Medical Mycology April 2004, 42, 95 /106

Case Report and Literature Review

Protothecosis
BEATRIZ CONSUELO QUINET LEIMANN*, PAULO CEZAR FIALHO MONTEIRO*, MÁRCIA LAZÉRA*,
EDUARDO R. ULLOA CANDANOZA$ & BODO WANKE*
*Mycology Service, Evandro Chagas Institute of Clinical Research, IPEC/FIOCRUZ and $Pediatrics Service, São João Batista
Hospital, Rio de Janeiro, Brazil

Protothecosis is an infection caused by achlorophyllic algae of the genus

Prototheca which rarely affects humans. Some 100 cases have been described in

Downloaded from https://academic.oup.com/mmy/article/42/2/95/964350 by guest on 20 April 2021

the medical literature, the majority caused by the species P. wickerhamii. The skin is
the organ most frequently involved. Diagnosis is performed by isolation of the
microorganism in culture or by histopathology. The ideal treatment has not been
defined, with amphotericin B and the azoles having been employed. Surgical
excision is recommended for small, localized lesions. We describe a case of
cutaneous protothecosis on the right fourth finger of a female patient 59 years old
with no underlying disease. Administration of itraconazole 400 mg/day for 6 weeks
failed to produce an adequate clinical response. Treatment was then changed to
fluconazole 200 mg/day, with regression of the lesion.
Keywords amphotericin B, azoles, immunosuppression, Prototheca wickerhamii

Introduction Case report

Species of the genus Prototheca are microscopic
achlorophyllic unicellular algae described for the first
time in 1894 by Wilhem Krüger [1]. Their life cycle is
similar to that of algae from genus Chlorella.
The term protothecosis refers to the infection caused
by these algae in humans or animals. Human proto-
thecosis is rare. The clinical manifestations of reported
cases have included cutaneous lesions, olecranon bur-
sitis, or systemic involvement.
The purpose of this study is to report a case of
cutaneous protothecosis in a 59-year-old woman with
no underlying disease, and to review the clinical,
diagnostic and therapeutic characteristics of protothe-
cosis.
Accepted 6 November 2003
Correspondence: Beatriz Consuelo Quinet Leimann, Rua
Nascimento Silva 383/401, Ipanema, Rio de Janeiro, RJ 22421-020,
Brazil. Tel.: /55 21 2580 8732; Fax: /55 21 2522 4240; E-mail:
leimann@centroin.com.br
Bodo Wanke, Rua Campinas 26/1301, Grajaú, Rio de Janeiro, RJ
20561-250, Brazil. Tel.: /55 21 2598 4266, Ramal: 116; Fax: /55 21
2590 9988; E-mail: wanke@ipec.fiocruz.br
– 2004 ISHAM
A female patient, 59 years old, native of Rio de Janeiro,
Brazil, presented in July 2002 at the Mycology Out-
patient Clinic of the Evandro Chagas Institute of
Clinical Research at the Oswaldo Cruz Foundation
(FIOCRUZ), Rio de Janeiro, with a lesion on the right
fourth finger with a diagnosis of infection by Proto-
theca wickerhamii .
The history began in mid-1999 after a blunt trauma,
when the patient slammed a door on her right fourth
finger. For 1.5 years the patient was treated with
various anti-inflammatory drugs and local physical
therapy, with the inflammatory process waxing and
waning. In January 2002, the patient was submitted to
local steroid infiltration, resulting in partial improve-
ment. In May, after handling soil while gardening (sic.),
the patient observed an aggravation of the inflamma-
tion with the appearance of yellowish spots and
spontaneous drainage of purulent secretion. Surgical
excision of part of the lesion was performed and the
material was submitted to culture, resulting in the
growth of Prototheca wickerhamii . In late June 2002,
treatment with itraconazole 400 mg/day was started.
On 11 July 2002 the patient presented at the Mycology
DOI: 10.1080/13693780310001653653
96 Leimann et al.
Outpatient Clinic reporting slight improvement. Upon
examination, the lesion measured approximately 4 cm
in length and affected the proximal and medial
phalanges of the right fourth finger and the respective
joint, presenting pain, edema, hyperemia, and a discrete
serous discharge. Fresh-mount microscopy in KOH
20% and a PAS stain (Fig. 1) of the serous exudate
showed spherical sporangia with sporangiospores and
with cytoplasm undergoing cleavage. Culture on Sa-
bouraud agar grew a white yeast-like colony which, on
microscopic examination, showed sporangia with spor-
angiospores. No growth was observed in Mycosel
medium with cycloheximide. Both direct KOH wet-
mount and culture wet-mount stained with lactophenol
cotton blue were characteristic of genus Prototheca .
Inoculation on cornmeal agar was not performed.
Based on API 20 C AUX (BioMérieux), identification
was performed at the level of species of P. wickerhamii.
Susceptibility testing of the Prototheca isolated was
performed by the Clinical Analysis Department of the
Faculty of Pharmaceutical Sciences, UNESP (Arara-
quara, São Paulo). Susceptibility to antifungals was
tested with amphotericin B (AMB), 5-flucytosine
(5FC), fluconazole (FCZ) and itraconazole (ITZ)
through microdilution. The MIC was determined for
the isolate in accordance with the National Committee
for Clinical Laboratory Standards Guidelines
(NCCLS) with modifications. RPMI 1640 medium
(Sigma) buffered to pH 7.2 with morpholinepropane-
sulfonic acid (MOPS) buffer (Sigma) and 2% dextrose
[2] served as the growth medium. The incubation
temperature was 358C for 48 h, under constant shak-
ing. The MIC of fluconazole, itraconazole or flucyto-
sine was defined as the lowest concentration of drug
which resulted in a 50% reduction of Prototheca growth
compared to control. The amphotericin B MIC was
defined as the lowest concentration of drug which
resulted in complete inhibition of visible growth. The
following MIC values were observed: amphotericin B:
0.5 mg/ml; 5-fluorocytosine: /64 mg/ml; itraconazole: 2
mg/ml; fluconazole: /64 mg/ml. Itraconazole 400 mg/
day was maintained.
On 22 July, the patient returned with the lesion
having worsened, with an increase in the edema,
hyperemia, and purulent discharge (Fig. 2a), suggesting
Downloaded from https://academic.oup.com/mmy/article/42/2/95/964350 by guest on 20 April 2021
secondary infection. Culture of the purulent material in
Sabouraud agar and blood agar revealed P. wickerha-
mii and Staphylococcus aureus, respectively. Radiologi-
cal examination of the affected area showed no evide-
nce of osteomyelitis; total blood count was normal and
ESR was 2 mm in the first hour. Itraconazole was
maintained and cephalexin was added at 500 mg q.i.d..
After 9 days treatment there was a clear resolution of
the secondary infection, with only a discrete exudate;
however, an induration had appeared in the lateral
region of the proximal phalange, suggesting progres-
sion of the underlying lesion. Wet-mount and culture
microscopy of the exudate remained positive for
Prototheca . Because Prototheca wickerhamii was re-
isolated after 5 weeks of itraconazole, the latter was
suspended and fluconazole was introduced at 200 mg/
day. Cephalexin was maintained for another 1 week.
Twenty days after introducing fluconazole a signifi-
cant improvement was observed in the lesion, and both
Fig. 1 Prototheca wickerhamii (arrows) in
serous exudates of skin lesion stained with
PAS (/1000): sporangia with internal septa-
tion and, in upper right corner, typical spor-
agium with sporangiospores.
– 2004 ISHAM, Medical Mycology, 42, 95 /106

