                   INFECTIOUS DISEASES OF MICE AND RATS












                    Stephen W. Barthold, D.V.M., Ph.D.
                            Diplomate, A.C.V.P.

                     Professor of Comparative Medicine
                    Yale University School of Medicine
                              P.O. Box 20816
                         New Haven, CT  06520-8016

                        telephone:  (203) 785-2522













Recommended Reading:  

Dean H. Percy and Stephen W. Barthold.   Pathology of Laboratory Rodents and Rabbits.   Iowa State
University Press, Ames, 1993.
                         INFECTIOUS AGENTS OF MICE



I.  VIRUSES
     
     
     A.  DNA

          Adenovirus          MAd-1 (FL), MAd-2 (K87)

          Herpesvirus         mouse cytomegalovirus (MCMV)
                         mouse thymic virus (MTV)

          Papovavirus         K virus
                         polyomavirus

          Parvovirus          minute virus of mice (MVM)
                         mouse orphan parvovirus (OPV)

          Poxvirus       ectromelia virus


     B.  RNA

          Arenavirus          lymphocytic choriomeningitis virus (LCMV)

          Arterivirus         lactate dehydrogenase elevating virus (LDHV)

          Coronavirus         mouse hepatitis virus (MHV)

          Paramyxovirus       pneumonia virus of mice (PVM)
                         Sendai virus

          Picornavirus        mouse encephalomyelitis virus (MEV)

          Reovirus       epizootic diarrhea of infant mice (EDIM) virus
                         reovirus 1, 2, 3

          Retrovirus          murine leukemia virus (MuLV)
                         murine mammary tumor virus (MuMTV)Mouse Adenovirus 
MAd-1 (FL)
MAd-2 (K87)

1.  Prevalence:   MAd-1 rare or nonexistent in laboratory mice.  MAd-2 moderate. 
2.  Diagnosis:  Serology, lesions (intranuclear inclusions)
3.  Disease:  MAd-1 (FL) causes multisystemic infection with viruria in young and immunodeficient mice. 
Lethal in suckling and SCID mice.  Subclinical in older mice, including athymic nude mice.  Type A intranuclear
inclusions, especially in renal tubules, adrenal cortex.  Animal model for adrenal necrosis.  Infection of SCID
and nude mice associated with enteritis, inclusions in enterocytes.  Intestinal component has not been carefully
examined.   MAd-2 (K87) is strictly enterotropic and less virulent, even in infant and immunodeficient mice. 
Inclusions in enterocytes.  Usually subclinical, but can cause runting and low mortality in suckling mice.  
4.  Transmission:  nose, urine, feces.  
5.  Duration:   acute to chronic
6.  Comment:  MAd-1 probably extinct.  MAd-1 antigen does not cross-react with MAd-2 antibody, but  MAd-2
antigen will react with MAd-1 antibody.  


Murine Cytomegalovirus (MCMV)

1.  Prevalence:  rare in laboratory mice; common in wild mice. 
2.  Diagnosis:  serology (not generally used); salivary gland lesions
3.  Disease:  Natural infections and experimental infections in adult immunocompetent mice are subclinical and
limited to salivary glands.  Submaxillary glands preferentially involved, with intranuclear and intracytoplasmic
inclusions in tubular epithelium and nonsuppurative interstitial inflammation.  Disseminated infection in
experimentally inoculated infant mice and immunosuppressed mice, including SCID mice.   
4.  Transmission:  saliva, tears, urine.  In utero transmission rare, even in experimentally inoculated mice.  Not
likely to be significant.  
5.  Duration:  chronic and latent
6.  Comment:  Betaherpesvirus.  Studied as model for human disease.  


Mouse Thymic Agent (MTV); thymic necrosis virus; thymic agent

1.  Prevalence:  nonexistent or rare in laboratory mice;  common in wild mice 
2.  Diagnosis:  serology (not generally used); mouse bioassay (thymic necrosis in neonates)
3.  Disease:  Natural infection and infection in adult mice subclinical.  Experimental inoculation of neonates
causes thymic necrosis and generalized lymphoid (T cell) necrosis, with intranuclear inclusions.  Infection of
older mice largely restricted to salivary glands, but no lesions have been found.  
4.  Transmission: saliva.  
5.  Duration:  chronic
6.  Comment:  Unclassified herpesvirus.  Because of salivary tropism, MTV is a frequent contaminant of
MCMV stocks.K Virus

1.  Prevalence:  rare or nonexistent
2.  Diagnosis:  serology
3.  Disease:  Subclinical in adult mice.  Necrosis, intranuclear inclusions in endothelial cells of villus lamina
propria.  Neonates (immunodeficient mice???) develop viremic dissemination to pulmonary and hepatic vascular
fields.  Pulmonary endothelial damage with hemorrhage, edema, death.  Viremia blocked in older mice by early
neutralizing antibody response.
4.  Transmission:  fecal
5.  Duration:  acute to chronic
6.  Comment:  Polyomavirus subgroup of Papovaviridae


Polyoma Virus (parotid tumor agent; salivary gland tumor virus)

1.  Prevalence:  rare as natural infection in laboratory mice.  Common in wild mice.
2.  Diagnosis: serology
3.  Disease:  Usually subclinical.  Experimental inoculation of neonates with high doses of oncogenic strains
results in multisystemic infection, followed by multiple hyperplastic and neoplastic foci in a variety of tissues
(poly-oma).  Natural infection in young mice multisystemic, but tumors are exceedingly unlikely.  Renal tubules
important target with viruria, as with many polyomaviruses of other species.  Mild necrosis, inclusions,
interstitial inflammation.  Older mice clear infection rapidly, with no virus shedding.  Natural and experimental
infection of athymic nude mice resulted in chronic infection and posterior paresis due to vertebral tumors and
progressive multifocal leukoencephalopathy.  
4.  Transmission:  urine, contamination of environment (wild mouse nests)
5.  Duration: acute to chronic
6.  Comment:  laboratory animal husbandry practices preclude life cycle of this virus.  Type species of
Polyomavirus subgroup of Papoviridae.


Minute Virus of Mice (MVM)

1.  Prevalence:  common
2.  Diagnosis:  serology (HAI, ELISA, IFA)
3.  Disease: Subclinical.  Experimental infection of neonates multisystemic, with cerebellar hypoplasia, renal
infarcts, anemia, etc.  Virus infection requries receptor and replication (cytolysis) requires S phase in dividing
cells. 
4.  Transmission:  Contact.  Vertical transmission shown experimentally
5.  Duration: variable; chronic, possibly latent
6.  Comment:  2 named strains, MVM-p (prototype) and MVM-i (immunosuppressive).  Lymphoid tissues
common target, with immunomodulation.Orphan Parvovirus (OPV) 

1.  Prevalence: common
2.  Diagnosis: serology (IFA)
3.  Disease:  Natural infections subclinical, but immunomodulation common, as with MVM.  
4.  Transmission:  fecal?
5.  Duration: chronic, possibly latent
6.  Comment:  Does not share virus structural antigens with MVM.  Does not possess a hemagglutinin.  HAI and
MVM-based ELISA therefore inaccurate.  Shares common non-structural antigens with other parvoviruses,
including MVM.  Thus MVM- infected cell IFA works.  Differs from orphan parvovirus of rats.  Number of
strains unknown. 


Ectromelia Virus

1.  Prevalence:  rare.  Unknown natural origin.
2.  Diagnosis: serology, lesions.
3.  Disease: natural disease varies from subclinical or high mortality, depending upon mouse genotype, age, virus
strain.  Resistant adult mice recover early, with minimal virus shedding.  Susceptible mice develop disseminated
disease, with multifocal necrosis of liver, lymphoid tissue, intestine, spleen, integument, etc.  Fulminant infection
may result in death with minimal virus excretion.  Semi-susceptible mice develop disseminated infection with
full manifestations, including rash and ectromelia (shortening of extremities due to dry gangrene).  These mice
serve as the major sourc of virus excretion.  Pox inclusions (Cowdry A & B) in skin and mucosal epithelium. 
4.  Transmission: skin, respiratory, urinary, fecal, etc.
5.  Duration: acute
6.  Comment:  Orthopox.  Several strains, including NIH-79, Wash-U, Moscow, Hampstead, St. Louis-69,
Beijing-70, Ishibashi I-III, which vary in virulence.  First description in England.  Disease called mouse pox,
virus called ectromelia virus.  Vaccine available (IHD-T), but modified live virus, prevents mortality but not
infection with street virus, and causes seroconversion.  Thus, not recommended except to protect valuable mice
in imminent danger of exposure.   


