Paragonimus(lung fluke)

Background

: Trematodes of the Paragonimus genus cause paragonimiasis, a parasitic disease that strikes carnivores, causing a subacute to chronic inflammatory disease of the lung. Of the 10 or more Paragonimus species that are human pathogens, only 8 cause significant infections in humans. The most common is the Oriental lung fluke, Paragonimus westermani. The adult trematode is reddish-brown and ovoid. Adults have 2 muscular suckers, an oral sucker situated anteriorly and a ventral sucker at mid-body on the ventral surface. The eggs, golden brown and asymmetrically ovoid, have a thick shell with an operculum.

Pathophysiology

: The life cycle of these flukes involves 2 intermediate hosts plus humans. Its complex life cycle involves 7 distinct phases: egg, miracidium, sporocyst, redia, cercaria, metacercaria, and adult. Adult flukes live in human lungs and deposit eggs into the bronchi. Eggs are expelled either by coughing or by being swallowed and passed in human feces. Eggs then develop in water for 2-3 weeks and ultimately release miracidia, which invade the first intermediate host, ie, a specific species of fresh water snail. These miracidia develop through sporocyst and rediae stages into cercariae. The cercariae emerge and invade the second intermediate host, ie, a crustacean such as crabs or crayfish, in which they become metacercariae.

When humans ingest raw infected crustaceans, larval flukes develop in the small intestine, penetrate the intestinal wall into the peritoneal cavity 30 minutes to 48 hours after excysting. They then migrate into the abdominal wall or liver, where they undergo further development. Approximately 1 week later, adult flukes reenter from the abdominal cavity and penetrate the diaphragm to reach the pleural space and lungs. Flukes mature, a fibrous cyst wall develops around them, and then egg deposition starts 5-6 weeks after infection. Lung flukes may live 20 years or more. In Japan, transmission has also occurred following human ingestion of raw pork from wild pigs that contained the juvenile stages of Paragonimus species.

Frequency:

· In the US: Generally, small numbers of cases have occurred in immigrants from endemic areas; however, the first case of paragonimiasis was reported in the United States in 1986 in a nonimmigrant adult. It is an important infection to consider in Southeast Asians who have settled in various areas of the United States.

· Internationally: Paragonimus species are found in Asia, Africa, and Latin America. An estimated 20 million people are infected worldwide. Prevalence of infection in endemic areas ranges from 0.1-23.75%.

Mortality/Morbidity

: Death may occur during the acute phase of infection. For those who survive the acute phase, spontaneous recovery usually occurs within 1-2 months, but symptoms may recur intermittently over several years. Complications of untreated heavy infection include interstitial pneumonia, bronchitis, and bronchiectasis. Secondary complications may include bronchopneumonia, lung abscess, pleural effusion, or empyema. Untreated cerebral paragonimiasis has a mortality rate of approximately 5%.

Race: Paragonimiasis is most common in Asians, Africans, and Hispanics.

Sex: Prevalence of infection is higher among females. An increase in infection in men, most notably those who are middle aged, because of their traditional culinary habits, has been observed in Japan.

Age: Prevalence reportedly increases with age to a peak prevalence in older adolescents and young adults; prevalence then declines progressively with age. By the sixth decade of life, prevalence is less than 25% of its peak in young adulthood.


History

About 20% of patients with paragonimiasis are asymptomatic. Abdominal pain, diarrhea, and urticaria occur during the acute phase, which corresponds to the period of invasion and migration of immature flukes. These initial symptoms are followed a few days later by fever, cough, dyspnea, chest pain, malaise, and sweats. The acute phase usually persists several weeks. During the chronic phase, manifestations may be pulmonary or extrapulmonary. Chronic pulmonary symptoms consist of dry cough followed by a cough productive of tenacious and rusty or golden sputum. Pulmonary symptoms begin approximately 6 months after infection and are often mistaken for symptoms of tuberculosis (TB). Eosinophilia and lack of fever suggest the true diagnosis. Patients frequently report vague chest discomfort, dyspnea on exertion, or wheezing. Life-threatening hemoptysis may occur in some cases. Extrapulmonary paragonimiasis can be divided into cerebral, abdominal, subcutaneous, and miscellaneous forms of the disease.

· Extrapulmonary paragonimiasis can occur either from the migration of young or mature flukes to various organs or from eggs that enter the circulation and are carried to the following sites:

o Liver

o Spleen

o Kidney

o Brain

o Intestinal wall

o Peritoneum

o Mesenteric lymph nodes

o Muscle

o Testis/ovary

o Subcutaneous tissues

o Spinal cord

· Although cerebral paragonimiasis occurs in fewer than 1% of symptomatic patients, this form of the disease is particularly common in children. It is the most commonly recognized form of extrapulmonary disease and is seen in as many as 25% of patients requiring hospitalization. Early symptoms resemble meningoencephalitis and may persist 1-2 months. Chronic phase symptoms include headache, vomiting, seizures, or weakness.