Fig. 2 Cutaneous infection with Prototheca wickerhamii : (a) edema,
hyperemia and purulent discharge due to secondary infection by
Staphylococcus aureus ; (b) aspect after 2 weeks cephalexin and 3
months fluconazole.
KOH wet-mount and culture of a residual exudate no
longer showed Prototheca wickerhamii. However, 2
weeks later a slight increase was observed in the
exudate, from which only Staphylococcus aureus was
isolated. The patient was maintained on fluconazole,
and norfloxacin was introduced at 800 mg/day for 1
month. The patient had already had a course of a
cephalosporin, so norfloxacin was chosen based on the
results of the susceptibility test and the drug availability
from the hospital pharmacy. There was a gradual
improvement with a reduction of the inflammatory
process.
In November, 3 months after introducing flucona-
zole, the lesion was undergoing a clear healing process
(Fig. 2b). In January 2003, after 6 months fluconazole,
the scar was still reddish and sensitive, while at the last
visit, in June, the inflammation signs had resolved. The
treatment plan was to maintain fluconazole for 1 year,
that is, until July 2003.
Literature review
The first case of protothecosis in humans was described
by Davies et al. [3] in 1964. One hundred and six cases
have been described in the medical literature. Genus
Prototheca consists of achlorophyllic aerobic algae
with a ubiquitous distribution in nature. The algae
are heterotrophic, requiring an exogenous source of
carbon and nitrogen, and adapted to both natural and
manmade environments, having been isolated from
– 2004 ISHAM, Medical Mycology, 42, 95 /106
Protothecosis 97
trees, various aquatic sources such as lakes and rivers,
sewage treatment plants, garbage dumps, and house-
hold garbage [4]. They can be isolated from skin, feces,
or sputum of humans or animals in the absence of
clinical manifestations [5]. As chlorination is not
uniformly effective in eliminating potentially patho-
genic protothecae from the effluent of sewage water
and household waste, the algae persist and return to the
environment [6].
Protothecae are unicellular microorganisms, 3/30
mm in diameter. Cells of Prototheca wickerhamii are
round in comparison to the oval or cylindrical shape of
most strains of Prototheca zopfii [7] or to the capsu-
Downloaded from https://academic.oup.com/mmy/article/42/2/95/964350 by guest on 20 April 2021
lated ellipsoidal cells of Prototheca stagnora [8]. They
reproduce asexually by internal septation and cleavage,
with the formation of sporangia, which contain spor-
angiospores. The number and size of spores varies
among species. Sporangiospores of P. wickerhamii are
spherical and 2/11 mm in diameter. The largest
sporangia may contain as many as 50 sporangiospores.
Size range of sporangia is 7 /13 mm. Sporangiospores
of P. zopfii are 9/11 mm in diameter; the size range of
sporangia is 14/25 mm, containing 2/20 sporangios-
pores. The size range of P. stagnora is close to that of P.
wickerhamii. Rupture of mother cells passively liberates
infective organisms. The cell wall is thick and does not
contain glucosamine, a characteristic component of the
fungal wall [3,9 /15]. In histological cross-section they
stain well with PAS, are eosinophilic, and impregnate
well with Grocott silver. At first sight Prototheca can
be confused with Lacazia loboi, Coccidioides immitis,
Pneumocystis carinii, Histoplasma duboisii and Blasto-
myces dermatitidis [15]. However Lacazia loboi multi-
plies by budding and thus mother cells with single buds
attached by a narrow tubular connection are often
encountered, and cannot be recovered in culture;
Histoplasma duboisii and Blastomyces dermatitidis
also multiply by budding. The typical budding form
of B. dermatitidis is broad-based while H. duboisii buds
by a narrower base with typical hour-glass forms.
Spherules of Coccidioidis immitis are 20/200 mm
diameter with smaller and more numerous endospores
than Prototheca spp. [16]. Pneumocystis carinii presents
cysts and trophozoites and cannot be recovered in
culture [8]. Of the three species of Prototheca currently
recognized (P. wickerhamii , P. zopfii and P. stagnora),
only P. wickerhamii and P. zopfii have been associated
with infection in humans.
Protothecosis can manifest itself clinically in three
forms: cutaneous, olecranon bursitis and systemic
protothecosis [17]. The clinical evolution is that of a
chronic infection with low-grade inflammation. It is
believed that the incubation period is several weeks and
98 Leimann et al.
that the algae penetrate the skin following post-trau-
matic damage. The lesions generally remain localized;
however, in immunocompromized patients there is a
risk of dissemination of the disease, particularly in
patients with cellular immunodeficiency [3]. To note is
the fact that only six cases of Prototheca infection have
been described in AIDS patients: four cutaneous [18 /
21] and two non cutaneous forms / meningitis [22] and
tenosynovitis [19]. The fact that there are relatively
fewer cases of protothecosis in AIDS patients than
other opportunistic infections suggests that a type of
immunodeficiency other than that caused by AIDS
may contribute to susceptibility to protothecosis [19].
Neutrophils engulf the protothecae, and their degranu-
lation and oxidative metabolism are necessary for the
killing [6]. There are reports of HIV-negative indivi-
duals with neutrophils incapable of killing Prototheca
[19]. A local or systemic immunosuppressive factor is
found in half the cases of protothecosis. The cutaneous
lesions are located mainly in exposed areas like the
extremities and face; other infection sites described are
the peritoneum, gall bladder, liver, intestine, catheter
entry site, CNS and nasopharynx. From the 107
reported cases (including the present one), 71 are
cutaneous protothecosis, 18 olecranon bursitis and 18
systemic protothecosis. Table 1 lists the location of
lesions, predisposing factors, treatment and therapeutic
response in the cases described in the literature.
The skin lesions have a variable appearance: erythe-
matous plaques, pustules, papules, nodules, verrucous
lesions, vesicles, ulcers and hypo-pigmented or atrophic
lesions [3,5,17,23,26]. Manifestations of post-operative
infection include synovitis, tenosynovitis and chronic
discharge from the surgical wound [3]. The majority of
patients with protothecosis are over 30 years of age, but
cases have been described in children [3,31,44]. Cases of
disseminated infection have been observed in both
immunocompromized and immunocompetent indivi-
duals. Protothecosis is generally not suspected clini-
cally, and patients are submitted to various treatment
modalities for long periods of time without satisfactory
results. Nevertheless, when there is a suspicion of
fungal infection and a biopsy and/or culture for fungus
is requested, the correct diagnosis is reached without
difficulty. For example, if a skin biopsy is sent only for
routine smear and culture, the organisms are not easily
recognized on Gram stain. However, considering that
in a Gram smear from blood agar most cells stain deep
purple with no internal structure discernible resembling
yeasts [12], a suspicion of fungal etiology could be
raised at this point. The H&E stain is of limited value
for studying Prototheca cells in details, as the organ-
isms are usually visible but do not stain uniformly.
Often only the outlines of organisms are observed and
Prototheca cells may be overlooked when they are
sparse. Usually, however, because of their distinctive
appearance and tendency to grow in large compact
clusters, Prototheca cells can be easily detected [16].
The etiological diagnosis depends on the morpholo-
gical identification of the microorganism in culture or
directly in the tissue. Prototheca spp. grow rapidly in
Sabouraud agar without cycloheximide at 25 /328C,
forming white or creamy colonies in 48 h, with an
appearance similar to that of yeast colonies. Lactophe-
nol cotton blue slide preparations of these colonies
reveal the characteristic sporangia of various sizes,
Downloaded from https://academic.oup.com/mmy/article/42/2/95/964350 by guest on 20 April 2021
containing sporangiospores. A lactophenol cotton blue
wet mount should be performed with every fungal
culture to prevent misidentification if, for instance, it
occurs with the utilization of API 20C [43]. PAS,
Gridley and Gomori /Grocott are superior to H&E
for detecting Prototheca cells; the cell wall and internal
sporangiospores of intact cells are well delineated with
these stains [15,16,49]. The histological characteristics
of the lesions include granulomatous inflammation
with giant cells, histiocytes, lymphocytes, plasmocytes
and the abundant presence of extracellular microorgan-
isms [3,5,17,23]. The species can be differentiated by
sugar assimilation tests and by the use of 50 mg
clotrimazole discs [50,51] (Table 2). In the study of
Casal [51] inhibition was defined as a zone of inhibition
of 10 mm or more. All strains of P. zopfii (n /21) were
resistant to clotrimazole (inhibition zone: 0). All strains
of P. wickerhamii (n /44) were susceptible with an
average inhibitory zone diameter of 23 mm (range 10/
36 mm). Similarly, all strains of P. stagnora (n /10)
were susceptible with an average inhibitory zone
diameter of 20 (range 10/30) mm, although P. stagnora
does not grow well at 378C, the temperature of the
incubation. Fluorescein-bound species-specific antibo-
dies are also used for species differentiation [52]. In the
literature, from the 74 cases of protothecosis identified
to the species level, 70 involved Prototheca wickerhamii
and four Prototheca zopfii (all from different loca-
tions).
Since the first reported human case, various treat-
ment regimens have been attempted, but there has been
no consistency in the clinical response. Antifungals like
ketoconazole, itraconazole, fluconazole and amphoter-
icin B are the most effective drugs to date. Among these
drugs, amphotericin B displays the best activity against
Prototheca. Table 3 shows the minimum inhibitory
concentrations for various drugs used against Proto-
theca . Takaki et al . [41], in a case with 6 years’
evolution without having achieved elimination of the
microorganism, report that in a 3-year interval, the
– 2004 ISHAM, Medical Mycology, 42, 95 /106
 Protothecosis 99

