Schatz J, Fooks AR, McElhinney L, Horton D, Echevarria J, Vazquez-Moron S, Kooi EA, Rasmussen TB, Mueller T, Freuling CM (2013) Bat Rabies Surveillance in Europe, ZOONOSES AND PUBLIC HEALTH60(1)pp. 22-34 WILEY-BLACKWELL
Marston DA, Horton DL, Ngeleja C, Hampson K, McElhinney LM, Banyard AC, Haydon D, Cleaveland S, Rupprecht CE, Bigambo M, Fooks AR, Lembo T (2012) Ikoma Lyssavirus, Highly Divergent Novel Lyssavirus in an African Civet, EMERGING INFECTIOUS DISEASES18(4)pp. 664-667 CENTERS DISEASE CONTROL
Baker KS, Suu-Ire R, Barr J, Hayman DTS, Broder CC, Horton DL, Durrant C, Murcia PR, Cunningham AA, Wood JLN (2014) Viral antibody dynamics in a chiropteran host, Journal of Animal Ecology83(2)pp. 415-428
Bats host many viruses that are significant for human and domestic animal health, but the dynamics of these infections in their natural reservoir hosts remain poorly elucidated. In these, and other, systems, there is evidence that seasonal life-cycle events drive infection dynamics, directly impacting the risk of exposure to spillover hosts. Understanding these dynamics improves our ability to predict zoonotic spillover from the reservoir hosts. To this end, we followed henipavirus antibody levels of >100 individual E. helvum in a closed, captive, breeding population over a 30-month period, using a powerful novel antibody quantitation method. We demonstrate the presence of maternal antibodies in this system and accurately determine their longevity. We also present evidence of population-level persistence of viral infection and demonstrate periods of increased horizontal virus transmission associated with the pregnancy/lactation period. The novel findings of infection persistence and the effect of pregnancy on viral transmission, as well as an accurate quantitation of chiropteran maternal antiviral antibody half-life, provide fundamental baseline data for the continued study of viral infections in these important reservoir hosts. © 2013 The Authors. Journal of Animal Ecology © 2013 British Ecological Society.
Hayman DTS, Fooks AR, Horton D, Suu-Ire R, Breed AC, Cunningham AA, Wood JLN (2008) Antibodies against Lagos bat virus in megachiroptera from West Africa, EMERGING INFECTIOUS DISEASES14(6)pp. 926-928 CENTER DISEASE CONTROL
Both L, Banyard AC, van Dolleweerd C, Horton DL, Ma JK-C, Fooks AR (2012) Passive immunity in the prevention of rabies, LANCET INFECTIOUS DISEASES12(5)pp. 397-407 ELSEVIER SCIENCE INC
Wright E, McNabb S, Goddard T, Horton DL, Lembo T, Nel LH, Weiss RA, Cleaveland S, Fooks AR (2009) A robust lentiviral pseudotype neutralisation assay for in-field serosurveillance of rabies and lyssaviruses in Africa, VACCINE27(51)pp. 7178-7186 ELSEVIER SCI LTD
Evans JS, Horton DL, Easton AJ, Fooks AR, Banyard AC (2012) Rabies virus vaccines: Is there a need for a pan-lyssavirus vaccine?, Vaccine30(52)pp. 7447-7454
All members of the lyssavirus genus are capable of causing disease that invariably results in death following the development of clinical symptoms. The recent detection of several novel lyssavirus species across the globe, in different animal species, has demonstrated that the lyssavirus genus contains a greater degree of genetic and antigenic variation than previously suspected. The divergence of species within the genus has led to a differentiation of lyssavirus isolates based on both antigenic and genetic data into two, and potentially a third phylogroup. Critically, from both a human and animal health perspective, current rabies vaccines appear able to protect against lyssaviruses classified within phylogroup I. However no protection is afforded against phylogroup II viruses or other more divergent viruses. Here we review current knowledge regarding the diversity and antigenicity of the lyssavirus glycoprotein. We review the degree of cross protection afforded by rabies vaccines, the genetic and antigenic divergence of the lyssaviruses and potential mechanisms for the development of novel lyssavirus vaccines for use in areas where divergent lyssaviruses are known to circulate, as well as for use by those at occupational risk from these pathogens. © 2012.
Horton DL, McElhinney LM, Freuling CM, Marston DA, Banyard AC, Goharrriz H, Wise E, Breed AC, Saturday G, Kolodziejek J, Zilahi E, Al-Kobaisi MF, Nowotny N, Mueller T, Fooks AR (2015) Complex epidemiology of a zoonotic disease in a culturally diverse region: phylogeography of rabies virus in the Middle East., PLoS Negl Trop Dis9(3)
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.
