Causal Agent:Human echinococcosis (hydatidosis, or hydatid disease) is caused by the larval stages of cestodes (tapeworms) of the genus Echinococcus.  Echinococcus granulosus causes cystic echinococcosis, the form most frequently encountered; E. multilocularis causes alveolar echinococcosis; E. vogeli causes polycystic echinococcosis; and E. oligarthrus is an extremely rare cause of human echinococcosis.

Life Cycle:

The adult Echinococcus granulosus (3 to 6 mm long) resides in the small bowel of the definitive hosts, dogs or other canids.  Gravid proglottids release eggs that are passed in the feces.  After ingestion by a suitable intermediate host (under natural conditions: sheep, goat, swine, cattle, horses, camel), the egg hatches in the small bowel and releases an oncosphere that penetrates the intestinal wall and migrates through the circulatory system into various organs, especially the liver and lungs.  In these organs, the oncosphere develops into a cyst  that enlarges gradually, producing protoscolices and daughter cysts that fill the cyst interior.  The definitive host becomes infected by ingesting the cyst-containing organs of the infected intermediate host.  After ingestion, the protoscolices evaginate, attach to the intestinal mucosa , and develop into adult stages in 32 to 80 days.  The same life cycle occurs with E. multilocularis (1.2 to 3.7 mm), with the following differences: the definitive hosts are foxes, and to a lesser extent dogs, cats, coyotes and wolves; the intermediate host are small rodents; and larval growth (in the liver) remains indefinitely in the proliferative stage, resulting in invasion of the surrounding tissues.  With E. vogeli (up to 5.6 mm long), the definitive hosts are bush dogs and dogs; the intermediate hosts are rodents; and the larval stage (in the liver, lungs and other organs) develops both externally and internally, resulting in multiple vesicles.  E. oligarthrus (up to 2.9 mm long) has a life cycle that involves wild felids as definitive hosts and rodents as intermediate hosts.  Humans become infected by ingesting eggs , with resulting release of oncospheres

in the intestine and the development of cysts , , ,  , ,   in various organs.

Geographic Distribution:E. granulosus occurs practically worldwide, and more frequently in rural, grazing areas where dogs ingest organs from infected animals.  E. multilocularis occurs in the northern hemisphere, including central Europe and the northern parts of Europe, Asia, and North America.  E. vogeli and E. oligarthrus occur in Central and South America.

Clinical Features:Echinococcus granulosus infections remain silent for years before the enlarging cysts cause symptoms in the affected organs.  Hepatic involvement can result in abdominal pain, a mass in the hepatic area, and biliary duct obstruction.  Pulmonary involvement can produce chest pain, cough, and hemoptysis.  Rupture of the cysts can produce fever, urticaria, eosinophilia, and anaphylactic shock, as well as cyst dissemination.  In addition to the liver and lungs, other organs (brain, bone, heart) can also be involved, with resulting symptoms.  Echinococcus multilocularis affects the liver as a slow growing, destructive tumor, with abdominal pain, biliary obstruction, and occasionally metastatic lesions into the lungs and brain.  Echinococcus vogeli affects mainly the liver, where it acts as a slow growing tumor; secondary cystic development is common.

Laboratory Diagnosis:The diagnosis of echinococcosis relies mainly on findings by ultrasonography and/or other imaging techniques supported by positive serologic tests.  In seronegative patients with hepatic image findings compatible with echinococcosis, ultrasound guided fine needle biopsy may be useful for confirmation of diagnosis; during such procedures precautions must be taken to control allergic reactions or prevent secondary recurrence in the event of leakage of hydatid fluid or protoscolices.

Diagnostic findings

Microscopy Antibody detection

Treatment:Surgery is the most common form of treatment for echinococcosis, although removal of the parasite mass is not usually 100% effective.  After surgery, medication may be necessary to keep the cyst from recurring.  The drug of choice for treatment echinococcosis is albendazole (Echinococcus granulosus).  Some reports have suggested the use of albendazole or mebendazole for Echinococcus multilocularis infections.  For additional information, see the recommendations in The Medical Letter (Drugs for Parasitic Infections).

Microscopy

Dogs and other canids are the definitive hosts for Echinococcus spp.; humans are are only infected by the larvae after ingestion of eggs from food, water or fomites contaminated with dog feces.  Upon ingestion of the eggs by the human host, the oncospheres migrate from the intestinal lumen to other body sites and develop into hydatid cysts.  These cysts can be found in any part of the body, but are most common in the liver, lung and central nervous system.

A B

A: Protoscoleces in a hydatid cyst removed from lung tissue, stained with hematoxylin and eosin (H&E).  Image taken at 200x magnification.  Image courtesy of Phoenix Children's Hospital, Phoenix, AZ.B: Higher magnification (600x) of the protoscoleces in Figure A.

C D

C: Cross-section of an E. granulosus cyst, stained with H&E.  The cyst wall is composed of an acellular laminated external layer (green arrow) and a thin, germinal (nucleated) inner layer (yellow arrow).  Note the brood capsule (black arrow) with protoscoleces (blue arrows) inside.  Image taken at 40× magnification.D: Higher magnification (200×) of the cyst in Figure C, showing daughter cyst (brood capsule).  Note the hooklets (purple arrow) inside one of the protoscoleces and the calcareous corpuscles (light blue arrows) along the germinal layer.

E F

E: Echinococcus multilocularis in liver tissue, stained with hematoxylin and eosin (H&E).  Magnification at 200xF: Higher magnification (400x) of the specimen in Figure E.  Notice a pair of hooks (yellow arrows) and the refractile nature of the hooks.  Cestode hooks do not stain with H&E but may be visible with proper adjustment of the microscope.

G H

G: Echinococcus multilocularis is tissue, stained with H&E.  Magnification at 200x.H: Higher magnification (400x) of the specimen in Figure G.  Notice the refractile hook (green arrow).

I J

I, J: Contents of a degenerating hydatid cyst from a liver cyst aspirate, stained with Papanicolaou (PAP).  Figure I shows a degenerating protoscolex with hooklets and calcareous corpuscles.  Figure J shows free hooklets in hydatid sand.

 Antibody DetectionImmunodiagnostic tests can be very helpful in the diagnosis of echinococcal disease and should be used before invasive methods.  However, the clinician must have some knowledge of the characteristics of the available tests and the patient and parasite factors associated with false results.  False-positive reactions may occur in persons with other helminthic infections, cancer, and chronic immune disorders.  Negative test results do not rule out echinococcosis because some cyst carriers do not have detectable antibodies.  Whether the patient has detectable antibodies depends on the physical location, integrity, and vitality of the larval cyst.  Cysts in the liver are more likely to elicit antibody response than cysts in the lungs, and, regardless of localization, antibody detection tests are least sensitive in patients with intact hyaline cysts.  Cysts in the lungs, brain, and spleen are associated with lowered serodiagnostic reactivity, whereas those in bone appear to more regularly stimulate detectable antibody.  Fissuration or rupture of a cyst is followed by an abrupt stimulation of antibodies.  A patient with senescent, calcified, or dead cysts is generally found to be seronegative.

Cystic echinococcal disease (Echinococcus granulosus).  Indirect hemagglutination (IHA), indirect fluorescent antibody (IFA) tests, and enzyme immunoassays (EIA) are sensitive tests for detecting antibodies in serum of patients with cystic disease; sensitivity rates vary from 60% to 90%, depending on the characteristics of the cases.  Crude hydatid cyst fluid is generally employed as antigen.  At present, the best available serologic diagnosis is obtained by using combinations of tests.  EIA or IHA is used to screen all specimens; a positive reaction is confirmed by immunoblot assay or any gel diffusion assay that demonstrates the echinococcal "Arc 5."  Although these confirmatory assays give false-positive reactions with sera of 5% to 25% of persons with neurocysticercosis, the clinical and epidemiological presentation of neurocysticercosis patients should be rarely confused with that of cystic echinococcosis.  A commercial EIA kit is available in the United States.

Antibody responses have also been monitored as a way of evaluating the results of treatment, but with mixed results.  Following successful radical surgery, antibody titers decline and sometimes disappear; titers rise again if secondary cysts develop.  Tests for Arc 5 or IgE antibodies appear to reflect antibody decline during the first 24 months postsurgery, whereas the IHA and other tests remain positive for at least 4 years.  Chemotherapy has not been followed by consistent declines in antibody titers.  Consequently, the usefulness of serology to monitor the course of disease is limited; imaging techniques provide a more accurate assessment of the patient's condition.

Alveolar echinococcal disease (Echinococcus multilocularis).  Most patients with alveolar disease have detectable antibodies in serologic tests using heterologous E. granulosus or homologous Echinococcus multilocularis antigens.  With crude Echinococcus antigens, nonspecific reactions create the same difficulties as described above, however, immunoaffinity-purified E. multilocularis antigens (Em2) used in EIA allow the detection of positive antibody reactions in more than 95% of alveolar cases.  Comparing serologic reactivity to Em2 antigen with that to antigens containing components of both E. multilocularis and E. granulosus permits discrimination of patients with alveolar from those with cystic disease.  Combining two purified E. multilocularis antigens (Em2 and recombinant antigen II/3-10) in a single immunoassay optimized sensitivity and specificity.  These antigens are sold in a commercial EIA kit in Europe, but not in the United States.  As in cystic echinococcosis, Em2 tests are more useful for postoperative follow-up than for monitoring the effectiveness of chemotherapy.

Reference:

Lightowlers MW, Gottstein B.  Echinococcosis/hydatidosis: antigens, immunological and molecular diagnosis. In: Thompson RCA, Lymbery AJ, editors. Echinococcus and hydatid disease. Wallingford, UK: CAB International; 1995. p. 355-410.