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Meta-Analysis
. 2005 Oct 19;2005(4):CD004529.
doi: 10.1002/14651858.CD004529.pub2.

Atovaquone-proguanil for treating uncomplicated malaria

A Osei-Akoto  1 , L Orton, S P O Owusu-Ofori
Affiliations
Meta-Analysis

Atovaquone-proguanil for treating uncomplicated malaria

A Osei-Akoto et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Many conventional treatments for uncomplicated malaria are failing because malaria parasites develop resistance to them. One way to combat this resistance is to treat people with a combination of drugs, such as atovaquone-proguanil.

Objectives: To compare atovaquone-proguanil with other antimalarial drugs (alone or in combination) for treating children and adults with uncomplicated Plasmodium falciparum malaria.

Search strategy: We searched the Cochrane Infectious Diseases Group Specialized Register (June 2005), CENTRAL (The Cochrane Library Issue 2, 2005), MEDLINE (1966 to June 2005), EMBASE (1980 to June 2005), LILACS (1982 to June 2005), reference lists, and conference abstracts. We also contacted relevant pharmaceutical manufacturers and researchers.

Selection criteria: Randomized controlled trials comparing atovaquone-proguanil with other antimalarial drugs for treating children and adults confirmed to have uncomplicated P. falciparum malaria.

Data collection and analysis: Three authors independently assessed trial eligibility and methodological quality, and extracted data for an intention-to-treat analysis (where possible). We used relative risk (RR) and 95% confidence intervals (CI) for dichotomous data. We contacted trial authors for additional information where needed.

Main results: Ten trials, with a total of 2345 participants, met the inclusion criteria. The trials were conducted in four geographical regions and were often small, but they included comparisons across eight drugs. Nine trials were funded by a pharmaceutical company, only three carried out an intention-to-treat analysis, and allocation concealment was unclear in seven. Atovaquone-proguanil had fewer treatment failures by day 28 than chloroquine (RR 0.04, 95% CI 0.00 to 0.57; 27 participants, 1 trial), amodiaquine (RR 0.22, 95% CI 0.13 to 0.36; 342 participants, 2 trials), and mefloquine (RR 0.04, 95% CI 0.00 to 0.73; 158 participants, 1 trial). There were insufficient data to draw a conclusion for this outcome from comparisons with sulfadoxine-pyrimethamine (172 participants, 2 trials), halofantrine (205 participants, 1 trial), artesunate plus mefloquine (1063 participants, 1 trial), quinine plus tetracycline (154 participants, 1 trial), and dihydroartemisinin-piperaquine-trimethoprim-primaquine (161 participants, 1 trial). Adverse events were mainly common symptoms of malaria and did not differ in frequency between groups.

Authors' conclusions: Data are limited but appear to suggest that atovaquone-proguanil is more effective than chloroquine, amodiaquine, and mefloquine. There are insufficient data for comparisons against sulfadoxine-pyrimethamine, halofantrine, artesunate plus mefloquine, quinine plus tetracycline, and dihydroartemisinin-piperaquine-trimethoprim-primaquine in treating malaria. There are not enough data to assess safety, but a number of adverse events were identified with all drugs. Large trials comparing atovaquone-proguanil with other new combination therapies are needed.

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Conflict of interest statement

None known.

