Experimental Hendra virus infection of dogs: virus replication, shedding and potential for transmission.

OBJECTIVE: Characterisation of experimental Hendra virus (HeV) infection in dogs and assessment of associated transmission risk. METHODS: Beagle dogs were exposed oronasally to Hendra virus/Australia/Horse/2008/Redlands or to blood collected from HeV-infected ferrets. Ferrets were exposed to oral fluids collected from dogs after canine exposure to HeV. Observations made and samples tested post-exposure were used to assess the clinical course and replication sites of HeV in dogs, the infectivity for ferrets of canine oral fluids and features of HeV infection in dogs following contact with infective blood. RESULTS: Dogs were reliably infected with HeV and were generally asymptomatic. HeV was re-isolated from the oral cavity and virus clearance was associated with development of virus neutralising antibody. Major sites of HeV replication in dogs were the tonsils, lower respiratory tract and associated lymph nodes. Virus replication was documented in canine kidney and spleen, confirming a viraemic phase for canine HeV infection and suggesting that urine may be a source of infectious virus. Infection was transmitted to ferrets via canine oral secretions, with copy numbers for the HeV N gene in canine oral swabs comparable to those reported for nasal swabs of experimentally infected horses. CONCLUSION: HeV is not highly pathogenic for dogs, but their oral secretions pose a potential transmission risk to people. The time-window for transmission risk is circumscribed and corresponds to the period of acute infection before establishment of an adaptive immune response. The likelihood of central nervous system involvement in canine HeV infection is unclear, as is any long-term consequence.

Atypical scrapie in Australia.

BACKGROUND: Since its initial detection in Norway in 1998, atypical scrapie ('atypical/Nor98 scrapie') has been reported in sheep in the majority of European countries (including in regions free of classical scrapie) and in the Falkland Islands, the USA, Canada, New Zealand and Australia. CASE SERIES: The diagnosis in Australia of atypical scrapie in four Merino and one Merino-cross sheep showing clinical signs of neurological disease was based on the detection of grey matter neuropil vacuolation (spongiform change) in the brain (particularly in the molecular layer of the cerebellar cortex) and associated abnormal prion protein (PrPSc ) deposition in both grey and white matter. Changes were minimal in the caudal brainstem, the predilection site for lesions of classical scrapie. CONCLUSION: The distinctive lesion profile of atypical scrapie in these five sheep highlights the diagnostic importance of routine histological evaluation of the cerebellum for evidence of neuropil vacuolation and associated PrPSc deposition in adult sheep with suspected neurological disease.

Henipaviruses in their natural animal hosts.

Hendra virus (HeV) and Nipah virus (NiV) form a separate genus Henipavirus within the family Paramyxoviridae, and are classified as biosafety level 4 pathogens due to their high case fatality rate following human infection and because of the lack of effective vaccines or therapy. Both viruses emerged from their natural reservoir during the last decade of the twentieth century, causing severe disease in humans, horses and swine, and infecting a number of other mammalian species. The current review summarizes our up to date understanding of pathology and pathogenesis in the natural reservoir species, the Pteropus bat, and in the equine and porcine spill over species.

Infection trials in pigs with a human isolate of Brucella ( isolate 02/611 'marine mammal type' ).

AIM: To determine if pigs could support infection of a human Brucella isolate (Brucella 02/611) from New Zealand, and to study seroconversion to this isolate using a competitive ELISA. METHODS: Ten weaner piglets were challenged with 4.8 x 10(8) cfu of organisms by the oral and ocular routes. Culture was attempted on blood samples taken prior to challenge, and 4, 7, 9, 11, 14, 21 and 28 days post-challenge, and on tissue samples taken at the termination of the trial, 1 month after challenge. Sera were analysed for antibody using an ELISA. For reference comparison, similar trials were conducted in two pigs using an isolate of Brucella suis biovar 1, and two pigs using an isolate of B. suis biovar 3. RESULTS: Brucella 02/611 organisms were re-isolated from one lymph node each from three pigs; all other samples were negative. Low and transient antibody titres were detected using a competitive ELISA in three pigs, two of which were culture negative. Organisms of B. suis reference strains were re-isolated from multiple samples from each of the four animals. CONCLUSION: Brucella 02/611 does not seem to replicate readily in pigs. It is unlikely that pigs were the original maintenance hosts for Brucella 02/611.

Experimental Nipah virus infection in pteropid bats (Pteropus poliocephalus).

Seventeen grey-headed fruit bats (Pteropus poliocephalus) were inoculated subcutaneously with an isolate of Nipah virus derived from a fatally infected human. A control group of eight guinea-pigs was inoculated intraperitoneally with the same isolate in order to confirm virulence. Three of eight infected guinea-pigs developed clinical signs 7-9 days post-inoculation. Infected fruit bats developed a subclinical infection characterized by the transient presence of virus within selected viscera, episodic viral excretion and seroconversion. A range of histopathological changes was observed within the tissues of infected bats. Nipah virus was excreted in bat urine while neutralizing antibody was present in serum. This intermittent, low-level excretion of Nipah virus in the urine of bats may be sufficient to sustain the net reproductive value of the virus in a species where there is regular urine contamination of the fur, mutual grooming, and where urine droplets are a feature of the environment.

