From the ratlist.... Message 85702

THE RAT-LOVER'S GUIDE TO RESPIRATORY DISEASE
WHAT CAUSES IT AND WHAT YOU CAN DO ABOUT IT


(5/2/2002 R.S. Hines DVM PhD)
http://www.2ndchance.info

Dear ssaftler,

Some time ago you asked me why your ratty was sneezing. It is part of
a long, complicated story that I have faced most of my career and it
has taken me a while to piece everything together and send you this
answer:


Some Day, You or a Friend Will Face This Situation:

You feel sorry for a sweet "feeder" ratling at some
seedy pet store. You take it home. It becomes your buddy. Everything
goes well for a year or so but then, especially in the evening, you
hear sneezing. The rat seems to have just as much energy and
enthusiasm as before. But as time goes by, its nose becomes crusty.
As this progresses, you notice that the rat is breathing harder,
wheezing and it's weight has dropped. Now it is sneezing off and on
all day. Mucusy or crusty brownish material drains from its nose and
gets sneezed onto the walls of its terrarium. You are getting
worried. You take your rat to a veterinarian. He thumbs through some
books and puts it on antibiotics. He tells you it has an upper
respiratory infection. Perhaps the rat gets better for a while. But
the problem comes back again and again and the pet is now definitely
uncomfortable.


The History of Your Pet Rat

Your rat's Latin name is Rattus norvegicus.
He now comes in innumerable colors and styles but he was once a brown
creature living wild in southern Asia (not Norway). He found plenty
of food and shelter near people, and by 1340 had become a pest that
moved to all habitable areas in sailing ships. He was quite an
unwelcome visitor. He arrived in Europe about 1346, and soon, over 23
million people became ill – 20-40% of the population. But it wasn't
the rat's fault, he was as sweet and gentle as any of God's
creatures; it was just a flea he was carrying and the poor sanitation
of the times. By 1856, folks were experimenting with rats in France.
Living this life of ease, in cages, the rat's genes changed and he
became quite mellow. Finally, a (white) litter was born in
Switzerland, around 1906. Its descents were sent to Philadelphia PA
where the Wistar Scientific Institute used its bloodline to develop
more new strains of rats than ever before or after. As I said, these
rats didn't join us alone. They brought along old "friends" when they
jumped ship. Friends they had had since the dawn of time. Besides the
plague, those friends included the Mycoplasma, some viruses and
bacteria that are now making your rat sneeze.


Life Span
Rats were designed to live 3-4 years. Some genetic strains live
longer than others – certain ones no more than 1-1 1/2 years. As in
people, female rats tend to live longer than male rats. It has also
been discovered that limiting their protein and caloric intake as
pups increases the length of their lives.
Rat Strains and Genetics
I come from a research laboratory background, so I know lab
rat strains best. Some are Out-bred. That is, bred to maintain the
largest pool of genes possible. It takes about 5 generations and 100
pairs to establish an outbred strain. A few of the common outbred
strains include the Sprague Dawley, Wistar and Long Evans rat - often
called a hooded or piebald rat.
Other strains are Inbred. They result from 20 or more generations of
brother to sister matings. These strains have the smallest possible
gene pool and so are very ,very alike in all respects. By the
fortieth generation, they are 99.5% genetically alike. Scientists
love them, because they are such predictable cookie cutter rats. The
most frequently used inbred strains include the Fisher 344, the Lewis
rat, the Brown Norway rat and the Wistar-Furth rat.

How the Scientific Community Deals With Rat Respiratory Disease
Until the 1960s, laboratory rats suffered from the same
respiratory problems that your rat has. But as my first job, out of
veterinary school in 1966, I was posted to the National Institutes of
Health to help develop "clean" rats and mice that did not have these
diseases.
What we did was perform cesarean sections on Sprague Dawley
rats, that were big-bodied and great mothers. We passed the infants
into sterile rooms or isolettes and bottle-fed them wearing gloves
sterile clothing and masks. Some, we kept sterile. We called them
Axenic rats or germ-free rats. The problem was that without bacteria,
their intestines (cecums) didn't function well and they did not live
long. So we had a microbiologist brew up the "Shadler Cocktail" -
some innocent but important bacteria that we could give to them. They
did great then. But now we had to think up a new word for them. We
call them Gnotobiotic rats or defined flora rats.
Because they were so expensive to produce, our production
colonies were less controlled. We just tested them frequently to be
sure they contained no virus, Mycoplasma, dangerous bacteria or
parasites. We called these huge colonies Pathogen-Free rats.
The rat you bought had no such controls – anything goes in
the pet and snake-food trade. These are just called Conventional
rats. They can have every murine (rat & mouse) parasite, Mycoplasma,
bacteria and virus under the sun. It is the respiratory Mycoplasma -
assisted by certain viruses and bacteria that are causing the
problems your rat is now experiencing.

