key: cord-0040174-f6wi7axg authors: Sherding, Robert G. title: Intestinal Viruses date: 2009-05-15 journal: Saunders Manual of Small Animal Practice DOI: 10.1016/b0-72-160422-6/50016-4 sha: ef3ef64bf21c28672f5b140121939a336e0fc4b3 doc_id: 40174 cord_uid: f6wi7axg nan M Parvoviruses, coronaviruses, and rotaviruses are established causes of viral enteritis and diarrhea in dogs and cats and are discussed in this chapter. In addition, numerous other viruses of uncertain significance and enteropathogenicity have been found in the feces or intestines of dogs and cats. • In dogs these include herpesvirus, enteroviruses, calicivirus, parainfluenza virus, adenovirus, and picornavirus. • In cats these include astrovirus, calicivirus, reoviruses (types 1, 2, and 3), torovirus, and togavirus. • In addition, the intestine may be involved as part of generalized viral infections in disorders such as canine distemper in dogs (see Chapter 13), and feline leukemia virus (see Chapter 8), feline immunodeficiency virus (see Chapter 9), and feline infectious peritonitis (see Chapter 10) in cats. Canine parvovirus type 2 (CPV-2), a non-enveloped, single-stranded DNA virus, causes an acute, highly contagious enteritis of dogs that has been prevalent worldwide since the late 1970s. CPV is believed to have evolved from the feline panleukopenia virus or a closely related virus. Since 1980, variants designated CPV-2a and CPV-2b have evolved, the latter now being the predominant strain in North America. Both of these variants and a newer CPV-2c variant can also infect and replicate in cats. CPV infection occurs by the fecal-oral route. During acute illness, and for about 1 to 2 weeks after recovery, massive amounts of parvovirus (over 1 billion virions per gram of feces) are shed in the feces of infected dogs. Because the virus can survive and remain infectious for 5 to 7 months in the environment, fomites and environmental contamination play a major role in transmission. A peak seasonal incidence in the months of July, August, and September was found in a Canadian study, but this may vary by climatologic region. Signs of enteric disease usually begin 4 to 7 days after exposure, coincident with localization of virus in the mitotically active zones of intestinal crypt epithelia. Dogs of any age can be infected, but the incidence of clinical disease is highest in puppies between weaning and 6 months of age. Puppies younger than 6 weeks of age generally are protected by passive maternal antibody, whereas most mature animals have been immunized or have seroconverted from natural exposure. All dogs are susceptible to infection; however, certain breeds have a higher risk for parvovirus infection and appear to be more susceptible to a severe form of the disease. These include rottweilers, Doberman pinschers, American pit bull terriers, German shepherds, and possibly Labrador retrievers. The biologic basis for these breed susceptibilities is unclear. M Key Point CPV has an affinity for the rapidly dividing cells of the intestines, bone marrow, and lymphoid tissues and thus causes intestinal crypt necrosis, severe diarrhea, leukopenia, and lymphoid depletion. • Intestinal epithelial damage from CPV causes breakdown of the intestinal mucosal barrier. This allows translocation of bacteria (especially Escherichia coli) and absorption of endotoxin, predisposing to bacteremia, endotoxemia, and the development of fatal systemic inflammatory response syndrome (SIRS). • CPV causes sudden onset of anorexia, depression, fever, vomiting, diarrhea, and severe dehydration. The diarrhea can be profuse, foul smelling, and hemorrhagic. Abdominal palpation may reveal intestinal loops that are painful and distended with fluid and gas. • Hypothermia, hypovolemic shock, icterus, hemorrhagic diathesis (disseminated intravascular coagulation), and pulmonary edema because of acute respiratory distress syndrome may develop terminally in cases complicated by bacterial septicemia, endotoxemia, and SIRS. • Death may occur in severe cases, particularly in very young puppies and in the highly susceptible breeds, and is usually attributable to dehydration, electrolyte depletion, endotoxic shock, or overwhelming bacterial sepsis associated with severe leukopenia. Septic puppies often develop hypoglycemia. • The severity of clinical illness may be increased by factors such as stress, overcrowded or unsanitary kennel conditions, secondary bacterial infection, and concurrent diseases such as canine distemper, coronavirus, salmonellosis, campylobacteriosis, and intestinal parasitism (e.g., nematodes or giardia). • In susceptible mature dogs, mild or inapparent infection that results in seroconversion without obvious clinical signs is common. • In