Marston DA, McElhinney LM, Ellis RJ, Horton DL, Wise EL, Leech SL, David D, de Lamballerie X, Fooks AR (2013) Next generation sequencing of viral RNA genomes, BMC GENOMICS14ARTN 444 BIOMED CENTRAL LTD
Horton DL, McElhinney LM, Marston DA, Wood JLN, Russell CA, Lewis N, Kuzmin IV, Fouchier RAM, Osterhaus ADME, Fooks AR, Smith DJ (2010) Quantifying Antigenic Relationships among the Lyssaviruses, JOURNAL OF VIROLOGY84(22)pp. 11841-11848 AMER SOC MICROBIOLOGY
Morters MK, McKinley TJ, Horton DL, Cleaveland S, Schoeman JP, Restif O, Whay HR, Goddard A, Fooks AR, Damriyasa IM, Wood JL (2014) Achieving population-level immunity to rabies in free-roaming dogs in Africa and Asia., PLoS Negl Trop Dis8(11)
Canine rabies can be effectively controlled by vaccination with readily available, high-quality vaccines. These vaccines should provide protection from challenge in healthy dogs, for the claimed period, for duration of immunity, which is often two or three years. It has been suggested that, in free-roaming dog populations where rabies is endemic, vaccine-induced protection may be compromised by immuno-suppression through malnutrition, infection and other stressors. This may reduce the proportion of dogs that seroconvert to the vaccine during vaccination campaigns and the duration of immunity of those dogs that seroconvert. Vaccination coverage may also be limited through insufficient vaccine delivery during vaccination campaigns and the loss of vaccinated individuals from populations through demographic processes. This is the first longitudinal study to evaluate temporal variations in rabies vaccine-induced serological responses, and factors associated with these variations, at the individual level in previously unvaccinated free-roaming dog populations. Individual-level serological and health-based data were collected from three cohorts of dogs in regions where rabies is endemic, one in South Africa and two in Indonesia. We found that the vast majority of dogs seroconverted to the vaccine; however, there was considerable variation in titres, partly attributable to illness and lactation at the time of vaccination. Furthermore, >70% of the dogs were vaccinated through community engagement and door-to-door vaccine delivery, even in Indonesia where the majority of the dogs needed to be caught by net on successive occasions for repeat blood sampling and vaccination. This demonstrates the feasibility of achieving population-level immunity in free-roaming dog populations in rabies-endemic regions. However, attrition of immune individuals through demographic processes and waning immunity necessitates repeat vaccination of populations within at least two years to ensure communities are protected from rabies. These findings support annual mass vaccination campaigns as the most effective means to control canine rabies.
Horton DL, Voller K, Haxton B, Johnson N, Leech S, Goddard T, Wilson C, McElhinney LM, Fooks AR (2009) European bat lyssavirus type 2 in a Daubenton's bat in Scotland, VETERINARY RECORD165(13)pp. 383-384 BRITISH VETERINARY ASSOC
Lewis NS, Daly JM, Russell CA, Horton DL, Skepner E, Bryant NA, Burke DF, Rash AS, Wood JLN, Chambers TM, Fouchier RAM, Mumford JA, Elton DM, Smith DJ (2011) Antigenic and Genetic Evolution of Equine Influenza A (H3N8) Virus from 1968 to 2007, JOURNAL OF VIROLOGY85(23)pp. 12742-12749 AMER SOC MICROBIOLOGY
Horton DL, Ismail MZ, Siryan ES, Wali ARA, Ab-dulla HE, Wise E, Voller K, Harkess G, Marston DA, McElhinney LM, Abbas SF, Fooks AR (2013) Rabies in Iraq: Trends in Human Cases 2001-2010 and Characterisation of Animal Rabies Strains from Baghdad, PLOS NEGLECTED TROPICAL DISEASES7(2)ARTN e2075 PUBLIC LIBRARY SCIENCE
Horton DL, Lawson B, Egbetade A, Jeffries C, Johnson N, Cunningham AA, Fooks AR (2013) Targeted surveillance for Usutu virus in British birds (2005-2011), VETERINARY RECORD172(1) BMJ PUBLISHING GROUP
Lumley S, Horton DL, Marston DA, Johnson N, Ellis RJ, Fooks AR, Hewson R (2016) Complete Genome Sequence of Rift Valley Fever Virus Strain Lunyo, Genome Announcements4(2)pp. e00170-16-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.
