Diversity and within-host evolution of Leishmania donovani from visceral leishmaniasis patients with and without HIV coinfection in northern Ethiopia

Franssen, S. U., Takele, Y., Adem, E., Sanders, M. J., Müller, I., Kropf, P., Cotton, J. A. and Weiss, L. M. (2021) Diversity and within-host evolution of Leishmania donovani from visceral leishmaniasis patients with and without HIV coinfection in northern Ethiopia. mBio, 12(3), e00971-21. (doi: 10.1128/mBio.00971-21) (PMID:34182785) (PMCID:PMC8262925)

Abstract

Visceral leishmaniasis (VL) is a fatal disease and a growing public health problem in East Africa, where Ethiopia has one of the highest VL burdens. The largest focus of VL in Ethiopia is driven by high prevalence in migrant agricultural workers and associated with a high rate of coinfection with HIV. This coinfection makes VL more difficult to treat successfully and is associated with a high rate of relapse, with VL/HIV patients frequently experiencing many relapses of VL before succumbing to this infection. We present genome-wide data on Leishmania donovani isolates from a longitudinal study of cohorts of VL and VL/HIV patients reporting to a single clinic in Ethiopia. Extensive clinical data allow us to investigate the influence of coinfection and relapse on the populations of parasites infecting these patients. We find that the same parasite population is responsible for both VL and VL/HIV infections and that, in most cases, disease relapse is caused by recrudescence of the population of parasites that caused primary VL. Complex, multiclonal infections are present in both primary and relapse cases, but the infrapopulation of parasites within a patient loses genetic diversity between primary disease presentation and subsequent relapses, presumably due to a population bottleneck induced by treatment. These data suggest that VL/HIV relapses are not caused by genetically distinct parasite infections or by reinfection. Treatment of VL does not lead to sterile cure, and in VL/HIV, the infecting parasites are able to reestablish after clinically successful treatment, leading to repeated relapse of VL.

• Item Type: Articles
• Additional Information: This work was supported by Wellcome via a Training Fellowship in Public Health and Tropical Medicine to Y.T. (grant 204797/Z/16/Z) and core support for the Wellcome Sanger Institute (WT206194) and jointly by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement via grants MR/R01020X/1 and MR/R021600/1.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cotton, Professor James
• Authors: Franssen, S. U., Takele, Y., Adem, E., Sanders, M. J., Müller, I., Kropf, P., Cotton, J. A., and Weiss, L. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: mBio
• Publisher: American Society for Microbiology
• ISSN: 2161-2129
• ISSN (Online): 2150-7511
• Copyright Holders: Copyright © 2021 Franssen et al.
• First Published: First published in mBio 12(3): e00971-21
• Publisher Policy: Reproduced under a Creative Commons License