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CHEST

Special Features

Parasites of the Air Passages


Danai Khemasuwan, MD, MBA; Carol F. Farver, MD; and Atul C. Mehta, MD, FCCP

Parasitic infestations affect millions of the worlds population. Global immigration and climate
change have led to changes in the natural distribution of parasitic diseases far removed from
endemic areas. A broad spectrum of helminthic and protozoal parasitic diseases frequently affects
the respiratory system. The wide varieties of clinical and radiographic presentations of parasitic
diseases make the diagnosis of this entity challenging. Pulmonologists need to become familiar
with the epidemiology, clinical presentation, pathophysiologic characteristics, and bronchoscopic
ndings to provide proper management in a timely fashion. This review provides a comprehensive view of both helminthic and protozoal parasitic diseases that affect the respiratory system,
especially the airways.
CHEST 2014; 145(4):883895
Abbreviations: BALF 5 BAL fluid; DEC 5 diethylcarbamazine; ELISA 5 enzyme-linked immunosorbent assay;
PAH 5 pulmonary artery hypertension; TPE 5 tropical pulmonary eosinophilia

and protozoal infestations cause signifHelminthic


icant morbidity and mortality worldwide. A decline

in parasitic infestations has been observed in the past


decade as a result of improved socioeconomic conditions and better hygiene practices. However, the rapid
urbanization of cities around the world, global warming, international traveling, and increasing numbers
of immunocompromised individuals have increased
the vulnerability of the world population to parasitic
diseases.1 The diagnosis of parasitic diseases of the
respiratory system is challenging because the clinical
manifestations and radiologic ndings are nonspecic.
Thus, a high index of suspicion and detailed interrogation regarding travel history are critical. Most parasitic infestations of the respiratory system either involve
the airways or require bronchoscopy for diagnosis. Helminthes can affect the airways during both the larval
and the mature adult phases of their life cycle. The
larvae can cause airway inammation (paragonimiasis),

Manuscript received September 1, 2013; revision accepted


December 16, 2013.
Afliations: From Pulmonary, Allergy and Critical Care Medicine
(Drs Khemasuwan and Mehta), Respiratory Institute, and the
Department of Anatomical Pathology (Dr Farver), Cleveland Clinic
Foundation, Cleveland OH.
Correspondence to: Atul C. Mehta, MD, FCCP, Pulmonary,
Allergy and Critical Care Medicine, Respiratory Institute, Cleveland
Clinic Foundation, 9500 Euclid Ave, A-90, Cleveland, OH 44195;
e-mail: Mehtaa1@ccf.org
2014 American College of Chest Physicians. Reproduction
of this article is prohibited without written permission from the
American College of Chest Physicians. See online for more details.
DOI: 10.1378/chest.13-2072
journal.publications.chestnet.org

whereas migration of the mature adult worms may


cause mechanical obstruction of the airways (ascariasis).
This article provides a comprehensive review of both
helminthic and protozoal infestations, including clinical, radiographic, bronchoscopic, and pathologic manifestations, that may be helpful to pulmonologists in
managing this important entity (Table 1).

Nematodes
Nematodes, also known as roundworms, have a symmetrical, tube-like body with an anterior mouth and a
longitudinal digestive tract.
Ascariasis
Ascaris lumbricoides is one of the most common
parasitic infestations, affecting . 1 billion of the worlds
population and causing . 1,000 deaths annually.1 A
lumbricoides is transmitted via the feco-oral route. An
Ascaris larva migrates to the lungs through either the
lymphatics or the venules of the portal system. Larval
ascariasis causes Lfers syndrome, a concomitance
of wheezing, pulmonary inltrations, and eosinophilia.2
It can cause alveolar inammation, necrosis, and hemorrhage. Diagnosis of an ascariasis infestation during its
larval phase is difcult. The sputum may show numerous eosinophils; stool examination, however, remains
negative for eggs during the larval stage.3 The diagnosis requires a high degree of suspicion. Occasionally,
CHEST / 145 / 4 / APRIL 2014

