Echinococcosis Workup

  • Author: Dominique A Vuitton, MD, PhD; Chief Editor: Burke A Cunha, MD   more...
 
Updated: Oct 20, 2011
 

Laboratory Studies

  • Blood cell count
    • Hypereosinophilia is a rare feature of disease (< 10%).
    • Lymphopenia develops in 45% of cases.
  • Immunoglobulin concentrations
    • Increase in levels of gammaglobulins is common, primarily resulting from an increase in immunoglobulin G (IgG) levels and, to a lesser degree, levels of immunoglobulin A (IgA) and immunoglobulin M (IgM).
    • Increased immunoglobulin E (IgE) levels are uncommon.
  • Inflammatory proteins
    • Tests usually show increased levels of haptoglobin, alpha1 acid glycoprotein, C3 and C4, and ceruloplasmin despite the absence of increased C-reactive protein (CRP) levels.
    • CRP levels increase in cases complicated by bacterial superinfection.
  • Hepatic function
    • Results may be normal in asymptomatic cases.
    • Gamma-glutamyl transferase (GGT) levels usually increase before the patient is symptomatic. GGT levels also increase if bile ducts are obstructed. Levels can reach 20 times the reference range.
    • Alkaline phosphatase levels increase later than GGT levels and are observed only in symptomatic patients.
    • Conjugated bilirubin levels increase in symptomatic patients who are diagnosed with jaundice.
    • Levels of aminotransferases increase only when associated with necrosis. Aspartate aminotransferase (AST) is equal to alanine aminotransferase (ALT).
    • Prothrombin time decreases because of cholestasis, which can usually be corrected with vitamin K supplementation.
    • Factor V levels decrease in rare cases of hepatic failure (eg, secondary biliary cirrhosis, Budd-Chiari syndrome).
  • Specific serology
    • Serology results usually confirm a diagnosis suspected based on ultrasonography or CT scanning findings obtained in a clinical setting. These studies are also used for mass screenings.
    • Results from routine tests using heterologous antigen (E granulosus cyst fluid) are positive for indirect hemagglutination in 75-80% of cases with a threshold value at 1/300 dilution and 94% of cases with a threshold value at 1/80 (with a very poor specificity, often positive in other helminth infections). Immunofluorescence using protoscoleces as an antigen yields similar results.
    • Immunoelectrophoresis using Echinococcus crude extract yield low sensitivity and specificity. Arc 5, considered typical of E granulosus, is observed in nearly 60% of patients with alveolar echinococcosis.
    • Enzyme-linked immunosorbent assay (ELISA) results using heterologous antigen (E granulosus cyst fluid) are positive in 97% of cases, positive in abortive cases, and positive before species-specific tests in cases that recur after radical surgery or transplantation. ELISA results may also be positive in other types of cestode infections, especially cysticercosis (Taenia solium infection in humans) and, although less frequently, in other helminth infections.
      • ELISA results using homologous antigen (E multilocularis extract) are positive in 95% of cases but may be positive in other cestode infections.
      • ELISA results using recombinant and purified antigens of E multilocularis (Em2+ or recombinant Em18) are positive in 95% of cases and have better specificity. The EM2+ test is commercially available.
      • Combined ELISA for the diagnosis of echinococcosis and discrimination between E granulosus and E multilocularis, as a rapid test that does not require laboratory facilities, is commercially available in the People's Republic of China.
      • ELISA using the purified alkaline phosphatase of E multilocularis is both highly sensitive and specific (nearly 100%) but is not commercially available.
    • Western blot tests using combined extracts of E granulosus and E multilocularis or E multilocularis alone result in patterns specific for alveolar echinococcosis. Two narrow bands at 18 kDa are associated with 1 band at 26-27 kDa or only 1 band at 26-28 kDa. A pattern consisting of 1 band at 7 kDa and 1 band at 26-28 kDa without an intermediate band cannot differentiate E multilocularis infection from that of E granulosus. Western blot tests are highly sensitive (97%), and cross-reactions resulting in a similar pattern are observed only with sera from patients with neurocysticercosis. Western blot tests are commercially available. Specific Western blot using Em18 antigen or Em18 recombinant protein has comparable diagnostic value but is not commercially available.
    • Specific IgE are present in the serum of 50% of patients and cannot be used for diagnosis.
  • Cellular immunology
    • These tests are used primarily for research purposes.
    • Specific histamine release by basophils, using a homologous antigen, is observed in all cases.
    • Specific proliferation of peripheral blood lymphocytes can be induced using specific homologous extracts but is not routinely used.
    • Spontaneous secretion of IL-10 by peripheral lymphocytes in culture is observed in most patients with a progressive form of the disease.
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Imaging Studies

