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Parasitic Sinusitis and Otitis in Patients Infected with Human Immunodeficiency
Virus: Report of Five Cases and Review
Viviane A. Dunand, Scott M. Hammer, Renee Rossi,
Mark Poulin, Mary A. Albrecht, John P. Doweiko,
Paola C. DeGirolami, Eoin Coakley, Eva Piessens, and
Christine A. Wanke
From the Department of Medicine, the Department of Surgery, and the
Department of Pathology, Beth Israel Deaconess Medical Center,
Boston, and Harvard Medical School, Boston, Massachusetts
We describe five cases of parasitic sinusitis and otitis in patients infected with human immunodeficiency virus (HIV) and review 14 reported cases. The pathogens identified in our group of patients
included agents such as Microsporidium, Cryptosporidium, and Acanthamoeba species. The clinical
features common to these patients included a long history of HIV seropositivity associated with
advanced immunosuppression and multiple opportunistic infections as well as long-standing local
symptoms refractory to multiple courses of antibacterial agents. Symptoms often included fever and
chills in addition to local tenderness and discharge. Invasive diagnostic procedures were necessary
to obtain the final diagnosis and to initiate appropriate therapy. Although most patients responded
at least partially to specific therapy, relapses and recurrences were frequent in patients who did not
receive long-term suppressive therapy. The general outcome for HIV-infected patients with parasitic
sinusitis and otitis was poor; however, deaths were generally associated with other complications
of the underlying HIV infection.
Optimal management of chronic HIV infection must include
recognition of and therapy for opportunistic infectious complications, including otolaryngological infections. A variety of
otolaryngological syndromes have been described in patients
with AIDS. Although bacterial and fungal sinusitis and otitis
in association with HIV infection has been reviewed [1], less
has been written about parasitic sinusitis and otitis in patients
with AIDS. Parasitic sinusitis and otitis, although still relatively
unusual, is being reported with increasing frequency in patients
with AIDS.
This report describes the clinical, radiographic, and laboratory features of parasitic sinusitis and otitis in patients with
advanced HIV infection who were seen at our institution. The
five patients described in this series were identified from records of HIV-infected patients seen at our Infectious Disease
Clinic between January 1993 and December 1995. The Infectious Disease Clinic provides primary and/or consultative care
for more than 500 HIV-infected patients in an urban setting.
We also review the 14 cases of HIV-infected patients with
sinusitis and otitis due to parasitic pathogens that were reported
in the literature.
Case Reports
Case 1. A 37-year-old homosexual man with AIDS presented to our facility with a history of chronic intermittent
Received 22 October 1996; revised 18 February 1997.
Reprints or correspondence: Dr. Christine A. Wanke, Division of Infectious
Diseases, Beth Israel Deaconess Medical Center, One Deaconess Road, West
Campus, Boston, Massachusetts 02215.
Clinical Infectious Diseases 1997;25:267–72
q 1997 by The University of Chicago. All rights reserved.
1058–4838/97/2502–0016$03.00
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sinusitis for 5 – 7 years; the infection was ultimately resistant
to multiple courses of antibiotics. He had ongoing severe nasal
congestion and loss of taste. Physical examination was remarkable for thickened and granular-appearing mucosa with polypoid tissue in the middle meatus and extending to the nasopharynx. He had not had any major opportunistic infections,
although his CD4 cell count at presentation was 0/mm3. Sinus
roentgenograms showed pansinusitis, which was confirmed by
a CT scan of the head. The scan did not reveal any bony
involvement.
The patient underwent endoscopic sinus surgery, which was
remarkable for granular tissue in the sinus cavities. The results
of routine bacterial cultures were negative. Electron microscopic examination of this sinus biopsy material revealed a
large number of microorganisms that were consistent with the
microsporidial species Encephalitozoon hellem. Examination
of stool and urine for microsporidia was negative. The patient
was treated with 400 mg of albendazole twice a day, and his
sinus symptoms decreased moderately. He received suppressive therapy until his death, which occurred 8 months later.
Case 2. A 32-year-old male homosexual with AIDS, hairy
leukoplakia, and a history of cytomegalovirus (CMV) pneumonitis presented to the hospital because of fevers, chills, sinus
congestion, and drainage. His CD4 cell count was 29/mm3.