883

the diagnosis can be conrmed by identifying larvae


in the sputum. Solitary pulmonary nodules can also
develop if the larva dies causing granulomatous inammation.4 Adult ascaris has been reported to cause airways obstruction in a child, producing a complete lobar
collapse.5 Mebendazole and albendazole are the most
effective agents against ascariasis.
Ancylostomiasis (Hookworm Disease)
The most common hookworms are Ancylostoma duodenale and Necator americanus. The latter is found
in parts of the southern United States. Hookworm larvae enter human hosts via the skin, producing itching
and local infection. The larvae are also infective via
the oral route.6 Hookworm infestations involve larval
migration through the lungs via the bloodstream, resulting in a hypersensitivity reaction. Patients usually present with transient eosinophilic pneumonia (Lfers
syndrome).6 If the patient ingests a large number of larvae, he/she may develop a condition known as Wakana
disease, characterized by nausea, vomiting, dyspnea,
and eosinophilia. This clinical picture represents a severe
hypersensitivity-like reaction to A duodenale.6 Larval
migration may also cause alveolar hemorrhage.7 Similar to ascariasis, the diagnosis of a hookworm infestation during the larvae phase could be difcult to make.
CT scanning of the chest may reveal transient, migratory, patchy alveolar inltrates.8 Sputum examination
may reveal occult blood, eosinophils and, rarely, migrating larvae (Fig 1A).9 Bronchoscopic examination may
reveal airway erythema and high eosinophil counts in
BAL uid (BALF).10 Patients can become profoundly
anemic and malnourished. These manifestations may
provide clinical clues to support the diagnosis. The antiparasitic agents for hookworm are mebendazole and
albendazole.
Strongyloidiasis
Strongyloides stercoralis is a common roundworm
that is endemic throughout the tropics but is found
worldwide in all climates. Infective lariform larvae
can penetrate the skin and infect human hosts. The larvae migrate through the soft tissues and enter the lungs
via the bloodstream. A majority of roundworms migrate
up the bronchial tree to the pharynx and are swallowed,
entering the GI tract.11 The larvae can reenter the circulatory system, returning to the lungs and causing
autoinfection.11 The life cycle of Strongyloides can be
completed entirely within one host. The term hyperinfection syndrome describes the presentation of sepsis from enteric ora, mostly in immunocompromised
patients.12 The hallmarks of hyperinfection are an exacerbation of GI and pulmonary symptoms and the detection of more larvae in the stool and sputum.13 Common
pulmonary symptoms include wheezing, hoarseness,
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dyspnea, and hemoptysis. A chest radiograph usually


demonstrates focal or bilateral interstitial inltrates.
Pleural effusions are present in 40% of patients, and
lung abscess is found in 15%.14 Diffuse alveolar hemorrhage is usually found in patients with disseminated
strongyloidiasis. ARDS may result as a reaction to the
death of the organisms. Migration of a massive number
of larvae through the intestinal wall can result in sepsis, because larvae may convey gram-negative bacteria
into the bloodstream.13
The diagnosis can be conrmed by the presence of
larvae in the stool, duodenal aspirate, sputum, pleural
uid, or BALF or lung biopsy specimens (Figs 1B, 1C).15
The sensitivity of a stool examination for ova and larvae
is 92% when performed on three consecutive samples.16
An enzyme-linked immunosorbent assay (ELISA) measures IgG responses to the Strongyloides antigen. However, false-negative results can occur during acute
infection because it takes 4 to 6 weeks to mount the
immune response.17 The ELISA is sensitive but nonspecic because of cross-reactivity with larial infestations.15 Oral ivermectin remains the treatment of
choice for uncomplicated Strongyloides infestation.13,18
Syngamosis
Nematoda of the genus Mammomonogamus affect
the respiratory tract of domestic mammals. Occasionally, however, humans can become infested via the
respiratory tract. Most cases of human syngamosis are
reported from tropical areas, including South America,
the Caribbean, and Southeast Asia.19 Two hypotheses
have been proposed regarding its life cycle. One is that
humans become infested via the ingestion of food or
water contaminated with larvae or embryonated eggs.
The larvae complete the life cycle in the pulmonary
system, and the adult worms migrate to the central airways as the preferred site of infection.20 An alternative
hypothesis is that patients are infected by the adult
worms present in contaminated food or water. This
mode of transmission is supported by its short incubation period (6-11 days).21 The diagnosis requires exible bronchoscopy unless the worms are expelled
through vigorous coughing (Fig 1D). The removal of
parasites through bronchoscopy is sufcient to improve
symptoms. To date, no studies have supported the
effectiveness of antihelminthic therapy.21,22
Dirolariasis
Dirolaria immitis is the larial nematode that primarily infects dogs. Humans are considered accidental
hosts because D immitis is unable to mature to an adult
form. D immitis is transmitted to humans by mosquitoes harboring infective third-stage larvae. The larva
travels to the right ventricle and develops into an immature adult worm. It is then swept into the pulmonary
Special Features

journal.publications.chestnet.org

Table 1Parasitic Infection of Respiratory System


Parasite
Nematodes
Ascariasis (Ascaris lumbricoides)

