Over 126 people registered for the Infection and Immunity Network's event on 17 November 2021 which explored how we identify, survey and deal with zoonoses on a local and global scale. The Network is supported by the Elizabeth Blackwell Institute.

Fernando Sanchez-Vizcaino (Bristol Vetenary School) spoke on Updating the epidemiology of canine leishmaniasis in the UK and its implications for human health. Leishmania infantum is a protozoan parasite which causes infantile visceral leishmaniasis in the Mediterranean region and Latin America which infects between 50,000-90,000 people every year, and cutaneous leishmaniasis which affects between 600,000 and 1 million people every year. The parasite is carried by both wild and domestic dogs. Fernando's research applies a One Health informatics approach linking animal, human and environmental data together to provide new understanding of emerging zoonotic infections and how to mitigate their risk. With increased numbers of infected dogs being detected in southern and eastern England, researchers are recommending a strengthening of pet travel legislation that would restrict movement of stray dogs with severe/zoonotic diseases not commonly found in UK and mandatory testing for Leishmania and other severe/zoonotic diseases not commonly found in the UK in dogs before travelling from countries were leishmaniasis is endemic. Veterinarians should also be routinely diagnosing for leishmaniosis to allow for earlier treatment and thus decrease infectivity for both dogs and humans. 

Laura Rivino's talk (School of Cellular and Molecular Medicine) was entitled Deciphering the human T cell response to Dengue virus. Laura's team is interested in understanding how T cells (a type of white blood cell which is essential to the human immune system) contribute to protective immunity and/or immunopathology during viral infection, particularly in the context of Dengue virus infection. Understanding these mechanisms is critical for the development of effective vaccines and therapeutics. Dengue virus (DENV) is a mosquito-borne infection found in tropical and sub-tropical climates worldwide which causes dengue fever; there are four DENV serotypes, meaning that it is possible to be infected four times. Severe dengue is a leading cause of serious illness and death in some Asian and Latin American countries. She and her team are developing a peptide-human leukocyte antigen (HLA, a complex of genes on chromosome 6 in humans which encode cell-surface proteins responsible for the regulation of the immune system) toolkit to track Dengue-specific CD8+ T cells. CD8+, or cytotoxic T cells, are a type of white blood cell that kills cancer cells, cells that are infected (particularly with viruses), or other damaged cells. They found a distinct signature of Dengue virus-specific effector CD8+ T cells, which are key players in steering the immune responses to execute immune functions (i.e. fighting infection). In skin, DENV-specific effector T cells are present at high frequencies and persist as memory cells after resolved infection. 

Joining virtually from Kenya, Eric Fèvre (jointly based at the University of Liverpool and the International Livestock Research Institute in Nairobi) presented on Surveillance for the emergence of zoonoses in intensifying food systems in the tropics. The term "emerging zoonosis" is commonly used to describe newly evolved or previously undetected diseases, but it can also refer to pathogens that are increasing their geographic spread and impact, or moving into human hosts for the first time. Pressures brought about by human-induced changes on the environment, such as urbanisation, are projected to increase the frequency of pathogen emergence in the future. Africa is experiencing massive increases in urban and peri-urban populations. Responding to an increase in food demands, small farm holdings are expanding and growing and food supplies are also being imported from outside local food systems. A greater number of animals, including those obtained from outside the community, inceases the risk of introducing parasites and pathogens that were not previously present in the food chain. Changes in livestock numbers and demands create challenges for farmers that can also contribute to wider healthcare issues, such as antimicrobial resistance. The use of antibiotics for livestock is often based on financial concerns rather than choosing the drug that will best target an infection, causing a rise in the spread of "superbugs", or bacteria, viruses, fungi and parasites which have changed over time and no longer respond to medicines that treat infection. Eric's work applies a One Health approach to the study of zoonoses, through which he and his colleagues try to understand how these diseases behave at the intersection between wildlife, livestock and human health.  

Based in the School of Biological Sciences, Richard Wall talked about Measuring the prevalence of ticks and tick-borne disease in the UK: lessons from large-scale surveillance. Ticks are blood-sucking ectoparasites. Their hosts include all animals (including humans) and their numbers and geographical spread in the UK is increasing. This is likely due to a number of factors including a warmer climate, environmental schemes increasing tick habitats, and sheep being dipped less frequently. The many species of tick which exist act as vectors for a range of pathogens including tick-borne encephalitis and Lyme disease; ticks, in fact, transmit a greater diversity of pathogens than any other arthropod. Ixodes ricinus, or the forest/sheep tick, have been steadily increasing in number in the UK over a 35-year period; this tick carries several pathogens, some of which lead to tick-borne fever, tick-borne encephalitis and tick pyaemia, a staphylococcus infection in lambs which causes abscesses in the tendons, joints, muscles and brain and causes ‘crippled lambs’ with severe lameness and paralysis. Dermacentor reticulatis, or the ornate dog tick, has been moving rapidly in the past ten years; the infection causes canine babesiosis, symptoms for which include fever, weakness, depression, swollen lymph nodes, and an enlarged spleen. Richard and his team set up the Big Tick Project, the first active large-scale surveillance project looking at ticks and their distribution, which signed up hundreds of veterinary practices across the UK to collect tick samples from dogs and cats which were then analysed and mapped. Although the data did not show a high level of pathogens present, continued surveillance is necessary to maintain oversight of tick habitats and disease transmission. 

