Dr Dan Horton


Associate Dean Research and Innovation (FHMS), Reader In Veterinary Virology
MA VetMB MSc PhD FHEA MRCVS DipECZM

Academic and research departments

School of Veterinary Medicine.

Biography

Areas of specialism

Veterinary Science

My qualifications

1999
MA Zoology
University of Cambridge
2002
Vet MB
University of Cambridge
2005
MSc Wild Animal Health
Royal Veterinary College and Institute of Zoology, London
2009
PhD
University of Cambridge
2014
Diplomate of the European College of Zoological Medicine (Wildlife Population Health sub-speciality)
European College of Zoological Medicine
2016
Graduate Certificate in Higher Education
University of Surrey

Research

Research interests

Supervision

Postgraduate research supervision

My teaching

My publications

Publications

Louisa Elizabeth Wallace (2020)Dengue virus antagonism of the Aedes aegypti IMD immune response. University of Surrey

Dengue virus (DENV) is the most significant arthropod-borne virus (arbovirus) of humans, primarily transmitted by Aedes aegypti mosquitoes. Currently there are no specific therapeutics and the existing vaccine exhibits limited efficacy. Therefore, vector control remains the best approach to manage disease spread. We previously demonstrated that DENV-2 infection does not induce innate immunodeficiency (IMD) signalling in the Ae. aegypti Aag2 cell line, recapitulating in vivo data from other groups. Furthermore, prior infection with DENV-2 reduces IMD signalling activation by classical immune stimuli. This project aimed to identify DENV-2 antagonist(s) responsible for this immune inhibition using an RT-qPCR-based screening platform in which IMD signalling is stimulated in cells expressing DENV-2 proteins individually. Our results identified NS4A as a tentative antagonist, which can now be used to enhance our understanding of Ae. aegypti antiviral immunity by investigating virus-host interactions. The study of vector immunity is hampered by the lack of tools such as antibodies and cell lines. Our group previously created CRISPR-Cas9 knockout Aag2 cell lines, which lack genes essential in the innate immune pathways. These knockout cell lines were created from clonally selected Aag2 cells derived from the heterogeneous parental cell line, and this report also describes the final characterisation of these clones. Results confirm that the cells are embryonic in origin, which confounded our sex analysis. Aag2 clones were confirmed to be persistently infected insect-specific viruses, cell fusing agent virus and Phasi Charoen-like virus. Transfection efficiencies were also determined for the clones of interest. Finally, mutations introduced by CRISPR-Cas9 were characterised in cells derived from one of the clonally selected lines, with one clone identified as the intended mutant, however the IMD pathway-deficient cell clones were determined as wild type. Ultimately insights into vector antiviral immunity may contribute towards development of transmission-incompetent mosquitoes, thereby reducing the global burden of dengue.

Daniel L. Horton, Sarah Lumley, LAURA HUNTER, Kirsty Emery, Roger Hewson, Anthony R. Fooks, Nicholas Johnson (2021)Detection of Rift Valley Fever Virus RNA in Formalin-Fixed Mosquitoes by In Situ Hybridization (RNAscope®), In: Viruses13(6)1079 MDPI

Rift Valley fever virus (RVFV) causes a zoonotic mosquito-borne haemorrhagic disease that emerges to produce rapid large-scale outbreaks in livestock within sub-Saharan Africa. A range of mosquito species in Africa have been shown to transmit RVFV, and recent studies have assessed whether temperate mosquito species are also capable of transmission. In order to support vector competence studies, the ability to visualize virus localization in mosquito cells and tissue would enhance the understanding of the infection process within the mosquito body. Here, the application of in situ hybridization utilizing RNAscope® to detect RVFV infection within the mosquito species, Culex pipiens, derived from the United Kingdom was demonstrated. Extensive RVFV replication was detected in many tissues of the mosquito with the notable exception of the interior of ovarian follicles.

DL Horton, AC Banyard, DA Marston, E Wise, D Selden, A Nunez, D Hicks, T Lembo, S Cleaveland, AJ Peel, IV Kuzmin, CE Rupprecht, AR Fooks (2014)Antigenic and genetic characterization of a divergent African virus, Ikoma lyssavirus, In: JOURNAL OF GENERAL VIROLOGY95pp. 1025-1032 SOC GENERAL MICROBIOLOGY
Emma Taylor, Victor Del Rio Vilas, Terence Scott, Andre Coetzer, Joaquin M Prada, Gholami Alireza, Nasr A Alqadi, Atika Berry, Bassel Bazzal, Abdelaziz Barkia, Firuzjon Davlyatov, Firoozeh Farahtaj, Khaouther Harabech, Paata Imnadze, Fazia Mahiout, Mohammed Ismael Majeed, Vitalii Nedosekov, Louis Nel, Hassan Rich, Abderazak Soufi, Radovan Vodopija, Nenad Vranjes, Valentina Sanchez Picot, Daniel Horton (2021)Rabies in the Middle East, Eastern Europe, Central Asia, North Africa: Building, In: Journal of Infection and Public Health14(6)pp. 787-794 Elsevier Ltd

The Middle East, Eastern Europe, Central Asia and North Africa Rabies Control Network (MERACON), is built upon the achievements of the Middle East and Eastern Europe Rabies Expert Bureau (MEEREB). MERACON aims to foster collaboration among Member States (MS) and develop shared regional objectives, building momentum towards dog-mediated rabies control and elimination. Here we assess the epidemiology of rabies and preparedness in twelve participating MS, using case and rabies capacity data for 2017, and compare our findings with previous published reports and a predictive burden model. Across MS, the number of reported cases of dog rabies per 100,000 dog population and the number of reported human deaths per 100,000 population as a result of dog-mediated rabies appeared weakly associated. Compared to 2014 there has been a decrease in the number of reported human cases in five of the twelve MS, three MS reported an increase, two MS continued to report zero cases, and the remaining two MS were not listed in the 2014 study and therefore no comparison could be drawn. Vaccination coverage in dogs has increased since 2014 in half (4/8) of the MS where data are available. Most importantly, it is evident that there is a need for improved data collection, sharing and reporting at both the national and international levels. With the formation of the MERACON network, MS will be able to align with international best practices, while also fostering international support with other MS and international organisations.

R Suu-Ire, L Begeman, A Banyard, A Breed, C Drosten, E Eggerbauer, C Freuling, L Gibson, H Goharriz, Daniel Horton, D Jennings, I Kuzmin, D Marston, Y Ntiamoa-Baidu, S Sbarbaro, D Selden, E Wise, T Kuiken, A Fooks, T Müller, J Wood, A Cunningham (2018)Pathogenesis of bat rabies in a natural reservoir: comparative susceptibility of the straw-colored fruit bat (Eidolon helvum) to three strains of Lagos bat virus, In: PLOS Neglected Tropical Diseases.12(3)e0006311 Public Library of Science

Rabies is a fatal neurologic disease caused by lyssavirus infection. People are infected through contact with infected animals. The relative increase of human rabies acquired from bats calls for a better understanding of lyssavirus infections in their natural hosts. So far, there is no experimental model that mimics natural lyssavirus infection in the reservoir bat species. Lagos bat virus is a lyssavirus that is endemic in straw-colored fruit bats (Eidolon helvum) in Africa. Here we compared the susceptibility of these bats to three strains of Lagos bat virus (from Senegal, Nigeria, and Ghana) by intracranial inoculation. To allow comparison between strains, we ensured the same titer of virus was inoculated in the same location of the brain of each bat. All bats (n = 3 per strain) were infected, and developed neurological signs, and fatal meningoencephalitis with lyssavirus antigen expression in neurons. There were three main differences among the groups. First, time to death was substantially shorter in the Senegal and Ghana groups (4 to 6 days) than in the Nigeria group (8 days). Second, each virus strain produced a distinct clinical syndrome. Third, the spread of virus to peripheral tissues, tested by hemi-nested reverse transcriptase PCR, was frequent (3 of 3 bats) and widespread (8 to 10 tissues positive of 11 tissues examined) in the Ghana group, was frequent and less widespread in the Senegal group (3/3 bats, 3 to 6 tissues positive), and was rare and restricted in the Nigeria group (1/3 bats, 2 tissues positive). Centrifugal spread of virus from brain to tissue of excretion in the oral cavity is required to enable lyssavirus transmission. Therefore, the Senegal and Ghana strains seem most suitable for further pathogenesis, and for transmission, studies in the straw-colored fruit bat.

