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Antiviral Research Aug 2018Rift Valley fever virus (RVFV) is a mosquito-borne pathogen endemic to sub-Saharan Africa and the Arabian Peninsula. There are no approved antiviral therapies or...
Rift Valley fever virus (RVFV) is a mosquito-borne pathogen endemic to sub-Saharan Africa and the Arabian Peninsula. There are no approved antiviral therapies or vaccines available to treat or prevent severe disease associated with RVFV infection in humans. The adenosine analog, galidesivir (BCX4430), is a broad-spectrum antiviral drug candidate with in vitro antiviral potency (EC of less than 50 μM) in more than 20 different viruses across eight different virus families. Here we report on the activity of galidesivir in the hamster model of peracute RVFV infection. Intramuscular and intraperitoneal treatments effectively limited systemic RVFV (strain ZH501) infection as demonstrated by significantly improved survival outcomes and the absence of infectious virus in the spleen and the majority of the serum, brain, and liver samples collected from infected animals. Our findings support the further development of galidesivir as an antiviral therapy for use in treating severe RVFV infection, and possibly other related phleboviral diseases.
Topics: Adenine; Adenosine; Animals; Antiviral Agents; Disease Models, Animal; Injections, Intramuscular; Injections, Intraperitoneal; Liver; Mesocricetus; Purine Nucleosides; Pyrrolidines; Rift Valley Fever; Rift Valley fever virus; Spleen; Survival Analysis; Treatment Outcome
PubMed: 29864447
DOI: 10.1016/j.antiviral.2018.05.013 -
PloS One 2017Rift Valley fever phlebovirus (RVFV) causes high rates of abortions and fetal malformations in ruminants, and hemorrhagic fever, encephalitis, or blindness in humans....
Rift Valley fever phlebovirus (RVFV) causes high rates of abortions and fetal malformations in ruminants, and hemorrhagic fever, encephalitis, or blindness in humans. Viral transmission occurs via mosquito vectors in endemic areas, which necessitates regular vaccination of susceptible livestock animals to prevent the RVF outbreaks. Although ZH501 strain has been used as a challenge strain for past vaccine efficacy studies, further characterization of other RVFV strains is important to optimize ruminant and nonhuman primate RVFV challenge models. This study aimed to characterize the virulence of wild-type RVFV strains belonging to different genetic lineages in outbred CD1 mice. Mice were intraperitoneally infected with 1x103 PFU of wild-type ZH501, Kenya 9800523, Kenya 90058, Saudi Arabia 200010911, OS1, OS7, SA75, Entebbe, or SA51 strains. Among them, mice infected with SA51, Entebbe, or OS7 strain showed rapid dissemination of virus in livers and peracute necrotic hepatitis at 2-3 dpi. Recombinant SA51 (rSA51) and Zinga (rZinga) strains were recovered by reverse genetics, and their virulence was also tested in CD1 mice. The rSA51 strain reproduced peracute RVF disease in mice, whereas the rZinga strain showed a similar virulence with that of rZH501 strain. This study showed that RVFV strains in different genetic lineages display distinct virulence in outbred mice. Importantly, since wild-type RVFV strains contain defective-interfering RNA or various genetic subpopulations during passage from original viral isolations, recombinant RVFV strains generated by reverse genetics will be better suitable for reproducible challenge studies for vaccine development as well as pathological studies.
Topics: Animals; Cell Line; Disease Models, Animal; Dose-Response Relationship, Immunologic; Female; Liver; Mice; Rift Valley fever virus; Serial Passage; Spleen; Viral Vaccines; Virulence
PubMed: 29267298
DOI: 10.1371/journal.pone.0189250 -
Veterinary Sciences Apr 2022In human medicine, pituitary apoplexy (PA) is a clinical syndrome characterised by the sudden onset of neurological signs because of haemorrhage or infarction occurring...
In human medicine, pituitary apoplexy (PA) is a clinical syndrome characterised by the sudden onset of neurological signs because of haemorrhage or infarction occurring within a normal or tumoral pituitary gland. The diagnosis is usually performed combining neurological signs and imaging findings. The aim of the present study is to describe the abnormal neurological signs, the diagnostic imaging findings, based on Computed Tomography (CT) and/or Magnetic Resonance Imaging (MRI), and the outcome in a population of dogs with suspected PA. Clinical cases were retrospectively reviewed. Nineteen cases of suspected PA were included. The majority of dogs showed behavioural abnormalities (11/19). Neurological signs more frequently identified were obtundation (7/19), vestibular signs (7/19) and epileptic seizures (6/19). The onset of neurological signs was per-acute in 14 out of 19 cases. Data regarding CT and MRI were available in 18 and 9 cases, respectively. Neurological signs resolved in less than 24 h in seven patients. The short-term prognosis was defined as favourable in the majority of our study population. The median survival time was of 7 months from the time of PA diagnosis. This is the first description of neurological signs, imaging findings and outcome in a large group of dogs with PA.
