Rayamajhi A.,University of Liverpool |
Rayamajhi A.,National Academy of Medical science |
Rayamajhi A.,Kanti Childrens Hospital |
Nightingale S.,University of Liverpool |
And 18 more authors.
PLoS ONE | Year: 2015
Background: Japanese encephalitis (JE) virus (JEV) is a mosquito-borne flavivirus found across Asia that is closely related to West Nile virus. There is no known antiviral treatment for any flavivirus. Results from in vitro studies and animal models suggest intravenous immunoglobulin (IVIG) containing virus-specific neutralizing antibody may be effective in improving outcome in viral encephalitis. IVIG' s anti-inflammatory properties may also be beneficial. Methodology/Principal Findings: We performed a pilot feasibility randomized double-blind placebo-controlled trial of IVIG containing anti-JEV neutralizing antibody (ImmunoRel, 400mg/kg/day for 5 days) in children with suspected JE at two sites in Nepal; we also examined the effect on serum neutralizing antibody titre and cytokine profiles. 22 children were recruited, 13 of whom had confirmed JE; 11 received IVIG and 11 placebo, with no protocol violations. One child (IVIG group) died during treatment and two (placebo) subsequently following hospital discharge. Overall, there was no difference in outcome between treatment groups at discharge or follow up. Passive transfer of anti-JEV antibody was seen in JEV negative children. JEV positive children treated with IVIG had JEV-specific neutralizing antibody titres approximately 16 times higher than those treated with placebo (p=0.2), which was more than could be explained by passive transfer alone. IL-4 and IL-6 were higher in the IVIG group. Conclusions/Significance: A trial of IVIG for JE in Nepal is feasible. IVIG may augment the development of neutralizing antibodies in JEV positive patients. IVIG appears an appealing option for JE treatment that warrants further study. Trial Registration: ClinicalTrials.gov NCT01856205. © 2015, Public Library of Science. All rights reserved.
Marston D.A.,Animal Health and Veterinary Laboratories Agency AHVLA |
Marston D.A.,Aix - Marseille University |
McElhinney L.M.,Animal Health and Veterinary Laboratories Agency AHVLA |
McElhinney L.M.,National Consortium for Zoonosis Research |
And 8 more authors.
BMC Genomics | Year: 2013
Background: With the advent of Next Generation Sequencing (NGS) technologies, the ability to generate large amounts of sequence data has revolutionized the genomics field. Most RNA viruses have relatively small genomes in comparison to other organisms and as such, would appear to be an obvious success story for the use of NGS technologies. However, due to the relatively low abundance of viral RNA in relation to host RNA, RNA viruses have proved relatively difficult to sequence using NGS technologies. Here we detail a simple, robust methodology, without the use of ultra-centrifugation, filtration or viral enrichment protocols, to prepare RNA from diagnostic clinical tissue samples, cell monolayers and tissue culture supernatant, for subsequent sequencing on the Roche 454 platform.Results: As representative RNA viruses, full genome sequence was successfully obtained from known lyssaviruses belonging to recognized species and a novel lyssavirus species using these protocols and assembling the reads using de novo algorithms. Furthermore, genome sequences were generated from considerably less than 200 ng RNA, indicating that manufacturers' minimum template guidance is conservative. In addition to obtaining genome consensus sequence, a high proportion of SNPs (Single Nucleotide Polymorphisms) were identified in the majority of samples analyzed.Conclusions: The approaches reported clearly facilitate successful full genome lyssavirus sequencing and can be universally applied to discovering and obtaining consensus genome sequences of RNA viruses from a variety of sources. © 2013 Marston et al.; licensee BioMed Central Ltd.
Marston D.A.,Animal Health and Veterinary Laboratories Agency |
Horton D.L.,Animal Health and Veterinary Laboratories Agency |
Ngeleja C.,Central Veterinary Laboratory |
Hampson K.,University of Glasgow |
And 10 more authors.
Emerging Infectious Diseases | Year: 2012
Evidence in support of a novel lyssavirus was obtained from brain samples of an African civet in Tanzania. Results of phylogenetic analysis of nucleoprotein gene sequences from representative Lyssavirus species and this novel lyssavirus provided strong empirical evidence that this is a new lyssavirus species, designated Ikoma lyssavirus.
Jones P.H.,University of Liverpool |
Jones P.H.,National Consortium for Zoonosis Research |
Dawson S.,University of Liverpool |
Gaskell R.M.,University of Liverpool |
And 5 more authors.