Yakobson B, Goga I, Freuling CM, Fooks AR, Gjinovci V, Hulaj B, Horton D, Johnson N, Muhaxhiri J, Recica I, David D, O'Flaherty R, Taylor N, Wilsmore T, Müller T (2014) Implementation and monitoring of oral rabies vaccination of foxes in Kosovo between 2010 and 2013-An international and intersectorial effort, International Journal of Medical Microbiology304(7)pp. 902-910
© 2014 Elsevier GmbH.The European Union has used instrument for pre-accession (IPA) funds to provide technical assistance and supplies for the eradication, monitoring and control of rabies in several pre-accession countries. As a result, since 2010, multi-annual oral rabies vaccination (ORV) programmes for eliminating fox rabies have been launched in six Western Balkan countries. Here the implementation of the ORV programme in Kosovo, the smallest of the West Balkan countries, is described. Associated challenges under difficult political conditions, potential biases, and the results of rabies surveillance and monitoring of ORV campaigns (bait uptake and immunisation rates) since 2010 are reported.
Zieger U, Marston DA, Sharma R, Chikweto A, Tiwari K, Sayyid M, Louison B, Goharriz H, Voller K, Breed AC, Werling D, Fooks AR, Horton DL (2014) The phylogeography of rabies in Grenada, West Indies, and implications for control., PLoS Negl Trop Dis8(10)
In Grenada, West Indies, rabies is endemic, and is thought to be maintained in a wildlife host, the small Indian mongoose (Herpestes auropunctatus) with occasional spillover into other hosts. Therefore, the present study was undertaken to improve understanding of rabies epidemiology in Grenada and to inform rabies control policy. Mongooses were trapped island-wide between April 2011 and March 2013 and examined for the presence of Rabies virus (RABV) antigen using the direct fluorescent antibody test (dFAT) and PCR, and for serum neutralizing antibodies (SNA) using the fluorescent antibody virus neutralization test (FAVN). An additional cohort of brain samples from clinical rabies suspects submitted between April 2011 and March 2014 were also investigated for the presence of virus. Two of the 171 (1.7%) live-trapped mongooses were RABV positive by FAT and PCR, and 20 (11.7%) had SNAs. Rabies was diagnosed in 31 of the submitted animals with suspicious clinical signs: 16 mongooses, 12 dogs, 2 cats and 1 goat. Our investigation has revealed that rabies infection spread from the northeast to the southwest of Grenada within the study period. Phylogenetic analysis revealed that the viruses from Grenada formed a monophyletic clade within the cosmopolitan lineage with a common ancestor predicted to have occurred recently (6-23 years ago), and are distinct from those found in Cuba and Puerto Rico, where mongoose rabies is also endemic. These data suggest that it is likely that this specific strain of RABV was imported from European regions rather than the Americas. These data contribute essential information for any potential rabies control program in Grenada and demonstrate the importance of a sound evidence base for planning interventions.
Zeynalova S, Shikhiyev M, Aliyeva T, Ismayilova R, Wise E, Abdullayev R, Asadov K, Rustamova S, Quliyev F, Whatmore AM, others (2014) Epidemiological Characteristics of Human and Animal Rabies in Azerbaijan, Zoonoses and public health
Marston DA, McElhinney LM, Banyard AC, Horton DL, Nunez A, Koser ML, Schnell MJ, Fooks AR (2013) Interspecies protein substitution to investigate the role of the lyssavirus glycoprotein, JOURNAL OF GENERAL VIROLOGY94pp. 284-292 SOC GENERAL MICROBIOLOGY
Fooks AR, Banyard AC, Horton DL, Johnson N, McElhinney LM, Jackson AC (2014) Current status of rabies and prospects for elimination, The Lancet384(9951)pp. 1389-1399
© 2014 Elsevier Ltd.Rabies is one of the most deadly infectious diseases, with a case-fatality rate approaching 100%. The disease is established on all continents apart from Antarctica; most cases are reported in Africa and Asia, with thousands of deaths recorded annually. However, the estimated annual figure of almost 60 000 human rabies fatalities is probably an underestimate. Almost all cases of human rabies result from bites from infected dogs. Therefore, the most cost-effective approach to elimination of the global burden of human rabies is to control canine rabies rather than expansion of the availability of human prophylaxis. Mass vaccination campaigns with parenteral vaccines, and advances in oral vaccines for wildlife, have allowed the elimination of rabies in terrestrial carnivores in several countries worldwide. The subsequent reduction in cases of human rabies in such regions advocates the multidisciplinary One Health approach to rabies control through the mass vaccination of dogs and control of canine populations.
