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

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.