Part 9. Parasitic Infections–Trematodes

Hundreds of millions of people, particularly those who live in rural areas or deprived urban settings in the developing world, are at risk of acquiring foodborne trematodiasis and schistosomiasis.1-3

Foodborne trematodiasis include clonorchiasis, paragonimiasis, fascioliasis, and opisthorchiasis. These and schistosomiasis all belong to the subclass of Digenea, class of Trematoda, phylum of Platyhelminthes. The taxonomy of Platyhelminthes is shown in eFigure 335.1. Digeneans, also known as flatworms, are characterized by dorsoventral flattening, presence of an oral sucker and often a ventral sucker, and lack of a circulatory system.4Figure 335-1 shows, by means of scanning electron microscopy, the head portion of an adult Clonorchis sinensis (a liver fluke), clearly depicting some of the typical features of the Digeneans.

Epidemiology

The endemic regions of the world, global burden and at risk populations for infection with clonorchiasis, fascioliasis, fasciolopsiasis, opisthorchiasis, paragonimiasis, and schistosomiasis are summarized in Table 335-1.3,5-10

The major species from the subclass Digenea parasitizing humans include the blood flukes (5 species of Schistosoma), liver flukes (C sinensis, Fasciola gigantica, F hepatica, Opisthorchis felineus, and O viverrini), lung flukes (Paragonimus spp), and intestinal flukes (eg, Fasciolopsis buski).

Schistosomiasis exhibits the largest geographic distribution; the disease is endemic in over 70 countries and territories of the world with an estimated 779 million people at risk and 207 million infections (eFig. 335.2).3 The global burden due to schistosomiasis might be as high as 4.5 million disability-adjusted life years (DALYs). The DALY is a metric used to express the number of healthy life years lost due to a disease or injury, taking into account both premature death and living with disabilities. DALYs are extremely difficult to calculate for helminthic diseases and other chronic conditions. Schistosoma haematobium and S mansoni are responsible for the majority of the disease burden, morbidity and mortality from schistosomiasis, with disease being concentrated in sub-Saharan Africa.3,11

An estimated 750 million people are at risk of foodborne trematodiasis with over 40 million infections. Southeast Asia and the Western Pacific are the regions most impacted by foodborne trematodiasis.2,12 Estimates for at-risk populations for clonorchiasis, paragonimiasis, fascioliasis, and opisthorchiasis are 601 million, 293 million, 91 million, and greater than 60 million, respectively.

The patterns of age distribution of infections are not uniform, but in general the highest rates of infection with Schistosoma species, Fasciola species, and F buski is found among school-age children and young adults.9 On the other hand, in the case of clonorchiasis and opisthorchiasis, the prevalence of infection increases with age, and hence adults are more affected than their younger counterparts.8

Profound demographic, ecologic, and socioeconomic transformations have altered the epidemiology of schistosomiasis and foodborne trematodiasis. The development and management of water resources (ie, irrigation schemes and large dams) has resulted in outbreaks of schitosomiasis, or intensified disease transmission. Indeed, living in close proximity to such water resources is a key risk factor for acquiring the disease.3 Similarly, socio-economic changes including the expansion of aquaculture for production of freshwater fish and shrimp, inadequate sanitation, domestic migration, and wider distribution networks of food without proper inspections are some of the key features explaining an increase in foodborne trematodiasis.6

The expansion of schistosomiasis and foodborne trematodiasis into previously nonendemic areas may also be partly explained by global warming and human modification of the landscape.9,13 In the case of foodborne trematodiasis, increases in international travel and growing consumption of imported aquatic foods may also play a role. On the other hand, socioeconomic development and implementation of morbidity control programs dramatically lowered the burden due to schistosomiasis and foodborne trematodiasis in some regions.3,6

Pathophysiology

eFigure 335.3 shows the life cycle of the digeneans, distinguishing between schistosomes and foodborne trematodes. A characteristic feature is the alternation of asexual and sexual reproductive phases.4 Parasite eggs are excreted from humans (or a range of domestic animals that can also act as definitive hosts in the sputum (Paragonimus spp), feces (C sinensis, Fasciola spp, Opisthorchis spp, Paragonimus spp, S mansoni, S japonicum, S intercalatum, and S mekongi), or urine (S haematobium). Once eggs have reached a freshwater body, they develop and release a tiny larva, the so-called miracidium, which seeks a specific snail species (usually small aquatic snails), the first intermediate host. Within the snail, larval development and asexual multiplication takes place and cercariae are released from snails.

Schistosoma cercariae infect humans subcutaneously when they come into contact with infested freshwater during recreational (eg, playing in stagnant freshwater ponds) and occupational activities (eg, irrigated rice farming). The tailless cercariae are transported through blood or lymphatics to the right side of the heart and lungs. The adult worms do not multiply inside the human body, but mate and the female lays eggs about 4 to 6 weeks following cercarial penetration. This phase of infection can be associated with Katayama fever (see below) which is believed to result from immune complex formation with high antigenic stimulation due to the worm or egg antigens. The female adult worm continues to live for up to 8 years and lays eggs throughout her life span. The chronic sequelae of Schistosomiasis are due to immunologic reactions to the eggs trapped in tissues that lead to a granulomatous reaction.