DANIEL LEO HORTON, Lorraine McElhinney, CM Freuling, Denise Marston, AC Banyard, H Goharrriz, EMMA WISE, Andrew C. Breed, G Saturday, J Kolodziejek, E Zilahi, MF Al-Kobaisi, N Nowotny, T Mueller, A. R. Fooks (2015)Complex epidemiology of a zoonotic disease in a culturally diverse region: phylogeography of rabies virus in the Middle East, In: PLoS Neglected Tropical Diseases9(3)e0003569 Public Library of Science

The Middle East is a culturally and politically diverse region at the gateway between Europe, Africa and Asia. Spatial dynamics of the fatal zoonotic disease rabies among countries of the Middle East and surrounding regions is poorly understood. An improved understanding of virus distribution is necessary to direct control methods. Previous studies have suggested regular trans-boundary movement, but have been unable to infer direction. Here we address these issues, by investigating the evolution of 183 rabies virus isolates collected from over 20 countries between 1972 and 2014. We have undertaken a discrete phylogeographic analysis on a subset of 139 samples to infer where and when movements of rabies have occurred. We provide evidence for four genetically distinct clades with separate origins currently circulating in the Middle East and surrounding countries. Introductions of these viruses have been followed by regular and multidirectional trans-boundary movements in some parts of the region, but relative isolation in others. There is evidence for minimal regular incursion of rabies from Central and Eastern Asia. These data support current initiatives for regional collaboration that are essential for rabies elimination.

EMMA WISE, Denise Marston, AC Banyard, H. Goharriz, D Selden, N MACLAREN, T Goddard, N. Johnson, Lorraine McElhinney, Adam Brouwer, James N Aegerter, GC Smith, DANIEL LEO HORTON, Andrew C. Breed, A. R. Fooks (2017)Passive surveillance of United Kingdom bats for lyssaviruses (2005–2015), In: Epidemiology and infection145(12)pp. 2445-2457 Cambridge University Press

Passive surveillance for lyssaviruses in UK bats has been ongoing since 1987 and has identified 13 cases of EBLV-2 from a single species; Myotis daubentonii. No other lyssavirus species has been detected. Between 2005 and 2015, 10 656 bats were submitted, representing 18 species, creating a spatially and temporally uneven sample of British bat fauna. Uniquely, three UK cases originate from a roost at Stokesay Castle in Shropshire, England, where daily checks for grounded and dead bats are undertaken and bat carcasses have been submitted for testing since 2007. Twenty per cent of Daubenton's bats submitted from Stokesay Castle since surveillance began, have tested positive for EBLV-2. Phylogenetic analysis reveals geographical clustering of UK viruses. Isolates from Stokesay Castle are more closely related to one another than to viruses from other regions. Daubenton's bats from Stokesay Castle represent a unique opportunity to study a natural population that appears to maintain EBLV-2 infection and may represent endemic infection at this site. Although the risk to public health from EBLV-2 is low, consequences of infection are severe and effective communication on the need for prompt post-exposure prophylaxis for anyone that has been bitten by a bat is essential.

Denise Marston, RJ Ellis, DANIEL LEO HORTON, I Kuzmin, EMMA WISE, Lorraine McElhinney, AC Banyard, C Ngeleja, J Keyyu, S Cleaveland, T Lembo, CE Rupprecht, A. R. Fooks (2012)Complete Genome Sequence of Ikoma Lyssavirus, In: Journal of virology86(18)pp. 10242-10243 American Society for Microbiology

Lyssaviruses (family Rhabdoviridae ) constitute one of the most important groups of viral zoonoses globally. All lyssaviruses cause the disease rabies, an acute progressive encephalitis for which, once symptoms occur, there is no effective cure. Currently available vaccines are highly protective against the predominantly circulating lyssavirus species. Using next-generation sequencing technologies, we have obtained the whole-genome sequence for a novel lyssavirus, Ikoma lyssavirus (IKOV), isolated from an African civet in Tanzania displaying clinical signs of rabies. Genetically, this virus is the most divergent within the genus Lyssavirus . Characterization of the genome will help to improve our understanding of lyssavirus diversity and enable investigation into vaccine-induced immunity and protection.

DANIEL LEO HORTON, Mashair Z Ismail, ES Siryan, Abdul Raheem A Wali, HE Ab-dulla, EMMA WISE, K Voller, G Harkess, Denise Marston, Lorraine McElhinney, SF Abbas, A. R. Fooks (2013)Rabies in Iraq: trends in human cases 2001-2010 and characterisation of animal rabies strains from Baghdad, In: PLoS neglected tropical diseases7(2)pp. e2075-e2075

Control of rabies requires a consistent supply of dependable resources, constructive cooperation between veterinary and public health authorities, and systematic surveillance. These are challenging in any circumstances, but particularly during conflict. Here we describe available human rabies surveillance data from Iraq, results of renewed sampling for rabies in animals, and the first genetic characterisation of circulating rabies strains from Iraq. Human rabies is notifiable, with reported cases increasing since 2003, and a marked increase in Baghdad between 2009 and 2010. These changes coincide with increasing numbers of reported dog bites. There is no laboratory confirmation of disease or virus characterisation and no systematic surveillance for rabies in animals. To address these issues, brain samples were collected from domestic animals in the greater Baghdad region and tested for rabies. Three of 40 brain samples were positive using the fluorescent antibody test and hemi-nested RT-PCR for rabies virus (RABV). Bayesian phylogenetic analysis using partial nucleoprotein gene sequences derived from the samples demonstrated the viruses belong to a single virus variant and share a common ancestor with viruses from neighbouring countries, 22 (95% HPD 14-32) years ago. These include countries lying to the west, north and east of Iraq, some of which also have other virus variants circulating concurrently. These results suggest possible multiple introductions of rabies into the Middle East, and regular trans-boundary movement of disease. Although 4000 years have passed since the original description of disease consistent with rabies, animals and humans are still dying of this preventable and neglected zoonosis.

