Canine Parvo Virus-1

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published in Recent Advances in Canine Infectious Diseases, Carmichael L. (Ed.)
International Veterinary Information Service, Ithaca NY (www.ivis.org), 2004; A0102.0899 http://www.ivis.org/proceedings/Baker_Can_Inf_Dis/toc.asp

Canine Parvo Virus-1

J.K. Veatch, D.V.M., Ph.D.

Dept. of Veterinary Diagnostic Investigations

College of Veterinary Medicine

Kansas State University

Manhattan, KS 66506

For those of you who have had to deal with parvo virus (CPV-2) in puppies the signs of vomiting, hemorrhagic diarrhea, dehydration, and death in puppies that are approximately 6 weeks of age and older are all too familiar. Outbreaks of parvo starting in the late 1970's were recognized by researchers at Cornell and much work went into the study of the virus due to the high mortality rates. Vaccines were developed to help control the problem; however, parvo outbreaks still continue. There is some question as to the exact origin of the parvo virus (CPV-2) and there are those that feel it may have come from the enteritis of mink or feline parvo.

With time there have been some changes in CPV-2 and a second strain, CPV-2a, was identified in the late 1980's. It can present with fewer signs and more rapid death than the original picture of parvo in the late 70's.

The parvo of hemorrhagic enteritis was designated CPV-2 because it was the second one to be found. In the late 60's and early 70's a small virus was isolated from dog feces and after study it was named canine parvo virus-1 (CPV-1) or minute virus due to its small size. Studies comparing the two forms of parvo show that the viruses differ in there antigenic structure and CPV-1 is not like any of the other parvo viruses known in animals or people. Its origin is a source of speculation.

Early work on CPV-1 found it to cause mild enteritis in adults and in puppies greater than 8 weeks of age. The damage to the intestines, when viewed under a microscope was distinctly different from CPV-2. Experimental work at Cornell showed that exposing pregnant bitches to the virus via the oral/nasal route could result in fetal death and resorbtions, stillbirths, weak puppies, or early neonatal deaths. Rarely, the stillborn puppies had abundant edema throughout the body and mineralization of the heart. The virus chose the placenta as one site of infection and in some respects the behavior is not unlike the porcine parvo virus which also can cause early embryonic deaths and weak births.

For those puppies that died in the first few days to week of life there was an enteritis, again very different from CPV-2, and pneumonia. Virus could be found and isolated from the intestines, lungs, placenta and heart. In experimental situations there generally was no illness in the bitch.

In the world of research when viruses or bacteria are studied the research tries to isolate the animals from other things that cause illness, and change only one variable at a time. This is not possible in the real world and often other factors may change the nature of a disease. In the late 1980's and early 1990's thirteen deaths due to CPV-1 were found in several different kennels. The puppies exhibited enteritis and pneumonia but nothing was documented as to the status of the dams. In 1991 CPV-1 was found to be the cause of death in a puppy, and illness in the remaining litter mates of a show collie kennel. In this case the bitch was also ill.

The question is raised as to whether there has been some change in the virus or it is different environmental conditions that change how the virus acts? For the past several years the same

kennel has had sporadic cases of CPV-1 resulting in some neonatal mortalities. With the continued presence of the virus it brings up the question - is the maternal antibody able to

neutralize the virus, and how long does the maternal antibody last. All affected puppies had similar signs of "colic" and have shown pneumonia.

CPV-2 is known to at least transiently affect the immune system as evidenced by a marked drop in lymphocyte count as the puppies begin to show clinical signs. It is not known if CPV-1 has a similar effect, and could any changes in the immune system be long lasting in breeds that are genetically predisposed to problems such as collies with dermatomyositis. Research between Kansas State University, Michigan State University, and DermatoDiagnostic of Washington State has started the slow process to see if something such as CPV-1 could be involved in an autoimmune problem.