What Mycoplasmal does to your Rat
The root of your rat's problem is a very tiny organism – smaller than
a bacteria-but a bacteria none-the-less, but bigger than a virus. It
is named Mycoplasma pulmonis. In articles it is often just called MRM
for Murine Respiratory Mycoplasmosis. It lives in mice, guinea pigs,
and rabbits as well as rats but doesn't seem to be as big a problem
in them. It can even exist in your nasal passages where it does no
harm. It was lurking there from the day of your rat's birth;
clinically silent but causing a slowly progressive disease from the
nose to the lungs. Although we think primarily about its effect on
the lungs, it occasionally causes genital infections, sterility and
arthritis as well. It is the most important and common disease of
rats.
Mycoplasma pulmonis is very infectious to rats and mice.
Mycoplasmosis has been called many things: murine pneumonitis,
infectious catarrh, enzootic bronchietasis, chronic respiratory
disease (CRD), endemic murine pneumonia, viral pneumonia of rats,
labyrinthitis, and chronic murine pneumonia.

It is very infectious and generally passes through a sneeze - but it
can even pass through the womb into a ratling before it is born. Once
inside the rodent, it begins its life living in the nose and middle
ear but causes no immediate disease. Its often accompanied by other
buddies (co-pathogens): Sendai virus, K virus, Cilia-Associated
Respiratory Bacillus, Streptococcus pneumoniae, Corynebacterium
kutscheri, Rat Coronavirus, Pneumonia Virus of Mice, Mycobacterium
avium-intracellulare, Pneumocystis carinii, Chlamydia trachomatis,
Chlamydia psittaci, Klebsiella pneunoniae, Streptococcus pyogenes,
Mycoplasma neurolyticum and Mycoplasma collis (co- pathogens - think
of them all as bad bugs).
Signs and Symptoms You See with Mycoplasma Respiratory Disease
What happens, and when it happens depends on a lot of interacting
factors: some Mycoplasma are stronger (more virulent) than others.
More importantly, the number of other bacteria and virus that hitched
a ride in your rat is very important as to when or if this disease
develops. The symptoms include sneezing, crusty and runny nose and
watery eyes. Over time this can progresses to loss of appetite, hair
coat, wheezing, difficulty breathing and unkempt hair coat. Later,
bronchitis, pneumonia, and emphysema develop. I would sometimes visit
my conventional (contaminated) colonies at Baltimore City Hospital in
the middle of the night – the sound was like a host of hoarse
crickets all chirping and sneezing together.
Some Scientific Information about this Bug
Mycoplasmas are bacteria that do not have a cell wall and have the
smallest number of genes necessary for any free-living thing. There
are lots of kinds of Mycoplasma. They affect all kinds of animals and
even plants and some of the "flu"s we get are actually due to
Mycoplasma pneumoniae. Physicians call this "Walking Pneumonia" and
it is also linked to arthritis and neurological disorders. But don't
be frightened, this is an entirely different Mycoplasma. When I look
for ways to treat your rat, I must look as to how physicians treat
Mycoplasmal pneumonia because no other recent information is
available.
Ways to Prevent the Disease from Entering Your Rodent Colonies
For private rat breeders and owners the key to keeping
disease out of your animal(s) can be reduced to three words,
isolation, sanitation & isolation.

Prevention of murine mycoplasmosis involves placing
Mycoplasma-free rats into a barrier-sustained facility. These are
closed, scrupulously clean, structures where strict husbandry
standards, exclusion of wild rodents, serologic and postmortem
monitoring, good ventilation, and low population densities in cages
and rooms contribute to the maintenance of Mycoplasma-free
conditions. Needless to say, it is expensive.

Hysterectomy (Cesarean) delivery is the only known means of
establishing an M. Pulmonis-free breeding colony from previously
infected stock. Due to the frequent localization of this
microorganism around and in the uterus, not every litter will end up
mycoplasm-free.

Rats used in research colonies are obtained from various commercial
and institutional sources. It is important that the Mycoplasma
status of these animals is known and that the rats are housed by
vendor or in groups with a similar microbial (bacterial) status. I
check them frequently by attempting to grow Mycoplasma from swabs of
the nasal cavity, middle ear, trachea, and uterus-oviduct (remember,
this bug hangs out frequently in the reproductive system). We also do
blood tests that tell us if Mycoplasm has slipped in. One suspicious
sign is when the rats start having smaller weaker litters. Older
females seem more susceptible to this reproductive form of the
disease. It can also show itself as creaky, puffy and arthritic legs
in older animals.

