Pythiosis is a rare and deadly tropical disease caused by the
oomycete
Oomycota forms a distinct phylogenetic lineage of fungus-like eukaryotic microorganisms, called oomycetes (). They are filamentous and heterotrophic, and can reproduce both sexually and asexually. Sexual reproduction of an oospore is the resul ...
''
Pythium insidiosum
''Pythium insidiosum'' is a species of ''Pythium'' and a member of the class oomycota. ''Pythium insidiosum'' is mainly found in standing water and occasionally soil. Unlike most ''Pythium'' species, which are generally pathogens of terrestrial ...
''. 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, with isolated cases in other large mammals.
The disease is contracted after exposure to stagnant fresh water such as swamps, ponds, lakes, and rice paddies. ''P. insidiosum'' is different from other members of the genus in that human and horse hair, skin, and decaying animal and plant tissue are
chemoattractant
Chemotaxis (from '' chemo-'' + ''taxis'') is the movement of an organism or entity in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemical ...
s for its
zoospore
A zoospore is a motile asexual spore that uses a flagellum for locomotion. Also called a swarm spore, these spores are created by some protists, bacteria, and fungi to propagate themselves.
Diversity Flagella types
Zoospores may possess one or mo ...
s.
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 well-known plant diseases.
Epidemiology
Pythiosis occurs in areas with mild winters because the organism survives in standing water that does not reach freezing temperatures.
In the United States, it is most commonly found in the Southern Gulf states, especially
Louisiana
Louisiana , group=pronunciation (French: ''La Louisiane'') is a state in the Deep South and South Central regions of the United States. It is the 20th-smallest by area and the 25th most populous of the 50 U.S. states. Louisiana is borde ...
,
Florida
Florida is a state located in the Southeastern region of the United States. Florida is bordered to the west by the Gulf of Mexico, to the northwest by Alabama, to the north by Georgia, to the east by the Bahamas and Atlantic Ocean, and to ...
, and
Texas
Texas (, ; Spanish language, Spanish: ''Texas'', ''Tejas'') is a state in the South Central United States, South Central region of the United States. At 268,596 square miles (695,662 km2), and with more than 29.1 million residents in 2 ...
, but has also been reported as far away as
California
California is a U.S. state, state in the Western United States, located along the West Coast of the United States, Pacific Coast. With nearly 39.2million residents across a total area of approximately , it is the List of states and territori ...
and
Wisconsin
Wisconsin () is a state in the upper Midwestern United States. Wisconsin is the 25th-largest state by total area and the 20th-most populous. It is bordered by Minnesota to the west, Iowa to the southwest, Illinois to the south, Lake M ...
. It is also found in
southeast Asia
Southeast Asia, also spelled South East Asia and South-East Asia, and also known as Southeastern Asia, South-eastern Asia or SEA, is the geographical United Nations geoscheme for Asia#South-eastern Asia, south-eastern region of Asia, consistin ...
, eastern
Australia
Australia, officially the Commonwealth of Australia, is a Sovereign state, sovereign country comprising the mainland of the Australia (continent), Australian continent, the island of Tasmania, and numerous List of islands of Australia, sma ...
,
New Zealand
New Zealand ( mi, Aotearoa ) is an island country in the southwestern Pacific Ocean. It consists of two main landmasses—the North Island () and the South Island ()—and over 700 smaller islands. It is the sixth-largest island count ...
, and
South America
South America is a continent entirely in the Western Hemisphere and mostly in the Southern Hemisphere, with a relatively small portion in the Northern Hemisphere at the northern tip of the continent. It can also be described as the southe ...
.
Pathophysiology
Pythiosis is suspected to be caused by invasion of the organism into wounds, either in the skin or in the gastrointestinal tract.
The disease grows slowly in the
stomach
The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach i ...
and
small intestine
The small intestine or small bowel is an organ in the gastrointestinal tract where most of the absorption of nutrients from food takes place. It lies between the stomach and large intestine, and receives bile and pancreatic juice through the p ...
