Chemotherapy for second-stage Human African trypanosomiasis

Overview

Human African trypanosomiasis (HAT), or sleeping sickness, is a painful and protracted disease transmitted through the bite of infected tsetse flies and it is found in rural parts of sub-Saharan Africa. Sleeping sickness has two clinical phases but this review focuses only on treatment of the second-stage, which is characterized by neurological changes and almost invariably fatal without treatment. There are only a few drugs currently available for second-stage sleeping sickness, all with considerable adverse events and variable efficacy.

The review includes nine trials with 2577 participants. Each trial reported different comparisons of the drugs currently available to treat second stage HAT (melarsoprol, eflornithine, nifurtimox) so no meta-analysis was possible.

Melarsoprol administration is intravenous and very painful, with many adverse reactions including a severe dysfunction of the brain, that can result in death. For this reason, trials were designed to evaluate shorter melarsoprol regimens. Giving melarsoprol for 10 days was found to be as effective as giving it for 26 days. Recently, nifurtimox and eflornithine combination therapy (NECT) was assessed. Few patients relapsed after NECT, which was generally well tolerated. It also has practical advantages: eflornithine has to be administered as a slow intravenous infusion thus requiring specialized health facilities and personnel, but nifurtimox is given orally. NECT uses less eflornithine doses and reduces the burden on health personnel and patients.

Considering that none of the current therapeutic options for HAT is optimal in terms of adverse events and ease of administration, it is essential that new anti-trypanosomal compounds are developed and tested in experimental and clinical studies. In the meantime, local availability of the drugs and the status of health facilities and personnel will dictate choice of treatment. It is envisioned that melarsoprol, with its high level of adverse events, will be phased out in favour of eflornithine and NECT. The development of parasite resistance to the drugs needs to be carefully monitored. Future research should also focus on the reduction of the adverse effects of currently used drugs and better diagnostic tests.