Johnson N, Freuling C, Horton D, Mueller T, Fooks AR (2011) Imported Rabies, European Union and Switzerland, 2001-2010, EMERGING INFECTIOUS DISEASES17(4)pp. 753-754 CENTERS DISEASE CONTROL
Banyard AC, Horton DL, Freuling C, Mueller T, Fooks AR (2013) Control and prevention of canine rabies: The need for building laboratory-based surveillance capacity, ANTIVIRAL RESEARCH98(3)pp. 357-364 ELSEVIER SCIENCE BV
Ludi AB, Horton DL, Li Y, Mahapatra M, King DP, Knowles NJ, Russell CA, Paton DJ, Wood JL, Smith DJ, Hammond JM (2014) Antigenic variation of foot-and-mouth disease virus serotype A., 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.
Horton DL, Banyard AC, Marston DA, Wise E, Selden D, Nunez A, Hicks D, Lembo T, Cleaveland S, Peel AJ, Kuzmin IV, Rupprecht CE, Fooks AR (2014) Antigenic and genetic characterization of a divergent African virus, Ikoma lyssavirus., J Gen Virol95(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.
Gilbert AT, Fooks AR, Hayman DTS, Horton DL, Mueller T, Plowright R, Peel AJ, Bowen R, Wood JLN, Mills J, Cunningham AA, Rupprecht CE (2013) Deciphering Serology to Understand the Ecology of Infectious Diseases in Wildlife, ECOHEALTH10(3)pp. 298-313 SPRINGER
Pathak S, Horton DL, Lucas S, Brown D, Quaderi S, Polhill S, Walker D, Nastouli E, Nunez A, Wise EL, Fooks AR, Brown M (2014) Diagnosis, management and post-mortem findings of a human case of rabies imported into the United Kingdom from India: a case report, VIROLOGY JOURNAL11ARTN 63 BIOMED CENTRAL LTD
Brugman VA, Horton DL, Phipps LP, Johnson N, Cook AJC, Fooks AR, Breed AC (2013) Epidemiological perspectives on West Nile virus surveillance in wild birds in Great Britain, EPIDEMIOLOGY AND INFECTION141(6)pp. 1134-1142 CAMBRIDGE UNIV PRESS
Cliquet F, Freuling C, Smreczak M, Van der Poel WHM, Horton DL, Fooks AR, Robardet E, Picard-Meyer E, Müller T (2010) Development of harmonised schemes for monitoring and reporting of rabies in animals in the European Union, Scientific Report submitted to EFSA (Q-2010?00078)
Goddard AD, Donaldson NM, Horton DL, Kosmider R, Kelly LA, Sayers AR, Breed AC, Freuling CM, Mueller T, Shaw SE, Hallgren G, Fooks AR, Snary EL (2012) A Quantitative Release Assessment for the Noncommercial Movement of Companion Animals: Risk of Rabies Reintroduction to the United Kingdom, RISK ANALYSIS32(10)pp. 1769-1783 WILEY-BLACKWELL
McElhinney LM, Marston DA, Leech S, Freuling CM, van der Poel WHM, Echevarria J, Vazquez-Moron S, Horton DL, Mueller T, Fooks AR (2013) Molecular Epidemiology of Bat Lyssaviruses in Europe, ZOONOSES AND PUBLIC HEALTH60(1)pp. 35-45 WILEY-BLACKWELL
Mansfield KL, Banyard AC, McElhinney L, Johnson N, Horton DL, Hernandez-Triana LM, Fooks AR (2015) Rift Valley fever virus: A review of diagnosis and vaccination, and implications for emergence in Europe, VACCINE33(42)pp. 5520-5531 ELSEVIER SCI LTD
Evans JS, Horton DL, Fooks AR, Banyard AC, Evans JS, Easton AJ, Fooks AR (2012) Rabies virus vaccines: Is there a need for a pan-lyssavirus vaccine?, Vaccine
All members of the lyssavirus genus are capable of causing disease that invariably results in death following the development of clinical symptoms. The recent detection of several novel lyssavirus species across the globe, in different animal species, has demonstrated that the lyssavirus genus contains a greater degree of genetic and antigenic variation than previously suspected. The divergence of species within the genus has led to a differentiation of lyssavirus isolates based on both antigenic and genetic data into two, and potentially a third phylogroup. Critically, from both a human and animal health perspective, current rabies vaccines appear able to protect against lyssaviruses classified within phylogroup I. However no protection is afforded against phylogroup II viruses or other more divergent viruses. Here we review current knowledge regarding the diversity and antigenicity of the lyssavirus glycoprotein. We review the degree of cross protection afforded by rabies vaccines, the genetic and antigenic divergence of the lyssaviruses and potential mechanisms for the development of novel lyssavirus vaccines for use in areas where divergent lyssaviruses are known to circulate, as well as for use by those at occupational risk from these pathogens. Crown Copyright © 2012.
