PHE research 2019 to 2020: annual review
Updated 25 May 2021
During 2019 to 2020, Public Health England (PHE) continued to enhance its status as an excellent research organisation, collaborating in and undertaking studies that resulted in 986 peer-reviewed articles, many in the world’s most acclaimed scientific and clinical journals. We also implemented research findings so our evidence-based scientific services, advice and guidance are the best they can be.
Research is essential for a public health organisation to progress, to develop and to apply its evidence base and expertise. Every public health programme, every emergency response is a learning opportunity but only if we apply appropriate research methodologies with scientific rigour so that the knowledge we gain, document and disseminate is reliable. This report profiles some of our research and its beneficial impacts on programmes to protect and improve public health. It demonstrates how PHE discharges its responsibilities as a world-leading, innovative, evidence-based public health organisation.
Findings published by PHE with our collaborators during the year include analysis of suicide among people with a cancer diagnosis, modelling the impact of potential changes to the pneumococcal vaccine schedule and investigations of possible risks to health from a range of environmental issues.
Our published, peer-reviewed outputs demonstrate the front-line use of data analysis techniques, the contributions our researchers make to data on novel pathogens and the contribution of our data collection functions to prevention strategies.
PHE also offers a rich learning and training environment, contributing significantly to supporting excellent researchers towards rewarding careers. Each year, over 70 PhD students from a wide range of universities spend some – or all – of their training time in PHE. These students gain insights into how research informs practice and policy, either in national or local public health programmes or in mitigating the impacts of outbreaks, disasters and other emergencies globally.
The following case studies provide examples of how our research provides evidence to solve public health problems and each is based upon a well-received publication. They include research from some of our Health Protection Research Units (HPRU), partnerships between PHE and academic centres of excellence, funded through the National Institute for Health Research (NIHR).
We are proud to be among the world’s most research-intensive public health agencies. These same skills and expertise were deployed rapidly to find evidence to inform the UK and global response to the pandemic that has shaped our world in 2020. A future review will detail that research.
Case studies on preventing ill health
- Ultraviolet radiation exposure during daylight photodynamic therapy
- The first UK survey of dose indices from radiotherapy treatment planning computed tomography scans for adult patients
- Risk of suicide after cancer diagnosis in England
- Applying behavioural science to increase uptake of the NHS Health Check
- From ‘Stoptober’ to ‘Moi(s) Sans Tabac’: how to import a social marketing campaign
- The first 5 years of Part 2A Orders: the use of powers from court applications to protect public health in England 2010 to 2015
- Developing gender-specific evidence-based standards to improve the health and wellbeing of women in prison in England
- National mycology laboratory diagnostic capacity for invasive fungal diseases in 2017: evidence of sub-optimal practice
Case study 1: Ultraviolet radiation exposure during daylight photodynamic therapy
The challenge
An actinic keratosis (AK) is a common, generally superficial, sun-induced scaly lesion, which has the potential to become malignant. Around 23% of the UK population aged 60 and above have such lesions. Although the risk of an actinic keratosis transforming into a carcinoma is very low, this risk increases over time and with larger numbers of lesions. Field-change refers to areas of skin that have multiple lesions associated with a background of other changes seen in sun-damaged skin. These areas are probably more at risk of developing carcinoma, especially if left untreated, so it is recommended that they should be treated. Daylight photodynamic therapy is an effective, convenient, almost painless and patient-preferred option for the management of field-change actinic keratoses, particularly on the face and scalp. Actinic keratoses can be caused by chronic solar ultraviolet (UV) exposure, but, paradoxically, solar visible radiation is used during photodynamic therapy. Treatment involves application of sunscreen to limit UV-induced erythema and application of a photosensitiser pro-drug to the affected areas prior to exposure to continuous daylight for at least 2 hours.
This study, undertaken by the University of Dundee and Ninewells Hospital in Dundee in association with PHE, investigates the nature and levels of UV exposure occurring during daylight photodynamic therapy.
Impact
PHE operates the United Kingdom’s solar monitoring network and collects readings from locations throughout the UK, Republic of Ireland, Cyprus and Gibraltar. Measurements were collated to indicate periods during which it is currently thought that daylight photodynamic therapy would be ineffective at each location. In general, northern locations experienced less useful light levels and also had therapeutic light levels which fell below the minimal threshold value more frequently during the autumn and winter months. However, when looked at on a day-to-day basis, it’s still possible to have several bright sunny days within the autumn and winter months at northern latitudes which would be suitable for therapy.
The research provides clinicians with useful guidance about the times of day that could be scheduled for effective daylight photodynamic therapy, whilst minimising UV exposure. This could be particularly useful if treating high-risk patients, such as those who are immunosuppressed or with a history of skin cancer.
