Carlier Yves, Dumonteil Eric, Herrera Claudia, Waleckx Etienne, Tibayrenc Michel, Buekens Pierre, Truyens Carine, Muraille Eric
Laboratoire de Parasitologie, Faculté de Médecine, Université Libre de Bruxelles (ULB), Brussels, Belgium.
European Plotkin Institute for Vaccinology, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Microbiol Mol Biol Rev. 2025 Jun 25;89(2):e0024224. doi: 10.1128/mmbr.00242-24. Epub 2025 Mar 21.
SUMMARYChagas disease (CD) is caused by the protozoan parasite (Tc), infecting 6-7 million people. It is transmitted by insect vectors, orally, through infected tissues, or congenitally. Tc infection can progress toward chronic cardiac and/or digestive severe and fatal CD in 20%-40% of patients. Tc exhibits an important genetic and phenotypic intraspecies diversity and a preponderant clonal population structure. The impact of multiclonal coinfections has been little studied in CD patients. Relationships between the currently used discrete typing unit (DTU)-based classification of Tc lineages and the occurrence of the different clinical forms of CD, its congenital transmission, as well as the efficacy of trypanocidal molecules (benznidazole and nifurtimox) could not be established. In this review, we revisit the different aspects of Tc diversity and analyze the impact of infections with multiple clones and their variants on the dynamic and pathogenesis of CD and its maternal-fetal transmission. We propose to call "cruziome" all the Tc clones and their variants infecting a given host and provide strong evidence that (i) multiclonal Tc infections are likely the rule rather than the exception; (ii) each "cruziome" is associated with a unique combination of virulence factors, tissular tropisms, and host immune responses; (iii) accordingly, some particularly harmful "cruziomes" likely trigger the occurrence and progression of CD and might also favor the congenital transmission of parasites. We propose that our concept of "cruziome" should be taken into consideration because of its practical consequences in epidemiological studies, laboratory diagnosis, clinical management, and treatment of CD.
摘要
恰加斯病（CD）由原生动物寄生虫克氏锥虫（Tc）引起，感染人数达600 - 700万。它通过昆虫媒介、经口、通过感染组织或先天性方式传播。在20% - 40%的患者中，Tc感染可发展为慢性心脏和/或消化系统严重且致命的CD。Tc表现出重要的种内遗传和表型多样性以及优势克隆群体结构。多克隆共感染对CD患者的影响研究较少。目前基于离散分型单元（DTU）的Tc谱系分类与CD不同临床形式的发生、其先天性传播以及杀锥虫分子（苯并硝唑和硝呋替莫）的疗效之间的关系尚未确立。在本综述中，我们重新审视了Tc多样性的不同方面，并分析了多个克隆及其变体感染对CD动态和发病机制及其母婴传播的影响。我们建议将感染给定宿主的所有Tc克隆及其变体称为“克氏锥虫组”，并提供有力证据表明：（i）多克隆Tc感染可能是规律而非例外；（ii）每个“克氏锥虫组”都与毒力因子、组织嗜性和宿主免疫反应的独特组合相关；（iii）因此，一些特别有害的“克氏锥虫组”可能引发CD的发生和进展，也可能有利于寄生虫的先天性传播。我们建议应考虑我们的“克氏锥虫组”概念，因为它在CD的流行病学研究、实验室诊断、临床管理和治疗中具有实际意义。