When I examine a rat for Mycoplasma disease, I begin by looking in
its nasal cavity and the "cleft" in its palate (the naso-palatine
ducts). I look for snotty material, mucous, and little ulcers or red
dots – all signs of inflammation. Then I look in the rat's sinuses
for the same sort of problems. In older rats I look for
mineralization of the trachea (wind pipe) – although this is common
in all old rats. Normal lungs are a uniform light rosy pink color and
float high in water. Rats with advanced mycoplasmosis have grayer,
heavier, wetter lungs.
Husbandry -Ways You Can Delaying the Onset of Mycoplasmal
Pneumonia in Your Rat
If your rat came from a source like ssaftler"s, you can safely assume
it came with some Mycoplasma. How this will affect the life of your
ratty depends on some things that you can control and some things
that you can't.

First the things you can't change:

1) Some strains of Mycoplasma are stronger (more virulent) than
others – you don't know which strain(s) are present.
2) Some strains of rats are genetically hardier than others.
Fisher 344 strain seems the most resistant to Mycoplasma disease
while Lewis rats seem the most susceptible.
3) The Mycoplasma probably didn't come alone. Other freeloaders
came with it: most likely bacteria, and virus - maybe parasites as
well.
4) It had a rough life in the pet store and where ever it was
bred. The momma rat was probably worn out from producing litter after
litter and may not have passed much immunity on to the ratling.
5) A rat-year is about equal to 25 human years, so each
rat month equals about 2 of our years.
So the older the rat is when you get it,
the more advanced the disease is likely to be.

Now the Good News!

1) Early in the ratling's life, it should be checked for
intestinal and superficial parasites that can be eliminated. This
will improve its general health and immune system.

2) You need to put the rat on the highest-quality lowered
caloric, lowered protein diet you can find. One that meets or exceed
the nutritional requirements of rats as determined by the U.S.
National Research Council (N.R.C.). Some good ones are Mazuri 5663 or
ZuPreem Rodent Maintenance diet. Most quality brands meet N.R.C.
guidelines on rat nutrition. However, their protein content, 23.5%,
and caloric content is a bit too high for maximum longevity and their
fiber content (3.8%) is too low. You can get around this by mixing it
50-50 with an equine range pellet, like Mazuri 5661 with 13% protein
and 2.9% fat and 13.2% fiber. This will give you an 18% protein diet.
With this mixture, the rats will attain their top body weight later
in life, become reproductively active later in life, and, on the
whole, live longer lives*. They are also less likely to suffer from
kidney disease later in life. To this diet, I would add an
additional 10 -12 units (iu) of vitamin E as well as a portion of the
contents of a mixed anti-oxidant, anti-aging microcapsule, such as
those produced by Landco Corp and omega 3 and 6 fatty acids which
stimulate the immune system that mycoplasm suppresses. Vitamin A
deficiencies is known to speed the progress of mycoplasmosis in rats.
However, too much vitamin A is also toxic and the diet I suggested
has plenty of vitamin A. All these products or similar ones should be
available to you through my web page, http://www.2ndchance.info If
you are outside of the United States, I will try to set up something
locally available for you.

3) The temperatures of your rat's home should be kept between 65°
F and 80°F. Temperatures should be kept as constant as
possible - rats don't do well when their temperature varies up and
down a lot. Humidity should be between 30-70%. Twelve hours of light
and twelve of darkness is a good ration but some rats breed better
with 14 hours of light and 10 of darkness.

4) Good air quality is the most important thing you can provide
for your rat to minimize the lung damage Mycoplasma causes. It is
this lung damage that ultimately causes the rat's decline. First,
they need to be kept in a dust and mold-free room, preferably with
central heat and air-conditioning and at least four air changes an
hour. We used 14 air changes per hour at N.I.H. The bedding material
you use is extremely important. I like hard wood chips, next best is
dust-free pine shavings [NOTE: Dr. Hines was questioned on the safety
of pine and responded with more current information regarding pine].
Worst are corncobs, cedar shavings and
bentonite clays (cat litter products). Shredded ordinary newspaper
with black soya ink is probably also OK – I have never used it. What
you want to avoid is dust, mold, bacterial spores, airborne mineral
products and atmospheric pollutants. These are all known to produce
lung lesions in all animals. Of course, no wild rodents should have
access to your rat's room, food or utensils.

5) Frequent cleaning of the rat's cage and as much space
per individual rat as possible is also very important. Rat's
urine breaks down into ammonia. Over time, this causes lung damage.
Aromatic (pungent) cleaning compounds such as strong bleach, pine sol
and perfumed products are also a bad idea. Bleach is an excellent
cleaning product – but it should be diluted to 1 part standard bleach
in twenty parts water. The cages and utensils must be pre-cleaned in
soapy water before being soaked in this mixture. Cage construction is
very important. Cages should be made of durable smooth, non-porous
and easily cleaned materials such as plastic or non-toxic metals.

