Corporate report

UKHSA Advisory Board: Pathogen Genomics Strategy and Programme update

Updated 12 March 2024

Date: 13 March 2024

Sponsor: Susan Hopkins

Presenter: Meera Chand, Deborah Williamson and Sam Organ

1. Purpose of the paper

The purpose of this paper is to outline the ambition for genomics within UKHSA, including how the programme will deliver the recently published Genomics Strategy and the formation of a cross-agency programme to improve our understanding of infectious diseases risks, deliver and evaluate interventions to reduce these risks. An updated paper will be provided in 12 months with a focus on benefits quantification

2. Recommendations

The Advisory Board is asked to:

• note the published genomics strategy and the formation of the new genomics programme

• comment on the strategic priority areas, as well as the programme’s plans for engagement with strategic partners

3. Background

Pathogen genomics involves examining the genetic material of microorganisms (bacteria, viruses, fungi and parasites) that cause disease.  Advances in genomic science and technology have proved transformative for healthcare and health security and are now a core public health capability in many global regions. UKHSA’s genomic capability allows for:

• the rapid identification of different strains, or variants, of a pathogen as part of outbreak investigations

• surveillance to monitor the rate at which pathogens evolve or develop virulent/pathogenic features

• detection and monitoring of the emergence and spread of antimicrobial resistance genes

• identifying novel pathogens causing serious infections, ensuring effective and rapid responses to emerging infectious diseases 

Pathogen genomics is not new: the first bacteria were sequenced in 1995, and the COVID-19 pandemic brought genomics to public attention. The use of pathogen genomics in real-time demonstrated the real-time impact on public health globally by detecting and monitoring outbreaks, determining the effectiveness of interventions and allowing us to adapt the global pandemic response.

Since 2014, over one million genomes (excluding SARS-CoV-2 genomes) from routine hospital samples, outbreak investigations, environmental and food samples, and dedicated surveillance projects were sequenced by UKHSA and its legacy organisations.

UKHSA has engaged with Genome UK and Annex A highlights the components that UKHSA is delivering for the 2022-to-2025 Genome UK Programme implementation which this work has aligned with.

4. UKHSA and SAR-CoV-2 sequencing

By January 2024, the UK uploaded over 3 million SARS-CoV-2 genomes to public databases through collaborative partnerships between UKHSA, public health agencies in the devolved nations, NHS, academic and industry partners. The proactive sharing of genomic sequences in the public domain has made UKHSA an integral player in collaborative outbreak investigations across various agencies and countries.

UKHSA have used this sequence data to rapidly identify COVID-19 variants with unusual mutations, monitoring the effectiveness of diagnostic tests and vaccines, determining interventions and monitoring the response to public health measures. Automated data pipelines also allowed UKHSA to rapidly generate information through large-scale accessible genomic datasets, linked across local and national systems, which could then be shared with scientists globally.

The pandemic was transformational for understanding how fully integrated pathogen genomics could inform public health practice, and how characterising the continued evolution of the pandemic virus was integral to public health and clinical decision-making from national control measures to individual case treatment level. This advance was due to significant government investment (via COVID-19 Genomics Consortium-UK, NHS Test & Trace and UKHSA) which enabled:

• large-scale pathogen genome data generated in multiple sequencing centres with centralised real time analysis

• linkage of genomic data to epidemiological data such as hospitalisation, vaccination and contact tracing

• automated analysis pipelines with rapid dissemination in surveillance and public health reports

• rapid public genome data sharing and the ability to publish analysis within 48 hours, ensuring that it was available for policy making and international use

UKHSA’s overall in-house sequencing numbers have increased from 46,341 in 2018 to 2019, to 89,701 in 2022 to 2023. This increase in sequencing numbers is not only due to COVID-19 sequences, shown in more detail in Annex B.

5. Strategy and programme

In 2023, UKHSA built on this experience and obtained ministerial approval for setting up a programmatic approach to genomics with core funding agreed. A genomics strategy and organisational accountabilities were also developed.

The 5-year UKHSA Genomics Strategy was endorsed by the Executive Committee in November 2023 and published in January 2024, launching at the Festival of Genomics. This sets the direction for how UKHSA will invest in pathogen genomics to prepare for and respond to infectious public health threats to support delivery of its science strategy and organisational strategic plan.

The strategy also sets out the main strategic aims and objectives which will enable the UKHSA to build cutting-edge pathogen genomics services and infrastructure that not only safeguards public health in the UK but positions the UKHSA as a global leader in the development, implementation and evaluation of pathogen genomics by:

• using genomic data to optimise clinical and public health decision-making, from local to global settings

• using genomic data to drive improvements in diagnostics, vaccines and therapeutics

• providing a nationally coordinated, high throughput pathogen genomics sequencing and analysis service

• undertaking a genomics workforce transformation within and beyond UKHSA

• committing to pathogen genomic data sharing and global collaboration

• driving innovation in pathogen genomics

• building high-impact services that are good value for money

These will be supported by 4 strategic enablers:

• developing ethical guidelines

• addressing data privacy concerns

• promoting equitable access to pathogen genomic data

• delivering public communication

Through the strategy, UKHSA has developed 3 priority areas where the evidence base best supports deployment: antimicrobial resistance, emerging infections and diseases with global aims to reduce health harms (global elimination and vaccines).

6. Programme governance

To deliver the strategy, UKHSA has developed a cross-agency genomics programme, with leadership from Clinical Public Health, Science and Data Analytics and Surveillance groups and cross-cutting technology support, reporting to the Chief Medical Advisor as Senior Responsible Office.  

The programme has links to the current National Institute for health Research Health Protection Research Units (HPRUs) and will develop links with the future commissioned HPRUs. Importantly, pathogen genomics work will be through both the dedicated HPRU in Public Health Genomics, and also through topic specific HPRUs.  This will ensure UKHSA has access to the latest evidence-based research, with rapid translation into public health policy and practice.

The programme will achieve the following improvements (as outlined in the Programme Mandate):

• providing access to genomic data within environments that enables efficient and effective processing and the ability to deliver insight for a range of internal and external stakeholders and partners

• allowing for rapid detection of potential emerging infections and outbreaks, including for those with undiagnosed severe infection

• achieving cost effectiveness, as genomic sequencing for rapid and early diagnosis, early detection of outbreaks, and utility in improving diagnostics, therapeutics and vaccines has been shown to achieve value for money

• providing a mechanism for deciding and agreeing priority pathogens for forward programme deliverables

• attracting and retain the right people in the right roles across the end-to-end genomics services by providing training and career development pathways

• providing a clear governance structure including an improved reporting mechanism, with defined routes to escalation

Workshops have commenced to scope and prioritise deliverables with national clinical and academic subject matter experts.

7. Key challenges

Specialist workforce development and education: implementation of genomics in public health hinges on the availability of a specialist workforce skilled in genomics, bioinformatics, and related fields. This necessitates targeted efforts to develop such expertise within UKHSA, including the creation of specialised training programs and the establishment of clear career pathways for genomics professionals. The competitive landscape for these specialists, particularly against the private biotech sector, highlights the need for UKHSA to offer attractive career development opportunities and academic collaborations that can match or exceed those found in private industry.

There is also a critical need for a broader transformation towards genomic literacy across the public health workforce. This involves embedding genomics education into the training and professional development of public health professionals, not just those working directly with genomic data. Such an initiative would ensure that the benefits of genomics are fully understood and leveraged across the public health spectrum, from policy making to outbreak response.

Demonstrating value for money: implementing genomics at a large scale in public health comes with significant financial investment. Demonstrating value for money of genomic initiatives is crucial to securing ongoing support and funding. This involves conducting rigorous cost-effectiveness analyses to showcase how genomic sequencing and analysis can lead to more efficient outbreak responses, reduce healthcare costs by enabling targeted treatments, and prevent widespread transmission of infectious diseases. The programme will work with evaluation and health economic specialists to determine the metrics and data that need to be collected routinely to facilitate this analysis. Annex C contains further details on demonstrating value for money within individual pathogen genomic services.

Securing long-term funding: sustainable funding is critical for the long-term success and expansion of genomic capabilities. This requires not only initial investment in UKHSA to build and scale genomic operations but also ongoing funding to support the maintenance of genomic infrastructure, ensure workforce development, and regularly update technology and methodologies.

8. Stakeholders and relationships

Due to the nature of the genomics programme, internal and external stakeholders and partnerships must continue to be built upon to achieve successful programme delivery. The key relationships are covered below.

NHSE Genomics networks of excellence: these networks, funded by NHSE, aim to foster excellence in genomics by creating pathogen genomics hubs that link closely with UKHSA. These hubs are intended to serve as centres for innovation, expertise, and resource pooling, facilitating the rapid identification and characterisation of pathogens using metagenomics. Collaboration between UKHSA and NHSE will ensure that genomic insights are seamlessly integrated into clinical care, enhancing patient outcomes and public health responses.

Global pathogen hubs: the World Health Organization plays an important role in international health security, including coordination of global efforts in pathogen genomics. These agencies aim to standardise genomic surveillance practices, facilitate data sharing, and support capacity building in countries with limited genomic surveillance capabilities. The programme must collaborate with them for global outbreak preparedness and response.

Four Nations Subgroup on Genomics: this subgroup fosters collaboration across the UK’s four nations on genomic surveillance and policy. It ensures that efforts in pathogen genomics are harmonised, and best practices are shared, enhancing the collective genomic capability across the UK for detecting and responding to infectious disease threats.

International data sharing and analysis platforms: there are a number of platforms for global sharing and analysis of genomic data. UKHSA must ensure that data is supplied to appropriate public domain platforms and that we model values of transparency and collaboration, in order to contribute to strengthening the global genomic surveillance capability.

Industry: companies like Oxford Nanopore Technologies, Illumina, and cloud compute providers such as Oracle and AWS, are integral to the advancement of pathogen genomics in UKHSA. These partners provide sequencing technologies (both short-read and long-read sequencing) and computational infrastructure necessary for genomic data analysis. Their ongoing innovation and support are essential to UKHSA for the scalability, efficiency, and accessibility of genomic surveillance operations.

Academics: as well as our work with HPRUs, we also engage with the Wellcome Sanger Institute, UK Research and Innovation, Horizon Europe on research priorities within genomics. We work closely and directly with academia through our specific collaborations with a wide range of UK universities and the UK Pandemic Sciences Network.

9. Annexe A. Genome UK: 2022 to 2025 implementation plan for England – GOV.UK

The Genome UK 2022 to 2025 implementation plan for England set out specific genomics commitments listed below:

• ensure the NHS is ready to evaluate and implement all clinically relevant, genomic technologies and novel genomic healthcare applications based on the latest, robust evidence from experts at the forefront of their fields across the UK and globally

• offer all patients with a rare genetic disorder a definitive molecular diagnosis using tests that will support research into their condition wherever possible

• offer genomic testing to all people with cancer where it would be of clinical benefit

• support the join-up of the NHS and research community with scalable and secure informatics systems, both for clinical decision support and large-scale data processing and analytics

• secure the best value per clinical whole genome sequencing anywhere in the world, and help ensure that new clinically relevant technologies become more widely available at a competitive price

• have a clear, evidence-based position on whether and how pharmacogenomics should be implemented in the health service at scale

• sequence pathogens quickly and easily using point of care sequencing technology, helping us control outbreaks and fight antimicrobial resistance

• understand the role of the genome in differing patient outcomes from infectious disease

• rapidly utilise advances in sequencing technology to develop and deploy new diagnostics and support better, more integrated surveillance of infectious diseases

• provide international leadership in supporting the development of best practice in infectious disease genomics and public health, through international projects such as the Global Alliance for Genomic Health and the Public Health Alliance for Genomic Epidemiology

10. Annexe B. UKHSA Pathogen sequencing output from Central Sequencing Laboratories, Colindale before (2018 to 2019) and after the COVID-19 pandemic (2022 to 2023)

Next-generation sequencing	2018 to 2019	2022 to 2023
COVID-19	N/A	25,338
Mycobacteria spp.	9,845	8,925
Gastrointestinal pathogens (note 1)	18,843	22,358
Staphylococcus	6,232	5,003
Streptococcus	7,362	5,369
Influenza	2,401	6,633
Rare and Imported pathogens (note 2)	369	1,008
Other	1,289	15,067
Total	46,341	89,701

Sanger sequencing	2018 to 2019	2022 to 2023
Bacterial identification service	10,080	13,124
Sexually transmitted infection	4,503	5,432
Streptococcus	4,700	6,686
Opportunistic pathogens	2,516	2,792
Legionella and Mycoplasma	4,901	5,035
Atypical pneumonia	1,286	28
Antiviral reference unit	4,402	8,314
Blood borne virus unit	5,927	11,200
Enteric virus unit	12,884	38,462
Immunisation diagnostic unit	1,879	675
Respiratory virus unit	1,539	6,796
Culture collections	628	190
Total	58,653	98,734

Note 1: E. coli, Shigella, Listeria, Campylobacter, Salmonella

Note 2: Bacillus anthracis, Brucella spp., Borrelia spp., Coxiella burnetii, Chikungunya virus, Crimean-Congo Haemorrhagic Fever Virus, Cowpox virus, Dengue virus, Ebola virus, Francisella spp, Hantavirus, Lassa virus, Neisseria lactamica, Marburg virus, Mpox virus, Oropouche orthobunyavirus, Tick Borne Encephalitis Virus, Yellow Fever virus, Zika virus

11. Annexe C. Quantifying genomics effectiveness to demonstrate value for money

There is a paucity of robust health economic evaluations of the impact of genomics on healthcare outcomes, in part because it is a relatively new technology being used for specific pathogens (foodborne pathogens and healthcare associated infections) and in different settings (hospitals versus public health, mostly high-income countries). As the pathogen genomics programme continues to develop, we will focus attention on how to measure both health evaluation and health economic impacts for our genomics services. 

Here we outline the ways in which adding pathogen genomic data to the existing public health workflows for disease outbreaks, as the main example, could demonstrate health benefits. As pathogen genomics can be applied to a range of different microorganisms, viruses, bacteria, fungi and protozoa, we have given a broad overview of the benefits, as there will be multiple pathogens to which this applies over the next 2 years.

11.1 Individual pathogen genomic services for outbreak management

Pathogen genomics offers high-resolution information of a specific pathogen’s characteristics and ancestry, which can be used for pathogen identification, understanding disease transmission or spread and devising optimal prevention and therapeutic strategies. 

When the first few cases of an outbreak or cluster occur, conventional microbiology or virology laboratory methods to characterise these are generally through culture (bacteria and fungi) or PCR (viruses) and provide reliable information about species and potential antimicrobial treatments, but limited information about relatedness. Therefore, it may take many unusual/severe cases to be identified (sometimes across different geographic locations and communication between them or with UKHSA) before there is suspicion of a community or hospital outbreak, which would require public health or infection control measures. During this time, the infection continues to spread and more people become unwell, potentially requiring medical care, diagnostics, hospital admission and treatment. When an outbreak is eventually identified, public health actions can be instituted but then the extent of the outbreak cases also results in many more people having been exposed to the infective agent (known as contacts). Contact tracing of these people is necessary if there is an option for public health interventions including antibiotics or vaccine to prevent spread or development of disease. The health impact and costs associated with an outbreak include: attendance to healthcare (111 use, GP, emergency department), diagnostic testing, admission to hospital, hospital stay, intensive care admission/death depending on severity, short/medium/long term morbidity, inability to return to work (short or long term). 

The addition of pathogen genomic data of early disease cases allows rapid, accurate characterisation that can provide information on how best to treat the patient, but also can identify related cases and raise the alarm to public health action much earlier than with conventional methods. The benefits are driven by the assumption that all the subsequent steps kick in earlier and with better data to inform preventative and therapeutic strategies (shorter hospital admission, less treatment failure, less complications of infection, less spread of disease to healthy contacts), demonstrated for tuberculosis molecular diagnostics combined with genomics in healthcare. In theory, pathogen genomic data would help to reduce the overall size of the outbreak with associated benefits in terms of reduced ill health and resulting cost savings, with examples from the US and Canada saving in direct healthcare, indirect costs, governmental and food producer costs. For foodborne outbreaks, this also means potentially identifying the source of the outbreak and removing it from the food chain. 

A case study that exemplifies these points is a rapid investigation of a Salmonella Typhimurium outbreak amongst children in Europe, linked to a Belgian chocolate supplier at Easter time with potential to cause a large, protracted outbreak. UKHSA epidemiological investigations (February 2022) raised the suspicion based on age and exposure to chocolate and assessment of genomic data identified a small (n=8) very closely related cluster of UK cases, suggesting a likely point source. Escalation to European Union countries (February and March 2022) identified more cases (n=150) and a relatively high hospitalisation rate of 42% with associated costs (healthcare, diagnostics, therapeutics). Genomic data from Europe facilitated assessment of the extent of the outbreak with epidemiological information about chocolate products. Belgian manufacturer chocolate preparation equipment tested also identified the same strain, adding to the strength of evidence to issue product withdrawal, recall and news alerts in April 2022, all of which potentially reduced exposure and further infections occurring and the associated negative health impacts and costs.