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XDR 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
European Respiratory Journal 2018; DOI: 10.1183/13993003.00246-2018
Sara C. Auld
Emory University School of Medicine, Atlanta, GA, USAEmory University Rollins School of Public Health, Atlanta, GA, USA
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N. Sarita Shah
Emory University Rollins School of Public Health, Atlanta, GA, USACenters for Disease Control and Prevention, Atlanta, GA, USA
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Barun Mathema
Columbia University Mailman School of Public Health, New York, NY, USA
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Tyler S. Brown
Columbia University Mailman School of Public Health, New York, NY, USAMassachusetts General Hospital, Boston, MA, USA
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Nazir Ismail
National Institute for Communicable Diseases, Johannesburg, South AfricaDepartment of Medical Microbiology, University of Pretoria, Pretoria, South Africa
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Shaheed Vally Omar
National Institute for Communicable Diseases, Johannesburg, South Africa
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James C.M. Brust
Albert Einstein College of Medicine, Bronx, NY, USA
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Kristin N. Nelson
Emory University Rollins School of Public Health, Atlanta, GA, USA
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Salim Allana
Emory University Rollins School of Public Health, Atlanta, GA, USA
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Angela Campbell
Emory University Rollins School of Public Health, Atlanta, GA, USA
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Koleka Mlisana
School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South AfricaNational Health Laboratory Service, Durban, South Africa
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Pravi Moodley
National Health Laboratory Service, Durban, South Africa
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Neel R. Gandhi
Emory University School of Medicine, Atlanta, GA, USAEmory University Rollins School of Public Health, Atlanta, GA, USA
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Abstract

Background: Despite evidence that transmission is driving an extensively drug-resistant (XDR) tuberculosis 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.

Methods: We conducted a prospective study of XDR tuberculosis patients in KwaZulu-Natal, South Africa, during 2011–2014. We collected sociodemographic and clinical data, and identified epidemiologic links based on person-to-person or hospital-based connections. We performed whole-genome sequencing on the Mycobacterium tuberculosis isolates and determined pairwise single nucleotide polymorphism (SNP) differences.

Findings: 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 (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); half of unlinked participants were within 7 SNPs of at least five participants.

Conclusions: The majority of epidemiologically unlinked XDR tuberculosis patients had low pairwise SNP differences, consistent with transmission, with at least one other participant. These data suggest that much of transmission may result from casual contact in community settings between individuals not known to one another.

Abstract

Much of XDR tuberculosis transmission may arise from casual contact between individuals not known to one another.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Dr. Auld has nothing to disclose.

Conflict of interest: Dr. Brown has nothing to disclose.

Conflict of interest: Dr. Omar has nothing to disclose.

Conflict of interest: Dr. Brust has nothing to disclose.

Conflict of interest: Dr. Nelson has nothing to disclose.

Conflict of interest: Dr. Allana has nothing to disclose.

Conflict of interest: Ms. Campbell has nothing to disclose.

Conflict of interest: Dr. Mlisana has nothing to disclose.

Conflict of interest: Dr. Moodley has nothing to disclose.

Conflict of interest: Dr. Gandhi has nothing to disclose.

Conflict of interest: Dr. Ismail has nothing to disclose.

Conflict of interest: Dr. Mathema has nothing to disclose.

Conflict of interest: Dr. Shah has nothing to disclose.

  • Copyright ©ERS 2018
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XDR 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
European Respiratory Journal Jan 2018, 1800246; DOI: 10.1183/13993003.00246-2018

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XDR 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
European Respiratory Journal Jan 2018, 1800246; DOI: 10.1183/13993003.00246-2018
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