Characterising the influence of parasite variation on visceral leishmaniasis

Leishmaniasis is a major neglected disease of poverty. Around 1.5 million cases occur each year in 98 countries, which results in 20,000-40,000 deaths per year. The few anti-leishmanial drugs licensed produce significant adverse effects and/or are limited by drug resistance. Currently no vaccines are licensed for human leishmaniasis. In a previous collaborative study with the Mottram group it was shown that genetic variation in the visceral leishmaniasis parasite Leishmania infantum is the main cause of drug-relapse in Brazil (1). At present we have little understanding of how evolutionary factors such as genetic variation within Leishmania parasites, hybridisation or ecological adaptation affect disease symptoms/severity and drug treatment outcomes. Dr Jeffares’ current projects include work with partners in Africa and Brazil.

Wellcome Trust Seed and MRC Newton funded research with the UK:Brazil Joint Centre Partnership in Leishmaniasis, in collaboration with Professor Costa (Federal University of Piauí) has shown that L. infantum parasite genotypes influence visceral disease outcomes and that parasite genotypes are associated with patient gender and age. Collaboration with Professor Cupolillo (Oswaldo Cruz Foundation) will characterise L. infantum genetic diversity and parasite drug tolerance throughout Brazil.

A MRC New Investigator Research Grant works in coordination with the PREV_PKDL project (that involves carrying out extensive phenotyping of patients before and after treatment in Sudan, Uganda, Ethiopia and Kenya). This research will describe the population demography of Leishmania in Africa and utilise detailed immune cell characterisation to describe how genetic variation affects host-parasite interactions. Ultimately this work will contribute to human health by establishing whether drug resistance alleles exist in East Africa and describe how different parasites result in more severe or more transmissible disease.

References

(1) J. B. T. Carnielli et al., EBioMedicine. 36, [83–91] (2018).