Temporal Progression of Lesions in Guinea Pigs Infected With Lassa Virus.

Lassa virus (LASV) infection causes an acute, multisystemic viral hemorrhagic fever that annually infects an estimated 100 000 to 300 000 persons in West Africa. This pathogenesis study evaluated the temporal progression of disease in guinea pigs following aerosol and subcutaneous inoculation of the Josiah strain of LASV as well as the usefulness of Strain 13 guinea pigs as an animal model for Lassa fever. After experimental infection, guinea pigs ( Cavia porcellus; n = 67) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and serum chemistry and hematologic changes. Guinea pigs developed viremia on day 5 to 6 postexposure (PE), with clinical signs appearing by day 7 to 8 PE. Complete blood counts revealed lymphopenia and thrombocytopenia. Gross pathologic findings included skin lesions and congested lungs. Histologic lesions consisted of cortical lymphoid depletion by day 6 to 7 PE with lymphohistiocytic interstitial pneumonia at 7 to 8 days PE. Scattered hepatocellular degeneration and cell death were also noted in the liver and, to a lesser extent, in other tissues including the haired skin, lung, heart, adrenal gland, lymph nodes, thymus, and spleen. The first cell types to demonstrate staining for viral antigen were fibroblastic reticular cells and macrophages/dendritic cells in the lymph nodes on day 5 to 6 PE. This study demonstrates similarities between Lassa viral disease in human infections and experimental guinea pig infection. These shared pathologic characteristics support the utility of guinea pigs as an additional animal model for vaccine and therapeutic development under the Food and Drug Administration's Animal Rule.

Sclerosing cholangitis in baboons (Papio spp) resembling primary sclerosing cholangitis of humans.

Primary sclerosing cholangitis is a chronic and progressive cholestatic liver disease that has been extensively documented in the human literature. Although it shares many features in common with chronic lymphocytic cholangitis in cats, primary sclerosing cholangitis has never been reported in a nonhuman primate. Primary sclerosing cholangitis is characterized by the presence of intrahepatic and/or extrahepatic inflammation and concentric fibrosis of bile ducts, eventually leading to cirrhosis and hepatic failure. The pathogenesis and cause remain unknown, but the disease likely involves a multifactorial mechanism with genetic- and immune-mediated components. The authors report 2 cases that histologically resemble the condition in humans; they consist of 2 adult male baboons with a clinical history of chronic elevated liver enzymes. In both cases, the liver was histologically characterized by thick bands of fibrosis and mild lymphoplasmacytic periportal cholangiohepatitis with concentric periductal fibrosis, resulting in atrophy and loss of bile ducts. Immunohistochemical analysis revealed positivity of hepatocytes to cytokeratin 7. Masson stain demonstrated marked biliary fibrosis. This is the first report that resembles sclerosing cholangitis in a nonhuman primate, and it suggests that the baboon may provide a useful animal model for this condition in humans.

Histologic, immunohistochemical, and clinical features of 27 mammary tumors in 18 male dogs.

Twenty-seven mammary tumors from 18 male (3 intact, 15 neutered) dogs were collected. The average age at diagnosis was 9.2 years (range, 2-14 years). Seven of the dogs were Cocker Spaniels. Five dogs had multiple mammary tumors. All tumors were benign. Twenty-six were simple adenomas with mixed acinar and papillary patterns. The acinar pattern was predominant in 17 cases. One adenoma was complex with a prominent myoepithelial component. The myoepithelial component of 25 of the 25 tumors was immunohistochemically positive for calponin and p63. In the cases for which relevant clinical information was available, there was no reported history of obesity, testicular tumors, or sex hormone therapy. Surgery was the only reported treatment for these tumors. Only 1 dog was reported to have developed an additional mammary tumor. None of the dogs for which case outcome was known died or was euthanatized as a result of mammary tumor. Although uncommon, mammary tumors do occur in male dogs. Although mammary tumors may be quite cellular, the presence of an intact myoepithelium, which can be demonstrated with immunohistochemistry for calponin and p63, indicates benignancy, as the clinical behavior documents.