This event provided further insights into how zoonoses are detected and how researchers across the globe are working to understand how a zoonoses develops, transmits and infects. By studying patterns and learning about the mechanisms that cause diseases, researchers across disciplines and borders are working together to protect, treat and prevent existing and emerging zoonosis infections 

Another speaker from Bristol Veterinary School, Mick Miller spoke on “Where there’s livestock there’s deadstock”: Surveillance for new and emerging diseases via post-mortem examination of farm animals.As a farm animal pathologist, Mick identifies new and emerging diseases through post-mortem examination, a method which is recognised as being more efficient at reaching a diagnosis than other laboratory submissions such as blood and faeces. A post-mortem can identify new strains or changes in endemic diseases already in the UK, new diseases or pathogens, and exotic diseases not seen in the UK. However, not every animal is or can be autopsied, meaning that only a small percentage of animals in the country are being diagnosed this way. Subsidised post-mortem services are available to farmers through partnership with veterinary schools across the country to help ease the process. Bovine spongiform encephalopathy (BSE) is a perfect example of the detection of a new and emerging zoonotic disease which was identified by routine surveillance in 1986. A progressive neurological disorder of cattle that results from infection by an unusual transmissible agent called a prion, BSE (or mad cow disease), is believed to be the agent responsible for the outbreak of variant Creutzfeldt-Jakob disease (vCJD) in humans first described in the UK in 1996. vCJD is a fatal brain disease with an unusually long incubation period measured in years. Animal post-mortem results are fed into a national database maintained by the Animal and Plant Health Agency (APHA) which monitors trends and liaises with surveillance units nationwide, the UK Health Security Agency and the Human Animal Infections and Risk Surveillance (HAIRS) and further afield, depending on the threat identified.  

Andrew Davidson (School of Cellular and Molecular Medicine) has been studying coronaviruses for over 20 years alongside colleague David Matthews, and their lab was one of the first in the UK to conduct research on the SARS-CoV-2, the virus which caused the COVID-19 pandemic. His talk, The role of the furin cleavage site in the SARS-CoV-2 spike protein in viral infection, looked at one aspect of the research he has been conducting to understand the pathogenesis of the virus – how it causes disease, and how it interacts with our bodies – which is critical to the development of diagnostic tools, drugs and vaccines to tackle the virus. Furin is a protease (or "speed-up") enzyme which activates inactive proteins by removing (cleaving) certain sections. SARS-CoV-2 entry requires sequential cleavage of the virus' spike glycoprotein and it has a polybasic insertion at the S1/S2 cleavage site that can be cleaved by furin. Combined ‘omics analysis of SARS-CoV-2 infected cells identified a deletion in the protein furin cleavage site. The furin cleavage site directs cell-type specific infectivity, cell-to-cell fusion and the interaction with neuropilins, a protein receptor active in neurons. The cryogenic electron microscopy structure of the BrisSΔ spike reveals it is in a closed form, but the spike can interact with angiotensin-converting enzyme 2 (ACE2) and antibodies suggesting different openings dynamics to the wild type spike. SARS-CoV-2 virus lacking the S1/S2 furin cleavage site (BrisSΔ) was shed to lower titres from infected ferrets and was not transmitted to cohoused sentinel animals, unlike wild-type virus; deletions in the spike can occur during human infection. These results reveal that the furin cleavage site is an important determinant of SARS-CoV-2 transmission.  

Leah Cowan joined us from the University of Toronto where she presented on Identifying vulnerabilities in fungal pathogens through functional and chemical genomic analyses. Functional genomics efforts are enabled by genome-scale mutant collections of Candida albicans, which is a leading fungal pathogen of humans. Candida species account for 88% of all hospital-acquired fungal infections and cost the health care system over 1 billion USD annually in the United States alone. C. albicansis the primary cause of systemic candidiasis with mortality rates of around 40%, even with current treatments. Her team also uses chemical genomics to map genetic interaction networks that control key virulence traits, and to link biologically active small molecules to their targets. We heard how a focussed analysis of C. albicans essential genes identified candidate antifungal targets, as with the Gln4 glutaminyl-tRNA synthetase and how translation inhibition by rocaglates activates a species-specific cell death programme in C. auris via inhibition of the essential elF4a. Development of fungal-selective inhibitors of antifungal efflux and stress response provides a powerful strategy to advance antifungal drug discovery; chemical genonic and functional genomic analyses provide a powerful strategy to identify vulnerabilities in fungal pathogens that can be leveraged to understand host-pathogen interactions and to guide development of novel therapeutic strategies.  

The event closed with a panel discussion during which speakers answered a few more questions and discussed how climate change is and is expected to affect the number of zoonoses in circulation and their distribution on a global scale.