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The understanding of the pathogenic mechanisms and the clinicopathological forms caused by currently circulating African swine fever virus (ASFV) isolates is incomplete. So far, most of the studies have been focused on isolates classified within genotypes I and II, the only genotypes that have circulated outside of Africa. However, less is known about the clinical presentations and lesions induced by isolates belonging to the other twenty-two genotypes. Therefore, the early clinicopathological identification of disease outbreaks caused by isolates belonging to, as yet, not well-characterised ASFV genotypes may be compromised, which might cause a delay in the implementation of control measures to halt the virus spread. To improve the pathological characterisation of disease caused by diverse isolates, we have refined the macroscopic and histopathological evaluation protocols to standardise the scoring of lesions. Domestic pigs were inoculated intranasally with different doses (high, medium and low) of ASFV isolate Ken05/Tk1 (genotype X). To complement previous studies, the distribution and severity of macroscopic and histopathological lesions, along with the amount and distribution of viral antigen in tissues, were characterised by applying the new scoring protocols. The intranasal inoculation of domestic pigs with high doses of the Ken05/Tk1 isolate induced acute forms of ASF in most of the animals. Inoculation with medium doses mainly induced acute forms of disease. A less severe but longer clinical course, typical of subacute forms, characterised by the presence of more widespread and severe haemorrhages and oedema, was observed in one pig inoculated with the medium dose. The severity of vascular lesions (haemorrhages and oedema) induced by high and medium doses was not associated with the amount of virus antigen detected in tissues, therefore these might be attributed to indirect mechanisms not evaluated in the present study. The absence of clinical signs, lesions and detectable levels of virus genome or antigen in blood from the animals inoculated with the lowest dose ruled out the existence of possible asymptomatic carriers or persistently infected pigs, at least for the 21 days period of the study. The results corroborate the moderate virulence of the Ken05/Tk1 isolate, as well as its capacity to induce both the acute and, occasionally, subacute forms of ASF when high and medium doses were administered intranasally.
Pedro Sánchez-Cordón; Tobias Floyd; Daniel Hicks; Helen Crooke; Stephen McCleary; Ronan McCarthy; Rebecca Strong; Linda Dixon; Aleksija Neimanis; Emil Wikström-Lassa; Dolores Gavier-Widén; Alejandro Núñez. Evaluation of Lesions and Viral Antigen Distribution in Domestic Pigs Inoculated Intranasally with African Swine Fever Virus Ken05/Tk1 (Genotype X). Pathogens 2021, 10, 768 .
AMA StylePedro Sánchez-Cordón, Tobias Floyd, Daniel Hicks, Helen Crooke, Stephen McCleary, Ronan McCarthy, Rebecca Strong, Linda Dixon, Aleksija Neimanis, Emil Wikström-Lassa, Dolores Gavier-Widén, Alejandro Núñez. Evaluation of Lesions and Viral Antigen Distribution in Domestic Pigs Inoculated Intranasally with African Swine Fever Virus Ken05/Tk1 (Genotype X). Pathogens. 2021; 10 (6):768.
Chicago/Turabian StylePedro Sánchez-Cordón; Tobias Floyd; Daniel Hicks; Helen Crooke; Stephen McCleary; Ronan McCarthy; Rebecca Strong; Linda Dixon; Aleksija Neimanis; Emil Wikström-Lassa; Dolores Gavier-Widén; Alejandro Núñez. 2021. "Evaluation of Lesions and Viral Antigen Distribution in Domestic Pigs Inoculated Intranasally with African Swine Fever Virus Ken05/Tk1 (Genotype X)." Pathogens 10, no. 6: 768.
Burkholderia pseudomallei is the causative agent of melioidosis, which is a Gram negative, facultative intracellular bacterium. Disease is prevalent in SE Asia and in northern Australia, as well as in other tropical and subtropical regions. Recently, there is an increasing awareness of the importance of bacterial ingestion as a potential route of infection, particularly in cases of unexplained origin of the disease. The marmoset is a New World Monkey (NWM) species that is being developed as an alternative NHP model to complement the more traditionally used Old World Monkeys (OWM). Models have been developed for the traditional routes of disease acquisition, subcutaneous and inhalational. This manuscript details the development and characterisation of an ingestion model of melioidosis. Dose-ranging study assessed the lethality of B. pseudomallei and disease progression was assessed by euthanizing animals at predetermined time points, 12, 36, 48 and 54 hours post-challenge. Challenge doses of greater than 6.2 x 106 cfu resulted in an acute, lethal, febrile disease. Following challenge the lung was the first organ, outside of the gastrointestinal tract, to become colonised. Enteritis (duodenitis, ileitis and/or jejunitis) was observed in sections of the small intestine from animals that succumbed to disease. However, the most severe pathological features were observed in the mesenteric lymph nodes from these animals. These findings are consistent with lymphatic draining as route of dissemination.
Michelle Nelson; Alejandro Nunez; Sarah A. Ngugi; Timothy P. Atkins. The lymphatic system as a potential mechanism of spread of melioidosis following ingestion of Burkholderia pseudomallei. PLOS Neglected Tropical Diseases 2021, 15, e0009016 .
AMA StyleMichelle Nelson, Alejandro Nunez, Sarah A. Ngugi, Timothy P. Atkins. The lymphatic system as a potential mechanism of spread of melioidosis following ingestion of Burkholderia pseudomallei. PLOS Neglected Tropical Diseases. 2021; 15 (2):e0009016.
Chicago/Turabian StyleMichelle Nelson; Alejandro Nunez; Sarah A. Ngugi; Timothy P. Atkins. 2021. "The lymphatic system as a potential mechanism of spread of melioidosis following ingestion of Burkholderia pseudomallei." PLOS Neglected Tropical Diseases 15, no. 2: e0009016.
Avian influenza virus (AIV) subtypes H5 and H7 are capable of mutating from low to high pathogenicity strains, causing high mortality in poultry with significant economic losses globally. During 2015, two outbreaks of H7N7 low pathogenicity AIV (LPAIV) in Germany, and one each in the United Kingdom (UK) and The Netherlands occurred, as well as single outbreaks of H7N7 high pathogenicity AIV (HPAIV) in Germany and the UK. Both HPAIV outbreaks were linked to precursor H7N7 LPAIV outbreaks on the same or adjacent premises. Herein, we describe the clinical, epidemiological, and virological investigations for the H7N7 UK HPAIV outbreak on a farm with layer chickens in mixed free-range and caged units. H7N7 HPAIV was identified and isolated from clinical samples, as well as H7N7 LPAIV, which could not be isolated. Using serological and molecular evidence, we postulate how the viruses spread throughout the premises, indicating potential points of incursion and possible locations for the mutation event. Serological and mortality data suggested that the LPAIV infection preceded the HPAIV infection and afforded some clinical protection against the HPAIV. These results document the identification of a LPAIV to HPAIV mutation in nature, providing insights into factors that drive its manifestation during outbreaks.