DANIEL LEO HORTON, AC Banyard, Denise Marston, EMMA WISE, D Selden, A Nunez, D Hicks, T Lembo, S Cleaveland, AJ Peel, I Kuzmin, CE Rupprecht, A. R. Fooks (2014)Antigenic and genetic characterization of a divergent African virus, Ikoma lyssavirus, In: Journal of general virology95(Pt 5)pp. 1025-1032

In 2009, a novel lyssavirus (subsequently named Ikoma lyssavirus, IKOV) was detected in the brain of an African civet (Civettictis civetta) with clinical rabies in the Serengeti National Park of Tanzania. The degree of nucleotide divergence between the genome of IKOV and those of other lyssaviruses predicted antigenic distinction from, and lack of protection provided by, available rabies vaccines. In addition, the index case was considered likely to be an incidental spillover event, and therefore the true reservoir of IKOV remained to be identified. The advent of sensitive molecular techniques has led to a rapid increase in the discovery of novel viruses. Detecting viral sequence alone, however, only allows for prediction of phenotypic characteristics and not their measurement. In the present study we describe the in vitro and in vivo characterization of IKOV, demonstrating that it is (1) pathogenic by peripheral inoculation in an animal model, (2) antigenically distinct from current rabies vaccine strains and (3) poorly neutralized by sera from humans and animals immunized against rabies. In a laboratory mouse model, no protection was elicited by a licensed rabies vaccine. We also investigated the role of bats as reservoirs of IKOV. We found no evidence for infection among 483 individuals of at least 13 bat species sampled across sites in the Serengeti and Southern Kenya.

Emma Taylor, Ashley C Banyard, Hervé Bourhy, Florence Cliquet, Hildegund Ertl, Christine Fehlner-Gardiner, Daniel L Horton, Reeta S Mani, Thomas Müller, Charles E Rupprecht, Matthias J Schnell, Victor Del Rio Vilas, Anthony R Fooks (2019)Avoiding preventable deaths: The scourge of counterfeit rabies vaccines, In: Vaccine37(17)pp. 2285-2287 Elsevier Ltd

Rabies is a feared global disease, largely due to the extreme case-fatality rate, which approaches 100% once a patient becomes ill [4]. The true burden of disease remains undefined, but rabies causes tens of thousands of human deaths annually and is responsible for major economic losses, including dog vaccination costs in excess of US$130 million, and US$512 million in livestock deaths in rabies-endemic countries. After exposure, rabies virus causes an acute, progressive fatal encephalitis, which is prevented with timely post-exposure prophylaxis (PEP). Pre-immunisation in populations at risk, using modern, safe and efficacious cell culture vaccines, also prevents rabies. Where the disease burden is greatest, vaccines are not always readily available, and they can be prohibitively expensive. Rabies cases in vaccinated individuals are becoming increasingly recognised [6]. The challenge of ineffective vaccines is complex and multifactorial but could be part of an apparent growing global trend for counterfeit vaccines [2]. The World Health Organization (WHO) defines counterfeit medicines, including vaccines, as products containing either incorrect, little or no active ingredient, which are marketed and sold as authentic medicines. Such products are illegal if the contents have been altered deliberately and the authorisation forged. The increasing availability and administration of counterfeit rabies vaccines, especially for PEP, may result in otherwise preventable deaths. In 2015, the WHO, the World Organisation for Animal Health, and the Food and Agriculture Organization of the United Nations, in partnership with the Global Alliance for Rabies Control, proposed the global goal of zero human deaths as a result of dog-mediated rabies, by 2030. This goal is supported by a strategic plan, aiming to save lives, reduce costs, and enable clear communications on the validation of canine rabies elimination in endemic countries.

Helen L Brown, Jade L Passey, Maria Getino, Isabella Pursley, Piyali Basu, Daniel L Horton, Roberto M La Ragione (2020)The One Health European Joint Programme (OHEJP), 2018–2022: an exemplary One Health initiative, In: Journal of medical microbiology69(8)pp. 1037-1039 Microbiology Society

Overview One Health is an increasingly popular approach used to tackle complex health problems. The One Health concept recognizes that human health is tightly connected to the health of animals and the environment. Although the related fields are now more aware of the benefits of collaborative working, the full benefits have not yet been realized as research efforts are often focussed on just one of these health domains. To address regional and global issues such as foodborne zoonoses (FBZ), antimicrobial resistance (AMR) and emerging infectious threats (ET), there must be transdisciplinary collaboration between the health domains, in addition to active dialogue between scientists and international policy makers. This editorial introduces the One Health European Joint Programme (OHEJP) as an example of a One Health initiative. Zoonoses, AMR and their global burden Zoonoses are infectious diseases that can be transmitted directly or indirectly between humans and animals. Although the severity of zoonotic infections varies, their global impact is undisputable. The World Bank estimates that just six zoonotic disease outbreaks between 1997 and 2009 led to a global economic loss of US$ 80 billion [1]. This high cost is due to medical costs, loss of individual productivity and restrictions on trade and movement during outbreaks. Despite improvements in the management and treatment of zoonotic outbreaks, high disease burdens caused by zoonotic pathogens continue to be reported globally. These problems have been amply demonstrated recently by the SARS-CoV-2 pandemic. Although it is still too soon to fully assess the total economic and societal cost of this virus, recent publications, such as Nicola et al. [2] have begun to highlight just how widespread the impact of a truly global zoonotic disease can be. Alongside zoonoses, AMR is a growing international issue. The World Health Organization (WHO) has listed AMR as one of the ten greatest global health threats in 2019 [3]. AMR is defined as the ability of microorganisms to survive the effect of antimicrobial drugs, hindering not only our ability to treat infectious diseases, but also to perform medical procedures requiring prophylactic antibiotic administration. It has been predicted that by 2050, the number of deaths due to unresponsive infections will reach 10 million annually, with the associated costs being estimated at US$ 100 trillion [4]. Increased and inappropriate use of antimicrobials has contributed to the development and spread of AMR, which can be transmitted between humans, animals and the environment. The history of the ‘One Health’ concept The origins of One Health go as far back as 1855, when Rudolf Virchow founded comparative pathology, which could be seen as the origin of the One Health concept. Building upon this, Calvin W. Schwabe argued in the twentieth century against compartmentalization in medical research, using the term ‘One Medicine’. The term One Health was then popularized in 2004 by the Wildlife Conservation Society at a conference in New York [5], and its use has continued to evolve since then, fostering the revival of comparative medicine (Fig. 1, and reviewed in Gibbs [6]). One Health has now been adopted by the WHO [7], the Food and Agriculture Organization (FAO) [8] and the World Organization for Animal Health (OIE) [9].

Claude T Sabeta, Denise A Marston, Lorraine M McElhinney, Daniel L Horton, Baby M N Phahladira, Anthony R Fooks (2020)Rabies in the African Civet: An Incidental Host for Lyssaviruses?, In: Viruses12(4) MDPI

In South Africa, canid rabies virus (RABV) infection is maintained in domestic and wildlife species. The identification of rabies in African civets raised the question of whether this wildlife carnivore is a potential reservoir host of RABVs of direct and ancestral dog origin (dog-maintained and dog-derived origins) with an independent cycle of transmission. Genetic analyses of African civet nucleoprotein sequences for 23 African civet RABVs and historically published sequences demonstrated that RABVs from African civets have two origins related to dog and mongoose rabies enzootics. The data support observations of the interaction of civets with domestic dogs and wildlife mongooses, mostly in Northern South Africa and North-East Zimbabwe. Within each host species clade, African civet RABVs group exclusively together, implying intra-species virus transfer occurs readily. The canid RABV clade appears to support virus transfer more readily between hosts than mongoose RABVs. Furthermore, these data probably indicate short transmission chains with conspecifics that may be related to transient rabies maintenance in African civets. Hence, it is important to continue monitoring the emergence of lyssaviruses in this host. Observations from this study are supported by ongoing and independent similar cases, in which bat-eared foxes and black-backed jackal species maintain independent rabies cycles of what were once dog-maintained RABVs.