  • Aspect and location of alveolar echinococcosis lesions in the liver
    • In 50% of cases, lesions are located in a single hepatic lobe (right liver, 75%; left liver, 15%). Involvement of both right and left liver lobes by a single lesion is observed in 50% of cases.
    • The infiltrative lesions may be larger than 10 cm in diameter and invade or surround vascular and/or biliary structures. Some lesions are more nodular, 3-6 cm in diameter, and more calcified.
    • Two or more distinct parasitic foci may be observed.
    • Thoroughly investigate ultrasonographic evidence of bile duct dilation, portal hypertension, ascites, and splenomegaly. Doppler studies are a useful complement to better characterize hepatic and portal vessels and blood flow.
  • Ultrasonography
    • Ultrasonographic examination (see image below) is used to assess the morphology of alveolar echinococcosis both for diagnosis in hospital settings and in mass field screenings. It should be used as a first-line imaging technique. Sonogram of a typical form of alveolar echinococcoSonogram of a typical form of alveolar echinococcosis of the liver, discovered at a screening in China. Courtesy of Dominique A. Vuitton, MD, PhD; Brigitte Bartholomot, MD; and Philip S. Craig, PhD.
    • In most cases, ultrasonographic images show a pseudoneoplastic intrahepatic mass with a heterogeneous ultrasonographic structure that is mainly hyperechoic and contains scattered calcifications and irregular, poorly defined edges.
    • A central necrotic cavity with a hypoechoic pseudoliquid structure and anfractuous borders may be observed.
    • Hyperechoic nodular homogenous hemangiomalike lesions, 1-2 cm diameter, may be associated with typical lesions and observed as a recurrence after surgery or observed in patients who are asymptomatic at screening. These lesions may represent an early stage of development.
    • Disclosure of nodular or scattered calcified lesions in the liver is common in mass surveys and can be observed in hospital settings in endemic areas (see image below). If the calcifications are associated with a positive result on specific serology, they may represent abortive forms of the disease. Sonogram of an abortive form of alveolar echinococSonogram of an abortive form of alveolar echinococcosis of the liver, discovered at a screening in China. Courtesy of Dominique A. Vuitton, MD, PhD; Brigitte Bartholomot, MD; and Philip S. Craig, PhD.
  • CT scanning
    • Abdominal CT scanning reveals the morphologic aspect of the lesions (see image below). This is the best examination to show the typical calcifications inside the lesions and is particularly useful for very calcified lesions that are difficult to delineate with ultrasonography because of the induced shadow. Ultrasonographic, CT scan, and perioperative aspecUltrasonographic, CT scan, and perioperative aspect of a typical lesion of alveolar echinococcosis with central necrosis. Courtesy of Jean-Philippe Miguet, MD.
    • Abdominal CT scanning is also useful for preoperative evaluation to assess vascular involvement and extension to adjacent organs and tissues (eg, diaphragm and lungs, stomach, spleen, left kidney, adrenal gland).
    • Perform thoracic and cerebral CT scanning before any radical surgery, especially liver transplantation. Metastatic lesions appear as tumorlike structures, single or multiple, in the lungs and/or brain.
  • Magnetic resonance imaging
    • The cancerlike intrahepatic lesions appear as low signal intensity with a possible isointense component on T2-weighted images, and they produce variable signals on T2-weighted images, including necrotic areas in high signal intensity and some areas in low signal intensity.