6) Mycoplasma are more complex that virus. They never cause sudden
(acute) disease. Because they utilize primarily RNA instead of DNA
to reproduce, they are only killed by the protein-synthesis
inhibiting, neucleophylic, antibiotics -the macrolides. These include
DIRITHROMYCIN (Dynabac®), BIAXIN: Clarithromycin (kla-RITH-roe-mye-
sin) and Azithromycin (Zithromax).
Biaxin can be given to rats at 3.5 mg/kg three times a day for 20
days in combination with ranitidine and corticosteroids. Zithromax
can be given at 3.5mg/kg three times a day for 20 days. Dynabac can
be given at 2.5mg/kg three times a day for a twenty to thirty day
period. After 30 days, the daily total dose must be lowered. All can
cause loose stools and other digestive problems in rodents and must
be given, supplemented with a good horse and ruminant bacterial jelly
and brewer's yeast. They are all best when given four times a day
after food is consumed. They should be used at the lowest possible
dose since double the pediatric dose can cause liver and kidney
problems in rats. Most indigestion remedies interfere with macrolide
absorption. I compound most in berry syrups, which must be shaken and
kept refrigerated.**

Older remedies relied on destroying the freeloading bacteria
that accompany the mycoplasma, such as Streptococci, Pasteurella,
Klebsiella and Pseudomonas bacteria. We have nothing that will affect
Sendai virus – another freeloader. Traditionally, chlortetracycline
was given in the rat's drinking water at 0.25mg/ml for 14-20 days or
tetracycline, mixed fresh daily, in the drinking water at 2-5mg/ml
and sweetened with Karo syrup. Some used Tylosin (a sulfa) at
25mg/378 ml of water (see my weights and measure FAQ).**


Obtaining Mycoplasmal-free Rats
University origin rats are not necessarily
clean. Rats from the conventional colonies at Emory University, have
enzootic Rat Parvovirus (RPV), Kilham's Rat Virus (KRV, RV) and
Toolan's H-1 and have cultured positive for Helicobacter spp,
Pasteurella pneumotropica, Proteus spp, staphylococci, fecal
coliforms and enterococci.
I can arrange to have your rat's serum or pooled colony rat serum
tested for antibody to: Mycoplasma Pulmonis, Pneumonia virus of mice
(PVM); Kilhams rat virus (KRV); Toolans H-1 virus; Rat coronavirus
(RCV); Sendai virus; CAR bacillus; Reovirus (Reo); Lymphocytic
choriomenginitis virus (LCM); Mouse Adenovirus (Ms.Ad.); Tracheal
cultures can be examined by any competent local lab for Pasteurella,
Bordetella, Corynebacterium, Salmonella, and pathogenic streptococci.
Sophisticated labs can culture for Mycoplasma pulmonis.
New Research Discoveries That May Soon Help Us
Currently, work is going on in Europe and the United States to decode
the approximate 677 proteins that make up rat Mycoplasma. The hope is
that soon a vaccine will be developed against the disease. The reason
this work is going on is that if a vaccine could be produced against
rat respiratory Mycoplasma, it could probably also be produced
against the serious Mycoplasma diseases of people. It is the surface
proteins that most intrigue researchers. These are the ones that give
the Mycoplasma stealth, suppress the rat's immune system and prevent
it from killing the bug. They also produce oxidative stress through
the production of superoxide radicals, which is why antioxidants are
so important to give your rats.
Sources of Mycoplasma-Free Rats
The three largest commercial vendors of Mycoplasma-
free rats in the United States presently are Charles Rivers
Laboratories http://www.bioresearchonline.com/storefronts/crl.html,
Harlan Sprague Dawley Inc. http://www.harlan.com/us/index.htm, and
Taconic Farms http://www.taconic.com/ Some strains may be available
from the Roscoe B. Jackson Laboratories. These institutions accept
orders only from Universities and Research Establishments throughout
the World. I could attempt to make contact with these breeders if
enough rat enthusiasts were willing to pool their resources

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* In 1935,Clyde McCay published a groundbreaking paper that
showed that rats on calorically restricted (CR), nutritionally sound
diets lived longer than rats that were allowed to eat as much as they
wanted. Animals fed about 30 percent less than controls allowed to
eat as much as they want, achieved an increase of about 40 percent in
maximum life span. It has also been shown that CR retards or
eliminates various chronic disorders, such as cancer, diabetes, and
renal disease, and improves immune system function in lab animals (E.
Masaro, American Journal of Clinical Nutrition, 55:1250S-52S, 1992).

**Newer drugs are never approved for use in pocket pets. But in 1988,
Drs. Sedgwick and Pokras published a method of determining
theoretical drug dosages for all warm-blooded animals using a process
they called "Allometric scaling". I have mislaid my copy of this
article, but essentially it relies on the body weight of the animal
and its core body temperature – both of which are easy to determine.
Dr. Pokras can be reached at markpokras@i... I used
this and FDA studies of the drugs in rats to determine the dosages.