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Liverpool, United Kingdom

The trials, undertaken by the University of Oxford, the Ethiopian Wildlife Conservation Authority and the UK Animal and Plant Health Agency in the Bale Mountains of Ethiopia, are the first ever conducted in wild populations of an endangered carnivore. Researchers from Ethiopia and the UK tested various types of baits and ways to deliver the vaccine, trialling SAG2 in three wolf packs. Of 21 wolves trapped after vaccinations, 14 were positive for a biomarker indicating that the animal had ingested the bait; of these, half showed antibody titres in blood above the universally recognised threshold, and 86% had levels considered sufficient to provide protective immunity to wildlife. Wolves were closely monitored after the vaccination, and all but one of the wolves vaccinated were alive 14 months later (higher than average survival). Oral vaccination proved to be the answer to controlling rabies in wild populations of red foxes and northern raccoons in Europe and North America, but the approach has never been tested in wild populations of endangered carnivores such as Ethiopian wolves and African wild dogs, which are at risk of extinction because of outbreaks of infectious diseases. Rabies is a virus that kills people, domestic livestock and wild animals worldwide, and is particularly prevalent in the highlands of Ethiopia, where rabies recurrently jumps from domestic dogs into their wild relatives, the charismatic Ethiopian wolves. With fewer than 500 adult wolves left in half a dozen mountain ranges, and no captive populations, Ethiopian wolves are much rarer than giant pandas and unlikely to sustain the immediate and present threats rising from growing numbers of dogs and people living in and around their mountain enclaves. But with wolves living in a sea of domestic dogs, in shrinking habitat islands, there is no time left to waste. Oral vaccination offers a more cost-efficient, safe and proactive approach to protect Ethiopian wolves and other threatened canids from rabies. Lead author Professor Claudio Sillero-Zubiri, of the Wildlife Conservation Research Unit (WildCRU) in the Department of Zoology at the University of Oxford, said: 'We now have a safe vaccine, a suitable bait, an efficient delivery method, and trained monitoring teams in place - all crucial steps which open up the possibility for scaling up the oral vaccination and protecting the wolf populations at risk, before disease strikes again.' Head wolf monitor Alo Hussein, of the Ethiopian Wolf Conservation Programme (EWCP), said: 'In spite of investing in excess of US$30,000 a year vaccinating thousands of domestic dogs, it has been impossible to attain a level of dog vaccinations that would remove the risk of wolves getting infected, due to the large and dynamic dog population in the Bale Mountains.' Professor Tony Fooks, of the Institute of Infection and Global Health, University of Liverpool, and the Animal and Plant Health Agency, said: 'These preliminary results using an oral vaccination strategy to protect Ethiopian wolves against rabies are encouraging and provide proof-of-principle for the use of this approach in wild canids.' Dr Fekede Regassa, of the Ethiopian Wildlife Conservation Authority, said: 'Since 1990, four major rabies outbreaks led each time to the crash of the Bale Mountains wolf population, the world's largest, typically killing 50-75% of the subpopulation affected. EWCP vaccinates wolves reactively whenever a rabies outbreak is confirmed, contributing to contain the disease, but only after many wolves die - by the time rabies is detected, the virus is well established, and as wolves are highly social, it spreads fast.' More information: Claudio Sillero-Zubiri et al, Feasibility and efficacy of oral rabies vaccine SAG2 in endangered Ethiopian wolves, Vaccine (2016). DOI: 10.1016/j.vaccine.2016.08.021

Prorok-Hamon M.,Institute of Translational Medicine | Friswell M.K.,Institute of Translational Medicine | Alswied A.,Institute of Translational Medicine | Roberts C.L.,Institute of Translational Medicine | And 10 more authors.
Gut | Year: 2014

