This article is from the Jan.-Mar. 1994 AFRMA Rat & Mouse Tales news-magazine.

By Karen Robbins

To catch you up on the respiratory problems going through my rats (see ND93:2). We got the culture of the swollen lymph nodes back the middle of December, but it showed “no organisms found.”; I had all the rats on Panmycin for 2 weeks. Three days later (December 17) I put them on Tylan (tylosin; 1¾ tsp/gal water). I used the Tylan for 1 month.

The three rats’ tissue samples (liver, lung, and spleen samples from each animal) came back (finally), the beginning of January. In the young six-week-old female, the diagnosis was acute pneumonia; the four-month-old female with the enlarged lymph node, which is the one that was cultured, came back chronic sialoadenitis (si-al-o-ad-e-ni-tis)(inflammation of salivary glands) and pneumonitis; and the one-year-old male just starting to show severe symptoms, was subacute broncho-pneumonia with a positive identification of CAR bacillus (see the copies of the histopathology reports).

Click on images for larger view

We sent in these tests to the County of Los Angeles Department of Health Services, Comparative Medical and Veterinary Services. They do free testing when you are having an outbreak such as I had. They also do routine testing for a fee. For example, a skin biopsy from a rat is only $19. So have your vet check out county facilities or university schools for alternatives to typical lab testing. There are cheaper ways to getting your animals tested.

My vet talked to the pathologist to find out what this means and where we go from here. The pathologist, which I also talked to myself to answer further questions, said both the sialoadenitis (SDAV or SDA) and the CAR bacillus cause primary and secondary respiratory disease. SDAV stands for sialodacryoadenitis virus. There is poor long-term prognosis; all exposed are infectious; no immunity is passed from mom to baby; all are chronic carriers; you will have intermittent outbreaks where they continue to be ill; the SDA coronavirus will run its course but with the CAR bacillus you have problems; no medicine will work; mice can get it; labs that get this type of thing wait 6 weeks to 2 months after getting rid of everything and cleaning before getting any new stock; the only way to get rid of it is to cull everything and start over. After I talked to him, he gave me the number of a vet out at U.S.C. to talk to for further information and told me they do serological testing.

The vet at U.S.C. said it is not pathogenic to mice—they get their own coronavirus; she suggested three different methods of control: 1. cull everything, 2. have a 6-month breeding moratorium and then acquire pathogen-free lab rats (rats that were not exposed to any bacteria or viruses) and put them with my rats for a period of time then have the lab rats tested (serological antigen test) to see what they caught, 3. at least quarantine any new animals.

This testing she talked about only takes ½ cc blood per rat and they test for the five most common bugs (Sendai, mycoplasma, corona, KRV, and PVM) for $30 [now $33], plus for $6 they will test for CAR bacillus. For the complete panel it is $60. The only thing they can’t test for is the HANTA virus—they have to send out for that. After talking to her, I decided to go with the breeding moratorium/get lab rats.

If anyone is interested in getting their rats or mice tested serologically, have your vet contact Dr. Dixie Fisher, University of Southern California, Veterinary Diagnostic and Research Support Laboratory. For those out-of-state members, your vet could probably find out from Dr. Fisher where there is similar testing in your area.

The animals were looking much better with no new sick rats. January 17 I took them off the Tylan and was planning on putting them on Terramycin (oxytetracycline HCI; ½ tsp/8 oz water changed daily), but the earthquake changed all that. Because of the earthquake everyone was put on plain water.

Two weeks later (February 1) I put them on Sulmet (sodium sulfamethazine; 1 tbls/gal water) for 1 week. The day after I put them on Sulmet I had to put down half of a litter born January 11. Some had a “dry eye”; and others were thin and sick with respiratory. This was the first I had of symptoms of the eye problems. (ED. NOTE: After talking to Carmen recently, I found out this drug is known to cause dry eye or keratoconjuntivitis sicca.)

February 3 when I came back from Riverside, Craig told me about Lizzie and Snippet not looking right (two of the pets in the house). They were breathing hard but otherwise looked and acted okay.

The next morning (Friday) Snippet died and Lizzie was very ill. That evening Mary Ann came here and brought some extra drugs I didn’t have and some Lactated Ringer’s. We gave Lizzie a dose of the lactated ringer’s under her skin (10 cc; for dehydration), Gentocin injection (gentamicin 50 mg; .025 cc/lb sub-q every 12 hours, 2 weeks maximum treatment), and amoxicillin (50 mg/ml; .10 cc orally every 12 hours). Sunday I also started her on Brondecon Elixir (.10 cc/lb every 8 hrs). Brondecon is a mild diuretic, opens bronchial tubes, and is a cough suppressant and expectorant. I gave her the Gentocin/amoxicillin/Brondecon for almost two weeks. I also had to force-feed her during this time as she wouldn’t eat on her own. I tried everything I have ever heard of anyone giving an ill rat. She is now eating on her own but is very thin and is permanently damaged. Last year she had a bout with respiratory and was a bit thin as a result with an occasional wheeze. Now she doesn’t sneeze or wheeze and is very alert and active but won’t eat enough to fatten up.