Table 1 Cases of human protothecosis reported in the literature

Patient Age Medical history Site or type of Diagnosis Treatment Dose Outcome Reference
no. (years)/ infection
sex

1 30/M DM, renal Forearm and thigh Histopathology Gentamicin, 120 mg i.v./ Death by Gram- Wolfe, 1976
transplantation vesicles and culture P. tetracycline day, 1 g/day negative sepsis
wickerhamii
2 65/M Alcoholism Olecranon bursitis Histopathology Bursectomy Cure Kapica, 1981
and culture P.
wickerhamii
3 34/F Chronic sinusitis, Scaling plaques Histopathology Am B i.v., 150 mg/week Cure Venezio, 1982
pneumonia (/4) (50% of skin and culture P. tetracycline for 6 weeks, 2
surface) wickerha g/day for 5
weeks
4 72/M None given Elbow nodule Histopathology Excision Cure Agostini, 1983
Prototheca spp.

Downloaded from https://academic.oup.com/mmy/article/42/2/95/964350 by guest on 20 April 2021

5 46/F Steroids: topical and Postoperative incision, Histopathology Ketoconazole 200 mg/day Cure Pegram, 1983
systemic, moderate infection (wrist and culture P. for 10 weeks
alcoholism tenolysis) wickerhamii
6 45/M DM, steroi- Arm nodule Culture P. Ketoconazole, 400 mg/day No response McAnally, 1985
dependent asthma, wickerhamii Am B/tetracycline for 6 weeks, Cure
chromomycosis 6 1956 mg/2 g
months ago per day for 3
months
7 44/M DM, renal Fingers, ulcerative Histopathology Am B Long course Cure Wolfson, 1985
transplantation celullitis Prototheca spp. Debridement
8 65/F Steroids: topical and Chest papules Histopathology Tetracycline 500 mg/day Cure Tyring, 1989
systemic and culture P. Am B: topical for 6 months
wickerhamii cream 6 months
9 62/F Wrist surgery Tenosynovitis Histopathology Ketoconazole, 400 mg/day No response Moyer, 1990
and culture P. Am B 865 mg Cure
wickerhamii
10 39/M None considered Elbow nodular Histopathology Itraconazole 50 mg/day for Cure Pierard, 1990
lesions Prototheca spp. 2 months
11 7/M Hodgkin’s Catheter tip Culture P. Am B 90 mg Cure Heney, 1991
lymphoma wickerhamii Catheter removal
12 30/M None given Left foot Histopathology Emetine, 1.8 g, three No response Iacoviello, 1992
and culture P. penicillin i.m. KI, courses; 2 g (Davies, 1964)
zopfi griseofulvine d.i.a. for 158
days
13 45/F Breast cancer, DM, Lower extremity Culture P. Topical therapies, No response Iacoviello, 1992
Cushing’s syndrome lesions wickerhamii radiotherapy (Tindall, 1971)
14 63/M None given Olecranon bursitis Histopathology Bursectomy Cure Iacoviello, 1992
Prototheca spp. (Tindall, 1971)
15 62/M None given Olecranon bursitis Histopathology Bursectomy Cure Iacoviello, 1992
Prototheca spp. (Tindall, 1971)
16 43/M Surgery Left hand nodule Histopathology Resection ? Iacoviello, 1992
Prototheca spp. (Tindall, 1971)
17 58/M None given Olecranon bursitis Culture P. Bursectomy, 4 weeks Cure Iacoviello, 1992
wickerhamii isoniazide (Nozanchuk, 1973)
18 29/M None given Rash on forehead Culture (blood, Am B/transfer 3300 mg/2 U Great Iacoviello, 1992
forehead) P. wick- factor improvement (Cox, 1974)
erhamii
19 30/F DM Wound infection Culture P. None ? Iacoviello, 1992
wickerhamii (Lee, 1975)
20 20/F Excellent health Cheek Culture P. Am B 616 mg Improvement Iacoviello, 1992
wickerhamii (Mayhall, 1976)
21 39/M None given Olecranon bursitis Histopathology Bursectomy Cure Iacoviello, 1992
Prototheca spp. (Grocott, 1979)
22 72/M None given Olecranon bursitis Histopathology Bursectomy Cure Iacoviello, 1992
Prototheca spp. (Ahbel, 1980)
23 17/F Surgery, ganglion Hand abscess Culture P. Multiple Cure Iacoviello, 1992
removal wickerhamii excisions (Holcomb, 1981)
24 48/F Renal Forearm cellulitis Culture P. None ? Iacoviello, 1992
transplantation, wickerhamii (Mezger, 1981)
steroids,
cyclophosphamide

