H Bukirwa1, P Garner, J Critchley. 1. Makerere University Malaria Project, Mulago Hospital Complex, Kampala, PO BOX 7423, Uganda. hbukirwa@liv.ac.uk
Abstract
BACKGROUND: In Africa, malaria is often resistant to chloroquine and sulfadoxine-pyrimethamine. Chlorproguanil-dapsone is a potential alternative. OBJECTIVES: To compare chlorproguanil-dapsone with other antimalarial drugs for treating uncomplicated falciparum malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (May 2004), CENTRAL (The Cochrane Library Issue 2, 2004), MEDLINE (1966 to May 2004), EMBASE (1988 to May 2004), LILACS (May 2004), Biosis Previews (1985 to May 2004), conference proceedings, and reference lists, and contacted researchers working in this field. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing chlorproguanil-dapsone to other antimalarial drugs. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria, extracted data, and assessed methodological quality. We calculated the relative risk (RR) for dichotomous data and weighted mean difference for continuous data, and presented them with 95% confidence intervals (CI). MAIN RESULTS: Six trials (n = 3352) met the inclusion criteria. Chlorproguanil-dapsone (with 1.2 mg chlorproguanil) as a single dose had fewer treatment failures than chloroquine (1 trial), but more treatment failures and people with parasitaemia at day 28 than sulfadoxine-pyrimethamine (3 trials). Two trials compared the three-dose chlorproguanil-dapsone (with 2 mg chlorproguanil) regimen with sulfadoxine-pyrimethamine in new attendees. There were fewer treatment failures with chlorproguanil-dapsone by day 7 (RR 0.30, CI 0.19 to 0.49; n = 827, 1 trial) and day 14 (RR 0.36, CI 0.24 to 0.53; n = 1709, 1 trial). Neither trial reported total failures by day 28. A further trial was carried out in participants selected because they had previously failed sulfadoxine-pyrimethamine. Adverse event reporting was inconsistent between trials, but chlorproguanil-dapsone was associated with more adverse events leading to discontinuation of treatment compared with sulfadoxine-pyrimethamine (RR 4.54, CI 1.74 to 11.82; n = 829, 1 trial). It was also associated with more red blood cell disorders (RR 2.86, CI 1.33 to 6.13; n = 1850, 1 trial). REVIEWERS' CONCLUSIONS: There are insufficient data about the effects of the current standard chlorproguanil-dapsone regimen (three-dose, 2 mg chlorproguanil). Randomized controlled trials that follow up to day 28, record adverse events, and use an intention-to-treat analysis are required to inform any policy decisions.
BACKGROUND: In Africa, malaria is often resistant to chloroquine and sulfadoxine-pyrimethamine. Chlorproguanil-dapsone is a potential alternative. OBJECTIVES: To compare chlorproguanil-dapsone with other antimalarial drugs for treating uncomplicated falciparum malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (May 2004), CENTRAL (The Cochrane Library Issue 2, 2004), MEDLINE (1966 to May 2004), EMBASE (1988 to May 2004), LILACS (May 2004), Biosis Previews (1985 to May 2004), conference proceedings, and reference lists, and contacted researchers working in this field. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing chlorproguanil-dapsone to other antimalarial drugs. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria, extracted data, and assessed methodological quality. We calculated the relative risk (RR) for dichotomous data and weighted mean difference for continuous data, and presented them with 95% confidence intervals (CI). MAIN RESULTS: Six trials (n = 3352) met the inclusion criteria. Chlorproguanil-dapsone (with 1.2 mg chlorproguanil) as a single dose had fewer treatment failures than chloroquine (1 trial), but more treatment failures and people with parasitaemia at day 28 than sulfadoxine-pyrimethamine (3 trials). Two trials compared the three-dose chlorproguanil-dapsone (with 2 mg chlorproguanil) regimen with sulfadoxine-pyrimethamine in new attendees. There were fewer treatment failures with chlorproguanil-dapsone by day 7 (RR 0.30, CI 0.19 to 0.49; n = 827, 1 trial) and day 14 (RR 0.36, CI 0.24 to 0.53; n = 1709, 1 trial). Neither trial reported total failures by day 28. A further trial was carried out in participants selected because they had previously failed sulfadoxine-pyrimethamine. Adverse event reporting was inconsistent between trials, but chlorproguanil-dapsone was associated with more adverse events leading to discontinuation of treatment compared with sulfadoxine-pyrimethamine (RR 4.54, CI 1.74 to 11.82; n = 829, 1 trial). It was also associated with more red blood cell disorders (RR 2.86, CI 1.33 to 6.13; n = 1850, 1 trial). REVIEWERS' CONCLUSIONS: There are insufficient data about the effects of the current standard chlorproguanil-dapsone regimen (three-dose, 2 mg chlorproguanil). Randomized controlled trials that follow up to day 28, record adverse events, and use an intention-to-treat analysis are required to inform any policy decisions.
Authors: Theonest K Mutabingwa; Kandi Muze; Rosalynn Ord; Marnie Briceño; Brian M Greenwood; Chris Drakeley; Christopher J M Whitty Journal: PLoS One Date: 2009-04-08 Impact factor: 3.240