The Introduction of Diphtheria-Tetanus-Pertussis and Oral Polio Vaccine Among Young Infants in an Urban African Community: A Natural Experiment

Abstract

BackgroundWe examined the introduction of diphtheria-tetanus-pertussis (DTP) and oral polio vaccine (OPV) in an urban community in Guinea-Bissau in the early 1980s.MethodsThe child population had been followed with 3-monthly nutritional weighing sessions since 1978. From June 1981 DTP and OPV were offered from 3 months of age at these sessions. Due to the 3-monthly intervals between sessions, the children were allocated by birthday in a ‘natural experiment’ to receive vaccinations early or late between 3 and 5 months of age. We included children who were < 6 months of age when vaccinations started and children born until the end of December 1983. We compared mortality between 3 and 5 months of age of DTP-vaccinated and not-yet-DTP-vaccinated children in Cox proportional hazard models.ResultsAmong 3–5-month-old children, having received DTP (± OPV) was associated with a mortality hazard ratio (HR) of 5.00 (95% CI 1.53–16.3) compared with not-yet-DTP-vaccinated children. Differences in background factors did not explain the effect. The negative effect was particularly strong for children who had received DTP-only and no OPV (HR = 10.0 (2.61–38.6)). All-cause infant mortality after 3 months of age increased after the introduction of these vaccines (HR = 2.12 (1.07–4.19)).ConclusionDTP was associated with increased mortality; OPV may modify the effect of DTP.

How to evaluate potential non-specific effects of vaccines: the quest for randomized trials or time for triangulation?

“…Fifth, several studies have shown that mortality is lower when OPV-only rather than the recommended combination of OPV and DTP has been given [49,50].…”

“…Sixth, two studies of the introduction of DTP and OPV in the rural and urban areas of Guinea-Bissau showed that mortality was higher when DTP-only was administered rather than DTP and OPV simultaneously [50,51]. In other words, OPV appears to have reduced the potential negative effects of DTP.…”

“…Peer reviewers on this manuscript have no relevant financial or other relationships to disclose. Changes in overall mortality/morbidity rates which are not explained by the effect of the "natural experiment vaccine" on the target disease [50] Observational studies:…”

Measles, mumps and rubella vs diphtheria–tetanus–acellular-pertussis–inactivated-polio–Haemophilus influenzae type b as the most recent vaccine and risk of early ‘childhood asthma’

“…(1)(2)(3)(4) Live vaccines affect the innate immune system beneficially leading to increased response to unrelated pathogens (2) and are associated with lower morbidity and mortality from non-targeted diseases. (1,(3)(4)(5)(6)(7) Studies suggest that live vaccines induce a T-helper 1 cell dominant shift reducing atopic diseases. (4,8,9) In contrast, non-live vaccines can induce tolerance of the innate immune system leading to decreased responses to unrelated pathogens (2) and have been associated with higher morbidity and mortality from non-targeted diseases.…”

Unspezifische Auswirkungen von Impfungen auf die allgemeine Gesundheit

“…"All currently available evidence suggests that DTP vaccine may kill more children from other causes than it saves from diphtheria, tetanus or pertussis" 1 (Peter Aaby [14])…”