Mashair Z Ismail, Najlaa K Al-Hamdi, Ali N Al-Amery, Denise A Marston, Lorraine McElhinney, Emma Taylor, Victor Del Rio Vilas, Thani M Dadan, Anthony R Fooks, Daniel L Horton (2020)Quantifying and mapping the burden of human and animal rabies in Iraq, In: PLoS neglected tropical diseases14(10)e0008622 Public Library of Science

Rabies was first reported in ancient Iraqi civilizations, yet it remains a poorly quantified and important public health threat in the region. Efforts to control rabies in Iraq including dog population control, and vaccination of livestock and dogs, have increased since 2010. Officially reported data on human rabies, dog bites, and animal rabies cases between 2012 and 2017 are analysed here to assess the effect of existing control efforts, to inform future strategies, and to highlight gaps in surveillance and reporting. The results of molecular characterization of 32 viruses from animal cases from throughout Iraq are presented, to improve the understanding of rabies dynamics in the animal reservoir. Although annual numbers of reported human cases were lower in the period between 2012 and 2017 than prior to 2010, human cases continue. There was a distinct gender and age bias among human cases with nine cases in males for every one female and twice as many cases in children than adults. Spatial clustering analysis and phylogenetic evidence suggests rabies is endemic throughout the country, with no regional variation in risk, but better surveillance and reporting is required to underpin control strategies.

Lineke Begeman, Richard Suu-Ire, Ashley C Banyard, Christian Drosten, Elisa Eggerbauer, Conrad M Freuling, Louise Gibson, Hooman Goharriz, Daniel L Horton, Daisy Jennings, Denise A Marston, Yaa Ntiamoa-Baidu, Silke Riesle Sbarbaro, David Selden, Emma L Wise, Thijs Kuiken, Anthony R Fooks, Thomas Müller, James L N Wood, Andrew A Cunningham (2020)Experimental Lagos bat virus infection in straw-colored fruit bats: A suitable model for bat rabies in a natural reservoir species, In: PLoS neglected tropical diseases14(12)e0008898 Public Library of Science

Rabies is a fatal neurologic disease caused by lyssavirus infection. Bats are important natural reservoir hosts of various lyssaviruses that can be transmitted to people. The epidemiology and pathogenesis of rabies in bats are poorly understood, making it difficult to prevent zoonotic transmission. To further our understanding of lyssavirus pathogenesis in a natural bat host, an experimental model using straw-colored fruit bats (Eidolon helvum) and Lagos bat virus, an endemic lyssavirus in this species, was developed. To determine the lowest viral dose resulting in 100% productive infection, bats in five groups (four bats per group) were inoculated intramuscularly with one of five doses, ranging from 100.1 to 104.1 median tissue culture infectious dose (TCID50). More bats died due to the development of rabies after the middle dose (102.1 TCID50, 4/4 bats) than after lower (101.1, 2/4; 101.1, 2/4) or higher (103.1, 2/4; 104.1, 2/4) doses of virus. In the two highest dose groups, 4/8 bats developed rabies. Of those bats that remained healthy 3/4 bats seroconverted, suggesting that high antigen loads can trigger a strong immune response that abrogates a productive infection. In contrast, in the two lowest dose groups, 3/8 bats developed rabies, 1/8 remained healthy and seroconverted and 4/8 bats remained healthy and did not seroconvert, suggesting these doses are too low to reliably induce infection. The main lesion in all clinically affected bats was meningoencephalitis associated with lyssavirus-positive neurons. Lyssavirus antigen was detected in tongue epithelium (5/11 infected bats) rather than in salivary gland epithelium (0/11), suggesting viral excretion via the tongue. Thus, intramuscular inoculation of 102.1 TCID50 of Lagos bat virus into straw-colored fruit bats is a suitable model for lyssavirus associated bat rabies in a natural reservoir host, and can help with the investigation of lyssavirus infection dynamics in bats.

Daniel L Horton, Andrew C Breed, Mark E Arnold, Graham C Smith, James N Aegerter, Lorraine M McElhinney, Nick Johnson, Ashley C Banyard, Robert Raynor, Iain Mackie, Matthew J Denwood, Dominic J Mellor, Sue Swift, Paul A Racey, Anthony R Fooks (2020)Between roost contact is essential for maintenance of European bat lyssavirus type-2 in Myotis daubentonii bat reservoir: 'The Swarming Hypothesis', In: Scientific reports10(1)pp. 1740-1740 Nature Research

Many high-consequence human and animal pathogens persist in wildlife reservoirs. An understanding of the dynamics of these pathogens in their reservoir hosts is crucial to inform the risk of spill-over events, yet our understanding of these dynamics is frequently insufficient. Viral persistence in a wild bat population was investigated by combining empirical data and in-silico analyses to test hypotheses on mechanisms for viral persistence. A fatal zoonotic virus, European Bat lyssavirus type 2 (EBLV-2), in Daubenton's bats (Myotis daubentonii) was used as a model system. A total of 1839 M. daubentonii were sampled for evidence of virus exposure and excretion during a prospective nine year serial cross-sectional survey. Multivariable statistical models demonstrated age-related differences in seroprevalence, with significant variation in seropositivity over time and among roosts. An Approximate Bayesian Computation approach was used to model the infection dynamics incorporating the known host ecology. The results demonstrate that EBLV-2 is endemic in the study population, and suggest that mixing between roosts during seasonal swarming events is necessary to maintain EBLV-2 in the population. These findings contribute to understanding how bat viruses can persist despite low prevalence of infection, and why infection is constrained to certain bat species in multispecies roosts and ecosystems.

E. HASANOV, S. ZEYNALOVA, M. GELEISHVILI, E. MAES, E. TONGREN, E. MARSHALL, A. BANYARD, L. M. MCELHINNEY, A. M. WHATMORE, A. R. FOOKS, DANIEL HORTON (2017)Assessing the impact of public education on a preventable zoonotic disease: rabies, In: Epidemiology and Infection146(2)pp. 227-235 Cambridge University Press

Effective methods to increase awareness of preventable infectious diseases are key components of successful control programs. Rabies is an example of a disease with significant impact, where public awareness is variable. A recent awareness campaign in a rabies endemic region of Azerbaijan provided a unique opportunity to assess the efficacy of such campaigns. A cluster-cross sectional survey concerning rabies was undertaken following the awareness campaign in 600 households in 38 randomly selected towns, in districts covered by the campaign and matched control regions. This survey demonstrated that the relatively simple awareness campaign was effective at improving knowledge of rabies symptoms and vaccination schedules. Crucially, those in the awareness campaign group were also 1·4 times more likely to report that they had vaccinated their pets, an essential component of human rabies prevention. In addition, low knowledge of appropriate post-exposure treatment and animal sources of rabies provide information useful for future public awareness campaigns in the region and other similar areas.