PubMed: 35448689
DOI: 10.3390/vetsci9040191 -
Frontiers in Veterinary Science 2021A 9-year-old, neutered male, domestic shorthair cat from Arizona, was presented for evaluation of a 7-day history of hind limb paraparesis that progressed to paraplegia....
A 9-year-old, neutered male, domestic shorthair cat from Arizona, was presented for evaluation of a 7-day history of hind limb paraparesis that progressed to paraplegia. There was no history of respiratory abnormalities. Neurologic examination supported localization of a T3-L3 myelopathy. Computed tomography (CT) revealed an expansile widening of the spinal canal dorsal to L4 associated with a strongly contrast-enhancing mass. Moreover, CT series of the thorax revealed a diffuse miliary pulmonary pattern, as well as tracheobronchial, sternal, and cranial mediastinal lymphadenomegaly. Transthoracic lung lobe and sternal lymph node fine needle aspiration revealed pyogranulomatous inflammation with spp. spherules and endospores. A suspected diagnosis of spinal coccidioidomycosis was made; fluconazole (10.9 mg/kg PO q12h) treatment was initiated, and decompressive neurosurgery was performed. The granuloma was removed en bloc and histopathology revealed marked, chronic-active, pyogranulomatous myelitis with intralesional spp. spherules with endosporulation. Serum anti- spp. antibody titer results revealed a negative IgM and a positive IgG (1:4). The cat was treated with fluconazole for 445 days and examined at various time points, with the last examination 2 years after initial presentation. The cat returned to full ambulation with only mild functional deficits of the right hind limb. In conclusion, this report documents the diagnosis, treatment, and long-term follow up of a cat with a compressive spp. spinal cord granuloma. This case highlights the importance of including coccidioidomycosis as a differential diagnosis for cats with peracute hindlimb paraplegia that have lived in or traveled to regions where spp. is endemic, and demonstrates the potential for a good long-term outcome with decompressive neurosurgery and antifungal therapy.
PubMed: 35036415
DOI: 10.3389/fvets.2021.801885 -
Revue Scientifique Et Technique... Aug 2014Anthrax is a peracute, acute or subacute multispecies bacterial infection that occurs on many continents. It is one of the oldest infectious diseases known; the biblical...
Anthrax is a peracute, acute or subacute multispecies bacterial infection that occurs on many continents. It is one of the oldest infectious diseases known; the biblical fifth and sixth plagues (Exodus chapters 7 to 9) that affected first livestock and then humans were probably anthrax. From the earliest historical records until development of an effective vaccine midway through the 20th Century, anthrax was one of the foremost causes of uncontrolled mortality in cattle, sheep, goats, horses and pigs, with 'spill over' into humans, worldwide. With the development of the Sterne spore vaccine, a sharp decline in anthrax outbreaks in livestock occurred during the 1930-1980 era. There were successful national vaccination programmes in many countries during this period, complemented by the liberal use of antibiotics and the implementation of quarantine regulations and carcass disposal. However, a resurgence of this disease in livestock has been reported recently in some regions, where complacency and a false sense of security have hindered vaccination programmes. The epidemiology of anthrax involves an environmental component, as well as livestock, wildlife and human components. This makes anthrax an ideal example for discussion in the One Health context. Many outbreaks of anthrax in wildlife are undetected or unreported, owing to surveillance inadequacies and difficulties. Human disease is generally acquired accidentally during outbreaks of anthrax in domestic livestock and wildlife. The exception is deliberate targeting of humans with anthrax in the course of biowarfare or bioterrorism.
Topics: Africa; Animals; Animals, Wild; Anthrax; Anti-Bacterial Agents; Bacterial Vaccines; Global Health; Humans; Internationality; Zoonoses
PubMed: 25707186
DOI: 10.20506/rst.33.2.2309 -
Journal of Medical Microbiology Mar 2022The Gram-negative bacterium is the causative agent of pleuropneumonia in pigs, its only known natural host. Typical symptoms of peracute disease include fever, apathy...