    • MRI demonstrates a pathognomonic image of alveolar echinococcosis lesions that resembles bunches of grapes or a honeycomb. These lesions are more commonly observed on high-intensity T2-weighted images and are composed of many rounded cavities smaller than 1 cm in diameter (see image below). Pathognomonic aspect of alveolar echinococcosis lePathognomonic aspect of alveolar echinococcosis lesions invading the adrenal gland (resembling a honeycomb) that shows a necrotic area in the contiguous left liver lesion; MRI showing multiple parasitic cysts smaller than 1 cm in diameter appearing in high signal intensity on T2-weighted sequence. Courtesy of Brigitte Bartholomot, MD.
    • Gadolinium reveals an absence of contrast enhancement of the focus and the perilesional area in 60% of the cases.
    • In 40% of cases, an abnormal and delayed contrast enhancement is observed on the flash 2D sequences after contrast medium enhancement, especially on delayed T1-weighted images. They may correspond to the active neovascularized granuloma surrounding the parasitic lesions.
    • MRI is not effective for showing typical calcifications, but it is the best technique, when available, to differentiate an early homogenous hyperechoic parasitic lesion and a more common hemangioma.
    • When available, use MRI for preoperative evaluation, especially to disclose invasion of vessels and neighboring organs and tissues (see image below). Magnetic resonance (MR) cholangiopancreatography has generally replaced percutaneous cholangiography as a technique to study the relationship between the alveolar echinococcosis lesion and the biliary tree. Pathognomonic aspect of alveolar echinococcosis lePathognomonic aspect of alveolar echinococcosis lesions invading the adrenal gland (resembling a honeycomb) that shows a necrotic area in the contiguous left liver lesion; MRI showing multiple parasitic cysts smaller than 1 cm in diameter appearing in high signal intensity on T2-weighted sequence. Courtesy of Brigitte Bartholomot, MD.
  • Cholangiography
    • Because lesions typically are intrahepatic, use percutaneous cholangiography instead of endoscopic retrograde cholangiopancreatography if jaundice is present.
    • Cholangiography may show the precise level of bile duct obstruction and/or may be used to assess communication between bile ducts and the central necrotic area of the lesions and/or demonstrate communication between bile ducts and bronchi.
    • Percutaneous transhepatic cholangiography may be the first stage of an interventional procedure.
    • Endoscopic retrograde cholangiopancreatography may also be used as the first stage of intrabiliary stent insertion.
  • Angiography
    • MRI, ultrasonography with Doppler, and CT scanning have replaced angiographic procedures in most cases, but angiographic procedures may be indicated in rare cases before surgery.
    • Angiography may reveal invasion of hepatic arteries, portal vein obstruction or thrombosis, portocaval anastomoses, and obstruction or thrombosis of hepatic veins and vena cava.
  • Chest radiography
    • Chest radiography is the initial examination to assess the presence of lung metastases.
    • Lung metastases may be unique or multiple and appear as nodular images that resemble primary or metastatic tumors.
    • Complement radiography with lung CT scanning is indicated before any surgical intervention is planned, especially liver transplantation.
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Other Tests

