The ever-changing PRRS virus keeps producers and researchers off balance in their efforts to control it.

In the past several years, control schemes have been on the rise. There has been more talk of herds successfully cleaning up and staying negative to PRRS orPorcine Reproductive and Respiratory Syndrome. The industry has been pressuring breeding stock firms to guarantee their product is free of PRRS. And, the outlook has been positive for controlling PRRS.

But well into 1998, sentiments may be on the verge of changing. Top PRRS researchers now are saying strains or isolates of PRRS are mutating in ways that make them tougher to deal with, and may require different control strategies. Several industry leaders are saying better PRRS vaccines will be needed.

Crisis Coming? Many view the so-called atypical PRRS outbreak of 1996 as something besides PRRS virus because it was characterized by abortion storms and numerous sow deaths, the likes of which hadn't been seen since the early days of the disease in the late '80s.

But now it appears that maybe those hot strains of atypical PRRS are starting to become more typical of mainstream PRRS problems.

USDA officials at the National Animal Disease Center (NADC) believe much of the early confusion regarding atypical PRRS was due to inadequate sampling procedures for virus isolation.

"More recent studies have almost conclusively established that the unusually high incidence of abortion, and sometimes sow death, were caused by new, hotter strains of the PRRS virus," explains William Mengeling, DVM, research leader of the Swine Virology Unit at NADC.

He goes on to point out that what was seen in the field has now basically been reproduced in the lab. Origin of these new strains is still in question. But Mengeling speculates they simply arose from mutations that markedly increased their ability to cause clinical disease.

PRRS is an RNA class virus known for its ability to mutate and adapt readily to its environment. This ability has raised two emerging concerns:

* Strains or isolates of PRRS seem to mutate frequently, getting hotter and harder to control as they do so;

* Some so-called stable sow herds don't appear to have stable immunity after all, and are being implicated in infecting their piglets before birth.

"My belief is that there have been some more virulent strains that have evolved during the last several years," observes Mengeling.

Any response to infection by the pig's immune defense mechanism can be counteracted by a viral mutation that makes it less easy to control. Neutralizing antibodies which normally prevent the virus from infecting cells may be neutralized themselves by other virus mutations that are both antigenically different and more difficult to control. "We suspect that is what happened with the strains associated with atypical PRRS," says Mengeling.

Besides the body's natural defenses, antibody titers are also produced when the pig is vaccinated against PRRS. But here again, the challenge is becoming stiffer.

According to Mengeling, the current modified live virus (MLV) vaccines for PRRS seemed more effective prior to the emergence of these new strains of PRRS virus. He explains there may be several reasons for this change, the most likely just the added virulence of new strains.

Mengeling observes: "For example, when young pigs were infected experimentally at the NADC with strains isolated before 1996, they sometimes became listless and failed to gain weight at the same rate as uninfected controls. But they rarely had any noticeable clinical signs.

"Conversely, pigs infected under the same conditions with strains from more recent cases of atypical PRRS were severely affected and some died without complications of other secondary diseases," he says.

Viral Recombination Viral recombination or joining of two viruses to form a virus with a different molecular structure is being touted as one source of proof that PRRS strains have altered, according to a research trial reported on by molecular biologist Michael Murtaugh, University of Minnesota at the Leman Swine Conference in Brooklyn Park, MN, in mid-September.

Molecular analysis of 10 U.S. strains during 1990-1992 showed significant genetic variation and that viral recombination may be involved. Another study of 50 PRRS samples isolated in a seven-year time period from the start of PRRS outbreaks, showed that an isolate in North Carolina in 1993 was the product of recombination between two strains on farms in adjacent counties.

When developing vaccines, steps should be taken to avoid viral recombination and undesirable offshoots of the vaccine, points out Murtaugh.

All that doesn't mean that the current MLV vaccines aren't any good. PRRS virus is showing up in vaccinated herds simply because there are quite a lot of PRRS-vaccinated herds in the U.S., notes Mengeling. But it's also a fact that the vaccines are having a tougher job protecting the pig from the newer, hotter strains.

Key is to vaccinate well before the time the pigs become exposed to the field virus, he emphasizes. "That's because it takes more time for pigs to develop immunity to PRRS virus than to most other viruses," states the USDA researcher.

