Editor’s note: First in a BRD roundtable series.

Respiratory disease in feedlot cattle is caused by a mixed bag of pathogens. Notable among the viral pathogens are bovine respiratory syncytial virus (BRSV), bovine herpesvirus-1 (BHV-1) which causes infectious bovine rhinotracheitis, bovine viral diarrhea virus (BVDV) and parainfluenza-3 virus (PI3V). It would probably be easier to manage bovine respiratory disease (BRD) caused by these viruses if they behaved the same way, but Mother Nature has given them unique attributes that challenge their prevention and control to this day.

John Ellis, DVM, PhD, Dipl. ACVP, Dipl. ACVM, Western College of Veterinary Medicine, University of Saskatchewan, says there are more differences than there are commonalities between bovine respiratory viruses and how they interact with the immune system.

“That’s a potential problem in terms of expecting similar vaccine efficacy,” he says. “Just because a viral vaccine has all of the agents in it, that doesn’t mean the requirements for immunity are the same for each. Looking at commonalities, BRSV and PI3V are both paramyxo viruses, so they are somewhat related in terms of their genetic makeup and biology. But there are significant differences between those two paramyxo viruses in that BRSV really only infects epithelial cells, whereas PI3V also affects macrophages and has potential immunosuppressive effects.”

BHV-1, on the other hand, infects epithelium cells, lymphoid cells and also nerve cells. Ellis also believes coronavirus is a big player as well.

BVDV is a conundrum when grouping it with respiratory pathogens. “To me, a respiratory pathogen infects the cells of the respiratory tract, those being pulmonary or airway epithelial cells and not just macrophages,” explains Ellis. “I left BVDV for last because very few data indicate that most BVDV isolates infect the respiratory epithelium, but it’s included because of its more systemic effects and it is often included as a respiratory pathogen.”

Dan Givens, DVM, PhD, Dipl. ACT, Dipl. ACVM, College of Veterinary Medicine, Auburn University, argues that while the effects of an infection with BVDV are mainly systemic, because of timing of infection, challenges and other stress factors, resulting pathology normally shows up in the respiratory tract.

“So while it’s not a respiratory pathogen, the timing of exposure causes BVDV to be closely associated with respiratory disease, and in some ways often a baseline etiology that might have started the whole shipwreck,” Givens notes. “For example, the decrease in white blood cells caused by BVDV might be a key precipitating factor in the susceptibility to stress and other pathogens resulting in the respiratory disease that you see. I think BVDV plays a significant role there, especially as we look at the timing, stress, and exposure to other pathogens. It’s pretty amazing when you look at some of the drops in the white blood cell counts we can see with different strains of BVDV by themselves.”

What’s different about BVDV, says Ellis, are some of the protective immune responses. “A mucosal IgA response is going to be very effective against BRSV, PI3V and coronavirus, whereas maybe not so much against BVDV. With BVDV a systemic response is probably more important.”

BRSV and the immune system

There’s a school of thought that says BRSV-associated disease is in large part mediated by IgE, Ellis says.

“Part of the confusion relates to the similarity in the pathology between allergic respiratory disease and some of the things we see in BRSV associated with respiratory disease, and I think that’s maybe where some of the confusion stems from.”

Ellis says a lot of the BRSV information is based on studies in mice.

“They can’t be infected to any extent with BRSV. But much of the literature on BRSV examines disease enhancement, often associated somehow with IgE and TH2 responses, which I think has really muddied the waters in bovine research. That’s not to say that in individual cattle there’s not that going on. There is some IgE probably made in the course of virtually every immune response. It’s a question of how much of a role that actually plays in the pathogenesis in most cattle. I think close to zero.”

Ellis says a large part of the disease is actually the inflammatory response to the virus.

“The virus, when you really look at it, probably isn’t that pathogenic per se,” he says. “A lot of the disease is the body’s response to that pathogen. It’s being recognized that much of the disease associated with paramyxo viruses is actually due to the inflammatory response that they cause. There is a really nice paper recently out of Iowa State looking at the upregulation of Cox-2 following PI3V and BRSV in the infection of lambs, so that fits into the whole idea that a lot of the disease we see in BRSV, and for that matter PI3V, is due to the inflammatory response, which is different from an IgE-mediated hypersensitivity reaction. It’s more of an innate immune response that’s probably contributing to the disease.”

Because of that, Kelly Lechtenberg, DVM, PhD, Midwest Veterinary Services, Oakland, Neb., believes we should try to manage inflammation associated with respiratory disease. “I think we’re obliged to manage it from an animal care perspective.” The same is true with bacterial pneumonia, he says. “I remain convinced that we can and should make cattle more comfortable if we can decrease inflammation associated with BRD.”