utero or postnatal infection can cause acute neonatal myocarditis in neonatal puppies that did not receive maternal antibodies. However, this form of perinatal parvoviral infection is rare because most nursing puppies receive abundant maternal antibodies from colostrum. Signs of parvoviral myocarditis include dyspnea caused by acute heart failure, sudden death caused by arrhythmias, and sometimes delayed-onset chronic congestive heart failure caused by chronic myocardial fibrosis. Suspect parvovirus infection in young dogs that have an abrupt onset of vomiting and foul-smelling bloody diarrhea, especially if associated with severe depression, fever, or leukopenia or if these signs follow potential exposure to infected dogs or fomites. M Key Point Because of the difficulty in breaking through maternal antibody interference with vaccination in young puppies, prior vaccination does not necessarily exclude parvoviral infection, especially in puppies 6 to 20 weeks of age. • A complete blood count is particularly useful because approximately 50% of dogs with parvoviral enteritis develop severe leukopenia caused by lymphopenia and granulocytopenia, often with a total of only 500 to 2000 leukocytes/ml and sometimes less. Depletion of circulating mature neutrophils is caused by extensive loss of neutrophils through the damaged intestinal mucosa coupled with impaired myelopoiesis caused by bone marrow disruption from the virus. The severity of the leukopenia is generally proportional to the severity of the clinical illness. A rebound neutrophilia is a positive indicator of impending recovery. • The hematocrit is variable. The PCV is often normal but can be moderately decreased (especially after rehydration with fluids) in some dogs because of intestinal hemorrhage. In some dogs, the PCV can be elevated initially because of hemoconcentration from dehydration. Serum chemistry abnormalities are variable and nonspecific. Findings may include electrolyte abnormalities (most frequently hypokalemia), prerenal azotemia, hypoglycemia, hypoalbuminemia, increased bilirubin, and increased liver enzymes (alanine transaminase and alkaline phosphatase). Gas and fluid distention of the gastrointestinal (GI) tract due to generalized ileus is frequent in parvoviral enteritis and must be differentiated from small intestinal obstruction (e.g., foreign body or intussusception). Carefully palpate the abdomen to help rule out mechanical obstruction, including complicating intussusception. Barium contrast radiography often reveals mucosal irregularity (corrugation or scalloping) and prolonged transit time. • Determination of an anti-CPV antibody titer in serum is not sufficient for diagnosis because up to 95% of dogs in the population have seroconverted from prior vaccination or natural exposure. • Detection of early-appearing immunoglobulin (Ig) M antibodies by an indirect fluorescent antibody (IFA) test or 2-mercaptoethanol procedure provides presumptive evidence of recent infection because IgM antibodies are only found during or a few weeks after infection. M Key Point Definitive diagnosis of parvoviral enteritis requires demonstration of active excretion of virus or viral antigen in the feces. • Massive quantities of virus are shed in the feces during the acute illness, and shedding is over within 1 to 2 weeks after recovery. The most practical methods for detecting parvovirus in the feces are the commercially available, rapid in-office tests; including the enzyme-linked immunosorbent assays (ELISAs), such as the SNAP-Parvo Test (IDEXX Lab-replacement of ongoing losses. Two to three times normal maintenance levels are often required. Continue fluid therapy until vomiting ceases and oral intake resumes. • Add potassium (20-30 mEq/L) to IV fluids to control hypokalemia. • Add dextrose to IV fluids at a 2.5% solution to control complicating hypoglycemia of sepsis. Monitor serum glucose and increase to 5% if needed to maintain serum glucose from 120 to 160 mg/dl. • Consider supplementing magnesium according to guidelines in Chapter 5, as magnesium is often deficient in severe cases of parvoviral enteritis. • Infuse colloid solution (e.g., hetastarch) at 20 ml/kg, IV, if infusion of balanced crystalloid solution does not restore hemodynamic stability or if serum albumin drops below 2 g/dl. • Avoid administration of fluids by the subcutaneous route, especially in dogs with severe leukopenia, because this has been associated with secondary infection, cellulitis, and skin necrosis at administration sites. • Monitor fluid therapy by tracking body weight, physical parameters, urine output, estimates of ongoing fluid losses (vomitus, diarrhea), and hematocrit and total plasma protein. Also evaluate serum