PROJECT SUMMARY/ABSTRACT
This F31 project aims to close gaps in knowledge that could inform vaccine policy and facilitate implementation
of maternal influenza vaccines in low- and middle-income countries (LMICs). Influenza causes 3-5 million cases
of severe illnesses and 290,000-650,000 deaths globally each year. Pregnant people are at increased risk of
influenza morbidity and mortality, making vaccination a high priority in this population to protect themselves, their
fetuses, as well as their infants via maternal antibodies. Although influenza mortality rates are estimated to be
higher in LMICs, empiric data on the influenza disease burden are limited. In addition, the impact of maternal
influenza vaccination on infant growth has not been evaluated while accounting for bias induced by undefined
infant growth outcomes due to fetal or early infant death. Best practices for implementing maternal immunization
programs have also not been established including the optimal timing of vaccination. Moreover, potential costs
must be considered since LMIC health budgets often need to prioritize which interventions to implement due to
resource constraints. The proposed F31 research project leverages data collected between 2011-2014 as part
of a maternal influenza vaccine RCT in Sarlahi District, Nepal (NCT01034254) among pregnant people (18-40
years) and their infants who were followed through 6-months postpartum. The parent study included enrollment
visits, weekly household-based active surveillance for respiratory pathogens, illness surveys on symptoms and
care seeking behaviors, maternal/infant birth assessments, monthly maternal comorbidity assessments, and
infant anthropometry visits at birth and 6 months to measure weight (g), length (cm), and head circumference
(cm). Using log-binomial regression methods, Aim 1 will assess the impact of influenza vaccination during
pregnancy on maternal influenza disease severity among pregnant participants (n=3693). Aim 2 will characterize
the effect of maternal influenza vaccination on infant z-scores at birth and 6 months of age accounting for
outcomes truncated by death among all singleton births using multinomial logistic regression (n=3520). Aim 3
will evaluate the optimal timing and cost-effectiveness of administering seasonal influenza vaccine during
pregnancy using an existing decision tree model to project the potential impact of maternal influenza vaccine
timing strategies (second versus third trimester compared to no vaccination) and calculate incremental cost-
effectiveness ratios. Data generated from this project will expand the current maternal influenza vaccine
evidence base in LMICs, which may motivate changes in vaccine policy, implementation, and investment
decisions. As a long-term goal, the F31 study team seeks to contribute to reducing disparities in global influenza
vaccine access so that all communities can benefit from this critical public health intervention. This research plan
will provide the F31 candidate rigorous predoctoral training including (1) performing advanced analyses in
infectious disease epidemiology; (2) developing content-area expertise in maternal immunization; (3) acquiring
methods to evaluate vaccine cost-effectiveness; and (4) gaining further experience in research dissemination.
