Genistein-supplemented diet decreases malaria liver infection in mice and constitutes a potential prophylactic strategy.

In tropical regions millions of people still live at risk of malaria infection. Indeed the emergence of resistance to chloroquine and other drugs in use in these areas reinforces the need to implement alternative prophylactic strategies. Genistein is a naturally occurring compound that is widely used as a food supplement and is thought to be effective in countering several pathologies. Results presented here show that genistein inhibits liver infection by the Plasmodium parasite, the causative agent of malaria. In vitro, genistein decreased the infection rates of both mouse and human hepatoma cells by inhibiting the early stages of the parasite's intracellular development. Oral or intraperitoneal administration of genistein decreased the liver parasite load of P. berghei-infected mice. Moreover, mice fed on a genistein-supplemented diet showed a significant reduction in Plasmodium liver infection as well as a reduced blood parasitemia and partial protection from severe disease. Since genistein is a safe, low-cost, natural compound that can be used permanently in a diet, we propose its use as a prophylactic agent against malaria for endemic populations and long-time travelers.

Antimalarial drugs - host targets (re)visited.

Every year, forty percent of the world population is at risk of contracting malaria. Hopes for the erradication of this disease during the 20th century were dashed by the ability of Plasmodium falciparum, its most deadly causative agent, to develop resistance to available drugs. Efforts to produce an effective vaccine have so far been unsuccessful, enhancing the need to develop novel antimalarial drugs. In this review, we summarize our knowledge concerning existing antimalarials, mechanisms of drug-resistance development, the use of drug combination strategies and the quest for novel anti-plasmodial compounds. We emphasize the potential role of host genes and molecules as novel targets for newly developed drugs. Recent results from our laboratory have shown Hepatocyte Growth Factor/MET signaling to be essential for the establishment of infection in hepatocytes. We discuss the potential use of this pathway in the prophylaxis of malaria infection.