This issue has been the subject of previous deliberations and review by GACVS.³ At its December 2003 meeting,⁴ GACVS commissioned a special task force, independent of the Committee, to review the evidence for a deleterious effect (if any) of DTP vaccination on child survival. The terms of reference of the task force were to determine whether, from published work and any other sources known to the task force, evidence exists to support a nonspecific increased mortality in infants caused by DTP vaccination in the first year of life. On the basis of its findings and conclusions, the task force was charged to advise: (i) whether WHO should recommend changes in vaccination policies, with particular reference to DTP vaccination; and (ii) what further work, if any, might be done to resolve the matter.

The review group considered published papers, and unpublished work that had been supplied to WHO by the authors, relevant to the hypothesis that DTP vaccination might adversely influence subsequent child mortality. The group considered seven papers from the group involved with the study in Guinea-Bissau, published in the British Medical Journal in 2000, in which a deleterious effect of DTP on child survival had been postulated, nine papers from other investigators in other countries and one review article.

Members were unanimous that the totality of evidence provided in all the material before the task force did not support a deleterious effect of DTP vaccination on child survival; indeed, the papers provide substantial evidence against such a conclusion. The task force also concluded that the potential effects of DTP and OPV cannot be distinguished when the two vaccines are given together, as happened in the majority of settings.

Advised by the report of the task force, GACVS decided to regard the issue of a deleterious effect on childhood survival of DTP vaccination as not supported by the evidence and to set the matter aside unless new and persuasive evidence were to emerge in the future. GACVS restated the importance of keeping an open mind on the unexpected outcomes of immunization and of the necessity of doing so through a comprehensive system of signal generation, collation of evidence and review of causality. The Committee stressed the importance of evaluating signals through rigorous studies responding to a priori research and clinical questions.

The Committee will keep a watching brief on any evidence suggesting other nonspecific effects of vaccination.

³See WER No. 47, 2002, pp. 389–394 and No. 32, 2003, pp. 282–284.

⁴See WER No. 3, 2004, pp. 16–20.

Full report of GACVS meeting of 10-11 June 2004, published in the WHO Weekly Epidemiological Record on 16 July 2004

GACVS had received a series of published and unpublished epidemiological studies dealing with the nonspecific and, in some cases, potentially adverse effects of diphtheria–tetanus –pertussis (DTP), measles and bacille Calmette- Guérin (BCG) vaccines on morbidity and mortality in children in the developing world. The issue has been the subject of previous deliberations and review by GACVS.³ A small team, the majority of whose members will come from outside GACVS to ensure independence from earlier deliberations, will be asked to review the latest information, concentrating initially on the potential adverse and nonspecific effects of DTP in childhood immunization. The review will be convened early in 2004, to report back to GACVS at its June 2004 meeting. This review will be included in a broader and more general research, clinical and theoretical assessment to define whether perturbation of the immune system by infant immunization may occur and whether this might be deleterious in certain circumstances.

³ See No. 47, 2002, pp. 389–394 and No. 32, 2003, pp. 282–284.

Full report of GACVS meeting of 3-4 December 2003, published in the WHO Weekly Epidemiological Record on 16 January 2004

A study in Guinea-Bissau published in the British Medical Journal in December 2000 suggested a nonspecific effect of routine vaccination that might influence survival in infants, either negatively or positively, depending upon the vaccine. Increased mortality was reported in children vaccinated with DPT in the 6 months following vaccination. Female gender was suggested as a modifier of the outcome.

GACVS reviewed this issue and urged WHO to arrange for testing of the hypothesis on different data sets from different countries where vaccination data, death, and other factors possibly influencing mortality had been recorded. Following an open call for proposals, WHO funded or cofunded studies in Bangladesh, Burkina Faso, Indonesia, and Papua New Guinea.

Analysis of those studies was completed: all of them showed reduced mortality in the children vaccinated with all of the vaccines. In particular, the studies showed no negative effect of DPT vaccination and no difference between males and females. Preliminary results of an independent analysis conducted to test the hypothesis on another six data sets have been communicated to GACVS. None of these confirmed the observations from Guinea-Bissau with respect to the DPT vaccine.

GACVS concluded that the evidence is sufficient to reject the hypothesis for an increased nonspecific mortality following vaccination.

For the discussions on thiomersal, Bell palsy, viral hepatitis B and MS, and MMF and aluminium-containing vaccines, GACVS invited additional experts to participate in the discussions.

Full report of GACVS meeting of 20-21 June 2002, published in the WHO Weekly Epidemiological Record on 22 November 2002

Reassurance from the Global Advisory Committee on Vaccine Safety about a purported negative impact of routine vaccination with Diphtheria, Tetanus and Pertussis vaccine (DTP) on child survival

A study in Guinea-Bissau (GB) published in the British Medical Journal in December 2000 by Kristensen et al.¹ suggested a non-specific effect of routine vaccination that might influence survival in infants, either negatively or positively, depending upon the vaccine. Increased mortality was reported in children vaccinated with DTP in the six months following vaccination. It was suggested that females were more likely to suffer increased mortality. The Global Advisory Committee on Vaccine Safety (GACVS) reviewed this issue and urged WHO to arrange for testing of the hypothesis on different data sets from different countries where vaccination data, death and other factors possibly influencing mortality had been recorded. Following an open call for proposals, WHO funded or co-funded studies in Bangladesh, Burkina Faso, Indonesia and Papua New Guinea.

Analysis of the WHO-sponsored studies is now complete. All the studies show reduced mortality rates in the children vaccinated with all of the vaccines. In particular, the studies showed no negative effect of DTP vaccination and no difference was found between males and females.

The Committee concluded that the evidence is sufficient to reject the hypothesis for an increased non-specific mortality following vaccination.