Outcomes, infectiousness, and transmission dynamics of patients with extensively drug-resistant tuberculosis and home-discharged patients with programmatically incurable tuberculosis: a prospective cohort study

Keertan Dheda, Jason D Limberis, Elize Pietersen, Jody Phelan, Aliasgar Esmail, Maia Lesosky, Kevin P Fennelly, Julian te Riele, Barbara Mastrapa, Elizabeth M Streicher, Tania Dolby, Abdallah Abdallah, Fathia Ben Rached, John Simpson, Liezel Smith, Tawanda Gumbo, Paul van Helden, Frederick A Sirgel, Ruth McNerney, Grant TheronArnab Pain, Taane G. Clark, Robin M Warren

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Background: The emergence of programmatically incurable tuberculosis threatens to destabilise control efforts. The aim of this study was to collect prospective patient-level data to inform treatment and containment strategies. Methods: In a prospective cohort study, 273 South African patients with extensively drug-resistant tuberculosis, or resistance beyond extensively drug-resistant tuberculosis, were followed up over a period of 6 years. Transmission dynamics, infectiousness, and drug susceptibility were analysed in a subset of patients from the Western Cape using whole-genome sequencing (WGS; n=149), a cough aerosol sampling system (CASS; n=26), and phenotypic testing for 18 drugs (n=179). Findings: Between Oct 1, 2008, and Oct 31, 2012, we enrolled and followed up 273 patients for a median of 20·3 months (IQR 9·6-27·8). 203 (74%) had programmatically incurable tuberculosis and unfavourable outcomes (treatment failure, relapse, default, or death despite treatment with a regimen based on capreomycin, aminosalicylic acid, or both). 172 (63%) patients were discharged home, of whom 104 (60%) had an unfavourable outcome. 54 (31%) home-discharged patients had failed treatment, with a median time to death after discharge of 9·9 months (IQR 4·2-17·4). 35 (20%) home-discharged cases were smear-positive at discharge. Using CASS, six (23%) of 26 home-discharged cases with data available expectorated infectious culture-positive cough aerosols in the respirable range (
Original languageEnglish (US)
Pages (from-to)269-281
Number of pages13
JournalThe Lancet Respiratory Medicine
Issue number4
StatePublished - Jan 19 2017

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