JOURNAL OF CLINICAL MICROBIOLOGY, Apr. 2005, p.

14951504
0095-1137/05/$08.000 doi:10.1128/JCM.43.4.14951504.2005
Copyright 2005, American Society for Microbiology. All Rights Reserved.

Vol. 43, No. 4

MINIREVIEW
Unusual Fungal and Pseudofungal Infections of Humans
M. A. Pfaller1,2* and D. J. Diekema1,3
Departments of Pathology1 and Medicine,3 College of Medicine, and
Department of Epidemiology, College of Public Health,2
University of Iowa, Iowa City, Iowa
spherules that measure 200 to 400 m or more in diameter
(Table 1). The walls of the spherule are refractile and when
stained with hematoxylin-eosin (H&E) appear to be comprised
of two layers: a narrow, outer, eosinophilic layer containing
periodic fenestrations and a broad, hyaline, inner layer composed predominantly of chitin (Fig. 1A) (27, 102). The conidial
walls stain with Gomoris methenamine silver (GMS), periodic
acid-Schiff (PAS), and the Gridley fungus stains but not with
Mayers mucicarmine (Table 2). In human lung tissue, the
adiaconidia are usually empty but may contain small eosinophilic globules along the inner surface of the walls (102).
Human adiaspiromycosis is uncommon (27), but it has been
reported from South and Central America, Israel, Europe, and
the United States (24, 27, 66, 95, 102). Both pulmonary and
disseminated adiaspiromycosis have been found in patients
with AIDS (24, 95). Rodents may serve as a zoonotic reservoir
for the disease, although the fungus causing disease in rodents,
Emmonsia parva (formerly Chrysosporium parvum var. parvum), rarely infects humans (24, 26, 72, 86). E. crescens is
found in nature predominantly in temperate zones, and the
likely mode of human infection is accidental inhalation of
fungal conidia aerosolized from contaminated soil.
Three forms of human adiaspiromycosis are recognized: (i)
solitary granuloma, (ii) localized granulomatous disease, and
(iii) diffuse, disseminated granulomatous disease (27, 95). The
severity of the disease depends upon the number of spores
inhaled (27). Most cases of documented adiaspiromycosis have
been asymptomatic. In the case of a limited inoculum, the
disease remains localized, and pulmonary nodules may be detected radiographically or incidentally at autopsy or in surgical
specimens of lung removed for another reason (95). Patients
with the disseminated granulomatous form of pulmonary adiaspiromycosis may experience fever, cough, and progressive
dyspnea due to compression and displacement of distal airways
and alveolar parenchyma by the expanding granulomas (27,
95). Fungal replication in the lungs does not occur; however,
other organs may be involved (rarely), including the skin (42),
peritoneum (23), and bone (24). Extrapulmonary dissemination causing extensive osteomyelitis and bone marrow involvement was found in a patient with AIDS (24).
Adiaspiromycosis is diagnosed by histopathologic examination of affected tissue and identification of the characteristic
adiaconidia (27, 95, 102). The organism is not easily cultured
and is not readily observed in sputum, and serological and skin
tests are unreliable and not widely available (27, 95). Histologically, each adiaconidium is surrounded by an epithelioid

The spectrum of mycotic disease continues to expand well

beyond the familiar entities of candidiasis and aspergillosis (73,
99). The field of medical mycology has become a challenging
study of infections caused by a wide and taxonomically diverse
array of opportunistic fungi (73). Previously we reviewed some
of the less-common emerging opportunistic fungal pathogens with an emphasis on resistance to new and established
antifungal therapies (73). In this article, we discuss several
exotic and unusual infections that historically have been considered fungal or pseudofungal infections based on their clinical and histopathologic presentation but have been difficult to
classify because they grow poorly or not at all on artificial
media. In one instance, recent molecular evidence has indicated that an organism previously considered to be a fungus
(Rhinosporidium seeberi) is in fact a protistan parasite (29, 37).
We also discuss a nonreplicative pulmonary infection (adiaspiromycosis), two subcutaneous mycoses (entomophthoromycosis and lobomycosis), two algal infections (chlorellosis and protothecosis), and an infection due to the oomycete Pythium
insidiosum. The diagnosis of these rare infections is based
largely on detection of characteristic structures observed on
histopathologic examination of tissue. A listing of the infections, the etiologic agents, and the typical morphology in tissue
is provided in Table 1 and Fig. 1 and 2.
UNUSUAL FUNGAL INFECTIONS
Adiaspiromycosis. Adiaspiromycosis (also known as adiaspirosis or haplomycosis) of humans is a rare, self-limited pulmonary infection caused by inhalation of the asexual conidia of
the saprophytic soil fungus Emmonsia crescens (formerly
Chrysosporium parvum var. crescens) (72, 86). E. crescens grows
as a mold in nature and in culture at room temperature. The
hyphae are hyaline, septate, and branched, with small (2 to
4 m) aleurioconidia borne on conidiophores arising at
right angles to the vegetative hyphae. When introduced into
the lungs or upon incubation in vitro at 40C, the conidia
transform into spherical adiaconidia, which subsequently undergo massive enlargement but show no evidence of replication (e.g., no budding or endospore formation).
The mature adiaconidia are thick walled (20 to 70 m)

* Corresponding author. Mailing address: Medical Microbiology Division, C606 GH, Department of Pathology, University of Iowa College of Medicine, Iowa City, IA 52242. Phone: (319) 384-9566. Fax:
(319) 356-4916. E-mail: michael-pfaller@uiowa.edu.
1495

1496

MINIREVIEW

J. CLIN. MICROBIOL.

TABLE 1. Morphologic features of fungal and pseudofungal infections of unusual or uncertain etiologya
Disease

Unusual fungal infections

Adiaspiromycosis

Etiologic agents(s)

Emmonsia crescens, E. parva

Entomophthoromycosis

Conidiobolus coronatus, C.
incongruous, Basidiobolus
ranarum

Lobomycosis

Lacazia loboi (Loboa loboi)

Unusual pseudofungal infections

Chlorellosis

Chlorella spp. (chlorophyllous

green algae)

Protothecosis

Prototheca wickerhamii, P. zopfii

(achlorophyllous green algae)

Pythiosis insidiosi

Pythium insidiosum (not a true

fungus; belongs to class
Oomycetes)

Rhinosporidiosis

Rhinosporidium seeberi (aquatic

protistan parasite of the
Mesomycetozoan clade)

Typical morphology in tissue

Large adiaconidia, 200400-m diameter

with thick (2070-m) walls; see Fig.
1A
Short, poorly stained hyphal fragments,
625-m diameter, nonparallel sides,
pausi-septate, random branches; see
Fig. 1B
Spherical budding yeasts, 512-m
diameter, that form chains of 610
cells connected by tube-like structures;
secondary budding may be present;
see Fig. 1C and D
Unicellular, endosporulating round
organisms, 415-m diameter,
containing multiple cytoplasmic
granules (chloroplasts); see Fig. 2A;
lesions are green pigmented
Spherical, oval, or polyhedral spherules,
330-m diameter, containing 220
endospores when mature; morula
form; see Fig. 2B
Hyphae and short hyphal fragments that
are hyaline, thin walled, pausi-septate,
irregularly branched, 57 m wide,
nonparallel contours; angioinvasive;
see Fig. 2C
Large sporangia, 100350-m diameter
with thin walls (35 m) that enclose
numerous endospores, 510-m
diameter, with a zonal distribution;
see Fig. 2D

Usual host reaction

Granulomatous, fibrotic,
and noncaseating
Eosinophilic abscesses and
granulation tissue,
Splendori-Hoeppli
material around hyphae
Granulomatous; asteroid
bodies in giant cells
present in 25% of cases

Pyogranulomatous

Variable; no reaction to
granulomatous
Granulomatous, necrotizing,
suppurative arteritis

Nonspecific chronic
inflammatory or
granulomatous

Copyright 1987 American Society of Clinial Pathologists. Adapted from reference 14 with permission. Some data are from reference 15.

and giant-cell granulomatous response, which is further encompassed by a dense capsule of fibrous tissue (Fig. 1A) (102).
Importantly, all of the granulomas are at similar stages of
development, reflecting a one-time exposure without subsequent replication within the lung.
Adiaconidia should not be confused with the spherules of
Coccidioides immitis or Rhinosporidium seeberi, two other organisms that produce large spherules in tissue (Table 2) (102).
In contrast to those of C. immitis, the adiaconidia of E. crescens
are much larger, have a thicker wall, and do not contain endospores (Fig. 1A). The sporangia of R. seeberi are distinguished from those of both C. immitis and E. crescens by the
zonation of the internal sporangiospores and by the presence
of distinctive eosinophilic globules contained within the mature sporangiospores (Table 2 and Fig. 2D). No other fungus
of medical importance has walls as thick as those of the adiaconidia of E. crescens.
Human pulmonary adiaspiromycosis is self-limited, and specific antifungal therapy is usually not necessary (27). Surgical
intervention with limited resection may be required if the condition progresses. The organism appears to be susceptible to
azole antifungal agents (68), and treatment with ketoconazole
(55, 84), fluconazole (95), and amphotericin B (24, 66, 95) has
been used with success in severe or progressive infection in
immunocompromised individuals.