The three girls left, after Snippet died, ended up having to be on sulfamethoxazole trimethoprim (.15 cc/lb orally every 12 hours) and have recovered fine but Little Squirt has an occasional wheeze. The two girls from my mom that have so far gone through this whole thing okay because I’ve ignored them, are still doing great and have never caught anything.

One of our members has had an interest in this whole ordeal as her animals are the ones that were ill during October/November. Her vet talked to the pathologist and did some research on CAR bacillus. I decided to test some of my rats now using the serological testing rather than waiting after I found out some additional information. Also, I did some research on my own in the literature I have and was finding out a lot more about SDA coronavirus and CAR bacillus.

Monday, February 7, I again went to the vet, this time to send in 6 rats for serological testing at U.S.C. I was having another outbreak. In the first batch of babies that were here during the initial outbreak, there were a lot I put down, mostly respiratory symptoms. The second batch born in December were doing great until they had been off the medicine because of the earthquake and then a lot of those babies had to be put down (the medication could have been keeping things under control or they just hit that crucial age and the virus hit them since all the adults had already been through it). In the third batch of babies born January 11, February 4, and February 7, only some of those born January 11 had problems. The other two litters born 3½ weeks later have not had one sniffle. Because of this second outbreak, I ended up putting down 21 more animals after I got back from the vet. Since that time, everything seems to be holding steady.

The vet ended up doing a panel of 11 tests rather than just the 6. For PVM (Pneumonia Virus of Mice Infection) they were all negative; Sendai, all negative; Mycoplasma, all positive; TMEV (Theiler’s Mouse Encephalomyelitis or GD7), all negative; Reo 3 (Reovirus Infection), all negative with one a positive/negative which my vet says doesn’t mean much as one of the other rats that was his brother was negative; LCM (Lymphocytic Choriomeningitis), all negative; RCV (Rat Corona Virus), all positive; KRV (Kilham Rat Virus), two positive, four negative; E. cun (E. cunniculi), all negative; CAR (CAR bacillus), two positive, four negative; Tyz (Tyzzer’s), all negative; see table 1.

Table 1
Karen Robbins' rats' Serology
2/10/94

Rat No.	PVM	SEN	Myco	TMEV	Reo3	LCM	RCV	KRV	E.cun	CAR	Tyz
1	—	—	+	—	—	—	+	+	—	—	—
2	—	—	+	—	—	—	+	+	—	+	—
3	—	—	+	—	±	—	+	—	—	+	—
4	—	—	+	—	—	—	+	—	—	—	—
5	—	—	+	—	—	—	+	—	—	—	—
6	—	—	+	—	—	—	+	—	—	—	—

• Rats #1 and 2 were sisters—they went to the show in November but never showed anything more than sneezing and some wheezing; they were 4 months old
• Rat #3 was a 3- to 4-month-old male, never showed more than sneezing/wheezing; in his breeding cage of parents and siblings, during the initial outbreak some siblings got very ill, dad just wheezed a bit then got over it; recently the latest batch of babies in this cage got very ill after the earthquake—they were born January 9—before that didn’t even sneeze and I then put down the whole cage
• Rat #4 was a 8½-week-old female that developed severe symptoms (thin, rough coat, lethargic, etc.) but her sister never got sick; by the time we took the blood she looked great and you wouldn’t know she looked like she was going to die just shortly before; the interesting thing is that the mom of this rat had another litter right after this litter and they are the ones that some developed eye problems (“dry eye”;); I ended up keeping only one from the first batch and one from the second batch that didn’t show any signs of illness.
• Rat #5 was a 6-week-old female; her and her littermates had been sneezing bad after they were off the medication 2 weeks.
• Rat #6 was a 7-week-old male from the same parents as rat #3; he just sneezed a bit.

