About Me
know the muscles are there in a human body
yes our body gets its shape from the skeleton that supports it. The bones give the body strength and the muscles which are around the bones is what gives definition to the body, help in movement and store energy. The various muscles which are intertwined with tendons and nerves make the movement possible for the body.
Different organs and parts need various types of muscles and depending upon the nature of requirement, striated or non striated or voluntary or involuntary type of muscles are present there. Since our whole body is a mass of muscles, their volume is indeed huge.
There are more than 639 skeletal muscles in your body. Some sources will say 640 muscles in the human body. On average, your body weight is 40% muscle. Out of the 639/640 muscles, 30 of them are facial muscles, which help you create all those different faces of happiness, surprise, joy, sorrow, sadness, fright, etc. The muscles surrounding your eye are the busiest muscles in your body. Research indicates that you probably blink them more than 100,000 times a day
muscle is to move your body :
Without muscles you couldn't move your skeleton. There would be no way to animate your physical body or even speak your mind. You wouldn't be able to blink, digest your food, breathe, pump your heart or have one for that matter since your heart is a muscle. You couldn't smile, urinate, defecate or sniff with your nose.
Muscles are a type of tissue that is composed of contractile cells or fibers :
The cells or fibers actually contract! And when they contract, they create movement on the bone that they attached to. The really cool thing about muscles tissue is its ability to shorten (contract). Muscle tissue also has the property of irritability, conductivity and elasticity.
Remember, there are three different types of muscle tissue :
Smooth muscle:
This muscle tissue is called involuntary because it is NOT under conscious control. Involuntary means you do not have to think about it. Involuntary muscle tissue is found in the internal organs; namely the digestive tract, respiratory passages, urinary and genital ducts, urinary bladder, gallbladder, walls of the blood vessels. Yep! Your blood vessel walls are also muscle tissue.
Another great reason to exercise and pump the blood.
Striated muscle :
This muscle tissue is found in all skeletal muscles, and movement is under conscious control. It also occurs in the tongue, pharynx, and upper portion of the esoophagus. Voluntary muscles are under conscious control because you would consciously tell them what to do. If you say, "arm, move" it moves!
Cardiac muscle :
This muscle tissue is only found in the heart. The fibers branch and form a continuous network. At certain intervals, there are prominent bands or intercalated disks that cross the fibers. Some fibers are called Purkinje fibers, and they form the impulse-conducting system of the heart.
Muscles work by contracting and relaxing :
Pump your bicep for a second. Make a fist and bring it up to your ear. Notice how your bicep gets bigger when the muscle tightens and shortens. And when you relax your arm, the muscle gets longer and smaller. Muscles do not push, they pull. The tiny muscle fibers work like a sliding glass door on a track. And these tiny muscle fibers get their energy from the food you eat. Without food to feed the muscles, your muscles couldn't make the energy to contract. The reason you can move your arm back and forth is because muscles work in pairs. One is a synergist, the other a antagonist. It's a support thing and so they can pull in opposing directions.
Have you ever heard the term "Move it or Lose it!" This term can be directly applied to a sarcomere.
A sarcomere is portion of a striated muscle fibril. Tiny pieces of your muscle. If you don't move and exercise those muscles by contracting and relaxing them, you will in fact lose 100 sarcomere's a day. YIKES!
In order for a muscle to work, it has to cross a joint. Connecting from one end of a bone to the other without crossing the joint would be pretty much useless because it wouldn't be able to shorten or lengthen with the movement of the joint. So in order to bend your knee, the muscles in your thigh have to cross over to the other side of the knee joint and attach. Then when you tighten the muscle, the knee bends. Cool huh?
The muscles that are voluntary get their signals from the peripheral nervous system, and it's because of this that the skeletal muscles are under conscious or voluntary control. The involuntary muscles (smooth and cardiac muscles) receive their nerve supply from the central nervous system and functions involuntarily without conscious control.
It is possible to hurt a muscle because they can become pulled, hence "pulled muscle." You can actually tear a muscle the same way that a ligament or tendon gets torn or a bone gets broke. And the cool thing is, they can heal themselves with rest and time.
Tag :
General Health,
People at a stroke
A stroke is serious - just like a heart attack. A stroke is sometimes called a "brain attack." Most often, stroke occurs when blood flow to the brain stops because it is blocked by a clot. The brain cells in the immediate area begin to die because they stop getting the oxygen and nutrients they need to function.
What causes a stroke?
There are two kinds of stroke. The most common kind of stroke, called ischemic stroke, is caused by a blood clot that blocks or plugs a blood vessel in the brain. The other kind of stroke, called hemorrhagic stroke, is caused by a blood vessel that breaks and bleeds into the brain.
Anyone can have a stroke, but there are some things that increase your risk
What should you do?
Because stroke injures the brain, you may not realize that you are having a stroke. The people around you might not know it either. Your family, friends, or neighbors may think you are confused. You may not be able to call on your own. That's why everyone should know the signs of stroke - and know how to act fast.
Don't wait for the symptoms to improve or worsen. If you believe you are having a stroke - or someone you know is having a stroke - call immediately. Making the decision to call for medical help can make the difference in avoiding a lifelong disability.
Streetsign image with text: Trouble Walking
What causes a stroke?
There are two kinds of stroke. The most common kind of stroke, called ischemic stroke, is caused by a blood clot that blocks or plugs a blood vessel in the brain. The other kind of stroke, called hemorrhagic stroke, is caused by a blood vessel that breaks and bleeds into the brain.
Anyone can have a stroke, but there are some things that increase your risk
Your age
The largest number of people who have strokes are aged over 55, and the risk increases as you get older. This is because our arteries naturally become narrower and harder as we get older.
Your ethnicity
If you are South Asian, black African or black Caribbean you are at a higher risk of stroke than other people in the UK. It isn’t completely understood why this is, but it’s probably connected to the fact that you are more likely to have conditions like high blood pressure or diabetes.
Family history
If a close relative (parent, grandparent, brother or sister) has had a stroke, your risk is likely to be higher.
Genetic conditions
Certain genetic conditions can cause strokes. Sickle cell disease, for example, is a genetic disorder that affects your red blood cells and makes them more likely to block your blood vessels.
None of these factors mean that you will necessarily have a stroke, but it’s important to be aware of them and do what you can about the factors you can change.What should you do?
Because stroke injures the brain, you may not realize that you are having a stroke. The people around you might not know it either. Your family, friends, or neighbors may think you are confused. You may not be able to call on your own. That's why everyone should know the signs of stroke - and know how to act fast.
Don't wait for the symptoms to improve or worsen. If you believe you are having a stroke - or someone you know is having a stroke - call immediately. Making the decision to call for medical help can make the difference in avoiding a lifelong disability.
Streetsign image with text: Trouble Walking
Tag :
General Health,
Causes polio in Africa
Polio (poliomyelitis) is a highly infectious disease caused by a virus. It invades the nervous system and can cause irreversible paralysis in a matter of hours.
Causes Polio
Poliovirus is often transmitted from person-to-person through fecal matter. People living in areas with limited access to running water or flush toilets often get the virus from drinking water contaminated by human waste that contains the virus.
In addition, the virus can be spread by contaminated food or water or direct contact with another infected person. According to the May Clinic, the virus that causes polio is so contagious that anyone living with an infected person will likely become infected themselves. (Mayo Clinic)
Pregnant women, people with weakened immune systems, such as HIV+ people, and young children are the most susceptible to the polio virus. If you have not been vaccinated, you increase your risk of contracting polio by:
traveling to an area that has had a recent polio outbreak
taking care of or living with someone infected with polio
handling a laboratory specimen of the virus
having your tonsils removed
extreme stress, which can compromise immune system function
Poliovirus is often transmitted from person-to-person through fecal matter. People living in areas with limited access to running water or flush toilets often get the virus from drinking water contaminated by human waste that contains the virus.
In addition, the virus can be spread by contaminated food or water or direct contact with another infected person. According to the May Clinic, the virus that causes polio is so contagious that anyone living with an infected person will likely become infected themselves. (Mayo Clinic)
Pregnant women, people with weakened immune systems, such as HIV+ people, and young children are the most susceptible to the polio virus. If you have not been vaccinated, you increase your risk of contracting polio by:
traveling to an area that has had a recent polio outbreak
taking care of or living with someone infected with polio
handling a laboratory specimen of the virus
having your tonsils removed
extreme stress, which can compromise immune system function
Types of Polio
There are three types of polio infections:
Prevent Polio
The best way to prevent polio is to get vaccinated. Children should get polio shots according to the CDC vaccination schedule, shown below.
Rarely, the shots can cause mild or severe allergic reactions, including:
breathing problems
high fever
dizziness
hives
swelling of throat
rapid heart rate
Adults in the United States are not at a high risk for contracting polio. The greatest risk is when traveling to an area where polio is still common. Make sure to get a series of shots before you travel.
Center for Disease Control Vaccination Schedule
Age
2 months One dose
4 months One dose
6 to 18 months One dose
4 to 6 years Booster dose
- Sub-clinical: Approximately 95 percent of polio cases are sub-clinical, and patients may not experience any symptoms. This form of polio does not affect the central nervous system (the brain and spinal cord).
- Non-paralytic: This form, which does affect the central nervous system, produces only mild symptoms and does not result in paralysis.
- Paralytic: This is the rarest and most serious form of polio, which produces full or partial paralysis in the patient. There are three types of paralytic polio: spinal polio (affects the spine), bulbar polio (affects the brainstem), and bulbospinal polio (affects the spine and brainstem).
Prevent Polio
The best way to prevent polio is to get vaccinated. Children should get polio shots according to the CDC vaccination schedule, shown below.
Rarely, the shots can cause mild or severe allergic reactions, including:
breathing problems
high fever
dizziness
hives
swelling of throat
rapid heart rate
Adults in the United States are not at a high risk for contracting polio. The greatest risk is when traveling to an area where polio is still common. Make sure to get a series of shots before you travel.
Center for Disease Control Vaccination Schedule
Age
2 months One dose
4 months One dose
6 to 18 months One dose
4 to 6 years Booster dose
Tag :
Pregnancy and Birth,
The negative effect of cholesterol on the heart
Cholesterol is a fatty substance carried around the body by proteins. When cholesterol and proteins are combined, they are called lipoproteins. There are two
main types of lipoproteins:
Low-density lipoproteins (LDL) is known as the bad type of cholesterol. LDL carry cholesterol from your liver to the cells that need it.
High-density lipoprotein (HDL) is known as the good type of cholesterol. HDL carry cholesterol away from the cells and back to the liver to be broken down.
Too much bad cholesterol (LDL) in your blood can cause fatty material to build up in your artery walls. The risk is particularly high if you have a high level of bad cholesterol and a low level of good cholesterol.
If you need to have your cholesterol measured, it will be in units called millimols per litre of blood (mmol/l). You should aim to have a total cholesterol level under 4mmol/l especially if you are at risk of, or already have, heart and circulatory disease. You should also aim to have your LDL under 2 mmol/l and your HDL above 1 mmol/l.
- High cholesterol can create a bile imbalance, leading to gallstones. According to the National Digestive Disease Information Clearinghouse, more than 80 percent of gallstones are cholesterol stones.