Infective Form

Endemic Area

Mode of Transmission

CHEST / 145 / 4 / APRIL 2014

Eggs and larva

Asia, Africa, and


South America

Ingestion

Hookworm (Ancyclostoma
duodenale) (Necator
americanus)

Larva

Tropical and
subtropical areas

Skin penetration

Strongyloidiasis
(Strongyloides stercoralis)

Filariform larvae

Tropical and
subtropical areas

Skin penetration

Syngamosis (Mammomonogamus
laryngeus)

Eggs or adult
worms

Asia, Africa, and


South America

Ingestion

Dirolariasis (Dirolaria immitis)

Larva

Tropical and
subtropical areas

Mosquito-borne
infection

Tropical pulmonary
eosinophilia (Brugia malayi)
(Wuchereria bancrofti)

Larva

Tropical and
subtropical areas
(South and
Southeast Asia)

Mosquito-borne infection

Visceral larva migrans


(Toxocara canis)
(Toxocara catis)
Trichinella infection
(Trichinella spiralis)

Larva

Worldwide

Ingestion

Larva

Worldwide

Ingestion

Cercarial larvae

East Asia,
South America,
Sub-Saharan Africa

Skin penetration

Trematodes
Schistosomiasis
(Schistosoma species)

Pulmonary Presentation
Eosinophilic
pneumonia, cough,
wheezing, dyspnea
Eosinophilic
pneumonia, cough,
wheezing, dyspnea,
alveolar hemorrhage

Bronchoscopic
Evaluation

Treatment

Presence of parasite
in the airways

Mebendazole and
albendazole

Presence of hookworm
in sputum, a
marked eosinophil
predominance
from BAL
Bloody BAL and
presence of parasite
from BAL under
microscopic
examination
Presence of parasite
in the airways

Mebendazole and
albendazole

Surgical lung biopsy

None (self-limited)

BAL shows
eosinophils more
than 50% of
the total cells

Diethylcarbamazine

N/A

Diethylcarbamazine

Cough, pulmonary
inltrates, dyspnea
due to respiratory
muscles involvement

N/A

Mebendazole

Pulmonary
hypertension and
Katayama fever

An eosinophil
predominance from
BAL in the absences
of parasites

Praziquantel

Eosinophilic
pneumonia, cough,
wheezing, dyspnea,
hyperinfection
syndrome
Foreign body-like
lesion in bronchus,
nocturnal cough
Cough, chest pain,
fever, dyspnea, mild
eosinophilia, and
lung nodules
Eosinophilic
pneumonia, cough,
wheezing, dyspnea,
restrictive pattern on
spirometry, decreased
diffusion lung capacity
Eosinophilic pneumonia,
episodic wheezing

Ivermectin and
albendazole

Removal through
bronchoscopy

(Continued)

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Therapeutic
bronchoscopy
and dapsone
Bronchoscopy
revealed pinkish
mulberry-like
rhinosporidiosis
mass in the airway

Tropical Pulmonary Eosinophilia


Tropical pulmonary eosinophilia (TPE) is a syndrome
of immunologic reaction to microlaria of the lymphaticdwelling organisms Brugia malayi and Wuchereria
bancrofti. It is a mosquito-borne infestation. The larvae reside in the lymphatics and develop into mature
adult worms. The microlariae are released into the
circulation and may be trapped in the pulmonary circulation.28 Trapped microlariae demonstrate a strong
immunogenicity and trigger antimicrolarial antibodies, resulting in asthma-like symptoms. The hallmark
of TPE is a high absolute eosinophil count (5,00080,000/mm3).29 The radiologic features include reticulonodular opacities, predominantly in the middle and
the lower lung zones; miliary mottling; and predominant hila with increased vascular markings at the bases.30
Chest CT scanning may demonstrate bronchiectasis,
air trapping, calcication, and mediastinal lymphadenopathy.31 Pulmonary functions indicate a restrictive
defect with mild airways obstruction.29 BALF may contain numerous eosinophils. Occasionally, microlaria
can be identied on brushings or needle biopsy specimens.32 The chronic phase of TPE may lead to progressive and irreversible pulmonary brosis.28
The standard treatment of TPE is diethylcarbamazine (DEC). Patients usually show improvement within
3 weeks. However, a mild form of interstitial lung disease with diffusion impairment may remain.33
Toxocariasis
N/A 5 not available.

