Leishmania is an obligate intracellular protozoan parasite of mammals and has a number of clinical manifestations, from local cutaneous lesions to life-threatening visceral disease. Leishmaniasis is spread by the bite of infected sand flies and is an important health problem in many developing countries in the tropics and subtropics, with some 2 million new cases each year. The sand flies inject the infective stage—the flagellated promastigote—during blood meals. Promastigotes are phagocytized by macrophages and transform into amastigotes, which multiply in infected cells and affect different tissues. An important feature of leishmaniasis and other infectious diseases is the ability of the pathogens to establish long-term persistence and eventually to reactivate, leading to severe forms of the disease. In the August 29 Science, Gerald Späth and colleagues at the Washington University School of Medicine show that mutant Leishmania parasites can persist without leading to acute disease (Science, 301:1241-1243, August...

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