Disease of rat and mice

Bacterial Diseases

> Tyzzer's disease

> Pseudotuberculosis

Salmonellosis

Viral Diseases

> Infectious ectromelia

Infantile diarrhea

> Murine hepatitis virus

> Lymphocytic choriomeningitis

TYZZER'S DISEASE

Tyzzer's disease was first recognized and characterized by Ernest Tyzzer in 1917
Etiology.: Clostridium piliforme, spore-forming, Gram-negative, filamentous bacterium that
propagates only in living cells.
hamsters,
Host: produce disease in a wide variety of other species, including mice, rats, gerbils,
guinea pigs, and rabbits
Pathogenesis:
contaminated bedding for at least l year,
Spores are shed in the feces and it can survive in
and in the natural environment for at least 5 years
animals
Infection occurs by ingestion of spores from environment or feces of infected
> epithelial cells.
ingestion of the spores, the bacterium is phagocytosed by intestinal
> After
vegetative form escapes the phagosome and begins replication in the
Inside the cell, the
cytoplasm
epithelium
> Produce toxins lead tonecrosis of intestinal
into the lumen, or sometimes find their way deeper into
Bacteriaare either deposited back portal
smooth muscle cells or gain access to the
the intestinal wall, where they may infect
circulation
> From the portal vein bacteria mayinfect the liver and/or heart
> Hepatitis and occasionally myocarditis.
1
 Most infections are subclinical.
clinical disease Various host and environmental stressors may
precipitate
Exposure is considered to be primarily by ingestion of
> Organism invades
spores.
intestinal
to the liver via the portal mucosal of the ileum and cecum, the spread of the pathogen
circulation, and hematogenous spread to other tissues such as the
myocardium (and disseminates to other organs, particularly liver and heart
This triad of organ involvement is the
hallmark of Tyzzer's disease.
Clinical signs occur most commonly in suckling and
Sudden death weanling rodents and includes
Watery diarrhea
Lethargy
Ruffled fur
Lesions: Intestine
The primary lesion arises in the
mucosa of the intestine, with grossly visible
and hemorrhages of the ileum and
cecum. congestion
Microscopically, fociof degeneration, inflammation, edema, and necrosis are present in
the intestinal mucosa and muscularis.
Clusters of organisms are apparent in enterocytes and also in
the smooth muscle
Lymphatic vessels and sinuses of mesenteric lymph nodes may contain
cellular debris
Liver:

Miliary pale foci up to 5mm indiameter are usually visible throughout the
the liver, but foci can be large and umbilicated in immunodeficient mice. parenchyma of
Lesions are characterized by multifocal coagulation to caseation hepatic necrosis, with
polymorphonuclear leukocyte infiltration.
Heart

Grey foci in the ventricular myocardium may be present, with myocyte degeneration,
myocarditis, and intracellular bacteria.
Lesions are similar in rats, except that megaloileitis is a common finding
typical
In tissue sections stained with the Warthin-Starry, Giemsa, or PAS methods,
intracytoplasmic bundles of bacilli are usually readily seen in enterocytes, hepatocytes
adjacent to necrotic foci, and myocardial cells.
 Diagnosis
The of Tyzzer's disease can be confirmed by
diagnosis
demonstration of the pathognomonic clusters of intracellular bacilli in tissue sections,
using the Warthin-Starry
The typical bacilli may also be visualized in impression smears prepared from liver lesions
andstained using the Giemsa stain.
Serologic assays are available and utilize whole bacterial lysates as antigen.
Clostridium piliforne can be isolated by inoculation of embryonated hen's eggs, primary
mouse or chick embryo cellcultures, primary mouse or chick liver cells

PSEUDOTUBERCULOSIS

Eiology: Corynebacterium kutscheri is a Gram-positive diphtheroid bacillus affecting rat

and mice

Transmission: The bacteria are spread by direct contact.

Pathogenesis
Entry through oral or enteric mucosa, from which the organisms spread to regional lymph
nodes and hametogenous route to other internal organs.
persist subclinical infection
The organism may as

for long periods with no detectable circulating antibodies.

usual sites for the colonization of C
The
kutscheri in mice are the oral cavity, cecum, and colon.
Clinical manifestations of the disease usually OCcur in

conjunction with predisposing factors that compromise the immune response.

Clinical signs
Infections with C. kutscheri are rare- and usualy clinically silent.
Nonspecific clinical signs may be observed in advanced disease, such as ruffled fur,
hunched posture, dyspnea and rales, porphyria, mucopurulent ocular and nasal discharges,
lethargy, and lameness.
These are usually followed by death in 1-7 days.
Lesions-Gross

Cervical lymph nodes of carrier animals may be enlarged (reactive) but without
abscessation.