Lymphocytic Choriomeningitis Virus (LCMV)

1.  Prevalence:  rare in laboratory mice, common in wild mice
2.  Diagnosis:  serology; bioassay (intracerebral inoculation of infant and adult mice with suspect material)
3.  Disease:  subclinical to mild in mice.  Adult, immunocompetent mice recover rapidly without overt illness
(requires T cell immunity).  Infant and immunodeficient mice develop disseminated infection, but non-cytolytic
virus does not cause severe disease.  Infection is chronic, with persistent virus shedding, particularly in urine.  If
mice are exposed in utero or as neonates, they develop partial immunological tolerance, allowing persistent
infection and shedding.  Tolerance eventually breaks down later in life, with lymphocytic infiltration of multiple
organs and antigen-antibody complex glomerulonephritis ("Late Disease"). Adoptive transfer of T cells from
immune mice to subclinically infected mice leads to disease (lymphocytic choriomeningitis) and death.   
Endocrinopathy also reported experimentally.  Virus strains are classified as "docile" or "aggressive" and
"neurotropic" or "viscerotropic" for experimental purposes.  Natural infection of nude mice reported. 
4.  Transmission: in utero transmission is important in the natural cycle of infection.  Virus transmitted via
multiple routes, including mouse biological products.  
5.  Duration: acute to chronic, depending on age, tolerance and immune status. 
6.  Comment:  Mouse is natural host.   Zoonotic agent.  Hamsters pose a serious risk, as they develop persistent
infections following naturaly exposure as adults (unlike mice).  Rats not naturally susceptible.  
Lactate Dehydrogenase Elevating Virus (LDHV) 

1.  Prevalence: rare in laboratory mice, common in wild mice
2.  Diagnosis: persistent enzyme elevation in blood.  Serology reported to be poor because of high avidity
antigen-antibody complexes in serum.  
3.  Disease:  Subclinical.  Late onset demyelination in immunosuppressed C58 and AKR mice, but disease is
associated with retrovirus.  
4.  Transmission: natural salivary transmission via bite wounds
5.  Duration:  persistent
6.  Comment: macrophages and monocytes are selective target of virus.  Can contaminate transplantable tumor
lines, but can eliminate the virus by transient passage through rats.  This virus is now classified as an arterivirus,
within the now Coronavirus-like group, which includes coronaviruses, arteriviruses, and togaviruses. 


Mouse Hepatitis Virus (MHV)

1.  Prevalence: very common
2.  Diagnosis: serology, lesions
3.  Disease:  epizootic - high mortality among neonates to subclinical among adults.  Enzootic - usually
subclinical in all ages.  Many virus strains, indistinguishable antigenically, but represented by 2 biotypes: 
respiratory and enteric.  Respiratory strains replicate in nasal epithelium (minimal visible lesions in nose) and
disseminate to varying degrees to secondary target organs, including liver, lymphoid tissues, etc. in susceptible
hosts.  Focal necrosis with syncytia.  Enteric strains largely restricted to bowel mucosa, with minimal
dissemination.  Ascending colon and cecum are major targets, with hallmark syncytia.  Infant mice rapidly
develop severe enteritis; adults infected but subclinically.  Enteric disease is age-dependent, even in
immunodeficient mice.  Immunosuppression or co-infection with other agents increases susceptibility to MHV,
but only during active infection.    
4.  Transmission:  orofecal.  In utero possible, but not likely.
5.  Duration: acute.  NOT LATENT
6.  Comment:  Coronavirus of mice antigenically related to rat coronavirus, but biologically different. Immunity
to MHV is virus strain-specific and short-lived.  Thus, mice can be repeatedly infected, which has led to much
confusion about the issue of latency.  Coronaviruses readily mutate and recombine, with evolution of new strains
and repeated infection features of enzootic infection.  


Pneumonia Virus of Mice (PVM)

1.  Prevalence:  common
2.  Diagnosis:  serology; lesions in immunodeficient mice
3.  Disease:  subclinical upper respiratory infection in immunocompetent mice. Can cause lower respiratory
disease in experimentally infected mice.  Nude and SCID mice develop wasting disease due to progressive
pneumonia (bronchiolar epithelium and type 2 pneumocytes).   
4.  Transmission: respiratory
5.  Duration:  acute (except immunodeficient mice)
6.  Comment:  Pneumovirus Subgroup of Paramyxoviridae.
Sendai Virus

1.  Prevalence:  common
2.  Diagnosis:  serology, lesions
3.  Disease:  Sendai virus is the most clinically significant virus infection in laboratory mice because of its
prevalence and likelihood to cause clinical disease in mice of all ages.  Lesions are necrotizing rhinitis,
tracheobronchitis, bronchiolitis and interstitial pneumonia.  Target cells are respiratory epithelium and type 2
pneumocytes.  Recovery phase characterized by hyperplasia and squamous metaplasia of respiratory epithelium,
cuboidal metaplasia of alveoli, focal fibrosis.  Virus is not cytolytic.  Disease due to host immune attack on
infected cells.  Infection of athymic and SCID mice results in proliferative bronchiolitis and interstitial
pneumonia, without necrosis.  Marked variation in genetic susceptibility related to kinetics of immune response
and mucociliary clearance.  Predisposes to bacterial respiratory and ear infections.  
4.  Transmission: respiratory
5.  Duration: acute (except immunodeficient mice)
6.  Comment:  Parainfluenza 1 virus/Paramyxoviridae.


Mouse Encephalomyelitis Virus (MEV), mouse polio

1.  Prevalence: common
2.  Diagnosis: serology, lesions (when present)
3.  Disease: majority of infections are subclinical.  CNS signs include convulsions, posterior paresis (flaccid) in
a small fraction of mice.  Infects enterocytes with minimal effect.  CNS infection due to dissemination with acute
encephalomyelitis and demyelination (primary and immune-mediated attack on infected oligodendroglia). 
Severity of CNS disease virus strain, host age and genotype dependent.
4.  Transmission: orofecal
5.  Duration: variable with intermittent shedding.  Must be considered persistent.
6.  Comment:  Cardiovirus related antigenically to encephalomyocarditis (EMC) virus.  Several strains including
high virulence GDVII, FA and less virulent TO, DA.  


Epizootic Diarrhea of Infant Mice (EDIM) Virus

1.  Prevalence:  common
2.  Diagnosis:  serology, lesions (if present), antigen in feces, E.M. of feces (many virions)
3.  Disease: Lesions and diarrhea in mice infected at 12 or less days of age.  All ages are susceptible to infection. 
Hydropic swelling of villus tip epithelium, malabsorption, diarrhea, runting.  E. coli overgrowth.  Maternal
immunity abrogates disease in enzootic infection. 
4.  Transmission: orofecal
5.  Duration:  acute, but not fully characterized
6.  Comment:  typical rotavirus, antigenically related to rotaviruses of other species.  Commercially available
ELISA for fecal antigen is useful, but false-positive reactions can occur with some feeds. 
 Reovirus 

1.  Prevalence:  moderate
2.  Diagnosis:  serology
3.  Disease:  Usually subclinical.  Historical literature describes CNS disease, hepatitis, diarrhea with
steatorrhea and oily hair effect.  Experimental inoculation of neonatal mice with Reovirus 1 and 3 results in
myocarditis, encephalitis and hepatitis, with virus replication in many tissues.  Reovirus 2 causes EDIM-like
disease.  
4.  Transmission:  orofecal
5.  Duration:  acute
6.  Comment:  Mammalian reoviruses are divided into 3 serotypes: 1, 2 and 3, which represent many different
strains.  Reovirus 3 only serotype known to cause natural disease in mice, but mice are susceptible to infection
by all.  Cross-react serologically, so cannot accurately distinguish infecting serotype.  


