BB Ch 4 134-158 KD

Question 1

Several species of Streptococcus are opportunistic pathogens in rats. Streptococcus pneumoniae is the species of most historic concern but now considered a pathogen of low significance in laboratory animals.

a) What is the primary route of transmission?
b) Who is the natural host?
c) What is the clinical relevance?
d) What are the most common pathological changes affiliated with S. pneumoniae infection in rats?

Answer 1

a) aerosol; fomites play a role
b) humans
c) Usually a subclinical infection with colonization in the nasopharynx
d) suppurative inflammation of upper respiratory tract, bronchopneumonia, fibrinosuppurative polyserositis.

Question 2

What is the etiologic agent of pseudotuberculosis?

Which species are susceptible to it?

Since the diagnosis of the active disease can be achieved by culture what tissues should be cultured?

Answer 2

Corynebacterium kutscheri

rats, mice, rarely guinea pigs, hamsters

cervical lymph nodes, oropharynx, nasopharynx, middle ears, preputial gland

Question 3

What selective media is used for isolation of C. kutscheri

Answer 3

Furazolidone-malidixic-colimycin agar

Question 4

What should the list of differential diagnosis comprise when multiple abscesses are detected at necropsy?

Answer 4

• Streptococcosis
• Pseudotuberculosis
• Streptobacillosis
• Mycoplasmosis (pulmonary)
• CAR bacillus (pulmonary)

Question 5

Tyzzer’s Disease has a very broad host range, including rodents, rabbits, carnivores, horses, and both human and nonhuman primates.

a) What is the etiologic agent and what is its gram reaction? What are the most common clinical signs
b) What is the most consistent gross lesion and what other lesions may also be seen?
c) In what anatomic location are the causative organisms most readily observed using a silver stain?
d) What are typical histopathological changes?

Answer 5

a) Clostridum piliforme, gram negative; signs are unspecfic: anorexia, lethargy, emaciation, ruffled fur, diarrhea with mucous and blood; disease is usually latent and is more clinical in young, recently weaned animals.
b) megaloileitis, also pale foci in the liver and pale linear lesions on the myocardium
c) cytoplasm of viable cells along the margin of areas of necrosis
d) necrotizing enteritis, coagulative hepatic necrosis, myocardial degernation and necrosis

Question 6

Why is colony screening for latent infection with Tyzzer’s Disease problematic? What is a widely used follow-up test after a serologic positive result?

Answer 6

False positive results are common; disease provocation tests or stress tests to exacerbate latent infections

Question 7

• Pasteurella pneumotropica* is a gram-negative coccobacillus with a low significance in immunocompetent rats, which causes mainly subclinical infections.
  a) When clinical disease occurs what are typical manifestations?
  b) How can it be transmitted?
  c) P. pneumotropica is usually an opportunist and can be a co-pathogen to which two primary infections?

Answer 7

a) conjunctivitis, metritis, mastitis, subcutaneous abscesses, respiratory disease
b) horizontal by fecal-oral and direct contact, vertical
c) M. pulmonis or Sendai virus

Question 8

Salmonellosis may be virtually not existent in laboratory rats in the US but are prevalent among other species and the potential for introduction remains.

a) Is diarrhea the most important clinical sign in salmonellosis?
b) What factors increase the susceptibility to salmonella infection?
c) What are the most common gross lesions?
d) Why is treatment not recommended?

Answer 8

a) no, diarrhea in less than 20% of affected animals; usually unspecific signs like hunched posture, ruffled fur, lethargy, weight loss, conjunctivitis.
b) food and water deprivation, iron deficiency, administration of morphine with slowing of GI motility, pretreatment with sodium bicarbonate by oral gavage.
c) thickening and mucosal ulcers in ileum and cecum, hepatomegaly, splenomegaly
d) induction of chronic carrier state, potential for zoonotic disease

Question 9

List the differential diagnosis for diarrheal disease in rats.

