INSTITUTE OF INFECTION AND GLOBAL HEALTH

ANNUAL 2019 REPORT INTRODUCTION

CONTENTS It gives me great pleasure to introduce this infection and global health threats, and we annual report, as I complete one year as will continue to develop internal and external Dean of Institute. The past 12 months has partnerships to achieve this. 4 Global Change seen the Institute make strong progress Over the past year, the Institute has made against each of its five research challenges, several strategic appointments to support and this report describes some of those 6 Food Security its research challenges, including of both achievements. established and early career researchers. This year’s report also contains a special The Institute has also supported several 8 Antimicrobial Resistance feature to mark the 70th Anniversary of successful Fellowship applications. Career the NHS; several case histories detail the development of all staff and students will 10 NHS at 70 Institute’s contribution to tackling the continue to represent a vital part of our burden of infectious diseases in Merseyside. strategy. 12 Diagnostics Veterinary infection research in Liverpool Finally, I would like to thank all staff, both also has a notably long and distinguished academic and professional services, for history, and a distinctive feature of the 14 Vaccines their continued hard work and exceptional Institute’s strategy is to address its contributions. I hope you enjoy reading challenges by bringing together Liverpool’s 16 Our People this report and I look forward to another medical and veterinary researchers in exciting year ahead. a “One Health” approach to infection. 18 Public Engagement Multidisciplinary working is essential to Professor Nigel Cunliffe comprehensively tackle the world’s major

2017/18 Research Income £10.6M INSTITUTE OF INFECTION AND GLOBAL HEALTH (IGH) MAJOR CHALLENGES Department Department of Clinical Department of 2016/17 of Infection Infection, Microbiology Epidemiology and Biology and Immunology Population Health 2015/16 £10M 1 GLOBAL CHANGE £9.9M Theme 1 Understanding how pathogens cause disease FOOD SECURITY Theme 2 Pioneering diagnostics, treatments and vaccines 2 ANTIMICROBIAL 2014/15 Theme 3 Enhancing food safety and security 3 RESISTANCE £9.3M RCUK Theme 4 Tracking emerging and zoonotic infections £1,977,227 Research Themes Research 4 DIAGNOSTICS Theme 5 Improving the health of pets, working animals and their owners 5 VACCINES Non-UK & other Research The Institute is organised into three departments with cross-cutting research themes. Through them £2,828,748 Awards we are addressing the five major research challenges identified in our strategic plan. 2017/18 Image on cover shows mammalian cells infected with Zika virus. Infected cells appear round Total: £9.1M and slightly detached in comparison with elongated healthy cells. Gaps show where cells have UK Industry been destroyed due to viral infection. Credit: Shona Moore, Postdoctoral Researcher £90,363 UK Charities £2,325,666

UK Govt & Health £1,889,393 MAJOR CHALLENGE 1

Zoonoses in Livestock in Kenya (ZooLinK)

Parts of East Africa are currently experiencing cases of Rift Valley Fever, an GLOBAL CHANGE acute, fever-causing viral disease that is transmitted by insects and usually seen in livestock but can also infect humans. The current cases are thought to result in part from unusual weather patterns that allowed proliferation of the mosquito vector. ZooLinK is a collaborative project that aims to enable Kenya to develop an effective surveillance programme for such zoonotic diseases Rapid climatic, environmental and societal changes are (diseases transmitted between animals and humans). Recent research from the team, led by Professor Eric Fèvre, measured antibodies to the disease in leading to the emergence of new diseases and the spread people in western Kenya, a tropical region where transmission was assumed not of existing ones. The Institute is providing evidence to help to occur. The research showed that while low, there was a risk of local infection and that in particular, certain occupational animal exposures such as working in a predict and mitigate the impacts of climate, environmental, slaughterhouse in this region were particularly risky. During this year’s outbreak and societal change on human and animal health. of Rift Valley Fever in Kenya, at least one slaughterhouse worker contracted the disease and died. The results highlight the need to expand existing climate based risk models to account for occupational risks and animal movement networks, and recommendations have been fed in to national decision making processes in Kenya. Further zoonotic disease surveillance activities are essential to enable early detection of such transmission events. Cook E, et al. PLoS Negl Trop Dis. 2017;11:e0005731

