden. Influenza infection of healthy working adults can have a marked effect on companies due to lost work days and reduced productivity. Studies in corporate settings have shown that vaccination programmes reduce this burden, although there is a lack of data in Eastern European countries. To determine the effectiveness of influenza vaccination in healthy working adults in Russia and the economic benefits of such a programme from an employer's perspective. In a prospective, non-randomized, non-placebo-controlled, observational study, healthy vaccinated and unvaccinated adults employed at the Russian Railways Public Corporation were followed for 8 months during the 2005-6 influenza season using questionnaires. A first questionnaire was administered at inclusion to collect general employee information; a second questionnaire was administered to collect data on post-vaccination adverse events; and monthly questionnaires were used to gather data on influenza-like illness (ILI). Effectiveness calculations and cost analyses were performed to evaluate the impact of the influenza vaccination programme on employee productivity and costs for the employer. The study vaccine used was the trivalent, inactivated, split vaccine Vaxigrip® (sanofi pasteur, France). A total of 1331 employees volunteered for the study: 701 were vaccinated and 630 were not. The vaccine effectiveness was 70.4% against ILI events and 80.8% against sick leave days. Assuming that employees working with ILI symptoms had a reduced level of productivity (30-70% of normal), cost savings per vaccinated employee ranged from &U20AC;2.13 to &U20AC;5.43. This study showed that an influenza vaccination programme significantly reduced ILI episodes and absenteeism, and may provide a positive return on investment for the employer.

Postvaccination Adverse Events

Postvaccination Adverse Events

Post-Marketing Safety Evaluation of a Tetanus Toxoid, Reduced Diphtheria Toxoid and 3-Component Acellular Pertussis Vaccine Administered to a Cohort of Adolescents in a United States Health Maintenance Organization

Prelicensure clinical studies may not include sufficient numbers of subjects to assess the potential for rare postvaccination adverse events. The aim of this postlicensure study (NCT00297856) was to evaluate uncommon outcomes following vaccination with a tetanus, reduced-antigen-content diphtheria, and acellular pertussis vaccine (Tdap, Boostrix GlaxoSmithKline) in a large adolescent cohort. We monitored safety outcomes among 13,427 10 to 18-year-old adolescents enrolled in the Northern California Kaiser Permanente Health Care Plan who received Tdap vaccination as part of their normal health care. Subjects were evaluated using self-control analysis comparing days 0 to 29 to days 30 to 59 postvaccination for neurologic events, hematologic events and allergic reactions. We evaluated new onset chronic illnesses within 6 months of Tdap vaccination by comparing with historical Td controls matched for age at vaccination, season, sex, and geographic area. We also compared the incidence of events of interest between the Tdap and historical cohorts as exploratory analyses. No increased risk for medically attended neurologic (odds ratio [OR], 0.962; 95% confidence interval [CI], 0.533-1.733) or allergic reactions (OR, 1.091; 95% CI, 0.441-2.729) was observed following Tdap vaccination when comparing the first 30 postvaccination days to the second 30 postvaccination days. There was one hematologic event within 30 days of Tdap, compared with 0 events within days 30 to 59 (P = 1.0). When compared with matched historical Td recipients, no increase in new onset chronic illnesses (OR, 0.634; 95% CI, 0.475-0.840) was seen after Tdap. No deaths occurred in the Tdap cohort during the study. This study provides no evidence for an increased risk for neurologic, hematologic, allergic events, or new onset of chronic illnesses among adolescents vaccinated with Tdap.

