Severe Illness Associated With Respiratory Viruses: Burden and Temporal Dynamics

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.PHDEpidemiological ScienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/166143/1/jkubale_1.pd

Simulation models predict that school-age children are responsible for most human-to-mosquito Plasmodium falciparum transmission in southern Malawi

Abstract Background Malaria persists in some high-transmission areas despite extensive control efforts. Progress toward elimination may require effective targeting of specific human populations that act as key transmission reservoirs. Methods Parameterized using molecular-based Plasmodium falciparum infection data from cross-sectional community studies in southern Malawi, a simulation model was developed to predict the proportions of human-to-mosquito transmission arising from (a) children under 5 years old (U5s), (b) school-age children (SAC, 5–15 years), (c) young adults (16–30 years), and (d) adults > 30 years. The model incorporates mosquito biting heterogeneity and differential infectivity (i.e. probability that a blood-fed mosquito develops oocysts) by age and gametocyte density. Results The model predicted that SAC were responsible for more than 60% of new mosquito infections in both dry and rainy seasons, even though they comprise only 30% of this southern Malawi population. Young adults were the second largest contributors, while U5s and adults over 30 were each responsible for < 10% of transmission. While the specific predicted values are sensitive to the relative infectiousness of SAC, this group remained the most important contributor to mosquito infections under all realistic estimates. Conclusions These results suggest that U5 children play a small role compared to SAC in maintaining P. falciparum transmission in southern Malawi. Models that assume biting homogeneity overestimate the importance of U5s. To reduce transmission, interventions will need to reach more SAC and young adults. This publicly available model can be used by others to estimate age-specific transmission contributions in epidemiologically similar sites with local parameter estimates of P. falciparum prevalence and bed net use.https://deepblue.lib.umich.edu/bitstream/2027.42/143001/1/12936_2018_Article_2295.pd

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