In a simple but striking trial at NADC, it was found when pigs were exposed to a mixture of vaccine and field strains of PRRS virus, the field strain quickly dominated - even when the mixture contained a 10-million-fold excess of vaccine virus. "More importantly, from a practical perspective," says Mengeling, "there was no evidence that the simultaneous administration of vaccine virus had any effect on the outcome of the infection."

Vaccine Rotation What about rotation of current MLV PRRS vaccines to improve overall effectiveness?

Minnesota's Murtaugh advises against it, suggesting that "deliberate mixing of different PRRS strains by simultaneous vaccination with multiple products increases the likelihood of recombination and could artificially accelerate the rate of genetic change in PRRS."

In contrast, Mengeling says he isn't sure the potential drawbacks outweigh the potential advantages. He says it is possible that vaccination with two or more attenuated, vaccine strains would provide broader protection. This dual infection already occurs to a degree when vaccine is used during an outbreak.

But he cautions that without further study, it is premature to adopt either vaccine rotation, or the use of multi-strain vaccines. "Although I don't see any clear downside to such procedures, I think that before someone buys into it wholesale, the idea ought to be thoroughly tested for safety and efficacy."

Need For New Vaccines In order to deal with what could be a never-ending parade of new PRRS strains, it may be necessary to periodically alter the strain content of vaccines. That may lead to second generation and, eventually, third and fourth generation vaccines for PRRS.

It may be that the cost of constantly testing and licensing new vaccines could be a problem - especially during times of unfavorable hog markets, notes Mengeling.

Of course, the PRRS vaccines are like any others in that they are one of several management tools necessary for effective PRRS virus control, according to Reid Philips, DVM, Professional Services, Boehringer Ingelheim/NOBL Laboratories, Inc., makers of RespPRRS, an MLV PRRS vaccine. Another MLV PRRS vaccine, Prime Pac PRRS, is sold by Schering-Plough Animal Health.

The vaccines must be used properly, according to label recommendations, and properly stored when not in use to preserve vaccine potency, Philips says.

Veterinarians and producers have learned that they must also focus on management strategies and vaccine for effective control of PRRS, he says.

Philips agrees the PRRS virus is changing and the challenge will be to develop new generation vaccines. He says BI/NOBL is dedicated in its efforts toward ongoing and improved PRRS virus protection. The company and its swine-focused staff strive to learn more about the virus, control and prevention measures and continue to investigate new products to provide greater protection against PRRS.

Pork producers have been advised to only bring in PRRS-negative replacement gilts. Some would argue that a PRRS-positive gilt affords some protection from breakdown upon entry into the new herd.

But PRRS researcher and veterinarian Scott Dee of Swine Health Center, Morris, MN, says it's just a lot easier to control PRRS by starting out with a negative, uninfected gilt. He strongly advises now, more than ever, against purchasing previously infected, incoming replacement gilts.

Infected Before Birth Preliminary data is also producing a new concern: gilt litters that are infected early in life.

Dee has detected piglets from gilt litters which are infected on day 1 or 2 of life. They may have been infected during gestation as the virus crossed the placenta, or from the sow during lactation, he says.

Declares Dee: "I think a lot of the problems with perceived vaccine failure are due to suckling piglets that are infected prior to vaccination. The common practice is to vaccinate pigs at weaning in an attempt to control the disease in the nursery. However, if piglets are infected very early, it's difficult to time our vaccination correctly. Vaccinating animals which are viremic (virus circulating in the bloodstream) following infection with field virus reduces vaccine efficacy."

According to Dee, who will add his PRRS expertise to the University of Minnesota when he joins the Swine Medicine faculty in January 1999, molecular diagnostics are helping him to realize that PRRS infections can now start early in life.

"The scary thing about it is that infection of the suckling piglet can occur in herds that appeared to be very strong candidates for stability, according to serology, and clinical presentation of excellent reproductive performance.

"But in some of those cases, we found viral infection of piglets as early as 1-2 days of life," states Dee. He says through use of PCR (polymerase chain reaction) molecular diagnostic technology he was able to detect the PRRS virus and then sequence it to prove that it was a field virus, not vaccine virus.

Dee says he is not able to pinpoint in his research whether actual infection with PRRS occurred transplacentally or through colostrum. But he points out that other scientists have proven both means are possible.