potassium concentration daily and adjust potassium level added to IV fluids accordingly. • Administer bactericidal, broad-spectrum antibiotics to control bacterial complications. Initially, administer antibiotics parenterally. • Use cefazolin or ampicillin in mild cases. • Use cefazolin, ampicillin, or penicillin combined with an aminoglycoside (e.g., gentamicin or amikacin) or a fluoroquinolone (e.g., enrofloxacin) in severe and leukopenic cases. Fluoroquinolones may damage joint cartilage in young, growing pups. If an aminoglycoside is used, maintain hydration to prevent nephrotoxicity and monitor the urine daily for casts and proteinuria as early indicators of nephrotoxicosis. • Consider a third-generation cephalosporin (e.g., ceftiofur; Naxel) combined with clindamycin in dogs with severe life-threatening bacterial sepsis. • Give nothing per os (fluid needs are met by IV infusion) for the first 12 to 24 hours. Prolonged food restriction may be detrimental to intestinal recovery. One study showed improved outcome in dogs treated with early enteral nutrition (using a nasoesophageal tube feeding starting at 12 hours) compared with dogs treated by prolonged dietary restriction. • Persistent vomiting can sometimes take 3 to 5 days to abate in severe cases, sometimes requiring partial parenteral nutrition. oratories) and ASSURE-Parvo Test (Synbiotics), or the rapid immunomigration assay, such as Witness CPV (Synbiotics). These tests are sensitive and accurate. • Consider that false-positive results are occasionally seen on these CPV immunoassays 5 to 12 days following vaccination with modified live virus (MLV) vaccines. False-negative results occur rarely when fecal antigen is bound to neutralizing antibodies or viral shedding stops early. • Other methods for detecting fecal excretion of parvovirus, such as hemagglutination, latex agglutination, electron microscopy (EM), virus isolation, and polymerase chain reaction (PCR) assay, are less convenient for routine clinical use because they require a commercial or research laboratory. Necropsy diagnosis of parvovirus is based on identification of the characteristic intestinal lesions of necrosis of the intestinal crypt cells with secondary villous collapse and dilatation of the crypts with necrotic debris. Myeloid degeneration and widespread lymphoid depletion also are seen. Parvovirus can be demonstrated in frozen tissue samples by immunofluorescence and in fixed specimens by PCR. The treatment of parvovirus is mainly supportive and similar in most ways to the treatments used for other types of severe gastroenteritis. The intensity of the treatment depends on the severity of the signs. In dogs with fully developed clinical signs, withhold food and water for 12 to 24 hours to rest the GI tract, administer IV crystalloids to replace fluid and electrolytes, and give parenteral antibiotics to control bacterial complications. Initiate therapy whether or not definitive tests are done or while awaiting the return of results. M Key Point The cornerstone of treatment for CPV infection is IV fluid and electrolyte therapy. See Chapter 5 for specific guidelines and procedures for fluid and electrolyte therapy. • Use the intravenous route for fluid and electrolyte replacement using a balanced crystalloid solution (e.g., lactated Ringer's solution, Plasma-Lyte 148, or Normosol-R). For animals presented in hypovolemic shock, administer up to 90 ml/kg IV in the first 1 to 2 hours to restore hemodynamic stability (see Chapter 156), then switch to a maintenance rate. For most other animals, correct dehydration over the first 24 hours, then use a maintenance rate for fluids plus • When feeding is resumed, give small, frequent feedings of a bland and digestible diet, such as a commercial GI diet or cooked skinless chicken and rice, until GI function appears to have recovered. The transition back to regular feeding should be gradual. • For frequent or persistent vomiting associated with delayed gastric emptying that sometimes occurs in parvoviral infection, administer metoclopramide, a dopaminergic antagonist, at 0.5 mg/kg every 8 hours SC or most effectively as a constant rate infusion of 1 to 2 mg/kg every 24 hours diluted in IV fluids. • For gastritis, control gastric acid secretion with an H 2 receptor blocker, for example, ranitidine (Zantac; 2 mg/kg IV, q8-12h), or famotidine (Pepcid; 0.5 mg/kg IV, q12-24h). • If these are unsuccessful for controlling vomiting, consider the broad-spectrum phenothiazine antiemetic, chlorpromazine (0.5 mg/kg SC or IM, q6-12h), but not until dehydration has been corrected because phenothiazines have a hypotensive effect. Avoid the use of metoclopramide and chlorpromazine together because they can produce central