A buildup of plaque in your arteries can also block blood flow to your kidneys and stomach. Intestinal ischemic syndrome is when there’s a blockage in arteries leading to the intestines or bowel. Symptoms include abdominal pain, nausea, vomiting, and bloody stools.
- causes high cholesterol
There is no one single cause for high cholesterol. Many different factors can contribute to high cholesterol such as:
eating a diet that is high in saturated fat
smoking
lack of physical activity
high alcohol intake, or
kidney or liver disease.
Having an inherited condition known as familial hypercholesterolaemia (FH) can also cause exceptionally high cholesterol even if you have a healthy lifestyle.
"If you want to see what it looks like in a solidified form, go get yourself a can of Crisco at the grocery store," says Gregory Dehmer, MD, director of the division of cardiology at the Texas A&M College of Medicine. "If you open up a can of Crisco, its this white, lard-like substance."
main types of lipoproteins:
Low-density lipoproteins (LDL) is known as the bad type of cholesterol. LDL carry cholesterol from your liver to the cells that need it.
High-density lipoprotein (HDL) is known as the good type of cholesterol. HDL carry cholesterol away from the cells and back to the liver to be broken down.
Too much bad cholesterol (LDL) in your blood can cause fatty material to build up in your artery walls. The risk is particularly high if you have a high level of bad cholesterol and a low level of good cholesterol.
If you need to have your cholesterol measured, it will be in units called millimols per litre of blood (mmol/l). You should aim to have a total cholesterol level under 4mmol/l especially if you are at risk of, or already have, heart and circulatory disease. You should also aim to have your LDL under 2 mmol/l and your HDL above 1 mmol/l.
- High cholesterol can create a bile imbalance, leading to gallstones. According to the National Digestive Disease Information Clearinghouse, more than 80 percent of gallstones are cholesterol stones.
A buildup of plaque in your arteries can also block blood flow to your kidneys and stomach. Intestinal ischemic syndrome is when there’s a blockage in arteries leading to the intestines or bowel. Symptoms include abdominal pain, nausea, vomiting, and bloody stools.
- causes high cholesterol
There is no one single cause for high cholesterol. Many different factors can contribute to high cholesterol such as:
eating a diet that is high in saturated fat
smoking
lack of physical activity
high alcohol intake, or
kidney or liver disease.
Having an inherited condition known as familial hypercholesterolaemia (FH) can also cause exceptionally high cholesterol even if you have a healthy lifestyle.
"If you want to see what it looks like in a solidified form, go get yourself a can of Crisco at the grocery store," says Gregory Dehmer, MD, director of the division of cardiology at the Texas A&M College of Medicine. "If you open up a can of Crisco, its this white, lard-like substance."
His Heart Almost Stopped
How cholesterol can clog arteries
Not all cholesterol is created equal. It's a fatty substance, so cholesterol can't dissolve in the blood to be carried to where it's needed in the body. "Your body is mostly water, and fat and water don't mix," says Dr. Dehmer.
So cholesterol is packaged into proteins that can shuttle the fatty stuff around your body. One is high-density lipoprotein (HDL, or good cholesterol) and another is low-density lipoprotein (LDL, or bad cholesterol).
What's the difference? LDL can stick to the smooth lining of the blood vessels, where it is absorbed. HDL appears to do the opposite—it actually mops up excess cholesterol and removes it from the blood vessels.
The amount and type of cholesterol in your blood are determined by genetics, age, diet, and exercise. When you eat a diet that's rich in saturated and trans fats, or dietary cholesterol (which is found in animal products such as eggs, milk, and meat), LDL cholesterol levels go up.
"The problem is that many individuals—and probably including myself—eat a diet that is very excessive in all the wrong kind of fats, of which we are talking about animal fats and dairy fats, and therefore we get our cholesterol up too high," says Dr. Dehmer.
But when you exercise, HDL cholesterol goes up—and that's a good thing. "The bottom line is that there are some people out there who have fairly high levels of HDL cholesterol," says Stephen Nicholls, MBBS, PhD, a research cardiologist at the Cleveland Clinic. "That may drive their total cholesterol to look higher than it actually is in terms of how bad that level is."
How cholesterol affects the heart
If LDL cholesterol is too high, some is absorbed into the artery walls, where it acts like an irritant that triggers inflammation in the body. White blood cells crawl into the artery wall and start "gobbling up fatty particles" in a fruitless effort to heal the damage, says Dr. Dehmer.
The end result is big, fatty deposits in the blood vessels. This causes the vessels to become stiff, narrow, and less responsive to triggers to expand and constrict, a process that ensures a steady flow of life-giving oxygen to the body's tissues. (While you may think of blood vessels as akin to the plumbing in your house, they're more dynamic; they constantly adapt to meet the body's needs.)
open quoteIf you want to see what cholesterol looks like, go get yourself a can of Crisco at the grocery store.close quote
This process can happen all over your body. If the fatty buildup is in the blood vessels in the legs (a condition known as peripheral arterial disease), you may experience cramping and have difficulty walking; if it's in the penis, you can develop erectile dysfunction; and if it's in the neck arteries, it can cut off the blood supply to the brain and cause a stroke.
The biggest danger, however, is to the heart. The arteries that cover the surface of the heart are particularly prone to clogging. Once fatty plaques clog these blood vessels, blood flow to the heart tissue is reduced. This can cause chest pain, or angina.
If plaque ruptures, a clot can form and cause a heart attack—a dramatic decline in the blood supply that causes heart tissue to die. (To find out if youre at risk for having a heart attack, take this test.)
What you can do about bad cholesterol
The artery-clogging process can start early in life. A 2008 autopsy study of adults ages 16 to 64 who died of non-heart-disease-related causes found that 83% had signs of heart disease and 8% had advanced disease. "We're seeing evidence of abnormality of blood vessels and obvious plaque in teenagers," says Dr. Nicholls.
Luckily, there are many things you can do to help prevent this process. "We know that lowering LDL cholesterol, the bad form, is clearly a good thing," says Dr. Nicholls. "The other thing we would highlight is the emerging role of HDL, or good cholesterol, the other player here."
Diet and exercise are critical for lowering LDL and raising HDL, notes Dr. Nicholls. (Click here for specific lifestyle changes that can lower heart disease risk.)
Cholesterol-lowering medication can also help, but you still need to watch your diet and exercise. "You can't just say, 'I'm being treated, so I can therefore not exercise and eat whatever I want,'" says Dr. Nicholls. "It doesn't work that way."
How can I reduce my cholesterol level?
Eat a healthy balanced diet
Eating lots of fruit, vegetables, and wholegrain is better than eating foods high in saturated or trans fats. You can replace saturated fats with the healthy monounsaturated and polyunsaturated fats such as olive, rapeseed or sunflower oils and spreads.
Choose foods that are high in soluble fibre such as oats, beans, pulses, lentils, nuts, fruits and vegetables. Soluble fibre can help lower cholesterol.
Do regular exercise
Regular physical activity can help increase your HDL cholesterol (the good type of cholesterol). Staying active is great way to keep your heart healthy.
Quit smoking
Quitting smoking can help to lower your cholesterol and improve your heart health.
Will I need to take medication?
Whether or not you need to take cholesterol-lowering medicine depends on your overall risk of cardiovascular disease.
Cholesterol-lowering medicines such as statins are prescribed for people who are at greatest overall risk of cardiovascular disease. If you have questions about your medicines, speak with your doctor or call our Heart Helpline on 0300 330 3311. You can also look at our publications for more information.
Will eating sterol-enriched foods help reduce my cholesterol level?
Although the effect varies between individuals, there is evidence to show that plant sterols and stanols can help to reduce LDL cholesterol by levels up to 10-15% when 2g per day is regularly consumed as part of a healthy balanced diet.
But whilst there is an expectation that this would lead to fewer heart attacks, no clinical trials have been undertaken to show this. Sterols and stanols have been added to certain foods, including margarines, spreads, soft cheeses and yoghurts.
Will eating too many eggs raise my cholesterol?
For most people, the amount of saturated fat they eat has much more of an impact on their cholesterol than eating foods that contain cholesterol, like eggs, liver, kidneys and shellfish. Unless you have been told otherwise by your doctor or dietician, if you like eggs, they can be included as part of a balanced and varied diet
How cholesterol can clog arteries
Not all cholesterol is created equal. It's a fatty substance, so cholesterol can't dissolve in the blood to be carried to where it's needed in the body. "Your body is mostly water, and fat and water don't mix," says Dr. Dehmer.
So cholesterol is packaged into proteins that can shuttle the fatty stuff around your body. One is high-density lipoprotein (HDL, or good cholesterol) and another is low-density lipoprotein (LDL, or bad cholesterol).
What's the difference? LDL can stick to the smooth lining of the blood vessels, where it is absorbed. HDL appears to do the opposite—it actually mops up excess cholesterol and removes it from the blood vessels.
The amount and type of cholesterol in your blood are determined by genetics, age, diet, and exercise. When you eat a diet that's rich in saturated and trans fats, or dietary cholesterol (which is found in animal products such as eggs, milk, and meat), LDL cholesterol levels go up.
"The problem is that many individuals—and probably including myself—eat a diet that is very excessive in all the wrong kind of fats, of which we are talking about animal fats and dairy fats, and therefore we get our cholesterol up too high," says Dr. Dehmer.
But when you exercise, HDL cholesterol goes up—and that's a good thing. "The bottom line is that there are some people out there who have fairly high levels of HDL cholesterol," says Stephen Nicholls, MBBS, PhD, a research cardiologist at the Cleveland Clinic. "That may drive their total cholesterol to look higher than it actually is in terms of how bad that level is."
How cholesterol affects the heart
If LDL cholesterol is too high, some is absorbed into the artery walls, where it acts like an irritant that triggers inflammation in the body. White blood cells crawl into the artery wall and start "gobbling up fatty particles" in a fruitless effort to heal the damage, says Dr. Dehmer.
The end result is big, fatty deposits in the blood vessels. This causes the vessels to become stiff, narrow, and less responsive to triggers to expand and constrict, a process that ensures a steady flow of life-giving oxygen to the body's tissues. (While you may think of blood vessels as akin to the plumbing in your house, they're more dynamic; they constantly adapt to meet the body's needs.)
open quoteIf you want to see what cholesterol looks like, go get yourself a can of Crisco at the grocery store.close quote
This process can happen all over your body. If the fatty buildup is in the blood vessels in the legs (a condition known as peripheral arterial disease), you may experience cramping and have difficulty walking; if it's in the penis, you can develop erectile dysfunction; and if it's in the neck arteries, it can cut off the blood supply to the brain and cause a stroke.
The biggest danger, however, is to the heart. The arteries that cover the surface of the heart are particularly prone to clogging. Once fatty plaques clog these blood vessels, blood flow to the heart tissue is reduced. This can cause chest pain, or angina.
If plaque ruptures, a clot can form and cause a heart attack—a dramatic decline in the blood supply that causes heart tissue to die. (To find out if youre at risk for having a heart attack, take this test.)
What you can do about bad cholesterol
The artery-clogging process can start early in life. A 2008 autopsy study of adults ages 16 to 64 who died of non-heart-disease-related causes found that 83% had signs of heart disease and 8% had advanced disease. "We're seeing evidence of abnormality of blood vessels and obvious plaque in teenagers," says Dr. Nicholls.