· Eggs and worms may also cause surrounding cysts, abscesses, or granulomas to form. Cysts may occur in the intestinal wall, liver, spleen, abdominal wall, peritoneal cavity, or mesenteric lymph nodes. Symptoms may include bloody diarrhea or abdominal pain.

Physical: Physical findings usually are not impressive in pulmonary paragonimiasis.

· Clubbing of the fingers occasionally occurs.

· Rales, egophony, or dullness to percussion may occur with complications such as pneumonia or pleural effusion. The late clinical picture is similar to chronic bronchitis or bronchiectasis with profuse expectoration, pleuritic chest pain, dyspnea, cough, and occasional hemoptysis.

· Signs of cerebral paragonimiasis include facial palsy, hemiplegia, seizures, and paraplegia.

· Ocular signs include impaired visual acuity because of optic atrophy, papilledema, and hemianopsia.

· Spinal involvement may produce monoplegia, paraplegia, lower extremity paresthesias, or sensory loss.

· Findings in cases of abdominal involvement may include palpable masses.

· Hematuria may be observed with kidney involvement, and eggs may sometimes be detected in the urine.

· Patients with subcutaneous paragonimiasis can present with migratory swelling or subcutaneous nodules containing immature flukes. These firm, mobile, and tender subcutaneous nodules are often found in the lower abdominal and inguinal region.

· Scrotal paragonimiasis may mimic epididymitis or an incarcerated hernia.

Causes: Among the factors that facilitate the life cycle of the flukes and subsequent transmission of infection to humans are (1) large numbers of reservoir and intermediate hosts, (2) behaviors such as spitting, and (3) culinary habits. In Asia, raw and undercooked crab or crayfish are popular foods. In Korea and Japan, raw crayfish are used to treat measles, diarrhea, and skin conditions. Some tribes in Africa eat raw crustaceans to cure infertility. Peruvians eat raw crab with vegetables and lemon juice. Paragonimiasis may also be acquired by consuming raw meat from a paratenic host that contains young flukes (eg, wild boar as "shashimi"). Infection may also be transmitted via contaminated kitchen utensils (eg, cutting boards, knives) or from cloths used to squeeze and strain juices from crabs for the preparation of soup.

Lab Studies:

· A complete blood count with differential usually reveals eosinophilia in the range of 10-30% of patients. The degree of eosinophilia is significantly higher in patients who have pleurisy. Despite remarkable eosinophilia, total WBC count remains in the normal range or slightly elevated.

· Clinical samples for ova and parasites

o Diagnosis of paragonimiasis is confirmed by finding eggs in sputum, eggs in feces, pleural fluid, cerebrospinal fluid (CSF), or pus.

o Worms or eggs may be found in biopsies of pulmonary, cerebral, subcutaneous, or intra-abdominal nodules or cystic lesions. The specific species causing paragonimiasis can be identified from adult or immature flukes found in surgical specimens (rarely in the sputum).

o Egg detection rates for paragonimiasis average 25-35% for a single sputum specimen but may reach 50% with multiple examinations. (As many as 7 examinations have been recommended.) The yield for specimens obtained via bronchoscopy is 53-67%.

o Stool examinations are very useful to diagnose paragonimiasis in children because children tend to swallow sputum.

Imaging Studies:

· Chest radiography reveals abnormalities in approximately 80-90% of patients. The abnormalities may include ring shadows, which represent cavitating lesions, fibrosis, nodules or linear infiltrates with calcified foci, loculated pleural effusions, and pleural thickening.

· Computed tomographic imaging or magnetic resonance imaging of the head may reveal cerebral calcification, cystic lesions, or hydrocephalus. Chronic cerebral paragonimiasis may be suspected by the presence of a "soap bubble lesion", with scattered calcifications.

Other Tests:

· Serology for paragonimiasis is useful because of the relatively low percentage of egg detection.

o The complement fixation test is sensitive and can be used following therapy because antibody levels fall 6-12 months after effective treatment.

o The technical difficulties inherent in the complement fixation test make enzyme-linked immunosorbent assay (ELISA) the serological test of choice. ELISA has 92% sensitivity and is specific; however, antibody levels often take longer (ie, <24 mo) to return to the reference range after successful treatment. Low-level positive results may occur with other trematode infections.

o A rapid immunoblot test developed by the Centers for Disease Control and Prevention is 96% sensitive and 99% specific, but it cannot be used to differentiate active from past infection.

· Skin testing

o Intradermal skin testing with an extract of adult Paragonimus is reasonably sensitive, although rare false-negative results could occur. Results may remain positive for as long as 20 years after cure.

o Skin testing is useful as an epidemiologic tool to detect prevalence of infection.

