Maternal Influenza Immunization and Prevention of Severe Clinical Pneumonia in Young Infants: Analysis of Randomized Controlled Trials Conducted in Nepal, Mali, and South Africa

Abstract

Background: To evaluate the effect of antenatal influenza vaccination on all-cause severe infant pneumonia, we performed pooled analysis of three randomized-controlled trials conducted in Nepal, Mali, and South Africa. Methods: The trials were coordinated from the planning phase. The follow-up period was 0–6 months post-partum in Nepal and Mali, and 0-24 weeks in South Africa. Pregnant women with gestational age 17-34 weeks in Nepal, ≥28 weeks in Mali, and 20-36 weeks in South Africa were enrolled. Trivalent Inactivated Influenza Vaccine (IIV). was compared with either saline placebo (Nepal and South Africa) or quadrivalent meningococcal conjugate vaccine (MCV) (Mali). In South Africa, cases were hospitalized, and were therefore considered to have severe pneumonia. In Nepal and Mali, severe infant pneumonia diagnosis was based on the WHO Integrated Management of Childhood Illness (IMCI) definition. Results: A total of 10,002 mothers and 9,801 live-born eligible infants were included in the present analysis. Incidence rate of severe pneumonia was 31% lower in the IIV group compared to the control group (incidence rate ratio [IRR]: 0.69, 95% CI: 0.50 - 0.94, P = 0.02). During periods with high influenza circulation there was lower incidence of severe pneumonia among the IIV group (IRR: 0.20, 95% CI: 0.06 - 0.74, P = 0.02), however, there was no difference in pneumonia incidence between study groups during periods of low and no influenza circulation. Conclusions: Maternal influenza immunization may reduce severe pneumonia episodes among infants –particularly those too young to be completely vaccinated against S. pneumoniae and influenza.