Humans acquire paragonimiasis after consumption of raw, salted, or wine-soaked crustacea (freshwater crabs or crayfish) infested with the metacercarial stage of lung flukes belonging to the genus Paragonimus (the life cycle of Paragonimus is illustrated in the CDC PHIL [http://phil.cdc.gov/Phil]; photograph 3415). It is estimated that 20 million people are infected with Parago-nimus species.70 P. westermani is endemic in parts of China, Korea, Japan, the Philippines, and Taiwan. Other Paragonimus species infect humans in western Africa and Central and South America. Although paragonimiasis is rare in the United States, it has developed in persons in Missouri from indigenous Paragonimus species.
Ingested metacercariae undergo excystation in the duodenum and migrate through the wall of the gut into the peritoneal cavi-ty. Most pass through the diaphragm and penetrate the parenchyma of the lung. Neutrophilic and eosinophilic reactions, followed by a mononuclear leukocytic inflammatory reaction, develop around the fluke. As the lung parenchyma necrotizes, a fibrous capsule begins to surround the fluke. By about 5 to 6 weeks after ingestion, the flukes have matured and start laying eggs, which causes the capsule to enlarge and rupture, often into a bronchiole. The most common presentation of paragonimiasis is the production of brown-tinged sputum or hemoptysis, which derives from the admixture of eggs, inflammatory cells, and blood in the sputum. Sputum is often gelatinous and purulent as well as bloody. Patients usually appear well but may have a chronic cough, pleuritic pain, or night sweats.
Figure 13 Eggs of S. japonicum (a), S. haematobium (b), or S. mansoni (c) detected by microscopic examination of the stool, urine, or rectal mucosa biopsy specimens confirm the diagnosis of schistosomiasis. The magnification is about 400 times. (d) This S. mekongi egg was found in the stool of a Laotian refugee in the United States. The magnification is about 1,000 times.
Young flukes may migrate to nonpulmonary sites. Localization in the CNS produces signs and symptoms from a cerebral or spinal inflammatory mass lesion, which may calcify.72 Less commonly, the parasites lodge in cutaneous or peritoneal sites.
During the early stages of infection, when the larvae migrate, blood eosinophilia is prominent. The chest x-ray may show transient, often basilar, infiltrations, as in Loffler syndrome. Later in the course of the disease, blood eosinophilia commonly disappears, and the chest x-ray may show areas of cavitation; ill-defined, so-called cotton-wool and streaky densities; and bubblelike cavities.73 Pleural reaction, with or without pleural effusion or pneumothorax, can occur.
The diagnosis of paragonimiasis should be considered for patients from endemic areas with compatible clinical presenta-tions.74 Examination of the sputum for ova may confirm the diagnosis by revealing the operculated eggs of Paragonimus. Swallowed eggs appear in the stool; therefore, examining the stool for eggs may be helpful, especially in children. Fine-needle aspiration of pulmonary lesions also yields diagnostic eggs.75 Paragon-imiasis may resemble pulmonary tuberculosis both clinically and radiographically, yet Paragonimus eggs are usually not seen in acid-fast stains. Serologic tests are available.
Praziquantel is an effective treatment of paragonimiasis, although its use remains investigational. The dosage is 25 mg/kg orally three times a day for 2 days.19 Bithionol is somewhat effective, but its use is limited because of side effects such as diarrhea. Triclabendazole has been used and has been reported to cure cases in which praziquantel and bithionol had failed.
Clonorchis sinensis, the Chinese liver fluke, infects approximately seven million persons in the Far East, including South China, Hong Kong, Taiwan, Japan, Korea, and Vietnam.76 Humans become infected with C. sinensis, a parasite of freshwater fish, by eating raw or undercooked fish containing encysted metacercariae (the life cycle of C. sinensis is illustrated in the CDC PHIL [http://phil.cdc.gov/Phil]; photograph 3385). Larvae, liberated by trypsin in the duodenum, migrate to the common bile duct and then to the distal biliary tree. There they mature into adult worms, which may persist for more than 20 years. Less commonly, adult worms are found in the gallbladder and pancreatic ducts.