Pant GR, Horton DL, Dahal M, Rai JN, Ide S, Leech S, Marston DA, McElhinney LM, Fooks AR (2011) Characterization of rabies virus from a human case in Nepal, ARCHIVES OF VIROLOGY156(4)pp. 681-684 SPRINGER WIEN
Garcia G, Cunningham AA, Horton DL, Garner TWJ, Hyatt A, Hengstberger S, Lopez J, Ogrodowczyk A, Fenton C, Fa JE (2007) Mountain chickens Leptodactylus fallax and sympatric amphibians appear to be disease free on Montserrat, Oryx4103pp. 398-401 Cambridge Univ Press
Hayman DTS, Johnson N, Horton DL, Hedge J, Wakeley PR, Banyard AC, Zhang S, Alhassan A, Fooks AR (2011) Evolutionary History of Rabies in Ghana, PLOS NEGLECTED TROPICAL DISEASES5(4)ARTN e1001 PUBLIC LIBRARY SCIENCE
Yakobson B, Goga I, Freuling CM, Fooks AR, Gjinovci V, Hulaj B, Horton D, Johnson N, Muhaxhiri J, Recica I, David D, O'Flaherty R, Taylor N, Wilsmore T, Müller T (2014) Implementation and monitoring of oral rabies vaccination of foxes in Kosovo between 2010 and 2013--an international and intersectorial effort., Int J Med Microbiol304(7)pp. 902-910
The European Union has used instrument for pre-accession (IPA) funds to provide technical assistance and supplies for the eradication, monitoring and control of rabies in several pre-accession countries. As a result, since 2010, multi-annual oral rabies vaccination (ORV) programmes for eliminating fox rabies have been launched in six Western Balkan countries. Here the implementation of the ORV programme in Kosovo, the smallest of the West Balkan countries, is described. Associated challenges under difficult political conditions, potential biases, and the results of rabies surveillance and monitoring of ORV campaigns (bait uptake and immunisation rates) since 2010 are reported.
Viana M, Cleaveland S, Matthiopoulos J, Halliday J, Packer C, Craft ME, Hampson K, Czupryna A, Dobson AP, Dubovi EJ, Ernest E, Fyumagwa R, Hoare R, Hopcraft JG, Horton DL, Kaare MT, Kanellos T, Lankester F, Mentzel C, Mlengeya T, Mzimbiri I, Takahashi E, Willett B, Haydon DT, Lembo T (2015) Dynamics of a morbillivirus at the domestic-wildlife interface: Canine distemper virus in domestic dogs and lions., Proc Natl Acad Sci U S A112(5)pp. 1464-1469
Morbilliviruses cause many diseases of medical and veterinary importance, and although some (e.g., measles and rinderpest) have been controlled successfully, others, such as canine distemper virus (CDV), are a growing concern. A propensity for host-switching has resulted in CDV emergence in new species, including endangered wildlife, posing challenges for controlling disease in multispecies communities. CDV is typically associated with domestic dogs, but little is known about its maintenance and transmission in species-rich areas or about the potential role of domestic dog vaccination as a means of reducing disease threats to wildlife. We address these questions by analyzing a long-term serological dataset of CDV in lions and domestic dogs from Tanzania's Serengeti ecosystem. Using a Bayesian state-space model, we show that dynamics of CDV have changed considerably over the past three decades. Initially, peaks of CDV infection in dogs preceded those in lions, suggesting that spill-over from dogs was the main driver of infection in wildlife. However, despite dog-to-lion transmission dominating cross-species transmission models, infection peaks in lions became more frequent and asynchronous from those in dogs, suggesting that other wildlife species may play a role in a potentially complex maintenance community. Widespread mass vaccination of domestic dogs reduced the probability of infection in dogs and the size of outbreaks but did not prevent transmission to or peaks of infection in lions. This study demonstrates the complexity of CDV dynamics in natural ecosystems and the value of long-term, large-scale datasets for investigating transmission patterns and evaluating disease control strategies.