Viremia can affect cattle feeding and ultimately gain. Do we want to lessen it or is it a useful process? Viremia is a good proxy for incidence of disease, Givens says, so we would probably desire to lessen it. “However, there are some situations where I look at a viremia as a good thing. A significant viremia at the right time in a calf with minimal stress is likely to produce the greatest immunity. So do we desire to lessen viremia in the feedlot? To do that we need to increase immunity. If we can increase immunity to an adequate level, such as with BHV-1, well-vaccinated cattle exposed to BHV-1 will still shed nasal BHV-1 when they’re challenged but they are not exhibiting disease and their viremia is lessened. To me that’s an example of how effective immunity is decreasing the viremia and creating a scenario where we’re not seeing disease, even though there still is some degree of viremia.”

How feedlot viruses spread

It’s important to understand how these feedlot respiratory viruses exist in the environment and how they infect cattle.

“As documented in the human literature, your grandmother was right, you get colds in the fall, and there’s probably a reason for that because of the humidity and the temperature affect the stability of the virus in the environment,” Ellis explains. “But it’s really difficult to approach experimentally. Some of it has been done in humans. Fomites are recognized as very important in the transmission of RSV and human parainfluenza virus, but it has not been very well-examined in veterinary medicine.”

Ellis says the sneeze and breathing the virus into the lung is probably very important in the rate at which disease happens.

“In research, we generally aerosolize a very low dose of BRSV in a closed, contained area. It’s somewhat similar to what happens in transport of cattle, and you’ve seen the pictures of the sneeze and how that spreads out. We have taken more than a thousand times more BRSV and put it up the nose, the same isolate, the same lot, and get virtually nothing, which to me says that the aerosolization of the virus and breathing it deep into the lung is important; maybe those are the animals that get clinically ill.”

He adds that the reason for that might be that the micro-anatomy that prevents pathogens from getting into the lung is overridden in those cases. “I think those kinds of biophysical aspects are really difficult to measure but ultimately they are very important in transmission and the efficacy of transmission.”

Relatively speaking, cattle lungs are small for their body and as they get older that disparity becomes bigger.

“So anything that puts a stress on an already over compromised pulmonary system (such as a poor environment) is going to contribute to breathing pathogens down deeper into the lung,” Ellis says. “It’s actually overriding the anatomical protection. Anything that does that is going to have a tendency to enhance transmission.”

Viral shedding is enhanced by close proximity, Lechtenberg says.

“Cattle coughing across a fence is probably adequate for horizontal transfer. We can provide 500 square foot per head, but if it’s 100°F with 95 percent humidity and you’ve got sprinklers, your effective pen density is just under ‘crawl on top of the next guy,’ — it’s just too hot and that’s the effective density that all of these deep breathing, ‘sucking-in-air-as-fast-as-they-can’ cattle are going to experience for that period of time. That period of time might run from noon until 6p.m., with just a little bit of pushing and shoving to see who’s going to get closest to the sprinkler.”

Exposure to viruses at the feedlot is clearly there, notes Shawn Blood, DVM, Hitch Consulting Service, Guymon, Okla. “We have no idea, looking at the cattle clinically, what that is, the amount of it, how long it lasts, etc. We know we’re going to have that natural exposure and we’re still going to use our core vaccination program.”

“My knee-jerk response is that we’d want to minimize natural exposure at the feedlot the best we possibly can,” Lechtenberg adds. “We’ve got a bed pack farm that accounts for about 15–20 percent of our production and we poured 5-foot high concrete walls in that when we built it. One of the mistakes we made was we didn’t pour them 8 feet high. Once we get a group of cattle brought in commingled, basically they are 300 head pens. We like to do everything we possibly can do to minimize the exposure of those cattle to any other cattle to the point where we’ve got an in-pen treatment system, where we actually treat those cattle in the pen, and we don’t share tanks. We don’t have enough numbers to know if we’re making a difference but there are certain things that we do that you just intuitively know you’re doing the right thing.”

Lechtenberg says it can be done in the feedlot with double fencing and other management, and the virus shed risk in our hospital environments needs to be recognized.

“In our research application, it’s amazing how much biosecurity we can create simply by having an empty pen between groups of calves that are challenged and not challenged,” Lechtenberg adds. “We raise a lot of colostrum-deprived baby calves in huts and we’ve got feedlot cattle from numerous source farms at any given time within about 75 feet of these fragile calves. It is amazing how well we can maintain serologically negative calves during all weather conditions, despite that fact that feedlots have inherent risk factors such as flies, wind, and dust. If our crew does common things uncommonly well, we can make difference with respect to biosecurity.”

These common practices include changing gloves, boots and coveralls to minimize the chance of becoming the biological vector in the transmission of disease causing organisms in Lechtenberg’s unique situation. Common practices that can be considered in a feedlot production viral break include minimizing hospital pen mixing, consideration of shared fence lines and water tanks with respect to new cattle coming in. “This experience makes me realize that we may be able to more to minimize horizontal transmission during an epidemic between pens of cattle in our production settings,” Lechtenberg says.

It’s easy to see how viruses are passed around in a commingled, high-density feedlot situation, but how are they maintained in the cowherd? That’s one of the “$64,000 questions” with PI3V and BRSV, Ellis says.

