II. Coronaviruses (RCV and SDAV)
III. Murine Respiratory Mycoplasmosis (MRM)
IV. Pseudotuberculosis (Corynebacteriosis)
V. Rat Respiratory Virus
VI. Respiratory Viruses (Sendai Virus and PVM)
VII. Streptococcal Disease
A. Etiology: Cilia - Associated Respiratory (CAR) Bacillus is a filamentous bacterium of unknown taxonomy found parallel to and among the cilia of the respiratory tract. The bacterium is frequently found in rats concurrently colonized with Mycoplasma pulmonis; however, CAR bacillus is capable of causing respiratory disease as a mono-infection.
B. Transmission: Direct contact is the likely mode of transmission. The bacillus is not readily transmitted by fomites. The incidence of infection is not known.
C. Clinical signs: Chronic respiratory disease similar to mycoplasmosis have been described.
D. Pathology: The bronchopneumonia from CAR bacillus
infection is similar to that of mycoplasmosis. The right middle lobe
appears to be the most commonly affected site. 
Peribronchiolar lymphoid hyperplasia with transmucosal lymphocyte
migration as in mycoplasmosis is suggestive of CAR bacillus. Silver stains
and immunofluorescent techniques will demonstrate the organism (arrow)
in tissues.
E. Diagnosis: The inability to culture CAR bacillus in cell-free media and poor staining with aniline dyes make the diagnosis difficult. PCR can be used to identify the organism from nasal swabs collected from infected animals. A commercially available ELISA can detect an antibody response to infection.
F. Control: The disease is poorly understood, so control of infection is unknown at this time. Antibiotic treatment with ampicillin has been proven effective in mice. CAR bacillus often accompanies infection with Mycoplasma pulmonis, so antibiotic treatment may not resolve clinical disease. Identification of infected colonies and rederivation along with good husbandry would be reasonable control methods.
II. Coronaviruses (RCV and SDAV)
A. Etiology: Coronavirus is an RNA virus with 2 strains identified to cause disease in rats. Rat coronavirus (RCV) causes respiratory infection while sialodacryoadenitis virus (SDAV) infects the upper respiratory tract, Hardarian and exorbital lacrimal glands, and the submandibular and parotid salivary glands. The SDAV strain causes clinical disease.
B. Transmission: RCV/SDAV is highly contagious and is spread by aerosol, direct contact, and fomites. No latent infection or carrier state occurs. The incidence of infection is high.
C. Clinical Signs: Viral infection is not fatal, and is
generally subclinical. Rats infected with SDAV may exhibit a porphyrin
oculonasal discharge. The submandibular salivary gland may be palpably
enlarged due to sialoadenitis (see photo). Dacryoadenitis may cause
exophthalmos, which can lead to keratitis and corneal ulcers. Symptomatic
rats are at a greater risk for inhalation anesthesia. Chronic exophthalmos
can result in exposure keratitis. 
D. Pathology: Lesions include enlarged submandibular and
parotid salivary glands, edematous cervical lymph nodes, swollen lacrimal
glands, and yellow-grey foci in Harderian glands (brown-red mottling of
the Harderian gland is normal due to porphyrin production). 
Histopathological examination of submandibular salivary glands
reveals degenerative changes including acinar and ductal epithelial necrosis,
interstitial edema, squamous metaplasia of ductular epithelium followed
by proliferation of hyperchromatic acinar cells. Chronic lesions
include replacement of acini with fibrous connective tissue and an infiltration
of lymphocytes. Similar lesions are present in the lacrimal and Harderian
glands. The sublingual salivary gland (mucous gland) is usually not
affected.
E. Diagnosis: The most common diagnostic test is serologic screen for antibody and include ELISA and immunofluorescent antibody assays. Coronavirus PCR assays will help detect RCV or SDAV in acute infections. SDAV PCR samples include Hardarian gland or submandibular salivary gland, and while lung is the optimal RCV sample.
F. Control: No carrier state exists, and recovered rats are free of virus and are immune. Cessation of all breeding activity in a production colony for 60 days and concomitant removal of all suckling and weanling animals or intentional exposure of these young rats by frequent mixing will eliminate the infection in the colony. The immune status of the colony and of any new rats to be introduced should be monitored serologically.
III. Murine Respiratory Mycoplasmosis (MRM)
A. Etiology: MRM is caused by Mycoplasma pulmonis. MRM is typically a chronic disease of the upper and lower respiratory tract. MRM shortens the life span of the rat, and leads to experimental results of dubious value.
B. Transmission: Direct contact, aerosol, and intrauterine (congenital) are three known modes of transmission. M. pulmonis has been identified in many conventionally-housed colonies and pet store animals.