Epidemic of bloodstream infections currently killing around First case of oriental eye Single DNA change 400,000 people worm reported in UK in Salmonella linked each year Researchers have diagnosed the UK’s first to deadly African known case of canine oriental eyeworm in a dog that had been recently imported epidemic from Romania. The disease is caused by a A single genetic change has been The Institute’s Professor Melita Gordon vector-borne parasite (Thelazia callipaeda) identified in Salmonella that is playing a who was involved in the project, and who and is spread by the males of a species of Vapers are vulnerable to key role in the devastating epidemic of first described the epidemics of disease fruit fly Phortica( variegata) that is found in bloodstream infections currently killing caused by ST313 strains in Africa, said: the UK. Documented cases of the disease pneumococcal infection around 400,000 people each year in sub- “The ability of Salmonella strains to cause have been growing across several European Saharan Africa. The collaborative study, led such serious disease leads to devastating countries including France, Italy, Spain, Whilst the impact of tobacco smoking on by Professor Jay Hinton at the University’s and frequently fatal consequences for Greece, Croatia and Romania, but until now health has long been known, the impact of Institute of Integrative Biology, has very young children, and for adults who there have been no recorded cases in the using e-cigarettes is less clear. However, identified a single nucleotide difference may be the chief breadwinners in their UK. Lead author of the report, John Graham- new research by Professor Aras Kadioglu that is unique to the African ST313 strain homes and communities. It is now urgent Brown said: “This case raises awareness of and colleagues has shown that exposure and causes high expression of a virulence that a vaccine is developed to combat this a new imported disease and highlights the to inhaled e-cigarette vapour significantly factor called PgtE that prevents Salmonella dangerous infection.” ongoing risks associated with pet travel and increases colonisation of bacteria in the being killed in the bloodstream. Hammarlöf D, et al. PNAS. 2017;115:E2614-E2623 importation, and the need for vigilance when mouse nasopharynx, making them more examining these animals.” susceptible to invasive pneumococcal Graham-Brown J, et al. Vet Rec. 2017;181(13):346 disease. Increased bacterial adherence to airway lining cells is caused by e-cigarette consultations collected from UK veterinary vapour increasing the level of Platelet- Targeted advice for practices to identify the risk factors for Activating Factor Receptor (PAFR), a deadly rabbit disease flystrike across the nation. molecule which pneumococcal bacteria use it remains difficult for researchers to understand the circumstances One of the key findings was to precisely Assessing the burden of dog bites to stick to airway cells, and subsequently leading up to dog bites, with most studies relying on evidence Flystrike is a serious condition for pet define the impact of temperature on disease invade body tissues and cause disease. collected after bites happen. In a new study researchers have, for rabbits, and is caused by larvae of the green risk. For every 1°C rise in the average local Preventing dog bites is an increasingly recognised public health Professor Kadioglu said: “Our studies show the first time, used YouTube videos to directly observe and analyse bottle fly feeding on the surface of the skin. temperature, there was a 33% increase and political issue with implications for both human and animal health that vaping significantly increases PAFR This can lead to severe tissue damage, and welfare; it is of particular importance in Merseyside which has the dog bites in situ. expression in the mouse nasopharynx, in the risk of flystrike, with risk peaking secondary bacterial infections and may between June and August. Rabbits over highest number of dog-related injuries and deaths in the UK. Lead author of this study Sara Owczarczak-Garstecka said: “Online which is consequently associated with result in death of the animal. It is completely the age of five were also more likely to be Dog bite studies usually rely on hospital records, but research led videos present us with an unexplored opportunity to observe dog increased bacterial colonisation density. preventable and is treatable if identified affected.Professor Alan Radford, who leads by Dr Carri Westgarth has shown that the actual number of dog bites first-hand, something which is just not possible using other As pneumococcal disease is preceded early, however there is a lack of awareness SAVSNET, said: “These results can be used bites may be much higher than hospital records indicate, with only methods. Making more use of this type of shared content for by colonisation of the nasopharynx, vape amongst rabbit owners. induced expression of PAFR may be for targeted health messaging to reduce 0.6% of people in the study who had been bitten requiring hospital research could help us better understand how and why bites occur clinically significant and lead to increased The University’s Small Animal Veterinary the impact of this deadly disease for rabbits, admission. The research also showed that personality type may and contribute to the development of bite prevention strategies.” susceptibility to pneumococcal infection.” Surveillance Network (SAVSNET) team have and also highlight the value of using health be linked to a heightened risk of being bitten by a dog, with people Westgarth C, et al. J Epidemiol Community Health. 2018;72:331-336 published research that analysed electronic records in this way.” of a more anxious disposition more likely to be nipped. However, Owczarczak-Garstecka S, et al. Sci Rep. 2018;8:7147 Miyashita L, et al. Eur Respir J. 2018;51:1701592 health records from over 40,000 pet rabbit Turner R, et al. Prev Vet Med. 2018;153:77-83

4 Institute of Infection and Global Health Institute of Infection and Global Health 5 MAJOR CHALLENGE 2 FOOD SECURITY 1 in 10 people globally lack sufficient food for a healthy, active life. Feeding current and future populations requires a secure and safe supply of food. The Institute is an international leader in food security research, especially through improved control of infectious disease in food producing animals, and improved food safety.

Launch of Launch of HORN £7.8M Network Research with impact: approximately £250M annually. Infectious causes of lameness, including Bovine Digital for the Horn of helping farmers to Dermatitis in cattle and Contagious Ovine February 2018 saw the official launch Africa (HORN) in Nairobi, Kenya, of the £7.8M Global Digital Dermatitis and Footrot in sheep, are project. manage disease Challenges Research Fund (GCRF) One responsible for a significant proportion of all Health Regional Network for the Horn of resistance lameness cases in livestock, and remain one Africa (HORN) project. This multidisciplinary, of the greatest unresolved challenges facing The parasitic liver fluke,Fasciola international partnership will develop a the modern farming industry. hepatica, is a significant cause of network of individuals and organisations disease and production losses in sheep The newly formed Liverpool Livestock across the Horn of Africa that can undertake and cattle worldwide. It is common in Lameness Group is primarily focused on high quality research into the link between the UK and its prevalence is likely to undertaking research into the aetiology, people’s health and wealth, and that of increase as a result of climate change. epidemiology, management and prevention livestock and the environment. of infectious dermatological disorders of the Control of the parasite relies almost The launch brought together partners, Reducing livestock foot in which lameness is the primary clinical exclusively on the use of a limited stakeholders and non-governmental feature. As part of the group’s portfolio of number of drugs; for one of these, lameness organisations to establish the One Health research, Professor George Oikonomou triclabendazole (TCBZ), resistance to Regional Network, and identify key research and Professor Stuart Carter, together the drug is being increasingly reported. Lameness in domesticated ruminants, priorities in the area of One Health. Over with collaborators from the Scottish Rural Research led by Professor Diana including cattle, sheep and goats, both the next four years, the HORN project will: College and the Royal Veterinary College, Williams in 2012 described a field test to compromises farm animal welfare and undertake research capability assessments have received over £1M in funding from detect resistance to TCBZ in populations threatens global food security. of partner Institutes across the Horn of the Biotechnology and Biological Sciences of fluke affecting sheep. Researchers Africa, to assess current and target One Recent studies have suggested that nearly Research Council to study risk factors, then worked with farmers’ organisations Health research capacity; provide training half the dairy cows in the UK face reduced genetics and breeding strategies to reduce in England and Wales to measure the and placements for research support mobility and lameness issues at some the impact of non-infectious claw horn levels of resistance on participating staff; advance the knowledge and skills of point in their life, costing the dairy sector disruption lesions on dairy cattle. farms, and subsequently shared the researchers conducting One Health research; findings with the industry to highlight the undertake basic and applied research in the problem of resistance and to provide area of One Health, through the co-creation microbiome in the transmission of these advice as to how to reduce its impact. Controlling disease of research projects at sandpit events; and diseases, and how earlier establishment create the One Health Regional Network. Using funding from the University’s and improving gut health of a ‘chicken microbiome’ alters the immune Impact Accelerator fund, a study was in chickens system and reduces susceptibility to conducted earlier this year to evaluate infection. Launch of the Centre of Excellence the range of work the University carries out across the food system, if the information and advice provided In many countries, poultry meat and eggs are The research will also seek to determine from production through to consumption as well as public health and to farmers in 2012/13 has helped them an important source of food and nutrition, if indigenous breeds of poultry and modern for Sustainable Food Systems economic impacts. manage resistance on their farms and whether produced in large commercial units hybrid birds differ in their genetics, gut improve control of the disease. with modern breeds, or in small scale flocks microbiome and immunological parameters The IGH food security group led by Professor Jonathan Rushton Work to take concept of the Global Burden of Animal Diseases The evaluation showed that the using indigenous breeds. However, the and establish if these differences can and Professor Jane Hodgkinson supported the launch in March (GBADs) to a programme has begun with a workshop in Paris, led by information provided to the farmers led bacterial zoonotic pathogens, Salmonella be exploited for disease control and 2018 of the University’s Centre of Excellence for Sustainable Food Professor Rushton, which brought together 47 academics working to a change in practice in about half enterica and Campylobacter jejuni, management. Systems (CESFS). The CESFS is a cross faculty initiative directed by in the fields of animal health and the global burden of disease, of the farms, including better choice frequently colonise poultry and consequently Professor Rushton, and is supported by the N8 Agrifood programme. representatives of major development agencies, and key players in The information will be used to develop and application of products other than present a very significant human health risk The Centre has been created in order to address real world issues the private livestock industries. a probiotic to competitively exclude TCBZ and improved knowledge about due to contamination of meat or eggs. affecting both humans and animals, such as climate change, access Salmonella and/or Campylobacter, and will This initiative aims to redefine the landscape in which worldwide the parasite and its transmission. The to safe and sufficient food, and food choice. It will address these Professor Paul Wigley has received over provide both commercial and backyard investment in animal health and welfare is made by building a data evaluation demonstrates the real impact issues via innovative research projects, techniques, and cutting £500K in two grants from the Biotechnology producers with a much-needed management collection and analysis system coordinated at global, national and that engaging key stakeholders in our edge technology and resources, capitalising on strategic cross and Biological Sciences Research Council tool to reduce the disease burden and health sector levels. research can have. disciplinary collaborations. The launch of the Centre showcased to understand the importance of the gut risk associated with poultry products. Rushton J, et al. Lancet. 2018;392:538-540 6 Institute of Infection and Global Health Institute of Infection and Global Health 7 MAJOR CHALLENGE 3