U Zieger, DA Marston, R Sharma, A Chikweto, K Tiwari, M Sayyid, B Louison, H Goharriz, K Voller, AC Breed, D Werling, AR Fooks, DL Horton (2014)The Phylogeography of Rabies in Grenada, West Indies, and Implications for Control, In: PLOS NEGLECTED TROPICAL DISEASES8(10)ARTN e3251 PUBLIC LIBRARY SCIENCE
S Pathak, DL Horton, S Lucas, D Brown, S Quaderi, S Polhill, D Walker, E Nastouli, A Nunez, EL Wise, AR Fooks, M Brown (2014)Diagnosis, management and post-mortem findings of a human case of rabies imported into the United Kingdom from India: a case report, In: VIROLOGY JOURNAL11ARTN 63 BIOMED CENTRAL LTD
MK Morters, S McNabb, DL Horton, AR Fooks, JP Schoeman, HR Whay, JLN Wood, S Cleaveland (2015)Effective vaccination against rabies in puppies in rabies endemic regions, In: VETERINARY RECORD177(6)pp. 150-+ BMJ PUBLISHING GROUP
S Lumley, DL Horton, DA Marston, N Johnson, RJ Ellis, AR Fooks, R Hewson (2016)Complete Genome Sequence of Rift Valley Fever Virus Strain Lunyo, In: Genome Announcements4(2)pp. e00170-16

Using next-generation sequencing technologies, the first complete genome sequence of Rift Valley fever virus strain Lunyo is reported here. Originally reported as an attenuated antigenic variant strain from Uganda, genomic sequence analysis shows that Lunyo clusters together with other Ugandan isolates.

Alessio Lorusso, Valeria Marini, Annapia Di Gennaro, Gaetano Federico Ronchi, Claudia Casaccia, Grazia Carelli, Giuseppe Passantino, Nicola D’Alterio, Vincenzo D’Innocenzo, Giovanni Savini, Federica Monaco, Daniel Horton (2019)Antigenic relationship among zoonotic flaviviruses from Italy, In: Infection, Genetics and Evolution68pp. 91-97 Elsevier

Here we report studies of the antigenic relationship of West Nile virus (WNV) and Usutu virus (USUV), two zoonotic flaviviruses from Italy, together with a Japanese encephalitis virus (JEV) strain and compared them with their genetic relationship using the immunodominant viral E protein. Thirty-nine isolates and reference strains were inactivated and used to immunize rabbits to produce hyper immune sera. Serum samples were tested by neutralization against all isolates and results visualized by generating antigenic map. Strains of WNV, USUV, and JEV grouped in separate clusters on the antigenic map. JEV was closer antigenically to USUV (mean of 3.5 Antigenic Unit, AU, equivalent to a 2-fold change in antibody titer) than to WNV strains (mean of 6 AU). A linear regression model predicted, on average, one unit of antigenic change, equivalent to a 2-fold change in antibody titer, for every 22 amino acid substitutions in the E protein ectodomain. Overall, antigenic map was demonstrated to be robust and consistent with phylogeny of the E protein. Indeed, the map provided a reliable means of visualizing and quantifying the relationship between these flaviviruses. Further antigenic analyses employing representative strains of extant serocomplexes are currently underway. This will provide a more in deep knowledge of antigenic relationships between flaviviruses.

G Massei, AR Fooks, DL Horton, R Callaby, K Sharma, IP Dhakal, U Dahal (2016)Free roaming dogs in Central Nepal: demographics, health and public knowledge, attitudes and practices, In: Zoonoses and Public Health Wiley

In Nepal most dogs are free to roam and may transmit diseases to humans and animals. These dogs often suffer from malnutrition and lack basic health care. Minimal information is available about their demographics and about public attitudes concerning dogs and diseases. We carried out a study in Chitwan District (central Nepal), to collect baseline data on free-roaming owned dog demographics, assess knowledge, attitudes and practices of dog owners concerning dogs and rabies, evaluate rabies vaccination coverage and anthelmintic treatment of dogs, measure dogs’ response to rabies vaccination and assess dog health through body condition scores and parasites. We conducted household interviews with owners of free-roaming female dogs (n=60) and administered dogs with rabies vaccination and anthelmintics. Dog owners regularly fed free-roaming dogs but provided minimal health care; 42% of respondents did not claim ownership of the dog for which they provided care. We collected skin, faecal and blood samples for parasite identification and for measuring rabies virus-specific antibodies. Ninety-two percent of dog owners were aware of the routes of rabies virus transmission but only 35% described the correct post-exposure prophylaxis (PEP) following a dog bite. Twenty-seven percent of the dogs had measurable rabies virus-specific antibody titres and 14% had received anthelmintics in the previous year. Following rabies vaccination, 97% of dogs maintained an adequate antibody titre for > 6 months. Most dogs appeared healthy, although haemoprotozoans, endoparasites and ectoparasites were identified in 12%, 73% and 40% of the dogs, respectively. Poor skin condition and parasite load were associated. Seventy-four percent of the females had litters in one year (mean litter size= 4.5). Births occurred between September and February; we estimated 60% mortality in puppies. We concluded that vaccination coverage, PEP awareness and anthelmintic treatment should be emphasized in educational programmes focussed on animal welfare, veterinary and public health.

DA Marston, LM McElhinney, RJ Ellis, DL Horton, EL Wise, SL Leech, D David, X de Lamballerie, AR Fooks (2013)Next generation sequencing of viral RNA genomes, In: BMC GENOMICS14ARTN 444 BIOMED CENTRAL LTD
DL Horton, MZ Ismail, ES Siryan, ARA Wali, HE Ab-dulla, E Wise, K Voller, G Harkess, DA Marston, LM McElhinney, SF Abbas, AR Fooks (2013)Rabies in Iraq: Trends in Human Cases 2001-2010 and Characterisation of Animal Rabies Strains from Baghdad, In: PLOS NEGLECTED TROPICAL DISEASES7(2)ARTN e2075 PUBLIC LIBRARY SCIENCE
DA Marston, DL Horton, C Ngeleja, K Hampson, LM McElhinney, AC Banyard, D Haydon, S Cleaveland, CE Rupprecht, M Bigambo, AR Fooks, T Lembo (2012)Ikoma Lyssavirus, Highly Divergent Novel Lyssavirus in an African Civet, In: EMERGING INFECTIOUS DISEASES18(4)pp. 664-667 CENTERS DISEASE CONTROL
LM McElhinney, DA Marston, S Leech, CM Freuling, WHM van der Poel, J Echevarria, S Vazquez-Moron, DL Horton, T Mueller, AR Fooks (2013)Molecular Epidemiology of Bat Lyssaviruses in Europe, In: ZOONOSES AND PUBLIC HEALTH60(1)pp. 35-45 WILEY-BLACKWELL
DL Horton, LM McElhinney, DA Marston, JLN Wood, CA Russell, N Lewis, IV Kuzmin, RAM Fouchier, ADME Osterhaus, AR Fooks, DJ Smith (2010)Quantifying Antigenic Relationships among the Lyssaviruses, In: JOURNAL OF VIROLOGY84(22)pp. 11841-11848 AMER SOC MICROBIOLOGY
GR Pant, DL Horton, M Dahal, JN Rai, S Ide, S Leech, DA Marston, LM McElhinney, AR Fooks (2011)Characterization of rabies virus from a human case in Nepal, In: ARCHIVES OF VIROLOGY156(4)pp. 681-684 SPRINGER WIEN
VA Brugman, DL Horton, LP Phipps, N Johnson, AJC Cook, AR Fooks, AC Breed (2013)Epidemiological perspectives on West Nile virus surveillance in wild birds in Great Britain, In: EPIDEMIOLOGY AND INFECTION141(6)pp. 1134-1142 CAMBRIDGE UNIV PRESS
Lisa Yon, J. Paul Duff, Erik O. Ågren, Károly Erdélyi, Ezio Ferroglio, Jacques Godfroid, Jean Hars, Gete Hestvik, Dan Horton, Thijs Kuiken, Antonio Lavazza, Iwona Markowska-Daniel, An Martel, Aleksija Neimanis, Frank Pasmans, Stephen Price, Francisco Ruiz-Fons, Marie-Pierre Ryser-Degiorgis, Frederik Widén, Dolores Gavier-Widén (2018)Recent changes in infectious diseases in European wildlife, In: Journal of Wildlife Diseases55(1)pp. 3-43 Wildlife Disease Association