I talked to Carmen Booth, D.V.M., the club’s vet in Massachusetts, February 10, the day before I got the official results of the blood testing. What I found out from her is coronavirus in rats clears through in 1 month. Mice don’t get rat coronavirus. People need to stop breeding for 2 months from the last baby born (the whole club should do this since so many of us have had serious illness in our rats) to clear the virus. Some of the symptoms are swollen glands, sneezing, and eye problems. The coronavirus is passed by air, direct contact, and fomites. There is about a 7 day latent period from infection to clinical signs. There are different strains of SDAV. CAR bacillus has been known about since around 1980 and it is associated with mycoplasma causing respiratory disease. CAR bacillus on its own is not known to cause problems. It works with other bugs; control with C-section if possible. You should use a 3% bleach solution when washing your cages. [Use Parvosol, Rocal, or Nolvasan when cleaning cages in between the washing out. ED.] And, quarantine! Whether it is coming back from a show or buying a new animal— quarantine!

She also told me of Charles River laboratories. They do comprehensive rodent health monitoring where they test for everything—serological, parasitological, bacteriological, and pathological for $184 per animal. A bit steep, but worth it to really find out what your critters have. Carmen is even willing to be the go-between if we need her. She has also offered to do what she can in regards to testing—we just have to get the animal or tissues to her. She sent me information on the Charles River testing if anyone is interested, or you may contact Carmen yourself. Carmen is sending in a detailed article about the SDA coronavirus, CAR bacillus, KRV, etc. I will have to wait and put it in the next issue because of time restraints.

What I have also found out from the information Carmen sent me and the books I have is, that rats are natural hosts and it is seen primarily in young rats. It is a coronavirus (RNA) antigenically related to the mouse hepatitis virus (MHV), rat coronavirus (RCV), and the human coronavirus OC₃₈.

you need to stop breeding for 2 months from the last baby born to clear the virus

Sialodacryoadenitis (si-al-o-dac-re-o-ad-e-ni-tis) (SDA) virus causes inflammation and necrosis of the salivary and ophthalmic glands of rats (sialo=salivary). The infection is highly contagious and causes high morbidity but low mortality. In the rapid course of the disease, treatment can only alleviate the secondary ophthalmic bacterial infections.

Affected animals show exophthalmos, porphyrin pigment staining around the eyes, and swollen face and neck. Exophthalmos may cause corneal drying with severe secondary ocular lesions leading to keratitis and corneal ulcers. The disease is self-limiting with most lesions resolving within 14 days. Lesions include enlarged submaxillary and parotid salivary glands, edematous cervical lymph nodes, swollen lacrimal glands, and yellow-gray foci in Harderian glands.

Clinical signs include squinting, photophobia, blinking, and eye rubbing followed by sneezing and cervical swelling within 5 to 7 days post infection. Sneezing is caused by acute rhinitis. Swelling under the neck is caused by cervical edema, enlarged cervical lymph nodes, and necrotic inflamed salivary glands. Bilateral or unilateral suborbital or periorbital swelling, prominent or bulging eyes, and often chromodacryorrhea (“red tears”;) and ophthalmic lesions develop secondarily to decreased lacrimation; self-mutilation may occur as a result of scratching of affected areas. Very young animals may enucleate the eye.

Within 2 days of intranasal inoculation, SDAV causes rhinitis followed by necrosis of the ductular and acinar epithelium of salivary and lacrimal glands, accompanied by intense inflammation and edema. Salivary glands appear swollen. One, some, or all of the salivary or lacrimal glands can be affected, with the exception of the sublingual glands, which are spared. Cervical lymph nodes become enlarged. Interstitial pneumonia can occur in suckling, but not adult rats. Conjunctivitis, keratitis, corneal ulcers, synechia, hypopyon, and hyphema can arise due to lacrimal dysfunction. Eye lesions usually resolve, but can proceed to chronic keratitis, megaloglobus, and retinal degeneration.

During the infection, rats usually remain active and eating, although certain behavioral activities may be depressed. The infection may be fatally exacerbated by concomitant Sendai virus infection or mycoplasmosis. The infection progresses rapidly from the respiratory epithelium to the lacrimal and serous or serous-mucous salivary glands, associated lymph nodes, and contiguous tissues.

Sialodacryoadenitis virus is highly contagious and spreads rapidly among susceptible rats by direct contact, aerosol, or fomites. No latent infection or carrier state occurs. The incidence of infection is high. The disease is not fatal and may be subclinical. Infection is subclinical in weanling or older rats, but intranasally inoculated neonates die and sucklings develop lower respiratory disease. Susceptible young animals, 2- to 4-weeks of age, with no maternal antibody, develop the more serious forms of the disease. Infected animals carry and secrete the virus for about 7 days. Infection is acute, lasting only about 1 week, at which time rats seroconvert with no carrier state.

Susceptible rats of any age can be infected. When epizootic (whole group), clinical signs are seen in a colony for several weeks with individual animals showing signs for up to a week. When enzootic (limited animals) within a colony, clinical disease occurs only in sucklings, since adults are immune.

