Prediction of visceral leishmaniasis development in a highly exposed HIV cohort in Ethiopia based on Leishmania infection markers: results from the PreLeisH studyResearch in context
Johan van Griensven,
Saskia van Henten,
Aderajew Kibret,
Mekibib Kassa,
Hailemariam Beyene,
Saïd Abdellati,
Dagnew Mersha,
Kasaye Sisay,
Hailemicheal Seyum,
Hamid Eshetie,
Fikadu Kassa,
Tadfe Bogale,
Roma Melkamu,
Arega Yeshanew,
Bart Smekens,
Christophe Burm,
Hanne Landuyt,
Annelies de Hondt,
Dorien Van den Bossche,
Rezika Mohammed,
Myrthe Pareyn,
Florian Vogt,
Wim Adriaensen,
Koert Ritmeijer,
Ermias Diro
Affiliations
Johan van Griensven
Institute of Tropical Medicine, Antwerp, Belgium; Corresponding author.
Saskia van Henten
Institute of Tropical Medicine, Antwerp, Belgium
Aderajew Kibret
Medecins Sans Frontières, Abdurafi, Ethiopia
Mekibib Kassa
Leishmaniasis Research and Treatment Centre, University of Gondar, Gondar, Ethiopia
Hailemariam Beyene
Medecins Sans Frontières, Abdurafi, Ethiopia
Saïd Abdellati
Institute of Tropical Medicine, Antwerp, Belgium
Dagnew Mersha
Medecins Sans Frontières, Abdurafi, Ethiopia
Kasaye Sisay
Medecins Sans Frontières, Abdurafi, Ethiopia
Hailemicheal Seyum
Medecins Sans Frontières, Abdurafi, Ethiopia
Hamid Eshetie
Medecins Sans Frontières, Abdurafi, Ethiopia
Fikadu Kassa
Medecins Sans Frontières, Abdurafi, Ethiopia
Tadfe Bogale
Leishmaniasis Research and Treatment Centre, University of Gondar, Gondar, Ethiopia
Roma Melkamu
Leishmaniasis Research and Treatment Centre, University of Gondar, Gondar, Ethiopia
Arega Yeshanew
Leishmaniasis Research and Treatment Centre, University of Gondar, Gondar, Ethiopia
Bart Smekens
Institute of Tropical Medicine, Antwerp, Belgium
Christophe Burm
Institute of Tropical Medicine, Antwerp, Belgium
Hanne Landuyt
Institute of Tropical Medicine, Antwerp, Belgium
Annelies de Hondt
Institute of Tropical Medicine, Antwerp, Belgium
Dorien Van den Bossche
Institute of Tropical Medicine, Antwerp, Belgium
Rezika Mohammed
Leishmaniasis Research and Treatment Centre, University of Gondar, Gondar, Ethiopia; University of Gondar, Gondar, Ethiopia
Myrthe Pareyn
Institute of Tropical Medicine, Antwerp, Belgium
Florian Vogt
Institute of Tropical Medicine, Antwerp, Belgium; The Kirby Institute, University of New South Wales, Sydney, Australia; National Centre for Epidemiology and Population Health, Australian National University, Canberra, Australia
Wim Adriaensen
Institute of Tropical Medicine, Antwerp, Belgium
Koert Ritmeijer
Médecins Sans Frontières, Amsterdam, the Netherlands
Ermias Diro
University of Gondar, Gondar, Ethiopia; Department of General Internal Medicine, University of Washington, Seattle, USA
Summary: 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).
