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BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2022

Open Access 01-12-2022 | Isoniazid | Research

Evolution and spread of a highly drug resistant strain of Mycobacterium tuberculosis in Papua New Guinea

Authors: Arnold Bainomugisa, Evelyn Lavu, Sushil Pandey, Suman Majumdar, Jennifer Banamu, Chris Coulter, Ben Marais, Lachlan Coin, Stephen M. Graham, Philipp du Cros

Published in: BMC Infectious Diseases | Issue 1/2022

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Abstract

Background

Molecular mechanisms determining the transmission and prevalence of drug resistant tuberculosis (DR-TB) in Papua New Guinea (PNG) are poorly understood. We used genomic and drug susceptibility data to explore the evolutionary history, temporal acquisition of resistance and transmission dynamics of DR-TB across PNG.

Methods

We performed whole genome sequencing on isolates from Central Public Health Laboratory, PNG, collected 2017–2019. Data analysis was done on a composite dataset that also included 100 genomes previously sequenced from Daru, PNG (2012–2015).

Results

Sampled isolates represented 14 of the 22 PNG provinces, the majority (66/94; 70%) came from the National Capital District (NCD). In the composite dataset, 91% of strains were Beijing 2.2.1.1, identified in 13 provinces. Phylogenetic tree of Beijing strains revealed two clades, Daru dominant clade (A) and NCD dominant clade (B). Multi-drug resistance (MDR) was repeatedly and independently acquired, with the first MDR cases in both clades noted to have emerged in the early 1990s, while fluoroquinolone resistance emerged in 2009 (95% highest posterior density 2000–2016). We identified the presence of a frameshift mutation within Rv0678 (p.Asp47fs) which has been suggested to confer resistance to bedaquiline, despite no known exposure to the drug. Overall genomic clustering was significantly associated with rpoC compensatory and inhA promoter mutations (p < 0.001), with high percentage of most genomic clusters (12/14) identified in NCD, reflecting its role as a potential national amplifier.

Conclusions

The acquisition and evolution of drug resistance among the major clades of Beijing strain threaten the success of DR-TB treatment in PNG. With continued transmission of this strain in PNG, genotypic drug resistance surveillance using whole genome sequencing is essential for improved public health response to outbreaks. With occurrence of resistance to newer drugs such as bedaquiline, knowledge of full drug resistance profiles will be important for optimal treatment selection.
Appendix
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Metadata
Title
Evolution and spread of a highly drug resistant strain of Mycobacterium tuberculosis in Papua New Guinea
Authors
Arnold Bainomugisa
Evelyn Lavu
Sushil Pandey
Suman Majumdar
Jennifer Banamu
Chris Coulter
Ben Marais
Lachlan Coin
Stephen M. Graham
Philipp du Cros
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2022
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-022-07414-2

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