Diagnosis of SDAV is based on clinical signs, histologic lesions, and the detection of serum antibodies to the virus. Harderian gland lesions caused by damage associated with periorbital bleeding can be confused with lesions of SDAV infection. Conjunctivitis from other causes may mimic a prominent but secondary sign of an SDAV infection. Rats without antibody titers to mouse hepatitis virus or rat coronavirus can be assumed to be free of SDAV antibodies.

Recovered rats are free of virus and are immune. No effective vaccines are available. The immune status of the colony and of any new rats to be introduced should be monitored serologically. If your rats become immune to this particular strain of coronavirus they can become ill all over again if you bring in rats that carry a different strain; just like the flu in people—every year there is a new strain that everyone has to be immunized for and/or go through it to build up immunities.

Rats can be kept free of SDAV if they are isolated and if newly introduced rats are immune or unexposed. Introduction of a single subclinically infected rat can precipitate epizootic disease among naive rats. If an outbreak occurs, the infections will run its course and die out within 3-4 weeks if new rats are not introduced into the room and if breeding is temporarily ceased. Routine disinfection of rooms and equipment is sufficient to destroy environmental sources of virus. If you want to keep the sialodacryoadenitis virus in your colony, you need to continually introduce new babies or new rats.

Cilia-Associated Respiratory (CAR) Bacillus is transmitted by aerosol and direct contact. The incidence of infection is not known. Signs of clinical respiratory disease similar to Mycoplasmosis have been described. Signs are nonspecific, but may include: hunched posture, ruffled coat, wheezing, decreased body weight, inactivity, “head tilt,”; and accumulation of porphyrin pigment around the eyes and external nares in rats. It may be that in rats M. pulmonis is the primary pathogen and the CAR bacillus is a promoter of MRM. The disease resembles murine CRD, i.e. murine respiratory mycoplasmosis (MRM) except for the presence of CAR bacillus. Results of experimental testing suggest that CAR bacillus alone can produce a murine respiratory disease in pathogen-free rats and that 2 weeks are needed for serological and pathological changes to develop. Fourteen days were needed for pathological lesions to develop, with the lesions progressing and expanding from upper to lower airways with time.

The inability to culture in cell-free media and poor staining with aniline dyes makes the diagnosis difficult.

The inability to culture in cell-free media and poor staining with aniline dyes makes the diagnosis difficult. Silver stains and immunofluorescent techniques will demonstrate the organism in tissues. A commercially available ELISA will detect a serological response. The organism withstands freezing and thawing and has been stored at -70°C and 23°C for short periods.

Hosts are laboratory and wild rats (Rattus norvegicus), African white-tailed rats (Mystromys albicaudatus), laboratory rabbits, and laboratory mice. The disease is poorly understood, so control of infection is unknown at this time but identification of infected colonies and rederivation along with good husbandry would be a reasonable course.

Transmission experiments in mice were performed on specific pathogen-free mice 5 weeks of age. The mice were inoculated intranasally with 2 x 10.6. SMR strain of CAR bacillus under light anesthesia. The CAR bacillus was transmitted among mice by 4 weeks old. Clinically, body weight loss, decreased activity with ruffled fur and wheezing were observed in all mice by 8 weeks. By intracage infection (placing diseased animals with nondiseased animals), a few diseased mice with similar clinical signs to those mentioned above appeared from 8 weeks after contact. Serum IFA antibody to CAR bacillus became detectable in 4 of 9 cases at 8 weeks after contact. The morbidity and antibody titers increased gradually until 12 weeks after contact. In an intercage airborne route of infection, no clinical signs, no antibodies, and no lesions in the lungs were detectable in the uninfected mice until 12 weeks after placement of the infected mice cage.

The study of mice demonstrated that uninfected mice inoculated intranasally with infected rat lung homogenate and in direct contact with infected mice acquired the CAR bacillus infection, but uninfected mice failed to acquire the infection by the airborne route during the 12-week observation period.

According to the experiments, the tracheal epithelium may be one of the most desirable sites for the CAR bacillus to colonize. However, damage to the respiratory tract epithelium found in the CAR bacillus infection of rats and mice seems to be less than that described for murine respiratory mycoplasmosis, which shows similar respiratory lesions.

The airborne infection in rats occurs in rats at 7 months after transmission. The possibility of accidental contamination by fomite materials such as bedding cannot be excluded in long-term experiments. The spread of CAR bacillus infection in colonies of rats and mice seems to be dependent either on direct contact between infected and uninfected rodents or on contaminations of the environment with infected materials. Airborne transmission appeared to play little part in the maintenance and spread of infection.

