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The Cochrane Database of Systematic... Oct 2005Many conventional treatments for uncomplicated malaria are failing because malaria parasites develop resistance to them. One way to combat this resistance is to treat... (Meta-Analysis)
Meta-Analysis Review
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.
Topics: Antimalarials; Atovaquone; Drug Combinations; Humans; Malaria, Falciparum; Naphthoquinones; Proguanil; Randomized Controlled Trials as Topic
PubMed: 16235366
DOI: 10.1002/14651858.CD004529.pub2 -
The Cochrane Database of Systematic... Oct 2005Chloroquine (CQ), amodiaquine (AQ), and sulfadoxine-pyrimethamine (SP) are inexpensive drugs, but treatment failure is a problem. Combination therapy may reduce... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chloroquine (CQ), amodiaquine (AQ), and sulfadoxine-pyrimethamine (SP) are inexpensive drugs, but treatment failure is a problem. Combination therapy may reduce treatment failure. CQ or AQ plus SP are affordable options of combination treatment, but there is debate about their effectiveness.
OBJECTIVES
To assess the combination of CQ or AQ plus SP compared with SP alone for first-line treatment of uncomplicated falciparum malaria.
SEARCH STRATEGY
We searched the Cochrane Infectious Diseases Group Specialized Register (April 2005), CENTRAL (The Cochrane Library Issue 2, 2005), MEDLINE (1966 to April 2005), EMBASE (1974 to April 2005), LILACS (1982 to April 2005), Science Citation Index (1981 to April 2005), African Index Medicus (1993 to 1998), and reference lists. We also contacted researchers at relevant organizations and a pharmaceutical company.
SELECTION CRITERIA
Randomized controlled trials in adults or children with uncomplicated Plasmodium falciparum malaria were eligible for inclusion. The main outcomes of interest were total and clinical failure at day 28 follow up and serious adverse events.
DATA COLLECTION AND ANALYSIS
Two people independently applied the inclusion criteria. One author extracted data and another checked them independently. We used relative risk (RR) and 95% confidence intervals (CI).
MAIN RESULTS
Twelve trials (2107 participants) met the inclusion criteria. A meta-analysis of five AQ trials (461 participants) showed a statistically significant reduction in total failure at day 28 with the combination therapy (RR 0.64, 95% CI 0.46 to 0.91), and meta-analysis of three trials (384 participants) showed a significant reduction in clinical failure at day 28 (RR 0.23, 95% CI 0.11 to 0.49). The statistical significance in the total failure analysis was sensitive to losses to follow up. Data from two CQ trials showed no advantage for total failure with combination therapy at day 28. There was no evidence from the included trials of serious adverse events.
AUTHORS' CONCLUSIONS
The evidence base is not strong enough to support firm conclusions. The available evidence suggests that AQ plus SP can achieve less treatment failure than SP, but this might depend on existing levels of parasite resistance to the individual drugs.
Topics: Adult; Amodiaquine; Chloroquine; Drug Combinations; Drug Therapy, Combination; Humans; Malaria; Malaria, Falciparum; Pyrimethamine; Sulfadoxine
PubMed: 16235276
DOI: 10.1002/14651858.CD000386.pub2 -
The Cochrane Database of Systematic... 2000Amodiaquine has been widely used to treat malaria. Due to reports of fatal adverse drug reactions, discontinuation or modification of its use has been suggested. (Review)
Review
BACKGROUND
Amodiaquine has been widely used to treat malaria. Due to reports of fatal adverse drug reactions, discontinuation or modification of its use has been suggested.
OBJECTIVES
The objective of this review was to assess the effects of amodiaquine for treating malaria.
SEARCH STRATEGY
We searched the Cochrane Infectious Diseases Group trials register and Medline. We also contacted researchers in the field and drug companies.
SELECTION CRITERIA
Randomised and quasi-randomised trials comparing amodiaquine with other treatment for uncomplicated malarial infections in adults and children.
