02959nas a2200289   4500000000100000008004100001653001900042653002400061653002300085653002300108653001200131653002500143653002400168100001600192700001200208700001200220700001300232700001100245700001700256700001200273245005400285856007000339300000800409490000600417520223200423022001402655       2018                            d10aAdverse events10aBCG (re)vaccination10aBiomarker profiles10aHousehold contacts10aleprosy10aMycobacterium leprae10aProtective immunity1 aRichardus R1 aHooij A1 aEeden S1 aWilson L1 aAlam K1 aRichardus JH1 aGeluk A00aBCG and adverse events in the context of leprosy.  uhttps://www.frontiersin.org/articles/10.3389/fimmu.2018.00629/pdf  a6290 v93 a<p><strong>Background: </strong>Notwithstanding 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.</p>

<p><strong>Methods: </strong>Within 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 () antigens in overnight whole-blood assays (WBA). phenolic glycolipid-I-specific antibodies and 32 cytokines were determined in WBAs of 13 individuals with and 13 individuals without adverse events after vaccination.</p>

<p><strong>Results: </strong>Out 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 -specific proteins in WBA. However, decreased levels of sCD40L in serum and GRO (CXCL1) in response to simultaneously indicated less T-cell regulation in these individuals, potentially causing uncontrolled T-cell immunity damaging the skin.</p>

<p><strong>Conclusion: </strong>Skin complications after BCG vaccination present surrogate markers for protective immunity against leprosy, but also indicate a higher risk of developing tuberculoid leprosy.</p>

<p><strong>Clinical Trial Registration: </strong>Netherlands Trial Register: NTR3087.</p>
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