pulling blood

Vets are using serum amyloid A, a naturally produced protein, to detect equine infections and monitor treatment

Our horses have many blood components capable of alerting our veterinarians about everything from dehydration status to tissue damage. Scientists have been on the search for substances that act as reliable biomarkers for various problems; these could help remove some of the guesswork when making a diagnosis. Enter serum amyloid A (SAA), a protein the liver produces in the face of inflammation that’s changing the way veterinarians detect infections in horses.

“Serum amyloid A, classified as an acute-phase protein, helps the immune system fight infection early in the course of disease,” says Luis Castro, DVM, a racehorse practitioner with Teigland, Franklin & Brokken, in Boynton Beach, Florida, and Saratoga Springs, New York. “Within a mere six hours of the body being exposed to an infectious agent, the liver produces sufficient levels of SAA that can be measured in the circulation. Normally, SAA levels are negligible. This means that veterinarians can rapidly diagnose a patient with an infectious condition often prior to the development of full-blown clinical signs such as fever, nasal discharge, diarrhea, and more.”

Indeed, in normal, healthy horses, SAA levels are either undetectable or very low. Faced with an inflammatory condition, circulating SAA levels rise 100 to 1,000 times higher than baseline.

Levels also decrease quickly, allowing veterinarians to use SAA to monitor horses’ response to treatment.

“Once we know a horse has an ­infection, the best way to determine if our treatments are working is to continue measuring SAA,” says Castro. “Instead of counting the days that a horse has been on antibiotics, for example, we keep the horse on antibiotics until the SAA drops down to a certain level.”

At that point the horse’s own immune system can manage the infection.

The levels can also tell you when treatments are not working—if, for example, the incorrect antimicrobial is on board. “In the past, we used to rely on white blood cell counts for this purpose, which wasn’t always precise,” says Castro. “Now, if we see SAA levels continue to rise we know that a change in antibiotic is ­indicated. If they decrease, we know we are on the right track.”

Monitoring response to antibiotics to determine when to stop treatment is one of the most common ways racehorse practitioners use SAA, he says, but it’s just one of the ways veterinarians are putting this biomarker into practice.

In this article we’ll describe how veterinarians are using SAA to help diagnose and treat common equine ailments of the respiratory, musculoskeletal, and abdominal tract. We’ll also outline the benefits of testing SAA levels in healthy horses, including foals.

Respiratory Tract Conditions

Veterinarians are commonly called out to diagnose and treat horses with poor performance, exercise intolerance, coughing, and nasal discharge. The list of potential causes for these complaints can be quite long, including equine influenza (the flu), equine herpesvirus (EHV), infection with the bacterium Streptococcus equi subspecies equi, and even noninfectious inflammatory airway disease (IAD), which is now known as equine asthma. In a recently published study, Nicola Pusterla, DVM, PhD, Dipl. ACVIM, an internal medicine clinician from the Department of Medicine and Epidemiology at the University of California, Davis, School of Veterinary Medicine, determined that SAA helps differentiate between these conditions.

In their study, published in 2016 in the Journal of Equine Veterinary Science, he and colleagues measured SAA levels in 207 horses. Those horses were diagnosed with one of the following—influenza (42), equine herpesvirus-4 (43), IAD (38), S. equi ss equi (44)—or served as healthy controls (40). Key findings were:

  • Most healthy horses had undetectable SAA levels (0-2 mg of SAA/L of serum);
  • Only six horses with IAD had detectable SAA values, with a maximum of 586 mg/L;
  • Horses confirmed to have influenza had SAA values ranging from 0 to >3,000 mg/L and a median value of 731 mg/L;
  • Horses diagnosed with EHV-4 had similar ranges of SAA (from 0 to >3,000 mg/L) but a median value of 1,173 mg/L; and
  • Infection with S. equi ss equi resulted in SAA levels from 0 to >3,000 mg/L with a median value of 1,953 mg/L.

“All three groups of horses diagnosed with a respiratory condition had SAA levels significantly higher than the healthy control horses, including the IAD group,” says Pusterla. “The IAD group had significantly lower SAA values than each of the three groups with infectious respiratory disease. Horses diagnosed with bacterial respiratory infection, in this case S. equi ss equi, had significantly higher SAA levels than horses with the viral respiratory tract infections.”

Pusterla did point out, however, that despite the signi?cant difference in SAA values between horses with bacterial and viral infectious respiratory diseases, there is a lot of overlap in SAA values between these two groups.

“The findings of this study do not suggest that SAA levels alone be used to distinguish between bacterial and viral respiratory diseases,” he says. “Other tests must be conducted, such as culturing nasal secretions or polymerase chain reaction.

“This test can also be used in apparently healthy horses prior to transport, competition, or even surgery to ensure the health of their respiratory tracts for maximal health and performance,” Pusterla adds.

Specifically, measuring SAA levels in horses to ensure they’re normal prior to transport could be useful because horses commonly develop respiratory disease during and following long-distance trailering. Transport can also exacerbate an underlying respiratory tract infection, making it important to identify horses with latent respiratory issues.

