Abstract
Human African trypanosomiasis or sleeping sickness is resurgent [1,2]. The disease is caused by subspecies of the parasitic haemoflagellate, Trypanosoma brucei. Infection starts with the bite of an infected tsetse fly (Glossina spp.). Parasites move from the site of infection to the draining lymphatic vessels and blood stream. The parasites proliferate within the bloodstream and later invade other tissues including the central nervous system. Once they have established themselves within the CNS, a progressive breakdown of neurological function accompanies the disease. Coma precedes death during this late phase. Two forms of the disease are recognised, one caused by Trypanosoma brucei rhodesiense, endemic in Eastern and Southern Africa, in which parasites rapidly invade the CNS causing death within weeks if untreated. T. b. gambiense, originally described in West Africa, but also widespread in Central Africa, proliferates more slowly and can take several years before establishing a CNS-involved infection. Many countries are in the midst of epidemics caused by gambiense-type parasites. Four drugs have been licensed to treat the disease [3] two of them, pentamidine and suramin, are used prior to CNS involvement. The arsenic-based drug, melarsoprol is used once parasites are established in the CNS. The fourth, eflornithine, is effective against late stage disease caused by T. b. gambiense, but is ineffective against T. b. rhodesiense. Another drug, nifurtimox is licensed for South American trypanosomiasis but also been used in trials against melarsoprol-refractory late sage disease. This review focuses on what is known about modes of action of current drugs and discusses targets for future drug development.
Keywords: Trypanosomiasis, Trypanosoma, Trypanosoma brucei rhodesiense, Suramin, Pentamidine, Melarsoprol, Eflornithine, Nifurtimox
Current Pharmaceutical Design
Title: Chemotherapy of Human African Trypanosomiasis
Volume: 8 Issue: 4
Author(s): Richard J.S. Burchmore, Patrick O.J. Ogbunude, Bertin Enanga and Michael P. Barrett
Affiliation:
Keywords: Trypanosomiasis, Trypanosoma, Trypanosoma brucei rhodesiense, Suramin, Pentamidine, Melarsoprol, Eflornithine, Nifurtimox
Abstract: Human African trypanosomiasis or sleeping sickness is resurgent [1,2]. The disease is caused by subspecies of the parasitic haemoflagellate, Trypanosoma brucei. Infection starts with the bite of an infected tsetse fly (Glossina spp.). Parasites move from the site of infection to the draining lymphatic vessels and blood stream. The parasites proliferate within the bloodstream and later invade other tissues including the central nervous system. Once they have established themselves within the CNS, a progressive breakdown of neurological function accompanies the disease. Coma precedes death during this late phase. Two forms of the disease are recognised, one caused by Trypanosoma brucei rhodesiense, endemic in Eastern and Southern Africa, in which parasites rapidly invade the CNS causing death within weeks if untreated. T. b. gambiense, originally described in West Africa, but also widespread in Central Africa, proliferates more slowly and can take several years before establishing a CNS-involved infection. Many countries are in the midst of epidemics caused by gambiense-type parasites. Four drugs have been licensed to treat the disease [3] two of them, pentamidine and suramin, are used prior to CNS involvement. The arsenic-based drug, melarsoprol is used once parasites are established in the CNS. The fourth, eflornithine, is effective against late stage disease caused by T. b. gambiense, but is ineffective against T. b. rhodesiense. Another drug, nifurtimox is licensed for South American trypanosomiasis but also been used in trials against melarsoprol-refractory late sage disease. This review focuses on what is known about modes of action of current drugs and discusses targets for future drug development.
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Cite this article as:
Burchmore J.S. Richard, Ogbunude O.J. Patrick, Enanga Bertin and Barrett P. Michael, Chemotherapy of Human African Trypanosomiasis, Current Pharmaceutical Design 2002; 8 (4) . https://dx.doi.org/10.2174/1381612023396159
DOI https://dx.doi.org/10.2174/1381612023396159 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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