Sinus roentgenograms as well as a CT scan of the head showed
pansinusitis without bony involvement. He underwent bilateral
maxillary antrostomies, and electron microscopic examination
of the sinus biopsy material showed microsporidia consistent
with E. hellem (figure 1). The results of routine bacterial cultures were negative. Examination of stool and urine for routine
microsporidia was negative. Therapy with albendazole (400
mg b.i.d.) was started. His sinus symptoms initially decreased
after 1 month of treatment. He did not receive suppressive
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Dunand et al.
Figure 1. Electron micrograph of microsporidial spores within a
parasitophorous vacuole in the sinus mucosa. The sinus specimen was
obtained from a 32-year-old male AIDS patient. Note the single row
of polar tube filaments in the spore, which is consistent with an
Encephalitozoon species (bar Å 1 mm; original magnification,
112,500).
therapy, and within 5 months the symptoms recurred. The patient was successfully retreated with the same medication. Suppressive therapy was continued, and there was no recurrence
of sinus symptoms at a follow-up visit 9 months later.
Case 3. A 35-year-old homosexual man with cutaneous
and mucosal Kaposi’s sarcoma had a 3-year history of cryptosporidial diarrhea, CMV retinitis, recurrent right otitis, and
chronic sinusitis that was refractory to multiple courses of
antibacterial agents. He presented to the hospital with hallucinations, fever, headaches, and malaise. His CD4 cell count
was õ10/mm3. Physical examination was remarkable for an
abnormal mental status examination, which predominantly revealed confusion. An MRI of the head showed pansinusitis and
periventricular signals consistent with CMV ventriculitis.
Electron microscopic examination of the middle turbinate
biopsy material demonstrated microsporidia that were consistent with E. hellem. The results of routine bacterial cultures
were negative. Examination of stool and urine for microsporidia was negative. PCR analysis of CSF specimens was positive for CMV. Therapy with ganciclovir was started. Albendazole treatment was not begun because of multiple complications
of the underlying illnesses.
Case 4. A 42-year-old homosexual man with AIDS had a
history of CMV infection, cryptosporidial gastrointestinal tract
infection, and a 5-year history of recurrent otitis. He presented
to the hospital with fevers, nasal stuffiness, and ear congestion
that had been increasingly symptomatic for 3 months. Physical
examination revealed fluid behind the right tympanic membrane. His CD4 cell count was 40/mm3, and liver function tests
revealed mildly elevated values. A CT scan of the head showed
clouding in the mastoids and a soft-tissue abnormality in the
middle ear bilaterally.
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The patient underwent bilateral myringotomies, and the
smear of the fluid from the middle ear showed numerous cryptosporidial oocysts (figure 2). He was treated with drainage
and topical acetazole drops. The initial response to treatment
was good, but when the tubes were removed, the patient experienced a recurrence of symptoms. The patient died 4 months
later of complications of his underlying illness. To our knowledge, no other case of cryptosporidial sinusitis or otitis has
ever been reported.
Case 5. A 37-year-old homosexual man with AIDS presented to our facility with a 3-month history of nasal discharge
that was refractory to multiple courses of antimicrobial agents.
He had ongoing severe nasal congestion with headaches and
facial pain. Physical examination was remarkable for nasal
passages that were impacted with hard brown crusts with pockets of purulence. The nasal septum and inferior turbinates were
eroded. The patient also had nodules (1 – 2 cm in diameter) and
papules that were disseminated on the lower extremities. His
CD4 cell count was 178/mm3. A CT scan of the head showed
mucosal thickening in the nasal vaults and osteomeatal complex.
The patient underwent endoscopic anterior ethmoidectomy
and maxillary antrostomies as well as skin biopsies. Histological examination of nasal biopsy and skin biopsy specimens
showed Acanthamoeba species in both locations (figure 3). The
patient was treated with 5-fluorocytosine, and he had some
response. This patient was not a swimmer and did not have a
history of exposure to fresh water that would have predisposed
him to Acanthamoeba species.
Discussion
We reviewed five cases of sinusitis and otitis in AIDS patients that were caused by Microsporidium, Cryptosporidium,
Figure 2. Cryptosporidial organisms (arrows) in a smear of fluid
from the middle ear of a 42-year-old male AIDS patient. On modified
Kinyoun stain, these organisms are clearly acid-fast (bar Å 5 mm;
original magnification, 11,200).
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Parasitic Sinusitis and Otitis in HIV
269
Figure 3. A: Septal perforation ( left ) and a nasal polypoid mass ( right ) caused by Acanthamoeba species in a 37-year-old man with AIDS.