Entomophthoromycosis. Entomophthoromycosis is caused

by zygomycetes of the order Entomophthorales: Conidiobolus
coronatus, Conidiobolus incongruous, and Basidiobolus ranarum (previously Basidiobolus haptosporus). These fungi cause a
chronic subcutaneous form of zygomycosis that occurs sporadically as a result of traumatic implantation of the fungus that is
present in plant debris in tropical environments. The predilection for host and anatomic site of infection is species specific:
B. ranarum causes subcutaneous infection of the proximal
limbs in children, whereas Conidiobolus spp. infection is localized to the facial area predominately in adults (14, 31, 78, 96).
The appearance of the agents of entomophthoromycosis in
tissue differs from that of the mucoraceous zygomycetes.
The hyphal elements are sparse, often fragmentary, and surrounded by intensely eosinophilic Splendori-Hoeppli material
(Fig. 1B) (14). The inflammatory response is granulomatous,
containing eosinophils, lymphocytes, plasma cells and macrophages (Table 1). Septations within the hyphae are infrequent;
however, they are more prominent than those seen with the
Mucorales. In contrast to those of the Mucorales, the hyphae
of the Entomophthorales are rarely angioinvasive.
Both types of entomophthoromycosis are seen most commonly in Africa and to a lesser extent in India (16, 31, 62, 78,
96). Infection due to Basidiobolus spp. has also been reported
from the Middle East, Asia, and Europe (62, 78, 96), whereas

VOL. 43, 2005

MINIREVIEW

1497

FIG. 1. Examples of unusual fungal infections. (A) Pulmonary adiaspiromycosis. The hematoxylin-eosin stain defines three layers in the wall
of the adiaconidium. Each adioconidium has evoked a fibrogranulomatous response. Magnification, 30.4. Reprinted from reference 15 with
permission of the publisher. (B) Entomophthoromycosis. The hematoxylin- and eosin-stained section of tissue shows broad septate hyphae
surrounded by an eosinophilic sheath (Splenodore-Hoeppli phenomenon). Copyright 1987 American Society of Clinical Pathologists. Reprinted
from reference 14 with permission. Panels C and D show lobomycosis caused by Lacazia loboi, which forms a single chain with individual cells
joined by tubelike bridges. (C) Organism revealed by Gridley staining. Magnification, 304. Copyright 1987 American Society of Clinical
Pathologists. Reprinted from reference 14 with permission. (D) Organism revealed by GMS. Reproduced from the DoctorFungus website
(www.doctorfungus.org) with permission.

that due to Conidiobolus spp. has been reported from Latin

America as well (16, 31). Cases of basidiobolomycosis and
conidiobolomycosis in the United States are extremely rare
and appear to be more acutely invasive than those seen more
commonly in the tropics (25, 40, 53, 91, 97, 98).
Both basidiobolomycosis and conidiobolomycosis are rare
diseases without known predisposing factors such as acidosis or
immunodeficiency. Infection due to B. ranarum is thought to
occur following traumatic implantation of the fungus into the
subcutaneous tissues of the thighs, buttocks, and trunk. This
form of zygomycosis occurs mainly in children (80% under the
age of 20 years) with a male/female ratio of 3:1 (6, 19, 32).
Infections with Conidiobolus spp. occur following inhalation of
the fungal spores, which then invade the tissues of the nasal
cavity, the paranasal sinuses and facial soft tissues. There is a
10:1 male/female ratio, and the disease is seen predominantly
in young adults (31, 78). Infection among children is rare.
Basidiobolomycosis is characterized by disk-shaped rubbery,

movable masses that may be quite large and are localized to

the shoulder, pelvis, hips, and thighs (14, 32). The masses may
expand locally and eventually ulcerate. Gastrointestinal basidiobolomycosis is extremely rare, with only 15 cases reported
worldwide (46, 53, 70, 101, 106, 107). Notably, all seven cases
of gastrointestinal basidiobolomycosis reported from the
United States have occurred in adults residing in Arizona.
Potential risk factors include prior ranitidine use and longer
residence in Arizona (53). This suggests ingestion and environmental exposure as important factors in this unusual mycosis.
Widespread fatal systemic dissemination was recently reported
for a previously healthy woman, with involvement of brain,
pancreas, kidney, stomach, lung, and spleen (5).
Infection with Conidiobolus spp. is often confined to the
rhinofacial area and usually does not come to medical attention until there is noticeable swelling of the upper lip or face
(16, 31). The swelling is firm and painless and may progress
slowly to involve the nasal bridge and the upper and lower face,

1498

MINIREVIEW

J. CLIN. MICROBIOL.

FIG. 2. Examples of unusual pseudofungal infections. (A) Chlorellosis. Chlorella sp. stained by GMS and showing intracellular chloroplasts and
doubly contoured cell wall. Reprinted from reference 15 with permission of the publisher. (B) Protothecosis. Prototheca wickerhamii. Single and
endosporulating algal cells that are readily demonstrated with the PAS stain are shown. A classic morula form is present. Magnification, 740.
(C) Pythiosis. Pythium insidiosum invading an arterial wall. GMS reveals infrequently septate, weakly stained hyphae, and hyphal fragments
resemble those of Zygomycetes. Magnification, 118.4. Reprinted from reference 15 with permission of the publisher. (D) Rhinosporidiosis:
mature sporangium of Rhinosporidium seeberi showing the zonal arrangement of immature, maturing, and fully mature sporangiospores. Magnification, 355.2. Copyright 1987 American Society of Clinical Pathologists. Reprinted from reference 14 with permission.

including the orbit. The facial deformity can be quite impressive; however, due to the lack of angioinvasion, intracranial
extension or dissemination is rare. As with basidiobolomycosis,
cases of conidiobolomycosis originating in the United States
are rare but appear to be more acutely invasive than those seen
in the tropics (25, 40, 91, 97, 98). In particular, conidiobolomycosis in immunocompromised patients is more deeply invasive and can cause endocarditis and widespread fatal dissemination (40, 97, 98).
Entomophthoromycosis requires biopsy for diagnosis, despite the characteristic clinical features of the infections. The
histopathologic picture is the same for both organisms and is
marked by focal clusters of inflammation and typical zygomycotic hyphae often surrounded by eosinophilic Splendori-Hoeppli material (Table 1). The organisms can be cultured from
clinical material on standard mycologic medium. Cultures
should be inoculated soon after tissue procurement, since the
organisms do not survive at 4C. In contrast to the Mucora-

ceae, the Entomophthorales grow as waxy and folded colonies

consisting of hyphae with rare septae and sporophores bearing
single-celled round spores. At maturity the spores are forcibly
ejected into the surrounding environment. B. ranarum produces abundant zygospores with thick walls and a prominent
beak-like appendage.
Both types of infection may be treated with itraconazole
(30). Alternatively, potassium iodide, amphotericin B, fluconazole, or terbinafine or combinations of these drugs have been
used (28, 31, 33, 53). The role of new and investigational azoles
(e.g., posaconazole, which is active against some Mucorales) in
treatment of entomophthoromycosis is not known. Facial reconstructive surgery may be necessary in the case of conidiobolomycosis, as the extensive fibrosis remains after eradication of
the fungus. In the case of gastrointestinal basidiobolomycosis,
it is recommended that patients undergo resection of all affected bowel and debridement of other involved tissues, fol-