  • Fluorodeoxyglucose (FDG)–positron emission tomography (PET) scanning: PET scanning, and especially morpho-PET scanning (PET combined with CT scanning, using image fusion), may be used to assess the viability of the parasitic lesions and the level of periparasitic cellular inflammation.
  • FDG is actively metabolized by the parasitic lesions; thus, lesional or perilesional enhancement ("hot spots") may be seen if the lesions are metabolically active. This technique may be used for the follow-up of patients treated with chemotherapy. Inactive lesions and calcified lesions do not uptake fluorodeoxyglucose.
  • Delayed acquisition of PET images (3 hours after FDG injection) increases the sensitivity of the procedure and is recommended before any decision of medical treatment withdrawal is made.
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Procedures

  • Esophagogastroduodenoscopy may show esophageal varices in cases that involve portal hypertension; it may be used as the first step of retrograde cholangiography and perendoscopic intervention (drainage of stenting) to relieve bile duct obstruction.
  • Bronchoscopy may be useful in cases of lung invasion or metastases.
  • Avoid needle liver biopsy if the diagnosis has been assessed on epidemiologic grounds using ultrasonography and/or CT scanning/MRI and confirmed with serology. Needle liver biopsy carries the risk of dissemination and subsequent growth of parasitic cells.
  • Fine-needle aspiration to characterize E multilocularis using polymerase chain reaction (PCR) may be used if all other techniques have failed to confirm alveolar echinococcosis.
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Histologic Findings

Surgical liver biopsy results show parasitic vesicles delineated by a periodic acid-Schiff–positive laminated layer and surrounded by granulomatous infiltrate, either cellular in younger lesions or mostly fibrotic and acellular in older lesions. Protoscoleces are observed in 15% of lesions.

From the center to the periphery, the periparasitic granuloma (see image below) is composed of epithelioid cells lining the parasitic vesicles, macrophages, fibroblasts and myofibroblasts, giant multinucleated cells, and various cells of the nonspecific immune response. Collagen and other extracellular matrix protein deposits are present. The granuloma is usually surrounded by lymphocytes (mainly of the CD8+ subpopulation).

Histologic features of alveolar echinococcosis vesHistologic features of alveolar echinococcosis vesicles and periparasitic granuloma in humans, periodic acid-Schiff staining of the laminated layer. Courtesy of Bernadette Kantelip, MD.

E multilocularis may be identified with polymerase chain reaction using specific probes; however, a negative result on a thin needle aspiration sample does not rule out disease.

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Staging

Staging the disease is essential to allow comparisons between series of patients and to perform multicenter trials. Until recently, no international system of staging was available. The World Health Organization (WHO) Informal Working Group on Echinococcosis/Network on Alveolar Echinococcosis Staging has recently developed such staging. The PNM (parasite, neighboring organ and tissue invasion, metastases) staging system has been evaluated prospectively in 220 cases from 4 centers in France, Germany, China, and Japan.

  • Hepatic localization of the parasite (For classification, the plane that projects between the bed of the gallbladder and the inferior vena cava divides the liver into 2 lobes.)
    • PX - Primary tumor cannot be assessed
    • P0 - No detectable tumor in the liver
    • P1 - Peripheral lesions without proximal vascular or biliary involvement
    • P3 - Central lesions with hilar vascular or biliary involvement of both lobes or involvement of 2 hepatic veins
    • P4 - Any liver lesion with extension along the vessels (vessels meaning inferior vena cava, portal vein, and arteries) and the biliary tree
  • Extrahepatic involvement of neighboring organs (diaphragm, lung, pleura, pericardium, heart, gastric and duodenal wall, adrenal glands, peritoneum, retroperitoneum, parietal wall [muscles, skin, bone], pancreas, regional lymph nodes, liver ligaments, kidney)
    • NX - Cannot be evaluated
    • N0 - No regional involvement
    • N1 - Regional involvement of contiguous organs or tissues
  • The absence or presence of distant metastasis (lung, distant lymph nodes, spleen, CNS, orbital, bone, skin, muscle, kidney, distant peritoneum and retroperitoneum)
    • MX - Not completely evaluated
    • M0 - No metastasis (negative findings on chest radiograph and cerebral CT scan)
    • M1 - Metastasis
  • Once the parasite (P), neighboring organ and tissue invasion (N), and metastases (M) are determined, they are combined, and an overall stage of I, II, III, or IV is assigned. Stage III is subdivided using letters such as A and B. The formal stage of alveolar echinococcosis does not change over time, even if the disease progresses. Alveolar echinococcosis that regresses or spreads is still referred to by the stage it was given when it was first diagnosed.
  • The following is the PNM stage grouping of alveolar echinococcosis:
    • Stage I - P1, N0, M0
    • Stage II - P2, N0, M0
    • Stage IIIa - P3, N0, M0
    • Stage IIIb - P1-3, N1, M0 or P4, N0, M0
    • Stage IV - P4, N1, M0 or any P, any N, M1
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Contributor Information and Disclosures
Author

Dominique A Vuitton, MD, PhD  Coordinator of International Affairs, WHO Collaborating Center for Prevention and Treatment of Echinococcosis, Professor Emeritus in Clinical Immunology, University of Franche-Comté, Besançon, France

Dominique A Vuitton, MD, PhD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology

Disclosure: Nothing to disclose.