Spores
Mesomycetozoea
Rhinosporidiosis
(Rhinosporidium seeberi)

South Asia

Ingestion of
contaminated
water

Strawberry-like,
nasopharyngeal
polyps, epitasis,
nasal congestion

Surgical removal of
cysts, followed
by mebendazole
and albendazole
Bronchoscopic
examination reveals
sac-like cyst in the
airway
Chest pain, cough,
hemoptysis, pleural
lesion, expectoration
of cyst contents,
and hypersensitivity
reaction
Ingestion
Worldwide
(especially Middle East)
Eggs
Cestodes
Hydatid disease
(Echinococcus granulosus)

Treatment

Praziquantel and
triclabendazole
Bronchial stenosis due
to mucosal edema
and mucosal
nodularity
Fever, cough,
hemoptysis, chest
pain, and pleural
effusion
Ingestion of
infested crustaceans
Southeast Asia,
South America,
Africa
Metacercaria
(infective larvae)
Paragonimiasis (Paragonimus
species)

Bronchoscopic
Evaluation
Pulmonary Presentation
Mode of Transmission
Parasite

Infective Form

Endemic Area

Table 1Continued
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arteries. The worm dies as a result of the inammatory


response and evokes granuloma formation.23 A majority
of patients with pulmonary dirolariasis are asymptomatic. However, some patients (about 5%) may develop
cough, hemoptysis, chest pain, fever, dyspnea, and mild
eosinophilia.24 A peripheral or a pleural-based solitary
pulmonary nodule is a typical presentation. The nodule may show increased uorodeoxyglucose avidity on
a PET scan25,26 and is often confused with malignancy.
Calcication occurs within only 10% of these nodules.
CT scanning may show a branch of the pulmonary artery
entering the nodule.27 Serology has poor specificity
because of cross-reactivity with other helminths. The
diagnosis is established by identifying the worm in the
excised lung tissue (Fig 1E). Needle biopsy and brushings are usually nondiagnostic because of the small
sample size. The condition does not require any specic treatment because it is a self-limiting condition.24

Toxocara canis and cati are roundworms that affect


the dog and cat, respectively. These roundworms are
common parasites that cause visceral larva migrans
and eosinophilic lung disease in humans. Toxocariasis
is transmitted to humans via ingestion of food that is
contaminated with parasite eggs. The larvae can migrate
Special Features

Figure 1. A, Hookworm larva in the sputum sample (wet smear, original magnication 3 88). Morphologically, hookworm larvae have long
buccal cavities, whereas Strongyloides larvae have short buccal cavities. (Reprinted with permission from Beigel et al.9) B, Bloody aliquot
from BAL sample and Strongyloides larvae from BAL (hematoxylin and eosin [H&E], original magnication 3 200). Note: short buccal
cavity distinguishes Strongyloides from the hookworm (inset) (H&E, original magnication 3 400). C, Strongyloides larvae (arrow) present
in alveolar space in lung with diffuse alveolar damage (H&E, original magnication 3 400). D, Bronchoscopic ndings in anterior basal
segment of right lower lobe. The syngamosis male is smaller and attached to the copulatory bursa of the female body (arrow). The parasite
can be seen in bronchoscopy because they reside in the bronchial mucosa. (Reprinted with permission from Kim et al.19) E, Cross-sections
of coiled Dirolaria worms within involved artery causing surrounding infarction of lung tissue. Note the smooth cuticle at the external
layer (Movat stain, original magnication 3 200). F, Schistosomal ova in the lung biopsy specimen. The arrow points to ova within the
granulomatous reaction (H&E, original magnication 3 100).

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887

Figure 2. A, Bronchoscopic ndings showed mucosal nodularity on the right upper lobe (RUL). (Reprinted with permission from Jeon et al.51)
B, Microscopic examination of bronchial tissue obtained from the RUL bronchus showing thickening of the basement membrane and
chronic inammation with eosinophilic inltration (H&E, original magnication 3 200). (Reprinted with permission from Jeon et al.51)
Inset: Paragonimus kellicotti egg in a BAL sample. The arrow points to the operculum ridges of the egg (Papanicolaou, original magnication 3 400). (Image courtesy by Gary Procop, MD.) C, Granulomas in the pleura in a patient with paragonimiasis. The arrow points to
a light brown egg within the granuloma (H&E, original magnication 3 100). (Image courtesy by Gary Procop, MD.) D, Protruded hydatid
cyst from left lower lobe bronchus. (Image courtesy by Farid Rashidi, MD.) E, Echinococcus cyst fragments in lung biopsy specimen. The
arrows highlight the collapsed chitinous layer of a death hydatid cyst (H&E, original magnication 3 44). F, Echinococcus cyst fragments
in lung biopsy specimen. The fragmented ecchinococus cyst with collapsed chitinous layer resides within the granulomatous reaction
(H&E, original magnication 3 200). See Figure 1 legend for expansion of other abbreviation.

