Early diagnosis crucial for foal pneumonia

Young foals are susceptible to respiratory disease of the lower airway, especially Rhodococcus equi pneumonia prior to 6 months of age. Though not the most common foal pneumonia, the illness caused by Rhodococcus equi continues to be a major cause of loss of life and is a particularly insidious in foals.

The organism, a gram-positive coccobacillus, commonly causes infection in hot, dry environments via the inhalation of dust from manure-contaminated soil. Organic acids normally found in horse manure promote the growth of the bacteria, which also is enhanced by summer heat. The dry conditions promote aerosolization of the bacteria. The pneumonia progresses fairly rapidly as the infected foal gradually loses condition and develops a chronic cough, wheezing, fever and increased respiratory rate.

Untreated foals develop progressive crackling sounds noted upon thoracic auscultation within the entire lung, accompanied by harsh inspiratory sounds. Foals also can develop an intestinal infection due to swallowed infected sputum. An infected foal frequently appears quite well until just before death, which is why the disease is often missed. The mortality rate can be as high as 60 percent to 70 percent in untreated foals. Even those foals that recover sometimes are limited in their performance later in life. To be successful, treatment must be started in the early stages of the condition.

Some farms endemic, others not

It is curious that on some farms the disease is endemic but not on others. John Prescott, DVM, Department of Pathobiology at the Ontario Veterinary College, says it is primarily a matter of numbers and concentration of foals. Others factors include the sandiness and acidity, and possibly other properties of the soil, the amount of dust generated, and the length and extent of heat in the summer. Established horse farms, those that have raised horses for several years, are more likely to show greater incidence of disease. Contamination does not come from adult horses that are immune and do not shed bacteria in their manure, though foals younger than 3 months readily shed

R. equi

from their intestinal tract, contaminating the soil.

Adult horses can shed the organism in their feces, says Stephen A. Hines, DVM, PhD, Dipl. ACVP, professor in the Department of Veterinary Microbiology & Pathology at Washington State University's College of Veterinary Medicine. It's just that they don't tend to share near as high of numbers as even asymptomatic foals.

"If you have a horse on your place, you've almost certainly got R. equi there — even though it may not be causing a big problem," Hines says. "Heck, if you've got a farm of any kind, I'm confident you can find R. equi in the soil and manure."

Virulence of the organism also plays a role in differentiating farms of heavy incidence of disease from those with few cases because farms with endemic disease have larger proportions of virulent R. equi

According to Keith Chaffin, DVM, MS, Dipl. ACVIM, Texas A&M University, there have been several studies that have looked at farm-level risk factors for R. equi. Chaffin and colleagues did a study at 64 farms with and without R. equi pneumonia. They found several farm-level risk factors, including large acreage and a large population of mares and foals. The higher the density of foals, the higher the risk of disease.

Not a disease of neglect, management factors were not found to be important.

"The farms that had R. equi pneumonia were more likely to be well-managed," Chaffin says. "Those that would do all the things that we as veterinarians tell them to do — test for failure of passive transfer of immunity, attend foaling, vaccinate and deworm are at high risk."

The density of foals is the biggest factor, Hines agrees.

"If there are a lot of foals, there is a lot of Rhodococcus," he says. "The foals are the high shedders. You get a cycle with high environmental load and high infectious doses. The thing that is correlated best is the number of horses per acre."

Since it has been determined that foals may be most susceptible to R. equi in the first few days of life, the foal can become initially infected at the breeder's farm and bring the resulting contamination back to the home farm, says Bonnie R. Rush, DVM, MS, Dipl. ACVIM, professor and section head of equine internal medicine at Kansas State University.

"Therefore, it is important for the owner to understand where the infection came from and to recognize that foals that are sick are shedding a lot of bacteria and serve as a source of R. equi," she says.

Although a farm did not have a serious heavy load of R. equi previously, once the foal sheds bacteria, it is a reservoir of disease to infect the farm where it is housed. If it is a farm's only foal, then it should try to confine and contain the spread of infection. It is then important to dispose of the foal's manure, and try to keep them away from other newborn foals.

"But once the environment is contaminated, it is pretty hard to get it completely clean again," Rush says.

To the contrary, Hines suggests that the evidence that foals are infected only during the first few days of life is really quite controversial, though they can be infected very early in life; definitely many are in some settings. However, even in the studies that report the earliest onset of disease, the disease is diagnosed at 40-plus days of age, and there is no experimental evidence for a 40-plus day incubation period. Foals likely can be infected for a significant period of time, not just in the first week. Experimentally, foals at 6-10 weeks of age typically have been used, and they have always been susceptible.

Virulence, foals show more susceptibility

There is a particular genetic construct or plasmid of

R. equi

that is essential to development of the disease. It allows the organism to penetrate and replicate within the macrophage. This plasmid contains genes that encode for several proteins that have been named virulence associated protein (VAP) and are noted as 'A through H'.

"VAP A appears to be one of the keys to how this bacterium thrives in macrophages, but we still don't know why," Prescott explains. "The other VAP genes appear less important, perhaps because they are secreted rather than staying on the bacterial surface, but what their function is also is still a mystery."

All foal strains contain VAP A and the same other VAP genes. Without VAP A, these strains don't cause disease. The bacterium seems to like to get into macrophages through the "back door" by getting itself taken up by complement or other receptors. If it goes through the "front door", that is through antibody receptors, it is more likely to be killed. It really seems to want to get inside macrophages as the safest place it can find in the body, which is strange because macrophages are usually bacterial hell, Prescott says.

