| Summary: | Ever since the discovery of the first case of chloroquine resistance along the Thai-Combodian borderin the late 1950s, Southeast Asia has played an important role as a focus for the development of drugresistance in Plasmodium falciparum. Although the first case of quinine resistance had been reportedmuch earlier from South America, the onset of chloroquine resistance marked the beginning of a newchapter in the history of malaria in Southeast Asia and by 1973 chloroquine finally had to be replacedby the combination of sulphadoxine and pyrimethamine (SP) as first line drug for the treatment ofuncomplicated malaria in Thailand and more than 10 African countries have also switched their firstline drug to SP. In 1985, eventually SP was replaced by mefloquine. The rapid development of resistanceto this new drug leads to the introduction of artemisinin as a combination drug in the mid-1990s.It is mandatory to mention here that therapeutic regimens for prevention and treatment of chloroquineresistantP. falciparum are associated with higher costs and side-effects compared to chloroquine.Additionally, some of these alternative treatments are associated with more side-effects, take longertime for cure and are more difficult to comply with than chloroquine.Urgent efforts are needed to identify effective, affordable, alternative antimalarial regimens. Molecularmarkers for antimalarial resistance have been identified, including pfmdr-1 and pfcrt polymorphismsassociated with chloroquine resistance and dhfr and dhps polymorphisms associated with SP resistance.Polymorphisms in pfmdr-1 may also be associated with resistance to chloroquine, mefloquine andartemisinin. Use of such genetic information for the early detection of resistance foci and futuremonitoring of drug resistant malaria is a potentially useful epidemiological tool, in conjunction withthe conventional in vitro and in vivo drug sensitivity assessments. The purpose of this review is todescribe the state of knowledge regarding drug resistant malaria and to outline the changing patternsof drug resistance including its determinants, current status in diverse geographical areas, molecularmarkers and their implications to limit the advent, spread and intensification of drug resistant malaria.
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