VOL. 43, 2005

MINIREVIEW

1499

TABLE 2. Comparative morphologic features of fungi and pseudofungal organisms that appear as large spherules in tissuea
Characteristic or value for organism
Feature
Coccidioides immitis

Rhinosporidium seeberib

Emmonsia crescensc

Diameter of spherule (m)

Thickness of spherule wall (m)
Diameter of endospores (m)
Hyphae or arthroconidia
Host reaction

20200
12
25
Rare
Necrotic granulomas

200400
2070
None
None
Fibrotic granulomas

Growth in culture
Special stain reaction
GMS
PAS
Mucicarmine

10350
35
610d
None
Mucosal polyps with acute and
chronic inflammation

Copyright 1987 American Society of Clinical Pathologists. Adapted from reference 14 with permission. Some data are from reference 15.
Not a fungus. Newly classified as an aquatic protistan parasite of the Mesomycetozoan clade.
Adiacondida.
d
Endospores arranged in a characteristic zonal distribution. Mature endospores contain distinctive eosinophilic globules.
e
Grows as a mold on agar medium. Organism not recoverable from tissue.
b
c

lowed by 3 months of antifungal therapy with itraconazole

(53).
Lobomycosis. Lobomycosis is a chronic mycosis of the skin
caused by the fungus Lacazia loboi (formerly Loboa loboi)
(89). The disease is seen primarily in the South and Central
American tropics. Natural infection occurs only in humans and
dolphins, although it has been reproduced by injecting infected
tissue into hamsters and armadillos (79). There is also one
well-documented case of experimental inoculation in a human
volunteer who developed a single lesion 3 months after intradermal injection of infected tissue (7). The organism has never
been cultured in vitro.
L. loboi is globose, thick-walled, and yeast-like in appearance (9). The cells are 6 to 12 m in diameter and have a
hyaline double refractile cell wall. The organism reproduces by
sequential budding, leading to the production of chains of cells
linked to one another by a tubular connection, or isthmus (Fig.
1C and D). Some of the cells may have secondary buds, giving
rise to branched or radiating chains of cells (9, 80). The globose budding cells of L. loboi may resemble the mariners
wheel form of Paracoccidioides brasiliensis in tissue; however,
the consistent diameter and chain-like arrangement of the
yeast cells of L. loboi distinguish it from P. brasiliensis (9). L.
loboi is usually intracellular, although extracellular forms may
be seen.
Lobomycosis is endemic in the tropical regions of Central
and South America and has been reported in central and
western Brazil, Bolivia, Colombia, Costa Rica, Ecuador, Guyana, French Guiana, Mexico, Panama, Peru, Surinam, and
Venezuela (8, 9, 80, 89). Isolated cases have been reported
from Holland (88), and a single case recently was reported in
the United States with a patient with a history of travel to
Venezuela (9).
Although a plant reservoir has not been identified, L. loboi
is believed to be a saprophyte of soil or vegetation. Lobomycosis predominates in tropical regions with thick vegetation,
such as the Amazon rain forests, and among agricultural workers, hunters, fishermen, and miners (8, 80). Cutaneous trauma
is believed to be the mode of infection.
Given the fact that lobomycosis occurs in marine and fresh-

water dolphins (17, 21, 60, 88), an aquatic habitat is likely as

well. Infection among dolphins has been reported in Florida,
the Texas coast, the Spanish-French coast, the south Brazilian
coast, and the Surinam River estuary (10, 17, 21, 60, 89).
Possible dolphin-to-human transmission has been reported for
a handler of an affected dolphin (88), but there is no evidence
of human-to-human transmission.
Lobomycosis occurs primarily in men, although it may also
be seen in women who are involved in farming and jungle
clearing. Farmers, miners, hunters, and rubber plant workers
have an increased incidence of disease (8, 80). There is no
apparent racial or ethnic predilection, and lobomycosis affects
all age groups, with the peak age of onset being 20 to 40 years
(80).
Lobomycosis is characterized by slowly developing cutaneous nodules of various sizes and shapes that tend to arise on
traumatized areas of skin, such as the face, ears, arms, legs, and
feet. Local cutaneous spread may occur through autoinoculation. The dermal lesions are polymorphic, ranging from macules, papules, keloidal nodules, and plaques to verrucous and
ulcerated lesions, all of which may be present in a single patient. The nodular keloid-like lesion is the most common (8).
The disease is characterized by a long dormancy period of
months to years, and the increase in the number and size of
lesions may progress slowly over a period of 40 to 50 years (8,
9, 80). The disease does not involve mucous membranes or
internal organs; however, it has been found to affect regional
lymph nodes in 10 to 25% of cases (3). Squamous cell carcinoma has been described developing in old scar lesions of
lobomycosis (4). There are no systemic manifestations of the
disease, and aside from occasional pruritis and hypesthesia or
anesthesia of the affected area, patients are asymptomatic (80).
Diagnosis is based on demonstrating the presence of the
characteristic yeast cells in lesion exudates or tissue sections (8,
9, 80, 89). Biopsy reveals a dispersed granulomatous infiltrate
with giant cells, macrophages, epithelioid cells, and numerous
round yeast cells in chains of 6 to 10 (Table 1 and Fig. 1C and
D) (8, 64). The epidermis is usually atrophic but may show
pseudoepitheliomatous hyperplasia or ulceration. L. loboi is

1500

MINIREVIEW

mostly intracellular within giant cells and macrophages. Fibrosis is infrequent, and there is no necrosis (8).
L. loboi stains intensely with both GMS and PAS stains. The
cell wall of L. loboi contains constitutive melanin that is readily
detectable by use of the Fontana-Masson histologic stain (89,
90). H&E stain reveals the thick doubly contoured hyaline cell
wall and one or more hematoxylinophilic nuclei (64). Asteroid
bodies in giant cells are present in approximately 25% of biopsies of lobomycosis (79).
Despite a gross appearance that resembles a keloid, microscopically the lesions of lobomycosis are not fibrotic, whereas
keloids exhibit marked fibrosis (64). Conversely, keloids lack
granulomas and fungal elements. The morphology and pattern
of budding of L. loboi are distinctive and should not be confused with that of P. brasiliensis (multiple buds, variable size,
melanin negative), Blastomyces dermatitidis and Histoplasma
capsulatum var. duboisii (no chains of cells), or Sporothrix
schenckeii and H. capsulatum var. capsulatum (both smaller, 2
to 8 m versus 5 to 12 m) (8, 64, 89, 90). These fungi will also
grow in culture, whereas L. loboi has never been cultured in
vitro (80, 89).
There is no effective medical treatment for lobomycosis,
although clofazimine has been reported to be partially effective
in some cases (8). Early lesions are managed by surgical excision with wide margins (4). More-widespread disease usually
recurs when treated surgically and does not respond to antifungal therapy due to the slow generation time of L. loboi (77).
UNUSUAL PSEUDOFUNGAL INFECTIONS
Although not caused by true fungi, the infections discussed
in this section have historically been included with the mycoses
due to their clinical and histopathologic presentations. Medical
treatment of these infections is problematic. Successful therapy
usually involves surgical excision coupled with administration
of antifungal agents.
Chlorellosis. Chlorellosis is caused by a unicellular green
alga of the genus Chlorella. In contrast to Prototheca, another
alga that causes human infection (Table 1), Chlorella contains
chloroplasts that give the lesions of chlorellosis a distinct green
color (34, 63, 81). A single human infection has been reported
thus far (41).
Chlorella spp. are unicellular, ovoid, spherical, or polygonal,
4 to 5 m in diameter, and reproduce asexually by internal
septation and cytoplasmic cleavage (endosporulation), producing up to 20 daughter cells (sporangiospores) within the parent
cell (sporangium) (Table 1) (34, 83). The organisms contain
numerous green chloroplasts, which appear as cytoplasmic
granules and stain intensely with GMS, PAS, and Gridley fungal stains (Fig. 2A) (83). Upon maturation, the outer wall of
the sporangium ruptures, releasing the sporangiospores, each
of which goes on to produce sporangiospores of its own.
The single human case of chlorellosis took place in Nebraska
and resulted from exposure of a surgical wound to river water
(41). The wound drained a greenish-yellow exudate, and infected tissues contained endosporulating organisms ranging
from 6 to 9 m in diameter. The organisms contained multiple,
strongly PAS-, GMS-, and Gridley fungus-positive cytoplasmic
granules, which with electron microscopy were shown to be
chloroplasts. The organisms did not stain with immunofluores-

