Paragonimiasis

INTRODUCTION — Paragonimiasis is a trematode (fluke) infection predominantly transmitted via consumption of raw or undercooked crab or crayfish. Almost 50 species and subspecies of Paragonimus have been described, most of which are found in carnivorous animal hosts. Approximately 16 species have been reported to cause disease in humans, the most common of which is the oriental lung fluke, Paragonimus westermani. Paragonimiasis can have pulmonary and extrapulmonary manifestations, as discussed in the following sections.

EPIDEMIOLOGY — Paragonimiasis occurs in several parts of the Far East, West Africa, and the Americas. It is estimated that over 20 million people are infected worldwide and more than 290 million are at risk [1]. The prevalence of infection increases in areas with numerous human and animal reservoir hosts, an abundance of first and second intermediate hosts (snails and crabs or crayfish, respectively), and social customs of eating raw or undercooked seafood. In addition, paragonimiasis can be acquired by ingesting raw meat from carnivorous animal paratenic hosts that contain young flukes (such as wild boars or deer). Transmission has also been reported via contaminated utensils, such as knives or chopping boards.

Species distribution varies by geographic region (table 1) [2]:

●P. westermani is found in Asia, particularly in China, Korea, Japan, the Philippines, Taiwan, India, Cambodia, Laos, Vietnam, and Malaysia.

●Paragonimus heterotremus is the main causative agent of paragonimiasis in Thailand, and also occurs in India, southern China, and Vietnam.

●Paragonimus skrjabini complex occurs in Japan, Thailand, and China [3].

●Paragonimus africanus and Paragonimus uterobilateralis occur in Africa; in one meta-analysis, the majority of cases occurred in the rainforest zone of West and Central Africa [4]. 

●Paragonimus mexicanus occurs in Central and South America. In North America, the disease is observed most frequently among immigrants from endemic countries, but local transmission has been described [5].

●Paragonimus kellicotti, the only species endemic to North America, has been found in various mammals including mink, raccoon, bobcats, and opossums [6]. Twenty-one autochthonous human cases of P. kellicotti infections have been reported from Ohio, Michigan, Nebraska, Iowa, Missouri, Oklahoma, Colorado, and Montreal, Canada [7-14]. Fifteen cases were acquired in Missouri and followed consumption of crayfish while on river float trips. Alcohol intoxication by these boaters may have disinhibited the consumption of undercooked or raw crayfish [14].

Life cycle — The life cycle of paragonimiasis begins with expectoration of unembryonated eggs in the sputum; alternatively, eggs may be swallowed and passed in the stool (figure 1). In fresh water, the eggs become embryonated; after a few weeks, the resulting miracidia hatch and penetrate the soft tissues of a snail (the first intermediate host). Miracidia go through several developmental stages inside the snail (sporocysts, rediae, and cercariae) over three to five months. Cercariae emerge from the snail and invade a crustacean such as a crab or crayfish (the second intermediate host) where they encyst and become metacercariae over six to eight weeks.

Metacercariae are the infective form for the mammalian host (humans, pigs, dogs, cats, and rodents). Infection is most commonly acquired by eating inadequately cooked or pickled crab or crayfish that harbor metacercariae. The metacercariae excyst in the duodenum, penetrate the intestinal wall into the peritoneal cavity, and migrate through the abdominal wall and diaphragm into the lung parenchyma, where they become encapsulated and develop into adults over five to six weeks.

Upon reaching maturity, the adult worms, which often occur in pairs in lung cysts, deposit eggs that may pass into the bronchioles and be coughed up with sputum or swallowed and passed in the stool. The time from infection to oviposition is 65 to 90 days. An individual generally carries ≤20 worms, which can persist within humans for 20 years.

The worms can also reach other tissues such as the brain and striated muscles. When this occurs, however, completion of the life cycle cannot be achieved because the eggs laid cannot exit these sites.

CLINICAL MANIFESTATIONS — Most clinical infections are asymptomatic. The likelihood of symptomatic infection depends upon the intensity of infection and the organs involved. Most symptomatic infections consist of pulmonary disease; extrapulmonary disease is relatively uncommon. The incubation period is typically from 2 to 20 days following ingestion.