Murine Leukemia Virus (MuLV)

1.  Prevalence:   100%
2.  Diagnosis:  not done
3.  Disease:  variable, depending upon genotype of mouse.  Disease manifestations may include neoplasia,
demyelination, greyness, etc.  Most MuLVs are not oncogenic.  
4.  Transmission: vertical, inherited as Mendelian genetic characteristics via DNA provirus.  
5.  Duration:  persistent, chronic and latent
6.  Comment:  Retroviruses can be exogenous or endogenous.  Exogenous viruses are horizontally transmitted
like conventional viruses, but no longer exist in laboratory mice.  Wild mice have exogenous retroviruses and
these are probably the historical source of some laboratory strains, including Friend, Moloney and Rauscher
viruses.  Endogenous viruses are part of the mouse genome and all mouse strains carry one or more endogenous
MuLVs.  Ecotropic, xenotropic and polytropic behavior and host receptors are important in evolution of
recombinant viruses which are pathogenic.  Expression of non-oncogenic endogenous MuLVs occurs at different
times and in different tissues, with evolution of recombinant, oncogenic variants.  


Murine Mammary Tumor Virus (MuMTV)

1.  Prevalence:  100%
2.  Diagnosis:  not done
3.  Disease:  variable expression of mammary neoplasia, depending upon genotype
4.  Transmission:  same as MuLV. Exogenous (Bittner milk agent or MuMTV-S) transmitted via milk, saliva +/-
semem.  Endogenous in genome of all strains.
5.  Duration:  persistent
6.  Comment:  Exogenous viruses eliminated by foster nursing or rederivation.  Bittner agent maintained
purposefully in some populations of C3H mice as a model system.  Others (MuMTV-O, -L, -P, -X) are
endogenous.  Differ in virulence, tumor type.

                         INFECTIOUS AGENTS OF MICE



II.  BACTERIA

     
     Bacillus piliformis
     
     Cilia-Associated Respiratory (CAR) Bacillus
     
     Citrobacter freundii
     
     Corynebacterium kutscheri
     
     Corynebacterium pseudodiphtheriticum
     
     Clostridium perfringens

     Escherichia coli

     Klebsiella oxytoca

     Leptospira ballum

     Mycobacterium avium

     Mycoplasma spp.

     Pasteurella pneumotropica

     Proteus mirabilis

     Pseudomonas aeruginosa

     Salmonella enteritidis

     Staphylococcus aureus

     Streptobacillus moniliformis

     Streptococcus spp. 

Bacillus piliformis  (Tyzzer's Disease)

1.  Prevalence:  rare (once common)
2.  Diagnosis:  lesions, serology developed but not used
3.  Disease:  Sudden death with or without diarrhea.  Colitis with dissemination to liver (focal hepatitis) and
occasionally heart (myocarditis).  Special stains (silver, Giemsa, PAS) reveal intracytoplasmic fascicles of
bacteria.  Immunosuppression exacerbates disease in carrier mice and stress predisposes to disease.  Resistance
to disease is B cell mediated.  Nude mice are no more susceptible to disease than immunocompetent mice.  
4.  Transmission:  Orofecal via spores.  Spores survive for > 1 year
5.  Duration:  unknown
6.  Comment:  Cannot be grown in cell-free medium.  Partial species-specificity of isolates.  Depopulate. 
Gerbils frequently infected.


Cilia-Associated Respiratory (CAR) Bacillus

1.  Prevalence:  common
2.  Diagnosis:  serology available, but not used much in US.  Lesions with special stains.
3.  Disease:  None to chronic respiratory disease.  Mice are more susceptible to experimental infection than rats,
but natural disease is more prevalent in rats.  Often a co-infection with Mycoplasma pulmonis.    Silver stains
reveal filamentous organisms among cilia of respiratory epithelium. 
4.  Transmission:  contact
5.  Duration:   chronic
6.  Comment:  Rats, rabbits, humans also infected.  


Citrobacter freundii (Transmissible Murine Colonic Hyperplasia)

1.  Prevalence:  rare
2.  Diagnosis: culture, lesions.  Must culture multiple mice in early stage of infection, as agent is often absent
when clinical signs and lesions are overt.
3.  Disease:  rectal prolapse, sticky feces.  Thickening of the descending colon and cecum due to mucosal
hyperplasia.  Inflammation and erosion variable, but tend to occur most in young mice.  Genotype, age and diet
are factors.  Agent attaches to surface mucosa, but disappears at the time of peak disease (around 2 weeks).  
4.  Transmission:  direct contact, inefficient
5.  Duration: acute (around 2 weeks) with no carrier state
6.  Comment:  pathogenic strain (4280) is non-motile with characteristic sugar fermentation profile.  Not all C.
freundii are pathogenic in mice and 4280 does not cause disease in other species.  Eliminate by improving
husbandry.    Corynebacterium kutscheri (Pseudotuberculosis)

1.  Prevalence:  rare (once common)
2.  Diagnosis:  culture, gram stain of lesions, serology (not used)
3.  Disease:  Caseopurulent abscesses containing prominent colonies of Gram-positive bacilli (Chinese letter
configurations) at edge of lesions.  Lesions in liver,  kidney, lung and other sites.  Cervical lymph nodes may be
enlarged, but not abscessed.  Subclinical carrier state common.  Immunosuppression and other stressors cause
exacerbation of disease.
4.  Transmission: direct contact
5.  Duration: chronic, but probably not latent
6.  Comment:  Pathogenesis not fully understood in mouse (see rat).  Depopulate.


Corynebacterium hoffmani

1.  Prevalence:  common
2.  Diagnosis:  culture, lesions
3.  Disease:  this agent is often isolated from mice with conjunctivitis, but a cause and effect relationship has not
been established.  
4.  Transmission:  direct contact, opportunistic bacterium
5.  Duration:  unknown
6.  Comment:  probably not a primary pathogen


Corynebacterium pseudodiphtheriticum

1.  Prevalence:  rare
2.  Diagnosis:  culture, lesions
3.  Disease:  orthokeratotic dermatitis in nude mice.  High mortality in suckling mice, transient disease in
weanlings, asymptomatic in adults.  
4.  Transmission:  contact
5.  Duration:  unknown
6.  Comment:  sporadic problem in nude mouse colonies


Clostridium perfringens

1.  Prevalence:  rare
2.  Diagnosis:  culture, toxin assay, lesions
3.  Disease:  sporadic outbreaks of necrotizing enterocolitis in post-weaning mice and lactating mice.  Lesions
consist of mucosal necrosis, hyperplasia and edema.  
4.  Transmission:  orofecal
5.  Duration:  unknown
6.  Comment:






Escherichia coli

1.  Prevalence:  common intestinal inhabitant, disease variable
2.  Diagnosis:  culture, lesions
3.  Disease:  hyperplastic typhlocolitis in immunodeficient mice (SCID and multiple deficient, but not nude). 
Overgrowth in infant mice with viral enteritis.
4.  Transmission:  orofecal
5.  Duration:  chronic
6.  Comment:  Immunodeficient mice infected with an otherwise non-pathogenic, non-lactose fermenting E. coli. 
Other typical strains may overgrow in infant mice with viral enteritis.  


Klebsiella oxytoca

1.  Prevalence:  low
2.  Diagnosis:  culture
3.  Disease:  unusually high prevalence of suppurative female reproductive tract lesions reported in an infected
colony of aging mice.
4.  Transmission:  contact
5.  Duration:  chronic
6.  Comment:  cause-effect relationship not proven


Leptospira ballum 

1.  Prevalence:  rare in laboratory mice, common in wild mice
2.  Diagnosis: culture
3.  Disease:  none in mice.  
4.  Transmission:  urine
5.  Duration:  chronic
6.  Comment:  L. ballum most commonly associated with mice and mouse-associated zoonoses.  Mice do not
generally develop lesions.  


