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Fatal if untreated, human African trypanosomiasis (HAT; sleeping sickness) afflicts an estimated 50,000–70,000 people each year [1], all in sub-Saharan Africa, with only a minority of cases (nearly 12,000 in 2008) being reported [2]. HAT is one of four neglected tropical diseases (NTDs) identified by the World Health Organization (WHO) as requiring Innovative and Intensified Disease Management (IDM), along with Chagas disease, leishmaniasis, and Buruli ulcer [3]. These particular NTDs have poorly understood burdens, lack optimal control tools, receive insufficient research and development (R&D) investment, and affect people who often live in remote or insecure areas with limited access to health care. Excluding Buruli ulcer, these IDM diseases have the highest death rates of all NTDs [4].  HAT in west and central Africa is caused by the protozoan parasite Trypanosoma brucei gambiense, transmitted through tsetse flies. The disease progresses from first stage (infecting blood and lymph) to second stage (infecting the central nervous system), which can lead to severe sleep disturbances, neurological and psychiatric disorders, coma, and death. Primary elements of HAT management are surveillance, diagnosis, treatment, and vector control.  Drug treatments for T. b. gambiense HAT have been limited: pentamidine for first-stage disease, and melarsoprol or eflornithine for second-stage disease. Eflornithine is safer and often more effective than melarsoprol, which is associated with high toxicity, even fatal at times, and exhibits high rates of treatment failure in numerous HAT-endemic foci. However, despite an increasing proportion of second-stage HAT treated with eflornithine during recent years [5], melarsoprol remains in use in many treatment centers due to eflornithine's long, burdensome treatment administration requirements, which are difficult to implement in resource-constrained settings.  In April 2009, a new treatment option, nifurtimox-eflornithine combination therapy (NECT), was added to the WHO Essential Medicines List (EML) for the treatment of second-stage T. b. gambiense HAT [6]. NECT was added to the EML based on the high efficacy and good safety profile observed in all studies done to date, against a background of recognized severity of stage 2 disease and toxicity of existing treatments. Surveillance of adverse events was strongly recommended [7]. Compared with eflornithine monotherapy, NECT is easier to administer and requires fewer human and material resources. In the current context, NECT stands as the most promising first-line treatment for second-stage T. b. gambiense HAT. Here we describe the developments and challenges in rolling out and implementing NECT in HAT-endemic areas.

NECT Is Next: Implementing the New Drug Combination Therapy for Trypanosoma brucei gambiense Sleeping Sickness