C. Clinical signs: Most infections are subclinical with Mycoplasma
carried in the upper respiratory tract and uterus. The acquisition of primary
viral or bacterial respiratory pathogens enhances subclinical mycoplasmal
infections. Early signs of overt disease may include a red (porphyrin)
oculonasal discharge, and nasal stridor.
As the organism travels along the respiratory tract, otitis media, labored breathing, ungroomed hair coat, anorexia, chattering and coughing, and hunched posture may be observed. Chronic uterine infections may result in decreased litter size, but usually no clinical reproductive disorder is noticed.
D. Pathology: A purulent discharge may be found on the nasal
mucosa and within the tympanic bullae. Purulent exudate can be found
in the trachea and in the bronchi. In some cases, the lungs may be
grossly normal. In pneumonic lungs yellow foci of bronchiectasis
and red to grey areas of consolidation are found in the lung (A.).
Infected uteri may contain fluid in the horns and oviduct (hydrosalpinx).
Histopathological examination of the lungs may show peribronchiolar lymphoid
hyperplasia (B.). Care should be taken not to confuse the bronchiole-associated
lymphoid tissue (BALT), which is normally present in rat lungs, with a
lesion of mycoplasmosis. A purulent bronchopneumonia may also be present.
Immunocytochemical techniques can also be used to identify the organism
on tracheobronchial histologic sections.
. 
E. Diagnosis: The mycoplasma media needed for primary recovery must contain swine or horse serum and yeast extract supplementation. Commercially available mycoplasma media can be purchased for isolation of M. pulmonis. An ELISA is commercially available for serological screening for Mycoplasma pulmonis infections in mouse and rat colonies. Sera from animals older than 2 months of age are preferable since infected rats less than 8 weeks of age are often serologically negative. There is also a PCR test for M. pulmonis.
F. Treatment: The overt disease is suppressed by antibiotic therapy. Long-acting oxytetracycline (60 mg/kg subQ every 3 days), tetracycline (3 to 5 mg/ml water), and sulfamerazine (0.02% in water or 1 mg/4 gm food) have all been reported to reduce mortality. A carrier state will probably remain after treatment. Rats on research projects are usually not treated.
G. Control: Quarterly screening of animals in "at risk" colonies by performing ELISA on sera from adult rats and cesarian derivation and fostering of pups from infected dams are recommended control measures. Since intrauterine infection can occur, infection may persist despite cesarian derivation. Cultural and serologic screening by ELISA of fostered litters and foster dams will allow assessment of the success of the rederivation. Rigid sanitary measures are essential.
IV. Pseudotuberculosis (Corynebacteriosis)
A. Etiology: Corynebacterium kutscheri is a gram-positive short rod.
B. Transmission: The bacteria are spread by direct contact. The bacteria is thought to be harbored in the nasopharynx resulting in a chronically colonized animal. A subclinical infection is the most common form of infection. Overt disease is precipitated by physiological stressors (disease, pregnancy, corticosteroids). The incidence of infection is unknown, but sporadic epizootics occur.
C. Clinical Signs: Once stressed, the rat may exhibit the typical sick rat syndrome (rough hair coat, hunched posture, anorexia) accompanied with dyspnea and an oculonasal discharge.
D. Pathology: Large, often coalescing, white caseated purulent
foci are present in the lungs (A.). Unlike the disease in the mouse,
lesions in organs other than the lungs are uncommon. Histologically, purulent
foci are parenchymal (B.) and generally do not involve the large airways
since the bacterium is believed to gain access to the lungs via the vasculature.
Gram-stained lung sections or impression smears of lesions will reveal
small gram-positive rods (C.).
. 
. 
E. Diagnosis: Culture of pulmonary abscesses on 5% blood agar provides the definitive diagnosis. A selective medium has been developed which enhances C. kutscheri isolation from nasopharynx and intestinal contents, sites of colonization in subclinically colonized rats. The FCN agar is brain heart infusion agar with 80 ug/ml furazlidone, 15 ug/ml naladixic acid, and 10 ug/ml colimycin. To date, there is no commercially available serologic test.
F. Treatment: There is no recommended antibiotic treatment based in part from the difficulty in identifying subclinically infected rats.
G. Control: Colonies can be replaced with uninfected rats, or cleaned up by identification and elimination of carrier animals and their contacts, or by cesarean rederivation.
A. Etiology: A respiratory disease has been identified in research rats and is believed to be caused by a virus tentatively identified as "Rat Respiratory Virus" or RRV. This agent has been cultivated from infected rat lungs and has been used to reproduce the disease, however, the taxonomic classification of the virus has not been completed.
B. Transmission: This virus is believed to be transmitted by direct contact and through fomites. RRV infection has been identified in rats from research colonies world-wide.