Case study 2: The first UK survey of dose indices from radiotherapy treatment planning computed tomography scans for adult patients
Institute of Physics and Engineering in Medicine (IPEM) topical report.
The challenge
CT (Computed Tomography) scans are an integral part of modern radiotherapy treatments, enabling the accurate localisation of the treatment target and organs-at-risk. The scans also provide tissue density information required for the calculation of dose in the treatment planning system. It’s important to ensure CT exposures are optimised to give the required clinical image quality with radiation doses that are as low as reasonably achievable. However, there is little guidance in the literature on dose levels in radiotherapy CT imaging either within the UK or internationally.
This report, undertaken by a working party of the IPEM Radiotherapy and Diagnostic Radiology Special Interest Groups, including PHE, presents the results of the first UK-wide survey of dose indices in radiotherapy CT planning scans.
Impact
Patient dose indices were collected for prostate, gynaecological, breast, 3D-lung, 4D-lung, brain and head or neck scans. Median values per scanner and examination type were calculated. National dose reference levels and ‘achievable levels’ of CT dose index and scan length were proposed.
Significant variations in dose indices were noted, with head or neck and 4D-lung yielding a factor of 18 difference between the lowest and highest dose scanners. There was also evidence of some clustering in the data by scanner manufacturer, which may indicate a lack of local optimisation of individual systems to the clinical task. Scan protocol adjustments to change dose indices should always be accompanied by a rigorous quality assessment to ensure that the images remain suitable for radiotherapy planning. Providing this data to the UK and wider radiotherapy community is expected to aid the optimisation of treatment planning CT scan protocols.
Case study 3: Risk of suicide after cancer diagnosis in England
The challenge
A diagnosis of cancer carries a substantial risk of psychological distress for a person. As there has not yet been a national population-based study in England of the risk of suicide after cancer diagnosis, PHE, several NHS partners and colleagues from University College London carried out a population-based study using data from the National Cancer Registration and Analysis Service in England, linked to death certification data for 4.7 million people.
Impact
Of the 4.7 million patients with cancer who were studied, 50.3% were men and 49.7% were women. A total of 3.5 million patients in the cohort (74.3%) were aged 60 years or older when their diagnosis was made. A total of 2491 patients (1719 men and 772 women) with cancer were found to have died by suicide, corresponding to a 20% increased risk of suicide compared with the general population. Patients with mesothelioma, pancreatic, oesophageal, and lung cancer had the highest risk. These cancer types tend to be characterised by poor prognosis. Suicide risk was highest in the first 6 months following cancer diagnosis, with the first week after diagnosis being critical.
The increased risk in the first 6 months after diagnosis may indicate an unmet need for psychological support. The increased risk of suicide persisted for 3 years after diagnosis, identifying a period during which cancer care pathways should pay attention to the psychological health needs of the patients. The findings of this study suggest a need for improved psychological support for all patients with cancer, and for attention to modifiable risk factors, such as pain, particularly in specific cancer groups.
Case study 4: Applying behavioural science to increase uptake of the NHS Health Check
The challenge
The NHS Health Check is a national programme for the prevention of non-communicable diseases such as stroke, kidney disease, heart disease, type 2 diabetes and dementia. All adults between 40 and 74 should receive an invitation to an NHS Health Check every 5 years. An important aspect of the programme is to encourage behaviour change for everyone in the general population who has sub-optimal diet or physical activity, and tobacco or alcohol consumption. The programme has increased the detection of risk factors and disease and research shows it has led to small reductions in the risk of cardiovascular disease in the general population. The anticipated uptake level of the programme is 75% but the national average uptake for 2014 to 2019 was 48%. The most common invitation method is a letter from the patient’s GP accompanied by a patient information leaflet, supplied by PHE. The invitation letter template has already been updated on the basis of previous research. This study, undertaken by PHE in association with the University of Oxford and the London School of Economics, was designed to apply behavioural science to the NHS Health Check patient information leaflet.
Impact
A double-blind 3-armed randomised controlled trial was conducted. The new leaflets were shorter (2 pages, instead of 4), one was loss-framed (‘don’t miss out’) and the other was gain-framed (‘make the most of life’). Both were compared with the current national leaflet. There were no significant differences in uptake of the NHS Health Check between patients who received the gain-framed (18.2%), loss-framed (17.4%), or control (17.6%) leaflet with their NHS Health Check invitation letter. Overall, it was concluded that changes to the leaflet were not successful at increasing uptake of NHS Health Checks. This result was generalised across 2 geographical areas, one a metropolitan area and one which encompasses both towns and rural areas. This was the first trial to use behavioural insights in a patient information leaflet in order to influence attendance, as well as the first trial on the NHS Health Check leaflet. The lack of effect was considered surprising, given that behaviourally informed letters have improved the uptake of NHS Health Checks previously. However, the result was considered to be consistent with a body of research which indicated that leaflets might increase knowledge but had no effect on uptake. For ethical reasons, patient information leaflets are still required to be provided hence more work may be required to assess their impact.
