Equid Blog : Horse Health & Diseases : University of Guelph : Ontario Veterinary College : Equine Infectious Diseases

A new study was recently published in the Journal of Veterinary Internal Medicine (Frederick et al. 2009) which looked at infectious agents found in the feces of foals with diarrhea. Specifically, they looked for rotavirus, Clostridium perfringens, C. difficile, Salmonella, parasite eggs and Cryptosporidium oocysts.

They found at least one infectious agent in the feces of 122 (55%) of the 233 foals in the study. That means, despite testing for a wide range of pathogens, they could not identify an infectious agent in 45% of the diarrheic foals. This is very similar to the situation typically found in adult horses with diarrhea. This could have happened for a number of reasons:

1. No test is perfect. It’s possible that in some of the cases one of the test results was a “false negative,” meaning it did not detect the infectious agent even though it was there.
2. A few cases may have been caused by other infectious agents that were not included in the diagnostic panel.  For example, Rhodococcus equi is a common cause of respiratory disease in foals, but it has also been associated with diarrhea in some cases.
3. The diarrhea was caused by an agent of which we are unaware, and for which we have no test. Researchers are constantly looking for other bacteria, viruses or parasites that may be capable of causing or contributing to diarrhea in foals and adult horses.
4. The diarrhea was not caused by an infectious agent. For example, the authors failed to discuss foal heat diarrhea as a cause of clinical diarrhea in very young foals. This is a well recognized cause of foal diarrhea, but no infectious agents are involved.

The most commonly identified pathogens were rotavirus (20% of cases), Clostridium perfringens (18%), Salmonella (12%) and C. difficile (5%). Overall 191 (87%%) of the foals survived, and survival was not associated with any pathogen identified in the feces (i.e. in this study, foals were not more likely to die if they had one particular pathogen in their feces than another). This must be interpreted very cautiously, however, because the study does not account for other kinds of illness in these foals, or even whether diarrhea was the primary problem for which they were referred to the hospital. Diarrhea, especially in very young foals, can be very serious because they can dehydrate very quickly and are very susceptible to shock of various kinds.

There were a few other issues with this study that are important to keep in mind as well:

1. The group of foals they looked at ranged in age from newborns to 10-months old. The digestive tract of a foal undergoes drastic changes in the first year of life, and it is well known that certain infectious agents only cause disease in foals of particular ages. For example, different parasites may take weeks to months to develop within the intestine of a foal, so even if a foal is infected as soon as it’s born, these parasites cannot cause disease for quite some time. For this reason, it would have perhaps been more useful to look at the data separately for different age groups.
2. There was no control group in this study. Most of the time, if an animal has diarrhea and the test you perform tells you there is a known diarrhea-causing pathogen in the feces , you assume the diarrhea is due to that agent. This is not necessarily always the case. Some pathogens are carried around by totally normal animals, who may get diarrhea for a completely different reason. So what we really need to know now is: if the authors tested 233 foals with normal feces (and the same ages), how common would each of these pathogens be?

While the data may be interesting to look at, this paper doesn't really tell us anything new that will change the way we treat or manage foals with diarrhea in general.  Nonetheless, the information may still be useful for helping to design and interpret future research studies about these pathogens and diarrheal disease in foals.

Image source: www.bbc.co.uk (credit: George Ring)

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This post was written by guest author Dr. John Prescott, Professor, Department of Pathobiology, University of Guelph.

April’s "bug of the month" is Streptococcus equi subspecies equi, the cause of equine strangles, specifically strain 4047. This is the first strangles strain to have its entire genome (i.e. all of its DNA, including every gene) sequenced. The March 2009 issue of the open-access journal Pathogens, published by the Public Library of Science (PLoS), describes how British scientists think the strangles organism evolved to be such a scourge of horses, by comparing its genome to that of the first equine Streptococcus equi subspecies zooepidemicus strain to also have its genome sequenced, strain H70. It is believed that S. zooepidemicus was the ancestor of the S. equi that causes strangles.

