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PART II Disease Agents BACTERIA, FUNGI, AND VIRUSES Adenoviruses Agent. DNA virus. Two strains, MAd- 1 and MAd-2 (formerly called FL and K87, respectively), are recognized. Animals Affected. Mice and rats. Epizootiology. Prevalence is probably low. MAd- 1 is shed in urine, and MAd- 2 is shed in feces. Transmission is by the oral route. Clinical. Natural infection does not cause clinical disease. Pathology. There are no pathologic lesions associated with natural infections of MAd-l. Viral inclusions in intestinal mucosa are associated with MAd-2 infec- tions. Diagnosis. The preferred diagnostic procedures are the ELISA and the IFA test, which test sera for antigens of both MAd- 1 and MAd-2. Presumptive diagnosis of MAd-2 can be made by demonstration of characteristic intranuclear inclusions in histologic sections of intestinal epithelium. A fluorescent antibody method has been used for detecting MAd-2 antigen in the intestine. Definitive diagnosis requires virus isolation in tissue culture. Control. Cesarean derivation and barrier maintenance may be necessary for eliminating either virus strain. Interference with Research. MAd- 1 can produce extensive persistent lesions in the kidneys of adult mice and render them more susceptible to experimental Escherichia coli-induced pyelonephritis. MAd (strain not given) has been reported to accelerate experimental scrapie in mice. 9
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10 COMPANION GUIDE TO INFECTIOUS DISEASES OF MICE AND RATS Suggested Reading Hamelin, C., C. Jacques, and G. Lussier. 1988. Genome typing of mouse adenoviruses. J. Clin. Microbiol. 26:31-33. Hasnelin, C., and G. Lussier. 1988. Genotypic differences between the mouse adenovirus strains FL and K87. Exper~entia 44:65-66. Luethans, T. N., and J. E. Wagner. 1983. A naturally occurring intestinal mouse adenov~rus infection associated with negative serologic findings. Lab. Anim. Sci. 33:270-272. Lussier G., A. L. Smith, D. Guenette, and J. P. Descoteaux. 1987. Serological relationship between mouse adenovirus strains FL and K87. Lab Anim. Sci. 37:55-57. Otten, J. A., and R. W. Tennant. 1982. Mouse adenovirus. Pp. 335-340 in The Mouse in BiomedicalResearch. Vol. II: Diseases, H. L. Foster, J. D. Small, and J. G. Fox, eds. New York: Academic Press. Smith, A. L., D. F. W~nograd, and T. G. Burrage.1986. Comparative biological characterization of mouse adenovirus strains FL and K87 and seroprevalence in laboratory rodents. Arch. Virol. 91:233-246. Bacillus piliformis Agent. Unclassified gram-negative bacterium, having vegetative and spore fonn ~ Animals Affected. Mice, rats, gerbils, hamsters, guineapigs, rabbits, cats, dogs, nonhuman primates, horses, and others. Epizootiology. Prevalence in the United States is unknown. Natural infection is thought to be caused by ingestion of spore-contaminated food or bedding. Clinical. Subclinical infection is probably more common than clinical disease (commonly called Tyzzer's disease). Contributors to clinical disease include poor sanitation, overcrowding, transportation stress, food deprivation, dietary modifi- cations, and altered host immune status. Clinical disease occurs most frequently in sucklings and weanlings, but animals of any age can be affected. Morbidity and mortality vary from low to high. Unexpected deaths, watery diarrhea, pasting of feces around the perineum, ruffled fur, and inactivity are the most common signs. Homozygous female and hemizygous male CBA/N-xid and C3.CBA/N-xid mice, which are deficient in a specific subpopulation of B cells, are highly susceptible, whereas T-cell-deficient athymic (nu/nu) mice are as resistant as immunocompe tent mice. Pathology. Primary infection occurs in the ileum and cecum, followed by ascension of the organisms by the portal vein to the liver and bacteremic spread to othertissues, most notably the myocardium. The organism preferentially replicates in the intestinal epithelium, smooth muscle, hepatocytes, and myocardium, but the degree of replication (and lesions) varies considerably between animals and between species. Intestinal lesions are usually more severe in rats than in mice. Myocardial lesions occur inconsistently. Gross lesions range from none to severe involvement of the intestine, liver, and/or heart. In mice, the most consistent finding is multiple pale to yellow foci in the liver. Infrequently, the ileum and cecum appear
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DISEASE AGENTS 1 1 thickened, edematous, and hyperemic, and the myocardium contains circumscribed pale gray areas. Lesions in rats are similar, except that the ileum often appears dilated, atonic, and edematous (megaloileitis). The mesenteric lymph nodes are usually enlarged. In the ileum, in the cecum, and sometimes in the proximal colon, there is mild to severe loss of the mucosal epithelium, with blunting of villi in the ileum, thinning of the surface epithelium, and severe ulceration and hemorrhage. In more advanced stages, there is hyperplasia of crypt epithelium. Transmural acute to subacute inflammation can occur in areas of severe epithelial loss. In the liver there are multiple foci of coagulative necrosis that are rapidly converted to microabscesses. If the myocardium is affected, there is focal to diffuse myocardial necrosis with acute to subacute inflammation. In affected tissues, the characteristic large, filamentous bacilli are best demonstrated histologically in the cytoplasm of viable cells along the margin of necrotic tissues by the use of silver strains (Warthin- Starry or methenamine silver). Diagnosis. Diagnosis of clinical disease is based on finding typical gross and microscopic lesions and characteristic organisms in silver-stained histologic sec- tions. Both the IFA and the CF tests have been used for the diagnosis of subclinical infections, but neither test is available commercially in the United States. Alter- natively, weanling animals can be immunosuppressed by the administration of 100- 200 mg/kg cortisone acetate. Subclinical infection, if present, will become active disease, and characteristic lesions and organisms can be demonstrated histologically 7 days after cortisone administration. The presence of B. piliformis in tissues can be demonstrated by the finding of characteristic lesions and organisms histologi- cally 5-7 days following inoculation of the tissue into gerbils or into homozygous xid female or hemizygous xid male mice. Control. Cesarean-derivation and barrier-maintenance procedures, reduction of stress, and good sanitation procedures appear to minimize the occurrence of clinical disease. Good sanitation practices, avoidance of crowding, autoclaving of food and bedding, and the use of 0.3% sodium hypochlorite for disinfecting room surfaces are recommended for reducing spore contamination in conventional animal facilities. Oral administration of tetracycline can be helpful in controlling losses during outbreaks. Interference with Research. Tyzzer's disease can cause high mortality in breeding colonies of mice and in mice used in long-term carcinogenesis studies. Administration of cortisone or adrenocorticotropic hormone, whole-body x-irra- diation, transplantation of ascites tumors, and a high-protein diet can induce clinical disease. Tyzzer's disease alters the pharmacokinetics of warfarin and trimethoprim and the activity of hepatic transaminases. Suggested Reading Fries, A. S. 1980. Antibodies to Bacillus piliformis (Tyzzer's disease) in sera from man and
