Extensively drug-resistant tuberculosis in South Africa: genomic evidence supporting transmission in communities.
Sara C Auld, N Sarita Shah, Barun Mathema, Tyler S Brown, Nazir Ismail, Shaheed Vally Omar, James C M Brust, Kristin N Nelson, Salim Allana, Angela Campbell, Koleka Mlisana, Pravi Moodley, Neel R Gandhi
Author Information
Sara C Auld: School of Medicine, Emory University, Atlanta, GA, USA.
N Sarita Shah: Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Barun Mathema: Mailman School of Public Health, Columbia University, New York, NY, USA.
Tyler S Brown: Mailman School of Public Health, Columbia University, New York, NY, USA.
Nazir Ismail: National Institute for Communicable Diseases, Johannesburg, South Africa.
Shaheed Vally Omar: National Institute for Communicable Diseases, Johannesburg, South Africa.
James C M Brust: Albert Einstein College of Medicine, Bronx, NY, USA.
Kristin N Nelson: Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Salim Allana: Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Angela Campbell: Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Koleka Mlisana: School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
Pravi Moodley: National Health Laboratory Service, Durban, South Africa.
Neel R Gandhi: School of Medicine, Emory University, Atlanta, GA, USA.
Despite evidence that transmission is driving an extensively drug-resistant TB (XDR-TB) epidemic, our understanding of where and between whom transmission occurs is limited. We sought to determine whether there was genomic evidence of transmission between individuals without an epidemiologic connection.We conducted a prospective study of XDR-TB patients in KwaZulu-Natal, South Africa, during the 2011-2014 period. We collected sociodemographic and clinical data, and identified epidemiologic links based on person-to-person or hospital-based connections. We performed whole-genome sequencing (WGS) on the isolates and determined pairwise single nucleotide polymorphism (SNP) differences.Among 404 participants, 123 (30%) had person-to-person or hospital-based links, leaving 281 (70%) epidemiologically unlinked. The median SNP difference between participants with person-to-person and hospital-based links was 10 (interquartile range (IQR) 8-24) and 16 (IQR 10-23), respectively. The median SNP difference between unlinked participants and their closest genomic link was 5 (IQR 3-9) and half of unlinked participants were within 7 SNPs of at least five participants.The majority of epidemiologically-unlinked XDR-TB patients had low pairwise SNP differences with at least one other participant, consistent with transmission. These data suggest that much of transmission may result from casual contact in community settings between individuals not known to one another.