Mycobacterium avium-intracellulare

1.  Prevalence:  rare
2.  Diagnosis:  lesions, Acid-fast stains, culture
3.  Disease:  granulomata in lungs, liver, mesenteric lymph nodes reported in C57BL/6 mice. 
4.  Transmission:  water?
5.  Duration:  chronic
6.  Comment:  single report.  C3H/HeN and B6C3F1 mice, F344 rats negative. Mycoplasma pulmonis  (Mycoplasmosis)
M. arthritidis
M. neurolyticum
M. collis

1.  Prevalence:  M. pulmonis moderate.  M. arthritidis less common and others rare or nonexistent.
2.  Diagnosis: culture, serology, lesions (if present)
3.  Disease:  M. pulmonis is associated with chronic respiratory disease.  It tends to produce chronic suppurative
rhinitis, otitis and bronchopneumonia in mice, often in concert with other agents (Sendai virus, CAR bacillus,
etc.).  Mycoplasmas attach to apical cell membranes of mucosal epithelial cells.  M. pulmonis, M. arthritidis and
M. neurolyticum inhabit the upper respiratory tract and M. collis inhabits the genital tract.  Only M. pulmonis is
a significant natural pathogen.  Infections are often subclinical, but disease can be precipitated by viral
infections.  M. arthritidis and M. pulmonis cause arthritis when given intravenously and M. neurolyticum elicits
an exotoxin causing neurolytic "rolling disease" when given intracerebrally.  
4.  Transmission:  respiratory, other
5.  Duration:  chronic
6.  Comment:  depopulate.  Test and cull can be effective.  Serology utilizes M. pulmonis as antigen, with
variable cross-reactivity among different strains.  M. arthritidis infection can cause seroconversion to M.
pulmonis.  


Pasteurella pneumotropica

1.  Prevalence:  high
2.  Diagnosis:  culture, lesions
3.  Disease:  opportunistic organism.  Normal gut microflora.  High frequency of isolation from nasopharynx, gut
or normal mice.  Associated with conjunctivitis, otitis, pneumonia, cystitis, prepucial gland abscesses, etc. 
Dermatitis in nude mice.   
4.  Transmission:  normal flora
5.  Duration:  chronic


Proteus mirabilis

1.  Prevalence:  agent common, disease rare
2.  Diagnosis:  culture, lesions
3.  Disease:  genitourinary infections, otitis.  Septicemia in immunodeficient mice, with fibrinopurulent
peritonitis, hepatitis, pneumonitis, splenomegaly and significant mortality noted in SCID mice.  
4.  Transmission: contact, environmental
5.  Duration:  unknown


Pseudomonas aeruginosa

1.  Prevalence:  agent common, disease conditional
2.  Diagnosis:  culture, clincial disease associated with immunosuppression 
3.  Disease:  Opportunistic organism.  Mice that are exposed to organism while immunosuppressed (neutropenic)
develop bacteremia and high mortality.  Pseudomonas does not permanently colonize mice, but passes transiently
through following exposure from water bottle sipper tubes.  Organisms invade naso-squamous junction in nose.
4.  Transmission: water bottle contamination 
5.  Duration:  transient but repeated infection
6.  Comment:  control with water treatment (acidification or chlorination)


Salmonella enteritidis  (Salmonellosis)

1.  Prevalence:  rare (once common)
2.  Diagnosis:  culture, lesions.  Mesenteric lymph nodes are most consistent site for culture.
3.  Disease:  normal microflora contribute resistance.  Bacteria invade Peyer's patches of ileum to mesenteric
lymph nodes to liver, spleen and blood, bile ducts, intestine (enterohepatic cycle).  Disease dependent upon
host/agent factors.  Lesions include enteritis (terminal small intestine and cecum), mesenteric lymphadenopathy,
Peyer's patch hyperplasia, hepatic granulomas, splenomegaly.  Infection often subclinical.
4.  Transmission:  intermittent fecal shedding
5.  Duration:  usually less than 1 month.  Approximately 5% carrier rate in mice.  
6.  Comment:  3 species: S. cholerae-suis, S. typhi and S. enteritiidis.  Many serotypes, all potentially
pathogenic, but serotype typhimurium most common.  Depopulate. 


Staphylococcus aureus 

1.  Prevalence:  common 
2.  Diagnosis:  culture, lesions
3.  Disease:  Abscesses, especially cervical lymph nodes with botryomycotic features in immunocompetent mice. 
Furunculosis and cervical lymph node abscesses in nude mice.  Ulcerative dermatitis, often secondary to
acariasis.  
4.  Transmission:  environmental
5.  Duration:  chronic
Streptobacillus moniliformis

1.  Prevalence:  rare in laboratory mice
2.  Diagnosis:  culture - pleomorphic, non-motile filamentous rods
3.  Disease:  septicemia, diarrhea, conjunctivitis, hepatitis, serosal hemorrhages, and suppurative arthritis in
survivors.  
4.  Transmission:  carried and introduced by rats, then mouse-to-mouse contact transmission
5.  Duration:  chronic
6.  Comment:  carried in oropharynx of rats.  Cause of rat-bite fever in humans


Streptococcus spp.

1.  Prevalence:  low
2.  Diagnosis:  culture, lesions
3.  Disease:  outbreaks of high incidence ulcerative dermatitis reported with beta hemolytic Streptococcus. 
Alpha hemolytic Streptococcus also reported in SCID mouse septicemia.  
4.  Transmission:  contact
5.  Duration:  chronic
6.  Comment:  mice resistant to Streptococcus pneumoniae (Diplococcus)

                         INFECTIOUS AGENTS OF MICE



     
III.  RICKETTSIA

     
     Eperythrozoon coccoides


IV.  FUNGUS

     
     Trichophyton mentagrophytes


V.  PNEUMOCYSTIS

     Pneumocystis carinii


Eperythrozoon coccoides

1.  Prevalence:  rare (once common)
2.  Diagnosis:  blood smear, Giemsa stain; splenectomy/immunosuppression
3.  Disease:  subclinical or anemia, splenomegaly, RE proliferation.  Intra- and extracellular forms
4.  Transmission:  via blood; Polyplax serrata vector
5.  Duration:  chronic
6.  Comment:  potentiates MHV, LCMV, LDHEV.  Occasional contaminant of biological products.


Trichophyton mentagrophytes

1.  Prevalence:  rare disease
2.  Diagnosis:  lesions, culture, histochemistry
3.  Disease:  infection usually subclinical.  Alopecia, focal crusts, especially on head.  Favus in severe cases
(yellow crusts on muzzle, head, ears, tail, extremities).  Hair invasion is not a feature of mouse dermatomycosis.
4.  Transmission:  contact.  Non-selective host range, including humans
5.  Duration:  unknown
6.  Comment:  nearly non-pathogenic in mouse.  Disease/lesions exceedingly rare


Pneumocystis carinii

1.  Prevalence:  high rate of infection; disease rate low, except in immunodeficient mice (common)
2.  Diagnosis:  silver stain of lung lesions 
3.  Disease:  not pathogenic for immunocompetent host.  Steroids/low protein diet and immunodeficient
genotypes allow overgrowth.  Lungs firm, pale, mottled and do not collapse.  Alveoli contain eosinophilic
proteinaceous exudate containing numerous cysts visible with silver stain.  Interstitial pneumonia to varying
degrees, depending upon host. 
4.  Transmission: contact
5.  Duration:  chronic
6.  Comment:  depopulate, rederive.  Serious life-limiting disease in nude and SCID mice
                         INFECTIOUS AGENTS OF MICE




VI.  PROTOZOA

     
     Cryptosporidium muris, parvum

     Eimeria spp.

     Giardia muris

     Klossiella muris

     Spironucleus muris

Cryptosporidium muris, C. parvum


1.  Prevalence:  rare
2.  Diagnosis:  histology, cysts in feces
3.  Disease:  both agents are mildly pathogenic and opportunistic, associated with enteritides of various primary
origin and malnutrition.  Attach to brush border of surface epithelium of stomach (C. muris) or small intestine
(C. parvum).  Cholangitis with focal hepatic necrosis observed in nude mice infected with C. parvum.   
4.  Transmission:  orofecal, cysts
5.  Duration:  unknown
6.  Comment:  opportunistic overgrowth.  Treat primary problem


Eimeria spp. 