nervous system excitation and, rarely, seizures. • For persistent vomiting that is refractory to other treatments, give ondansetron (Zofran; 0.1-0.2 mg/kg slow IV, q6-12h), a serotonin-antagonist antiemetic. • Avoid the use of anticholinergics in parvoviral enteritis because they can worsen GI hypomotility. • Parvoviral diarrhea is usually self-limiting, and treatment to control diarrhea is rarely needed as long as fluid needs are met; however, when diarrhea is profuse and persistent, administer loperamide (Imodium; 0.2 mg/kg PO, q8h). • Consider whole blood transfusion (5-10 ml/kg IV) for treatment of severe blood loss anemia and hypoproteinemia. • Consider plasma infusion (5-10 ml/kg IV) for cases that develop disseminated intravascular coagulopathy. Plasma may also help correct hypoproteinemia, but hetastarch is a preferred source of colloid for raising colloid osmotic pressure. Plasma may also provide anti-CPV antibodies, but the benefit of this is questionable. • Use the recommendations in Chapter 156 for fluid therapy in shock. • Dexamethasone (2-4 mg/kg IV) can be used as a single dose to treat septic shock. • Flunixin meglumine (Banamine), a nonsteroidal anti-inflammatory drug, is an alternative to corticosteroids as a single injection to treat septic shock. Beware of gastric ulceration; do not give repeated doses or combine with corticosteroids. • Equine-origin, antiendotoxin hyperimmune serum (Septi-Serum, Immvac) is intended to bind and neutralize endotoxin, but efficacy is uncertain. The following experimental treatments have been used for CPV infection: • Recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been used to treat other causes of neutropenia, but studies have failed to show improved survival or any beneficial effects in parvoviral neutropenia. • Recombinant human bactericidal/permeabilityincreasing protein is used to treat human SIRS, but in a preliminary study in dogs with CPV enteritis it did not decrease circulating endotoxin or improve survival. • Recombinant feline interferon-omega (rFeIFN-w) (Virbagen Omega, Virbac), 2.5 million U/kg IV, daily for 3 consecutive days, decreased the severity of enteritis and improved survival in dogs with CPV enteritis in preliminary studies. This product is currently available in France but needs further study as a treatment for CPV. M Key Point Most dogs with CPV enteritis recover if treated appropriately to control dehydration and bacterial complications. • Most animals that survive the first 3 to 4 days of illness recover uneventfully. The survival rate with intensive therapy is 80% to 95%. • Some animals succumb to bacterial sepsis and endotoxemia resulting from leukopenia, immunosuppression, and breakdown of the intestinal mucosal barrier caused by CPV. In general, the mortality rate is highest in young puppies. • Complications may include hypoproteinemia, anemia, hypoglycemia (secondary to sepsis), disseminated intravascular coagulation (sepsis), SIRS, intussusception, liver disease, central nervous system signs (likely due to concomitant canine distemper), and various secondary bacterial infections, such as endocarditis, thrombophlebitis, pneumonia (caused by aspiration in some dogs), urinary tract infection, injection site abscesses, and intestinal salmonellosis and campylobacteriosis. • Dogs with CPV infection shed massive amounts of virus in the feces during their illness. The excreted virus as well as the fomites and premises that become contaminated are highly infectious for other dogs. Thus, instruct the owner of a CPV-infected dog to keep the dog isolated from other dogs until at least 1 week after full recovery. • CPV is ubiquitous, and because it is so stable outside of the animal and easily transmitted by fomites, prevention of exposure is almost impossible. Nevertheless, until vaccinations are complete, keep young puppies isolated as much as possible from other animals and from potentially infected premises. M Key Point Elimination of CPV from infected premises is difficult because the virus is so resistant; however, cleanup followed by disinfection with a 1:32 dilution of sodium hypochlorite bleach is effective. Vaccination is highly effective for prevention and control of parvovirus infection. Although widespread vaccination against parvovirus has markedly reduced the incidence of the disease in North America, parvoviral enteritis continues to be a problem in puppies as they are nearing the end of their maternal antibody protection between 6 and 18 weeks of age. This is because of a period of susceptibility when maternal antibodies are too low to protect but at the same time high enough to interfere with the response to vaccination, especially when killed or low-titer MLV vaccines are used. M