Pulmonary paragonimiasis

Early infection — The early phase of paragonimiasis occurs between the time of infection and the first egg production (about two months). During the period of larval migration within the peritoneal cavity, some patients experience fever, malaise, diarrhea, or epigastric pain. Urticaria may also develop. As larvae penetrate the diaphragm and migrate within the pleural cavity, pleuritic chest pain (often bilateral) may develop. At this time (about one month after infection), the chest radiograph may demonstrate pneumothorax or pleural effusions. Pleural effusions are generally exudative and laden with eosinophils.

As migration progresses, symptoms may include chest pain, dyspnea, cough, and malaise. Less common symptoms include low-grade fever and blood-streaked sputum. Radiographic findings associated with pulmonary parenchymal migration consist of transient, migratory pulmonary infiltrates. Leukocytosis and peripheral eosinophilia (10 to 30 percent) are common.

Early pulmonary paragonimiasis may resemble Loeffler's syndrome.

Late infection — The second phase of infection refers to the period when mature flukes inhabit the lungs or ectopic locations; this phase may last for years, during which worms induce inflammation and fibrosis in the locations. Clinical manifestations depend on the duration, intensity, and site of infection.

Among patients with lung infection, recurrent blood-tinged sputum or hemoptysis is the most common symptom; malaise may be observed, although patients may not feel or appear ill. The expectorated material typically has a characteristic chocolate color and may have a foul odor [15]; it is composed of blood, inflammatory cells, and eggs released when the capsules around mature flukes rupture into a bronchiole. Fever is generally absent. Pleural effusions may be a presenting manifestation of the disease in the absence of radiographic evidence for parenchymal involvement [16]. Bronchopleural fistula is an uncommon complication. Pleural lesions are more frequently observed in patients infected by P. skrjabini than with other species [17].

Chest radiograph may demonstrate one or more lesions at the sites of localized encysted flukes or their burrowing tracts in about 80 percent of cases. Findings may include [18]:

●Ring shadow lesions, due to the relative lucency of cystic cavities [19-21]

●Patchy pulmonary infiltrates, nodules, and/or calcifications

●Pleural effusion [22]

●Irregular linear streaks, often adjacent to the ring shadows; these represent burrowing tracts of the flukes [19]

●Parenchymal mass lesions [23]

●Pleural thickening

Radiographic findings may resolve spontaneously, and new lesions may appear. The pulmonary lesions may be mistaken for tuberculosis or malignancy [15,23]. Paragonimiasis lesions are located more peripherally and are much more common in the mid- and lower lung zones; tuberculous cavities are predominantly apical lesions [24]. (See 'Differential diagnosis' below.)

On computed tomography (CT), focal fibrotic pleural thickening adjacent to a pulmonary nodule can be an important clue to the diagnosis of pleuropulmonary paragonimiasis [25]. In addition, subpleural or subfissural nodules, often containing a necrotic low-attenuation area, may be observed.

Extrapulmonary paragonimiasis — Immature flukes can also migrate to extrapulmonary tissues, such as the brain, abdomen (including the intestinal wall, liver, spleen, pancreas, kidney, adrenal glands, peritoneal cavity, ovaries, and mesenteric lymph nodes), and subcutaneous tissues. Other ectopic localizations such as the heart, mediastinum, striated muscle, spinal cord, parotid gland, testes, and breasts have also been described [26-29]. Eggs can be deposited in ectopic sites, either via release from mature worms that have migrated to these sites or via carriage of eggs to distal sites following their release from worms in the lung. Eggs or flukes in ectopic sites can provoke an inflammatory reaction, resulting in cyst, abscess, or granuloma formation.

Extrapulmonary manifestations seem to occur more frequently with certain species of Paragonimus, particularly P. skrjabini, which is endemic in China. Extrapulmonary paragonimiasis is generally considered to be uncommon; however, one report of a Paragonimus westermanii outbreak in Japan found that eight of the nine cases had extrapulmonary lesions on CT (subcutaneous nodules, ascites mesenteric inflammation, muscle swelling, or hepatic nodules) [30]. These findings suggest that extrapulmonary lesions may be identified more frequently if more extensive imaging is performed.

