Pythiosis

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Ulcerative and destructive skin lesion on a dog caused by Pythium insidiosum
Pythium hyphae

Pythiosis is a rare and deadly tropical disease caused by the fungus-like Pythium insidiosum. Long regarded as being caused by a fungus, the causative agent was not discovered until 1987. It occurs most commonly in horses, dogs and humans, and there have been isolated cases in other large mammals.[1] The disease is contracted after exposure to stagnant freshwater such as swamps, ponds, lakes, and rice paddies. Pythium insidiosum is different from other members of the genus in that human and horse hair, skin, and decaying animal and plant tissue are chemoattractants for its zoospores.[2] Additionally, it is the only member in the genus known to infect mammals, while other members are pathogenic to plants and are responsible for some very well known diseases in plants.

Epidemiology

Pythiosis occurs in areas with mild winters because the organism survives in standing water that does not reach freezing temperatures.[3] In the United States it is most commonly found in the Southern Gulf states, especially Louisiana, Florida, and Texas but has also been reported as far away as California and Wisconsin.[4] It is also found in southeast Asia, eastern Australia, New Zealand, and South America.

Pathophysiology

It is suspected that pythiosis is caused by invasion of the organism into wounds, either in the skin or in the gastrointestinal tract.[3] The disease grows slowly in the stomach and small intestine, eventually forming large lumps of granulation tissue. It can also invade surrounding lymph nodes.

Pythiosis in different animals

The following section deals with the different pathalogies of pythiosis in different species. The species are listed in decreasing frequency of infection.

Horses

In horses, subcutaneous pythiosis is the most common form and infection occurs through a wound while standing in water containing the pathogen.[2] The disease is also known as leeches, swamp cancer, and bursatti. Lesions are most commonly found on the lower limbs, abdomen, chest, and genitals. They are granulomatous and itchy, and may be ulcerated or fistulated. The lesions often contain yellow, firm masses of dead tissue known as kunkers.[5] It is possible with chronic infection for the disease to spread to underlying bone.[6] In humans it can cause arteritis, keratitis, and periorbital cellulitis.[7]

Dogs

Pythiosis of the skin in dogs is very rare, and appears as ulcerated lumps. Primary infection can also occur in the bones and lungs. Dogs with the gastrointestinal form of pythiosis will have severe thickening of one or more portions of the GI tract that may include the stomach, small intestine, colon, rectum, or in rare cases, even the esophagus. The resulting pathology will result in anorexia (no appetite), vomiting, diarrhea (sometimes bloody), and abdominal straining. Extensive weight loss may be evident.[8]

Humans

This a rare disease with only 28 case reported in the literature up to 1996.[9] Although this disease was first reported in 1884[10] the species infecting humans - Pythium insidiosum - was only formally recognised in 1987.[11] Diagnosis can be difficult in part because of a lack of awareness of the disease.[12] It does not appear to be transmissible either animal to animal or animal to human. There appear to be three clades of this organism: one in the Americas, a second from Asia and Australia and a third with isolates from Thailand and the USA.[13] The most probable origin of the organism seems to be in Asia.

Most human cases have been reported in Thailand, although there have been cases reported elsewhere. In humans, there are four forms of the disease: subcutaneous, disseminated, ocular and vascular.[14] The ocular form of the disease is the only one known to infect otherwise healthy humans, and has been associated with contact lens use while swimming in infected water. This is also the rarest form with most cases requiring enucleation of the eye.[15] The other forms of the disease requires a preexisting medical condition, usually associated with thalassemic hemoglobinopathy.[14] Prognosis is poor to guarded and treatments include aggressive surgical resection of infected tissue, with amputation suggested if the infection is limited to a distal limb followed by immunotherapy and chemotherapy.[15] A recently published review lists 9 cases of vascular pythiosis with 5 survivors receiving surgery with free margins and all except one requiring amputation. The same review lists 9 cases of ocular pythiosis with 5 patients requiring enucnleation of the infected eye and 4 patients requiring a corneal transplant.[15]

Cats and other animals

In cats pythioisis is almost always confined to the skin as hairless and edematous lesions. It is usually found on the limbs, perineum, and at the base of the tail.[16] Lesions may also develop in the nasopharynx.[5]

The only animals that have been successfully infected with the disease are rabbits which are used for in vivo studies of the disease.

Other animals reported to have contracted pythiosis are bears, jaguars, camels, and birds although these have only been singular events.

Diagnosis and Treatment

Pythiosis is suspected to be heavily underdiagnosed due to unfamiliarity with the disease, the rapid progression and morbidity, and the difficulty in making a diagnosis. Symptoms often appear once the disease has progressed to the point where treatment are less effective. As the organism is neither a bacteria, virus or fungus, routine tests often fail to diagnose it. In cytology and histology, the organism does not stain using Geisma, H&E, or Diff-Quick. GMS staining is required to identify the hyphae in slides. Additionally, the symptoms are usually non-specific and the disease is not normally included in a differential diagnosis.