Monitoring the Safety of a Smallpox Vaccination Program in the United States: Report of the Joint Smallpox Vaccine Safety Working Group of the Advisory Committee on Immunization Practices and the Armed Forces Epidemiological Board

In December 2002, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices and the Department of Defense Armed Forces Epidemiological Board formed a joint Smallpox Vaccine Safety Working Group (SVS WG) to provide independent safety oversight for smallpox vaccination safety-monitoring systems. From January 2003 through June 2004, the SVS WG reviewed individual and aggregate safety data on postvaccination adverse events. Serious adverse events were rare because of careful education, prevaccination screening, and strict attention to vaccination-site management. Recent vaccinees safely cared for high-risk patients, adhering to recommended site care. Human immunodeficiency virus-infected individuals without severe immunosuppression had uncomplicated vaccination reactions. Epidemiological studies supported a causal relationship between myocarditis and/or pericarditis and smallpox vaccination. Data supported neutrality regarding hypothesized causal associations between vaccination and dilated cardiomyopathy or ischemic cardiac disease. The SVS WG concurs with recommendations to defer from vaccination any person with >/=3 ischemic cardiac disease risk factors.

Safety, immunogenicity, and antibody persistence of a new meningococcal group A conjugate vaccine in healthy Indian adults

We performed a double-blind, randomized, controlled phase I study to assess safety, immunogenicity, and antibody persistence of the new meningococcal group A conjugate vaccine (PsA-TT) in healthy volunteers aged 18-35 years. Of the 74 male subjects enrolled, 24 received the PsA-TT vaccine (Group 1), 25 received the Meningococcal Polysaccharide Vaccine A+C, Pasteur, Lyon, France (Group 2), and 25 received the Tetanus Toxoid Vaccine Adsorbed, SIIL, Pune India (Group 3). No immediate reactions were observed. Local and systemic solicited reactions within 7 days post-vaccination and unsolicited adverse events (AEs) were mild and similar among the three groups and resolved without sequelae. No serious AEs were notified up to 1 year post-vaccination. Four weeks post-vaccination, a slightly higher proportion of Group 1 subjects had a four-fold increase in SBA titers compared to Group 2 subjects (83% versus 72%, p>0.05). SBA GMTs in Groups 2 and 3 were higher than in Group 3 (p<0.05). Serogroup A-specific IgG GMCs were significantly higher in Group 1 than in Groups 2 (p<0.05) and 3 (p<0.05). After 1 year SBA titers were significantly higher in Group 1 than in Group 2 (p<0.05). The new PsA-TT vaccine was shown to be safe, immunogenic, and able to elicit persistent functional antibody titers in adults. This opens the prospective for further development and licensure of this vaccine to eliminate epidemic meningitis in sub-Saharan Africa.

Cuban Meningococcal BC Vaccine: Experiences &amp; Contributions from 20 Years of Application

This paper reviews 20 years of experience and scientific contributions of the Cuban meningococcal BC vaccine (VA-MENGOC-BC®) obtained by the Finlay Institute in Havana, Cuba. The vaccine is the first of its type in the world that is safe, effective, and commercially available for preventing meningococcal disease caused by serogroup B meningococcus; it is also effective against serogroup C. VA-MENGOC-BC® has shown satisfactory results, with no serious adverse events, after application of approximately 55 million doses in some 15 countries. Also included is background information on meningococcal disease, as well as the main characteristics of VA-MENGOC-BC®, the strategy used for controlling meningococcal disease and its prevention in Cuba, and a summary of the main scientific results obtained in basic research, development, clinical evaluation, and post-marketing results (safety, efficacy-effectiveness, post-vaccination adverse events, etc.) in Cuba and elsewhere.

Immunogenicity and Safety of Measles-Mumps-Rubella, Varicella and Haemophilus influenzae Type b Vaccines Administered Concurrently With a Fourth Dose of Heptavalent Pneumococcal Conjugate Vaccine Compared With the Vaccines Administered Without Heptavalent Pneumococcal Conjugate Vaccine

