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Case study: Tracking global antimicrobial resistance with genomic sequencing

Tackling emerging AMR threats in four countries

Antimicrobial resistance (AMR) is a serious and growing threat to global public health. In 2019, AMR was associated with nearly five million deaths globally. The rise in AMR threatens healthcare at all levels in every country, with infectious diseases such as pneumonia, tuberculosis, soil and food-borne diseases becoming more difficult to treat.

Low and middle income countries (LMICs) bear the greatest impacts of AMR, as they have high rates of infectious diseases and lack of access to health care, diagnostic microbiology and surveillance facilities. In recent years, AMR surveillance has been transformed by innovative tools for rapid whole genome sequencing of pathogens. This technology is increasingly cost-effective, but, most LMICs lack both the facilities and the training to deploy it effectively.

In 2017, the NIHR Global Health Research Unit on Genomic Surveillance of Antimicrobial Resistance (AMR) was set up with a £6.8 million contract, funded by UK Official Development Assistance (ODA) through NIHR, to develop a genomic surveillance network among four LMIC partners.

Coordinated by the Centre for Genomic Pathogen Surveillance at the University of Oxford with partners in India, the Philippines, Nigeria and Colombia, the Unit has successfully implemented genomic surveillance of AMR at reference sites in each of those countries, working with national and local public health authorities to track and prevent the spread of diseases.Using samples from national networks of hospitals and centres, the Unit’s laboratories produced sequencing results that informed both local control measures and national policies for infectious disease outbreaks.

For example, the team at Ibadan, Nigeria, identified an outbreak of E.coli within a hospital’s intensive care unit and supported the hospital to manage the infection. In the Philippines, outbreaks of Klebsiella pneumoniae were halted as a result of the application of Whole Genome Sequencing (WGS). K. pneumoniae is a leading cause of hospital-acquired infection especially among the immunocompromised and can be resistant to multiple antibiotics. The Unit’s study published in Clinical Infectious Diseases, identified three previously unrecognised local outbreaks among newborns, demonstrating the value of understanding the epidemiology of this bacteria and helping to inform public health services. 

In India, samples have been collected and sequenced through laboratories to create an extensive genome database of more than 5000 samples that helps inform local transmission patterns. Data collected on Streptococcus pneumoniae has provided information on circulating subtypes that are being used to inform vaccine development. 

Training future generations across 12 countries

To address the local need for specialised skills within public health units and local research groups, the Unit worked with Wellcome Connecting Science to develop a ‘train-the-trainer’ course. This was designed to build laboratory and data skills to develop local expertise and capacity for AMR surveillance.

Researchers from 12 LMICs attended the first course in 2019 and learned techniques to teach and share new skills within their own countries. Published in a special issue of Clinical Infectious Diseases, the Unit’s approach to training provided a framework for future training and capacity building programmes that allows researchers to pass on knowledge and expertise directly to others.

The Unit’s funding has also enabled its partners to develop wider genomic surveillance infrastructure including laboratory start-up, training, logistics and financial management. Templates for implementation in other countries were also developed and published.

Professor Iruka Okeke, the chief investigator for the Unit, is based at the University of Ibadan in Nigeria. Reflecting on the benefits of working in partnerships with other developing countries to build AMR surveillance systems, she said: “It’s really helpful to have other developing country partners in this process. We’ve been able to look to the Philippines - how they spent over three decades developing a surveillance system and learn from that and be able to do something similar in a much shorter timeline.”

Through sampling and sequencing the DNA of both resistant and sensitive bacteria within the partners' countries, the Unit has enabled public health and research capacity for spotting, tracking and delivering interventions to tackle resistant strains. 

“Data generated has supported local understanding of bacterial antibiotic resistance while contributing to national and international monitoring of key bacterial infections. This will ultimately help to improve the public health response of entire regions.”

Professor David Aanensen, Director of the NIHR Global Health Research Unit on Genomic Surveillance of Antimicrobial Resistance

 

Influencing global policy and practice through Covid and beyond

During the outbreak of the Covid-19 pandemic in early 2020, all partners were able to pivot their sequencing facilities to provide information on the spread of the virus through their countries. The COVID-19 pandemic has raised awareness of the importance of monitoring the evolution of pathogens in real time. Genomic surveillance is vital to enable more rapid interventions in response to AMR outbreaks and to inform national and international policies.

In support of this, the Unit developed a ‘roadmap’ outlining key steps to guide other researchers. Published in the journal BMJ Global Health, the steps were informed by the team’s experiences of developing sequencing in partner countries’ laboratories.

The work of the Unit is also informing WHO guidelines by contributing to the development of two WHO Technical Notes. The first note is about the uptake and use of molecular methods for AMR surveillance, and the second note, on the use of whole genome sequencing for global surveillance of AMR.

Professor Aanensen said: “Our contribution to the technical notes has been informed by our strong international partnerships with public health surveillance teams across the world and builds on the formation of the NIHR Global Health Research Unit on Genomic Surveillance of Antimicrobial Resistance. We hope this will have a significant impact on informed choices that different laboratories and countries may make to improve AMR surveillance.”

In June 2022, the new NIHR Global Health Research Unit on Genomics and enabling data for Surveillance of Antimicrobial Resistance was launched with funding from NIHR of £7 million over the next 5 years. Led jointly by Profs. Aanensen and Okeke, it will build on the success achieved to date to advance the uptake and dissemination of Whole Genome Sequencing technology in LMICs. The new Unit will deploy rapid data linkage and reporting to transform the use of whole genome sequencing into policy and practice at national and international levels. It focuses on capacity building in data science and local ownership of methods and reporting frameworks, as well as more rapid spotting and stopping of outbreaks.

“Looking ahead, we are building on the foundations and partnerships we have developed over the past 5 years to deliver technical support for the rollout of Whole Genome Sequencing. We are also partnering with key institutions and WHO to deliver regional capacity building for data science and engineering to enable local public health authorities to curb the threat of AMR in their countries and worldwide.”

Professor Iruka Okeke, co-Director of the NIHR Global Health Research Unit on Genomics and enabling data for Surveillance of Antimicrobial Resistance