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Special Features

throughout the hosts body, including the lungs.34 The


pathology of visceral larva migrans is a hypersensitivity response to the migrating larvae. Visceral larva
migrans can present with fever, cough, wheezing, seizures, and anemia. Leukocytosis and severe eosinophilia are demonstrated in a peripheral smear. A chest
radiograph reveals pulmonary inltrates with hilar and
mediastinal lymphadenopathy. Bilateral pleural effusion can occur.35 Noncavitating pulmonary nodules
have also been reported.36 The diagnosis of toxocariasis
is established by an ELISA for the larval antigens.37
The treatment of choice is DEC; however, it may
exacerbate the inammatory reaction because of the
resulting death of the larvae. It is advisable to combine
DEC with corticosteroids.34
Trichinella Infection
Trichinella spiralis is the most common Trichinella
species that infects humans. Trichinella is a foodborne disease from undercooked pork containing larval
trichinellae. In addition to the pork meat, meat from
wild animals such as bear may contain T spiralis.38 The
larvae migrate and reside in the GI tract until they
develop into an adult form. Fertilized female worms
release rst-stage larvae into the bloodstream and the
lymphatics.39 Pulmonary involvement, although uncommon, produces shortness of breath and pulmonary inltrates. Dyspnea is caused by parasitic invasion of the
diaphragm and the accessory respiratory muscles.39
The diagnosis is conrmed by muscle biopsy, which
may demonstrate T spiralis larvae. An ELISA using
anti-Trichinella IgG antibodies can conrm the diagnosis in humans.40 A 2-week course of mebendazole,
along with analgesics and corticosteroids, is the recommended treatment.39
Trematodes
Trematodes (atworms) have a at body with a sucker
near the mouth that is used for attachment to the host.
Most atworms are hermaphrodites, except Schistosoma species, which have separate sexes.

tive larva). After the cercarias have penetrated the skin,


they migrate to the lung and the liver. There are several case reports of a high incidence of acute schistosomiasis (Katayama fever) among travelers with a history
of swimming in Lake Malawi and rafting in sub-Saharan
Africa.41
In acute schistosomiasis, patients present with dyspnea, wheezing, dry cough, abdominal pain, hepatosplenomegaly, myalgia, and eosinophilia.42 Patients
experience shortness of breath because of an immunologic reaction to antigens released by the worms. The
level of circulating immune complexes correlates with
the symptoms and with the intensity of infection.
In chronic schistosomiasis, embolization of the eggs
in the portal system causes periportal brosis and portal hypertension. Pulmonary involvement can occur
as a result of the systemic migration of parasitic eggs
from the portal system. The eggs trigger an inammatory response that leads to pulmonary arterial hypertension (PAH) and subsequent development of cor
pulmonale in 2% to 6% of patients.43 Apoptosis of the
endothelial cells in the pulmonary vasculature plays
a role in the pathogenesis of schistosomal-associated
cor pulmonale.44
Chest radiographs and CT scanning may show a diffuse reticulonodular pattern or ground-glass opacities.45
In the acute phase, BALF may reveal eosinophilia in
the absence of parasites. The diagnosis is conrmed by
microscopic examination of stool and urine or by rectal biopsy. However, the sensitivity of these tests is low
for an early infection. ELISA can be used as a screening test and is conrmed by enzyme-linked immuneelectrotransfer blot. These tests become positive within
2 weeks after the infestation. Schistosomal ova can
be found in the lung biopsy specimen (Fig 1F).
Acute schistosomiasis is treated with praziquantel.
The treatment is repeated within several weeks because
it has no antihelminthic effect on the juvenile stages
of the parasites.46 Acute pneumonitis, which is believed
to be related to lung embolization by adult worms in
the pelvic veins, can be observed 2 weeks after the
treatment.47 Patients with schistosomal-associated PAH
can be treated with PAH-specic therapy along with
antiparasitic medications.47

