Immunologic Markers of Protection in Leishmania (Viannia) braziliensis Infection: A 5-Year Cohort Study.

BACKGROUND The control of Leishmania braziliensis by individuals with subclinical infection (SC) are unknown. METHODS A cohort of 308 household contacts (HCs) of patients with cutaneous leishmaniasis (CL) was established in 2010 in an endemic area and followed up for 5 years. Whole-blood cultures stimulated with soluble Leishmania antigen and a Leishmania skin test (LST) were performed in years 0, 2, and 4. The identification of the lymphocyte subsets secreting interferon (IFN) γ and the ability of monocytes to control Leishmania were determined. RESULTS During follow-up, 118 subjects (38.3%) had evidence of L. braziliensis infection. Of the HCs, CL was documented in 45 (14.6%), 101 (32.8%) had SC infection, and 162 (52.6%) did not have evidence of exposure to L. braziliensis The ratio of infection to disease was 3.2:1. IFN-γ production, mainly by natural killer cells, was associated with protection, and a positive LST result did not prevent development of disease. Moreover, monocytes from subjects with SC infection were less permissive to parasite penetration and had a greater ability to control L. braziliensis than cells from patients with CL. CONCLUSIONS Protection against CL was associated with IFN-γ production, negative LST results, impaired ability of Leishmania to penetrate monocytes, and increased ability to control Leishmania growth.