Specialty Editor Board

John M Leedom, MD  Professor Emeritus of Medicine, Keck School of Medicine of the University of Southern California

John M Leedom, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society for Microbiology, Infectious Diseases Society of America, International AIDS Society, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

John W King, MD  Professor of Medicine, Chief, Section of Infectious Diseases, Director, Viral Therapeutics Clinics for Hepatitis, Louisiana State University Health Sciences Center; Consultant in Infectious Diseases, Overton Brooks Veterans Affairs Medical Center

John W King, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Association of Subspecialty Professors, Infectious Diseases Society of America, and Sigma Xi

Disclosure: emedicine $50.00 Author of chapter; MERCK None Other

Eleftherios Mylonakis, MD  Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital

Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD  Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

Thanks to all colleagues who are actively working within the framework of the WHO-Collaborating Centre for Prevention and Treatment of Human Echinococcosis, and more generally within the framework of the WHO-Informal Working Group on Echinococcosis.

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Foxes are the definitive hosts of the cestode Echinococcus multilocularis. Courtesy of Dominique A. Vuitton, MD, PhD.
Macroscopic aspect of alveolar echinococcosis lesions in the liver. Courtesy of Bernadette Kantelip, MD.
Ultrasonographic, CT scan, and perioperative aspect of a typical lesion of alveolar echinococcosis with central necrosis. Courtesy of Jean-Philippe Miguet, MD.
Microtus larvalis (common vole) is one of the most common intermediate hosts of Echinococcus multilocularis in Europe. Courtesy of Patrick Giraudoux, PhD.
Sonogram of a typical form of alveolar echinococcosis of the liver, discovered at a screening in China. Courtesy of Dominique A. Vuitton, MD, PhD; Brigitte Bartholomot, MD; and Philip S. Craig, PhD.
Sonogram of an abortive form of alveolar echinococcosis of the liver, discovered at a screening in China. Courtesy of Dominique A. Vuitton, MD, PhD; Brigitte Bartholomot, MD; and Philip S. Craig, PhD.
Pathognomonic aspect of alveolar echinococcosis lesions invading the adrenal gland (resembling a honeycomb) that shows a necrotic area in the contiguous left liver lesion; MRI showing multiple parasitic cysts smaller than 1 cm in diameter appearing in high signal intensity on T2-weighted sequence. Courtesy of Brigitte Bartholomot, MD.
Brain metastasis of alveolar echinococcosis. Courtesy of Jean-Philippe Miguet, MD.
Skin metastasis of alveolar echinococcosis. Courtesy of Solange Bresson-Hadni, MD, PhD.
Histologic features of alveolar echinococcosis vesicles and periparasitic granuloma in humans, periodic acid-Schiff staining of the laminated layer. Courtesy of Bernadette Kantelip, MD.
Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scan aspect of active alveolar echinococcosis. White-yellow colors show a very high FDG uptake due to the periparasitic granulomatous infiltration and/or active germinal layer of Echinococcus multilocularis, and green-gray colors show the absence of the FDG uptake by inactive parasitic lesions (mostly necrotic). Courtesy of Solange Bresson-Hadni, MD, PhD, and Oleg Blagosklonov, MD, PhD.
Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scan aspect of inactive alveolar echinococcosis. No abnormal FDG uptake by the parasitic lesions after several years of albendazole treatment. Courtesy of Solange Bresson-Hadni, MD, PhD, and Oleg Blagosklonov, MD, PhD.
 
 
 
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