Luckily, there are many things you can do to help prevent this process. "We know that lowering LDL cholesterol, the bad form, is clearly a good thing," says Dr. Nicholls. "The other thing we would highlight is the emerging role of HDL, or good cholesterol, the other player here."
Diet and exercise are critical for lowering LDL and raising HDL, notes Dr. Nicholls. (Click here for specific lifestyle changes that can lower heart disease risk.)
Cholesterol-lowering medication can also help, but you still need to watch your diet and exercise. "You can't just say, 'I'm being treated, so I can therefore not exercise and eat whatever I want,'" says Dr. Nicholls. "It doesn't work that way."
How can I reduce my cholesterol level?
Eat a healthy balanced diet
Eating lots of fruit, vegetables, and wholegrain is better than eating foods high in saturated or trans fats. You can replace saturated fats with the healthy monounsaturated and polyunsaturated fats such as olive, rapeseed or sunflower oils and spreads.
Choose foods that are high in soluble fibre such as oats, beans, pulses, lentils, nuts, fruits and vegetables. Soluble fibre can help lower cholesterol.
Do regular exercise
Regular physical activity can help increase your HDL cholesterol (the good type of cholesterol). Staying active is great way to keep your heart healthy.
Quit smoking
Quitting smoking can help to lower your cholesterol and improve your heart health.
Will I need to take medication?
Whether or not you need to take cholesterol-lowering medicine depends on your overall risk of cardiovascular disease.
Cholesterol-lowering medicines such as statins are prescribed for people who are at greatest overall risk of cardiovascular disease. If you have questions about your medicines, speak with your doctor or call our Heart Helpline on 0300 330 3311. You can also look at our publications for more information.
Will eating sterol-enriched foods help reduce my cholesterol level?
Although the effect varies between individuals, there is evidence to show that plant sterols and stanols can help to reduce LDL cholesterol by levels up to 10-15% when 2g per day is regularly consumed as part of a healthy balanced diet.
But whilst there is an expectation that this would lead to fewer heart attacks, no clinical trials have been undertaken to show this. Sterols and stanols have been added to certain foods, including margarines, spreads, soft cheeses and yoghurts.
Will eating too many eggs raise my cholesterol?
For most people, the amount of saturated fat they eat has much more of an impact on their cholesterol than eating foods that contain cholesterol, like eggs, liver, kidneys and shellfish. Unless you have been told otherwise by your doctor or dietician, if you like eggs, they can be included as part of a balanced and varied diet
Tag :
General Health,
Some infectious diseases
Infectious diseases are caused by microorganisms such as viruses, bacteria, fungi or parasites and can spread between individuals.
Mouse pox
Mouse pox is a highly infectious disease to which all strains of mice are susceptible, some more than others. Ectromelia is an excellent example of a virus carried and spread by apparently healthy mice. There may be no signs of illness, yet active virus may be readily recovered from viscera by blind passage. The virus obviously not only persists and multiplies despite a certain suppression by antibody, but also is shed through the feces. The virus was first described in England, but has since been reported from continental Europe as well as the United States ( Saunders, 1958a; Trentin, 1953). It is from 100 to 150 μ in diameter, is destroyed by exposure to 55°C for 30 minutes, but withstands 50 per cent glycerol and 0.5 per cent phenol for several months at refrigerator temperature. Clinical aspects of the disease have been described in detail by Fenner ( 1949) and Trentin ( 1953). The disease is generalized, the virus multiplying in cells of the skin, lymph nodes, liver, spleen, and other organs. In all these tissues intracellular eosinophilic inclusion bodies develop. The acute form, occurring in previously unexposed mice, is characterized by visceral lesions, usually hepatic necroses, the animals dying within days without external signs of illness. Sometimes inconspicuous external primary lesions are present such as swollen eyelids or pocked noses. The disease usually spreads rapidly throughout a susceptible colony, killing 50 to 95 per cent of the mice within weeks. The surviving mice develop circulating antibodies and often show a chronic form of the disease characterized by necrosis of the extremities, gangrene, crusting and scarring of skin, and regenerative lesions of internal organs. The foot lesions must be distinguished from those caused by Streptobacillus moniliformis. The most reliable diagnostic test for ectromelia infection is hemagglutination inhibition (HI). Either vaccinia or ectromelia virus is used as a red blood cell-agglutinating antigen. Serum from mice recovered from acute mouse pox will inhibit such agglutination of blood cells ( Burnet and Boake, 1946; Briody, 1959). The test can be quickly and conveniently carried out with as little as 0.05 ml of serum. The virus is demonstrated by intraperitoneal inoculation of visceral suspensions into susceptible mice. These animals ordinarily die 4 to 6 days after inoculation and show the visible lesions of multiple focal necroses of the livers.
Mouse colonies can be protected from ectromelia by strict isolation to preclude contamination by infected mice and other materials. Once the disease is recognized, however, infected colonies should be destroyed and all presumably infected animals incinerated. Another preventative measure, applicable to valuable inbred stocks, is vaccination, either by scarification or intranasal instillation with vaccinia virus or with formolized liver suspensions from infected mice ( Shope, 1954). Although both Levaditi and IHD-T strains of vaccinia virus have been successfully employed, IHD-T is preferred because it is more immunogenic, does not induce HI antibodies, and will not interfere with the HI test for diagnosis of infection. It is therefore possible to distinguish between antibodies formed as a result of infection and those formed as a result of vaccination. Vaccinated mice may transfer the infection to unvaccinated cage mates but not to mice in other cages of the same room. DBA mice seem to be more resistant to contact infection than other stocks ( Briody, 1959).
Hepatoencephalitis group of viruses
Some viruses are capable of causing hepatitis, encephalitis, or both in suckling mice. These are designated as MHV, JHM, EHF 120, and H747 and are related by degrees of cross-immunity (complement-fixation, neutralization tests). All produce qualitatively similar histological lesions affecting mesothelial and endothelial surfaces. These viruses, particularly the neurotropic ones, have similar susceptible host species ranges and occur in latent form in mouse stocks. All are heat-labile and ether-sensitive and range in size from 80 to 120 μ. The MHV or mouse hepatitis virus gives rise to intranuclear inclusion bodies, but to produce active disease requires the synergistic action of Eperythrozoön coccoides, a red blood cell parasite. The link between the two agents is complex. References may be found in Gledhill and Niven ( 1955) and Gledhill ( 1962).
Neurotropic viruses causing spontaneous encephalitis
There are three groups of viruses causing spontaneous encephalitis with distinctions based on the type of pathological lesion. Theiler's FV, FA, FO, and GD-VII affect the gray matter primarily, producing lesions comparable to those found in poliomyelitis ( Theiler and Gard, 1940; Thompson et al., 1951). The second group includes the JHM virus which causes demyelinization ( Olitsky and Lee, 1955; Pappenheimer, 1958a). The third group, which does not cause demyelinization, consists of SK, the Columbia strain of Jungeblut, LCM or lymphatic choriomeningitis ( Traub, 1939; Haas, 1954), EK virus, herpes simplex, and eastern equine encephalitis.
Theiler's mouse encephalomyelitis. Spontaneous infections of the central nervous system due to this virus are considerably more prevalent in younger mice. Unless the disease is rapidly fatal, gradual flaccid paralysis, usually of the hind limbs, develops. Microscopically, anterior-horn lesions quite similar to those of human poliomyelitis (ganglionic cell destruction) are observed. However, there is no serological relationship between Theiler's virus and that of poliomyelitis. Theiler's virus is recoverable from the intestinal tract or central nervous system. Artificial infections are possible by virtually all routes, although the level of infective dose differs considerably. For a more detailed review see Maurer ( 1958a).
Lymphocytic choriomeningitis. Although mice of laboratory colonies may harbor this virus, the disease is carried in latent form with few animals showing clinical signs or dying. Clinical illness occurs only in young animals which may show photophobia, conjuctivitis, and convulsive leg movements. Tremors, spastic convulsions, and paralysis are observed in Artificial infections. Microscopically, leukocytic infiltration of the meninges, pleural exudation, and splenomegaly are found. Virus is detected by intracerebral inoculation of mice with sterile suspensions of brain, blood, or spleen from suspect animals. In view of the wide host range (mice, monkeys, dogs, guinea pigs, and man) LCM represents a hazard to both experimental animals and man. Aside from direct contact transmission, as by the urine of infected mice, the virus may also be spread by ectoparasites and mosquitoes. For a review see Maurer ( 1958b).
Pneumotropic viruses
A number of viruses have been implicated as causes of respiratory disease in mice. Among these are Nigg's pneumonitis ( Nigg and Eaton, 1944) and PVM or pneumonia virus of mice ( Mirick et al., 1952; Volkert and Horsfall, 1947).
K virus
K virus infection is also a respiratory disease. In suckling mice the clinical signs are labored breathing and early death. Large basophilic inclusion bodies are observed in greatly hypertrophied alveolar lining cells. On occasion, focal disseminated fatty liver dystrophy is found. Since the first description of the disease and isolation of the virus, the K virus has been isolated in several parts of the world, notably Australia ( Fisher and Kilham, 1953; Holt, 1959; Derrick and Pope, 1960). The virus presumably spreads by way of the urine and saliva, yet serological surveys of both laboratory and wild mouse colonies indicate that antibodies occur in only a small proportion of mice from infected colonies.
Livers of moribund suckling mice provide a source for a suitable complement-fixing antigen so that the virus may be detected by the presence of specific antibody, although intracerebral inoculation of newborn mice with suspect tissues is a more sensitive test. It has been suggested that the K virus may be generically related to polyoma in view of certain common biological properties such as size, stability, etc. (Kilham, cited by Rowe et al., 1962.
Salivary gland virus
This virus is ubiquitous in wild mouse populations, but has been observed in only a few laboratory colonies. Apparently the virus does not spread with ease ( Rowe et al., 1962) since even in infected colonies its incidence is 3 per cent or less. Virus isolation techniques must be used for laboratory diagnosis. Serological techniques are of little value, and inclusion bodies are rarely observed despite continual excretion of virus in saliva ( Rowe et al., 1962; Brodsky and Rowe, 1958). Two procedures (utilizing mouth swabs as a convenient source of virus) are generally employed: (1) isolation of the virus in mouse embryo tissue culture, and (2) inoculation of newborn mice. The disease may be suspected in suckling mice by their malnourished appearance and at necropsy by the gross yellow discoloration of the edges of the liver.
Thymic virus
The thymic agent has been discovered in as high as one-half the mice of one laboratory colony and is highly prevalent in wild mice. It is pathogenic only for newborn mice and is recognizable by the production of gross thymic necroses, visible about 2 weeks after inoculation. Direct virus isolation is the most reliable diagnostic means, although infected mice produce neutralizing antibodies in low titer. The salivary glands represent the best source of virus since naturally or artificially infected mice excrete the virus in saliva for periods of more than one year. In contrast to the mouse salivary gland virus, the thymic agent does not propagate in tissue culture ( Rowe and Capps, 1961).
Adenovirus
This virus regularly infects recently weaned mice after prolonged exposure to urine of carrier animals. Infection induces a good complement-fixing and neutralizing-antibody response. Spontaneous clinical disease rarely occurs. However, virus inoculation into suckling mice induces a fatal disease consisting in inflammation and necrosis of the heart, adrenals, and brown fat. Acidophilic intranuclear inclusion bodies occur in these and other tissues ( Hartley and Rowe, 1960). The virus produces cytopathic effects in mouse kidney tissue cultures. Fluids from such infected cultures contain an excellent complement-fixing antigen which reacts strongly with adenoviral antisera prepared in guinea pigs (but not with human, monkey, or dog antisera). Apparently the virus does not cross the placental barrier, since it has not been encountered in caesarian-derived colonies ( Rowe et al., 1962).
