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
| Autor: | Basil Sambou, Robindra Basu Roy, Artemis Koukounari, Muhamed Sissoko, Beth Holder, Beate Kampmann, Marie P. Gomez, Abdou K. Sillah, Uzochukwu Egere |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Mycobacterial growth inhibition assay Tuberculosis Tuberculin Asymptomatic General Biochemistry Genetics and Molecular Biology 1117 Public Health and Health Services Mycobacterium tuberculosis 03 medical and health sciences 0302 clinical medicine Correlates of protection medicine media_common.cataloged_instance Humans Latent tuberculosis infection European union Tuberculosis Vaccines media_common biology business.industry Case-control study 1103 Clinical Sciences General Medicine medicine.disease biology.organism_classification 030104 developmental biology Clinical research Paediatric 030220 oncology & carcinogenesis Immunology Sputum medicine.symptom business Research Paper |
| Zdroj: | EBioMedicine |
| Popis: | 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–Guerin (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). |
| Databáze: | OpenAIRE |
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