Biopsies of infected tissues are known to be difficult to culture but can help narrow the diagnosis to several different organisms. A definite diagnosis is confirmed using ELISA testing of serum for pythiosis antibodies, or by PCR testing of infected tissues or cultures.

Due to the poor efficacy of single treatments, pythiosis infections are often treated using a variety of different treatments all with varying success. Most successful treatments include surgery, immunotherapy, and chemotherapy.[15]

Aggressive surgical resection is the treatment of choice for pythiosis.[17] Because it provides the best opportunity for cure, complete excision of infected tissue should be pursued whenever possible. When cutaneous lesions are limited to a single distal extremity, amputation is often recommended. In animals with gastrointestinal pythiosis, segmental lesions should be resected with 5-cm margins whenever possible. Unfortunately, surgical excision of tissue and amputation do not guarantee complete success and lesions can re-appear. For this reason, surgery is often followed by other treatment methods.[15]

An immunotherapy product derived from antigens of P. insidiosum has been used successfully to treat pythiosis in horses and people. Unfortunately, although controlled trials have not been completed, the efficacy of this product in dogs appears to be poor.[18]

Case reports indicate the use of the following chemotherapy treatments with varying success: potassium iodide,[19] amphotericin B,[19] terbinafine,[19][20] itraconazole,[15][20] fluconazole,[15] ketoconazole,[15] natamycin,[15] posaconazole,[15] voriconazole,[15] prednisone,[21] flucytosine,[21] and liposomal nystatin.[21]

In vivo studies on rabbits indicate the following chemotherapy treatments with varying success:

In vitro studies on Pythium insidiosum indicate the following chemotherapy treatments with varying success:

References

  1. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ 2.0 2.1 Lua error in package.lua at line 80: module 'strict' not found.
  3. ↑ 3.0 3.1 Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ Gastrointestinal pythiosis in 10 dogs from California. J Vet Intern Med. 2008 Jul-Aug; 22(4):1065-9. Berryessa NA, Marks SL, Pesavento PA, Krasnansky T, Yoshimoto SK, Johnson EG, Grooters AM. Department of Medicine and Epidemiology, University of California, School of Veterinary Medicine, Davis, CA, USA.
  5. ↑ 5.0 5.1 Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ Dr. Susan Muller, DVM. http://www.critterology.com/articles/pythiosis-dog
  9. ↑ Thianprasit M, Chaiprasert A, Imwidthaya P (1996) Human pythiosis. Curr Top Med Mycol 7(1):43-54
  10. ↑ Gaastra W, Lipman LJ, De Cock AW, Exel TK, Pegge RB, Scheurwater J, Vilela R, Mendoza L (2010) Pythium insidiosum: an overview. Vet Microbiol 146(1-2):1-16. doi: 10.1016/j.vetmic.2010.07.019
  11. ↑ De Cock AW, Mendoza L, Padhye AA, Ajello L, Kaufman L (1987) Pythium insidiosum sp. nov., the etiologic agent of pythiosis. J Clin Microbiol 25(2):344-349
  12. ↑ Botton SA, Pereira DI, Costa MM, Azevedo MI, Argenta JS, Jesus FP, Alves SH, Santurio JM (2011) Identification of Pythium insidiosum by nested PCR in cutaneous lesions of Brazilian horses and rabbits. Curr Microbiol 62(4):1225-1229 doi: 10.1007/s00284-010-9781-4
  13. ↑ Schurko AM, Mendoza L, Lévesque CA, Désaulniers NL, de Cock AW, Klassen GR. A molecular phylogeny of Pythium insidiosum. Mycol Res 107(Pt 5):537-544
  14. ↑ 14.0 14.1 Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ 15.00 15.01 15.02 15.03 15.04 15.05 15.06 15.07 15.08 15.09 15.10 Lua error in package.lua at line 80: module 'strict' not found.
  16. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  17. ↑ Thieman KM, Kirkby KA, Flynn-Lurie A, et al. Diagnosis and treatment of truncal cutaneous pythiosis in a dog. J Am Vet Med Assoc 2011;239:1232-1235.
  18. ↑ Grooters AM, Foil CS. Miscellaneous fungal infections. In: Greene CE, ed. Infectious Diseases of the Dog and Cat, 4th ed. Elsevier Saunders, St. Louis, MO, 2012; 675-688.
  19. ↑ 19.0 19.1 19.2 Lua error in package.lua at line 80: module 'strict' not found.
  20. ↑ 20.0 20.1 Grooters AM. Pythiosis and Lagenidiosis. In: Bonagura, ed. Kirk’s Current Veterinary Therapy XIV. Saunders Elsevier, St. Louis, MO, 2008; 1268-1271.
  21. ↑ 21.0 21.1 21.2 Lua error in package.lua at line 80: module 'strict' not found.
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