Case study 5: From ‘Stoptober’ to ‘Moi(s) Sans Tabac’: how to import a social marketing campaign
The challenge
In 2016, Santé Publique France, the French national public health agency, launched for the first time ‘Moi(s) Sans Tabac’, a positive social marketing campaign inspired by PHE’s ‘Stoptober’ campaign, aimed at triggering mass quit attempts among smokers. Both programmes include a mass-media campaign, national and local cessation-help interventions, and the diffusion of various tools to help smokers quit. The purpose of this joint paper is to analyse the specific national contexts of the 2 programmes and to describe resulting similarities and differences regarding campaign development. Smoking prevalence is about twice as high in France as in the UK, leading to a lower degree of de-normalisation of smoking. Cessation support services are also much more structured in the UK than in France and in particular, the local elements of such services do not exist in France.
Impact
The first iteration of ‘Moi(s) Sans Tabac’ in 2016 benefited from lessons learned from the implementation of Stoptober. Elements such as the roadshow and the quit kit for smoking cessation were taken from the PHE campaign, while all media content was specifically recreated for the French culture and language. Although a large number of French smokers (180,113) signed up for the inaugural ‘Moi(s) Sans Tabac’ in 2016, this figure was lower than that observed for the first iteration of Stoptober. Going forward, Santé Publique France aims to involve more GPs, as 16 % of French doctors were smokers versus only 4 % in England in 1999. Smoking cessation support is mainly provided by tobacco specialists in France while such support in the UK comes from professionals in various fields, so the intention is to engage other types of healthcare professionals in the future. These substantial differences between France and the UK may explain the lower sign up numbers for the first iteration of the campaign. Both Santé Publique France and PHE intend to continue to collaborate on the development of their campaigns.
Case study 6: The first 5 years of Part 2A Orders: the use of powers from court applications to protect public health in England 2010 to 2015
The challenge
Part 2A Orders were introduced in 2010 as the new legal mechanism under the Public Health (Control of Disease) Act 1984 to allow local authorities to apply to a Justice of the Peace for various powers to protect public health. The powers encompass new and emerging infections and non-infectious threats in an ‘all hazards’ approach. Part 2A Orders can be applied for and used against persons (including detention in hospital or other suitable establishment), things or places where voluntary co-operation and other methods to avert a risk or hazard are not possible. One feature of Part 2A Orders is that each order must be reported to PHE. To undertake an online survey aiming to understand the usage of the orders, these reports were used by investigators from St. George’s University of London and PHE to identify the main professionals involved in the application.
Impact
Fifty-five orders had been issued during the period of the study: 29 against persons (28 concerned patients with tuberculosis), 23 against things (22 for seizing tattoo equipment) and 3 against premises. Orders were found to be straightforward to obtain but could be difficult to implement, particularly in relation to persons. Respondents stated that multiple interventions had taken place prior to the application for an order, indicating use as a last resort and the orders were considered to have met the desired outcomes in the majority of cases. The authors concluded that there was no evidence of abuse of the order system but noted that respondents were necessarily those who had originally defined the aims of use of an order and that different responses may have been obtained from physicians or patients.
Case study 7: Developing gender-specific evidence-based standards to improve the health and wellbeing of women in prison in England
The challenge
Of the 85,000 people in prison in England and Wales, approximately 5% are female and the number of women in prison is increasing, more than doubling over the last 25 years, with a high proportion serving short sentences. There are significant health inequalities experienced by women in prison. They face distinct challenges and have particular and complex needs, specifically with regard to their physical and mental health. Although there are gender-specific standards for working with women prisoners, which women’s prisons have to comply with, there are no gender-specific standards for women in prison focusing on the health and wellbeing of this vulnerable group. The purpose of this study, undertaken by PHE as the WHO UK Collaborating Centre for Health in Prisons Programme and in association with the University of Oxford, is to describe the approach taken to develop a set of health and wellbeing standards for the women’s prison estate in England, which can be applied elsewhere. A structured literature review of standard healthcare databases and grey literature was used to inform development of suggested standards. A multidisciplinary expert panel provided consensus on the standards through an online survey and women with a history of contact with the criminal justice system were consulted through consensus groups.
Impact
The process resulted in the development of 6 overarching principles and 122 standards, across 10 topic areas (see table below). These standards are the most extensive that are known to exist for health and wellbeing of women in prison and provide a holistic approach to improving the health and wellbeing of this vulnerable group. A large evidence-based and expert opinion forms the basis of the methodology, ensuring a robust outcome with high validity, acceptability and feasibility. The methodology can be adopted and modified for use elsewhere. The standards themselves will provide support to commissioners and providers of health and prison services and, if implemented effectively, have the potential to contribute to reducing the vast inequalities facing women in prison, not just within the UK but also internationally.
