PCVAD – A New Clinical Presentation?

December 2, 2009 — 

Dr. Steve Henry has been working with diagnosticians at Kansas State University to investigate an on-going case of Porcine Circovirus Associated Disease (PCVAD) in well-vaccinated animals. The affected animals are exhibiting a unique clinical presentation. He describes the case in detail and subsequent diagnostic updates on the KSU Veterinary Diagnostic Laboratory website and has reached out to colleagues via the AASV listserv for additional input.

Clinical circovirus disease appeared in 11 separate groups of pigs over a 6 week period beginning the first of September, 2009. Groups affected ranged from 7 to 14 weeks of age at onset of clinical signs. Mortality associated with the acute outbreaks was from 4%-17% with ongoing losses expected due to ill-thrift animals that remain in some of the affected groups, although some groups appear to be resolving as mortality rates are returning to normal levels. Cohort animals on other sites, vaccinated with the same protocol and product remain normal.

All groups demonstrated a pattern of acute onset accompanied by the rather specific gross lesion of pulmonary interlobular edema. All pigs had been immunized at 4 and 7 weeks of age. The protocol employed for vaccination has remained unchanged on these farms since the introduction of circovirus vaccines in 2007 and has been highly efficacious as no circovirus disease has been detected in over 2 years. This expression of circovirus disease appears clinically unique in three aspects:

• Appearance of clinical signs across several different age groups from separate production flows during the same short 6 week time frame.
• Absence of clinical signs in same-source, same-age pigs from these sow farms at other grow-out sites. These non-affected pigs were vaccinated with the same protocol and product.
• Consistent gross pathology lesions of severe interlobular pulmonary edema along with pleural fluid accumulation in nearly all animals examined. Affected pigs were in good body condition, not wasting and rarely presented appreciable lymphadenopathy clinically.

Weaned pigs from two separate breed-to-wean sow farms go to one of 18 separate production facilities either as stand-alone nurseries or nursery-finishing sites. Approximately 2,200 pigs per week and 1,000 pigs per week are weaned from these farms respectively. Both sow farms produce PRRS negative pigs and have done so for over 2 consecutive years. Growing pig sites vary from a few miles distant to over 100 miles from the source sow farms. Pigs in 9 of the 18 facilities remain PRRS negative through the entire growing period; PRRS infection and seroconversion is frequently observed in the other 9 sites, occurring at 8-10 weeks of age in most cases. Of the 11 affected lots to date, all have been co-infected with PRRS. Not all sites are affected. There is no clinical evidence of infection in 11 of the 18 sites. Isolated nursery sites have not been affected while nurseries on sites that also contain finishing barns have been affected. All but one of the groups that first showed disease in finishing were on sites that contained nurseries.

Diagnostic confirmation in affected sites and groups was based on clinical signs, gross necropsy lesions, demonstration of lymphoid depletion and other histopathologic changes, demonstration of PCV in tissues with immunohistochemistry and PCR. PCV virus sequencing and serum antibody testing by IFA characterized the virus and the immune status of animals in affected and unaffected groups. PCV2 Differential ELISA and the Tween 20 mycoplasma ELISA were used to assess vaccine administration compliance. Additionally, PRRS virus status was assessed by PCR, ELISA, virus isolation and viral sequencing. Testing was accomplished at Kansas State and Iowa State Veterinary Diagnostic Laboratories.

Laboratory evaluations to date suggest:

• On the basis of viral genome sequencing the circovirus present is very similar to those known historically to this region.
• Concentrations of circovirus detected in tissue and serum were considered extremely high in most cases with Ct<10 for many tissues and Ct<20 for serum pools.
• Co-infection of affected lots of pigs with PRRS virus was confirmed in most but not all of the acute circovirus-affected groups.
• PRRS genome sequencing demonstrated virus known to have been present in these production flows in the past, and it is known that PRRS infection frequently occurred in these sites/flows in the past 2 years.
• IFA antibody levels of weaned pigs are at levels suggesting they are not likely to suffer interference from passive maternal antibody. Accordingly, the pigs appear to be "vaccinatable", meaning that under normal circumstances, we would have expected these pigs to have an immune response post-vaccination.
• Compliance antibody evaluations initially revealed poor responses to vaccination although groups evaluated later exhibited excellent responses to vaccination and several groups that exhibited disease appeared to have been well vaccinated based on compliance tests performed prior to the onset of disease. The negative results are most likely the result of too long of intervals between the second vaccination and sample collection. Other, less likely reasons include administration non-compliance or profound immune suppression (caused by an unknown agent) resulting in failure to produce measurable antibody levels to both PCV2 and mycoplasma vaccination.
• Antigen (vaccine) failure was explored directly through company review of product. Nine different serial lots were employed in vaccination of both affected and unaffected lots of pigs with no relationship discovered relative to administered product.
,li>Post-vaccination IFA titers were stimulated as expected with most individuals having titers of at least 1:5120 prior to clinical disease in the groups for which sampling preceded detection of illness. Post-vaccination antibody titer was as predicted in unaffected groups of pigs. However, it was difficult to distinguish between titers induced by vaccination versus those induced by infection.
• No other agents except for PCV2 and PRRSV have been isolated or identified thus far in the investigation. We have demonstrated torque teno virus (TTV) genotypes 1 and 2 in some of the pigs and do not know if this means anything or not.
• Vaccination apparently does not eliminate the virus from from the environment as had been hoped.

Speculation as to the actual causes and mechanisms at work in these cases continues and this material is both a report and a query to others who may have similar observations. Diagnostic efforts continue with the obvious following questions in mind:

• Is there an undetected circovirus agent present that is not neutralized with present products and protocols?
• Is there, or are there, other active co-infection agents, including and besides PRRSV?
• Suggested by the commonality of time, what insult might have been introduced to some, but not all, of the various sites housing common lots of pigs?
• Is the clinical expression of acute mortality in pigs of good body condition a new manifestation of circovirus disease?
• The consistent pulmonary finding as well as the severity and acute nature of the lesion appears to be a new expression of circovirus disease. This lesion was certainly recognized in the era before vaccines were available but not in nearly all pigs. Is this merely an expression of acute circovirus disease or a new variant of pathogenesis?

Source: KSU-VDL