Paragonimiasis 

Updated: Oct 11, 2019
Author: Seth D Rosenbaum, MD; Chief Editor: Russell W Steele, MD 

Overview

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 first case described in humans was at autopsy in Taiwan in 1879, when adult flukes were found in the lung.[1] 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.

See the image below.

This micrograph depicts an egg from the trematode This micrograph depicts an egg from the trematode parasite Paragonimus westermani. Eggs range in size from 68-118 µm x 39-67 µm. They are yellow-brown and ovoidal or elongated, with a thick shell. They are often asymmetrical, with one end slightly flattened. At the large end, the operculum (ie, lid or covering) is visible. Photo courtesy of The Centers for Disease Control and Prevention.

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.

See the image below.

This is an illustration of the life cycle of Parag This is an illustration of the life cycle of Paragonimus westermani, one of the causal agents of paragonimiasis. Photo courtesy of The Centers for Disease Control and Prevention.

When humans ingest raw infected crustaceans, larval flukes develop in the small intestine and 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. The eggs may then be expectorated or swallowed. If these eggs reach a water source, the life cycle will start over again.[2] 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.

Etiology

Factors that facilitate the life cycle of the flukes and subsequent transmission of infection to humans include the following:

  • Large numbers of reservoir and intermediate hosts
  • Behaviors such as spitting
  • 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 "sashimi"). Raw crawfish is also popular in the Mississippi Basin.[3] 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.

Epidemiology

Frequency

United States

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.[4, 5]

International

Paragonimus species are endemic to Southeast Asia, Latin America (most commonly in Peru), and Africa (most commonly in Nigeria). Paragonimiasis is less commonly found in West Africa and Central and South America.[2] An estimated 22 million people are infected worldwide. Prevalence of infection in endemic areas ranges from 0.1-23.75%.

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 and peaks 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.

Prognosis

The prognosis is good, with therapeutic cure rates of 90-100%. 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.)

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%. Cerebral infections may be associated with persistent seizures.

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

 

Patient Education

Safe food preparation and consumption must be emphasized.

 

Presentation

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 for 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). The American College of Chest Physicians has established clinical practice guidelines for chronic due to TB and other infections.[6]

Eosinophilia and lack of fever suggest the true diagnosis. Peripheral eosinophilia is present in as many as 25% of patients.[7] 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.[8]

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:

  • Liver
  • Spleen
  • Kidney
  • Brain
  • Intestinal wall
  • Peritoneum
  • Mesenteric lymph nodes
  • Muscle
  • Testis/ovary
  • Subcutaneous tissues
  • Spinal cord

Although cerebral paragonimiasis occurs in fewer than 1% of symptomatic patients, it is the most common extrapulmonary site of infection and is responsible for 50% of all extrapulmonary disease.[1] Moreover, it is seen in as many as 25% of patients requiring hospitalization. This form of the disease is also particularly common in children. 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.

Xia et al conducted a retrospective analysis of clinical characteristics and treatment of recently diagnosed cases of cerebral paragonimiasis.[9] Their study cohort consisted of 27 patients who were diagnosed between September 2008 and September 2013. These diagnoses were confirmed by IgG enzyme-linked immunosorbent assays. Follow-up was performed for 24 patients during a period of 6 to 56 months. Cerebral paragonimiasis accounted for 27 of 125 cases (21.6%) of paragonimiasis. The average duration from onset to treatment with praziquantel was 69 days. All patients resided in rural areas. Positive lung results were found in 20 patients; of these patients, visible lung lesions were found in 14. The lesions were surgically removed in 8 of these cases. High eosinophil counts were found in 24 patients, and eosinophilic meningitis was noted in 17. The rate of misdiagnosis and missed diagnosis was 30.4%. Most symptoms markedly improved aftertreatment, but mild movement disorders in conjunction with impaired memory and personality changes persisted in a small number of patients. The investigators advised that clinicians be alert to the possibility of cerebral paragonimiasis in young patients (aged 4-16 years) who have primary symptoms of epilepsy and hemorrhage. Liquid-based cytologic examination of cerebral spinal fluid and peripheral blood eosinophil counts can aid in differentiating cerebral paragonimiasis from similar diseases.[9]

Physical Examination

Physical findings are usually not impressive in pulmonary paragonimiasis, but they may include findings described below.

Clubbing of the fingers occasionally occurs.

Lungs are normally clear but rales, egophony, or dullness to percussion may occur with complications such as pneumonia or pleural effusion.

Cough begins as dry and progresses to productive with blood-tinged sputum.[1] 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.

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.

 

DDx

 

Workup

Laboratory Studies

A CBC count with differential usually reveals eosinophilia in 10-30% of patients with paragonimiasis. The degree of eosinophilia is significantly higher in patients who have pleurisy. Leukocytosis with eosinophilia occurs early in the course of disease but then resolves over time.[2] Despite remarkable eosinophilia, total WBC count remains in the normal range or slightly elevated.

