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Meta-Analysis
. 2013 Jun 28;2013(6):CD006201.
doi: 10.1002/14651858.CD006201.pub3.

Chemotherapy for second-stage human African trypanosomiasis

Vittoria Lutje  1 , Jorge Seixas, Adrian Kennedy
Affiliations
Meta-Analysis

Chemotherapy for second-stage human African trypanosomiasis

Vittoria Lutje et al. Cochrane Database Syst Rev. .

Abstract

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.

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

Search methods: We searched the Cochrane Infectious Diseases Group Specialized Register (January 2013), CENTRAL (The Cochrane Library Issue 12 2012) , MEDLINE (1966 to January 2013), EMBASE (1974 to January 2013), LILACS (1982 to January 2013 ), BIOSIS (1926-January 2013), mRCT (January 2013) and reference lists. We contacted researchers working in the field and organizations.

Selection criteria: Randomized and quasi-randomized controlled trials including adults and children with second-stage HAT, treated with anti-trypanosomal drugs.

Data collection and analysis: 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).

Main 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. The frequency of death and number of adverse events were similar between patients treated with fixed 10-day regimens of melarsoprol or 26-days regimens. 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 frequency and number of eflornithine slow infusions to twice a day, thus easing the burden on health personnel and patients.

Authors' 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.

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Conflict of interest statement

None known.

Figures

1
1
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
2
2
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1 Melarsoprol monotherapy: Drug A vs Drug B, Outcome 1 Death during treatment.
1.2
1.2. Analysis
Comparison 1 Melarsoprol monotherapy: Drug A vs Drug B, Outcome 2 Overall mortality.
1.3
1.3. Analysis
Comparison 1 Melarsoprol monotherapy: Drug A vs Drug B, Outcome 3 Relapse during follow up.
2.1
2.1. Analysis
Comparison 2 Eflornithine monotherapy: Drug A vs Drug B, Outcome 1 Death during treatment.
2.2
2.2. Analysis
Comparison 2 Eflornithine monotherapy: Drug A vs Drug B, Outcome 2 Overall mortality.
2.3
2.3. Analysis
Comparison 2 Eflornithine monotherapy: Drug A vs Drug B, Outcome 3 Relapse during follow up.
3.1
3.1. Analysis
Comparison 3 Comparisons between single drugs: Drug A vs Drug B, Outcome 1 Death during treatment.
3.2
3.2. Analysis
Comparison 3 Comparisons between single drugs: Drug A vs Drug B, Outcome 2 Overall mortality.
3.3
3.3. Analysis
Comparison 3 Comparisons between single drugs: Drug A vs Drug B, Outcome 3 Relapse during follow up.
3.4
3.4. Analysis
Comparison 3 Comparisons between single drugs: Drug A vs Drug B, Outcome 4 Relapse.
4.1
4.1. Analysis
Comparison 4 Combination therapies: Drug A vs Drug B, Outcome 1 Death due to HAT.
4.2
4.2. Analysis
Comparison 4 Combination therapies: Drug A vs Drug B, Outcome 2 Death during treatment.
4.3
4.3. Analysis
Comparison 4 Combination therapies: Drug A vs Drug B, Outcome 3 Overall mortality.
4.4
4.4. Analysis
Comparison 4 Combination therapies: Drug A vs Drug B, Outcome 4 Relapse during follow up.
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