Postweaning multisystemic wasting syndrome

From Pig
PK/15 cells infected with Porcine circovirus type 2 and immunostained using a FITC-conjugated PCV2-specific monoclonal antibody. Courtesy of Dr. Gordon Allan

Postweaning multisystemic wasting syndrome (PMWS) is a rare vial disease of swine.

PMWS was identified in western Canada in 1991; however, retrospective studies from several countries indicate PMWS was present in the previous decade. PMWS is distributed worldwide and most swine-producing countries report variable prevalence of the disease. The primary manifestations are poor growth rate, ill thrift, and/or wasting. PMWS often occurs after weaning in pigs 4-14 wk old. The disease can also be seen in older pigs, particularly finishing pigs that weigh 45-70 kg. Morbidity is typically 5-20% among cohorts in the nursery or finishing stages. Mortality in swine that show signs of PMWS often is >50%. In addition to death loss, PMWS in finishing pigs may prevent, or substantially delay, affected pigs from reaching market weight, which can result in economic loss for the producer.

Cause

PMWS is a multifactorial disease in which porcine circovirus type 2 (PCV2) is the necessary infectious agent. Circoviruses are small (17-22 nm in diameter), nonenveloped viruses that contain a single strand of circular DNA. There are 2 genotypes of porcine circovirus; only PCV2 has been shown to induce PMWS. Serologic cross-reaction occurs between PCV1 and PCV2, but antigenic differences between the viral genotypes allow separation of viruses using some serologic assays. Serologic surveys show that PCV2 is widespread in swine. Some reports have suggested that animals other than swine may be infected with PCV2 or PCV-like viruses. However, results of serologic studies for antibody against PCV in cattle and other livestock have been contradictory, and experimental induction of disease using PCV1 or PCV2 in species of livestock other than swine has not been successful. Initially, PMWS was identified in high health herds that were free of most common swine pathogens but were infected with PCV2. Results from retrospective serologic studies indicate that PCV2 infected swine decades before PMWS was identified. Comparison of DNA from numerous recent isolates has shown high nucleic acid sequence homology exists among PCV2 and has not revealed a genetic determinant for virulence. Under field conditions, swine that show signs of PMWS usually are infected with multiple agents, but PCV2 is present consistently. Porcine parvovirus, porcine reproductive and respiratory syndrome virus, Actinobacillus , Pasteurella , Staphlylococcus , and Streptococcus are common pathogens frequently isolated from pigs that show signs of PMWS.

The frequent finding of mixed infection in nursery pigs with PMWS may be attributable to waning protection from colostral antibody, making the pig more susceptible to simultaneous infection with PCV2 and multiple other pathogens. Affected pigs are probably immunosuppressed. Pigs that show signs of PMWS have reduced populations of CD8+ and IgM+ lymphocytes in circulation. Microscopically, affected pigs show generalized lymphocyte depletion in lymphoid tissue. Substantial amounts of viral antigen and DNA are found in the cytoplasm of macrophages, dendritic cells, and other antigen presenting cells. Severe disease has been reproduced in pigs co-infected with PCV2 and other viruses or immunostimulant noninfectious products; however, the mechanism of this synergy is not known. Because PCV2 replication depends on cellular enzymes expressed during the S phase of the cell cycle, it has been hypothesized that previous activation of those cells supporting viral replication (not yet fully known) may promote replication of PCV2. Enhanced viral replication might lead to extensive loss of lymphoid cells and promote onset of PMWS. However, under field conditions, stimulation of the immune system of piglets with adjuvants, or with commercially available vaccines, appears to favor induction of PMWS after infection with PCV2.

Transmission may be by direct contact with infected pigs, and although not clearly demonstrated, by semen, contact with contaminated fomites, exposure to contaminated feeds or biologic products, multiple use of hypodermic needles, or by biting insects. The virus is found in blood, saliva, feces, urine, and semen of infected swine. PCV2 is known to persist in swine for several months under either experimental or field conditions. Convalescent swine may carry virus for extended periods and be important in disease transmission. PCV2 is fairly resistant to commonly used disinfectants and to irradiation, probably allowing it to accumulate in an environment and be infective for new groups of susceptible pigs if rigorous sanitary measures are not followed.

Longitudinal serologic studies show that the decline of colostral antibody titer in pigs is associated with onset of PMWS in nursery or finishing pigs. Transplacental infection with PCV2 has been documented. Transplacentally infected cohorts entering a nursery from a farrowing facility are a potential source of virus for other pigs in the nursery. Similarly, convalescent pigs or those subclinically infected with PCV2 in the nursery may carry virus and serve as a source of infection for cohorts in the finishing building.

