Tomorrow's Tools

Try to battle BRD (bovine respiratory disease) on a single front with outdated weapons - either management or technology - and you may as well face a forest fire with a squirt gun. The bacteria and viruses causing the disease complex and its assorted ills are too many, too varied and too changeable."To control the disease, we need to impart resistance to a wide variety of bacteria and viruses, limit

Try to battle BRD (bovine respiratory disease) on a single front with outdated weapons - either management or technology - and you may as well face a forest fire with a squirt gun. The bacteria and viruses causing the disease complex and its assorted ills are too many, too varied and too changeable.

"To control the disease, we need to impart resistance to a wide variety of bacteria and viruses, limit exposure to the infectious agents, limit stress, provide good nutrition and hydration, and control parasite loads. It's a disease of management as much as it is an infectious process," says Robert Briggs, a research veterinarian with USDA's Agricultural Research Service (ARS).

In fact, this complexity means the industry will probably never eliminate the disease. But, innovative thinking and a commitment to management should help the industry stem the estimated $1 billion lost to BRD each year.

Feeding Against Pasteurella As an example, Briggs and fellow researcher, Fred Tatum, recently developed the world's first genetically engineered injectable and oral mucosal Pasteurella vaccines, built without foreign DNA or a genetic marker for antibiotic resistance.

"We've developed molecular genetic technology which allows us to very specifically control attenuation (the degree of disease-causing bacterial virulence). We target genes critical to the production of the disease and remove essential portions of them, but leave no foreign DNA," says Briggs. He explains attenuation is a reduction of virulence, compared with the bacterial parent strain.

In a nutshell, the new Pasteurella haemolytica vaccine allows immune response to the bacteria without allowing the disease to develop. Briggs says it should be possible to add other primary BRD bacteria - Pasteurella multocida and Haemophilus somnus - and major BRD viruses to the vaccine with the same technology. He says they started with P. haemolytica because it is responsible for most of the dollars lost to BRD bacteria.

Although not yet commercially available - the injectable form, which includes P. haemolytica, P. multocida and H. somnus, is licensed - this development is significant.

First, even though bacteria are the main culprits in BRD, the industry's weapon of choice so far has been vaccines aimed at controlling the viruses that weaken the immune system enough for the bacteria to take over. Vaccines aimed at such things as IBR, BVD, BRSV and PI3.

"Pasteurella are tough organisms to deal with. As a result, a lot of people have been working on viral vaccines, thinking if they get rid of those, bacteria can't become a secondary invader. But we know bacteria can be a primary invader," says James Cullor, director of the Veterinary Medicine and Teaching Resource Center for the University of California's College of Veterinary Medicine.

According to Bob Bohlender, of the Animal Clinic in North Platte, NE, "One of the problems we have with all bacterin vaccines are endotoxin levels in the product. An animal can only tolerate so much endotoxin without getting an adverse reaction."

These endotoxins go part and parcel with bacteria and are necessary to direct immune response. Too much, though, and problems can occur. What's more, no one is sure how much is too much.

"IBR, BVD (and other virals) and Pasteurellas (and other bacterin vaccines) all most likely have some level of endotoxin (bacterins more than virals). You wind up stacking it as you give each and have a better chance of hitting that threshold," says Cullor. He explains the threshold between positive and negative impact varies with the age of the animal, type of endotoxin and amount of stress on the immune system.

Even in its injectable form, the new ARS vaccine has lower levels of endotoxin than some other modified-live vaccines. More exciting, however, with the oral mucosal version, endotoxin levels aren't a concern because the nose, where these bacteria live, is already alive with them.

Plus, Cullor explains, "Injectables prompt the immune system through circulating in the blood, then going out to the tissues as needed.

Conversely, Briggs says a local mucosal response can be observed only days after the vaccination, whereas other vaccines usually need 10-14 days to elicit a primary immune response. He explains mucosal immunity is on the mucosal surface, right where it's needed to fight the bacteria.