1.  Prevalence:  rare (common in wild mice)
2.  Diagnosis:  oocysts in feces, lesions
3.  Disease:  enteritis, typhlitis, colitis with diarrhea, blood.  Especially found in young (weaning age) mice
4.  Transmission:  orofecal
5.  Duration:  moderate chronicity with recovery and strong immunity
6.  Comment:  6 species in Mus (E. falciformis, E. musculi, E. schueffneri, E. krijgsmanni, E. keilini, E. hindlei). 



Giardia muris

1.  Prevalence:  low
2.  Diagnosis:  cysts in feces; trophozoites in small intestine (wet mounts or histology)
3.  Disease:  often subclinical.  Abdominal distention, yellow-white watery digesta in small intestine. 
Trophozoites aligned along brush border of villi.  Lymphoplasmacytic infiltrates of lamina propria. 
Opportunistic pathogen in mice, usually associated with other primary disease or immunodeficiency.  Nude mice
develop chronic enteritis, weight loss.
4.  Transmission:  orofecal
5.  Duration:  approximately 1 month, except in immunodeficient mice
6.  Comment:  treatment controls disease.  Hamsters frequently infected and infections are chronic with chronic
malabsorption, enteritis, diarrhea, weight loss.


Klossiella muris

1.  Prevalence:  rare, except in wild mice
2.  Diagnosis:  histology, oocysts in urine
3.  Disease:  usually subclinical.  Key target is kidney.  Sporocysts enter bloodstream after ingestion, spread
throughout the body.  Schizogony in glomerular endothelium (usually not apparent); gametogeny and sporogony
in tubular epithelium is obvious feature, with nonsuppurative interstitial nephritis.  
4.  Transmission:  urine
5.  Duration:  chronic.  
6.  Comment:  depopulate or rederive
Spironucleus muris  (Hexamita muris)

1.  Prevalence:  common
2.  Diagnosis:  cysts in feces (Easter eggs); trophozoites in small intestine (wet mounts, histology)
3.  Disease:  usually subclinical.  Opportunistic overgrowth with immunosuppression, immunodeficiency,
enteritides of various origin, especially enterotropic MHV.  Watery fluid and gas in upper small intestine. 
Trophozoites seek refugfe in crypts and may distend them.  Mucosa hyperplastic and trophozoites may invade
lamina propria.  Nude mice develop chronic hyperplastic enteritis. 
4.  Transmission:  orofecal
5.  Duration:  chronic
6.  Comment:  treatment controls disease.  Eliminate primary pathogen.  The syndrome of spironucleosis is rare
and if present, other pathogens should be sought.  



                         INFECTIOUS AGENTS OF MICE



VII.  HELMINTHS

     
     A.  NEMATODES

          Aspicularis tetraptera

          Syphacia obvelata


     B.  CESTODES

          Cysticercus fasciolaris (Taenia taeniaeformis)

          Hymenolepis nana, diminuta, microstoma

Aspicularis tetraptera, Syphacia obvelata

1.  Prevalence:  high
2.  Diagnosis:  ova in feces.  Scotch-tape test for Syphacia.  Adults in gut lumen.  Aspicularis ova are
symmetrical, Syphacia asymetrical.   
3.  Disease:  minimal or none.  Rectal prolapse attributed to heavy infestations.  Syphacia deposits eggs around
anus, Aspicularis does not.  
4.  Transmission:  orofecal.  Ova very resistant to dessication and drift in air, dust
5.  Duration:  chronic.  Immunity develops with age
6.  Comment:  treatment controls, but seldom eradicates worms.  Immune effects reported.


Cysticercus fasciolaris (Taenia taeniaeformis)

1.  Prevalence:  rare
2.  Diagnosis:  gross, microscopic lesions
3.  Disease:  strobilocercus in liver incidental finding in assymptomatic host
4.  Transmission: contamination of food and bedding with cat feces
5.  Duration:  chronic
6.  Comment:  rodent is intermediate host for cat tapeworm


Hymenolepis nana, diminuta, microstoma

1.  Prevalence: low in laboratory mice.  Common in wild mice.  Order of prevalence in wild mice listed above.
2.  Diagnosis:  ova in feces, adults in intestine
3.  Disease:  usually subclinical.  Local enteritis or pancreatitis.  H. nana and H. diminuta in intestine.  H.
microstoma in bile/pancreatic ducts and duodenum.
4.  Transmission:  All have arthropod intermediate host.  Intermediate host for H. nana optional.  
5.  Duration:  chronic
6.  Comment:  H. diminuta and H. microstoma ova have polar filaments.  H. nana adult is smallest of the three
(dwarf tapeworm).  Zoonotic hazard, especially with H. nana, as no intermediate host required.  
                         INFECTIOUS AGENTS OF MICE




VIII.  ARTHROPODS


     A.  LICE

          Polyplax serrata


     B.  MITES

          Myobia musculi

          Myocoptes musculinis

          Radfordia affinis

          Psorergates simplex

          Ornithonyssus bacoti


     C.  INSECTS

          Xenopsylla cheopsis

          Nasopsyllus fasciatus

          Leptopsylla segnis

Polyplax serrata

1.  Prevalence:  rare
2.  Diagnosis:  lice in fur, nits
3.  Disease:  irritabilitiy, pruritis, anemia, dermatitis
4.  Transmission:  contact
5.  Duration:  chronic, with developing immunity
6.  Comment:  sucking lice.  Vector for E. coccoides.  


Myobia musculi

1.  Prevalence:  common
2.  Diagnosis:  mites in fur, prefers fur of dorsal neck, shoulders.  Single empodial claw on second pair of legs.
3.  Disease:  often subclinical.  Hypersensitivity can occur with ulcerative dermatitiis, pruritis, trauma and
erosion of pinnae.  Genotype-dependent (C57BL)
4.  Transmission: contact
5.  Duration:  chronic, with immune-mediated equillibrium
6.  Comment:  usually mixed infestations with other fur mites.  Malnutrition, disease predisposes to overgrowth.  


Myocoptes musculinis

1.  Prevalence:  common
2.  Diagnosis:  mites in fur, generalized distribution.  Suckers on feet and pigmented third and fourth pair of legs. 

3.  Disease:  usually inapparent, but mild alopecia can occur.  
4.  Transmission:  contact
5.  Duration:  chronic
6.  Comment:  usually mixed infestations with other fur mites.  Myocoptes dominates and is most common fur
mite in laboratory mice.  


Radfordia affinis

1.  Prevalence:  common
2.  Diagnosis:  double embodial claws on second pair of legs.
3.  Disease:  subclinical
4.  Transmission:  contact
5.  Duration:  chronic
6.  Comment:  usually mixed infestation with other fur mites.Psorergates simplex

1.  Prevalence:  rare in laboratory mice, common in wild mice
2.  Diagnosis:  1 mm white nodules visible on underside of skin around head and neck
3.  Disease:  follicular cysts filled with keratinized epithelium and mites at the epidermal junction.  
4.  Transmission:  contact
5.  Duration:  chronic
6.  Comment:  once common, now rare


Ornithonyssus bacoti

See rat.

Fleas

See rat.  Rare.  Xenopsylla most common in laboratory mouse colonies.  Leptopsylla can serve as intermediate
host for Hymenolepis.  
                         INFECTIOUS AGENTS OF RATS



I. VIRUSES

     
     A.  DNA

          Adenovirus          rat adenovirus
          
          Herpesvirus         rat cytomegalovirus (RCMV)

          Papovavirus         ?