Key Point In puppies from dams with high CPV titers, maternally derived antibody can persist at interfering levels for 18 weeks or more; thus, killed and low-potency MLV vaccines may not be able to break through this maternal antibody interference until as late as 18 weeks of age. • In the first weeks of life, maternal antibody protects the puppy from infection, but at the same time it also interferes with active immunization. • As the level of this maternal antibody gradually declines, there is a period of 2 to 4 weeks when puppies may be refractory to vaccination but susceptible to infection if exposed. • Most suspected "vaccination failures" in puppies probably result from exposure to infection during this critical period of susceptibility. • Because the age at which pups can respond to vaccination for CPV is unpredictable, vaccination proto-cols for puppies use a series of vaccinations in 3-to 4week intervals. • Attenuated (MLV) CPV-2 vaccines that are high titer and low passage (i.e., contain a high titer of a highly immunogenic strain of virus) are most effective at breaking through maternal antibody interference at a young age. M Key Point Vaccination against CPV is highly recommended for all dogs, and the efficacy of MLV vaccines is considered high. • Vaccinate puppies using high-titer MLV CPV-2 vaccines at 6 to 8 weeks, 9 to 11 weeks, and 12 to 14 weeks of age. Give the first booster 1 year later and additional MLV boosters every 3 years thereafter (see Chapter 7). • Advantages of MLV CPV-2 vaccines over killed vaccines are as follows: • Better magnitude of protection • More rapid onset of protection (as early as 1-3 days) • Longer duration of protection (≥3 years) • Better able to break through maternal antibody interference • Prevention of shedding of virulent CPV if exposed (killed vaccines protect only against clinical disease but do not prevent subclinical infection or shedding) M Key Point Commercially available CPV-2 vaccines effectively crossprotect against all known field strains and variants of CPV. • In unvaccinated dogs 16 weeks of age or older, give two initial doses of vaccine 2 to 4 weeks apart, although when high-titer MLV vaccine is used, a single primary dose is probably adequate. • Avoid vaccinating pregnant dogs, but if necessary, use killed CPV vaccine instead of MLV. Also use killed instead of MLV in puppies less than 5 weeks of age, such as when early vaccination is needed in colostrum-deprived pups. Canine coronaviral enteritis is an acute contagious disease of dogs caused by an epitheliotropic virus that preferentially invades the mature enterocytes of the villous tips. The resulting villous damage, atrophy, and fusion cause diarrhea of variable severity. Canine coronavirus (CCV) is an enveloped, single-stranded RNA virus. • CCV is considered of minor importance as a cause of enteritis in dogs. • CCV is shed subclinically for months postinfection in chronic carriers and spreads rapidly by fecal-oral transmission. The incubation period is 1 to 4 days. • CCV is closely related to feline coronavirus (see Chapter 10). Cats experimentally infected with CCV develop enteritis and sometimes feline infectious peritonitis. • CCV rarely causes clinical disease, and when signs do occur they are typically mild and self-limiting. Acute diarrhea is the most frequent clinical sign. This may be accompanied by mild anorexia, depression, and vomiting. The character of the diarrhea varies from soft to watery and sometimes contains mucus. Bloody diarrhea and fever are infrequent. • The signs are mild and easily confused with various other nonspecific causes of mild diarrhea of brief duration. M Key Point Most CCV infections are subclinical; however, occasional epizootics of severe enteritis have occurred, primarily in puppies associated with kennels and dog shows. Consider coronaviral enteritis in dogs with an acute onset of signs of gastroenteritis, especially if other dogs on the premises are affected. Because coronaviral enteritis is usually non-fatal and the only treatment is supportive, definitive laboratory confirmation is not needed for effective case management except to document an epizootic outbreak. Coronaviral enteritis should, however, be distinguished from parvoviral infection, a more serious systemic infection. M Key Point In contrast to CPV infection, fever, leukopenia, hematochezia, and fatalities are not typical of coronaviral enteritis. • Routine hematology, serum chemistries, and abdominal radiography are usually normal. • Definitive diagnosis requires laboratory detection of CCV in feces by EM, virus isolation, or PCR during the acute illness. Fecal examination by EM requires fresh feces (specimens can be kept refrigerated but not