Figures

1.1
1.1. Analysis
Comparison 1 Atovaquone‐proguanil (AP) versus chloroquine, Outcome 1 Treatment failure on or by day 28.
1.2
1.2. Analysis
Comparison 1 Atovaquone‐proguanil (AP) versus chloroquine, Outcome 2 Parasite clearance time (mean; h).
1.3
1.3. Analysis
Comparison 1 Atovaquone‐proguanil (AP) versus chloroquine, Outcome 3 Fever clearance time (mean; h).
1.4
1.4. Analysis
Comparison 1 Atovaquone‐proguanil (AP) versus chloroquine, Outcome 4 Adverse events.
2.1
2.1. Analysis
Comparison 2 Atovaquone‐proguanil (AP) versus amodiaquine, Outcome 1 Treatment failure on or by day 28.
2.2
2.2. Analysis
Comparison 2 Atovaquone‐proguanil (AP) versus amodiaquine, Outcome 2 Treatment failure on or by day 14.
2.3
2.3. Analysis
Comparison 2 Atovaquone‐proguanil (AP) versus amodiaquine, Outcome 3 Parasite clearance time (mean; h).
2.4
2.4. Analysis
Comparison 2 Atovaquone‐proguanil (AP) versus amodiaquine, Outcome 4 Fever clearance time (mean; h).
2.5
2.5. Analysis
Comparison 2 Atovaquone‐proguanil (AP) versus amodiaquine, Outcome 5 Adverse events.
3.1
3.1. Analysis
Comparison 3 Atovaquone‐proguanil (AP) versus sulfadoxine‐pyrimethamine (SP), Outcome 1 Treatment failure on or by day 28.
3.2
3.2. Analysis
Comparison 3 Atovaquone‐proguanil (AP) versus sulfadoxine‐pyrimethamine (SP), Outcome 2 Parasite clearance time (mean; h).
3.3
3.3. Analysis
Comparison 3 Atovaquone‐proguanil (AP) versus sulfadoxine‐pyrimethamine (SP), Outcome 3 Fever clearance time (mean; h).
3.4
3.4. Analysis
Comparison 3 Atovaquone‐proguanil (AP) versus sulfadoxine‐pyrimethamine (SP), Outcome 4 Progression to severe disease.
3.5
3.5. Analysis
Comparison 3 Atovaquone‐proguanil (AP) versus sulfadoxine‐pyrimethamine (SP), Outcome 5 Adverse events.
4.1
4.1. Analysis
Comparison 4 Atovaquone‐proguanil (AP) versus quinine plus tetracycline (Q plus T), Outcome 1 Treatment failure on or by day 28.
4.2
4.2. Analysis
Comparison 4 Atovaquone‐proguanil (AP) versus quinine plus tetracycline (Q plus T), Outcome 2 Parasite clearance time (mean; h).
4.3
4.3. Analysis
Comparison 4 Atovaquone‐proguanil (AP) versus quinine plus tetracycline (Q plus T), Outcome 3 Fever clearance time (mean; h).
4.4
4.4. Analysis
Comparison 4 Atovaquone‐proguanil (AP) versus quinine plus tetracycline (Q plus T), Outcome 4 Adverse events.
5.1
5.1. Analysis
Comparison 5 Atovaquone‐proguanil (AP) versus halofantrine, Outcome 1 Treatment failure on or by day 28.
5.2
5.2. Analysis
Comparison 5 Atovaquone‐proguanil (AP) versus halofantrine, Outcome 2 Parasite clearance time (mean; h).
5.3
5.3. Analysis
Comparison 5 Atovaquone‐proguanil (AP) versus halofantrine, Outcome 3 Fever clearance time (mean; h).
5.4
5.4. Analysis
Comparison 5 Atovaquone‐proguanil (AP) versus halofantrine, Outcome 4 Adverse events.
6.1
6.1. Analysis
Comparison 6 Atovaquone‐proguanil (AP) versus mefloquine, Outcome 1 Treatment failure on or by day 28.
6.2
6.2. Analysis
Comparison 6 Atovaquone‐proguanil (AP) versus mefloquine, Outcome 2 Parasite clearance time (mean; h).
6.3
6.3. Analysis
Comparison 6 Atovaquone‐proguanil (AP) versus mefloquine, Outcome 3 Fever clearance time (mean; h).
6.4
6.4. Analysis
Comparison 6 Atovaquone‐proguanil (AP) versus mefloquine, Outcome 4 Adverse events.
7.1
7.1. Analysis
Comparison 7 Atovaquone‐proguanil (AP) versus artesunate plus mefloquine (AS plus MQ), Outcome 1 Treatment failure on or by day 14.
7.2
7.2. Analysis
Comparison 7 Atovaquone‐proguanil (AP) versus artesunate plus mefloquine (AS plus MQ), Outcome 2 Treatment failure on or by day 28 adjusted by PCR.
7.3
7.3. Analysis
Comparison 7 Atovaquone‐proguanil (AP) versus artesunate plus mefloquine (AS plus MQ), Outcome 3 Adverse events.
8.1
8.1. Analysis
Comparison 8 Atovaquone‐proguanil (AP) versus dihydroartemisinin, piperaquine, trimethoprim, and primaquine (CV8), Outcome 1 Treatment failure on or by day 28.
8.2
8.2. Analysis
Comparison 8 Atovaquone‐proguanil (AP) versus dihydroartemisinin, piperaquine, trimethoprim, and primaquine (CV8), Outcome 2 Parasite clearance time (mean; h).
8.3
8.3. Analysis
Comparison 8 Atovaquone‐proguanil (AP) versus dihydroartemisinin, piperaquine, trimethoprim, and primaquine (CV8), Outcome 3 Fever clearance time (mean; h).
8.4
8.4. Analysis
Comparison 8 Atovaquone‐proguanil (AP) versus dihydroartemisinin, piperaquine, trimethoprim, and primaquine (CV8), Outcome 4 Adverse events.
See this image and copyright information in PMC

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