International team of scientists studies malaria drug resistance in Southeast Asia

Saturday, August 2, 2014

Researchers from Asia, Africa, Europe, and the United States have mapped resistance of malaria-causing parasite Plasmodium falciparum to antimalarial drug artemisinin, mainly in Southeast Asia; correlated the resistance-causing mutation with slow parasite clearance; and found that prolonged therapy is highly effective against drug-resistant malaria. Their study was published in New England Journal of Medicine on Thursday.

The mutation considered in this study was identified last year as the molecular marker of artemisinin-resistant malaria. The current study found the mutation, located in the propeller domain of a Kelch protein on human chromosome 13, predicted when parasite clearance half-life would exceed five hours with 91.8% sensitivity and 88.4% specificity — usually correct in predicting both when long half-life would occur, and when it wouldn't. OpenClinica web-based database was used for collection of data which was used to assess parasite clearance rate.

The study found a six-day treatment course effective against artemisinin-resistant malaria. The standard regimen consists of three-day dihydroartemisinin–piperaquine treatment, and had a 25% rate of failure at day 42 in another recent study in Pailin, Cambodia. The prolonged regimen which includes three days of artesunate followed by three days of dihydroartemisinin–piperaquine, has shown 2% rate of failure at day 42 in the same area. Geometric mean of the half-life values were similar in two treatment groups of 60 patients each at each study site: one group received artesunate at a daily dose of 2 mg per patient's body-weight kilogram and the other 4 mg per kilogram. Afterwards, patients at several study sites were followed for 42 days — Pailin, Cambodia; Attapeu, Laos; Binh Phuoc, Vietnam; Shwe Kyin, Myanmar; and Pingilikani, Kenya — and for 28 days in Kinshasa, DR Congo. The treatment regimens were highly effective at all the study sites.

Support for the study came from the UK Department for International Development, the Worldwide Antimalarial Resistance Network, the Intramural Research Program of the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, and the Bill and Melinda Gates Foundation. Also, the UK-based Wellcome Trust funds one of the participating research organizations, the Mahidol–Oxford Tropical Medicine Research Programme.

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Sister links

Artemisinin-based combination therapies

Sources

Elizabeth A. Ashley, et al.. "Spread of Artemisinin Resistance in Plasmodium falciparum Malaria" — July 31, 2014
Jennifer Routh (National Institute of Allergy and Infectious Diseases). "Resistance to key malaria drug spreading at alarming rate in Southeast Asia" — EurekAlert!, July 30, 2014

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