– 2004 ISHAM, Medical Mycology, 42, 95 /106

100 Leimann et al.

Table 1 (Continued )

Patient Age Medical history Site or type of Diagnosis Treatment Dose Outcome Reference
no. (years)/ infection
sex

25 41/F SLE Skin (extensive) Culture P. Am B 2 months Cure Iacoviello, 1992

wickerhamii (Thianprasit, 1983)
26 ?/M None given Left leg Culture P. Excision Cure Iacoviello, 1992
wickerhamii (Thianprasit, 1983)
27 74/M None given Olecranon bursitis Histopathology Bursectomy Cure Iacoviello, 1992
Prototheca spp. (Vernon, 1983)
28 8 weeks None given Gastroenteritis Culture P. None ? Iacoviello, 1992
/? wickerhamii (Casal, 1983)
29 62/F COPD, CHF, Elbow, hand Culture P. Tetracycline, ? No response, Iacoviello, 1992
hypothyroidism, wickerhamii chlorhexidine death from (Heitzmar, 1984)
DJD, steroids other causes
30 41/F CAPD, analgesic Peritonitis Culture (PD PD catheter 250 mg i.p. Cure Iacoviello, 1992

Downloaded from https://academic.oup.com/mmy/article/42/2/95/964350 by guest on 20 April 2021

nephropaty fluid) P. removal, Am B (O’Connor, 1986)
wickerhamii i.p., i.v.
31 52/F Connective-tissue Olecranon bursitis Culture P. Am B intrabursal 2 mg/s.e.m. Cure Iacoviello, 1992
disease, steroids wickerhamii /6 s.e.m. (Cochrane, 1986)
32 61/F Myasthenia gravis Presternal blister-like Histopathology Topical polymixin Cure Iacoviello, 1992
lesions Prototheca spp. B, bacitracin, (Goldstein, 1986)
neosporin
33 68/M None given Olecranon bursitis Culture P. zopfi Bursectomy Cure Iacoviello, 1992
(Naryshkin, 1987)
34 6/F None given Vulva Culture P. Gentian violet, ? Cure Iacoviello, 1992
wickerhamii steroids (Nelson, 1987)
35 ?/F None given Leg Culture P. None Cure Iacoviello, 1992
wickerhamii (Nelson, 1987)
36 28/F Dermatitis Fingers Culture P. None Cure Iacoviello, 1992
wickerhamii (Nelson, 1987)
37 46/M Asthma, Finger Culture P. None ? Iacoviello, 1992
alcoholism wickerhamii (Nelson, 1987)
38 39/F Psoriasis Scalp Culture P. None ? Iacoviello, 1992
wickerhamii (Nelson, 1987)
39 30/F None given Gastroenteritis Culture P. None ? Iacoviello, 1992
wickerhamii (Nelson, 1987)
40 72/M None given Olecranon bursitis ? Prototheca spp. Bursectomy ? Iacoviello, 1992
(Nelson, 1987)
41 36/F None given Olecranon bursitis Histopathology Bursectomy Cure Iacoviello, 1992
Prototheca spp. (Nelson, 1987)
42 60/M None given Histopathology None ? Iacoviello, 1992
Prototheca spp. (Nelson, 1987)
43 40/M Alcoholism, Forehead, scalp Histopathology ? Regression/ Iacoviello, 1992
malnutrition Prototheca spp. recurrence (Nelson, 1987)
44 ?/F None given Cheek, conjunctiva Histopathology Excision ? Iacoviello, 1992
Prototheca spp. (Nelson, 1987)
45 17/F None given Leg Histopathology Topical and No response Iacoviello, 1992
Prototheca spp. systemic (Nelson, 1987)
antibiotics
46 48/M None given Olecranon bursitis Culture P. Bursectomy Cure Iacoviello, 1992
wickerhamii (Nelson, 1987)
47 70/M Arthritis, Olecranon bursitis Culture P. ? ? Iacoviello, 1992
leucopenia, Felty’s wickerhamii (Nelson,1987)
syndrome, steroids
48 61/F Uterine cancer, Fingers Culture P. ? Death from Iacoviello, 1992
radiotherapy wickerhamii other events (Nelson, 1987)
49 65/M None given Thumb Culture P. None ? Iacoviello, 1992
wickerhamii (Nelson, 1987)
50 12/M None given Inguinal skin Histopathology None ? Iacoviello, 1992
Prototheca spp. (Nelson, 1987)
51 42/M None given Olecranon bursitis Culture P. Bursectomy ? Iacoviello, 1992
wickerhamii (Nelson, 1987)
52 65/M None given Olecranon bursitis Culture P. Bursectomy ? Iacoviello, 1992
wickerhamii (Nelson, 1987)
53 18/F Surgery Hand Histopathology None ? Iacoviello, 1992
Prototheca spp. (Nelson, 1987)
54 ?/? None given Foot Histopathology None ? Iacoviello, 1992
Prototheca spp. (Nelson, 1987)

– 2004 ISHAM, Medical Mycology, 42, 95 /106

 Protothecosis 101

Table 1 (Continued )

Patient Age Medical history Site or type of Diagnosis Treatment Dose Outcome Reference
no. (years)/ infection
sex

55 73/F DM, breast cancer, Skin Culture P. None ? Iacoviello, 1992

renal failure, heart wickerhamii (Nelson, 1987)
failure, LL
56 5/F None given Upper lip Culture P. Ketoconazole ? Good response Iacoviello, 1992
wickerhamii (Kuo, 1987)
57 24/F Surgery Hand Histopathology Excision Am B ? Cure Iacoviello, 1992
Prototheca spp. (1 dose)/ (Sirikulchayanonta,
tetracycline 1989)
58 62/M None given Lower back Culture P. 5 FC, oral 2 months No effect Iacoviello, 1992
wickerhamii Excision Cure (Otoyama, 1989)
59 39/M None given Gall bladder, liver, Culture P. Am B, 570 mg Cure Iacoviello, 1992
peritoneum wickerhamii ketoconazole 3 months (Chan, 1990)

