Pleural Effusion Due to Parasitic Infection

Pleural effusions secondary to parasitic infections are uncommon in the United States, but in some
countries, they account for a sizable percentage of all pleural effusions. With worldwide travel being
more prevalent, one can anticipate that the incidence of pleural effusions secondary to parasitic disease
will gradually increase in the United States.

AMEBIASIS

Amebiasis, the disease caused by Entamoeba histolytica, occurs throughout the world. Humans acquire
the disease by ingesting the cyst, which is the infectious form of the organism. After ingestion by the
host, eight daughter trophozoites develop and colonize the proximal large intestine. The trophozoites,
which can proliferate, are the potentially invasive form. These trophozoites may migrate through the
portal system to the liver, where the liberation of cytolytic enzymes gives rise to liver abscesses. The
trophozoite can also revert to a cyst. When the cyst is passed in the stool, it can be ingested by another
individual to complete the parasite's life cycle. Trophozoites can also be passed in the stool but are not
infectious (1). The prevalence of amebiasis is most dependent on the level of sanitation in the
community, as would be expected from the life cycle of this parasite. Approximately 5% of the
population in the United States are carriers. Amebiasis is most prevalent in southeastern United States,
but the condition is reported with low frequency from every state. Amebic abscess is not unusual in the
United States. For example, there were 30 patients seen with hepatic amebiasis at the Santa Clara Valley
Medical Center in San Jose, California, during the period from 1981 to 1988. None of the patients,
however, were born in the United States (2).

Pathogenesis Pleural effusions arise by two mechanisms in association with amebic liver abscess. The
first occurs when an amebic abscess produces diaphragmatic irritation and a sympathetic pleural
effusion in a manner analogous to that seen with pyogenic liver abscesses (3,4) (see Chapter 18). Amebic
liver abscesses also produce pleural effusions when the abscess ruptures through the diaphragm into the
pleural space (3,4). In this situation, the pleural fluid is described as "chocolate sauce" or "anchovy
paste" (1). Such pleural fluid does not contain purulent material but is rather a mixture of blood,
cytolyzed liver tissue, and small solid particles of liver parenchyma that have resisted dissolution.

Clinical Manifestations and Diagnosis The sympathetic effusion seen with amebic liver abscess is more
common than rupture of an abscess through the diaphragm into the pleural space (2,3,5). Approximately
20% to 35% of patients with an amebic liver abscess will have a sympathetic pleural effusion (2). Patients
with the sympathetic effusion frequently experience pleuritic chest pain referred to the tip of the scapula
or the shoulder. Most patients have a tender enlarged liver (6). Eosinophilia is not associated with
extraintestinal amebiasis. The level of alkaline phosphatase is elevated in more than 75% of patients,
whereas the levels of transaminases are elevated in 50% (1). The chest radiograph reveals a pleural
effusion of small-to-moderate size, often with a concomitant elevation of the hemidiaphragm and plate-
like atelectasis at the base (2-4). The pleural fluid in this situation has not been well characterized, but is
an exudate (2,5).

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272 PLEURAL DISEASES

The diagnosis of amebiasis should be considered in all patients with right-sided pleural effusions for
which no other explanation is obvious. Ultrasonic studies and computed tomography (CT) scan can
demonstrate the hepatic abscess but cannot differentiate the pyogenic from amebic abscesses (7). The
diagnosis is aided by the use of serologic tests. The sensitivity of antibody tests for E. histolytica is 95%
for patients with extraintestinal amebiasis (8). Serology is limited as a diagnostic tool in highly endemic
areas, as individuals will remain seropositive for years after an infection has cleared and seropositivity
rates of greater than 25% may exist in some areas (8). Polymerase chain reaction (PCR) techniques are
being more frequently used for the diagnosis of amebiasis but there is yet no standardized commercially
available test (8).

Treatment The treatment of choice is metronidazole, 500 to 750 mg t.i.d. orally, for 10 days (8). If the
patient is dyspneic from the pleural effusion, a single therapeutic thoracentesis is usually sufficient to
control the symptoms. More than 90% of patients can be cured with the aforementioned regimen.
Catheter drainage adds no significant benefit to amebicidal therapy alone (1).

