CAR bacillus

Filobacterium rodentium (formerly CAR Bacillus, Cilia-associated Respiratory Bacillus)

Definition

CAR bacillus (as of 2016 renamed Filobacterium rodentium) is a Gram-negative, gliding, filamentous rod-shaped bacterium that colonizes the ciliated epithelium of the respiratory tract consisting of the lungs, the middle ears, the trachea, larynx, and the nasal passages. It is elongated with rounded ends and has a three-layered cell wall. It has yet to be classified.

Clinical Signs

Signs of infection, in rats, are like those of Murine Respiratory Mycoplasmosis and may include any of the following:

Rattled breathing
Labored breathing
Rapid weight loss
Hunching posture
Rough coat
Wheezing
Lethargy
Head tilt
Porphyrin discharge from eyes and nose

Rats may also be colonized by CAR bacillus, but not show clinical signs (asymptomatic disease).

*Note: Being a prey species, rats often will not show signs of illness until they are very sick. Clinical signs would indicate the need for immediate treatment by a veterinarian.

Etiology

CAR bacillus is spread by direct contact between rats. There is conflicting evidence as to whether or not it can be spread through fomites such as bedding and cage litter. CAR bacillus is not likely spread by aerosol transmission.

CAR bacillus is highly contagious. It occurs naturally in a percentage of both domesticated and wild rats. It also occurs in several species of mice and in rabbits.

CAR bacillus resides among and parallel to the cilia throughout the respiratory system. Cilia are tiny hair-like protrusions that extend from the surface of some cells and move in a wave-like fashion. Through a continuous beating movement, they function to move mucus and fluid that included entrapped contaminants out of the respiratory tree. Being mechanisms that have not been elucidated, CAR bacillus infection may disrupt this function resulting in accumulation of airway mucus airways and possible destruction of cilia. When cilia are damaged or missing, the body’s natural defenses against invading bacteria and ability to handle infection are decreased.

As a natural defense the body will send neutrophils (a type of white blood cell) in an attempt to envelope and destroy the invading bacteria. Unfortunately, not only are these neutrophils unable to destroy the CAR bacillus they also produce antibacterial compounds and pus that can damage the host.

When clinical signs of disease are present, bronchopneumonia, bronchiectasis (dilatation of one or more bronchioles with filling of bronchi with mucus and pus) and atelectasis (failure of lung to inflate leading to consolidation of lungs, obstruction and prevention of air intake) may be found.

CAR bacillus can act as a primary pathogen and result in a chronic progressive respiratory disease. More typically it is seen as a co-pathogen, often in association with Mycoplasma pulmonis. It may increase the severity of disease caused by M. pulmonis and other respiratory pathogens. The host produces antibodies to CAR bacillus, however, these antibodies are ineffective at clearing the infection.¹

Antibiotics can be used to help manage the clinical signs of CAR bacillus infection, but will not eradicate the pathogen.

Figure

Fig.1: Photos of CAR bacillus infection in lung and tissue, courtesy of:
University of Missouri – Comparative Medicine Program and IDEXX-BioAnalytics (IDEXX RADIL),
and Craig Franklin, DVM, PhD, Associate Professor.

Diagnostics

Diagnosis of CAR bacillus infection can be difficult. Diagnostic methods include serology (ELISA), PCR and microscopic examination of tissues (can only be performed on a rat that has died).

Serology (ELISA; enzyme-linked immunosorbent assay) can be used to test for CAR bacillus. ELISA measures antibodies produced by the host (must be at least 6 weeks old) and found in the serum. An animal with an intact immune system exposed to CAR bacillus will produce antibodies (for testing purposes) within 7-10 days. Serology serves as a good screening tool because it is inexpensive, relatively sensitive, and can be performed on blood collected from a live rat. However, as with most bacterial ELISAs, this test is subject to false positive results. As a result, all positive serology results should be confirmed by other means. Negative serologic results likely indicate that CAR bacillus is not a problem; however repeat testing may be warranted in some cases due to the aforementioned delay between infection and antibody production.

PCR (polymerase chain reaction) is a fast and specific test for this bacterium. It can be performed on nasal swabs (use small uro-genital swabs). To collect a nasal swab, you will need to have your rat anesthetized during the collection.

