"Swamp cancer": The increasing threat of equine pythiosis

Pythiosis is a relatively uncommon fungal-like infection causing cutaneous or subcutaneous, gastrointestinal, respiratory or multisystemic disease in many species of animals including humans. Horses are most commonly infected, and the devastating tumor-like nodular skin masses seen in these cases are likely to be remembered long after the actual name of the organism—Pythium insidiosum—is forgotten. The extremely rapid rate of growth of these lesions and the generally fatal outcome in these cases makes remembering this disease crucial for equine practitioners since early recognition and appropriate treatment are the only hope for survival for infected horses.

An increasing problem

Pythium insidiosum is referred to as an aquatic fungi or water mold, but, although it has some characteristics in common with typical molds, it is phylogenetically distinct. It was first identified in 1901 and has caused problems throughout North, Central and South America, the Caribbean Islands, Australia, the Pacific Islands and Asia. (It is interesting that tropical conditions support pythiosis, but to date no cases have been reported in Africa).

Photo 1: A lateral view of an aggressive pythiosis lesion in a Quarter Horse mare. The initial irritation on this horse's lower chest just caudal to the elbow looked like a minor scrape or puncture and was initially treated as a nonresponding wound.

Pythiosis has been called a number of names throughout the world, from swamp cancer, Florida horse leeches and summer sores to bursautee. This lack of scientific or descriptive terminology reflects the lack of knowledge about this disease.

Recently, however, new research and better diagnostic methodologies seem to indicate that pythiosis, and infection by another member of the same class of organisms—Lagenidium—might be responsible for an increasing number of infections in horses and other species. Bob Glass, an allergy specialist and owner of Pan American Veterinary Labs, has been investigating pythiosis for years.

Photo 2: The same horse in Photo 1 seen from a three-quarters view. As this lesion continued to grow, it was treated with antibiotics, corticosteroids and various topical products without response. Pythiosis was diagnosed through a blood test, and vaccine treatment was initiated but, as of publication, this mare has failed to change her allergic response into a repairative one.

"Although we've been interested in Pythium, Lagenidium and the hundreds of other related species for years, it has typically been a small number of researchers looking at a small number of confirmed cases," says Glass. "Better diagnostic tests and increased awareness have brought us many more cases, and these diseases seem to be on the rise, so we are now making more rapid strides in our research." Ten years ago, Pan American Veterinary Labs recorded fewer than 10 cases of pythiosis in dogs per year. Currently, they are identifying about 20 cases per month.

Why the increase in infection?

Climatic changes may have as much to do with increased pythiosis cases as any other single factor. In the United States, most cases of this disease come from two states: Florida is responsible for 60 percent of recorded infections, and Texas accounts for another 25 percent. Georgia, Louisiana, Mississippi and Alabama contribute another 10 percent, so the hot, generally wet and humid south is the ideal area for pythiosis and related fungal infections.

Photo 3: An angry, red, ulcerated lesion can be seen on the medial RF of this horse. It has been kept under a wrap but is not responding to treatment.

This area has experienced various stages and degrees of drought followed by wetter weather over the last few years. In times of low rainfall, lakes, ponds and streams recede, and plant growth occurs in these previously flooded locations. When wetter conditions follow and water covers this new vegetation, the ideal situation for fugal infection is created.

"We know that pythiosis and similar organisms parasitize plants, fish, algae and crustaceans," says Glass. "These organisms produce spores that move through the water looking for new plants to invade, and when horses, dogs or humans are in that wet environment, they are at risk of becoming infected."

Photo 4: The same horse in Photo 3 after vaccine treatment. The lesion is much drier and not as red, moist or angry. The horse is also no longer pruritic, indicating an end to the allergic phase.

Such situations are essentially "dead-end infections" because Pythium species cannot replicate outside of a plant environment. "We know that there is no animal-to-animal transmission of pythiosis, and we are highly confident that an infected horse cannot contaminate the environment," says Glass. "Ninety-nine percent of the cases in horses are dermal infections that start with a break in the skin." This explains the much higher incidence of pythiosis in hunting dogs and horses, both of which spend a great deal of time in wet grasses, swampy or boggy locations exposed to weeds, briars and other irritative objects that can cause small lacerations on the lower limbs.

