Graduation Date
Summer 8-14-2026
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Programs
Immunology, Pathology & Infectious Disease
First Advisor
Dr. Larisa Poluektova
Second Advisor
Dr. Benson Edagwa
Abstract
Hepatitis B (HBV) and malaria are highest global challenges for infectious diseases. Both are substantial global health and socioeconomic challenges for higher risks of disease and early death. Cure and therapies are absent and limited. Prolonged treatment regimens are mandated with common suboptimal patient adherence and drug resistance. All underscore the need for newer therapeutic approaches that can achieve durable pathogen control. To this end, we examined the feasibility of combinatorial long-acting (LA) therapeutic approaches to improve the treatment outcomes of chronic HBV (CHB) infection which remains a major risk factor for progressive cirrhosis and hepatocellular carcinoma. Although available nucleos(t)ide analog therapies effectively suppress viral replication, they require long-term daily administration. We employed a three-pronged therapeutic strategy using LA prodrug formulations of tenofovir (TFV), a potent nucleos(t)ide analog, and tizoxanide (TIZ), an innate immune enhancer, to sustain viral suppression and improve immune homeostasis. We co-administered LA medicines (termed M5TFV and M2TIZ) in a CHB mouse model. The resulting multi-mechanistic strategy provided sustained antiviral suppression and reduced inflammation and fibrosis. An added part of the dissertation focused on improving limitations in bioavailability, half-life, resistance, and efficacy for existing malaria therapies.
Rights
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Recommended Citation
Ogunnaike, Mojisola O., "Multi-Mechanistic Treatment Approaches for Hepatitis B and Malaria" (2026). Theses & Dissertations. 1101.
https://digitalcommons.unmc.edu/etd/1101