Like all evolution, the story involves both loss and gain. As far as loss is concerned, the strangles organism has more genes that have been "turned-off" (inactivated genes) than does S. zooepidemicus. These genes were turned off by a large number of extra pieces of DNA called insertion sequences which S. equi picked up over time. These sequences get inserted in many different places within the bacterium's DNA (its genome) leading to inactivation or loss of various genes. Loss of genes in this manner can often result in bacteria becoming restricted to a particular type of host - S. equi essentially only infects horses and other equids, while S. zooepidemicus still has a broader host range.

What S. equi lost by becoming restricted to equids, it gained by becoming a nastier bug. It did this by becoming "infected" by four unique bacterial viruses. (Bacterial viruses are viruses that only infect bacteria. Some of these viruses "transmit" (transfer) genes to the bacteria they infect but leave the bacteria alive. Other bacterial viruses can kill bacteria after infecting them). Most bacteria have anti-viral defense mechanisms to protect themselves from these viruses, but S. equi's defenses may have been damaged or turned-off by insertion sequences. Being infected by these four bacterial viruses gave S. equi many genes not found in S. zooepidemicus. One of these viruses is thought to be capable of leaving S. equi and killing S. zooepemidicus in the horse’s throat - a useful trick for S. equi to wipe out the competition in this area so it can move in more easily and cause infection. A second virus gives the strangles organism a phospholipase enzyme which is known to be involved in the bacterium's ability to cause disease. The third and fourth viruses each donated two different superantigen genes – these genes help S. equi to cause inflammation and impair the ability of the immune system to fight off the bacteria. A unique additional piece of “foreign” DNA that S. equi acquired is associated with the ability to capture iron. This allows S. equi to grow better in infections than S. zooepidemicus, because the body of the infected host will often try to bind up as much iron as possible so the bacteria can’t use it to grow. The scientists speculate that this iron-capturing gene was the key to starting S. equi on its evolutionary spiral to becoming a major horse pathogen.

A final thought is that the bacterial viruses that made S. equi what it is today have many similar DNA sequences to bacterial viruses found in Streptococcus pyogenes, a major human bacterial pathogen. Humans might have had an unwitting hand in creating this pathogen from one of their own.

More information on strangles can be found on the equIDblog Resources page.

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Infectious disease surveillance is an important part of the infection control program. Equine hospitals with good infection control programs have put thought and effort into designing a surveillance program that is right for them. Like many (or most) aspects of infectious diseases, there is no "standard" program, because the risks and benefits vary greatly between facilities.

There are various types of surveillance that can be used. Here are some examples:

Active surveillance
This involves going out and "actively" collecting information that would not otherwise be collected for other reasons. This includes things like taking extra samples from horses for testing strictly for infection control reasons. This is discussed further below.

Passive surveillance
This involves using data that are already available. It's a cheaper and somewhat easier form of surveillance, but it doesn't provide as much detailed information as active surveillance. An example of this is compiling all the culture results from fecal samples that were already submitted for routine testing (as required by the case).  This helps us know what bugs tend to cause certain infections, and to what antibiotics they are usually susceptible.

Syndromic surveillance
Syndromic surveillance can be active or passive. It involves looking at the occurrence of specific clinical signs (syndromes), not specific diseases/diagnoses. For example, routine monitoring for fever in hospitalized animals is a useful tool. It doesn't tell us what the specific problem is, but it can alert us that something might be going on.

I'll outline the active surveillance component of the Ontario Veterinary College's active surveillance program here (I'll get to the other types some other time):

Salmonella

• All horses that are at high-risk for shedding Salmonella in their feces (i.e. horses with colic) and all horses that are at increased risk for becoming infected (i.e. horses undergoing anesthesia and surgery) are tested.  Horses with diarrhea - the highest risk group for shedding Salmonella - are also tested as part of the routine case work-up.
• Stalls that have housed diarrheic horses are quarantined until they have been tested for Salmonella. The stall environment is sampled and culture is performed. Stalls are not opened until negative culture results are received.

