International collaboration as a model to integrate whole-genome sequencing into national antimicrobial resistance surveillance systems in low- and middle-income countries

Whole-genome sequencing can aid the containment of antimicrobial resistance (AMR) by improving outbreak investigations and epidemiological surveillance. International collaboration can help transfer ownership of the technology and expertise to those countries that are most impacted by AMR.
Published in Microbiology
International collaboration as a model to integrate whole-genome sequencing into national antimicrobial resistance surveillance systems in low- and middle-income countries

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The rise of antimicrobial resistance (AMR) is serious threat to global public health and the economy. Without AMR containment, an adverse impact on medical costs, global gross domestic product (GDP), livestock production and international trade is expected by 2050. The Global Action Plan developed by the World Health Organization (WHO) to tackle AMR highlights the need to strengthen our understanding of how resistance develops and spreads. Whole-genome sequencing (WGS) has improved our understanding of the spread of antimicrobial-resistant strains and the mechanisms of resistance, and is routinely used for infectious disease epidemiology in several high-income countries around the world. However, WGS is still rare in low- and middle-income countries (LMICs), which are predicted to be the most affected by AMR.

The Antimicrobial Resistance Surveillance Program (ARSP), the national surveillance system of the Philippine Department of Health (DOH), has been conducting laboratory-based surveillance of AMR for over 30 years via sentinel sites throughout the country, and coordinated by the Antimicrobial Resistance Surveillance Reference Laboratory (ARSRL) in Metro Manila. In response to the first UK-Philippines Joint Health Research Call sponsored by the Newton Fund, a proposal was developed between the ARSRL and the Centre for Genomic Surveillance Program (CGPS), UK, jointly securing funding from the Department of Science and Technology (DOST) and the Medical Research Council (MRC) for the genomic surveillance of antimicrobial resistant pathogenic clones within the Philippines.

Implementing WGS for AMR surveillance in the Philippines

The overarching aim of the project was to establish local capacity and expertise for WGS within the ARSRL via a multi-faceted approach that included technology transfer and capacity building in laboratory and bioinformatics protocols, as well as in interpretation of genomic data. In parallel, we sequenced the genomes of over one thousand isolates from eight bacterial pathogens, which served as a conduit for training and as contextual background for local prospective sequencing. The interpretation of the retrospective sequence data uncovered several high-risk clones and provided a deeper understanding of AMR dynamics. In our study in Nature Communications, by complementing laboratory data with WGS, we revealed a diversity of genetic lineages, AMR mechanisms, and vehicles underlying the expansion of carbapenem resistance phenotypes at different geographical scales. We presented three examples of this, from an plasmid-driven local outbreak of K. pneumoniae ST340, to the regional dissemination of a K. pneumoniae ST147 clone across several hospitals carrying plasmid-borne NDM-1, to the independent introductions of international epidemic clone E. coli ST410 that can acquire NDM plasmids of local circulation.

First project meeting at the Research Institute for Tropical Medicine in Metro Manila

Our experience “behind the paper” was perhaps even richer, as this project was an unparalleled opportunity to learn through our partnership. Members of the ARSRL visited the UK for training, presenting at public health conferences, and experiencing the British winter. Members of the CGPS had the opportunity to visit the ARSRL and attend the ARSP annual meetings, learning about lab-based surveillance, the resourcefulness of the sentinel sites, and about the importance of having several full, delicious meals per day. There were project meetings, workshops, and even lip-synch battles, but most of the collaborative work was done remotely, highlighting the utility of web tools for collective interpretation of results.

Left: Drs. Sia, Carlos and Hufano visit PHE in London to learn about their applications of WGS. Right: June Gayeta and Melissa Masim during their bioinformatics training at the Wellcome Genome Campus in Hinxton

The ARSRL started sequencing locally in 2018 and conducted its first independent outbreak investigation using WGS in 2019. Consistent with the Philippine Action Plan to Combat AMR, the ARSRL has sought to strengthening surveillance and laboratory capacity, and foster innovation, research, and development. Establishing an international project, however, takes considerable time, especially to assess and measure full benefits of translation to public health. Our commitment to strengthen our collaborative work and to openly generalise principles and lessons-learned, continues through a broader project funded by the UK National Institute for Health Research.

Photos provided by Melissa Masim and Silvia Argimón.

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