These experiments suggest, that rat origin CAR bacillus can be transmitted to mice, rabbits, and guinea pigs, and that the CAR bacillus has the potential to spread to other species of rodents and rabbits.

Kilham Rat Virus (KRV) is a parvovirus that causes cerebellar necrosis in suckling rats, fetal resorption, and congenital malformations but do not pose significant clinical disease problems in laboratory colonies.

In a couple months when I start to rebreed, I will retest those babies born at different ages to see if I really did clear this thing up.

My mom had her animals tested and they came back negative for coronavirus, so she is the only one I know that can say she has corona-free rats (see Table 2).

Table 2 Geri Hauser's rats' Serology 2/18/94

Rat No.	PVM	SEN	Myco	RCV	KRV	CAR
A	—	—	+	—	+	+
B	—	—	+	—	+	+
C	—	—	+	—	+	—
D	—	—	+	—	+	+

• Rat #A was born July 1992
• Rat #B was born May 1993
• Rat #C was 7–8 weeks old
• Rat #D was born December 1992
  all just did some sneezing/rattling

 
I hope everyone who breeds rats and mice will consider having their animals tested serologically to determine what exactly they have in their colony. You don’t have to have 100+ animals before you consider yourself a breeder. As long as you have babies born and sell to pet shops or other fanciers, then you are a breeder. I would not recommend the “mini panel”; at $33, but rather the full panel, because you can’t assume because my animals came back negative for those additional tests other than CAR bacillus, that your animals will be the same because you got animals from me in the past or have exchanged animals with other members in the area.

I would definitely recommend anyone who has had cultures or tissue samples where the results were insignificant, to have some animals tested serologically! If we don’t try and stop this virus by not breeding for 2 months and quarantining new animals and being careful where we get or take our animals, then we will continue to see outbreaks of this disease. Some people may say they can’t afford to stop breeding for that length of time because of the loss of money from babies sold. But if you don’t, then in future outbreaks think of the animals you will lose or will be damaged from the illness and unable to breed after that point and all the money you will spend on medications that will only work to help with the symptoms and does nothing to kill the virus. Since this is one virus we can do something about and rid it from our stock, then we should be doing everything we can as a club to stop it. We tell people to buy from a breeder as they usually have healthier, friendlier stock than what you will find in most pet shops. But when the breeders sell animals that get sick or make the person’s existing animals ill or die, than we are no better than those people who only breed for snake food and may not care about the health of the animal.

One member told me at the March show she heard of outbreaks of this same problem in many different labs across the country. Some have been totally wiped out from this and will just close down, others will try to rebuild. So when we are having an outbreak here in southern California, it probably is not an isolated case. The more we try to learn about these problems we encounter the better off we will be, not only as individuals but as a club.

ED. NOTE: Use caution when giving gentamicin as it causes kidney toxicity/damage and can cause deafness in cats. Carmen says Baytril is best for rodents.

If we don't try and stop this virus by not breeding for 2 months and quarantining new animals and being careful where we get or take our animals, then we will continue to see outbreaks of this disease.

BIBLIOGRAPHIES

• Bean-Knudsen, David E., “The Laboratory Rat,”; VMD 411A (a textbook Carmen let me have a copy of), Winter 1991, pp. 80, 84.
• Booth, Carmen J., Conversations with her February – March 1994.
• Fox, James G., et al, (eds.). Laboratory Animal Medicine, Academic Press, Inc., San Diego, CA, 1984, pp. 108–10.
• Fraser, Clarence M., et al, The Merck Veterinary Manual. Sixth Edition, Merck & Co., Inc., Rahway, NJ, 1986, pp. 935–39.
• Harkness, John E. and J. E. Wagner, The Biology and Medicine of Rabbits and Rodents, Third Edition, Lea & Febiger, Philadelphia, PA, 1989, pp. 186–88.
• Matsushita, S. and H. Joshima, Laboratory Animals, “Pathology of rats intranasally inoculated with the cilia-associated respiratory bacillus,”; 1989, 23, 89–95.
• Matsushita, S., et al, Laboratory Animals, “Transmission experiments of cilia-associated respiratory bacillus in mice, rabbits, and guinea pigs,”; 1989, 23, 96–102.
• National Research Council, Infectious Diseases of Mice and Rats, National Academy Press, Washington, D.C., 1991, pp. 48–50.

Back to Respiratory Outbreak At Karen’s Kritters

Go to Carmen Booth, D.V.M., notes 2/28/94 RE: Respiratory Outbreak at Karen’s Kritters

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