Bacteria adapted to the lungs are easier to kill ANTIMICROBIAL with antibiotics

A study published in Nature Communications has found evidence that as bacteria adapt RESISTANCE to the human body, they can sometimes become more susceptible to antibiotics and therefore easier to kill. Pseudomonas aeruginosa is an ‘opportunistic’ bacterium that can cause serious infection when the Microbes are gaining resistance to the treatments used to body’s normal defences are weakened, control them, making antimicrobial resistance one of the and is a major cause of lung infections in patients with cystic fibrosis. Using models of greatest current threats to human and animal health. long-term lung infection, the team identified The Institute will investigate the clinical and environmental mutations that appeared in the bacterial DNA which led to changes in the ability of factors that drive the evolution and development of resistance, Pseudomonas to survive in the lungs. The and develop novel antimicrobial treatment strategies. mutations enabled the bacteria to attach to lung cells more effectively; however, the same changes also made Pseudomonas more susceptible to antibiotics. Dr Dan Neill was part of the team that led the study, alongside Professor Craig Addressing antibiotic New trial to tackle long to treat the infection for, and doctors Winstanley, Professor Aras Kadioglu and may treat for longer than is necessary, Dr Jo Fothergill, and said: “This study resistance in antibiotic overuse in leading to overuse of antibiotics, which raises hopes that even bacteria that are well contributes to antimicrobial resistance. adapted to the lung environment could be pneumococcal infections hospitalised children combatted with conventional antibiotics, and The BATCH trial will use a personalised may lead to better diagnosis and treatment A new European research project to tackle A new £1.4M national clinical trial to tackle approach to safely reduce antibiotic of Pseudomonas aeruginosa infection in the emergence and spread of drug-resistant antibiotic overuse in hospitalised children duration in children hospitalised with people with cystic fibrosis.” bacteria is underway at the Institute. Funded and thus reduce the spread of antimicrobial bacterial infection, through the use of a by the Joint Programming Initiative on resistance is being led by the Institute and specific blood test called Procalcitonin. Bricio-Moreno L, et al. Nat Commun. 2018;9:2635 Antimicrobial Resistance (JPI-AMR), the Alder Hey Children’s NHS Foundation Professor Enitan Carrol who is project focuses on antibiotic resistance Trust. The ‘Biomarker-guided duration £1.4M leading the study said: “Our work in Streptococcus pneumoniae; a major of Antibiotic Treatment in Children national on diagnostic and prognostic human pathogen causing 1.3 million deaths Hospitalised with confirmed or biomarkers of infection in clinical worldwide annually due to diseases such as suspected bacterial infection’ children with bacterial infection pneumonia, meningitis and sepsis. (BATCH) trial is funded by the National trial over the past five years has Institute for Health Research Health Epidemiological studies have demonstrated generated evidence suggesting Technology Assessment Programme (NIHR that resistance is spread globally by a limited that a personalised approach will lead HTA) and will be conducted across ten to improved safety and quality of care number of particularly successful multi- An interdisciplinary project Chicken or Egg: Drivers sites in the UK. Currently, when children are in hospitalised children with infections, drug resistant pneumococcal clones. It is that will address the gaps in hospitalised with bacterial infections there reductions in the spread of antimicrobial not known however, how these resistant for Antimicrobial knowledge in antimicrobial use are no evidence-based guidelines on how resistance, and reduced time in hospital.” pneumococcal clones are acquired or Resistance in Poultry in and the development of AMR in spread globally. India (DARPI) the whole broiler supply chain The €1.6M three year project brings ‘Inspirational’ tuberculosis Dr Tom Wingfield, who is leading studies with colleagues at Harvard University and in the UK, Peru and Nepal that fight poverty Socios en Salud, Professor Gerry Davies together world leading researchers in the The emergence of Antimicrobial Resistance to control TB. carried out a Phase II clinical trial in Lima, Karolinska Institute, the Institute of Infection (AMR) is a major threat to human and animal research highlighted at £3M award Peru which doubled the dose of rifampicin, Immunology, Hannover and the Royal health. It affects livestock productivity, Treatment of TB, caused by the bacterium parliamentary debate showing that higher doses accelerated Institute of Technology Stockholm, with the impacting farmer livelihoods, food security Mycobacterium tuberculosis, is long and elimination of tuberculosis bacteria and Bacterial Pathogenesis and Immunity Group and safety. Poultry is the fastest growing Liverpool’s world-leading infectious arduous, lasting at least six months and did not result in any safety problems. at University of Liverpool. Professor Aras livestock sector in India, supplying an diseases research has been highlighted involving combinations of four antibiotics. project that will address the gaps in The trial also showed that the higher the Kadioglu who Heads the Group said: “We affordable source of protein. However, at a parliamentary debate on ending Rifampicin is the key drug in achieving a knowledge by characterizing the use concentration of rifampicin in the blood the know that vaccination has decreased AMR there is evidence that AMR of significance tuberculosis (TB). Louise Ellman, Labour successful cure and patients with bacterial and drivers for antimicrobial use and the better the response, and that many patients among vaccine-covered pneumococcal to human health is highly prevalent within MP for Liverpool, Riverside spoke at the strains that are resistant to it require strains, but AMR now emerges by development of AMR in the whole broiler on standard doses probably had suboptimal the poultry industry, but the practices and House of Commons debate in June to draw treatment with more and much older drugs expansion of non-vaccine covered strains supply chain in three of the main poultry- concentrations. These results suggest that pressures which inform antimicrobial use attention to the collaborative work being led for three times longer at much greater cost. of pneumococci. The goal of our project is producing states of India. It will be the first higher doses of rifampicin should be urgently and select for AMR in poultry production are by the University of Liverpool and Liverpool to understand the genetic and functional study in India to link and make visible social However, since its introduction in the 1970s studied in Phase III trials as part of a shorter, not understood. School of Tropical Medicine to tackle properties of these AMR clones with the aim and economic behaviours which contribute there has been concern that the dose of more effective treatment for TB patients of targeting and stopping their transmission Professor Nicola Williams and collaborators to antimicrobial use with AMR selection the disease. She went on to talk in detail rifampicin in TB is not optimised, raising everywhere. in the carrier population.” have been awarded a £3M Newton Funded and transmission in an intensive animal about the PreDiCT-TB project being led by the possibility that it could be used at much Velásquez G, et al. Am J Respir Crit Care Med. project to undertake an interdisciplinary production system. Professor Gerry Davies and the work of higher doses to shorten treatment. Working 2018;98:657-666