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12 COMPANION GUIDE TO INFECTIOUS DISEASES OF MICE AND RATS other species. Pp. 249-250 in Animal Quality and Models in Research, A. Spiegel, S. Enchsen, and H. A. Solleveld, eds. Stuttgart: Gustav Fischer Verlag. Fujiwara, K., M. Nakayama, and K. Takahashi. 1981. Serologic detection of inapparent Tyzzer's disease in rats. Jpn. J. Exp. Med. 51:197-200. Ganaway, J. R. 1980. Effect of heat and selected chemical disinfectants upon infectivity of spores of Bacillus piliformis (Tyzzer's disease). Lab. Anim. Sci. 30:192-196. Ganaway, J. R. 1982. Bacterial and mycotic diseases of the digestive system. Pp. 1-20 in The Mouse in Biomedical Research. Vol. II: Diseases, H. L. Foster, J. D. Small, and J. G. Fox, eds. New York: Academic Press. Waggle, K. S., C. T. Hansen, J. R. Ganaway, and T. S. Spencer. 1981. A study of mouse strain susceptibility to Bacillus piliformis (Tyzzer's disease): The associahonofB-cellfunction and resistance. Lab. Anim. Sci. 31 :139-142. Weisbroth, S. H. 1979. Bacterial and mycotic diseases. Pp.191-241 in The Laboratory Rat. Vol.1: Biology and Diseases, H. J. Baker, J. R. Lindsey, and S. H. Weisbroth, eds. New York: Academic Press. Cilia-Associated Respiratory Bacillus Agent. Gram-negative bacterium. Animals Affected. Laboratory rats and mice, wild rats (Rattus norvegicus), African white-tailed rats (Mystromys albicaudatus), and rabbits. Epizootiology. Unknown. Clinical. Clinical manifestations in rats are similar to those of severe murine respiratory mycoplasmosis (MRM) and can include hunched posture, ruffled coat, inactivity, head tilt, and accumulation of prophyrin pigment around the eyes and external nares. No description of clinical disease in mice has been published. Pathology. In those instances in which cilia-associated respiratory (CAR) bacillus has been found in rats with natural disease, Mycoplasma pulmonis also was present. It is possible that M. pulmonis was the primary pathogen and the CAR bacillus increased disease severity. It is not known whether the CAR bacillus alone can cause natural clinical disease. The predominant lesions in rats are those of advanced MRM due to M. pulmonis with some additional distinctive features. Severe bronchiectasis andbronchiolectasis, pulmonary abscesses, and atelectasis are associated with the accumulation of purulent or mucopurulent exudate in airways. An abundance of mucus often is present in peribronchiolar alveoli. Multifocal necrosis and acute inflammation of bronchiolar and bronchial epithelia often progress to severe granulomatous in- flammation in airway walls and abscess formation in airway lumens. Disordered repair may result in distorted, scarred bronchioles and bronchiolitis obliterans. The ciliated border of the respiratory epithelium in affected airways often appears quite dense in hematoxylin- and eosin-stained sections because of the large numbers of CAR bacilli present between the cilia. The CAR bacillus can also be found on epithelial surfaces associated with MRM lesions in nasal passages, larynx, trachea, and middle ears. CAR bacillus-associated respiratory lesions similar to those seen in rats have been reported in C57BL/6J-ob/ob mice.
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DISEASE AGENTS 13 Diagnosis. Recognition of the argyrophilic CAR bacillus in Warthin-Starry silver-stained histologic sections of affected lungs has been the main diagnostic method used. The organism also can be demonstrated by transmission electron microscopy. The ELISA and the IFA test for this infection are in use in some laboratories but have not been fully evaluated. Control. The infection probably can be eliminated by cesarean derivation, but definitive data are not available. Interference with Research. Uncertain. The organism might be an important contributor to the morbidity and mortality caused by MRM in rats. Suggested Reading Ganaway, J. R., T. H. Spencer, T. D. Moore, and A. M. Allen. 1985. Isolation, propagation, and characterization of a newly recognized pathogen, cilia-associated respiratory (CAR) bacillus of rats, an etiological agent of chronic respiratory disease. Infect. Immun. 47:472-479. Griffith, J. W., W. J. Whim, P. J. Danneman, and C. M. Lang. 1988. Cilia-associated respiratory bacillus infection of obese mice. Vet. Pathol. 25:72-76. Mackenzie, W. F., L. S. Magill, and M. Hulse. 1981. A filamentous bacterium associated with respiratory disease in wild rats. Vet. Pathol. 18:836-839. Matsushita, S. 1986. Spontaneous respiratory disease associated with cilia-associated respiratory (CARJ bacillus in a rat. Jpn. J. Vet. Sci. 48:437-440. Matsushita, S., M. Kashima, and H. Joshima. 1987. Serodiagnosis of cilia-associated respiratory bacillus infection by the indirect immunofluorescence assay technique. Lab. Anim. (London) 21:356-359. van Zwieten, M. J., H. A. Solleveld, J. R. Lindsey, F. G. deGroot, C. Zurcher, and C. F. Hollander. 1980. Respiratory disease in rats associated with a filamentous bacterium. Lab. Anim. Sci. 30:215-221. gen. Citrobacterfreundii Biotype 4280 Agent. Gram-negative bacterium. Usually considered an opportunistic patho Animals Affected. Mice. Epizootiology. Transmission is presumed to be by the fecal-oral route. The organism is rarely found in cesarean-derived, barrier-maintained mice. Clinical. Signs of disease are nonspecific and include ruffled fur, listlessness, weight loss, stunting, pasty feces around the anus and perineum, and rectal prolapse. Suckling mice are more susceptible to disease than are adults. Mortality can reach 60%, and the occurrence of rectal prolapse can reach 15 %. Mortality is significantly higher in C3H/HeJ than in DBA/2J, C57BL/6J, or N:NIHS (Swiss) mice. Pathology. Infection in mice lasts only about 4 weeks. Even if the infection is eliminated as early as 2 days postinfection by administration of neomycin sulfate or tetracycline hydrochloride, mucosal hyperplasia still occurs. Presence of the infection in the intestine for 10 days results in maximum hyperplasia. The descend
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14 COMPANION GUIDE TO INFECTIOUS DISEASES OF MICE AND RATS ing colon is most commonly affected, but the entire colon and cecum can be involved. Grossly, affected bowel is thickened and rigid in appearance. Micro- scopically, crypt height is increased threefold, mitotic activity is increased, goblet cells are decreased, and basophilia of the epithelium is increased. Crypt abscesses are common, and mucosal erosions and ulcers can occur. The occurrence of necrotizing and inflammatory lesions tends to parallel mortality. Variable numbers of neutrophils or mononuclear leukocytes can be present in the lamina propria, but there is often a paucity of inflammatory cells. Goblet-cell hyperplasia with muci- nous distension of crypts and streaming of mucin into the gut lumen can occur during regression of mucosal hyperplasia. Diagnosis. Diagnosis is by demonstration of characteristic lesions in the large intestine and isolation of organisms of the pathogenic biotype. Control. Definitive data are lacking. Control probably requires depopulation and restocking with cesarean-derived mice. Neomycin or tetracycline administered in drinking water reduces losses during outbreaks but probably does not completely eliminate infection. Interference with Research. The cytokinetics of the mucosal epithelium in the large intestine is profoundly altered in infected mice. Susceptibility to the carcinogen 1,2-dimethylhydrazine is increased, and the latent period for neoplasia induction is reduced. Suggested Reading Barthold, S. W. 1980. The microbiology of transmissible munne colonic hyperplasia. Lab. Anim. Sci. 30:167-173. Barthold, S. W., G. L. Coleman, P. N. Bhatt, G. W. Osbaldiston, and A. M. Jonas.1976. The etiology of transmissible murine colonic hypeIplasia. Lab. Anim. Sci. 26:889-894. Barthold, S. W., G. L. Coleman, R. O. Jacoby, E. M. Livstone, and A. M. Jonas. 1978. Transmissible murine colonic hype~plasia. Vet. Pathol. 15:223-236. Johnson, E., and S. W. Barthold. 1979. The ultrastructure of transmissible munne colonic hyperplasia. Am. J. Pathol. 97:291-313. Corynebacter~um kutscher~ Agent. Gram-positive bacterium. Animals Affected. Mice, rats, and rarely guinea pigs. Epizootiology. Persistent subclinical infections are thought to be common in conventionally reared stocks and rare in barrier-maintained stocks. The main sites of infection are probably the oropharynx, submaxillary lymph nodes, and large intestine, with transmission mainly by the fecal-oral route. Clinical Signs. Infection is usually inapparent. Disease occurs only after the immune system is compromised by experimental procedures, dietary deficiency, or concurrent infections with other agents. Signs of clinical disease in rats are usually those of a respiratory infection: dyspnea, rales, weight loss, humped posture, and
