Combination Therapy for Malaria

Abstract

Unless new strategies are deployed to combat malaria, the already enormous health and economic burden related to the disease in tropical countries is bound to worsen. The main obstacle to malaria control is the emergence of drug resistant strains of Plasmodium falciparum. As for HIV/AIDS and tuberculosis, the use of combinations of antimalarial drugs reduces the risk of selecting for resistant mutants of the plasmodial parasites. In large field trials, the combination of an artemisinin derivative and a partner drug with an unrelated mode of action (in this case mefloquine), has shown a remarkable double effect: preventing the emergence and spread of drug resistance, and interrupting the transmission of P. falciparum. This has opened the way for a new approach to the deployment of antimalarial drugs. Coupled with early detection and confirmed diagnosis, this strategy represents the only way forward in the chemotherapy of malaria. Massive economic assistance will be needed to detect and treat adequately the estimated 500 million cases of malaria per year, but without radical action there is no prospect of 'Rolling Back' malaria.

Malaria: current status of control, diagnosis, treatment, and a proposed agenda for research and development

“…The sequential introduction of drugs as monotherapy has led to sequential selection and spread of mutant drug-resistant malaria parasites and ultimately to multidrug resistance. 82,83 Artemisinin-based combinations, which provide mutual protection against resistance, high efficacy, excellent tolerability, and reduced transmissibility, are judged the most effective strategy to provide highly effective treatment that will not fall to resistance. 84,85 The artemisinin-based combinations also reduce the transmissibility of malaria by preventing gametocyte development.…”

Efficacy of chloroquine and sulfadoxine/pyrimethamine for the treatment of uncomplicated falciparum malaria in Koumantou, Mali

“…This approach, already in use for tuberculosis and AIDS, is essential not only to improve efficacy but also to protect remaining viable antimalarials against further spread of resistant strains (Nosten and Brasseur, 2002). Currently, the WHO recommends that combinations including an artemisinin derivative be prioritised for deployment (WHO, 2002).…”

Efficacy of chloroquine, sulfadoxine–pyrimethamine and amodiaquine for treatment of uncomplicated Plasmodium falciparum malaria among children under five in Bongor and Koumra, Chad

“…In recent years, a new strategy to hold parasite resistance in check has been the use of appropriate combination therapies, which reduces the probability of selection of resistant parasite strains by a mechanism of mutual protection (Nosten and Brasseur, 2002;White and Olliaro, 1996). In this perspective, WHO currently recommends that African countries prioritize artemisinin-based combinations (WHO, 2001).…”

“…The use of artemisinin-based combination therapies (ACTs) is currently seen as the best option for the treatment of malaria (Nosten and Brasseur, 2002;White and Olliaro, 1996;White et al, 1999) because of their high efficacy and their potential to reduce the risk for resistance. WHO recommends that countries experiencing resistance to monotherapies shift to combination therapies, preferably to those containing an artemisinin derivative (WHO, 2001).…”