An inexpensive drug that has lost much of its punch against malaria over the past 20 years is showing signs of regaining its strength in the African nation of Malawi. But researchers warn that the entire continent would have to coordinate its fight against the disease in order for the drug to regain a prominent place among malaria fighters.
Doctors have used the drug, chloroquine, to treat malaria for 60 years, but Plasmodium falciparum, the protozoan that causes severe malaria, has become increasingly resistant. Malawi abandoned the drug in 1993, and doctors there replaced it with an inexpensive combination pill containing sulfadoxine and pyrimethamine. Scientists took note.
The Malawi strategy worked for several years. But eventually, the combination drug became less and less effective against P. falciparum. The emerging therapy of choice in Africa is now a more expensive, more complex treatment that includes derivatives of artemisinin—an extract of the Chinese herbal remedy called sweet wormwood (SN: 2/7/04, p. 94: Available to subscribers at Malaria drug boosts recovery rates).
Meanwhile, scientists working in Malawi have found that the malaria protozoan recovered from patients no longer harbored a mutation that makes it resistant to chloroquine, says Miriam K. Laufer, a pediatric infectious-disease physician at the University of Maryland School of Medicine in Baltimore.
To find out whether the drug might again be effective, Laufer and her colleagues last year identified 210 Malawian children with malaria and gave half of them chloroquine and half of them the sulfadoxine-pyrimethamine combination.
Of 80 children who had received chloroquine and were monitored over 4 weeks, all but one cleared the parasite from their blood. In contrast, 71 of 87 children who were reexamined after getting the sulfadoxine-pyrimethamine combination failed to improve and received other drugs, the scientists report in the Nov. 9 New England Journal of Medicine. Some children weren't available for follow-up.
The Malawi experience establishes that P. falciparum can become susceptible again to chloroquine after the drug has been absent, says physician Nicholas J. White of Mahidol University in Bangkok, writing in the same journal issue.
"It's a fascinating finding, but it's too early to say whether a public health policy will come out of it," says Paul Garner of the Liverpool School of Tropical Medicine in England. Although most countries in Africa discourage chloroquine use, people take the drug to reduce fever and feel better, he says. Unfortunately, resistant P. falciparum isn't wiped out in such patients, so they remain infected and risk the fever's return.
Because nearby countries harbor resistant malaria strains that could reenter Malawi, Laufer says, reintroducing chloroquine as a standard treatment is unlikely. Any push to stop chloroquine use "would need to be continentwide," she says.
If chloroquine were to replace failing sulfadoxine-pyrimethamine therapy across Africa before chloroquine resistance had disappeared from P. falciparum, the result could be a parasite impervious to both treatments, warns Toshihiro Mita, a physician at Tokyo Women's Medical University.
International Health Division
Liverpool School of Tropical Medicine
University of Liverpool
Liverpool L3 5QA
Miriam K. Laufer
University of Maryland, Baltimore
School of Medicine
685 West Baltimore Street
Baltimore, MD 21201
Department of International Affairs and Tropical Medicine
Tokyo Women's Medical University
Shinjuku-ku, Tokyo 162-8666
Nicholas J. White
Oxford Tropical Medicine Research Programme
420/6 Rajvithi Road
Alifrangis, M., et al. 2005. A simple, high-throughput method to detect Plasmodium falciparum single nucleotide polymorphisms in the dihydrofolate reductase, dihydropteroate synthase, and P. falciparum chloroquine resistance transporter genes using polymerase chain reaction—and enzyme-linked immunosorbent assay-based technology. American Journal of Tropical Medicine and Hygiene 72(February):155-162. Available at [Go to].
Mita, T., et al. 2003. Recovery of chloroquine sensitivity and low prevalence of the Plasmodium falciparum chloroquine resistance transporter gene mutation K76T following the discontinuance of chloroquine use in Malawi. American Journal of Tropical Medicine and Hygiene 68(April):413-415. Available at [Go to].
Pinder, M., et al. 2006. Immunoglobulin G antibodies to merozoite surface antigens are associated with recovery from chloroquine-resistant Plasmodium falciparum in Gambian children. Infection and Immunity 74(May):2887-2893. Available at [Go to].
Plowe, C.V. 2003. Monitoring antimalarial drug resistance: Making the most of the tools at hand. Journal of Experimental Biology 206(Nov. 1):3745-3752. Available at [Go to].
Seppa, N. 2004. Malaria drug boosts recovery rates. Science News 165(Feb. 7):94. Available to subscribers at [Go to].
White, N.J. 2006. Malaria—time to act. New England Journal of Medicine 355(Nov. 9):1956-1957. Available at [Go to].
______. 2004. Antimalarial drug resistance. Journal of Clinical Investigations 113(April 15):1084-1092. Available at [Go to].
Zimmerman, P.A. 2003. Roll back of Plasmodium falciparum antifolate resistance by insectide-treated nets. American Journal of Tropical Medicine and Hygiene 69(September):236-237. Available at [Go to].