J. CLIN. MICROBIOL.

cence conjugates specific for Prototheca wickerhamii and Prototheca zopfii. The infection was cured by surgical debridement
over a 10-month period.
Infections in domestic (sheep and cattle) and wild (beaver,
gazelle, and camel) animals range from lymph node and deep
organ involvement to cutaneous and subcutaneous lesions,
presumably related to exposure to water containing the organism (34, 44, 50, 81, 87). Fresh lesions in liver, lymph nodes, and
subcutaneous tissue are green in color on gross examination,
and smears reveal organisms that contain green refractile granules (chloroplasts) (14, 83).
Infections due to Chlorella spp. may be diagnosed by culture
and by histopathologic examination of infected tissue (14, 83).
The organisms grow readily on solid media and produce characteristic bright green colonies (14). Wet mounts of wound
exudates or touch preparations of infected tissue reveal ovoid,
endosporulating cells with typical green cytoplasmic granules
representing chloroplasts (Table 1). The organisms in tissue
stain intensely with GMS and PAS but not H&E stains. They
are easily distinguished from Prototheca by the intracellular
chloroplasts (Fig. 2A and B).
Treatment of the only human case of chlorellosis consisted
of debridement, irrigation, and gauze packing and removal to
ensure drainage and granulation (41). Medical treatment with
amphotericin B plus tetracycline has proven efficacious in the
treatment of protothecosis and may be useful for chlorellosis
should surgical excision prove inadequate.
Protothecosis. Protothecosis is an uncommon infection of
humans and animals caused by an achlorophyllous algae of the
genus Prototheca. Two species, P. wickerhamii and P. zopfii, are
known to cause infection, though the majority of human
infections are due to P. wickerhamii (47, 49). These organisms belong to the same family as the green algae of the
genus Chlorella.
The protothecae are unicellular, oval or spherical organisms
that reproduce asexually by internal septation and irregular
cleavage to produce between 2 and 20 sporangiospores within
a hyaline sporangium. The sporangiospores are arranged in a
characteristic morula configuration and upon rupture of the
sporangium are released to develop in turn into additional
endosporulating forms (Fig. 2B). The cells measure 3 to 30 m
in diameter and differ from those of Chlorella in the lack of
chloroplasts (Table 1). Protothecae differ from fungi by the
lack of glucosamine in their cell walls. The two species of
Prototheca that cause human disease are readily stained with
PAS, GMS, and the Gridley fungus stain and are gram positive
(76). They differ from one another in size: P. wickerhamii
measures 3 to 15 m in diameter, whereas P. zopfii measures 7
to 30 m in diameter.
Prototheca spp. are ubiquitous in nature, where they can be
isolated from grass, soil, water, and both wild and domesticated animals (39, 63, 74). They have also been found colonizing the human skin, fingernails, respiratory tract, and digestive
system (39, 104). Prototheca infection is generally introduced
via traumatic inoculation and has been reported on all continents except Antarctica (63). In the United States, protothecosis is reported most often in the Southeast (93, 105).
Three forms of human protothecosis are described: (i) cutaneous, (ii) olecranon bursitis, and (iii) disseminated (47, 49,
93). At least half of protothecosis cases are simple cutaneous

VOL. 43, 2005

infections (47, 49). The majority of these infections occur in

individuals who are compromised by immunosuppressive therapy, AIDS, malnutrition, renal or hepatic disease, cancer, or
autoimmune disorders (11, 49, 93, 104, 105). Lesions usually
arise in areas exposed to traumatic implantation and present in
an indolent fashion as nodules, papules, or an eczematoid
eruption.
In contrast, individuals presenting with olecranon bursitis
are usually not immunocompromised but report penetrating or
nonpenetrating trauma to the affected elbow (20, 65, 76). Signs
and symptoms appear gradually several weeks following the
trauma and include mild induration of the bursa accompanied
by tenderness, erythema, and production of a variable amount
of serosanguinous fluid.
Disseminated protothecosis is rare and almost always occurs
in individuals with severe immunocompromise from cancer
treatment, a prior solid organ transplant, or AIDS (36, 43, 48,
54, 93, 104). The organs most commonly affected in disseminated infection are skin, subcutaneous tissue, and spleen (93).
Central venous catheter-related algaemia has been reported
with accompanying fever, chills, and sepsis syndrome (48, 93).
One patient with visceral protothecosis has been described
who presented with signs and symptoms of cholangitis (13).
The patient had multiple peritoneal nodules that resembled
metastatic cancer but were in fact manifestations of protothecosis.
Prototheca spp. grow readily on a variety of synthetic media
at 30 to 37C (22). Colonies are creamy, white, and yeast-like
in appearance and consistency. A wet mount of the culture
material may be stained with lactophenol cotton blue to reveal
the characteristic endosporulating sporangia (so-called morula
form) (76). The organisms are quite metabolically active and
may be identified using one of several commercially available
yeast identification systems to determine the carbohydrate assimilation profile (22, 69).
Histopathologic examination of infected tissue may be accomplished using the PAS, GMS, or Gridley fungus stain to
visualize the endosporulating sporangia (morula form) of Prototheca spp. (Fig. 2B) (76). In addition to the size differences
noted previously (Table 1), the two species of Prototheca differ
in that P. wickerhamii tends to form symmetrical morula forms,
whereas these forms are rare with P. zopfii, which exhibits more
random internal segmentation (76). The inflammatory response in protothecosis is predominantly granulomatous but
can consist of lymphocytes, plasma cells, eosinophils, neutrophils, macrophages, epithelioid cells, and giant cells.
Treatment of cutaneous protothecosis with a variety of topical and systemic antibacterial, antifungal, and antiprotozoal
agents has met with variable success (47, 49). Surgical excision
is recommended for small localized lesions. Amphotericin B
and the azoles (itraconazole, fluconazole, and ketoconazole)
appear to be the most effective medical treatment (11, 49, 67,
71, 93). Cure of olecranon bursitis generally requires bursectomy (47, 49). Repeated drainage has failed; however, drainage coupled with local instillation of amphotericin B has been
curative (20, 76). Treatment of disseminated protothecosis is
best accomplished with amphotericin B, although the optimal
dose and duration of therapy are uncertain (49, 93).
Pythiosis insidiosi. Pythiosis is a pseudofungal infection of
humans and animals caused by the oomycete Pythium insidio-