Reoviruses
The reovirus group is composed of three serotypes ( Sabin, 1959). Antibodies to reoviruses are assayed by hemagglutination inhibition, neutralization, or complement-fixation tests. Reo 3 virus can be detected by tissue-culture cytopathogenicity, inoculation of suckling mice, or mouse antibody production tests. The sera of some mice contain hemagglutination inhibitor which is undoubtedly nonspecific since it is commonly encountered even in specific-pathogen-free and germ-free mouse colonies.
Only Reo 3 is indigenous to mice and has been isolated from tissue suspensions containing Molony virus. The oncolytic virus of Nelson, obtained from a transplanted ascites tumor ( Nelson and Tarnowski, 1960) has been identified as Reo 3. Reo 2 has been encountered as a focal infection in several wild mouse populations which may have acquired infection by contact with other species, such as man and cattle ( Rowe et al., 1962).
Oncogenic and tumor-associated viruses
Gross ( 1961) has discussed the status of virus-induced neoplasms, including mouse leukemias as produced by cell-free leukemic filtrates, the induction of leukemia by filtrates of solid mouse tumors, and the filterable agent causing mouse mammary tumors (Bittner's milk factor). Sinkovics ( 1962) has reviewed viral leukemias in mice and oncogenic viruses are discussed in Chapters 27 and 28. We refer here only to mouse polyoma infection and the lactic dehydrogenase-stimulating viruses ( Gross, 1953; Stewart, 1953; Riley et al., 1960).
A detailed epidemiology of mouse polyoma infection has been developed after intensive studies. The classic techniques of virology for detection of antibodies reveal that mouse polyoma virus is widely disseminated among laboratory colonies and wild mouse populations. Focal reservoirs of infection are maintained by routes of transmission involving virus excretion in urine, feces, and saliva. Apparently the virus is not transferred transplacentally since mice derived by caesarean section for specific-pathogen-free or germ-free colonies have been negative to antibody tests. Polyoma virus (e.g., infected tissue culture fluid) induces multiple tumors when inoculated into newborn mice. Such tumors are of multicentric and multiple histological origins, with mixed tumors of the salivary glands most frequent. The virus is capable of producing tumors in other species as well.
From the epidemiology of polyoma virus infection several points are notable: (10 Resistance of infant mice is perfectly correlated with presence of maternal antibody titers; no tumors develop in offspring of positive mothers; (2) spontaneous parotid tumors are rarely found in naturally infected mouse colonies; (3) high antibody titers are present in milk of infected mice; and (4) maternally derived antibodies are presumably present in fetuses, since it has been shown that mice born of resistant mothers but not having access to immune mouse milk are resistant to polyoma infection.
Certain transmissible agents have been found to be associated with many transplanted and induced spontaneous tumors of mice ( Riley et al., 1960). These are manifested by biochemical response. Susceptible animals respond with five- to tenfold increases in serum lactic dehydrogenase (LDH) and by induction of other glycolytic enzymes after inoculation with plasma or organ extracts from tumor-bearing hosts. Natural transmission of the lactic dehydrogenase-stimulating agents(s) (LDH) occurs when normal mice are placed in the same cage with agent-infected mice or tumor-bearing mice. In most infected animals moderate splenomegaly occurs. Serum LDH elevation has been induced by inoculation with preparations of cells from infected mice ( Riley et al., 1961). Although there is a close correlation between LDH levels and the growth of several transplanted tumors, elevation is not directly related to the neoplastic process. There is evidence to indicate that the LDH factor is a virus, specifically of mouse origin, and that changes in the LDH level of a tumor-bearing animal depend on whether or not the LDH factor has become associated with that tumor ( Notkins et al., 1962). An increase in lactate dehydrogenase levels can also be induced by injection of several of the mouse hepatitis viruses. LDH virus may be eliminated as a contaminant of transplantable tumors by passage of such material through tissue culture. However, it has been reported that the agent can be propagated and maintained by serial passage on primary mouse embryo tissue-culture ( Yaffee, 1962). It can be inactivated by radiation and is unstable in the presence of ether ( Notkins et al., 1962).
Infantile diarrhea
Diarrheal disease of unweaned mice is a complex syndrome caused by a number of agents ( Pappenheimer, 1958b; Runner and Palm, 1953; Kraft, 1962). As is true for diarrheal disease in human infants, there is considerable evidence that no single pathogen is the causative agent ( Thomlinson, 1964; Erlandson et al., 1964; Altman, 1964; Payne, 1960; Barua et al., 1962). Rather, under certain environmental conditions (crowding, poor sanitation, improper nutrition, variable temperatures, too low or too high humidity, inadequate ventilation, etc.) ubiquitous viral or bacterial organisms may be incriminated as producing diarrheal or septicemic signs in unweaned mice. We find that host factors, such as strain of mouse and parity play a determining role in morbidity and degree of clinical signs.
The clinical signs of the syndrome are: slight-to-severe diarrhea in which fecal material ranges from bright yellow to light brown in color. Nursing mothers will sometimes very efficiently clean up the anal region of the affected animal so that only a slight "pasting up" condition is noted. Animals affected by diarrhea (usually 4 to 10 days of age) usually recover, but many are discarded as runts at weaning time. The diarrhea is often followed by constipation contributing to later mortality, Mortality more often occurs in animals not showing signs of diarrhea. Such deaths occur early, 1 to 2 days after onset of the disease in a litter. Survivors in these litters show varying degrees of diarrhea.
At necropsy, the only common finding is the presence of light colored and watery fecal material in the intestinal tract, with occasional bubbles of gas. Histologically the tissues demonstrate a mild catarrhal inflammation. Some workers have reported inclusion bodies in epithelial cells from live and intestinal tract.
Viral agents such as those described by Kraft ( 1962) are found in the intestinal contents and reportedly can be transmitted directly to susceptible animals through this medium. Various types of bacteria, coliforms, Proteus sp., and pseudomonads have been found in separate outbreaks of the disease.
Epidemiologically the disease usually occurs in cycles. In certain affected mouse colonies, diarrheal disease is rarely seen until the fall and winter months. Our studies suggest that lower humidity and less fresh outside air are involved in seasonal recurrence rather than length of day and seasonal variation in quality of diet.
Colonies in which diarrheal disease is enzootic may show longer periods between epizootic outbreaks when moved to new quarters. During an outbreak the disease can be controlled by the use of broad-spectrum antibiotics such as the oxytetracyclines or tetracyclines administered in the drinking water. Therapeutic doses are administered over a 2-week period to all animals in a breeding colony. The preferable medication period is during the last third of pregnancy. This treatment is repeated in 2 weeks. Such therapy results in marked increase in the numbers of healthy-looking mice weaned and a decrease in the incidence of diarrhea. Similar effects are produced by the use of air-filtering material placed around each breeding cage or by the use of aluminum foil covering 50 per cent or more of open cage surfaces. The effects shown by cage modification (air filtering, foil covers) may be due to decreased aerosol dose levels. The use of certain types of highly absorbent bedding material also results in a higher recovery rate and a decrease in diarrheal disease. All of these control measures singly or in combination result initially in marked improvement of colony health, but usually over a period of months the disease reappears. Also, the effects of combining such control measures are not additive but only as good as the best measure used alone. Other effective control and prevention measures entail a variety of steps to isolate each breeding pen completely.
Much remains to be learned of the causes of infantile diarrheal disease, but the diarrhea should be considered as an accompaniment of certain diseases of suckling mice and not as a disease entity in itself.
BACTERIAL DISEASES
The spontaneously occurring or latently present bacterial diseases of mice are numerous, and the mouse is also susceptible to experimental infection by many pathogens from other species. Because of the small size of the animal, its habits, and the complexity of husbandry methods applied, it is extremely difficult to evaluate the health of a single animal by the usual clinical methods. Instead, an epidemiological approach is necessary. The population or a percentage thereof is observed for common factors which can be related to the various signs of morbidity and to mortality rates ( Shope, 1964).
Salmonellosis
Infection by Salmonella sp. is one of the more common types of bacteriological infections of mice ( Habermann and Williams, 1958a; Lane-Petter, 1963). The most commonly found strain is Salmonella typhimurium. However, mice are highly susceptible to infection by most of the Salmonella sp. organisms and other strains have been reported as responsible for epizootics or as latently infecting a few mice in a colony ( Wetmore and Hoag, 1960; Hoag et al., 1964a). The degree of virulence is dependent largely upon the dose and route of infection and the strain of host mouse as well as upon the inherent virulence of the organism itself. Salmonellosis is characterized initially by diarrhea or soft stools, sudden deaths, anorexia, and cachexia. Large number of animals are often lost not by death, but by the culling of underweight and poor-looking mice. The initial outbreak of salmonellosis soon subsides into a chronic form of the disease wherein the organisms are shed in fecal material. The adult carriers often appear healthy, but suckling and growing mice show great variation in body weight and rates of gain. Occasional breeding pairs are affected by attacks of mild diarrhea evidenced by soft, light-colored fecal pellets. Cull rates are high chiefly because of variations in weight and the poor appearance of weanling mice. At necropsy only a few animals show the classic "white spotted livers." Many will show enlarged spleens, but no gross necropsy findings are pathognomonic. Spleen, liver, and both large and small intestine are the tissues of choice for bacteriological examination. Tissues should be separately cultured for the presence of the organisms. In moribund or sick-looking animals the liver and spleen will yield Salmonella, whereas the chronically infected cases will usually yield organisms from the intestinal tract only.
For the isolation of Salmonella sp. enrichment media, preferably Tetrathionate Broth (Difco Laboratories), should be inoculated with a quantity of minced or ground tissues and the media incubated at 37°C for 72 hours ( Hoag and Rogers, 1961). During this period subcultures to Brilliant Green Agar (Difco) are incubated at 37°C for 48 hours before being discarded as negative for salmonella growths. Serological identification of suspect bacterial colonies is then carried out with polyvalent or group-specific antisera. Specific identification is dependent upon further serological techniques.
The disease is not controllable by any known therapeutic measures. Broad-spectrum antibiotics such as tetracycline or oxytetracycline seem to be of some use in epizootics in increasing the numbers of survivors, but they will not cure chronically infected animals. Vaccines of various types have been found to be highly effective against clinical signs and mortality from the disease but do not prevent chronic infection and carrier states from developing ( Hoag et. al., 1964b). We have demonstrated that three differently prepared S. typhimurium vaccines were effective against as many as 100 LD50 challenge doses of S. typhimurium but all of the surviving animals, although appearing perfectly healthy, were shedding organisms in fecal material and had infected livers and spleens as long as 6 weeks after the challenge.
The disease is controlled by elimination of infected or carrier stocks. Several (at least two and preferably six) weekly fecal tests should be performed before concluding that an animal is free of infection, since intermittent and low-level shedders are commonly encountered in a chronically infected colony. Sanitation is an important part of preventing spread of the disease, since an important mode of transmission is by contact with contaminated objects. Food supplies and bedding material should be treated as potential sources of infection. Occasional parathyphoid carriers are found among mouse handlers, but are not important sources of animal infection.
