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Prediction of Visceral Leishmaniasis Development in a Highly Exposed HIV Cohort in Ethiopia Based on Leishmania Infection Markers: Results from the Preleish Study
34 Pages Posted: 5 Mar 2024
More...Abstract
Background: Targeted preventive strategies in HIV-infected individuals require markers to predict visceral leishmaniasis (VL). We conducted a longitudinal study in an 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 HIV-infected adults free of VL at enrolment for upto two years (2017-2021). Blood 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 & PCR).
Results: 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, 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).
Conclusions: Leishmania infection markers can predict VL risk in HIV-patients. Interventional studies targeting those at high risk are needed.
Funding: The PreLeish study was funded by 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).
Declaration of Interest: None to declare.
Ethical Approval: The study was approved by the institutional review board of the ITM-A and the ethics review committee of the University of Antwerp (Belgium), the University of Gondar (Ethiopia), MSF, the Amhara Regional Health Bureau (Ethiopia) and the national research ethics review committee in Ethiopia.
Keywords: visceral leishmaniasis, HIV, kala-azar, prediction, asymptomatic infection
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