MINIREVIEW

1501

sum (59, 75). Although described as an aquatic fungus, this

organism is not a true fungus. It belongs to the kingdom Stramenopila, phylum Oomycota, class Oomycetes, and family
Pythiaceae (1).
P. insidiosum grows in culture as white colonies with submerged vegetative hyphae and short aerial hyphae (56). A
plant pathogen, P. insidiosum requires water cultures containing the appropriate leaves to produce zoosporangia and zoospores in vitro (18, 58). In nature, it produces biflagellate
zoospores that attach and penetrate the leaves of various
grasses and water lilies. The zoospores have a tropism for skin
and hair, as well as water lilies and grass leaves (58). If zoospores contact injured tissue, they encyst, form germ tubes that
produce hyphae, and cause invasive disease.
In tissue, P. insidiosum exists as hyaline, pausi-septate, thinwalled hyphae or hyphal fragments that branch infrequently
(56). The hyphae are 5 to 7 m wide with nonparallel walls and
superficially resemble those of Zygomycetes (Table 1 and Fig.
2C). Similar to the Zygomycetes, P. insidiosum is angioinvasive
and stains weakly with GMS and other fungal stains (56). In
contrast to true fungi, the cell walls of P. insidiosum are composed of cellulose rather than glucan, mannan, and chitin.
P. insidiosum grows in aquatic to wet environments in tropical and subtropical regions, and pythiosis has been reported
from Thailand, the United States, Australia, New Zealand,
Malaysia, and Haiti (75). The risk of this infection is high for
those who are exposed to water in rice fields without wearing
boots.
Human disease due to P. insidiosum can be classified into
three forms (75): ocular, cutaneous, and arterial. The ocular
form of pythiosis is manifest as keratitis that can be severe and
result in corneal perforation. The cutaneous and subcutaneous
form most often presents as a periorbital cellulitis or mass with
progressive local invasion of soft tissue (85, 94). The arterial
form is the most serious and is largely limited to farmers in
Thailand who also suffer from thalassemia (56, 75, 82, 92, 100).
The disease process is marked by pain, swelling, and chronic
ulcers of the lower extremities with progressive ischemia, necrosis, and thrombosis of major arteries due to hyphal invasion.
Limb gangrene, aneurysm formation of the femoral, popliteal,
and iliac arteries and the aorta, and ultimately fatal hemorrhage is common (41% overall mortality) despite aggressive
medical and surgical intervention (75). The importance of
thalassemia in this process in unknown, since this is a very
common condition in Thailand. Additional reported sites of
infection with P. insidiosum include head and neck arteries in
a 14-year-old Thai boy (92) and pleuropericarditis and pneumonia in a 12-year-old child with leukemia (35). The latter
child was of Pakistani ancestry but was born and lived in the
United States.
In animals (cats, dogs, horses, and cattle), pythiosis is an
osseous, subcutaneous, or pulmonary infection. Equine pythiosis is marked by chronic ulcerated lesions with numerous yellow coral-like bodies (kunkers) on the limbs, chest, and
abdomen (58, 59). Dogs and horses may also present with
intestinal obstruction due to pythium granuloma in the duodenum or jejunum (51, 56).
The organism may be isolated from fresh clinical material
seeded onto mycologic medium, such as Sabourauds glucose
agar (56). Demonstration of biflagellate zoospores may be

1502

MINIREVIEW

accomplished using water cultures with grass or water lily bait

at 37C for 1 h (12).
Immunodiagnosis using an immunodiffusion or a fluorescent-antibody assay to detect antibodies to P. insidiosum has
been useful (75, 85). Likewise, the presence of the organism in
tissue may be confirmed by staining with specific fluorescentantibody conjugates (57).
Histopathologic examination of infected tissue shows a necrotizing arteritis and thrombosis (Table 1). Vascular invasion
by sparsely septate, irregularly branched hyphae is seen (56).
The infectious process spreads along the vessel walls proximally, and the organism may be visualized in the arterial wall
or in the outer part of the thrombus using GMS or PAS stains.
Eventually the acute perivascular inflammatory reaction is replaced by granulomas containing sparse hyphae and hyphal
fragments (56, 100).
Treatment of ocular pythiosis involves keratoplasty coupled
with both topical (amphotericin B, natamycin, miconazole, and
ketoconazole) and systemic (amphotericin B, ketoconazole,
and itraconazole) antifungal agents (75). Despite these efforts,
enucleation or evisceration is usually necessary. In contrast,
treatment of cutaneous and subcutaneous infection with surgical debridement and antifungal therapy is generally successful (75). One notable case in the United States of deep facial
infection in a child demonstrated that pharmacological cure
with itraconazole plus terbinafine is feasible (85).
Given the serious nature of arterial pythiosis, prompt recognition and aggressive medical and surgical therapy are warranted. Surgical debridement, amputation, and aneurismectomy may be necessary to limit the extent of the infection and
prevent fatal hemorrhage (75). Antifungal therapy with amphotericin B, itraconazole, and terbinafine, sequentially or in
combination, has been used with some success (35, 75, 85).
One patient with life-threatening arteritic infection with P.
insidiosum was treated successfully with aneurismectomy and
the use of P. insidiosum vaccine immunotherapy after failing
medical treatment with amphotericin B, iodides, and ketoconazole (92). The vaccine employed in this case was a modified
therapeutic vaccine that had been used successfully in treating
equine pythiosis.
Rhinosporidiosis. Rhinosporidiosis is a granulomatous disease of humans and animals that is characterized by the development of mucosal polyps that primarily affect the nasopharynx and ocular conjunctiva of infected individuals (2, 52,
103). The condition is caused by Rhinosporidium seeberi, an
organism with a confusing taxonomic history. R. seeberi has
been considered to be a protozoan and a fungus and most
recently has been placed in a novel clade of aquatic protistan
parasites, the Mezomycetozoa (29, 37). Since R. seeberi will not
grow in synthetic media nor in human or animal cell lines, this
reclassification was based on sequence analysis of the 18S
small-subunit ribosomal DNA of this organism. This analysis,
performed in two independent laboratories, placed R. seeberi
among the Mesomycetozoa (formerly DRIP clade; Dermocystidium, Rosette agent, Ichthyophonus, and Psorospermium), a
clade of fish parasites that form a branch of the evolutionary
tree near the animal-fungus divergence (29, 37).
Two developmental forms of R. seeberi are seen in tissue
(Table 1): the large endosporulating spherical form, or sporangia, and the smaller trophocyte (103). The sporangium is

J. CLIN. MICROBIOL.

considered to represent the mature form of the organism and

measures 100 to 350 m in diameter with a thin (3 to 5 m
thick) wall that is composed of an inner hyaline layer and an
outer eosinophilic layer. Within the sporangium are numerous
endospores (sporangiospores) arranged in a characteristic
zonal formation with the small, flattened, immature uninucleate sporangiospores (1 to 2 m) forming a crescent-shaped
mass at the periphery of one wall of the sporangium and larger
maturing and mature sporangiospores arranged sequentially
toward the center (Fig. 2D) (103). When fully mature, the
sporangiospores range in size from 5 to 10 m in diameter and
contain numerous refractile cytoplasmic globules. This zonal
arrangement of immature, maturing, and fully mature sporangiospores within the sporangium is pathognomonic of R. seeberi and distinguishes it from other spherical endosporulating
organisms in tissue (Table 2).
The mature sporangia have been estimated to contain as
many as 12,000 sporangiospores that are discharged through a
pore in the sporangium. The trophocyte form is thought to
develop directly from sporangiospores that have been liberated
from the sporangium. The trophocytes range in size from 10 to
100 m in diameter and have refractile eosinophilic walls (2 to
3 m thick), granular cytoplasm, and a round pale nucleus with
a prominent nucleolus (103).
Approximately 90% of all known cases of rhinosporidiosis
occur in India and Sri Lanka, where the prevalence is estimated at 1.4% (61). The disease has also been reported from
the Americas, Europe, and Africa (2, 52). The natural habitat
and extent of distribution of R. seeberi is unknown, although
studies have linked infection to swimming or bathing in freshwater ponds, lakes, or rivers (45). There is no evidence that
rhinosporidiosis is contagious.
Rhinosporidiosis occurs primarily in young men, 20 to 40
years old, and manifests as slow-growing polypoid or tumorlike masses, usually of the nasal mucosa or conjunctiva (52).
Lesions may also be seen in the paranasal sinuses, larynx, and
external genitalia. Limited systemic dissemination has been
reported but is rare (38). In most patients the disease remains
localized, and symptoms are primarily nasal obstruction and
epistaxis (52).
Rhinosporidiosis is diagnosed by histopathologic examination of the affected tissue. The distinctive appearance of the
trophocytes and sporangia in routine H&E-stained sections is
diagnostic (Table 1). The walls of both the sporangia and
sporangiospores stain with both GMS and PAS fungal stains
(103). In addition, the walls of the sporangiospores and the
inner wall of the sporangium stain positively with Mayers
mucicarmine (Table 2). Although other organisms that occur
in tissue in the form of large spherules may be mistaken for
R. seeberi (i.e., C. immitis and E. crescens [adiaspores]), they
usually can be differentiated one from another by consideration of the tissue involved and the morphological and staining
characteristics of the spherule and the endospores (Table 2).
The only effective treatment for rhinosporidiosis is surgical
excision of the lesions. Recurrences are common, especially in
mucosal sites, such as the oropharynx and the paranasal sinuses, where complete excision is often difficult to achieve (2,
52).

