Effect of pneumococcal vaccine on morbidity from acute lower respiratory tract infections in Papua New Guinean children

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Abstract
The effect of a 14-valent pneumococcal polysaccharide vaccine on morbidity from acute lower respiratory tract infection (ALRI) was determined in a randomized double-blind controlled trial in children under the age of 5 years living in the Papua New Guinea highlands. The vaccine did not protect against mild ALRI. Vaccine efficacy in the study as a whole was 28% for moderate/severe ALRI, which was not statistically significant though consistent with the significant effect on mortality. Children entered the trial in five separate cohorts 4 months apart. The incidence of disease and vaccine efficacy varied between cohorts and with age. There was no vaccine effect in the first cohort, which had a much higher proportion of older children. The effect was greatest and statistically significant among those groups encountering an epidemic of moderate and severe ALRI at a young age. It was therefore in children at the most vulnerable age in times of greatest incidence of disease that the vaccine had its most potent effect. It is postulated that the efficacy of pneumococcal vaccine is dependent on the predominant invading serotypes in the period after vaccination, the age at which children develop immuno-competence to specific vaccine serotypes, and the levels of naturally acquired specific immunity already present in children at the time of vaccination, and that for all of these conditions there will be a cohort effect.

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