Pasteurellosis
Pasteurellosis due to Pasteurella pseudotuberculosis, P. septica, or P. pneumotropica may occur spontaneously in laboratory mice ( Sellers et al., 1961; Tuffery, 1958; Hoag et al., 1962). The latter two organisms may be found in various tissues of apparently normal mice. Latently infected animals subjected to various types of stress (radiation, abrupt temperature changes) will often produce signs of acute disease: anorexia, lassitude, sudden deaths. The livers of animals infected with P. pseudotuberculosis present multiple focal abscesses. P. pneumotropica has been reported in outbreaks of pneumonia in mice and has also been found in normal-appearing lung tissue ( Jawetz, 1948; Jawetz and Baker, 1948). In other instances this organism has been isolated from the brain, uterus, testes, liver, or spleen of normal-appearing mice. In rare instances septicemic deaths have been attributed to P. pneumotropica. Pasteurellosis is probably a stress-induced disease and the causative organism most commonly a latent infective one.
The pasteurella organism is susceptible to the tetracycline or oxytetracycline types of broad-spectrum antibiotics but is usually resistant to penicillin. Outbreaks in which signs of disease are thought to be caused by pasteurella organisms (on the basis of isolations from organ tissue) may be treated by administering the effective antibiotics in the drinking water. Response to the drugs is immediate and favorable.
Pseudomonas infections
Infection with Pseudomonas aeruginosa is common in laboratory mouse colonies ( Flynn, 1963a). No signs of infection are manifest unless animals are subjected to radiation or other types of stress (cortisone, etc.) ( Flynn, 1963a; Wensinck et al. 1957; Verder and Rosenthal, 1961). Such treatment results in rapid onset of septicemic disease (anorexia, listlessness) and high mortality. At necropsy the organisms are easily cultured from all organs, particularly liver and spleen. Although not important as a spontaneous disease-causing organism, P. aeruginosa is of major concern to investigators using mice in experiments employing radiation. The organism is shed in feces and urine from chronically infected animals. Nearly 100 per cent of the animals in a colony may become rapidly infected by contamination and recontamination of drinking water, caging equipment, and feeds. The infection can be controlled by hyperchlorination and acidification of water used for drinking and cleaning ( Hoag et al., 1965). Sanitation procedures must be of the highest efficiency and detectable carriers eliminated. Carrier detection should not serve as a criterion for culling until after control procedures such as water treatment and intensified sanitation have been inaugurated, since it has been shown that most fecal shedders of the organisms are only transiently infected and will seemingly spontaneously "recover" if not exposed to further doses of the organisms in contaminated water. After control procedures have been in effect for several weeks, a test-and-slaughter program should be started. Pens containing mice shedding the organism should be provided from the colony.
Antibiotics and other drugs are of no value in treating the infection. In one instance when oxytetracycline was being administered in drinking water to inbred mice, it was found that the organism grew more rapidly in water containing hypertherapeutic levels of the drug ( Hoag et al., 1965).
Klebsiella infections
Latent infections with capsulated lactose-fermenting bacilli, often loosely identified as Klebsiella group organisms, are not uncommon ( Wilson and Miles, 1964). Such organisms are occasionally isolated from lung tissue of normal-appearing mice. Sometimes the organism is found in the nasopharyngeal region or in various body wastes. In certain outbreaks of pneumonia in mice, Klebsiella sp. can be recovered from 100 per cent of the lungs of sick or moribund mice. The organisms recovered vary greatly in virulence. Rarely, the bacterium can be recovered from abscesses of lung or from other internal organs and cutaneous areas. Improved sanitation and environmental constancy are recommended control measures.
Tyzzer's disease
Disease caused by Bacillus piliformis has been described by several workers ( Fujiwara et al., 1963; Fujiwara et al., 1964; Saunders, 1958b). Most agree that the organism occurs in an infected colony as an intestinal saprophyte and that clinical disease occurs only after animals have been stressed, as by adverse nutrition or by the effects of stressors introduced during the course of an experiment. Onset of disease signs is abrupt with death occurring 2 to 3 days afterward. Diarrhea may occur as the major sing or may affect only a few of the sick animals. Anorexia and other signs of septicemia are manifest. Some immunity develops in recovered animals.
The condition may occur in mice of all ages, but the highest mortality rate is observed in 3- to 7-week-old animals. The most striking necropsy finding is the occurrence of numerous grayish-white spots (up to 2.5 mm in diameter) on the outer and cut surfaces of the liver. Mesenteric lymph nodes are usually enlarged and sometimes abscessed. Microscopically the organisms (long, thin, Gram-negative rods) are found intercellularly, surrounding the necrotic tissue areas, but are also seen in intact liver cells as well. the organisms have been reported as cultivatable in tissue culture, but cannot be grown on defined bacteriological media. Diagnosis is by histological sectioning and staining of tissues with subsequent demonstration of stained organisms.
Differences between mouse strains in susceptibility have been demonstrated, but it is emphasized that any incidence in a mouse colony represents a disease potential and infected colonies must therefore be considered as hazardous for other research. Little work has been done to demonstrate the effectiveness of therapy, although oxytetracycline has been of value ( Tuffery, 1958).
PPLO (Pleuropneumonia-like organisms)
Infections with organisms described as PPLO have been chiefly reported as causing catarrhal disease in mice ( Nelson, 1958). Some outbreaks of disease of the upper respiratory tract are characterized by sudden onset and involvement of a large percentage of a colony usually after chilling or overheating. Chattering and sniffling with variable nasal discharge are the observable signs of infection. Mortality rates are low, and recovery from the exudative catarrh is spontaneous. A few animals succumb to bronchopneumonia or may develop a chronic bronchiectatic pneumonia. In other types of upper respiratory disease caused by PPLO the onset is gradual and the outbreak appears enzootic in character, Because of the chronic nature and long course of the disease, the eventual involvement of large numbers of animals may give the appearance of a suddenly occurring epizootic disease, particularly if the mild symptoms in the early stages of the condition are unnoted. Labyrinthitis (manifested by disequilibrium) may occur in a few of the mice.
PPLO organisms are often found in animals from an apparently healthy colony and may be recovered from various tissues other than lung material ( Freundt, 1959). The pathogenic potential of latent infections is always manifest but has not been quantitatively evaluated.
Streptobacillus moniliformis
Infections with Streptobacillus moniliformis are usually latent. In certain outbreaks where clinical signs include lameness and swelling of joints and extremities (due to edema), the organism is readily isolated from blood and organs, including affected joints ( Wilson and Miles, 1964; Freundt, 1956). In other instances the organism is not found in the bacterial cell state, but is isolated with extreme difficulty in L form by PPLO culture techniques ( Freundt, 1959). Clinical signs are often confused with those seen in chronic ectromelia, and for this reason an early differential diagnosis is indicated ( Lane-Petter, 1963). Stress plays an important role in the activation of latent infection. In many outbreaks mice will arrive in apparently good health after exposure to adverse shipping conditions, but within 3 to 4 days 10 to 50 per cent will develop signs of the disease — swellings and ulcerations of feet and tail after the appearance of a sharp band of demarcation proximal to the swelling. Recovery is usually spontaneous, although severely affected animals are deformed because of deranged circulation to extremities with subsequent sloughing of the entire area distal to the necrotic demarcation band. In our experience antibiotics such as tetracycline and oxytetracycline seem to be useful in controlling outbreaks. In clinically affected animals these drugs serve to mitigate the severity of developing lesions.
PARASITIC DISEASES
Helminth infections
Mice may become infected with helminths from other species ( Haberman and Williams, 1958b). Outbreaks of infection with Taenia taeniformis can occur when mice are housed in the same area with cats. Infections with the various helminths rarely produce clinical signs and are only potentially important as producing unpredictable variables in animals used in research. Heavily infected animals are below norms in weight and may be anemic. Some mouse colonies may be infected with Hymenolopis nana (the dwarf tapeworm). The life cycle of this parasite does not involve any secondary hosts, with infection taking place directly from eggs excreted in feces. Upon necropsy, the tapeworm is easily observed through the walls of the unopened intestinal tract.
Mouse colonies are often infected with the oxyurids Syphacia obvelata and Aspiculuris tetraptera. These mouse pinworms have a direct life cycle and spread through a colony rapidly because of the large numbers of eggs excreted and the ease with which the eggs are airborne. There are no clinical signs of oxyuriasis. There may be some weight and growth variation between infected and noninfected animals, but other signs such as poor hair coat, etc., are not clear-cut. There is some evidence that oxyuriasis may contribute to rectal prolapse. Diagnosis can be made by examination of fecal material or the anal region for oxyurid eggs by the various flotation or contact-tape techniques. Pinworm infection may be eliminated by treatment with various drugs such as the piperazine compounds, usually most efficacious when administered via drinking water ( Hoag, 1961). Treatment must be accompanied by through cleaning of the room and caging equipment to remove the possibility of reinfection from egg-contaminated dust.
Arthropod infections
Lice (Polyplax serrata) and mites (Myobia musculi, Myocoptes musculinus, Myocoptes romboutsi, Radfordia affinis, and Psoregates simplex) are the chief ectoparasites of laboratory mice ( Flynn, 1963b). Their presence is manifested by hair loss and scratching, which may give rise to bacterially infected ulcerative wounds. It is not unusual for mice to die in a heavily infested colony as a result of these infected sores.
Control of ectoparasites is difficult. Various dusting powders containing DDT, methoxyclor, rotenone, or other parasiticides, and dips containing aramite or other materials have been used, but must be regularly or periodically applied. Bedding materials either treated with aromatic hydrocarbons (such as crude cedar wood oil) or naturally containing such materials (cedar wood shavings) are successful in suppressing infestations.
PROTOZOAN INFECTIONS
Several types of protozoan diseases have been reported in mice. Most are inapparent infections, noted only after synergistic activity with other agents such as viruses or after interference with immunological body defenses as by splenectomy, Control is usually by improving hygiene after elimination of infected animals or whole colonies.
Eperythrozoön coccoides occurs as a blood parasite in the form of disc-shaped structures on the surface of red blood cells. Splenectomy of infected mice results in a marked increase in the numbers of parasitized cells and onset of transient mild anemia. The presence of this parasite increases susceptibility to such infectious agents as the mouse hepatitis virus, lymphocytic choriomeningitis virus, and lactate dehydrogenase-elevating virus ( Seamer et al., 1961; Riley, 1964).
Hemobartonella muris is another red blood cell parasite activated in infected mice after splenectomy ( Griesemer, 1958). Infectivity is very low. The anemia produced is mild and transitory.
Eperythrozoön cuniculi causes mild febrile disease in mice, infects epithelial cells of the kidney papillae, and produces granulomatous lesions in brain tissue ( Yost, 1958). These organisms occur as 1.5- to 2.0-μ Gram-positive rods. Transmission is apparently by way of urine, which may contain large numbers of organisms.
Klosiella muris has been described as causing an infection of mouse kidney epithelial cells ( Dunn, 1949). Signs of disease are inapparent although, on necropsy, kidneys of infected animals may be surface-marked with varying numbers of tiny grayish-white foci. Transmission is by way of spore cysts released into the urine.