In the case of lung, liver, and intestinal flukes, the cercariae encyst in the flesh of the second intermediate hosts—fish (eg, C sinensis, Opisthorchis spp) or shellfish (eg, Paragonimus spp)—or encyst on aquatic plants (eg, Fasciola spp, F buski). Humans become infected when eating raw or undercooked aquatic products harboring metacercariae.12 Upon ingestion, the acid environment of the stomach begins the process of excystment, and in the duodenum the worm burrows through the intestinal lining into the peritoneal cavity where it traverses to the lung, or through the liver to the bile ducts, where the mature worm resides and excretes eggs. The C sinensis, Fasciola spp and Opisthorchis spp reside in the bile ducts of the liver and eggs are excreted in stool. F buski resides in the duodenum. Paragonimus reside in the lungs and eggs are excreted in the sputum, or swallowed and excreted in stool.

Clinical Manifestations

Schistosomiasis

Schistosomiasis denotes a complex of acute, or chronic infections with varying clinical manifestations at different stages. The clinical manifestations depend on the species of parasite, intensity of worm burden, and immunity of the person to the parasite. Cercarial skin penetration can result in local and temporary irritation and trigger a dermal rush, manifesting within hours and persisting for a couple of days as maculopapular lesions.

Katayama syndrome is a systemic hypersensitivity reaction that results from high quantities of antigens being released by migrating schistosomula, adult worms, or eggs, coupled with significant levels of circulating IgG. It may occur 2 to 12 weeks after a primary infection or a heavy reinfection. It occurs more frequently with S japonicum infections than the other schistosome species. Typically, the onset of Katayama syndrome is sudden, but symptoms are non-specific, including fever, headache, general malaise, and tiredness. Eosinophilia is usually present. Involvement of the lung can manifest with a dry cough, and can be seen radiologically as a patchy infiltrate.

Following infection, chronic symptoms evolve slowly, being due to inflammatory reactions to the eggs that are deposited in various organs. Symptoms vary depending upon the organism. The adult worms do not cause an immune reaction and are generally not the cause of symptoms. S haematobium infection causes granulomatous inflammation of the bladder wall, often causing ulceration resulting in both microscopic and macroscopic hematuria. Infection can cause substantial scarring, with ureteral obstruction. The damaged mucosal epithelium can undergo malignant changes, with squamous cell carcinomas. Fibrosis and bladder calcification are characteristic of late-stage infections and can eventually lead to parenchymal damage and kidney failure.11

S japonicum and S mansoni, infection is characterized by egg deposition in the intestine, particularly in the rectum and distal bowel. The mucosa may ulcerate. Typical symptoms include abdominal pain and (bloody) diarrhea.15 Eggs often embolize through the portal vein to the liver where they cause a granulomatous hepatitis and marked fibrosis. Typically, portal hypertension develops. The liver disease may progress to cirrhosis and liver failure.11

Foodborne Trematodiasis

Infections with foodborne trematodes have a wide array of clinical signs and symptoms that are often non-specific. While light infections are in general asymptomatic, large parasite loads, prolonged durations of infection, hypersensitivity, or concomitant parasitic infections can cause considerable morbidity, and the diseases can even be fatal.

With regard to liver fluke infections, high fever, hepatitis-like symptoms and eosinophilia have been described for symptomatic O felineus infections.8 Symptomatic cases of clonorchiasis, fascioliasis, and infections with O viverrini are characterized by abdominal pain, flatulence, dyspepsia, anorexia, weakness, lassitude, weight loss, fever, rash, swollen abdomen, or enlargement of the liver. Jaundice, pruritus, and biliary colic are frequent complications of severe infections with Fasciola species.9 Ascending cholangitis, obstructive jaundice, and cholangiocarcinoma (bile duct cancer) are the most serious complication of clonorchiasis and opisthorchiasis.8,16

Clinical features due to an infection with the intestinal fluke F buski include abdominal pain, fever, nausea, diarrhea, constipation, eosinophilia, headache, dizziness, and malnutrition. Heavy infections are associated with generalized toxic and allergic symptoms such as edema of the face, abdominal wall, and lower extremities.9

Clinical symptoms of lung fluke infection include cough, fever, bloody sputum, loss of appetite, chest pain, and headache in the early stage of infection. Once the infection has been established, cough and bloody sputum are common.10 Extrapulmonary paragonimiasis is caused by migrating worms into ectopic locations, for example the skin, liver, eye, abdominal organs, or the brain. Cerebral paragonimiasis is particularly severe and can cause a variety of neurologic complications (headache, convulsions, paralysis, or behavioral changes).10

The pathologic changes of foodborne trematode infections are confined to the target organs of the adult flukes. The intestinal fluke F buski causes extensive duodenal and intestinal erosions, ulceration, hemorrhage, abscesses, and catarrhal inflammation.9 Pleural and pulmonary manifestations of paragonimiasis include multifocal pleural hemorrhage, eosinophilic pleuritis, pleural effusion, pneumothorax, thickened pleura, peribronchiolar infiltration of lymphocytes and plasma cells, hyperplasia of bronchioles and peribronchiolar glands, and chronic active eosinophilic granulomatous pneumonia.10 In case of liver fluke infections, the bile duct, liver, and gallbladder are affected. In C sinensis and O viverrini infections, the biliary epithelium becomes edematous, often accompanied by periductal infiltrates of mononuclear cells. Metaplasia of the biliary cells into mucin-producing cells can lead to persistent and high mucus content of the bile. Desquamation of the biliary epithelium, epithelial hyperplasia, bile duct hyperplasia, and periductal fibrosis have been described in chronic infections.8 Finally, in the parynchymal phase of fascioliasis, mechanical destruction of the liver tissues, chronic ulceration, desquamation, and hemorrhage are caused by the migrating flukes. The mechanical liver damage is accompanied by a cellular inflammatory reaction by the host. Furthermore, factors produced or induced by the fluke as proteases might contribute to liver damage.

