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" Enteric Pathogens: Measurement, Metrics, and Mitigation "
Grembi, Jessica Anne
Spormann, Alfred M.
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Latin Dissertation
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| Language of Document
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English
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| Record Number
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1054650
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| Doc. No
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TL53767
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| Main Entry
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Grembi, Jessica Anne
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| Title & Author
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Enteric Pathogens: Measurement, Metrics, and Mitigation\ Grembi, Jessica Anne Spormann, Alfred M.
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| College
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Stanford University
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| Date
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2019
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| Degree
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Ph.D.
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2019
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| Note
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125 p.
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| Abstract
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Enteric pathogens, long acknowledged for their role in diarrheal disease, are increasingly recognized as important factors in child growth and development, even when detected in subclinical quantities. Polymicrobial pathogen carriage is common in low- and middle-income countries, frequently occurring without diarrheal symptoms. Comprehensive enteric pathogen panels are cost-prohibitive, and thus infrequently used in large population-based studies. However, these studies are necessary to evaluate the complex interactions between asymptomatic pathogen carriage and long-term outcomes such a growth and development. Furthermore, Koch's postulates, implying a single etiologic agent for a disease, discount the synergistic potential of enteric pathogens to disrupt host gut physiology and upset microbial ecological niches. Information on both the presence and quantity of known pathogens is important for understanding these complex systems; but the current analytical methods for assessing polymicrobal infection fail to integrate the quantitative data afforded by modern molecular techniques. Finally, quantitative enteropathogen measures are needed to assess the efficacy of low-cost water, sanitation, and handwashing interventions to reduce pathogen transmission and exposure in low-income countries, in lieu of the caregiver reported diarrhea outcomes commonly used. To address these gaps, the work that comprises this dissertation offers a lower-cost measurement option, provides a metric for composite pathogen assessment, and evaluates the potential for low-cost interventions to mitigate enteric pathogen carriage for children in rural Bangladesh. Chapter 2 describes the design and evaluation of a novel nano-liter qPCR chip that detects 17 intestinal pathogens for a quarter of the cost and 12x higher throughput than the leading technology, allowing for pathogen panels to be used in large-scale epidemiological studies. In Chapter 3, I developed a new enteric pathogen composite metric - a single endpoint that incorporates quantitative data across multiple intestinal pathogens - as a measure of total pathogen load within the gut. I show that this metric is associated with symptomatic diarrheal disease, child growth, and subsequent cognitive development. Finally, Chapter 4 evaluated the potential of low-cost water, sanitation, handwashing (WSH) and nutritional interventions to mitigate enteric pathogen carriage in a cohort of 1411 children 14 months old from a randomized controlled trial in rural Bangladesh. I found that WSH interventions reduce the burden of enteric viruses for children, but do not substantially reduce bacterial or parasitic pathogens - the pathogens that have displayed the strongest associations with child growth deficits in observational studies. My work offers new means of measuring and evaluating panels of multiple enteric pathogens and provides insights for directing the efforts of the WSH field toward interventions that mitigate bacterial and parasitic enteropathogens.
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| Descriptor
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Civil engineering
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Environmental engineering
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Spormann, Alfred M.
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Stanford University
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