For those of you that are experiencing early deaths in litters it is important to try to determine the cause and not just say it is fading puppy syndrome. We now know that CPV-1 can cause significant neonatal mortality, but until more cases are found it is difficult to know the extent of the problem. Whenever dogs are grouped together in large numbers it is a potential for spread of viruses and bacteria. At this point there is no vaccine for CPV-1. Veterinarians and diagnostic labs rely on concerned breeders to help alert them to possible cases. Please work closely with your local veterinarian, and diagnostic lab to help provide samples to determined the cause of death.

Samples to be submitted:

Entire puppies that have died should be kept cool but not frozen. These can be sent to a diagnostic lab preferably by next day shipment. Cornell has sent a protocol to labs to help determine the incidence of the disease.

Fecal samples from the other puppies ( if it is possible to get some) and from adults should be sent along with any bodies. The stool samples need to be examined by electron

microscopy to detect parvo viral particles. If the sample is positive it should be checked by hemagglutination (HA) testing. For most labs the HA test performed is for CPV-2 and uses pig blood. CPV-1 does not agglutinate pig blood so the HA will be negative; thus if the stool sample is positive on EM and negative on HA it is highly suspicious of CPV-1.

A serum sample from the dam collected at the time of illness and a second sample 10-14 days later should be included. This will allow examination of the titer to CPV-1 if it is confirmed in the puppies.

Indeed, this is why there is currently no vaccine for CPV-1. As a "minute virus" it was not considered to be a problem in the past, under laboratory conditions. However, with the changes it has made while in our normal environments, it poses a very real and very deadly threat which is escalating with each year. The development of a vaccine is directly related to accurate reporting and diagnosis which is the responsibility of both the breeder and the veterinarian. Insist that stool samples from suspected animals (neonate puppies to adults) be sent to a diagnostic facility with an electron microscope. And always have any unexplained neonatal deaths completely necropsied at the nearest University Veterinary Diagnostic Laboratory. They are many times more thorough than a state laboratory. There is no such thing as a "fading puppy syndrome" if CPV-1 is properly identified as the culprit. The more frequently this virus is accused, the more interest it will generate in the vaccine development

field, which may expedite the creation of a method of immunity. Until that time, recognize that your animals will be exposed to CPV-1, either at dog shows, on a walk in the park, after a visit

to the vet , or after you have been off your own property and carried it back. Encourage and allow exposure if you are dealing with CPV-1, since your only hope of a brief period of immunity lies in the animal's own immune system.

Link to August 2004 Article by Dr. Carmichael: Canine Herpes Virus & MinuteVirus of Canines (aka Canine Parvovirus1) technical but worth reading as it supports this page.

A Survival Guide to Managing Canine Parvo Virus-1 (CPV-1)

Drs. K. Brown, P McIntyre and E. Stuck

Animal Health Center

Falls City, NE

Leslie Mamer, CBSW

Heirlair Collies

Auburn, NE

Symptoms and treatment of the post-whelp bitch;

The stress of pregnancy and whelping, regardless of how good the prenatal care has been, is often rendered more complicated for the new mother by the appearance of the CPV-1 virus in her system or environment. She may not have adequate strength to manage it on her own; and you can be sure that her puppies will have no defense at all. The bitch will usually break with the viral symptoms immediately after whelping. They may run a moderate to very high fever, between 102.8 to 105 degrees. The normal temperature of most dogs is 101.8 Post-whelping bitches will often run a slightly higher temperature, but when it climbs near 103 within 24 hours of whelping, it is imperative that you monitor the bitch and the litter continuously. The CPV-1 fever is intractable and not readily reduced with aspirin or dipyrone. Only Banamine (Schering), an injectable non-steroidal anti-inflammatory, antipyretic and analgesic drug developed for use in large animals, seems to have any transient effect. Because CPV-1 seems to be able to cross placental barriers and is suspected of "hiding" in the placenta or amniotic fluid itself, you must do everything possible to prevent the bitch from eating the placentas. Eating them tends to increase the virulence of the symptoms and prolong the illness.