Diagnosis

A number of different diagnostic approaches, referred to as direct parasitologic techniques (detection of parasite eggs in biological samples), indirect immunologic tests, molecular diagnosis, or noninvasive diagnostic techniques, are available for the diagnosis of schistosome, intestinal, liver, and lung fluke infections.

Schistosomiasis

The most widely used technique in epidemiologic surveys for diagnosis of S mansoni and S japonicum is the Kato-Katz technique, that is, microscopic examination, usually of approximately 42 mg of stool, prepared as a thick smear on a microscope slide. This technique is quantitative and allows infection intensity to be expressed as the number of schistosome eggs per gram of stool.18 Additionally, direct fecal smears (only a very small amount of stool is examined), sedimentation of fresh stool samples, or an ether-concentration method applied on preserved stool samples are used for subsequent examination under a microscope.18 A wide array of immunologic tests have been developed and widely used in China for large-scale population screening of S japonicum.19 For S haematobium, filtration of 10 mL of urine, preferably collected between 10 am and 2 pm (coinciding with maximal egg excretion rates) and subsequent microscopic examination is the most widely used method in epidemiologic surveys. This method is quantitative and infection intensity is expressed as the number of S haematobium eggs per 10 mL of urine. Reagent strip testing for detection of blood (microhematuria) and protein in urine (proteinuria) is also widely used and allows semiquantitative appraisal of infection intensity.18 A convenient method for appraisal of pathology due to schistosomiasis is ultrasonography for examination of the liver and bladder. It is mainly applied in hospital settings, but progress made with portable devices now allows using ultrasound in epidemiologic surveys.20

Foodborne Trematodiasis

Quantitative microscopic coprologic analyses (and sputum in the case of Paragonimus spp) are the most widely employed techniques for diagnosis of an infection with foodborne trematodes. Simple direct smears, simple sedimentation techniques, Kato-Katz thick smears, Stoll’s dilution egg count technique, or the formalin-ether concentration technique are used.8,12 However, multiple stool examinations are warranted to improve upon the diagnostic sensitivity. Serologic tests, mostly based on the detection of circulating antibodies, have been developed for the diagnosis of liver and lung fluke infections and have the advantage that they can be applied during all stages of the disease. Immunodiagnostic tests include intradermal tests, an indirect hemagglutination assay, an indirect fluorescent antibody test, and an indirect ELISA.8,10 Significant progress has been made in recent years regarding molecular methods, most notably the use of polymerase chain reaction–based (PCR-based) methods for the diagnosis of O viverrini, C sinensis, Paragonimus species, and F hepatica infections.8,10 Finally, noninvasive techniques to reveal pathologic alterations include radiology, ultrasound, computed tomography, or magnetic resonance imaging.

Treatment

There are two drugs currently recommended for the treatment of schistosomiasis and foodborne trematodiasis; namely praziquantel and triclabendazole (see Chapter 323 and Table 323-1).21-24

Praziquantel is the drug of choice for schistosomiasis, clonorchiasis, opisthorchiasis, paragonimiasis, and intestinal fluke infections in adults and children older than 2 years (in the case of schistosomiasis) and 4 years (in the case of foodborne trematodiasis).2,22 Triclabendazole is used against fascioliasis in patients aged 6 years and above.24

A third drug, bithionol, is still often used for fascioliasis and paragonimiasis if triclabendazole is not available, praziquantel failed to cure the infection, or patients displayed previous idiosyncratic or allergic reactions and praziquantel should not be given. Bithionol has been used in children below the age of 5 years.2 For schistosomiasis, oxamniquine has been widely and effectively used against S mansoni, particularly in Brazil.5 Metrifonate shows activity against S haematobium and has been widely used in the 1960s and 1970s, but due to economic, operational, and therapeutic reasons (eg, multiple doses are necessary to achieve good clinical outcomes), it has been suggested that schistosomiasis chemotherapy can do without this drug.5

Prevention

Preventive chemotherapy (eg, regular administration of praziquantel to at-risk populations without prior diagnosis) is increasingly promoted by WHO and other international organizations to limit the morbidity of schistosomiasis and food-borne trematodiasis.1,12,21 However, this strategy alone falls short of addressing the root behavioral and environmental causes of foodborne trematodiasis, schistosomiasis, and other often neglected tropical diseases. Sound information, education, and communication strategies to change human water contact behavior (in the case of schistosomiasis), to properly cook fish and other aquatic products, and to boil water (in the case of foodborne trematodiasis), as well as food safety measures and improved sanitary conditions, are key factors to achieve long-lasting effects on the control or even local elimination of foodborne trematodiasis and schistosomiasis.22,25 Linking preventive chemotherapy with health education and improved sanitary conditions, as well as collaboration with different sectors (eg, educational sectors or the food industry), will be required to ensure long-term parasite control and in turn boost social and economic development in areas where schistosomiasis and foodborne trematodiasis are still rampant.

