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Member Research and Reports

Member Research and Reports

Columbia: Study Reports on Using Whole-Genome Sequencing for Early ID and Containment of AMR Pathogens

A study published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) examines the evolutionary and epidemiologic history of an epidemic strain of extensively drug-resistant tuberculosis (XDR-TB) – LAM4/KZN- in KwaZulu-Natal, South Africa. This strain was first reported in a 2005 outbreak, where it was associated with 90 percent mortality among predominantly human immunodeficiency virus (HIV) infected individuals, and has since become widespread throughout the province. A new study identifies key host, pathogen and environmental factors that facilitated the success of this XDR-TB strain and steps that can be taken for early identification and containment of future epidemics.

The study, led by Columbia University Mailman School of Public Health, with researchers from South Africa, U.S., and Norway, used genomic, spatial and protein modeling to answer when and where this strain emerged, and how and why it became widespread.

Researchers localized the origin of the strain to a rural district, bordering Mozambique and eSwatini, with high preexisting rates of drug-resistant TB located 400 hundred kilometers from where the first outbreak was reported.

Results also indicate that the strain emerged in the early 1990s, acquiring key mutations prior to its marked expansion concurrent with the onset of the generalized HIV epidemic, and suggest cyclical rural-urban migration in its rapid dissemination.

“Our results indicate that this strain of XDR-TB emerged approximately 12 years before it was identified,” said lead author Dr. Barun Mathema, epidemiologist at Columbia Mailman. “Our research highlights multiple environmental and pathogen-specific factors must align in order for these pathogens to establish sustained transmission and disperse, processes that take place years before the pathogens are first noticed as public health threats.”

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