Transdiaphragmatic Rupture of Liver Abscess The transdiaphragmatic rupture of an amebic liver abscess
is usually signaled by an abrupt exacerbation of pain in the right upper quadrant and may be
accompanied by a tearing sensation (3). These symptoms are followed by the development of rapidly
progressive respiratory distress and sepsis, occasionally with shock (3). The pleural effusion is frequently
massive, with opacification of the entire hemithorax and shift of the mediastinum to the contralateral
side (3). The rupture is into the right pleural space in more than 90% of patients. The symptoms are
sometimes subacute or chronic in nature (9). The diagnosis of amebic abscess with transdiaphragmatic
rupture is suggested by the discovery of anchovy paste or chocolate sauce pleural fluid on diagnostic
thoracentesis. Amebas can be demonstrated in the pleural fluid in fewer than 10% of patients.
Concomitant rupture into the airways occurs in approximately 30% of patients (3), and this complication
is usually manifested by the expectoration of chocolate sauce sputum that may be confused with
hemoptysis by the patient and the physician.

The diagnosis is established by the characteristic appearance of the pleural fluid and can be confirmed by
serologic tests for amebiasis. Ultrasound or CT scanning of the abdomen can delineate the extent of the
intrahepatic disease and the presence or absence of a subphrenic abscess. Patients with
transdiaphragmatic rupture should be treated with the same drugs as patients with sympathetic pleural
effusions due to amebic hepatic abscess. Patients with transdiaphragmatic rupture should also undergo
percutaneous drainage of both the liver abscess and the collection of material in the pleural space. The
drainage can be accomplished with small tubes (12 to 14 F) (10). The combination of the drugs and the
percutaneous drainage tubes results in clinical cure in almost all patients (10). Approximately one third
of patients with transhepatic rupture also have a bacterial infection of their pleural space (4,9). Such
patients should be treated with the appropriate antibiotics. In addition, an open-drainage procedure or
decortication is frequently necessary, indications for which are outlined in Chapter 12. In patients who
undergo decortication, the visceral pleura is found to be covered with a thick membrane (9), but this
membrane can easily be stripped off the visceral pleura (9). Even when no bacterial superinfection is
present, decortication should be performed if the lung has not fully expanded in 10 days (9). The
prognosis with transdiaphragmatic rupture is excellent if the patient is not too debilitated initially or if
the diagnosis is not delayed (3,4,9).

ECHINOCOCCOSIS (HYDATID DISEASE)

Echinococcosis is caused by the tapeworm Echinococcus granulosus. The definitive host for this small
tapeworm is the dog or wolf When dog feces containing the parasite's eggs are ingested by humans,
larvae emerge in the duodenum, enter the blood, and usually lodge in either the liver or the lung. In
these tissues, the parasite grows gradually, and years may pass before symptoms appear. It takes
approximately 6 months for the cyst to reach a diameter of 1 cm and thereafter it increases in size by 2
to 3 cm/year (11). The dog becomes infected by eating meat containing the larvae. Echinococcosis is
seen in most sheep- and cattle-raising areas of the world including Australia, New Zealand, Argentina,
Uruguay, Chile, parts of Africa, Eastern Europe, and the Middle East. The disease is particularly common
in Turkey, Lebanon, and Greece.

CHAPTER 15 I PLEURAL EFFUSION DUE TO PARASITIC INFECTION 273

Pathogenesis Pleural involvement with hydatid disease can occur in one of four situations (12,13): (a) a
hepatic hydatid cyst or, on rare occasions, a splenic cyst may rupture through the diaphragm into the
pleural space; (b) a pulmonary hydatid cyst may rupture into the pleural space; (c) on rare occasions, the
pleura may be primarily involved by the slowly enlarging cyst (12); or (d) a pulmonary or hepatic hydatid
cyst may be accompanied by a pleural effusion (14-16). The incidence of pulmonary and hepatic cyst
rupture into the pleural space is equivalent (12). Fewer than 5% of hepatic (12, 13) or pulmonary hydatid
cysts (16) are complicated by intrapleural rupture. Approximately 5% of patients with a hepatic or a
pulmonary hydatid cyst have a pleural effusion (14). The pleural fluid has been described as an exudate
(16) which can be eosinophilic (17). Patients who are being treated medically for hydatid cysts may
develop pleural complications. In one retrospective study, 11 of 36 patients who were treated medically
developed pleural complications (18). All the patients who developed complications had cysts that
exceeded 6 cm in diameter. The complications included pleural empyema in seven and pulmonary
abscess with pleural fluid in four (18). The authors of the article recommended that large pulmonary
hydatid cysts should not be treated medically (18).

