Experimental Sendai virus infection in laboratory rats. I. Virus replication and immune response.

Sixty 5 to 8 week old Sprague-Dawley (Crl:CD(SD)BR) rats were inoculated intranasally with 2000 egg infectious doses of egg-propagated Sendai virus. Virus was recovered from the upper respiratory tract and lungs on days 1 through 8 post-inoculation (PI). Serum antibody responses were measured for 12 rats over a 9 month period PI. Antibody was first detected at 7 days, peaked at 21 days, and was detected in 5 of the 12 rats at 9 months. A cell-mediated response, as measured by lymphocyte blastogenesis, also was detected at 7 days and peaked at 21 days, but was not detected at 6 months PI. Lung and serum interferon (IFN) was first detected at 3 hours and peaked at 6 hours, but was not detected by 160 hours. Lung IFN levels were 4 to 10 times those in the serum. These studies indicate that pathogenesis of Sendai virus infection in the rat is similar to that reported in the mouse, but that there are differences in the kinetics of both viral replication and morphologic changes, as described in the companion paper.

Dichlorvos toxicity in the white-footed mouse (Peromyscus leucopus).

The organophosphate pesticide, dichlorvos (DDVP), is used commonly to control ectoparasites in laboratory rodents colonies. This compound is relatively nontoxic to Mus musculus at dosages several times the therapeutic level. However, usage of a similar therapeutic level in the white-footed mouse (Peromyscus leucopus) resulted in substantial mortality. To determine whether P. leucopus is more susceptible than M. musculus to the toxic effects of DDVP, both species were exposed to 0, 3 and 6 g of pelleted DDVP per cage. In a subsequent experiment, P. leucopus were exposed to 0 and 1 g of DDVP per cage. Mortality was not observed in M. musculus at any dosage level. P. leucopus exposed to 1, 3 and 6 g of DDVP exhibited mortalities of 3%, 20% and 53%, respectively. Mean serum cholinesterase in P. leucopus exposed to 3 and 6 g of DDVP was 0.35 and 0.21 U/ml as compared to 3.13 U/ml in unexposed mice. The analogous values for M. musculus were 1.60 and 0.79 U/ml while the level in unexposed mice was 6.79 U/ml. In the second experiment, mean serum cholinesterase in P. leucopus exposed to 1 g of DDVP was 0.32 U/ml as compared to 2.33 U/ml in unexposed mice. Histopathology revealed no lesions in the brain, liver or kidneys. The increased susceptibility of P. leucopus to the toxic effects of DDVP was related to the lowered serum cholinesterase. This indicates that DDVP should not be used for control of ectoparasites in P. leucopus.

Experimental Sendai virus infection in laboratory rats. II. Pathology and immunohistochemistry.

Intranasal inoculation of 5 to 8 week old specific pathogen-free Sprague-Dawley rats with 5 X 10(3) egg infectious doses of Sendai virus resulted in severe rhinitis, bronchiolitis and alveolitis. The most severe rhinitis occurred on postinoculation (PI) days 4-6, and pneumonia on day 4. Rhinitis and pneumonia persisted to PI day 21, with peribronchial lymphoid infiltration detectable at PI day 42. Immunohistochemical studies showed that Sendai virus antigens were present primarily in columnar epithelial cells of the respiratory mucosa of the nasal cavity and in bronchiolar and alveolar epithelium. Antigen was first detectable at PI day 1, was most prominent at days 3-4 and was undetectable after day 7. More antigen could be seen in the nasal mucosa than in the lung at any stage in the infection. These studies show that Sendai virus by itself is capable of evoking severe, although transient, rhinitis and pneumonia in laboratory rats free of other significant pathogens.

Subacute nonsuppurative hepatitis associated with hepatitis B virus infection in two cynomolgus monkeys.

Subacute, nonsuppurative hepatitis was diagnosed in a cynomolgus monkey (Macaca fascicularis) based on histopathologic examination of a liver biopsy specimen. Clinical signs of illness included anorexia, lethargy and hepatomegaly. Abnormal laboratory findings included elevations of serum liver enzymes, bilirubin and a monocytosis. Circulating antibody (anti-HBs) against Hepatitis B surface antigen (HBsAg) was present in serum and antigens reactive with anti-HBsAg antiserum were found in the liver using an immunoperoxidase technique. Of the remaining 18 healthy monkeys in the same room, another cynomolgus monkey was HBsAg seropositive. Both of the seropositive monkeys involved arrived on the same shipment from Indonesia and had been quarantined and housed together continuously during the preceding two years.