Veterinary Journal | Year: 2014
Using the Small Animal Veterinary Surveillance Network (SAVSNET), a national small animal disease-surveillance scheme, information on gastrointestinal disease was collected for a total of 76days between 10 May 2010 and 8 August 2011 from 16,223 consultations (including data from 9115 individual dogs and 3462 individual cats) from 42 premises belonging to 19 UK veterinary practices. During that period, 7% of dogs and 3% of cats presented with diarrhoea.Adult dogs had a higher proportional morbidity of diarrhoea (PMD) than adult cats (P<. 0.001). This difference was not observed in animals <1year old. Younger animals in both species had higher PMDs than adult animals (P<0.001). Neutering was associated with reduced PMD in young male dogs. In adult dogs, miniature Schnauzers had the highest PMD. Most animals with diarrhoea (51%) presented having been ill for 2-4days, but a history of vomiting or haemorrhagic diarrhoea was associated with a shorter time to presentation. The most common treatments employed were dietary modification (66% of dogs; 63% of cats) and antibacterials (63% of dogs; 49% of cats). There was variability in PMD between different practices.The SAVNET methodology facilitates rapid collection of cross-sectional data regarding diarrhoea, a recognised sentinel for infectious disease, and characterises data that could benchmark clinical practice and support the development of evidence-based medicine. © 2014 Elsevier Ltd.
McIntyre K.M.,University of Liverpool |
McIntyre K.M.,National Consortium for Zoonosis Research |
Setzkorn C.,University of Liverpool |
Setzkorn C.,National Consortium for Zoonosis Research |
And 5 more authors.
PLoS ONE | Year: 2014
Disease or pathogen risk prioritisations aid understanding of infectious agent impact within surveillance or mitigation and biosecurity work, but take significant development. Previous work has shown the H-(Hirsch-)index as an alternative proxy. We present a weighted risk analysis describing infectious pathogen impact for human health (human pathogens) and wellbeing (domestic animal pathogens) using an objective, evidence-based, repeatable approach; the H-index. This study established the highest H-index European pathogens. Commonalities amongst pathogens not included in previous surveillance or risk analyses were examined. Differences between host types (humans/animals/zoonotic) in pathogen H-indices were explored as a One Health impact indicator. Finally, the acceptability of the H-index proxy for animal pathogen impact was examined by comparison with other measures. 57 pathogens appeared solely in the top 100 highest H-indices (1) human or (2) animal pathogens list, and 43 occurred in both. Of human pathogens, 66 were zoonotic and 67 were emerging, compared to 67 and 57 for animals. There were statistically significant differences between H-indices for host types (humans, animal, zoonotic), and there was limited evidence that H-indices are a reasonable proxy for animal pathogen impact. This work addresses measures outlined by the European Commission to strengthen climate change resilience and biosecurity for infectious diseases. The results include a quantitative evaluation of infectious pathogen impact, and suggest greater impacts of human-only compared to zoonotic pathogens or scientific under-representation of zoonoses. The outputs separate high and low impact pathogens, and should be combined with other risk assessment methods relying on expert opinion or qualitative data for priority setting, or could be used to prioritise diseases for which formal risk assessments are not possible because of data gaps. © 2014 McIntyre et al.
Christley R.M.,University of Liverpool |
Christley R.M.,National Consortium for Zoonosis Research |
Mort M.,Lancaster University |
Wynne B.,Lancaster University |
And 7 more authors.
PLoS ONE | Year: 2013
For infectious disease dynamical models to inform policy for containment of infectious diseases the models must be able to predict; however, it is well recognised that such prediction will never be perfect. Nevertheless, the consensus is that although models are uncertain, some may yet inform effective action. This assumes that the quality of a model can be ascertained in order to evaluate sufficiently model uncertainties, and to decide whether or not, or in what ways or under what conditions, the model should be 'used'. We examined uncertainty in modelling, utilising a range of data: interviews with scientists, policy-makers and advisors, and analysis of policy documents, scientific publications and reports of major inquiries into key livestock epidemics. We show that the discourse of uncertainty in infectious disease models is multi-layered, flexible, contingent, embedded in context and plays a critical role in negotiating model credibility. We argue that usability and stability of a model is an outcome of the negotiation that occurs within the networks and discourses surrounding it. This negotiation employs a range of discursive devices that renders uncertainty in infectious disease modelling a plastic quality that is amenable to 'interpretive flexibility'. The utility of models in the face of uncertainty is a function of this flexibility, the negotiation this allows, and the contexts in which model outputs are framed and interpreted in the decision making process. We contend that rather than being based predominantly on beliefs about quality, the usefulness and authority of a model may at times be primarily based on its functional status within the broad social and political environment in which it acts. © 2013 Christley et al.
