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The Use Of Tamiflu In Treating Parvoenteritis:

On April 24,2004, the concept of treating Parvoenteritis in dogs with a neuraminidase inhibitor (Tamiflu) was introduced by Dr.Jack Broadhurst published on the Veterinary Information Network's Infectious Disease Board.

Because of a limited budget, the shelter was unable to use expensive IV fluids and hospitalization. It was one visit to a veterinarian, SQ fluids and antibiotics and back to the shelter on oral electrolytes and antibiotics.

The mortality rate was 75%. When Dr. Broadhurst added Tamiflu orally at 1mg/lb, twice a day; they went from 75% mortality to 100% survival (5). When the powder is reconstituted, you have a suspension of 25ml at 12mg/cc. The amount that is given to a small puppy, the most common patient, is 0.4 ml for a 10 lb puppy. This amount is so small it usually does not trigger vomiting if given slowly (5).No, there have been no collaborated controlled studies and the purist will question whether the Tamiflu is making any difference. After five months the success rate is in excess of 95%. Try it. You be the judge.


Since then, Tamiflu has been used successfully by veterinarians, shelter workers and rescue groups to treat Parvoenteritis in thousands of dogs, cats and raccoons throughout the world. Tamiflu: Oseltamivir is one of two commercially available sources of a neuraminidase inhibitor that has been used successfully in treating i nfectious parvoenteritis. Neuraminidase: An enzyme that is produced by both bacteria and viruses. It is considered a virulence factor in viral and bacterial lnfections that require neuraminidase to remove biological barriers that protect the host. Superinfections: Any infection that requires both a virus and bacteria to pioduce an infection that is more pathogenic than either infectious agent can produce alone. Veterinary examples: canine and feline Parvoenteritis, canine kennel cough and influenza, feline URI, Parvoenteritis in raccoons, and bloody scowls in deer.' The use of Tamiflu in canine, feline, and raccoon parvoenteritis: The success of using a neuraminidase inhibitor in treating canine and feline Parvoenteritis is due to the suppression of the production of bacterial neuraminidase, and has no effect on the Parvovirus' ability to replicate. Puppies can still develop myocarditis and CHF...kittens can Still develop cere.pellar hypoplasia...the patient's feces will still contain the viral antigen even while the animal is recovering. Tamiflu does not interfere with the replication of the Parvovirus, and as a result, no mutant or resistant strains of the Parvovirus will be created from the use of Tamiflu.


Tamiflu should never be used to treat any animal that does not test (+) using the fecal antigen test. All of the guidelines for using Tamiflu have been developed in cases that have had a (+) fecal Parvo test. Dose: 1mg/lb that dose given every 12 hours for 10 consecutive treatments...requires a (+) fecal antigen test.... There is a direct relationship between clinical response and the time treatment is started..,Tamiflu should be given w/in 48 hrs of onset of clinical signs...if no response after the first dose...double to 2mgllb for the second, third dose, etc. specific Breeds of Dogs: Dobies, Rotties, Retrievers, Pit Bulldogs, and Alaskan sled dogs...all require at least 2mgllb as the starting dose as these breeds respond poorly to Parvo infections... As a preventive: Animals that have been exposed, but are not currently showing any clinical signs should be given lmg/lb once a day for 5 days...if these animals develop one or more clinical signs (vomiting/bloody diarrhea/anorexia)...treatment should be changed so that they are given lmg/lb every 12 hr for a total of 10 treatments. Animals requiring IV supoort: Animals sick enough to require IV su pport (fluids/a ntibiotics/a ntiemetics) respond poorly to Tamiflu. Their clinical condition is the result of a damaged GI tract with the introduction of GI bacteria and toxins beyond Tamiflu's ability to protect the patient. If used, Tamiflu can be stafted at 2mgllb and the dose adjusted according to the patient's response every 12 hours.


Animals that vomit after being given oral Tamiflu: These patients can be given the same dose as an enema. You can also divide the contents of a 75mg capsule into lines and mix the appropriate amount into pancake syrup or honey and place under the tongue or in the lip fold.


Tamiflu Products: There is a suspension that you add 23 cc of water to get 25cc of LZmglcc. There is also a flat of ten 75 mg capsules. To use capsules to treat a 5 lb pupp)G Mix the contents of 1 capsule into 10 cc of a liquid diet like Canine Rebound...this will create a 1Occ suspension with a concentration of 7.5mglcc....Refrigerate and shake well and give 1cc q. 12 hrs x 10 treatments.... Do not mix capsules with water as this water suspension is very bitter and can cause the patient to vomit. One can also use liquid VAL or similar vitamin prep.


To use the suspension (12m9/cc) to treat a 5 lb puppv: Shake well and give the puppy 0.5cc of the suspension q. 12 hrs x 10 treatments. Refrigerate the suspension after adding water and between treatments. Tamiflu and FDA:"On March 20,2006, the FDA banned the use of Tamiflu and other neuraminidase inhibitors in treating chickens, ducks, turkeys and other birds...goes into effect in June 2006.. You can still use Tamiflu in dogs, cats, and raccoons.


