Date of Award

Spring 2016

Document Type

Thesis

Primary Advisor

Dr. Todd Schraw

Abstract

Human African Trypanosomiasis (HAT) is one of 17 neglected tropical disease prioritized by the World Health Organization (WHO). Neglected tropical diseases are diseases which affect poor or developing countries and which do not get as much as attention as the ‘big three’: malaria, tuberculosis and HIV/AIDS. HAT specifically affects coutries in Sub-Saharan Africa and is caused by a parasitic protozoa, Trypanosoma brucei. There are two stages of HAT: the early haemolymphatic and late meningo-encephalitic stages. There are also two subtypes of the disease caused by either T. b. gambiense or T.b rhodesiense forms of the parasite. There are four drugs currently used to treat HAT, depending on the subtype of disease and whichever stage a patient is in. The nitroheterocyclic drug, Fexinidazole is currently in clinical trials for the treatment of both the early and late stages of HAT as well as the two subtypes. However, as with most antiparasitic drugs, potential parasitic resistance of the target parasite to Fexinidazole is an issue which must be taken into consideration and dealt with. Combination therapy is a method by which the likelihood of potential parasite resistance is reduced. The therapy uses two chemically unrelated drugs to treat a disease and is based on the theory that parasitic resistance to a combination therapy is less likely than resistance to a monotherapy. The combined drugs usually work additively or synergistically to treat the disease as well. Eflornithine (also known as α-difluoromethylorntihine or DFMO) is a drug currently used in combination with nifurtimox to treat the second stage of HAT caused by T.b gambiense. Nifurtimox and Fexinidazole are both nitroheterocyclic drugs and as a result, have similar modes of action. Therefore, I believe that eflornithine is the ideal partner drug to be used in conjunction with Fexinidazole since it has been shown to be effective in combination with a Fexinidazole-related drug (nifurtimox) but is not chemically related to Fexinidazole. The use of this combination therapy will allow prolonged use of Fexinidazole in treating HAT and contribute towards the eventual elimination of the disease

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