Answer 9

Tyzzer’s disease, rotavirus infection, enterococcal enteropathy, cryptosporidiosis, salmonellosis, dietary problems

Question 10

Pseudomonas aeruginosa is what type of bacteria? What is the significance of pseudomoniasis in rats/lab animals? Why is it extraordinarily resistant to chlorine?

Answer 10

• motile, aerobic, oxidase-positive, almost ubiquitous (water, soil, sewage, skin, and GI tract of most animals)
• low significance in immunocompetent rats, reported as consequence of infection of indwelling jugular catheters
• form biofilm = layers of bacteria, usually with reduced metabolic activity, embedded in a dense glycocalyx

Question 11

Although Streptobacillus moniliformis is non-pathogenic in rats why is it important to keep in mind?

Answer 11

zoonotic agent; on cause of rat-bite fever, wild rats are the reservoir

Question 12

Which Helicobacter spp. have currently been identified in rats?

Answer 12

H. bilis, H. trogontum, H. muridarum

Question 13

What pathogens of rats are transmitted by direct contact only and cannot be detected easily with a dirty bedding sentinel program?

Answer 13

CAR bacillus, Sendai virus

Question 14

CAR bacillus can be detected by ELISA or IFA but false-positive results can occur. What further test(s) should be employed to confirm any positive serology result?

Answer 14

• Steiner stain of tracheal mucosal scraping
• histopathology with use of microwave Steiner silver impregnation technique or Warthrin-Starry silver impregnation technique
• PCR

Question 15

Murine respiratory mycoplasmosis (MRM) is also known as chronic respiratory disease, caused by Mycoplasma pulmonis, and usually clinically silent in young animals. Of all the pathogens in laboratory rats, M. pulmonis has had the greatest negative impact on research.

a) What are the clinical signs seen in older animals?
b) How can it be transmitted?
c) What intercurrent infections are common with MRM?
d) What other factors influence the disease outcome?
e) What is the best site to obtain a sample for a culture?
f) Is it true that MRM alters ciliary function, cell kinetics, and immunity in the respiratory tract?
g) What media, including enrichment media are used to culture Mycoplasma?

Answer 15

a) rales and dyspnea, snuffling and chattering, ocular and nasal discharges, chromodacryorrhea, rubbing of eyes, torticollis, reduced reproductive efficiency
b) horizontal by direct contact and aerosol, vertical, venereal transmission
c) CAR bacillus, Sendai virus, and SDAV, pneumoniavirus of mice
d) host factors like age, strain, immune status, and lymphoreticular function, intercurrent infections, nutritional deficiencies (vitamin A and E) virulence of mycoplasma isolate, environmental factors like intracage ammonia, temperature, humidity
e) nasopharynx, but culturing from multiple sites such as middle ear, trachea, and uterus, improves isolation rate
f) yes
g) Mycoplasma agar, SP4, Chalquest agars, Hayflick’s broth, Frey’s BHI

Question 16

• Mycoplasma hemomuris* is a gram-negative bacterium, order Rickettsiales, family Anaplasmataceae, that parasitizes erythrocytes, is an obligate parasite and cannot be grown in vitro.
  a) When should Mycoplasma hemomuris be suspected?
  b) What are the effects of M. hemomuris on research?

Answer 16

Suspect Mycoplasma hemomuris:

• whenever lice (spiny rat louse - Polyplax spinulosa) are found in a rat colony
• whenever anemia and hemoglobinuria are observed
• whenever biologic material is introduced into a colony

Effect on research:

• reduces the half-life of erythrocytes
• can alter function of mononuclear phagocyte system
• can increase rejection of transplantable tumors
• interfere with research in other blood-borne parasitic disease such as malaria and trypanosomiasis

Question 17

Sendai virus is an RNA virus.

a) What is its classification regarding family, genus, and species?
b) What are clinical significance, contagiousness, and route of transmission?
c) What testing should be done on transplantable tumors, cell lines, and other biological materials to prevent transmission of Sendai virus?
d) What should be done if Sendai virus is introduced into a rat colony of immunocompetent rats?