Infection with fish tapeworms of the genus Diphyllobothrium is called diphyllobothriasis. Humans become infected by eating raw or poorly cooked fish. The most frequent species found in humans is the broad fish tapeworm, Diphyllobothrium latum, geographically located in regions of North America, especially Alaska and northern Canada, Europe, Japan, and Russia, including Siberia. In Latin America, D pacificum has also been found in humans on the Pacific coast of Peru, Chile, and Ecuador (where raw marine fish are prepared with lemon as cebiche), and Japan.1 Several other species of Diphyllobothrium also infect humans, especially in Alaska. Usually, other definitive hosts, such as bears, dogs, and cats, maintain the infections in nature, and humans are incidentally involved.1,2

The adult tapeworm lives in the small intestine, where it may attain a length greater than 10 m. The proglottids are wider than they are long, hence the name broad fish tapeworm. Gravid proglottids continuously expel eggs into the intestinal lumen through a uterine pore. More than 1 million eggs may be passed in the feces each day. The eggs measure approximately 60 μm by 40 μm and have a lidlike structure called an operculum. If the eggs reach water, a ciliated embryo develops within the egg in about 2 weeks. This ciliated stage or coracidia then hatches through the opened operculum and is ingested by one of several species of copepod (water flea). In this minute crustacean, the embryo develops into a first-stage, or procercoid, larva in 2 to 3 weeks. When a freshwater fish eats the infected copepod, the larva penetrates the fish’s intestinal wall and migrates to the muscles, where it grows into a ribbonlike plerocercoid larva (also called a sparganum) in approximately 1 month. Larger fish such as salmon, pike, perch, and trout may eat the initial fish host, and the larva again invades the muscle of the second fish. If the game fish is eaten raw or inadequately cooked, the plerocercoid larva develops in the small intestine of the definitive host into a mature adult after approximately 5 weeks (eFig. 336.1).3,4

Clinical Manifestations

Most patients with diphyllobothriasis are asymptomatic and only recognize their infection when they pass a chain of proglottids in their stool. Gastrointestinal complaints are uncommon, but there are isolated reports of intestinal obstruction associated with vomiting of masses of tapeworm. As many as 2% of individuals infected with D latum in northern Europe may develop a megaloblastic anemia that is indistinguishable from pernicious anemia (rare or nonexistent in D pacificum–infected individuals). This “tapeworm anemia” is rare in other parts of the world. This condition is the result of several factors, including (1) the location of the tapeworm high in the jejunum, (2) an affinity of the geographic strain of D. latum for uptake of vitamin B12 that is 7 times that of strains from North America, and (3) a reduced level of intrinsic factor or a decreased ability to absorb vitamin B12 in the affected population. Neurologic complications of vitamin B12 deficiency may develop even in the absence of anemia. The megaloblastic anemia associated with diphyllobothriasis usually affects individuals over the age of 50, but may be seen in children.

Diagnosis and Treatment

Fecal examination should easily reveal the characteristic eggs of Diphyllobothrium. The central uterine rosette and the dimensions of the proglottids are also diagnostic.

Praziquantel in a single dose of 5 to 10 mg/kg provides highly effective treatment. Patients should be informed that the drug is considered investigational by the FDA if used for this purpose. Niclosamide is also effective, but is no longer available in the United States. If present, anemia should be treated concomitantly with vitamin B12.3

Dogs and cats are often infected with the dog tapeworm, Dipylidium caninum. Gravid proglottids may actively migrate from the animal’s anus or from fecal material and disintegrate, spreading tapeworm eggs in the environment. Larvae of dog and cat fleas (more rarely the dog louse and the human flea) ingest the eggs and act as intermediate hosts, with the tapeworm larvae maturing in the flea. When a dog or cat ingests an infected adult flea, the larvae are released, and the adult tapeworm develops in the animal’s small intestine about 1 month after infection. A single flea may contain multiple tapeworm larvae, and infection with more than 1 tapeworm is possible.1,2

Humans can acquire the infection by accidental ingestion of an infected flea. Dipylidiasis in humans is much more common in young children and infants than in adolescents and adults; infection in a 5-week-old infant has been described. As in animals, the larvae in the child grow to maturity in the small intestine, and gravid segments of the adult tapeworm continually detach singly or in chains and migrate out of the anus, independently of stool.2,3

Clinical Manifestations, Diagnosis, and Treatment

The infection is often asymptomatic, but some patients may show loss of appetite, indigestion, abdominal pain, diarrhea, anal pruritus, poor weight gain, and irritability. Clinically, an initial diagnostic suspicion may arise from the description of the worm given by the parent or caretaker. Eosinophilia and urticaria have also been described, but are not consistent findings.4

The diagnosis is made by the identification of excreted proglottids or the finding of characteristic egg packets in stool. Routine fecal examinations may be falsely negative, because the eggs disintegrate rapidly, are not routinely released in the intestine, and proglottids migrate out of fresh fecal specimens. The first sign of infection is often the appearance of the proglottids on the stool or in the infant’s diaper. A common error is to assume that these motile objects are pinworms or fly larvae. The parent should be asked to collect the proglottids in saline (alcohol or other fixatives make the proglottids opaque and brittle) and bring them to the laboratory. Compression of the proglottid between glass microscope slides will reveal the bilateral genital pores.1,3

While human infection is self-limited unless there is repeated exposure from the environment, praziquantel is effective when given in a single dose of 5 to 10 mg/kg. Patients should be informed that the drug is considered investigational by the FDA if used for this purpose. Niclosamide is also effective but is no longer available in the United States.3,4

Five species of Echinococcus have been recognized to date. Echinococcus granulosus, E multilocularis, and more rarely E vogeli and E oligarthrus infect humans with their larval stages. The definitive hosts are canids, except for E oligarthrus, which includes wild felids as intermediate hosts. Humans become accidental intermediate hosts when the eggs from the feces of dogs, wolves, or other canids are ingested. A fifth species, E. shiquicus, has been recently recognized, but it is not known whether it may infect humans.1,2