8 Institute of Infection and Global Health Institute of Infection and Global Health 9 Tracking and preventing Tackling chronic lung than patients infected with other strains. Improving the diagnosis In collaboration with clinicians in Liverpool, HIV transmission infections in cystic fibrosis Professor Craig Winstanley and and management of brain Dr Jo Fothergill have developed diagnostic Infections NHS The UK has a relatively small HIV epidemic of ~100,000 people. Cystic Fibrosis (CF) affects over 9,000 PCR assays for identification of the LES and In 2016, the number of new diagnoses declined for the first time people in the UK alone, and patients with other UK epidemic strains of P. aeruginosa. Infections of the brain, such as meningitis since records began over three decades ago, mainly as a result CF require lifelong healthcare. Chronic The NHS clinicians use these tests to (inflammation of the brain membranes) and of reduced HIV transmission among men who have sex with lung infections due to Pseudomonas make informed decisions about patient encephalitis (inflammation of the brain itself) men (MSM). aeruginosa are the major cause of morbidity segregation to avoid cross infection. This are major causes of death and disability and mortality associated with CF. It is very AT 70: HIV care has achieved a remarkable success in the UK: over 90% has led to a significant reduction in the across the UK. Over the last 15 important that patients are kept free of people diagnosed with HIV are accessing antiretroviral treatment proportion of patients infected with years, the University of Liverpool’s from infection with P. aeruginosa for (ART) and are virally suppressed. Professor Anna Maria Geretti’s the LES in Liverpool. Further Brain Infections Group, led by as long as possible because once work is contributing to the fundamental understanding that collaborations with clinicians at Professor Tom Solomon, has CELEBRATING a chronic infection is established, suppressing HIV replication with ART is both beneficial to patients’ both the adult and children’s been conducting research it is never eradicated, and the health and effective in preventing HIV transmission. CF units in Liverpool, using to address this through earlier the infection, the worse the THE INSTITUTE’S genomic and microbiological BrainInfectionsUK; this is a The Europe-wide PARTNER study provided an affirmative answer patient prognosis. approaches, have also helped us to £10M portfolio of studies, funded to two key questions: Does effective treatment prevent HIV The University of Liverpool has played better understand the characteristics by the NIHR and MRC, running CONTRIBUTION transmission among couples that engage in unprotected sexual the main role in recognising the important of transmissible strains, the way that P. across a network of 70 NHS Trusts. intercourse? Does the protection apply equally to heterosexual contribution in CF of a limited number aeruginosa evolves and adapts during couples and couples formed by MSM? Not a single case of HIV Working with Public Health England, the of epidemic (transmissible) strains of chronic lung infections (including the TO THE NHS transmission occurred within heterosexual and MSM couples in the Group showed that the most common cause of P. aeruginosa, in particular the Liverpool switch to antibiotic resistance), and the PARTNER study. Some of the initially HIV-negative partners in some viral encephalitis in the UK is herpes simplex Epidemic Strain (LES), identified in the 1990s influence onP. aeruginosa virulence of other couples became HIV-positive during follow-up. However, using virus, but that autoimmune encephalitis caused at Alder Hey Children’s Hospital. Patients microorganisms in the CF lung microbiome. phylogenetics, Professor Geretti demonstrated that the viruses of by the body’s own defences attacking the infected with the LES suffer greater morbidity Williams D, et al. Microb Genom. 2018;4 the two partners were not related and that transmission did not brain, is also important. More recently the The Institute is committed to helping occur within the couple. Group has shown that viruses are also now the most common cause of meningitis in the UK, These results underline the importance of diagnosing HIV early and reduce the burden of infection in with a significant health economic impact. starting treatment promptly. Yet, despite many advances, around Merseyside. As the NHS turns 70 12% of people living with HIV remain undiagnosed, and about 42% For both meningitis and encephalitis, delays this year, we look back at some of the of HIV diagnoses continue to occur late in the disease course. in diagnosis and treatment lead to worse outcomes. Working closely with patients and Professor Geretti’s group is investigating ways of improving the public, especially the Encephalitis Society inspiring research the Institute has diagnosis of infection with HIV, as well hepatitis B and hepatitis C. and Meningitis Research Foundation, the Research ranges from pioneering new diagnostic platforms that carried out in conjunction with the Group has examined where the delays occur, allow sensitive and rapid virus detection at point of care using a and found that many patients were not being NHS to make real progress in the drop of blood collected by fingerprick, to outreach initiatives among treated quickly enough, because doctors were the homeless to understand how improvements in diagnostics fight against infectious diseases. failing to recognise the condition or were and therapeutics can benefit the most vulnerable and excluded wasting time with unnecessary tests. The populations in our society. Liverpool Group led the production of national Rodger A, et al. 22nd International AIDS Conference, Amsterdam, the Netherlands, guidelines, and through their implementation July 2018 patient management and outcomes have Aldridge R, et al. Thorax 2018;73:557-564 been improved. Solomon T, et al. J Infect. 2012;64:347-73 McGill F,et al. J Infect. 2016;72:405-38