Answer 17

a) Paramyxoviridae, Respirovirus, Sendai virus (SeV)
b) Usually induces an asymptomatic and self-limiting disease in rats; highly contagious; aerosol, direct contact, and infected material inserted into rats
c) mouse and rat antibody production (MAP, RAP) testing; PCR
d) euthanize pregnant and preweanling rats, halt breeding and introduction of antibody naive rats for 4-8 weeks

Question 18

a) What are the two pathogenic strains of Coronavirus found in laboratory rats? Do they produce distinct clinical signs?
b) Does neutralizing antibodies to one virus prototype offer cross protection to the other strain? Is the induced immunity life-long?
c) What is the tissue tropism of SDAV?
d) What is required to maintain SDAV in a colony?
e) What should the list of differential diagnosis for Coronavirus infection in rats include?

Answer 18

a) Sialodacryoadenitis virus (SDAV) and Parker’s rat coronavirus (RCV-P); No there is no differentiation possible by clincial signs, pathogenicity, or histological lesions.
b) No antigenic differences between RCV-P and SDAV are significant enough to allow cross-infection with either virus; No, rats are susceptible to reinfection as early as 6 months after initial infection
c) Salivary glands, lacrimal glands, Harderian glands, vomeronasal organ, respiratory epithelium
d) Continuous introduction of susceptible stock (weanlings or naive rats) because no carrier state
e) Mycoplasma, Sendai virus, pneumonia virus of mice, stress-associated factors that induce chromodacryorrhea

Question 19

Parvoviruses are single-stranded DNA viruses that have a predilection for mitotically active host cells.

a) What are the names of the parvoviruses that can infect rats? Which of these is associated with natural disease?
b) What is the clinical importance of a RV infection in a laboratory rodent colony?
c) What are possible research complications?
d) To distinguish between the different Parvoviruses what test(s) has to be performed?
e) What are RV, H-3, X-14, L5, HB, SpRV, HER, HHP, KIRK?
f) What are the factors that influence whether the RV infection is persistent?

Answer 19

a) Kilham Rat Virus (RV), Toolan’s H-1 Virus, Rat Parvovirus; only RV is associated with natural disease
b) Mainly subclinical, clinical signs sporadically in preweanling animals, breeding problems may occur such as reduced litter size, runted litters, fetal and neonatal death; no clincial disease with H-1 virus or RVP
c) research complicaitons associated with tropism for mitotically active cells of fetuses, neonates, cell cultures, and tumors; modulates immune function through its tropism for T-cell lymphocytes

• RV infection leads to autoimmune diabetes in the diabetes-resistant BioBreeding rat due to increase expression of macrophage cytokines
• changes NK cell activity in a rat strain dependent manner

d) PCR, hemagglutination inhibition for RV and H-1; ELISA used for diagnosis of Parvovirus infection but no delineation between RV, H-1, or RPV.
e) Strains of RV which contaminate rat tissue or rat-passaged biologic tumors
f) Dependent on RV strain and/or immune-status of host

Question 20

What species beside mice are susceptible to PVM (pneumonia virus of mice)? What are prominent lesions seen in the acute phase?

Answer 20

• rats, gerbils, hamsters, guinea pigs, rabbits
• virus does not cause clinicial disease, but lesions are multifocal, nonsuppurative vasculitis and interstitial pneumonitis with necrosis, which may persist for several weeks.

Question 21

Which are the two important Paramyxoviruses in rats and what 2 lab species serve as a source of infection?

Answer 21

• Sendai virus, PVM
• mice and hamsters

Question 22

What clinical symptoms could be caused by the Rota-virus like agent?

Answer 22

Diarrhea in suckling rats, erythema and hemorrhage of the perianal skin; cross infectivity between rats and humans is suspected.