Overarching principles | Key topic areas | Number of standards (total=122) |
---|---|---|
1. The whole prison environment should be focussed on promoting the mental and physical health and wellbeing of all women in prison | General health and wellbeing Mental health, self-harm and suicide prevention |
10 17 |
2. The prison environment for women needs to be trauma-informed | Substance misuse | 10 |
3. User involvement should be integrated into the development and delivery of health and wellbeing programmes within the prison | Violence and abuse Sexual and reproductive health |
5 5 |
4. All women in prison should have access to purposeful activity and time out of cell | Pregnancy and families Older women |
18 21 |
5. A structured programme of peer support should be available to all women | Nutrition and diet | 20 |
6. Prepare for and ensure continuity of care for women on release into the community | Physical activity Weight management |
13 3 |
Case study 8: National mycology laboratory diagnostic capacity for invasive fungal diseases in 2017: evidence of sub-optimal practice
The challenge
A survey of laboratory testing capabilities for systemic fungal pathogens was undertaken in the UK to identify where improved compliance with published standards and guidelines is required and to inform antifungal stewardship. The survey was undertaken by Royal Brompton Hospital & Harefield Hospitals NHS Foundation Trust, Manchester University NHS Foundation Trust, Cambridge University Hospitals NHS Foundation Trust, Leeds Teaching Hospitals NHS Trust, Queen Mary University of London and PHE. The survey captured information from laboratories in the UK on diagnostic capacity for invasive fungal diseases, including identification, serology, molecular diagnostics and susceptibility testing.
Impact
Fifty-two per cent of laboratories providing diagnostic mycology services in the UK responded to the survey. Results indicated that most respondents identified fungal isolates from high risk patients to species level, and that many laboratories could access local susceptibility testing for yeasts. A much smaller proportion could access susceptibility testing for Aspergillus species.
Direct microscopy was only used in about half of the laboratories as a first line investigation on samples where it would be appropriate. A low number of respondents identified yeasts cultured from intravascular lines to species level and even fewer fully identified urine isolates from critically ill patients or the immunocompromised. Therapeutic drug monitoring to reduce toxicity and to ensure that appropriate drug levels are achieved is important for several antifungal drugs but less than half of respondents advised on such monitoring for flucytosine which has a known concentration-toxicity relationship.
The survey highlights that the current level of fungal diagnostic services in the UK is below accepted best practice with an urgent need for improvement across many diagnostic areas including the timely accessibility of fungal biomarkers, susceptibility testing and provision of therapeutic drug monitoring testing. Improvements are important to facilitate the delivery of diagnostic driven antifungal stewardship strategies as well as appropriate management of invasive fungal diseases.
Case studies on healthy environments
- Environmental public health risks in European metropolitan areas
- Setting up a collaborative European human biological monitoring study on occupational exposure to hexavalent chromium
- Deep learning for relevance filtering in syndromic surveillance: a case study in asthma and difficulty breathing
Case study 9: Environmental public health risks in European metropolitan areas
The challenge
The identification and quantification of the public health risks associated with exposure to environmental conditions are important for prioritising policies and interventions that aim to diminish the risks and improve the health of the population. This project used a consistent approach to assess the impact of main environmental risk factors and urban environmental determinants on public health in European metropolitan areas. A number of environmental public health indicators, which are closely tied to the physical and built environment, were identified through stakeholder consultation. Data was collected from 6 European metropolitan areas (Athens, Barcelona, Lisbon, London, Stockholm and Turin) covering the period 2000 to 2014, and a health impact assessment framework enabled the quantification of health effects (attributable deaths) associated with these indicators. The Euro-Healthy project received funding from the European Union’s Horizon 2020 research and innovation programme and involves 16 collaborative partners across Europe, including PHE.
Impact
The greatest mortality impacts were estimated to be associated with long-term exposure to air pollution. The numbers of deaths due to road traffic injuries and those attributed to exposure to road traffic noise were in general similar to each other, while the health benefits associated with urban green spaces mostly outweighed both. Categories of interventions that were recommended in order to reduce environmental public health risks and potentially provide co-benefits, such as reduction of social inequalities, in the areas studied include planning interventions, such as the development of green spaces in urban areas, and traffic management measures that control vehicle flows and pollutant emissions.
The health impact assessment framework used in the study enabled the characterisation and quantification of the environmental public health risks across 6 European metropolitan areas and the identification of specific parts of the areas that required improvements in their environmental conditions. The development of a composite metric for characterising environmental public health quality was also recommended.
