Diversity of Mycobacterium tuberculosis and drug resistance in different provinces of Papua New Guinea

Abstract

BackgroundPapua New Guinea (PNG) is a high tuberculosis (TB) burden country of the WHO Western Pacific Region, but so far research on drug resistance (DR) and genotypes of Mycobacterium tuberculosis (M. tuberculosis) was only conducted in few provinces in the country. The aim of the present study was to obtain baseline data on the level of drug resistance and the genotypic diversity of circulating M. tuberculosis in additional provinces and to investigate the differences between three selected sites across PNG.ResultsGenotyping of 147 M. tuberculosis clinical isolates collected in Goroka, Eastern Highlands Province, in Alotau, Milne Bay Province and in Madang, Madang Province revealed three main lineages of M. tuberculosis: Lineage 4 (European-American lineage), Lineage 2 (East-Asian lineage) and Lineage 1 (Indo-Oceanic lineage). All three lineages were detected in all three sites, but the individual lineage compositions varied significantly between sites. In Madang Lineage 4 was the most prevalent lineage (76.6%), whereas in Goroka and Alotau Lineage 2 was dominating (60.5% and 84.4%, respectively) (p < 0.001). Overall, phenotypic drug susceptibility testing showed 10.8% resistance to at least one of the first-line drugs tested. Of all resistant strains (23/212) 30.4% were Streptomycin mono-resistant, 17.4% were Isoniazid mono-resistant and 13% were Rifampicin mono-resistant. Multi-drug resistant (MDR) TB was found in 2.8% of all tested cases (6/212). The highest amount of MDR TB was found in Alotau in Milne Bay Province (4.6%).ConclusionA large number of drug resistant TB infections are present in the country and MDR TB has already been detected in all three surveyed regions of PNG, highlighting the importance of monitoring drug resistance and making it a high priority for the National Control Program. Due to the high prevalence of Lineage 2 in Milne Bay Province and given the frequent association of this lineage with drug resistance, monitoring of the latter should especially be scaled up in that province.

Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages

“…they showed no homoplasy. We selected a subset of these sublineage-specific SNPs and used these to screen a global collection of 3,366 Lineage 4 clinical isolates from 100 countries using various genotyping platforms30–35. First, we developed a novel sublineage-specific multiplexed SNP-typing assay using the Luminex platform as previously reported36, and used that method to screen 2,001 isolates (Supplementary Table 2).…”

“…These represented the largest collection of Lineage 4 whole-genome sequences available at that time. For the SNP-screening of clinical isolates for sublineage-classification, we used a retrospective global collection of 3,366 MTBC Lineage 4 isolates from 100 countries (Supplementary Table 5)15,30–35. All isolates had previously been identified as MTBC Lineage 4 by SNP-typing, genomic deletion analysis or spoligotyping.…”

The Burden of Drug-Resistant Tuberculosis in Papua New Guinea: Results of a Large Population-Based Survey

“…A study from Kikori in Gulf Province of PNG reported 9% (3 of 32 TB cases) of rifampicin resistant cases among TB patients (Cross, Coles et al .) [ 8 ] and another one reported MDR-TB in 2.8% of all cases tested in three sites (Ley, Harino et al) [ 9 ]. These studies were small in nature and not designed to obtain population-representative data, therefore a large representative survey was needed to determine the real burden of anti-TB drug resistance in PNG.…”

Multi-clonal evolution of MDR/XDRM. tuberculosisin a high prevalence setting in Papua New Guinea over three decades

“…Our findings indicate that the large number of MDR TB cases detected on Daru Island in the Western Province of Papua New Guinea is driven by the transmission of a highly drug resistant cluster of modern Beijing lineage strain. Studies from other parts of Papua New Guinea demonstrated a dominance of Euro-American lineage strains, (20, 21) although the contribution of Beijing lineage strains may have been underestimated in these limited surveys. We cannot comment on the geographic spread of this outbreak cluster, but phylogenetic analysis combined with detailed molecular dating suggests that it has been in local circulation since the 1940s and first acquired drug resistance mutations in the 1960s.…”