Pyrimethamine–sulfadoxine resistance in Plasmodium falciparum must be delayed in Africa

Abstract

The letter from Rieckmann and Cheng highlights important issues, with which we agree. Many African countries have committed to artemisinin combination therapy for falciparum malaria in the hope that this strategy will slow the selection of resistant parasites without any important increase in drug toxicity. However, all of these countries lack the available resources to effect the change from monotherapy. There are new initiatives such as the Global Fund for AIDS, TB and Malaria that might provide the increased funds required for artemisinin combinations, but unless this initiative is successful, alternative strategies will be needed to use the current affordable and available drugs to their optimum. Rieckmann and Cheng point out that a change from chloroquine to pyrimethamine–sulfadoxine monotherapy ignores the advantages to be gained from a combination of a 4-aminoquinoline with an antifolate. Where this route has been taken in East Africa, pyrimethamine–sulfadoxine monotherapy has risked a short useful therapeutic life. Despite the problems of implementation, some countries have opted already to use either chloroquine plus pyrimethamine–sulfadoxine (Uganda) or amodiaquine plus pyrimethamine–sulfadoxine (Rwanda) for first-line treatment, using precisely the rationale given by Rieckmann and Cheng. Chloroquine is still effective against vivax malaria, and Ethiopia and Papua New Guinea are now using chloroquine plus pyrimethamine–sulfadoxine with the expectation that patients will be effectively treated even if definitive diagnosis for falciparum or vivax cannot be made. These antifolate plus 4-aminoquinoline combinations have been chosen as interim measures, with the hope that they will have an extended therapeutic life that will enable long-term solutions such as artemisinin combinations to be identified and implemented. These countries recognize that combinations such as amodiaquine–artesunate, lumefantrine–artemether or chlorproguanil–dapsone–artesunate probably represent the best solution to drug-resistant falciparum malaria, in the long term. However, use of these treatments awaits the fulfilment of two essential prerequisites: in-country clinical experience, including studies of effectiveness, safety and tolerability; and sustainable funding.