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DISEASE AGENTS 15 anorexia. Signs in mice are usually those of severe septicemia: dead and moribund animals. Arthritis or abscesses can occur in either species. Pathology. Septicemia results in septic emboli in many organs. In mice, large bacterial emboli lodge in capillary beds, particularly in the kidney and liver. Em- bolic glomerulitis is characteristic. Abscess formation can occur at the focus of infection. In rats, bacterial emboli lodge in the capillaries of the lungs. Alveoli become packed with polymorphonuclear leukocytes and can form large necro- purulent centers. Fibrinous or fibrous pleuritis often develops. Occasionally, abscesses occur in the liver, kidneys, subcutis, peritoneal cavity, and other sites. Diagnosis. Detection of persistent subclinical infections is very difficult. Available methods are unsatisfactory for detecting persistent subclinical infections, although an ELISA has been developed that shows promise for detecting anti- bodies. There is also a new DNA probe method, but its usefulness has not been determined. Cortisone acetate can be given to provoke active disease, which is then diagnosed by culture of the organism, demonstration of characteristic lesions, and exclusion of other infectious agents and disease processes. Control. Cesarean derivation and barrier maintenance are effective means of control. Interference with Research. Infection with C. kutscheri can complicate ex- periments involving immunologically compromised mice or rats. Suggested Reading Ackerman, J. I., I. G. Fox, and J. C. Murphy. 1984. An enzyme linked immunosorbent assay for detection of antibodies to Corynebacterium kutscheri. Lab. Anim. Sci. 34:38-43. Barthold, S. W., and D. G. Brownstein. 1988. The effect of selected viruses on Coryne bacterium kutscheri infection in rats. Lab. Anim. Sci. 38:580-583. Brownstein, D. G., S. W. Barthold,R. L. Adams, G. A. Terwilliger, and J. G. Aftosmis. 1985. Experimental Corynebacterium kutscheri infection in rats: Bacteriology and serology. Lab. Anim. Sci. 36:135-138. Saltzgaber-Muller, J., and B. A. Stone. 1986. Detection of Corynebacterium kutscheri in animal tissues by DNA-DNA hybridization. J. Clin. Microbiol. 24:759-763. Suzuki, E., K. Mochida, and M. Nakagawa. 1988. Naturally occurring subclinical Corynebacterium kutscheri infection in laboratory rats: Strain and age related antibody response. Lab. Anim. Sci. 38:42-45. Weisbroth, S. H., and S. Scher. 1968. Corynebacterium kutscheri infection in the mouse. II. Diagnostic serology. Lab. Anim. Care 18:459-468. Cytomegalovirus, Mouse Agent. Double-stranded DNA virus, family Herpesviridae. Animals Affected. Wild mice and laboratory mice that have contracted the infection from wild mice. Epizootiology. Prevalence in laboratory mice is uncertain but is probably very low. Transmission occurs through the saliva, and infection persists throughout life.
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16 COMPANION GUIDE TO INFECTIOUS DISEASES OF MICE kD RATS Vertical transmission also can occur but has not been fully explained. Direct passage of the virus across the placenta to the fetus and/or transmission via germ cells have been suggested. Clinical Signs. Natural infections are subclinical. Pathology. In natural infections, large acidophilic intranuclear inclusions are found in salivary gland acinar and duct cells. Affected cells typically are enlarged three to four times normal. The submaxillary glands are affected most, the sublingual glands less, and the parotid glands least. Diagnosis. The IFA and CF tests have been shown to be sensitive for acute experimental infections, and the ELISA has been shown to be sensitive for persistent experimental infections. These methods may prove useful for monitoring laboratory mice for cytomegalovirus infection in selected situations. Virus isola- tion can be accomplished using mouse embryo fibroblasts or other tissue culture systems. Control. Wild mice must be excluded from rodent facilities. Interference with Research. Natural infections have not been reported to Interfere with research. Suggested Reading Classen, D. C., J. M. Moringstar, and J. D. Shanley. 1987. Detection of antibody to murine cytomegalovirus by enzyme-linked immunosorbent and indirect immunofluorescence assays. J. Clin. Microbiol. 25:600-604. Lussier, G., D. Guenette, and J. P. Descoteaux. 1987. Comparison of serological tests for the detection of antibody to natural and experimental munne cytomegalovirus. Can. J. Vet. Res. 51:249-252. Mercer, J. A., C. A. Wiley, and D. H. Spector. 1988. Pathogenesis of murine cytomegalovrirus infection: Identification of infected cells in the spleen during acute and latent infections. J. Virol. 62:987-997. Mims, C. A., and J. Gould. 1979. Infection of salivary glands, kidneys, adrenals, ovaries, end epitheliabymur~necytomegalovirus. J.Med.Microbiol.12:113-122. Osborn, J. E. 1982. Cytomegalovirus and other he~pesviruses. Pp. 267-292 in The Mouse in Biomedical Research. Vol. II: Diseases, H. L. Foster, J. D. Small, and J. G. Fox, eds. New York: Academic Press. Quinnan, G. V., and J. E. Manischewitz. 1987. Genetically detennined resistance to lethal mur~ne cytomegalovirus infection is mediated by interferon-dependent and -independent restriction of virus replication. J. Virol. 61: 1875-1881. Ectromelia Virus Agent. DNA virus, family Poxviridae. Animals Affected. Mice. Epizootiology. Ectromelia virus is possibly enzootic in some mouse colonies. Periodic epizootics have occurred in the United States since 1950, most commonly
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DISEASE AGENTS 17 in research laboratories that exchange live mice and their tissues, sera, or transplant- able tumors. Natural transmission is dependent on direct contact and fomites. Skin abrasions are thought to be the main route of virus entry. Infected animals begin shedding virus about 10 days postinfection when characteristic skin lesions appear. Persistent infection (carrier state) was previously thought to be important in the epizootiology of mousepox. More recent data suggest that significant numbers of virus particles are shed from skin lesions for only about 3 weeks. Clinical. The severity of clinical disease (mousepox) varies greatly and depends on mouse strain, virus strain, length of time infection has been present in the colony, and husbandry practices. Inapparent infections occur mainly in resistant inbred mouse strains such as C57BL/6 or C57BL/10. Resistance in the these strains appears to be due to a single autosomal dominant trait. The more susceptible mouse strains include A, CBA, C3H, DBA/2, and BALB/c. Clinical manifestations include one or more of the following: ruffled hair; hunched posture; facial edema; conjunctivitis; swelling of the feet; cutaneous papules, erosions, or encrustations, mainly on the face, ears, feet, or tail; and necrotic amputation (ectromelia) of limbs or tails. Mortality varies from less than 1% to greater than 80%. Pathology. The incubation period is 7-10 days. Virus replicates in the skin and then in the regional lymph nodes, resulting in a mild primary viremia. Virus