The Gram-negative bacterium is the causative agent of pleuropneumonia in pigs, its only known natural host. Typical symptoms of peracute disease include fever, apathy and anorexia, and time from infection to death may only be 6 h. Severe lung lesions result from presence of one or two of the ApxI-III toxins. Control is through good husbandry practice, vaccines and antibiotic use. Culture and presence of the species-specific gene by PCR confirms diagnosis, and identification of serovar, of which 19 are known, informs on appropriate vaccine use and epidemiology.
Topics: Actinobacillus Infections; Actinobacillus pleuropneumoniae; Animals; Bacterial Proteins; Bacterial Vaccines; Pleuropneumonia; Swine; Swine Diseases
PubMed: 35262474
DOI: 10.1099/jmm.0.001483 -
Journal of Feline Medicine and Surgery Jun 2020The aim of this study was to evaluate if a combination of discrete clinical characteristics can be used to identify the most likely differential diagnoses in cats with...
OBJECTIVES
The aim of this study was to evaluate if a combination of discrete clinical characteristics can be used to identify the most likely differential diagnoses in cats with spinal disease.
METHODS
Two hundred and twenty-one cats referred for further evaluation of spinal disease were included and categorised as follows: non-lymphoid neoplasia (n = 44); intervertebral disc disease (n = 42); fracture/luxation (n = 34); ischaemic myelopathy (n = 22); feline infectious peritonitis virus myelitis (n = 18); lymphoma (n = 16); thoracic vertebral canal stenosis (n = 11); acute non-compressive nucleus pulposus extrusion (n = 11); traumatic spinal cord contusion (n = 8); spinal arachnoid diverticula (n = 7); lumbosacral stenosis (n = 5); and spinal empyema (n = 3). Information retrieved from the medical records included signalment, clinical history and clinical presentation. Univariate analyses of variables (clinical history, breed, age, sex, general physical examination findings, onset, progression, spinal hyperaesthesia, asymmetry, ambulatory status and neuroanatomical location) were performed, and variables were retained in a multivariate logistic regression model if <0.05.
RESULTS
Multivariate logistic regression revealed that intervertebral disc disease most often occurred in middle-aged, purebred cats with a normal general physical examination and an acute onset of painful and progressive clinical signs. Ischaemic myelopathy occurred most often in older cats with a stable or improving, non-painful, lateralising, C6-T2 myelopathy. Spinal fracture/luxation occurred most often in younger cats and resulted most often in a peracute onset, painful, non-ambulatory neurological status. Concurrent systemic abnormalities or abnormal findings detected on general physical examination were significantly associated with feline infectious peritonitis virus myelitis, spinal lymphoma or spinal empyema.
CONCLUSIONS AND RELEVANCE
This study suggests that using easily identifiable characteristics from the history and clinical examination can assist in obtaining a preliminary differential diagnosis when evaluating cats with spinal disease. This information could aid veterinary practitioners in clinical decision-making.
Topics: Animals; Cat Diseases; Cats; Clinical Reasoning; Diagnosis, Differential; Female; Male; Retrospective Studies; Spinal Diseases; Spinal Injuries
PubMed: 31251096
DOI: 10.1177/1098612X19858447 -
Frontiers in Veterinary Science 2020Common bottlenose dolphins ( exposed to freshwater or low salinity (<10 practical salinity units; PSU) for prolonged periods of time have been documented to develop skin...
Common bottlenose dolphins ( exposed to freshwater or low salinity (<10 practical salinity units; PSU) for prolonged periods of time have been documented to develop skin lesions, corneal edema and electrolyte abnormalities, and in some instances they have died. Here we review a case of an out-of-habitat subadult, female common bottlenose dolphin that remained in a freshwater lake in Seminole, Alabama for at least 32 days. Due to concerns for the dolphin's health a rescue was initiated. At the time of rescue bloodwork results indicated minor electrolyte abnormalities (hyponatremia, hypochloremia, hypoosmolality). Renal function was not affected (normal creatinine and urea nitrogen) and all other bloodwork parameters (hemogram; serum biochemistry analytes) were within normal limits. The dolphin was deemed healthy enough for immediate relocation and release. A satellite-linked tag was attached to the dorsal fin to track the dolphin following its relocation to a nearby brackish water bay (Perdido Bay, AL), a known habitat for bottlenose dolphins. Twelve weeks following release, the dolphin was found dead as a result of a fisheries interaction (peracute underwater entrapment). A full necropsy was conducted and there was complete resolution of the skin pallor and skin lesions and no evidence of chronic renal or central nervous system lesions. Post-mortem analysis of vitreous humor (used as a proxy for serum analytes and to determine post-mortem interval) was challenging to interpret and has not been validated in dolphins. This supports the need for future research in cetaceans to establish a species-specific approach. Elevated barium (Ba) concentrations in tooth dentin corresponded to increased seasonal freshwater discharge patterns, confirming repeated annual exposure to low salinity conditions prior to death and indicating freshwater exposure may pose an ongoing threat to dolphins in the region. This case provides a unique opportunity to follow the progression of prolonged freshwater exposure and recovery in a bottlenose dolphin and highlights that dolphins in nearshore habitats face a combination of persistent natural and human associated threats.
