Clinical and immunological evaluation after BCG-id vaccine in leprosy patients in a 5-year follow-up study

Abstract

IntroductionThe use of bacillus Calmette–Guérin (BCG) has long been considered a stimulus for immune reactivity in leprosy household contacts. Probably, the combination of multidrug therapy with BCG could facilitate the clearance of leprosy bacilli in the host, reduce relapse rates, and shorten the duration of skin-smear positivity.MethodsTo investigate the mechanism of action of BCG, a study involving 19 leprosy patients, eleven multibacillary (MB) and eight paucibacillary, was performed to assess the in vitro production of interleukin (IL)-10, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-6, and IL-17 in the supernatant of peripheral blood mononuclear cells, before and 30 days after inoculation with BCG intradermally (BCG-id). Peripheral blood mononuclear cells isolated by Ficoll–Hypaque gradient were cultivated with Concanavalin-A (Con-A), lipopolysccharides (LPS), or BCG. The supernatant was collected for ELISA quantification of cytokines. The immunohistochemistry of IFN-γ, IL-1, IL-10, IL-12, transforming growth factor (TGF)-β, and TNF-α was carried out in biopsies of skin lesions of leprosy patients before and 30 days after inoculation of BCG-id. These patients were followed up for 5 years to assess the therapeutic response to multidrug therapy, the occurrence of leprosy reactions, and the results of bacterial index and anti-PGL-1 serology after the end of treatment.ResultsThe results showed increased production of cytokines after BCG-id administration in MB and paucibacillary leprosy patients. There was statistically higher levels of TNF-α (P = 0.017) in MB patients and of IL-17 (P = 0.008) and IFN-γ (P = 0.037) in paucibacillary patients. Immunohistochemical staining, especially for TNF-α, was more intense in biopsies of MB leprosy patients taken after BCG-id administration, probably for induction of innate human immunity. The clinical evaluation suggests that BCG-id is able to induce a more effective therapeutic response, with reduction of the number and the intensity of leprosy reactions.ConclusionThese results suggest that BCG-id induces activation of the initial phase of immunocellular activity: innate human immunity (increase in TNF-α, IL-12 and macrophage activation). Therefore, we conclude that the use of BCG-id could be indicated as an adjuvant to multidrug therapy in treatment of leprosy patients.

Social and environmental conditions related to Mycobacterium leprae infection in children and adolescents from three leprosy endemic regions of Colombia

“…Among the factors that appeared protective, BCG immunization was associated with reduced M. leprae infection frequencies among the children and adolescents in our study cohorts. The BCG vaccine can enhance cellular immune responses against M. leprae , and immunization with BCG has been recommended for HHC of diagnosed leprosy index cases [22]. Our findings are therefore compatible with both our previous research as well studies in Brazilian populations.…”

Factors associated with seropositivity for APGL-Iamong household contacts of leprosy patients

“…Vaccination increased the rate of developing clinical manifestations of PB in APGL-I-positive HC (19) . BCG vaccination increases tumor necrosis factor alpha (TNF-α) production in MB patients, and interferon gamma (IFN-γ and interleukin-17 (IL-17) production in PB patients (22) .…”

Widespread nasal carriage of Mycobacterium lepraeamong a healthy population in a hyperendemic region of northeastern Brazil

“…These results corroborate other studies that demonstrate the protection of BCG in leprosy prevention ( Kerr-Pontes et al 2006 , Zodpey 2007 , Merle et al 2010 ). BCG improves the immunological response of leprosy cases by inducing the activation of the initial phase of immunocellular activity, innate human immunity (increase in tumour necrosis factor alpha, interleukin-12 and macrophage activation) ( Zenha et al 2012 ).…”