          Parvovirus          rat virus (RV)
                         H-1 virus (H-1)
                         rat orphan parvovirus (OPV)

          Poxvirus       cowpox virus


     B.  RNA

          Bunyavirus          hemorrhagic fever with renal syndrome (HFRS) virus

          Coronavirus         sialodacryoadenitis virus (SDAV)

          Paramyxovirus  pneumonia virus of mice (PVM)
                         Sendai virus

          Picornavirus        mouse encephalomyelitis virus (MEV)

          Reovirus       infectious diarrhea of infant rats (IDIR) virus
                         reovirus 1, 2, 3

          Retrovirus          rat leukemia virus (RLV)
Rat Adenovirus

1.  Prevalence:  common
2.  Diagnosis: serology, inclusions.  Cross-reacts antigenically with MAd-2
3.  Disease:  subclinical.  Intranuclear inclusions in enterocytes of small intestine found incidentally.  Inclusions
more common in young rats.  
4.  Transmission:  orofecal 
5.  Duration:  unknown
6.  Comment:  high prevalence of seroconversion with K87 antigen.  Rats not susceptible to MAd-1 or -2, so
probably separate, but related viruses.  Enteric inclusions found only occasionally, but unknown if this is the
only adenovirus of rats.  Isolation attempts have failed.


Rat Cytomegalovirus (RCMV)

1.  Prevalence:  rare or non-existent in laboratory rats, common in wild rats
2.  Diagnosis:  histology.  Serology, but seldom used
3.  Disease:  cytomegaly, inclusions in acinar and duct epithelium of salivary and lacrimal glands, especially
submandibular gland.  Mild nonsuppurative interstitial inflammation.  Do not confuse with normal exorbital
gland morphology.
4.  Transmission:  unknown (salivary?)
5.  Duration: chronic


Papovavirus

1.  Prevalence:  unknown
2.  Diagnosis:  histology
3.  Disease:  sialoadenitis noted in a colony of rnu/rnu (athymic) rats with wasting syndrome.  Parotid gland duct
epithelial cells had intranuclear inclusions.  Antigen also in laryngeal and bronchiolar epithelium and kidney.
4.  Transmission:  unknown
5.  Duration:  unknown
6.  Comment:  seen only in NIH rnu/rnu rats.  Does not cross-react with K or polyoma virus of mice.  Probably
more widespread, but only apparent in athymic rats.  Agent not characterized.Rat Parvoviruses
     Rat Virus
     H-1 Virus
     Rat Orphan Parvovirus

1.  Prevalence:  common (all 3)
2.  Diagnosis:  serology, lesions (RV).  As with mouse OPV, rat OPV does not share virus structural antigens
with RV, H-1.  Rat and mouse OPVs are different viruses.
3.  Disease:  RV associated with natural disease.  Others subclinical.  Most RV infections are subclinical, but
can cause fetal resorption, neonatal cerebellar hypoplasia with ataxia, hepatitis, jaundice, steatorrhea. 
Hemorrhagic disease in adults, especially when stressed or immunosuppressed.  Hemorrhage in CNS and
peritesticular reported.
4.  Transmission:  various routes of excretion, in utero possible but not likely
5.  Duration:  acute to chronic (latent?)
6.  Comment:  RV and H-1 antigenically cross-reactive, but serologically distinct.  OPV not cross-reactive, but
shares non-structural antigens.  IFA serology, using infected cells therefore most useful seroassay.  


Cowpox Virus

1.  Prevalence:  rare
2.  Diagnosis:  lesions
3.  Disease:  subclinical.  Necrotizing rhinitis.
4.  Transmission:  unknown
5.  Duration:  unknown
6.  Comment:  Soviet satellite Cosmos 1129


Hemorrhagic Fever with Renal Syndrome (HFRS) Virus

1.  Prevalence:  widespread in wild Norway rats.  Rare in laboratory rats.  
2.  Diagnosis:  serology
3.  Disease:  none reported in rats, but not thoroughly evaluated
4.  Transmission:  urine, saliva, respiratory
5.  Duration: chronic
6.  Comment:  Zoonotic.  Synonyms:  Korean hemorrhagic fever, muroid virus nephropathy, Hantaan virus
(single virus), Hanta virus.  Proteinuria, azotemia, petechiae, hemoconcentration, hypotension, renal failure, etc.
in humans.  Recovery usual, but several fatal cases recently reported in Southwest associated with Peromyscus
mouse reservoir.  Rat Coronaviruses

1.  Prevalence:  common
2.  Diagnosis:  serology, lesions
3.  Disease:  cervical edema, nasal/ocular discharge, photophobia, keratitis, megaloglobus, anestrus, fetal
resorption.  Virus replicates in upper respiratory mucosa (necrotizing rhinitis, tracheitis, bronchitis), with
secondary involvement of salivary, lacrimal and lower respiratory tissues (sialodacryoadenitis and interstitial
pneumonia).  Sublingual salivary gland usually spared.  Lacrimal gland dysfunction results in secondary keratitis
sicca, ulcers, uveitis, megaloglobus, etc.  Chronic wasting disease in athymic rats due to progressive pneumonia
and salivary gland lesions.  Olfactory mucosal dysfunction in sucklings may lead to failure to nurse, mortality. 
Pneumonia is common in infant rats.
4.  Transmission:  respiratory
5.  Duration:  acute (except in athymic rats)
6.  Comment:  many strains (like MHV), including "Parker's Rat Coronavirus"


Pneumonia Virus of Mice (PVM)

1.  Prevalence:  common
2.  Diagnosis:  serology, lesions
3.  Disease:  subclinical.  Lungs develop perivascular and focal interstitial lymphocytic infiltrates in seropositive
(recovered) rats.  Lesions persist after virus is cleared.   Athymic rats likely to have persistent infections with
chronic lung disease, but never reported. 
4.  Transmission:  respiratory
5.  Duration:  acute
6.  Comment:  PVM more apt to produce lung lesions in naturally infected rats than mice.


Sendai Virus

1.  Prevalence:  common
2.  Diagnosis:  serology, lesions
3.  Disease:  subclinical or mild in rats.  Infant mortality.  Disease similar to Sendai virus infection in genetically
resistant mice (mild).  Chronic wasting syndrome/pneumonitis in rnu/rnu rats.  
4.  Transmission:  respiratory
5.  Duration:  acute


Mouse Encephalomyelitis Virus (MEV)

1.  Prevalence:  seroconversion rare to moderate
2.  Diagnosis:  serology
3.  Disease:  none
4.  Transmission:  orofecal
5.  Duration:  unknown
6.  Comment:  MHG virus isolated from rats.  Antigenically cross-reactive with MEV of mice.  Probably mouse
origin.



Infectious Diarrhea of Rats (IDIR) Virus

1.  Prevalence:  rare
2.  Diagnosis:  lesions.  Serology available, but not used.
3.  Disease:  suckling rats (less than 12 days of age) develop diarrhea, erythema of anus, runting.  Malabsorption
with watery digesta.  Villus attenuation, necrosis, enterocytic syncytia and intracytoplasmic inclusions,
especially distal small intestine.
4.  Transmission:  orofecal
5.  Duration:  acute
6.  Comment:  antigenically distinct rotavirus (separate from typical or type 1 rotaviruses).  Pathogenesis similar
to EDIM in mice, with age-dependent susceptibility to disease but not infection.  Infectious to humans and
humans probable source of infection in laboratory rats.


Reovirus

1.  Prevalence:  moderate
2.  Diagnosis:  serology
3.  Disease:  none
4.  Transmission:  orofecal, respiratory
5.  Duration:  unknown
6.  Comment:  see mouse.  No disease reported in naturally or experimentally infected neonatal rats.


Rat Leukemia Virus (RLV)

1.  Prevalence:  100%
2.  Diagnosis:  not done
3.  Disease:  none
4.  Transmission:  germ line, endogenous provirus
5.  Duration:  chronic, latent
6.  Comment:  minimal significance in rat.  RLV sequences have been combined with MuLV or other RLVs to
form experimental rat sarcoma viruses (Kirsten, Harvey, etc.)                         INFECTIOUS AGENTS OF RATS



II.  BACTERIA

     Bacillus piliformis

     Bordetella bronchiseptica

     Campylobacter spp.

     Cilia-Associated Respiratory (CAR) Bacillus

     Corynebacterium kutscheri

     Erysipelas rusiopathiae

     Hemophilus spp.

     Klebsiella pneumoniae

     Leptospira icterohemorrhagiae

     Mycoplasma spp.