is taken up by splenic and hepatic macrophages, where there is extensive multiplication that results in a massive secondary viremia and sometimes in death due to diffuse splenic and hepatic necrosis. Virus from the secondary viremia localizes in a wide variety of tissues, especially the skin (basal cells), conjunctive, and lymphoid tissues. A primary lesion may appear at the site of skin inoculation about 4-7 days postinfection. Foot swelling and secondary generalized rash (pocks) may appear 7-10 days postinfection. Skin lesions heal within 2 weeks, leaving scars. In acute mousepox, there is severe necrosis of liver, spleen, lymph nodes, Peyer's patches, and thymus. Jejunal hemorrhage often results from mucosal erosions. Character- istic large eosinophilic cytoplasmic inclusions may be present in skin lesions. Diagnosis. The ELISA is sensitive and specific in unvaccinated mice; however, it may give false-positive results in NZW and NZB mice. The HAI is relatively insensitive but does not give positive reactions to sera from mice vaccinated with the IlID-T strain of vaccinia virus. Diagnosis of acute disease is based on sero- logic testing of survivors or on the demonstration, using transmission electron microscopy, of characteristic large virus particles in affected tissues. Differential diagnosis of skin lesions should exclude bite wounds and loss of limbs due to Streptobacillus moniliformis. Biologic materials such as cells and blood can be screened for ectromelia virus by injecting the tissue into known pathogen-free mice followed by serologic testing. Control. Quarantine and testing of incoming mice and mouse tissues from sources other than commercial barrier facilities are the best way to prevent the introduction of infection. In the past, the accepted practice for eradicating ectromelia virus was elimination of infected mouse colonies and all infected biologic materials,
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18 COMPANION GUIDE TO INFECTIOUS DISEASES OF MICE ED RATS along with rigorous decontamination of rooms and equipment. Cesarean derivation of infected mouse stocks was not acceptable because intrauterine infection is known to occur in mice infected during pregnancy. More recently it has been suggested that quarantine and cessation of breeding might successfully eliminate the virus. Vaccination with a live-virus vaccine, the IHD-T strain of vaccinia virus adapted to growth in embryonated eggs, can be useful in eliminating disease from small closed colonies where all offspring can be vaccinated by 6 weeks of age. Vaccination can protect mice from fatal disease but does not prevent infection or virus transmission. Interference with Research. Up to 100% of the animals in an experiment can die in an explosive outbreak. Manipulations that exacerbate ectromelia virus infections or promote epizootics include experimental infection with tubercle bacilli, x-irradiation, administration of various toxic chemicals, shipping, tissue transplantation, castration, and tumors. Ectromelia virus infection can alter phagocytic response. Conversely, procedures that decrease phagocytosis can increase sus- ceptibility to ectromelia virus, e.g., large doses of endotoxin or splenectomy. Suggested Reading AALAS (American Association of Laboratory Animal Science).1981. Ec~omelia (mousepox) in the United States. Proceedings of a seminar presented at the 31st Annual Meeting of AALAS held in Indianapolis, Indiana, October 8,1980. Lab. Anim. Sci.31:549-631. Bhatt, P. N., and R. O. Jacoby. 1987. Mousepox in inbred mice innately resistant or susceptible to lethal infection with ectromelia virus. I. Clinical responses. Lab. Anim. Sci. 37:11-15. Bhatt, P. N., and R. O. Jacoby. 1987. Mousepox in inbred mice innately resistant or susceptible to lethal infection with ectromelia virus. III. Experimental transmission of infection and derivation of virus-free progeny from previously infected dams. Lab. Anim. Sci. 37:23-28. Bhatt, P. N., and R. O. Jacoby. 1987. Effect of vaccination on the clinical response, pathogenesis and transmission of mousepox. Lab. Anim. Sci. 37:610-614. Bhatt, P. N., R. O. Jacoby, and L. Gras. 1988. Mousepox in inbred mice innately resistant or susceptible to lethal infection with ectromelia virus. IV. Studies with the Moscow strain. Arch. Virol. 100:221-230. Penner, F. 1982. Mousepox. Pp. 209-230 in The Mouse in Biomedical Research. Vol. II: Diseases, H. L. Foster, J. D. Small, and J. G. Fox, eds. New York: Academic Press. Encephalitozoon cuniculi Agent. A protozoan, order Microsporidia. Animals Affected. Mice, rats, rabbits, hamsters, guinea pigs, humans, end many other mammals. Epizootiology. Prevalence in mouse and rat stocks is not known but is thought to be very low in comparison with that in rabbits, in which the organism is considered ubiquitous. Rabbits undoubtedly provide the major source of infection
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DISEASE AGENTS 19 for mice and rats in research facilities. Spores of E. cuniculi are shed in the urine and ingested by another host. Clinical. Natural infections usually are inapparent. Pathology. In cases of clinical disease, the classic lesion in rats and rabbits is meningoencephalitis with multifocal granulomatous inflmnmation. Activated macrophages form glial nodules in response to the organism. These nodules have necrotic centers or appear as solid sheets of cells. Varying numbers of lymphocytes and plasma cells are seen in the meninges and around vessels. The brain lesions in mice are similar, except for the lack ofthe granulomatous foci. The organism occurs intracellularly in the renal tubular epithelium with or without the presence of an inflammatory response. In chronic infections, focal destruction of tubules and replacement by fibrous connective tissue results in small pits on the cortical surface. Lesions in organs other than the kidney and brain are less consistent. Intrapentoneal inoculation of E. cuniculi, as when contaminated transplantable tumors are pas ~ . . . . saged, results In ascribes In mice. Diagnosis. Several serologic tests have been developed for diagnosis of the infection in rabbits; however, only the IFA and immunoperoxidase tests have been used in surveying mouse and rat colonies. Other methods used for diagnosis include detection of parasites in unne, demonstration of typical lesions and organisms in tissue sections, and an intradennal skin test. Control. Mice and rats should not be exposed to infected rabbits. Serologic testing of adult animals with selection of E. cuniculi-free breeding stocks has been used successfully for eradicating the infection in rabbits. Interference with Research. The histologic changes caused by E. cuniculi infection in the brain and kidneys can complicate the interpretation of lesions in studies requiring histopathology. E. cuniculi can contaminate transplantable tu- mors and alter host responses during tumor passage in mice. Mice experimentally infected with E. cuniculi have reduced humoral antibody titers to sheep erythro- cytes, reduced proliferative spleen cell responses to mitogens, and altered natural killer cell activity. Suggested Reading Beckwith, C., N. Peterson, J. J. Liu. and J. A. Shadduck. 1988. Dot enzyme-linked immunosorbent essay (dot ELISA) for antibodies toEncephalitozoon cuniculi. Lab. Anim. Sci. 38:573-576. Didier, E. S., and J. A. Shadduck. 1988. Modulated immune responsiveness associated with experimental Encephalitozoon cuniculi infection in BALB/c mice. Lab. Anim. Sci. 38:680-684. Cannon, J. 1980. The course of infection of Encephalitozoon cuniculi in immunodeficient and immunocompetent mice. Lab. Anim. (London) 14:189-192. Majeed, S. K., and A. J. Zubaidy. 1982. Histopathological lesions associated with Encephalitozoon cuniculi (nosematosis) infection in a colony of Wistar rats. Lab. Anim. (London) 16:244-247.
