This article is from the April–June 1994 AFRMA Rat & Mouse Tales news-magazine.
By Carmen Jane Booth, D.V.M.
Simona Gortlerova, Mission Hills, CA
Q It has been one day after the last show [March show] and I found some strange illness around my rats (it has not been brought from the show, since I bought my last rat about 6 months ago). I hope after describing the symptoms you’ll recognize the problem or know somebody with a similar problem.
I had my three males in one big cage for about a year. One day I noticed that one of them was getting very thin. Shortly after that he seemed to be having trouble with balance (drunk-like movements). I put him on antibiotics, fed him Nutri-cal, etc.
Nothing seemed to help. After a month of getting skinny to the bone, he died. First I thought that maybe it was something internal, even though when the first symptoms occurred, I separated him away from the other two rats. When I came home from the show and saw the other male, of the three former cagemates, walking like he was drunk and lost lots of weight, I knew it was something more serious than internal problems. From the time the first male showed the first symptom to the next rat showing the same symptoms has been 2 months in between. I think it is too long for some kind of virus. Now I recognize that at this point it would be a good idea to have them tested. Please, could you give me a name of a vet that you like to use for your rats, or is any vet okay, since they have to send it to the lab anyway. Are there any specific questions that you recommend I should ask. Basically, do you have any advice.
Thank you very much.
A A vet would need to take a look at your rats since two of the three cagemates were affected. Karen Robbins, Winnetka, CA
Response to Simona Gortlerova from Carmen Jane Booth, D.V.M.
A In summary: You are having rats that are not eating, lose weight, and walk abnormally as if they were drunk. The medical terminology for this is anorexia and ataxia. Without having seen the rats or diagnostic testing, the exact cause is impossible to determine from the limited amount of information provided.
Ataxia: Incoordination of movements, without spasticity, paresis, or involuntary movement. Ataxia is caused by disorders of the proprioceptive sensory systems, disorders of the cerebellum, or disorders of the vestibular system. The proprioceptive system provides information about location of the parts of the body and the receptors are located in the skin, joints, tendons, and muscles. The nerve pathways end in the cerebellum and cerebral cortex. The cerebellum coordinates movement by comparing the desired action with the performance. The vestibular system detects the position and movement of the head so that normal posture is maintained. Although ataxia is usually a symptom of nervous system disease, generalized weakness may make the way an animal walks appear ataxic. There are numerous causes of ataxia including: neoplastic, degenerative, inflammatory, toxic, and vascular.
Anorexia: The lack or disinterest in the ingestion of food; can be pathologic, physiologic, or psychologic. There are so many causes of anorexia that I have listed them in Table 1.
In any event, I would recommend a complete physical examination of any remaining rats, a complete history of diet, environment, etc., and a complete work-up of any affected animals. Because the two rats died, I would recommend a complete necropsy of any animals that are severely affected that do not respond to treatment. The diagnostic work-up and necropsy of a severely affected animal increases the chances of finding the cause(s) of their problems over mildly affected or dead animals.
In looking over the reports from your mother’s rats (Geri Hauser) and then from your rats, the only significant difference between the two is that your mother’s rats are negative for Rat coronavirus or sialodacryoadenitis virus and your rats are positive. You had one equivocal result for Reovirus-3. Unless they retest that sample, it’s meaningless because you can’t really say if it’s positive or if it’s negative. If everybody stops breeding for a couple months, the rats should seroconvert to being negative after a period of time. I can’t exactly tell you when that would be, but I would suspect it would take a few weeks to a month for complete seroconversion.
You should be aware that some strains of rats are more susceptible to rat coronavirus than others. For example, Fischer rats are much more susceptible than Wistar. I don’t know what the founding stocks are for the rat club. If they have a lot of Fischer rat background, then they would be more susceptible to that virus. In the rat coronavirus, the rats are able to clear the virus after a period of time.
In 1961, two epizootics of this disease were reported. You see swollen, thickened necks, a lot of the red porphyrin pigment around the eyelid margins, and marked inflammation of the submaxillary salivary glands and the Harderian glands (eye glands).