Schistosomiasis
Five schistosomes species cause disease in humans:
Haematobium, Mansoni, Japonicum, Intercalatum,
and Mekongi.7 After malaria, schistosomiasis is the most
common cause of mortality among parasitic infections,
annually affecting 200 million individuals worldwide.1
Schistosoma haematobium resides in the urinary bladder, whereas Schistosoma mansoni and Schistosoma
japonicum reside in the mesenteric beds.34 Humans
become infested through the skin from contact with
fresh water containing Schistosomal cercaria (infecjournal.publications.chestnet.org

Paragonimiasis
Paragonimus species, including westernmani, cause
paragonimiasis that usually involves the lungs. The
mode of transmission is ingestion of the metacercaria
(infective larvae) from undercooked crustaceans. Undercooked meat of crab-eating mammals (wild boars, rats)
can infect humans as an indirect route of transmission.48
The larvae penetrate the intestinal wall and migrate
through the diaphragm and the pleura into the bronchioles.49 The eggs are produced by the mature adult
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889

worms, which are expelled in the sputum or swallowed


and passed with the stool. Typically acute symptoms
include fever, chest pain, and chronic cough with hemoptysis.50 Pleural effusion and pneumothorax may be the
rst manifestation during the migration of the juvenile
worms through the pleura. A chest radiograph demonstrates patchy inltrates, nodular opacities, pleural
effusion, and uid-lled cysts with ring shadows.34 Chest
CT scans may reveal a band-like opacity abutting the
visceral pleura (worm migration tracks), bronchial wall
thickening, and centrilobular nodules. Bronchoscopic
examination may reveal airway narrowing from mucosal
edema (Fig 2A).51 A lung biopsy specimen may show
chronic eosinophilic inammation (Fig 2B). The diagnosis is conrmed by the presence of eggs or larvae in
the sputum sample or BALF (Fig 2C). The pleural uid,
when present, is an acidic exudate with eosinophilia,
mostly sterile, without the presence of any organisms.52
Eosinophilia and elevated serum IgE levels are also
observed in more than 80% of infected patients.34 Serologic tests with ELISA and a direct uorescent antibody are highly sensitive and specic for establishing
the diagnosis.53 Praziquantel and triclabendazole are
the treatments of choice, with a cure rate of 90% and
98.5%, respectively.34
Cestodes
Cestodes are a subclass of tapeworms; parasites in
this group have no digestive system. These parasites
live in the digestive tract of mammals. The body is composed of multiple, successive segments (proglottids).
Tapeworms are exclusively hermaphrodites with both
male and female reproductive systems in their body.

include cough, fever, dyspnea, and chest pain. The


cyst may rupture into a bronchus and cause hemoptysis and/or expectoration of cystic uid containing
parasitic components (hydatoptysis), which is considered a pathognomonic nding of cystic rupture.55
The patients may present with hydropneumothorax
or empyema. Occasionally, a ruptured cyst can cause
an anaphylactic-like reaction and pneumonia.8 Cystic
hydatidosis is diagnosed by chest radiography, which
demonstrates a well-dened, homogenous, uid-lled,
round opacity. Ruptured cysts may have characteristic
features, including air crescent, pneumocyst, oating
membrane (water lily sign) (Fig 3), or completely
empty cavity images.56 A meniscus or crescent sign
or Cumbos sign (onion peel) have also been described.
Thoracic ultrasonography may be useful to conrm
the cystic structure, demonstrating the characteristic
double-contour (pericyst and parasitic membrane
endocyst) of intact cysts. However, daughter cysts are
also observed occasionally in pulmonary hydatidosis.56
Bronchoscopic examination reveals sac-like cysts in
the airway (Fig 2D). A surgical lung biopsy may reveal
echinococcus cyst fragments (Figs 2E, 2F).
Bronchoscopic extraction of the hydatid cyst is possible; however, because of the risk of cyst rupture, it
should be considered on a case-by-case basis. Serologic
tests are more sensitive in patients with liver involvement (80%-94%) than in those with lung hydatidosis
(65%).34 Hydatid cyst rupture can increase the sensitivity of serologic tests to . 90%.55
Cystic hydatidosis is the only infestation that needs
surgical treatment. Complete resection of the cyst
is the cornerstone of the management of pulmonary
hydatidosis: to remove the intact cyst, preserve as much
viable lung tissue as possible, and treat the associated