Clinical Manifestations and Diagnosis When a hepatic cyst ruptures into the pleural space, the patient
usually becomes acutely ill, with sudden tearing chest pain, dyspnea, and shock from the antigenic
challenge to the body (19). In approximately 50% of patients with rupture into the pleural space,
simultaneous rupture into the tracheobronchial tree occurs (19). Such patients may cough up large
quantities of pus and membranes of the cyst. When a pulmonary cyst ruptures into the pleural space,
similar symptoms are frequently present. In addition, a bronchopleural fistula often produces a
hydropneumothorax that may become secondarily infected. The diagnosis of pleural echinococcosis is
established by the demonstration of echinococcal scolices with hooklets in the pleural fluid (20). A CT
scan demonstrating multiple round cysts is suggestive of the diagnosis (21). Most patients who have a
ruptured hydatid cyst have a hydropneumothorax (16). An occasional patient will even have a tension
hydropneumothorax (22). Eosinophils are frequently

present in the pleural fluid unless it becomes secondarily infected (13,20). The Casoni skin test is positive
in approximately 75% of patients (19), and the Weinberg complement fixation (CF) test is positive in a
higher percentage.

Treatment Attempts should be made to remove the cyst in patients with hydatid disease. In the past, all
thoracic cysts have been removed through thoracotomy. However, it appears that the cysts can be
removed by percutaneous catheter drainage (23) or thoracoscopy (24). An immediate thoracotomy is
recommended for patients who have rupture of a hepatic cyst into the pleural space (19). When a
hepatic cyst has ruptured, the objectives of surgical treatment are to remove the parasite, to drain the
hepatic cavity, and to reexpand the lung immediately (19). If the surgical procedure is delayed, a
decortication may also be required (19). An exploratory thoracotomy should also be performed when a
pulmonary hydatid cyst ruptures into the pleural space, to remove the parasite, to excise the original
cyst, and to close the bronchopleural fistula. Patients with hydatid cysts should be treated with
antiprotozoal therapy if all the cysts cannot be removed or when rupture of a cyst has occurred. The
treatment of choice is albendazole, 400 mg b.i.d. over 28 days (25).

PARAGONIMIASIS

Paragonimiasis is caused by the lung flukes Paragonimus westermani, Paragonimus miyazakii (26),
Paragonimus heterotremus (27), and Paragonimus kellicotti (28) which have a fascinating life cycle.
Humans acquire the disease by eating raw or undercooked crabs or crayfish containing the larvae of
these parasites (29,30). Once ingested, the larvae bore through the intestinal wall and enter the
peritoneal cavity. They then migrate upward in the peritoneal cavity to the diaphragm, bore through the
diaphragm, and then, after traversing the pleural space, bore through the visceral pleura and enter the
lung (29,30). In the lung, the larvae lodge near small bronchi and mature into the adult lung flukes that
persist in the lungs for years while producing approximately 10,000 eggs daily. The eggs produced by the
mature flukes are expectorated or are swallowed and excreted in the feces. Once in water, the eggs
develop into ciliated miracidia that infect freshwater snails. Another larval

274 PLEURAL DISEASES

form develops in the snails and is eventually liberated as cercariae that penetrate crayfish and crabs, to
complete the cycle (29,30).