frozen). Both false-positive and false-negative results are a problem with EM because of misidentification of fecal particles. Virus isolation and PCR are performed in research labs and are not readily available to the clinician. The mere identification of CCV in a dog's feces is not proof that it is the cause of diarrhea or illness because CCV is shed in the feces of many healthy dogs. • Serology can provide only a retrospective diagnosis via demonstration of a fourfold or greater rise in serum antibody titer in paired sera (at the time of illness and 2-6 weeks later). Treat coronaviral enteritis with nonspecific supportive measures such as fluid therapy and dietary restriction for 12 to 24 hours. Antibiotics are not necessary. Most dogs recover rapidly, although occasionally diarrhea persists 3 to 4 weeks. Rare fatalities have been reported, especially in neonates and mixed infections involving CPV or enteropathogenic bacteria. • Killed (inactivated) and modified-live CCV vaccines are commercially available; however, the efficacy, duration of immunity, and benefit from these products is questionable. Thus, CCV vaccination is not routinely recommended for most dogs (see Chapter 7). The CCV vaccine may be considered in selected situations in which exposure risk is high, such as in show and field trial dogs and kenneled (boarded) dogs. • In general, immunity to coronaviruses is brief and is mediated by local (immunoglobulin A) immunity rather than the serum antibodies that would result from a parenteral vaccine. Parenteral vaccination does not prevent CCV infection, but it may reduce intestinal replication of virus and minimize clinical signs. Rotaviruses are non-enveloped, double-stranded RNA viruses that frequently cause neonatal diarrhea in humans and many other species of mammals and birds; however, canine rotavirus rarely causes diarrhea or clinical illness in dogs. M Key Point Canine rotavirus is not an enteropathogen of major clinical importance in the dog. • Antirotavirus antibodies are prevalent in surveys of normal dogs, indicating widespread subclinical infection. • Rotaviruses are highly infectious and can persist in the environment for prolonged periods. Transmission is by the fecal-oral route. • Rotaviruses replicate exclusively in the mature enterocytes of the villus tip, causing damage and blunting of the tips of the small intestinal villi. • In adult dogs, rotaviral infection is usually subclinical. In young puppies, clinical signs of acute enteritis occasionally are seen. • The diarrhea, which may be watery to mucoid, is usually self-limiting and of brief duration (5-7 days), although rare fatalities attributable to dehydration have been reported. • Experimental inoculation of newborn gnotobiotic puppies with canine rotavirus results in diarrhea and mild to moderate villous atrophy. Deprivation of colostrum predisposes the patient to much more severe diarrhea. • It is not possible to produce clinical disease or signs from experimental rotavirus infection in dogs older than 6 months of age. Definitive diagnosis is based on detection of rotavirus in feces by EM, virus isolation, or PCR. ELISA-based kits marketed for humans may not be reliable for detecting canine rotavirus. Rotaviral enteritis is treated like other types of acute diarrhea, with emphasis on supportive measures such as fluid therapy and dietary restriction or modification. Antibiotics are not needed. Most animals recover uneventfully with minimal treatment. Vaccines are not available for canine rotavirus. In neonates, the only group significantly threatened by rotavirus infection, the best protection is to ensure nursing of colostral antibodies in the first hours after birth. Feline panleukopenia virus (FPV) is a severe, highly contagious parvoviral infection of cats. Panleukopenia is now a relatively rare disease in pet cats because of highly effective vaccines. Occasional infections are seen in unvaccinated kittens, especially those from shelters, farms, and urban stray populations. Cats also are susceptible to the closely related CPV variants CPV-2a, CPV-2b, and CPV-2c, but these only seem to infect cats sporadically. • FPV can infect all species of Felidae as well as raccoon, ferrets, and mink. • FPV is shed in all body excretions for up to 6 weeks, especially feces. • FPV is very resistant to inactivation but can be inactivated with a 1:32 dilution of sodium hypochlorite bleach. • FPV is ubiquitous in the environment, where it can survive readily for more than 1 year and can be transmitted by oropharyngeal contact with contaminated fomites. • FPV has a predilection for rapidly dividing cells, particularly the following: • Intestinal crypt epithelium, resulting in acute enteritis • Hemopoietic