Alexander Byrne; Scott Reid; Amanda Seekings; Alejandro Núñez; Ana Obeso Prieto; Susan Ridout; Caroline Warren; Anita Puranik; Vanessa Ceeraz; Stephen Essen; Marek Slomka; Jill Banks; Ian Brown; Sharon Brookes. H7N7 Avian Influenza Virus Mutation from Low to High Pathogenicity on a Layer Chicken Farm in the UK. Viruses 2021, 13, 259 .
AMA StyleAlexander Byrne, Scott Reid, Amanda Seekings, Alejandro Núñez, Ana Obeso Prieto, Susan Ridout, Caroline Warren, Anita Puranik, Vanessa Ceeraz, Stephen Essen, Marek Slomka, Jill Banks, Ian Brown, Sharon Brookes. H7N7 Avian Influenza Virus Mutation from Low to High Pathogenicity on a Layer Chicken Farm in the UK. Viruses. 2021; 13 (2):259.
Chicago/Turabian StyleAlexander Byrne; Scott Reid; Amanda Seekings; Alejandro Núñez; Ana Obeso Prieto; Susan Ridout; Caroline Warren; Anita Puranik; Vanessa Ceeraz; Stephen Essen; Marek Slomka; Jill Banks; Ian Brown; Sharon Brookes. 2021. "H7N7 Avian Influenza Virus Mutation from Low to High Pathogenicity on a Layer Chicken Farm in the UK." Viruses 13, no. 2: 259.
Ferrets were experimentally inoculated with SARS-CoV-2 (severe acute respiratory syndrome (SARS)-related coronavirus 2) to assess infection dynamics and host response. During the resulting subclinical infection, viral RNA was monitored between 2 and 21 days post-inoculation (dpi), and reached a peak in the upper respiratory cavity between 4 and 6 dpi. Viral genomic sequence analysis in samples from three animals identified the Y453F nucleotide substitution relative to the inoculum. Viral RNA was also detected in environmental samples, specifically in swabs of ferret fur. Microscopy analysis revealed viral protein and RNA in upper respiratory tract tissues, notably in cells of the respiratory and olfactory mucosae of the nasal turbinates, including olfactory neuronal cells. Antibody responses to the spike and nucleoprotein were detected from 21 dpi, but virus-neutralizing activity was low. A second intranasal inoculation (re-exposure) of two ferrets after a 17-day interval did not produce re-initiation of viral RNA shedding, but did amplify the humoral response in one animal. Therefore, ferrets can be experimentally infected with SARS-CoV-2 to model human asymptomatic infection.
Helen Everett; Fabian Lean; Alexander Byrne; Pauline van Diemen; Shelley Rhodes; Joe James; Benjamin Mollett; Vivien Coward; Paul Skinner; Caroline Warren; Kevin Bewley; Samantha Watson; Shellene Hurley; Kathryn Ryan; Yper Hall; Hugh Simmons; Alejandro Núñez; Miles Carroll; Ian Brown; Sharon Brookes. Intranasal Infection of Ferrets with SARS-CoV-2 as a Model for Asymptomatic Human Infection. Viruses 2021, 13, 113 .
AMA StyleHelen Everett, Fabian Lean, Alexander Byrne, Pauline van Diemen, Shelley Rhodes, Joe James, Benjamin Mollett, Vivien Coward, Paul Skinner, Caroline Warren, Kevin Bewley, Samantha Watson, Shellene Hurley, Kathryn Ryan, Yper Hall, Hugh Simmons, Alejandro Núñez, Miles Carroll, Ian Brown, Sharon Brookes. Intranasal Infection of Ferrets with SARS-CoV-2 as a Model for Asymptomatic Human Infection. Viruses. 2021; 13 (1):113.
Chicago/Turabian StyleHelen Everett; Fabian Lean; Alexander Byrne; Pauline van Diemen; Shelley Rhodes; Joe James; Benjamin Mollett; Vivien Coward; Paul Skinner; Caroline Warren; Kevin Bewley; Samantha Watson; Shellene Hurley; Kathryn Ryan; Yper Hall; Hugh Simmons; Alejandro Núñez; Miles Carroll; Ian Brown; Sharon Brookes. 2021. "Intranasal Infection of Ferrets with SARS-CoV-2 as a Model for Asymptomatic Human Infection." Viruses 13, no. 1: 113.
A vaccine providing both powerful antibody and cross-reactive T cell immune responses against influenza viruses would be beneficial for both humans and pigs. Here we evaluated intramuscular (IM), aerosol (Aer) and simultaneous immunization (SIM) by both routes in pigs, using the single cycle candidate influenza vaccine S-FLU. After prime and boost immunization pigs were challenged with H1N1pdm09 virus. IM immunized pigs generated high titer of neutralizing antibodies but poor T cell responses, while Aer induced powerful respiratory tract T cell responses, but a low titer of antibodies. SIM pigs combined high antibody titers and strong local T cell responses. SIM pigs showed the most complete suppression of virus shedding and the greatest improvement in pathology. We conclude that SIM regimes for immunization against respiratory pathogens warrant further study.
Veronica Martini; Basu Paudyal; Tiphany Chrun; Adam McNee; Matthew Edmans; Emmanuel Maze; Becky Clark; Alejandro Nunez; Garry Dolton; Andrew Sewell; Peter Beverley; Ronan MacLoughlin; Alain Townsend; Elma Tchilian. Simultaneous aerosol and intra-muscular immunization with influenza vaccine induces powerful protective local T cell and systemic Ab immune responses in pigs. 2020, 1 .
AMA StyleVeronica Martini, Basu Paudyal, Tiphany Chrun, Adam McNee, Matthew Edmans, Emmanuel Maze, Becky Clark, Alejandro Nunez, Garry Dolton, Andrew Sewell, Peter Beverley, Ronan MacLoughlin, Alain Townsend, Elma Tchilian. Simultaneous aerosol and intra-muscular immunization with influenza vaccine induces powerful protective local T cell and systemic Ab immune responses in pigs. . 2020; ():1.
Chicago/Turabian StyleVeronica Martini; Basu Paudyal; Tiphany Chrun; Adam McNee; Matthew Edmans; Emmanuel Maze; Becky Clark; Alejandro Nunez; Garry Dolton; Andrew Sewell; Peter Beverley; Ronan MacLoughlin; Alain Townsend; Elma Tchilian. 2020. "Simultaneous aerosol and intra-muscular immunization with influenza vaccine induces powerful protective local T cell and systemic Ab immune responses in pigs." , no. : 1.
