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Neonatal BCG vaccination and child survival in TB-exposed and TB-unexposed children: a prospective cohort study.

ABSTRACT: OBJECTIVES:To assess the association between neonatal BCG vaccination and mortality between 28 days and 3 years of age among tuberculosis (TB)-exposed and TB-unexposed children. DESIGN:Prospective cohort study. SETTING:Bandim Health Project runs an urban Health and Demographic Surveillance site in Guinea-Bissau with registration of mortality, vaccination status and TB cases. PARTICIPANTS:Children entered the analysis when their vaccination card was inspected after 28 days of age and remained under surveillance to 3 years of age. Children residing in the same house as a TB case were classified as TB-exposed from 3 months prior to case registration to the end of follow-up. METHODS:Using Cox-proportional hazards models with age as underlying time scale, we compared mortality of children with and without neonatal BCG between October 2003 and September 2017. MAIN OUTCOME MEASURE:HR for neonatal BCG compared with no neonatal BCG by TB-exposure status. RESULTS:Among the 39?421 children who entered the analyses, 3022 (8%) had observation time as TB-exposed. In total, 84% of children received neonatal BCG. Children with neonatal BCG had lower mortality both in TB-exposed (adjusted HR: 0.57 (0.26 to 1.27)) and in TB-unexposed children (HR: 0.57 (95% CI 0.47 to 0.69)) than children without neonatal BCG. Children exposed to TB had higher mortality than TB-unexposed children if they had not received neonatal BCG. CONCLUSION:Neonatal BCG vaccination was associated with lower mortality among both TB-exposed and TB-unexposed children, consistent with neonatal BCG vaccination having beneficial non-specific effects. Interventions to increase timely BCG vaccination are urgently warranted.

SUBMITTER: Thysen SM

PROVIDER: S-EPMC7050365 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Neonatal BCG vaccination and child survival in TB-exposed and TB-unexposed children: a prospective cohort study.

Thysen Sanne M SM Benn Christine Stabell CS Gomes Victor Francisco VF Rudolf Frauke F Wejse Christian C Roth Adam A Kallestrup Per P Aaby Peter P Fisker Ane A

BMJ open 20200228 2

<h4>Objectives</h4>To assess the association between neonatal BCG vaccination and mortality between 28 days and 3 years of age among tuberculosis (TB)-exposed and TB-unexposed children.<h4>Design</h4>Prospective cohort study.<h4>Setting</h4>Bandim Health Project runs an urban Health and Demographic Surveillance site in Guinea-Bissau with registration of mortality, vaccination status and TB cases.<h4>Participants</h4>Children entered the analysis when their vaccination card was inspected after 28 ...[more]

PMID: 32114478

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Project description:BackgroundHow far the role of innate immunity and adaptive immunity do in children who have been BCG vaccinated in controlling the course and the severity of the TB disease has not been completely known. Mycobacterium tuberculosis entry to the body will be recognized by Toll-like receptors found on macrophages, neutrophils, and dendritic cells as part of the innate immune response, after which the dendritic cells will then present the antigen to lymphocyte T0 cells and initiate the adaptive immune response (of which CD4 T cells have an important role in). Was one or were both of these immune responses function well or not in a BCG Vaccinated Children with TB?ObjectiveThis study aim to find a better understanding of the role of innate immune response assessed by TLR2/TLR4 mRNA gene expression and serum TLR2/TLR4 levels, while the role of adaptive immune response is assessed by analyzing serum CD4 level in children with TB who have had BCG vaccination.MethodsThis cross-sectional study was conducted among children with TB at the outpatient and inpatient wards at Bhakti Medicare and Jakarta Islamic Hospital. Expression of mRNA gene was measured using the Boom method and protein serum levels were measured using the ELISA method. The results were analyzed by using the SPSS v.23 program.ResultsSixty-nine children were recruited as subjects. In this study, 68.1% of whom had BCG scars. TLR4 mRNA gene expression was found to be higher than TLR2 mRNA gene expression. Serum CD4 level was found to be highest out of TLR2 and TLR4 level, but serum TLR2 level was higher than TLR4 level. TLR2/TLR4 mRNA gene expression, serum TLR2/TLR4 levels, and CD4 levels in subjects with BCG scar were also found to be significantly higher than in subjects without BCG scar (p < 0.001). There was a significant positive correlation between TLR2/TLR4 mRNA gene expression and serum TLR2/TLR4 levels (r = 0.860; r = 0.864; p < 0.001) and between serum levels TLR2/TLR4 with serum CD4 levels (r = 0.822; r = 0.832 p < 0.001).ConclusionAs early as possible, BCG vaccine administration is needed in endemic countries, but it must be ensured that scars can be formed. It is also important to control Latent TB Infection (LTBI) to prevent transmission and relapse of disease.

Project description:IntroductionExposure to maternal HIV may affect early child development (ECD), although previous studies have reported heterogeneous findings. We evaluated ECD among children who were HIV-exposed uninfected (CHEU) and children who were HIV-unexposed (CHU) recruited to the SHINE trial in rural Zimbabwe.MethodsSHINE was a community-based cluster-randomized trial of improved infant feeding and/or improved water, sanitation and hygiene. Pregnant women were enrolled between 2012 and 2015. We assessed ECD in a sub-study at 24 months of age, between 2016 and 2017, using the Malawi Developmental Assessment Tool (MDAT; assessing motor, cognitive, language and social development); MacArthur-Bates Communicative Development Inventory (CDI) (assessing vocabulary and grammar); A-not-B test (assessing object permanence); and a self-control task. Mothers and infants were tested longitudinally for HIV. We used generalized estimating equations to compare ECD scores between CHEU and CHU, accounting for the cluster-randomized design. Primary results were adjusted for trial-related factors that could affect measurement reliability of ECD: study nurse, age of child, calendar month of birth, sex and randomized arm.ResultsA total of 205 CHEU and 1175 CHU were evaluated. Mean total MDAT score was 90.6 (SD 8.7) in CHEU compared to 92.4 (9.1) in CHU (adjusted mean difference -1.3, 95% CI: -2.3, -0.3), driven mostly by differences in gross motor (-0.5, 95% CI: -0.9, -0.2) and language scores (-0.6, 95% CI: -1.1, -0.1). There was evidence that fine motor scores were lower in CHEU (adjusted mean difference -0.4, 95% CI: -0.8, 0.0) but no evidence of a difference in social scores (0.1, 95% CI: -0.2, 0.4). Mean MacArthur-Bates CDI vocabulary score was 57.9 (SD 19.2) in CHEU compared to 61.3 (18.8) in CHU (adjusted mean difference -2.9 words, 95% CI: -5.7, -0.1). Object permanence and self-control scores were similar between groups.ConclusionsCHEU in rural Zimbabwe had total child development and vocabulary scores that were approximately 0.15 standard deviations lower than CHU at two years of age. More detailed and specific studies are now needed to unravel the reasons for developmental delay in CHEU and the likelihood that these delays persist in the longer term.

Dataset Information

Neonatal BCG vaccination and child survival in TB-exposed and TB-unexposed children: a prospective cohort study.

Publications

Neonatal BCG vaccination and child survival in TB-exposed and TB-unexposed children: a prospective cohort study.

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