Leishmaniasis, also known as kala-azar, Dumdum fever, Oriental sore, Baghdad boil, etc, are a  spectrum of diseases caused by protozoan parasites belonging to the genus Leishmania.  The  disease is endemic in 88 countries and affects 1 to 2 million people worldwide each year with an  estimated 12 million more at risk.  There are three major forms of the disease: • cutaneous leishmaniasis, • visceral leishmaniasis,   • mucocutaneous leishmaniasis.       Cutaneous leishmaniasis causes skin lesions that are usually self-healing but can cause  extensive scarring. However, treatment is usually given to accelerate cure, reduce scarring especially  at cosmetic sites, and to attempt to prevent dissemination (e.g., mucosal disease) or relapse. Self-  cure of cutaneous leishmaniasis usually results in life-long protection from the disease.    Visceral leishmaniasis is the most severe form of the disease and affects visceral organ systems  including the spleen, liver and bone marrow. The signs and symptoms of visceral leishmaniasis are  non-specific but include fever, weight loss, mucosal ulcers, fatigue, anemia and highly visible  enlargement of the spleen and liver termed splenomegaly and hepatomegaly, respectively. If left  untreated, visceral leishmaniasis (unlike the cutaneous disease) will almost always result in the death  of the host. Of particular concern, according to the WHO is the emerging problem of HIV/VL co-  infection, particularly in the Indian subcontinent.    Mucocutaneous leishmaniasis also known as espundia, affects the mucus membranes and  leads to severe destruction of underlying tissue of the skin, mouth and nose. Because parasites are  usually rare in the lesions, tissue destruction is possibly related to uncontrolled immunological  mechanisms. At present 90% of all mucocutaneous leishmaniasis occurs in Bolivia, Peru and Brazil.      The main species of Leishmania we work with in our lab are Leishmania major and Leishmania  donovani (which causes cutaneous and visceral leishmaniasis, respectively). Both parasites are  transmitted by the bite of a female Sandfly, similar to transmission of malaria parasites by the  mosquito.  When an infected Sandfly takes a blood meal from an uninfected person, the elongate  flagellated parasites (termed promastigotes) are injected into the host, enter the bloodstream and  primarily invade macrophages and dendritic cells.  Within these cells, the parasites quickly transform  into the mammalian stage (termed amastigotes). They replicate inside these cells until the cells are  lysed and free parasites are released and ready to invade new cells.  The next time the host is bitten  by a Sandfly, the parasites are ingested and differentiate back into the more infective promastigote  form. You can view a life cycle diagram for leishmaniasis and find more information here  http://www.who.int/leishmaniasis/en/ and http://www.who.int/tdr/diseases/leish/lifecycle.htm.     There is no vaccine for leishmaniasis and current medications are toxic and/or have serious side  effects. Interestingly, recovery from natural or experimental infections with L. major results in long-  lasting immunity against reinfection. This so called infection-induced resistance is the strongest anti-  Leishmania immunity known. We believe that understanding the factors that regulate the induction,  maintenance and loss of infection-induced resistance is critical for rational vaccine designs and  vaccination strategies against leishmaniasis. We hypothesize that parasite dose, virulence  (determined by the rate of replication in macrophages after infection) and initial rate of T cell  expansion are key determinants that regulate the magnitude and quality of memory T cell responses  during infection or vaccination. In general, some questions the lab is currently addressing include: • Are persistent parasites required to maintain anti-Leishmania immunity? • Are there differences (in function, phenotype and migratory properties) of CD4+ memory cell  subsets (central and effector, Tcm and Tem, respectively) following infection with low and high  dose L. major? • How long do memory cells persist in the absence of live parasites?   • Can non-replicating parasites maintain memory (both Tcm and Tem) cells induced by  vaccination with non-replicating avirulent live parasites? • What is the nature of memory T cell subsets induced following vaccination with heat killed  parasites? • How do Tcm and Tem cells mediate secondary anti-Leishmania immunity? • What is/are the immunodominant antigens that maintain the memory T cell pool following  recovery from primary infection? © copyright 2011 Leishmania Promastigotes Leishmania Amastigotes in Macrophages Leishmania Amastigotes in Bone Marrow Dendritic Cells