Plastic particle migration during intravenous infusion assisted by a peristaltic finger pump in an animal model.

The contamination of intravenously administered fluid with foreign material has always been of major concern, but the in-vivo impact of silicone embolisation from administration of fluid via a peristaltic finger pump (PFP) has not previously been assessed. To determine whether silicone particles enter the lungs and to review the histological response, 10 rabbits received an IV infusion of 0.9% saline at 10 ml/kg per hour over a 72-h period, via an IVAC 591 PFP. The lungs were analysed for silicone particles with scanning electron microscopy (SEM) and energy-dispersive X-ray analysis (EDXA). These results were compared with a control group of non-infused animals. Silicone particles were found in 8 of 10 animals in the experimental group and in 2 of 9 control animals, indicating that silicone particles are dislodged during pump-assisted IV infusions. The difference between the control and infused animals was statistically significant using Fisher's exact test (P = 0.023). However, silicone plastic particles in control animals suggest that there is also environmental exposure to silicone in addition to those particles that come from a therapeutic source. The additional finding of elemental silicon (which is one of the constituents of silicone plastic) in both infused and control animals in which silicone plastic was not found indicates that not all elemental silicon in animals reflects the presence of silicone plastic. The clinical significance of each of these two findings is yet to be determined.

Experimental Nipah virus infection in pigs and cats.

A human isolate of Nipah virus from an outbreak of febrile encephalitis in Malaysia that coincided with a field outbreak of disease in pigs was used to infect eight 6-week-old pigs orally or subcutaneously and two cats oronasally. In pigs, the virus induced a respiratory and neurological syndrome consistent with that observed in the Malaysian pigs. Not all the pigs showed clinical signs, but Nipah virus was recovered from the nose and oropharynx of both clinically and sub-clinically infected animals. Natural infection of in-contact pigs, which was readily demonstrated, appeared to be acute and self-limiting. Subclinical infections occurred in both inoculated and in-contact pigs. Respiratory and neurological disease was also produced in the cats, with recovery of virus from urine as well as from the oropharynx. The clinical and pathological syndrome induced by Nipah virus in cats was comparable with that associated with Hendra virus infection in this species, except that in fatal infection with Nipah virus there was extensive inflammation of the respiratory epithelium, associated with the presence of viral antigen. Viral shedding via the nasopharynx, as observed in pigs and cats in the present study, was not a regular feature of earlier reports of experimental Hendra virus infection in cats and horses. The findings indicate the possibility of field transmission of Nipah virus between pigs via respiratory and oropharyngeal secretions.

Simian immunodeficiency virus infections in vervet monkeys (Clorocebus aethiops) at an Australian zoo.

A number of monkey species, including African green monkeys and African vervet monkeys (Chlorocebus aethiops), are frequently infected in the wild and in captivity with a Simian immunodeficiency virus strain, SIVagm, a primate lentivirus. Up to 50% of African green monkeys are estimated to be infected with SIVagm. SIV strains are very closely related to HIV-2 strains, which are a cause of AIDS in humans, predominantly in western Africa, although cases in Australia have also been reported. It is generally thought that SIV is non-pathogenic in several natural hosts, including African green monkeys. Nevertheless many SIV strains induce a profound immunodeficiency virtually identical to HIV-1 induced AIDS in humans when administered to Asian macaque species such as rhesus (Macaca mulatta) or pigtailed macaques (M nemestrina). SIV infection of Asian macaque species is frequently employed as an animal model for AIDS vaccine studies. In November 1996 a group of 10 African vervet monkeys were imported from the USA for display at Victoria's Open Range Zoo in Werribee. Two animals in this group of monkeys later developed a fatal gastroenteric illness. These diagnoses led us to initiate SIV testing of the colony.

Transient glucose malabsorption in two horses--fact or artefact?

Two horses, presented for investigation of chronic weight loss despite normal to increased feed intake, had flat oral glucose absorption curves, suggesting malabsorption. The cause of the apparent malabsorption was not evident grossly or on light microscopic examination of the intestinal tract. Both horses survived long term and at follow-up examination had regained weight and their capacity to absorb glucose. These cases illustrate that flat glucose absorption curves may occur in horses with no obvious intestinal lesions, that they may revert to normal and that the results of these tests should be interpreted with caution.

Proliferative histiocytic disorders of canine skin.

Proliferative histiocytic disorders of canine skin present a clinical spectrum from the innocuous self-limiting solitary dermal lesion of cutaneous histiocytoma, through the recurrent deep dermal nodules of cutaneous histiocytosis to the generally fatal condition of Bernese Mountain Dogs termed systemic histiocytosis, in which visceral involvement is commonly encountered. Immunocytochemical characterization of the constituent histiocytic cells and accompanying lymphoid infiltrate using canine species specific reagents has elucidated considerably the mechanism by which these conditions exhibit their various biologic behaviours.