Developing bedside because conventional which are expensive and take hours for Improving the DNA detection in blood and also allows for better public health blood cultures take over 24 hours to a result. Research on the underlying cerebrospinal fluid by PCR. surveillance and assessment of the impact diagnostic tests generate a result. molecular mechanisms has also enabled of introducing new vaccines. The test was management of The research demonstrated the feasibility of the development of new assays for sepsis, recommended in the National Institute for sepsis Research at the University of Liverpool whole blood PCR testing for MCD diagnosis. which form the key technology platform meningococcal disease for Health and Care Excellence (NICE) has developed and successfully evaluated Professor Carrol evaluated the method in for routine point-of-care tests to be used guideline in 2010: Meningitis (bacterial) and Sepsis is a bacterial infection of the a straightforward diagnostic test method for Meningococcal disease (MCD) is a a “real-life” clinical settings, as opposed in clinical settings. meningococcal septicaemia in under 16s: blood that causes whole body inflammation bacterial blood infections. The pioneering major cause of morbidity and mortality to simply using laboratory samples, and recognition, diagnosis and management. and is the leading cause of death worldwide. research, led by Professor Cheng-Hock Thanks to this research, there are in children and adults worldwide. The demonstrated that the meningococcal PCR It affects 18 million people, is increasing by Toh, demonstrated that a simple optical test now established UK and international University of Liverpool, through the late test significantly increased the diagnostic The children recruited by Professor Carrol 1.5% each year and 30% of cases die from that can be conducted during routine testing laboratory standards in place. In 2010 Professor Tony Hart, has undertaken sensitivity in children presenting to Alder between 1997 and 1999 contributed 25% it. A major problem is that prompt diagnosis of coagulation is an effective diagnostic, a spinout company was formed to ground-breaking meningococcal research Hey Children’s Hospital from 31% to 88%, of patients to a multi-centre European of sepsis is difficult. Early diagnosis is crucial prognostic and monitoring marker for sepsis exploit four patents and incorporate since 1977. Under Professor Hart’s establishing this test as the gold standard study which conducted the first whole to avoid clinical complications, secure that can be routinely applied in clinical the technology into a point-of-care supervision, Professor Enitan Carrol in for confirming cases of MCD. genome screening of confirmed MCD. This appropriate antibiotic treatment and thus settings. It can detect sepsis at an earlier device suitable for all clinical settings. collaboration with the Meningococcal study demonstrated the importance of The outcome of better diagnosis is better can be life-saving. There is a pressing stage which enables earlier diagnosis and The company, Sepsis Ltd, has Reference Unit, which provides a national host genetic variation in the regulation of management and therefore, impact on need for rapid detection systems that can treatment, and is at least as sensitive as two attracted £1.45M of investment. diagnosis and surveillance service, complement activation. indicate bacterial infection at the patient existing sepsis biomarker measurements evaluated the impact of meningococcal health and welfare of patients, and on Toh CH, et al. Blood. 2002;100:2522-9 practitioners. Improved case confirmation Davila S, et al. Nature Genetics. 2010;42:772-776

10 Institute of Infection and Global Health Institute of Infection and Global Health 11 MAJOR CHALLENGE 4 DIAGNOSTICS

Many people and animals remain untreated for infectious diseases because of a lack of accurate, affordable and available diagnostic tests. The Institute is undertaking research to develop New pen-side test for liver leaving farmers a very small period of time Diagnosis of urogenital new diagnostic tests for diseases of humans and animals, as well to administer it. As a result, many farmers infections in low resource as improving existing diagnostic tests. fluke in development end up blanket treating their cattle and sheep leading to growing resistance to the settings Liver fluke is a common parasite which is common treatments. growing in prevalence across the UK. The Sexually transmitted infections (STIs) and Researcher Dr Tessa Walsh has developed parasite infects sheep and cattle and has other urogenital infections cause a major a pen-side test based around lateral significant implications for the productivity of burden of disease worldwide. Long-term flow technology (similar to that used for the UK’s agricultural sector. Current methods complications include increased risk of the home pregnancy test) which could for testing for liver fluke infection are both HIV acquisition and transmission, pelvic soon be made available to farmers for costly and time consuming, and the window inflammatory disease, cervical cancer, Diagnostic delays in meningitis use on their farms. Equipped with an within which treatment can be given is short, pregnancy complications, and invasive easy to use testing kit, farmers will be neonatal infections. Meningitis, a brain infection, is a devastating illness that causes able to pin point which animals require death and disability in the UK and worldwide. The first major the treatment, reducing their costs and Most low- and middle-income countries paper looking at the causes and consequences of meningitis in reducing the spread of resistance to manage genital infections when symptoms the UK has found that viruses are the most common cause of the treatments used to control fluke. are reported, however, many women with meningitis in adults and cause substantial long-term ill health. The team has recently been awarded a urogenital infections do not have symptoms, The study also found that the management of many patients £23,500 Biotechnology and Biological and such asymptomatic infections can also with meningitis is sub-optimal. Diagnosis of meningitis was Sciences Research Council follow-on-fund cause the above complications. pathfinder grant to continue the work. often delayed due to unnecessary brain scans being performed Professor van de Wijgert’s team conducted before lumbar puncture – which is the essential investigation to a study in Kigali, Rwanda, aimed at improving determine the cause of the illness. Recommendations in national STI and urogenital infection control in high guidelines urge doctors to perform a lumbar puncture within the risk women by introducing diagnostic first hour in patients with suspected meningitis unless the patient point-of-care tests (POCTs) for the most has specific features which make it unsafe to do so. Being able to common infections. POCTs are designed quickly determine which bacteria or virus is causing the illness is for use in clinic and outreach settings, in essential for the appropriate treatment of patients. the absence of a laboratory. The POCTs Lead author on the study Dr Fiona McGill said: “Diagnosing a greatly improved case-finding and infection specific cause of meningitis quickly is key to getting the right management in these women compared to treatment. Rapid diagnostics will enable appropriate treatment syndromic management, and most POCTs to be given in a timely manner to those who need it, and allow performed well compared to gold-standard patients who don’t need treatment to be discharged quicker.” testing. These results were shared with McGill F, et al. Lancet Infect Dis. 2018;18(9):992-1003 the Rwanda Ministry of Health and other key stakeholders and with the WHO team responsible for STI control guidelines.