VOL. 43, 2005

MINIREVIEW
REFERENCES

1. Alexopoulos, C. J., C. W. Mims, and M. Blackwell. 1996. Introductory

mycology, 4th ed. John Wiley & Sons, New York, N.Y.
2. Ali, A., D. Flieder, G. Guiter, and S. A. Hoda. 2001. Rhinosporidiosis: an
unusual affliction. Arch. Pathol. Lab. Med. 125:13921393.
3. Azulay, R. D., J. Carneiro, and M. G. S. Cunha. 1976. Keloidal blastomycosis (Lobos disease) with lymphatic involvement: a case report. Int. J.
Dermatol. 15:4042.
4. Baruzzi, R. G., D. A. Rodrigues, N. S. Michalany, and R. Salomao. 1989.
Squamous-cell carcinoma and lobomycosis (Jorge Lobos disease). Int. J.
Dermatol. 28:183185.
5. Bigliazzi, C., V. Poletti, D. DellAmore, L. Saragomi, and T. V. Colby. 2004.
Disseminated basidiobolomycosis in an immunocompetent woman. J. Clin.
Microbiol. 42:13671369.
6. Bittencourt, A. L., S. M. Arruda, J. A. de Andreade, and E. M. Cavalho.
1991. Basidiobolomycosis: a case report. Pediatr. Dermatol. 8:325328.
7. Borelli, D. 1961. Lobomicosis experimental. Dermatol. Venez. 3:7282.
8. Brun, A. M. 1999. Lobomycosis in three Venezuelan patients. Int. J. Dermatol. 38:298305.
9. Burns, R. A., J. S. Roy, C. Woods, A. A. Padhye, and D. W. Warnock. 2000.
Report of the first human case of lobomycosis in the United States. J. Clin.
Microbiol. 38:12831285.
10. Caldwell, D. K., M. C. Caldwell, J. C. Woodard, L. Ajello, W. Kaplan, and
H. M. McClure. 1995. Lobomycosis as a disease of the Atlantic bottle-nosed
dolphin (Tursiops truncatus Montagu, 1821). Am. J. Trop. Med. Hyg. 24:
105114.
11. Carey, W. P., Y. Kaykova, J. C. Bandres, G. S. Sidhu, and N. Brau. 1997.
Cutaneous protothecosis in a patient with AIDS and a severe functional
neutrophil defect: successful therapy with amphotericin B. Clin. Infect. Dis.
25:12651266.
12. Chaiprasert, A., K. Samerpitak, W. Wanachiwanawin, and P. Thasnakorn.
1990. Induction of zoospore formation in Thai isolates of Pythuim insidiosum. Mycoses 33:317323.
13. Chan, J. C., L. J. Jeffers, and E. W. Gould. 1990. Visceral protothecosis
mimicking sclerosing cholangitis in an immunocompetent host: successful
antifungal therapy. Rev. Infect. Dis. 12:802807.
14. Chandler, F. W., and J. C. Watts. 1987. Pathologic diagnosis of fungal
infections. ASCP Press, Chicago, Ill.
15. Connor, D. H., F. W. Chandler, D. A. Schwartz, H. J. Manz, and E. E. Lack.
1997. Pathology of infectious diseases, vol. II. Appleton & Lange, Stamford,
Conn.
16. Costa, A. R., E. Porto, J. R. P. Pegas, V. M. Silva dos Reis, M. C. Pires, C.
da Silva Lacaz, M. C. Rodriguez, H. Muller, and L. L. Cuce. 1991. Rhinofacial zygomycosis caused by Conidiobolus coronatus. A case report. Mycopathologia 115:18.
17. Cowan, D. F. 1993. Lobos disease in a bottlenose dolphin (Tursiops truncatus) from Matagorda Bay, Texas. J. Wildl. Dis. 29:488489.
18. deCock, A. W. A. M., L. Mendoza, A. A. Padhye, L. Ajello, and L. Kaufman.
1987. Pythium insidiosum sp. nov., the etiologic agent of pythiosis. J. Clin.
Microbiol. 25:344349.
19. de Leon-Borjorge, B., R. Ruiz-Maldonado, and R. Lopez-Martinez. 1988.
Subcutaneous phycomycosis caused by Basidiobolus haptosporus: a clinicopathologic and mycologic study in a child. Pediatr. Dermatol. 5:3336.
20. de Montclos, M., G. Chatte, M. Perrin-Fayolle, and J. L. Flandrois. 1995.
Olecranon bursitis due to Prototheca wickerhamii, an algal opportunistic
pathogen. Eur. J. Clin. Microbiol. Infect. Dis. 14:561562.
21. DeVries, G. A., and J. J. Laarman. 1973. A case of Lobos disease in the
dolphin Sotalia guianensis. Aquat. Mamm. 1:18.
22. DiPersio, J. R. 2001. Prototheca and protothecosis. Clin. Microbiol. Newslett. 23:115121.
23. Drapela, J., J. Viklicky, J. Novak, J. Tousek, and M. Vana. 1980. Peritoneal
form of adiaspiromycosis. Z. Erkr. Atmungsorgane 155:393398.
24. Echavarria, E., E. L. Cano, and A. Restrepo. 1993. Disseminated adiaspiromycosis in a patient with AIDS. J. Med. Vet. Mycol. 31:9197.
25. Eckert, H. L., G. H. Khoury, R. S. Pore, E. F. Gilbert, and J. R. Gaskill.
1972. Deep entomophthora phycomycotic infection reported for the first
time in the United States. Chest 61:392394.
26. Emmons, C. W., and W. L. Jellison. 1960. Emmonsia crescens sp. n and
adiaspiromycosis (haplomycosis) in mammals. Ann. N. Y. Acad. Sci. 89:
91101.
27. England, D. M., and L. Hochholzer. 1993. Adiaspiromycosis: an unusual
fungal infection of the lung. Report of 11 cases. Am. J. Surg. Pathol.
17:876886.
28. Foss, N. T., M. R. Rocha, V. T. Lima, M. A. Velludo, and A. M. Roselino.
1996. Entomophthoromycosis: therapeutic success by using amphotericin B
and terbinafine. Otolaryngology 193:258260.
29. Fredricks, D. M., J. A. Jolley, P. W. Lepp, J. C. Kosek, and D. A. Relman.
2000. Rhinosporidium seeberi: a human pathogen from a novel group of
aquatic protistan parasites. Emerg. Infect. Dis. 6:273282.
30. Guaro, J., C. Aguilar, and I. Pujol. 1999. In-vitro antifungal susceptibilities

31.
32.
33.
34.
35.

36.
37.

38.
39.
40.
41.
42.
43.
44.
45.

46.

47.
48.
49.
50.
51.
52.
53.

54.
55.
56.

57.
58.

1503

of Basidiobolus and Conidiobolus spp. strains. J. Antimicrob. Chemother.