The agent is an RNA virus from the Coronaviridae family, genus Coronavirus. It is related to mouse hepatitis virus (MHV) and human coronavirus. Mice have been shown to be susceptible experimentally, but natural infection in mice has not been found.
SDA virus is one of the most common viruses in rats. It is highly contagious and spreads through rooms by contact and by aerosol. The virus is present in tissues for about 7 days and there’s no carrier state. SDA exacerbates Mycoplasma pulmonis infection.
In an enzootic infection, adults are immune due to previous infection. Suckling rats have a transient (1 week or less) conjunctivitis (inflammation of the tissues in the eye). This form is usually mild and subtle. Usually the clinical signs disappear by the time they get a little older.
The epizootic infection in fully susceptible weanlings and adults (animals that haven’t been exposed before) has an incubation period less than 1 week and you get a sudden high prevalence of overt disease. You can get cervical edema (swelling around the neck), sneezing, photophobia (a phobia against light—they shun light), and nasal and eye discharge (serous, which is water-like, to more purulent, which is cloudy). The rats often have porphyrin staining and you may also see corneal ulcers and dry eyes. Usually you see high morbidity (number of animals with severe clinical disease), but no mortality (death). Clinical signs usually disappear in about a week, but the eyes may be more prominent than normal for a couple of weeks.
Diagnosis is based on serology. The rats shed virus for only 7 days and latent infections do not occur. Infections in breeding colonies can be eliminated by quarantining rooms, suspending breeding completely, and destroying all new pups for about 6 to 8 weeks —that’s why I recommended to stop breeding for 2 months.
In a non-breeding population, have an 8-week quarantine before introducing new animals. I would advise for people going to shows who want to protect their animals at home, keep exposed animals isolated for 2 months. I know that may be hard to do.
Recovered animals are considered free of the virus, but there is some question as to whether they could get infected later on with the same strain or a different strain of virus (from a paper written in 1979).
SDA resists environmental conditions poorly, so fomites probably do not play a huge role in transmission, unless you’re moving things quickly between animals.
KRV stands for Kilham Rat Virus. Kilham rat virus was discovered in 1959. The main affect of this virus is on the brain, which causes cerebellar hypoplasia (that’s where the brain doesn’t completely develop and you get a small brain; obviously they wouldn’t be able to think/function properly and the rats would probably have neurological problems). There are few reported incidences of natural disease where this virus interferes with research, but the prevalence (the number of rats in the general rat population that are infected) is rather high. It’s propensity for damaging cells in vivo (in the animal) makes it a significant pathogen.
The agent is a single strand of DNA virus from the family of Parvoviridae and the genus is Parvovirus. This is the same family of viruses that causes the disease parvo in dogs, which is usually fatal to highly morbid (many animals get very sick). The genus Parvovirus contains 13 different serotypes. Of these 13 distinct serotypes, 3 occur in rodents. There’s the Kilham Rat Virus, H-1 virus, and Minute Virus of Mice.
The host where this virus lives is usually Rattus norvegicus. They are pretty much the natural host. Syrian hamsters and other species have been infected experimentally.
In rats, the disease is mostly asymptomatic in the adults; although in a few cases you can get nervous disorders, sudden death, and hemorrhagic diathesis (they bleed from a variety of sites). You also get a decrease in fertility in breeding colonies. They sometimes have liver problems and they get jaundiced (they look a little yellow when you look at their skin). Sometimes you see neurological problems in suckling rats.
What you see pathologically with Kilham rat virus is that the fetuses die in utero and they get resorbed. You see this at necropsy. Basically you see lesions in the brain and the liver of newborn rats. In the early stages of the disease you can see intranuclear inclusion bodies in the cells. Most people can test for this using either ELISA, IFA, etc.