Outbreaks of highly pathogenic avian influenza virus (HPAIV) often result in the infection of millions of poultry, causing up to 100% mortality. HPAIV has been shown to emerge from low pathogenicity avian influenza virus (LPAIV) in field outbreaks. Direct evidence for the emergence of H7N7 HPAIV from a LPAIV precursor with a rare di-basic cleavage site (DBCS) was identified in the UK in 2008. The DBCS contained an additional basic amino acid compared to commonly circulating LPAIVs that harbor a single-basic amino acid at the cleavage site (SBCS). Using reverse genetics, outbreak HPAIVs were rescued with a DBCS (H7N7DB), as seen in the LPAIV precursor or an SBCS representative of common H7 LPAIVs (H7N7SB). Passage of H7N7DB in chicken embryo tissues showed spontaneous evolution to a HPAIV. In contrast, deep sequencing of extracts from embryo tissues in which H7N7SB was serially passaged showed retention of the LPAIV genotype. Thus, in chicken embryos, an H7N7 virus containing a DBCS appears naturally unstable, enabling rapid evolution to HPAIV. Evaluation in embryo tissue presents a useful approach to study AIV evolution and allows a laboratory-based dissection of molecular mechanisms behind the emergence of HPAIV.
Amanda H. Seekings; Wendy A. Howard; Alejandro Nuñéz; Marek J. Slomka; Ashley C. Banyard; Daniel Hicks; Richard J. Ellis; Javier Nuñéz-García; Lorian C. Hartgroves; Wendy S. Barclay; Jill Banks; Ian H. Brown. The Emergence of H7N7 Highly Pathogenic Avian Influenza Virus from Low Pathogenicity Avian Influenza Virus Using an in ovo Embryo Culture Model. Viruses 2020, 12, 920 .
AMA StyleAmanda H. Seekings, Wendy A. Howard, Alejandro Nuñéz, Marek J. Slomka, Ashley C. Banyard, Daniel Hicks, Richard J. Ellis, Javier Nuñéz-García, Lorian C. Hartgroves, Wendy S. Barclay, Jill Banks, Ian H. Brown. The Emergence of H7N7 Highly Pathogenic Avian Influenza Virus from Low Pathogenicity Avian Influenza Virus Using an in ovo Embryo Culture Model. Viruses. 2020; 12 (9):920.
Chicago/Turabian StyleAmanda H. Seekings; Wendy A. Howard; Alejandro Nuñéz; Marek J. Slomka; Ashley C. Banyard; Daniel Hicks; Richard J. Ellis; Javier Nuñéz-García; Lorian C. Hartgroves; Wendy S. Barclay; Jill Banks; Ian H. Brown. 2020. "The Emergence of H7N7 Highly Pathogenic Avian Influenza Virus from Low Pathogenicity Avian Influenza Virus Using an in ovo Embryo Culture Model." Viruses 12, no. 9: 920.
Bovine tuberculosis (TB) in Great Britain adversely affects animal health and welfare and is a cause of considerable economic loss. The situation is exacerbated by European badgers (Meles meles) acting as a wildlife source of recurrent Mycobacterium bovis infection to cattle. Vaccination of badgers against TB is a possible means to reduce and control bovine TB. The delivery of vaccine in oral bait holds the best prospect for vaccinating badgers over a wide geographical area. There are practical limitations over the volume and concentration of Bacillus of Calmette and Guérin (BCG) that can be prepared for inclusion in bait. The production of BCG in a bioreactor may overcome these issues. We evaluated the efficacy of oral, bioreactor-grown BCG against experimental TB in badgers. We demonstrated repeatable protection through the direct administration of at least 2.0 × 108 colony forming units of BCG to the oral cavity, whereas vaccination via voluntary consumption of bait containing the same preparation of BCG did not result in demonstrable protection at the group-level, although a minority of badgers consuming bait showed immunological responses and protection after challenge equivalent to badgers receiving oral vaccine by direct administration. The need to deliver oral BCG in the context of a palatable and environmentally robust bait appears to introduce such variation in BCG delivery to sites of immune induction in the badger as to render experimental studies variable and inconsistent.
Sandrine Lesellier; Colin P. D. Birch; Dipesh Dave; Deanna Dalley; Sonya Gowtage; Simonette Palmer; Claire McKenna; Gareth A. Williams; Roland Ashford; Ute Weyer; Sarah Beatham; Julia Coats; Alex Nunez; Pedro Sánchez Cordón; John Spiropoulos; Stephen Powell; Jason Sawyer; Jordan Pascoe; Charlotte Hendon-Dunn; Joanna Bacon; Mark A. Chambers. Bioreactor-Grown Bacillus of Calmette and Guérin (BCG) Vaccine Protects Badgers against Virulent Mycobacterium bovis When Administered Orally: Identifying Limitations in Baited Vaccine Delivery. Pharmaceutics 2020, 12, 782 .
AMA StyleSandrine Lesellier, Colin P. D. Birch, Dipesh Dave, Deanna Dalley, Sonya Gowtage, Simonette Palmer, Claire McKenna, Gareth A. Williams, Roland Ashford, Ute Weyer, Sarah Beatham, Julia Coats, Alex Nunez, Pedro Sánchez Cordón, John Spiropoulos, Stephen Powell, Jason Sawyer, Jordan Pascoe, Charlotte Hendon-Dunn, Joanna Bacon, Mark A. Chambers. Bioreactor-Grown Bacillus of Calmette and Guérin (BCG) Vaccine Protects Badgers against Virulent Mycobacterium bovis When Administered Orally: Identifying Limitations in Baited Vaccine Delivery. Pharmaceutics. 2020; 12 (8):782.
Chicago/Turabian StyleSandrine Lesellier; Colin P. D. Birch; Dipesh Dave; Deanna Dalley; Sonya Gowtage; Simonette Palmer; Claire McKenna; Gareth A. Williams; Roland Ashford; Ute Weyer; Sarah Beatham; Julia Coats; Alex Nunez; Pedro Sánchez Cordón; John Spiropoulos; Stephen Powell; Jason Sawyer; Jordan Pascoe; Charlotte Hendon-Dunn; Joanna Bacon; Mark A. Chambers. 2020. "Bioreactor-Grown Bacillus of Calmette and Guérin (BCG) Vaccine Protects Badgers against Virulent Mycobacterium bovis When Administered Orally: Identifying Limitations in Baited Vaccine Delivery." Pharmaceutics 12, no. 8: 782.
In order to develop improved vaccinations against tuberculosis, it is essential to understand the effect of vaccination on the immune response, and to overcome the mechanisms by which mycobacteria regulate this immune response. In this study, we examine the effect of intradermal vaccination with Mycobacterium bovis bacille Calmette-Guèrin on macrophage phenotype following intranasal challenge with virulent Mycobacterium bovis. Preserved lung tissues used in the present study were obtained from a previous vaccination trial in BALB/c mice. Vaccinated mice showed less extensive pulmonary lesions along with a significant decrease in bacterial lung burden when compared to control mice. Immunohistochemical markers of classically activated macrophages (iNOS) and alternatively activated macrophages (Arg1, FIZZ1) were applied to lung sections. Vaccination led to a statistically significant decrease in the number of Arg1+ macrophages. The presence of macrophages that expressed Arginase 1 in pulmonary lesions was much smaller than the presence of macrophages expressing iNOS. The low presence of Arg1+ macrophages induced by vaccination may be caused by Th1 polarization and may reduce alternative activation of macrophages, with an overall more effective intracellular killing of bacteria.