Horton D, Wise E (2011) Raising awareness of rabies., The Veterinary record16911pp. 271-271
Vaux AGC, Gibson G, Hernandez-Triana LM, Cheke RA, McCracken F, Jeffries CL, Horton DL, Springate S, Johnson N, Fooks AR, Leach S, Medlock JM (2015) Enhanced West Nile virus surveillance in the North Kent marshes, UK, Parasites and Vectors8(1)
© 2015 Vaux et al.; licensee BioMed Central.Background: As part of efforts to more fully understand the potential risks posed by West Nile virus (WNV) and Usutu virus (USUV) in the UK, and following on from previous reports of a potential bridge vector Culex modestus for these viruses, at wetland sites in North Kent, mosquito surveillance was undertaken more widely across the Isle of Sheppey, the Hoo Peninsula and the Kent mainland. Methods: Larval surveys were conducted and Mosquito Magnet® adult traps were used to collect adult mosquitoes. Pools of female mosquitoes were tested for the presence of WNV using real-time reverse transcriptase polymerase chain reaction. A subset of samples was tested for USUV. Results: Culex modestus was found in both the pre-imaginal and imago stage at all five locations surveyed, accounting for 90% of adult mosquitoes collected. WNV or USUV were not detected in any sample. Conclusions: Although no mosquitoes have been shown to be virus positive, the field survey data from this study demonstrated the dominance of an important bridge vector species for WNV in this region. Its wide geographical distribution highlights the need to update risk assessments on WNV introduction, and to maintain vigilance for WNV in the South East of England.
Marston DA, Ellis RJ, Horton DL, Kuzmin IV, Wise EL, McElhinney LM, Banyard AC, Ngeleja C, Keyyu J, Cleaveland S, Lembo T, Rupprecht CE, Fooks AR (2012) Complete Genome Sequence of Ikoma Lyssavirus, JOURNAL OF VIROLOGY86(18)pp. 10242-10243 AMER SOC MICROBIOLOGY
Nolden T, Banyard AC, Finke S, Fooks AR, Hanke D, Höper D, Horton DL, Mettenleiter TC, Müller T, Teifke JP, Freuling CM (2014) Comparative studies on the genetic, antigenic and pathogenic characteristics of Bokeloh bat lyssavirus., J Gen Virol95(Pt 8)pp. 1647-1653
Bokeloh bat lyssavirus (BBLV), a novel lyssavirus, was isolated from a Natterer's bat (Myotis nattererii), a chiropteran species with a widespread and abundant distribution across Europe. As a novel lyssavirus, the risks of BBLV to animal and human health are unknown and as such characterization both in vitro and in vivo was required to assess pathogenicity and vaccine protection. Full genome sequence analysis and antigenic cartography demonstrated that the German BBLV isolates are most closely related to European bat lyssavirus type 2 (EBLV-2) and Khujand virus and can be characterized within phylogroup I. In vivo characterization demonstrated that BBLV was pathogenic in mice when inoculated peripherally causing clinical signs typical for rabies encephalitis, with higher pathogenicity observed in juvenile mice. A limited vaccination-challenge experiment in mice was conducted and suggested that current vaccines would afford some protection against BBLV although further studies are warranted to determine a serological cut-off for protection.
Mansfield KL, Horton DL, Johnson N, Li L, Barrett ADT, Smith DJ, Galbraith SE, Solomon T, Fooks AR (2011) Flavivirus-induced antibody cross-reactivity, JOURNAL OF GENERAL VIROLOGY92pp. 2821-2829 SOC GENERAL MICROBIOLOGY
Morters MK, McNabb S, Horton DL, Fooks AR, Schoeman JP, Whay HR, Wood JL, Cleaveland S (2015) Effective vaccination against rabies in puppies in rabies endemic regions., Vet Rec177(6)
In rabies endemic regions, a proportionally higher incidence of rabies is often reported in dogs younger than 12?months of age, which includes puppies less than 3 months of age; this presents a serious risk to public health. The higher incidence of rabies in young dogs may be the effect of low vaccination coverage in this age class, partly as a result of the perception that immature immune systems and maternal antibodies inhibit seroconversion to rabies vaccine in puppies less than three months of age. Therefore, to test this perception, the authors report the virus neutralising antibody titres from 27 dogs that were vaccinated with high quality, inactivated rabies vaccine aged three months of age and under as part of larger serological studies undertaken in Gauteng Province, South Africa, and the Serengeti District, Tanzania. All of these dogs seroconverted to a single dose of vaccine with no adverse reactions reported and with postvaccinal peak titres ranging from 2.0 IU/ml to 90.5?IU/ml. In light of these results, and the risk of human beings contracting rabies from close contact with puppies, the authors recommend that all dogs in rabies endemic regions, including those less than three months of age, are vaccinated with high quality, inactivated vaccine.