"Why young foals are so susceptible is probably because of VAP A strains, which are essentially unique to the horse, which like to take advantage of the window in the immune system when immunoglobulins are at their lowest levels to get inside macrophages through the back door," Prescott says. "There may also be some heritable predisposition in some foals and perhaps also a general tendency of young foals not to be good at mounting the correct type of immune response, perhaps because they are overwhelmed by the numbers of R. equi they encounter, perhaps because they have intercurrent equine herpesvirus-4 infection, or for a combination of these and other reasons."

"Foals are seeing R. equi for the first time, so they don't have pre-existing immunity," states Hines. "Like any other neonate, their immune system is just not well developed yet. The big question is do they have the capability to respond as adults do? They do not. I think part of it is the immaturity of their immune system."

Steeve Giguère, DVM, PhD, Dipl. ACVIM, Department of Large Animal Clinical Sciences at the University of Florida, currently is working on a study to look at why foals are more susceptible than adult horses; it will be presented at the ACVIM meeting in June.

"We will probably have some insight as far as what is different in the immune system of foals, or why foals are more susceptible."

An ounce of prevention

Limiting the number of foals infected is important to reduce its prevalence and reduce the rate of further contamination and incidence.

A cost-effective and clinically-effective way to screen for early cases of R. equi was determined to be CBC and fibrinogen. It was found that it is useful to monitor foals every two weeks by taking a CBC and fibrinogen, beginning at about 4 weeks of age. If you have a high CBC and fibrinogen, it does not necessarily mean the foal has R. equi, but further testing is warranted. You might pull that foal out and do more intensive diagnostics to figure out if in fact it was R. equi or some other cause of infection.

"One thing that some people are suggesting is treating all foals early to reduce their shedding and reduce their exposure," Hines suggests. "One thing they are studying at Texas (A&M) is treating all foals with antibiotics to see if you can reduce the number of cases and the amount they shed. But there are problems with doing that, the bacteria may build-up resistance. But it uses the foals to reduce the environmental load."

Chaffin and colleagues began the study January 2005. The study is being done at numerous farms around the country, endemic farms that have greater than 20 percent of their foals infected with R. equi annually. The study is aimed at determining the prophylactic effects of azithromycin on the prevalence of R.equi pneumonia. Based on two findings, the hypothesis is that the administration of azithromycin every other day for the first two weeks of life will decrease the prevalence of R. equi pneumonia. First, foals become infected with R.equi during the first few days of life, and second, there is a window of opportunity for R.equi to establish infection in those foals at that time. Also based on some work in neonatal foals with azithromycin, showing that it does have good absorption, and does achieve high intracellular concentration.

"We hope to generate enough data with 2005 to answer our hypothesis," Chaffin says. "I really don't know if it will work or not. I think we have enough foals enrolled in the study. Assuming enough foals complete the study, we should be able to shed some light or doubt on this hypothesis, by the end of 2005."

Another promising tool for prevention of R. equi pneumonia is hyperimmune plasma. "The bottom line is that hyperimmune plasma probably helps reduce the incidence of R. equi pneumonia, however it doesn't totally prevent the disease," Giguère states. "What's important to remember is that if you are going to give hyperimmune plasma, which is fairly time consuming and expensive, you shouldn't be lulled into a false sense of security. You should still be vigilant and try to use other methods to diagnose cases early. Basically it's not like if you give it, you can be sure that the foal will not develop R. equi pneumonia, but it does seem to help."

According to Giguère, it is important to use other methods to help prevent onset of or catch the disease early. Maybe to do some blood work at regular intervals on all the foals on those farms with a high prevalence of the disease, perhaps do routine ultrasound of the chest, every couple of weeks. On some farms, they do chest ultrasounds of all the foals to detect lesions before the foals start having clinical signs.

"The earlier you make a diagnosis, the more successful you're likely to be with your therapy," Giguère recommends. "We found that the CBC, especially the WBC count, was more effective as far predicting those foals that would subsequently develop R. equi pneumonia."

Vaccine in the future?

Considerable progress is being made toward developing effective vaccines against this infection based on understanding how

R. equi

causes disease and identifying the key immunogen(s), Prescott says. "I would expect to see one within the next few years."

Mary Hondalus, DVM, University of Georgia, is studying the use of a particular strain of R. equi (a strain that requires riboflavin supplementation in order to grow) to create an immune response. The particular non-virulent strain is described as a live-attenuated riboflavin auxotropic strain.

"There are a lot of approaches to develop a vaccine. To use attenuated strains of bacteria is what Dr. Hondalus is doing," Hines says. "We are trying to do some DNA-vaccine work here at WSU. I think a vaccine is a long way off. You just have to try different things. You try something and you modify it, it just has to be an experimental approach. The problem with all these studies is that you have to immunize foals. The big question is: Can you prime them very early in life to respond appropriately since neonates are so unique? Some researchers suggest that it is not possible. To me, that's just speculation. You have to try and see. Certainly, it will be a challenge. Can you get a foal to respond the way you want, is the big question."

R. equi is a huge killer, especially in Florida and Kentucky, where the climate and density of horses on breeding farms is optimal for the disease. Some of these farms have many cases, and it is very insidious.

"The big reason they see so much of it is that they have the concentration of animals, the big numbers of foals," Hines explains. "Fortunately most foals don't get sick, and if they do and recover, they're immune for life. In nature, most of the time, they respond appropriately."

Dr. Kane earned his doctorate in equine nutrition and physiology from the University of Kentucky in 1978. He works within the animal-feed industry with a specialty in horses.