India Needs to Consider Planning a Change to Artemether–Lumefantrine to Treat Plasmodium falciparum Malaria

Abstract

ABSTRACT. As the malaria elimination target draws closer for India, it must be ensured that the country’s policies, strategies, and tools remain effective. Artemisinin-based combination therapies are the mainstay of Plasmodium falciparum malaria management. India has a differential standard therapy for uncomplicated falciparum malaria in the form of artemether–lumefantrine in its northeastern states and artesunate + sulfadoxine–pyrimethamine in the rest of the country. The clinical failure of artesunate + sulfadoxine–pyrimethamine in the northeast regions was attributed primarily to parasite resistance resulting from mutations in the enzymes dihydropteroate synthase and dihydrofolate reductase. Artemether–lumefantrine was therefore substituted for artesunate + sulfadoxine–pyrimethamine in the region. The change has been a success, as evidenced by the therapeutic efficacy studies conducted at regular intervals in India. However, studies suggest that resistance may be emerging toward sulfadoxine–pyrimethamine in multiple parts of the nation. Hence, there is a possibility that the artesunate + sulfadoxine–pyrimethamine combination may be acting in part as a monotherapy, and this makes the longevity of the artesunate + sulfadoxine–pyrimethamine drug combination therapy uncertain. The increasing presence of drug-resistant mutants in P. falciparum dhps and dhfr genes suggests the need for a policy switch for uncomplicated P. falciparum malaria from artesunate + sulfadoxine–pyrimethamine to artemether–lumefantrine.