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DISEASE AGENTS 59 inside mature females. Eggs hatch in about 7 days, and completion of the entire life cycle requires about 23 days. Animals Affected. Mice and rarely rats and other laboratory rodents. Epizootiology. Mites can be seen anywhere on the body but are most numerous alongside the hair bases in the more densely furred parts of the body (i.e., over the head and back). Transmission is by direct contact. The dynamics of mite popula- tions on a host are very complex and are influenced by factors that include grooming, strain susceptibility, and host immune responses. Athymic (nu/nu) and other furless mice are not susceptible to infestation. Clinical. The general appearance of infested mice is not directly related to the size of the mite population. Infestations are commonly subclinical. Clinical signs include scruffiness, pruritis, patchy alopecia, self-trauma, ulceration of the skin, and pyoderma. Close inspection often reveals bran-like hyperkeratotic debris and mites on the skin around the base of the hairs. Pathology. Mice of the C57BL strains and their congeneic sublines are particularly susceptible to severe M. musculi-related skin disease. Lesions vary from mild to severe. Initially there is mild hyperkeratosis, but this often progresses to severe hyperkeratosis with fine bran-like material on the skin over virtually all of the body but particularly abundant over the dorsum, head, and shoulders. In more advanced cases, there is patchy alopecia and chronic ulcerative dermatitis most frequently distributed asymmetrically in the shoulder and neck regions. Second- ary bacterial infection commonly leads to suppurative and granulomatous in- flammation. Hyperplasia of regional lymph nodes, splenic lymphoid hypeIplasia, and increased serum immunoglobulins are common. Diagnosis. Diagnosis requires demonstration and identification of mites, while excluding other causes of dermatitis such as fungi (ringworm) or Staphylococcus aureus. Mites can be demonstrated by using a stereoscopic microscope or hand lens to examine the pelage, particularly over the back and head. Alternatively, mice can be killed and placed either on black paper and left at room temperature or in tape- sealed Petri dishes and refrigerated for an hour. As the body cools, the mites leave it and can be collected from the paper or Petri dish. The mites are mounted under a coverslip on glass slides with immersion oil and identified microscopically on the basis of anatomic features. Control. Cesarean derivation and barrier maintenance are the most effective methods for eradication of mite infestations. Insecticides can be used, but they may alter experimental results. Interference with Research. Behavioral patterns are likely to be altered by hypersensitivity to these mites. Secondary amyloidosis caused by chronic infes- tation can interfere with research results. Suggested Reading Flynn, R. J. 1973. Parasites of Laboratory Animals. Ames, Iowa: Iowa State University Press. 884 pp.
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60 COMPANION GUIDE TO INFECTIOUS DISEASES OF MICE AND RATS Friedman, S., and S. H. Weisbroth. 1977. The parasitic ecology of the rodent mite, Myobia musculi. IV. Life cycle. Lab. Anim. Sci. 27:34-37. Gallon, M. 1963. Myobic mange in the mouse leading to skin ulceration and amyloidosis. Am. J. Pathol. 43:855-865. Weisbroth, S. H.1982. Arthropods. Pp.385-402 in The Mouse in BiomedicalResearch. Vol. II: Diseases, H. L. Foster, J. D. Small, and J. G. Fox, eds. New York: Academic Press. Weisbroth, S. H., S. Friedman, and S. Scher.1976. The parasitic ecology of the rodent mite Myobia musculi. III. Lesions in certain host strains. Lab. Anim. Sci. 26:725-735. Myocoptes masculines and Radfordia affinis Agent. Mites, order Acanna. Pathology. M. musculinus causes lesions similar to, but usually milder than, those caused by Myobia musculi. R. affinis is not a significant pathogen. Interference with Research. Mite infestations due to M. musculinus have been reported to reduce the contact sensitivity of mice to oxazolone. Suggested Reading Flynn, R. J. 1973. Parasites of Laboratory Animals. Ames, Iowa: Iowa State University Press. 884 pp. Laltoo, H., and L. S. Kind. 1979. Reduction in contact sensitivity reactions to oxazolone in mite-infested mice. Infect. Immun. 26:30-35. Weisbroth, S. H. 1982. Arthropods. Pp. 385-402 in The Mouse in Biomedical Research. Vol. II: Diseases, H. L. Foster, J. D. Small, and J. G. Fox, eds. New York: Academic Press. Other Ectoparasites For more in-depth coverage or information on less common ectoparasites of mice and rats, consult comprehensive reference works on the subject. Suggested Reading Flynn, R. J. 1973. Parasites of Laboratory Animals. Ames, Iowa: Iowa State University Press. 884 pp. Hsu, C.-K.1979. Parasitic diseases. Pp.307-331 in The Laboratory Rat. Vol. I: Biology and Diseases, H. J. Baker, J. R. Lindsey, and S. H. Weisbroth, eds. New York: Academic Press. Owen, D. 1972. Common Parasites of Laboratory Rodents and Lagomorphs. MRC Labo- ratory Animals Centre Handbook No. 1. London: Medical Research Council. 64 pp. Pratt, H. D., and J. S. Wiseman.1962. Fleas of Public Health Importance and Their Control. Insect Control Series: Part VIII. PHS Publ. No.772. Washington, D.C.: U.S. Department of Health, Education, and Welfare. Weisbroth, S. H.1982. Arthropods. Pp.385-402 in The Mouse in Biomedical Research. Vol. II: Diseases, H. L. Foster, J. D. Small, and J. G. Fox, eds. New York: Academic Press.