Cerebral infection — Cerebral paragonimiasis is the most common form of extrapulmonary disease but is relatively rare; it occurs in less than 1 percent of individuals with symptomatic paragonimiasis infection [12,31,32]. It is more common in younger patients; 90 percent of patients diagnosed are <30 years old [31].

The parasite can penetrate the meninges and invade brain parenchyma, leading to meningitis, encephalitis, arachnoiditis, hemorrhage, or a space-occupying lesion. Meningitis tends to occur as an acute manifestation and is the initial presenting feature in one-third of cases of cerebral paragonimiasis [33]. It is commonly associated with headache, fever, and vomiting and may persist for as long as one to two months. Eosinophilic meningitis may be present [12]. Cerebral paragonimiasis can mimic stroke.

Chronic manifestations include headache, vomiting, seizures, visual disturbances (particularly diplopia and homonymous hemianopsia), and motor or sensory disturbances related to a space-occupying lesion. Up to 10 cerebral cysts may be seen, predominantly in the temporal and occipital lobes. Examination may demonstrate papilledema, paresis, and/or paresthesia.

In the setting of chronic cerebral paragonimiasis, CT scans or magnetic resonance imaging (MRI) may demonstrate multiple, conglomerated, cystic, ring-enhancing lesions (1 to 3 cm), with surrounding edema. Bilateral hemispheric involvement may be present [34]. Calcification of the lesions occurs in approximately 50 percent of cases [35]. The appearance has been described as being like "soap-bubble calcifications" on skull imaging or as having a "grape cluster"-like quality on CT or MRI (image 1) [36-39]. Hydrocephalus may also be evident, and localized hemorrhages may be seen.

Spinal cord involvement is rare; it can cause focal neurologic signs, such as paralysis or sensory loss.

Abdominal infection — Cysts may develop in the intestinal wall, causing nausea, vomiting, or bloody diarrhea. Cysts or abscess formation in the liver, spleen, peritoneal cavity, or mesenteric lymph nodes can lead to abdominal pain or palpable masses [40]. Renal involvement results in hematuria, and eggs may be detectable in the urine (picture 1).

In the setting of abdominal paragonimiasis, CT scanning may show a cystic mass or conglomerate of ring-enhancing nodules (image 2) [41,42]. The most common findings on CT in the setting of hepatic involvement are peripheral lesions, connected cysts with tortuous tract formation, and tubular enhancement due to migration of the worm [43]. Imaging characteristics favoring a diagnosis of paragonimiasis over hepatocellular carcinoma include presence of lesions in the hepatic subcapsular region, characteristic tubular or tunnel features, and rim enhancement with irregular tract-like nonenhanced internal areas with a characteristic target loop [44].

Subcutaneous infection — Paragonimus infection can be associated with painless, migratory subcutaneous swellings of various sizes or tender, firm mobile nodules containing immature flukes. One or more nodules may be present. They occur most commonly on the lower abdominal wall, inguinal area, and proximal lower extremities (picture 2). The manifestations are similar to those of cutaneous larva migrans. (See "Hookworm-related cutaneous larva migrans".)

DIAGNOSIS — Diagnostic tools include microscopy, serology, and imaging. The diagnostic approach depends on the stage of infection, the nature of clinical manifestations, and the diagnostic tools available. Nonspecific findings may include a peripheral eosinophilia and a raised IgE. Cerebrospinal fluid findings often, but not uniformly, demonstrate an eosinophilic pleocytosis [45].

Establishing the diagnosis of paragonimiasis during early infection (prior to egg production) is difficult. It can be made only presumptively on the basis of compatible clinical manifestations in a patient with eosinophilia and appropriate exposure history.

In the late phase of infection, the diagnosis is suggested by a history of recurrent hemoptysis in a patient from an endemic area. It can often be confirmed by finding the characteristic eggs of Paragonimus in the sputum or bronchoalveolar lavage (BAL) [7].