In the acute phase of the infection, the epithelium of the biliary tree undergoes early desquamation, which is followed by hyperplasia and increased mucin production by the epithelial cells. The hyperplasia may progress to adenomatous changes. With chronic infection, fibrosis develops around dilated bile ducts. Clinically, the syndrome of acute clonorchiasis, manifested by fever, chills, and tender hepatomegaly, may develop 1 week after ingestion of infected fish. Later in the course of the infection, however, most patients with light infection and many with heavy infection are asymptomatic.77 Occasionally, adult worms block pancreatic ducts, causing pancreatitis. By occluding the biliary tract, worms may contribute to acute suppurative cholangitis. Clonorchiasis predisposes to intrahepatic bile duct stone formation and to recurrent pyogenic cholangitis; infection with C. sinensis has been associated with cholangiocarcinoma.
Leukocytosis, prominent eosinophilia, and elevation of alkaline phosphatase levels occur in symptomatic acute clonorchia-sis. Sonography often detects diffuse dilatation of small intra-hepatic bile ducts without dilatation of large intrahepatic or ex-trahepatic ducts. Adult flukes may be visualized in the gallbladder by ultrasonography and in the bile ducts by cholangiography.79 In asymptomatic chronic clonorchiasis, eosinophilia is not present, and liver function tests and liver scans are normal. Egg laying begins within 2 to 3 weeks after infection; eggs may be found either in the stool or in duodenal aspirate. Diagnostic serologic tests are neither sensitive nor specific. The diagnosis should be considered in patients who have a history of travel or residence in the Far East, have eaten undercooked fish, and have a compatible clinical syndrome.
Praziquantel, which is considered investigational for clonor-chiasis, constitutes effective and well-tolerated therapy for this disease. Praziquantel is administered at a dosage of 25 mg/kg orally three times a day for 1 day.19 An alternative investigative therapy is albendazole, 10 mg/kg/day for 7 days.19 Initially, complications of C. sinensis infection, including calculi, cholangi-tis, and pancreatitis, are managed medically, although surgical drainage may be required.
Opisthorchiasis represents infection by either Opisthorchis fe-lineus or O. viverrini. O. felineus infects 1.5 million persons in Kazakhstan, the Ukraine, central Europe, western Siberia, and parts of Asia; O. viverrini infects nine million persons in Thailand, Laos, and Cambodia.
Cats and wild carnivores are the definitive hosts of these species. Humans acquire infection by eating raw or undercooked fish that contains metacercariae of the parasite. Metacercariae undergo excystation in the duodenum and migrate into the bile ducts, where they mature.
Clinical features of opisthorchiasis are similar to those of clonorchiasis; complications include the development of cholan-giocarcinomas.77,78,80 The diagnosis is made by finding eggs in fe-ces or in duodenal aspirate.
Therapy, which is considered investigational by the FDA, consists of praziquantel (25 mg/kg orally three times in 1 day).19 Complications involving biliary tract sepsis require the administration of antibacterial agents.
Fasciola hepatica, the liver fluke of sheep and cattle, is a major veterinary problem and can give rise to human fascioliasis.78,81,82 Human infection with F. hepatica shows a wide geographic distribution that includes Europe, China, Africa, and Latin America; the disease is considered a public health problem in the Andean countries of South America, Iran, and western Europe.82 Despite the prevalence of the parasite in sheep and cattle of the southern and western United States, autochthonous human cases are rare. Humans generally become infected by ingesting parasitic cysts attached to aquatic plants, most notably wild watercress.
Ingested metacercariae burrow through the intestinal wall into the peritoneal cavity and then penetrate the hepatic capsule and parenchyma; they then enter the bile ducts, where they mature into adults after 3 to 4 months. Acute fascioliasis runs its course during the months of penetration and maturation. Symptoms may be minimal or include fever, upper abdominal pain, hepatomegaly, and malaise. Pruritus, urticaria, jaundice, nonproductive coughing, and anemia occur less often.