Methicillin-resistant Staphylococcus aureus (MRSA)

• A nasal swab is collected from all horses at the time of admission, weekly during hospitalization (if they stay that long) and at the time of discharge.

Other

• Additional active surveillance for Salmonella and MRSA can be conducted at the discretion of the Chief of Infection Control (i.e. me). If I have any concerns about a particular disease, I institute additional active surveillance.

Who pays for it?
Active surveillance costs (as opposed to routine diagnostic testing like Salmonella culture in a horse with diarrhea) are covered by the Hospital. It's a cost of doing business. Financially, it also makes sense, because it is cheaper to prevent infections than it is to deal with hospital-acquired infections and outbreaks.

Don't be afraid to ask about the infection control program at your equine hospital. A hospital should be more than willing to tell you what they're doing to help reduce the risk of your horse developing an infection.

More information on equine hospital infection control can be found in on the equIDblog Resources page.

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Diarrhea is a potentially life-threatening condition in horses. It's also frustrating from a diagnostic standpoint because, even with the most complete/comprehensive testing, a cause is only identified in a minority of cases. This is true for other species too, including people, and is a reflection of the complex nature of the intestinal tract and the numerous possible causes of intestinal disease. Diagnostic testing obviously costs money, so if it gives us an answer less than half the time anyway, it begs the question - why bother? Well, here are some points to consider:

• In some situations, you may find a cause that requires a different treatment, so diagnosis has a direct impact on patient care and probably the outcome.
• Many causes of diarrhea are infectious and it's important to know if other horses may have been exposed to a transmissible pathogen.
• Some causes of diarrhea, especially Salmonella, can also infect people, and it's important to know to what people have been exposed.
• It's also important to know whether a horse might still be shedding a transmissible pathogen after its diarrhea resolves. For example, horses with salmonellosis can shed Salmonella for a while (often a few weeks, sometimes longer) after they have recovered from their diarrhea. This could be a source of infection for other horses and people.
• Outbreaks of diarrhea can occur. It's much better to know early on what you are dealing with, rather than waiting until mulitple horses have been infected.

I consider diagnostic testing money well spent in cases of diarrhea. Some people don't want to test because they don't want to know, particularly about Salmonella. However, it's been proven again and again that the "head-in-the-sand" approach will backfire when it comes to infectious diseases.

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Salmonellosis is an important problem in horses. Infection with Salmonella can cause disease ranging from fever and/or mild diarrhea, to severe diarrhea (see picture right), bloodstream infection and death. Horses can also carry Salmonella in their intestinal tract without any signs of illness at all!  Testing of horses with diarrhea for Salmonella is commonly performed, but diagnosing Salmonella infection is not as straighforward as you may think:

• The primary means of diagnosing salmonellosis is to culture the bacterium from the animal's feces, but fecal culture is far from a perfect test. Isolating Salmonella from all the other bacteria that are present in the manure can sometimes be difficult, and often takes at least 48-72 hours. Multiple cultures may need to be performed over several days, because sometimes horses with Salmonella only shed the bacterium intermittently in their feces. It is generally recommended that a horse have five negative fecal cultures in a row before it can be safely called "Salmonella-negative". If a horse has diarrhea caused by Salmonella, it's uncommon to need five samples before a positive culture is obtained, but it can happen.
• Culture of a rectal mucosal biospy is more likely to detect of Salmonella than fecal culture, but this procedure is rarely performed.  Rectal mucosal biopsy involves removing a small piece of tissue from the lining of the rectum using a pair of biopsy foreceps.  Culture of such a biopsy may be more useful for identifying horses that are carrying Salmonella but have no clinical signs of illness.  Serial fecal cultures are usually adequate for finding Salmonella in horses that have diarrhea.
• Molecular tests (such as PCR) for Salmonella are available from some laboraties. These tests tend to be faster and may be more sensitive, but there are also numerous potential problems with them, as discussed in the equIDblog post entitled "Molecular Diagnostic Testing: Pros and Cons".
• Clinical signs are not adequate for diagnosing salmonellosis. Other microorganisms (e.g. Clostridium difficile) can cause disease that appears exactly the same.

