Pre-detection history of extensively drug-resistant tuberculosis in KwaZulu-Natal, South Africa
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AuthorBrown, Tyler S.
Baugh, Evan H.
Omar, Shaheed Vally
Auld, Sara C.
Shah, N. Sarita
Kreiswirth, Barry N.
Brust, James C. M.
Nelson, Kristin N.
Robinson, D. Ashley
Gandhi, Neel R.
Journal titleProceedings of the National Academy of Sciences
Publication Begin page23284
Publication End page23291
MetadataShow full item record
AbstractAntimicrobial-resistant (AMR) infections pose a major threat to global public health. Similar to other AMR pathogens, both historical and ongoing drug-resistant tuberculosis (TB) epidemics are characterized by transmission of a limited number of predominant Mycobacterium tuberculosis (Mtb) strains. Understanding how these predominant strains achieve sustained transmission, particularly during the critical period before they are detected via clinical or public health surveillance, can inform strategies for prevention and containment. In this study, we employ whole-genome sequence (WGS) data from TB clinical isolates collected in KwaZulu-Natal, South Africa to examine the pre-detection history of a successful strain of extensively drug-resistant (XDR) TB known as LAM4/KZN, first identified in a widely reported cluster of cases in 2005. We identify marked expansion of this strain concurrent with the onset of the generalized HIV epidemic 12 y prior to 2005, localize its geographic origin to a location in northeastern KwaZulu-Natal ∼400 km away from the site of the 2005 outbreak, and use protein structural modeling to propose a mechanism for how strain-specific rpoB mutations offset fitness costs associated with rifampin resistance in LAM4/KZN. Our findings highlight the importance of HIV coinfection, high preexisting rates of drug-resistant TB, human migration, and pathoadaptive evolution in the emergence and dispersal of this critical public health threat. We propose that integrating whole-genome sequencing into routine public health surveillance can enable the early detection and local containment of AMR pathogens before they achieve widespread dispersal.
CitationBrown TS, Challagundla L, Baugh EH, Omar SV, Mustaev A, Auld SC, Shah NS, Kreiswirth BN, Brust JCM, Nelson KN, Narechania A, Kurepina N, Mlisana K, Bonneau R, Eldholm V, Ismail N, Kolokotronis SO, Robinson DA, Gandhi NR, Mathema B. Pre-detection history of extensively drug-resistant tuberculosis in KwaZulu-Natal, South Africa. Proc Natl Acad Sci U S A. 2019 Nov 12;116(46):23284-23291. doi: 10.1073/pnas.1906636116. Epub 2019 Oct 28. PMID: 31659018; PMCID: PMC6859317.
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