Objective: Colonic mucosa-associated Escherichia coli are increased in Crohn's disease (CD) and colorectal cancer (CRC). They variously haemagglutinate, invade epithelial cell lines, replicate within macrophages, translocate across M (microfold) cells and damage DNA. We investigated genes responsible for these effects and their co-association in colonic mucosal isolates. Design: A fosmid library yielding 968 clones was prepared in E coli EPI300-T1 using DNA from a haemagglutinating CRC isolate, and resulting haemagglutinating clones were 454-pyrosequenced. PCR screening was performed on 281 colonic E coli isolates from inflammatory bowel disease (IBD) (35 patients), CRC (21) and controls (24; sporadic polyps or irritable bowel syndrome). Results: 454-Pyrosequencing of fosmids from the haemagglutinating clones (n=8) identified the afimbrial adhesin afa-1 operon. Transfection of afa-1 into E coli K-12 predictably conferred diffuse adherence plus invasion of HEp-2 and I-407 epithelial cells, and upregulation of vascular endothelial growth factor. E coli expressing afaC were common in CRC (14/21, p=0.0009) and CD (9/14, p=0.005) but not ulcerative colitis (UC; 8/21) compared with controls (4/24). E coli expressing both afaC and lpfA (relevant to M-cell translocation) were common in CD (8/14, p=0.0019) and CRC (14/21, p=0.0001), but not UC (6/21) compared with controls (2/24). E coli expressing both afaC and pks (genotoxic) were common in CRC (11/21, p=0.0015) and UC (8/21, p=0.022), but not CD (4/14) compared with controls (2/24). All isolates expressed dsbA and htrA relevant to intra-macrophage replication, and 242/281 expressed fimH encoding type-1 fimbrial adhesin. Conclusions: IBD and CRC commonly have colonic mucosal E coli that express genes that confer properties relevant to pathogenesis including M-cell translocation, angiogenesis and genotoxicity.

Howell A.,University of Liverpool | Baylis M.,University of Liverpool | Baylis M.,Institute of Infection and Global Health | Smith R.,University of Liverpool | And 3 more authors.
Preventive Veterinary Medicine | Year: 2015

The liver fluke Fasciola hepatica is a trematode parasite with a worldwide distribution and is the cause of important production losses in the dairy industry. The aim of this observational study was to assess the prevalence of exposure to F. hepatica in a group of high yielding dairy herds, to determine the risk factors and investigate their associations with production and fertility parameters. Bulk milk tank samples from 606 herds that supply a single retailer with liquid milk were tested with an antibody ELISA for F. hepatica. Multivariable linear regression was used to investigate the effect of farm management and environmental risk factors on F. hepatica exposure. Higher rainfall, grazing boggy pasture, presence of beef cattle on farm, access to a stream or pond and smaller herd size were associated with an increased risk of exposure. Univariable regression was used to look for associations between fluke exposure and production-related variables including milk yield, composition, somatic cell count and calving index. Although causation cannot be assumed, a significant (. p<. 0.001) negative association was seen between F. hepatica exposure and estimated milk yield at the herd level, representing a 15% decrease in yield for an increase in F. hepatica exposure from the 25th to the 75th percentile. This remained significant when fertility, farm management and environmental factors were controlled for. No associations were found between F. hepatica exposure and any of the other production, disease or fertility variables. © 2015 The Authors.

Defres S.,University of Liverpool | Mayer J.,Institute of Infection and Global Health | Backman R.,Institute of Infection and Global Health | Kneen R.,University of Liverpool
British Journal of Hospital Medicine | Year: 2015

Lumbar punctures are essential in the management of suspected CNS infections. However, despite clear guidelines their use can be haphazard. This survey investigated the training, knowledge and experience of UK doctors in training in relation to lumbar punctures. © 2015 MA Healthcare Ltd.

Gray C.,Institute of Infection and Global Health | Ahmed M.S.,Institute of Infection and Global Health | Mubarak A.,Institute of Infection and Global Health | Kasbekar A.V.,Alder Hey Childrens Hospital | And 6 more authors.
Mucosal Immunology | Year: 2014

Pneumococcal carriageiscommon in children thatmay account for the high incidenceofdisease in thisagegroup.Recent studies in animals suggest an important role for CD4 Tcells, T helper type 17 (Th17) cells in particular, in pneumococcal clearance. Whether this Th17-mediated mechanism operates in humans and what pneumococcal components activate Th17 are unknown.We investigated the ability of domain 4 pneumolysin (D4Ply) to activateCD4 Tcells including Th17 in human nasopharynx-associated lymphoid tissue (NALT) and peripheral blood.We show that D4Ply elicited a prominent CD4 T-cell proliferative response. More importantly, D4Ply elicited a significant memory Th17 response in NALT, and a moderate response inperipheral bloodmononuclear cells (PBMCs). ThisD4Ply-elicitedmemory Th17 responsewasmore marked in carriage than in carriage children in bothNALTand PBMCs. In contrast, no differencewas shown inD4Plyinduced Th1 response between the two groups. We also show D4Ply activated human monocytes and murine macrophages that was in part dependent on Toll-like receptor 4 (TLR-4). Our results support a protective role of Th17 against pneumococcal carriage in human nasopharynx, and identify a novel property of D4Ply to activate Th17 in NALT that may offer an attractive vaccine candidate in intranasal immunization against pneumococcal infection. © 2014 Society for Mucosal Immunology.

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