PubMed: 32457921
DOI: 10.3389/fvets.2020.00235 -
Virus Genes Jun 2015Guinea fowl coronavirus (GfCoV), a recently characterized avian coronavirus, was identified from outbreaks of fulminating disease (peracute enteritis) in guinea fowl in...
Guinea fowl coronavirus (GfCoV), a recently characterized avian coronavirus, was identified from outbreaks of fulminating disease (peracute enteritis) in guinea fowl in France. The full-length genomic sequence was determined to better understand its genetic relationship with avian coronaviruses. The full-length coding genome sequence was 26,985 nucleotides long with 11 open reading frames and no hemagglutinin-esterase gene: a genome organization identical to that of turkey coronavirus [5' untranslated region (UTR)-replicase (ORFs 1a, 1ab)-spike (S) protein-ORF3 (ORFs 3a, 3b)-small envelop (E or 3c) protein-membrane (M) protein-ORF5 (ORFs 4b, 4c, 5a, 5b)-nucleocapsid (N) protein (ORFs N and 6b)-3' UTR]. This is the first complete genome sequence of a GfCoV and confirms that the new virus belongs to group gammacoronaviruses.
Topics: Animals; Bird Diseases; Birds; Cluster Analysis; Coronavirus; Coronavirus Infections; France; Gene Order; Genome, Viral; Molecular Sequence Data; Open Reading Frames; Phylogeny; RNA, Viral; Sequence Analysis, DNA; Sequence Homology; Synteny
PubMed: 25712772
DOI: 10.1007/s11262-015-1183-z -
PloS One 2022Hypervirulent Klebsiella pneumoniae infection causes significant mortality of endangered New Zealand sea lion pups at Enderby Island, Auckland Islands. Gross necropsy... (Randomized Controlled Trial)
Randomized Controlled Trial
Hypervirulent Klebsiella pneumoniae infection causes significant mortality of endangered New Zealand sea lion pups at Enderby Island, Auckland Islands. Gross necropsy and histopathology findings are well reported, but little is known about the clinical course of disease in affected pups. To determine factors feasible as clinical screening tools for hypervirulent K. pneumoniae in live pups, 150 pups over two field seasons (2016-18) were recruited shortly after birth for a prospective cohort study. A randomised controlled clinical treatment trial with the anthelmintic ivermectin was conducted concurrently and risk factor data and biological samples were collected approximately fortnightly. Treatment with ivermectin has been demonstrated to reduce the risk of hypervirulent K. pneumoniae mortality in pups, so effects on clinical parameters between the treated and control cohorts were also investigated. A broader sample of pups were monitored for clinical signs to investigate the course of disease in affected pups. Clinical signs, haematology and oral and rectal swabs to detect gastrointestinal carriage of hypervirulent K. pneumoniae were not useful for detection of disease prior to death. Of those pups that died due to hypervirulent K. pneumoniae, only 26.1% (18/69) had any clinical signs prior, likely a reflection of the peracute course of disease. On comparison of haematological parameters between ivermectin-treated and control pups, significantly lower total plasma protein and higher eosinophil counts were seen in control versus treated pups, however standard length as a surrogate for age was a more important influence on parameters overall than ivermectin treatment. This study also highlighted a cohort of pups with severe clinical signs suggestive of hypervirulent K. pneumoniae infection were lost to follow up at the end of the monitored season, which could be contributing to cryptic juvenile mortality.
Topics: Animals; Humans; Ivermectin; Klebsiella Infections; Klebsiella pneumoniae; New Zealand; Prospective Studies; Sea Lions
PubMed: 35239682
DOI: 10.1371/journal.pone.0264582