Fooks AR, Horton DL, Johnson N, Toth B, Roberts HC (2011) Changes to pet travel rules: rabies, ticks and tapeworms, VETERINARY RECORD169(4)pp. 97-98 BRITISH VETERINARY ASSOC
Brunker K, Hampson K, Horton DL, Biek R (2012) Integrating the landscape epidemiology and genetics of RNA viruses: rabies in domestic dogs as a model, PARASITOLOGY139(14)pp. 1899-1913 CAMBRIDGE UNIV PRESS
Brunker K, Marston DA, Horton DL, Cleaveland S, Fooks AR, Kazwala R, Ngeleja C, Lembo T, Sambo M, Mtema ZJ, Sikana L, Wilkie G, Biek R, Hampson K (2015) Elucidating the phylodynamics of endemic rabies virus in eastern Africa using whole-genome sequencing.,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.
Hayman DTS, Fooks AR, Rowcliffe JM, McCrea R, Restif O, Baker KS, Horton DL, Suu-Ire R, Cunningham AA, Wood JLN (2012) Endemic Lagos bat virus infection in Eidolon helvum, EPIDEMIOLOGY AND INFECTION140(12)pp. 2163-2171 CAMBRIDGE UNIV PRESS
Baker KS, Wood JLN, Durrant C, Cunningham AA, Suu-Ire R, Barr J, Hayman DTS, Broder CC, Horton DL, Murcia PR (2013) Viral antibody dynamics in a chiropteran host, Journal of Animal Ecology
Bats host many viruses that are significant for human and domestic animal health, but the dynamics of these infections in their natural reservoir hosts remain poorly elucidated. In these, and other, systems, there is evidence that seasonal life-cycle events drive infection dynamics, directly impacting the risk of exposure to spillover hosts. Understanding these dynamics improves our ability to predict zoonotic spillover from the reservoir hosts. To this end, we followed henipavirus antibody levels of >100 individual E. helvum in a closed, captive, breeding population over a 30-month period, using a powerful novel antibody quantitation method. We demonstrate the presence of maternal antibodies in this system and accurately determine their longevity. We also present evidence of population-level persistence of viral infection and demonstrate periods of increased horizontal virus transmission associated with the pregnancy/lactation period. The novel findings of infection persistence and the effect of pregnancy on viral transmission, as well as an accurate quantitation of chiropteran maternal antiviral antibody half-life, provide fundamental baseline data for the continued study of viral infections in these important reservoir hosts. This is the first study of henipaviral infection dynamics in a fully closed population of the natural reservoir hosts. The authors detect population-level infection persistence as well as increased periods of viral transmission related to life-cycle events. These data help us to understand the seasonality of recurrent zoonotic spillovers of viruses from bat populations. © 2013 The Authors.
Healy DM, Horton DL (2013) Claire L. leffries, Ashley C. Banyard, Neuroviral Infections: RNA Viruses and Retroviruses2pp. 373-373 CRC Press
Fooks AR, Banyard AC, Horton DL, Johnson N, McElhinney LM, Jackson AC (2014) Current status of rabies and prospects for elimination., Lancet384(9951)pp. 1389-1399
Rabies is one of the most deadly infectious diseases, with a case-fatality rate approaching 100%. The disease is established on all continents apart from Antarctica; most cases are reported in Africa and Asia, with thousands of deaths recorded annually. However, the estimated annual figure of almost 60,000 human rabies fatalities is probably an underestimate. Almost all cases of human rabies result from bites from infected dogs. Therefore, the most cost-effective approach to elimination of the global burden of human rabies is to control canine rabies rather than expansion of the availability of human prophylaxis. Mass vaccination campaigns with parenteral vaccines, and advances in oral vaccines for wildlife, have allowed the elimination of rabies in terrestrial carnivores in several countries worldwide. The subsequent reduction in cases of human rabies in such regions advocates the multidisciplinary One Health approach to rabies control through the mass vaccination of dogs and control of canine populations.