Downloaded from https://academic.oup.com/mmy/article/42/2/95/964350 by guest on 20 April 2021

60 72/M CAPD, Peritonitis Culture (PD PD catheter 650 mg IV /? Cure Iacoviello, 1992
hypertension, fluid) P. removal, Am B (Sands, 1991)
atherosclerosis wickerhamii i.v./doxycycline
61 45/M DM, CAPD Peritonitis Culture P. Am B IP (5 mg/L)1/ Cure Iacoviello, 1992
wickerhamii 5 FC IP (100 mg/L)/1 (Gibb, 1991)
Fluconazole 6 weeks
Catheter removal
62 24/F DM, coma, renal Nasopharynx soft Histopathology Am B, excision 2000 mg Cure Iacoviello, 1992
failure tissue mass and culture P.
wickerhamii
63 25/F AIDS Meningitis (1, Culture Am B 5 FLU 7.8 g for 6.5 Death Kaminski, 1992
Cryptococcus ; 2, P. wickerhamii months 1250
Prototheca ) mg q.i.d. for 4
months
64 ?/M None given Olecranon bursitis Histopathology ? ? Ravisse, 1993
Prototheca spp. (Nosanchuk, 1973)
65 ?/F None given Olecranon bursitis Histopathology ? ? Ravisse, 1993
Prototheca spp. (Nosanchuk, 1973)
66 ?/M None given Face Culture P. ? ? Ravisse, 1993
wickerhamii (Sudman, 1974)
67 29/F None considered Face Histopathology Am Bp
/ olymyxin ? ? Ravisse, 1993
Prototheca spp. (Yip, 1976)
68 18/F Cleanning, steroids Hand (surgery scar) Histopathology ? ? Ravisse, 1993
Prototheca spp. (Walker, 1981)
69 42/F None given Skin Histopathology Ketoconazole ? ? Ravisse, 1993
and culture P. (Shibata, 1983)
wickerhamii
70 30/F Trauma Foot Histopathology ? ? Ravisse, 1993 (Jones,
Prototheca spp. 1983)
71 30/F None given Enteritis Culture ? ? Ravisse, 1993
P. wickerhamii (Casal, 1983)
72 ?/M None considered Calf Histopathology ? ? Ravisse, 1993
and culture P. (Vernon, 1983)
wickerhamii
73 52/M Liver failure Arm, leg Histopathology Clotrimazole ? ? Ravisse, 1993
Prototheca spp. (Matsuda, 1991)
74 15/M None given Small intestine, liver Histopathology Am B/ ? ? Ravisse, 1993
and culture P. fluconazole (Matsuda, 1991)
wickerhamii
75 80/M None considered Arm Histopathology Ketoconazole ? ? Ravisse, 1993
and culture P. (Matsuda, 1991)
wickerhamii
76 13/M Anemia Small intestine/lymph Histopathology Am B ? ? Ravisse, 1993
nodes and culture P. (Matsuda, 1991)
wickerhamii
77 81/M Fisherman: Erythematous nodules Histopathology Ketoconazole 15 days No Response Ravisse, 1993
hypoproteinemia in hand and culture P. Itraconazole 200 mg/day Cure
wickerhamii for 30 days
78 44/M Fisherman: renal Ulcerate erythematous Histopathology Local excision/ Cure Tejada, 1994
transplantation, nodules in finger and culture P. tetracycline oral
azatioprine/ wickerhamii
steroids

– 2004 ISHAM, Medical Mycology, 42, 95 /106

102 Leimann et al.

Table 1 (Continued )

Patient Age Medical history Site or type of Diagnosis Treatment Dose Outcome Reference
no. (years)/ infection
sex

79 33/M AIDS/leg skin B Erythematous Histopathology Am B Death from Woolrich, 1994

cell lymphoma verrucous plaque in and culture other events
hand P. wickerhamii
80 64/M None considered Verrucous plaque in leg Histopathology No return Mendez, 1995
and culture P.
zopfi
81 51/M Methastatic lung Olecranon bursitis Histopathology 1. doxycycline, 200 mg/day Cure Montclos, 1995
cancer/car and culture P. 2. topical am B, for 2 months,
accident wickerhamii 3. resection 1m
82 70/M Farmer; B hepatitis Erythematous ulcerate Histopathology Itraconazole/ 200 mg/day Incomplete Tang, 1995
plaque in leg and culture P. debridement for 5 weeks resolution
wickerhamii

Downloaded from https://academic.oup.com/mmy/article/42/2/95/964350 by guest on 20 April 2021

83 20/M Local trauma Plaque with ulcer on Histopathology Local 200 mg/day Great Monopoli, 1995
knee and culture P. tioconazol/ for 1 month, improvement
wickerhamii itraconazole/ 100 mg/day
doxycycline for 1 month
84 80/F COPD, CHF, Erythema and papules Histopathology Erythromycin ? Failure Boyd, 1995
hypertension, DM, of the arm, forearm and culture P. itraconazole 200 mg/day Cure
chronic use of and hand wickerhamii for 2 weeks
oral steroids
85 55/F Intralesional Erythematous nodules Histopathology Itraconazole, 200 mg/day No response Kim, 1996
injections of steroids on left foot and culture P. fluconazole for 8 weeks, Cure
for lichen simplex wickerhamii 200 mg/day
for 4 weeks
86 59/F End-stage COPD, Disseminated Culture P. zopfi Death from Kwok, 1996
single lung protothecosis (blood pulmonary
transplant and urine) hemorrage
87 20/M Anemia 1, liver/abdominal 1, histopathology 1, micon./am ? 1, cure, 2 Takaki, 1996
and in ileum Prototheca spp., B IV Prototheca not
submucosa lymph 2, culture P. wick- 2, micon./ erradicated in 6
nodes, 2, meningitis erhamii fluconazole IV; years,
am B IV and observation
intraventricular;
itraconazole
88 39/M AIDS-related Hypopigmented Histopathology itraconazole 400 mg/day No response Carey, 1997
lymphoma papules on nose and and culture P. am B for 9 days, 0.5 Cure
forehead wickerhamii mg/[kg/day]
for 2 w
89 ? AIDS Tenosynovitis ? Surgery Cure Carey, 1997
(Laeng, 1994)
90 27/F None considered Onychoprothotecosis Culture P. Fluconazole 100 mg/day Cure Gálan, 1997
wickerhamii for 12 weeks
91 75/M Myasthenia gravis Blood (three positive Culture P. Am B, Am B 635 mg, 5 mg/ Cure Mohabeer, 1997
for 2 years, steroid samples), papulonodu- wickerhamii lipossomal [kg/day] for
and cyclosporin use lar rash on hand 21 days
92 25/M AIDS, local trauma Skin lesion Histopathology Surgical excision Temporarily Polk, 1997
and swimming in and culture P. asymptomatic
lake wickerhamii (recidivation
after 8 months)
93 78 Preterm neonate (26 Endocarditis Histopathology Resection of 20 mg (total) Cure Buendı́a, 1998
days/ weeks) with and culture atrium mass
M respiratory support Prototheca spp. (thrombus)/Am
B
94 61/M Corticosteroid- Disseminated Histopathology Fluconazole IV 400 mg/day Death Marr, 1998
dependent COPD, protothecosis and culture P. for 2 weeks
chronic aseptic wickerhamii
olecranon bursitis,
adenocarcinoma
95 36/M Chronic Abdominal pain/diar- Histopathology Am B itracona- 5 g for 4 No response Raz, 1998
mucocutaneous can- rhea/terminal ileum Prototheca spp. zole itra/INF-g months, 400 No response
didiasis and duodenal polyps s.c. mg/day for 4 reduction in size
months/300 of polyps
mg/week for 6
months