"It's a very sporadic, low level of shedding. On observation, you can't detect it in the piglets prior to weaning, because they are suckling and have maternal antibodies from the gilt/sow. Clinical problems become evident postweaning.

Therefore, it may provide an explanation for PRRS problems in the nursery in spite of top management and vaccine regimes. Production data indicates an increase in nursery mortality of 1-2% and clinically 5-10% of the pigs appear to be affected.

For their part, pork producers are frustrated spending money on vaccine and having it fail. Dee says he is advising producers they are going to have to also spend some money on diagnostics to determine if infection is occurring at the suckling piglet level. PCR testing followed by virus isolation is needed in order to determine the actual point of infection in the life of the suckling piglet, he says.

NADC Research Several projects on PRRS are being pursued at NADC in a relentless effort to find a weak spot in the PRRS virus, says Mengeling.

Besides the ease with which strains mutate, he is especially concerned with persistence of the virus in the pig. "When you infect a pig and the virus is still there six weeks later or longer, you know it is going to be problematic as far as immunity and developing a vaccine are concerned," he comments.

NADC is using the new strains of PRRS in efforts to develop their own modified live virus and killed PRRS vaccines, at the Ames, IA, research facilities.

Already, NADC has developed a quick genetic test to help differentiate between PRRS field virus and the vaccine. NADC and Boehringer Ingelheim/NOBL jointly evaluated the diagnostic test and the company has now secured a license for the test.

General information on PRRS including cause, clinical signs, diagnosis, transmission, prevention and control can be obtained on a website on the Internet at: www.vetsci.sdstate.edu/Prrs.htm

The site is produced by South Dakota State University Extension Veterinary Science, in cooperation with the American Association of Swine Practitioners. Checkoff dollars from the National Pork Board also are used to provide the website.

Minnesota veterinarian Scott Dee believes that when its comes to control of PRRS (Porcine Reproductive and Respiratory Syndrome), gilt management is indeed the key to a successful PRRS control program. Follow these four tips and you enhance your chances of keeping PRRS at bay:

1. Only buy naive, uninfected animals. Buying negative gilts reduces your overall risk of PRRS spread throughout the herd.

2. Don't rely solely on natural exposure. Vaccinate incoming naive gilts and provide four weeks in isolation before moving them to acclimation. Make sure to vaccinate gilts with a modified live virus (MLV) vaccine that ensures consistent exposure to an attentuated live virus (from the vaccine), something that natural exposure fails to do on a consistent basis. Gilts are to be revaccinated upon selection (5 months of age).

Dee just completed a field trial which shows the inconsistency of natural exposure. Thirty PRRS-negative replacement gilts were housed three to a pen for acclimation. Two PRRS-infected nursery pigs or "seeder pigs" were placed within each pen of gilts for 30 days. Field data showed the seeder pigs shed virus sporadically during the 30-day acclimation period. From that exposure, only 50% of the gilts tested positive for PRRS.

3. Gilts may need to be vaccinated at day 50 of gestation to prevent the formation of susceptible animals. Duration of immunity of MLV PRRS vaccines has been demonstrated to be four months. Often, gilts are introduced as weaned piglets 16-18 days of age and selected for breeding at 5 months of age. If an animal is bred at 7-8 months of age, allowed to gestate and lactate, 6.5-7 months of time may elapse before revaccination during lactation or prior to breeding.

One option, Dee suggests, is to revaccinate gilts at day 50 of gestation. "Controlled studies have shown that day 50 of gestation is a very safe point in which to vaccinate pregnant sows." It should eliminate infection of the litter before birth.

Dee stresses that this is not a "6-60" vaccination protocol. The "6-60" program consists of vaccination at day 6 of lactation and day 60 of gestation in all animals in the herd on a routine basis.

The use of vaccination at day 50 should be only practiced if a replacement gilt vaccination (as above) is used. Plus, diagnostic evidence of viral shedding from gilts down to suckling pigs should be demonstrated as well. There has been no such data described for the 6-60 program.

4. Document with diagnostics the point of infection of the suckling pig before starting control strategies. Monitor when infection is taking place in lactation and if there is a parity involvement. Random sampling of pigs from day 1 up to weaning using molecular diagnostics is more accurate than serological profiling.

It becomes critical to pinpoint the exact point of infection in the pre-weaned pig when vaccination is being used to control PRRS infection postweaning, says Dee.