Treatment of falciparum malaria in the age of drug resistance

Abstract

The growing problem of drug resistance has greatly complicated the treatment for falciparum malaria. Whereas chloroquine and sulfadoxine/pyrimethamine could once cure most infections, this is no longer true and requires examination of alternative regimens. Not all treatment failures are drug resistant and other issues such as expired antimalarials and patient compliance need to be considered. Continuation of a failing treatment policy after drug resistance is established suppresses infections rather than curing them, leading to increased transmission of malaria, promotion of epidemics and loss of public confidence in malaria control programs. Antifolate drug resistance (i.e. pyrimethamine) means that new combinations are urgently needed particularly because addition of a single drug to an already failing regimen is rarely effective for very long. Atovaquone/proguanil and mefloquine have been used against multiple drug resistant falciparum malaria with resistance to each having been documented soon after drug introduction. Drug combinations delay further transmission of resistant parasites by increasing cure rates and inhibiting formation of gametocytes. Most currently recommended drug combinations for falciparum malaria are variants of artemisinin combination therapy where a rapidly acting artemisinin compound is combined with a longer half-life drug of a different class. Artemisinins used include dihydroartemisinin, artesunate, artemether and companion drugs include mefloquine, amodiaquine,sulfadoxine/pyrimethamine, lumefantrine, piperaquine, pyronaridine, chlorproguanil/dapsone. The standard of care must be to cure malaria by killing the last parasite. Combination antimalarial treatment is vital not only to the successful treatment of individual patients but also for public health control of malaria.