Intersection of Childhood Undernutrition and Postinfectious Hydrocephalus
Open Access
- Author:
- Ssentongo, Paddy
- Graduate Program:
- Epidemiology
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- March 26, 2021
- Committee Members:
- Vernon Michael Chinchilli, Dissertation Advisor/Co-Advisor
Vernon Michael Chinchilli, Committee Chair/Co-Chair
Jessica E. Ericson, Outside Field Member
Laila Al-Shaar, Committee Member
Laura E Murray-Kolb, Outside Unit Member
Steven Schiff, Co-Chair & Dissertation Advisor
Douglas L Leslie, Program Head/Chair
Ming Wang, Committee Member - Keywords:
- Postinfectious hydrocephalus
Paenibacillus thiaminolyticus
Childhood undernutrition
Global health
Remote sensing - Abstract:
- Postinfectious hydrocephalus (PIH) is the most prevalent form of infantile hydrocephalus in low- and middle-income countries and the leading cause of neurological morbidity and mortality. PIH is preceded by exposure to viral and bacterial infections. Recently we characterized cytomegalovirus (CMV) and the newly discovered Paenibacillus thiaminolyticus Mbale as significant contributing infections to the incidence of PIH. Even with treatment, the neurocognitive and brain development outcomes of PIH are dismal; hence its prevention measures targeted at fine-scale geographical regions, such as a village, have the potential to reduce the incidence of PIH. Despite the geographical burden of PIH mirroring that of undernutrition globally, subnational effects of childhood undernutrition on PIH’s spatial distribution in Uganda are yet to be defined. In this dissertation, we 1) estimated the global and regional burden and epidemiology of childhood undernutrition and congenital CMV, 2) characterized the spatiotemporal dynamics of child undernutrition in Uganda and developed operational village-level risk maps of undernutrition, 3) linked the nutritional deficiencies (micro and macro) to the spatial dynamics of the incidence of PIH at the district/village level, 4) delineated the mediation effects of undernutrition on the association between hydrocephalus and suboptimal brain development in children, and 5) developed a murine model of undernutrition and showed how undernutrition increases susceptibility to bacterial infection. The present dissertation shows that 1 in 3 children under 5 years of age in low- and middle-income countries is undernourished and that this burden is associated with low human development index. We show that undernutrition in infantile hydrocephalus is 3-fold higher than that of the general population of children in Uganda. These rates are higher in infants with PIH than non-PIH. Also, we establish that undernutrition mediates the negative impact of PIH on brain development. Finally, we demonstrate that location-specific rates of micro and macronutrient deficiencies, in addition to meteorological and environmental covariates, are risk factors for the incidence of PIH. Our high spatial resolution health risk maps will improve the accuracy of our prediction models of neonatal sepsis risk and its neurologic sequelae, including PIH. Furthermore, the present findings will guide population and individual-level "precision-renourishment" interventions to prevent, control, and treat childhood undernutrition to optimize survival and brain development.