– 2004 ISHAM, Medical Mycology, 42, 95 /106

 Protothecosis 103

Table 1 (Continued )

Patient Age Medical history Site or type of Diagnosis Treatment Dose Outcome Reference
no. (years)/ infection
sex

96 63/F DM/topical Erythematous plaque/ Histopathology 1, ketoconazole 8 months 1, partial Walsh, 1998
steroids/swimming papules on and culture P. 2, excision resolution
in inland waters elbow wickerhamii 2, cure
97 52/M Excision of foot Surgical scar with Histopathology 1, antibiotics/ 12 days 1, no response, Walsh, 1998
neuroma/topical chronic discharge on Prototheca spp. fluconazole i.v., 2, 2, cure
corticosteroid foot (negative Am B i.v./exci-
injection/water culture)) sion
physiotherapy
98 60/F Acute myelocytic Violaceous Histopathology Am B 10 days Cure Wirth, 1999
leukemia subcutaneous nodules Prototheca spp.
on extremities (negative culture)
99 72/F DM, hemodyalisis Erythematous plaques, Histopathology Am B ? ? Schumann, 2000

Downloaded from https://academic.oup.com/mmy/article/42/2/95/964350 by guest on 20 April 2021

small ulcerations, fistu- Prototheca spp.
lous tracts on leg (negative culture)
100 72/F Trauma on arm, Infiltrated erythema- Histopathology Fluconazole VO 150 mg/day Cure Follador, 2001
long-term topical tous plaques on arm and culture P. for 1 month,
steroid cream and forearm wickerhamii 150 mg/week
for 2 months
101 77/M DM Erythematous plaque/ Histopathology Am B i.v./ 2 g/day Cure Chao, 2002
pustules/ and culture P. tetracycline
ulcers on leg wickerhamii oral
102 71/M Arthritis, steroid Erythematous scaling Histopathology Am B intrale- 3 weeks Cure Chao, 2002
misuse, topical plaque/ papules on and culture P. sional
steroid forearm wickerhamii
103 69/M Bronchial asthma, Diffuse erythema and Histopathology Itraconazole, 200 mg/day No response, Chao, 2002
arthritis, long-term infiltrating nodules and culture P. fluconazole/ for 3 weeks, death from
steroid use on both forearms wickerhamii topical Am B 200 mg/d other events
twice a day
104 67/F DM, iatrogenic Pyoderma-like Histopathology Fluconazole VO 200 mg/day Cure Chao, 2002
Cushing syndrome papules/plaques with and culture P. for 3 weeks
ulcers wickerhamii
105 43/F Topical steroids Erythematous plaque Histopathology Ketoconazole VO 200 mg/day Cure Chao, 2002
on nose Prototheca spp. d.f. for 7
weeks
106 42/M AIDS Erythematous papules Histopathology Ketoconazole VO 400 mg/day No response Piyophirapong,
on back and culture P. am B IV for 3 weeks, Cure 2002
wickerhamii cumulative 2 g
107 59/F Local steroid Finger Culture P. wicker- Itraconazole, Failure Present report
infiltration hamii fluconazole Improvement

5FC, flucytosine; Am B, amphotericin B; CAPD, continuous ambulatory peritoneal dialysis; CHF, congestive heart failure; COPD, chronic
obstructive pulmonary disease; DJD, degenerative joint disease; DM, diabetes mellitus; IP, intraperitoneal; LL, lymphocytic leukemia; PD,
peritoneal dyalisis; SLE, systemic lupus erythematous.

minimum inhibitory concentration of amphotericin B
increased from 0.39 to 3.13 mg/ml and that of flucona-
zole from 50 to 200 mg/ml. Venezio [5] reports algicidal
action by amphotericin B at a concentration of 0.39 mg/
ml and resistance by Prototheca to 5-fluorocytosine
(MIC /50 mg/ml), miconazole (MIC /12.5 mg/ml) and
tetracycline (MIC /200 mg/ml); synergistic action be-
tween amphotericin B (at a concentration of 0.1 mg/ml)
and tetracycline (at a concentration of 6.25 mg/ml) was
shown in vitro. The author refers to studies on the

Table 2 Physiological characteristics in the differentiation of Prototheca species

Species Clotrimazole Carbohydrates

(50 mg discs)
saccharose trehalose n-propanol

P. stagnora / /** / /
P. wickerharmii /* / /*** /
P. zopfii / / / /

*Production of inhibition zone; **assimilation after 14 days; ***assimilation within 7 days.