DATA COLLECTION AND ANALYSIS
Both reviewers independently extracted data and assessed trial quality.
MAIN RESULTS
Forty trials were included. Allocation was adequately concealed in three trials. Amodiaquine was more effective than chloroquine for parasite clearance. The combined results of parasite clearance at seven days from 24 trials was 83% for amodiaquine and 56% for chloroquine (odds ratio 4.29, 95% confidence interval 3.51 to 5.24). The odds ratio for parasite clearance at 14 days was 6.00, 95% confidence interval 4.38 to 8.21. Amodiaquine and sulfadoxine/pyrimethamine showed similar results for parasite clearance on day seven, but sulfadoxine/pyrimethamine appeared to be more effective on day 14 and 28. No significant difference for adverse events was observed between amodiaquine and chloroquine and sulfadoxine/pyrimethamine. Reported adverse effects were minor or moderate, not life threatening.
REVIEWER'S CONCLUSIONS
There is some evidence to support the continued use of amodiaquine in the treatment of uncomplicated malaria, although drug resistance should be considered. Monitoring for toxicity should also continue.
Topics: Amodiaquine; Antimalarials; Humans; Malaria
PubMed: 10796468
DOI: 10.1002/14651858.CD000016 -
Lancet (London, England) Nov 1996Opinion and policy over the use of amodiaquine for treating malaria vary. Amodiaquine is more palatable than chloroquine and may be more effective but serious adverse... (Comparative Study)
Comparative Study Review
BACKGROUND
Opinion and policy over the use of amodiaquine for treating malaria vary. Amodiaquine is more palatable than chloroquine and may be more effective but serious adverse events have been reported in travellers taking it as prophylaxis. It is not recommended as first-line treatment. In the light of the global debate over the use of this drug, we conducted a systematic review of the effectiveness and tolerability of amodiaquine in the treatment of uncomplicated falciparum malaria.
METHODS
This is a systematic review of published and unpublished randomised or pseudorandomised trials of amodiaquine. Observational reports were also systematically identified and reviewed to access evidence of serious adverse events.
FINDINGS
40 trials met the inclusion criteria. Symptomatic patients were enrolled in 24 studies in comparisons of amodiaquine (n = 1071) with chloroquine (n = 1097). Amodiaquine was significantly more effective than chloroquine, with odds ratios and 99% confidence intervals (OR [99% CI]) of 4.29 (3.30-5.58) on day 7 and 6.00 (3.97-9.06) on day 14. Time to parasite clearance was significantly shorter with amodiaquine and fever clearance times were marginally faster. Eight studies compared amodiaquine with chloroquine in asymptomatic parasitaemia, with effects on parasitological outcomes similar to those for symptomatic malaria. At twelve sites, 692 amodiaquine and 679 sulfadoxine/pyrimethamine (S/P) recipients were enrolled. The two drugs did not differ significantly on day 7 (OR 0.74 [0.48-1.15]) but the odds ratios favoured S/P on day 14 (OR 0.51 [0.28-0.93]) and on day 28 (OR 0.30 [0.16-0.55]). The time to parasitological clearance was similar in the two groups; fever clearance times were significantly shorter with amodiaquine. Tolerability was assessed for both comparative and non-comparative trials. The rates of adverse events in controlled trials were 10.7%, 8.8%, and 14.3% with amodiaquine, chloroquine, and S/P, respectively. No life-threatening adverse events and no significant shifts in laboratory indices were reported.
INTERPRETATION
This systematic review of published and unpublished trials supports the use of amodiaquine in the treatment of uncomplicated malaria. However, there is partial cross-resistance between chloroquine and amodiaquine, and monitoring of the effectiveness of this drug and surveillance for evidence of toxicity must continue.
Topics: Amodiaquine; Antimalarials; Chloroquine; Humans; Malaria, Falciparum; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 8898036
DOI: 10.1016/S0140-6736(96)06217-4