The adult worm of E granulosus is found in the intestine of dogs, wolves, and other canids. The worm measures only about 0.5 cm in length. It has a scolex with hooks; a neck region; one immature, one mature, and one gravid proglottid. The dog usually harbors hundreds or thousands of adult tapeworms.1,3 The eggs, which are morphologically similar to those of Taenia species, are excreted in the feces. When an intermediate host, such as sheep, ingests the eggs, the embryo hatches from the egg, penetrates the intestinal mucosa, and enters lymphatics or blood vessels. The host defense mechanisms destroy many embryos, but those surviving develop into expanding cystic structures called hydatid cysts (Fig. 338-1). The rapidity of cyst growth is quite variable and partially dependent upon the tissue localization, but an increase in diameter of 1 cm or more per year is not uncommon, with faster growth in children. Spherical brood capsules arise from the inner germinal membrane of the cyst wall. Protoscolices, the precursors to the scolices of the adult worms, develop from germinal membrane and the inner surface of the brood capsules and accumulate within the cyst as “hydatid sand” (Fig. 338-2). If the cyst, or a portion of it, is eaten by a suitable definitive host, adult tapeworms develop in the small intestine. Hydatid cysts are capable of developing in nearly any tissue, including the central nervous system and bone; however, 90% of them develop in either the liver or the lung, most frequently in the liver.3,4

Human infection with hydatid cysts is most common in sheep- and cattle-raising areas such as the countries bordering the Mediterranean, Australia, New Zealand, and the Andean region in South America, particularly Peru and Argentina.1,5 In the United States, most infections are found among immigrants from endemic areas. However, there have been foci of infection among Basque shepherds in California, Mormon ranchers in Utah, and Native Americans in Arizona and New Mexico. Uganda and Kenya have very high prevalence rates of human infection.

Adult worms of Echinococcus multilocularis are smaller but morphologically similar to E granulosus. The larval stage of E multilocularis in the intermediate host grows by external budding, resembling a malignant tumor, and does not produce large cystic structures (alveolar hydatid disease). Liver tissue is progressively destroyed, contiguous structures are invaded, and more rarely, metastatic lesions may develop in distant sites. Foxes are usually the definitive hosts, and rodents are intermediate hosts. Hunters and fur traders exposed to foxes and fox fur are at risk. This infection occurs only in the Northern Hemisphere. It has a wide distribution in the northern midwestern states of the United States, in Canada, the former Soviet Union, Switzerland and adjacent countries, and in northern Japan. Sled dogs in Arctic villages may be sources of human infection.6

Human polycystic echinococcosis, caused by E vogeli or E oligarthrus, occurs much less frequently, always in Central and South America. Polycystic disease consists of multiple fluid-filled cysts, up to 3 cm in diameter, often interconnected and multichambered.

Clinical Manifestations

The majority (70%) of patients with hydatid disease caused by E granulosus have single cysts. When multiple cysts are present, they are most commonly in the same organ, but they can develop in multiple sites. Some investigators feel that pulmonary echinococcosis is more common in children and requires special attention and unique surgical approaches.7 About 20% of children with pulmonary hydatid cysts will also have hepatic cysts. Both hepatic and pulmonary cysts may attain considerable dimensions and lead to parenchymal damage,7 or conversely, some may resolve by natural evolution.5 It is not uncommon to find asymptomatic calcified cysts in the liver or spleen of infected adults as an incidental finding on radiologic studies or at autopsy. It takes many years for cysts to die and calcify; therefore calcifications are rarely seen in children.1,3

Large hepatic cysts may cause pain and tenderness in the right upper quadrant. In some instances, a mass may be palpable. Biliary tract obstruction may develop, depending upon the size and location of the hepatic cyst. Between 5% and 15% of hepatic cysts rupture into the biliary tract, causing fever, pain, and jaundice. The release of antigenic cyst fluid may cause severe allergic reactions including anaphylaxis. Patients who survive intraperitoneal cyst rupture are in danger of multiple secondary cysts developing as a secondary infection within the abdomen.

Although pulmonary cysts often are asymptomatic, about one third of them rupture into a bronchus or into the pleural space. Secondarily infected lung cysts appear as lung abscesses. Cysts that rupture into a bronchus may be coughed up. The patient may describe the membranes in the sputum. Complete evacuation of a pulmonary cyst results in a cure. Partial evacuation of the cyst sets the scene for bacterial growth and the production of a lung abscess.

Bone involvement may present as a bone deformity or as a pathologic fracture. The hydatid begins growth within the marrow cavity. The typical laminated membrane does not develop. Bone destruction by the parasite resembles that caused by tumor or infection. Involvement of the vertebral body causes pain and tenderness to palpation and may produce spinal cord or nerve root compression with neurologic signs and symptoms. Intracranial hydatid cysts are rare and occur most frequently in children. The symptoms are those of an expanding mass, usually causing intracranial hypertension with headache, nausea, and vomiting. Seizures may also develop.

Although alveolar hydatid disease caused by E multilocularis has been described in a 5-year-old child, it is usually a disease of adults. The progressive destruction of the liver takes many years. Tender hepatomegaly, abdominal masses arising from the liver, and jaundice are common presenting findings. Extension of the parasite into large vessels may result in metastatic lesions in the lungs or brain.3,6

Diagnosis

A history of exposure to dogs or other canids in an area endemic for echinococcosis is very helpful. Imaging techniques such as ultrasound are effective in delineating the contents of cystic structures. The presence of daughter cysts can be diagnostic. Features noted from CT scanning or MRI may be highly characteristic septate densities. Intact pulmonary cysts appear as sharply demarcated smooth, spherical, or ovoid radiopaque “cannonball” lesions. If the cyst has ruptured, an air-fluid level may be present. A collapsed membrane on the surface of the fluid may produce the classic “water lily” sign. The WHO classification provides a very useful tool for ultrasound staging and follow-up of liver cysts.8

Serologic testing using ELISA, immunoblots, or indirect hemagglutination tests is available through a few reference laboratories and the CDC. False-negative serologic tests have been problematic, particularly in lung cysts and other sites outside of the liver. Cross-reactivity has been noted with cysticercosis, hymenolepiasis, and other cestode infections.