Alexander N. Civello; John Spiropoulos; Pedro J. Sánchez-Cordón; Daniel J. Hicks; Philip J. Hogarth; Colin Birch; Alejandro Núñez. The effect of BCG vaccination on macrophage phenotype in a mouse model of intranasal Mycobacterium bovis challenge. Vaccine 2020, 38, 4755 -4761.
AMA StyleAlexander N. Civello, John Spiropoulos, Pedro J. Sánchez-Cordón, Daniel J. Hicks, Philip J. Hogarth, Colin Birch, Alejandro Núñez. The effect of BCG vaccination on macrophage phenotype in a mouse model of intranasal Mycobacterium bovis challenge. Vaccine. 2020; 38 (30):4755-4761.
Chicago/Turabian StyleAlexander N. Civello; John Spiropoulos; Pedro J. Sánchez-Cordón; Daniel J. Hicks; Philip J. Hogarth; Colin Birch; Alejandro Núñez. 2020. "The effect of BCG vaccination on macrophage phenotype in a mouse model of intranasal Mycobacterium bovis challenge." Vaccine 38, no. 30: 4755-4761.
Monoclonal antibodies are a possible adjunct to vaccination and drugs in treatment of influenza virus infection. However questions remain whether small animal models accurately predict efficacy in humans. We have established the pig, a large natural host animal for influenza, with many physiological similarities to humans, as a robust model for testing monoclonal antibodies. We show that a strongly neutralizing monoclonal antibody (2-12C) against the hemagglutinin head administered prophylactically at 15 mg/kg reduced viral load and lung pathology after pandemic H1N1 influenza challenge. A lower dose of 1 mg/kg of 2-12C or a DNA plasmid encoded version of 2-12C, reduced pathology and viral load in the lungs, but not viral shedding in nasal swabs. We propose that the pig influenza model will be useful for testing candidate monoclonal antibodies and emerging delivery platforms prior to human trials.
Adam McNee; Trevor Smith; Barbara Holzer; Becky Clark; Emily Bessell; Ghiabe Guibinga; Heather Brown; Katherine Schultheis; Paul Fisher; Stephanie Ramos; Alejandro Nunez; Matthieu Bernard; Veronica Martini; Tiphany Chrun; Yongli Xiao; John C. Kash; Jeffery K. Taubenberger; Sarah Elliott; Ami Patel; Peter Beverley; Pramila Rijal; David Weiner; Alain Townsend; Kate Broderick; Elma Tchilian. Establishment of a pig influenza challenge model for evaluation of monoclonal antibody delivery platforms. 2020, 1 .
AMA StyleAdam McNee, Trevor Smith, Barbara Holzer, Becky Clark, Emily Bessell, Ghiabe Guibinga, Heather Brown, Katherine Schultheis, Paul Fisher, Stephanie Ramos, Alejandro Nunez, Matthieu Bernard, Veronica Martini, Tiphany Chrun, Yongli Xiao, John C. Kash, Jeffery K. Taubenberger, Sarah Elliott, Ami Patel, Peter Beverley, Pramila Rijal, David Weiner, Alain Townsend, Kate Broderick, Elma Tchilian. Establishment of a pig influenza challenge model for evaluation of monoclonal antibody delivery platforms. . 2020; ():1.
Chicago/Turabian StyleAdam McNee; Trevor Smith; Barbara Holzer; Becky Clark; Emily Bessell; Ghiabe Guibinga; Heather Brown; Katherine Schultheis; Paul Fisher; Stephanie Ramos; Alejandro Nunez; Matthieu Bernard; Veronica Martini; Tiphany Chrun; Yongli Xiao; John C. Kash; Jeffery K. Taubenberger; Sarah Elliott; Ami Patel; Peter Beverley; Pramila Rijal; David Weiner; Alain Townsend; Kate Broderick; Elma Tchilian. 2020. "Establishment of a pig influenza challenge model for evaluation of monoclonal antibody delivery platforms." , no. : 1.
After the re-introduction of African swine fever virus (ASFV) genotype II isolates into Georgia in 2007, the disease spread from Eastern to Western Europe and then jumped first up to Mongolian borders and later into China in August 2018, spreading out of control and reaching different countries of Southeast Asia in 2019. From the initial incursion, along with domestic pigs, wild boar displayed a high susceptibility to ASFV and disease development. The disease established self-sustaining cycles within the wild boar population, a key fact that helped its spread and that pointed to the wild boar population as a substantial reservoir in Europe and probably also in Asia, which may hinder eradication and serve as the source for further geographic expansion. The present review gathers the most relevant information available regarding infection dynamics, disease pathogenesis and immune response that experimental infections with different ASFV isolates belonging to genotype I and II in wild boar and feral pigs have generated. Knowledge gaps in areas such as disease pathogenesis and immune response highlights the importance of focusing future studies on unravelling the early mechanisms of virus-cell interaction and innate and/or adaptive immune responses, knowledge that will contribute to the development of efficacious treatments/vaccines against ASFV.
Pedro J. Sánchez-Cordón; Alejandro Nunez; Aleksija Neimanis; Emil Wikström-Lassa; María Montoya; Helen Crooke; Dolores Gavier-Widén. African Swine Fever: Disease Dynamics in Wild Boar Experimentally Infected with ASFV Isolates Belonging to Genotype I and II. Viruses 2019, 11, 852 .
AMA StylePedro J. Sánchez-Cordón, Alejandro Nunez, Aleksija Neimanis, Emil Wikström-Lassa, María Montoya, Helen Crooke, Dolores Gavier-Widén. African Swine Fever: Disease Dynamics in Wild Boar Experimentally Infected with ASFV Isolates Belonging to Genotype I and II. Viruses. 2019; 11 (9):852.
Chicago/Turabian StylePedro J. Sánchez-Cordón; Alejandro Nunez; Aleksija Neimanis; Emil Wikström-Lassa; María Montoya; Helen Crooke; Dolores Gavier-Widén. 2019. "African Swine Fever: Disease Dynamics in Wild Boar Experimentally Infected with ASFV Isolates Belonging to Genotype I and II." Viruses 11, no. 9: 852.
