BACTERIAL DISEASES

I. 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 some conventionally-housed research 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.

II. CAR Bacillus

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.

III. Streptococcal Disease

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.

VI. Staphylococcal Dermatitis

A syndrome of ulcerated to scabby skin lesions on the dorsal cervical or cranial regions occur frequently in some rat colonies (A.). This syndrome appears to be seasonal with most cases occurring in the spring and occasionally the fall. Trauma to the skin from fighting, scratching, etc. is thought to be an inciting factor. In colonies of rats on dermal toxicity studies, the shaving of the skin as well as the substance application provides the skin irritation necessary to initiate scratching. In many cases, Staphylococcus sp., including S. aureus and S. epidermidis, have been isolated from the wounds. Since Staphylococcus sp. can be frequently isolated from the nasopharynx and feces of rats with dermatitis, the fastidious grooming and scratching activities of the rat provide a constant source of staphylococcal inoculum for the wound. The skin lesions are excoriations of varying sizes with a serous to sanguinous discharge. Successful treatment of the dermatitis with topical antibiotic or antibiotic/steroid ointments has been reported. Combination therapy of oral benadryl (10 mg/kg) and chloramphenicol (50 mg/kg) has resulted in resolution of ulcerative lesions. Length of therapy may be prolonged if the initial irritating stimulus is not corrected. Clipping toenails of the hind foot has allowed healing of the wounds without antibiotic therapy.

V. 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.

VI. Tyzzer's Disease

A. Etiology: Clostridium piliforme is a gram-negative, obligate intracellular rod that produces spores.

B. Transmission: Infection is established via the fecal-oral route by ingestion of spores. Predisposing factors to disease include age (commonly 3 to 7 weeks) and physiological stresses such as concurrent infections, experimental manipulations, or poor housing conditions. Incidence of disease is low in the rat.

C. Clinical Signs: Subclinical infection is the most common form of infection in the rat. Clinical manifestations of Tyzzer's disease include anorexia, hunched posture, distended abdomen, rough hair coat and death. Diarrhea has not been reported in the rat.

D. Gross Pathology: A "fat rat" syndrome with a flaccid segmental dilatation of the intestine (especially of the ileum) has been described. The liver typically has multiple pale foci throughout. Circumscribed, greyish foci may sometimes be observed in the myocardium. Multiple necrotic foci in sections of liver and myocardium are often surrounded by a pyogranulomatous cellular infiltrate. Silver stains (Steiner or Warthin-Starry) will help deliniate the bacterium (arrow), which can be observed within the cytoplasm of viable cells bordering the necrotic foci.

E. Diagnosis: Since the organism cannot be propagated on artificial media, histopathologic diagnoses are made by demonstration of the bacillus in the enterocytes, hepatocytes or cardiac myocytes bordering necrotic foci in tissues stained with silver stains. A serological assay and a PCR assay have been developed to identify C. piliforme infected rats.

F. Treatment: Oxytetracycline at 0.1 mg/ml water for 30 days was reported to abate mortality of an epizootic in mice. Treatment is usually not warranted.

G. Control: Avoidance of stress and strict sanitation help prevent outbreaks. Spores are very resistant to deterioration in the environment and are resistent to most disinfectants except bleach. Cages and bedding should be decontaminated by autoclaving prior to routine washing.

VII. Other Bacterial Diseases

Rats are reservoirs for bacterial diseases that are pathogenic to man. Salmonellosis, especially Salmonella enterica serovars Enteritidis and Typhimurium have been diagnosed in research and pet rats. Salmonellae are Gram-negative toxin-producing enteric bacteria that are transmitted through contact with infected feces. Rats are frequently asymptomatically infected, and rarely exhibit systemic infection. Definitive diagnosis of infection is provided by culture on selective media such as selenite, brilliant green and MacConkey agars, with subsequent serotyping of the isolate. Another zoonotic pathogen harbored by rats is the agent of rat bite or Haverhill fever. The most common etiologic agent is Streptobacillus moniliformis, and rats carry S. moniliformis asymptomatically in the nasopharynx. The bacterium is a Gram-negative pleomorphic rod which requires media supplemented with 20% serum or ascites fluid for cultivation. The incidence of infection of either of these agents in laboratory rats is rare. There is no information about the incidence of infections in pet rats.

Public Health Significance: Humans ingesting Salmonella - contaminated food or water experience a transient diarrhea. Children or immunosuppressed adults are susceptible to more serious clinical disease from Salmonella infection. People infected with S. moniliformis develop irregular recurrent fever with lymphadenopathy, petechial hemorrhages, polyarthritis and endocarditis. Bacterial infections respond well to tetracycline therapy.