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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

Basu Roy, Robindra, Sambou, Basil, Sissoko, Muhamed, Holder, Beth, Gomez, Marie, Egere, Uzochukwu, Sillah, Abdou, Koukounari, Artemis and Kampmann, Beate (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, Issue 102891.

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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

Item Type: Article
Subjects: QW Microbiology and Immunology > Bacteria > QW 125 Actinibacteria, Actinomycetales.
WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries
WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General)
WS Pediatrics > Diseases of Children and Adolescents > By System > WS 280 Respiratory system
Faculty: Department: Clinical Sciences & International Health > International Public Health Department
Digital Object Identifer (DOI): https://doi.org/10.1016/j.ebiom.2020.102891
Depositing User: Elly Wallis
Date Deposited: 10 Aug 2020 12:50
Last Modified: 29 Oct 2020 11:37
URI: https://archive.lstmed.ac.uk/id/eprint/15244

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