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DISEASE AGENTS 61 ENDOPARASITES Aspicularzs tetraptera (Mouse Pinworm) Agent. Roundworm, order Ascarida, suborder Oxyurina. Life Cycle. Direct, requires 23-25 days. The adults reside in the colon. Females lay their eggs in the colon, and the eggs subsequently leave the host on fecal pellets. The eggs become infective after 6-7 days et room temperature. Transmission occurs when the infective eggs are ingested by another host. The eggs hatch in the colon, where the larvae develop to maturity, and the cycle begins again. Animals Affected. Mice, rats (rarely), and wild rodents. Epizootiology. A. tetraptera inhabits and lays eggs in the colon. The eggs . ,% . . . ~ . survive for weeks in animal room environments. Clinical. Infections are subclinical. Pathology. A. tetraptera is not considered pathogenic. Diagnosis. Diagnosis is made by demonstration of distinctive eggs by fecal flotation (the cellophane tape method is of no value) and by demonstration and identification of the adult worms in the colon at necropsy. Control. Cesarean derivation and barrier maintenance are effective. Infection can be controlled to some extent by using hygienic methods, such as frequent cage and room sanitization. Cage-to-cage transmission can be prevented by using filter- top cages. Several anthelminthics are effective in eliminating a high percentage of adult worms, but many are inefficient in clearing immature worms or eggs. Interference with Research. See Syphacia obvelata (p. 661. Suggested Reading Flynn, R. J. 1973. Nematodes. Pp. 203-320 in Parasites of Laboratory Animals. Ames, Iowa: Iowa State University Press. Hsu, C.-K. 1979. Parasitic diseases. Pp. 307-331 in The Laboratory Rat. Vol. I: Biology and Diseases, H. J. Baker, J. R. Lindsey, and S. H. Weisbroth, eds. New York: Aca demic Press. Wescott, R. B. 1982. Helminths. Pp. 374-384 in The Mouse in Biomedical Research. Vol. II: Diseases, H. L. Foster, J. D. Small, and J. G. Fox, eds. New York: Academic Press. Entamoeba muris Agent. Protozoan, order Amoebida, family Entamoebidae. Life Cycle. Direct. Trophozoites, which inhabit the cecum and colon, form cysts that are passed in the feces. Transmission is by ingestion of cysts. Animals Affected. Mice, rats, hamsters, and other rodent species. Epizootiology. Trophozoites are most commonly found at the interface between the fecal stream and the intestinal epithelium in the cecum and colon. Cysts are resistant to environmental conditions.
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62 COMPANION GUIDE TO INFECTIOUS DISEASES OF MICE AND RATS Clinical. Infection is subclinical. Pathology. The organism is nonpathogenic. Diagnosis. Diagnosis is made by demonstrating cysts in the feces or trophozoi- tes in wet mounts of intestinal contents from the cecum or colon. In sections stained by hematoxylin and eosin, the trophozoites usually have a distinct magenta-stained nucleus and violet-stained cytoplasm that can appear vacuolated. The outer cell membrane of the trophozoites is usually distinctly visible. Control. Entamoeba muris can be eliminated by cesarean derivation and barrier maintenance; however, infection with this agent is generally considered inconse- quential, and control measures are usually not necessary. Interference with Research. There have been no reports of interference with research results. Suggested Reading Levine, N. D. 1961. Protozoan Parasites of Domestic Animals and of Man. Minneapolis, Minn.: Burgess. 412 pp. Levine, N. D. 1974. Diseases of laboratory animals-parasitic. Pp. 209-327 in CRC Handbook of Laboratory Animal Science, vol. II, E. C. Melby and N. H. Altman, eds. Cleveland: CRC Press. Giardia mutts Agent. Flagellated protozoan, order Diplomonadida, family Hexamitidae, subfamily Giardinae. Life Cycle. Direct. Trophozoites reproduce by longitudinal fission and form cysts that are passed in the feces. Transmission is by ingestion of cysts. The minimal infectious dose for a mouse is approximately 10 cysts. Animals Affected. Mice, rats, hamsters, humans, and many other species. Epizootiology. Trophozoites colonize the proximal one-fourth of the small intestine, where they are found mainly adhering to columnar cells of the villi and *lee in the adjacent mucous layer. The number of trophozoites in the small intes- tine correlates directly with the number of cysts in the large intestine and feces. Cysts are resistant to most environmental conditions but are inactivated by treat- ment with a 2.5% phenol solution and by temperatures above 50°C. Clinical. Infections in mice and rats are usually subclinical but can cause reduced weight gain, rough hair coats, and enlarged abdomens. Infection may be associated with morbidity and mortality in athymic (nu/nu) and other immunocompromised mice. Pathology. Pathogenesis has been studied most extensively in mice. The acute phase of infection involves the proliferation of trophozoites in the small intestine, with the peak period of cyst release occurring during the second week of infection. In the elimination phase, cysts released in the feces are reduced to undetectable
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DISEASE AGENTS 63 levels. Resistant strains, including DBA/2, B;lO.A, C57BL/6, B~4LB/c, and SJL/J, eliminate the infection in 5 weeks. Susceptible strains and stocks, including C3H/ He and A/J and outbred Crl:ICR (CD@-1), require 10 weeks to eliminate the infection. Highly susceptible athymic (nu/nu) mice have prolonged infections. Resistance during the acute phase of infection is thought to be controlled by several genes not linked to the H-2 locus, while resistance during the elimination phase is inherited as a dominant trait. Protective immunity is probably dependent on both antibody- and cell-mediated mechanisms. The milk of immune mice contains both IgA and IgG antibodies against Giardia muris and conveys passive protection. In uncomplicated G. muris infection, morphological changes in the small intestine are usually minimal. The villus to crypt ratio may be reduced, and variable numbers of lymphocytes may be present. Diagnosis. Infection by other possible primary or contributing pathogens must be excluded. The organism is diagnosed histologically by identifying character- istic "monkey-faced" trophozoites in sections of the small intestine. Trophozoites also can be recognized in wet mounts of intestinal contents by their characteristic shape and their rolling and tumbling motion. Cysts can be demonstrated in wet mounts of feces. Control. The most practical approach to controlling infection is to procure rodents from breeding populations shown by health surveillance testing to be free of G. muris and to maintain them in a barrier facility. Cesarean derivation is re- quired to eliminate the parasite from infected stocks. Metronidazole can be used for treatment of infected animals but does not completely eradicate infection. Interference with Research. Infection with G. muris can increase the severity and mortality of wasting syndrome (presumably caused by mouse hepatitis virus) in athymic (nu/nu) mice. The organism causes a transient reduction in immunoresponsiveness of mice to sheep erythrocytes during the second and third weeks of infection. It also alters intestinal fluid accumulation and mucosal im- mune responses caused by cholera toxin in mice. Suggested Reading Belosevic, M., G. M. Faubert, E. Skamene, and J. D. MacLean. 1984. Susceptibility and resistance of inbred mice to Giardia muris. Infect. Immun. 44:282-286. Boorman, G. A., P. H. C. Lina, C. Zurcher, and H. T. M. Nieuwerkerk. 1973. Hexamita and Giardia as a cause of mortality in congenitally thymus-less (nude) mice. Clin. Exp. Immunol. 15:623-637. Brett, S. J.1983. Immunodepression in Giardia muris and Spironucleus muris infections in mice. Parasitology 87:507-515. Brett, S. J., and F. E. G. Cox.1982. Immunological aspects of Giardia muris and Spironucleus muris infections in inbred and outbred strains of laboratory mice: A comparative study. Parasitology 85:85-99. Hsu, C.-K. 1982. Protozoa. Pp. 359-372 in The Mouse in Biomedical Research. Vol. II: Diseases, H. L. Foster, J. D. Small, and J. G. Fox, eds. New York: Academic Press.