Eastern equine encephalitis virus is an alphavirus that naturally cycles between mosquitoes and birds or rodents in Eastern States of the US. Equine infection occurs by being bitten by cross-feeding mosquitoes, with a case fatality rate of up to 75% in humans during epizootic outbreaks. There are no licensed medical countermeasures, and with an anticipated increase in mortality when exposed by the aerosol route based on anecdotal human data and experimental animal data, it is important to understand the pathogenesis of this disease in pursuit of treatment options. This report details the clinical and pathological findings of mice infected with EEEV by the aerosol route, and use as a model for EEEV infection in humans. Mice were exposed by the aerosol route to a dose range of EEEV to establish the median lethal dose. A pathogenesis study followed whereby mice were exposed to a defined dose of virus and sacrificed at time-points thereafter for histopathological analysis and virology. Clinical signs of disease appeared within 2 days post challenge, culminating in severe clinical signs within 24 h, neuro-invasion and dose dependent lethality. EEEV was first detected in the lung 1 day post challenge, and by day 3 peak viral titres were observed in the brain, spleen and blood, corresponding with severe meningoencephalitis, indicative of encephalitic disease. Lethality follows severe neurological signs, and may be linked to a threshold level of virus replication in the brain. Effective medical countermeasures for EEEV may necessitate early inoculation to inhibit infection of the brain in zoonotic incidents, and be able to traverse the blood-brain barrier to sufficiently interrupt replication in the brain in cases of aerosol infection. There is little human data on the hazard posed by aerosol infection with encephalitic alphaviruses, and use of EEEV as a bioweapon may be by the aerosol route. A well characterized model of aerosol exposure that recapitulates some of the most severe human clinical features is necessary to evaluate the efficacy of putative medical countermeasures, and to increase our understanding about how this route of infection induces such rapid neuro-invasion and resulting disease.
Amanda L. Phelps; Lyn M. O’Brien; Lin S. Eastaugh; Carwyn Davies; Mark S. Lever; Jane Ennis; Larry Zeitlin; Alejandro Nunez; David O. Ulaeto. Aerosol infection of Balb/c mice with eastern equine encephalitis virus; susceptibility and lethality. Virology Journal 2019, 16, 2 .
AMA StyleAmanda L. Phelps, Lyn M. O’Brien, Lin S. Eastaugh, Carwyn Davies, Mark S. Lever, Jane Ennis, Larry Zeitlin, Alejandro Nunez, David O. Ulaeto. Aerosol infection of Balb/c mice with eastern equine encephalitis virus; susceptibility and lethality. Virology Journal. 2019; 16 (1):2.
Chicago/Turabian StyleAmanda L. Phelps; Lyn M. O’Brien; Lin S. Eastaugh; Carwyn Davies; Mark S. Lever; Jane Ennis; Larry Zeitlin; Alejandro Nunez; David O. Ulaeto. 2019. "Aerosol infection of Balb/c mice with eastern equine encephalitis virus; susceptibility and lethality." Virology Journal 16, no. 1: 2.
Classical swine fever (CSF) is a highly contagious and often fatal viral disease of domestic pigs and wild boar. Pulmonary oedema and haemorrhages in lung parenchyma are common lesions in the acute forms of CSF that may compromise pig survival and whose pathogenetic mechanisms remain unclear. The appearance of pulmonary lesions in pigs infected with Alfort/187 strain of classical swine fever virus (CSFV) euthanized between 2 and 17 days postinfection (dpi) and the role played by cytokines secreted by different pulmonary macrophage populations in the evolution of lesions was evaluated in this study. Microscopic changes of alveolar septal thickening along with oedema and haemorrhages became more severe at middle‐late stages of the experiment. A significant increase in the number of pulmonary macrophages, mainly pulmonary intravascular macrophages (PIMs), was observed coinciding with the onset of alveolar septal thickening from Day 4 pi. PIMs were the main target of CSFV from initial stages of infection while the presence of infected pulmonary alveolar macrophages (PAMs) was scarce and late. Initial infection of PIMs induced phagocytic and biosynthetic activation with subsequent release of chemotactic cytokines. TNFα and, to a lesser extent, IL‐1α secreted by PIMs were the major cytokines involved, while IL‐6 played only a minor role. On the contrary, results suggested only a secondary role of PAMs as source of cytokines. The presence of vascular changes from Day 9 pi coincided with the highest levels of infected PIMs and the highest number of pro‐inflammatory cytokines secreting PIMs. Activation and phagocytosis of platelets were observed in the lungs of infected pigs from early stages, also coinciding with the expression of cytokines with a proven procoagulant activity. The existence of intravascular coagulation phenomena in lung was ruled out.
Alejandro Núñez; Pedro Sánchez Cordón; Miriam Pedrera; Jose C. Gómez-Villamandos; Librado Carrasco. Pulmonary intravascular macrophages regulate the pathogenetic mechanisms of pulmonary lesions during acute courses of classical swine fever. Transboundary and Emerging Diseases 2018, 65, 1885 -1897.
AMA StyleAlejandro Núñez, Pedro Sánchez Cordón, Miriam Pedrera, Jose C. Gómez-Villamandos, Librado Carrasco. Pulmonary intravascular macrophages regulate the pathogenetic mechanisms of pulmonary lesions during acute courses of classical swine fever. Transboundary and Emerging Diseases. 2018; 65 (6):1885-1897.
Chicago/Turabian StyleAlejandro Núñez; Pedro Sánchez Cordón; Miriam Pedrera; Jose C. Gómez-Villamandos; Librado Carrasco. 2018. "Pulmonary intravascular macrophages regulate the pathogenetic mechanisms of pulmonary lesions during acute courses of classical swine fever." Transboundary and Emerging Diseases 65, no. 6: 1885-1897.
H5 and H7 subtypes of low pathogenicity avian influenza viruses (LPAIVs) have the potential to evolve into highly pathogenic avian influenza viruses (HPAIVs), causing high mortality in galliforme poultry with substantial economic losses for the poultry industry. This study provides direct evidence of H7N7 LPAIV mutation to HPAIV on a single poultry premises during an outbreak that occurred in June 2008 in free range laying hens in Oxfordshire, UK. We report the first detection of a rare di-basic cleavage site (CS) motif (PEIPKKRGLF), unique to galliformes, that has previously been associated with a LPAIV phenotype. Three distinct HPAIV CS sequences (PEIPKRKKRGLF, PEIPKKKKRGLF and PEIPKKKKKKRGLF) were identified in the infected sheds suggesting molecular evolution at the outbreak premises. Further evidence for H7N7 LPAIV preceding mutation to HPAIV was derived by examining clinical signs, epidemiological descriptions and analysing laboratory results on the timing and proportions of seroconversion and virus shedding at each infected shed on the premises. In addition to describing how the outbreak was diagnosed and managed via statutory laboratory testing, phylogenetic analysis revealed reassortant events during 2006–2008 that suggested likely incursion of a wild bird origin LPAIV precursor to the H7N7 HPAIV outbreak. Identifying a precursor LPAIV is important for understanding the molecular changes and mechanisms involved in the emergence of HPAIV. This information can lead to understanding how and why only some H7 LPAIVs appear to readily mutate to HPAIV.
A.H. Seekings; M.J. Slomka; C. Russell; W.A. Howard; B. Choudhury; Alejandro Nunez; B.Z. Löndt; W. Cox; V. Ceeraz; P. Thorén; R.M. Irvine; R.J. Manvell; J. Banks; I.H. Brown. Direct evidence of H7N7 avian influenza virus mutation from low to high virulence on a single poultry premises during an outbreak in free range chickens in the UK, 2008. Infection, Genetics and Evolution 2018, 64, 13 -31.