B: Acanthamoeba (arrow) in a nasal biopsy specimen with inflammatory response (bar Å 15 mm; original magnification, 11,200).
and Acanthamoeba species. Although other parasites such as
Toxoplasma gondii cause respiratory illnesses in HIV-infected
patients, we found no reported cases of sinusitis or otitis caused
by these or other parasitic organisms.
Ten cases of microsporidial sinusitis in patients infected with
HIV have been reported [2 – 7] (table 1). It is possible that one
case was reported twice [4, 5]. Only two of the patients presented with symptoms limited to the sinus [3, 7]. Most of the
patients presented with symptoms consistent with multi-organ
microsporidial infection (e.g., fever, diarrhea, dysuria, bronchitis, nasal obstruction, and ocular discomfort). Accordingly, the
parasite was found most frequently at various sites (stool, urine,
sputum, sinus, and conjunctivae).
Two species, E. hellem and Septata intestinalis, were reported to be the cause of these infections with equal frequency.
S. intestinalis has been reclassified as Encephalitozoon intestinalis. Different diagnostic methods were used in these reports,
but the diagnosis was confirmed in each case by histologic
examination or electron microscopy [4]. Every patient except
one received albendazole therapy (400 mg b.i.d. orally) for 15
days to 1 month; this one patient received topical treatment
with propamidine isethionate (0.1% 6 times daily) [3]. There
was clear reduction in the sinus symptoms in all reported cases.
Symptomatic relapses were frequent, even for patients who
received suppressive therapy.
Acanthamoeba infection is a rare complication in immunocompetent or immunocompromised patients. This free-living
amoeba typically involves the skin and CNS by disseminating
from a primary focus in the lungs or respiratory tree [9]. It has
been reported to occasionally cause skin nodules and ulcerations in patients with AIDS. To our knowledge, only four
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cases of acanthamoeba infection involving the sinuses and skin
without CNS involvement have been described in patients with
AIDS [8 – 11]. (table 2).
Microsporidia are the most frequently recognized causes of
parasitic sinusitis in patients with AIDS. However, awareness
that parasitic agents can produce otolaryngological infections
in HIV-infected patients may lead to increased recognition of
cases and may potentially, through more-aggressive diagnostic
procedures and earlier initiation of specific therapy, lead to a
better understanding of the true prevalence of disease, its natural history, and outcome.
In our cases and in cases reported in the literature, parasitic
otolaryngological infections occurred in patients who had advanced AIDS and who were severely immunocompromised,
i.e., with CD4 cell of counts õ20/mm3. To our knowledge,
none of the patients described in this report used nasal drugs.
Most patients had symptomatic sinus or otic disease for prolonged periods before the pathogenic agent of the sinusitis or
otitis was identified. The most prominent clinical symptoms
were fever, headaches, nasal obstruction and/or rhinorrhea,
otorrhea, local pain, and swelling. Most patients had involvement of multiple sinuses with occasional invasion of the surrounding tissues. It is impossible to say whether the parasitic
pathogen was responsible for the entire duration of symptoms
in these patients.
Diagnostic procedures. Aggressive diagnostic procedures
were necessary for patients with nonbacterial infections to obtain tissue samples for culture and for histological and electron
microscopic examination. Microsporidial infection may be diagnosed by a variety of techniques. Uvitex 2B is a fluorochrome
stain that binds to chitin, a component of the microsporidial
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Table 1. Summary of data on 10 HIV-infected patients with microsporidial sinusitis who were previously described in the literature (including
three patients in the present report).
CD4
cell count
(/mm3)
Patient
no.
