Visceral leishmaniasis: Immunopathology

Visceral leishmaniasis (kala-azar) is caused by the protozoan parasites Leishmania donovani and Leishmania infantum. There are an estimated 50,000-90,000 new cases occurring annually worldwide. If left untreated it proves fatal with an estimated 20,000-30,000 deaths annually.

In experimental models of visceral leishmaniasis, parasites can be found in multiple systemic organs, but immune control of parasite burden is tissue-specific. In the liver, granulomatous inflammation provides the means for parasite containment and eventual elimination. In contrast, the spleen undergoes tremendous enlargement, accompanied by extensive remodelling of tissue architecture and parasite persistence.

These diverse settings provide unique opportunities to examine how microenvironment affects myeloid cell differentiation and function and how this changes over the natural history of infection. Ongoing projects span fundamental research into myeloid cell biology, and studies on how immunopathology affects transmission to sand flies and contributes to parasite dissemination.  

Clinical research includes studies of  immunopathology across the L. donovani disease spectrum (including cutaneous leishmaniasis and post kala azar dermal leishmaniasis), clinical trials of a new vaccine for VL/PKDL and the development of a human infection model of cutaneous leishmaniasis. His research group has active collaborations in Brazil, India, Sri Lanka and across East Africa.

Many research methods adopted by the group place emphasis on the spatial context in which immune cells and parasites interact, and the group is at the leading edge in applying techniques for spatially-resolved transcriptomics, proteomics and metabolomics, the latter in collaboration with Maastricht University.