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64 COMPANION GUIDE TO INFECTIOUS DISEASES OF MICE AND RATS Stevens, D. P. 1982. Giardiasis: Immunity, immunopathology and immunodiagnosis. Pp. 192-203 in Immunology of Parasitic Infections, 2nd ea., S. Cohen and K. S. Warren, eds. Oxford: Blackwell Scientific. Hymenolepis nana Agent. Tapeworm, order Cyclophyllidea, family Hymenolepidae. Life Cycle. Direct or indirect. The life cycle includes adult, egg (with embryo or oncosphere), and larval (cercocystis) stages. In direct transmission, eggs hatch in the small intestine. Larvae penetrate and develop as cercocystis in the intestin- al villi, then return to the lumen to become mature adults. The cycle requires only 1-16 days. In indirect transmission, the eggs are ingested by an arthropod interrnedi- ate host such as a flour beetle, and the cercocystis develops in the intestine of the beetle. The intermediate host is eaten by the definitive host, and adult H. nana develop in the lumen of the small intestine. The entire life cycle by indirect transmission requires 20-30 days. Animals Affected. Mice, rats, hamsters, other rodents, nonhuman Inmates, and humans. Epizootiology. Weanling and young adult rodents are most frequently infected. The duration of infection by adult worms in the small intestine is usually only a few weeks. Clinical. Most infections are subclinical. Severe infections have been reported to cause retarded growth and weight loss in mice and intestinal occlusion, intestin- al impaction, and death in hamsters. Pathology. Presence of adult worms in the small intestine is usually associated with mild ententis. Larval stages occasionally reach the lymph nodes, liver, or lung, where they incite a granulomatous inflmnmatory response. Diagnosis. Diagnosis is made by demonstration and identification of adult tapeworms in the small intestine. Eggs can be demonstrated in feces. Also, histologic sections occasionally are successful in demonstrating the cercocystis in intestinal villi and lymph nodes. Control. The most practical method of control is to obtain rodents from stocks demonstrated to be free of H. nana. Cesarean derivation and barrier maintenance are the most effective methods for eliminating infection. Interference with Research. H. nana is a potential zoonotic infection to humans. It can interfere with studies involving the intestinal tract. Suggested Reading Flynn, R. J. 1973. Cestodes. Pp. 155-202 in Parasites of Laboratory Animals. Ames, Iowa: Iowa State University Press. Hsu, C.-K. 1979. Parasitic diseases. Pp. 307-331 in The Laboratory Rat. Vol. I: Biology and Diseases, H. J. Baker, J. R. Lindsey, and S. H. Weisbroth, eds. New York: Academic Press.
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DISEASE AGENTS 65 Kunstyr, I., and K. T. Fr~edhoff. 1980. Parasitic and mycotic infections in laboratory animals. Pp. 181-192 in Animal Quality and Models in Biomedical Research, A. Spiegel, S. Erichsen, and H. A. Solleveld, eds. Stuttgart: Gustav Fischer Verlag. Wescott, R. B. 1982. Helminths. Pp. 373-384 in The Mouse in Biomedical Research. Vol. II: Diseases, H. L. Foster, J. D. Small, and J. G. Fox, eds. New York: Academic Press. Spironucleus musts Agent. Flagellated protozoan, order Diplomonadida, family Hexamitidae, subfamily Hexamitinae. Formerly called Hexamita muris. Life Cycle. Direct. Trophozoites reproduce by longitudinal fission and form highly resistant cysts. The minimal infectious dose for a mouse is one cyst. Animals Affected. Mice, rats, and hamsters. Epizootiology. Two- to 6-week-old mice are most susceptible to infection with S. muris. Trophozoites usually inhabit the crypts of Lieberkuhn in the small intestine, but in young animals the lumen can also contain large numbers of troph- ozoites. In older mice and in rats there are very few trophozoites, and those that are present can be found only in glands of the gastric pyloris. Transmission is by ingestion of cysts that are shed in the feces. The greatest numbers are shed by young or immunocompromised hosts. Cysts are inactivated by some disinfectants and high temperature (45°C for 30 minutes) but are highly resistant to most other environmental conditions. Infectivity is retained for 6 months at-20°C, for 1 day at pH 2.2, for 14 days at room temperature, or for 1 hour in 0.1% glutaraldehyde. Clinical. Infection is usually subclinical in immunocompetent hosts. In athy- mic (nu/nu) and lethally irradiated mice, S. muris infection has been associated with severe chronic enteritis with weight loss. Pathology. After ingestion of cysts, trophozoite (and cyst) numbers in the intestines of immunocompetent rodents peak at 1-2 weeks and decline to low numbers by 4-5 weeks in BALB/c mice; 7-9 weeks in CBA, SJL/J, and C3H/He mice; and 13 weeks in A and B.B10 mice. Numbers in athymic (nu/nu) mice persist indefinitely at high levels. In severe infections, the small intestine may appear reddened and contain watery fluid and gas. Smears of the intestinal contents con- tain numerous motile trophozoites, and cysts can be demonstrated in the cecum and colon. The best indicator of S. muris infection in hematoxylin and eosin-stained sections of the small intestine is distension of the crypts of Lieberkuhn by masses of granular-appearing trophozoites. Trophozoites can cause shortening of micro- villi on the crypt epithelium and increased turnover of enterocytes. There is usual- ly little or no inflammatory response in immunocompetent animals, but heavily parasitized, immunodeficient animals can have moderate to severe enteritis. Diagnosis. Other possible causes of digestive tract disease (e.g., enterotrophic strains of mouse hepatitis virus) must be ruled out. Characteristic trophozoites can be demonstrated in the contents of the small intestine, or cysts can be demonstrated in the contents of the large intestine or feces using wet mounts under reduced light.
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66 COMPANION GUIDE TO INFECTIOUS DISEASES OF MICE AND RATS For routine health surveillance that includes histopathology, the examination of multiple histologic sections of the small intestine and gastric pylorus is probably superior to other methods because there may be very few parasites present, and they may be localized in distribution. Trophozoites can be stained by silver or periodic acid-Schiff methods. Control. Cesarean derivation and barrier maintenance are recommended for control of the organism. Treatment of mice with 0.04-0.1% dimetridazole in drinking water for 14 days can ameliorate clinical signs but does not completely eliminate the infection. Interference with Research. S. muris can increase the severity and mortality of the wasting syndrome (presumably due to mouse hepatitis virus) in athymic (nu/nu) mice. S. muris has been reported to increase mortality in cadmium-treated mice; alter macrophage function; reduce spleen plaque-forming cell responses to sheep erythrocytes; reduce lymphocyte responsiveness to mitogens such as phytohemagglutinin, concanavalin A, and pokeweed mitogen; and alter im- mune responsiveness to tetanus toxoid and type 3 pneumococcal polysaccharide. Whole-body irradiation increases susceptibility to S. muris infection and disease. Suggested Reading Brett, S. J. 1983. Immunodepression in Giardia muris and Spironucleus muris infections in mice. Parasitology 87:507-515. Brett, S. J., and F. E. G. Cox. 1982. Interactions between the intestinal flagellates Giardia muris and Spironucleus muris and the blood parasites Babesia microti, Plasmodiumyoelii and Plasmodium berghei in mice. Parasitology 85: 101-1 10. Keast, D., and F. C. Chesterman. 1972. Changes in macrophage metabolism in mice heavily infected with Hexamita muris. Lab. Anim. (London) 6:33-39. Kunstyr, I., E. Amme~pohl, and B. Meyer. 1977. Experimental spironucleosis (hexamitiasis) in the nude mouse as a model for immunologic and pharmacologic studies. Lab. Anim. Sci. 27:782-788. Stachan, R., and I. Kunstyr. 1983. Minimal infectious doses and prepatent periods in Giardia muris, Spironucleus muris and Tritrichomonas muris. Z. Bakt. Hyg. A256:249-256. Wagner, J. E., R. E. Doyle, N. C. Ronald, R. G. Garrison, and J. A. Schmitz. 1974. Hexamitiasis in laboratory mice, hamsters, and rats. Lab. Anim. Sci. 24:349-354. Syphacia obvelata (Mouse Pinworm) and Syphacia muris (Rat Pinworm) Agents. Roundworms, order Ascarida, suborder Oxyurina. Life Cycle. Direct; requires only 11-15 days for completion. Gravid females migrate from the large intestine to the perianal area, deposit their eggs, and then die. Eggs become infective in about 6 hours. Following ingestion by another host, eggs hatch in the small intestine, and the larvae reach the cecum in 24 hours. The parasites spend 10-11 days in the cecum where they mature and mate, thus continuing the cycle.
