Clinical predictors of pulmonary tuberculosis among South African adults with HIV

Simon C. Mendelsohn; Andrew Fiore-Gartland; Denis Awany; Humphrey Mulenga; Stanley Kimbung Mbandi; Michèle Tameris; Gerhard Walzl; Kogieleum Naidoo; Gavin Churchyard; Thomas J. Scriba; Mark Hatherill

EClinicalMedicine (Mar 2022)

Clinical predictors of pulmonary tuberculosis among South African adults with HIV

Simon C. Mendelsohn,
Andrew Fiore-Gartland,
Denis Awany,
Humphrey Mulenga,
Stanley Kimbung Mbandi,
Michèle Tameris,
Gerhard Walzl,
Kogieleum Naidoo,
Gavin Churchyard,
Thomas J. Scriba,
Mark Hatherill

Affiliations

Simon C. Mendelsohn: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa
Andrew Fiore-Gartland: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Denis Awany: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa
Humphrey Mulenga: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa
Stanley Kimbung Mbandi: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa
Michèle Tameris: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa
Gerhard Walzl: DST/NRF Centre of Excellence for Biomedical TB Research, South African Medical Research Council Centre for TB Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 7505, South Africa
Kogieleum Naidoo: Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban 4001, South Africa; MRC-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban 4001, South Africa
Gavin Churchyard: The Aurum Institute, Johannesburg 2194, South Africa; School of Public Health, University of Witwatersrand, Johannesburg 2193, South Africa; Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA
Thomas J. Scriba: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa
Mark Hatherill: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa; Corresponding author.

Journal volume & issue: Vol. 45
p. 101328

Abstract

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Summary: Background: Tuberculosis (TB) clinical prediction rules rely on presence of symptoms, however many undiagnosed cases in the community are asymptomatic. This study aimed to explore the utility of clinical factors in predicting TB among people with HIV not seeking care. Methods: Baseline data were analysed from an observational cohort of ambulant adults with HIV in South Africa. Participants were tested for Mycobacterium tuberculosis (Mtb) sensitisation (interferon-γ release assay, IGRA) and microbiologically-confirmed prevalent pulmonary TB disease at baseline, and actively surveilled for incident TB through 15 months. Multivariable LASSO regression with post-selection inference was used to test associations with Mtb sensitisation and TB disease. Findings: Between March 22, 2017, and May 15, 2018, 861 participants were enrolled; Among 851 participants included in the analysis, 94·5% were asymptomatic and 45·9% sensitised to Mtb. TB prevalence was 2·0% at baseline and incidence 2·3/100 person-years through 15 months follow-up. Study site was associated with baseline Mtb sensitisation (p 1000, p = 0·005) and antiretroviral initiation (aHR 1·48, 95%CI 1·01–929·93, p = 0·023) were independently associated with incident TB. Models incorporating clinical features alone performed poorly in diagnosing prevalent (AUC 0·65, 95%CI 0·44–0·85) or predicting progression to incident (0·67, 0·46–0·88) TB. Interpretation: CD4 count and antiretroviral initiation, proxies for immune status and HIV stage, were associated with Mtb sensitisation and TB disease. Inadequate performance of clinical prediction models may reflect predominantly subclinical disease diagnosed in this setting and unmeasured local site factors affecting transmission and progression. Funding: The CORTIS-HR study was funded by the Bill & Melinda Gates Foundation (OPP1151915) and by the Strategic Health Innovation Partnerships Unit of the South African Medical Research Council with funds received from the South African Department of Science and Technology. The regulatory sponsor was the University of Cape Town.

Published in EClinicalMedicine

ISSN: 2589-5370 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Medicine (General)
Website: https://www.thelancet.com/journals/eclinm/home

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