The cost of an individual PCR test can range from approximately $50.00 – $80.00. The University of Missouri’s IDEXX RADIL, Research Animal Diagnostic Laboratory, charges $55.00 per PCR assay test. *Note: cost may be subject to change.

Microscopic examination of tissues is very specific test for CAR bacillus as the presence of the organism can be verified in the lung tissue. Tissue sent in for testing should be stained using both hematoxylin and eosin (a general stain for tissue lesions) and a silver stain such as Warthin-Starry or Steiner (used to identify bacteria colonizing the respiratory mucosa). Specific immunohistochemical techniques may also be employed, but these are often expensive and do not provide sufficient additional information to be cost effective.⁶ CAR bacillus spreads through the respiratory system in a descending manner. Therefore, the nasal passages and trachea will usually show infection first. This testing is restricted to postmortem examinations.

Electron microscopic examination of affected areas of the respiratory tract tissue will show the CAR bacillus residing amongst the ciliated regions.

Electron microscopy is very expensive and used primarily as a research tool.

Testing Facilities

University of Missouri-IDEXX-BioAnalytics Animal Health Monitoring Laboratories (IDEXX RADIL):
https://www.idexxbioanalytics.com/microbiology

Charles Rivers Laboratories: (800)338-9680
https://www.criver.com/products-services/research-models-services/animal-health-surveillance?region=3601

UGA Veterinary Diagnostic Lab:
https://vet.uga.edu/diagnostic-service-labs/veterinary-diagnostic-laboratory/

Treatment

There is no specific antibiotic indicated for treating CAR bacillus at this time. In the lab it has shown sensitivity to multiple antibiotics, and in the test tube it has been killed. Unfortunately, this has not translated well into actual treatment success in infected rats.

Since CAR bacillus infection is often seen in conjunction with M. pulmonis infection, it may help to treat the rat with broad-spectrum antibiotics that typically help to control the signs of that disease. If the rat is not responding, then switching to a different antibiotic(s) may be appropriate. Nebulized antibiotics, or a combination of nebulized and oral antibiotics, may prove to be more effective in treating this bacteria.

For a listing of antimicrobials and broad-spectrum antibiotics see the Rat Medication Guide. Also refer to listings in the Rat Health Guide articles: Mycoplasmosis, or Pneumonia, for additional therapies based on severity of signs.

*Note: In Japan, research studies on mice have shown some success in controlling, preventing, and even eradicating CAR bacillus using sulfamerazine³. Ampicillin has also been reported to have successful results in treating mice with CAR bacillus². It is unknown whether these treatment regimens will also work with rats.

Nursing Care

In the event that respiratory signs surface:

Give probiotics such as Bene-Bac or yogurt with live active cultures when using antibiotics, to prevent normal gut flora from being destroyed.
Provide additional warmth to maintain body temperature within normal limits. It is essential that the rat does not become overheated or dehydrated. The rat should also be able to move away from the heat source if it becomes uncomfortable. If the rat is unconscious or immobile extreme care must be taken to keep the heat low and stable.
- You can use an isothermic product that is heated in the microwave such as SnuggleSafe®. Make sure to follow the product directions carefully and wrap in a towel before placing in the cage. SnuggleSafe® will provide heat for 12 hours before needing to be reheated. Other similar types of products may vary in re-heat time. Check directions for individual product.
- If using a heating pad (good for long term use) use only the low heat setting, put a thick towel in between the pad and the cage bottom, and place beneath a corner of the cage.
- If none of these options are available you can use a plastic bottle filled with hot water, and wrapped in a towel, in the corner of the cage.
Provide additional nutritional supplements to help maintain strength.
Provide fluids to prevent dehydration (orally or warmed SQ fluids if necessary).
Make sure food and water are easily accessible.
Provide humidification to loosen secretions.
Provide nebulized breathing treatments if indicated.
Contact veterinarian to discuss changes in treatment options if condition does not seem to be improving.
If condition continues to deteriorate and precludes further comfort or quality, discuss euthanasia with veterinarian.

*Note: For more in-depth nursing care information refer to the Rat Health Guide articles: Mycoplasmosis or Pneumonia.