Despite these challenges, trying to diagnose salmonellosis is important. Salmonella can cause serious outbreaks of disease - it's important to know with what you are dealing, especially since Salmonella can also be spread to people and other animal species. Additionally, isolating Salmonella allows the bacterium to be tested for its susceptibility to antibiotics. Antibiotics are rarely indicated for the treatment of salmonellosis, but when they are needed, it is much better to know which ones are more likely to work.

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An outbreak of salmonellosis has killed at least 22 horses in Kjalarnes, Iceland. A total of 41 horses were infected.  This is a very high mortality rate (>50%) for what I assume is a group of otherwise healthy horses, as compared to the more compromised populations which are usually present in equine hospital outbreaks. It is unclear whether the high mortality rate may be due to a particularly nasty (virulent) strain of Salmonella or the unavailability of aggressive supportive medical care which is needed in severe cases of diarrhea in horses.

The source of infection was thought to have been a sedimentation pond in the horses' pasture. The article contained no information about potential sources of contamination of the pond, or about the the strain of Salmonella involved.

• Outbreaks of salmonellosis are uncommon on farms, but they can occur.
• Mortality rates with salmonellosis can be high, especially without (but sometimes even in spite of) aggressive (and expensive) medical care.
• Prompt investigation is critical to identify the source(s) of infection and try to prevent further exposure and additional cases.
• Good routine infection control measures should be in place to reduce the risk of entry of Salmonella onto a farm, as well as transmission of Salmonella between horses (and between horses and humans) if it makes in onto a farm.

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Diarrhea is a relatively common problem in many animal species (including people). It's often mild and typically goes away on its own, and is more of a cosmetic or convenience problem than a serious health concern. However, that's not necessarily the case in horses. Although horses can get mild diarrhea that gets better on is own, severe diarrhea (colitis) is a very serious problem that can even be fatal. There are many potential causes of diarrhea in horses, including Salmonella, Clostridium difficile, Clostridium perfringens, Neorickettsia risticii (Potomac Horse Fever) and Lawsonia intracellularis. It is likely that numerous other bacteria can also cause diarrhea, but we just don't know how to diagnose them.  In fact, a specific pathogen is identifed as the cause of diarrhea in horses in less than 50% of cases.

Diarrhea can be rapidly life-threatening in horses. Some reports have described fatality rates as high as 40%, however these are based on cases from referral hospitals which presumably treat the sickest horses. Nonetheless, this high fatality rate needs to be taken seriously. In severe cases, death may occur in less than 24 hours, and may be due to the intestinal disease itself, or any number of complications that can accompany colitis.

The picture (left) is of the intestinal tract of a six-month-old foal with severe diarrhea that threw a blood clot to one of the major blood vessels suppling the large intestine, killing that section of the gut (the dark purple/black intestine in the picture), and the foal. Laminitis (founder) is also a common complication.

There is no way to completely prevent diarrhea from occuring in horses, but some basic measures should help reduce the risk:

• Only use antibiotics when absolutely necessary, and only when prescribed by your veterinarian. Antibiotic-associated diarrhea is big problem in horses.
• Avoid sudden management changes, such as feed changes and transportation, as much as possible.  If something needs to be changed, try to introduce the change(s) as slowly as possible.
• Isolate new arrivals so that the risk that they will introduce pathogenic bacteria like Salmonella to other animals on the property is reduced.
• Have a good basic infection control program in place to reduce the risk of transmission of infections of all types.
• Immediately isolate all horses with diarrhea, and contact your veterinarian.

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Stomach ulcers are common in horses (especially race horses), and anti-ulcer medications are widely used. The most common of these drugs is omeprazole (sold under the brand name Gastrogard), which is a proton pump inhibitor. There is no doubt that gastric ulcers can cause problems in horses and treatment is necessary in these situations. However, there are a lot of horses being treated for mild ulcers or for prevention of ulcers, and it's unclear whether this is really needed, and whether it could even cause problems.