Development of a whether the meningitis is of bacterial or viral Major new global and disability globally. There is relatively origin. Symptoms of both can be similar, little global research expertise in tackling novel blood test to but bacterial meningitis requires urgent brain infections project them. For many brain infections appropriate The three-year, £2M diagnose meningitis treatment with antibiotics for the best therapies exist, but doctors fail to diagnose, project will establish possible outcome. launched and thus treat them properly. a NIHR Global Health A new commercial blood test is being This test will help Research Group on Brain Project lead Dr Mike Griffiths said: “Due Funding has been secured from the National To tackle this, the new Global Health developed to improve the diagnosis and doctors to rule out Infections, which will be to a fear of ‘missing’ bacterial meningitis, Institute for Health Research (NIHR) to Research Group will link Liverpool, with its management of patients with suspected led by Professor Tom doctors can end up giving unnecessary bacterial meningitis improve the management of devastating outstanding reputation in brain infections meningitis. The £1.6M project, which is Solomon in partnership antibiotics to patients who are really more quickly and reduce brain infections in low and middle income research, to the internationally renowned funded by the Medical Research Council and with seven leading suffering from viral meningitis. This test will unnecessary antibiotic countries. The three-year, £2M project will Warwick Centre for Applied Health Research industrial partner Fast Track Diagnostics, research organisations. help doctors to rule out bacterial meningitis treatment. establish a NIHR Global Health Research and Delivery, and to leading research could also help cut unnecessary antibiotic more quickly, reducing unnecessary Group on Brain Infections, which will be led institutes in Malawi, India and Brazil. The treatment – a practice that is contributing to antibiotic treatment, shorten in-patient stay by Professor Tom Solomon in partnership overall aim is to improve the diagnosis of the growing antimicrobial resistance crisis. and reduce the burden on health care”. with seven leading research organisations. acute brain infections in adults and children A key decision for doctors is to decide Acute brain infections, such as meningitis in these countries, to guide treatment and £2M Award and encephalitis, are a major cause of death improve outcomes.

12 Institute of Infection and Global Health Institute of Infection and Global Health 13 MAJOR CHALLENGE 5

Developing a vaccine for considered unfeasible because, while in the bloodstream, the trypanosome surface animal Trypanosomiasis structure constantly changes such that no VACCINES antibody can become effective. African animal trypanosomiasis (AAT) is a livestock disease caused by blood parasites In a new £801K Biotechnology and Biological spread by tsetse flies, and is endemic in 37 Sciences Research Council funded study, sub-Saharan countries. AAT causes chronic Dr Andrew Jackson and colleagues will Vaccines are the single most effective method to anaemia and severe loss of condition, evaluate a panel of novel vaccine candidates resulting in death of the animal if untreated. for AAT, focusing on proteins expressed by reduce the burden of infectious diseases in humans the parasite only while it inhabits the tsetse and animals, but many major diseases lack The Food and Agriculture Organization of fly, which are typically invariant but produce the United Nations considers AAT to “lie at strong immune responses. Dr Jackson said: effective vaccines for their control. The Institute is the heart of Africa’s struggle against poverty” “The potential commercial application of undertaking research to improve the effectiveness of with 50 million cattle at risk and billions AAT vaccines is enormous, and the likely of dollars lost in agricultural productivity positive effect on animal health and livestock current vaccines and drive the development of new annually. Resolving AAT is an enormous productivity across Africa and South America vaccines for major diseases of humans and animals. challenge; vaccines have always been would be profound.”

First child vaccinated with typhoid Liverpool leads new conjugate vaccine in Africa Zika vaccine project