MYCOTIC INFECTIONS
Mycotic infections of mice usually produce a dermatitis. Such infections, which can be caused by any one of several Trichophyton or Microsporum sp., result in circumscribed encrusted areas with hair loss and are empirically called ringworm. The fungus from the lesions may be easily demonstrated by microscopic examination of skin scrapings ( La Touche, 1957). Control of the colony infection is difficult. Outbreaks are chiefly important as sources of human infection as most of these fungi cause similar lesions in man.
SUMMARY
The mouse is susceptible to an array of infectious agents. Many of these agents produce signs of disease and must be eliminated or controlled if only to maintain sizable mouse populations. On the other hand, because the mouse is so important as a biological yardstick for measurement of varied procedures, it becomes important as well to eliminate or control those infectious agents which do not produce observable disease, but which may affect the outcome of an experiment. The development of mouse colonies from caesarean-derived stock is an effective panacea for eliminating those disease agents which cannot penetrate the placental barriers. In another respect, it is important to study the synergistic or antagonistic effect of various disease agents either in combination with each other or with other factors so that information so derived may contribute toward man's understanding of his own disease problems. It would be unfortunate to eliminate completely all disease of mice before obtaining more complete knowledge of the etiology, epidemiology, and pathology of such naturally occurring conditions.
Mouse pox is a highly infectious disease to which all strains of mice are susceptible, some more than others. Ectromelia is an excellent example of a virus carried and spread by apparently healthy mice. There may be no signs of illness, yet active virus may be readily recovered from viscera by blind passage. The virus obviously not only persists and multiplies despite a certain suppression by antibody, but also is shed through the feces. The virus was first described in England, but has since been reported from continental Europe as well as the United States ( Saunders, 1958a; Trentin, 1953). It is from 100 to 150 μ in diameter, is destroyed by exposure to 55°C for 30 minutes, but withstands 50 per cent glycerol and 0.5 per cent phenol for several months at refrigerator temperature. Clinical aspects of the disease have been described in detail by Fenner ( 1949) and Trentin ( 1953). The disease is generalized, the virus multiplying in cells of the skin, lymph nodes, liver, spleen, and other organs. In all these tissues intracellular eosinophilic inclusion bodies develop. The acute form, occurring in previously unexposed mice, is characterized by visceral lesions, usually hepatic necroses, the animals dying within days without external signs of illness. Sometimes inconspicuous external primary lesions are present such as swollen eyelids or pocked noses. The disease usually spreads rapidly throughout a susceptible colony, killing 50 to 95 per cent of the mice within weeks. The surviving mice develop circulating antibodies and often show a chronic form of the disease characterized by necrosis of the extremities, gangrene, crusting and scarring of skin, and regenerative lesions of internal organs. The foot lesions must be distinguished from those caused by Streptobacillus moniliformis. The most reliable diagnostic test for ectromelia infection is hemagglutination inhibition (HI). Either vaccinia or ectromelia virus is used as a red blood cell-agglutinating antigen. Serum from mice recovered from acute mouse pox will inhibit such agglutination of blood cells ( Burnet and Boake, 1946; Briody, 1959). The test can be quickly and conveniently carried out with as little as 0.05 ml of serum. The virus is demonstrated by intraperitoneal inoculation of visceral suspensions into susceptible mice. These animals ordinarily die 4 to 6 days after inoculation and show the visible lesions of multiple focal necroses of the livers.
Mouse colonies can be protected from ectromelia by strict isolation to preclude contamination by infected mice and other materials. Once the disease is recognized, however, infected colonies should be destroyed and all presumably infected animals incinerated. Another preventative measure, applicable to valuable inbred stocks, is vaccination, either by scarification or intranasal instillation with vaccinia virus or with formolized liver suspensions from infected mice ( Shope, 1954). Although both Levaditi and IHD-T strains of vaccinia virus have been successfully employed, IHD-T is preferred because it is more immunogenic, does not induce HI antibodies, and will not interfere with the HI test for diagnosis of infection. It is therefore possible to distinguish between antibodies formed as a result of infection and those formed as a result of vaccination. Vaccinated mice may transfer the infection to unvaccinated cage mates but not to mice in other cages of the same room. DBA mice seem to be more resistant to contact infection than other stocks ( Briody, 1959).
Hepatoencephalitis group of viruses
Some viruses are capable of causing hepatitis, encephalitis, or both in suckling mice. These are designated as MHV, JHM, EHF 120, and H747 and are related by degrees of cross-immunity (complement-fixation, neutralization tests). All produce qualitatively similar histological lesions affecting mesothelial and endothelial surfaces. These viruses, particularly the neurotropic ones, have similar susceptible host species ranges and occur in latent form in mouse stocks. All are heat-labile and ether-sensitive and range in size from 80 to 120 μ. The MHV or mouse hepatitis virus gives rise to intranuclear inclusion bodies, but to produce active disease requires the synergistic action of Eperythrozoön coccoides, a red blood cell parasite. The link between the two agents is complex. References may be found in Gledhill and Niven ( 1955) and Gledhill ( 1962).
Neurotropic viruses causing spontaneous encephalitis
There are three groups of viruses causing spontaneous encephalitis with distinctions based on the type of pathological lesion. Theiler's FV, FA, FO, and GD-VII affect the gray matter primarily, producing lesions comparable to those found in poliomyelitis ( Theiler and Gard, 1940; Thompson et al., 1951). The second group includes the JHM virus which causes demyelinization ( Olitsky and Lee, 1955; Pappenheimer, 1958a). The third group, which does not cause demyelinization, consists of SK, the Columbia strain of Jungeblut, LCM or lymphatic choriomeningitis ( Traub, 1939; Haas, 1954), EK virus, herpes simplex, and eastern equine encephalitis.
Theiler's mouse encephalomyelitis. Spontaneous infections of the central nervous system due to this virus are considerably more prevalent in younger mice. Unless the disease is rapidly fatal, gradual flaccid paralysis, usually of the hind limbs, develops. Microscopically, anterior-horn lesions quite similar to those of human poliomyelitis (ganglionic cell destruction) are observed. However, there is no serological relationship between Theiler's virus and that of poliomyelitis. Theiler's virus is recoverable from the intestinal tract or central nervous system. Artificial infections are possible by virtually all routes, although the level of infective dose differs considerably. For a more detailed review see Maurer ( 1958a).
Lymphocytic choriomeningitis. Although mice of laboratory colonies may harbor this virus, the disease is carried in latent form with few animals showing clinical signs or dying. Clinical illness occurs only in young animals which may show photophobia, conjuctivitis, and convulsive leg movements. Tremors, spastic convulsions, and paralysis are observed in Artificial infections. Microscopically, leukocytic infiltration of the meninges, pleural exudation, and splenomegaly are found. Virus is detected by intracerebral inoculation of mice with sterile suspensions of brain, blood, or spleen from suspect animals. In view of the wide host range (mice, monkeys, dogs, guinea pigs, and man) LCM represents a hazard to both experimental animals and man. Aside from direct contact transmission, as by the urine of infected mice, the virus may also be spread by ectoparasites and mosquitoes. For a review see Maurer ( 1958b).
Pneumotropic viruses
A number of viruses have been implicated as causes of respiratory disease in mice. Among these are Nigg's pneumonitis ( Nigg and Eaton, 1944) and PVM or pneumonia virus of mice ( Mirick et al., 1952; Volkert and Horsfall, 1947).
K virus
K virus infection is also a respiratory disease. In suckling mice the clinical signs are labored breathing and early death. Large basophilic inclusion bodies are observed in greatly hypertrophied alveolar lining cells. On occasion, focal disseminated fatty liver dystrophy is found. Since the first description of the disease and isolation of the virus, the K virus has been isolated in several parts of the world, notably Australia ( Fisher and Kilham, 1953; Holt, 1959; Derrick and Pope, 1960). The virus presumably spreads by way of the urine and saliva, yet serological surveys of both laboratory and wild mouse colonies indicate that antibodies occur in only a small proportion of mice from infected colonies.
Livers of moribund suckling mice provide a source for a suitable complement-fixing antigen so that the virus may be detected by the presence of specific antibody, although intracerebral inoculation of newborn mice with suspect tissues is a more sensitive test. It has been suggested that the K virus may be generically related to polyoma in view of certain common biological properties such as size, stability, etc. (Kilham, cited by Rowe et al., 1962.
Salivary gland virus
This virus is ubiquitous in wild mouse populations, but has been observed in only a few laboratory colonies. Apparently the virus does not spread with ease ( Rowe et al., 1962) since even in infected colonies its incidence is 3 per cent or less. Virus isolation techniques must be used for laboratory diagnosis. Serological techniques are of little value, and inclusion bodies are rarely observed despite continual excretion of virus in saliva ( Rowe et al., 1962; Brodsky and Rowe, 1958). Two procedures (utilizing mouth swabs as a convenient source of virus) are generally employed: (1) isolation of the virus in mouse embryo tissue culture, and (2) inoculation of newborn mice. The disease may be suspected in suckling mice by their malnourished appearance and at necropsy by the gross yellow discoloration of the edges of the liver.
Thymic virus
The thymic agent has been discovered in as high as one-half the mice of one laboratory colony and is highly prevalent in wild mice. It is pathogenic only for newborn mice and is recognizable by the production of gross thymic necroses, visible about 2 weeks after inoculation. Direct virus isolation is the most reliable diagnostic means, although infected mice produce neutralizing antibodies in low titer. The salivary glands represent the best source of virus since naturally or artificially infected mice excrete the virus in saliva for periods of more than one year. In contrast to the mouse salivary gland virus, the thymic agent does not propagate in tissue culture ( Rowe and Capps, 1961).
Adenovirus
This virus regularly infects recently weaned mice after prolonged exposure to urine of carrier animals. Infection induces a good complement-fixing and neutralizing-antibody response. Spontaneous clinical disease rarely occurs. However, virus inoculation into suckling mice induces a fatal disease consisting in inflammation and necrosis of the heart, adrenals, and brown fat. Acidophilic intranuclear inclusion bodies occur in these and other tissues ( Hartley and Rowe, 1960). The virus produces cytopathic effects in mouse kidney tissue cultures. Fluids from such infected cultures contain an excellent complement-fixing antigen which reacts strongly with adenoviral antisera prepared in guinea pigs (but not with human, monkey, or dog antisera). Apparently the virus does not cross the placental barrier, since it has not been encountered in caesarian-derived colonies ( Rowe et al., 1962).
Reoviruses
The reovirus group is composed of three serotypes ( Sabin, 1959). Antibodies to reoviruses are assayed by hemagglutination inhibition, neutralization, or complement-fixation tests. Reo 3 virus can be detected by tissue-culture cytopathogenicity, inoculation of suckling mice, or mouse antibody production tests. The sera of some mice contain hemagglutination inhibitor which is undoubtedly nonspecific since it is commonly encountered even in specific-pathogen-free and germ-free mouse colonies.
Only Reo 3 is indigenous to mice and has been isolated from tissue suspensions containing Molony virus. The oncolytic virus of Nelson, obtained from a transplanted ascites tumor ( Nelson and Tarnowski, 1960) has been identified as Reo 3. Reo 2 has been encountered as a focal infection in several wild mouse populations which may have acquired infection by contact with other species, such as man and cattle ( Rowe et al., 1962).