AMA StyleA.H. Seekings, M.J. Slomka, C. Russell, W.A. Howard, B. Choudhury, Alejandro Nunez, B.Z. Löndt, W. Cox, V. Ceeraz, P. Thorén, R.M. Irvine, R.J. Manvell, J. Banks, I.H. Brown. Direct evidence of H7N7 avian influenza virus mutation from low to high virulence on a single poultry premises during an outbreak in free range chickens in the UK, 2008. Infection, Genetics and Evolution. 2018; 64 ():13-31.
Chicago/Turabian StyleA.H. Seekings; M.J. Slomka; C. Russell; W.A. Howard; B. Choudhury; Alejandro Nunez; B.Z. Löndt; W. Cox; V. Ceeraz; P. Thorén; R.M. Irvine; R.J. Manvell; J. Banks; I.H. Brown. 2018. "Direct evidence of H7N7 avian influenza virus mutation from low to high virulence on a single poultry premises during an outbreak in free range chickens in the UK, 2008." Infection, Genetics and Evolution 64, no. : 13-31.
The China-origin H7N9 low pathogenicity avian influenza virus (LPAIV) emerged as a zoonotic threat in 2013 where it continues to circulate in live poultry markets. Absence of overt clinical signs in poultry is a typical LPAIV infection outcome, and has contributed to its insidious maintenance in China. This study is the first description of H7N9 LPAIV (A/Anhui/1/13) infection in turkeys, with efficient transmission to two additional rounds of introduced contact turkeys which all became infected during cohousing. Surprisingly, mortality was observed in six of eight (75%) second-round contact turkeys which is unusual for LPAIV infection, with unexpected systemic dissemination to many organs beyond the respiratory and enteric tracts, but interestingly no accompanying mutation to highly pathogenic AIV. The intravenous pathogenicity index score for a turkey-derived isolate (0.39) affirmed the LPAIV phenotype. However, the amino acid change L235Q in the haemagglutinin gene occurred in directly-infected turkeys and transmitted to the contacts, including those that died and the two which resolved infection to survive to the end of the study. This polymorphism was indicative of a reversion from mammalian to avian adaptation for the H7N9 virus. This study underlined a new risk to poultry in the event of H7N9 spread beyond China.
Marek J. Slomka; Amanda H. Seekings; Sahar Mahmood; Saumya Thomas; Anita Puranik; Samantha Watson; Alexander M. P. Byrne; Daniel Hicks; Alejandro Nunez; Ian H. Brown; Sharon M Brookes. Unexpected infection outcomes of China-origin H7N9 low pathogenicity avian influenza virus in turkeys. Scientific Reports 2018, 8, 1 -13.
AMA StyleMarek J. Slomka, Amanda H. Seekings, Sahar Mahmood, Saumya Thomas, Anita Puranik, Samantha Watson, Alexander M. P. Byrne, Daniel Hicks, Alejandro Nunez, Ian H. Brown, Sharon M Brookes. Unexpected infection outcomes of China-origin H7N9 low pathogenicity avian influenza virus in turkeys. Scientific Reports. 2018; 8 (1):1-13.
Chicago/Turabian StyleMarek J. Slomka; Amanda H. Seekings; Sahar Mahmood; Saumya Thomas; Anita Puranik; Samantha Watson; Alexander M. P. Byrne; Daniel Hicks; Alejandro Nunez; Ian H. Brown; Sharon M Brookes. 2018. "Unexpected infection outcomes of China-origin H7N9 low pathogenicity avian influenza virus in turkeys." Scientific Reports 8, no. 1: 1-13.
European badgers (Meles meles) are a wildlife reservoir for Mycobacterium bovis (M. bovis) in parts of England, Wales and Ireland, constituting a potential source of tuberculosis (TB) infection for cattle. Vaccination of badgers against TB is one of the tools available for helping reduce the prevalence of bovine TB in badgers, made possible by the licensing in 2010 of Bacillus Calmette-Guérin (BCG) vaccine for intramuscular administration to badgers (BadgerBCG). However, practical limitations associated with administering an injected vaccine to wild animals make an oral, bait-delivered form of the vaccine highly desirable. Evaluation of the safety of oral BCG to badgers and the environment is a mandatory step on the road to licensing an oral vaccine. This study had the following objectives: (a) to determine whether adverse effects followed the oral administration of BCG vaccine to badgers; (b) to measure the quantity and frequency of BCG excreted in the faeces of vaccinated badgers; and (c) to assess whether there was evidence of the vaccine spreading to unvaccinated, ‘sentinel’ badgers sharing the same environment as vaccinated animals. We report here that the oral administration per badger of ≥6.4 × 109 cfu BCG, followed 14 days later by a single oral dose of ≥6.4 × 107 cfu BCG caused no adverse physical effects and did not affect the social behaviour and feeding habits of the vaccinated animals. BCG was cultured from the faeces of two of nine vaccinated animals (372 cfu/g and 996 cfu/g, respectively) approximately 48 h after the higher dose of BCG was administered and by one of the nine vaccinated animal (80 cfu/g) approximately 24 h after receiving the lower dose of BCG. We found no evidence for the transmission of BCG to unvaccinated, sentinel, badgers housed with the vaccinated animals despite the occasional excretion of BCG in faeces.
Simon Perrett; Sandrine Lesellier; Fiona Rogers; Gareth A. Williams; Sonya Gowtage; Si Palmer; Deanna Dalley; Dipesh Davé; Ute Weyer; Emma Wood; Francisco J. Salguero; Alejandro Nunez; Nick Reed; Mark A. Chambers. Assessment of the safety of Bacillus Calmette-Guérin vaccine administered orally to badgers ( Meles meles ). Vaccine 2018, 36, 1990 -1995.
AMA StyleSimon Perrett, Sandrine Lesellier, Fiona Rogers, Gareth A. Williams, Sonya Gowtage, Si Palmer, Deanna Dalley, Dipesh Davé, Ute Weyer, Emma Wood, Francisco J. Salguero, Alejandro Nunez, Nick Reed, Mark A. Chambers. Assessment of the safety of Bacillus Calmette-Guérin vaccine administered orally to badgers ( Meles meles ). Vaccine. 2018; 36 (15):1990-1995.
Chicago/Turabian StyleSimon Perrett; Sandrine Lesellier; Fiona Rogers; Gareth A. Williams; Sonya Gowtage; Si Palmer; Deanna Dalley; Dipesh Davé; Ute Weyer; Emma Wood; Francisco J. Salguero; Alejandro Nunez; Nick Reed; Mark A. Chambers. 2018. "Assessment of the safety of Bacillus Calmette-Guérin vaccine administered orally to badgers ( Meles meles )." Vaccine 36, no. 15: 1990-1995.