Weight Is A Better Yardstick In a field trial comparing low and high risk calves - half unvaccinated and the other half vaccinated by top-dressing the ARS oral vaccine on the feed - mortality was reduced in the high-risk calves from 16% to 4%. P. haemolytica quickly killed 16% of the non-vaccinates, while vaccinate mortality resulted from Pasteurella multocida and Mycoplasma bovis. There was no mortality in the low-risk vaccinates, but their average daily gain increased 25% during the first 28 days on feed.

"I've been an advocate of that for years, looking at weight gain, and not just deads and pulls," says Bohlender. He explains that subpar performance pointing to subclinical disease can cost the industry more than animals with clinical symptoms.

Development of the oral mucosal vaccine may also point to the future of vaccine application. For one thing, the oral delivery is convenient, and might allow more producers an opportunity to vaccinate prior to shipment. "I think it's a great opportunity," says Bohlender, although he thinks the oral vaccine might be best used as a drench or paste. "It would get us away from the 5-20 percent of the cattle that aren't eating when we administer it."

Plus, oral vaccinations mean there are no injection site lesions costing the industry money. Bohlender also serves as chairman of the Animal Disease Research Sub-committee for the National Cattlemen's Beef Association. "This is exactly what we've been asking for, more products that don't jeopardize the quality of our product."

The genetically engineered vaccine proved its metal in a clinical trial, too (Table 1). Calves vaccinated with the injectable or oral ARS vaccine had more and faster immune response when exposed to virulent Pasteurella haemolytica than unvaccinated calves. The vaccinates also showed less lung damage (Table 2). By both measures, the oral vaccine proved the most powerful.

If someone licenses the oral vaccine, Briggs estimates it would take at least three years for it to become commercially available.

Management Is Always The Key While producers wait for new technology, each of these animal health professionals says management is the key to controlling BRD, no matter what products become available (See "Bustin' BRD," page 8).

"Poor management can overcome good immunology any time," says Cullor. "The first dollar you spend should be on management, and the second and the third, then you should talk about vaccines, and the last dollar you spend should be on antibiotics."

Although antibiotics have proven useful in BRD treatment and as prevention, with metyphylactic use, Jim Roth, believes increased government and public pressure on their use could shift even more weight to vaccines and management. Roth is a professor of immunology at Iowa State University's College of Veterinary Medicine.

Incidentally, Roth is involved in research with another potential BRD tool called immunomodulators. Where vaccines are aimed at prevention against specific infection, immunomodulators seek to improve overall immune resistance. Immunomodulators consist of proteins found in the body which increase immune response or chemicals which stimulate increased production of these proteins.

In this case, reducing stress has to do with everything from environmental stress to ensuring cattle have the nutrition needed to build and maintain a strong immune system.

"Good nutrition, housing, vaccines, bedding, transportation that is optimum; all of these things we need to do and keep fine-tuning," says Cullor. "We need to do more to understand BRD completely. Maybe it's time for the industry to call for a symposium on BRD, share all of the research and come out with some industry-wide recommendations."

Embracing The Reality What's more, it may be time to consider BRD within the context of the current and evolving industry.

"The cow/calf industry isn't like it used to be," says Bohlender. "We have one cowboy to 500-750 cows. We have fewer people on these ranches, so we can't have sick cattle. On the other hand, we need convenience for delivering the product." He says more of his cow/calf clients are retaining ownership past the ranch gate, too. That means they're paying more attention to health management and reaping the benefits.

That's good news when you consider that in some other ways the industry is more like it has always been.

"We fundamentally don't want to change the way we do business because our business currently exists by adding value to someone else's mistake," says Gerald Stokka, extension beef veterinarian at Kansas State University. Say what you want about quality, in an average-based market, folks can buy light-weight mismanaged cattle under the market, play compensatory gain against health risk, and still make a buck.

"We know BRD is expensive, yet we have our current marketing system. The time you can take advantage of someone else's mistake is when calves come off the cows," says Stokka. Coincidentally, that's exactly when calves are most susceptible to BRD.

That's why Stokka believes an industry shift toward more coordinated production and marketing systems could alter the course of BRD as much as anything. In those systems, management rules.