Three randomized trials of maternal influenza immunization in Mali, Nepal, and South Africa: Methods and expectations

Abstract

Influenza infection in pregnancy can have adverse impacts on maternal, fetal, and infant outcomes. Influenza vaccination in pregnancy is an appealing strategy to protect pregnant women and their infants. The Bill & Melinda Gates Foundation is supporting three large, randomized trials in Nepal, Mali, and South Africa evaluating the efficacy and safety of maternal immunization to prevent influenza disease in pregnant women and their infants <6 months of age. Results from these individual studies are expected in 2014 and 2015. While the results from the three maternal immunization trials are likely to strengthen the evidence base regarding the impact of influenza immunization in pregnancy, expectations for these results should be realistic. For example, evidence from previous influenza vaccine studies - conducted in general, non-pregnant populations - suggests substantial geographic and year-to-year variability in influenza incidence and vaccine efficacy/effectiveness. Since the evidence generated from the three maternal influenza immunization trials will be complementary, in this paper we present a side-by-side description of the three studies as well as the similarities and differences between these trials in terms of study location, design, outcome evaluation, and laboratory and epidemiological methods. We also describe the likely remaining knowledge gap after the results from these trials become available along with a description of the analyses that will be conducted when the results from these individual data are pooled. Moreover, we highlight that additional research on logistics of seasonal influenza vaccine supply, surveillance and strain matching, and optimal delivery strategies for pregnant women will be important for informing global policy related to maternal influenza immunization.

The Effects of Influenza Vaccination during Pregnancy on Birth Outcomes: A Systematic Review and Meta-Analysis

“…We determined an assumed baseline rate for PTB, SGA, and LBW outcomes based on three sources of information from three regions in the world using PubMed and study reports. [16][17][18][19] Sensitivity analyses were performed, including all published studies irrespective of sample size. The main analyses only included observational studies, in separate sensitivity analyses, the RCTs were also included.…”

Paediatric respiratory infections

“…A number of studies have reviewed the impact of this change in policy, with studies from the UK [25] and USA [26] indicating that the strategy appears to be safe and effective, although a very recent study has highlighted the impact of maternal immunisation on the response to postnatal pertussis immunisation and other vaccines in the routine immunisation programme that are conjugated to the diphtheria toxin variant [27]. Other groups report a reduction of morbidity in the mothers and their infants when mothers are immunised with influenza vaccine during pregnancy [28]. The effect is not as great as that observed with pertussis and the authors do note the challenges in interpreting the data and providing recommendations, given seasonal and year-to-year variations in disease severity and incidence.…”

Maternal immunization: where are we now and how to move forward?

“…In Nepal, yearround maternal influenza immunization significantly reduced maternal influenza-like illness, influenza in infants and low birth weight, suggesting that this strategy could be useful in subtropical regions where influenza is present for many months [61]. Regarding safety, IIV did not increase risk of foetal death, spontaneous abortion or congenital malformations [59][60][61][62].…”

“…Results from a randomized controlled trial in Bangladesh provided a proof of concept that maternal vaccination could reduce infant influenza disease in developing countries, with 36% efficacy against febrile respiratory illness in mothers and 29% in infants and 63% efficacy against confirmed influenza illness in infants, compared to the 23-valent pneumococcal polysaccharide vaccine [58]. Three large, controlled, randomized trials in Nepal, Mali and South Africa then evaluated the efficacy and safety of maternal immunization to prevent influenza disease in pregnant women and their infants aged <6 months [59]. In the South African placebo-controlled trial, vaccine efficacy against confirmed influenza was approximately 50% both in mothers and infants [60].…”