Outcome

Reduced severity of signs by treating with appropriate antibiotics
Disease is kept under control
Disease is not spread
Quality of life is not severely compromised

Impact on pet owner/breeders

CAR bacillus occurs naturally in many rat colonies, both wild and domestic, and is highly contagious in rats with direct contact. There is no cure or quarantine for this disease, only symptom management and/or segregation. Because CAR bacillus is a chronically festering disease, it would be in the best interest of the rat to avoid exposure.

CAR bacillus can not be spotted in a quarantine situation unless ongoing disease is severe enough to result in clinical disease. When combined with M. pulmonis infection, which unfortunately infects many pet rat populations, it may pose additional health issues. When combined with viral infections (such as SDA or Sendai) it can cause an increase in morbidity and mortality. CAR bacillus infection may also be sub clinical, with little or no obvious impact.

In a colony or subgroup, with a high prevalence of infection, testing may help to determine if the group is infected.

In a pet scenario, with good husbandry practices, an infection with the CAR bacillus may not cause overt clinical signs. If rats are kept in a healthy manner, have no immune deficiencies, and/or have adequate resistance, then signs relating to CAR bacillus infection may not be a major issue. On the other hand, if these scenarios are not in place, CAR bacillus may amplify, speed up, and complicate new or existing respiratory diseases.

If a rat has tested positive for CAR bacillus it is best not to add it to a colony that is CAR bacillus free. In the event it is decided to add the rat, it will need to be caged separately so as not to spread the pathogen to the rest of the colony.

Use proper basic hygiene methods and allow no contact between an infected rat and the uninfected rats to help contain the disease.

Breeding sick or positive rats will spread the CAR bacillus. To establish whether a breeding colony is contaminated, multiple rats (over 6 weeks of age) from separate cages should be tested.

Prevention

Preventing Active Illness

Treat early upper respiratory signs as appropriate.
Maintain nutritional requirements.
Prevent stress (physical and emotional).
Maintain proper environmental temperature.
Prevent ammonia build up by maintaining clean cage environment.
Use appropriate bedding (phenol free).
Quarantine new rats to prevent exposure to viruses that can weaken the immune system.

Preventing Exposure

Avoid bringing actively ill rats or known positive rats into the colony.
Limit contact with outside rats (wild as well as domestic).
Consider keeping separate sub colonies within your group.

*Note: If you choose to maintain a CAR bacillus-free colony accept rats only from closed colonies that are known to be free of CAR bacillus and that are routinely tested for this agent.

Consultation and Technical Assistance

Dr. Craig L. Franklin, DVM, Ph.D., ACLAM, University of Missouri Research Animal Diagnostic and Investigative Laboratory (IDEXX RADIL). Consultation and proofing.
Charles River Laboratories- Technical Assistance Department.
University of Missouri – Comparative Medicine Program and IDEXX-BioAnalytics (IDEXX RADIL). Photographs of Filobacterium rodentium (formerly CAR Bacillus).

References

Kendall, L., Riley, L., Hook, R., Besch-Williford, C., & Franklin, C. (2000). Antibody and cytokine responses to the cilium-associated respiratory bacillus in BALB/c and C57BL/6 mice. Infect Immun, 68(9), 4961-7. Retrieved December 21, 2008, from the PubMed database.
Bacterial Diseases. (n.d.). Retrieved December 21, 2008, from http://www.IDEXX RADIL.missouri.edu/info/dora/RATPAGE/Bac.htm.
Matsushita, S., & Suzuki, E. (1995). Prevention and treatment of cilia-associated respiratory bacillus in mice by use of antibiotics nursing rats in Pharmacological section [Abstract]. Lab Anim Sci, 45(5), 503-7. Retrieved December 21, 2008, from the PubMed database.
Matsushita, S., & Joshima, H. (1989). Pathology of rats intranasally inoculated with the cilia-associated respiratory bacillus [Abstract]. Lab Anim, 23(2), 89-95. Retrieved December 21, 2008, from the PubMed database.
(1991). Companion Guide to Infectious Diseases of Mice and Rats. Washington D.C.: National Academy Press.
Cundiff, D., Besch-Williford, C., & Riley, L. (1992, October 1). A Review of the Cilia-Associated Respiratory Bacillus. Retrieved December 21, 2008, from http://info.criver.com/flex_content_area/documents/rm_rm_r_cilia_assoc_respiratory_bacillus.pdf.