You will also notice that the bitch appears to be very uncomfortable, as if she has more puppies to deliver. She will not easily settle down with her new babies, and pants heavily and continuously. An X-ray taken within 24 hours of whelping will show excessive amounts of gas in the belly and digestive tract. The bitch may vomit, refuse food for up to five days, drool excessively, develop a cough, runny stool and/or diarrhea. Her blood values will not usually show any "lymphopenia" or significant lack of circulating white blood cells; however, a slightly lowered white blood cell count is generally indicative of a "virus-like" illness, and any other serological irregularities might be considered as good indicators of the presence of CPV-1. An accurate diagnosis requires that a stool sample be sent to the nearest veterinary diagnostic laboratory associated with a university or college of veterinary medicine, for examination under an electron microscope. It should show positive for parvovirus and possibly corona virus. The hemagglutination test, which checks the feces for parvo viral particles with be negative, because CPV-1 does not agglutinate the pig red blood cells that are used to check for CPV-2. Therefore a positive EM and a negative HA usually equals CPV-1, which equals trouble.

And finally, but not always, appearing within 24-36 hours from the onset of the other symptoms you may find a clear "marker" for CPV-1; the appearance of an ulcer on the bitch's tongue, generally found by one of the lower canine teeth.

Laboratory tests take time and you must not wait. Quick and aggressive therapy is the difference between life and a painful death for the puppies, and perhaps the bitch. You will need to work very closely with your own veterinarian in treatment management.

Treating The Bitch (Adult)

We have found that the combination use of antibiotics is essential. Begin with both penicillin and gentamycin in injectable forms, particularly if there is vomiting. Although benzathine penicillin is a "long-acting" antibiotic, use it as 6-7 cc's every day for 5-7 days. Give gentamicin (50mg/ml) at 2.2mg per lb. twice the first day (every 12 hours) and then reduce to one injection per day for no more than 5 to 7 days. Administer Reglan (A.H. Robins), a human drug, for nausea and vomiting at 0.2 mg per lb three times a day. This drug serves many purposes. It also quiets the gut and protects the lining where the virus has interrupted the protective lining of cells in the intestines, which allow bacteria to proliferate and enter the rest of the body through the blood or lymph. Do not use Reglan (metoclopromide) for more than 2 days unless instructed by your veterinarian. Likewise administer Tagamet (cimetadine, Smith, Kline & French) oral syrup at 5 mg per lb every 8 hours. Also a human drug, the cimetadine will help prevent gastric and stress ulcers which can be caused by the illness and/or the administration of Banamine. ( If you can't get Reglan, or Tagamet immediately, use atropine sulfate for the vomiting at 1 ml per 10 lbs and another older drug known as corrective mixture with paregoric for the diarrhea. These are just temporary medications, not substitutes for the Reglan and Tagamet). Give Banamine (100

mg/ml) at l mg per lb every 12 hours for not more than two days to manage the fever. In extreme cases you may need to administer refrigerated Lactated Ringers solution IV or SQ at 1000 ml every 24 hours to help bring the fever down and keep the bitch hydrated, since she may vomit up any water she has taken in.

If you see no improvement in the bitch's condition within 3-4 days of the above therapy you must stop the pen/gent combination antibiotics and wait about 8 hours. Then begin the administration of chloramphenicol at 20 to 25 mg per lb. (max 500 mg per dose) three times a day for 5 days total. Chloramphenicol must not be combined with another antibiotics as it has an antagonistic effect when combined with penicillin and can do more damage than good.

Chloramphenicol is the drug of last resort, so do not use it unless you must, and only at the instruction and supervision of your veterinarian. Finally, a big dose of injectable B-complex vitamins given twice a week and at least 500 mg of vitamin C in liquid form twice a day helps a lot.