History has been made in the fight against typhoid fever this year A major new collaborative project has as the first child in Africa was vaccinated using a new generation begun to develop a Zika virus vaccine that of typhoid vaccines. The clinical trial in Malawi is being led by is suitable for use in pregnancy. Supported Professor Melita Gordon and the Malawi-Liverpool-Wellcome Trust by a £4.7M award from Department of Health Clinical Research Programme, and will recruit and vaccinate over and Social Care, and managed by Innovate 24,000 children in Blantyre, Malawi. The goal of the trial is to assess UK, the new project aims to take two new the efficacy and cost-effectiveness of a new typhoid conjugate vaccine candidates through to a clinical trial vaccine (TCV) in African children. TCVs are the first major advance in in humans within the next three years. typhoid vaccines in a generation. They have been found to improve Pregnant women continue to be the immunological response and memory, with the promise of increasing population at highest risk following Zika virus vaccine efficacy from around 55% to over 90%. infection as the virus can cause severe fetal “This clinical trial is the culmination of over 20 years of research birth defects. However, no approved vaccine focused on Salmonella disease here in Malawi,” said Professor or treatment is currently available. Gordon. “Our teams of health workers, our local scientists, and our The research is being led at the Institute longstanding partners in the Malawi Ministry of Health and College by Professor Neil French and Dr Lance of Medicine are tremendously excited to see the impact our research Turtle through the Centre for Global Vaccine could finally have for health. We’re ready to go, and really feel like Research. Professor French said: “Although Africa is watching us, with hope.” Typhoid vaccination field team the current Zika outbreak has slowed, there remains a significant risk of fetal abnormality when pregnant mothers become infected, and the changing climate raises the Rotavirus vaccine benefits young children in many countries in Africa to be greatest among the most deprived Centre for Global This year has seen the culmination of several possibility of major epidemics occurring in and Asia. Our findings strongly advocate for populations despite lower vaccine uptake in important studies for the Centre, which have previously unaffected parts of the world. vulnerable populations in the incorporation of rotavirus vaccine into these areas. Vaccine Research led to new avenues of research and also A ready to use vaccine would dramatically the childhood immunisation programmes of informed public health. As members of the reduce the threat that we face from Zika.” Lead author Dr Dan Hungerford said: “For Malawi and Merseyside countries with high rates of diarrhoea deaths, GCRF funded IMPRINT (Immunising Pregnant infants in the most deprived communities and support continued use in such countries Women and Infant Network), we are at the A new study has shown that rotavirus of Merseyside, the hospitalisations averted where a vaccine has been introduced.” centre of an international collaboration to vaccination reduced infant diarrhoea deaths for acute gastroenteritis was double that in The new project aims to take prevent disease in mothers and their new- by a third in rural Malawi, and provides the Meanwhile a study from Merseyside the least deprived communities. Therefore, two new Zika vaccine candidates born babies. Funding through this network first population-level evidence from a low- led by the Institute in collaboration with if we prioritise increasing vaccine uptake in through to a clinical trial in humans has led to a fellowship award for Dr Shadia income country that rotavirus vaccination Public Health England, has demonstrated the most deprived populations the rotavirus within the next three years Khandaker to better understand Group B saves lives. that rotavirus vaccine has reduced vaccine is likely to give the greatest health Streptococcus immunity, and a project award hospitalisations, outpatient attendances and benefit and can contribute to reducing health Professor Nigel Cunliffe, who led the study to Dr Qibo Zhang to investigate the maternal GP visits for diarrhoea since its introduction inequalities.” published in Lancet Global Health, said: whooping cough vaccination and impact on in the national immunisation programme in £4.7M Award “Rotavirus remains a leading cause of severe Bar-Zeev N, et al. Lancet Glob Health. 2018;6:e1036–44 infant response. diarrhoea and death among infants and 2013. Importantly, vaccine impact was found Hungerford D, et al. BMC Med. 2018;16:10

14 Institute of Infection and Global Health Institute of Infection and Global Health 15 Academic OUR PEOPLE 66 Staff 171 Professional 53 Services Staff

Our Institute continues to be a reflection of the excellent work of our dedicated team Postdoctoral of staff and students, all working to further the understanding, diagnosis, treatment 52 Researchers and prevention of today’s prevalent and emerging infectious diseases affecting “Doing my PhD in IGH has humans and animals. We continue to encourage and support the next generation of been a fantastic experience, not researchers through our active Postgraduate Society and Post-Doctoral Association, only due to the excellence of the which run training and career progression activities through the year. Postgraduate Students academics and fellow students 144 that I’ve met here but also because of the opportunity to create profound relationships. Through the challenging nature of my work I have become more creative, skilled and confident. All of which has been invaluable for my personal Some of our new Fellows MARCUS BLAGROVE SHADIA KHANDAKER MAYAH WARDEH Marcus was recently Shadia has been awarded Mayah has been awarded development and has certainly appointments improved my professional path.” MICHAEL ABOUYANNIS appointed as Tenure Track a two -year post-doctoral a Fellowship from the Michael joins the Institute as Fellow after working in the Fellowship from IMPRINT, Biotechnology and Biological Arturo Hernandez Colina, a Wellcome Trust Clinical PhD Institute as a postdoctoral a network focusing on Sciences Research Council, PhD Student fellow primarily working on scientist. His research maternal and neonatal through which she will Academic Staff the epidemiology of infectious interests lie in investigating immunisation, funded by the develop a network model diseases. His academic vector competence for arboviruses, Medical Research Council / Biotechnology to investigate sharing, transmission and PEERS DAVIES experience includes HIV particularly the effect of temperature on and Biological Sciences Research Council emergence of pathogens between host Peers joins the Institute research at the Infectious Diseases Institute virus transmission, to identify regions at Global Challenges Research Fund. species. The research will utilise existing as a Senior lecturer in Uganda, and an MDR-TB national risk from invasive or endemic viruses. Shadia’s Fellowship is addressing Group data to examine networks between different in Livestock Health prevalence survey in Malawi. He is also interested in the potential for B Streptococcal pathogenesis and host species and help to identify potential future and Welfare and is viruses to adapt to different conditions, immunity, bringing together collaborators emerging pathogens. based at Leahurst. CHARALAMPOS ATTIPA and consequently, the risk they may pose from Bangladesh, Imperial College London, Professional CATHERINE WILSON His research interests Charalampos is a Diplomate in the future. and the University of Liverpool. Catherine is a veterinary Services Staff have focused on production limiting of the American College of KHUZWAYO JERE BENEDICT MICHAEL surgeon and first year infectious diseases of sheep as well Veterinary Pathology with Khuzwayo is a Wellcome Ben is a Senior Clinical Wellcome Trust Clinical PhD NATASHA LAMB as antibiotic usage and resistance in a special research interest Trust Training Fellow based Research Fellow at the Fellow currently based at the Natasha has re-joined cattle and sheep production systems. in zoonotic infections. in Malawi at the College of Institute and an Honorary Malawi-Liverpool Wellcome the Institute as a He is currently responsible for the His academic experience Medicine and at the Malawi- Consultant Neurologist Trust Clinical Research Management Services emerging ‘iceberg’ diseases of sheep includes veterinary pathology, canine Liverpool Wellcome Trust at the Walton Centre. Programme, Blantyre, Malawi. Her PhD Administrator after project funded by the Agriculture and leishmaniosis, zoonotic vector borne Clinical Research Programme. His research focuses on investigates the epidemiology of E. coli and completing her Horticulture Development Board. He infections and diagnostics. Charalampos He previously worked as a postdoctoral neuro-immunological responses to infection, non-typhoidal Salmonella in Malawi at a apprenticeship with works with a network of farmers and joints the Institute as a Wellcome Trust scientist at the Institute and has been in collaboration with Harvard University, and household level, determining the prevalence the Institute in 2014. Natasha will be industrial collaborators, primarily in Clinical PhD fellow working on zoonotic recently appointed as Tenure Track Research the clinical management of central nervous of these bacteria and the antimicrobial working closely with The Centre for the commercial sheep sector, seeking parasitic infections. Fellow. Khuzwayo’s research investigates system infections. resistance determinants which they carry Global Vaccine Research, providing innovative approaches to emerging NATALIE BEVERIDGE how rotaviruses evolve in nature and in samples taken from humans, livestock, administrative support to various health and production challenges. HANNAH ROSE VINEER Natalie is a newly appointed characterises immune responses induced domestic animals, peri-domestic wildlife and academic staff members and taking on a SIOBHAN MOR Academic Clinical Lecturer, by rotavirus vaccination in infants from low- Hannah is a newly appointed the environment. wide range of tasks across the Institute. Tenure Track Research Siobhan is an infectious and was previously a Clinical income settings. Fellow and was previously a DANIEL WOOTTON disease epidemiologist Fellow at the Institute. In 2014 NAHIDA MIAH postdoc at Bristol Veterinary Daniel is a Consultant from Australia and has she moved to Liverpool for Nahida joined the Institute School. Her research interests Respiratory Physician at joined the Institute as a clinical training in Infectious in August 2017 as a Core include modelling the impact Aintree University Hospital Reader in One Health. Diseases, based at the Royal Liverpool Technician. As well as “I’m proud to be a of environmental change on parasites and was appointed to work A veterinary scientist by University Hospital. Natalie’s research providing laboratory infecting livestock and wildlife, and applied with the Institute as a Senior original training, she did her PhD on interests include mucosal and T cell member of the Institute; and technical assistance parasitology to improve food security and Clinical Research Fellow in cryptosporidiosis in children in Uganda immunology, pneumococcal disease we’re doing exciting science and to staff and students in conservation. Infection. His interest is in acute respiratory at Tufts University in the United States. and HIV. there is a real sense of community here. the Department of Clinical Infection, tract infection – in pneumonia. She will be based in Addis Ababa That’s all down to my colleagues and Microbiology & Immunology, she uses where she will be leading the Ethiopian the way we collaborate together; they’re genomic and molecular techniques to hub of the HORN project. what make it enjoyable to work here.” provide support to the Gram-negative Bacterial Pathogens research group. Nicola Beesley, Postdoctoral Researcher

