TY - JOUR
T1 - Outcomes, infectiousness, and transmission dynamics of patients with extensively drug-resistant tuberculosis and home-discharged patients with programmatically incurable tuberculosis: a prospective cohort study
AU - Dheda, Keertan
AU - Limberis, Jason D
AU - Pietersen, Elize
AU - Phelan, Jody
AU - Esmail, Aliasgar
AU - Lesosky, Maia
AU - Fennelly, Kevin P
AU - te Riele, Julian
AU - Mastrapa, Barbara
AU - Streicher, Elizabeth M
AU - Dolby, Tania
AU - Abdallah, Abdallah
AU - Ben Rached, Fathia
AU - Simpson, John
AU - Smith, Liezel
AU - Gumbo, Tawanda
AU - van Helden, Paul
AU - Sirgel, Frederick A
AU - McNerney, Ruth
AU - Theron, Grant
AU - Pain, Arnab
AU - Clark, Taane G.
AU - Warren, Robin M
N1 - KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: Medical Research Council[grant no MR/K000551/1, MR/M01360X/1, MR/N010469/1]
PY - 2017/1/19
Y1 - 2017/1/19
N2 - 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 (
AB - 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 (
UR - http://hdl.handle.net/10754/622901
UR - http://www.sciencedirect.com/science/article/pii/S2213260016304337
UR - http://www.scopus.com/inward/record.url?scp=85009742332&partnerID=8YFLogxK
U2 - 10.1016/S2213-2600(16)30433-7
DO - 10.1016/S2213-2600(16)30433-7
M3 - Article
C2 - 28109869
SN - 2213-2600
VL - 5
SP - 269
EP - 281
JO - The Lancet Respiratory Medicine
JF - The Lancet Respiratory Medicine
IS - 4
ER -