The bitch will go off her feed during this time. Stop all commercial dog food and offer a mixture (in small but frequent amounts ) of cooked and drained lean hamburger or ground lamb, and cooked white rice. You may add some garlic powder to the mixture for flavor. You can also try a little canned Prescription Diet by Science Diet in the I/D formula or the feline C/D which is tastier. The bitch won't really eat until she's ready and you want to minimize the strain on the gut at this time anyway. She should retain enough pre-whelping fat to handle any significant weight loss. However, she can become feverish enough to temporarily dry up her milk supply. Try not to become too concerned about this since you will be hand or tube feeding the puppies anyway. Always keep fresh, cold water available to the bitch at all times, with or without an electrolyte solution (such as K-9 Blue Lite powder) mixed in.

Your bitch should be fully recovered within 7 days. Remember, there is no vaccine for CPV-1. Therefore, no boosters are available other than what's in the environment. She will be subject to this "flu" again, but usually in a milder form. Incidentally, if you have other adult dogs or bitch exhibiting some or all of these symptoms perhaps due to excessive stressors (ie dog shows, shipping, or drastic changes in the environment) give strong consideration to CPV-1 as the culprit and treat as recommended above. A greenish, mucous-laden, runny stool, with a foul parvo or coccidia smell, depression, anorexia and/or fever are the most visible signals of impending disaster, and means that the dogs demand immediate attention and care.

Symptoms and treatment of neonate puppies;

Management of CPV-1 in the newborn puppy is very complex and carries a high risk of death despite your efforts. Time is your greatest enemy because you cannot know exactly when they become affected; in the uterus, down the birth canal or some other time prior to 14 days after birth. They often appear to have colic, exhibiting signs of acute distress, curling into a fetal position, emitting long cries to accompany their pain, showing a reluctance or failure to nurse and signs of first-stage dehydration (skin-tenting), while producing bright yellow or green stools of a grainy but loose consistency. In the last stages signs of respiratory distress appear in the form of exudate from the nose or mouth and difficulty in breathing. At this point the puppies usually die within the hour. If this happens, please have them necropsied. However, if you act quickly at the first signs you should be able to save most or all of the litter. I have had to manage and treat CPV-1 for nearly 4 years now and out of the total of 60 puppies whelped I have lost only 8. (This includes those born dead and proven sero-positive for CPV-1)

Immediate intervention is vital and begins with the use of combination antibiotics. For the puppies you must administer amoxicillin (50 mg/ml) at 5 to 10 mgs per lb. Use the trihydrate form (Amoxi-Drops by Beecham) for ease of administration either by eye-dropper or through the feeding tube. This is given 2 to 3 times a day for 5 to 7 days. Concurrently give gentamycin injectable subcutaneously at 10.5 mg/ml or 0.2 cc's per lb. Use insulin or tuberculin needles and syringes. Give the gentamicin twice the first day and once a day thereafter for 5 days only. You will have to tube feed these puppies because they rapidly become

too weak to nurse properly, or the bitch's milk had dried up, or both. Tube feeding also minimizes the risk of aspiration pneumonia, which can come from bottle feeding, because of a probable respiratory infection which may be settling in and make proper air-exchange problematic. Regardless of the condition of the puppies or the bitch, be sure that these puppies receive colostrum within the first 24 hours.

The feeding formula is crucial to their survival. The base mixis made up of a milk replacer (ie. Puppy-Lac or Vet-A-Lac) a pre-mixed electrolyte solution (ie, the K-9 Blue Lite powder which you have already mixed up for the bitch) or the Lactated Ringers, which should also be on hand, and water. Rehydrate your milk replacer powder with 1/2 to 2/3's the water it calls for. Depending on the size and breed of your litter you will only use about a cup per

feeding so place the rest of the milk replacer in the refrigerator. Warm it in the microwave or under hot running water if you don't have a microwave. Add the following after heating: 15 to 20 cc's of lactated Ringers, 5 to 10 cc's of K-9 Blue Lite (avoid Pedialyte if you can, as it is not balanced to canine electrolytes parameters ), your oral does of amoxicillin if it's due, and 0.1 ml of Tagamet syrup per puppy. It is best to dose the Tagamet and amoxicillin individually, so draw them into the feeding syringe after you have drawn up the amount of milk/electrolyte solution that you plan to give each puppy ( usually not more than 6 cc's per feeding the first day.) And if you are working with three day old or less puppies, plan to be tube feeding every two hours. You will administer the Tagamet and the amoxicillin every 4th feeding.

