Treatment of visceral leishmaniasis (kala-azar): a decade of progress and future approaches

Abstract

In 1990, there was essentially one treatment regimen in use for visceral leishmaniasis (kala-azar) around the world: 20 to 28 days of daily injections of pentavalent antimony (Sb). During the past 10 years, however, new agents have been tested alone or in combination, in more than 50 studies carried out worldwide. This renewed clinical effort was spurred by a variety of factors, including the emergence of large-scale Sb unresponsiveness in India, where up to one-half of the world's cases of kala-azar now are found. As this new decade opens, the success of this clinical research effort is tangible: three additional, highly effective parenteral regimens now are available (amphotericin B, lipid formulations of amphotericin B, aminosidine), and an active oral agent, a long sought after objective in kala-azar, has been identified (miltefosine). This report reviews the evolution of treatment of visceral leishmaniasis, considers the interaction of the immune response and chemotherapy, highlights therapeutic successes and failures, examines advantages and disadvantages of current treatments, and looks at future therapeutic approaches to the management of this disseminated intracellular protozoal infection.