Rivers, rainfall, and risk factors : geostatistical and epidemiological approaches to disentangle potential transmission routes of typhoid fever

Gauld, Jillian and Diggle, Peter and Read, Jonathan (2020) Rivers, rainfall, and risk factors : geostatistical and epidemiological approaches to disentangle potential transmission routes of typhoid fever. PhD thesis, Lancaster University.

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Abstract

Typhoid fever, caused by the bacterium Salmonella Typhi, is a severe febrile illness, with over 20 million cases and 100 thousand deaths occurring annually. In 2011, Blantyre, Malawi experienced a sharp increase in the incidence of typhoid fever, and transmission continues today. Although the disease is generally known to spread through the fecal-oral route, the precise mechanisms of transmission in endemic locations are not well characterized. Therefore, a challenge exists in determining which water and sanitation interventions may be the most important for control of typhoid fever. This thesis attempts to identify risk factors for typhoid fever in this setting, and employs geostatistical, epidemiological, and genomic approaches to data collected as part of routine disease surveillance as well as typhoid-specific epidemiological studies. The findings from this thesis indicate that transmission of typhoid fever in Blantyre is complex, with both environmental and social factors important components. Evidence of environmental transmission as found, through the use of non-drinking water from local rivers identified as a risk factor. This finding was used to generate hypotheses: testing whether river catchments are predictors of genomic patterns, and exploring rainfall anomalies as time-dependent predictors of incidence. Both investigations yielded significant results: river catchments were predictors of genomic patterns, and rainfall anomalies were found to be protective, further bolstering the hypothesized environmental component of transmission. Typhoid fever can also lead to severe clinical complications, and a methodological contribution was included that enabled the attribution of intestinal perforations to typhoid fever, independent of microbiological testing. Although new vaccines for typhoid offer a promising tool for control, investment in non-vaccine interventions will likely be critical for elimination, and the work presented suggests possible opportunities for interventions focused around hydrological systems and water usage.