Treatment of human African trypanosomiasis--present situation and needs for research and development.
Human African trypanosomiasis re-emerged in the 1980s. However, little progress has been made in the treatment of this disease over the past decades. The first-line treatment for second-stage cases is melarsoprol, a toxic drug in use since 1949. High therapeutic failure rates have been reported recently in several foci. The alternative, eflornithine, is better tolerated but difficult to administer. A third drug, nifurtimox, is a cheap, orally administered drug not yet fully validated for use in human African trypanosomiasis. No new drugs for second-stage cases are expected in the near future. Because of resistance to and limited number of current treatments, there may soon be no effective drugs available to treat trypanosomiasis patients, especially second-stage cases. Additional research and development efforts must be made for the development of new compounds, including: testing combinations of current trypanocidal drugs, completing the clinical development of nifurtimox and registering it for trypanosomiasis, completing the clinical development of an oral form of eflornithine, pursuing the development of DB 289 and its derivatives, and advancing the pre-clinical development of megazol, eventually engaging firmly in its clinical development. Partners from the public and private sector are already engaged in joint initiatives to maintain the production of current drugs. This network should go further and be responsible for assigning selected teams to urgently needed research projects with funds provided by industry and governments. At the same time, on a long term basis, ambitious research programmes for new compounds must be supported to ensure the sustainable development of new drugs.
Legros
Dominique
D
Epicentre, Paris, France. dlegros@epicentre.msf.org
Ollivier
Gaëlle
G
Gastellu-Etchegorry
Marc
M
Paquet
Christophe
C
Burri
Christian
C
Jannin
Jean
J
Büscher
Philippe
P
D017954:Africa South of the Sahara; D000818:Animals; D001550:Benzamidines / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D000518:Eflornithine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008549:Melarsoprol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D009547:Nifurtimox / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013830:Thiadiazoles / Q000627:therapeutic use; D014344:Trypanocidal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014347:Trypanosoma brucei gambiense; D016833:Trypanosoma brucei rhodesiense; D014353:Trypanosomiasis, African / Q000188:drug therapy*
D001550:Benzamidines; D013830:Thiadiazoles; D014344:Trypanocidal Agents; C013378:megazol; C458513:pafuramidine; D009547:Nifurtimox; D008549:Melarsoprol; D000518:Eflornithine