Age (y)/
sex
[2]
1
28/NR
14
[2]
2
36/NR
9
[2]
3
41/NR
0
[2]
4
36/NR
15
[3]
5
22/M
NR
[4]
6
NR/NR
NR
Nasal obstruction, mild
ocular discomfort,
loss of visual acuity
Diarrhea
[4]
7
NR/NR
NR
Diarrhea
[5]
8
NR/NR
NR
[6]
9
26/M
50
[7]
10
26/M
NR
[PR]
1
37/M
0
[PR]
2
32/M
29
[PR]
3
35/M
õ10
Diarrhea, nasal
discharge
Fever, abdominal pain,
dysuria, sinusitis,
ocular pain
Nasal discharge,
conjunctivitis
Nasal discharge, loss of
sensation of taste
Fever, chills, nasal
discharge, headaches
Fever, headache
Reference
Symptoms at
presentation
Fever, diarrhea, dysuria,
cholangitis, sinusitis,
conjunctivitis
Fever, diarrhea,
cholangitis, sinusitis,
bronchitis
Fever, diarrhea,
cholangitis, sinusitis,
conjunctivitis,
bronchitis
Fever, diarrhea,
sinusitis, bronchitis
Sites of infection
Pathogen isolated
Treatment
Response
Stool, urine, duodenum,
nose, conjunctivae
Septata intestinalis
Albendazole
Improvement
Stool, urine, duodenum,
bronchoalveolar lavage
S. intestinalis
Albendazole
Improvement
Stool, urine, duodenum,
colon, nose,
conjunctiva, sputum
S. intestinalis
Albendazole
Improvement
Stool, urine, duodenum,
nose, bronchoalveolar
lavage
Nasal polyps,
conjunctivae
S. intestinalis
Albendazole
Improvement
Encephalitozoon
cuniculi
Propamidine
isethionate
Improvement
Small bowel, urine, sinus,
sputum
Small bowel, urine, sinus,
sputum
Small bowel, urine, sinus
NR
NR
NR
NR
Albendazole
Improvement
Albendazole
Improvement
Albendazole
Improvement
Sinuses
Encephalitozoon
species
Encephalitozoon
species
Encephalitozoon
species
Encephalitozoon
hellem
or S. intestinalis
Encephalitozoon
species
Microsporidia
Albendazole
Sinuses
Microsporidia
Albendazole
Marginal
response
Improvement
Sinuses
Microsporidia
Albendazole
Improvement
Small bowel, stool
specimens, urine, nose,
conjunctivae
Nasal polyps, cornea
NOTE. NR Å not reported; PR Å present report.
Table 2. Summary of data on four HIV-infected patients with Acanthamoeba species sinusitis who were previously described in the literature
(including one patient in the present report).
Age (y)/
sex
CD4
cell count
(/mm3)
[8]
8/M
50
[9]
33/M
0
[10]
29/M
NR
[11]
34/M
NR
[PR]
37/M
178
Reference
Symptoms at presentation
Sites of infection
Pathogen
Treatment
Nasal discharge, recurrent
epistaxis, nasal crusting
Fever, sinusitis
Skin, bilateral ethmoid
and maxillary sinuses
Skin, sinuses
Acanthamoeba species
Sinus congestion, epistaxis,
nasal crusting, frontal
headache
Sinus congestion, frontal
and occipital headache
Sinus congestion, facial pain
Skin, bilateral ethmoid
and maxillary sinuses
Acanthamoeba
castellanii
Ketoconazole
Sulfadiazine
Ketoconazole
5 FC
Rifampin,
ketoconazole
No
No
No
Recovery
No
Skin, sinuses
Acanthamoeba species
No
Sinuses
Acanthamoeba species
Pentamidine /
itraconazole
5 FC
Acanthamoeba species
NOTE. 5 FC Å 5-fluorocytosine; NR Å not reported; PR Å present report.
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Response
Minimal
response
CID 1997;25 (August)
Parasitic Sinusitis and Otitis in HIV
wall; although this stain is not specific for microsporidia, it will
highlight the spores and sporoblasts in sinus debris, allowing
identification of the organism. The modified trichrome stain
may also be useful for identifying organisms [4].
Although the diagnosis of microsporidial infection may be
made by examining sinus biopsy specimens by light microscopy, identification of microsporidial organisms to the species
level is not possible with use of light microscopy. Electron
microscopy permits differentiation of Enterocytozoon bieneusi
from Encephalitozoon intestinalis and E. hellem but does not
distinguish between the latter two organisms. This distinction
must be based on immunohistochemical identification or genetic analysis [5, 12, 13]. The diagnosis of sinusitis or otitis
caused by Cryptosporidium or Acanthamoeba species must be
made histologically [9, 14].
Microsporidia. Microsporidia are small obligate intracellular spore-forming protozoan parasites. The phylum Microspora
consists of Ç80 genera and more than 700 species that may
be differentiated by their morphological characteristics with use
of electron microscopy [12]. They parasitize multiple species of
vertebrates and invertebrates and may coexist as commensals
with their animal hosts. In HIV-infected or other immunocompromised patients, infections with a variety of microsporidia
are being recognized with increasing frequency. Single-organ
involvement as well as systemic disseminated infections due
to microsporidia have been reported [13].