These viruses are extremely resistant to environmental conditions. They can remain infective after heating to 80°C for 2 hours or 40°C for up to 60 days. They are resistant to dessication (drying out), low pH, chloroform, ether, and alcohol. I know in dogs they recommend using a dilute bleach solution (1:32) as a foot bath and cleaning everything when you have puppies before they are completely vaccinated. I know that parvovirus (in dogs) can be infective and live on your shoes for up to 2 years. So it’s important with this virus to be as clean as possible and disinfect things properly. I would suspect with the way things have been, that everybody’s rats are pretty much exposed to this virus so they may not have clinical signs.
The epizootiology is common in wild and laboratory rats. Kilham (the person who found the virus) found antibodies in 40–62 percent of wild rats in four different locations around New Hampshire, and in 89 percent of the lab rat population.
The transmission of this virus is primarily horizontal through direct contact or fomites. Contaminated fomites are important because these viruses are extremely stable to dessication. People can act as a fomite if you’re not washing your hands. Rat show boxes and equipment can also be a method of transmitting this virus. The efficiency of horizontal transmission may depend on the strain of virus and the age which the rats are infected. The virus has been reported to be shed in milk, feces, urine, and nasal secretions. If you have rats with Mycoplasma, you know they sneeze quite a bit, and they are just spreading virus that way from one cage to the next.
Some information on transmission that I think is interesting. Rats infected via sneezing, and the other rats swallowing or getting that nasal secretion on their mouth, at 2 days of age, transmitted the virus to their cagemates for 10 weeks, whereas rats that were infected at 4 days of age were only able to infect their cagemates for 3 weeks post infection. Transplacental infection has been suggested, but it’s occurrence is questioned because it has not been able to be proven experimentally in all cases. Persistent infection has been shown to occur for up to 14 weeks in rats infected as infants. Clinically, natural infections are nearly always subclinical. Clinical disease is a rare event so few examples have been reported. Natural disease was observed in 13-day pregnant rats. They reported an increase in the number of uterine absorption (the pups die and they get resorbed). You see really small pups with cerebellar hypoplasia. Usually you see neurologic signs where the animals do not walk normally. They circle, their heads tilt, and they look really odd. You can see pups with jaundice and they don’t do very well. You can see spontaneous deaths, abdominal swelling, and dehydration in juvenile and 7-week-old rats that are positive to this disease.
I would doubt that this particular virus is causing too much of a problem in your rats. It may be more of a problem because you have CAR bacillus and Rat Coronavirus occurring at the same time. The way to diagnose this disease is by doing serology. Control is by obtaining rats that are free of this virus through regular serologic monitoring. I don’t think eliminating and repopulation is a viable alternative for most people. With this particular virus you have to just live with it in the colony and do the best you can. If all the other stresses are eliminated or reduced, it shouldn’t be causing too much of a problem. You’ll probably have more significant problems because of the Mycoplasma, the Rat Coronavirus, Sialodacryoadenitis virus, and CAR bacillus in combination.
The other Parvovirus is the Minute Virus of Mice. I don’t know if you’ve had any of your mice tested, but Minute virus of mice is close to Kilham rat virus and again, natural infections aren’t really apparent in mice.
The significance of this disease can be great for both people showing animals and for those in research. MHV is the term for Mouse Hepatitis Virus and it designates a large group of RNA viruses belonging to the family Coronaviridae. That’s the same family as Rat coronavirus. There are about 25 different strains of MHV and some are more pathogenic (cause disease) than others. Some are closely related to Rat coronavirus or Sialodacryoadenitis virus. Mice are considered the natural hosts, but suckling rats have been found to be moderately susceptible to experimental infection.
Mouse hepatitis virus is extremely contagious, and the majority of mice housed under conventional systems will become infected with this if exposed. There are three different types of disease that’s seen clinically with MHV. One is called enzootic (a subclinical infection). This has been the most common pattern seen in the United States. Adults are immune due to prior infection. Newborn mice are protected by maternal antibodies they get in the milk. Infection is perpetuated among partially protected weanlings with little or no clinical disease unless they are compromised by extreme stress.
The next type is epizootic. This is a clinically apparent infection. This pattern is usually seen in young infant mice where none of the population has been exposed. I would say this is probably rare in the rat and mouse club because with people going to shows, they’ve been spreading things to each other.
