A Comparative Review of Animal Models of Middle East Respiratory Syndrome Coronavirus Infection.

Middle East respiratory syndrome coronavirus (MERS-CoV) was initially isolated from a Saudi Arabian man with fatal pneumonia. Since the original case in 2012, MERS-CoV infections have been reported in >1500 humans, and the case fatality rate is currently 35%. This lineage C betacoronavirus has been reported to cause a wide range of disease severity in humans, ranging from asymptomatic to progressive fatal pneumonia that may be accompanied by renal or multiorgan failure. Although the clinical presentation of human MERS-CoV infection has been documented, many facets of this emerging disease are still unknown and could be studied with animal models. Several animal models of MERS-CoV have been developed, including New Zealand white rabbits, transduced or transgenic mice that express human dipeptidyl peptidase 4, rhesus macaques, and common marmosets. This review provides an overview of the current state of knowledge on human MERS-CoV infections, the probable origin of MERS-CoV, and the available animal models of MERS-CoV infection. Evaluation of the benefits and limitations of these models will aid in appropriate model selection for studying viral pathogenesis and transmission, as well as for testing vaccines and antivirals against MERS-CoV.

Syrian hamsters (Mesocricetus auratus) oronasally inoculated with a Nipah virus isolate from Bangladesh or Malaysia develop similar respiratory tract lesions.

Nipah virus is a paramyxovirus in the genus Henipavirus, which has caused outbreaks in humans in Malaysia, India, Singapore, and Bangladesh. Whereas the human cases in Malaysia were characterized mainly by neurological symptoms and a case fatality rate of ∼40%, cases in Bangladesh also exhibited respiratory disease and had a case fatality rate of ∼70%. Here, we compared the histopathologic changes in the respiratory tract of Syrian hamsters, a well-established small animal disease model for Nipah virus, inoculated oronasally with Nipah virus isolates from human cases in Malaysia and Bangladesh. The Nipah virus isolate from Bangladesh caused slightly more severe rhinitis and bronchointerstitial pneumonia 2 days after inoculation in Syrian hamsters. By day 4, differences in lesion severity could no longer be detected. Immunohistochemistry demonstrated Nipah virus antigen in the nasal cavity and pulmonary lesions; the amount of Nipah virus antigen present correlated with lesion severity. Immunohistochemistry indicated that both Nipah virus isolates exhibited endotheliotropism in small- and medium-caliber arteries and arterioles, but not in veins, in the lung. This correlated with the location of ephrin B2, the main receptor for Nipah virus, in the vasculature. In conclusion, Nipah virus isolates from outbreaks in Malaysia and Bangladesh caused a similar type and severity of respiratory tract lesions in Syrian hamsters, suggesting that the differences in human disease reported in the outbreaks in Malaysia and Bangladesh are unlikely to have been caused by intrinsic differences in these 2 virus isolates.

Arsenic toxicosis in cattle: meta-analysis of 156 cases.

BACKGROUND: Arsenic toxicosis is uncommon in cattle and successful treatment is rarely reported. OBJECTIVES: This analysis reviews all cases of acute arsenic toxicosis in cattle reported in the literature and describes cases from Purdue University that had a favorable outcome. Clinical presentation of the disease, treatments, and variables associated with survival are described. ANIMALS: One hundred and fifty-six cattle with arsenic toxicosis from 16 outbreaks. METHODS: Meta-analysis. RESULTS: The most common clinical signs were sudden death (68%), diarrhea (33%), ataxia (29%), dehydration (22%), and respiratory distress (4%). The most common clinicopathologic abnormalities included azotemia (100%), hematuria (100%), increased liver enzyme activity (86%), and increased hematocrit (60%). One percent of cattle survived and the survival time for nonsurvivors ranged from 20 hours to 21 days. None of the clinical signs or clinicopathologic findings was associated with survival. Treatment was attempted in 24% of cases and was not associated with survival (P = .055), but administration of an antidote and administration of fluids were associated with better outcome (P = .036 and P = .009, respectively). In the animals presented to Purdue University, treatment with IV fluids and sodium thiosulfate resulted in decreased blood arsenic concentrations in all animals (P = .009) and a survival rate of 50%. CONCLUSIONS AND CLINICAL IMPORTANCE: Although acute arsenic toxicosis has a poor prognosis, survival is possible if aggressive fluid therapy and antidotes are administered.