Disseminated cytomegalovirus disease in the guinea pig.

Two guinea pigs (Cavia porcellus), which were housed conventionally in separate animal facilities and had not been experimentally manipulated, were found to have evidence of disseminated cytomegalovirus disease at necropsy. Microscopic examination revealed multiple focal areas of necrosis in numerous organs. The spleen, liver, kidney and lungs were affected particularly. These lesions contained numerous cells with large intranuclear and cytoplasmic inclusion bodies resembling cytomegalovirus inclusions. Characteristic cytomegalovirus virions were observed by electron microscopy in both cases. Antigens of guinea pig cytomegalovirus were detected in paraffin sections of lesions from both cases with an immunoperoxidase technique. Although subclinical infection is common, this is the only contemporary report of disseminated disease due to cytomegalovirus in guinea pigs.

Natural history of infection with Pasteurella multocida in rabbits.

Monitoring of rabbits at a commercial rabbitry for Pasteurella multocida infection revealed that the nares of 10 litters of New Zealand White rabbits were not colonized before weaning at 8 weeks of age, regardless of whether or not the does were infected. The earliest nasal infection was detected at 12 weeks of age, and by 22 weeks of age, 23% had P multocida infection. Rhinitis developed 2 or more weeks after infection was detected in most rabbits. A survey of 76 adult rabbits in the breeding colony revealed that 72% had P multocida infection. In 31 rabbits with rhinitis, 90% were infected, whereas in 55 rabbits with P multocida infection, only 50% had rhinitis. During the period of surveillance, there was an epizootic of rhinitis caused by P multocida. All age groups except preweanlings were affected. Serotyping of 29 isolates of P multocida revealed that 93% were somatic type 12. Surveillance of rabbits for pasteurellosis at a laboratory animal facility revealed that the following clinical syndromes developed in decreasing order of magnitude: rhinitis, conjunctivitis, abscesses, and otitis media.

Selective media for Pasteurella multocida and Bordetella bronchiseptica.

Easily prepared and inexpensive culture medium for the isolation of Pasteurella multocida and Bordetella bronchiseptica from the nares of laboratory rabbits was prepared by incorporating 2 micrograms/ml clindamycin into standard blood agar. Using this medium, the time and materials required to identify and isolate Pasteurella multocida was substantially reduced with only a slight loss in sensitivity. The combination of 2 micrograms/ml clindamycin and 4 micrograms/ml neomycin was effective in isolating Bordetella bronchiseptica from rabbits.

Heterotransplantation of feline malignant tumors in nude thymusless mice.

The nude mouse was used to evaluate transplantation of feline tumors and subsequent doxorubicin chemotherapy. Three mammary gland adenocarcinomas and one salivary gland adnoecarcinoma were readily transplanted. All were successfully passed at least once. The two sarcomas, a fibrosarcoma and a malignant hemangioendothelioma, failed to grow when transplanted. Growth rates for the adenocarcinomas appeared to be specific for individual tumors. Generally, tumor weights increased five to eight times by days 40 to 50. Structural changes were not observed histopathologically in tumors transplanted several times. When doxorubicin was given intraperitoneally (1 mg/kg of body weight) weekly for 6 weeks to nude mice with transplanted feline mammary gland adenocarcinoma, there was no significant difference (P less than 0.05) in weights of tumors of experimental (n = 150 and control (n = 10) mice.

The role of respiratory infection in intrathoracic petechiae. Implications for sudden infant death.

Intrathoracic petechiae are characteristic of the postmortem changes found in sudden infant death syndrome. The presence and distribution of these petechiae have been claimed as evidence for airway obstruction as the mechanism of death. In a group of young, mature rats that were free of infection, hypoxic asphyxia produced an insignificant number of petechiae, whereas in all littermates infected with an enzootic virus (Sendai) large numbers of petechiae with hypoxic asphyxia developed. Rats similarly infected, but killed with an overdose of pentobarbital sodium, had no petechiae. Most importantly, infected rats with unremitting airway obstruction were free of petechiae. Thus, the experimental conditions necessary for the presence of intrathoracic petechiae are profound hypoxia and infection, with persistent circulation and respiratory effort; persistent airway obstruction does not produce petechiae, with or without infection.

