Porcine Circovirus type 2: A focus on respiratory disease
By Gabriel Gomez, DVM, PhD, Pam Ferro, MS, PhD, and Binu Velayudhan, BVSc, MVSc, PhD
A 13-pound, juvenile, male intact, crossbred pig was submitted to the Texas A&M Veterinary Medical Diagnostic Laboratory (TVMDL) for necropsy and ancillary testing. The animal was described as a piglet and no age was stated on the submission form. The piglet was euthanized by the referring veterinarian for submission to the laboratory.
The history indicated that multiple other animals from the same premise had died over the last few months. Prior to euthanasia, the animal was unable to stand, and nasal drainage was observed. On necropsy, the thoracic cavity contained a small amount of serosanguineous fluid and the lungs were mottled red to tan suggesting an inflammatory disease process. On cut section, the lungs oozed a moderate amount of serosanguineous fluid consistent with pulmonary edema. The nasal turbinates were congested and covered with a small amount of mucus. The thoracic and mesenteric lymph nodes were enlarged and edematous on cut section. Histopathological examination was declined by the client in this case.
Sections of fresh tissue were submitted to the virology and bacteriology sections. These samples were tested via PCR for porcine circovirus type 2 (PCV-2) and porcine reproductive and respiratory disease virus (PRRSV), North American and European strains. The tissues were positive for PCV-2 and negative for PRRSV. Bacterial culture of the lung yielded Klebsiella pneumoniae, Escherichia coli, Staphylococcus spp., and Streptococcus equisimilis.
Respiratory disease is one of the most common disease syndromes affecting the swine population. Proper treatment and management rely upon a prompt and accurate diagnosis. Typically, arriving at a diagnosis starts with a history of clinical signs consistent with respiratory disease and/or identification of gross and microscopic lesions that suggest an infectious disease agent. At that point, suspicions of an infectious disease agent must be subsequently confirmed with additional testing at a diagnostic laboratory. Porcine Respiratory Disease Complex (PRDC) consists of both viral and bacterial components. The most common viral organisms are PRRSV, swine influenza virus (SIV), and PCV2 and the most common bacterial organisms are Pasteurella multocida, Mycoplasma hyopneumoniae, Streptococcus suis, Actinobacillus pleuropneumoniae, and Haemophilus parasuis.
There are two genetically related porcine circoviruses. Porcine circovirus type 1 (PCV-1) is considered to be widespread in the pig population and nonpathogenic in that it has not been associated with clinical signs, although it has been isolated from stillborn piglets. PCV-1 was originally identified in 1974 as a contaminant of a pig kidney cell line (PK15). PCV-2 is a viral pathogen with worldwide distribution that was originally linked to Postweaning Multisystemic Wasting Syndrome (PMWS) in Canada, Europe, and the United States in the early 1990s. However, retrospective serological studies have revealed evidence for infection that dates back to 1969 in Belgium.
The original name of PMWS was modified by the American Association of Swine Veterinarians (AASV) in 2006 to porcine circovirus-associated disease (PCVAD) in order to include the various disease manifestations associated with PCV-2 infection. These diseases include PMWS, PCV-2 associated pneumonia, PCV-2 associated enteritis, PCV-2 associated reproductive failure, PCV-2 associated neuropathy (cerebellar vasculitis), and porcine dermatitis and nephropathy syndrome (PDNS).
PCVAD is a low morbidity disease with a high incidence of infection. Accordingly, not all animals will develop clinical disease despite infection. There are reports that close to 100% of animals in some commercial herds are seropositive. However, only approximately 5-30% of infected animals will develop clinical disease. There are four factors that have been identified to play a role in developing the disease:
- Viral Factors. There are reports indicating that minor alterations in the viral genome can lead to altered viral function and result in a change in the degree of severity of gross and microscopic lesions.
- Host Factors.While all pigs are susceptible to infection with PCV-2, there is evidence to support breed-associated susceptibility. The basis for this observation is not clear but it is hypothesized that it may be linked to a difference in mounting an effective adaptive immune response amongst different breeds.
- Co-infection.PCV-2 infection is part of a co-infection in greater than 95% of the cases. One mechanism by which co-infection is believed to favor the establishment of PCV-2 infection is via the immunoproliferation that follows infection with other viral and bacterial pathogens. The most significant pathogen associated with PCV-2 co-infection is PRRSV. Porcine parvovirus (PPV), hyopneumoniae, other bacterial infections, and SIV are also implicated in co-infections.