Diagnostic screening of family members of index cases is warranted since treatment for asymptomatic infection is indicated [35].

Microscopy — In the late phase of infection (following egg production, 8 to 10 weeks after infection), the diagnosis can sometimes be made by finding the characteristic eggs in the sputum, BAL, or stool (picture 1) [7]. The eggs are brown, ovoid, measure approximately 100 mcm by 55 mcm, and have a thick shell. Microscopic demonstration of parasite eggs in the stool, sputum, and BAL fluid is observed in only about 50 percent of cases [22]. A 24-hour sputum collection enhances the sensitivity of egg detection [35]. Eggs may sometimes be detectable with Ziehl Nielsen staining, particularly if combined with a concentration step [46,47], but the acid-fast stain used for tuberculosis testing may destroy eggs. The diagnosis can also be made by visualization of eosinophils and eggs on fine needle aspiration, thoracoscopy, or transbronchial biopsy [23,48].

Most patients with pleuropulmonary paragonimiasis have pleural fluid with low levels of lymphocytes (<50 percent), eosinophilia (>10 percent), low glucose (<10 mg/L), low pH (<7.10), and high LDH (>1000 international units/L) [49]. In contrast, pleural fluid in cases of tuberculosis typically demonstrates an exudate with a normal-to-low glucose concentration, a predominance of lymphocytes, and a high adenosine deaminase level. (See "Tuberculous pleural effusion".)

In cerebral infection, the cerebrospinal fluid is typically bloody and often contains numerous eosinophils [45], but visualization of eggs is rare. Biopsy of cerebral, intraabdominal, or subcutaneous nodules or cysts may contain eggs or adult flukes that confirm the diagnosis, although the worm may not always be present even if an eosinophilic infiltrate is found. Biopsy is not required for diagnosis if noninvasive microscopy, serologic, or radiographic tools can be used to establish the diagnosis.

Species identification can be confirmed by examination of immature or adult flukes (picture 3) [50]. The adult parasites are approximately 10 by 5 mm. They are reddish-brown, ovoid or coffee-bean shaped, and are covered with cuticular spines.

Serology — Serologic tests include complement fixation, countercurrent immunoelectrophoresis, enzyme-linked immunosorbent assay (ELISA), and immunoblot [51]:

●Serology is useful for all sites of infection but may be particularly helpful in the setting of extrapulmonary disease, when eggs are not being shed in sputum or stool.

●The ELISA test is sensitive and specific (92 and >90 percent, respectively) and can be performed on serum or cerebrospinal fluid [36,52-54].

●Antigens that have been used include crude antigen extracts, excretory-secretory products, recombinant peptides, and various purified or partially purified antigens including cysteine proteases [2].

Point of care serodiagnostic tests are being developed. One such immunochromatography test uses excretory-secretory antigen from P. heterotremus with reported sensitivity, specificity, positive, and negative predictive values of 98, 88, 78, and 99 percent, respectively [55]. Cross reactivity with other parasitic infections are often observed with serologic tests, although multiple-dot and micro-plate ELISAs to screen for multiple parasites simultaneously have been reported to improve both sensitivity and specificity [3].

Antibodies against selected Paragonimus proteins are detectable as early as 2 to 3 weeks after infection. However, serology has limited utility for monitoring patients following therapy since antibody levels may not decrease for two years after successful therapy [56]. Antigen detection techniques using monoclonal antibodies against P. westermani antigens or recombinant antigens from other Paragonimus species have also been developed, with variable reported sensitivity and specificity, but are not yet available for widespread use [51,57,58].

Complement fixation is no longer used; problems with this test included cross-reactivity with other trematodes, labor intensity, and false-negative results in the setting of chronic infection with calcification. It has been replaced by immunoblot (available from the United States Centers for Disease Control and Prevention) or ELISA (available from some commercial laboratories) [2].

Other laboratory tests — Polymerase chain reaction is in development for species diagnosis of paragonimiasis, but it is not yet commercially available [2,59].

