MOBILE VIEW  | 

PLANTS-PROTOTHECA

Classification   |    Detailed evidence-based information

Therapeutic Toxic Class

    A) Prototheca is a ubiquitous, aerobic, achlorophyllic saprophytic algae. It produces rare, local, cutaneous or systemic infections (Iaccoviello et al, 1992; (Boyd et al, 1995).

Specific Substances

    A) CONSTITUENTS OF THE GROUP
    1) Prototheca
    2) P. moriformis
    3) P. portoricensis
    4) P. segbwema
    5) P. ciferii
    6) P. ubrizsyi
    7) P. stagnora
    8) P. wickerhamii
    9) P. zopfi (caused the most reports of disease)
    SYNONYMS
    1) Prototheca
    2) P. moriformis
    3) P. portoricensis
    4) P. segbwema
    5) P. ciferii
    6) P. ubrizsyi
    7) P. stagnora
    8) P. wickerhamii
    9) P. zopfi (caused the most reports of disease)

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Protothecosis is an infection caused by algae of the Prototheca genus. The most common sites of infection is the skin and the bursa; systemic infection has also been reported. Most infections cause inflammation, blisters, ulcers of the skin, but infections of the subcutaneous tissues, bursal sacs, abdomen, peritoneum, indwelling catheters, nasopharyngeal area, and lymph nodes have also been observed.
    B) Up to 50% of patients who develop protothecosis have some degree of immunocompromise. Risk factors include: kidney transplantation, soft tissue or hematologic malignancy, diabetes mellitus, or glucocorticoid administration.
    0.2.6) RESPIRATORY
    A) A case of Protocethosis causing nasopharyngeal ulceration and a neck mass in an intubated patient have been described.
    0.2.8) GASTROINTESTINAL
    A) Intestinal protothecosis has been observed. Diarrhea was reported in a patient with systemic protothecosis and subsequent liver damage. There have been cases of peritonitis complicating chronic ambulatory peritoneal dialysis (CAPD).
    0.2.9) HEPATIC
    A) Multiple lesions of the liver, hepatomegaly, and elevated liver transaminases have been described. Sclerosing cholangitis and a gall bladder mass have been reported in one patient.
    0.2.13) HEMATOLOGIC
    A) Eosinophilia may be observed.
    0.2.14) DERMATOLOGIC
    A) Prototheca may cause dermal infections after traumatic inoculation of contaminated water, and postoperative incisions, but have also been reported in patients with no obvious compromise in dermal integrity. These infections usually mimic other bacterial or viral infections. Cutaneous infections do not disseminate systemically.
    B) Lesions have been described as being: papulonodular, ulcerated, extensive granulomatous eruptions, indurated, scaling papules in a centrifugal pattern, plaques, and vesicles grouped in an erythomatous base. Eczematous and cellulitis-like lesions may also develop.
    0.2.15) MUSCULOSKELETAL
    A) Individual case reports (one each) of Prototheca infection manifested as olecranon bursitis and tenosynovitis have occurred.
    0.2.19) IMMUNOLOGIC
    A) Many immune system abnormalities include: neutrophil abnormalities, decreased natural killer cell activity, changes in immunoglobulin levels, and an elevated erythrocyte sedimentation rate (ESR) have been described. Lymphadenitis has also been reported.

Laboratory Monitoring

    A) Identification of the organism is made via examination of cultures. Histologic evaluation of infected tissue may reveal the presence of the organism.

Treatment Overview

    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) Surgical excision/drainage of the wound and/or removal of the nidus of infection (catheters) have been useful for localized infections.
    2) Amphotericin B is the most commonly used drug, however, oral antifungals such as ketoconazole or fluconazole have also been used. Most antibiotics are not effective for treating these infections, however, tetracycline may provide some synergistic activity when given with amphotericin.
    3) There have been few treatments that have successfully altered the course of cutaneous infection.
    4) Olecranon bursitis has responded to surgical intervention.

Range Of Toxicity

    A) Cases generally occur after exposure of a traumatized area to contaminated water.