Obtain clinical samples for ova and parasites. Definitive diagnosis of paragonimiasis requires detection of eggs in sputum, feces, pleural fluid, cerebrospinal fluid (CSF), or pus.[10, 11] However, eggs may not be present in feces and sputum for 2-3 months.[1]  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). 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%. 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; however, chest films are normal in 13-20% of confirmed cases.[2] Radiographic abnormalities may include ring shadows, which represent cavitating lesions, fibrosis, nodules or linear infiltrates with calcified foci, loculated pleural effusions, and pleural thickening.

Three radiographic stages of pulmonary infection have been described.[10]  Migration of larvae can result in pneumothorax with consolidation or exudative pleural effusions. During fluke maturation nodular or cystic lesions predominantly develop in the periphery of the middle and lower lobes. Bronchiectasis can also occur. Following treatment lesions gradually disappear over 3-26 months.

CT scanning or MRI of the head may reveal cerebral calcification,[12] 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. Serologic tests aid in diagnosing extrapulmonary disease where eggs are not shed in the sputum or stool. The complement fixation test is sensitive and is most useful following therapy because antibody levels fall 6-12 months after effective treatment. 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. A rapid immunoblot test developed by the Centers for Disease Control and Prevention is 96% sensitive and 99% specific but cannot be used to differentiate active from past infection.

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. Skin testing is useful as an epidemiologic tool to detect prevalence of infection and is the most commonly used test for screening. Because this test can cross react with Clonorchis sinensis and Schistosoma japonicum, it should only be used for purposes of screening.[1]

Procedures

With lumbar puncture, examination of infected CSF reveals bloody or turbid fluid containing numerous eosinophils.

With thoracentesis, infected pleural fluid is usually serosanguineous and has more than 1000 red cells with accompanying eosinophilia. The fluid is usually 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 vary and depend 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.

 

Treatment

Medical Care

Antiparasitic therapy is the mainstay of paragonimiasis treatment.

Triclabendazole was approved by the FDA in 2019 for fascioliasis after being available for many years from the CDC. The CDC recommends triclabendazole off-label for the treatment of paragonimiasis.[13] In areas where triclabendazole is available, it is becoming first-line therapy for the treatment of paragonimiasis. Triclabendazole has been administered at a dose of 10 mg/kg/d for 3 days or 20 mg/kg/d divided in 2 doses for 1 day for paragonimiasis. Cure rates have been as high as 98.5%.[1]

A study done in Ecuador randomized 62 patients with confirmed pulmonary paragonimiasis to one of four groups (praziquantel or one of three groups with differing doses of triclabendazole).[14] This study found improved clinical response and quicker decreases in sputum production in patients treated with triclabendazole. Parasitological response was found to be more rapid in those individuals treated with triclabendazole. The study suggested that triclabendazole may achieve a more rapid killing of adult flukes, but the mechanism of action remains unknown.

Older therapies (eg, bithionol, niclofolan), despite their effectiveness (cure rates ≥ 90%), have unacceptable adverse effect profiles compared with praziquantel and are not available in the United States for human use.

Therapy may also be required for seizures caused by an inflammatory reaction to dying worms in the setting of cerebral paragonimiasis. Patients with cerebral paragonimiasis may require care in an ICU for seizures and/or coma.

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 on the particular manifestations of disease:

  • Pulmonologist
  • Neurologist
  • Surgeon
  • Neurosurgeon

Activity

Activity should be based on patient tolerance.

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.

Long-Term Monitoring

Follow up initial treatment after a few weeks.

 

Medication

Medication Summary

Praziquantel and triclabendazole are the two agents that the World Health Organization (WHO) and CDC recommend to treat paragonimiasis. Praziquantel is the most commonly used and has a cure rate of 80-90%

Antiparasitic agents

Class Summary

Triclabendazole was approved by the FDA in 2019 for fascioliasis after being available for many years from the CDC. The CDC recommends triclabendazole off-label for treatment of paragonimiasis.

Praziquantel (Biltricide)

Praziquantel increases cell membrane permeability in susceptible worms, resulting in loss of intracellular calcium, massive contractions, and paralysis of musculature. It produces vacuolization and disintegration of schistosome tegument, followed by attachment of phagocytes to the parasite and death.

Swallow the tablet whole with some liquid during meals. Keeping the tablet in the mouth may reveal bitter taste, which can produce nausea or vomiting.

Triclabendazole (Egaten)

Triclabendazole is an anthelmintic agent. It is approved for fascioliasis, but off-label use for paragonimiasis is supported by recommendations from the CDC. Its mechanism of action is not fully elucidated. Studies in vitro and/or in infected animals suggest that triclabendazole and its active metabolites (sulfoxide and sulfone) are absorbed by the tegument of the immature and mature worms, leading to a decrease of the resting membrane potential, inhibition of tubulin function, and inhibition of protein and enzyme synthesis.