XDR tuberculosis in South Africa: genomic evidence supporting transmission in communities

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.