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

Robindra Basu Roy; Basil Sambou; Muhamed Sissoko; Beth Holder; Marie P. Gomez; Uzochukwu Egere; Abdou K. Sillah; Artemis Koukounari; Beate Kampmann

doi:10.1016/j.ebiom.2020.102891

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

Robindra Basu Roy
, Basil Sambou
, Muhamed Sissoko
, Beth Holder
, Marie P. Gomez
, Uzochukwu Egere
, Abdou K. Sillah
, Artemis Koukounari
, Beate Kampmann

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

Background

Children 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.

Methods

We 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.

Findings

29 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.

Interpretation

Highly 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.

Funding

Clinical 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).

Keywords

PaediatricTuberculosisLatent tuberculosis infectionCorrelates of protectionMycobacterial growth inhibition assay

Original language	English
Article number	102891
Journal	eBioMedicine
Volume	59
Early online date	13 Jul 2020
DOIs	https://doi.org/10.1016/j.ebiom.2020.102891
Publication status	Published - 1 Sept 2020

Keywords

Correlates of protection
Latent tuberculosis infection
Mycobacterial growth inhibition assay
Paediatric
Tuberculosis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

Basu Roy, R., Sambou, B., Sissoko, M., Holder, B., Gomez, M. P., Egere, U., Sillah, A. K., Koukounari, A., & Kampmann, B. (2020). 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. eBioMedicine, 59, Article 102891. https://doi.org/10.1016/j.ebiom.2020.102891

@article{f64fc658f7dc4c4391517487c764d04d,

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",

abstract = "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–Gu{\'e}rin (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).KeywordsPaediatricTuberculosisLatent tuberculosis infectionCorrelates of protectionMycobacterial growth inhibition assay",

keywords = "Correlates of protection, Latent tuberculosis infection, Mycobacterial growth inhibition assay, Paediatric, Tuberculosis",

author = "\{Basu Roy\}, Robindra and Basil Sambou and Muhamed Sissoko and Beth Holder and Gomez, \{Marie P.\} and Uzochukwu Egere and Sillah, \{Abdou K.\} and Artemis Koukounari and Beate Kampmann",

year = "2020",

month = sep,

day = "1",

doi = "10.1016/j.ebiom.2020.102891",

language = "English",

volume = "59",

journal = "eBioMedicine",

issn = "2352-3964",

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Basu Roy, R, Sambou, B, Sissoko, M, Holder, B, Gomez, MP, Egere, U, Sillah, AK, Koukounari, A & Kampmann, B 2020, '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', eBioMedicine, vol. 59, 102891. https://doi.org/10.1016/j.ebiom.2020.102891

TY - JOUR

T1 - 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

AU - Basu Roy, Robindra

AU - Sambou, Basil

AU - Sissoko, Muhamed

AU - Holder, Beth

AU - Gomez, Marie P.

AU - Egere, Uzochukwu

AU - Sillah, Abdou K.

AU - Koukounari, Artemis

AU - Kampmann, Beate

PY - 2020/9/1

Y1 - 2020/9/1

N2 - 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).KeywordsPaediatricTuberculosisLatent tuberculosis infectionCorrelates of protectionMycobacterial growth inhibition assay

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).KeywordsPaediatricTuberculosisLatent tuberculosis infectionCorrelates of protectionMycobacterial growth inhibition assay

KW - Correlates of protection

KW - Latent tuberculosis infection

KW - Mycobacterial growth inhibition assay

KW - Paediatric

KW - Tuberculosis

U2 - 10.1016/j.ebiom.2020.102891

DO - 10.1016/j.ebiom.2020.102891

M3 - Article

SN - 2352-3964

VL - 59

JO - eBioMedicine

JF - eBioMedicine

M1 - 102891

ER -

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

Abstract

Keywords

UN SDGs

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