tissue, resulting in panleukopenia • Lymphoid tissues, resulting in lymphoid depletion • In utero fetus, resulting in fetal death or cerebellar hypoplasia Infection in susceptible adult cats is often subclinical. Acute enteritis and panleukopenia occur rarely in healthy adults. One study has identified FPV in heart tissue from cats with myocarditis and idiopathic cardiomyopathy using a PCR assay. The clinical significance of this finding is uncertain. The incidence and mortality rate are highest in young kittens. Clinical features are similar to those of canine parvoviral enteritis, with acute onset of anorexia, depression, a high fever from 104∞F to 106∞F (40-41∞C), persistent vomiting, diarrhea, and progressive dehydration. Vomitus is usually a bile-stained fluid, and feces may be watery, mucoid, or bloody. Intestinal loops may be palpably thickened and firm (rope-like), fluid filled, and painful. There is increased susceptibility to bacterial sepsis and endotoxemia. In utero infection of the fetus at the end of gestation or of the neonate in the first 2 weeks after birth may permanently damage the central nervous system and cause cerebellar hypoplasia. Affected kittens show nonprogressive signs of ataxia, hypermetria, falling to the side, broad-based stance, and intention tremors. FPV also may invade the thymus of neonates, causing thymic atrophy and early neonatal mortality (fading kitten syndrome), and it may invade the retina, causing retinal dysplasia. The only manifestation of infection in the pregnant cat may be transplacental infection of the developing embryo or fetus, leading to early embryonic resorption (infertility), fetal death, fetal mummification, abortion, or stillbirth. Feline panleukopenia usually is diagnosed presumptively on the basis of typical clinical signs and leukopenia in a susceptible (unvaccinated) kitten. M Key Point Profound leukopenia (total leukocyte count often <500/ml) is frequent and usually lasts 2 to 4 days before rebounding during recovery. The degree of leukopenia is proportional to the severity of clinical illness. • Serum chemistry abnormalities are nonspecific and occur inconsistently but can include electrolyte depletion (especially hypokalemia), prerenal azotemia, and increased bilirubin and liver enzymes. • If leukopenia persists more than 5 days or is accompanied by severe nonregenerative anemia, consider the panleukopenia-like syndrome that is associated with feline leukemia virus infection (see Chapter 8). Other panleukopenia "look-alike" diseases include acute salmonellosis, acute bacterial sepsis with endotoxemia, and GI foreign body with perforation and peritonitis (e.g., linear foreign body). • Presumptive serologic diagnosis is based on paired neutralizing antibody titers. Definitive diagnosis requires fecal PCR or virus isolation, but these are not routinely available in clinical practice. • Necropsy diagnosis is based on lesions of severe necrosis of intestinal crypts. • The treatment for feline panleukopenia is similar to that for canine parvoviral enteritis, mainly nonspecific supportive treatment such as intensive fluid therapy, parenteral antibiotics, antiemetics, nursing care, and restriction of dietary intake followed by enteral or parenteral feeding. • In young kittens with panleukopenia, the mortality rate is high (50-90%). A guarded prognosis is justified until impending recovery is indicated by cessation of vomiting and diarrhea, return of appetite to normal, return of body temperature to normal, and rebound leukocytosis. However, serious complications that frequently indicate an impending fatal outcome include hypothermia, septic shock, overwhelming bacterial infection, jaundice, and disseminated intravascular coagulation. M Key Point Vaccination is highly effective for prevention of feline panleukopenia. • Both attenuated (MLV) and inactivated (killed) FPV vaccines are available, but MLV vaccines are more effective and produce a more rapid onset of immunity. This can be an important consideration in highrisk environments such as shelters, where cats are housed in groups. Side effects associated with adjuvants in killed vaccines are avoided when MLV vaccines are used. Parenteral and intranasal MLV vaccines are available. • Vaccinate kittens for FPV at least twice 3 weeks apart (usually 9 and 12 weeks of age) or every 3 to 4 weeks until 12 weeks of age. Give the first booster 1 year later and additional boosters every 3 years thereafter (see Chapter 7). Annual revaccination as recommended by manufacturers is not needed because antibody titers and resistance to FPV challenge persist 3 years or more after vaccination. • Give two doses of vaccine, 3 to 4 weeks apart, for primary vaccination of adult cats. M