Echinococcosis
Echinococcus granulosus and multilocularis are the
parasite species that cause hydatid disease in humans.
E granulosus is endemic in sheep-herding areas of the
Mediterranean, Eastern Europe, the Middle East, and
Australia. An estimated 65 million individuals in these
areas are infected.1 Humans become accidental hosts
either by direct contact with the primary hosts (usually
dogs) or by the ingestion of food contaminated with
feces, containing parasite eggs.34 The larvae reach the
lymphatics of the intestines and the bloodstream and
then migrate to the liver, the main habitat in human
hosts.
Two different presentations of echinococcosis are
noted: (1) cystic hydatidosis and (2) alveolar echinococcosis. An ecchinococcal infection becomes symptomatic after 5 to 15 years, secondary to local compression
or dysfunction of the affected organ. Pulmonary cysts
expand at a rate of 1 to 5 cm/y, and calcication is less
common.54 Pulmonary symptoms from the intact cyst
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Figure 3. Water lily sign. CT scan obtained at level of right middle


lobe shows ruptured hydatid cyst. After rupture and discharge of
cyst uid into pleural cavity, endocyst collapses, sediments, and oats
in remaining uid at bottom of original cyst. (Image courtesy by
Farid Rashidi, MD.)
Special Features

Figure 4. A, Bronchoscopy revealed pinkish mulberry-like rhinosporidiosis mass in the right main stem bronchus. (Reprint with permission
from Singh et al.64) B, Microscopic examination of the resected specimen shows bronchial subepithelium with sporangia of Rhinosporodium;
lled with small round endospores (H&E, original magnication 3 100). (Reprint with permission from Singh et al.64) C, Amebic lung
abscess from lung biopsy specimen. The arrows point to trophozoites of Entamoeba histolytica (H&E, original magnification 3 200).
D, Transbronchial needle biopsy specimen of a mediastinal lymph node shows histiocytes containing abundant Leishmania amastigotes
(arrows) (H&E, original magnication 3 1,000). Inset shows a close-up view of an amastigote. Its ovoid shape, eccentric nucleus, and kinetoplast are discerned (same magnication as image). (Reprint with permission from Kotsifas et al.68) E, Lung infected with Toxoplasmosis
gondii (arrow) with diffuse alveolar damage (H&E, original magnication 3 100). Inset shows bradyzoites of T gondii present in cytoplasm
of alveolar macrophage (H&E, original magnication 3 1,000). See Figure 1 legend for expansion of abbreviation.

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parenchymal and bronchial disease. The lung parenchyma around a hydatid cyst is often affected by the
lesion and may exhibit chronic congestion, hemorrhage,
and interstitial pneumonia, which often resolve after
the surgery.57 Spillage of hydatid uid must be avoided
to prevent secondary hydatidosis. Medical therapy may
have a role in poor surgical candidates and in intraoperative spillage of uid from a hydatid cyst. Antihelminthic agents, such as mebendazole or albendazole,
have shown only 25% to 34% cure rates.58 The drawback of antihelminthic therapy is that it weakens the
cyst wall and increases the risk of rupture. In addition, if the parasite dies because of the drug, the cyst
membrane may remain within the cavity and lead to
secondary complications, including infections.59 Percutaneous treatment by puncture-aspiration-injectionreaspiration has rarely been used in pulmonary cysts
because of the risk of anaphylactic shock, pneumothorax, pleural spillage, and bronchopleural stulae.60
Pulmonary alveolar echinococcosis is a rare but
severe and potentially fatal form of echinococcosis but
it is restricted to the Northern Hemisphere. The liver
is the rst target for the parasite, with a long, silent
incubation period. Pulmonary involvement results
from either dissemination or the direct extension of
the hepatic echinococcosis with intrathoracic rupture
through the diaphragm into the bronchial tree, pleural
cavity, or mediastinum. Chest radiograph or CT scanning may aid in the diagnosis. ELISAs and indirect
hemagglutination assay are available and offer early
detection in endemic areas. Radical resection of
localized lesions is the only curative treatment yet, is
rarely possible in invasive and disseminated disease.
Mebendazole and albendazole can be used, but the
required treatment duration need is a minimum of
2 years after the radical surgery.61

Mesomycetozoea
Mesomycetozoea is a group of organisms at the
border of the animal-fungal kingdom.62 They appear
in host tissues as sphere-shaped spores.
Rhinosporidiosis
Rhinosporidiosis is a chronic granulomatous infectious disease caused by Rhinosporidium seeberi. This
condition has a high prevalence in South Asia, especially
Sri Lanka.63 Patients usually present with recurrent
polypoidal, friable, hemorrhagic, lesions. The common sites of involvement are the nose and nasopharynx.
However, lesions can involve the tracheobronchial
tree, leading to partial or complete airway obstruction (Figs 4A, 4B).64 CT imaging is the preferred
study because it denes the extent of disease. Therapeutic bronchoscopy plays a major role in bronchial
rhinosporidiosis.
Dapsone is the only medication to arrest the maturation of the sporangia, but the lesions may recur after
months or years.65 Follow-up bronchoscopy is recommended to monitor signs of recurrence.

