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Circovirus


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Porcine Circovirus Associated Diseases (PCVD, PCVAD)

Definition

Porcine circovirus (PCV) is a common virus of pigs found throughout the world. This DNA virus is unique for its small size (~1800 bp), circular genome, and hardiness in the environment. In the late 1990s, a novel circovirus emerged in North American swine that appeared to be genetically distinct from the prototype PCV (now referred to as PCV Type 1) and was termed PCV Type 2 (PCV2). Porcine circovirus Type 1 had been recognized for several decades as a common contaminant of laboratory cell cultures but despite being widespread in commercial swine, was nonpathogenic. The emergence of PCV2 coincided with the occurrence of a new clinical syndrome of swine referred to as postweaning multisystemic wasting syndrome (PMWS). Since its appearance, PCV2 (and PMWS) has become widely distributed in most developed swine industries around the world. The term PCVAD (porcine circovirus associated disease) is now used in North America to refer to the different disease manifestations associated with PCV2. In Europe, the acronym PCVD (porcine circovirus disease) is used instead.

Occurrence

Porcine circovirus Type 2 infection has been reported from nearly every country with a significant commercial production industry. It is strongly associated with the occurrence of PMWS and also appears to have an association with porcine dermatitis and nephropathy syndrome (PDNS), porcine respiratory disease complex (PRDC), and occasionally reproductive failure. Postweaning multisystemic wasting syndrome usually occurs in nursery or growing pigs and is diagnosed on a herd level through the occurrence of multiple features: 

Microscopic lymphocytic depletion in lymph nodes often accompanied by histiocytic infiltration
Clinical loss of body condition in affected individuals, enlarged lymph nodes
Epidemiologic increased proportion of wasting pigs, lack of response to therapy in affected individual accompanied by a high case fatality rate

 

Numbers of reported cases of PCVAD have increased rather dramatically in recent years. PCVAD now is widespread in the United States, Europe, and reported from most swine-producing areas. An apparent immune-mediated sequel to viral (perhaps PCV2) infection, porcine dermatopathy and nephropathy syndrome (PDNS) is sporadically reported. Circovirus is often associated with both PMWS and PDNS but PCV2 as sole cause remains in dispute. Other agents or risk factors are likely to be involved.

In utero infection with PCV2 may be inapparent, associated with reproductive failure or abortion. Because PCV2 is ubiquitous in swine populations and other agents or risk factors are frequently present, disease associations with PCV2 are sometimes difficult to prove.

Porcine circovirus Type 2 can contribute to PRDC in some herds. Experimental co-infection studies as well as anecdotal evidence suggests that PCV2 is likely to increase the severity of pneumonia caused Mycoplasma hyopneumoniae, swine influenza virus, porcine reproductive and respiratory syndrome virus (PRRS) and others.

Historical information

Since 1994, outbreaks of PMWS have been reported in North America and Europe and most swine-rearing areas of the world. The outbreaks have been consistently associated with PCV2 infection. Continued research and characterization of PCV2 remains of major interest among swine practitioners, researchers and producers. Genomic sequencing and restriction fragment length polymorphism (RFLP) techniques have defined several distinct viral clades within the PCV2 genotype but the clinical relevance of these distinctions is not completely understood.

Etiology

In 1982, a circovirus was isolated from porcine kidney cell line (PK-15) as an adventitious virus. Circoviruses are small, nonenveloped animal viruses with single-stranded circular DNA. Porcine circoviruses are quite hardy in the environment and in organic substrates. They are sensitive to most disinfectants but chlorhexidine, ethanol, and iodine are less effective. Circoviruses now are known to cause psittacine beak and feather disease, an infectious anemia in chickens, and lethal infections of pigeons, canaries and ¬finches.
Two types of circoviruses in swine have been described. The PK-15 virus is referred to as Type I (PCV1). There is circumstantial evidence that PCV1 may be involved in congenital tremors but it is generally considered to be nonpathogenic for swine. Analysis has demonstrated that PCV associated with PCVAD in swine is distinctly different genetically and antigenically and it is now classified as PCV2. Antibodies between the two types have low cross-reactivity.

PCV2 is consistently present in pigs with PMWS, and disease has been reproduced by experimental infection with PCV2. Many but not all field cases of PCVAD have concurrent viral infections or some other evidence of immune stimulation that seems to allow permissive replication and pathologic effects of PCV2 in swine. Herds that are endemically infected with other significant pathogens, are operated on a continuous flow basis, are in swine dense areas, provide a suboptimal environment (air quality, hygiene), or practice poor biosecurity have been shown to be more likely to experience an outbreak of PCVAD. Once affected, these same herds often are presented with a more severe form of the disease.

Epidemiology

The epidemiology of porcine circovirus infections is speculative. Nearly all US swine herds are seropositive. Seroconversion usually occurs by two to four months of age irrespective of whether clinical signs of PCVAD are observed.

With PMWS, affected pigs are between two and four months of age and “waste away” while cohorts seem to grow normally. Morbidity varies from 2-30% but case fatality is high, approaching 80%. Transmission of the virus and conditions allowing virulence expression are being vigorously studied. Some risk factors purported include coinfection with other viruses (PRRSV, porcine parvovirus, etc.) or nonspecific immune stimulation (vaccination). Activated macrophages appear to be permissive for viral replication and persistence.

