PRESENTATION OF DIAGNOSTIC QUIZ #68 (August, 2006)

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A 33-year old man from Thailand was admitted to the hospital complaining of hemoptysis of about 5 weeks duration. Approximately 9 months prior to this visit, he developed a nocturnal cough; however, there was very little sputum produced. About a month later, he developed anterior chest pain followed by the first episodes of hemoptysis. Just prior to admission, he reported losing weight and having night sweats. In seeking further relevant history, he reported eating raw and cooked fresh water crayfish as a routine part of his diet.

1. The diagnosis in this case is probably what?

2. Why could tuberculosis be confused with this infection?

3. Where is this infection endemic?

Laboratory results revealed the following:

This is an saline wet preparation of stool; the organism was seen using the low power objective of the microscope. There appeared to be an operculum with opercular shoulders at one end of the egg.

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ANSWER AND DISCUSSION OF DIAGNOSTIC QUIZ #68 (August , 2006)

The image presented in Diagnostic Quiz #68 is the following:

This image contains a Paragonimus westermani egg; these eggs measure approximately 80 by 120 microns long by 45 by 65 microns wide. Although this organism was clearly seen in the wet mount, the morphology was unclear and somewhat shrunk from the permanent stained slide examination. This nematode is considered pathogenic.

COMMENT: Paragonimus westermani is endemic in Asia, P. mexicanus is an important human pathogen in Central and South America, while P. kellicotti infections are found in North and South America. However, most paragonimiasis infections are caused by P. westermani.

LIFE CYCLE: The adult worm is a plump, ovoid, reddish brown fluke found encapsulated in the lung. Eggs deposited by the worms are ovoid, brownish yellow, unembryonated, and thick shelled, with an operculum at one end and opercular shoulders. The eggs measure 80 to 120 µm by 45 to 65 µm. P. westermani eggs are often confused with Diphyllobothrium eggs because they are operculated, unembryonated, and somewhat similar in size. However, unlike Diphyllobothrium eggs, P. westermani eggs have opercular shoulders and a thickened shell at the abopercular end. Eggs escape from the encapsulated tissue through the bronchioles, are coughed up and voided in the sputum, or are swallowed and passed out in the feces. The eggs hatch in the water in 2 to 3 weeks, releasing a miracidium to infect a susceptible snail host. Cercariae are released after sporocyst and redia generations. Crabs and crayfish are infected by cercariae via the gill chamber or upon ingestion of an infected snail. Cercariae encyst in the gill vessels and muscles. Humans are infected by ingesting uncooked crabs or crayfish containing metacercariae. The metacercariae excyst in the duodenum and migrate through the intestinal wall into the abdominal cavity. The larvae migrate around or through the diaphragm into the pleural cavity and the lungs. The larvae mature to adults in the vicinity of the bronchioles, where they discharge their eggs into the bronchial secretions. Although these worms are hermaphroditic, two worms are usually required for fertilization to occur. The worms can live as long at 20 years, but most will die after about 6 years.

CLINICAL SYMPTOMS: Migration of the larval forms through the intestinal wall into the abdominal cavity is generally not associated with any significant pathologic changes or symptoms. If the larvae remain in the abdomen, some patients may have abdominal pain, intra-abdominal masses, tenderness, fever, diarrhea, nausea, vomiting, and eosinophilia. Once the larvae have reached the peritoneal cavity, they begin to migrate through organs and tissues, producing localized hemorrhage and leukocytic infiltrates.

PULMONARY DISEASE. When the worms finally reach the lungs and mature, a pronounced tissue reaction occurs with infiltration of eosinophils and neutrophils. A fibrotic capsule forms around the worm. The cysts contain purulent fluid with flecks or "iron filings" composed of brownish yellow eggs. Many of the cysts perforate into the bronchioles, releasing their contents of eggs, necrotic debris, metabolic by products, and blood into the respiratory tract. The eggs may also enter the pulmonary tissue, or they may be carried by the circulatory system to other body sites, where they cause a granulomatous reaction. As the cysts rupture, a cough develops with increased production of viscous blood tinged sputum (rusty sputum, which may have a foul fish odor) and increasing chest pain. The patient may experience increasing dyspnea with chronic bronchitis and be misdiagnosed as having tuberculosis or bronchial asthma. The individual will generally have a moderately high peripheral blood eosinophilia and leukocytosis with elevated levels of IgG and IgE in serum. Although some patients will exhibit symptoms continuously, others may remain asymptomatic for weeks to months between periods of hemoptysis.

CEREBRAL DISEASE: Larval forms may end up in many ectopic sites other than the lungs; ectopic infections are generally associated with P. heterotrema, P. mexicanus, and occasionally P. westermani. Cysts have been detected in the liver, intestinal wall, muscles, peritoneum, and brain. The most serious consequence of paragonimiasis consists of the cerebral complications, which are commonly found in younger age groups. Unlike adult flukes in other extrapulmonary sites, worms found in the brain usually contain eggs. The worms probably migrate from ruptured lung cysts and travel through the soft tissues surrounding veins into the brain area. The worms eventually encapsulate, but before being walled off, they cause necrosis within the brain tissue, as well as possible cerebral hemorrhage, edema, and meningitis.

DIAGNOSIS: Individuals with symptoms of chronic cough, vague chest pains, and hemoptysis who have resided in an area where infections are endemic and have a history of eating raw crayfish or crabs should be suspected of having paragonimiasis. Paragonimus eggs can be detected in the sputum and the stool, and concomitant examinations should be performed to improve the overall detection rate. In many individuals in whom the infection is eventually confirmed, small numbers of eggs are present intermittently in the sputum and feces. For patients with light infections, up to seven sputum examinations have been recommended. Frequently, pulmonary paragonimiasis is misdiagnosed as pulmonary tuberculosis. The Ziehl Neelsen method for detecting mycobacteria destroys Paragonimus eggs . It is important to remember that the typical findings of cough, hemoptysis, and eggs in the feces or sputum may be absent in patients with ectopic or pleural infection with Paragonimus spp.

TREATMENT: The drug of choice is praziquantel at 25 mg/kg three times at 4 h intervals after meals for 2 or 3 days. Very few patients will require retreatment; 100% cure is usually obtained with the exception of certain patients with a heavy worm burden. There is dramatic improvement in symptoms, and they are usually gone within a few months. The dose required in cerebral paragonimiasis is generally higher and may need to be adjusted relative to the clinical outcome; convulsions and coma have been seen. These patients should be hospitalized for therapy and should be monitored closely; corticosteroids may also have to be given when treating with praziquantel.

 
The image on the left is a Paragonimus egg seen in a sputum specimen. The image on the right shows a Paragonimus egg stained with iodine; note the operculum, opercular shoulders, and the thickened abopercular end.

 

REFERENCES:

Garcia, L.S. 2007. Diagnostic Medical Parasitology, 5th Ed., ASM Press, Washington, D.C.

Garcia, L.S. 1999. Practical Guide to Diagnostic Parasitology, ASM Press, Washington, D.C.