Examination of the cyst and its contents at surgery proves the diagnosis by the presence of protoscolices and hooklets (hydatid sand). Percutaneous needle aspiration for diagnostic purposes is usually not needed and should be done only after other techniques have failed.

Alveolar hydatid disease is usually suspected when plain films of the liver show amorphous calcification surrounding 2-mm to 4-mm radiolucent areas. The recent development of a highly sensitive and specific ELISA using an epitope, Em 18, which is not shared with E granulosus, appears very promising for diagnosis and for following the response to treatment.

Treatment

The advent of chemotherapy with benzimidazole compounds (initially mebendazole and later albendazole), and the success of percutaneous aspiration and injection techniques, make it necessary to carefully reassess the dominant role of surgery in the treatment of cystic hydatid disease caused by E granulosus.9,10

Surgery is still considered appropriate therapy for large liver cysts with multiple daughter cysts, superficial cysts that are subject to spontaneous or traumatic rupture, cysts communicating with the biliary tract, and infected cysts. Surgery should be preceded by antiparasitic treatment to decrease the risk of cyst rupture at surgery, by decreasing pressure inside the cyst and the viability of the protoscolices if rupture occurs. The combination of albendazole plus praziquantel seems more effective than albendazole alone for prevention of secondary infection.11 Some authors suggest continuing antiparasitic therapy for 1 month or more following surgery to prevent recurrence and/or the development of secondary cysts. It is common practice to cover the operatory field with pads soaked in hypertonic saline and to introduce a scolicidal substance such as hypertonic saline, alcohol, or cetrimide into the cyst during the surgical procedure. All of the commonly used scolicides have the potential to cause sclerosing cholangitis if there is communication between the cyst contents and the biliary tract.

Percutaneous aspiration, injection of protoscolicide, and reaspiration (the PAIR technique) have replaced surgery in select cases of liver cystic hydatid disease. The types of cyst that would mostly benefit from PAIR are those in stages I and III of the WHO ultrasound classification of liver cystic hydatid lesions.7 When feasible, PAIR eliminates the need for open surgery, decreases the hospital stay, and significantly reduces costs.

Chemotherapy alone may be effective. Albendazole has replaced mebendazole as the drug of choice. Recent studies show that a combination of albendazole and praziquantel is more successful than albendazole alone for the treatment of this disease. Smaller, uncomplicated cysts appear to respond to albendazole more readily than do larger cysts. There are reports of central nervous system lesions and muscle, vertebral, and other bone lesions resolving completely with medical therapy. Because of the evolving therapy of cystic echinococcosis, consultation with the CDC is advised to obtain current information (contact the United States CDC Parasitic Disease Service at 770-488-7775).

Alveolar hydatid disease is treated with aggressive surgery, including partial hepatectomy or lobectomy. Unfortunately, less than 30% of patients have resectable lesions at the time of diagnosis. Long-term albendazole therapy may benefit a significant number of patients with inoperable lesions. Liver transplantation has been used in select patients. However, there is the risk of regrowth and metastatic spread associated with the immunosuppression that is necessary to preserve the transplant.6 Albendazole also appears to be beneficial in the treatment of polycystic hydatid disease caused by E vogeli.

Prevention

Hydatid disease occurs in communities where the dog-livestock cycle is maintained, and usually dogs are given infested offal following nonsupervised slaughter. The disease has been eliminated in several countries after very long periods of sustained control, including dog treatment and purge and health education. New tools, including an effective livestock and/or dog vaccine for the tapeworm stage may reduce the time required for successful disease control to be achieved.1

Infection with Hymenolepis nana, the dwarf tapeworm, is the most common tapeworm infection in the world. H nana is found in 0.4% of fecal specimens submitted to state laboratories in the United States. Infections occur most frequently in warm countries. It is especially prevalent in the southern part of the former Soviet Union, the Mediterranean, the Indian subcontinent, and South America. Children are more commonly infected than adults, and high prevalence rates have been reported in institutionalized children because of fecal-oral transmission.1

In the usual cycle, H nana is passed between rodents as definitive host and beetles as intermediate hosts. H nana is unique among tapeworms, because humans can serve as both intermediate and definitive hosts and can close the cycle without the need for an animal intermediate host. This leads to human infection being directly acquired (from another human definitive host), thus contributing to its high prevalence.

The adult tapeworm measures 2 to 4 cm in length. It attaches to the mucosa of the small intestine by a scolex that has 4 circular suckers and a retractable structure called a rostellum. Eggs passed in the feces are immediately infectious for another human or for the original host (autoinfection). Ingested eggs hatch in the small intestine. The embryos penetrate the villi and transform into larval cysticercoids. After 4 or 5 days, the new adult tapeworms emerge from the tissue and attach to the intestinal mucosa. Egg production by the new worms begins about 2 to 4 weeks after infection. Eggs released from gravid proglottids in the intestine may hatch and cause internal autoinfection, producing hundreds or thousands of adult tapeworms in a single host.1,2

Clinical Manifestations, Diagnosis, and Treatment

Although well-controlled studies of clinical manifestations of H nana infections are scarce, most H nana infections are most probably asymptomatic or unnoticed.3 Symptoms reported from several series of H nana infections are anorexia or increased appetite, nausea, vomiting, pains in the extremities, dizziness, and headache. Other reported symptoms are abdominal pain, diarrhea, restlessness, restless sleep, irritability, and nasal and anal pruritus. There are conflicting reports about correlation between the numbers of parasites and the presence of symptoms. Although a mild eosinophilia is a common finding in H nana infections, it is often absent. Rarely, H diminuta may be diagnosed, mostly in asymptomatic cases in stool surveys.4 The few reported cases do not allow examination of differences in clinical manifestations or response to treatment between H nana and H diminuta.