Pathogenesis

Pigs infected with PCV2 develop viremia of variable duration, with replication and persistence most extensive in macrophages and monocytes of lymphoid organs and lung. Lymphoid depletion at multiple sites, chronic lymphohistiocytic to granulomatous inflammation, and an erosive bronchiolitis with fibrosis are characteristic. Reproduction of typical lesions by inoculation with PCV2 has been inconsistent but there is general agreement among researchers that the virus is at least necessary and perhaps causal in order for PCVAD to be expressed. Mechanisms that allow disease expression and/ or immunity are not definitively known but appear to be related to macrophage activation prior to infection with PCV2. Occasionally, pigs may develop blotchy purple skin lesions and nephropathy, likely as an immune mediated sequel to viral infection, which is termed porcine dermatopathy and nephropathy syndrome (PDNS).

Clinical signs

PCVAD: Clinical signs include gradual wasting, unthriftiness, rough hair coat, polypnea, dyspnea, pallor, diarrhea, and occasionally icterus. To be defined as PCVAD, there must also be histologic lesions of lymphoid depletion and/or lymphohistiocytic to granulomatous inflammation in affected organs with PCV2 demonstrable within lesions. Affected pigs usually die; clinical survivors are severely stunted; non-clinical pigs in the same groups perform quite well. Both signs and lesions, as reported by various investigators, vary considerably.

PDNS: Is mainly a condition of pigs from 8-18 weeks of age. There are red-purple blotches on the skin, sometimes slightly raised, most obvious on the hind legs and perineum but can extend over the abdomen eventually covering the whole body. Most pigs with PDNS eventually die.

Lesions

PCVAD: Gross lesions include pallor, marked enlargement of all lymph nodes and perhaps spleen, and interstitial pattern of pneumonia in lungs. Less often present are icterus, a fluid-filled intestine, subcapsular white foci on the kidneys, atrophy of the liver and ulcers of the pars esophagea of the stomach. Microscopy reveals depletion of germinal centers in lymphoid tissues with replacement by histiocytes and multinucleated giant cells. Basophilic intracytoplasmic inclusion bodies often can be seen in macrophages in lymph nodes, tonsils, spleen and Peyer’s patches. Lymphohistiocytic to granulomatous inflammation can be present in any organ, typically lungs and/or lymphoid tissues, and PCV2 antigen is abundantly present within characteristic lesions by immunohistochemistry (IHC) or in situ hybridization (ISH). Erosive bronchiolitis and fibrosis of airways is fairly typical.

PDNS: Often, there are small circumscribed circular to irregular, deep-purple discolorations of skin that become apparent on hind quarters, perineum, and flanks. Over the course of several days, the skin discolorations either resolve or expand and coalesce. Necropsy often reveals kidneys to be swollen with foci of pallor and/or hemorrhage in parenchyma. Microscopically, there is nonsuppurative vasculitis in sections of skin. Kidneys often have swollen glomerular tufts, inflammation, and protein in tubules. Multifocal nonsuppurative interstitial nephritis can also be a feature. The lesions are thought to be due to immune mediated (immune complex) vasculitis.

Lesions of PDNS are not specific for porcine circovirus.

Diagnosis

PCVAD: Diagnosis is made on clinical features, gross lesions, microscopic lesions, and demonstration of PCV2 within lesions. Using microscopy, characteristic lesions may be observed and virus inclusion bodies can often be identified in depleted lymph nodes, spleen, tonsils or Peyer’s patches. Immunohistochemical tests or in situ hybridization are used to confirm diagnosis of disease associated with PCV2. Polymerase chain reaction (PCR) will confirm the presence of virus but does not confirm the presence of disease. Similarly, isolation and identification of a circovirus is not useful for diagnosis since asymptomatic infection is widespread in swine populations. Serological testing for both types of PCV has been developed to confirm infection but finding antibodies to circovirus in the herd is not diagnostic since most herds are positive without discernible disease. PCVAD must be differentiated from other bacterial or viral diseases, especially PRRSV which has similarities in clinical signs and lesion. Concurrent infections are common.

PDNS: Diagnosis of PDNS is by observing typical clinical signs, gross lesions, and histopathology. PCV2 antigen is demonstrable in some but not all cases.

Reproductive failure: In cases where reproductive failure is observed as abortions, stillbirths, and mummification, PCV2 can be demonstrated by IHC in fetal hearts as well as other tissues, in a routine diagnostic investigation.

Control

There is no specific treatment for pigs with PCVAD. However, anti-inflammatory agents and/or antimicrobials are sometimes used with some success in groups of pigs experiencing disease. All in/all out pig flow, thorough cleaning and disinfection between batches of pigs and early segregation and euthanasia of affected pigs are measures that may help control the disease. Antibiotics in feed or water may suppress secondary infections. Better definition of risk factors and intervention strategies for those factors may aid in control. Anecdotally, control of other infections (PRRSV, parvovirus, others) or altering timing of administration of vaccines has been of benefit in reducing the severity of PCVAD. Studies in Denmark have shown that that PCVAD can be eradicated from an affected farm by total depopulation. The ubiquitous nature of PCV2 makes it unlikely that commercial farms can be maintained free of the virus by this technique but relief from clinical effects of PCVAD can likely be achieved. Until the epidemiology, transmission, and virulence factors relating to PCV2 and PCVAD are further understood, use of total depopulation as a control strategy is not often recommended.

Porcine circovirus Type 2 has been identified in the semen of acutely affected boars. However, transmission of the virus (or PCVAD) via this route has not been documented in a field setting.

Porcine circovirus Type 2 vaccines became commercially available in the US in summer of 2006. Field experiences have demonstrated that the vaccines are effective in reducing the severity and incidence rate of PCVAD on many farms. The timing of vaccination and population to be immunized (breeding herds, replacement stock, growing pigs) varies between farms depending on the characteristics of the affected populations and the physical operation of the farm.