Procedures:

· Lumbar puncture: Examination of infected CSF reveals bloody or turbid fluid containing numerous eosinophils.

· Thoracentesis: Infected pleural fluid usually is serosanguineous and has more than 1000 red cells with accompanying eosinophilia. The fluid usually is an exudate with a low glucose level. Parasitic eggs are rarely detected in the sediment of pleural effusions.

· Lung biopsy specimens usually reveal adult worms or eggs.

Histologic Findings: Pathological findings in the lung are variable and dependent on the worm burden and disease chronicity. Adult flukes are typically encapsulated in cysts, which tend to occur in the right lung. Patients usually have fewer than 20 cysts, each of which contains 2-4 flukes. The cyst wall is thick, sclerotic, and sometimes calcified. Microscopically, the cyst wall contains granulation tissue with fibroblasts, mononuclear cells, plasma cells, lymphoid cells, and eosinophils. Numerous Charcot-Leyden crystals and eggs are formed in the cavity, and egg-containing granuloma frequently develop near the cyst. Bronchial arteries may show hypertrophy or may rupture from damage.

Medical Care: Antiparasitic therapy is the mainstay of paragonimiasis treatment. Therapy may also be required for seizures caused by an inflammatory reaction to dying worms in the setting of cerebral paragonimiasis.

Surgical Care:

· Extrapulmonary lesions should be surgically excised.

· An intraventricular shunt may be needed to manage hydrocephalus.

Consultations: In addition to consultation with an infectious diseases specialist, the following may be helpful, depending upon the particular manifestations of disease.

· Pulmonologist

· Neurologist

· Surgeon

· Neurosurgeon

Activity: Activity should be based upon patient tolerance.
Drug Category: Antiparasitic agents -- Praziquantel is the DOC to treat paragonimiasis. Older therapies (eg, bithionol [30-50 mg/kg qod for 10-15 doses] or niclofolan), despite their effectiveness (cure rates >90%), have unacceptable adverse effect profiles compared to praziquantel.

Drug Name


Praziquantel (Biltricide) -- Increases cell membrane permeability in susceptible worms, resulting in loss of intracellular calcium, massive contractions, and paralysis of musculature. Produces vacuolization and disintegration of schistosome tegument, followed by attachment of phagocytes to parasite and death.
Tab should be swallowed whole with some liquid during meals. Keeping tab in mouth may reveal bitter taste, which can produce nausea or vomiting.

Adult Dose


25 mg/kg PO tid for 2 d

Pediatric Dose


Administer as in adults

Contraindications


Documented hypersensitivity; ocular cysticercosis

Interactions


Hydantoins may reduce serum praziquantel concentrations, possibly leading to treatment failures

Pregnancy


B - Usually safe but benefits must outweigh the risks.

Precautions


Destruction of parasite within eyes can cause irreparable lesions (do not treat ocular cysticercosis with praziquantel); caution while driving or performing other tasks requiring alertness on day of and day following treatment; minimal increases in liver enzymes reported; when schistosomiasis or fluke infection associated with cerebral cysticercosis occurs, hospitalize patient for duration of treatment; use during pregnancy only if clearly indicated; do not breastfeed during or 72 h after treatment; seizures and coma have been observed because of an inflammatory reaction that accompanies worm death (add corticosteroids when treating cerebral paragonimiasis to reduce this reaction); frequent adverse effects include abdominal pain, diarrhea, malaise, dizziness, and headache; other adverse effects include fever, nausea, rash, and pruritus

Further Inpatient Care:

· Patients with cerebral paragonimiasis may require care in an intensive care unit for seizures and/or coma.

Further Outpatient Care:

· Follow up initial treatment after a few weeks.

Deterrence/Prevention:

· In endemic areas, avoid eating uncooked or insufficiently cooked crustaceans and raw pork. Individuals should also refrain from using uncooked crustacean juice medicinally and for seasoning.

Complications:

· Pulmonary complications include pneumonia, bronchitis, bronchiectasis, lung abscess, pleural effusion, and empyema.

· Cerebral complications include seizures and coma.

· Skin complications include migratory allergic skin lesions.

Prognosis:

· The prognosis is good, with therapeutic cure rates between 90 and 100%.

· Symptoms resolve rapidly, and eggs disappear from the sputum in a few weeks following treatment. (Pulmonary paragonimiasis may be self-limited, with lesions resolving in 5-10 years in light infections.)

· Resolution of abnormalities on chest radiographs may take several months, depending on the chronicity of the disease.

· Cerebral infections may be associated with persistent seizures.

Patient Education:

· Safe food preparation and consumption must be emphasized

Medical/Legal Pitfalls:

· Failure to differentiate between paragonimiasis and tuberculosis