Prevnar [heptavalent pneumococcal conjugate vaccine (PCV7)] is licensed in the United States for routine administration in infants and may be coadministered with other infant vaccines. Safety and immunogenicity data on the coadministration of the fourth dose of PCV7 with measles-mumps-rubella (MMR), varicella and Haemophilus influenzae type b (Hib) vaccines are limited. Children 12-15 months of age received either MMR with PCV7 (group 1) or MMR without PCV7 (group 2). All subjects received Hib and varicella vaccines. Group 2 received PCV7 6-9 weeks after MMR vaccination. Sera for analysis of all non-PCV7 antibodies were collected just before administration of MMR vaccine and 6 weeks later. Optimal antigen responses were assessed with the use of predetermined antibody titers. The primary end point was >90% response rate (all antigens). Noninferiority was defined as <10% difference between groups. Local and systemic reactions and postvaccination adverse events were monitored and compared between groups. A total of 694 subjects (347 per group) were enrolled. After immunization with MMR plus PCV7 concurrently, or MMR followed 6 weeks later by PCV7, the percentages of subjects seroconverting were significantly greater than 90% for all antigens. The difference between the 2 groups was significantly less than 10%. The immune response to MMR, Hib and varicella vaccines, when administered concurrently with a 4th (booster) dose of PCV7, was noninferior to that of these vaccines when given without PCV7. These results support concomitant administration of PCV7 with MMR, varicella and Hib as part of the recommended immunization schedule for children 12-15 months of age.

Workplace Vaccination against Influenza in Malaysia: Does the Employer Benefit?

This study was designed to evaluate the health and economic benefits of a workplace vaccination programme against influenza funded by the employer. Employees of a Malaysian petrochemical plant volunteered to take part in this prospective, non-randomised, non-placebo-controlled study. Demographic and health information, including influenza-like symptoms, sick leave and post-vaccination adverse events were collected via questionnaires. Cost-benefit analyses were performed from the employer's perspective. A total of 1,022 employees took part in the study, with 504 choosing to be vaccinated against influenza, and 518 remaining unvaccinated. The rate of influenza-like illness (ILI) was lower among vaccinated (8.13%) than non-vaccinated subjects (30.31%). Fever and respiratory symptoms were associated with all ILI cases. ILI-related sick leave was taken by 58.54% of vaccinated employees with ILI and 71.34% of non-vaccinated employees with ILI. Vaccination was financially beneficial, with the employer saving up to US dollar 53.00 per vaccinated employee when labour costs only were considered. Savings rose to up to US dollar 899.70 when the operating income of each employee was also considered. Workplace vaccination of healthy adults against influenza had a clear impact on ILI rates, absenteeism and reduced productivity in this Malaysian company. The health benefits translated into financial benefits for the employer, with cost savings significantly outweighting the costs of the vaccination programme.

Comparative Evaluation of Safety and Immunogenicity of Two Dosages of an Oral Live Attenuated Human Rotavirus Vaccine

Rotavirus is a major cause of gastroenteritis in children worldwide and is estimated to be responsible for more than 500,000 physician visits, 50,000 hospitalizations and 20 deaths in the United States each year. To compare the safety and immunogenicity of 2 dosages of a live attenuated oral monovalent G1 human rotavirus (HRV) vaccine in healthy infants. In this randomized, double blind trial conducted in the United States and Canada, 529 healthy infants 5-15 weeks of age received HRV vaccine containing either 10 or 10 focus-forming units or placebo. Two doses were administered orally at a 2-month interval concomitantly with routine childhood vaccines. Symptoms of fever, irritability/fussiness, diarrhea, vomiting, loss of appetite and cough/runny nose were solicited for 15 days postvaccination, nonserious adverse events for 43 days postvaccination and serious adverse events throughout the study. Vaccine take was defined as appearance of serum antirotavirus IgA in postimmunization sera at a titer of > or =20 units/mL or vaccine virus shedding in any stool sample collected between the first dose and 2 months after the second dose. No serious adverse events considered related to vaccine were reported. The incidence of solicited symptoms was similar among treatment groups during the 15-day postvaccination surveillance periods. No significant difference in vaccine take after 2 doses (88.0% in high dose group and 81.5% in low dose group) was seen between vaccine groups (P = 0.153). Two doses of either dosage level of HRV vaccine administered concurrently with routine childhood vaccines to healthy infants 5-15 weeks of age were well-tolerated and were highly immunogenic.