C. Clinical Signs: Rats show no clinical signs associated with RRV infection.
D. Pathology: The lesions associated with RRV are unlike those of other spontaneous rat viral infections and occur sporadically in rats from infected colonies. Gross pulmonary lesions include 1 to 4 mm grey flat to raised foci randomly distributed throughout all lung lobes at the peak of disease (A.). Microscopically, pulmonary lesions consisted of angiocentric inflammatory cell infiltrates which extended to the surrounding interstitum. The character of the inflammatory cell infiltrates and severity of lesions vary with age of rat. In rats 8-10 weeks of age, granulocytic (neutrophil and eosinophils) perivascular infiltrates are the predominant lesion. Peak lesions are observed in rats 10-12 weeks-old and include pyogranulomatous perivascular infiltrates with interstitial pneumonia characterized by thickening of neighboring alveolar septae with neutrophils, lymphocytes and macrophages and pneumocyte hyperplasia (B and C.). Lymphocytes, neutrophils, red blood cells and macrophages frequently accumulate in alveolar lumina. In some cases, advanced pneumonia resulted in consolidation of focal regions of the lung. Lungs from rats 18 weeks and older in age have perivascular lymphoid infiltrates and multifocal alveolar macrophage aggregates with minimal consolidation suggestive of lesion resolution.
E. Diagnosis: Current diagnostic strategies are limited by the incomplete characterization of the viral agent. Histopathological survey of 10-12 week-old is the most commonly used method. An IFA test is under development, and correlates well with histopathology for disease diagnosis.
F. Control: Comprehensive control measures have not been established since there is so little known about the virus. Stocking of colonies with RRV-free rats is possible, and isolation of these rats from other rodents is important since there is some preliminary evidence that the rat may not be the only susceptible rodent host to RRV infection. Rederivation techniques have not been extensively evaluated for effectiveness in eliminating disease.
VI. Respiratory Viruses (Sendai Virus and PVM)
A. Etiology: Sendai virus is an RNA paramyxovirus of the parainfluenza type 1 group, and PVM is an RNA paramyxovirus of the pneumovirus group.
B. Transmission: The primary route of infection is by direct contact with infected animals during the first two weeks of infection when the virus is shed. The disease is usually enzootic in a colony in which susceptible animals are regularly introduced. The incidence of disease in research colonies is rare for Sendai virus and low for PVM.
C. Clinical Signs: Respiratory virus infections usually produce no clinical disease. Sendai virus is immunosuppressive and concomitant respiratory infections with the other respiratory pathogens of rats may occur.
D. Pathology: Gross lesions associated with uncomplicated respiratory virus infection are uncommon. Histologic lesions may include mild perivascular lymphocyte cuffs.
E. Diagnosis: Most respiratory virus infections are identified by screening sera by ELISA for anti-Sendai and for anti-PVM antibody.
F. Control: The viral infections are self-limiting. A constant introduction of naive rats will perpetuate infections in a colony. Cessation of all breeding activity in a production colony for 60 days and concomitant removal of all suckling and weanling animals or intentional exposure of these young rats by frequent mixing will eliminate virus infection in the colony.
A. Etiology: Streptococcus pneumoniae is an alpha-hemolytic, gram-positive diplococcus.
B. Transmission: Direct contact and aerosol are the known routes of infection. Guinea pigs may carry the bacteria in the upper respiratory tract. Humans also may carry the bacteria in the upper respiratory tract but there is no direct evidence that humans and rats have shared streptococcal infections. The incidence of infection in rats is low.
C. Clinical Signs: Typical "sick rat" signs such as serous to mucopurulent nasal discharge, rhinitis, sinusitis, and conjunctivitis may be observed. Younger age groups are particularly affected.
D. Pathology: Fibrinopurulent pleuritis and pericarditis,
fibrinous lobar pneumonia, consolidation of lung lobes, frothy, serosanguinous
fluid in trachea, and otitis media are common necropsy findings.
The fibrinopurulent nature of the exudate is characteristic of the bacterial
infection. Histopathologic examination of the lungs reveals a fibrinopurulent
bronchopneumonia.
E. Diagnosis: Diagnostic tests include gross pathology,
Gram stain of tissue impression smear revealing gram-positive lancet-shaped
bacteria in pairs (see phoito), histopathological examination of lungs
(a fibrinopurulent bronchopneumonia); and culture of affected tissues on
blood agar with observation of growth inhibition in the presence of optochin
discs.
F. Treatment: Oxytetracycline at 0.1 mg/ml in the drinking water for 7 days has controlled mortality in epizootics but has not eliminated the carrier state. Penicillin and enrofloxacin may also be tried.
G. Control: The basic practices of good husbandry apply in controlling the disease. Do not mix rats from different sources. Do not house rats in the same room as guinea pigs. Reduce environmental stresses.
Back to Disease Categories