“Work in The Netherlands indicates that it’s probably not cow-to-cow transmission of acute infection that maintains it. It’s more likely to be persistent, not in the same way that BVDV is, but persistent within the individual animals. There are carrier animals, but how that happens is unresolved. The cow-to-cow transmission that you think happens with most acute viral infections doesn’t really explain how BRSV is maintained in a herd, and that’s probably the same for PI3V.”

Ellis doesn’t think the term “latent” describes this. “I wouldn’t use the term latent, or even persistence, which for most people implies immunological tolerance. I don’t know what term to use aside from maybe ‘carrier animals’.”

What can fevers tell you?

The fever process can be misleading on a number of fronts. Cattle with fevers don’t necessarily look sick. Blood did some work with thermometer ear tags and consistently saw cattle with fevers of 105-107°F fevers, but when the cowboys rode the pens they couldn’t identify those cattle. “They looked clinically normal,” he says. “It’s an interesting observation that the fever is not the depressing agent, it’s something else in the disease process such as toxemia.”

Calvin Booker, DVM, Feedlot Health Management Services, Okotoks, Alberta, agrees. “That would be consistent with our experience when we’ve temped a lot of cattle over the years. In the absence of abnormal clinical signs, rectal temperature by itself is not a very good predictor of risk or outcome. In the presence of abnormal clinical signs, especially with evidence of depression, rectal temperature has a really good relationship with what the subsequent outcome is going to be.”

Booker notes that there are probably a lot of things that cause rectal temperature fluctuations that aren’t infection-related, such as 99°F heat in Missouri, Kansas and Oklahoma, especially with black-hided cattle, for example.

Another confounder is disease caused by multiple pathogens.

“The overlay of multiple pathogens in an experimental setting is very interesting, Givens says. “In work by Paul Walz and others, we see those high fevers when we’re looking at a pure viral infection, but if we overlay an endotoxemia on top of a viral infection, that’s when we start seeing the severe depression. We also see temps go down dramatically. It is experimental and not real world, but it’s very surprising to me when you overlay an endotoxemia on top of a viral infection you’ll push that fever down back to normal temperatures but the calf looks tremendously worse. With a viral infection alone, it can be standing up, eating, with a tremendously high fever and maybe a little bit depressed; with a viral infection and endotoxemia, it’s down and showing you signs of severe depression but the temp is normal. Multiple etiologies end up with some interesting disconnects between fever and depression.” 


Environment can maintain viruses

As with every living organism, viruses can be susceptible to fluctuations in the environment. John Ellis, DVM, PhD, says there have been years where it’s been a mild fall in Canada and there seems to be much more BRSV in the calf population. “BRSV tends to occur in the fall because it’s damp and not as sunny. Viruses don’t like ultraviolet light, either, so it’s cloudy and damp, and that’s when the virus seems to last longer in the environment.”

Kelly Lechtenberg, DVM, PhD, says respiratory disease can be associated with many situations but stressful environments such as cold, rainy weather are certainly predisposing factors.

“We can also have respiratory disease when we get the hot, dusty conditions. I think anything that’s stressful enough to where it’s immunosuppressive can lead us on a path to what we diagnose as BRD. Prolonged cold, wet conditions or hot, dusty conditions result in animals that for one reason or another aren’t finding it easy to get to the bunk, they’ve got some issues that are going to predispose them.”

Calvin Booker, DVM, says somewhere between 30-70°F and dry is an ideal climate with lower disease pressure.

“We get that kind of weather from about the beginning of September to all the way through to Dec.1. There’s generally pretty good fall weather where the vast majority of the feeding industry is located in southern Alberta. We get it again in the spring from the end of March through to the first week in June.”

Booker doesn’t see a lot of general respiratory problems in the spring, but one disease that does show up from time to time during the winter is IBR. “The IBR outbreaks that we’ve seen at the pen level or feedlot level in the last 20 years have all occurred in December, January and February.”

Booker says there are a couple major confounders at that time.

“One is we’ve got huge calf placements in the fall and those timeframes (Dec.-Feb.) tend to be when we get to 90, 100, 120 days on feed, which in theory, if you haven’t revaccinated, you’re going to get a population that’s at a higher risk of IBR.” It’s also a time generally associated with more crowding of cattle within the pen because it’s colder at that time of year. Cattle spend more time on the bedding pack and more time up against the wind shelter fences if the wind’s blowing. “I don’t know if that affects the transmission dynamics within the pen or not, but it would seem to me that it probably does because our effective pen density is much smaller at that time of the year and this becomes important if we have an outbreak going on.”

Hot weather can exacerbate disease transmission because the heat puts stress on the respiratory system, says Ellis. “If want to make disease, not just grow viruses, we definitely want to make it warm or even hot.”

The heat is an issue starting cattle in places like Oklahoma, says Shawn Blood, DVM.

“We see some pretty profound decreases in consumption across the feedyard when it gets to those 100°F days. Another factor in there is wind. We usually always have a lot of wind, but there’s usually a day or two in there that the wind will be less than 20 mph.”

Next issue: BRSV and PI3 in feedlot BRD.

This information is from a Bovine Veterinarian roundtable sponsored by Pfizer Animal Health and moderated by Jessica Laurin, DVM, Marion, Kan.