Definition, Etiology, PathogenesisTop
1. Etiologic agent: Cestode Echinococcus multilocularis (E granulosus infection: see Cystic Echinococcosis). The adult pathogen (1.2-3.7 mm) colonizes the small intestine of the definitive host (predominantly foxes), while small rodents (such as mice) are the natural intermediate hosts. Humans become infected upon ingesting invasive eggs, thus becoming accidental intermediate hosts. The oncosphere hatches in the small intestine, penetrates the intestinal wall, enters the portal circulation, and infects the liver, where it forms a conglomerate of multiple small cysts (each 0.5-10 mm in diameter), usually without protoscolices. The polycystic structure does not have a connective tissue capsule and invades the hepatic parenchyma along the blood vessels and biliary tree; it may infiltrate other organs by continuity or spread via the hematogenous route.
2. Reservoir and transmission: Foxes, sporadically wolves, raccoons, dogs, and cats (definitive hosts). Humans are infected via the oral route (hands or food contaminated with animal feces, eg, unwashed forest fruit).
3. Risk factors: Contact with foxes (hunters, farmers, wild fruit gatherers, woodcutters), contact with soil, consumption of unwashed forest fruit. Several members of the same family may be affected.
4. Incubation and contagious period: The disease may remain asymptomatic for a long time (5-15 years). The patient is not contagious for contacts.
E multilocularis is found only in the northern hemisphere. The disease is rarely registered and often remains asymptomatic for a long time. Its incidence in humans has been increasing in recent years.
Clinical Features And Natural HistoryTop
The disease may remain asymptomatic for years. In 99% of patients the primary lesion is located in the liver. In symptomatic cases clinical manifestations are similar to those of a slowly progressive primary hepatic tumor and include right upper abdominal discomfort, pain, or both; hepatosplenomegaly; features of portal hypertension. In the majority of patients the disease affects the biliary tree and causes cholestatic jaundice.
Proliferating parasites may infiltrate the adjacent tissues and organs (diaphragm, lungs, pleura, heart, pericardium, gastric and duodenal wall, peritoneum, kidneys, adrenal glands, lymph nodes). Patients with advanced disease may also have cachexia, ascites, features of liver failure, peritoneal metastases, and distant metastases to the lungs (cough, dyspnea, hemoptysis), brain (epilepsy, focal deficits), eye, and/or bones.
Identification of the etiologic agent:
1. Serologic testing: Detection of serum specific IgG against the Em2plus antigen of E multilocularis (enzyme-linked immunosorbent assay [ELISA]; sensitivity and specificity >90%). The diagnosis is confirmed by detection of antibodies against the Em16 and Em18 antigens using the Western blot assay (sensitivity ~98%, specificity 100%; this allows for a definitive differentiation between E multilocularis and E granulosus).
2. Other tests:
1) Imaging studies (depending on the location of the parasite):
a) Ultrasonography of the liver: A poorly demarcated, nonencapsulated, irregular focal lesion with heterogeneous echogenicity, areas of necrosis, calcifications, and infiltration of adjacent structures; dilation of intrahepatic biliary ducts as well as splenomegaly and/or hepatomegaly are often observed.
b) Chest radiography: Elevation of the right hemidiaphragm (in alveolar echinococcosis of the liver), round opacifications, mediastinal widening.
c) Computed tomography (CT) or magnetic resonance imaging (MRI) of the head: Central nervous system (CNS) lesions resembling glioblastoma with calcifications, which cause the mass effect (displacement and compression of the adjacent brain structures), brain edema.
2) Histologic examination of autopsy material or surgical samples (intraoperative or postoperative): A structure formed by multiple vesicles of varying sizes with periodic acid–Schiff (PAS)–positive walls and features of fibrosis, necrosis, and calcifications. Biopsy samples usually contain no protoscolices or hooks. Fine-needle biopsy is not relevant for diagnosis.
Differential diagnosis should include primary tumor, metastasis, abscess (of the liver, biliary tree, brain, lungs), cystic echinococcosis (also known as hydatid disease or hydatidosis).
Treatment should be conducted in experienced centers. The mainstay of therapy is surgical resection of the lesion combined with long-term treatment with albendazole, dosed 400 mg every 12 hours for ≥2 years. If albendazole is not tolerated, consider oral mebendazole 200 mg every 12 hours (less effective).
Symptomatic treatment should be used for impaired hepatic function or epileptic seizures.
Abdominal ultrasonography should be performed every 3 months to assess the size and features of the lesion and to evaluate the developmental stage of the parasite and clinical stage of multilocular echinococcosis (PNM classification). Depending on the clinical manifestations and involved organs, the following studies should be performed: chest radiography, CT of the head, ophthalmic examination, regular assessment of liver function tests and aminotransferase levels, serologic tests repeated every 6 months to assess the activity of the parasite.
Distant spread (peritoneum, brain, lungs, eye, bones), compression of the adjacent organs (eg, hydronephrosis), biliary obstruction and/or bacterial cholangitis, cirrhosis, liver failure, portal hypertension (esophageal varices and variceal hemorrhage), cachexia, anaphylactic shock (due to the release of high amounts of parasitic antigens during nonradical surgery or in patients with a high parasite burden).
In untreated patients the average survival is ~10 years. The most frequent causes of death are septic shock, portal hypertension, cirrhosis, chronic cholangitis, and Budd-Chiari syndrome (blocked outflow from hepatic veins and/or inferior vena cava).
Avoiding contact with foxes (skinning, farming), good hand hygiene, using protective gloves while working with soil or foxes, washing forest fruits and mushrooms prior to consumption.