Question 23

a) Which group of viruses causes HFRS and what stands the acronym for?
b) Is it zoonotic? How is it transmitted?

Answer 23

a) Hantavirus - Hemorrhagic Fever with Renal Syndrome
b) Yes, via infected lab or wild rats via aerosols from lung, saliva

Question 24

Protozoa are of little consequence in laboratory rats in recent decades.

a) Why?
b) Name 3 protozoa of potential significance.
c) What is the classic histopathological lesion of Encephalitozoon cuniculi and which species is the main reservoir?
d) How can Toxoplasma gondii be differentiated from E. cuniculi?
e) How is Spironucleus muris best diagnosed?
f) What is a special characteristic of Giardia muris trophozoites?

Answer 24

a) No spontaneous disease due to any naturally occurring enteric protozoa of lab rats has been reported; parenteral infections rare in lab rats becasue of absence of vectors; almost universal use of high-quality, heat-disinfected diets
b) Encephalitozoon cuniculi, Sprionucleus muris, Giardia muris
c) Meningoencephalitis with multifocal granulomatous inflammation, organism my occur intracellularly in the renal tubular epithelium with or without presence of an inflammatory response and in the renal tubular lumen; considered ubiquitous in rabbits, many other mammals susceptible such as mice, hamsters, guinea pigs, dogs, nonhuman primates, humans.
d) E.cuniculi stains poorly with H/E but well with gram stain(+) where T. gondii stains well with H/E and poorly with gram stain
e) Examination of wet mounts of duodenal scraping of weanling rats, phase-contrast microscopy and characterisitic rolling of flagellated trophozoites.
f) Characterisitic piriform or teardrop shape with a broad, rounded anterior tapering to a pointed posterior end.

Question 25

What 3 species of oxyurid nematodes occur in laboratory rats and how are the best diagnosed?

Answer 25

Syphacia muris, Syphacia obvelata, Aspicularis tetraptera

diagnosis most practically accomplished by direct examination of macerated cecum and colon under low magnification with stereomicroscope, perianal tape test for Syphacia and fecal flotation for Aspciularis less sensitive

Question 26

Is the trichurid nematode Trichosomoides crassicauda of importance in barrier maintained rodents? Explain the migratory pattern of this parasite in the rat.

Answer 26

Very rare, only found in rat, and is subclincial

adult parasite lives in urinary bladder, either free in the lumen or embedded in mucosa, embryonated eggs passed in the urine are ingested, hatch in the stomach, larvae penetrate the wall, pass through the peritoneal cavity or bloodstream to reach the lungs or other tissues, only those that reach kidney or bladder survive and mature; life cycle is 8-9 weeks.

Question 27

What are the primary differences of consequence between the two species of cestodes likely to be encountered in lab rats?

Answer 27

**Rodentolepis nana **– direct life cycle and zoonotic

R. diminuta - indirect life cycle and not zoonotic (intermediate hosts of grain beetle and flea)

Question 28

What is the most likely cause of acariasis in laboratory rats?

Answer 28

Radfordia ensifera

R. affinis or Myobia musculi also possible

Question 29

Which species is responsible for pediculosis in rats? How long is the entire life cycle? What other diagnostic test is considered mandatory if lice are detected in lab rats?

Answer 29

• Polyplax spinulosa
• 2-5 weeks
• blood smear to screen for Mycoplasma hemomuris

Question 30

Like in other species, fungal infections are usually only of relevance in rats when they are immunocompromised.

a) What fungal agent is latently present in the lungs of immunocompetent laboratory rats? How can clinical disease be elicited?
b) What is the characteristic of clinical disease and what are the histopathological features?
c) How can it be diagnosed and what is the antibiotic of choice to control the disease?

