CHAPTER 16 Viral Infections
Neonatal and puppy-kitten mortality rates (animals dying before 1 year of age) are often used as clinical indicators of the general level of health in the community, including the level of vaccination that is used in the area (Table 16-1). Infectious diseases are a major threat to the health of neonatal animals and may contribute to the mortality rate. Neonatal puppies and kittens depend in large part on the presence of sufficient maternal immunity, which provides short-term, passive immunity to protect them against microbial pathogens in the neonates’ environment. The severity of clinical symptoms (disease) in puppies and kittens that may result from infectious microorganisms depends on several key factors (Box 16-1). In addition to current maternal passive immunity, they include preexisting maternal infection status, maternal and neonatal nutrition, neonatal thermoregulation, concurrent neonatal infections and parasitism, and hereditary defects of the immune system.
|Effects on||High survivability||Low survivability|
|Survival of neonates||Increased||Decreased|
* Defined as 85% or greater of the population that are immune. Immunity is attained by regular vaccination boosters and/or continual boosters from natural infections from subclinical carrier animals.
BOX 16-1 Factors influencing the severity of clinical symptoms in puppies and kittens
Modified from Root Kustritz MV: Neonatology. In Root Kustritz MV (ed): Small animal theriogenology, St. Louis, 2003, Elsevier, p. 283.
Viral pathogens in particular can be life threatening for the neonate because for most infections, no specific antiviral therapy is available. Spread within a litter can be rapid as a result of the contagious nature of these pathogens. Adults with subclinical infections, including the dam, can be an important source of infection. Although some viruses, such as the feline retroviruses, are relatively labile outside the carrier host, others such as feline calicivirus and canine parvovirus are extremely hardy and can persist for months in contaminated environments. Transmission from dam to offspring can occur in utero or during birth of the neonate, whereas others are transmitted via nursing or grooming. The efficiency of the various modes of transmission varies with the agent involved.
Physical examination results will vary with the microbial pathogen involved. Fever may occur, but with peracute disease, animals may be hypothermic. Crying, restlessness, and anorexia may also be evident. Depending on the pathogen, evidence of specific organ involvement may be seen, such as nasal and ocular discharge with respiratory tract disease. Alternatively, multiorgan involvement may occur.
Diagnosis of viral infections of the neonate primarily involves direct detection of the virus, as serology in the neonate will not be useful. This can be done using three basic assays: antigen detection, nucleic acid detection, and viral cultivation. For antigen detection, cellular materials (mucosal swabs, fluid sediment, tissue impressions, and fixed tissues) on glass slides can be probed by fluorescent or immunoperoxidase-labeled specific antibody. Although rapid and inexpensive, these assays have relatively low sensitivity. For some pathogens, specific enzyme-linked immunosorbent assay (ELISA) tests are available. These include feline leukemia virus (FeLV) and parvoviral infections (canine parvovirus type 2 [CPV-2] and feline panleukopenia [FPL]). Sensitivity of these assays is regarded as high. Nucleic acid detection involves polymerase chain reaction (PCR) for amplification of the viral genetic material in biologic samples, including blood, mucosal swabs, feces, and fresh or fixed tissues. These assays are relatively fast and very sensitive. Viral cultivation, done on fresh samples, remains the gold standard but may take several (1 to 4) weeks. Serological analysis of the dam may provide information of previous infection or vaccination status but is often inconclusive.
In any investigation of reproductive disease, the veterinarian should consider the possibility of viral infections that are species specific (canine herpesvirus [CHV]), those that can be transmitted from one species to another (CPV-2), and those that are vector borne (West Nile virus). Such epidemiologic information is valuable both for establishing a diagnosis and for designing control strategies.
Control of neonatal viral infections involves screening for preexisting infections and vaccination (when available) of the dam, minimizing potential exposure during critical periods (Table 16-2) and ensuring adequate colostral intake by the neonates (see Chapter 14). The critical periods are preconception, pregnancy, periparturient, and postnatal. The outcome of infection during these periods depends on previous individual animal immunity and viral challenge from the environment.
Specific Viral Diseases of Pediatric Canine Patients
Canine Parvoviruses (CPV-2, CPV-1)
CPV-2 is endemic in most countries of the world. It is carried by a high percentage of dogs as a subclinical infection in the gastrointestinal (GI) tract and is shed intermittently in the feces. The virus can retain infectiousness outside the dog’s GI tract for up to 12 months if environmental conditions are optimum (moist, cold). The newer variants of CPV-2 (CPV-2b, CPV-2c) have also acquired the cat as a host, and control efforts must take this into consideration. The virus can be inactivated by disinfectants with oxidizing activity, heat, and diluted bleach (1:30 parts with water).