44:557560.
Gugnani, H. C. 1992. Entomophthoromycosis due to Conidiobolus. Eur. J.
Epidemiol. 8:391396.
Gugnani, H. C. 1999. A review of zygomycosis due to Basidiobolus ranarum.
Eur. J. Epidemiol. 15:923929.
Gugnani, H. C., B. C. Ezeanolue, M. Khalil, C. D. Amoah, E. U. Ajuiu, and
E. A. Oyewo. 1995. Fluconazole in the therapy of tropical deep mycoses.
Mycoses 38:485488.
Haenichen, T., E. Facker, G. Wanner, and W. Hermanns. 2002. Cutaneous
chlorellosis in a gazelle (Gazella dorcas). Vet. Pathol. 39:386389.
Heath, J. A., T. E. Kiehn, A. E. Brown, M. P. LaQuaglia, L. J. Steinherz, G.
Bearman, M. Wong, and P. G. Steinherz. 2002. Pythium insidiosum pleuropericarditis complicating pneumonia in a child with leukemia. Clin. Infect. Dis. 35:e60e64.
Heney, C., M. Greeff, and V. Davis. 1991. Hickman catheter-related protothecal algaemia in an immunocompromised child. J. Infect. Dis. 163:930
931.
Herr, R. A., L. Ajello, J. W. Taylor, S. N. Arseculeratne, and L. Mendoza.
1999. Phylogenetic analysis of Rhinosporidium seeberis 18S small-subunit
ribosomal DNA groups this pathogen among members of the protoctistan
Mesomycetozoa clade. J. Clin. Microbiol. 37:27502754.
Ho, M. S., and B. K. Tay. 1986. Disseminated rhinosporidiosis. Ann. Acad.
Med. Singapore 15:8083.
Huerre, M., P. Ravisse, and H. Solomon. 1993. Human protothecosis and
environment. Bull. Soc. Pathol. Exot. 86:484488.
Jaffey, P. B., A. K. Hague, M. El-Zaatari, L. Pasarell, and M. R. McGinnis.
1990. Disseminated Conidiobolus infection with endocarditis in a cocaine
abuser. Arch. Pathol. Lab. Med. 14:12761278.
Jones, J. W., H. W. McFadden, F. W. Chandler, W. Kaplan, and D. H.
Connor. 1983. Green algal infection in a human. Am. J. Clin. Pathol.
80:102107.
Kamalam, A., and A. S. Thambiah. 1979. Adiaspiromycosis of human skin
caused by Emmonsia crescens. Sabouraudia 17:377381.
Kaminski, Z. C., R. Kapila, L. R. Sharer, P. Kloser, and L. Kaufman. 1992.
Meningitis due to Prototheca wickerhamii in a patient with AIDS. Clin.
Infect. Dis. 15:704706.
Kaplan, W., F. W. Chandler, C. Choudary, and P. K. Ramachandran. 1983.
Disseminated unicellular green algal infection in two sheep in India. Am. J.
Trop. Med. Hyg. 32:405411.
Kennedy, F. A., R. R. Buggage, and L. Ajello. 1995. Rhinosporidiosis: a
description of an unprecedented outbreak in captive swans (Cygnus spp.)
and a proposal for revision of the ontogenic nomenclature of Rhinosporidium seeberi. J. Med. Vet. Mycol. 33:157165.
Khan, Z. U., M. Khoursheed, R. Makar, S. Al-Waheeb, I. Al-Bader, A.
Al-Muzaini, R. Chandy, and A. S. Mustafa. 2001. Basidiobolus ranarum as
an etiologic agent of gastrointestinal zygomycosis. J. Clin. Microbiol. 39:
23602363.
Krcmery, V., Jr. 2000. Systemic chlorellosis, an emerging infection in humans caused by algae. Int. J. Antimicrob. Agents 15:235237.
Kunova, A., T. Kollar, S. Spanik, and V. Krcmery, Jr. 1996. First report of
Prototheca wickerhamii algaemia in an adult leukemic patient. J. Chemother. 8:166167.
Leimann, B. C., P. C. Monteiro, M. Lazera, E. R. Candanoza, and B.
Wanke. 2004. Protothecosis. Med. Mycol. 42:95106.
Le Net, J. L., M. Fadl Ahmed, G. Saint-Martin, M. T. Masson, C. Montois,
and L. Longeart. 1993. Granulomatous enteritis in a dromedary (Camelus
dromedarius) due to green algal infection. Vet. Pathol. 30:370373.
Liljebjelke, K. A., C. Abramson, C. Brockus, and C. E. Greene. 2002.
Duodenal obstruction caused by infection with Pythium insidiosum in a
12-week old puppy. J. Am. Vet. Med. Assoc. 220:11881191.
Loh, K. S., S. M. Chong, Y. T. Pang, and K. Soh. 2001. Rhinosporidiosis:
differential diagnosis of a large nasal mass. Otolaryngol. Head Neck Surg.
124:121122.
Lyon, G. M., J. D. Smilack, K. K. Komatsu, T. M. Pasha, J. A. Leighton, J.
Guarner, T. V. Colby, M. D. Lindsley, M. Phelan, D. W. Warnock, and R. A.
Hajjeh. 2001. Gastrointestinal basidiobolomycosis in Arizona: clinical and
epidemiological characteristics and review of the literature. Clin. Infect.
Dis. 32:14481455.
Marr, K. A., J. V. Hirschmann, D. Thorning, and G. J. Raugi. 1998.
Protothecosis. Clin. Infect. Dis. 26:756757.
Martins, R. L., C. G. Santos, F. R. Franca, and M. A. Moraes. 1997. Human
adiaspiromycosis. A report of a case treated with ketoconazole. Rev. Soc.
Med. Trop. 30:507509.
McGinnis, M. R., and F. W. Chandler. 1997. Pythiosis insidiosi, p. 1081
1084. In D. H. Connor, F. W. Chandler, D. A. Schwartz, H. J. Manz, and
E. E. Lack (ed.), Pathology of infectious diseases. Appleton & Lange,
Stamford, Conn.
Mendoza, L., L. Kaufman, and P. G. Standard. 1987. Antigenic relationship
between the animal and human pathogen Pythium insidiosum and nonpathogenic Pythium species. J. Clin. Microbiol. 25:21592162.
Mendoza, L., F. Hernandez, and L. Ajello. 1993. Life cycle of the human

1504

59.
60.
61.
62.

63.
64.
65.
66.
67.
68.
69.
70.
71.

72.

73.
74.
75.
76.

77.
78.
79.
80.
81.
82.
83.

MINIREVIEW

and animal oomyete pathogen Pythium insidiosum. J. Clin. Microbiol. 31:

29672973.
Mendoza, L., L. Ajello, and M. R. McGinnis. 1996. Infections caused by the
oomycetous pathogen Pythium insidiosum. J. Mycol. Med. 6:151164.
Migaki, G., M. G. Valerio, B. Irvine, and F. M. Cardner. 1971. Lobos
disease in an Atlantic bottle-nosed dolphin. J. Am. Vet. Med. Assoc. 159:
578582.
Moses, J. D., and A. Shanmugham. 1987. Epidemiological survey of rhinosporidiosis in mana sample survey in a high school located in a hyperendemic area. Ind. Vet. J. 64:3438.
Nazir, Z., R. Hasan, S. Pervaiz, M. Alam, and F. Moazam. 1997. Invasive
retroperitoneal infection due to Basidiobolus ranarum with response to
potassium iodidecase report and review of the literature. Ann. Trop.
Paediatr. 17:161164.
Nelson, A. M., R. C. Neafie, and D. H. Connor. 1987. Cutaneous protothecosis and chlorellosis: extraordinary, aquatic-borne algal infections.
Clin. Dermatol. 5:7687.
Nikolaides, G., and T. Rosen. 1997. Lobomycosis, p. 10231028. In D. H.
Connor, F. W. Chandler, D. A. Schwartz, H. J. Manz, and E. E. Lack (ed.),
Pathology of infectious diseases. Appleton & Lange, Stamford, Conn.
Nosanchuck, J. S., and R. D. Greenberg. 1973. Protothecosis of the olecranon bursa caused by achloric algae. Am. J. Clin. Pathol. 59:567573.
Nuorva, K., R. Pitkanen, J. Issakainen, N. P. Huttunen, and M. Juhola.
1997. Pulmonary adiaspiromycosis in a two year old girl. J. Clin. Pathol.
50:8285.
Okuyama, T., T. Hamaguchi, T. Teramoto, and I. Takiuchi. 2001. A human
case of protothecosis successfully treated with itraconazole. Nippon
Ishinkin Gakkai Zasshi 42:143147.
Otcenasek, M., and O. Ditrich. 1983. Comparative susceptibility of the
agents of adiaspiromycosis to imidazole derivatives in vitro. Sabourudia
21:239242.
Padhye, A. A., J. G. Baker, and R. F. DAmato. 1979. Rapid identification
of Prototheca species by the API 20C system. J. Clin. Microbiol. 10:579582.
Pasha, T. M., J. A. Leighton, J. D. Smilack, J. Heppell, T. V. Colby, and L.
Kaufman. 1997. Basidiobolomycosis: an unusual fungal infection mimicking
inflammatory bowel disease. Gastroenterology 112:250254.
Pegram, R. S., Jr., F. T. Kerns, B. L. Wasilauskas, K. D. Hampton, M.
Scharyji, and J. G. Burke. 1983. Successful ketoconazole treatment of
protothecosis with ketoconazole-associated hepatotoxicity. Arch. Intern.
Med. 143:18021805.
Peterson, S. W., and L. Sigler. 1998. Molecular genetic variation in Emmonsia crescens and Emmonsia parva, etiologic agents of adiaspiromycosis,
and their phylogenetic relationship to Blastomyces dermatitidis (Ajellomyes
dermatitidis) and other systemic fungal pathogens. J. Clin. Microbiol. 36:
29182925.
Pfaller, M. A., and D. J. Diekema. 2004. Rare and emerging opportunistic
fungal pathogens: concerns for resistance beyond Candida albicans and
Aspergillus fumigatus. J. Clin. Microbiol. 42:44194431.
Pore, R. S., E. A. Barnett, W. C. Barnes, Jr., and J. D. Walker. 1983.
Prototheca ecology. Mycopathologia 81:4962.
Prasertwitayakij, N., W. Louthrenoo, N. Kasitanon, K. Thamprasert, and
N. Vanittanakom. 2003. Human pythiosis, a rare cause of arteritis: case
report and literature review. Semin. Arthritis Rheum. 33:204214.
Ramsay, E., F. W. Chandler, and D. H. Connor. 1997. Protothecosis, p.
10671072. In D. H. Connor, F. W. Chandler, D. A. Schwartz, H. J. Manz,
and E. E. Lack (ed.), Pathology of infectious diseases. Appleton & Lange,
Stamford, Conn.
Restrepo, A. 1994. Treatment of tropical mycoses. J. Am. Acad. Dermatol.
31:S91S102.
Ribes, J. A., C. L. Vanover-Sams, and D. J. Baker. 2000. Zygomycetes in
human disease. Clin. Microbiol. 13:236301.
Rodriguez, G., and G. P. Barrera. 1997. The asteroid body of lobomycosis.
Mycopathologia 136:7174.
Rodriguez-Toro, G. 1993. Lobomycosis. Int. J. Dermatol. 32:324332.
Rogers, R. J., M. D. Connole, J. Norton, A. Thomas, P. W. Ladds, and J.
Dickson. 1980. Lymphadenitis of cattle due to infection with green algae.
J. Comp. Pathol. 90:19.
Sathapatayavongs, B., P. Leelachaikul, R. Prachaktam, V. Atichartakarn,
S. Sriphojanart, and P. Trairatvorakul. 1989. Human pythiosis associated
with thalassemia hemoglobinopathy syndrome. J. Infect. Dis. 159:274280.
Seniw, C. M., F. W. Chandler, and D. H. Connor. 1997. Chlorellosis, p.
965970. In D. H. Connor, F. W. Chandler, D. A. Schwartz, H. J. Manz, and
E. E. Lack (ed.), Pathology of infectious diseases. Appleton & Lange,
Stamford, Conn.