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DISEASE AGENTS 67 Animals Affected. Laboratory mice, rats, hamsters, gerbils, and wild rodents. Epizootiology. Adults are found primarily in the cecum and colon of infected hosts. Eggs are efficiently disseminated from the perianal area of the host into the cage and room environments. The eggs can survive for weeks under most animal room conditions. Transmission is by ingestion of embryonated eggs. Clinical. Infections caused by Syphacia spp. alone are subclinical. Pathology. Pinworms of laboratory rodents are generally not considered pathogens. Pinworm burden in an infected rodent population is a function of age' sex, and host immune status. In enzootically infected colonies, weanling animals develop the greatest parasite loads, males are more heavily parasitized than females, and Syphacia numbers diminish with increasing age of the host. Athymic (nu/nu) mice have increased susceptibility to pinworm infection. Diagnosis. Diagnosis is made by demonstrating eggs on the perianal region using the cellophane tape technique or by finding adult worms in the cecum and colon at necropsy. Control. Cesarean derivation and barrier maintenance are effective methods of control. Hygienic methods, including frequent cage and room sanitization, can aid in controlling Syphacia in an infected rodentpopulation. Cage-to-cage transmission can be prevented by using filter-top cages. Several anthelminthics are effective in eliminating a high percentage of adult worms but are inefficient in clearing immature worms or eggs. Interference with Research. Pinwo~m infections in rats have been reported to reduce the occurrence of adjuvant-induced arthritis. Suggested Reading Flynn, R. J.1973. Nematodes. Pp.203-320 in Parasites of Laboratory Animals. Ames, Iowa: Iowa State University Press. Hsu, C.-K.1979. Parasitic diseases. Pp.307-331 in The Laboratory Rat. Vol. I: Biology and Diseases, H. J. Balcer, J. R. Lindsey, and S. H. Weisbroth, eds. New York: Academic Press. Pearson, D. J., and G. Taylor. 1975. The influence of the nematode Syphacia obvelata on adjuvant arthritis in rats. Immunology 29:391-396. Ross, C. R., J. E. Wagner, S. R. Wightman, and S. E. Dill.1980. Experimental transmission of Syphacia muris among rats, mice, hamsters, and gerbils. Lab. Anim. Sci. 30:35-37. Wescott, R. B. 1982. Helminths. Pp. 374-384 in The Mouse in Biomedical Research. Vol. II: Diseases, H. L. Foster, J. D. Small, and J. G. Fox, eds. New York: Academic Press. Wescott, R. B., A. Malczewski, and G. L. Van Hoosier. 1976. The influence of filter top caging on the transmission of pinworrn infections in mice. Lab. Anim. Sci. 26:742-745. Trichomonas mur7s Agent. Flagellated protozoan, order Trichomonadida. Life Cycle. If acyst stage exists, transmission is probably primarily by ingestion of cysts.
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68 COMPANION GUIDE TO INFECTIOUS DISEASES OF MICE AND RATS Animals Affected. Mice, rats, hamsters, and other rodents. Epizootiology. Trophozoites are found throughout the fecal mass in the cecum and colon. Clinical. Infections are subclinical. Pathology. T. muris is considered a commer~sal. Diagnosis. Diagnosis is by demonstration of trophozoites in wet mounts of contents from the cecum or colon. T. muris has characteristic wobbly or jerky movements. Trophozoites are found dispersed throughout the fecal stream in histologic sections of the cecum or colon prepared without disturbing the luminal contents. In hematoxylin and eosin-stained sections, the nucleus stains poorly, the nuclear membrane is indistinct, and the cell wall often appears wrinkled or folded upon itself. Control. Control measures are usually not necessary. Interference with Research. There have been no reports of interference with research results. Suggested Reading Hsu, C.-K. 1982. Protozoa. Pp. 359-372 in The Mouse in Biomedical Research. Vol. II: Diseases, H. L. Foster, J. D. Small, and J. G. Fox, eds. New York: Academic Press. Kunstyr, I., B. Meyer, and E. Ammerpohl. 1977. Spironucleosis in nude mice: An animal model for immuno-parasitologic studies. Pp. 17-27 in Proceedings of the Second International Workshop on Nude Mice. Stuttgart: Gustav Fischer Verlag. Levine, N. D. 1974. Diseases of laboratory animals parasitic. Pp. 209-327 in CRC Handbook of Laboratory Animal Science, vol. II, E. C. Melby and N. H. Altman, eds. Cleveland: CRC Press. Other Endoparasites Numerous other endoparasites have been reported in wild mice and rats and are encountered occasionally in laboratory animals maintained by conventional methods. For information, comprehensive works on endoparasites should be consulted. Suggested Reading Flynn, R. J. 1973. Parasites of Laboratory Animals. Ames, Iowa: Iowa State University Press. 884 pp. Griffiths, H. J. 1971. Some common parasites of small laboratory animals. Lab. Anim. (London) 5: 123-135. Hsu, C. K. 1979. Parasitic diseases. Pp. 307-331 in the Laboratory Rat. Vol. I: Biology and Diseases, H. J. Baker, J. R. Lindsey, and S. H. Weisbroth, eds. New York: Academic Press. Hsu, C.-K. 1982. Protozoa. Pp. 359-372 in The Mouse in Biomedical Research. Vol. II: Diseases, H. L. Foster, J. D. Small, and J. G. Fox, eds. New York: Academic Press.
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DISEASE AGENTS 69 Levine, N. D. 1974. Diseases of laboratory animals parasitic. Pp. 209-327 in CRC Handbook of Laboratory Animal Science, vol. II, E. C. Melby and N. H. Altman, eds. Cleveland: CRC Press. Levine, N. D., and V. Ivens.1965. The Coccidian Parasites (Protozoa, Sporozoa) of Rodents. Urbana, Ill.: University of Illinois Press. 365 pp. Oldham, J. N. 1967. Helminths, ectoparasites and protozoa in rats and mice. Pp. 641-678 in Pathology of Laboratory Rats and Mice, E. Cotchin and F. J. C. Roe, eds. Oxford: Blackwell Scientific. Wescott, R. B. 1982. Helminths. Pp. 374-384 in The Mouse in Biomedical Research. Vol. II: Diseases, H. L. Foster, J. D. Small, and J. G. Fox, eds. New York: Academic Press.
Representative terms from entire chapter: