Diagnosis
Clinical features Clinical signs and symptoms depend on the organ compromised by the cysticerci, the specific localization of a cysticercus within the organ, the state of inflammation surrounding the cysticerci, and the viability of the cestode. The most serious forms of cysticercosis are those with ocular, cardiac, and neurologic involvement. The manifestations of neurocysticerco-sis, which can be quite varied, depending on the site of lesions and the evolution of inflammatory reactions, include seizure disorders and focal deficits, hydrocephalus, arachnoiditis, and in-tracranial hypertension.95 In endemic regions, cysticercosis is the most common cause of late-onset seizure disorders.99
Laboratory findings and imaging studies The use of CT and MRI has facilitated the recognition of CNS cysticerco-sis,94,100,101 has helped delineate the various forms of neurocysticer-cosis,83 and has provided a means for assessing the adequacy of therapy.100,102 CNS imaging studies may reveal cysticerci in the brain parenchyma, within the ventricles, at the surface or the base of the brain, or within the subarachnoid space.
CT may miss early lesions, which have the same x-ray density as the brain, but hypodensity and contrast-enhancing ring lesions are seen with the development of inflammation around the cyst. As sclerosis occurs, a cystic lesion develops, and the cyst wall may calcify. Ultimately, degenerated cysts are replaced by small (1 to 4 mm in diameter) calcified lesions within the brain [see Figure 16].
The diagnosis of cysticercosis can be made with certainty only by biopsy of a cyst. Calcified cysts in subcutaneous tissue and muscle, which have a puffed-rice appearance on radiographs, should be sought. Although the signs and symptoms of neuro-cysticercosis are not specific, this diagnosis is supported by the finding of characteristic multiple cystic or calcified lesions on CT scans in a patient from an endemic area.
A serologic test, which should be used to test serum and CSF for antibody to T. solium, is available through the CDC. ELISA testing for antibody, however, may be negative in about 20% of patients with cysticercosis103 and may be falsely positive in those with echinococcosis. An enzyme-linked immunoelectrotransfer blot assay for antibody is highly sensitive in patients who have several enhancing intracranial lesions; it is less sensitive in those who have only one lesion or calcified lesions.101,104 Stool examination for Taenia eggs may detect concurrent infection with the tapeworm but is not directly pertinent to the diagnosis of cysticercosis.
Treatment
Therapy for cysticercosis may be medical or surgical. Patients with only calcified soft tissue or CNS lesions do not require medical therapy. Surgical excision was once the only approach for viable cysts, but praziquantel and albendazole have proved to be effective against neurocysticercosis.100,102,105 Despite the improvements noted after medical therapy, the absence of controlled trials specifically comparing medically treated patients with untreated patients has left room for uncertainty concerning the efficacy of medical therapy for neurocysticercosis.102,106 However, a randomized trial has demonstrated a trend toward fewer seizures in patients treated with albendazole and steroids, as compared with those treated with placebo.107
Albendazole is given in a dosage of 400 mg orally twice daily for 10 to 28 days; praziquantel is given in a dosage of 50 to 100 mg/kg/day in three divided doses for 30 days.19 Albendazole appears to be slightly more effective than praziquantel at killing cysticercosis cysts.102 Because treatment may cause inflammatory reactions to develop around cysticerci, ocular cysticercosis and spinal cysticercosis are not usually treated medically; an oph-thalmologic examination is indicated before drug therapy to rule out intraocular cysticercosis, which could lead to devastating inflammation. For patients with neurocysticercosis, corticosteroids (e.g., dexamethasone, 4 to 16 mg/day, or prednisone, 60 to 100 mg/day) are usually given 1 to 2 days before and during treatment with albendazole or praziquantel to minimize inflammatory reactions. Patients who are taking anticonvulsant medications for neurocysticercosis should continue to use them during this treatment, but many such patients can stop taking antiseizure medications after cysticercosis therapy.107,108 CT scanning should be repeated 3 to 6 months after therapy, to determine whether any of the cysts are still viable; therapy should be repeated if viable cysts remain.
Beef tapeworm
T. saginata, or beef tapeworm, causes an intestinal infection in persons who have eaten undercooked beef containing cysticer-ci.93 The infection is usually asymptomatic, although abdominal pain, weight loss, increased appetite, or passage of lengths of proglottids may be noticed because proglottids of T. saginata tend to be more motile than those of the other tapeworms [see Figure 17]. As noted, the detection of eggs in the feces or on the perianal skin is diagnostic of tapeworm infection, but differentiation between Taenia species requires identification of the proglottids. Therapy consists of praziquantel or niclosamide, as given for T. solium intestinal infection.19 Infection with T. saginata does not lead to cysticercosis in humans.
Dwarf tapeworm
Hymenolepis nana, a tapeworm measuring 3 to 4 cm long and 1 mm wide, has a broad geographic distribution.91 In the United States, it is most commonly encountered in persons living in the southern states, in institutionalized patients, and in children. Unlike the other tapeworms, the larval and adult stages of H. nana develop in the same host. Infection is spread by the fecal-oral route and occurs when eggs, which are immediately infectious, are ingested. Thus, H. nana is one of the few helminths (along with Enterobius, Capillaria, and Strongyloides) that can propagate by autoinfection; children, in particular, can develop huge worm burdens and become symptomatic.
After an egg of H. nana has been ingested, an oncosphere hatches from the egg and penetrates the intestinal villi, where it develops into a cerocyst; the cerocyst reenters the lumen of the small intestine and develops into an adult worm. Eggs are liberated from the distal segments of the adult worm, which lives for about 1 year.
Figure 16 Shown are CT scans of two patients (a, b) with seizures resulting from neurocysticercosis. The CT scans on the left are without contrast; those on the right are with contrast. Multiple cystic and calcified lesions are evident in both patients (the contrast agent enhances the cystic lesions). The scans from the first patient (a) show multiple cystic lesions, with a denser central spot that represents the scolex, a pathognomonic finding for neurocysticercosis.
The eggs may cause internal reinfection. Light infection is usually asymptomatic; diarrhea and abdominal pain may accompany heavy infection. Diagnosis is made by finding eggs in feces. Therapy consists of praziquantel (25 mg/kg given once); this use of praziquantel is currently considered investiga-tional. An alternative investigational therapy is nitazoxanide (500 mg p.o. daily for 3 days).
Other tapeworms
Human infection with H. diminuta, a tapeworm of mice and rats, occasionally occurs when humans ingest insects that harbor developing cerocysts of the tapeworm; one such insect is the flea. Infection is more common in children and is associated with few or no symptoms. Diagnosis and treatment are the same as described for the dwarf tapeworm H. nana (see above).
Children are also more commonly infected with the dog tapeworm Dipylidium caninum. Infection is acquired by consuming infected fleas or lice. Adult worms develop in the small intestine and measure 15 to 70 cm in length. Mild intestinal symptoms may or may not be present. Diagnosis is made by finding proglottids or eggs in feces. Therapy for adults consists of prazi-quantel (5 to 10 mg/kg given once).
Figure 17 Persons infected with the beef tapeworm, Taenia saginata, may pass lengths of proglottid in the stool. An entire adult beef tapeworm is shown.
Figure 18 Life cycle of Echinococcus granulosus. Adult E. granulosus cestodes live in the intestine of dogs and wolves. Infectious eggs are passed in the feces of these animals and may be ingested by intermediate hosts such as sheep, cattle, or humans. After the eggs are ingested, oncospheres are carried in the bloodstream to the liver, lungs, and other organs, where they form hydatid cysts. The cycle is maintained when dogs or wolves ingest the carcasses of intermediate hosts.
Human infection with dog tapeworms of the genus Multiceps results in a syndrome termed coenurosis, which is similar to cys-ticercosis.109 At present, surgical excision forms the basis of diagnosis and treatment.
Sparganosis represents infection by larval tapeworms of the genus Spirometra, which are closely related to tapeworms of the genus Diphyllobothrium. Most such infections occur in the Far East. Human infection results from drinking water containing microcrustacean Cyclops species that harbor procercoid larvae (spargana) of the parasite. Human infection may also be acquired by ingesting raw flesh of amphibians or snakes that contains larvae of the parasite or from applying such flesh to the skin as a poultice. After ingestion, the procercoid larvae migrate into subcutaneous tissues, where they usually present as a painless subcutaneous nodule that enlarges during the course of many months. Larvae may also migrate to the CNS.110,111 Blood eosinophilia is commonly elicited. Surgical excision of larvae-containing nodules remains the basis of diagnosis and treatment.
Hydatid disease
Echinococcosis in humans may result from infection with Echinococcus granulosus, which causes cystic hydatid disease; E. multilocularis, which causes alveolar hydatid disease; or E. vo-geli or E. oligarthus, which causes polycystic hydatid disease and is found in areas of Central and South America.93,112,113 Adult E. granulosus cestodes live in the intestine of dogs and wolves. Infectious eggs are passed in the feces of these animals and may be ingested by intermediate hosts such as sheep, cattle, or humans [see Figure 18]. The cycle is maintained when dogs or wolves ingest the carcasses of intermediate hosts. E. granulosus infection is most prevalent in sheep- and cattle-raising countries. It is also found in a number of western states, Alaska, and Canada, where autochthonous cases of human infection have been recorded.114
After the eggs are ingested, oncospheres are carried in the bloodstream to the liver, lungs, and other organs. Unilocular cysts, which may contain daughter cysts, develop most commonly in the liver; the second most common site is the lungs. In children, pulmonary involvement may be more common than hepatic involvement. Unilocular hydatid cysts enlarge concentrically, increasing in diameter by about 1 to 5 cm a year, depending on the density of the organs in which they are located. A cyst may attain a large size before the initial symptoms develop; these symptoms are usually attributable to a space-occupying mass lesion. The onset of symptoms has been reported to occur from before 1 year of age to 75 years of age, but in large series, most persons become symptomatic between 4 and 15 years of age. Pathologic fractures or neurologic symptoms can occur with osseous or CNS localization, respectively. When cysts leak, patients may experience bronchospasm, urticaria, or anaphylaxis; blood eosinophilia, which is otherwise usually not prominent, may increase. Communicating rupture of pulmonary or hepatic cysts can lead to the release of cyst contents into the bronchial or biliary systems. Because cysts contain multiple infective protoscolices, rupture of cysts can lead to dissemination of infection and the generation of new cysts from each released protoscolex.
E. multilocularis lives in the intestine of foxes and dogs. Its intermediate hosts are mice and other small mammals. E. multiloc-ularis is found only in the Northern Hemisphere, including central western Europe, Russia, the central Asian republics, China, northern Japan, Canada, Alaska, and the north central United States.113 Because the cysts of E. multilocularis lack a containing capsule, they progressively invade involved tissues and produce honeycombed alveolar hydatid cysts. The liver is most commonly affected. Severe damage caused by extensive alveolar hydatid cysts can result in jaundice and portal hypertension. The mortality in untreated alveolar disease is 90%.115
The diagnosis of hydatid disease can be strongly suggested by the results of radiographic studies.113,116 Plain films detect pulmonary cysts117 but often do not visualize cysts in other organs unless they are calcified—a process that occurs mostly in hepatic cysts. On CT and MRI, echinococcal cysts appear as well-defined, thick- or thin-walled cysts that may have calcified rims. 116-118 In older lesions, where scolices and daughter cysts form hydatid sand that settles in the dependent portion of the cyst, a layer of fluid can be visualized. Dependent movement of calcified hydatid sand, on repositioning and ultrasound monitoring, is strongly suggestive, if not pathognomonic, of a hydatid cyst. A pathognomonic CT finding in intact cysts is the presence of daughter cysts that are either free within the cyst or adherent to the inner germinal layer. Separation and collapse of cyst wall layers and the introduction of air into the space between the layers can be detected on plain films (as the meniscus, double arch, or water lily signs) and by CT scan.
Serologic tests can be helpful in making the diagnosis of echinococcosis but are not uniformly sensitive or specific.92,119 A sensitive assay, such as ELISA or indirect hemagglutination, is performed first. Because of the possibility of false positive results produced by cross-reacting helminthic infections, specificity is confirmed with a less sensitive but more specific assay, such as an antigen-specific immunoblot or a gel diffusion assay for the Echinococcus-specific arc 5 immunoprecipitin band. Even with these assays, 5% to 25% of patients with neurocys-ticercosis have false positive results. Conversely, negative tests do not exclude the diagnosis, because approximately 50% of patients with isolated pulmonary cysts and 10% to 15% of those with hepatic cysts lack detectable antibodies against Echinococcus. Although leakage of cyst fluid poses risks of ana-phylaxis or dissemination of infection, percutaneous aspiration of a cyst in a seronegative patient, with guidance provided by CT or ultrasonography, can yield diagnostic protoscolices or hydatid membranes.
Therapeutic approaches to cystic and alveolar hydatid disease are quite complex, and consultation for expert advice is highly recommended.113,115 For cystic hydatid disease, treatment should be reserved for symptomatic lesions or those affecting vital anatomic structures, because 75% of asymptomatic persons with cysts remain symptom-free for more than a decade.113 When therapy is needed, the options are surgery, PAIR (puncture, aspiration, injection, and reaspiration; see below), or chemotherapy. Surgery offers the potential for total parasite removal and complete cure; nevertheless, cysts recur in 2% to 25% of patients treated with surgery.113 Preoperative and postoperative albenda-zole therapy is highly advisable. The past practice of injecting protoscolicidal solutions (7% to 90% ethanol, 0.5% percent cetrimide, or 15% to 20% hypertonic saline) before resection is no longer recommended, because these agents are of uncertain efficacy and potentially dangerous to the patient because of chemical cholangitis and other complications.
The PAIR procedure, which consists of percutaneous aspiration, injection of protoscolicidal agents (e.g., 95% ethanol or 0.5% cetrimide), and reaspiration, has demonstrated efficacy as an alternative to surgery. A randomized, controlled trial showed PAIR to be as effective as surgery for hepatic cystic echinococcosis; moreover, patients treated with PAIR had lower postprocedure morbidity and a shorter hospital stay.121-123 Like surgery, PAIR should be performed with albendazole therapy before and after the procedure to minimize dissemination of any leaked fluids containing infectious protoscol-ices.124 PAIR is best used for liver cysts of 5 cm or greater that are anechoic, multiseptate, or multiple.113 The PAIR procedure should not be performed if hepatic cysts communicate with the biliary tract. Complications are more common when PAIR is used to treat pulmonary lesions. PAIR may provoke acute allergic reactions.113
If neither surgery nor PAIR therapy is an option, medical therapy with albendazole is administered (mebendazole is an alternative that is considered less effective). Albendazole is given as a 400 mg dose twice a day for 28 days, often with additional 28-day courses given in subsequent months, with each course separated by 14-day treatment-free periods.125 Most commonly, al-bendazole therapy is continued for 6 months. Patients need to be monitored for complications during long-term albendazole therapy, because hepatotoxicity, nausea, and neutropenia are common. Neither mebendazole nor albendazole is completely effective: 20% to 40% of patients experience no improvement. Alben-dazole therapy results in a cure in about one third of patients and leads to regression in cyst size and improvement in symptoms in another third. Both agents are contraindicated during pregnancy. Serial titers of echinococcal antibodies can be useful in monitoring therapeutic success.
Because alveolar hydatid disease is an aggressive and often fatal illness, the preferred therapy is radical resection of cysts, followed by albendazole therapy (up to 20 mg/kg/day) for at least 2 years.113 Long-term chemotherapy can benefit patients who are not candidates for operation, as well as those patients who have undergone nonradical resections or liver transplantation.