Case study 10: Setting up a collaborative European human biological monitoring study on occupational exposure to hexavalent chromium
The Challenge
The EU human biomonitoring initiative (HBM4EU) is a European Joint Programme which aims to harmonise and use biomonitoring to understand human exposure to chemicals in the environment, in occupational settings or through the use of consumer products, together with the related health risks. Its objective is to improve chemical risk management and to support policy in this area. It’s funded by the European Commission and national governments and includes experts from 28 countries, including the UK’s Health & Safety Executive and PHE.
Hexavalent chromium is an important occupational carcinogen and has been shown to cause lung cancer in humans. Exposure to hexavalent chromium may occur in welding, in chromium electroplating and other surface treatment activities such as paint application and removal of old paint containing hexavalent chromium. Hexavalent chromium compounds are listed under the European regulation concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) and all companies using such compounds have to apply for authorisation for their use. More than 100 authorisations for different uses have been requested, meaning that potentially thousands of workers could be exposed.
Impact
The study is collating data on hexavalent chromium internal exposures and early biological effects in occupational settings to be used as scientific evidence for regulatory risk assessment and decision-making under EU chemical legislation and under occupational safety and health legislation. The capability and validity of different human biomonitoring parameters for the specific assessment of chromium exposure are also being evaluated. Information is also being provided on welders’ and platers’ exposure to other relevant metals, especially to nickel and manganese and of chrome platers exposure to mist suppressants containing other harmful substances. The article describes the study protocol of this first human biomonitoring occupational study to be performed concurrently in multiple European countries using harmonised protocols for data gathering, sampling and (chemical) analyses. By combining national standardised surveys, the power of the study and the strength of the findings are greatly enhanced. This allows the comparison of several markers of exposure and effect in a variety of exposure scenarios.
Case study 11: Deep learning for relevance filtering in syndromic surveillance: a case study in asthma and difficulty breathing
The challenge
Syndromic surveillance is described as the real-time (or near real-time) collection, analysis, interpretation, and dissemination of health-related data to enable the early identification in a defined population of the impact (or absence of impact) of potential public health threats. This knowledge then informs the most effective action. The use of internet and social media data for disease surveillance has gained momentum with Twitter data in particular showing promise. The real-time-stream nature of Twitter data could advantage syndromic surveillance activities aimed at early detection of disease outbreaks. However, issues remain such as difficulties in dealing with the relevance of tweets and making maximum use of contextual information. In this study, the University of East Anglia, as part of the NIHR HPRU in Emergency Preparedness and Response, developed with PHE a syndromic surveillance framework using Twitter to monitor asthma and breathing difficulty in England.
Impact
With PHE epidemiologists a list of keywords was developed that may be connected to the symptoms for asthma and difficult breathing and was used to collect tweets that were geolocated to the UK. Deep learning is a technique that teaches computers to learn by example. Various deep learning concepts and computing system models (neural networks) were applied to the tweets. A positive correlation was found between Twitter activity concerning asthma and breathing difficulty, and syndromic surveillance data. However, the full detection capability of Twitter remains to be determined as there were no real-world outbreaks or major incidents during the investigation period. The deep learning methods used enabled the gathering of context and word-similarity information which should prove useful to further define the methods used to extract relevant tweets and could be a powerful feature in an adaptive system for Twitter data collection. Hence this study provides a basis on which to build for the use of Twitter in syndromic surveillance.
Case studies on infectious diseases
- Estimated impact of revising the 13-valent pneumococcal conjugate vaccine schedule England and Wales: a modelling study
- Improving drug treatments for Mycobacterium tuberculosis infection
- Learning from the epidemiological response to the 2014 to 15 Ebola virus disease outbreak
- Metagenomic sequencing at the epicentre of the Nigeria 2018 Lassa fever outbreak
- A probable case of tick-borne encephalitis acquired in England, July 2019
Case study 12: Estimated impact of revising the 13-valent pneumococcal conjugate vaccine schedule England and Wales: a modelling study
The challenge
The pneumococcus is a bacterium of global importance that causes pneumonia, septicaemia and meningitis with many associated deaths, particularly in young children and the elderly. Pneumococcal conjugate vaccines that protect against the development of pneumococcal disease in those who are vaccinated and also prevent transmission of the pneumococcus in the population, resulting in herd immunity, are highly effective but expensive. The booster dose given in the second year of life is thought to be key for maintaining herd immunity. In October 2017, the UK Joint Committee on Vaccination and Immunisation (JCVI) recommended removal of one primary dose of the 13-valent pneumococcal conjugate vaccine from the existing 2+1 schedule (given at 2, 4 and 12 months of age). PHE conducted a mathematical modelling study to investigate the potential impact of a 1+1 (given at 3 and 12 months) schedule on invasive pneumococcal disease and pneumococcal community-acquired pneumonia.