What you usually see is diarrhea with up to 100 percent mortality from the really highly virulent (really strong) strains of MHV. Infection in adults, that never have been exposed, is usually subclinical. So, it’s basically the infant mice that are severely affected in epizootic infections.
The last system you won’t really see is called Wasting syndrome in athymic mice (Hairless or Nude mice). They don’t usually survive.
Again, the diagnosis for any of these viruses is based on serology. For control, as with most of these, you’d have to eliminate the breeding population and start over which I don’t think is particularly relevant.
These viruses were recognized in the late 1980s in a lot of different places. One of the reasons I want to mention this is because this virus does cause problems in humans. They are currently having a problem in rodents on reservations here in Massachusetts and New England. If people start having problems, then this would be something you definitely would want to get tested for.
I’m going to summarize the clinical signs seen in people. The incubation period in people is 2–3 weeks and the signs include fever, headaches, muscular pains, bleeding from a variety of different places with easy bruising, and protein in the urine. Twenty percent of people develop shock, severe bleeding, and renal failure; this is why the other name for this disease is Hemorrhagic Fever with Renal Syndrome. Some mild cases that they found in Scandinavia with the mortality less than 0.5 percent were acute onset of fever, headache, nausea, and vomiting, followed by 3–6 days of proteinuria (bleeding in the urine), and low platelets. Most patients recovered in the low instance.
The virus that causes this is the family Bunyaviridae, the genus being Hantavirus. Another name for this virus is Korean hemorrhagic virus and they saw this in the early 1940s to the early 1970s in the Korean war. And only in the 1980s have they really been able to pinpoint what the problem is.
The natural hosts of these viruses are small mammals, primarily rodents. The likelihood of causing disease in humans varies from region to region. I haven’t been listening to the news too much lately and I think that few people have died. I don’t think we have this in AFRMA rats and mice. It is mostly in the wild rodents rather than in the pet or research animals. I think it’s more of a problem out here than it is in California and there has only been a few cases out here.
The diagnosis in rats may be unapparent and is usually made through surveillance. They recommend indirect fluorescent antibody tests or ELISAs or henaglutanation inhibition (HI). I don’t think there is any control for this. I don’t recommend bringing wild rodents into your breeding colony or even taking them to the rat shows unless they’ve been tested to make sure that they aren’t carrying some of the nastier viruses and bacteria that can really cause havoc in breeding animals. I know there are some people in the club that have wild rodents.
Comments on Bedding
I’d like to comment on bedding with rodents. A lot of research companies use an entirely paper-based product called Alpha-dri. It’s a white, clean, soft paper bedding and is highly absorbent. It can be purchased from Shepherd Specialty Papers (Christian M. Vernon, Sales Rep., (800) 382-5001). They also make the bedding that’s called Cellu-dri. Some people have used it and they say it leaches off toxins, etc., etc. That’s completely false. There is a wet paper smell to the bedding. It has been tested and it does not cause any respiratory or any health problems in rodents. It does smell funny. I don’t use it because it smells funny, not because it has any particular problem. I myself use the Alpha-dri at home. It’s a nice product. I’ve switched to that from the kitty-litter product that I was using just because it is cleaner and the rats don’t eat it.
RE: Jessica Jakubanis, Norridge, IL, Bug spray causes
bloody nose (M/J93:10). She asks, “Do you have any idea why it
affected her this way. No one else was affected. Is this common?”