     Pasteurella pneumotropica

     Pseudomonas aeruginosa

     Salmonella enteritidis

     Spirillum minus

     Staphylococcus aureus

     Streptobacillus moniliformis

     Streptococcus pneumoniae

     Streptococcus spp.
Bacillus piliformis (Tyzzer's disease, megaloileitis)
     
1.  Prevalence:  rare
2.  Diagnosis:  lesions, silver stains, serology developed but not used
3.  Disease:  ileitis with dissemination to liver and heart, especially in post-weaning rats.  Adynamic ileus can
occur, resulting in megaloileitis, but not a constant feature.  Silver stains reveal characteristic intracellular
bacteria.
4.  Transmission:  spores, orofecal.  In utero transmission possible in immunosuppressed rats, but not likely to be
significant means of transmission.  
5.  Duration:  unknown
6.  Comment:  see mouse.   


Bordetella bronchiseptica

1.  Prevalence:  rare, depending on population
2.  Diagnosis:  culture
3.  Disease:  may be associated with respiratory disease, but probably in association with primary pathogen,
such as Mycoplasma.  Rhinitis, otitis, lower respiratory disease.
4.  Transmission:  contact
5.  Duration:  unknown
6.  Comment:  minor primary significance in rats


Campylobacter spp.

1.  Prevalence:  variable
2.  Diagnosis:  culture, silver stains of lesions
3.  Disease:  there is a single report of intracytoplasmic organisms in apical cytoplasm of hyperplastic/neoplastic
enterocytes with colonic adenocarcinoma.  Agent not characterized, but morphologically reminiscent of
Campylobacter-like organisms in hyperplastic enteritides of a variety of species (rabbit, guinea pig, hamster,
ferret, lamb, calf, piglet, etc.).  Campylobacter jejuni can also be isolated from rats with soft feces.  This is
probably common and agent can be cultured.  
4.  Transmission:   orofecal  
5.  Duration:  unknown


Cilia-Associated Respiratory (CAR) Bacilllus

1.  Prevalence:  common
2.  Diagnosis:  silver stain, lesions, serology developed but not used
3.  Disease:  subclinical to chronic respiratory disease similar to mycoplasmosis.  Organisms on apical
membrane among cilia of respiratory epithelium.  Often co-infection with Mycoplasma.  
4.  Transmission:  respiratory, presumed
5.  Duration:  chronic
6.  Comment:  does not grow in cell-free medium.  Found in multiple species.  Experimental infection of SPF rats
with CAR bacillus will induce chronic respiratory disease and natural infections manifesting as chronic
respiratory disease have CAR bacillus in the absence of Mycoplasma, but natural infections are usually mixed.  
Corynebacterium kutscheri (pseudotuberculosis)

1.  Prevalence:  variable
2.  Diagnosis:  culture of lesions, oral washes, cervical lymph nodes.  Lesions with characteristic Gram +
colonies
3.  Disease:  rats may carry organisms in oral cavity and cervical lymph nodes without disease.  Infected cervical
lymph nodes may be slightly enlarged (reactive) without abscessation.  Stress, immunosuppression, other
unknown factors may precipitate bacteremic dissemination to lungs, kidneys, liver, etc. with formation of
abscesses.  Active lesions possess prominent colonies of Gram + bacilli at periphery, but eventually scar over
and resolve.
4.  Transmission: direct contact
5.  Duration: chronic
6.  Comment:  pathogenesis may differ from mice.  Different organ distribution.  Depopulate.


Erysipelas rusiopathiae

1.  Prevalence:  rare
2.  Diagnosis:  culture lesions
3.  Disease:  a single report from Scandinavia with chronic fibrinopurulent polyarthritis, myocarditis and
endocarditis.  Organism isolated from lesions. 
4.  Transmission:  unknown
5.  Duration:  unknown


Hemophilus spp. 

1.  Prevalence:  rare
2.  Diagnosis:  culture
3.  Disease:  mild inflammation of lower respiratory tract.  Isolation from nose, trachea, lung and female genital
tract.
4.  Transmission:  unknown
5.  Duration:  unknown
6.  Comment:  unclassified species.  Single report, but a high prevalence of infection within the colony.


Klebsiella pneumoniae

1.  Prevalence:  infection common, disease rare
2.  Diagnosis:  culture
3.  Disease:  opportunistic gut microflora, but can be associated with respiratory disease (mild rhinitis) and
abscesses.  
4.  Transmission:  orofecal, contact
5.  Duration:  unknown, probably chronic microflora
6.  Comment:  seldom significant
Leptospira icterohemorrhagiae

1.  Prevalence:  rare in laboratory rats, common in wild rats
2.  Diagnosis:  culture (see mouse)
3.  Disease:  subclinical
4.  Transmission:  urinary, contact, copulation, skin wounds
5.  Duration:  chronic
6.  Comment:  most common L. icterohemorrhagiae in rats, but other species too.  Human infection often
associated with rat origin.  


Mycoplasma spp.  (chronic respiratory disease, murine respiratory mycoplasmosis)
     M. pulmonis
     M. arthritidis
     M. neurolyticum
     M. collis

1.  Prevalence:  common  
2.  Diagnosis:  serology, culture, lesions.  Infected rats may be seronegative for months.
3.  Disease:  often subclinical.  Sneezing and snorting characteristic.  M. pulmonis is only significan natural
pathogen, causing rhinitis, otitis, laryngitis, tracheitis, bronchiolitis, bronchopneumonia with pronounced
bronchiolectasis, bronchiolar lymphoid hyperplasia (strong mitogen) and abscessation.  M. pulmonis can also
cause perioophoritis, salpingitis. Chronic respiratory disease often associated with CAR bacillus and
exacerbated by ammonia, Sendai virus, SDAV, etc.    Other mycoplasmas inhabit respiratory or genital tract
without disease.   M. arthritidis infection can result in seroconversion to M. pulmonis.  
4.  Transmission:  respiratory, contact
5.  Duration:  chronic
6.  Comment:  important rat pathogen


Pasteurella pneumotropica

1.  Prevalence:  common
2.  Diagnosis:  culture
3.  Disease:  opportunistic organism.  Associated with respiratory, ear, reproductive, mammary gland,
conjunctival and skin lesions, abortion.  Co-pathogen with respiratory pathogens (Sendai virus, mycoplasma)
4.  Transmission:  orofecal
5.  Duration:  chronic
6.  Comment:  inhabits respiratory, intestinal tracts as normal microflora


Pseudomonas aeruginosa  - see mouse

Salmonella enteritidis

1.  Prevalence:  low
2.  Diagnosis:  culture (especially mesenteric lymph nodes)
3.  Disease:  similar to mouse.  Often subclinical.  Starry coat, soft to fluid feces.  Cecal ulcers can persist.
4.  Transmission:  orofecal
5.  Duration: acute to chronic.  Approximately 60% of rats remain carriers with intermittent shedding.
6.  Comment:  infection in rats is currently more common than in mice.  Depopulate.
Spirillum minus - see Streptobacillus moniliformis


Staphylococcus aureus

1.  Prevalence:  moderate
2.  Diagnosis:  culture, lesions
3.  Disease:  ulcerative dermatitis over nape of neck, shoulders.  Prominent colonies of Staphylococcus on
surface.  
4.  Transmission:  environmental
5.  Duration:  chronic
6.  Comment:  ulcerative dermatitis probably associated with epidermolytic strains of bacteria, but Koch's
postulates not fullfilled.


Streptobacillus moniliformis

1.  Prevalence:  common in wild rats, rare in laboratory rats
2.  Diagnosis:  culture
3.  Disease:  commensal in rats.  Disease minimal or absent.  Inhabits oropharynx.  Can be transmitted by bite,
causing abscesses in rats, septicemia in mice (see mice) and rat-bite fever (Haverill fever) in humans. 
4.  Transmission:  rat bites, milk, contact
5.  Duration:  chronic carriers
6.  Comment:   Spirillum minus also a cause of rat-bite fever, but not found in laboratory rats. 


