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

IF 9.7 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

EBioMedicine Pub Date : 2024-12-01 Epub Date: 2024-11-29 DOI:10.1016/j.ebiom.2024.105474

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

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引用次数: 0

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).

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基于利什曼感染标记物预测埃塞俄比亚高暴露HIV人群内脏利什曼病发展：PreLeisH研究结果

背景：艾滋病毒感染者（PLWH）有针对性的预防策略需要标志物来预测内脏利什曼病（VL）。我们在埃塞俄比亚西北部流行VL的hiv队列中进行了一项纵向研究，以1)描述VL之前利什曼原虫标记物的模式；2)鉴定预测VL的利什曼原虫标志物；3)根据预测的VL风险等级，制定临床管理算法。方法：PreLeisH研究在入组时对490名无VL的成人PLWH进行了长达两年的随访（2017-2021）。每3 ~ 6个月进行血液靶向利什曼原虫kDNA的RT-PCR、利什曼原虫血清学和利什曼原虫尿抗原检测（KAtex）。我们计算了利什曼原虫标志物预测VL的敏感性/特异性，并开发了一种不同临床管理策略的算法，根据VL病史、CD4计数和利什曼原虫标志物（rK39 RDT和RT-PCR）定义了VL风险类别。研究结果：入组时，485名（99%）研究参与者正在接受抗逆转录病毒治疗；男性360/490例（73.5%）；中位基线CD4计数为392 （IQR 259 ~ 586）个细胞/μL；135例（27.5%）既往有VL。34例（6.9%）被诊断为VL，其中32例（94%）在VL前显示利什曼原虫标志物阳性。在没有VL病史的患者中，基线rK39 RDT预测VL的敏感性为60%，特异性为84%；在既往VL患者中，RT-PCR的敏感性为71%，特异性为95%。该算法定义了442例（92.3%）低VL风险个体（常规随访），31例（6.5%）中度风险个体（二级预防）和6例（1.2%）高风险个体（早期治疗）。结论：利什曼原虫感染标志物可预测PLWH患者的VL风险。需要针对高危人群的干预性研究。PreLeisH研究得到了比利时佛兰德政府经济、科学与创新部（757013）和比利时发展合作与人道主义援助总局（DGD）（BE-BCE_KBO-0410057701-prg2022-5-ET）的资助。

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来源期刊

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.