Costs and Benefits of Influenza Vaccination and Work Productivity in a Colombian Company from the Employer's Perspective

Objectives This study was designed to evaluate the effects of an employee influenza vaccination campaign, measured in terms of health and economic benefits. Methods Colombian bank employees volunteered to take part in this prospective observational study involving two groups: vaccinated and nonvaccinated. Socioeconomic and health status information, including influenza-like symptoms, sick leave, and postvaccination adverse events, were collected via questionnaires. Cost–benefit analyses were performed to determine whether the employer would save money overall by paying for the vaccination program. Results Between October 2000 and May 2001, 424 vaccinated subjects and 335 nonvaccinated subjects volunteered to join the study. Cumulative incidence of influenza-like illness (ILI) was lower among vaccinated (14.6%) than nonvaccinated subjects (39.4%). Fever was the most common ILI symptom (93% of all reported ILI). Absence rates because of ILI were similar in the two groups (2.59%−2.69%). Assuming that employees with ILI who continue to work have reduced effectiveness (30%−70% of normal) the employer can save US$6.4 to US$25.8 per vaccinated employee based on labor costs alone. This saving increases to US$89.3 to US$237.8 when operating income is also considered. Sensitivity analyses indicate that the vaccination program will be cost saving for vaccination coverage above 20% and ILI rates above 10%. Conclusions Among the studied volunteers, ILI has significant impact on work productivity in terms of indirect costs. Implementing an influenza vaccination program would reduce the burden of ILI and save substantial amounts of money for the company.

Hepatitis A Vaccines-Reply

In Reply. —Several points raised by Dr Krause merit clarification. First, Merck was granted a US license for Vaqta (hepatitis A vaccine, inactivated), its hepatitis A vaccine, on March 29,1996; Vaqta went on the market in May 1996. The compositions of Vaqta and Havrix differ (Table). Whether these compositional differences will translate into better safety and tolerability is a scientific question that can only be answered by comparative trials. These trials for rare postvaccination adverse events will, by definition, require adverseexperience report surveillance of large populations of vaccinees that should be accruable over 1 or 2 years.

Immunogenicity of High-Titer Edmonston-Zagreb Measles Vaccine in Human Immunodeficiency Virus-Infected Children in Kinshasa, Zaire

The response to Edmonston-Zagreb vaccine (titer, 5.4 log10 pfu) was evaluated among children in a study of perinatal transmission of human immunodeficiency virus (HIV) in Kinshasa. Acute postvaccination adverse events were monitored for 49 HIV-infected and 376 non-HIV-infected infants, and measles antibody responses were assessed by ELISA for 34 HIV-infected and 255 non-HIV-infected infants. There was no increase in the incidence of common symptoms 7-10 days after vaccination. HIV-infected infants were more likely to have detectable prevaccination measles antibody, and seroconversion after vaccination was somewhat lower in HIV-infected (76.5%) than non-HIV-infected infants (85.5%). Seroconversion rates did not differ among children with or without rhinitis or fever at vaccination. High-titer Edmonston-Zagreb vaccine given at 6 months of age has the potential to provide earlier protection against measles; however, this vaccine is no longer recommended for routine use, and two doses of standard-titer vaccines remains the preferred option for measles vaccination of HIV-infected infants.

Permanent brain damage and pertussis vaccination: is the end of the saga in sight?

