Clinical Immunology Unit, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
Adrem Data Lab, Department of Computer Science, University of Antwerp, Antwerp, Belgium.
PLoS Negl Trop Dis. 2024 Sep 30;18(9):e0012000. doi: 10.1371/journal.pntd.0012000. eCollection 2024 Sep.
Human immunodeficiency virus (HIV) co-infection is a major challenge for visceral leishmaniasis (VL) control, particularly in Ethiopia where the incidence of both pathogens is high. VL-HIV often leads to high rates of antileishmanial treatment failure and recurrent VL disease relapses. Considering the high prevalence of HIV and Leishmania in the Ethiopian population, preventing the progression of asymptomatic Leishmania infection to disease would be a valuable asset to VL disease control and to the clinical management of people living with HIV (PLWH). However, such a strategy requires good understanding of risk factors for VL development. In immunocompetent individuals living in Brazil, India, or Iran, the Human Leukocyte Antigen (HLA) gene region has been associated with VL development. We used NanoTYPE, an Oxford Nanopore Technologies sequencing-based HLA genotyping method, to detect associations between HLA genotype and VL development by comparing 78 PLWH with VL history and 46 PLWH that controlled a Leishmania infection, all living in a VL endemic region of North-West Ethiopia. We identified an association between HLA-A*03:01 and increased risk of VL development (OR = 3.89). These data provide candidate HLA alleles that can be further explored for inclusion in a potential Leishmania screen-and-treat strategy in VL endemic regions.
人类免疫缺陷病毒(HIV)合并感染是内脏利什曼病(VL)控制的主要挑战,特别是在 HIV 和利什曼原虫发病率都很高的埃塞俄比亚。VL-HIV 常导致抗利什曼病治疗失败率和复发性 VL 疾病发作率居高不下。考虑到 HIV 和利什曼原虫在埃塞俄比亚人群中的高流行率,预防无症状利什曼原虫感染向疾病的进展将是 VL 疾病控制和 HIV 感染者(PLWH)临床管理的宝贵资产。然而,这种策略需要很好地了解 VL 发展的风险因素。在巴西、印度或伊朗的免疫功能正常的个体中,人类白细胞抗原(HLA)基因区域与 VL 的发展有关。我们使用基于 Oxford Nanopore Technologies 测序的 NanoTYPE HLA 基因分型方法,通过比较居住在埃塞俄比亚西北部 VL 流行地区的 78 名有 VL 病史的 PLWH 和 46 名控制利什曼原虫感染的 PLWH,来检测 HLA 基因型与 VL 发展之间的关联。我们发现 HLA-A*03:01 与 VL 发展的风险增加之间存在关联(OR=3.89)。这些数据提供了候选 HLA 等位基因,可以进一步探索将其纳入 VL 流行地区潜在的利什曼筛查和治疗策略。