BCG and Adverse Events in the Context of Leprosy
BackgroundNotwithstanding its beneficial immunoprophylactic outcomes regarding leprosy and childhood TB, BCG vaccination may cause adverse events, particularly of the skin. However, this local hyper-immune reactivity cannot be predicted before vaccination, nor is its association with protection agai...
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doaj-1d5794d21860425191a5456104aa91d52020-11-24T23:41:00ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-04-01910.3389/fimmu.2018.00629338889BCG and Adverse Events in the Context of LeprosyRenate Richardus0Renate Richardus1Anouk van Hooij2Susan J. F. van den Eeden3Louis Wilson4Korshed Alam5Jan Hendrik Richardus6Annemieke Geluk7Department of Infectious Diseases, Leiden University Medical Center, Leiden, NetherlandsDepartment of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, NetherlandsDepartment of Infectious Diseases, Leiden University Medical Center, Leiden, NetherlandsDepartment of Infectious Diseases, Leiden University Medical Center, Leiden, NetherlandsDepartment of Infectious Diseases, Leiden University Medical Center, Leiden, NetherlandsRural Health Program, The Leprosy Mission International Bangladesh, Nilphamari, BangladeshDepartment of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, NetherlandsDepartment of Infectious Diseases, Leiden University Medical Center, Leiden, NetherlandsBackgroundNotwithstanding its beneficial immunoprophylactic outcomes regarding leprosy and childhood TB, BCG vaccination may cause adverse events, particularly of the skin. However, this local hyper-immune reactivity cannot be predicted before vaccination, nor is its association with protection against leprosy known. In this study we investigated the occurrence of adverse events after BCG (re)vaccination in contacts of leprosy patients and analyzed whether the concomitant systemic anti-mycobacterial immunity was associated with these skin manifestations.MethodsWithin a randomized controlled BCG vaccination trial in Bangladesh, 14,828 contacts of newly diagnosed leprosy patients received BCG vaccination between 2012 and 2017 and were examined for adverse events 8 to 12 weeks post-vaccination. From a selection of vaccinated contacts, venous blood was obtained at follow-up examination and stimulated with Mycobacterium leprae (M. leprae) antigens in overnight whole-blood assays (WBA). M. leprae phenolic glycolipid-I-specific antibodies and 32 cytokines were determined in WBAs of 13 individuals with and 13 individuals without adverse events after vaccination.ResultsOut of the 14,828 contacts who received BCG vaccination, 50 (0.34%) presented with adverse events, mainly (80%) consisting of skin ulcers. Based on the presence of BCG scars, 30 of these contacts (60%) had received BCG in this study as a booster vaccination. Similar to the pathological T-cell immunity observed for tuberculoid leprosy patients, contacts with adverse events at the site of BCG vaccination showed elevated IFN-γ levels in response to M. leprae-specific proteins in WBA. However, decreased levels of sCD40L in serum and GRO (CXCL1) in response to M. leprae simultaneously indicated less T-cell regulation in these individuals, potentially causing uncontrolled T-cell immunity damaging the skin.ConclusionSkin complications after BCG vaccination present surrogate markers for protective immunity against leprosy, but also indicate a higher risk of developing tuberculoid leprosy.Clinical Trial RegistrationNetherlands Trial Register: NTR3087.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00629/fulladverse eventsBCG (re)vaccinationbiomarker profileshousehold contactsprotective immunityleprosy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Renate Richardus Renate Richardus Anouk van Hooij Susan J. F. van den Eeden Louis Wilson Korshed Alam Jan Hendrik Richardus Annemieke Geluk |
spellingShingle |
Renate Richardus Renate Richardus Anouk van Hooij Susan J. F. van den Eeden Louis Wilson Korshed Alam Jan Hendrik Richardus Annemieke Geluk BCG and Adverse Events in the Context of Leprosy Frontiers in Immunology adverse events BCG (re)vaccination biomarker profiles household contacts protective immunity leprosy |
author_facet |
Renate Richardus Renate Richardus Anouk van Hooij Susan J. F. van den Eeden Louis Wilson Korshed Alam Jan Hendrik Richardus Annemieke Geluk |
author_sort |
Renate Richardus |
title |
BCG and Adverse Events in the Context of Leprosy |
title_short |
BCG and Adverse Events in the Context of Leprosy |
title_full |
BCG and Adverse Events in the Context of Leprosy |
title_fullStr |
BCG and Adverse Events in the Context of Leprosy |
title_full_unstemmed |
BCG and Adverse Events in the Context of Leprosy |
title_sort |
bcg and adverse events in the context of leprosy |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2018-04-01 |
description |
BackgroundNotwithstanding its beneficial immunoprophylactic outcomes regarding leprosy and childhood TB, BCG vaccination may cause adverse events, particularly of the skin. However, this local hyper-immune reactivity cannot be predicted before vaccination, nor is its association with protection against leprosy known. In this study we investigated the occurrence of adverse events after BCG (re)vaccination in contacts of leprosy patients and analyzed whether the concomitant systemic anti-mycobacterial immunity was associated with these skin manifestations.MethodsWithin a randomized controlled BCG vaccination trial in Bangladesh, 14,828 contacts of newly diagnosed leprosy patients received BCG vaccination between 2012 and 2017 and were examined for adverse events 8 to 12 weeks post-vaccination. From a selection of vaccinated contacts, venous blood was obtained at follow-up examination and stimulated with Mycobacterium leprae (M. leprae) antigens in overnight whole-blood assays (WBA). M. leprae phenolic glycolipid-I-specific antibodies and 32 cytokines were determined in WBAs of 13 individuals with and 13 individuals without adverse events after vaccination.ResultsOut of the 14,828 contacts who received BCG vaccination, 50 (0.34%) presented with adverse events, mainly (80%) consisting of skin ulcers. Based on the presence of BCG scars, 30 of these contacts (60%) had received BCG in this study as a booster vaccination. Similar to the pathological T-cell immunity observed for tuberculoid leprosy patients, contacts with adverse events at the site of BCG vaccination showed elevated IFN-γ levels in response to M. leprae-specific proteins in WBA. However, decreased levels of sCD40L in serum and GRO (CXCL1) in response to M. leprae simultaneously indicated less T-cell regulation in these individuals, potentially causing uncontrolled T-cell immunity damaging the skin.ConclusionSkin complications after BCG vaccination present surrogate markers for protective immunity against leprosy, but also indicate a higher risk of developing tuberculoid leprosy.Clinical Trial RegistrationNetherlands Trial Register: NTR3087. |
topic |
adverse events BCG (re)vaccination biomarker profiles household contacts protective immunity leprosy |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2018.00629/full |
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