3
 Raised, gray white nodules up to I cm in diameter may be present in liver, kidney, and
lungs and, to a lesser extent, inother tissues, including subcutis.
Suppurativeand erosive arthritis may also be present, particularly in the carpal/ metacarpal
or tarsal/metatarsal joints, with marked swelling and erythema.
Conjunctivitis is another manifestation that has been described. Lesions may contain
materialthat varies from friable caseous cxudate to liquefied pus.
Microscopically, lesions consist of coagulation to caseation necrosis, with peripheral
aggregations of leukocytes, dominated by neutrophils.
Suppurative thrombosis and embolization involving the pulmonary or mesenteric and
portal vessels

Clusters of Gram-positive bacilli are present, particularly in the junctional areas between
necrotic centers and peripheral reactive zones.
Diagnosis
Characteristic bacterial colonies, with Chinese letter configurations" of less dense
colonies, are readily evident within suppurative lesions and are best visualized in tissue
sections stained with Brown and Brenn or other Gram stains.

distribution and nature of the lesions

The
consistent with pseudotuberculosis require culture and identification of C. kutscheri.
Diferential Diagnoses include other disseminated chronic bacterial infections that induce
abscesses, including Staphylococcus and Streptococcus, and arthritis associated with
Mycoplasma or Streptobacillus.

SALMONELLOSIS

Etiology : Salmonella enteritidis roughly 1,500 serotypes of that species are gram
negative, non endospore-forming bacteria that colonize the intestinal tracts of a wide
variety of animal hosts.
S. enteritidis serotype typhimurium is the most common serotype infecting laboratory
rodents.

Transmission is via ingestion of contaminated feed ingredients and water and by contact with
contaminated bedding and animal facility personnel
Following ingestion, the mucosa and Peyer's patches in the distal ileum are initial sites
of invasion.

From those sites the organism reaches the mesenteric lymph nodes and gains access to the
vascular system, to be distributed throughout the body.

4
 Lesion development depends upon the distribution of the pathogen. The organs most
commonly infected include the terminal small intestine and the large intestine, lymph
nodes, liver, and spleen.
Pathogenesis
Infection is initiated by ingestion of contaminated feed or bedding
Organisms gain entry to mucosa via fimbrial attachment to Mcells
Uptake through type lll secretion systems that induce phagocytosis by enterocytes, and
modification of the intracellular environment of macrophages to allow survival.
Initial replication in enterocytes is followed by multiplication in gut-associated lymphoid
tissue

Spread to the systemic circulation.

In the liver, bacteria replicate intracellularly within macrophages
Producing focal histiocytic granulomata as the hallmark lesion.
Gross lesions
flecks of blood, and
Ileum and Cecum are frequently distended with liquid contents and
there is thickening of the gut wallin affected areas.
ileum.
Focal ulcerations may be present in the mucosa of the cecum and

Splenomegaly frequently occurs.

characterized by hyperplasia
On microscopic examination, lesions in the ileum and cecum are
with focal
leukocytic infiltration
of crypt epithelial cells, edema of the lamina propria, and
ulceration.
patches, with
There is hyperplasia of the mesenteric lymph nodes, spleen, and Peyer's
focal necrosis and leukocytic infiltration.
In the spleen, focal granulomas, fibrinous exudation, and focal necrosis are typical lesions
present in the red pulp.
Sinusoidal congestion and focal coagulation necrosis are frequent findings in the liver.
Focal embolization may occur in tissues such as spleen, liver, and lymph nodes.

Emboliconsist of bacteria, fibrinous exudate, and cellular debris

Diagnosis
Isolation and identification of the organism from animals with lesions or from inapparent
carriers are necessary to confirm the diagnosis of Salmonella infection.

5
 Diteretial diagmoses include pseudomoniasis, rotaviral enterítis, cryptosporidiosis,
management-related problems and Tyzzer'sdiseaSC.
LYMPHOCYTICCHORIOMENINGITIS
Etiology:
Lymphocytie choriomeningitis virus is a RNA virus of genus arenavirus of the family
Aremaviridae. The natural reservoir host for LCMV is Mus musculus. The primary importance of
LCMV is as azoonosis and as acontaminant of transplantable tumorsand cultured cell lines.
> Enzootic infection of population is maintained by
verticaltransmission from dam to fetus.
>Intection with LCM virus may occur by exposure to saliva or urine from animals
shedding the virus.
Portals of entry include the oronasal route and skin abrasions.
mouse strain
> Patterns of infection difer depending on host and pathogen factors, including
and age, inoculum dose, route.
which follows in utero or
> Typical clinical patterns include the persistent tolerant infection,
neonatal infection.
shedding occur.
> Persistent infection of T-helper lymphocytes, viremia, and lifelong viral
immune complex
Clinical signs include initial growth retardation and eventual
and,
glomerulonephritis accompanied by emaciation, ruffled fur, hunched posture, ascites,
occasionaly, death.
Pathologic features of this pattern include
Necrotizing hepatitis and
Generalized lymphoid depletion
Vasculitis, glomerulonephritis, and lymphocytic
infiltration in multiple tissues, including brain, liver,

adrenal, kidney, and lung.