Answer 30

a) Pneumocystis carinii; administration of corticosteroids or cyclosphosphamide, at least 6 weeks of treatment to elicit typical histopathological lesions.
b) chronic wasting and respiratory insufficiency; multifocal alveolar aggregates of cysts with interstitial and pervascular infiltrates in less severe cases or pulmonary consolidation with foamy, eosinophilic, honeycombed alveolar exudation and severe interstitial bibrosis
c) special stains such as methanamine silver demonstrate fungal cysts within alveoli and PCR; trimethoprim-sulfmehoxazole

Question 31

Which organism may cause ringworm in rats?

Answer 31

Trichophyton mentagrophytes

Question 32

List two reasons why nutritional deficiencies are uncommon in lab rats?

Answer 32

• High quality commercial diets are used universally
• rats store fat-soluble vitamins and vitamin B12
• rats manufacture C and fulfill many of their requirements by coprophagy

Question 33

Which injectable anesthetic may lead to lethargy, anorexia, and distended abdomen due to adynamic ileus?

Answer 33

Chloral hydrate

Question 34

What are the three most sporadically occurring neoplasms in aged animals in Sprague-Dawley and what in F-344?

Answer 34

• SD:
  
  • pituitary adenoma/carcinoma (~75%)
  • mammary gland tumors
    
    • fibroadenoma (31%)
    • carcinoma (18%)
• F-344:
  
  • testicular interstitial cell tumors (78%)
  • Large Granular Cell Leukemia (17%)
  • pituitary adenoma/carcinoma (16%)

Question 35

Large granular lymphocytic leukemia is a major cause of death in F-344 rats. Is it true that there is a virus etiology?

Answer 35

No; it is not associated with a retrovirus like in mice

Question 36

What is one of the more commonly reported congenital defects of rats?

Answer 36

• Hydronephrosis - uni- or bilateral dilation of renal pelvis
• inherited as a single dominant gene in the Gunn rat
• polygenic in SD and BN

Question 37

Which congenital and genetically determined ocular abnormalities have been reported in rats?

Answer 37

• Albino rats - retinal atrophy due to unpigmented tapetum lucidum
• F-344 - corneal mineralization that varies from 10-100% depending on subline
  
  • deposition of calcium salts, often visible in routinely stained sections as basophilic granules, along the interface of the corneal epithelium and stroma
• Various strains = retinal degeneration, catarats, osseous and cartilaginous metaplasia of the sclera

Question 38

What is the most important age-related non-neoplastic disease in rats, which gender is most often affected, and what are the gross lesions

Answer 38

• Chronic progressive nephropathy (CPN) in male rats
• pitting of the cortical surface, cortical fibrosis, irregular surface and tearing of capsule

Question 39

Chronic myocardial disease is a major cause of death in aged male rats of multiple strains. What are the most commonly affected myocardial sites?

Answer 39

Papillary muscles and interventricular septum

Question 40

Eosinophilic granulomatous pneumonia is a condition that spontaneously develops in what strain of rat?

Answer 40

Brown Norway

Question 41

Polyarteritis nodosa is a conditon most frequently described in what strains of rats? What is the sex predilection?

Answer 41

Sprague-Dawley and SHR

Males more frequently affected

Question 42

Which strain of rat has a hight incidence of interstitial cell testicular tumors? What is the cell of origin?

Answer 42

F-344

Leydig cells

Question 43

What is the most likely diagnosis and strain?

Answer 43

Large granulocytic leukemia

Fischer 344

Question 44

Recommendation to prevent this condition?

Answer 44

Light levels 325-400 lux measured at 1 meter above the floor

Question 45

In what strains is this condition more commonly seen?

Answer 45

Sprague-Dawley, Fischer 344

Question 46

Name age-related diseases and tumors for which F-344 rats have a higher incidence.

What about lower incidence?

Answer 46

Higher: chronic progressive nephrosis

nephrocalcinosis

testicular interstitial cell tumors

large granular lympocytic leukemia

Lower: adrenal gland pheochromocytoma