O'Shea T.J.,U.S. Geological Survey |
Cryan P.M.,U.S. Geological Survey |
Cunningham A.A.,Zoological Society of London |
Fooks A.R.,Animal Health and Veterinary Laboratories Agency Weybridge |
And 9 more authors.
Emerging Infectious Diseases | Year: 2014
Bats are sources of high viral diversity and high-profile zoonotic viruses worldwide. Although apparently not pathogenic in their reservoir hosts, some viruses from bats severely affect other mammals, including humans. Examples include severe acute respiratory syndrome coronaviruses, Ebola and Marburg viruses, and Nipah and Hendra viruses. Factors underlying high viral diversity in bats are the subject of speculation. We hypothesize that flight, a factor common to all bats but to no other mammals, provides an intensive selective force for coexistence with viral parasites through a daily cycle that elevates metabolism and body temperature analogous to the febrile response in other mammals. On an evolutionary scale, this host-virus interaction might have resulted in the large diversity of zoonotic viruses in bats, possibly through bat viruses adapting to be more tolerant of the fever response and less virulent to their natural hosts.
Luis A.D.,Colorado State University |
Luis A.D.,U.S. National Institutes of Health |
Hayman D.T.S.,Colorado State University |
Hayman D.T.S.,University of Cambridge |
And 16 more authors.
Proceedings of the Royal Society B: Biological Sciences | Year: 2013
Bats are the natural reservoirs of a number of high-impact viral zoonoses. We present a quantitative analysis to address the hypothesis that bats are unique in their propensity to host zoonotic viruses based on a comparison with rodents, another important host order. We found that bats indeed host more zoonotic viruses per species than rodents, and we identified life-history and ecological factors that promote zoonotic viral richness. More zoonotic viruses are hosted by species whose distributions overlap with a greater number of other species in the same taxonomic order (sympatry). Specifically in bats, there was evidence for increased zoonotic viral richness in species with smaller litters (one young), greater longevity and more litters per year. Furthermore, our results point to a new hypothesis to explain in part why bats host more zoonotic viruses per species: the stronger effect of sympatry in bats and more viruses shared between bat species suggests that interspecific transmission is more prevalent among bats than among rodents. Although bats host more zoonotic viruses per species, the total number of zoonotic viruses identified in bats (61) was lower than in rodents (68), a result of there being approximately twice the number of rodent species as bat species. Therefore, rodents should still be a serious concern as reservoirs of emerging viruses. These findings shed light on disease emergence and perpetuation mechanisms and may help lead to a predictive framework for identifying future emerging infectious virus reservoirs. © 2013 The Author(s) Published by the Royal Society. All rights reserved.
Horton D.L.,Animal Health and Veterinary Laboratories Agency |
Ismail M.Z.,Iraq State Company for Veterinary Services |
Siryan E.S.,Iraq State Company for Veterinary Services |
Wali A.R.A.,Iraq State Company for Veterinary Services |
And 10 more authors.
PLoS Neglected Tropical Diseases | Year: 2013
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. © 2013 Horton et al.
PubMed | University of Liverpool, Institute of Ageing and Chronic Disease and National Consortium for Zoonosis Research
Type: Journal Article | Journal: Equine veterinary journal | Year: 2015
Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections. While the epidemiology of antimicrobial resistance in bacteria from man has been studied extensively, less work has been undertaken in companionanimals, particularly horses. Methicillin-resistant Staphylococcus aureus has been identified as a cause of infections, with a low prevalence of nasal carriage by horses in the community but higher for hospitalised horses. Molecular characterisation has shown methicillin-resistant Staphylococcus aureus strains either to be predominantly of types associated with horses or of sequence type ST398. Antimicrobial-resistant Escherichia coli (including multidrug-resistant and extended spectrum -lactamase-producing isolates) have caused infections and been documented in faecal carriage by horses, with many significant resistance mechanisms identified. More sporadic reports and molecular characterisation exist for resistance in other bacteria such as enterococci, Salmonella, Acinetobacter and Pseudomonas species. Limited work has been undertaken evaluating risk factors and much of the epidemiology of antimicrobial resistance in bacteria from horses remains to be determined.