Streptococcus pneumoniae (Diplococcus, Pneumococcus)

1.  Prevalence:  low
2.  Diagnosis:  culture lesions, Gram stain exudate
3.  Disease:  subclinical carriers common (80%).  Rhinitis, fibrinopurulent pleuritis, pericarditis, peritonitis,
periorchitis, meningitis, otitis and pneumonia.  Abscesses.  
4.  Transmission:  respiratory, contact
5.  Duration:  chronic carriers/acute disease
6.  Comment:  pathogenicity varies with serotype.  Although mice are susceptible to infection, natural infection
and disease is rare.  Outbreaks of disease can occur among rats.


Streptococcus spp. 

1.  Prevalence:  organism(s) frequently isolated, but specific disease(s) rare
2.  Diagnosis:  culture, lesions
3.  Disease:  high morbitity epizootics with 50% mortality among suckling rats.  Runting, distended abdomens
and fecal staining of perineum.  Large numbers of Gram + cocci on surface of normal appearing villi with
minimal inflammation.  Enterococcus faecium-durans-2 and Enterococcus hirae identified in 2 outbreaks. 
Streptococcus spp. also an opportunistic pathogen.
4.  Transmission:  orofecal
5.  Duration:  unknown
6.  Comment:  likely to be encountered, but sporadic outbreaks

                         INFECTIOUS AGENTS OF RATS




III.  RICKETTSIA


     Hemobartonella muris


IV.  FUNGUS


     Trichophyton mentagrophytes


V.  PNEUMOCYSTIS

     
     Pneumocystis carinii



Hemobartonella muris

1.  Prevalence:  rare
2.  Diagnosis:  organisms on surface of erythrocytes; splenectomy of carriers
3.  Disease:  usually subclinical.  Transient parasitemia, anemia, splenomegaly/
4.  Transmission:  Polyplax spinulosa
5.  Duration:  chronic, but recovery in some
6.  Comment:  severe anemia, parasitemia within 2 weeks of splenectomy.  Steroids do not activate subclinical
infection.


Trichophyton mentagrophytes

1.  Prevalence:  rare in laboratory rats, can be common in wild rats
2.  Diagnosis:  skin scrapings/KOH of lesions, histology with methenamine silver stain
3.  Disease:  subclinical to florid ringworm on neck, back and base of tail.  Patchy hair loss, hyperkeratosis,
erythema.  Arthrospores investing keratin of hair follicles.  
4.  Transmission:  contact.  
5.  Duration:  chronic
6.  Comment:  zoonotic


Pneumocystis carinii

1.  Prevalence:  infection frequent, disease rare
2.  Diagnosis:  lesions, silver stain for cysts
3.  Disease:  pulmonary disease can be induced in naturally exposed young rats by low protein diet combined
with steroids.  Difficult to induce in older rats.  Spontaneous disease not seen in immunocompetent rats and not
reported as a problem in athymic rats.  
4.  Transmission:  unknown
5.  Duration:  chronic
6.  Comment:  carriers very common in conventional, "dirty" rats, especially rats from colonies infected with
multiple viruses (probably a reflection of overall dirtiness)
                         INFECTIOUS AGENTS OF RATS






VI.  PROTOZOA


     Cryptosporidium parvum

     Eimeria spp.

     Giardia muris

     Spironucleus muris




Cryptosporidium parvum

1.  Prevalence:   unknown
2.  Diagnosis:  organisms on brush border of villi
3.  Disease:  probably opportunistic or marginally pathogenic.  Outbreaks of diarrhea with high mortality among
infant rats has been reported.  Surviving pups runted.  Hyperplastic enteritis, especially jejunum, with organiss
toward villus tips.  
4.  Transmission:  orofecal, cysts
5.  Duration:   unknown
6.  Comment:  Experimental infection in rats is mild and transient, except in immunosuppressed or athymic rats.

Eimeria spp. 

1.  Prevalence:  common in wild rats, nonexistent in laboratory rats
2.  Diagnosis:  intestinal lesions, oocysts in feces
3.  Disease:  hyperplastic enteritis, especially in young rats.
4.  Transmission:  orofecal, oocysts
5.  Duration:  chronic
6.  Comment:  see mouse.  Rat has several of its own species.


Giardia muris

1.  Prevalence:  infrequent
2.  Diagnosis:  histology, cysts in feces
3.  Disease:  subclinical or diarrhea.  Low-grade chronic enteritis with trophozoites aligned along brush border
of villi.
4.  Transmission:  orofecal
5.  Duration:  chronic
6.  Comment:  see mouse


Spironucleus muris

1.  Prevalence:  high
2.  Diagnosis:  microscopy of intestine, wet mounts of small intestinal digesta, cysts in feces
3.  Disease:  none or rare in rats.  If disease present, probably opportunistic.  
4.  Transmission:  orofecal, cysts
5.  Duration:  chronic
6.  Comment:  probably not pathogenic in rats
                         INFECTIOUS AGENTS OF RATS






VII.  HELMINTHS


     A.  NEMATODES

          
          Aspicularis tetraptera

          Syphacia muris

          Trichosomoides crassicauda


     B.  CESTODES


          Cysticercus fasciolaris (Taenia taeniaeformis)         

          Hymenolepis nana, diminuta



Aspicularis tetraptera, Syphacia muris (pinworms)

1.  Prevalence:  common
2.  Diagnosis:  ova in feces.  Scotch tape test for Syphacia, adults in lumen
3.  Disease:  none.  Syphacia is only species that deposits ova on anus.  
4.  Transmission:  orofecal.  Ova resistant.
5.  Duration:  chronic
6.  Comment:  see mouse.  Syphacia obvelata and Syphacia muris may be same species.


Trichosomoides crassicauda (bladder thread worm)

1.  Prevalence:  infrequent
2.  Diagnosis:  bipolar ova in urine, worms in bladder, ureters and renal pelves
3.  Disease:  eggs hatch, penetrate stomach wall, migrate through lungs and other viscera and seek urinary tract
epithelium.  Migrating larvae incite eosinophilia and granulomata, especially in lungs.  Adult females burrow in
transitional epithelium, smaller males live in lumen or inside female uterus.  Reaction minimal, but dead worms
may serve as nidus for calculus formation.
4.  Transmission:  urine.  Egg masses stick to environmental surfaces, resistant to dessication
5.  Duration:  chronic
6.  Comment:  drug treatment can be effective


Cysticercus fasciolaris (Taenia taeniaeformis)

1.  Prevalence:  rare
2.  Diagnosis:  cysts in liver
3.  Disease:  incidental finding of strobilocerci, usually in liver.  Rats respond with fibroplasia.  Sarcomas can
develop from reactive zone.  Studied as a model for parasite-induced neoplasia. 
4.  Transmission:  contamination of feed and bedding with cat feces
5.  Duration:  chronic
6.  Comment:  intermediate state of cat tapeworm.  


Hymenolepis nana, diminuta - see mouse

                         INFECTIOUS AGENTS OF RATS





VIII.  ARTHROPODS


     A.  FLEAS


          Leptopsylla spp.
          
          Nosopsyllus spp.

          Xenopsylla spp.


     B.  LICE


          Polyplax spinulosa (spined rat louse)

          Hoplopleura pacifica (tropical rat louse)

     

     C.  MITES


          Demodex spp.  

          Laelaps echidninus (spiny rat mite)

          Notoedres muris

          Ornithonyssus bacoti (tropical rat mite)

          Radfordia ensifera



Rat arthropods

 Arthropods are rare in laboratory rats, except Radfordia fur mites.  Fleas can serve as intermediate hosts for
Hymenolepis and transmit other agents.  Lice can also serve as vectors of disease, including Hemobartonella
(Polyplax) and trypanosomes.  Mites are rare, except Radfordia, which can be common in some colonies.  Non-
pathogenic fur mite.  Demodex found in laboratory rats as an incidental finding, Laelaps transmits Hepatozoon,
but requires absolutely filthy conditions to survive.  Notoedres is ear mange mite.  Burrows in cornified
epithelium, causing pruritis and self-trauma.  Extremely rare in laboratory rats.   Ornithonyssus lives off host
and is non-selective in host range, including humans.  Can cause anemia, debilitation and death in rats.   


