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Francis, Abelanjo Freddy

University of British Columbia

Antibiotic resistance is the third largest contributor to mortality worldwide, and 30% of these deaths occur in newborns. The burden of resistant infections in children is disproportionately higher in low- and middle-income countries (LMICs) due to the overuse of antibiotics in food, food animals and health care settings. The prevalence of childhood co-morbidities like severe acute malnutrition (SAM) and human immunodeficiency virus (HIV) in LMICs increases the need for treatment and prophylactic antibiotic use. These conditions also increase the likelihood of secondary disease, thereby further increasing the need for antibiotics. Antibiotic resistance genes (ARGs) are the primary source of resistance in pathogens and are amplified with antibiotic exposure. There is an urgent need to understand the role of ARGs in diseases amongst infants and children, especially in LMICs, where their impact on mortality and morbidity is large. In this dissertation, chapter one reviews previous knowledge about the presence or carriage of ARGs and the impact ARGs have on morbidity and mortality in LMICs, especially morbidity and mortality due to SAM and HIV. Chapter 2 examines the natural acquisition of ARGs in healthy children living in rural areas of a LMIC using longitudinal data from the Sanitation Hygiene and Infant Nutrition Efficacy (SHINE) trial. Chapter 3 examines the changes in ARG carriage during hospitalization with SAM and HIV, and during SAM recovery using longitudinal data from the Health Outcomes, Pathogenesis and Epidemiology of Severe Acute Malnutrition (HOPE-SAM) observational study. Chapter 4 investigates the impact of stopping or continuing prophylactic antibiotic use in HIV-positive children using data from the Antiretroviral Research for Watoto (ARROW) trial. I find that healthy children acquire a diverse array of ARGs upon birth, ARG carriage decreases significantly with age in healthy children, and most ARGs are closely associated with the abundance of Enterobacteriaceae that colonize the infant gut. Hospitalization for SAM leads to a less mature microbiota, associated with increases in Enterobacteriaceae-related ARG abundance. This effect was transient and decayed over time following hospital discharge. Continued prophylactic antibiotic treatment in HIV-positive children does not significantly alter ARG carriage but does selectively increase resistance specific to antibiotics used.

Text

2023-10-12

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/86146

Experimental Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/