J. CLIN. MICROBIOL.
84. Severo, L. C., G. R. Geyer, J. J. Camargo, and N. S. Porto. 1989. Adiaspiromycosis treated successfully with ketoconazole. J. Med. Vet. Mycol. 27:
265268.
85. Shenep, J. L., B. K. English, L. Kaufman, T. A. Pearson, J. W. Thompson,
R. A. Kaufman, G. Frisch, and M. G. Rinaldi. 1998. Successful medical
therapy for deeply invasive facial infection due to Pythium insidiosum in a
child. Clin. Infect. Dis. 27:13881393.
86. Sigler, L. 1996. Ajellomyces crescens sp. nov., taxonomy of Emmonsia spp.,
and relatedness with Blastomyces dermatitidis (teleomorph Ajellomyces dermatitidis). J. Med. Vet. Mycol. 34:303314.
87. Sileo, L., and N. C. Palmer. 1973. Probable cutaneous protothecosis in a
beaver. J. Wildl. Dis. 9:320322.
88. Symmers, W. S. 1983. A possible case of Lobos disease acquired in Europe
from a bottle-nosed dolphin (Tursiops truncatus). Bull. Soc. Pathol. Exot.
77:777784.
89. Taborda, P. R., V. Taborda, and M. F. McGinnis. 1999. Lacazia loboi gen.
nov., comb. nov., the etiologic agent of lobomycosis. J. Clin. Microbiol.
37:20312033.
90. Taborda, V. B. A., P. R. O. Taborda, and M. F. McGinnis. 1999. Constitutive melanin in the cell wall of the etiologic agent of lobomycosis. Rev. Inst.
Med. Trop. Sao Paulo 41:912.
91. Temple, M. E., M. T. Brady, K. I. Koranyi, and M. C. Nahata. 2001.
Periorbital cellulitis secondary to Conidiobolus incongruous. Pharmacotherapy 21:351354.
92. Thitithanyanont, A., L. Mendoza, A. Chuansumrit, R. Pracharktam, J.
Laothamatas, B. Sathapatayavongs, S. Lolekha, and L. Ajello. 1998. Use of
an immunotherapeutic vaccine to treat a life-threatening human arteritic
infection caused by Pythium insidiosum. Clin. Infect. Dis. 27:13941400.
93. Torres, H. A., G. P. Bodey, J. J. Tarrand, and D. P. Kontoyiannis. 2003.
Protothecosis in patients with cancer: case series and literature review. Clin.
Microbiol. Infect. 9:786792.
94. Triscott, J. A., D. Weedon, and E. Cabana. 1993. Human subcutaneous
pythiosis. J. Cutan. Pathol. 20:267271.
95. Turner, D., M. Burke, E. Bashe, S. Blinder, and I. Yust. 1999. Pulmonary
adiaspiromycosis in a patient with acquired immunodeficiency syndrome.
Eur. J. Clin. Microbiol. Infect. Dis. 18:893895.
96. Vismer, H. F., H. A. DeBeer, and L. Dreyer. 1980. Subcutaneous phycomycosis caused by Basidiobolus haptosporus (Dreschler, 1947). S. Am. J. Med.
58:644647.
97. Walker, S. D., R. V. Clark, C. T. King, J. E. Humphries, L. S. Lyle, and D. E.
Butkus. 1992. Fatal disseminated Conidiobolus infection in a renal transplant patient. Am. J. Clin. Pathol. 98:559564.
98. Walsh, T. J., G. Renshaw, J. Andrews, J. Kwon-Chung, R. C. Cunnion, H. I.
Pass, J. Taubenberger, W. Wilson, and P. A. Pizzo. 1994. Invasive zygomycosis due to Conidiobolus incongruous. Clin. Infect. Dis. 19:423430.
99. Walsh, T. J., A. Groll, J. Hiemenz, R. Flemming, E. Roilides, and E.
Anaissie. 2004. Infections due to emerging and uncommon medically important fungal pathogens. Clin. Microbiol. Infect. 10(Suppl. 1):4866.
100. Wanachiwanawin, W., M. Thianprasit, S. Fucharoen, A. Chaiprasert, N.
Sudasna, N. Ayudhya, and N. Sirithanaratkul. 1993. Fatal arteritis due to
Pythium insidiosum infection in patients with thalassemia. Trans. R. Soc.
Trop. Med. Hyg. 87:296298.
101. Wasim, T., H. M. Assaf, and N. A. Rotowa. 2003. Invasive gastrointestinal
Basidiobolus ranarum infection in an immunocompetent child. Pediatr.
Infect. Dis. J. 22:281282.
102. Watts, J. C., and F. W. Chandler. 1997. Adiaspiromycosis, p. 929932. In
D. H. Connor, F. W. Chandler, D. A. Schwartz, H. J. Manz, and E. E. Lack
(ed.), Pathology of infectious diseases. Appleton & Lange, Stamford, Conn.
103. Watts, J. C., and F. W. Chandler. 1997. Rhinosporidiosis, p. 10851088. In
D. H. Connor, F. W. Chandler, D. A. Schwartz, H. J. Manz, and E. E. Lack
(ed.), Pathology of infectious diseases. Appleton & Lange, Stamford, Conn.
104. Wirth, F. A., J. A. Passalacqua, and G. Kao. 1999. Disseminated cutaneous
protothecosis in an immunocompromised host: a case report and literature
review. Cutis 63:185188.
105. Woolrich, A., E. Koestenblatt, P. Don, and W. Szaniawski. 1994. Cutaneous
protothecosis and AIDS. J. Am. Acad. Dermatol. 31:920924.
106. Yousef, O. M., J. D. Smilack, D. M. Kerr, R. Ramsey, L. Rosati, and T. V.
Colby. 1999. Gastrointestinal basidiobolomycosis. Morphologic findings in
a cluster of six cases. Am. J. Clin. Pathol. 112:610616.
107. Zavasky, D., T. Loftus, H. Segal, and K. Carrol. 1999. Gastrointestinal
zygomatic infection caused by Basidiobolus ranarum: case report and review. Clin. Infect. Dis. 28:12441248.