- Immune Status.PCV-2 infection may be altered depending on the immunological state of the susceptible pig. There is evidence that lymphostimulation prior to PCV-2 infection may enhance the clinical manifestation of PCVAD. Immunosuppression prior to PCV-2 infection has also been demonstrated to lead to enhanced clinical disease.
The virus is shed in the feces and urine as well as respiratory secretions (oral and nasal cavities). Transmission of the virus is via oronasal contact with infected fecal material, urine, placenta, semen, and direct contact with animals that are infected, regardless of whether they are showing clinical signs or not. However, viral transmission to gilts inseminated with infected semen does not appear to occur. The incubation period is approximately 2-4 weeks. The virus infects the tonsil and lymphoid tissues. B-cells are believed to aid in dissemination of the virus throughout the body via the lymphatic system. The organs primarily affected are the spleen, Peyer’s patches, and lymph nodes with infection and replication within T cells and peripheral blood mononuclear cells. Viremia is seen approximately 7-14 days after infection and can result in a prolonged infection with detection of the virus up to 125 days post-infection.
Many infected sows will be seropositive and weaned piglets remain passively immune anywhere from 4 weeks up to 13.5 weeks. It is believed that passive immunity is protective due to the observation that clinical disease in piglets is not seen until at least 4 weeks of age. Pigs that are 2-3 months of age can mount an antibody response between 14 and 28 days after infection with a peak in neutralizing antibodies at 21 days post-infection. PCVAD is mostly seen in animals that have low or undetectable levels of neutralizing antibodies.
Out of the seven different disease manifestations that encompass PCVAD, PMWS, and PCV-2 associated pneumonia are the two diseases for which lesions in the respiratory tract have been described.
PMWS. This syndrome is not restricted to the respiratory tract but rather affects multiple organ systems. Animals approximately 7-16 weeks of age are primarily affected. Viremia and lymphopenia precede clinical infection. Mortality is usually around 10% but can reach up to 50%. The clinical signs of this entity include progressive weight loss, diarrhea, lymphadenopathy, paleness, jaundice, abnormal respiration, and anemia. Gross lesions of PMWS may include plump lungs that fail to collapse, generalized lymph node enlargement, and kidneys with white areas. Microscopically, the lungs, heart, kidneys, liver, and intestines may have granulomatous inflammation.
PCV-2 associated pneumonia. PCV-2 is one of multiple infectious agents that have been identified as a significant pathogen in the PRDC. Pigs between the ages of 8 and 26 weeks are usually affected, and multiple pathogens can be involved. Decreased growth and feed efficiency, anorexia, fever, cough, and dyspnea are the most commonly encountered clinical signs. Grossly, affected animals are in poor body condition and have enlarged superficial and visceral lymph nodes. The lungs are plump and fail to collapse. Jaundice may be encountered in some carcasses. Microscopically, the interstitium of the lung is expanded with macrophages and lymphocytes. Other microscopic changes include Type II pneumocyte hyperplasia, peribronchiolar fibrosis and, sometimes, bronchiolar ulceration with peribronchiolar lymphoid hyperplasia.
Diagnosis of the disease is based on the detection of antigen or DNA in the tissues of animals that exhibit clinical signs and lesions consistent with PCVAD. The most commonly used methods for diagnosis include PCR, in situhybridization, and immunohistochemistry. The utility of serology in the diagnosis of PCVAD is of limited value as many animals that are clinically healthy are seropositive for PCV-2.
In summary, PCV-2 is a significant pathogen in swine that has many manifestations and is often found as a co-infection with other pathogens. Due to the complexity of the disease, high incidence of co-infections, and various clinical manifestations, diagnostics are important for detecting the pathogens and determining their affects.
Diagnostic tests available at TVMDL to aid in the diagnosis of PCV-2 include Necropsy, Histopathology, PCR, virus isolation, and Serology. The recommended samples for PCR include intestine, fecal swab, lung or fetal tissue. For serology, an ELISA test is available, and serum is the required sample.
To learn more about this case, contact Dr. Gabriel Gomez, veterinary pathologist, Dr. Pam Ferro, virology and molecular diagnostics section head in College Station, or Dr. Binu Velayudhan, virology section head in Amarillo. For more information about TVMDL’s test catalog, visit tvmdl.tamu.edu
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