About the disease

Introduction

The leishmaniases are a group of diseases caused by species of Leishmania with a diversity of epidemiological characteristics. Clinical manifestations range from simple self-healing cutaneous leishmaniasis to visceral leishmaniasis, which is fatal if untreated.

Leishmania parasites are transmitted by female phlebotomine sandflies, which inoculate the promastigote form (insect stage, flagellated) of the parasite into the skin of mammalian hosts during a blood meal. Parasites are taken up by dendritic cells and macrophages and transform into amastigotes (mammalian stage, non-flagellated), which reside and multiply in phagolysosomes of macrophages as the main host cell for Leishmania.

In general, following recovery from the disease, there is immunity to the disease and a strong T cell response can be demonstrated in immune individuals. Immunity is generally believed to be associated with a Th1-type immune response although this may not be to the exclusion of all Th-2 responses.

Visceral leishmaniasis (VL)

Infection is disseminated through lymphatic and vascular systems with bone marrow, liver, spleen and sometimes lymphnodes affected. Symptoms and signs of infection include fever associated with rigor and chills, fatigue, weight loss, enlarged liver, spleen and lymphnodes. Estimated numbers for new cases and deaths per year are 500 000 and 50 000 respectively. The major burden (>90%) is carried by only 6 countries (Bangladesh, India, Nepal, Sudan, Ethiopia and Brazil) and a strong association with poverty is recognised. Anti-leishmanial (systemic) drugs available for treatment of VL (pentavalent antimony, amphotericin B / AmBisome, miltefosine) have limitations with regard to drug toxicity, teratogenicity, resistance and availability and affordability in endemic areas.

Top left: Human blood derived macrophage experimentally infected with Leishmania donovani (Giemsa stain) in in vitro culture. Intracellular amastigotes are clearly visible with their nucleus and kinetoplast. 

Bottom left: Child with visceral leishmaniasis, swelling of the abdomen is seen associated with hepato- and splenomegaly.

Picture provided by Simon Croft.

Cutaneous leishmaniasis (CL)

Clinical manifestations in CL range from ulcerative skin lesions at the site of the sandfly bite (localized CL) to multiple non-ulcerative nodules (diffuse CL) and destructive mucosal inflammation (mucosal leishmaniasis). CL is endemic in 70 countries with the majority of cases in Afghanistan, Algeria, Brazil, Colombia, Peru and Syria. CL is treated to accelerate cure, reduce scarring and prevent parasite dissemination or relapse. However standard treatment still uses systemic anti-leishmanial drugs (e.g. pentavalent antimony) with invasive and lengthy treatment regimes resulting in poor patient compliance and incomplete treatment courses.

Pictures on the left demonstrate the diverse clinical manifestations of CL.  

References: Chappuis et al. (2007) Nature Reviews Microbiology 5, 873-882; Alvar et al. (2006) Advances in Parasitology 61, 223-274; Reithinger et al. (2007) Lancet Infectious Diseases 7, 581-596