Dataset Information

BCG and Adverse Events in the Context of Leprosy.

ABSTRACT:

Background

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.

Methods

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 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.

Results

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-? 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.

Conclusion

Skin complications after BCG vaccination present surrogate markers for protective immunity against leprosy, but also indicate a higher risk of developing tuberculoid leprosy.

Clinical trial registration

Netherlands Trial Register: NTR3087.

SUBMITTER: Richardus R

PROVIDER: S-EPMC5893643 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

BCG and Adverse Events in the Context of Leprosy.

Richardus Renate R van Hooij Anouk A van den Eeden Susan J F SJF Wilson Louis L Alam Korshed K Richardus Jan Hendrik JH Geluk Annemieke A

Frontiers in immunology 20180404

<h4>Background</h4>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- ...[more]

PMID: 29670618

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Project description:BACKGROUND:The only licensed live Bacille Calmette-Guérin (BCG) vaccine used to prevent severe childhood tuberculosis comprises genetically divergent strains with variable protective efficacy and rates of BCG-induced adverse events. The whole-genome sequencing (WGS) allowed evaluating the genome stability of BCG strains and the impact of spontaneous heterogeneity in seed and commercial lots on the efficacy of BCG-vaccines in different countries. Our study aimed to assess sequence variations and their putative effects on genes and protein functions in the BCG-1 (Russia) seed lots compared to their progeny isolates available from immunocompetent children with BCG-induced disease (mainly, osteitis). RESULTS:Based on the WGS data, we analyzed the links between seed lots 361, 367, and 368 used for vaccine manufacture in Russia in different periods, and their nine progeny isolates recovered from immunocompetent children with BCG-induced disease. The complete catalog of variants in genes relative to the reference genome (GenBank: CP013741) included 4 synonymous and 8 nonsynonymous single nucleotide polymorphisms, and 3 frameshift deletions. Seed lot 361 shared variants with 2 of 6 descendant isolates that had higher proportions of such polymorphisms in several genes, including ppsC, eccD5, and eccA5 involved in metabolism and cell wall processes and reportedly associated with virulence in mycobacteria. One isolate preserved variants of its parent seed lot 361 without gain of further changes in the sequence profile within 14?years. CONCLUSIONS:The background genomic information allowed us for the first time to follow the BCG diversity starting from the freeze-dried seed lots to descendant clinical isolates. Sequence variations in several genes of seed lot 361 did not alter the genomic stability and viability of the vaccine and appeared accumulated in isolates during the survival in the human organism. The impact of the observed variations in the context of association with the development of BCG-induced disease should be evaluated in parallel with the immune status and host genetics. Comparative genomic studies of BCG seed lots and their descendant clinical isolates represent a beneficial approach to better understand the molecular bases of efficacy and adverse events during the long-term survival of BCG in the host organism.

Project description:BackgroundLimited data are available on adverse events among children admitted to hospital. The Canadian Paediatric Adverse Events Study was done to describe the epidemiology of adverse events among children in hospital in Canada.MethodsWe performed a 2-stage medical record review at 8 academic pediatric centres and 14 community hospitals in Canada. We reviewed charts from patients admitted from April 2008 through March 2009, evenly distributed across 4 age groups (0 to 28 d; 29 to 365 d; > 1 to 5 yr and > 5 to 18 yr). In stage 1, nurses and health records personnel who had received training in the use of the Canadian Paediatric Trigger Tool reviewed medical records to detect triggers for possible adverse events. In stage 2, physicians reviewed the charts identified as having triggers and described the adverse events.ResultsA total of 3669 children were admitted to hospital during the study period. The weighted rate of adverse events was 9.2%. Adverse events were more frequent in academic pediatric centres than in community hospitals (adjusted odds ratio [OR] 2.98, 95% confidence interval [CI] 1.65-5.39). The incidence of preventable adverse events was not significantly different between types of hospital, but nonpreventable adverse events were more common in academic pediatric centres (adjusted OR 4.39, 95% CI 2.08-9.27). Surgical events predominated overall and occurred more frequently in academic pediatric centres than in community hospitals (37.2% v. 21.5%, relative risk [RR] 1.7, 95% CI 1.0-3.1), whereas events associated with diagnostic errors were significantly less frequent (11.1% v. 23.1%, RR 0.5, 95% CI 0.2-0.9).InterpretationMore children have adverse events in academic pediatric centres than in community hospitals; however, adverse events in the former are less likely to be preventable. There are many opportunities to reduce harm affecting children in hospital in Canada, particularly related to surgery, intensive care and diagnostic error.

Dataset Information

BCG and Adverse Events in the Context of Leprosy.

Background

Methods

Results

Conclusion

Clinical trial registration

Publications

BCG and Adverse Events in the Context of Leprosy.

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