Lymphocyticchoriomeningitis is generally seen only following experimental intracerebral
inoculation and is not afeature of natural infection
Diagnosis
LCMV can be confimed in suspect tissues
PCR
LCMV is the only virus of mice currently recognized that will kill adults but not
neonates when inoculated intracerebrally, which can be useful
diagnostic bioassay
6
 Serology isnot useful in diagnosis

INFECTIOUS ECTROMELIA/ MOUSEPOX

Marchal (1930) reported an epizootic disease with high mortality in adult mice and termed
it "infectious ectromelia," because of the frequency of limb amputation (ectromelia) in
surviving mice. Ectromelia virus is the causative agent of mousep0x. It is a dsDNA virus in the
family Poxviridae.
Pathogensis

Infectious ectromelia
Invasion of skin or mucus membrane and local replication
Spread and replicate in the regional lymph nodes
PrimaYy viremia
Reach and replicate in liver and spleen
Secondary iremia

Susceptible animals Resistant animals Intermediate animals

Develop disseminated Develop limited Develop disseminated

infection infection infection

Death with in hrs Recovery before Suvive long enough to

and shed little virus shedding irus spread virus toothers
 Infectious ectromelia
Intermediately susceptible animals
Virus disseminated into various organs

Skin Payers patches Liver Spleen Lymphoid organs

Rashes and Necrosis Necrosis Necrosis and Necrosis
gangrene Scaring of red
formation in limbs white pulp

Amputation Hemorhagic Mosaic

enteritis pattern

Clinical signs range from subclinical infection to sudden death.

Acute phase of infection in susceptible surviving mice include
Conjunctivitis
Alopecia
Cutaneous erythema
Erosions (rash)
Swelling and dry gangrene of extremity
Pathologic changes include : massive splenic, lymph node, thymic, and hepatic necrosis; small
intestinal mucosal erosions
Distal portions of the tail and limbs may necrosed and slough, giving rise to the name
ectromelia.

While virus persists for several months in the spleens of infected mice, it is shed in the
feces for only about 3 weeks.
Microscopic lesions
consist of focal coagulative necrosis in the liver, spleen, lymph nodes, Peyer's patches,
and thymus, as wellas other organs
Multiple basophilic to eosinophilic intracytoplasmic inclusion bodies (1.5-6 um) are
evident in infected cells,especially hepatocytes at the periphery of necrotic foci.
 Lymphoid tissue can be hyperplastic and/or focally necrotic, with occasional eosinophilic
cytoplasmic inclusion bodies (type Apox inclusions or Marchal bodies).
Erosive enteritis, often in association with Peyer's patches, is common, with type A
inclusions in enterocytes.
and ballooning of
Skin lesions- consist of focal epidermal hyperplasia, with hypertrophy
epithelial cells and formation of numerous prominent large type A inclusions Gai
Later, skin lesions become erosive and inflammatory in character. are Gals
and erosion
Inclusions, inflammation,
also found in conjunctiva, vagina, and nasal mucosa.

Diagnosis
Based on clinical signs and lesions
typical inclusions is
complex of liver, spleen, and epithelial lesions bearing
The
pathognomonic. mice is GiyC
in
recovered
Splenic fibrosis

also a unique feature of this disease. large

achieved by electron microscopic identification of the strikingly
Confirmation can be
poxvirus particles
Immunohistochemistry, PCR, or virus isolation

