Visceral leishmaniasis in West Pokot, Kenya Studies into the epidemiology, molecular diagnosis and immunology of a neglected disease

Visceral leishmaniasis (VL) is a severe disease caused by a systemic parasitic infection with protozoa of the Leishmania donovani complex. VL is endemic in arid and semi-arid areas of Kenya, where a major transmission focus is situated in West Pokot County. Despite rising case numbers, and a significant burden of morbidity and socioeconomic consequences, many aspects of VL in West Pokot have remained largely understudied. Therefore, this thesis aimed to investigate epidemiological, spatiotemporal, diagnostic and immunological characteristics of VL in West Pokot. Through a case-control questionnaire study, behavioural, household and environmental risk factors for VL were identified, which suggested parasite transmission occurs both peri-domestically and outside of villages. Spatiotemporal analysis of VL case data from hospital records revealed an outbreak of the disease between 2019 and 2022, as well as spatial clustering of cases in eastern regions of the county. Furthermore, a laboratory evaluation demonstrated that mini-dbPCR-NALFIA, a simplified molecular diagnostic platform, is a promising tool for accurate detection of VL infections directly in patient blood samples. Lastly, characterisation of serum cytokine profiles in symptomatic VL patients from West Pokot showed that the disease leads to elevated levels of type-1, type-2 and regulatory cytokines. In followed-up patients, completion of standard chemotherapy resulted in clinical, haematological and parasitological improvement. This coincided with a strong decrease in serum IL-10, which could be a potential biomarker for treatment effectiveness. Taken together, the research in this thesis has generated valuable insights into VL in West Pokot, which could inform local elimination efforts and guide future studies in this field.