The global malaria agenda has undergone a reorientation from control of clinical cases to entirely eradicating malaria. For that purpose, a key objective is blocking transmission of malaria parasites from humans to mosquito vectors. The new antimalarial drug candidate NITD609 was evaluated for its transmission-reducing potential and compared to a few established antimalarials (lumefantrine, artemether, primaquine), using a suite of in vitro assays. By the use of a microscopic readout, NITD609 was found to inhibit the early and late development of Plasmodium falciparum gametocytes in vitro in a dose-dependent fashion over a range of 5 to 500 nM. In addition, using the standard membrane feeding assay, NITD609 was also found to be a very effective drug in reducing transmission to the Anopheles stephensi mosquito vector. Collectively, our data suggest a strong transmission-reducing effect of NITD609 acting against different P. falciparum transmission stages. P lasmodium falciparum malaria is responsible for almost 800,000 deaths and 250 million clinical cases annually (35). The number of deaths associated with malaria gradually went down in several countries of sub-Saharan Africa during the previous decade, thanks to increased financial investments, implementation of long-lasting-insecticide-impregnated bed nets, and artemisinin-based combination therapy (35). As expressed by the MalEra initiative, the global malaria agenda has undergone a reorientation from control of clinical cases to malaria elimination and eventually eradication (5).For decades, antimalarial drug development has been almost entirely focused on asexual blood stages, which are directly responsible for morbidity and mortality, while mostly ignoring the nonpathogenic life cycle stages responsible for malaria transmission and subsequent spread of parasites in the population. Transmission stages emerging from asexual blood stages follow a number of transformation steps and eventually appear in the blood circulation as mature stage V male and female gametocytes (6). Once these mature gametocytes are ingested by blood-feeding Anopheles mosquitoes, the sporogonic cycle is initiated by rapid transition of male and female gametocytes into gametes, instantly followed by fertilization. The formed oocysts finally release sporozoites that migrate to the mosquito salivary glands. Infected mosquitoes inject a small number of sporozoites into the human host with every blood meal. A drug that substantially reduces or preferably entirely blocks transmission of malaria from human to mosquito would be an important tool (5).Here we describe a series of in vitro assays performed to test the effects of drugs on the early and late development of laboratoryadapted P. falciparum strain NF54 as well as in vivo oocyst development in mosquitoes. Data are shown for the new antimalarial drug candidate NITD609 as well as a few established antimalarial drugs (lumefantrine, artemether, primaquine) (24). Lumefantrine and artemether were chosen due to being the two compounds of the ...

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