Skin tests consisting of an extract of adult Paragonimus spp have been used for epidemiologic screening. Sensitivity is 80 to 90 percent, but they remain positive for many years after cure and cannot determine disease activity [60].

Imaging — A radiographic clue for pulmonary paragonimiasis is the combination of pleural effusion (present in 20 to 60 percent of cases) and multiple cysts, irregular linear lesions, or nodular opacities in the lung parenchyma [18]. The most frequent computed tomography (CT) finding is a subpleural or subfissural nodule containing a low-attenuation area, associated with pleural thickening [25]. Several cases of pulmonary paragonimiasis with high uptake on fluorodeoxyglucose-positron emission tomography (FDG-PET) CT images have been described (image 3). Such findings can be difficult to distinguish from malignancy radiographically [61,62]. Chest imaging is also discussed above. (See 'Late infection' above.)

In a study comparing CT findings in 75 patients with paragonimiasis or other parasite infestation, findings more frequently observed in the paragonimiasis group included perilesional centrilobular nodules, cavitary lesions, and worm migration tracts [63]. Findings observed in both groups included pleural effusion, consolidation, and bilateral and multisegmental abnormalities.

In the setting of acute cerebral paragonimiasis, imaging may be normal. In one review of brain magnetic resonance imaging (MRI) images of six children with early cerebral infection, the most common findings were irregular hemorrhage and conglomerated, irregular lesions with surrounding edema [64]. One patient had a "tunnel sign," demonstrating the migrating track of the adult worm. Computed tomography may demonstrate hemorrhagic stroke [65].

Imaging in the setting of chronic cerebral paragonimiasis and abdominal paragonimiasis are described above. (See 'Cerebral infection' above and 'Abdominal infection' above.)

One study suggested that pericardial and omental involvement on imaging may be more common findings in cases of North American paragonimiasis due to P. kellicotti than in cases due to Asian species [66]. Thoracic spine lesions may demonstrate intraspinal granulomas in the extradural space, connections between intraspinal lesions and pleural lesions through the intervertebral foramen, and hemorrhagic foci on MRI [67]. 

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of pulmonary paragonimiasis includes [23,24]:

●Tuberculosis – Both tuberculosis and paragonimiasis consist of pulmonary involvement including recurrent hemoptysis and cavitation. Tuberculous cavities are predominantly apical lesions, whereas paragonimiasis lesions are located peripherally and are common in the mid- and lower lung zones. (See "Pulmonary tuberculosis: Clinical manifestations and complications".)

●Loeffler’s syndrome – Early pulmonary paragonimiasis may resemble Loeffler’s syndrome; both illnesses consist of transient respiratory symptoms during migration of larvae through the lungs following ingestion of eggs. Diagnosis of ascariasis at the time of pulmonary symptoms requires detection of Ascaris larvae in respiratory secretions or gastric aspirate.

●Coccidioidomycosis – Both coccidioidomycosis and paragonimiasis can cause respiratory symptoms, fatigue, and eosinophilia. Relevant exposure history is an important component of diagnosis in both illnesses. The diagnosis of coccidioidomycosis is established by culture and/or serology. (See "Primary pulmonary coccidioidal infection".)

●Aspergillosis – Aspergillosis often presents with fever, pleuritic chest pain, and hemoptysis. It typically occurs in immunosuppressed patients who may present with fever in the absence of localizing pulmonary symptoms. Radiographically, it presents with single or multiple nodules, patchy or segmental consolidation, and/or peribronchial infiltrates. The diagnosis is established based on culture and/or biopsy. (See "Epidemiology and clinical manifestations of invasive aspergillosis".)

●Histoplasmosis – Histoplasmosis presents as a subacute pulmonary infection weeks to months following exposure. Clinical presentations include pneumonia with mediastinal or hilar adenopathy, pulmonary nodule, or cavitary lung disease. The diagnosis is established based on histopathology, culture, antigen detection, and/or serologic test. (See "Diagnosis and treatment of pulmonary histoplasmosis".)