The impacts of hedgehog (Erinaceus europaeus) Salmonella infection on public health and on animal welfare and conservation are unknown. We isolated Salmonella Enteritidis multi-locus sequence-type (ST)183 from 46/170 (27%) hedgehog carcasses (27 S. Enteritidis phage type (PT)11, 18 of a novel PT66 biotype and one with co-infection of these PTs) and from 6/208 (3%) hedgehog faecal samples (4 PT11, 2 PT66) from across Great Britain, 2012–2015. Whole genome phylogenetic analysis of the hedgehog isolates and ST183 from people in England and Wales found that PT11 and PT66 form two divergent clades. Hedgehog and human isolates were interspersed throughout the phylogeny indicating that infections in both species originate from a common population. PT11 was recovered from hedgehogs across England and Scotland, consistent with endemic infection. PT66 was isolated from Scotland only, possibly indicating a recent emergence event. People infected with ST183 were four times more likely to be aged 0–4 years than people infected by the more common ST11 S. Enteritidis. Evidence for human ST183 infection being non-foodborne included stronger correlation between geographic and genetic distance, and significantly increased likelihood of infection in rural areas, than for ST11. These results are consistent with hedgehogs acting as a source of zoonotic infection.
Becki Lawson; Lydia Franklinos; Julia Rodriguez-Ramos Fernandez; Clare Wend-Hansen; Satheesh Nair; Shaheed K. MacGregor; Shinto K. John; Romain Pizzi; Alejandro Nunez; Philip M. Ashton; Andrew A. Cunningham; Elizabeth M. De Pinna. Salmonella Enteritidis ST183: emerging and endemic biotypes affecting western European hedgehogs (Erinaceus europaeus) and people in Great Britain. Scientific Reports 2018, 8, 1 -11.
AMA StyleBecki Lawson, Lydia Franklinos, Julia Rodriguez-Ramos Fernandez, Clare Wend-Hansen, Satheesh Nair, Shaheed K. MacGregor, Shinto K. John, Romain Pizzi, Alejandro Nunez, Philip M. Ashton, Andrew A. Cunningham, Elizabeth M. De Pinna. Salmonella Enteritidis ST183: emerging and endemic biotypes affecting western European hedgehogs (Erinaceus europaeus) and people in Great Britain. Scientific Reports. 2018; 8 (1):1-11.
Chicago/Turabian StyleBecki Lawson; Lydia Franklinos; Julia Rodriguez-Ramos Fernandez; Clare Wend-Hansen; Satheesh Nair; Shaheed K. MacGregor; Shinto K. John; Romain Pizzi; Alejandro Nunez; Philip M. Ashton; Andrew A. Cunningham; Elizabeth M. De Pinna. 2018. "Salmonella Enteritidis ST183: emerging and endemic biotypes affecting western European hedgehogs (Erinaceus europaeus) and people in Great Britain." Scientific Reports 8, no. 1: 1-11.
SUMMARYAs part of further investigations into three linked haemorrhagic fever with renal syndrome (HFRS) cases in Wales and England, 21 rats from a breeding colony in Cherwell, and three rats from a household in Cheltenham were screened for hantavirus. Hantavirus RNA was detected in either the lungs and/or kidney of 17/21 (81%) of the Cherwell rats tested, higher than previously detected by blood testing alone (7/21, 33%), and in the kidneys of all three Cheltenham rats. The partial L gene sequences obtained from 10 of the Cherwell rats and the three Cheltenham rats were identical to each other and the previously reported UK Cherwell strain. Seoul hantavirus (SEOV) RNA was detected in the heart, kidney, lung, salivary gland and spleen (but not in the liver) of an individual rat from the Cherwell colony suspected of being the source of SEOV. Serum from 20/20 of the Cherwell rats and two associated HFRS cases had high levels of SEOV-specific antibodies (by virus neutralisation). The high prevalence of SEOV in both sites and the moderately severe disease in the pet rat owners suggest that SEOV in pet rats poses a greater public health risk than previously considered.
L. M. McElhinney; Denise Marston; K. C. Pounder; H. Goharriz; Emma Wise; J. Verner-Carlsson; D. Jennings; N. Johnson; A. Civello; Alejandro Nunez; T. Brooks; Andrew Breed; J. Lawes; Å. Lundkvist; C. A. Featherstone; A. R. Fooks. High prevalence of Seoul hantavirus in a breeding colony of pet rats. Epidemiology and Infection 2017, 145, 3115 -3124.
AMA StyleL. M. McElhinney, Denise Marston, K. C. Pounder, H. Goharriz, Emma Wise, J. Verner-Carlsson, D. Jennings, N. Johnson, A. Civello, Alejandro Nunez, T. Brooks, Andrew Breed, J. Lawes, Å. Lundkvist, C. A. Featherstone, A. R. Fooks. High prevalence of Seoul hantavirus in a breeding colony of pet rats. Epidemiology and Infection. 2017; 145 (15):3115-3124.
Chicago/Turabian StyleL. M. McElhinney; Denise Marston; K. C. Pounder; H. Goharriz; Emma Wise; J. Verner-Carlsson; D. Jennings; N. Johnson; A. Civello; Alejandro Nunez; T. Brooks; Andrew Breed; J. Lawes; Å. Lundkvist; C. A. Featherstone; A. R. Fooks. 2017. "High prevalence of Seoul hantavirus in a breeding colony of pet rats." Epidemiology and Infection 145, no. 15: 3115-3124.
Western equine encephalitis virus (WEEV) naturally cycles between mosquitos and birds or rodents, with a case fatality rate of up to 15% in humans during epizootic outbreaks. There are no medical countermeasures to treat WEEV infection, and accidental aerosol exposure increases the case fatality rate up to 40%. Understanding the pathogenesis of infection is required to develop and assess medical countermeasures. This study describes the clinical and pathological findings of mice infected with WEEV by the aerosol route, and use as a model for WEEV infection in humans. Balb/c mice were infected by the aerosol route with a dose range of high-virulence WEEV strain Fleming to establish the median lethal dose (MLD). The disease course was acute, culminating in severe clinical signs, neuroinvasion, and dose-dependent mortality. Further groups of mice were exposed by the aerosol route, periodically sacrificed, and tissues excised for histopathological examination and virology. Viral titres peaked four days post-challenge in the brain and lungs, corresponding with severe bilateral lesions in rostroventral regions of the encephalon, especially in the olfactory bulb and piriform cortex. Recapitulation of the most serious clinical presentations of human WEEV disease in mice may prove a useful tool in the evaluation of medical countermeasures.
Amanda L. Phelps; Lyn M. O’Brien; Lin S. Eastaugh; Carwyn Davies; Mark S. Lever; Jane Ennis; Larry Zeitlin; Alejandro Nunez; David O. Ulaeto. Susceptibility and Lethality of Western Equine Encephalitis Virus in Balb/c Mice When Infected by the Aerosol Route. Viruses 2017, 9, 163 .
AMA StyleAmanda L. Phelps, Lyn M. O’Brien, Lin S. Eastaugh, Carwyn Davies, Mark S. Lever, Jane Ennis, Larry Zeitlin, Alejandro Nunez, David O. Ulaeto. Susceptibility and Lethality of Western Equine Encephalitis Virus in Balb/c Mice When Infected by the Aerosol Route. Viruses. 2017; 9 (7):163.