Summary Of Exposure

    A) Protothecosis is an infection caused by algae of the Prototheca genus. The most common sites of infection is the skin and the bursa; systemic infection has also been reported. Most infections cause inflammation, blisters, ulcers of the skin, but infections of the subcutaneous tissues, bursal sacs, abdomen, peritoneum, indwelling catheters, nasopharyngeal area, and lymph nodes have also been observed.
    B) Up to 50% of patients who develop protothecosis have some degree of immunocompromise. Risk factors include: kidney transplantation, soft tissue or hematologic malignancy, diabetes mellitus, or glucocorticoid administration.

Respiratory

    3.6.1) SUMMARY
    A) A case of Protocethosis causing nasopharyngeal ulceration and a neck mass in an intubated patient have been described.
    3.6.2) CLINICAL EFFECTS
    A) DISORDER OF RESPIRATORY SYSTEM
    1) A case of Protocethosis causing nasopharyngeal ulceration and a neck mass in an intubated patient have been described (Iacoviello et al, 1992).

Gastrointestinal

    3.8.1) SUMMARY
    A) Intestinal protothecosis has been observed. Diarrhea was reported in a patient with systemic protothecosis and subsequent liver damage. There have been cases of peritonitis complicating chronic ambulatory peritoneal dialysis (CAPD).
    3.8.2) CLINICAL EFFECTS
    A) DIARRHEA
    1) Diarrhea and anorexia was noted in a patient with systemic Prototheca infection and liver damage (Cox et al, 1974). Prototheca was thought to be the causative organism in 2 patients with diarrheal disease in which the organism was isolated (Iacoviello et al, 1995).
    B) DRUG-INDUCED GASTROINTESTINAL DISTURBANCE
    1) Intestinal protothecosis has been reported in Puerto Rico (Ashford et al, 1930).
    C) PERITONITIS
    1) Three patients with chronic ambulatory peritoneal dialysis (CAPD) developed peritonitis; the source of the contamination was thought to be the dialysis equipment (Iacoviello et al, 1995; (Boyd et al, 1995).

Hepatic

    3.9.1) SUMMARY
    A) Multiple lesions of the liver, hepatomegaly, and elevated liver transaminases have been described. Sclerosing cholangitis and a gall bladder mass have been reported in one patient.
    3.9.2) CLINICAL EFFECTS
    A) TOXIC HEPATITIS
    1) Multiple mass lesions of the liver caused by Prototheca produced anemia, jaundice, and an enlarged liver (Cox et al, 1974). Multiple palpable nodules on the liver, with elevated liver transaminases have been described (Chan et al, 1990).
    B) GALLBLADDER FINDING
    1) Severe granulomatous inflammation and palpable nodules were observed in the gall bladder in one case (Chan et al, 1990).

Hematologic

    3.13.1) SUMMARY
    A) Eosinophilia may be observed.
    3.13.2) CLINICAL EFFECTS
    A) EOSINOPHIL COUNT RAISED
    1) Eosinophilia has been observed in several cases (Mars et al, 1971) Migaki et al, 1969; (Davies et al, 1964; Cox et al, 1974).

Dermatologic

    3.14.1) SUMMARY
    A) Prototheca may cause dermal infections after traumatic inoculation of contaminated water, and postoperative incisions, but have also been reported in patients with no obvious compromise in dermal integrity. These infections usually mimic other bacterial or viral infections. Cutaneous infections do not disseminate systemically.
    B) Lesions have been described as being: papulonodular, ulcerated, extensive granulomatous eruptions, indurated, scaling papules in a centrifugal pattern, plaques, and vesicles grouped in an erythomatous base. Eczematous and cellulitis-like lesions may also develop.
    3.14.2) CLINICAL EFFECTS
    A) INFECTION OF SKIN
    1) Prototheca may cause dermal infections after traumatic inoculation of contaminated water (Goldstein et al, 1986). These infections usually mimic other bacterial or viral infections.
    2) CUTANEOUS PROTOTHECOSIS -
    a) Lesions have been described as being: papulonodular, ulcerated, extensive granulomatous eruptions, indurated, scaling papules in a centrifugal pattern, plaques, and vesicles grouped in an erythematous base. Eczematous and cellulitis-like lesions may also occur. Cutaneous infections do not disseminate systemically (Boyd et al, 1995) Wolfe et al, 1976; (Davies et al, 1964; Mars et al, 1971; Klintworth et al, 1968) Icaviello et al, 1992; (Boyd et al, 1995).