– 2004 ISHAM, Medical Mycology, 42, 95 /106

104 Leimann et al.
Table 3 Minimum inhibitory concentration of different agents
against Prototheca
Drug MIC (mg/ml) References
Amphotericin B 0.15 /12.5 3,12,19,26,29,43,45,53
Ketoconazole 1 /60 3,5,25,26
Itraconazole 0.39 / /8 19,41,43,45
Fluconazole 8 / /200 19,41,43,45
Tetracycline /100 3,5,26
combination of amphotericin B and tetracycline as a
possible treatment for fungal infections in vitro and in
animal models of fungal infections. The patient with
cutaneous protothecosis was the first to receive this
combination ‘in an effort to improve serum algacidal
activity as predicted from in-vitro testing’ [5]. Following
were three more cases of cutaneous protothecosis
[17,26,28] also successfully treated with this combina-
tion. In one case [28], amphotericin B cream was used.
A study of some Prototheca isolates revealed good in-
vitro sensitivity to gentamicin at similar concentrations
to levels reached in blood serum; however, both cases in
which gentamicin was used resulted in treatment failure
[38]. The fact is that there is no direct correlation
between in-vitro activity and clinical response; further-
more, it is not clear whether susceptibility tests to
antifungal agents are reliable for evaluating algae.
Local application of amphotericin B has been reported
in some studies and in some cases cure was achieved by
using it as monotherapy [3,17,28,35]. Combined surgi-
cal and clinical treatment is recommended for localized
lesions. According to Boyd [38], patients with suspected
protothecosis should receive IV amphotericin B asso-
ciated with oral tetracycline (2 g/day). If oral therapy is
indicated, an azole antifungal agent should be con-
sidered. Debridement of the infected tissues is useful,
particularly in patients with contaminated surgical
wounds. Ideal treatment duration has not been deter-
mined, but it can vary from 2 weeks to 4/6 months,
according to the different published cases, depending
greatly on the severity of the infection.
Discussion
The majority of protothecosis cases present as localized
skin lesions. Some systemic or local predisposing factor
can be identified in nearly all patients. Our patient had
a history of local trauma followed by local steroid
infiltration and handling of soil during home garden-
ing, making it difficult to determine the precise
moment of Prototheca infection.
The diagnosis of protothecosis is not difficult. The
microorganism forming sporangia with their endo-
spores can be viewed in wet-mount microscopy of
secretion from the lesion or on histopathological
examination with specific staining; culture is positive
at 48 h in Sabouraud agar at room temperature.
Diagnosis of protothecosis should be considered and
investigated with the following: (i) skin lesions with
sub-acute or chronic evolution (suppurative lesions,
nodules, papules, erythematous plaques) with a poor
clinical response or relapse after conventional thera-
pies; (ii) olecranon bursitis; (iii) infection related to
catheter tips or systemic infections without isolation of
a specific agent or with treatment failure.
The ideal therapeutic approach has still not been
completely established. Intravenous amphotericin B
Downloaded from https://academic.oup.com/mmy/article/42/2/95/964350 by guest on 20 April 2021
associated with oral tetracycline can be the treatment
of choice in either systemic or disseminated cutaneous
cases. In other cases, intralesional application of
amphotericin B can be considered, and surgical exci-
sion has a precise indication; doubt remains as to the
azole to be employed. According to Lacaz [15],
ketoconazole is not active against Prototheca spp.
In the literature, as observed in the present case,
fluconazole appears to present clinical efficacy some-
what superior to that of itraconazole, despite the high
MIC values observed in vitro [19,41,43]. With the
exception of the combination of amphotericin B with
tetracycline due to the synergism against Prototheca
spp., the concomitant administration of antibiotics
based on the presence of secondary bacterial infection
has not been described. In our patient it was necessary
to use concomitant antibiotics twice in order to quell
the secondary bacterial infection.
Conclusion
As more immunodeficient patients are being treated
with invasive and aggressive protocols, for instance in
oncology and transplant units, the incidence of infec-
tions caused by unusual organisms is bound to increase.
Protothecosis usually is not suspected clinically. How-
ever, in most cases the clinical manifestations can often
raise suspicion of unusual or deep fungal infections. If
the diagnosis is not made promptly, Protothecae can
produce chronically destructive lesions, even in immu-
nocompetent hosts.
It is likely that protothecosis is underreported. At the
laboratory, Prototheca may be confused with yeasts
such as Candida or Cryptococcus species on Gram
stain. Also, unless special stains are performed, the
morphology of the organisms may be missed on tissue
sections. Nevertheless, the diagnosis of protothecosis
presents no difficulty. The typical aspect of sporangium
with sporangiospores can be easily viewed in wet-
– 2004 ISHAM, Medical Mycology, 42, 95 /106

