突尼斯人畜共患皮肤利什曼病前瞻性队列研究：临床和免疫学特征及免疫保护相关性

IF 3.8 2区医学 Q1 Medicine

PLoS Neglected Tropical Diseases Pub Date : 2023-12-08 DOI:10.1371/journal.pntd.0011784

Ikbel Naouar, Wafa Kammoun Rebai, A. Ben Salah, H. Bouguerra, A. Toumi, Nabil Belhadj Hamida, H. Louzir, A. Meddeb-Garnaoui

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引用次数: 0

摘要

本研究旨在确定暴露于L. major寄生虫的免疫学标记物，并确定其抗感染保护的相关因素。我们分析了生活在不同L. major感染流行率的流行地区的790名有患ZCL风险的个体。一个地区感染流行率高，利什曼素皮肤试验(LST)阳性受试者比例高，而其他地区是最近的疫源地，感染流行率较低。在传播季节前采集血样，测量外周血单个核细胞对寄生虫刺激的干扰素γ (IFN-γ)、白细胞介素10 (IL-10)和颗粒酶B (GrB)水平。为期一年的随访期间包括积极检测新的ZCL病例，以估计传播季节后的疾病发病率，并确定免疫保护的相关因素。从特定疤痕和/或LST阳性结果可以看出，研究人群在寄生虫接触方面表现出异质性，与最近的疫源地相比，旧疫源地的寄生虫接触明显更高。IFN-γ和GrB是寄生虫暴露的标志，也是对L. major免疫的可靠指标。IFN-γ/IL-10和GrB/IL-10比值与LST结果呈正相关。出乎意料的是，在一个传播季节后仅出现29例新的ZCL病例(4%)，其中最近疫源地报告了27例，最老疫源地报告了2例。我们的研究结果表明，无论LST状态如何，L.主要流行地区的个体都可能发生ZCL。我们发现，传播前季节由PBMC产生的高水平IFN-γ和GrB，以及高的IFN-γ/IL-10比值与保护有关。这项对ZCL风险大队列的研究证实IFN-γ和GrB是预防ZCL的保护因子。高IFN-γ/IL-10比值与耐药相关，而高GrB/IL-10比值与耐药无关。这些结果对研制和评价人类利什曼病疫苗有价值。

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A Prospective cohort study of zoonotic cutaneous leishmaniasis in tunisia: Clinical and Immunological features and immune correlates of protection

This study aimed to define immunological markers of exposure to L. major parasites and identify correlates of protection against infection. We analyzed a cohort of 790 individuals at risk of developing ZCL living in endemic areas with varying L. major infection prevalence. One area had a high infection prevalence indicated by high proportions of leishmanin skin test (LST) positive subjects, while the other areas were recent foci with lower infection prevalence. Blood samples were collected before the transmission season to measure Interferon gamma (IFN-γ), Interleukin 10 (IL-10), and Granzyme B (GrB) levels in response to parasite stimulation in peripheral blood mononuclear cells. A one-year follow-up period involved active detection of new ZCL cases to estimate disease incidence after a transmission season and identify immune correlates of protection. The study population showed heterogeneity in parasite contact, evident from specific scars and/or positive LST results, significantly higher in the old focus compared to recent foci. IFN-γ and GrB were markers of parasite exposure and reliable indicators of immunity to L. major. Positive correlations were observed between IFN-γ/IL-10 and GrB/IL-10 ratios and LST results. Unexpectedly, only 29 new ZCL cases (4%) appeared after a transmission season, with 27 cases reported in recent foci and 2 in the oldest focus. Our findings indicate that individuals in L. major endemic areas are likely to develop ZCL regardless of their LST status. We showed that high pre-transmission season levels of IFN-γ and GrB produced by PBMC, along with a high IFN-γ/IL-10 ratio, were associated with protection. This study on a large cohort at risk of ZCL confirmed IFN-γ and GrB as protective factors against the disease. A high IFN-γ/IL-10 ratio, but not GrB/IL-10 ratio was associated with resistance. These results are valuable for developing and evaluating of a vaccine against human leishmaniasis.

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来源期刊

PLoS Neglected Tropical Diseases Medicine-Infectious Diseases

CiteScore

7.40

自引率

10.50%

发文量

723

审稿时长

2-3 weeks

期刊介绍： PLOS Neglected Tropical Diseases publishes research devoted to the pathology, epidemiology, prevention, treatment and control of the neglected tropical diseases (NTDs), as well as relevant public policy. The NTDs are defined as a group of poverty-promoting chronic infectious diseases, which primarily occur in rural areas and poor urban areas of low-income and middle-income countries. Their impact on child health and development, pregnancy, and worker productivity, as well as their stigmatizing features limit economic stability. All aspects of these diseases are considered, including: Pathogenesis Clinical features Pharmacology and treatment Diagnosis Epidemiology Vector biology Vaccinology and prevention Demographic, ecological and social determinants Public health and policy aspects (including cost-effectiveness analyses).