Artesunate Reduces but Does Not Prevent Posttreatment Transmission ofPlasmodium falciparumtoAnopheles gambiae

Abstract

Combination therapy that includes artemisinin derivatives cures most falciparum malaria infections. Lowering transmission by reducing gametocyte infectivity would be an additional benefit. To examine the effect of such therapy on transmission, Gambian children with Plasmodium falciparum malaria were treated with standard regimens of chloroquine or pyrimethamine-sulfadoxine alone or in combination with 1 or 3 doses of artesunate. The infectivity to mosquitoes of gametocytes in peripheral blood was determined 4 or 7 days after treatment. Infection of mosquitoes was observed in all treatment groups and was positively associated with gametocyte density. The probability of transmission was lowest in those who received pyrimethamine-sulfadoxine and 3 doses of artesunate, and it was 8-fold higher in the group that received pyrimethamine-sulfadoxine alone. Artesunate reduced posttreatment infectivity dramatically but did not abolish it completely. The study raises questions about any policy to use pyrimethamine-sulfadoxine alone as the first-line treatment for malaria.

Quantitative assessment of Plasmodium falciparum sexual development reveals potent transmission-blocking activity by methylene blue

“…Nevertheless, the block in transmission, measured by the percentage of infected mosquitoes, was minimal. This finding is consistent with fieldbased studies that document a rather modest effect of artemisinins on transmission of mature gametocytes (8,9). A recent finding that artemisinins inhibit hemoglobin uptake and its subsequent hydrolysis may explain the marked activity of DHA against immature gametocytes (44).…”

“…These drugs include chloroquine and quinine, which interfere with heme detoxification, and atovaquone, which targets mitochondrial electron transport (6,7). Artemisinins have also been observed to inhibit immature sexual stages and reduce gametocyte carriage in infected human hosts (8,9). The experimental design of many of the studies, however, has often made it difficult to distinguish between direct gametocytocidal activity and the antiasexual properties that reduce the pool of parasites available to initiate gametocytogenesis.…”

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.…”

Gametocitemia en malaria por Plasmodium falciparum tratada con amodiaquina o artesunato

“…La conversión de célula asexual a gametocito es afectada por factores del ambiente parasitario (11,12) y, entre ellos, están los medicamentos antipalúdicos, algunos de los cuales quizás la aumentan (cloroquina, sulfadoxina-pirimetamina) y otros la reducen (derivados de la artemisinina) (13)(14)(15)(16)(17).…”