Biology

Dr. David Sacks
Senior Investigator and Chief of the Intracellular Parasite Biology Research Section, National Institute of Allergy and Infectious Diseases, NIH, USA

Abstract:

Leishmaniases refers to a group of neglected tropical diseases affecting individuals in equatorial and subequatorial regions around the globe. Leishmania parasites, which are spread by the bite of phlebotomine sand flies,cause different forms of disease in humans. The most common forms are cutaneous leishmaniasis, which causes skin sores, and visceral leishmaniasis, which affects multiple internal organs (usually spleen, liver, and bone marrow). Drugs against leishmaniasis are expensive, toxic, have intensive treatment regimes, and resistance is common.  There are 1–2 million new cases of leishmaniasis every year, an estimated 12 million people are infected worldwide, and 20,000–50,000 people die due to visceral leishmaniasis every year.  Leishmaniasis occurs when infected sand flies deposit the protozoan Leishmania  parasite into the skin of a mammalian host during feeding. Parasites establish infection within phagocytic cells of the immune system, the very cells typically associated with killing invading pathogens. Parasites establish chronic infection that varies depending on the strain from localized cutaneous leishmaniasis resulting in disfiguring skin sores and scarring; mucosal leishmaniasis, resulting in the destruction of the mucosa; or visceral leishmaniasis, resulting in disseminated infection of the internal organs and death in the absence of treatment.

There are no effective vaccines against any form of leishmanial disease. Leishmania have evolved numerous mechanisms of immune evasion that underlie the slow or incomplete development of naturally acquired immunity, and that compromise the development of vaccines and the efficacy of anti-parasitic drugs.  Nonetheless, even if it slow to develop, people often develop highly protective life-long immunity to reinfection following a single primary infection, indicating that protective “natural” immunity exists, thereby providing a blueprint that a vaccine need only emulate. Understanding the mechanisms of acquired resistance and immune evasion in Leishmaniasis will be required for the development of effective prophylactic or therapeutic vaccines. Similarly, understanding the molecular aspects of Leishmania survival and development in the sand fly vector will be essential to the development of transmission blocking vaccines.