●Nocardiosis – Nocardiosis can involve both the lungs and the central nervous system. The onset may be acute or chronic; symptoms may include fever, fatigue, dyspnea, cough, hemoptysis, and pleuritic chest pain. The diagnosis is established by isolation of the organism from a clinical specimen. (See "Nocardia infections: Epidemiology, clinical manifestations, and diagnosis".)

●Bronchiectasis – Bronchiectasis is characterized by abnormal dilatation and destruction of bronchial walls; there are numerous etiologies that contribute to the pathophysiologic processes that result in bronchiectasis. Clinical manifestations of bronchiectasis consist of productive cough, dyspnea, wheezing and pleuritic chest pain. The diagnosis is established radiographically. (See "Clinical manifestations and diagnosis of bronchiectasis in adults".)

●Malignancy – Clinical findings of lung cancer may mimic paragonimiasis; these include cough, hemoptysis, chest pain, and dyspnea. In addition, radiographic findings of paragonimiasis can be difficult to distinguish from malignancy; these include pleural effusions, nodular opacities, and findings of increased uptake on positron emission tomography imaging. The diagnosis of lung cancer is established by biopsy. (See "Clinical manifestations of lung cancer".)

The differential diagnosis of cerebral paragonimiasis includes:

●Neurocysticercosis – Both neurocysticercosis and paragonimiasis may present with headache and seizures together with radiographic evidence of cerebral cysts. Neurocysticercosis may be diagnosed based on clinical and radiographic features; identification of a scolex within a cystic lesion is a pathognomonic radiographic finding. (See "Cysticercosis: Clinical manifestations and diagnosis".)

●Bacterial meningitis – Bacterial meningitis typically presents with fever, nuchal rigidity, and altered mental status; other common symptoms include headache, vomiting, and visual disturbances. It may be distinguished from paragonimiasis based on lumbar puncture findings.

●Amebic meningoencephalitis – Amebic encephalitis presents with fever, headache, photophobia, vomiting, seizures, and altered mental status. Imaging findings on computed tomography and magnetic resonance imaging are nonspecific; the diagnosis is established via observation of motile trophozoites on examination of spinal fluid. (See "Free-living amebas and Prototheca".)

●Strongyloidiasis – The Strongyloides hyperinfection syndrome consists of multiorgan system dissemination of larvae, including the central nervous system. Gram negative bacteremia and meningitis may occur due to seeding of the bloodstream from the gastrointestinal tract. The diagnosis is established by stool microscopy. (See "Strongyloidiasis".)

●Eosinophilic meningitis – Cerebral paragonimiasis may be associated with eosinophilic pleocytosis. Other causes of eosinophilic meningitis include parasitic etiologies, nonparasitic infectious etiologies, and noninfectious etiologies. (See "Eosinophilic meningitis".)

The differential diagnosis of paragonimiasis in other ectopic sites includes other parasites that can also cause ectopic lesions such as Fasciola hepatica, Gnathostoma, Anisakis, and Spirometra species.

TREATMENT — Treatment of paragonimiasis consists of anthelminthic therapy with praziquantel; triclabendazole is an acceptable alternative agent. Treatment is indicated for individuals with symptomatic as well as asymptomatic paragonimiasis, given the potential for chronic complications.

Praziquantel — Praziquantel (75 mg/kg/day in three divided doses, for three days) is generally considered the treatment of choice for all species of paragonimiasis [68].

In cerebral paragonimiasis, steroids, anticonvulsant therapy, and/or an intraventricular shunt for hydrocephalus may also be warranted. The mortality of untreated cerebral paragonimiasis is approximately 5 percent [69]. Even when symptoms wane, it may take at least a few weeks for eggs to disappear, and radiographic improvement may lag behind improvement in clinical manifestations.

Treatment for involvement of other ectopic sites must be individualized based upon the patient's clinical response.

Triclabendazole — Triclabendazole (10 mg/kg orally once or twice) is an acceptable first-line agent for treatment of paragonimiasis in areas where available [70,71]. Triclabendazole prolongs the QTc interval but otherwise is generally better tolerated than praziquantel.