INFANT MICE
DIARRHEA/EPIZO0TIC DIARRHEA OF
INFANTILE
Reoviridae, genus
EDIM virus belongs to the family
Etiology:
Rotavirus
and transmission is by the oro-fecal route.
Rotaviruses are shed copiously in feces,
depending primarily upon age.
Clinical disease ranges from inapparent to severe,
susceptible to infection; however, disease is limited to mice less than
Allages of mice are
2 wk of age.
Pathogenesis:
selectively infects terminally differentiated enterocytes of villi and surface
Virus
respectively.
mucosa of the small and large intestine,
in the neonatal bowel and diminish in
These cells are most plentiful and widespread
differentiation as mucosal proliferative
number, distribution, and degree of terminal
microflora.
kinetics accelerate with acquisition of intestinal
replication is retricted to
Viremia is detectable during peak virus replication, but virus
intestinal mucosa.
ClinicalSigns : Diarthoea
" Runted and potbellicd, with loose, mustard-colored
Feces staining the perineum.
Steatorrhea with oily hair
Bowel is flaccid and distended with fluid and gas
Lesions : In infant mice, EDIM virus causes hydropic change and vacuolation of enterocytes at
the tips of villi and large intestinal surface mucosa.
Some nuclei may be pyknotic. Acidophilic intracytoplasmic inclusions are present but
are not diagnostic.
In addition, the lamina propria may be edematous and lymphatics dilated, although
inflammation is minimal.
Diagnosis
EDIM can be diagnosed presumptively on the basis of age, clinical signs, and lesions.
Differential diagnoses include enterotropic MHV, MAdV, reovirus, salmonellosis, and
Tyzzer's disease.
Vacuolation and intracytoplasmic inclusions must be differentiated from absorption
vacuoles of the neonatal apical tubular system that occur in the distal small
intestine,
which may contain solitary eosinophilic globules.
Definitive diagnosis can be achieved by electron microscopy of intestinal mucosa or feces.
Rotavirus antigen can be detected in feces by ELISA, and RNA can be
detected by PCR.
Antigen detection can be accomplished with commercially available rotavirus
diagnostic
kits.

MURINE HEPATITIS VIRUS

Etiology: MHV belongs to the order Nidovirales, family Coronaviridae, genus
Coronavirus. Its official name is Murine Hepatitis Virus (MHV)
Representatives of this type of MHV include the prototype strains MHV-JHM, MHV-A59,
MHV-S, and MHV-3, among others.
Those strains with respiratory tropism initially replicate in nasal
mucosa and disseminate
to avariety of other organs because of their
polytropic nature.
Virus attaches to CEACAMla on cell via spike protein
Primary tropism for upper respiratory tract mucosa
Secondary sites - lung, liver, CNS, intestines, ovaries, epididymis
Disseminated infection to multiple organs is favored by virulent strains of virus, mice less
than 2 wk of age, genetically susceptible strains of mice, or
immunocompromised mice.
10
 Dissemination of MHV from the nose occurs via the blood and lymphatics to pulmonary
vascular endotheliunm and draining lymph nodes, respectively
and
Secondary virenmia disseminates virus to multiple organs, with virus replication
tissues, bone marrow,
cytolytic lesions in central nervous system, liver, lymphoid
primarily in neonatal
Infection of central nervous system by viremicdissemination occurs
immunodeficient mice but not

older, immunocompetent mice.

extension of the virus along
Direct infection of adult mouse brain can also occur by
other organs.
olfactory neural pathways,even in the absence of dissemination to
natural infections
Infectionof mice after weaning age is usually subclinical, particularly in
caused by generally nonvirulent strains of virus.
no
Pathology: The majority of natural polytropic MHV infections are subclinical, with mild or
gross lesions.
of
Liver: Immunocompetent mice may have grossly discernable white foci on the surface
the liver, which can be profoundly obvious and often hemorrhagic in immunodeficient
mice.
In immunode ficient mice infected with relatively low virulence MHV strains, mice may
survive long enough to develop hepatic nodular hyperplasia with parenchymalcollapse
and fibrosis.
Spleen: Foci of splenic necrosis, with splenomegaly due to extramedullary hematopoeisis,
are often present in immunodeficient mice.
CNS: Neurologic manifestations may be observed in immunodeficient mice, and rarely
immunocompetent mice, including vestibular signs and posterior paresis.
Intestine: Lesions are most likely to be found in the terminal small intestine, cecum, and
ascending colon.
Typhlocololitis and meseneteric lymph adenopathy.
Mieroscopic findings in mice infected with polytropic MHV strains are characterized by focal
acute necrosis and syncytia of parenchymal cells and vascular endothelium in multiple
organs, including liver, splenic red and white pulp, lymph nodes, gut-associated lymphoid tissue,
thymus, and bone marrow. Focal peritonitis may also be present.
. Hallmark syncytia are not as obvious in immunocompetent mice, but residua of syncytia
may be found in liver, characterized by large degenerating cells at the periphery of
necrotic foci with dense basophilic apoptotic nuclear bodies.
Syncytia of pulmonary vascular endothelium are common in immunodeficient mice
11
Diagnosis : Diagnosis during the acute stage of infection can be made by visualization of
characteristic lesions with syncytia in target tissue.

12