Prediction of visceral leishmaniasis development in a highly exposed HIV cohort in Ethiopia based on Leishmania infection markers: results from the PreLeisH study

J van Griensven, S van Henten, A Kibret, M Kassa, H Beyene, S Abdellati, D Mersha, K Sisay, H Seyum, H Eshetie, F Kassa, T Bogale, R Melkamu, A Yeshanew, B Smekens, C Burm, H Landuyt, A de Hondt, D van den Bossche, R MohammedM Pareyn, F Vogt, W Adriaensen, K Ritmeijer, E Diro

Research output: Contribution to journalA1: Web of Science-articlepeer-review

Abstract

Background
Targeted preventive strategies in persons living with HIV (PLWH) require markers to predict visceral leishmaniasis (VL). We conducted a longitudinal study in a HIV-cohort in VL-endemic North-West Ethiopia to 1) describe the pattern of Leishmania markers preceding VL; 2) identify Leishmania markers predictive of VL; 3) develop a clinical management algorithm according to predicted VL risk levels.

Methods
The PreLeisH study followed 490 adult PLWH free of VL at enrolment for up to two years (2017–2021). Blood RT-PCR targeting Leishmania kDNA, Leishmania serology and Leishmania urine antigen test (KAtex) were performed every 3–6 months. We calculated the sensitivity/specificity of the Leishmania markers for predicting VL and developed an algorithm for distinct clinical management strategies, with VL risk categories defined based on VL history, CD4 count and Leishmania markers (rK39 RDT & RT-PCR).

Findings
At enrolment, 485 (99%) study participants were on antiretroviral treatment; 360/490 (73.5%) were male; the median baseline CD4 count was 392 (IQR 259–586) cells/μL; 135 (27.5%) had previous VL. Incident VL was diagnosed in 34 (6.9%), with 32 (94%) displaying positive Leishmania markers before VL. In those without VL history, baseline rK39 RDT had 60% sensitivity and 84% specificity to predict VL; in patients with previous VL, RT-PCR had 71% sensitivity and 95% specificity. The algorithm defined 442 (92.3%) individuals at low VL risk (routine follow-up), 31 (6.5%) as moderate risk (secondary prophylaxis) and six (1.2%) as high risk (early treatment).

Interpretation
Leishmania infection markers can predict VL risk in PLWH. Interventional studies targeting those at high risk are needed.

Funding
The PreLeisH study was supported by grants from the Department of Economy, Science and Innovation of the Flemish Government, Belgium (757013) and the Directorate-General for Development Cooperation and Humanitarian Aid (DGD), Belgium (BE-BCE_KBO-0410057701-prg2022-5-ET).
Original languageEnglish
Article number105474
JournalEBioMedicine
Volume110
Number of pages16
ISSN2352-3964
DOIs
Publication statusPublished - 2024

Keywords

  • Asymptomatic infection
  • HIV
  • Kala-azar
  • Prediction
  • Visceral leishmaniasis

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