Many infectious diseases originating from or carried by wildlife impact wildlife conservation and biodiversity, livestock health, and/or human health. We provide an update on changes in the epidemiology of 25 selected infectious wildlife–related diseases in Europe (from 2010-2016) that had an impact, or may have a future impact, on the health of wildlife, livestock, and humans. These pathogens were selected based on their: (1) identification in recent Europe–wide projects as important surveillance targets, (2) inclusion in European Union (EU) legislation as pathogens requiring obligatory surveillance, (3) presence in recent literature on wildlife-related disease in Europe since 2010, (4) inclusion in key pathogen lists released by the Office International des Epizooties (OIE), (5) identification in conference presentations and informal discussions on a group email list by a European network of wildlife disease scientists from the European Wildlife Disease Association, or (6) identification as pathogens with changes in their epidemiology during 2010–2016. The wildlife pathogens or diseases included in this review are: avian influenza virus, seal influenza virus, lagoviruses, rabies virus, bat lyssaviruses, filoviruses, canine distemper virus, morbilliviruses in aquatic mammals, bluetongue virus, West Nile virus, hantaviruses, Schmallenberg virus, Crimean-Congo hemorrhagic fever virus, African swine fever virus, amphibian ranavirus, hepatitis E virus, bovine tuberculosis (Mycobacterium bovis), tularemia (Francisella tularensis), brucellosis (Brucella spp.), salmonellosis (Salmonella spp.), Coxiella burnetii , chytridiomycosis, Echinococcus multilocularis, Leishmania infantum, and chronic wasting disease. Further work is needed to identify all of the key drivers of disease change and emergence, as they appear to be influencing the incidence and spread of these pathogens in Europe. We present a summary of these recent changes over a specified time period to discuss possible commonalities and drivers of disease change and to identify directions for future work on wildlife related diseases in Europe. Many of the pathogens are entering Europe from other continents, while at the same time others are expanding their ranges inside and beyond Europe. Surveillance for these wildlife-related diseases at a continental scale is therefore important for planet-wide assessment, awareness of, and preparedness for, the potential risks they may pose to wildlife, domestic animal, and human health.

DL Horton, B Lawson, A Egbetade, C Jeffries, N Johnson, AA Cunningham, AR Fooks (2013)Targeted surveillance for Usutu virus in British birds (2005-2011), In: VETERINARY RECORD172(1) BMJ PUBLISHING GROUP
KS Baker, R Suu-Ire, J Barr, DTS Hayman, CC Broder, DL Horton, C Durrant, PR Murcia, AA Cunningham, JLN Wood (2014)Viral antibody dynamics in a chiropteran host, In: JOURNAL OF ANIMAL ECOLOGY83(2)pp. 415-428 WILEY-BLACKWELL
AD Goddard, NM Donaldson, DL Horton, R Kosmider, LA Kelly, AR Sayers, AC Breed, CM Freuling, T Mueller, SE Shaw, G Hallgren, AR Fooks, EL Snary (2012)A Quantitative Release Assessment for the Noncommercial Movement of Companion Animals: Risk of Rabies Reintroduction to the United Kingdom, In: RISK ANALYSIS32(10)pp. 1769-1783 WILEY-BLACKWELL
DA Marston, LM McElhinney, AC Banyard, DL Horton, A Nunez, ML Koser, MJ Schnell, AR Fooks (2013)Interspecies protein substitution to investigate the role of the lyssavirus glycoprotein, In: JOURNAL OF GENERAL VIROLOGY94pp. 284-292 SOC GENERAL MICROBIOLOGY
DA Marston, RJ Ellis, DL Horton, IV Kuzmin, EL Wise, LM McElhinney, AC Banyard, C Ngeleja, J Keyyu, S Cleaveland, T Lembo, CE Rupprecht, AR Fooks (2012)Complete Genome Sequence of Ikoma Lyssavirus, In: JOURNAL OF VIROLOGY86(18)pp. 10242-10243 AMER SOC MICROBIOLOGY
DL Horton, LM McElhinney, CM Freuling, DA Marston, AC Banyard, H Goharrriz, E Wise, AC Breed, G Saturday, J Kolodziejek, E Zilahi, MF Al-Kobaisi, N Nowotny, T Mueller, AR Fooks (2015)Complex Epidemiology of a Zoonotic Disease in a Culturally Diverse Region: Phylogeography of Rabies Virus in the Middle East, In: PLOS NEGLECTED TROPICAL DISEASES9(3)ARTN e0003 PUBLIC LIBRARY SCIENCE
B Lawson, A Dastjerdi, S Shah, D Everest, A Nunez, A Pocknell, D Hicks, DL Horton, AA Cunningham, RM Irvine (2015)Mortality associated with avian reovirus infection in a free-living magpie (Pica pica) in Great Britain, In: BMC VETERINARY RESEARCH11ARTN 20 BIOMED CENTRAL LTD
J Schatz, AR Fooks, L McElhinney, D Horton, J Echevarria, S Vazquez-Moron, EA Kooi, TB Rasmussen, T Mueller, CM Freuling (2013)Bat Rabies Surveillance in Europe, In: ZOONOSES AND PUBLIC HEALTH60(1)pp. 22-34 WILEY-BLACKWELL
AT Gilbert, AR Fooks, DTS Hayman, DL Horton, T Mueller, R Plowright, AJ Peel, R Bowen, JLN Wood, J Mills, AA Cunningham, CE Rupprecht (2013)Deciphering Serology to Understand the Ecology of Infectious Diseases in Wildlife, In: ECOHEALTH10(3)pp. 298-313 SPRINGER
N Johnson, C Freuling, D Horton, T Mueller, AR Fooks (2011)Imported Rabies, European Union and Switzerland, 2001-2010, In: EMERGING INFECTIOUS DISEASES17(4)pp. 753-754 CENTERS DISEASE CONTROL
DTS Hayman, N Johnson, DL Horton, J Hedge, PR Wakeley, AC Banyard, S Zhang, A Alhassan, AR Fooks (2011)Evolutionary History of Rabies in Ghana, In: PLOS NEGLECTED TROPICAL DISEASES5(4)ARTN e1001 PUBLIC LIBRARY SCIENCE
AR Fooks, AC Banyard, DL Horton, N Johnson, LM McElhinney, AC Jackson (2014)Current status of rabies and prospects for elimination, In: LANCET384(9951)pp. 1389-1399 ELSEVIER SCIENCE INC
DTS Hayman, AR Fooks, D Horton, R Suu-Ire, AC Breed, AA Cunningham, JLN Wood (2008)Antibodies against Lagos bat virus in megachiroptera from West Africa, In: EMERGING INFECTIOUS DISEASES14(6)pp. 926-928 CENTER DISEASE CONTROL
F Cliquet, C Freuling, M Smreczak, WHM Van der Poel, DL Horton, AR Fooks, E Robardet, E Picard-Meyer, T Müller (2010)Development of harmonised schemes for monitoring and reporting of rabies in animals in the European Union, In: Scientific Report submitted to EFSA (Q-2010–00078)
AB Ludi, DL Horton, Y Li, M Mahapatra, DP King, NJ Knowles, CA Russell, DJ Paton, JL Wood, DJ Smith, JM Hammond (2014)Antigenic variation of foot-and-mouth disease virus serotype A., In: J Gen Virol95(Pt 2)pp. 384-392

