Chemotherapy for second-stage Human African trypanosomiasis.
BACKGROUND
Human African trypanosomiasis, or sleeping sickness, is a painful and protracted disease affecting people in the poorest parts of Africa and is fatal without treatment. Few drugs are currently available for second-stage sleeping sickness, with considerable adverse events and variable efficacy.


OBJECTIVE
To evaluate the effectiveness and safety of drugs for treating second-stage human African trypanosomiasis.


METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register (May 2010), CENTRAL (The Cochrane Library Issue 3 2010) , MEDLINE (1966 to May 2010), EMBASE (1974 to May 2010), LILACS (1982 to May 2010 ), BIOSIS (1926-May 2010), mRCT (May 2010) and reference lists. We contacted researchers working in the field and organizations.


METHODS
Randomized and quasi-randomized controlled trials.


METHODS
Two authors (VL and AK) extracted data and assessed methodological quality; a third author (JS) acted as an arbitrator. Included trials only reported dichotomous outcomes, and we present these as risk ratio (RR) with 95% confidence intervals (CI).


RESULTS
Nine trials with 2577 participants, all with Trypansoma brucei gambiense HAT, were included. Seven trials tested currently available drugs: melarsoprol, eflornithine, nifurtimox, alone or in combination; one trial tested pentamidine, and one trial assessed the addition of prednisolone to melarsoprol. Fixed 10-day regimens of melarsoprol were found to be as effective as those of 26 days, with similar numbers of adverse events. Melarsoprol monotherapy gave fewer relapses than pentamidine or nifurtimox, but resulted in more adverse events.Later trials evaluate nifurtimox combined with eflornithine (NECT), showing this gives few relapses and is well tolerated. It also has practical advantages in reducing the burden on health personnel and patients, when compared to eflornithine monotherapy.


CONCLUSIONS
Choice of therapy for second stage Gambiense HAT will continue to be determined by what is locally available, but eflornithine and NECT are likely to replace melarsoprol, with careful parasite resistance monitoring. We need research on reducing adverse effects of currently used drugs, testing different regimens, and experimental and clinical studies of new compounds, effective for both stages of the disease.
Lutje
Vittoria
V
International Health Group, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, UK, L3 5QA.
Seixas
Jorge
J
Kennedy
Adrian
A
D000818:Animals; D000981:Antiprotozoal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000379:methods; D000518:Eflornithine / Q000627:therapeutic use; D006801:Humans; D008549:Melarsoprol / Q000627:therapeutic use; D009547:Nifurtimox / Q000627:therapeutic use; D010419:Pentamidine / Q000627:therapeutic use; D011239:Prednisolone / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D014347:Trypanosoma brucei gambiense; D014353:Trypanosomiasis, African / Q000188:drug therapy*
D000981:Antiprotozoal Agents; D010419:Pentamidine; D011239:Prednisolone; D009547:Nifurtimox; D008549:Melarsoprol; D000518:Eflornithine