Impact of Influenza Vaccination during Pregnancy on Maternal Influenza Disease Severity in Rural Nepal

Although maternal influenza vaccination can prevent influenza morbidity and mortality, data are limited on vaccine efficacy/effectiveness against severe disease in low- and middle-income countries (LMICs) at the community level. We evaluated the impact of maternal influenza vaccination on maternal influenza disease severity across seasons in a rural subtropical area in South Asia by analyzing data from a vaccine clinical trial conducted between 2011 and 2014 in Sarlahi District, Nepal. Participants were randomized 1:1 to trivalent seasonal influenza vaccine or saline placebo and followed through 180 days postpartum. Weekly household-based active respiratory surveillance was conducted; if participants reported fever and respiratory symptoms, a midnasal swab was collected and tested for influenza using reverse transcription polymerase chain reaction. Among 3,693 participants (n = 1,847 vaccine; n = 1,846 placebo), we detected 75 influenza illness episodes, including 40 with care seeking and 22 with fever for more than 3 days. Using proportional hazards regression, maternal influenza vaccination reduced the estimated hazard of influenza-associated care-seeking visits and fever for more than 3 days by 36% and 21%, respectively, compared with placebo; however, these differences were not statistically significant. The estimated numbers needed to vaccinate to prevent one influenza illness with care seeking and fever for more than 3 days were 224 and 785, respectively, at 270 days postvaccination. These findings suggest that maternal immunization may reduce the risk of moderate influenza illness among pregnant/postpartum individuals in LMICs, particularly in rural areas where access to care is limited.