The current measures to control foot-and-mouth disease (FMD) include vaccination, movement control and slaughter of infected or susceptible animals. One of the difficulties in controlling FMD by vaccination arises due to the substantial diversity found among the seven serotypes of FMD virus (FMDV) and the strains within these serotypes. Therefore, vaccination using a single vaccine strain may not fully cross-protect against all strains within that serotype, and therefore selection of appropriate vaccines requires serological comparison of the field virus and potential vaccine viruses using relationship coefficients (r1 values). Limitations of this approach are that antigenic relationships among field viruses are not addressed, as comparisons are only with potential vaccine virus. Furthermore, inherent variation among vaccine sera may impair reproducibility of one-way relationship scores. Here, we used antigenic cartography to quantify and visualize the antigenic relationships among FMD serotype A viruses, aiming to improve the understanding of FMDV antigenic evolution and the scope and reliability of vaccine matching. Our results suggest that predicting antigenic difference using genetic sequence alone or by geographical location is not currently reliable. We found co-circulating lineages in one region that were genetically similar but antigenically distinct. Nevertheless, by comparing antigenic distances measured from the antigenic maps with the full capsid (P1) sequence, we identified a specific amino acid substitution associated with an antigenic mismatch among field viruses and a commonly used prototype vaccine strain, A22/IRQ/24/64.

NS Lewis, JM Daly, CA Russell, DL Horton, E Skepner, NA Bryant, DF Burke, AS Rash, JLN Wood, TM Chambers, RAM Fouchier, JA Mumford, DM Elton, DJ Smith (2011)Antigenic and Genetic Evolution of Equine Influenza A (H3N8) Virus from 1968 to 2007, In: JOURNAL OF VIROLOGY85(23)pp. 12742-12749 AMER SOC MICROBIOLOGY
AR Fooks, DL Horton, N Johnson, B Toth, HC Roberts (2011)Changes to pet travel rules: rabies, ticks and tapeworms, In: VETERINARY RECORD169(4)pp. 97-98 BRITISH VETERINARY ASSOC
E Robardet, S Andrieu, TB Rasmussen, M Dobrostana, DL Horton, P Hostnik, I Jaceviciene, T Juhasz, T Mueller, F Mutinelli, A Servat, M Smreczak, E Vanek, S Vazquez-Moron, F Cliquet (2013)Comparative assay of fluorescent antibody test results among twelve European National Reference Laboratories using various anti-rabies conjugates, In: JOURNAL OF VIROLOGICAL METHODS191(1)pp. 88-94 ELSEVIER SCIENCE BV
MK Morters, TJ McKinley, DL Horton, S Cleaveland, JP Schoeman, O Restif, HR Whay, A Goddard, AR Fooks, IM Damriyasa, JLN Wood (2014)Achieving Population-Level Immunity to Rabies in Free-Roaming Dogs in Africa and Asia, In: PLOS NEGLECTED TROPICAL DISEASES8(11)ARTN e3160 PUBLIC LIBRARY SCIENCE
D Horton, E Wise (2011)Raising awareness of rabies., In: The Veterinary record16911pp. 271-271
DTS Hayman, AR Fooks, JM Rowcliffe, R McCrea, O Restif, KS Baker, DL Horton, R Suu-Ire, AA Cunningham, JLN Wood (2012)Endemic Lagos bat virus infection in Eidolon helvum, In: EPIDEMIOLOGY AND INFECTION140(12)pp. 2163-2171 CAMBRIDGE UNIV PRESS
DM Healy, DL Horton (2013)Claire L. leffries, Ashley C. Banyard, In: Neuroviral Infections: RNA Viruses and Retroviruses2pp. 373-373 CRC Press
DL Horton, K Voller, B Haxton, N Johnson, S Leech, T Goddard, C Wilson, LM McElhinney, AR Fooks (2009)European bat lyssavirus type 2 in a Daubenton's bat in Scotland, In: VETERINARY RECORD165(13)pp. 383-384 BRITISH VETERINARY ASSOC
K Brunker, K Hampson, DL Horton, R Biek (2012)Integrating the landscape epidemiology and genetics of RNA viruses: rabies in domestic dogs as a model, In: PARASITOLOGY139(14)pp. 1899-1913 CAMBRIDGE UNIV PRESS
T Nolden, AC Banyard, S Finke, AR Fooks, D Hanke, D Hoeper, DL Horton, TC Mettenleiter, T Mueller, JP Teifke, CM Freuling (2014)Comparative studies on the genetic, antigenic and pathogenic characteristics of Bokeloh bat lyssavirus, In: JOURNAL OF GENERAL VIROLOGY95pp. 1647-1653 SOC GENERAL MICROBIOLOGY
G Garcia, AA Cunningham, DL Horton, TWJ Garner, A Hyatt, S Hengstberger, J Lopez, A Ogrodowczyk, C Fenton, JE Fa (2007)Mountain chickens Leptodactylus fallax and sympatric amphibians appear to be disease free on Montserrat, In: Oryx4103pp. 398-401 Cambridge Univ Press
Sarah Lumley, Daniel Horton, LLM Hernandez-Triana, N Johnson, AR Fooks, R Hewson (2017)Rift Valley fever virus: Strategies for maintenance, survival and vertical transmission in mosquitoes, In: Journal of General Virology98(5)pp. 875-887 Microbiology Society

Rift Valley fever virus (RVFV) is a mosquito-borne arbovirus causing severe disease in humans and ruminants. Spread of RVFV out of Africa has raised concerns that it could emerge in Europe or the USA. Virus persistence is dependent on successful infection of, replication in, and transmission to susceptible vertebrate and invertebrate hosts, modulated by virus-host and vector-virus interactions. The principal accepted theory for the long term maintenance of RVFV involves vertical transmission (VT) of virus to mosquito progeny, with the virus surviving long inter-epizootic periods within the egg. This VT hypothesis however, is yet to be comprehensively proven. Here, evidence for and against the VT of RVFV is reviewed along with the identification of factors limiting its detection in natural and experimental data. The observation of VT for other arboviruses in the genera alphavirus, flavivirus and orthobunyavirus are discussed within the context of RVFV. The review concludes that VT of RVFV is likely but that current data are insufficient to irrefutably prove this hypothesis.