Although reports in the literature suggest that microsporidial
infections of the sinuses in HIV-infected patients frequently
represent disseminated disease, the three cases in this report
demonstrate sinus involvement without evidence of dissemination of the organisms. Of the three species of microsporidia
that infect patients with HIV, E. bieneusi infection is limited
to epithelial cells of the small bowel and of the biliary tract
and presumably involves sinus or tracheobronchial mucosae
by direct inoculation; in contrast, Encephalitozoon and Septata
species may disseminate after infecting macrophages [12, 13].
Albendazole, a drug that blocks the division of microsporidia
by interfering with microtubule formation through its action
on tubulin, is probably the most promising potential therapeutic
agent for microsporidial infection [6, 12]. The clinical usefulness of atovaquone for the treatment of microsporidial sinus
disease remains to be defined. It is of interest that infections
with Encephalitozoon or Septata species seem to be more responsive to albendazole (therapy results in clear clinical improvement and clearance of the organisms) than are Enterocytozoon species [2].
Cryptosporidia. Cryptosporidium species is another protozoan parasite that is able to infect and reproduce in epithelial
cells lining the digestive or respiratory tracts of most vertebrates. Cryptosporidial infections of the gastrointestinal tract
are frequently reported in patients with AIDS. Cryptosporidial
infections of the respiratory tract are less common in these
patients [14]. To our knowledge, no case of cryptosporidial
sinusitis or otitis has been reported in a patient with AIDS.
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271
Cryptosporidial infection occurs after person-to-person, animal-to-person, and environmental transmission and has been
reported in individuals of all ages, with or without immunosuppressive underlying illness. No cases of disseminated cryptosporidial infection have been reported, as cryptosporidia are
not invasive organisms. Disease in the respiratory tract is due
to inhalation of the organisms and may represent colonization
by aspirated organisms or true infection [14].
A variety of agents have been tested as therapy for cryptosporidial infection but have met with little success. Paromomycin, a poorly absorbed antibiotic, may result in symptomatic
improvement and eradication of parasites when used to treat
intestinal disease [15]. The clinical usefulness of nitozaxanide
for cryptosporidial infection remains to be defined. The symptoms in the case of cryptosporidial otitis reported herein were
reasonably resolved with long-term drainage through myringotomy.
Acanthamoeba. Acanthamoeba species are ubiquitous freeliving amoeba that inhabit soil and water. Both cell-mediated
and humoral immunity may play a role in containing acanthamoeba infection in the healthy human host. In immunodeficient
patients, however, Acanthamoeba species can cause skin lesions, sinus infection, and granulomatous encephalitis [8, 9].
We describe the clinicopathological features of one case of
sinusitis due to Acanthamoeba species. Acanthamoeba species
have been isolated from human stool specimens, ear discharge
specimens, and corneal specimens as well as from the nasal,
pharyngeal, and bronchial secretions of healthy and sick individuals. Although Acanthamoeba species are known to cause
granulomatous encephalitis with concomitant skin and sinus
infection in immunocompromised hosts, infections of the skin
and sinuses without CNS involvement seem to be recognized
with increasing frequency in AIDS patients [9].
Little is known about the treatment of acanthamoeba infection. In general, the diamidine derivatives (propamidine, pentamidine, dibromopentamidine) have the greatest activity
against this particular amoeba. Other drugs active against Acanthamoeba species in vitro include ketoconazole, miconazole,
paromomycin, neomycin, 5-fluorocytosine, and, to a lesser extent, amphotericin B. Clinical isolates of Acanthamoeba may
be tested for drug susceptibilities [16].
Conclusion
Nonbacterial sinusitis and otitis progress frequently in patients with AIDS. This is not surprising considering that these
susceptible patient populations are severely immunocompromised and considering the difficulty of eradicating these pathogens in immunocompetent hosts. Although no controlled studies exist, suppressive therapy seems to be indicated for parasitic
otolaryngological infections in patients with AIDS.
The increasing recognition of parasitic agents as otolaryngological pathogens in patients with AIDS may be related to
the increased intensity of diagnostic evaluations. Aggressive
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Dunand et al.
surgical diagnostic procedures are indicated for patients with
chronic otolaryngological complaints that are unresponsive to
empirical therapy. Without suppressive therapy, progression of
disease is common. At this time, the outcome is poor for HIVinfected patients with otolaryngological infections due to these
nonbacterial pathogens, although it is not clear if this is due
to the refractory nature of the infections or to the advanced
state of disease in the patients in whom these infections occur.
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