Oncogenic and tumor-associated viruses
Gross ( 1961) has discussed the status of virus-induced neoplasms, including mouse leukemias as produced by cell-free leukemic filtrates, the induction of leukemia by filtrates of solid mouse tumors, and the filterable agent causing mouse mammary tumors (Bittner's milk factor). Sinkovics ( 1962) has reviewed viral leukemias in mice and oncogenic viruses are discussed in Chapters 27 and 28. We refer here only to mouse polyoma infection and the lactic dehydrogenase-stimulating viruses ( Gross, 1953; Stewart, 1953; Riley et al., 1960).
A detailed epidemiology of mouse polyoma infection has been developed after intensive studies. The classic techniques of virology for detection of antibodies reveal that mouse polyoma virus is widely disseminated among laboratory colonies and wild mouse populations. Focal reservoirs of infection are maintained by routes of transmission involving virus excretion in urine, feces, and saliva. Apparently the virus is not transferred transplacentally since mice derived by caesarean section for specific-pathogen-free or germ-free colonies have been negative to antibody tests. Polyoma virus (e.g., infected tissue culture fluid) induces multiple tumors when inoculated into newborn mice. Such tumors are of multicentric and multiple histological origins, with mixed tumors of the salivary glands most frequent. The virus is capable of producing tumors in other species as well.
From the epidemiology of polyoma virus infection several points are notable: (10 Resistance of infant mice is perfectly correlated with presence of maternal antibody titers; no tumors develop in offspring of positive mothers; (2) spontaneous parotid tumors are rarely found in naturally infected mouse colonies; (3) high antibody titers are present in milk of infected mice; and (4) maternally derived antibodies are presumably present in fetuses, since it has been shown that mice born of resistant mothers but not having access to immune mouse milk are resistant to polyoma infection.
Certain transmissible agents have been found to be associated with many transplanted and induced spontaneous tumors of mice ( Riley et al., 1960). These are manifested by biochemical response. Susceptible animals respond with five- to tenfold increases in serum lactic dehydrogenase (LDH) and by induction of other glycolytic enzymes after inoculation with plasma or organ extracts from tumor-bearing hosts. Natural transmission of the lactic dehydrogenase-stimulating agents(s) (LDH) occurs when normal mice are placed in the same cage with agent-infected mice or tumor-bearing mice. In most infected animals moderate splenomegaly occurs. Serum LDH elevation has been induced by inoculation with preparations of cells from infected mice ( Riley et al., 1961). Although there is a close correlation between LDH levels and the growth of several transplanted tumors, elevation is not directly related to the neoplastic process. There is evidence to indicate that the LDH factor is a virus, specifically of mouse origin, and that changes in the LDH level of a tumor-bearing animal depend on whether or not the LDH factor has become associated with that tumor ( Notkins et al., 1962). An increase in lactate dehydrogenase levels can also be induced by injection of several of the mouse hepatitis viruses. LDH virus may be eliminated as a contaminant of transplantable tumors by passage of such material through tissue culture. However, it has been reported that the agent can be propagated and maintained by serial passage on primary mouse embryo tissue-culture ( Yaffee, 1962). It can be inactivated by radiation and is unstable in the presence of ether ( Notkins et al., 1962).
Infantile diarrhea
Diarrheal disease of unweaned mice is a complex syndrome caused by a number of agents ( Pappenheimer, 1958b; Runner and Palm, 1953; Kraft, 1962). As is true for diarrheal disease in human infants, there is considerable evidence that no single pathogen is the causative agent ( Thomlinson, 1964; Erlandson et al., 1964; Altman, 1964; Payne, 1960; Barua et al., 1962). Rather, under certain environmental conditions (crowding, poor sanitation, improper nutrition, variable temperatures, too low or too high humidity, inadequate ventilation, etc.) ubiquitous viral or bacterial organisms may be incriminated as producing diarrheal or septicemic signs in unweaned mice. We find that host factors, such as strain of mouse and parity play a determining role in morbidity and degree of clinical signs.
The clinical signs of the syndrome are: slight-to-severe diarrhea in which fecal material ranges from bright yellow to light brown in color. Nursing mothers will sometimes very efficiently clean up the anal region of the affected animal so that only a slight "pasting up" condition is noted. Animals affected by diarrhea (usually 4 to 10 days of age) usually recover, but many are discarded as runts at weaning time. The diarrhea is often followed by constipation contributing to later mortality, Mortality more often occurs in animals not showing signs of diarrhea. Such deaths occur early, 1 to 2 days after onset of the disease in a litter. Survivors in these litters show varying degrees of diarrhea.
At necropsy, the only common finding is the presence of light colored and watery fecal material in the intestinal tract, with occasional bubbles of gas. Histologically the tissues demonstrate a mild catarrhal inflammation. Some workers have reported inclusion bodies in epithelial cells from live and intestinal tract.
Viral agents such as those described by Kraft ( 1962) are found in the intestinal contents and reportedly can be transmitted directly to susceptible animals through this medium. Various types of bacteria, coliforms, Proteus sp., and pseudomonads have been found in separate outbreaks of the disease.
Epidemiologically the disease usually occurs in cycles. In certain affected mouse colonies, diarrheal disease is rarely seen until the fall and winter months. Our studies suggest that lower humidity and less fresh outside air are involved in seasonal recurrence rather than length of day and seasonal variation in quality of diet.
Colonies in which diarrheal disease is enzootic may show longer periods between epizootic outbreaks when moved to new quarters. During an outbreak the disease can be controlled by the use of broad-spectrum antibiotics such as the oxytetracyclines or tetracyclines administered in the drinking water. Therapeutic doses are administered over a 2-week period to all animals in a breeding colony. The preferable medication period is during the last third of pregnancy. This treatment is repeated in 2 weeks. Such therapy results in marked increase in the numbers of healthy-looking mice weaned and a decrease in the incidence of diarrhea. Similar effects are produced by the use of air-filtering material placed around each breeding cage or by the use of aluminum foil covering 50 per cent or more of open cage surfaces. The effects shown by cage modification (air filtering, foil covers) may be due to decreased aerosol dose levels. The use of certain types of highly absorbent bedding material also results in a higher recovery rate and a decrease in diarrheal disease. All of these control measures singly or in combination result initially in marked improvement of colony health, but usually over a period of months the disease reappears. Also, the effects of combining such control measures are not additive but only as good as the best measure used alone. Other effective control and prevention measures entail a variety of steps to isolate each breeding pen completely.
Much remains to be learned of the causes of infantile diarrheal disease, but the diarrhea should be considered as an accompaniment of certain diseases of suckling mice and not as a disease entity in itself.
BACTERIAL DISEASES
The spontaneously occurring or latently present bacterial diseases of mice are numerous, and the mouse is also susceptible to experimental infection by many pathogens from other species. Because of the small size of the animal, its habits, and the complexity of husbandry methods applied, it is extremely difficult to evaluate the health of a single animal by the usual clinical methods. Instead, an epidemiological approach is necessary. The population or a percentage thereof is observed for common factors which can be related to the various signs of morbidity and to mortality rates ( Shope, 1964).
Salmonellosis
Infection by Salmonella sp. is one of the more common types of bacteriological infections of mice ( Habermann and Williams, 1958a; Lane-Petter, 1963). The most commonly found strain is Salmonella typhimurium. However, mice are highly susceptible to infection by most of the Salmonella sp. organisms and other strains have been reported as responsible for epizootics or as latently infecting a few mice in a colony ( Wetmore and Hoag, 1960; Hoag et al., 1964a). The degree of virulence is dependent largely upon the dose and route of infection and the strain of host mouse as well as upon the inherent virulence of the organism itself. Salmonellosis is characterized initially by diarrhea or soft stools, sudden deaths, anorexia, and cachexia. Large number of animals are often lost not by death, but by the culling of underweight and poor-looking mice. The initial outbreak of salmonellosis soon subsides into a chronic form of the disease wherein the organisms are shed in fecal material. The adult carriers often appear healthy, but suckling and growing mice show great variation in body weight and rates of gain. Occasional breeding pairs are affected by attacks of mild diarrhea evidenced by soft, light-colored fecal pellets. Cull rates are high chiefly because of variations in weight and the poor appearance of weanling mice. At necropsy only a few animals show the classic "white spotted livers." Many will show enlarged spleens, but no gross necropsy findings are pathognomonic. Spleen, liver, and both large and small intestine are the tissues of choice for bacteriological examination. Tissues should be separately cultured for the presence of the organisms. In moribund or sick-looking animals the liver and spleen will yield Salmonella, whereas the chronically infected cases will usually yield organisms from the intestinal tract only.
For the isolation of Salmonella sp. enrichment media, preferably Tetrathionate Broth (Difco Laboratories), should be inoculated with a quantity of minced or ground tissues and the media incubated at 37°C for 72 hours ( Hoag and Rogers, 1961). During this period subcultures to Brilliant Green Agar (Difco) are incubated at 37°C for 48 hours before being discarded as negative for salmonella growths. Serological identification of suspect bacterial colonies is then carried out with polyvalent or group-specific antisera. Specific identification is dependent upon further serological techniques.
The disease is not controllable by any known therapeutic measures. Broad-spectrum antibiotics such as tetracycline or oxytetracycline seem to be of some use in epizootics in increasing the numbers of survivors, but they will not cure chronically infected animals. Vaccines of various types have been found to be highly effective against clinical signs and mortality from the disease but do not prevent chronic infection and carrier states from developing ( Hoag et. al., 1964b). We have demonstrated that three differently prepared S. typhimurium vaccines were effective against as many as 100 LD50 challenge doses of S. typhimurium but all of the surviving animals, although appearing perfectly healthy, were shedding organisms in fecal material and had infected livers and spleens as long as 6 weeks after the challenge.
The disease is controlled by elimination of infected or carrier stocks. Several (at least two and preferably six) weekly fecal tests should be performed before concluding that an animal is free of infection, since intermittent and low-level shedders are commonly encountered in a chronically infected colony. Sanitation is an important part of preventing spread of the disease, since an important mode of transmission is by contact with contaminated objects. Food supplies and bedding material should be treated as potential sources of infection. Occasional parathyphoid carriers are found among mouse handlers, but are not important sources of animal infection.
Pasteurellosis
Pasteurellosis due to Pasteurella pseudotuberculosis, P. septica, or P. pneumotropica may occur spontaneously in laboratory mice ( Sellers et al., 1961; Tuffery, 1958; Hoag et al., 1962). The latter two organisms may be found in various tissues of apparently normal mice. Latently infected animals subjected to various types of stress (radiation, abrupt temperature changes) will often produce signs of acute disease: anorexia, lassitude, sudden deaths. The livers of animals infected with P. pseudotuberculosis present multiple focal abscesses. P. pneumotropica has been reported in outbreaks of pneumonia in mice and has also been found in normal-appearing lung tissue ( Jawetz, 1948; Jawetz and Baker, 1948). In other instances this organism has been isolated from the brain, uterus, testes, liver, or spleen of normal-appearing mice. In rare instances septicemic deaths have been attributed to P. pneumotropica. Pasteurellosis is probably a stress-induced disease and the causative organism most commonly a latent infective one.