Effects of proligestone and megestrol on plasma adrenocorticotrophic hormone, insulin and insulin-like growth factor-1 concentrations in cats.

This paper reports changes in adrenocorticotrophic hormone (ACTH), insulin and insulin-like growth factor-1 (IGF-1) concentrations in cats from a previously published study. The cats were given oral megestrol acetate (MA, 5 mg once daily for 14 days), subcutaneous proligestone (PRG, 100 mg on two occasions one week apart) or subcutaneous saline (1 ml as for PRG). In the cats given saline (n = 6), basal ACTH, insulin and IGF-1 did not change significantly throughout the following seven weeks. The cats given MA (n = 7) developed significant suppression of plasma ACTH concentrations and hyperinsulinaemia during treatment and for two to four weeks after MA dosage ceased. In the cats given PRG (n = 7), plasma ACTH concentrations were not significantly altered although three cats had markedly suppressed values for some time after PRG treatment had ceased. Serum insulin concentrations were not significantly altered in the PRG-treated cats. The results suggest PRG may be a preferable alternative to MA in some situations.

Failure to transmit bovine spongiform encephalopathy to mice by feeding them with extraneural tissues of affected cattle.

Single tissue pools of brain and five extraneural tissues were prepared from four clinical cases of bovine spongiform encephalopathy (BSE) and fed to C57B1 and/or CRH mice. The disease was transmitted only to C57B1 mice fed brain. Intracerebral passages at 12 and 18 months of spleen and spinal cord homogenates from this group of mice to C57B1 mice resulted in reduced incubation periods. Similar blind passages from all other groups failed to produce evidence of infection in a cumulative incubation period of 42 months. The results suggest that the probability of human infection occurring as a result of the consumption of non-neural bovine tissues is remote.

Use of ultrasound to diagnose testicular degeneration in a goat.

A seven-year-old infertile British alpine buck with small testes had bilateral testicular degeneration, as confirmed by the presence of a large number of dead and abnormal spermatozoa and a low percentage of progressively motile spermatozoa in its semen. Histopathological examination of the testes post mortem showed typical degenerative changes in the seminiferous tubules, with some tubules showing evidence of calcification. Ultrasonographically, the testicular parenchyma was uncharacteristically heterogeneous with an abundance of dense echogenic areas scattered through it.

Pituitary-dependent hyperadrenocorticism in a family of Dandie Dinmont terriers.

Adrenocortical function studies were performed in seven Dandie Dinmont terriers with pituitary-dependent hyperadrenocorticism. The ability of dexamethasone at a dose rate of 0.1 mg/kg body weight to suppress cortisol secretion was only moderate in four out of the six dogs tested. Concentrations of alpha-melanocyte-stimulating hormone in plasma were highly increased. Responses to stimulation with corticotrophin-releasing hormone and the dopamine-antagonist haloperidol, examined in three animals, were moderate or absent. These results indicate that adrenocortical stimulation, i.e. hyperadrenocorticotrophism, was caused by pituitary lesions which were functioning autonomously. In six of the seven animals there was a very close familial relationship and the coefficients of relationship and the coefficients of inbreeding were significantly higher than in a representative control population. It was concluded that these seven related terriers with hyperadrenocorticotrophism had the biochemical characteristics of de-novo neoplasms of proopiomelanocortin-producing cells, and there was evidence for a genetic involvement in tumorigenesis.

Effects of monensin on the bioavailability and elimination of selenium from blood in lambs.

A bioavailability study was conducted in lambs following intravenous and oral administration of sodium selenite (0.4 mg selenium/kg body weight) with and without concurrent oral monensin. Two- or three-compartment open models with first-order absorption after oral administration adequately described plasma selenium disposition irrespective of whether monensin was being administered. No significant differences were observed between groups of lambs receiving intravenous selenium with or without monensin with respect to distribution or elimination half-lives of selenium, areas under the concentration-time curve (AUC), volumes of distribution (Vd(ss)), or clearances (Cl). In lambs given selenium per os, no significant differences were observed with animals receiving monensin as well with respect to absorption and elimination half-lives, Vd(ss), or the time at which peak selenium concentrations occurred (tmax). However, peak selenium levels (Cmax) and AUC values were significantly higher in the group given monensin. The bioavailability of selenium with and without monensin was estimated to be 60% and 43%, respectively.

An investigation into the origin of the first fraction of the canine ejaculate.

Histological examination of the reproductive tract of the male dog failed to identify glandular tissue other than the prostate gland and its disseminated portion. A biochemical study of the three fractions of the ejaculate demonstrates similarities between the first and the third fractions. The composition of three ejaculates collected over 12 hours indicated that storage of prostatic secretion was a possible explanation for the biochemical differences observed. It is suggested that both the first and third fractions originate from the prostate gland.