Musculoskeletal

    3.15.1) SUMMARY
    A) Individual case reports (one each) of Prototheca infection manifested as olecranon bursitis and tenosynovitis have occurred.
    3.15.2) CLINICAL EFFECTS
    A) SYNOVITIS
    1) BURSITIS - At least 16 cases of Prototheca infection manifested as olecranon bursitis have been reported. Inoculation was due to trauma, contamination of a preexisting wound or in patients with chronic bursitis. Most of the patients had some degree of immunocompromise (Iacoviello et al, 1992). In cases where cultures were not positive, organisms were identified in histological sections (Tindall & Felter, 1971; Nosanchuk & Greenberg, 1973).
    2) TENOSYNOVITIS in a patient following surgery for carpal tunnel syndrome has been described (Moyer et al, 1990).

Immunologic

    3.19.1) SUMMARY
    A) Many immune system abnormalities include: neutrophil abnormalities, decreased natural killer cell activity, changes in immunoglobulin levels, and an elevated erythrocyte sedimentation rate (ESR) have been described. Lymphadenitis has also been reported.
    3.19.2) CLINICAL EFFECTS
    A) ESR RAISED
    1) Erythrocyte sedimentation rate (ESR) was elevated in two immunocompromised patients with systemic protocotheosis (Cox et al, 1974) Chan, 1990).
    B) INCREASED IMMUNOGLOBULIN
    1) Immunoglobulins may be increased, decreased or unchanged (Cox et al, 1974) Chan, 1990).
    C) CELLULAR IMMUNE DEFECT
    1) Natural killer cell activity was depressed in one patient with cutaneous protocthecosis, thought to be induced by the organism itself (Tyring et al, 1989).
    2) Neutrophil abnormalities have been reported, including the inability of the neutrophils to kill the organism (Boyd et al, 1995)
    3) Femoral lymphadenitis was reported in a severe protothecosis of the foot (Davies et al, 1964).

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Identification of the organism is made via examination of cultures. Histologic evaluation of infected tissue may reveal the presence of the organism.
    4.1.2) SERUM/BLOOD
    A) Serum antibodies against prototheca are produced and can be quantified, but may not be readily available.
    B) Elevated liver transaminase levels may be seen in cases of disseminated infection.
    4.1.4) OTHER
    A) OTHER
    1) Prototheca species endosporulating cells can be identified in PAS-stained tissue specimens, but non-sporulating cells may resemble cells of Rhinosporidium seeberi, Pneumosystis carinii, Blastomyces dermatitidis, Crytococcus neoformans, Loboa loboi, Coccidioides immitis, Histoplasma dubosii, or Paracoccidioides brasiliensis.
    2) Histologic examination of tissues reveals variable findings: granulomatous inflammation with necrosis; giant cells; a mixed infiltrate with plasma cells, lymphocytes and histiocytes; hyperkeratosis; focal parakeratosis; pseudoepithialization; hyperplastic lymphoid tissue; a dense chronic inflammation and presence of the organism (Boyd et al, 1995; Iacoviello et al, 1992).
    3) Minimum inhibitory concentrations and algicidal concentrations of various antimicrobial and antifungal agents are reviewed in Iacoviello et al, 1992.

Methods

    A) OTHER
    1) Prototheca species endosporulating cells can be identified in PAS-stained tissue specimens, but non-sporulating cells may resemble cells of Rhinosporidium seeber; Pneumocystis carinii, Blastomyces dermatitidis, Crytococcus neoformans, Loboa loboi, Coccidioides immitis, Histoplasma dubosii, or Paracoccidioides brasiliensis (Wolfe et al, 1976; (Arnold & Ahern, 1972; Iacoviello et al, 1992).
    2) Most culture mediums will support Prototheca growth, but cycloheximide will suppress its growth. When grown on Sauouraud agar, the colonies are yeast-like, smooth, and creamy (Wolfe et al, 1976).
    3) Species identification has been done via an indirect immunofluorescence technique (Sudman & Kaplan, 1973) or by differentiation by cell size, cell shape, colony shape, and carbohydrate assimilation testing (Wolfe et al, 1976; (Iacoviello et al, 1992).