Clinical Staqing Of Parvoenteritis Patients: Each patient should be placed into one of three Clinical Stages to insure uniform data between cases. Clinical Stage I: Presented because owner is observant and has noticed a decrease in activity and appetite. The stools are normal or soft. At this stage the virus has passed through the lymphatic system and is spreading through the GI mucosa and infecting GI epithelial cells. Fever may or may not be present. Clinical Stage II: May have all the signs of Stage I, but now is vomiting and/or having loose stools. There is no blood in either the vomitus or stools. In Stage II, the commensal bacteria have begun to produce bacterial neuraminidase, but have not attached to the GI epithelial cells and have not created holes within the intracellular cement to allow ingesta, GI bacteria and endotoxins and exotonins into the body cavity.


Clinical Stage III: This is the final stage and is characterized by the presence of blood in the vomitus and stools. All of the sialic acid reactions that could have been prevented with treatment started in Stage I or Stage II have now occurred. So, you have GI bacteria producing neuraminidase as well as endotoxins and exotoxins. The GI bacteria have denatured the GI IgA molecules, attached to the GI epithelial cells, created holes in the intracellular cement to allow ingesta, toxins and bacteria into the body cavity. Sialiac acid has been removed from the cell membranes of circulating PMNs and vascular endothelial cells, thus allowing the PMNs to marginate and attach to the endothelial cells and then move by diapedesis to the inflamed SI resulting in marked leucopenia. The CD4 and CD8 lymphocytes are leaving the lymphatic system and moving to the inflamed small intestine. The patient is in endotoxic shock as should be treated as a toxic patient and not one that is in an infectious stage.


In an uncomplicated case, presented within 48 hrs. from the onset of clinical signs, one should see no vomiting after the first dose...no diarrhea after the 2nd...and alert/eating after the 3rd dose. If there is no clinical response after the 3rd dose...you have either started using Tamiflu too late, have a secondary medical problem that needs to be addressed, or have the wrong diagnosis.


In summary, the introduction of the concept of using a neuraminidase inhibitor to treat canine, feline and raccoon Parvoenteritis, has opened many new doors into the understanding of the pathobiology and treatment of this disease. Prior to April24,2AO4, Parvovirus was thought of as viral enteritis. Based on this concept, vaccines were developed to help prevent or reduce the severity of the clinical disease.


With the introduction of using a neuraminidase inhibitor (Tamiflu), we have established that Parvoenteritis is not viral enteritis, but a superinfection that requires the presence of bacterial neuraminidase. When a neuraminidase ihhibitor is use under the strict guidelines developed since April 24,2A04, the disease is not allowed to develop into the clinical disease currently known as Stage III Parvoenteritis. The commensal bacteria do not transform into pathologic bacteria, and the patient's disease is not allowed to progress as described in the veterinary literature. In order to achieve this reversal, there has to be a definitive diagnosis and the neuraminidase inhibitor has to be given according to established guidelines,


Please keep in mind that any recommendations given in this article are not FDA approved. Roadrunner Pharmacy in Phoenix, AZ (877-5L8-4589) now has a Parvo Kit for veterinarians. This kit contains 500 mg of Oseltamivir granules and a vial containing l0cc of diluent. Once mixed, you will have 10ccs of an Oseltamivir suspension with a concentration of SOmg/cc. This suspension has to refrigerated between treatments. They can also make up capsules when requested.


Canine Parvovirus

Treatment for parvoviral infection centers on supportive care. This means that the clinical problems that come up in the course of the infection are addressed individually with the goal of keeping the patient alive long enough for an immune response to generate. We do not have effective antiviral drugs and must rely on the patient's immune system for cure.


BE PREPARED FOR A 5 to 7 DAY HOSPITAL STAY AND SUBSTANTIAL EXPENSE.


INTENSIVE CARE IS NEEDED TO TREAT THIS INFECTION.


There are certain basic treatment principles that can be viewed as "must haves" in addressing the parvo puppy.


Beyond these basics are some "added pluses" that may or may not contribute to the chance for survival. In order to achieve the usual survival rate of approximately 75-80%, the basics must be delivered. If an owner is less concerned about expense and simply wants to maximize survival chances, some of the optional treatments may be employed.


Fluid Therapy


One of the ways parvo can kill is via the metabolic derangements that occur with dehydration. It is crucial to replace the vast fluid losses (from vomiting and diarrhea) with intravenous fluids. Fluids are given as a steady drip rather than simply under the skin so that absorption into the circulation is direct. Potassium is usually added to the fluids in order to maintain electrolyte balance. Dextrose (sugar) is also frequently added as the stress of the disease may lower blood sugar, especially in a small puppy.


Antibiotics

The second way parvo kills is through bacterial invasion of the circulatory system (sepsis). The intestine is normally full of bacteria and when the parvovirus ulcerates the intestine there is little to prevent the bacteria from marching easily into the bloodstream. With the GI tract damaged, antibiotics cannot be given orally. They are given either as shots or are added into the IV fluid bag. There are a number of antibiotics that may be selected. Some antibiotics you may see in use include:

Baytril

Ampicillin/Clavamox/Penicillin

Gentamicin

Amikacin

Trimethoprim-sulfa

Metronidazole


Control of Nausea

Patient comfort is an important part of treatment for any disease but is especially important for parvo treatment as these puppies feel extremely nauseated. Again, the GI tract is too damaged for oral medication so medications are given as injections. There are several popular medications for nausea control:


Metoclopramide: (best given as a continuous drip in the IV fluid set up.) If used as separate injections, relief tends to be short lasting and does not provide around the clock control. If a continuous drip is used, nausea control lasts as long as the drip is running.