After the flukes mature in the biliary passages, hyperplasia and dilatation of the biliary ducts, as well as periductal fibrosis, develop. Clinical manifestations in the chronic stage of infection are variable and may include the same signs and symptoms experienced in the acute phase. Obstruction of the biliary tract, cholecystitis, and biliary cirrhosis are uncommon. In rare instances, flukes migrate to other tissues, including the lungs, muscles, and CNS.
Ingestion of raw sheep or goat liver containing young flukes produces halzoun, a disease recognized in the Near East. Lodging of the flukes in the pharynx produces a pharyngeal inflammatory mass lesion with attendant dysphagia and dyspnea.
Acute fascioliasis usually produces leukocytosis, marked eosinophilia, and cholestatic-type abnormalities on liver function testing. Eggs are not found until approximately 3 months after infection, when they may be detected in the stool or, with a higher yield, in biliary or duodenal fluid samples. Thus, the triad of fever, marked eosinophilia, and hepatomegaly suggests acute fascioliasis. A history of ingestion of potentially infected watercress supports the diagnosis. Serologic tests are available but may reflect cross-reactions with other helminthic parasites. Nodular hepatic lesions with diminished density may be visualized by CT or MRI.84,85 In chronic fascioliasis, the extent of the abnormalities in liver function tests and cholangiograms correlates with the magnitude of biliary tract obstruction and hepatocellu-lar damage.
Triclabendazole, given in a single oral dose of 10 mg/kg, is the drug of choice for fascioliasis, but in the United States it is available only from the manufacturer (Novartis). Bithionol (30 to 50 mg/kg on alternate days for 10 to 15 doses) and nitazoxamide (500 mg p.o., b.i.d. for 3 days) are alternatives.19 Praziquantel is not effective for fascioliasis.
Fasciolopsiasis results from infection with the intestinal fluke Fasciolopsis buski, which is found in many parts of Asia.86 This fluke principally parasitizes the intestine of the pig. Human infection is acquired by ingestion of water plants such as water chestnuts, which bear metacercariae of the parasite. The larvae undergo excystation in the duodenum and develop into large adult flukes, up to 7 cm long, that attach to the mucosa of the proximal small intestine. Inflammation and ulceration may occur at these intestinal sites. Light infection is asymptomatic; heavy infection is associated with abdominal pain, ulceration, hemorrhage, intestinal obstruction, malabsorption, and facial and generalized edema.87 Blood eosinophilia is common. Diagnosis is made by finding adult flukes or, more commonly, by finding in feces the eggs of F. buski, which are difficult to distinguish from the eggs of Fasciola hepatica. Fasciolopsiasis is treated, on an investigational basis, with praziquantel, 25 mg/kg orally three times in 1 day,10 although some sources advise that a single 15 mg/kg dose is effective.
Other Intestinal Flukes
Infection with two small intestinal flukes, Metagonimus yoko-gawai (found in the Far East and Indonesia) and Heterophyes het-erophyes (found in Tunisia, Egypt, and the Far East), occurs when humans ingest raw or undercooked fish that contains metacer-cariae of the parasites. The adult flukes are 2 to 3 cm long and attach to the mucosa of the small intestine. Heavy infection may cause abdominal pain and diarrhea.88 Diagnosis is made by finding eggs, which resemble the eggs of Clonorchis species, in feces. Therapy consists of the investigational drug praziquantel (25 mg/kg orally three times in 1 day).
Human infection with the intestinal fluke Metorchis conjunc-tus, acquired near Montreal, Canada, by consumption of the white sucker fish, has been described. Illness consisted of upper abdominal pain, low-grade fever, eosinophilia, and elevated liver enzyme levels. Diagnosis was made by finding eggs in the stool and by serology. Praziquantel (25 mg/kg three times in 1 day) is beneficial.
The intestinal fluke Nanophyetus salmonicola has been recognized in humans who ate raw or kippered salmon. In most patients, symptoms and infection resolved without therapy, although treatment can be provided with praziquantel (20 mg/kg given three times in 1 day).