One other drug must be used on this same schedule, especially if those previously described stools are present: Reglan. Inject 0.1 ml per lb SQ every 8 hours for a maximum of 3 days. I cannot stress the importance of the combined use of cimetadine and metoclopromide enough in the proper treatment approach to this illness. Because of their soothing effects on the stomach and intestines the puppies begin to relax immediately, reducing their stress and enabling them to gain much needed strength without expending energy on pain management. The use of Tagamet and Reglan can make the difference between life and death for the puppies. Tagamet in particular helps to rapidly dump the stomach contents safely into the small intestine, while reducing gas and slowing the gut down without constipation. Reglan and Tagamet both come in syrup form which can be combined at the proper dose given above directly into the feeding tube formula, if you prefer not to inject the puppies so often. You must also let the litter nurse if they want, provided that the bitch's milk is good. This will give them added strength and keep the mother involved. Since the entire litter is usually affected, the oral contact between the bitch and their tainted stools is irrelevant at this point. Keep the puppies warm and dry, with access to a warming pad, because they are probably

running fevers or sub-normal temperatures and will chill easily. Graduate the feeding schedule according to how you perceive the litter to be doing. If the rate of dehydration has slowed down and the puppies seem to be starting to properly digest their food, you can begin to lengthen the time between feedings to 3, 4, 5, 6, hrs etc., gradually. Remember, the antibiotic combinations must not go beyond 5 days or you may jeporadize renal function.

But what if you are still losing puppies or see no improvement after 3 days? Now you must stop the amoxi/ gent combination, wait 8 hours and then institute chloramphenicol therapy. When and if you must use this drug, stop the Reglan. It reacts adversely with the chloramphenicol. However, this is your last hope. Working with your veterinarian, mix from capsules into the feeding formula a dosage equal to 20 to 50 mg/lb. A 500 mg capsule mixed into 20 cc's formula equals 25 mg per ml. Add 1 to 2 mls to each individual feeding every 12 hours. Keep the chloramphenicol mixture in the refrigerator or make it fresh on a daily basis. You will only need to use this a maximum of 5 days. Another, much easier, alternative to mixing your own chloramphenicol solution is to ask your veterinarian to order Chloromycetin Palmitate, oral suspension, by Parke-Davis. The pharmacist can rehydrate it for you to the dosage prescribed by your veterinarian, which is usually a maximum of 25 mg per lb given every 8 to 12 hours. It is a fairly dangerous drug, but as a last resort it is proven to be highly effective.

Antibiotics, given either concurrently or singularly, may "sterilize" the gut of the puppy, but the addition of acidophilus paste twice daily will help forestall this event. The bitch should get some, too, as should any animal on antibiotic therapy. Probiocin by Pioneer is a gel form of acidophilus and other microbial replacements, specifically geared to dogs and cats. Your veterinarian should have this on hand as a rule. However, just in case you are unable to get some or all of the "over the counter" items in your area, you can order everything mentioned in this article (outside of the human prescription drugs) through a company called Omaha Vaccine Co. 3030 L. Street, Omaha, Nebraska 68107: 1-800-367-4444.

Neither CPV-1 nor any other virus can be cured with the use of antibiotics. What you are treating is the secondary bacterial infections which set in after the virus has damaged the lungs, gut, kidney, brain, or heart. Unless or until a necropsy is performed, you will not know exactly where the damage was done.

Symptoms in the Adults:

at least four of the following

1. Fever in excess of 102.8 starting suddenly

and lasting more than 24 hrs. Generally

unresponsive to standard antipyretics.

2. Hard panting, drooling and/or signs of

dehydration such as vomiting and diarrhea.

3. Lack of interest or refusal to eat. May be

accompanied by excessive water intake which

is lost almost immediately.

4. Runny yellow to green stools. Can be

tinged with blood or mucous.