Imperial College London
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Dr. Beth Holder

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Senior Lecturer in Maternal and Fetal Health
 
 
 
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Contact

 

+44 (0)20 7594 1773b.holder Website

 
 
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Location

 

3 008Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Basu:2020:10.1016/j.ebiom.2020.102891,
author = {Basu, Roy R and Sambou, B and Sissoko, M and Holder, B and Gomez, MP and Egere, U and Sillah, AK and Koukounari, A and Kampmann, B},
doi = {10.1016/j.ebiom.2020.102891},
journal = {EBioMedicine},
pages = {1--10},
title = {Protection against mycobacterial infection: A case-control study of mycobacterial immune responses in pairs of Gambian children with discordant infection status despite matched TB exposure},
url = {http://dx.doi.org/10.1016/j.ebiom.2020.102891},
volume = {59},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundChildren are particularly susceptible to tuberculosis. However, most children exposed to Mycobacterium tuberculosis are able to control the pathogen without evidence of infection. Correlates of human protective immunity against tuberculosis infection are lacking, and their identification would aid vaccine design.MethodsWe recruited pairs of asymptomatic children with discordant tuberculin skin test status but the same sleeping proximity to the same adult with sputum smear-positive tuberculosis in a matched case-control study in The Gambia. Participants were classified as either Highly TB-Exposed Uninfected or Highly TB-Exposed Infected children. Serial luminescence measurements using an in vitro functional auto-luminescent Bacillus Calmette–Guérin (BCG) whole blood assay quantified the dynamics of host control of mycobacterial growth. Assay supernatants were analysed with a multiplex cytokine assay to measure associated inflammatory responses.Findings29 pairs of matched Highly TB-Exposed Uninfected and Highly TB-Exposed Infected children aged 5 to 15 years old were enroled. Samples from Highly TB-Exposed Uninfected children had higher levels of mycobacterial luminescence at 96 hours than Highly TB-Exposed Infected children. Highly TB-Exposed Uninfected children also produced less BCG-specific interferon-γ than Highly TB-Exposed Infected children at 24 hours and at 96 hours.InterpretationHighly TB-Exposed Uninfected children showed less control of mycobacterial growth compared to Highly TB-Exposed Infected children in a functional assay, whilst cytokine responses mirrored infection status.FundingClinical Research Training Fellowship funded under UK Medical Research Council/Department for International Development Concordat agreement and part of EDCTP2 programme supported by European Union (MR/K023446/1). Also MRC Program Grants (MR/K007602/1, MR/K011944/1, MC_UP_A900/1122).
AU  - Basu,Roy R
AU  - Sambou,B
AU  - Sissoko,M
AU  - Holder,B
AU  - Gomez,MP
AU  - Egere,U
AU  - Sillah,AK
AU  - Koukounari,A
AU  - Kampmann,B
DO  - 10.1016/j.ebiom.2020.102891
EP  - 10
PY  - 2020///
SN  - 2352-3964
SP  - 1
TI  - Protection against mycobacterial infection: A case-control study of mycobacterial immune responses in pairs of Gambian children with discordant infection status despite matched TB exposure
T2  - EBioMedicine
UR  - http://dx.doi.org/10.1016/j.ebiom.2020.102891
UR  - https://www.sciencedirect.com/science/article/pii/S2352396420302668?via%3Dihub
UR  - http://hdl.handle.net/10044/1/80660
VL  - 59
ER  -
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