Protozoal Parasites
Protozoa parasites are single-celled organisms that
are mostly intracellular in humans (Table 2). Pulmonary
amebiasis is caused by Entamoeba histolytica trophozoites invading the intestinal mucosa and entering the
bloodstream, effecting systemic infection. Pleuropulmonary amebiasis occurs mainly by local extension from
the amoebic liver abscess. Patients usually present with
fever, right-upper-quadrant abdominal pain, and cough.
Sterile pleural effusion, lung abscess, hepatobronchial

Table 2Protozoal Infection of Respiratory System


Mode of
Transmission

Protozoal Parasites

Endemic Area

Pulmonary
amebiasis

Worldwide

Ingestion

Pulmonary
leishmaniasis

Asia, Africa,
Central and
South America

Sand y-borne
infection

Pulmonary
toxoplasmosis

Worldwide

Ingestion

892

Presentation
Fever, right upper
quadrant abdominal
pain, lung abscess,
hepatobronchial
stula
Pneumonitis, pleural
effusion, mediastinal
lymphadenopathy

Generalized
lymphadenopathy,
interstitial pneumonia,
diffuse alveolar
damage

Bronchoscopic Evaluation

Treatment

Surgical lung biopsy


specimen shows
Entamoeba histolytica
trophozoites

Metronidazole

Transbronchial needle biopsy


specimen of a mediastinal
lymph node showing
histiocytes containing
Leishmania donovani
organisms
Histologic examination of
lung biopsy specimen can
identify Toxoplasma gondii
tachyzoites in necrotic area

Pentavalent antimonials
and liposomal
amphotericin B

Pyrimethamine and
sulfadiazine

Special Features

stula, empyema, and pyopneumothorax have also


been reported.1 Live trophozoites of E histolytica
can be demonstrated in sputum, pleural pus, or lung
biopsy specimens (Fig 4C). The presence of amoeba
in the stool does not indicate an active E histolytica
infection because two other nonpathologic Entamoeba
species are found in humans.66 Metronidazole is the
treatment of choice for invasive amoebiasis.
Leishmania causes visceral leishmaniasis, which has
been reported in patients who have undergone lung
transplants.67 Pulmonary manifestations include pneumonitis, pleural effusion, and mediastinal lymphadenopathy.34 Leishmania organisms can also be found in
the alveoli (Fig 4D)68 and the BALF.69 The diagnosis
of leishmaniasis is conrmed by the presence of the
parasites in bone marrow aspirates or by polymerase
chain reaction identication in tissue biopsy specimens.
Treatments of choice include pentavalent antimonials
and liposomal amphotericin B. Miltefosine can be used
as an oral agent against visceral leishmaniasis.70
Toxoplasmosis is caused by the protozoan, Toxoplasma gondii. Cats are the primary hosts of T gondii.71
Humans become infected by consuming contaminated
undercooked food. Pulmonary toxoplasmosis has been
reported with increasing frequency in HIV-infected
patients. Pulmonary manifestations include interstitial
pneumonia, diffuse alveolar damage, or necrotizing
pneumonia.72 Histologic examination of lung biopsy
specimens can identify T gondii tachyzoites in necrotic
areas in both intracellular and extracellular forms
(Fig 4E).73 The diagnosis of toxoplasmosis is based on
the detection of the protozoa in bodily tissues. Diagnostic real-time polymerase chain reaction-based assays
of BALF have been reported for HIV-positive patients.
Toxoplasmosis can be treated with a combination of
pyrimethamine and sulfadiazine for 3 to 4 weeks.74
Conclusions
Although helminthic and protozoal parasitic infestations are dominant mainly in tropical and subtropical
areas, global warming, immigration, and an increasing
use of immunosupressives have changed their distribution. To manage these challenging clinical scenarios,
pulmonologists must understand the epidemiology,
life cycles, and clinical presentation of these infestations, as well as the bronchoscopic and laboratory ndings and treatment options.
Acknowledgments
Financial/nonnancial disclosures: The authors have reported
to CHEST that no potential conicts of interest exist with any
companies/organizations whose products or services may be discussed in this article.
Other contributions: We thank Gary Procop, MD, and Farid
Rashidi, MD, for contribution of gures.
journal.publications.chestnet.org

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