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Reversal of Chloroquine Resistance: Malaria in Malawi

More than a decade after chloroquine was removed from routine use in Malawi because of parasite resistance to it, the drug is again effective.

Malaria parasites have become increasingly drug-resistant, and resistance has spread geographically. In 1993, when the clinical efficacy of chloroquine (CQ) against falciparum malaria dropped below 50%, Malawi replaced this agent countrywide with sulfadoxine-pyrimethamine (SP) for first-line treatment of uncomplicated malaria.

In one Malawian city, researchers measured the prevalence of a molecular marker associated with CQ resistance before, during, and after CQ was withdrawn from use. Because the marker became less prevalent and then disappeared from this area in 2001, they decided to reassess the efficacy of CQ. In 2005, they randomized 210 children aged 6 months to 12 years with uncomplicated falciparum malaria (parasite level, 2000 to 200,000 per mm³) to receive directly observed CQ or SP and followed them for 28 days for clinical and parasitologic response. Nonresponders were treated with halofantrine.

Among study completers, treatment failure occurred in 1 of 80 in the CQ group and 71 of 87 in the SP group, for efficacies of 99% (95% confidence interval, 93–100) and 21% (95% CI, 13–30), respectively. Assays on blood collected at enrollment found that all specimens had the wild-type genotype associated with CQ susceptibility.

Comment: Although these findings suggest that SP is no longer effective in Malawi and that parasites in this population have become susceptible to CQ, the authors and an editorialist caution against returning to CQ as first-line monotherapy. CQ is safe, inexpensive, rapid-acting, and well tolerated, but it no longer works in most malarious areas, including countries neighboring Malawi. Its wide use favors emergence of resistance. Artemisinin-based combination therapy is now the preferred treatment for falciparum malaria, but these drugs are more expensive than CQ and SP and are still unavailable to most populations in Africa, where the benefit would be great. If CQ were withdrawn throughout Africa, it might become useful in some settings in the future.

— Mary E. Wilson, MD

Published in Journal Watch Infectious Diseases November 15, 2006

Citation(s):

Laufer MK et al. Return of chloroquine antimalarial efficacy in Malawi. N Engl J Med 2006 Nov 9; 355:1959-66.

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White NJ. Malaria — Time to act. N Engl J Med 2006 Nov 9; 355:1956-7.

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• Medline abstract (Free)