, eventually forming large lumps of
granulation tissue
Granulation tissue is new connective tissue and microscopic blood vessels that form on the surfaces of a wound during the healing process. Granulation tissue typically grows from the base of a wound and is able to fill wounds of almost any size ...
. It can also invade surrounding
lymph node
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...
s.
In different animals
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.
The disease is also known as leeches, swamp cancer, and bursatti. Lesions are most commonly found on the lower limbs, abdomen, chest, and
genitals
A sex organ (or reproductive organ) is any part of an animal or plant that is involved in sexual reproduction. The reproductive organs together constitute the reproductive system. In animals, the testis in the male, and the ovary in the female, a ...
. They are
granuloma
A granuloma is an aggregation of macrophages that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate. Such substances include infectious ...
tous and itchy, and may be ulcerated or
fistula
A fistula (plural: fistulas or fistulae ; from Latin ''fistula'', "tube, pipe") in anatomy is an abnormal connection between two hollow spaces (technically, two epithelialized surfaces), such as blood vessels, intestines, or other hollow or ...
ted. The lesions often contain yellow, firm masses of dead tissue known as 'kunkers'.
It is possible with chronic infection for the disease to spread to underlying bone.
Dogs
Pythiosis of the skin in dogs is rare, and appears as
ulcerated
An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...
lumps. Primary infection can also occur in the bones and lungs. Dogs with the gastrointestinal form of pythiosis have severe thickening of one or more portions of the gastrointestinal tract that may include the stomach, small intestine, colon, rectum, or in rare cases, even the esophagus. The resulting pathology results in anorexia, vomiting, diarrhea (sometimes bloody), and abdominal straining. Extensive weight loss may be evident.
Humans
In humans, it can cause
arteritis
Arteritis is the inflammation of the walls of arteries, usually as a result of infection or autoimmune response. Arteritis, a complex disorder, is still not entirely understood. Arteritis may be distinguished by its different types, based on the o ...
,
keratitis
Keratitis is a condition in which the eye's cornea, the clear dome on the front surface of the eye, becomes inflamed. The condition is often marked by moderate to intense pain and usually involves any of the following symptoms: pain, impaired e ...
, and periorbital cellulitis.
This has previously been thought to be a rare disease with only 28 cases reported in the literature up to 1996.
However, keratitis due to Pythium may be more common than previously thought, accounting for a proportion of cases that were due to unidentified pathogens. Although this disease was first reported in 1884
the species infecting humans - ''Pythium insidiosum'' - was only formally recognised in 1987.
Diagnosis can be difficult in part because of a lack of awareness of the disease.
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.
The most probable origin of the organism seems to be in Asia.
Most human cases have been reported in Thailand, although cases have been reported elsewhere. In humans, the four forms of the disease are: subcutaneous, disseminated, ocular, and vascular.
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
Enucleation is the removal of the eye that leaves the eye muscles and remaining orbital contents intact. This type of ocular surgery is indicated for a number of ocular tumors, in eyes that have sustained severe trauma, and in eyes that are other ...
.
The other forms of the disease require a pre-existing medical condition, usually associated with
thalassemic hemoglobinopathy.
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.
A recently published review lists nine cases of vascular pythiosis with five survivors receiving surgery with free margins and all except one requiring amputation. The same review lists nine cases of ocular pythiosis with five patients requiring enucnleation of the infected eye and four patients requiring a
corneal transplant
Corneal transplantation, also known as corneal grafting, is a surgical procedure where a damaged or diseased cornea is replaced by donated corneal tissue (the graft). When the entire cornea is replaced it is known as penetrating keratoplasty ...
.
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
The perineum in humans is the space between the anus and scrotum in the male, or between the anus and the vulva in the female. The perineum is the region of the body between the pubic symphysis (pubic arch) and the coccyx (tail bone), includi ...