The pasteurella organism is susceptible to the tetracycline or oxytetracycline types of broad-spectrum antibiotics but is usually resistant to penicillin. Outbreaks in which signs of disease are thought to be caused by pasteurella organisms (on the basis of isolations from organ tissue) may be treated by administering the effective antibiotics in the drinking water. Response to the drugs is immediate and favorable.
Pseudomonas infections
Infection with Pseudomonas aeruginosa is common in laboratory mouse colonies ( Flynn, 1963a). No signs of infection are manifest unless animals are subjected to radiation or other types of stress (cortisone, etc.) ( Flynn, 1963a; Wensinck et al. 1957; Verder and Rosenthal, 1961). Such treatment results in rapid onset of septicemic disease (anorexia, listlessness) and high mortality. At necropsy the organisms are easily cultured from all organs, particularly liver and spleen. Although not important as a spontaneous disease-causing organism, P. aeruginosa is of major concern to investigators using mice in experiments employing radiation. The organism is shed in feces and urine from chronically infected animals. Nearly 100 per cent of the animals in a colony may become rapidly infected by contamination and recontamination of drinking water, caging equipment, and feeds. The infection can be controlled by hyperchlorination and acidification of water used for drinking and cleaning ( Hoag et al., 1965). Sanitation procedures must be of the highest efficiency and detectable carriers eliminated. Carrier detection should not serve as a criterion for culling until after control procedures such as water treatment and intensified sanitation have been inaugurated, since it has been shown that most fecal shedders of the organisms are only transiently infected and will seemingly spontaneously "recover" if not exposed to further doses of the organisms in contaminated water. After control procedures have been in effect for several weeks, a test-and-slaughter program should be started. Pens containing mice shedding the organism should be provided from the colony.
Antibiotics and other drugs are of no value in treating the infection. In one instance when oxytetracycline was being administered in drinking water to inbred mice, it was found that the organism grew more rapidly in water containing hypertherapeutic levels of the drug ( Hoag et al., 1965).
Klebsiella infections
Latent infections with capsulated lactose-fermenting bacilli, often loosely identified as Klebsiella group organisms, are not uncommon ( Wilson and Miles, 1964). Such organisms are occasionally isolated from lung tissue of normal-appearing mice. Sometimes the organism is found in the nasopharyngeal region or in various body wastes. In certain outbreaks of pneumonia in mice, Klebsiella sp. can be recovered from 100 per cent of the lungs of sick or moribund mice. The organisms recovered vary greatly in virulence. Rarely, the bacterium can be recovered from abscesses of lung or from other internal organs and cutaneous areas. Improved sanitation and environmental constancy are recommended control measures.
Tyzzer's disease
Disease caused by Bacillus piliformis has been described by several workers ( Fujiwara et al., 1963; Fujiwara et al., 1964; Saunders, 1958b). Most agree that the organism occurs in an infected colony as an intestinal saprophyte and that clinical disease occurs only after animals have been stressed, as by adverse nutrition or by the effects of stressors introduced during the course of an experiment. Onset of disease signs is abrupt with death occurring 2 to 3 days afterward. Diarrhea may occur as the major sing or may affect only a few of the sick animals. Anorexia and other signs of septicemia are manifest. Some immunity develops in recovered animals.
The condition may occur in mice of all ages, but the highest mortality rate is observed in 3- to 7-week-old animals. The most striking necropsy finding is the occurrence of numerous grayish-white spots (up to 2.5 mm in diameter) on the outer and cut surfaces of the liver. Mesenteric lymph nodes are usually enlarged and sometimes abscessed. Microscopically the organisms (long, thin, Gram-negative rods) are found intercellularly, surrounding the necrotic tissue areas, but are also seen in intact liver cells as well. the organisms have been reported as cultivatable in tissue culture, but cannot be grown on defined bacteriological media. Diagnosis is by histological sectioning and staining of tissues with subsequent demonstration of stained organisms.
Differences between mouse strains in susceptibility have been demonstrated, but it is emphasized that any incidence in a mouse colony represents a disease potential and infected colonies must therefore be considered as hazardous for other research. Little work has been done to demonstrate the effectiveness of therapy, although oxytetracycline has been of value ( Tuffery, 1958).
PPLO (Pleuropneumonia-like organisms)
Infections with organisms described as PPLO have been chiefly reported as causing catarrhal disease in mice ( Nelson, 1958). Some outbreaks of disease of the upper respiratory tract are characterized by sudden onset and involvement of a large percentage of a colony usually after chilling or overheating. Chattering and sniffling with variable nasal discharge are the observable signs of infection. Mortality rates are low, and recovery from the exudative catarrh is spontaneous. A few animals succumb to bronchopneumonia or may develop a chronic bronchiectatic pneumonia. In other types of upper respiratory disease caused by PPLO the onset is gradual and the outbreak appears enzootic in character, Because of the chronic nature and long course of the disease, the eventual involvement of large numbers of animals may give the appearance of a suddenly occurring epizootic disease, particularly if the mild symptoms in the early stages of the condition are unnoted. Labyrinthitis (manifested by disequilibrium) may occur in a few of the mice.
PPLO organisms are often found in animals from an apparently healthy colony and may be recovered from various tissues other than lung material ( Freundt, 1959). The pathogenic potential of latent infections is always manifest but has not been quantitatively evaluated.
Streptobacillus moniliformis
Infections with Streptobacillus moniliformis are usually latent. In certain outbreaks where clinical signs include lameness and swelling of joints and extremities (due to edema), the organism is readily isolated from blood and organs, including affected joints ( Wilson and Miles, 1964; Freundt, 1956). In other instances the organism is not found in the bacterial cell state, but is isolated with extreme difficulty in L form by PPLO culture techniques ( Freundt, 1959). Clinical signs are often confused with those seen in chronic ectromelia, and for this reason an early differential diagnosis is indicated ( Lane-Petter, 1963). Stress plays an important role in the activation of latent infection. In many outbreaks mice will arrive in apparently good health after exposure to adverse shipping conditions, but within 3 to 4 days 10 to 50 per cent will develop signs of the disease — swellings and ulcerations of feet and tail after the appearance of a sharp band of demarcation proximal to the swelling. Recovery is usually spontaneous, although severely affected animals are deformed because of deranged circulation to extremities with subsequent sloughing of the entire area distal to the necrotic demarcation band. In our experience antibiotics such as tetracycline and oxytetracycline seem to be useful in controlling outbreaks. In clinically affected animals these drugs serve to mitigate the severity of developing lesions.
PARASITIC DISEASES
Helminth infections
Mice may become infected with helminths from other species ( Haberman and Williams, 1958b). Outbreaks of infection with Taenia taeniformis can occur when mice are housed in the same area with cats. Infections with the various helminths rarely produce clinical signs and are only potentially important as producing unpredictable variables in animals used in research. Heavily infected animals are below norms in weight and may be anemic. Some mouse colonies may be infected with Hymenolopis nana (the dwarf tapeworm). The life cycle of this parasite does not involve any secondary hosts, with infection taking place directly from eggs excreted in feces. Upon necropsy, the tapeworm is easily observed through the walls of the unopened intestinal tract.
Mouse colonies are often infected with the oxyurids Syphacia obvelata and Aspiculuris tetraptera. These mouse pinworms have a direct life cycle and spread through a colony rapidly because of the large numbers of eggs excreted and the ease with which the eggs are airborne. There are no clinical signs of oxyuriasis. There may be some weight and growth variation between infected and noninfected animals, but other signs such as poor hair coat, etc., are not clear-cut. There is some evidence that oxyuriasis may contribute to rectal prolapse. Diagnosis can be made by examination of fecal material or the anal region for oxyurid eggs by the various flotation or contact-tape techniques. Pinworm infection may be eliminated by treatment with various drugs such as the piperazine compounds, usually most efficacious when administered via drinking water ( Hoag, 1961). Treatment must be accompanied by through cleaning of the room and caging equipment to remove the possibility of reinfection from egg-contaminated dust.
Arthropod infections
Lice (Polyplax serrata) and mites (Myobia musculi, Myocoptes musculinus, Myocoptes romboutsi, Radfordia affinis, and Psoregates simplex) are the chief ectoparasites of laboratory mice ( Flynn, 1963b). Their presence is manifested by hair loss and scratching, which may give rise to bacterially infected ulcerative wounds. It is not unusual for mice to die in a heavily infested colony as a result of these infected sores.
Control of ectoparasites is difficult. Various dusting powders containing DDT, methoxyclor, rotenone, or other parasiticides, and dips containing aramite or other materials have been used, but must be regularly or periodically applied. Bedding materials either treated with aromatic hydrocarbons (such as crude cedar wood oil) or naturally containing such materials (cedar wood shavings) are successful in suppressing infestations.
PROTOZOAN INFECTIONS
Several types of protozoan diseases have been reported in mice. Most are inapparent infections, noted only after synergistic activity with other agents such as viruses or after interference with immunological body defenses as by splenectomy, Control is usually by improving hygiene after elimination of infected animals or whole colonies.
Eperythrozoön coccoides occurs as a blood parasite in the form of disc-shaped structures on the surface of red blood cells. Splenectomy of infected mice results in a marked increase in the numbers of parasitized cells and onset of transient mild anemia. The presence of this parasite increases susceptibility to such infectious agents as the mouse hepatitis virus, lymphocytic choriomeningitis virus, and lactate dehydrogenase-elevating virus ( Seamer et al., 1961; Riley, 1964).
Hemobartonella muris is another red blood cell parasite activated in infected mice after splenectomy ( Griesemer, 1958). Infectivity is very low. The anemia produced is mild and transitory.
Eperythrozoön cuniculi causes mild febrile disease in mice, infects epithelial cells of the kidney papillae, and produces granulomatous lesions in brain tissue ( Yost, 1958). These organisms occur as 1.5- to 2.0-μ Gram-positive rods. Transmission is apparently by way of urine, which may contain large numbers of organisms.
Klosiella muris has been described as causing an infection of mouse kidney epithelial cells ( Dunn, 1949). Signs of disease are inapparent although, on necropsy, kidneys of infected animals may be surface-marked with varying numbers of tiny grayish-white foci. Transmission is by way of spore cysts released into the urine.
MYCOTIC INFECTIONS
Mycotic infections of mice usually produce a dermatitis. Such infections, which can be caused by any one of several Trichophyton or Microsporum sp., result in circumscribed encrusted areas with hair loss and are empirically called ringworm. The fungus from the lesions may be easily demonstrated by microscopic examination of skin scrapings ( La Touche, 1957). Control of the colony infection is difficult. Outbreaks are chiefly important as sources of human infection as most of these fungi cause similar lesions in man.
SUMMARY
The mouse is susceptible to an array of infectious agents. Many of these agents produce signs of disease and must be eliminated or controlled if only to maintain sizable mouse populations. On the other hand, because the mouse is so important as a biological yardstick for measurement of varied procedures, it becomes important as well to eliminate or control those infectious agents which do not produce observable disease, but which may affect the outcome of an experiment. The development of mouse colonies from caesarean-derived stock is an effective panacea for eliminating those disease agents which cannot penetrate the placental barriers. In another respect, it is important to study the synergistic or antagonistic effect of various disease agents either in combination with each other or with other factors so that information so derived may contribute toward man's understanding of his own disease problems. It would be unfortunate to eliminate completely all disease of mice before obtaining more complete knowledge of the etiology, epidemiology, and pathology of such naturally occurring conditions.
Tag :
Epidemics,