KL Mansfield, DL Horton, N Johnson, L Li, ADT Barrett, DJ Smith, SE Galbraith, T Solomon, AR Fooks (2011)Flavivirus-induced antibody cross-reactivity, In: JOURNAL OF GENERAL VIROLOGY92pp. 2821-2829 SOC GENERAL MICROBIOLOGY
AGC Vaux, G Gibson, LM Hernandez-Triana, RA Cheke, F McCracken, CL Jeffries, DL Horton, S Springate, N Johnson, AR Fooks, S Leach, JM Medlock (2015)Enhanced West Nile virus surveillance in the North Kent marshes, UK, In: PARASITES & VECTORS8 BIOMED CENTRAL LTD
AC Banyard, DL Horton, C Freuling, T Mueller, AR Fooks (2013)Control and prevention of canine rabies: The need for building laboratory-based surveillance capacity, In: ANTIVIRAL RESEARCH98(3)pp. 357-364 ELSEVIER SCIENCE BV
M Viana, S Cleaveland, J Matthiopoulos, J Halliday, C Packer, ME Craft, K Hampson, A Czupryna, AP Dobson, EJ Dubovi, E Ernest, R Fyumagwa, R Hoare, JGC Hopcraft, DL Horton, MT Kaare, T Kanellos, F Lankester, C Mentzel, T Mlengeya, I Mzimbiri, E Takahashi, B Willett, DT Haydon, T Lembo (2015)Dynamics of a morbillivirus at the domestic-wildlife interface: Canine distemper virus in domestic dogs and lions, In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA112(5)pp. 1464-1469 NATL ACAD SCIENCES
KL Mansfield, AC Banyard, L McElhinney, N Johnson, DL Horton, LM Hernandez-Triana, AR Fooks (2015)Rift Valley fever virus: A review of diagnosis and vaccination, and implications for emergence in Europe, In: VACCINE33(42)pp. 5520-5531 ELSEVIER SCI LTD
K Brunker, DA Marston, DL Horton, S Cleaveland, AR Fooks, R Kazwala, C Ngeleja, T Lembo, M Sambo, ZJ Mtema, L Sikana, G Wilkie, R Biek, K Hampson (2015)Elucidating the phylodynamics of endemic rabies virus in eastern Africa using whole-genome sequencing., In: Virus Evolution1(1) Oxford University Press

Many of the pathogens perceived to pose the greatest risk to humans are viral zoonoses, responsible for a range of emerging and endemic infectious diseases. Phylogeography is a useful tool to understand the processes that give rise to spatial patterns and drive dynamics in virus populations. Increasingly, whole-genome information is being used to uncover these patterns, but the limits of phylogenetic resolution that can be achieved with this are unclear. Here, whole-genome variation was used to uncover fine-scale population structure in endemic canine rabies virus circulating in Tanzania. This is the first whole-genome population study of rabies virus and the first comprehensive phylogenetic analysis of rabies virus in East Africa, providing important insights into rabies transmission in an endemic system. In addition, sub-continental scale patterns of population structure were identified using partial gene data and used to determine population structure at larger spatial scales in Africa. While rabies virus has a defined spatial structure at large scales, increasingly frequent levels of admixture were observed at regional and local levels. Discrete phylogeographic analysis revealed long-distance dispersal within Tanzania, which could be attributed to human-mediated movement, and we found evidence of multiple persistent, co-circulating lineages at a very local scale in a single district, despite on-going mass dog vaccination campaigns. This may reflect the wider endemic circulation of these lineages over several decades alongside increased admixture due to human-mediated introductions. These data indicate that successful rabies control in Tanzania could be established at a national level, since most dispersal appears to be restricted within the confines of country borders but some coordination with neighbouring countries may be required to limit transboundary movements. Evidence of complex patterns of rabies circulation within Tanzania necessitates the use of whole-genome sequencing to delineate finer scale population structure that can that can guide interventions, such as the spatial scale and design of dog vaccination campaigns and dog movement controls to achieve and maintain freedom from disease.

L Both, AC Banyard, C van Dolleweerd, DL Horton, JK-C Ma, AR Fooks (2012)Passive immunity in the prevention of rabies, In: LANCET INFECTIOUS DISEASES12(5)pp. 397-407 ELSEVIER SCIENCE INC
I. F. Saldanha, B. Lawson, H. Goharriz, J. Rodriguez-Ramos Fernandez, S. K. John, A. R. Fooks, A. A. Cunningham, N. Johnson, D. L. Horton (2019)Extension of the known distribution of a novel clade C betacoronavirus in a wildlife host, In: Epidemiology and Infection147e169pp. 1-8 Cambridge University Press

Disease surveillance in wildlife populations presents a logistical challenge, yet is critical in gaining a deeper understanding of the presence and impact of wildlife pathogens. Erinaceus coronavirus (EriCoV), a clade C Betacoronavirus, was first described in Western European hedgehogs (Erinaceus europaeus) in Germany. Here, our objective was to determine whether EriCoV is present, and if it is associated with disease, in Great Britain (GB). An EriCoV-specific BRYT-Green® real-time reverse transcription PCR assay was used to test 351 samples of faeces or distal large intestinal tract contents collected from casualty or dead hedgehogs from a wide area across GB. Viral RNA was detected in 10.8% (38) samples; however, the virus was not detected in any of the 61 samples tested from Scotland. The full genome sequence of the British EriCoV strain was determined using next generation sequencing; it shared 94% identity with a German EriCoV sequence. Multivariate statistical models using hedgehog case history data, faecal specimen descriptions and post-mortem examination findings found no significant associations indicative of disease associated with EriCoV in hedgehogs. These findings indicate that the Western European hedgehog is a reservoir host of EriCoV in the absence of apparent disease.

JS Evans, DL Horton, AJ Easton, AR Fooks, AC Banyard (2012)Rabies virus vaccines: Is there a need for a pan-lyssavirus vaccine?, In: VACCINE30(52)pp. 7447-7454 ELSEVIER SCI LTD
B Yakobson, I Goga, CM Freuling, AR Fooks, V Gjinovci, B Hulaj, D Horton, N Johnson, J Muhaxhiri, I Recica, D David, R O'Flaherty, N Taylor, T Wilsmore, T Mueller (2014)Implementation and monitoring of oral rabies vaccination of foxes in Kosovo between 2010 and 2013-An international and intersectorial effort, In: INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY304(7)pp. 902-910 ELSEVIER GMBH, URBAN & FISCHER VERLAG
Denise Marston, Daniel Horton, Javier Nunez, Richard Ellis, Richard Orton, Nicholas Johnson, Ashley Banyard, Lorraine McElhinney, Conrad Freuling, Müge Firat, Nil Ünal, Mueller Thomas, Anthony Fooks (2017)Genetic analysis of a rabies virus host shift event reveals within-host viral dynamics in a new host, In: Virus Evolution3(2)vex038 Oxford University Press

Host shift events play an important role in epizootics as adaptation to new hosts can profoundly affect the spread of the disease and the measures needed to control it. During the late 1990s, an epizootic in Turkey resulted in a sustained maintenance of rabies virus (RABV) within the fox population. Utilisation of Bayesian inferences to investigate whole genome sequences from a cohort of fox and dog brain tissues from Turkey demonstrated that the epizootic occurred in 1997 (+/- 1 year). Furthermore, these data indicate that the epizootic was most likely due to a host shift from locally infected domestic dogs, rather than an incursion of a novel fox or dog RABV. No evidence was detected for virus adaptation to foxes at consensus sequence level; therefore, the deep sequence data was analysed to investigate the influence of sub-consensus populations on host shift events. Viral heterogeneity was measured in all RABV samples; viruses in the early phase after the host shift had increased heterogeneity, in relation to those in the later stage, possibly indicating a role in establishing transmission within a new host. The dynamics of majority and minority variants are consistent with genetic drift, rather than positive selection. The transient expansion of sub-consensus viral populations in the new host species likely represents the virus adapting to a new environment, perhaps due to increased replication within the CNS resulting in a larger population of viruses, or reflecting the lack of host constraints present in the new host reservoir.

E Wright, S McNabb, T Goddard, DL Horton, T Lembo, LH Nel, RA Weiss, S Cleaveland, AR Fooks (2009)A robust lentiviral pseudotype neutralisation assay for in-field serosurveillance of rabies and lyssaviruses in Africa, In: VACCINE27(51)pp. 7178-7186 ELSEVIER SCI LTD