In one study comparing triclabendazole and praziquantel for treatment of 62 patients with pulmonary Paragonimus mexicanus infection in Ecuador, efficacy was comparable between groups; resolution of symptoms and parasite clearance were more rapid among those who received triclabendazole. In addition, triclabendazole was better tolerated than praziquantel [71].

In a study comparing dosing for triclabendazole (a single 10 mg/kg dose versus two 10 mg/kg doses), at three months after treatment the cure rates were 84 and 90 percent, respectively [72].

Other drugs — Use of bithionol (30 to 50 mg/kg on alternate days for 10 to 15 doses) has been largely supplanted because of side effects. Niclosamide (2 mg/kg as a single dose) has also been used but is also associated with significant adverse effects. Mebendazole is not effective.

PREVENTION — Infection can be prevented by avoiding eating raw crabs and crayfish in endemic areas. Education about the potential for contamination of utensils is also important. Strict hygiene measures are needed to decrease fecal contamination of water and thereby prevent transmission. In China and Korea, local control programs have been successful in reducing prevalence rates of paragonimiasis.

SUMMARY AND RECOMMENDATIONS

●Paragonimiasis is a trematode (fluke) infection transmitted mainly via consumption of raw or undercooked crab or crayfish. The infection occurs in several parts of the Far East, West Africa, and the Americas. When clinical manifestations are present, pulmonary symptoms are most common; extrapulmonary manifestations have also been described. (See 'Introduction' above and 'Epidemiology' above.)

●Infection is usually acquired by ingestion of inadequately cooked or pickled crab or crayfish, but is occasionally acquired via consumption of infected raw meat (such as wild boar meat). Metacercariae excyst in the duodenum, penetrate the intestinal wall into the peritoneal cavity, and migrate into the lung parenchyma (figure 1). Upon reaching maturity, the adult worms deposit eggs that pass into the bronchioles and are coughed up with sputum or swallowed and passed in the stool. (See 'Life cycle' above.)

●Most clinical infections are asymptomatic; most symptomatic infections consist of pulmonary disease. Manifestations consist of early and late phases. The early phase occurs between initial infection and first egg production (about two months). During this period of larval migration within the peritoneal cavity, fever, malaise, diarrhea, epigastric pain, and/or urticaria may be observed. As larvae penetrate the diaphragm and migrate within the pleural cavity, pleuritic chest pain may develop. Additional symptoms may include dyspnea, cough, and malaise. (See 'Early infection' above.)

●The second phase of pulmonary infection refers to the period when mature flukes inhabit the lungs; this phase may last for years, during which worms induce inflammation and fibrosis. Recurrent hemoptysis is the most common symptom; malaise may be observed although patients may not feel or appear ill. (See 'Late infection' above.)

●Extrapulmonary disease is relatively uncommon. Immature flukes can migrate to the brain, abdomen (including the intestinal wall, liver, spleen, kidney, adrenal glands, peritoneal cavity, and mesenteric lymph nodes), subcutaneous tissues, and other ectopic localizations. Cerebral paragonimiasis is the most common form of extrapulmonary disease; it occurs in less than 1 percent of individuals with symptomatic paragonimiasis infection. (See 'Extrapulmonary paragonimiasis' above.)

●The diagnostic approach depends on the stage of infection and the nature of clinical manifestations. A diagnosis during early infection (prior to egg production) can be made only presumptively based on clinical manifestations in the setting of eosinophilia and appropriate exposure history. During late infection, the diagnosis is suggested by a history of recurrent hemoptysis in a patient with epidemiologic risk factors. It can usually be confirmed by identifying Paragonimus eggs in the sputum or bronchoalveolar lavage (picture 1). Serology and imaging may also be helpful tools. (See 'Diagnosis' above.)

●We suggest praziquantel for treatment of paragonimiasis (Grade 2B). Triclabendazole is an alternative treatment. Dosing is outlined above. Infection can be prevented by avoiding eating raw crabs and crayfish in endemic areas. Strict hygiene measures are needed to decrease fecal contamination of water and thereby prevent transmission. (See 'Treatment' above and 'Prevention' above.)