Pathogenesis and Incidence The pleural disease associated with paragonimiasis is thought to arise when
the parasites traverse the pleural space and penetrate the visceral pleura. Pleural disease is common
with paragonimiasis (31,32). In a series of 71 cases of pleuropulmonary paragonimiasis from Korea, 43
patients (61 %) had pleural disease including 26 with pleural effusions, 12 with hydrothorax, and 5 with
pleural thickening (32). Twelve of these patients had bilateral pleural effusions or hydrothoraces (32). In
another series from Japan, 9of13 patients ( 69%) had a pleural effusion (31). The prevalence of pleural
disease was less in a more recent study of 31 patients from Korea who underwent chest CT scans (33). In
this study, only nine patients (29%) had pleural disease that included six pleural effusions, two
hydropneumothoraces, and one pneumothorax (3). Although paragonimiasis is confined mainly to
residents of the Far East, there was an increased incidence of this disease in the United States in the
1980s with the influx of refugees from Southeast Asia (29,34). Johnson and Johnson (34) reported a
series of 25 cases of paragonimiasis that occurred in Indo-Chinese refugees between March 1980 and
December 1982. Seventeen cases occurred in Minneapolis, whereas eight cases occurred in Seattle (34).
Twelve of the patients (48%) had pleural effusions. The effusions were bilateral in three individuals and
were massive in six. Non-Asian individuals in the United States have developed paragonimiasis from
ingesting infected crayfish (35) or crabs (36). Indeed between July 2006 and September 2010, nine
patients in Missouri developed paragonimiasis after eating raw or undercooked crayfish and all had a
pleural effusion (28).

Diagnosis The diagnosis of pleural paragonimiasis should be suspected in Asian patients or in patients
with a pleural effusion who have recently traveled to the East. The diagnosis of paragonimiasis is made
either by detecting eggs in sputum, stool, fluid from bronchoscopic lavage, or biopsy specimens, or by a
positive anti-Paragonimus antibody test (29). Enzyme-linked immunosorbent assay (ELISA) is highly
sensitive and specific in detecting antibodies, whereas eggs are demonstrable in less than 50% of cases
(32).

The characteristics of the pleural fluid are virtually pathognomonic for paragonimiasis. The pleural fluid
with paragonimiasis is an exudate with a low glucose level (<10 mg/dL), a low pH (<7.10), and a high
lactic dehydrogenase (LDH) level (> 1,000 IU/L) (29,34). Pseudochylothorax with cholesterol crystals in
the pleural fluid occurs frequently with pleural paragonimiasis (37). Most patients with pleural
paragonimiasis have significant eosinophilia in their pleural fluid (26,34,38,39). In patients with pleural
paragonimiasis the pleural fluid interleukin 5 levels are markedly elevated and correlate with the
percentage of eosinophils in the pleural fluid (39). The only other disease that produces an eosinophilic
exudate with a low glucose level and a low pH is the ChurgStrauss syndrome (40). Yokogawa et al. (26)
reported that pleural fluid immunoglobulin E (Ig-E) levels are elevated and are higher than the
simultaneous serum IgE levels in patients with pleural paragonimiasis. Subsequently Ikeda et al. ( 41)
used ELISA to measure P. westermanispecific IgE and IgG in seven patients. They reported that the levels
of parasite-specific IgE and IgG were significantly higher in the pleural effusion than in the serum in all
patients ( 41). This latter study suggests that measurement of parasite-specific IgE and IgG is useful
diagnostically and indicates that these antibodies are produced in the pleural space.

Treatment The treatment of choice is praziquantel, 25 mg/kg body weight three times a day for 3 days. If
symptoms relapse, retreatment with praziquantel should be considered (42). Bithionol, 35 to 50 mg/kg
on alternate days for 10 to 15 doses, is also effective, but its toxic gastrointestinal effects can be
troublesome (41). If pleural disease has been present for such a prolonged period that the pleural
surfaces are abnormally thickened, penetration of the drugs into the pleural space is insufficient to
eradicate the infection, and thoracotomy with decortication may be necessary (29,43).

OTHER PARASITIC INFECTIONS

Pleural disease due to other parasites is uncommon. A rare patient with Pneumocystis carinii pneumonia
has a pleural effusion, but the effusion hardly ever dominates the clinical picture. Because P. carinii
infection usually occurs in patients with acquired immunodeficiency syndrome, this entity is discussed in
Chapter 16. Patients who die from malaria

CHAPTER 15 I PLEURAL EFFUSION DUE TO PARASITIC INFECTION 275

frequently have pleural effusions (6). The pleural effusions in this circumstance are probably secondary
to the pulmonary edema and have little, if any, clinical significance (5). There have been case reports of
pleural effusions due to Strongyloides sterocoralis (44), Trichomonas (45), Toxocara canis (46), loiasis
(47), gnathostomiasis ( 48), anisakiasis ( 49), toxoplasmosis (50), and sporotrichosis (51).