Infection is spread and acquired by the fecal-oral route. During the first 2 days after ingestion, viral replication occurs in the oropharynx and local lymphoid organs. Viremia from 3 to 4 days postinfection spreads virus throughout the body. Viremia is usually terminated when virus-neutralizing antibodies (IgG) are generated, usually 6 to 9 days postinfection. Clinical symptoms are most severe in puppies and may occur up to age 12 months. Parvoviral enteritis may present acutely or peracutely with anorexia and depression followed by vomiting and profuse, usually hemorrhagic, diarrhea. Newer variants of CPV-2 may cause a mild nonhemorrhagic diarrhea. Pyrexia, depression, anorexia, and dehydration are commonly observed. Intestinal damage in the rapidly developing crypt cells permits bacterial colonization that may result in endotoxic shock characterized by hypothermia, disseminated intravascular coagulation, and jaundice. Mortality rate may be as high as 25% and is a consequence of dehydration, endotoxic shock, electrolyte imbalances, and secondary bacterial infections (see Chapter 15). Mild or subclinical infections are common, especially in dogs aged more than 6 months.
CPV-2 variants can be detected in antemortem samples by in-clinic antigen (Ag) ELISA or by electron microscopy of fecal/diarrheal material. Affected dogs can also be tested by serology, as CPV-specific IgM titers can be detected in serum. Although PCR is available, it may detect dogs that are carriers of CPV-2, and the clinical predictive value may not be as high as the previously mentioned assays. Postmortem detection of CPV-2 uses a combination of histopathology and immunohistochemistry (IHC) for CPV-2–specific antigens. The tissues of choice are the small intestine, mesenteric lymph nodes, and spleen fixed in buffered formalin.
Although there is no specific treatment for CPV-2, viral-bacterial enteritides generally consist of treating dehydration, sepsis, and acidosis/electrolyte imbalances. Intravenous balanced electrolyte solutions, systemic antibiotics (see Chapter 27), and antiemetic therapy may be indicated if vomiting is a significant component of the symptoms. Control measures include disinfection to reduce (dilute) the viral challenge load and immunization with modified live CPV-2 vaccines of adult dogs in the population and the susceptible puppies (Table 16-3). The role of immunization is twofold: the first is protection of individual puppies, and the second is to hyperimmunize adults to minimize viral shedding.
Canine parvovirus type 1 (CPV-1) is also referred to as minute viruses of canines and was initially reported in military dogs with diarrhea. This virus is antigenically distinct from CPV-2 and is more closely related genetically to bovine parvovirus.
CPV-1 is usually a subclinical infection in dogs but may cause enteritis, pneumonitis, myocarditis, and lymphadenitis in puppies aged between 5 and 21 days. Most pups have mild symptoms, but those that worsen may be classified as having fading puppy syndrome. Affected pups may show diarrhea, vomiting, and dyspnea and constantly cry out. Systemic viral infections in naive dams may lead to failure to conceive, fetal death, or abortion.
Because of the similarities of CPV-1 clinical symptoms with CHV and CPV-2, a thorough diagnostic workup is recommended. More specific assays such as PCR or immunoelectron microscopy are required to diagnose CPV-1 presence in fecal matter. Histopathologic changes seen in the thymus, lymph nodes, small intestine, and myocardium are very similar to CPV-2, and without specific IHC or CPV-1–specific PCR, these lesions may be misdiagnosed.
Because there is no vaccine available for CPV-1 control, it is important to maintain a clean whelping environment and keep optimal temperatures for newborn pups.
Canine Distemper Virus
Canine distemper virus (CDV) is a multisystemic viral disease of dogs that affects puppies most commonly aged between 3 and 6 months. The virus can be carried by adult dogs in the respiratory tract and is commonly shed in aerosols. The virus is enveloped and highly susceptible to environmental and chemical inactivation. Although there is only one serotype of CDV, there are numerous strains that vary in their tissue tropism and pathogenicity. Although considered a disease of domestic dogs, many other canids are equally susceptible, as are mustelids (e.g., ferrets). Felines are reported to be infected, but clinical symptoms are rare except in exotic felines (e.g., lions, tigers).
The route of infection with CDV is usually by aerosols, saliva, or grooming. The virus spreads rapidly to the oropharyngeal lymphoid organs, where it then enters the first of two viremic phases. During the first phase, there is generalized immune suppression. There may be fever, anorexia, and mild respiratory symptoms during this phase (7 to 10 days postinfection). During the second viremic phase, the virus is more disseminated to the GI tract, central nervous system, and skin. Hemorrhagic diarrhea may occur 10 to 20 days postinfection. Mortality rate in dogs symptomatic with this form may be as high as 50%. In classic forms of distemper, conjunctivitis is observed first, followed by a dry cough. The cough becomes progressively wet and productive, concurrent with oculonasal discharge. The discharge becomes mucopurulent within several days. Affected dogs are usually pyretic (>104° F, 40° C), depressed, and anorectic. It is estimated that at least 50% of CDV infections are subclinical and that dogs may shed virus for up to 60 days postinfection.