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.5) DISPOSITION/DERMAL EXPOSURE
    6.3.5.3) CONSULT CRITERIA/DERMAL
    A) Some lesions appear similar to bacterial pyoderma. This illness should be ruled out (Wolfe et al, 1976).

Monitoring

    A) Identification of the organism is made via examination of cultures. Histologic evaluation of infected tissue may reveal the presence of the organism.

Dermal Exposure

    6.9.2) TREATMENT
    A) SURGICAL PROCEDURE
    1) SURGICAL EXCISION of the lesion if amenable, or debridement should be performed to remove infected tissue. Drainage of infected bursa and removal of the infected catheter should be performed to eliminate the nidus of infection. Bursectomy is frequently curative (Boyd et al, 1995; Iacoviello et al, 1992; Davies et al, 1964; Tindall & Felter, 1971).
    B) ANTIBIOTIC
    1) AMPHOTERICIN
    a) AMPHOTERICIN B has been the most successful therapy used for cutaneous and systemic infections (S Sweetman , 2001). It has been administered intravenously, topically, and in one case intralesionally into the bursa (Cochran, 1986) (Tyring et al, 1989; Cox et al, 1974; Mayhall et al, 1976). Intraperitoneal administration should be avoided in cases of peritonitis because peritoneal inflammation, pain, and scarring may occur (Gibb et al, 1991). The length of treatment varies from 6 weeks to 3 months.
    b) In a few cases, combining tetracycline (250 to 500 mg 4 times a day) with amphotericin B has been synergistic (Venezio et al, 1982; McAnally & Parry, 1985; Tyring et al, 1989).
    c) IMPORTANT NOTE: Doses used in case reports are variable. Standard dosing for age and weight should be used (Boyd et al, 1995; Iacoviello et al, 1992). In addition, Amphotericin B has numerous formulations and most are not interchangeable and have different dosing guidelines.
    d) INTRAVENOUS
    1) TEST DOSE: Prior to starting therapy, an intravenous test dose of 1 mg dissolved in 20 mL of 5% dextrose by slow infusion (over 10 to 30 minutes) is recommended by some sources in an attempt to avoid anaphylactic reactions. Monitor vital signs every 30 minutes for 4 hours with the amount of the next dose determined by the severity of reaction (Prod Info Fungizone(R), amphotericin injection, suspension, 1999; Hermans & Keys, 1983; Graybill & Craven, 1983; Kucers & Bennett, 1979).
    2) FUNGAL INFECTIONS: Usual dosage range in patients with normal renal function for the treatment of fungal infections is 0.25 to 1 mg/kg daily; the total daily dose should NOT exceed the maximum of 1.5 mg/kg daily. Alternate day therapy of 1.5 mg/kg administered every other day has also been used. Amphotericin B (0.1 mg/mL) should be infused over 2 to 6 hours. Total doses of up to 4 grams have been given to adults (Prod Info Fungizone(R), amphotericin injection, suspension, 1999).
    e) INTRAVENOUS FAT EMULSION PREPARATION
    1) AMPHOTERICIN B diluted with FAT EMULSION preparations is thought to reduce the incidence of adverse effects such as chills and reduce the risk of renal toxicity, as well as improve amphotericin B intolerance (Anderson & Clark, 1995; Caillot et al, 1994; Vita, 1994; Chavanet et al, 1992).
    2) INTRAVENOUS TEST DOSE
    a) An intravenous test dose of 1 mg dissolved in 20 mL of 5% dextrose by slow infusion (over 10 to 30 minutes) is recommended by some sources in an attempt to avoid anaphylactic reactions. Monitor vital signs every 30 minutes for 4 hours with the amount of the next dose determined by the severity of reaction (Prod Info Fungizone(R), amphotericin injection, suspension, 1999; Kucers & Bennett, 1979; Hermans & Keys, 1983; Graybill & Craven, 1983).
    b) LIPOSOMAL AMPHOTERICIN B/FUNGAL INFECTIONS SYSTEMIC: The manufacturer recommends 3 to 5 mg/kg/day infused over 120 minutes for adults and children for the treatment of systemic fungal infections due to Aspergillus, Candida, and Cryptococcus species (Prod Info Ambisome(R), 1997).
    C) IMIDAZOLE
    1) IMIDAZOLE ANTIFUNGALS such as ketoconazole, fluconazole, and itraconazole have been used with success in selected cases (Boyd et al, 1995; Iacoviello et al, 1992; Gibb et al, 1991) (Moyer et al, 1991)(Pelgam et al, 1983)(McAnally & Parry, 1985) (Tseng-tong et al, 1987). These drugs have been used as an alternative to amphotericin B in patients unable to tolerate therapy with amphotericin B.
    2) KETOCONAZOLE: ADULT: 100 to 400 m daily, depending upon the illness.
    3) FLUCONAZOLE
    a) ADULT: The dose is variable by infectious agent. In general, the recommended dose is 100 mg once daily, but doses up to 400 mg daily have been used in severe systemic infections (Prod Info Diflucan(R), 1998).
    4) ITRACONAZOLE
    a) ADULT: The dose is variable by infectious agent. In general, the recommended dose is 200 mg once daily. If no improvement, the dose may be increased in 100 mg increments to a maximum daily dose of 400 mg given in 2 divided doses.
    1) In life-threatening situations, a loading dose should be used whether given as oral capsules or intravenously.
    a) INTRAVENOUS: The recommended intravenous dose is 200 mg bid for four consecutive doses, followed by 200 mg once daily. Each intravenous dose should be infused over 1 hour. The safety and efficacy for greater than 14 days is not known (Prod Info Sporanox(R), capsules, Itraconazole, 2000).
    b) ORAL/CAPSULES: Although clinical studies have not provided for a loading dose, it is recommended, based on pharmacokinetic data, that a loading dose of 200 mg (2 capsules) three times daily (600 mg/day) be given for the first 3 days of treatment. Treatment should be continued for a minimum of three months and until clinical parameters and laboratory tests indicate that the active fungal infection has subsided (Prod Info Sporanox(R), capsules, Itraconazole, 2000).
    c) PEDIATRIC - Safety and efficacy in pediatric patients have not been established (Prod Info Sporanox(R), capsules, Itraconazole, 2000).
    2) A small number of patients from 3 to 16 years of age were administered 100 mg/day to treat systemic fungal infections. No serious adverse effects were reported (Prod Info Sporanox(R), capsules, Itraconazole, 2000).
    D) CONTRAINDICATED TREATMENT
    1) Failed treatments have included: Topically administered potassium permanganate, cupric sulfate, and antibiotics such as erythromycin. Although antibiotics often do NOT work, one case of blister-like lesions of the chest cleared after treatment with polymyxin B, bacitracin, and neomycin ointment (Wolfe et al, 1976)(Goldstein et al, 1986).
    2) Systemic treatments: Pentamidine isethionate, emetine hydrochloride, griseofulvin, penicillin, and x-ray treatment (Wolfe et al, 1976).