Picture (right): Endoscopic view of ulcers along the margo plicatus in the stomach of a horse.

In people, proton pump inhibitor treatment has been associated with an increased risk of diarrhea (particularly Clostridium difficile diarrhea). Biologically this makes  sense.  The acidic environment of the stomach normally helps kill harmful bacteria that a person (or a horse) may ingest. Treatment with anti-ulcer drugs to reduce the acidity of the fluid in the stomach may allow bad bacteria like Clostridium difficile and Salmonella to reach the intestinal tract in larger numbers, and therefore predispose the patient to developing diarrhea.  Theoretically the same thing could happen in horses.

Does this actually happen in horses? We don't know. It is certainly a possibility but there is no evidence either way.

Are certain horses at higher risk? We don't know. However, it's reasonable to suspect that this could be a greater concern in horses that are already at higher risk of developing diarrhea for other reasons, such as those being treated with antibiotics.

Should we avoid using anti-ulcer drugs in horses? Not always. These drugs are definitely needed for horses with clinically significant ulcers (i.e. their ulcers are actually painful or making them sick). However, we really need to consider whether treatment is necessary for horses that have very mild ulcers (i.e. that aren't causing clinical signs) or those that don't have ulcers at all and treatment is only "preventative".

Personally, I don't like to use anti-ulcer drugs in hospitalized horses unless they have severe ulcers that are causing problems. In cases where milder ulcers are present or people want to give anti-ulcer drugs for prevention, I prefer them to wait until the horse goes home. The same approach could be taken with horses that are on farms but at higher risk for diarrhea, such as those being treated with antibiotics.

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The discovery of antibiotics was one of the most important medical advances in history, and these drugs have had an immense impact on human and animal health. While antibiotics have saved countless lives, their use can also be associated with some very serious side effects and complications.  For example, in horses, antibiotic-associated diarrhea (colitis) is a major issue.

By the nature of their intestinal tract, horses at among the highest risk species for developing serious diarrhea associated with antibiotic use.  The intestinal tract of a horse is full of billions of bacteria of different types. These bacteria are important for normal digestion, and also help to prevent infection by "bad" bacteria such as Salmonella and Clostridium difficile.  Antibiotics can disrupt the balance of this complex bacterial population.  The imbalance itself can cause problems, and can also make it easier for bad bacteria to move in, grow and cause disease.

Here are some important points to remember about antibiotics, particularly in horses:

• Antibiotics can only kill bacteria. They should not be used when a bacterial infection is not present and not likely to occur. Antibiotics are too commonly misused for viral infections in horses, which puts the animals at unnecessary risk.
• Any antibiotic can cause diarrhea, but some drugs are considered higher risk. Erythromycin and tetracyclines are considered high-risk in most areas of North America. Certain drugs, such as lincomycin and oral penicillins, are such high risk that they should never be used in adult horses.
• Both oral and injectable antibiotics can also cause diarrhea. Drugs that are injected can still reach the intestinal tract and affect the bacteria there. Some drugs, like tetracycline, are actively pumped into the intestinal tract from the bloodstream, resulting in relatively high concentrations in the intestine, even if the drug was given by injection.
• While some antibiotics can be purchased over the counter in some areas, antibiotics should never be given without the direct recommendation of a veterinarian.
• If your horse is being treated with antibiotics and develops diarrhea, contact your veterinarian immediately.
• There is no known way to reduce the risk of antibiotic-associated diarrhea in horses, other than to avoid unecessary use of antibiotics. Some people treat horses with probiotics or yogurt, but currently there is no evidence that this is beneficial (but it probably doesn't hurt, at least in adult horses).

Another major concern with antibiotic use is the development of antibiotic resistance in bacteria, but that's a topic for another post (or two, or three or more!).

More information about Clostridium difficile and probiotics in horses can be found on the equIDblog Resources page.

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The following are infectious disease control resources that have been developed at the Ontario Veterinary College (OVC), as well as information regarding the infectious disease control polices of the Ontario Veterinary College Teaching Hospital (OVCTH) in Guelph, Ontario.

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