Routine fecal examinations using concentration techniques for ova and parasites should reveal eggs of H nana (Fig. 339-1) or more rarely H diminuta (Fig. 339-2). However, a single examination may not be adequate to rule out infection. Proglottids are rarely found in stools since they disintegrate after breaking from the tapeworm. ELISA tests for serum antibodies to H nana have been used in research but are of no clinical use.5

Praziquantel is the drug of choice for the treatment of hymenolepiasis. It is administered in a single dose of 25 mg/kg, although a second dose 10 to 15 days later seems to increase its efficacy. Patients should be informed that the drug is considered investigational by the FDA if used for this purpose. Niclosamide is also effective but is no longer available in the United States. Nitazoxanide can be used as an alternative with slightly lower efficacy.3 Because it is common for several individuals within a household to be infected, fecal examinations should be performed on all household members before initiating treatment. Posttreatment fecal examinations should be done at least 1 month after treatment.

The pork tapeworm Taenia solium and the beef tapeworm T saginata are the most common tapeworms of humans. The diseases associated with infection by these organisms have been known since ancient times, being found wherever insufficiently cooked pork or beef is eaten. Human infection with the pork tapeworm is uncommon in the United States and Canada, although larval infection (ie, cysticercosis) of swine may still occur. In many areas of the world, especially Mexico and parts of South and Central America, Africa, southeastern Europe, India, and China, infection with T solium is relatively common. Human infection with the larval stage of T solium (Cysticercus cellulosae), or cysticercosis, is found wherever adult T solium infection is common.1T saginata infection occurs among those who eat raw or insufficiently cooked beef. Human infection with larval T saginata (Cysticercus bovis) almost never occurs.

Humans are the mandatory definitive hosts who disseminate infection to porcine or bovine intermediate hosts. Transmission to swine usually occurs through contaminated soil, where gravid proglottids are deposited with human feces. Eggs can survive for weeks in moist soil. In cattle, grazing lands, water, or cattle feed that is contaminated with infected human feces are sources of infection. Intrauterine infection of calves has been reported.

Adult worms live in the upper small intestine, with T solium measuring 2 to 8 m and T saginata measuring 3 to 10 m. The scolex of the pork tapeworm is distinguished by a crown or rostellum with a double row of hooklets. The scolex of T saginata is without hooks. The gravid uterus holds thousands of eggs, each with a mature 6-hooked (ie, hexacanth) embryo. Eggs are 30 to 40 μm in diameter and similar in both human Taenia species. If the eggs are ingested by a suitable intermediate host such as swine (T solium) or cattle (T saginata), the embryo is liberated, penetrating the intestinal wall and disseminating via the bloodstream. The embryo of T solium may invade all tissues of the body and develops into a cysticercus or bladder worm. Cysticerci are ellipsoidal, white, translucent cysts into which the scolex is inverted.

When infected meat is eaten, the cysticercus is activated by gastric juices and bile, which stimulate evagination of the scolex. The scolex attaches to the jejunal wall, and the embryo becomes a mature tapeworm in 10 to 12 weeks for T saginata and 5 to 12 weeks for T solium. In humans, the eggs of T solium are ingested, and the larval stage may develop in every tissue of the body, a condition known as cysticercosis cellulosae. In tissue, the larvae cause an inflammatory infiltrate of eosinophils, plasma cells, neutrophils, and lymphocytes, with eventual necrosis and fibrosis and subsequent calcification of the parasite.

Clinical Manifestations

Infection with the adult T solium or T saginata is either asymptomatic or associated with only mild or moderate complaints including spontaneous discharge of proglottids from the rectum (98%), abdominal pain (36%) or nausea (34%), weakness (25%), loss of appetite (21%) or increased appetite (17%), headache (15%), constipation (9%), dizziness (8%), diarrhea (6%), or pruritus ani (4%). Rarely, infection can cause serious, life-threatening disease by intestinal or appendiceal obstruction, or by regurgitation and aspiration of a proglottid. Abdominal pain and nausea are most common in the morning and characteristically relieved by food. Children are more frequently symptomatic than adults. Eosinophilia occurs in 5 to 15% of cases.

The larvae of T solium, which are termed oncospheres, escape from the egg and penetrate the duodenum, enter the lymphatic and vascular systems, and are widely disseminated throughout the body causing human cysticercosis which is a serious and sometimes fatal disease. The disseminated larvae can be found throughout the body.

Cysticerci have been found in almost every tissue and organ of the body. Small numbers of cysts in muscle or subcutaneous tissue may be of little consequence, but invasion of the eye, brain, or heart may be serious. Cysts are most common (in order of frequency) in subcutaneous tissues, eyes, and brain. Except in the eye, cysts usually provoke development of a fibrous capsule. Neurocysticercosis is highly endemic throughout the Western Hemisphere from Mexico to Chile. In Mexico City, it accounts for as much as 10% of neurologic admissions and more than 25% of craniotomies: the prevalence in Mexico in the general population is approximately 4%. Cysticercosis is often observed in the United States, particularly in urban centers with large Latin American immigrant populations.