Maropitant (brand name: Cerenia): This powerful anti-nausea has not been adequately tested in puppies under 16 weeks of age. For older puppies, this should be an excellent choice to improve patient comfort. It is given once daily.


The vomiting typical of parvo infection is not only uncomfortable but can ulcerate the esophagus. The disease itself ulcerates the stomach and small intestine. Medications called gastroprotectants help heal ulcers and help minimize their formation. These medications include the injectable antacids (cimetidine, ranitidine, or famotidine) as well as sucralfate, which forms webbing over ulcers to facilitate healing.


Monitoring

The following tests are helpful in adjusting parvovirus treatment:

Fecal floatation to rule out worms/internal parasites

The last thing these patients need is a parasite burden contributing to their nausea and diarrhea. Since parvo victims are puppies and puppies are high risk for parasitism, it is important to test for worms and microbes that can contribute to the GI upset and eliminate them.

White blood cell counts/complete blood counts

One of the first acts of the parvovirus is to shut down the bone marrow production of immunologic cells (the white blood cells). White blood cell counts are often monitored as the infection is followed. The white blood cell count bottoms out at the height of the viral infection and recovers as the patient?s immune system gains the upper hand.

Urine specific gravity/Azostix

In order to assess the effectiveness of the fluid therapy, some objective evaluation of dehydration is useful. If adequate IV fluids have been provided then the urine produced will be dilute (as measured by specific gravity) and Azostix measures of protein metabolites, which build up in the blood stream, should be at normal levels.

Abdominal Palpation

Abnormal motility of the intestines occurs with this infection. Sometimes an area of intestine actually telescopes inside an adjacent area in a process called intussusception. This is a disastrous occurrence as intussusception can only be treated surgically and parvo puppies are in no shape for surgery. Euthanasia is usually elected in this event.

Total blood protein

Protein depletion is common when there is heavy diarrhea. If blood proteins drop too low, certain IV fluids or even plasma transfusions are needed to prevent massive, life-threatening edema, an abnormal collection of fluid.

Extra Treatment that May Help

Tamiflu (Oseltamivir)

While this particular addition to the parvo treatment plan has not caught on universally, news of its efficacy has spread far and wide. This oral medication is typically given for five days starting as soon as the diagnosis is made. It interferes with the reproduction of the parvovirus so that the patient's immune system essentially has fewer enemy soldiers to combat. This medication is helpful in the treatment of parvo patients plus can prevent development of the disease when given to exposed puppies. The key is to begin this treatment before the virus has had a chance to maximize its numbers; if treatment is started later in the infection, there may be so many viral particles that little benefit can be realized.

Plasma Transfusions

Plasma is the protein-rich fluid that remains when the red blood cells are removed from a sample of blood. These proteins may include antibodies against the parvovirus, albumin to help expand the patient's blood volume, as well as other healing proteins. Plasma can be obtained from donor dogs in the hospital or can be purchased from animal blood banks.

Cefoxitin (An Antibiotic)

The best antibiotic coverage controls both gram negative and gram positive organisms, both aerobic and anaerobic organisms and does so with minimal side effects. The use of Cefoxitin (brand name Mefoxitin) does an excellent job of covering for the organisms of concern without the kidney side effects of gentamicin or amikacin, and without the cartilage side effects of Baytril.

Septi-Serum

This product represents anti-serum (antibodies extracted from horses) that binds the toxins of any invading GI tract bacteria. The use of this product is controversial though the veterinary teaching hospital at Auburn University uses it commonly. It is usually given only one time as the equine origin of the product has potential for serious immunological reactions.

Anti-Inflammatory Drugs

There have been many studies indicating the benefits of single doses of these medications in the prevention of septic shock. Repeated doses may cause further GI ulceration (which is obviously something a parvo puppy has enough of). The usual medication is flunixin meglumine (Banamine).

Neupogen

Neupogen is the brand name of a genetically engineered hormone called granulocyte colony stimulating factor. This hormone is responsible for stimulating the bone marrow to produce white blood cells and its administration easily overcomes the bone marrow suppression caused by the parvovirus. In other words, Neupogen helps the white cell count recover. A recent study did not find increased survival with the addition of this product to the parvo regimen; however, in sicker puppies it may make a significant difference. It is expensive, usually adding $100-$200 to the basic treatment cost.

Home Treatment for Parvo

Home treatment for parvo infection is a bad idea when compared to hospitalization and intensive care. Mortality rises substantially and the heavy diarrhea and vomiting lead to heavy viral contamination in the home. Still, if financial concerns preclude hospitalization, home care may be the puppy's only chance. Fluids will have to be given under the skin at home as will injectable medicines.