Summary

    A) Cases generally occur after exposure of a traumatized area to contaminated water.

Clinical Effects

    11.1.2) BOVINE/CATTLE
    A) Protothecosis has been recognized as a cause of bovine mastitis (Lerche, 1952; Migaki et al, 1969; Ainsworth & Austwick, 1965).
    11.1.3) CANINE/DOG
    A) Disseminated illness of the liver, brain, eyes, and kidneys have been seen with Prototheca infections in dogs (Povey et al, 1969; Van Kruiningen, 1970; Van Kruiningen et al, 1969).

General Bibliography

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    7) Chan JC, Jeffers LJ, & Gould EW: Visceral Protothecosis mimicking sclerosing cholangitis in an immunocompetent host: successful antifungal therapy. Rev Infect Dis 1990; 12:802-807.
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    23) Moyer RA, Bush DC, & Dennehy JJ: Prototheca wickerhamii tenosynovitis. J Rheumatol 1990; 17:701-704.
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    25) Povey RC, Austwick PKC, & Pearson H: A case of protothecosis in a dog. Pathol Vet 1969; 6:396-402.
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    30) Tindall JP & Felter BF: Infections caused by achloric algae (protothecosis). Arch Dermatol 1971; 104:490-500.
    31) Tyring SK, Lee PC, & Walsh P: Papular protothecosis of the chest: Immunologic evaluation and treatment with a combination of oral tetracycline and topical amphotericin B. Arch Dermatol 1989; 125:1249-1252.
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