mount microscopy and on histopathologic examination
with specific staining. One only has to be alert.
Acknowledgements
We thank Patrı́cia Tavares, IPEC/FIOCRUZ, for con-
firming identification of P. wickerhamii and Maria José
Mendes-Giannini, Clinical Analysis Department, Fa-
culty of Pharmaceutical Sciences, UNESP (Arara-
quara, São Paulo), for performing the susceptibility
tests.
References
1 Rippon JW. Medical Mycology. Philadelphia: WB Saunders
Company, 1988.
2 Rodriguez-Tudela JL, Berenguer J, Martinez-Suarez JV, Sanchez
R. Comparison of a spectrophotometric microdilution method
with RPMI-2% glucose with the National Committee for Clinical
Laboratory Standards reference macrodilution method m27-p for
in-vitro susceptibility testing of amphotericin B, flucytosine and
fluconazole against Candida albicans. Antimicrob Agents Che-
mother 1996; 40: 1998 /2003.
3 Iacoviello VR, DeGirolami PC, Lucarini J, Sutker K, Williams
ME, Wanke CA. Protothecosis complicating prolonged endotra-
cheal intubation: Case report and literature reviews. Clin Infect
Dis 1992; 15: 959 /967.
4 Pore RS, Barnett EA, Barnes WC Jr, Walker JD. Prototheca
ecology. Mycopathologia 1983; 81: 49 /62.
5 Venezio FR, Lavoo E, Williams JE, Zeiss CR, Caro WA,
Mangkornkanok-Mark M, Phair JP. Progressive cutaneous pro-
tothecosis. Am J Clin Pathol 1982; 77: 485 /493.
6 Wirth FA, Passalacqua JA, Grace K. Disseminated cutaneous
protothecosis in an immunocompromised host: a case report and
literature review. Cutis 1999; 63: 185 /188.
7 Walsh SV, Johnson RA, Tahan SR. Protothecosis: an unusual
cause of chronic subcutaneous and soft tissue infection. Am J
Dermatopathol 1998; 20(4): 379 /382.
8 Zaitz C, Campbell I, Marques AS, Ruiz LRB, Souza VM.
Compêndio de Micologia Médica. Rio de Janeiro: MEDSI
Editora Médica e Cientı́fica, 1998.
9 El-Ani AS. Life cycle and variation of Prototheca wickerhamii .
Science 1967; 156: 1501 /1503.
10 Feo M. Cinco Cepas de Prototheca de origen humano. Mycopath
Mycol Appl 1972; 46: 53 /59.
11 Joshi KR, Gavin JB, Wheeler EE. The ultrastructure of Proto-
theca wickerhamii . Mycopathologia 1975; 56: 9 /13.
12 Kapica L. First case of human protothecosis in Canada:
Laboratory aspects. Mycopathologia 1981; 73: 43 /48.
13 Larone DH. Medically Important Fungi: A Guide to Identification ,
2nd edn. New York: Elsevier, 1987.
14 Patni NJ, Aaronson S. The nutrition, resistance to antibiotics and
ultrastructure of Prototheca wickerhamii . J Gen Microbiol 1974;
83: 179 /182.
15 Lacaz CS, Porto E, Martins JEC, Heins-Vaccari EM, Melo NT.
Tratado de Micologia Médica , 9th edn. São Paulo: SARVIER,
2002.
16 Chandler FW, Kaplan W, Ajello LA. Colour Atlas and Textbook
of the Histopathology of Mycotic Disease. Lochen: Wolfe Medical
Publications, 1980.
17 Chao S-C, Hsu M M-L, Lee JY-Y. Cutaneous protothecosis:
report of five cases. Br J Dermatol 2002; 146: 688 /693.
– 2004 ISHAM, Medical Mycology, 42, 95 /106
Protothecosis 105
18 Woolrich A, Koestenblatt E, Don P, Szaniawski W. Cutaneous
protothecosis and AIDS. J Am Acad Dermatol 1994; 31: 920 /924.
19 Carey WP, Kaykova Y, Bandres JC, Sidhu G, Bräu N. Cutaneous
protothecosis in a patient with AIDS and a severe functional,
neutrophil defect: successful therapy with amphotericin B. Clin
Infect Dis 1997; 25: 1265 /1266.
20 Polk P, Sanders DY. Cutaneous protothecosis in association with
the acquired immunodeficiency syndrome. South Med J 1997;
90(8): 831 /832.
21 Piyophirapong S, Linpiyawan R, Mahaisavariya P, Muanprasat
C, Chaiprasert A, Suthipinittharm P. Cutaneous protothecosis in
an AIDS patient. Br J Dermatol 2002; 146: 713 /715.
22 Kaminski ZC, Kapila R, Sharer RL, Kloser P, Kaufman L.
Meningitis due to Prototheca wickerhamii in a patient with AIDS.
Clin Infect Dis 1992; 15: 704 /706.
Downloaded from https://academic.oup.com/mmy/article/42/2/95/964350 by guest on 20 April 2021
23 Wolfe ID, Sacks HG, Samorodin CS, Robinson HM. Cutaneous
protothecosis in a patient receiving immunosuppressive therapy.
Arch Dermatol 1976; 112: 829 /832.
24 Agostini AA, Lisot JMC, Gonzales DHV. Protothecose do
cotovelo: relato de um caso. Rev Ass Med Bras 1983; 29: 178 /179.
25 Pegram PS, Kerns FT, Wasilauskas BL, Hampton KD, Scharyj
M, Burke JG. Successful ketoconazole treatment of protothecosis
with ketoconazole-associated hepatotoxicity. Arch Intern Med
1983; 143: 1802 /1805.
26 McAnally J, Parry EL. Cutaneous protothecosis presenting
as recurrent chromomycosis. Arch Dermatol 1985; 121: 1066 /
1069.
27 Wolfson JS, Sober AJ, Rubin RH. Dermatologic manifestations of
infections in immunocompromised patients. Medicine (Baltimore)
1983; 64: 115 /133.
28 Tyring SK, Lee PC, Walsh P, Garner JF, Little WP. 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.
29 Moyer RA, Bush DC, Denehy JJ. Prototheca wickerhamii
tenosynovitis. J Rheumatol 1990; 17: 701 /704.
30 Pierard GE, Rurangirwa A, Arresse Estrada J, Pierard-Franchi-
mont C. Protothecose cutanée traitée par itraconazole. Ann Soc
Belge Méd 1990; 70: 105 /112.
31 Heney C, Greef M, Davis V. Hickman catheter-related protothecal
algaemia in an immunocompromised child. J Infect Dis 1991; 163:
930 /933.
32 Ravisse P, de Bièvre C, Campos Magalhães M, Ramos I, Huerre
M. Protothecose cutanée traitée avec succès par l’itraconazole:
nouveau cas et revue générale dês protothécoses humaines. J
Mycol Méd 1993; 3: 84 /94.
33 Tejada E, Parker CM. Cutaneous erythematous nodular lesion in
a crab fisherman. Arch Dermatol 1994; 130(2): 244 /245, 247 /248.
34 Mendez CM, Silva-Lizana E, Logemann H. Human cutaneous
protothecosis. Int J Dermatol 1995; 34(8): 554 /555.
35 Montclos M, Chatté G, Perrin-Fayolle M, Flandrois JP. Olecra-
non bursitis due to Prototheca wickerhamii , an algal opportunistic
pathogen. Eur J Clin Microbiol Infect Dis 1995; 14: 561 /562.
36 Tang WYM, Lo KK, Lam WY, Fung KSC, Koehler A, Cheng
AFB. Cutaneous protothecosis: report of a case in Hong Kong. Br
J Dermatol 1995; 133: 479 /482.
37 Monopoli A, Accetturi MP, Lombardo G. Cutaneous protothe-
cosis. Int J Dermatol 1995; 34(11): 766 /767.
38 Boyd AS, Langley M, Kin LE. Cutaneous manifestation of
Prototheca infections. J Am Acad Dermatol 1995; 32(5): 758 /764.
39 Kim ST, Suh KS, Shae YS, Kim YJ. Successful treatment with
fluconazole of protothecosis developing at the site of an
106 Leimann et al.
intralesional corticosteroid injection. Br J Dermatol 1996; 135:
803 /806.
40 Kwok N, Schwartz SN. Prototheca sepsis in a lung transplant
patient. Clin Microbiol Newsletter 1996; 18(23): 183 /184.
41 Takaki K, Okada K, Umeno M, Tanaka M, Takeda T, Ohsaki K,
Takaki Y, Sawae Y. Chronic Prototheca meningitis. Scand Infect
Dis 1996; 28: 321 /323.
42 Galán F, Garcia-Martos P, Palomo MJ, Beltrán M, Gil JL, Mira
J. Onychoprotothecosis due to Prototheca wickerhamii . Myco-
pathologia 1997; 137: 75 /77.
43 Mohabeer AJ, Kaplan PJ, Southern PM, Gander RM. Algaemia
due to Prototheca wickerhamii in a patient with myasthenia gravis.
J Clin Microbiol 1997; 53(12): 3305 /3307.
44 Buendia A, Patiño E, Rijlaarsdam M, Loredo ML, Rivera E,
Ramı́rez S, Attie F. Endocarditis por alga del género Prototheca
sp. Saprofito del aga e de la savia de los árboles? Arch Inst Cardiol
Méx 1998; 68: 333 /336.
45 Marr KA, Hirschmann DT, Raugi GJ. Photo Quiz. Clin Infect
Dis 1998; 26: 575, 756 /757.
46 Raz R, Rottem M, Bisharat M, Sakran W, Nussinson E,
Trougouboff P, Sobel J. Intestinal protothecosis in a patient
with chronic mucocutaneous candidiasis. Clin Infect Dis 1998; 27:
399 /400.
47 Schumann K, Hollandworth K, Ormsby A. Non-healing leg
ulceration. Arch Dermatol 2000; 136(10): 1263 /1268.
48 Follador I, Bittencourt A, Duran F, Araújo MG. Cutaneous
protothecosis: report of the second Brazilian case. Rev Inst Med
Trop S Paulo 2001; 43(5): 1 /7.
49 Kwon-Chung KJ, Bennett JE. Medical Mycology. Philadelphia:
Lea & Febiger, 1992.
50 Lacaz CS, Porto E, Heins-Vaccari EM, Melo NT. Guia de
Identificação: Fungos, Actinomicetos e Algas de Interesse Médico.
São Paulo: SARVIER, 1998.
51 Casal M, Gutierrez J. Simple new test for rapid differentiation of
Prototheca wickerhamii from Prototheca zopfii . J Clin Microbiol
Downloaded from https://academic.oup.com/mmy/article/42/2/95/964350 by guest on 20 April 2021
1983; 18(4): 992 /993.
52 Sudman MS, Kaplan W. Identification of Prototheca species by
immunofluorescence. Appl Microbiol 1973; 25: 981 /990.
– 2004 ISHAM, Medical Mycology, 42, 95 /106