16 Institute of Infection and Global Health Institute of Infection and Global Health 17 Public Engagement work in Brazil

Researchers from the Institute have been working alongside Fiocruz PUBLIC and Saúde Criança in Brazil to develop workshops for parents with children who have microcephaly caused by infection with Zika virus. PhD student Raquel Medialdea Carrera has been leading the project in Brazil, which brings families together with physical and musical ENGAGEMENT therapists to help their children reach their full potential, and also to share our current research into the virus with parents. The work has been funded by Wellcome Trust.

PPI Panel

The Institute’s Public and Patient Involvement Panel (PPI) has been running for three years now, and has reviewed and PhD student crowned provided assistance on over 30 research proposals. From third in FameLab Spain commenting on patient questionnaires to advising on the feasibility of studies, the panel has helped Institute researchers FameLab is an international competition to secure funding and strengthen their studies, and will which celebrates effective science continue to play an important role in our research. communication in young scientists. Institute PhD student Raquel Medialdea Carrera, who gave a passionate and engaging talk about Ebola, was crowned third in the national final Summer School of FameLab Spain. Watched by a 400-strong audience, Raquel performed alongside Our summer school for 16-17 year olds interested in a career in seven other finalists in front of the King and research is now its fourth year, and has gone from strength to Queen of Spain at the event in Madrid. strength. This year we had an overwhelming number of applications and selected 16 students from across Merseyside to join us for a diverse range of activities, from hands on laboratory experience to careers talks from PhD students, and even a spot of crafting new vaccines with pipe cleaners and glitter!

IGH Podcast launched Engaging with food workers in Kenya Outbreak in a box!

Researchers at the Institute have Researchers looking at disease risks in animals entering the food Our popular Bug Terror activity, which sees begun delivering a monthly podcast chain have been engaging with slaughterhouse workers in Kenya. As researchers stage an interactive outbreak scenario series, covering the breadth of well as feeding back results and advice from the studies to the larger for participants, has been made into a resource pack research at the institute. The community, the team have also been investigating occupational for anyone to use. Styled as a board game, the box podcast will give researchers at the risk of disease spread to workers and have gone on to gain funding contains everything you would need to teach people Institute, from PhD students to senior to provide personal protective equipment to the 750 workers in about the role of an epidemiologist in an outbreak academics, the opportunity to share this region. These have been distributed alongside much needed situation in a fun and hands on manner! their research with a much wider information on animal welfare during slaughter, and recent funding audience. The podcasts will focus on has been awarded to assess the impact of this engagement. our five major research challenges, and can be found on our website.

Infectious fun at artworks. The Institute delivered an activity called Bad Bugs vs. Good Bugs: Make a Bluedot Festival Microbe!, which gave visitors the chance to see bacteria grown from everyday Staff and students from the Institute have items and to make their own petri dish taken part in the 2018 Bluedot Festival at filled with crafted bacteria. It was also a Jodrell Bank. Set against a backdrop of great opportunity to introduce people to the iconic Lovell Telescope in Cheshire, the research undertaken at the Institute Bluedot 2018 combined music with a in the fight against disease causing ground-breaking programme of live science microorganisms. experiments, expert talks and immersive

18 Institute of Infection and Global Health Institute of Infection and Global Health 19 Some of our major funders: Contacts Institute of Infection and Global Health University of Liverpool 8 West Derby Street Liverpool L69 7BE

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Institute Dean Professor Nigel Cunliffe

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Institute Departments Department of Infection Biology Professor Diana Williams

Department of Clinical Infection, Microbiology and Immunology Professor Neil French

Department of Epidemiology and Population Health Professor Rob Christley

A SANOFI COMPANY We would like to thank the following people for contributing images to this publication: Shona Moore (Front Cover), Hussain Ebrahim (page 3 & 9), Jonathan Grigg (page 4), Eric Fèvre (page 5), John Graham-Brown (page 5), Matthew Baylis (page 6), Alan Bannister (page 7), George Oikonomou (page 7), Craig Winstanley (page 9), Ben Michael (page 12), Tessa Walsh (page 13), Sabin Vaccine Institute/Thoko Chikondi (page 15).