Key Point Use only killed FPV vaccine in pregnant cats and in kittens younger than 4 weeks of age. MLV vaccine given perinatally can infect the unborn fetus or the neonatal cerebellum. Feline coronavirus is a ubiquitous enteric virus in the cat population that invades the epithelium of the villous tip, resulting in villous atrophy and mild enteritis. A mutant variant of feline coronavirus causes feline infectious peritonitis (see Chapter 10). M Key Point Feline coronavirus is shed in the feces of many normal cats, and a high percentage of cats are seropositive, indicating that inapparent infection is extremely prevalent. • In young kittens, especially those 4 to 12 weeks of age, feline coronavirus causes an acute onset of mild enteritis with diarrhea. Feces are soft to fluid and rarely contain mucus and blood. • Diarrhea is infrequently accompanied by vomiting, low-grade fever, anorexia, and lethargy. • Clinical signs are usually mild and self-limiting within 2 to 4 days. Rare fatalities have been seen in kittens. • In a small percentage of infected carrier cats, mutation of this coronavirus enables the virus to infect macrophages, leading to systemic dissemination and fatal feline infectious peritonitis (see Chapter 10 for a detailed discussion of FIP). Serology can identify a convalescent rise in coronaviral antibody titer. Subclinical coronavirus infection is widespread in cats; thus, seropositivity does not distinguish active and past infection. EM and PCR can be used to identify active shedding of coronavirus in fresh feces, but sensitivity is low with both of these diagnostic techniques. Uncomplicated coronaviral enteritis is usually selflimiting. Routine supportive measures such as fluid therapy and dietary restriction may be beneficial. This virus appears to be practically ubiquitous and spreads very efficiently through catteries; thus, prevention may not be practical. An intranasal feline coronavirus vaccine is available, but it does not appear to be effective and is not recommended. As in the canine, rotavirus has been isolated from the feces of both normal and diarrheic cats, especially kittens, but its enteropathogenic significance is unclear. Infection is restricted to the GI mucosa. Subclinical infection in mature animals is probably frequent, as indicated by surveys that found antibodies to rotavirus in 26 of 94 clinically healthy British cats and 23 of 50 cats in Louisiana. Subclinical infection is typical, except in neonatal kittens that may develop mild diarrhea of 1 to 2 days duration. As in dogs, feline rotavirus can be detected in feces by EM, PCR, or ELISA. Rotaviral enteritis is self-limiting but, as for other types of acute diarrhea, supportive measures such as fluid therapy and dietary restriction may be beneficial. Most cats recover uneventfully with minimal or no treatment. Vaccines are unavailable for rotavirus. Because natural immunity is short lived, vaccination is unlikely to be warranted. Very little is known concerning this viral agent, but a few reports have identified astroviruses in the feces of cats with diarrhea, and mild diarrhea was reproduced experimentally in kittens. A survey of British cats determined a seroprevalence of less than 10%. Astrovirus infections in other species are limited to infection of the mature villous epithelial cells of the intestinal mucosa. Transmission is by the fecal-oral route. Feline astrovirus appears to cause mild, nonspecific diarrhea 4 to 14 days in duration. Transient low-grade fever, depression, and inappetance also may occur, but affected cats otherwise remain well. Rarely, astrovirus has been implicated in diarrhea outbreaks in catteries. As with other enteropathogenic viruses, kittens are most likely to be affected. Feline astrovirus is detected in feces by EM or PCR. Some cats shed the virus subclinically. Serum antibody to astrovirus has been identified in cats, but its significance is uncertain. Diarrhea caused by astrovirus is treated like any other acute diarrhea with supportive measures such as fluid therapy and dietary restriction. Most animals recover uneventfully with minimal or no treatment. No preventive measures are available. A syndrome of mild diarrhea in conjunction with idiopathic protrusion of the nictitating membrane (third eyelid) has been observed in cats, in some cases affecting clusters of cats in the same household. In a small number of these cats, type 2 reoviruses and a novel torovirus have been identified in the feces. Each of these viruses produced mild diarrhea in experimentally inoculated kittens, but protrusion of the nictitating membrane did not occur. The clinical significance of these viral agents is uncertain. 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