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

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

doi:10.1186/s12879-022-07414-2

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

BMC Infect Dis. 2022 May 6;22(1):437. doi: 10.1186/s12879-022-07414-2.

Authors

Arnold Bainomugisa^#¹, Evelyn Lavu^#^{2

3}, Sushil Pandey¹, Suman Majumdar^{4

5}, Jennifer Banamu³, Chris Coulter¹, Ben Marais⁶, Lachlan Coin⁷, Stephen M Graham^{4

5}, Philipp du Cros⁸

Affiliations

¹ Queensland Mycobacteria Reference Laboratory, Brisbane, QLD, Australia.
² University of Papua New Guinea, Port Moresby, Papua New Guinea.
³ Central Public Health Laboratory, Port Moresby, Papua New Guinea.
⁴ Burnet Institute, 85 Commercial Road, Melbourne, VIC, 3004, Australia.
⁵ University of Melbourne Department of Paediatrics and Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, VIC, Australia.
⁶ University of Sydney, Sydney, NSW, Australia.
⁷ Peter Doherty Institute, Melbourne, VIC, Australia.
⁸ Burnet Institute, 85 Commercial Road, Melbourne, VIC, 3004, Australia. philipp.ducros@burnet.edu.au.

^# Contributed equally.

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.

Keywords: Drug resistance; Mycobacterium tuberculosis; Papua New Guinea; RR-TB; Whole genome sequencing.

MeSH terms

Antitubercular Agents / pharmacology
Antitubercular Agents / therapeutic use
Drug Resistance, Multiple, Bacterial / genetics
Humans
Microbial Sensitivity Tests
Mutation
Mycobacterium tuberculosis*
Noncommunicable Diseases*
Papua New Guinea / epidemiology
Phylogeny
Tuberculosis, Lymph Node* / drug therapy
Tuberculosis, Multidrug-Resistant* / drug therapy

Substances

Antitubercular Agents

Grants and funding

74431/Department of Foreign Affairs and Trade, Australian Government