Studies on adjuvant-induced arthritis, tumor transplantability, and serologic response to bovine serum albumin in Sendai virus-infected rats.

Sendai virus, one of the most prevalent of the murine viruses, was studied in regard to its capability to alter various functions of rats given a second, unrelated antigenic challenge. Rats given a single foot-pad injection of Freund's complete adjuvant (FCA) had an 85% incidence of adjuvant arthritis. The adjuvant disease was significantly less severe (P less than 0.01) in those rats given 0.05 ml of 10(5.5) median egg infective doses of egg-propagated Sendai virus intranasally 7 days before injection of adjuvant. Rats given Sendai virus concurrently with the FCA, or any time after FCA was injected, did not have a lessened severity of the arthritic reaction, as compared with that in control animals. Sendai virus infection had no detectable effect on median tumor dose requirement for Walker carcinosarcoma cells in rats or on the antibody response to bovine serum albumin.

Poditis in the rat as a complication of experiments in exercise physiology.

Experiments using the rat to study the effect of forced exercise on various physiologic and biochemical processes were complicated by the occurrence of poditis. Staphylococcus aureus was isolated from two affected rats and a tentative diagnosis of staphylococcal pododermatitis was made. In a subsequent study, poditis again occurred and S aureus was isolated from the rats, cages, exercise wheels, and attendants. Subcutaneous inoculation of six rats with the organism failed to reproduce the disease. The isolation of S aureus, and the apparent response to hygienic and therapeutic procedures and a change in exercise apparatus, suggested a traumatic and infectious etiology. However, the respective roles of trauma and S aureus or other microorganisms were not resolved.

The influence of filter top caging on the transmission of pinworm infections in mice.

The effectiveness of filter top cages in preventing infection of mice with pinworms, Aspiculuris tetraptera and Syphacia obvelata, was investigated by introducing mice from a pathogen-free colony into a colony in which both types of pinworms were enzootic. Half of the pathogen-free mice were maintained in filter top cages, while the remainder were held in similar cages without filters. All mice thus introduced were killed and examined after 3-8 week exposure periods. No pinworm were recovered from mice in 17 of 18 cages with filter tops while mice in 12 of 16 cages without filter tops were infected.

Transmission of enteritis in the Syrian hamster.

Twenty-six of 39 Syrian hamsters obtained by this laboratory from a pet supplier had enteritis and showed signs of "wet tail." An enteritis was reproduced in healthy hamsters by oral inoculation of homogenized ilea and jejuna from the diseased hamsters. The most characteristic pathologicfeatures were a variably enlarged distal jejunum and ileum and granulomatous lesions in the ileal subserosal wall. Histologic findings included a greatly hyperplastic jejunal and ileal mucosa that frequently contained submucosal accumulations of inflammatory cells. Often mucosal glands extended into these areas. The gross and histologic lesions produced were identical to those described in proliferative ileitis. Bacterial cultures from infected tissues consistently grew a slow lactose-fermenting Escherichia coli. Although diarrhea could be produced by oral inoculation of the organism, the typical morphologic lesions were not produced.

A survey of naturally occurring diseases of the Syrian hamster.

Questionnaires on research activities, mortality rates observed in various age groups, extent of examination of dead hamsters, and natural disease conditions and their relative importance were returned by 24 of 43 organisations surveyed in the United States. The average preweaning mortality rate due to all causes was 11-9%. Comparative data from 6 organisations that raised 87 880 hamsters in the calendar year 1971 indicated that 97-5% of total preweaning mortality was due to cannibalism. 13-7% of all animals died before use for experiments. "Wet tail" was the most frequently recognized disease (71%), and it was also listed as the most important. Pneumonia was recognized by 43% of the respondents and was most commonly listed as second in importance. A selective review of the literature is presented on those diseases recognized by more than one survey respondent.