I wonder about the blood being all over the cage. I have rats with Mycoplasma and they sneeze a red discharge which is the porphyrin secretion from the Harderian gland. They sneeze red and it’s not blood —just a pigment. Her rat in and of itself may have been extremely susceptible to the bug spray. Or, if her rat had some other problems where it ruptured a blood vessel in its’ lungs and then coughed up blood that way. But as far as bug spray or anything like that, I would recommend people to be extremely careful when spraying their houses. I’ve used flea products in the past, and I always take my rodents out of the house. I use one of the flea products that has quick kill (pyrethrins) because the adult fleas are usually killed in about half an hour. I make sure the product also has an insect growth-hormone regulator (precor is one of the products) to kill any of the developing larvae. But I never let my rodents crawl around on this and I make sure the house is extremely well aerated before I move the rats, the dogs, myself, or anybody else back into the house. I’ll usually leave the windows open for a couple of hours before I bring them in. One note on this, especially for those people who live in the warmer climates, if you are going to spray your house, make sure that your rodents are someplace safe out of the sunlight, so they don’t get overheated. I do know someone who, unfortunately, had her rodents and iguana in the shade and the shade moved. By the time she got back 2 hours later to open up the house from the bug bombing, she found all of her rats and iguana dead from heatstroke. So people really need to be careful.
RE: Dawn Kozak, Warren, MI, as far as spaying rats.
Spaying dogs before their first heat reduces a dog’s chance of mammary tumors by about 90 percent. Once they’ve been through their first heat and then their second heat, it goes down about another 10 percent. By the time they’ve had their third heat, there is no benefit from early spaying of female dogs.
As far as rats, if you were to spay female rats prior to their first estrus, or heat, you might get that benefit. Rats start estrus (cycling their normal estrous cycle), between 9 to 12 weeks. That is a small animal to do a spay on, I don’t think it’s really recommended, and it would be a lot more difficult, even for a person who does a lot of surgeries on rodents. So, after your rats are about 3 or 4 months old (mind you they start cycling at 9 to 12 weeks and they cycle about every 4 days) you’ve lost any benefit from early spaying after they’ve gone through a few cycles. I would say your veterinarian was taking what is true in dogs (who cycle every 7 months) and extrapolating it to rats, I think inappropriately. Rats, if they’re going to get mammary tumors, they’re going to get mammary tumors regardless of being spayed. Diet is probably more important and not exposing them to carcinogens, but rats, especially old rats, are going to get mammary tumors pretty much no matter what you do.
I would say to anybody who has a rat that is going under anesthesia, is to have the veterinarian listen to the lungs very carefully with a stethoscope. If the rat is wheezing, has a lot of crackling noises, or a dead area where you don’t hear anything, the rat probably is compromised respiratorilly and anesthesia is a risk. In that case, I would use a gas anesthesia that you can knock them out quickly and wake them up quickly. But there is always a risk of anesthesia no matter what anesthetic agent you’re using.
You can take a radiograph, although it’s difficult to diagnose radiographically a tumor versus infection in some of these rats because the Mycoplasma and CAR bacillus tend to destroy the lung tissue. A lot of tumors also tend to destroy the lung tissue or invade the lung tissue and it can be very difficult radiographically to determine exactly what’s going on.
When I was in High School, one of my rat’s lungs was so compromised from either tumor, or more likely from the Mycoplasma/CAR bacillus, that she had to go on oxygen and there was no way that we could take the tumor out. She was in such distress that I elected to put her to sleep because there wasn’t really anything I could do at that point. So again, anybody with a rat going under anesthesia, I usually recommend if the rat is less than a year, that surgery is usually indicated. With rats that are 1 to 2 years of age, because they usually have Mycoplasma, doing surgery is, I think, a case-by-case issue. If the rat’s severely affected with Mycoplasma/CAR bacillus, then I don’t usually recommend putting them through the stress of surgery. If they’re not severely affected (few clinical signs), even with the increased risk from doing the anesthesia, I would go ahead and do it provided the tumor is small enough that it can be a very quick surgery. I don’t recommend surgery, tumorectomies, or lumpectomies on rats over the age of 2–2½. Most of my rats don’t usually make it too much beyond 3. I found that getting another month or two of life does not seem worth it, when you have to put them through the big stress of a surgery and at this point they’re usually starting to suffer more severely from the Mycoplasma. I just don’t like to do that to my rats.
