The Philippines: Integrating Whole-Genome Sequencing into the National Antimicrobial Resistance Surveillance Program

Whole-genome sequencing (WGS) has improved outbreak investigations and epidemiological surveillance and enhanced our knowledge of the spread of antimicrobial-resistant strains and their resistance mechanisms. However, genomic surveillance is rare in low- and middle-income countries (LMICs), which are predicted to be the most affected by AMR.

Over 30 years of laboratory-based surveillance of antimicrobial resistance (AMR) in the Philippines has highlighted the increasing rates of drug-resistant bacterial pathogens.

While high-throughput sequencing in high-resource settings can produce a genomic background to contextualize local prospective sequencing, collaborative partnerships are paramount to enable technology transfer and capacity building with the ultimate goal of ownership transfer.

CGPS partnered with the well-established Antimicrobial Resistance Surveillance Program (ARSP) in the Philippines via a binational collaboration to integrate WGS into their program; including included technology transfer, utilization of user-friendly web applications, and capacity building in laboratory and bioinformatic procedures, as well as in interpretation of genomic data.

Whole genome sequencing commenced at the ARSP reference laboratory (ARSRL) in 2018 with the Illumina MiSeq equipment available locally. A new dedicated bioinformatics server was installed at ARSRL for sequence data storage and analysis.

Collective data interpretation was aided by data sharing via interactive web tools such as Microreact and Pathogenwatch to leverage the expertise from both CGPS and ARSRL.

Outcomes

Complementing epidemiological and phenotypic data from the ARSP with genomic data has vastly improved our understanding of the drivers of drug resistance in the Philippines.

ARSRL staff conducted their first outbreak investigation using WGS in July 2019, with sequencing, bioinformatics, and reporting to the DOH conducted locally, with a turnaround time of eight days from sample receipt to report preparation.

In parallel, we characterized bacterial populations of key bug-drug combinations via a retrospective sequencing survey.

By linking the resistance phenotypes to genomic data, our partnership revealed the interplay of genetic lineages (strains), AMR mechanisms, and AMR vehicles underlying the expansion of specific resistance phenotypes that coincide with the growing carbapenem resistance rates observed since 2010.

Our partnership also identified high-risk clones at different geographical scales, from an plasmid-driven local outbreak of K. pneumoniae ST340, to the regional dissemination across several hospitals of a K. pneumoniae ST147 clone carrying plasmid-borne NDM-1, to the independent introductions of international epidemic clone E. coli ST410 that can acquire plasmids of local circulation.

This partnership helped to support the foundations for the sustainable implementation of WGS and genomic epidemiology within national surveillance networks in the Philippines, which can be extended to other locations to tackle the global challenge of AMR.

This work was funded by a UK-Newton collaborative award to CGPS and RITM from the UK MRC) and The Department of Science and Technology, Phillipines.

https://www.nature.com/articles/s41467-020-16322-5

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