, and at the base of the tail.
Lesions may also develop in the
nasopharynx
The pharynx (plural: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the oesophagus and trachea (the tubes going down to the stomach and the lungs). It is found in vertebrates and invertebrates, though its struct ...
.
Rabbits are susceptible to pythiosis and 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 bacterium, virus, nor fungus, routine tests often fail to diagnose it. In cytology and histology, the organism does not stain using
Giemsa
Giemsa stain (), named after German chemist and bacteriologist Gustav Giemsa, is a nucleic acid stain used in cytogenetics and for the histopathological diagnosis of malaria and other parasites.
Uses
It is specific for the phosphate groups of ...
, H&E, or Diff-Quick, but the hyphae are outlined by surrounding tissue.
GMS staining is required to identify the hyphae in slides, and highlights the lack of septation which helps distinguish the organism from fungal hyphae. Granulomatous inflammation with numerous eosinophils is suggestive that the hyphae are oomycetes rather than fungi, which are less likely to attract eosinophils. The symptoms are usually nonspecific and the disease may not be included in a differential diagnosis in human medicine, though it is familiar to veterinarians.
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
The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presence ...
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.
Aggressive surgical resection is the treatment of choice for pythiosis. 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 reappear. So, surgery is often followed by other treatments.
An immunotherapy product derived from antigens of ''P. insidiosum'' has been used successfully to treat pythiosis.
[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.]
Case reports indicate the use of the following chemotherapy treatments with varying success:
potassium iodide
Potassium iodide is a chemical compound, medication, and dietary supplement. It is a medication used for treating hyperthyroidism, in radiation emergencies, and for protecting the thyroid gland when certain types of radiopharmaceuticals are us ...
,
amphotericin B
Amphotericin B is an antifungal medication used for serious fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, and cryptococcosis. Fo ...
,
terbinafine
Terbinafine, sold under the brand name Lamisil among others, is an antifungal medication used to treat pityriasis versicolor, fungal nail infections, and ringworm including jock itch and athlete's foot. It is either taken by mouth or applied to ...
,
[Grooters AM. Pythiosis and Lagenidiosis. In: Bonagura, ed. Kirk’s Current Veterinary Therapy XIV. Saunders Elsevier, St. Louis, MO, 2008; 1268-1271.] itraconazole
Itraconazole, sometimes abbreviated ITZ, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, blastomycosis, coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis. It may be given by mouth ...
,
fluconazole
Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidiodomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis versicolor. It is also used to prevent ...
,
ketoconazole
Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen and antifungal medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous candid ...
,
natamycin
Natamycin, also known as pimaricin, is an antifungal medication used to treat fungal infections around the eye. This includes infections of the eyelids, conjunctiva, and cornea. It is used as eyedrops. Natamycin is also used in the food indust ...
,
posaconazole
Posaconazole, sold under the brand name Noxafil among others, is a triazole antifungal medication.
It was approved for medical use in the United States in September 2006, and is available as a generic medication.
Medical uses
Posaconazole is u ...
,
voriconazole
Voriconazole, sold under the brand name Vfend among others, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, candidiasis, coccidioidomycosis, histoplasmosis, penicilliosis, and infections by '' ...
,
prednisone
Prednisone is a glucocorticoid medication mostly used to immunosuppressive drug, suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium ...
,
flucytosine
Flucytosine, also known as 5-fluorocytosine (5-FC), is an antifungal medication. It is specifically used, together with amphotericin B, for serious ''Candida'' infections and cryptococcosis. It may be used by itself or with other antifungals for ...
,
and liposomal
nystatin
Nystatin, sold under the brandname Mycostatin among others, is an antifungal medication. It is used to treat '' Candida'' infections of the skin including diaper rash, thrush, esophageal candidiasis, and vaginal yeast infections. It may also be ...
.
References
{{reflist, 2
Dog diseases
Horse diseases
Pythium