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
Abstract
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.
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).
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