Pathogenesis

Pythiosis typically begins as a small irritated area usually on the distal limb of a horse. This may be initially thought to be a sting, bite or small puncture, and the mild-looking lesion usually is not a cause of concern. Owners will generally begin cleaning the area and treating it with various topical antibiotic or anti-inflammatory creams. But within a few days, the lesion is markedly larger, red and irritated. It may also begin to be pruritic with the horse rubbing or even biting at the lesion.

Photo 5: An early red, uneven granulation bed is noted on the caudal heel and pastern of this horse, Ebony. She is slightly lame and pruritic as well.

Veterinary attention is sought at this point, and the lesion now looks more like a possible snake bite or foreign body puncture with significant reactive granulation tissue and necrosis. Radiography, ultrasonography and other diagnostic tests are unrewarding. Antibiotic and anti-inflammatory therapy is initiated at this stage, but the lesion continues to grow. It is tumor-like now, and serum freely leaks from the raw, irritated surface (Photos 1 and 2, p. 2E). Aggregates of necrotic cells form in the lesion, producing yellow to grey, pea-sized, gritty, coral-like bodies called kunkers. Although these structures are not specific to pythiosis, their presence is evidence enough to make one highly suspicious of fungal infection.

Histopathologic examination samples taken from the horse at this point may or may not be helpful. A report of "inflammatory response" with or without the presence of hypheal elements is usually returned. Special stains are needed to see the fungal hyphae in tissue, and even with correct staining the sensitivity is only 60 to 70 percent, so pythiosis can be missed unless fungal infection is suspected. If such an infection is suspected and antifungal therapy is started, the horse will likely still not respond. The lesion will continue to grow and eventually erode ligaments, tendons and bone and lead to death in 95 percent of cases within six months.

This rapid tissue destruction is solely the result of a massive allergic response to the presence of fungal hypheal elements on the part of the horse. T2 helper cells drive this reaction, and mast cells and eosinophils dominate the cellular population. Some horses (about 5 percent) are able to switch to a T1 helper cell response that effectively kills the organism and switches to a lymphocyte and monocyte population that promotes healing.

Photo 6: After vaccine treatment, the wound on Ebony as compared to Photo 5 looks drier, flatter and less irritated. The healing outer edges of the mass look almost burnt, and the central area is no longer oozing serum.

Glass notes that a serologic survey of hunting and retrieving dogs from at-risk areas showed that 15 to 20 percent of these animals have antibodies to Pythium, indicating previous exposure and successful destruction of the fungus. While no such serologic survey has been done in horses, Glass suspects similar findings, noting that it is "just not that easy for all horses to become infected with Pythium species since many more horses are exposed than become ill, and all the factors required for successful infection are not yet known."

Improved diagnosis and treatment

Pan American Veterinary Labs has developed an enzyme-linked immunosorbent assay (ELISA) that is specific for the presence of pythiosis fungal elements and has greatly helped in the recognition of these cases. A simple blood sample is evaluated, and the disease can be confirmed. This testing can also recognize the presence of Lagenidium (three cases in horses have been confirmed so far).

Photo 7: This view of Ebony shows a healed pastern/coronet, and she has been reshod to allow her to begin some conditioning and work.

"We have developed a 'vaccine' to pythiosis that can be used in confirmed cases, and this immunotherapeutic product works by helping the horse modulate the change from T2 helper to T1 helper cell response," says Glass. This product has been shown to have an almost 100 percent cure rate for acute cases (< 15 days) but is less effective in chronic cases (> 60 days). The overall rate of cure is 75 percent for all cases, strongly suggesting that early diagnosis and treatment are crucial to success (Photos 3-7).

Additionally, many clinicians attempt to debulk these large cancer-like growths if diagnosis and treatment have been delayed. This surgical tissue removal is generally associated with poorer skin healing and cosmetic appearance after infection than if the horse is allowed to heal itself slowly. This is another reason for early and proper diagnosis leading to correct treatment and perhaps lessening the need for surgical tissue removal.

"If I could emphasize one thing to veterinarians," Glass says, "it is to move pythiosis up on the diagnostic scale. If you see a horse that has a pythiosis-like lesion that does not respond to antibiotics and standard treatment in the first 10 days, you should think about pythiosis right away."

After getting a good look at these lesions, hopefully, no one will be able to forget.

Dr. Marcella is an equine practitioner in Canton, Ga.