Chicago/Turabian StyleAmanda L. Phelps; Lyn M. O’Brien; Lin S. Eastaugh; Carwyn Davies; Mark S. Lever; Jane Ennis; Larry Zeitlin; Alejandro Nunez; David O. Ulaeto. 2017. "Susceptibility and Lethality of Western Equine Encephalitis Virus in Balb/c Mice When Infected by the Aerosol Route." Viruses 9, no. 7: 163.
The recommended screening of rabies in ‘suspect’ animal cases involves testing fresh brain tissue. The preservation of fresh tissue however can be difficult under field conditions and formalin fixation provides a simple alternative that may allow a confirmatory diagnosis. The occurrence and location of histopathological changes and immunohistochemical (IHC) labelling for rabies in formalin fixed paraffin embedded (FFPE) canine brain is described in samples from 57 rabies suspect cases from Sri-Lanka. The presence of Negri bodies and immunohistochemical detection of rabies virus antigen were evaluated in the cortex, hippocampus, cerebellum and brainstem. The effect of autolysis and artefactual degeneration of the tissue was also assessed. Rabies was confirmed in 53 of 57 (93%) cases by IHC. IHC labelling was statistically more abundant in the brainstem. Negri bodies were observed in 32 of 53 (60.4%) of the positive cases. Although tissue degradation had no effect on IHC diagnosis, it was associated with an inability to detect Negri bodies. In 13 cases, a confirmatory Polymerase chain reaction (PCR) testing for rabies virus RNA was undertaken by extracting RNA from fresh frozen tissue, and also attempted using FFPE samples. PCR detection using fresh frozen samples was in agreement with the IHC results. The PCR method from FFPE tissues was suitable for control material but unsuccessful in our field cases. Histopathological examination of the brain is essential to define the differential diagnoses of behaviour modifying conditions in rabies virus negative cases, but it is unreliable as the sole method for rabies diagnosis, particularly where artefactual change has occurred. Formalin fixation and paraffin embedding does not prevent detection of rabies virus via IHC labelling even where artefactual degeneration has occurred. This could represent a pragmatic secondary assay for rabies diagnosis in the field because formalin fixation can prevent sample degeneration. The brain stem was shown to be the site with most viral immunoreactivity; supporting recommended sampling protocols in favour of improved necropsy safety in the field. PCR testing of formalin fixed tissue may be successful in certain circumstances as an alternative test.
S. Beck; P. Gunawardena; D. L. Horton; D. J. Hicks; D. A. Marston; A. Ortiz-Pelaez; A. R. Fooks; A. Núñez. Pathobiological investigation of naturally infected canine rabies cases from Sri Lanka. BMC Veterinary Research 2017, 13, 1 -9.
AMA StyleS. Beck, P. Gunawardena, D. L. Horton, D. J. Hicks, D. A. Marston, A. Ortiz-Pelaez, A. R. Fooks, A. Núñez. Pathobiological investigation of naturally infected canine rabies cases from Sri Lanka. BMC Veterinary Research. 2017; 13 (1):1-9.
Chicago/Turabian StyleS. Beck; P. Gunawardena; D. L. Horton; D. J. Hicks; D. A. Marston; A. Ortiz-Pelaez; A. R. Fooks; A. Núñez. 2017. "Pathobiological investigation of naturally infected canine rabies cases from Sri Lanka." BMC Veterinary Research 13, no. 1: 1-9.
The European badger (Meles meles) is a reservoir host of Mycobacterium bovis and responsible for a proportion of the tuberculosis (TB) cases seen in cattle in the United Kingdom and Republic of Ireland. An injectable preparation of the bacillus Calmette-Guérin (BCG) vaccine is licensed for use in badgers in the UK and its use forms part of the bovine TB eradication plans of England and Wales. However, there are practical limitations to the widespread application of an injectable vaccine for badgers and a research priority is the development of an oral vaccine deliverable to badgers in bait. Previous studies reported the successful vaccination of badgers with oral preparations of 108 colony forming units (CFU) of both Pasteur and Danish strains of BCG contained within a lipid matrix composed of triglycerides of fatty acids. Protection against TB in these studies was expressed as a reduction in the number and apparent progression of visible lesions, and reductions in the bacterial load and dissemination of infection. To reduce the cost of an oral vaccine and reduce the potential for environmental contamination with BCG, it is necessary to define the minimal efficacious dose of oral BCG for badgers. The objectives of the two studies reported here were to compare the efficacy of BCG Danish strain in a lipid matrix with unformulated BCG given orally, and to evaluate the efficacy of BCG Danish in a lipid matrix at a ten-fold lower dose than previously evaluated in badgers. In the first study, both BCG unformulated and in a lipid matrix reduced the number and apparent progression of visible lesions and the dissemination of infection from the lung. In the second study, vaccination with BCG in the lipid matrix at a ten-fold lower dose produced a similar outcome, but with greater intra-group variability than seen with the higher dose in the first study. Further research is needed before we are able to recommend a final dose of BCG for oral vaccination of badgers against TB or to know whether oral vaccination of wild badgers with BCG will significantly reduce transmission of the disease.
Mark A. Chambers; Frank Aldwell; Gareth A. Williams; Si Palmer; Sonya Gowtage; Roland Ashford; Deanna J. Dalley; Dipesh Davé; Ute Weyer; Francisco J. Salguero; Alejandro Nunez; Allan K. Nadian; Timothy Crawshaw; Leigh A. L. Corner; Sandrine Lesellier. The Effect of Oral Vaccination with Mycobacterium bovis BCG on the Development of Tuberculosis in Captive European Badgers (Meles meles). Frontiers in Cellular and Infection Microbiology 2017, 7, 6 .
AMA StyleMark A. Chambers, Frank Aldwell, Gareth A. Williams, Si Palmer, Sonya Gowtage, Roland Ashford, Deanna J. Dalley, Dipesh Davé, Ute Weyer, Francisco J. Salguero, Alejandro Nunez, Allan K. Nadian, Timothy Crawshaw, Leigh A. L. Corner, Sandrine Lesellier. The Effect of Oral Vaccination with Mycobacterium bovis BCG on the Development of Tuberculosis in Captive European Badgers (Meles meles). Frontiers in Cellular and Infection Microbiology. 2017; 7 ():6.
Chicago/Turabian StyleMark A. Chambers; Frank Aldwell; Gareth A. Williams; Si Palmer; Sonya Gowtage; Roland Ashford; Deanna J. Dalley; Dipesh Davé; Ute Weyer; Francisco J. Salguero; Alejandro Nunez; Allan K. Nadian; Timothy Crawshaw; Leigh A. L. Corner; Sandrine Lesellier. 2017. "The Effect of Oral Vaccination with Mycobacterium bovis BCG on the Development of Tuberculosis in Captive European Badgers (Meles meles)." Frontiers in Cellular and Infection Microbiology 7, no. : 6.