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Cascade Immune Mechanisms of Protection against Mycobacterium tuberculosis (IMPAc-TB): study protocol for the Household Contact Study in the Western Cape, South Africa.
Hiemstra, Andriёtte M; MacDonald, Candice E; van Rensburg, Ilana C; Stanley, Kim; Maasdorp, Elizna; Mc Anda, Shirley; Tönsing, Susanne; Shaw, Jane Alexandra; Tromp, Gerard; van der Spuy, Gian D; Urdahl, Kevin B; Lewinsohn, David M; Kuivaniemi, Helena; Du Plessis, Nelita; Malherbe, Stephanus T; Walzl, Gerhard.
Afiliação
  • Hiemstra AM; Biomedical Research Institute Clinical Team, Stellenbosch University, Cape Town, South Africa. ahiemstra@sun.ac.za.
  • MacDonald CE; Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa. ahiemstra@sun.ac.za.
  • van Rensburg IC; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa. ahiemstra@sun.ac.za.
  • Stanley K; South African Medical Research Council Centre for Tuberculosis Research, Stellenbosch University, Cape Town, South Africa. ahiemstra@sun.ac.za.
  • Maasdorp E; Biomedical Research Institute Clinical Team, Stellenbosch University, Cape Town, South Africa.
  • Mc Anda S; Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa.
  • Tönsing S; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.
  • Shaw JA; South African Medical Research Council Centre for Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.
  • Tromp G; Biomedical Research Institute Clinical Team, Stellenbosch University, Cape Town, South Africa.
  • van der Spuy GD; Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa.
  • Urdahl KB; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.
  • Lewinsohn DM; South African Medical Research Council Centre for Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.
  • Kuivaniemi H; Biomedical Research Institute Clinical Team, Stellenbosch University, Cape Town, South Africa.
  • Du Plessis N; Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa.
  • Malherbe ST; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.
  • Walzl G; South African Medical Research Council Centre for Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.
BMC Infect Dis ; 22(1): 381, 2022 Apr 15.
Article em En | MEDLINE | ID: mdl-35428268
ABSTRACT

BACKGROUND:

Natural immunity against Mycobacterium tuberculosis exists, and > 90% of those infected remain disease-free. Innate and adaptive immune responses required to mediate such protection against tuberculosis (TB) are, however, poorly understood.

METHODS:

This is an analytical study exploring protective and non-protective pathways of immunity against Mycobacterium tuberculosis. Adults without HIV infection are recruited at community healthcare clinics in high TB incidence areas of the Western Cape Province, South Africa. Data regarding participants' medical, social and medication usage will be collected, and clinical examinations and point-of-care tests documented. Reference tests for TB (chest radiographs and sputum tests for GeneXpert MTB/RIF Ultra®, Auramine smear and liquid cultures) and investigations to classify infection states [interferon-gamma release assay (IGRA) and SARS-CoV-2 polymerase chain reaction (PCR) nasopharyngeal swab and IgG], are done on all participants who meet the inclusion criteria. 18F-Fluorodeoxyglucose positron emission tomography combined with computerized tomography will be done on all close contacts (contacts) and healthy control (controls) participants. Participants are divided into 12 study groups representing a spectrum of TB clinical phenotypes and prior SARS-CoV-2 infection based on their TB status, exposure history, results of IGRA test at baseline and 3 months, SARS-CoV-2 serology, and PCR results, and for contacts and controls, PET-CT imaging findings indicative of sub-clinical TB lesions. Samples for experimental assays include whole blood for isolation of peripheral blood mononuclear cells and blood in PAXgene® tubes for RNA isolation. All SARS-CoV-2 PCR negative study participants undergo bronchoscopy for collecting bronchoalveolar lavage samples.

DISCUSSION:

The paired blood and BAL samples will be used for comprehensive analyses of the tissue-specific and systemic immunity that will include e.g., cytometry by time-of-flight analyses, RNA-sequencing, multiplex immunoassays, epigenetic analysis, and mechanistic studies of control of infection by Mycobacterium tuberculosis. Results will be integrated with those from mice and non-human primate studies to provide a comprehensive analysis of protective pathways in natural and vaccine-induced immunity against Mycobacterium tuberculosis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tuberculose dos Linfonodos / Infecções por HIV / COVID-19 / Mycobacterium tuberculosis Limite: Animals / Humans País/Região como assunto: Africa Idioma: En Revista: BMC Infect Dis Assunto da revista: DOENCAS TRANSMISSIVEIS Ano de publicação: 2022 Tipo de documento: Article País de afiliação: África do Sul

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tuberculose dos Linfonodos / Infecções por HIV / COVID-19 / Mycobacterium tuberculosis Limite: Animals / Humans País/Região como assunto: Africa Idioma: En Revista: BMC Infect Dis Assunto da revista: DOENCAS TRANSMISSIVEIS Ano de publicação: 2022 Tipo de documento: Article País de afiliação: África do Sul