In conclusion for this newsletter, I’d just like to reiterate that the Sialodacryoadenitis Virus is a virus that can be eliminated if people stop breeding and give the weanlings and the young rats a chance to clear the virus before breeding them. This virus was probably brought into the rat club from a young infected rodent, either from a pet store or somebody that had a wild rodent, or somebody who’s rats could have gotten exposed to wild rodents depending on where they are housing their rats. I think that Mycoplasma is definitely here to stay as far as the pet rat population. Kilham rat virus is definitely here to stay as well as CAR bacillus. The problem with the Sialodacryoadenitis virus is that it does cause some respiratory problems and it exacerbates or potentiates the problems you see with Mycoplasma and CAR bacillus. The only hope for the AFRMA pet rat population is to stop breeding for at least a 2 month period. There’s not a whole lot of information on exactly what is the best time. It only takes a few weeks to clear the virus but I would recommend that you do it at least 2 months from the last litter born to give the rats a chance to get up to a mature size before you start breeding again. I think that this is the only thing that’s going save animals from being severely affected. I would also recommend that maybe at some point to do a complete viral screen and see exactly what other viruses you have. I know they only tested for a few viruses in the rats, and I would suggest testing some of the mice as well. By knowing what you have in the population you may not be able to do anything about them, but at least you will know what you have to live with. The SDA virus is the only one that you can eliminate by stopping breeding.
National Research Council, Infectious Disease of Mice and Rats, National Academy Press, Washington, D.C., 1991.
From Karen Robbins, Winnetka, CA
I got two of my mice tested the beginning of April (full panel) and the results are in Table 2. MHV is Mouse Hepatitis Virus, SEN is Sendai Virus, Myco is Mycoplasma pulmonis, MVM is Minute Virus of Mice, TMEV is Theiler’s Murine Encephalomyelitis Virus, Reo 3 is Reovirus 3, EDIM is Epizootic Diarrhea of Infant Mice, K is K-Virus Infection, Poly is Polyoma virus, MCMV is Mouse cytomegalovirus, Ect is Ectromelia Virus, E. cun is Encephalitozoon cuniculi, CAR is CAR bacillus.
Karen Robbins’ mice Serology
|Mouse 4-93 was 1 year old showing no problems.
Mouse SN was 6 months old and was sneezing, but otherwise was okay.
I also got three rats from Tina Good when we were out in Arizona for the March 26 Maricopa County Fair. I used the oldest male, approximately 6 months old, for the serology test (Table 3); the other two young ones, born January 1994, I used for a fecal test. They didn’t have any parasites, but they did have either “isospora begemina or toxoplasma.”
Tina Good's rats' Serology
|PVM is Pneumonia Virus of Mice Infection; SEN is Sendai; Myco is Mycoplasma pulmonis; TMEV is Theiler's Mouse Encephalomyelitis or GD7; Reo 3 is Reovirus 3 Infection; LCM is Lymphocytic Choriomeningitis; RCV is Rat Coronavirus; KRV is Kilham Rat Virus; E. cun is E. cunniculi; CAR is CAR bacillus.|
It would be great to have more people test their rats and mice so we could see if these positives are found all over the country or varies by the area. This time, when we took blood from the rat for the serology, my vet was able to get all the blood she needed from the tail vein and didn’t have to sacrifice the animal. So, if your vet isn’t sure on getting blood and saving the animal, it can be done. You should knock the animal out completely so you don’t have it squirming and fussing when you stick it.
Since Carmen told about most of these mouse diseases earlier, you can check there for all the details.
I received the results of the viral screen from some of Karen’s mice. They were positive for MHV, Mycoplasma, Minute Virus of Mice, Theiler’s Mouse Encephalomyelitis Virus, and Mouse Cytomegalovirus, The only symptoms that her mice had were occasional sneezing. Other than Mycoplasma and MHV, these other viruses do not usually have any clinical symptoms and are often subclinical. Note: Virulent strains of some of these viruses are capable of causing disease. The strain of MHV is probably one of the subclinical types where there is no overt disease. Through selection of healthy breeding animals and culling of sick animals, you can often select for resistant lines of animals. That would be my conclusion for why Karen has so few problems with her mice in the presence of these viruses with the mycoplasma.