CDV can cause abortion, stillbirth, and birth of weak puppies. Neonatal infection in puppies aged less than 1 week may result in cardiomyopathy and cardiac failure less than 3 weeks postinfection.
CDV presentation is usually classical enough that antemortem diagnostic assays are not conducted. If a definitive diagnosis is of value, then fluorescent antibody-specific CDV staining can be done on either conjunctival smears or whole blood smears. Nucleic acid detection can be done by PCR on whole blood and urine, which offers a good clinical predictive value for a dog with viremia; tissue may be tested postmortem. Serologic detection can identify CDV-specific IgM in serum or CDV-specific IgG in cerebrospinal fluid. Postmortem diagnosis of CDV-induced disease can be verified by histopathology and, if necessary, CDV-specific IHC on fixed tissues from brain, lung, spleen, urinary bladder, and skin.
There are no specific antiviral drugs to treat CDV-induced disease. Treatment is supportive with fluids, expectorants, antiemetics, and antibiotics. Puppies that develop neurologic disease have a poor prognosis. Control measures rely predominately on the use of a modified live virus (MLV) immunization program in dogs. This consists of a thorough vaccination series in puppies, a booster at 6 months, and another booster at age 1 year. Adult dogs in proximity to pregnant dogs and puppies should receive regular boosters to minimize CDV shedding in the environment.
The canine adenoviruses (CAV) consist of two predominant serotypes, CAV type 1 and type 2 (CAV-1 and CAV-2). CAV-1 is predominately multisystemic and causes hepatocellular necrosis and vasculitis. The virus is moderately resistant in the environment but susceptible to heat (steam cleaning) and disinfection by quaternary ammonium compounds. Dogs may carry this virus subclinically despite high levels of neutralizing antibodies (immune carriers, see Chapter 14). The antigenically related CAV, CAV-2, is predominately associated with upper respiratory tract disease. It is shed for 8 to 9 days postinfection.
CAV-1 is considered to cause the more serious clinical symptoms in dogs when compared with CAV-2. CAV-1 infects by the oronasal route, where the virus replicates in the oropharyngeal lymph nodes. Viremia occurs wherein hepatocytes and reticuloendothelial cells in other organ systems are the sites of virus replication and subsequent lysis and necrosis. During the acute phase (7 to 9 days) of CAV-1 disease, the virus is excreted in the feces, urine, and oropharyngeal secretions. The occurrence of multisystemic symptoms carries a guarded prognosis. Infection during pregnancy by CAV-1 may result in the birth of dead puppies or weak puppies that die within a few days postwhelping. Carrier dams occur and may act as a source of infection for puppies or other pregnant dogs.
Infections by CAV-2 may result in bronchitis, bronchiolitis, and focal turbinate and tonsillar necrosis. The virus has been reported to be associated with kennel cough syndrome. The important feature of CAV-2 is its antigenic relatedness to CAV-1 and the use of this strain in vaccines, which provides protective immunity to CAV-1.
The diagnosis of CAV-1 is important to differentiate from the multisystemic CHV (see below). Antemortem diagnosis may be done by virus isolation from fecal samples and oral-pharyngeal swabs in viral transport media. Nucleic acid detection by PCR may be used to detect CAV in the same samples, but the clinical predictive value may be compromised because of the presence of known carrier dogs in the population. Postmortem diagnosis is considered to be the most reliable for CAV-1 disease. Hepatic lesions are pathognomonic and include mottling and fibrinous exudates attached to the liver capsule. The gall bladder may be edematous and hemorrhagic. Histopathology and CAV-specific IHC are confirmatory on the fixed liver tissue.
There is no specific antiviral therapy for CAV-1 disease. Symptomatic supportive therapy for acute liver failure is required for treatment. Immunization with CAV-2 MLV vaccine is an important control measure for CAV-1. This consists of a vaccination series in puppies, a booster at 6 months, and a second booster at age 1 year. Adult dogs in proximity to pregnant dogs and puppies should receive regular boosters to minimize viral shedding.
CHV has been recognized as one of the most common and virulent viral infections of neonatal puppies. Recent reports have indicated that this virus may be carried subclinically by up to 70% of some canine populations. As with other herpesviral infections, in particular, feline herpesvirus (see this chapter), CHV can be exacerbated following periods of physiologic, hormonal, and nutritional stress. CHV has several components that are important in control because there is no vaccine available in the United States. The virus is shed predominately in oronasal secretions from carrier dogs to susceptible dogs. This knowledge has been the basis for establishing the 6-week danger period, which includes the 3 weeks before whelping and 3 weeks postwhelping (Figure 16-1).
Figure 16-1 The 6-week danger period in relationship to whelping and the various sources of CHV for neonatal infections.
(Redrawn from Diagnosis of canine herpetic infections. In Kirk’s current veterinary therapy X, 1989, Elsevier.)