The development and widespread uptake of a safe and efficacious aluminium adsorbed diphtheria-tetanus-pertussis vaccine (DTP) in the United States between 1933 and 1944 led to a gradual decline in whooping cough morbidity and instilled confidence in a vaccination programme which has been effectively maintained for over 40 years. T his contrasts with the turbulent history of pertussis vaccination in the United Kingdom where doubts as to the efficacy of available vaccines delayed their active national promotion until 1957, after which various reports resulted in further doubts over efficacy and safety. In 1974, the mass media became involved in the safety issue when the National Hospital for Sick Children case series of neurological events, which had occurred after DTP vaccination was made core material for a television documentary. The Department of Health and Social Security (DHSS) responded by establishing two retrospective studies of case records of post vaccination adverse events and two prospective studies. One of the latter, the National Childhood Encephalopathy Study (NCES) was regarded as the definitive case control study. A claim for damages, Loveday v Renton and The Wellcome Foundation, heard in the High Court of Justice in London, from early October 1987 until late February 1988 dealt with the general issue of whether, on the balance of probabilities, pertussis vaccine could cause permanent brain damage. The cornerstone of the claim that pertussis vaccine can cause permanent brain damage has always been the apparent clustering of onset of neurological disorders within the first 24-48 h after vaccination. One of the main finds of the NCES, however, which was not divulged in any published report but emerged in the course of the hearing, was that permanent brain damage did not occur within 48 h of DTP vaccination in any child in England, Scotland and Wales from mid-1976 to mid-1979 when 2 million doses of vaccine were used. The NCES, in this respect, completely undermined the evidence provided by various published case series. After a 61 day hearing, High Court judgment was given to the effect that the judge was not satisfied on balance of probability that pertussis vaccine can cause permanent brain damage in young children. Were it not for the fact that The Wellcome Foundation intervened in the action and obtained a court order giving access to the NCES cases records, some crucial information collected by the NCES might not have been brought to light.(ABSTRACT TRUNCATED AT 400 WORDS)

Whooping Cough: Prevention and Treatment

The development and widespread uptake of a safe and efficacious aluminium adsorbed diphtheria—tetanus—pertussis vaccine (DTP) in the United States between 1933 and 1944 led to a gradual decline in whooping cough morbidity and instilled confidence in a vaccination programme which has been effectively maintained for over 40 years. T his contrasts with the turbulent history of pertussis vaccination in the United Kingdom where doubts as to the efficacy of available vaccines delayed their active national promotion until 1957, after which various reports resulted in further doubts over efficacy and safety. In 1974, the mass media became involved in the safety issue when the National Hospital for Sick Children case series of neurological events, which had occurred after DTP vaccination was made core material for a television documentary. The Department of Health and Social Security (DHSS) responded by establishing two retrospective studies of case records of post vaccination adverse events and two prospective studies. One of the latter, the National Childhood Encephalopathy Study (NCES) was regarded as the definitive case control study. A claim for damages, Loveday v Renton and The Wellcome Foundation, heard in the High Court of Justice in London, from early October 1987 until late February 1988 dealt with the general issue of whether, on the balance of probabilities, pertussis vaccine could cause permanent brain damage. The cornerstone of the claim that pertussis vaccine can cause permanent brain damage has always been the apparent clustering of onset of neurological disorders within the first 24–48 h after vaccination. One of the main finds of the NCES, however, which was not divulged in any published report but emerged in the course of the hearing, was that permanent brain damage did not occur within 48 h of DTP vaccination in any child in England, Scotland and Wales from mid-1976 to mid-1979 when 2 million doses of vaccine were used. T he NCES, in this respect, completely undermined the evidence provided by various published case series. After a 61 day hearing, High Court judgment was given to the effect that the judge was not satisfied on balance of probability that pertussis vaccine can cause permanent brain damage in young children. Were it not for the fact that The Wellcome Foundation intervened in the action and obtained a court order giving access to the NCES cases records, some crucial information collected by the NCES might not have been brought to light. Had all relevant information, collected and held by the NCES, been released when first available in 1981 some of the basic attitudes towards the issue might have taken a different course over the last 7–8 years.