Lawson B, Dastjerdi A, Shah S, Everest D, Nunez A, Pocknell A, Hicks D, Horton DL, Cunningham AA, Irvine RM (2015) Mortality associated with avian reovirus infection in a free-living magpie (Pica pica) in Great Britain, BMC VETERINARY RESEARCH11ARTN 20 BIOMED CENTRAL LTD
Robardet E, Andrieu S, Rasmussen TB, Dobrostana M, Horton DL, Hostnik P, Jaceviciene I, Juhasz T, Mueller T, Mutinelli F, Servat A, Smreczak M, Vanek E, Vazquez-Moron S, Cliquet F (2013) Comparative assay of fluorescent antibody test results among twelve European National Reference Laboratories using various anti-rabies conjugates, JOURNAL OF VIROLOGICAL METHODS191(1)pp. 88-94 ELSEVIER SCIENCE BV
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.
HASANOV E, ZEYNALOVA S, GELEISHVILI M, MAES E, TONGREN E, MARSHALL E, BANYARD A, MCELHINNEY L, WHATMORE A, FOOKS A, Horton D (2017) Assessing the impact of public education on a preventable zoonotic disease: rabies,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.
Marston D, Horton D, Nunez J, Ellis R, Orton R, Johnson N, Banyard A, McElhinney L, Freuling C, Firat M, Ünal N, Thomas M, Fooks A (2017) Genetic analysis of a rabies virus host shift event reveals within-host viral dynamics in a new host,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.
Suu-Ire R, Begeman L, Banyard A, Breed A, Drosten C, Eggerbauer E, Freuling C, Gibson L, Goharriz H, Horton D, Jennings D, Kuzmin I, Marston D, Ntiamoa-Baidu Y, Sbarbaro S, Selden D, Wise E, Kuiken T, Fooks A, Müller T, Wood J, Cunningham A (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,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.
Yon Lisa, Duff J. Paul, Ågren Erik O., Erdélyi Károly, Ferroglio Ezio, Godfroid Jacques, Hars Jean, Hestvik Gete, Horton Dan, Kuiken Thijs, Lavazza Antonio, Markowska-Daniel Iwona, Martel An, Neimanis Aleksija, Pasmans Frank, Price Stephen, Ruiz-Fons Francisco, Ryser-Degiorgis Marie-Pierre, Widén Frederik, Gavier-Widén Dolores (2018) Recent changes in infectious diseases in European wildlife,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.
Rift Valley fever phlebovirus (RVFV) is an arbovirus of medical and veterinary importance causing severe disease and mortality in humans and ruminants in endemic regions in Africa and the Arabian Peninsula. Understanding the capability, and limiting factors, of temperate British mosquitoes to support replication and transmission of RVFV is critical in order to understand the potential for RVFV establishment were it introduced to the UK. Using in vitro cell culture the effect of temperature on viral replication kinetics independently of the mosquito was investigated; demonstrating temperatures below 20ÚC negatively affect RVFV replication. The full replication cycle was supported at 20ÚC in vitro, and this was confirmed within in vivo mosquito experiments with wild-caught Aedes detritus demonstrating a transmission potential for RVFV at 20ÚC and 25ÚC. Experiments with two colonised lines of Cx. pipiens further demonstrated the transmission potential for RVFV by mosquitoes present in the UK. A novel RNA in situ hybridisation technique substantiated this result showing widespread dissemination of virus from the primary site of infection and evidence of secondary sites of replication within a single mosquito.
Characterisation of the consensus sequence of RVFV propagated within these British mosquitoes in comparison to an in vivo mouse model showed potential for virus adaptation when switching between disparate hosts. Reproducible changes at the consensus level within each host had not previously been shown in early passages of RVFV in studies utilising in vitro models of replication. This suggests that RVFV replication generates genomic variation that may lead to adaptations that could promote potential survival in temperate regions.
Taken together these findings indicate that transmission of RVFV within the UK by indigenous mosquitoes is possible. However, factors affecting mosquito survival including temperatures greater than 20ÚC and ingestion of the higher virus dose (10^7 PFU/mL) will limit the likelihood of such events occurring.
Lorusso Alessio, Marini Valeria, Di Gennaro Annapia, Ronchi Gaetano Federico, Casaccia Claudia, Carelli Grazia, Passantino Giuseppe, D?Alterio Nicola, D?Innocenzo Vincenzo, Savini Giovanni, Monaco Federica, Horton Daniel (2019) Antigenic relationship among zoonotic flaviviruses from Italy,Infection, Genetics and Evolution68pp. 91-97
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.
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.