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OCR for page 9
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
OCR for page 10
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
OCR for page 11
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
OCR for page 12
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.
OCR for page 13
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
OCR for page 14
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
OCR for page 15
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.
OCR for page 16
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
OCR for page 17
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
OCR for page 19
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.
OCR for page 61
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.
OCR for page 64
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.
OCR for page 69
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:
infectious diseases