Impact
Our results indicated that any increase in pneumococcal disease by dropping one infant dose would be extremely small such that the current health gains from the pneumococcal conjugate vaccine programme in England and Wales would be preserved. Our findings could help improve overall pneumococcal conjugate vaccine programmatic efficiency by saving on vaccine purchase costs with little adverse impact on disease control. Based on this modelling study, JCVI has already advised dropping one of the infant doses in the UK pneumococcal conjugate vaccines programme.
Our model findings could be applied to other countries with a similar mature pneumococcal conjugate vaccine programme and similar pneumococcal epidemiology to England and Wales.
For countries in regions such as Africa, where pneumococcal disease rates are higher, pneumococcal conjugate vaccines have only recently been introduced, and their impact in vaccinated and older age groups has not yet been fully elucidated. While our modelling results cannot be directly translated into policy in such regions, models such as ours could help in understanding epidemiological trends after pneumococcal conjugate vaccine introduction and in identifying optimal vaccination schedules.
Case study 13: Improving drug treatments for Mycobacterium tuberculosis infection
The challenge
Tuberculosis (TB) is one of the most serious bacterial infections with around 10 million new cases and an average of almost 1.3 million deaths globally in 2017 alone. The development of new drugs for the treatment of infections caused by multidrug-resistant Mycobacterium tuberculosis is a particularly urgent priority. One approach for TB drug development is the re-purposing of existing antibiotics.
Pyrrolobenzodiazepines (PBDs) are a promising class of antibacterial agents that were initially isolated in the 1960s and 70s. More recently some PBDs have shown notable antibacterial activity against multidrug-resistant Gram-positive bacteria and M. tuberculosis. Chemically modified versions of the drugs (conjugates) significantly inhibited the growth of M. tuberculosis. However, most are also toxic to eukaryotic cells because they bind to DNA, potentially limiting their usefulness as drugs for humans or animals. The aim of this study, by Kings College London and PHE, was to synthesize a hybrid compound which retained antibacterial activity yet was not toxic to eukaryotic cells.
Impact
The synthesized compound, compound 3, was designed to have a reduced ability to bind to DNA. Compound 3 did not show any notable toxicity for eukaryotic cells growing in the laboratory at the highest concentration tested, compared to standard versions which were highly cytotoxic. Very encouragingly, compound 3 displayed dose-dependent inhibition of growth of both clinical and laboratory strains of M. tuberculosis.
This is the first report of a nontoxic PBD hybrid with activity against M. tuberculosis and is a starting point for the development of PBD molecules that do not bind DNA so may act as new antibiotics to treat TB.
Case study 14: Learning from the epidemiological response to the 2014 to 2015 Ebola virus disease outbreak
The challenge
A large international response was needed to bring the 2014 to 2015 West African Ebola virus disease outbreak under control. This study, undertaken by the NIHR HPRU on Evaluation of Interventions, in collaboration with colleagues in Nigeria, sought to learn lessons from this epidemic to strengthen the response to future outbreaks of international significance by identifying priorities for epidemiology training and response. Epidemiologists who were deployed to West Africa were recruited and surveyed using an online anonymous questionnaire. Associations between demographics, training, qualifications, and role while in-country were explored alongside respondents’ experience during deployment.
Impact
As there is no central register of epidemiologists deployed as part of the response to outbreaks, professional networks and connections were used to identify participants for this study. Respondents originated in 25 countries worldwide and for many this was their first deployment abroad. The most common tasks carried out while deployed were surveillance, training, contact tracing and cluster investigation.
Over the past 20 years, there has been a rapid growth of Field Epidemiology Training Programmes (FETP) around the world that have graduated over 2550 field epidemiologists. Although there were no major differences between the responses of those who had completed such training prior to deployment and those who had not, the results indicated that nearly two-thirds of those deployed had completed or were completing FETP.
Epidemiologists would value more detailed pre-deployment briefings including organisational aspects of the response. Gaps in technical skills reported were mostly about geographical information systems. Respondents identified the need for future deployees to have greater knowledge about roles and responsibilities of organisations involved in the response, better cultural awareness and leadership and management skills.
Respondents felt that the public health community must improve the timeliness of future outbreak responses and strengthen collaboration and coordination between organisations.
Case study 15: Metagenomic sequencing at the epicentre of the Nigeria 2018 Lassa fever outbreak
The challenge
Lassa fever is an acute viral haemorrhagic illness, first described in 1969 in the town of Lassa, Nigeria. The 2018 Nigerian Lassa fever season saw the largest ever recorded upsurge of cases, raising concerns about the emergence of a strain with increased transmission rate. To understand the molecular epidemiology of this upsurge, PHE, with a range of collaborating partners, including the NIHR HPRU for Emerging and Zoonotic Infections, performed, for the first time at the epicentre of an unfolding outbreak, metagenomic nanopore sequencing directly from patient samples. This approach was required because of the highly variable genome of the target pathogen.
A pilot study was on-going within Nigeria when, at the height of the outbreak, a request for information on circulating strains was made on 28 February by the Nigerian authorities. The pilot study was expedited and the fact that the outbreak was fuelled by the circulating Lassa virus diversity and not by transmission of a new or divergent lineage was already evident by 10 March from the first 7 genomes generated. The final collection of 36 Lassa virus genome sequences generated on-site included representatives of genotypes II and III, further supporting spillover from the natural reservoir as the main source of the outbreak.
Impact
Genomic data and phylogenetic reconstructions were communicated immediately to Nigerian authorities and the World Health Organization to inform the public health response. The conclusions drawn from the first set of genome sequences immediately eased fears of extensive human-to-human transmission and allowed public health resources to be allocated appropriately. The response was focused on intensified community engagement in rodent control, environmental sanitation and safe food storage.
Portable metagenomic sequencing of genetically-diverse RNA viruses on the MinION platform, using samples directly from patients without the need to export material outside of the country of origin and with no pathogen-specific enrichment, was shown to be a feasible methodology enabling real-time characterisation of potential outbreaks in the field.
Case study 16: a probable case of tick-borne encephalitis acquired in England, July 2019
The challenge
The UK has thus far been considered to be free from tick-borne encephalitis, yet in July 2019, a German infant developed serologically diagnosed tick-borne encephalitis following a tick bite in southern England. This is the first report of a probable human case acquired in England and is reported by PHE, together with the Robert Koch Institute and the NIHR HPRU in Emerging and Zoonotic Infections. This report, together with recent confirmation of the presence of the disease-causing virus in ticks in certain areas of England, suggests that the disease could be acquired in parts of England and should be considered in patients experiencing similar symptoms without a confirmed cause.
Impact
This first probable human tick-borne encephalitis virus infection in England and the detection of the virus in ticks in other areas of the country fits with the patchy spread of the infection to new areas already observed in other parts of Europe. In Germany, the number of tick-borne encephalitis endemic districts increased from 129 in 2007 to 161 in 2019. The first cases from the Netherlands were reported in 2016 and a new focus was recently discovered in Denmark following 3 human cases in summer 2019. The virus can spread to new areas through mammalian hosts or migratory birds infested with virus-carrying ticks.
Seroprevalence studies in groups at high risk of tick bites and in the general population, tick sampling and enhanced surveillance of human encephalitis cases without confirmed cause are underway to better understand the human infection risk in areas where the virus was detected in ticks or wildlife. In England, the public health authorities currently assess the risk of tick-borne encephalitis virus infection as very low for the general population and also low for those who may be bitten by ticks in areas where infected ticks are located. PHE continues to promote tick awareness for those spending time outdoors.
Reflection: impact through training
From Adam Roberts, PhD student
Mycobacterium tuberculosis, which is the causative agent of the disease tuberculosis, caused 1.2 million deaths and 10 million cases globally in 2019 alone. Treatments for tuberculosis infection are toxic and lengthy with resistance to the antibiotics becoming increasingly common, so there is a direct need to identify new targets for treatment and develop mechanisms to combat the emergence of antimicrobial resistance. Efflux pumps have, in recent years, been shown to carry out essential macromolecular functions and contribute to antibiotic tolerance in M. tuberculosis. Despite this, efflux pumps and their role in these functions require much more characterisation. My PhD, funded by PHE and partnered with Brighton and Sussex Medical School, is tasked with understanding more about efflux pumps by characterising the unknown function of specific efflux pumps, or their role in antimicrobial resistance. Working primarily at PHE has been incredibly beneficial with the support, knowledge, and networking opportunities provided by the institution.
Working at PHE has allowed me to use the incredible containment level 3 facilities available at PHE and make use of the wide range of instruments and expertise available at Porton. Under the supervision of Dr Joanna Bacon, I have also been able to foster relationships with many different institutions involved in infectious disease research and has allowed me to make use of many novel techniques for my studies.
Due to the lack of clarity regarding efflux pumps in M. tuberculosis, many efflux pump genes remain without a defined role in their function in the cell or their contribution to antibiotic tolerance. As I progress through the final year of my PhD, collaborations with Royal Veterinary College and Brighton and Sussex Medical School, via PHE, have allowed me to utilise an inducible gene repression system, CRISPR interference, to study the function of an essential efflux pump gene in M. tuberculosis.
The current SARS-CoV-2 pandemic was a huge disruption to my studies and caused me to pause my PhD. PHE has been outstanding in supporting me by allowing me to work within COVID-19 serology for the pandemic response. I was able to work in sero-surveillance for 6 months whilst I suspended my PhD. This allowed me to contribute to the studies involved in assessing the proportion of the UK population who harboured antibodies to the virus, allowing me to actively contribute to the pandemic response during my suspension. This gave me great experience in teamwork, serology, and a sense of pride in that I was able to contribute to the fight against SARS-CoV-2. Upon returning to my studies recently, PHE has offered me 6 months of additional funding which will support me in continuing my research.
The post-graduate student committee within PHE has also been incredibly beneficial for me and other students at Porton. As the student representative, I’ve been able to input opinions of mine and other students and be involved in planning the PhD PHE away day, which has been useful in creating a student community within PHE. The group has enabled me to present my work to a large and varied audience and I look forward to giving a seminar to PHE Porton as my research progresses.
I look forward to continuing my studies in characterising efflux pumps in M. tuberculosis with the support of PHE and continuing to foster the relationships and expertise I have been enabled to develop as a result of studying at PHE.
Student lay writing competition
PHE has initiated an annual lay writing competition which is open to any student supported in part or full by PHE. The remit is a piece of writing that is easy to read, understandable by someone with no prior knowledge of the area or a non-scientist, that describes the student’s research and explains how it benefits public health in a maximum of 800 words. Competition is judged by the lay members of PHE’s Research Oversight Group. The winner of the 2020 competition, Samuel Hill, is a PhD student at PHE’s Centre for Radiation, Chemical and Environmental Hazards and his entry is below.
Student lay writing competition winning entry 2020 - Tracking one of asthma’s invisible menaces: fungal spores
Every breath we take contains microscopic particles called mould spores. Luckily, most of us experience no ill effect when we breathe in these spores, but for those with asthma, breathing in certain types of spores may trigger their symptoms.
As different fungi release their spores at different times of the year, it can be helpful to know when and which spores are likely to be in the air. We already know that cold and dry conditions are unfavourable for fungi, and therefore we see very small amounts of spores in the air during winter. As it gets warmer and we move into the warmer and wetter spring season, fungi begin to release their spores, which are then carried by the wind into the air. Spore release increases through the summer, especially when the weather is warm and humid. Levels peak in late summer, before falling back down as the cold winter returns. This ultimately means that we have seasonal patterns in the number and types of spores in the air depending on the time of year.
Asthma also tends to follow a seasonal pattern. In late summer, those with asthma are more likely to experience an asthma attack than at other times of the year. We know this from looking at anonymised information from healthcare centres like hospitals and GP practices. PHE’s real-time syndromic surveillance system allows us to see what symptoms people across England were seeking medical help for the previous day. Coded information from GP appointments (both in-hours and out-of-hours), emergency department visits, NHS 111 calls and ambulance call-outs are used to monitor a range of illnesses including asthma, but also other conditions, such as flu, stroke episodes, and heart attacks. Using this system, we can quickly see if more people are experiencing asthma symptoms than usual and try to determine the cause.
Unfortunately, little is known about the contribution of spores to the increases in asthma symptoms seen at certain times of the year. One of the main problems is identifying the types of fungal spores that are more likely to cause symptoms from the many thousands of spore types in the air. Other asthma triggers, such as air pollution, changing temperature, humidity, infections and pollen also make it difficult to see the effect of spores on asthma. Thanks to the availability of skin prick tests we know that certain fungi such as Alternaria alternata and Cladosporium herbarum can cause allergic effects. However, these are just 2 out of the thousands of species present in the air.
My work aims to use the latest DNA sequencing technologies to better analyse what fungal spores are present in the air over the course of a year. It is difficult to identify the full range of fungal spores using the traditional method of looking at them under a microscope as many spores look the same. By extracting and sequencing the DNA from spores collected within an air sample, it is possible to identify a much greater number of fungi. Comparing this data with seasonal peaks in asthma symptoms from the real-time syndromic surveillance system will enable us to find specific fungi that may be contributing to an increase in asthma symptoms, particularly if the other factors, such as significant air pollution or high pollen counts, are absent.
The combination of fungal DNA sequencing and real-time syndromic surveillance technologies is a first for asthma research. It has the potential to have a significant impact on the management of asthma, improving the health of asthma sufferers while saving healthcare costs. For example, future measures can be taken to limit the exposure of those most vulnerable to the spore types identified as high risk. Public health bulletins, such as those produced for pollen, could be produced to display alerts. These could include recommendations to advise those with asthma and sensitivity to fungal spores to ensure they have their medication available and take measures to take to help reduce their exposure, such as remaining indoors. Similar bulletins for healthcare providers could also ensure they are better prepared for the increasing number of people that may need treatment. If the findings on spore seasonality are combined with weather forecasts, a warning system could be designed to adjust accordingly with the expected conditions. Faster, more rapid ways of identifying these spore types could be designed in the laboratory to help develop a cost-effective routine spore monitoring and warning system.
The effects of asthma are well known, but the contribution of fungal spores is less so. With this work, associations between certain spore types, spore seasonality, and rates of asthma attacks may be able to be identified. This would lead on to future projects and actions working to make significant reductions in asthma-related symptoms and costs.