After 28 days of treatment, there were fewer cases of malaria among children taking a combination of the older sulfadoxine-pyrimethamine (sold under the brand name Fansidar) and amodiaquine than among patients taking a combination of Fansidar and artesunate, a drug based on the newer antimalarial called artemisinin.
However, the Fansidar-artesunate combination was more effective than the other drug combination at clearing malaria parasites from the blood at a particularly infectious stage of parasite development, according to Dr. Hasifa Bukirwa of the Uganda Malaria Surveillance Project and Julia Critchley of the Liverpool School of Tropical Medicine in England.
Bukirwa and Critchley say Fansidar-amodiaquine may be a useful stopgap treatment in areas without access to artemisinin drugs and areas where malaria resistance to Fansidar and amodiaquine is still low.
The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.
Artemisinin antimalarials are fast-acting and effective drugs that have proved useful against multi-drug resistant strains of the falciparum type of malaria. The World Health Organization recommends combination therapy that includes artemisinin drugs as the standard treatment in countries where malaria is resistant to older individual drugs such as chloroquine and amodiaquine.
However, "artemisinin drugs are not yet widely available in Africa and may not be for some time because of low production, comparatively high cost, dosing complexity and the lack of clinical experience with artemisinin-based combinations," Bukirwa and Critchley say.
The Cochrane reviewers analyzed four studies including 775 malaria patients, children age six months to five years. The studies compared the Fansidar-amodiaquine treatment to Fansidar-artesunate therapy for mild to moderate cases of falciparum malaria.
In three of the studies, the Fansidar-amodiaquine treatment reduced by nearly 40 percent the risk of still having malaria after 28 days of treatment, compared to Fansidar-artesunate treatment.
But the Fansidar-artesunate combination was more than twice as likely as the other drug combination to reduce the number of infectious malaria parasites in the blood to clinically insignificant levels. Reducing the parasite load is important because it reduces the spread of the disease, the reviewers say.
Bukirwa and Critchley stress that the Fansidar-amodiaquine combination should be considered useful and safe only in areas where resistance to both drugs is low. They warn that resistance may have increased since the studies in the review, conducted between 2002 and 2005, were completed.
"It is possible that sulfadoxine-pyrimethamine may not be recommended at all for first-line treatment of any malaria in Africa in the future," Bukirwa said.
Although combination malaria therapies are also being tried in Southeast Asia, where malaria is a major public health problem, the Fansidar-amodiaquine combination is probably not a viable treatment option for that region, says Dr. David Bell, a malaria expert at the University of Liverpool in England.
The failure rates for both amodiaquine and Fansidar "on their own tend to be considerable higher there than when they are used in Africa as monotherapies," he explains. "As such, I don't think the combination of amodiaquine and sulfadoxine-pyrimethamine would even be considered in that setting."
Malaria affects 300 to 500 million people worldwide every year and is the leading cause of illness and death in sub-Saharan Africa, according to a 2000 WHO report.
The Bukirwa study was supported by the Department for International Development, UK and the Makerere University Malaria Project, Uganda.
Bukirwa H, Critchley J. Sulfadoxine-pyrimethamine plus artesunate versus sulfadoxine-pyrimethamine plus amodiaquine for treating uncomplicated malaria. The Cochrane Database of Systematic Reviews 2006, Issue 1.
The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit http://www.cochrane.org for more information.
Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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