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Drug Resistance

The development of resistance to drugs poses one of the greatest threats to malaria control and has been linked to recent increases in malaria morbidity and mortality. Drug resistance has been confirmed in only 2 of the 4 human malaria parasite species, Plasmodium falciparum and P. vivax.

Drug-resistant P. falciparum

Chloroquine resistant P. falciparum (CRPF) first developed independently in 3 to 4 foci in Southeast Asia, Oceania , and South America in the late 1950's and early 1960's. Since then, chloroquine resistance has spread to nearly all areas of the world where falciparum malaria is transmitted.

P. falciparum has also developed resistance to nearly all of the other currently available antimalarial drugs, such as sulfadoxine/ pyrimethamine, mefloquine, halofantrine, and quinine. Although resistance to these drugs tends to be much less widespread geographically, in some areas of the world, the impact of multi-drug resistant malaria can be extensive.

Drug-resistant P. vivax

Chloroquine resistant P. vivax (CRPV) malaria was first identified in 1989 among Australians living in or traveling to Papua New Guinea. CRPV has also now been identified in Southeast Asia, on the Indian subcontinent, and in South America. Vivax malaria, particularly from Oceania, also exhibits decreased susceptibility to primaquine.

Tests for Drug Resistance

There are 4 basic methods for testing malaria for drug resistance: in vivo tests, in vitro tests, molecular characterization, and animal models. Of these, only the first 3 are routinely done.

In vivo tests: In these tests, patients with clinical malaria are given a treatment dose of an antimalarial drug under observation and are monitored over time for either failure to clear parasites or for reappearance of parasites.

In vitro tests: In these tests, blood samples from malaria patients are obtained and the malaria parasites are exposed to different concentrations of antimalarial drugs in the laboratory. Some methods call for adaptation of parasites to culture first, while others put blood directly from patients into the test system.

Molecular characterization: For some drugs (chloroquine, SP and similar drugs, atovaquone), molecular markers have been identified that confer resistance. Molecular techniques, such as polymerase chain reaction (PCR) or gene sequencing can identify these markers in blood taken from malaria-infected patients.

For a general overview of drug resistance and methods for testing for drug resistance in malaria:
Drug Resistance In Malaria (WHO, 2001)

For a detailed description of the in vivo methods:
Assessment And Monitoring of Antimalarial Drug Efficacy for The Treatment of Uncomplicated Falciparum Malaria (WHO, 2003) (471 KB/68 pages)

Drug Resistance: Malaria (WHO webpage)