Humans can harbor the adult form of fish, pork, and beef tapeworms (cestodes). These often do not cause disease but are noticed when segments of the worm are passed. Most often, these segments can be distinguished from other worms by their flat, tapelike appearance and their segmented proglottids. Examination of these proglottids or the head of the tapeworm can differentiate these three species. In general, larval forms of tapeworms, such as cysticercus (pork) and Echinococcus (dog), cause more severe disease by mass effect and inflammation.
Humans acquire fish tapeworm infection by ingestion of inadequately cooked fish containing the infective plerocercoid stage of parasitic Diphyllobothrium species, including D. latum (the life cycle of D. latum is illustrated in the CDC PHIL [http://phil.cdc.gov/Phil]; photograph 5257).91-93 The growing popularity of raw fish dishes, such as sushi, sashimi, seviche, and Dutch green herring, has increased the risk of acquiring di-phyllobothriasis. Freshwater fish, including pike and yellow perch caught in the United States, may harbor Diphyllobothrium species, as may anadromous salmon. Diphyllobothrium species other than D. latum are found in Pacific salmon and Alaskan blackfish.94 Adult tapeworms may grow up to 15 meters in length and live for 20 years or longer in the small intestine. Human infections are often asymptomatic, although some patients experience anorexia, nausea, or weight loss. Because D. latum competes with the host for vitamin B12, megaloblastic anemia and neuropathy from vitamin B12 deficiency may develop. Diagnosis is made by finding the operculated eggs in the stool or by recovering proglottids in the stool after a saline purge. Therapy is with praziquantel (5 to 10 mg/kg, given once), which is investigational for this use.19 An alternative is niclosamide, in a single oral dose of 2 g; however, this drug may be difficult to obtain in the United States and may be available only from compounding pharmacies.
Figure 14 Life cycle of Taenia solium, the pork tapeworm, which causes cysticercosis, and of T. saginata, the beef tapeworm.
Taenia solium, or pork tapeworm, causes two distinct types of disease, depending on the stage of the parasite that is ingested [see Figure 14].95 If cysticerci in inadequately cooked pork are ingested, the adult tapeworm develops in the intestine, causing symptoms such as abdominal pain, weight loss, and weakness. Patients may describe passing proglottid segments of the worm. Eggs of T. solium are also passed in the feces. Eggs can be detected with greater frequency by applying clear cellulose acetate tape to the perianal skin and examining the tape, as described for pin-worm [see Intestinal Nematode Infections, above]. T. solium eggs are indistinguishable from eggs of T. saginata (beef tapeworm); diagnostic differentiation between the two species requires recovery of mature proglottids or the head (scolex) from the stool [see Figure 15]. Therapy for adults infected with intestinal pork tapeworm consists of praziquantel (5 to 10 mg/kg, given once).19 Some authorities suggest using niclosamide (2 g in a single oral dose) because it is not absorbed and will not cause neurologic symptoms in patients with asymptomatic neurocysticercosis cysts; however, this drug may be difficult to obtain in the United States and may be available only from compounding pharmacies.
Cysticercosis, the second disease entity, is caused by the in-gestion of T. solium eggs. In an uninfected person, such ingestion may occur by consumption of food contaminated by egg-containing feces from an infected person. In persons with an intestinal worm, ingestion may occur by autoinfection involving hand-to-mouth fecal carriage or by regurgitation of egg-laden proglot-tids into the duodenum or stomach. Most infections are encountered in developing countries, where intestinal T. solium infections occur frequently. Experience in the United States has demonstrated, however, that cysticercosis may develop in those who have never traveled abroad, through transmission of infectious eggs from family members, domestic workers, or others infected with T. solium.
Figure 15 Hooklets on the scolex (head) of Taenia solium give it an "armed" appearance.
The ingested eggs hatch in the stomach and upper intestine, and the resultant oncospheres circulate in the blood to various tissues. Cysticerci develop most often in subcutaneous tissue, skeletal muscle, and the brain, as well as in other organs, including the eyes, heart, liver, and lungs. Developing cysticerci elicit little host reaction, but as the cysticerci begin to degenerate, usually after several years, inflammation develops. Ultimately, the cysts, which range from 0.5 to about 2.0 cm in diameter, undergo necrosis and may become calcified.