Drugs return as trypanosomiasis reemerges

The approval of the cosmetic formulation of eflornithine encouraged the reintroductions of its intravenous formulation and of nifurtimox, both used to treat African trypanosomiasis it was reported at an international conference on emerging infectious diseases sponsored by the Centers for Disease Control and Prevention. The production of both drugs had been halted when sleeping sickness was almost eradicated in the 1960s and surveillance and treatment programs were dismantled during subsequent civil unrest and wars in central Africa. Then trypanosomiasis began to reemerge and the universally fatal disease had soon infected more than half a million Africans. It looked like all our drugs were going away, and sleeping sickness was coming back, said one doctor of the division of parastic disease at the CDC. With most agents out of production or about to be discontinued, the situation looked bleak. Most Africans present with advanced cases of trypanosomiasis, which involved the CNS. Left untreated, the condition resulted in coma, and death, it was also reported at the conference, also sponsored by the American Society for Microbiology and the World Health Organization. The situation changed in the fall of 2000 when Bristol-Myers Squibb received Food and Drug Administration marketing clearance for a topical form of eflornithine, for treating unwanted facial hair in women. A coordinated effort by WHO and Doctors Without Borders convinced Bristol-Myers Squibb to donate their bulk material to allow for production of intravenous forms of eflornithine. Aventis Pasteur, which makes two other agents for sleeping sickness (pentamidine and melarsoprol), now manufactures the intravenous formulation of eflornithine.

They were overjoyed because the drug was being produced again, Aventis is donating a five-year supply of the three agents through a $20 million grant to WHO. Bayer had announced that it would discontinue making another treatment for sleeping sickness, nifurtimox. But, like Aventis, Bayer has agreed to continue making the drug and to donate it. Before these developments, melarsopol, an arsenic-based compound, was the one treatment widely available in Africa for the CNS form of disease. However it is very dangerous. It kills five percent of those who receive it from treatment. Melarsoprol treatment failures started growing significantly in 1997. Although challenges remain, with five drugs back in production, the outlook concerning African trypanosomiasis has improved. Now that we have at least some momentum, things are looking better, but the challenge is going to be getting into more remote areas of central Africa to identify cases, treat them, and establish effective surveillance programs. Part of the Aventis donation to the WHO will be used to expand global surveillance, increase sentinel surveillance for drug resistance and treatment failures, from clinical trials groups, and provide financial and technical support for population screening and treatment centers. The University of North Carolina at Chapel Hill is the center of a consortium for new drug development and research for African trypanosomiasis. The Gates Foundation funds the consortium.

Last year, seven Americans and one Canadian were diagnosed with sleeping sickness. The disease is imported to the United States by travelers and immigrants. With a limited number of domestic cases, the CDC filed an investigational drug application with the FDA to obtain the agents when needed. This approach gets the drugs to the patients and allows the CDC to track infectious diseases as they enter the United States. The resurgence in trypanosomiasis is currently confined to central Africa, with six countries reporting high or endemic levels of disease.