Severe Illness Associated With Respiratory Viruses: Burden and Temporal Dynamics

Abstract

Acute lower respiratory tract infections (ALRI) are a substantial source of global morbidity and mortality, particularly among young children. Respiratory syncytial virus (RSV) and influenza are consistently observed to be significant drivers of this burden, but substantial gaps in our understanding remain. Greater understanding of the burden of these pathogens at the community-level, and their association with severe illness has the potential to substantially reduce the toll of ALRI, particularly among young children. In chapter 2 of this dissertation we assess the community burden of RSV and RSV-associated severe illness among Nicaraguan children aged < 2 years. In chapters 3 and 4 we explore the individual-level association between influenza and subsequent pneumonia along with characterizing the risk period for pneumonia following symptomatic influenza infection. To explore these questions we use data from the Nicaragua Influenza Birth Cohort Study (2011-2016), the Nicaraguan Pediatric Influenza Cohort Study (2011-2018), and the Nicaragua Influenza Cohort Study (2007-2010). In chapter 2 we observed the highest incidence of RSV occurred among children aged 6-11 months, while the highest incidence of RSV-associated severe ALRI was highest among those aged < 3 months and generally decreased as age increased. RSV was also associated with at least 25% of illness deaths that occurred in the cohort, highlighting its importance in reducing in infant mortality. In chapters 3 and 4 we established that influenza is associated with increased risk of subsequent pneumonia at the individual level across types and subtypes with the exception of seasonal H1N1. We also observed distinct periods of elevated pneumonia risk following influenza among children aged <2 which is suggestive of multiple etiologic pathways existing between influenza and pneumonia. By better understanding the burden and temporal dynamics of RSV and influenza we can develop more effective interventions to prevent and mitigate their effects among children.