Neurocysticercosis is highly endemic throughout the Western Hemisphere from Mexico to Chile. In Mexico the prevalence in the general population is approximately 4%; and in Mexico City it accounts for up to 10% of neurologic admissions and more than 25% of craniotomies. Autochthonous cases of neurocysticercosis have been reported in the United States. In U.S. children neurocysticercosis has been characterized by symptoms of seizure (87%), headache (32%), nausea and vomiting (32%), and altered mental status (13%). Fewer than 10% of children may present with cranial nerve palsies, gait abnormalities, papilledema, or decreased visual acuity. Sensory changes or fever are never present.2

Neurocysticercosis may present as a leptomeningitis, resembling tuberculous meningitis, and may cause communicating hydrocephalus. Cysticerci may be present in the ventricles (most commonly the fourth ventricle) causing obstructive hydrocephalus. Cysts that are localized at various sites in brain parenchyma can remain silent for years, only to become evident when the cysts die, provoking an inflammatory response and edema. Cysts often calcify and may be found serendipitously. Spinal cord cysts present as transverse myelitis or arachnoiditis.

Cysts may be found asymptomatically in the vitreous, but if they occur in the retina, there may be visual impairment, scotoma, or retinal detachment. Cysticerci in the myocardium may cause arrhythmias and cardiac failure.

Diagnosis

Observation of gravid proglottids is required for a specific diagnosis; the presence of Taenia eggs in the stool is insufficient. Before initiating therapy, the species of Taenia must be identified because disseminated cysticercosis theoretically can be caused iatrogenically in individuals with T solium infection if, during therapy, they should regurgitate gravid proglottids into the upper GI tract where gastric and duodenal fluids activate the ova.

The species of the proglottid can be identified by pressing the segment between two glass microscope slides and counting the main lateral branches of the uterus. T solium usually has 7 to 13 branches on each side; T saginata usually has 15 to 20 lateral branches on each side (Fig. 340-1). Fecal examination, especially with T saginata infection, often is unrewarding because intact gravid proglottids tend to be eliminated or crawl out onto the perianal area before they disintegrate and release their eggs. Thus, the perianal cellophane-tape method, similar to that used to diagnose pinworms, may be more effective for recovering Taenia ova.

Approximately 10% of patients with neurocysticercosis have eosinophilia. The findings on lumbar puncture are rarely helpful, and findings range from normal to isolated high protein levels with or without an inflammatory pleocytosis. Eosinophilia may be present occasionally in the CSF. A lumbar puncture should not be done in the presence of suspected increased intracranial pressure.

Radiographic findings are often useful. Soft-tissue radiographic studies may reveal characteristic numerous, tiny, curvilinear calcifications in the muscle. MRI or CT will demonstrate cysts in all stages in the meninges and parenchyma (Fig. 340-2). Contrast-enhancement studies with metrizamide often are necessary to demonstrate isodense cysts in the ventricles.

In the past, ELISA has been the most frequently used diagnostic method to detect cysticercus antibodies in both serum and cerebrospinal fluid (CSF). This test can be highly sensitive, but may cross-react with other helminth antibodies, especially Echinococcus. The enzyme-linked immunoelectrotransfer blot (EITB) is highly specific and sensitive, although sensitivity is low when fewer than 2 parenchymal cysts are present. In a recent series of children presenting with neurocysticercosis in the United States, fewer than 30% had positive EITB. Examination of the serum is more sensitive than the CSF. In patients with clinical and radiologic features of cysticercosis, negative serology may be an indication for biopsy, especially if the patient is from an area of low endemicity. Elevated titers in CSF are particularly useful if they exceed those in the serum. High positive titers are more often seen in those individuals with hydrocephalus or meningeal involvement.

Treatment

Adult tapeworm infections are treated successfully if the scolex is eliminated. An effective agent with few untoward effects is niclosamide (Yomesan) but this agent is only inconsistently available in the United States. For Taenia infections, the single dose for adults consists of 4 tablets or 2 g chewed thoroughly after a light meal. For children weighing 11 to 34 kg, a single dose of 2 tablets (1 g) is recommended, and for those children weighing more than 34 kg, a single dose of 3 tablets (1.5 g) is recommended. For patients with T solium infection, therapy probably should be administered in the physician’s office. An antiemetic may be administered 30 minutes before the antihelminthic. If the patient does not have a bowel movement within 2 hours, a mild saline purge should be provided. Alternatively, praziquantel, an acylated isoquinole-pyrazine, is highly active against most tapeworm infections. It can be given in a single dose of 10 to 20 mg/kg in taeniasis.

Until recently, surgical intervention was the only definitive therapeutic option for the treatment of neurocysticercosis. Medical therapy remains controversial.1 When viable cysts are present, albendazole may be indicated. Currently, albendazole is the drug of choice; the daily dose is 15 mg/kg in 2 divided doses for 8 to 28 days. In recent studies, shorter courses have been as successful as longer courses of therapy.3 Corticosteroids may be given before and during therapy to ameliorate or attenuate symptoms associated with cyst death, ensuing inflammation, and possible cerebral edema. Currently, therapy is recommended for children with “active” cysts, indicated on computerized tomography as ring-enhancing lesions. Some physicians prefer to treat all children rather than waiting for the natural resolution of the cyst. Others recommend that children be treated only if they are symptomatic. It is uncertain whether children with few cysts, with or without seizures as the predominant symptom, will benefit from treatment. However, recent controlled studies show approximately 50% reduction of cyst size at 3 months posttreatment and a threefold reduction of seizures in albendazole-treated versus placebo-treated children. Hydrocephalus, which is a common complication of neurocysticercosis, can only be alleviated by the placement of a ventricular-peritoneal shunt. Intraventricular cysts will not respond to albendazole or praziquantel.

Seizures are not always relieved by treatment of the cysticercosis. Therefore, if a patient with cysticercosis is receiving anticonvulsive therapy, it should be continued and may be required indefinitely.4