“Underlying infections caused by respiratory viruses could potentially be identified via SAA measurements, and horses with elevated SAA levels prior to transport likely should not undergo transport until those SAA values return to normal levels, meaning almost undetectable,” says Pusterla.

Castro concurs, adding that veterinarians use SAA routinely not only in racehorse but also show horse populations. “They do a lot of traveling, and measuring pre- and post-transport levels of SAA continues to increase in popularity,” he says.

Musculoskeletal Conditions

There is a long history of researchers studying SAA in conjunction with various musculoskeletal issues. In general, SAA levels remain negligible in the face of inflammation (e.g., training-related strains to tendons or ligaments, fractures, etc.); infections cause much more profound SAA increases.

Take, for example, a condylar fracture: If there is inflammation but no infection, SAA levels should be normal. Monitoring that same horse after surgical repair of the fracture could reveal infection (e.g., from the implants used or surgical site contamination).

“SAA should not rise following surgery to repair a condylar fracture if there is no infection,” Castro says.

He gives another example: cellulitis, which is usually apparent as a severely swollen limb. “A simple cellulitis, although remarkable to look at in a horse, will not necessarily increase SAA levels unless there is an infectious component.”

Where SAA does come in handy is for detecting conditions such as joint infections (septic arthritis) following administration of intra-articular medications or puncture of a synovial structure.

The marker can also help veterinarians detect infection in horses that aren’t performing up to snuff.

“Precompetitive testing of SAA to determine if a horse has a subclinical disease despite having no cough or fever with a history of poor performance can be extremely helpful,” Castro says. “In some cases we find walled off abscesses in lungs that can’t easily be detected by other methods.”

Gastrointestinal Tract Disease

For decades veterinary researchers have tried to find a test that can clearly determine whether a colicky horse needs surgery. Can SAA fit the bill? Castro says the answer is no.

“Do not rely on SAA to determine if a colic is surgical or not,” he says. “Use the standard techniques, such as response to analgesics (pain-relievers). Monitoring horses that underwent surgery, however, is another case. SAA can indicate whether a horse is fighting an infection postoperatively. Infections can easily occur in horses that had a section of their gastrointestinal tract removed.”

Veterinarians can, however, use SAA readings to help differentiate between infectious causes of colic, such as peritonitis and colitis, and noninfectious forms, says Pusterla.

Sick Foal

Assessing Foal Health

Breeders often use an immunoglobulin G (IgG) kit to measure foals’ blood antibody levels to confirm passive transfer of immunity from the mare’s colostrum (first milk). While ingesting a sufficient amount of good-quality colostrum puts them on the path to thrive, these newborns still are delicate creatures that can easily contract life-threatening infections. Respiratory and gastrointestinal issues are not uncommon.

“Because the immune system in young foals is not mature, we often see SAA levels increase in sick foals a lot higher and a lot quicker than in more mature horses,” says Castro. “Anything greater than 200 is concerning.”

He adds, “SAA might also be used as a screening tool for Rhodococcus equi, which causes abscesses in the lungs. Right now, ultrasound is widely used to screen foals for lung abscesses … . Instead, SAA can first be measured. If the value is 0, there is no need to ultrasound.”

How to Test SAA

Like any blood test, there are several ways veterinarians can measure SAA. Some send a blood sample to a laboratory for analysis; however, SAA can degrade in the sample during transport, making the values 5-10% lower than the actual SAA levels. Also, test results won’t be available for a few days. Because one of SAA’s features is its “real-time” measure of inflammation, manufacturers have developed several stallside test kits that provide practitioners with accurate and immediate results.

Regardless of which process your veterinarian employs, it’s important to be sure the test’s units are consistent and match the reference ranges he or she is referring to. For example, the University of Miami Miller School of Medicine measures equine SAA in mg of SAA/L of serum, while Cornell University’s Animal Health Diagnostic Center measures micrograms g)/mL of serum. Conveniently, in this case mg/L is the same as μg/mL; however, other laboratories report SAA values in mg/dL (deciliter), which is not the same. Online calculators can help with SAA value conversions for comparing different lab values and horse test results. Regardless, the SAA value should come with various reference ranges for intrepretation (e.g., normal, mildly elevated, etc.).

Take-Home Message

Equine veterinarians are finding serum amyloid A values useful in a variety of cases, but it’s important to remember they are only one piece of a puzzle.

“Every infection has inflammation, but not all inflammation has infection,” says Castro. “Horses with pure inflammatory conditions, such as tying-up or laminitis, that do not have an underlying infectious component will not have increased SAA levels. In these cases, other diagnostic tests are needed to help diagnose disease and monitor response to treatment.”

Nonetheless, this test can help practitioners detect infectious conditions quickly and guide treatment strategies for optimal outcomes and return to function.

“The faster an infectious condition is diagnosed, the quicker the veterinarian and barn staff can work together, instituting appropriate biosecurity protocols to minimize disease spread,” Pusterla says.