Clinical signs

Wasting, ill thrift, and dyspnea are the clinical signs seen most frequently in outbreaks of PMWS. Pallor, anemia, jaundice, diarrhea, and palpable lymphadenopathy also are seen is some affected pigs. A low-grade fever (104-106°F [40-41°C]) of several days’ duration may be seen in affected pigs. Overcrowding, poor air quality, insufficient air exchange, and commingled age groups seems to exacerbate PMWS. Usually, only a few pigs in a group show signs of PMWS. The onset of disease may be acute, leading to death within a few days in some pigs. Other pigs show a more chronic disease and fail to gain weight or thrive.

Abortion, congenital tremors in neonatal pigs, and porcine dermatitis and nephropathy syndrome have been associated with PCV2 and may occur independently of PMWS (however, the link between PCV2 and some of these conditions remains controversial).

Gross and microscopic lesions of PMWS vary among affected pigs. Lymph nodes may be substantially enlarged, pale on cut surface, and show lymphocytic depletion and/or granulomatous inflammation on microscopic examination. Epithelioid macrophages and multinucleated giant cells are the main inflammatory cells. Variably sized, basophilic, intracytoplasmic inclusion bodies may be found in the histiocytic cells. Similar lesions are seen in the tonsils, spleen, thymus and Peyer’s patches of the intestine.

Lesions in the lung are common; their severity is influenced by duration of disease and presence of concurrent infections. Gross lung lesions may include failure to collapse, firmness, diffuse pulmonary edema, mottling, and consolidation. Microscopic lesions vary from mild, multifocal lymphohistiocytic interstitial pneumonia to granulomatous bronchointerstitial pneumonia with bronchiolitis and bronchiolar fibrosis.

Grossly, the liver may appear icteric and/or atrophic in a low proportion of PMWS-affected pigs. Interlobular connective tissue may be prominent. Microscopic lesions range from single cell necrosis (apoptosis) with mild lymphocytic infiltration of portal zones to extensive lymphohistiocytic periportal hepatitis with diffuse necrosis of hepatocytes. The kidneys may be enlarged and show scattered to diffuse white foci on the cortical surface. Microscopic lesions include interstitial lymphohistiocytic infiltration, nonsuppurative vasculitis, tubular atrophy, and in some cases extensive tubular necrosis. Other lesions seen in pigs with PMWS include gastric ulceration and occasional multifocal lymphohistiocytic myocarditis. Lesions in the kidneys and heart are more prominent in pigs that are chronically affected with PMWS.

Diagnosis

PMWS is diagnosed on the basis of clinical signs of wasting or ill thrift, presence of gross and microscopic lesions that are consistent with the disease, and presence of viral antigen or DNA in the microscopic lymphoid lesions. Differential diagnoses include salmonellosis, chronic respiratory disease, porcine reproductive and respiratory syndrome, swine dysentery, and porcine proliferative enteritis. Because PCV2 is ubiquitous and may infect swine for an extended period, isolation of virus or detection of antiviral antibody in serum is not sufficient to establish a diagnosis of PMWS. Similarly, detection of viral DNA in tissues or clinical specimens by PCR does not establish a diagnosis.

Antibody against PCV2 may be detected by ELISA, indirect fluorescent antibody, or immunoperoxidase staining of infected cell cultures. Several porcine cell lines support replication of PCV2. Viral isolation can be done using serum, bronchiolar lavage fluid, or tissue homogenates of lymphoid tissue, kidney, liver, or lung. Viral DNA can also be detected using PCR in most tissues or in serum from affected pigs. Visualization of viral DNA or antigen in lesions is usually done using in situ hybridization or immunohistochemistry, respectively. Several tissue samples from multiple pigs may be required for detection of virus in cases of chronic disease.

Treatment

There is no treatment for PMWS. Antibiotic therapy to control other infectious agents does not appear to affect the course once clinical signs appear. However, use of antibiotics may help prevent additional cases through control of intercurrent infections. Control of PMWS is possible through use of biosecurity and sanitary measures such as isolation of affected pigs and disinfection of pens after their use. Decreasing stressors (eg, high stocking density, inadequate ventilation, inadequate temperature control) is important. Other prevention and control measures that have been used on young pigs prior to the anticipated time of onset of PMWS include injection of vitamins, IP injection of serum harvested from finishing pigs, and vaccination against common pathogens.

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