Echinococcosis

Question 1

What is echinococcosis caused by?

Answer 1

Echinococcal disease is caused by infection with the tapeworm Echinococcus.

Question 2

How many different Echinococcus species infect humans? What are their names? Which two are responsible for the majority of disease?

Answer 2

Four species of Echinococcus cause infection in humans. E. granulosus and E. multilocularis are the most common, causing cystic echinococcosis (CE) and alveolar echinococcosis (AE), respectively. The two other species, E. vogeli and E. oligarthrus, cause polycystic echinococcosis and are less frequently associated with human infection.

Question 3

Describe the life-cycle of E. granulosus.

Answer 3

The life cycle of echinococcus includes a definitive host (usually dogs or related species) and an intermediate host (such as sheep, goats, camels, cervids, horses, cattle, and swine). Humans are incidental hosts; they do not play a role in the transmission cycle. E. granulosus adult tapeworms are usually found in dogs or other canids.

The adult tapeworm inhabits the small intestine of the definitive host. The tapeworm is composed of proglottid segments that have both male and female sexual organs and can produce parasite eggs 30 to 40 microm in size containing embryos (oncospheres). Each adult worm can produce thousands of eggs per day. The eggs are expelled in the stool of the definitive host and released to the environment, where they are infective to susceptible intermediate hosts and human incidental hosts. Eggs are highly resistant and can remain infective for a year in a moist environment at low temperature.

Following egg ingestion by the intermediate or incidental host, the oncospheres hatch from the eggs, penetrate the intestinal mucosa, enter the blood and/or lymphatic system, and migrate to the liver or other visceral organs. A few days later, a fluid-filled cyst begins to develop, with subsequent development of multiple layers to become a metacestode (hydatid cyst). The nature of the cyst is variable depending on the echinococcal species.

Subsequently, protoscolices develop within the hydatid cyst. In definitive hosts that ingest intermediate host visceral organs containing hydatid cysts composed of protoscolices, the protoscolices evaginate, attach to the intestinal mucosa, and develop into adult worms. Such development occurs over a period of four to seven weeks, completing the life cycle.

Question 4

Which kinds of areas are most conducive to the spread of E. granulosus?

Answer 4

The highest rates of cystic echinococcal endemic disease tend to occur in areas where sheep are raised. Transmission frequently occurs in settings where dogs eat the viscera of slaughtered animals. The dogs then excrete infectious eggs in their stool, which are passed on to other animals or humans via fecal-oral transmission. This may occur via environmental contamination of water and cultivated vegetables or contact between infected domestic dogs and humans (often in children).

Question 5

Does human-to-human transmission of Echinococcus occur?

Answer 5

Human-to-human transmission of echinococcosis does not occur.

Question 6

What is the geographic distribution of E. granulosus?

Answer 6

Cystic hydatidosis is a significant public health problem in South America, the Middle East and eastern Mediterranean, some sub-Saharan African countries, western China, and the former Soviet Union.

Question 7

What are the prevalence rates of E. granulosus infection in endemic areas?

Answer 7

In endemic rural areas, prevalence rates of 2 to 6 percent or higher have been recorded.

Question 8

Describe the pathology of E. granulosus.

Answer 8

The hydatid cyst is usually filled with fluid (table 2). The inner layer is the germinative layer that gives rise to the hydatid fluid and small secondary cysts (brood capsules), which bud internally from this layer.

After at least 10 to 12 months following infection, protoscolices are produced within the brood capsules. Cysts may contain liters of fluid and thousands of protoscolices. Cysts containing protoscolices are fertile and can produce daughter cysts, whereas cysts without protoscolices are sterile.

External to the germinative layer is an acellular, laminated membrane of variable thickness. A host granulomatous reaction occurs around this membrane; the resulting parenchyma and fibrous tissue reaction is known as the pericyst.

Question 9

Comment briefly on the host’s immune response to E. granulosus infection.

Answer 9

Intermediate and incidental hosts mount both humoral and cellular immune responses to the organism. The initial immune response occurs against the oncospheres that penetrate the gastrointestinal mucosa. Subsequently, the host mounts an immune response against the metacestode (hydatid cyst). Metacestodes have developed highly effective mechanisms for evading host defenses. The membranes and host capsule surrounding the cyst protect the E. granulosus parasite from immune destruction.

Studies have suggested that Th1 cell activation is crucial for protective immunity, whereas Th2 cell activation is associated with susceptibility to progressive hydatid disease.

Question 10

Describe the life-cycle of E. multilocularis.

Answer 10

Rodents serve as intermediate hosts for E. multilocularis; humans are incidental hosts who acquire infection by ingesting eggs shed in stool by the definitive host, typically foxes. The embryos or oncospheres hatch from the egg in the small intestine and are transported to the liver where they form multilocular hydatid cysts. In humans, the larval mass resembles a malignancy in appearance and behavior because it proliferates indefinitely by exogenous budding and invades the surrounding tissues. Unlike cystic echinococcosis, protoscolices are rarely observed in human infection due to E. multilocularis. Fox and coyote populations have increasingly encroached upon suburban and urban areas of many regions and, as a result, domestic dogs or cats may become infected when they eat infected wild rodents.

Question 11

What is the geographic distribution of E. multilocularis?

Answer 11

Alveolar echinococcosis due to E. multilocularis has been reported in parts of central Europe, much of Russia, the Central Asian republics, northeastern, northwestern, and western China, the northwestern portion of Canada, and western Alaska.

Question 12

What is the pathology of E. multilocularis?

Answer 12

E. multilocularis can cause severe infection in humans. The metacestode tissue behaves like a malignancy that invades and destroys tissue, extends beyond organ borders into adjacent structures, and can metastasize to distant sites. In humans, disease spreads from primary infection in the liver to other organs, including the lungs and the brain, either by direct extension or hematogenous dissemination.

The lesions are composed of numerous irregular cysts of various sizes, with no sharp demarcation from surrounding organ tissue. Mixed solid and cystic lesions are common. The lack of limiting membrane allows exogenous budding, proliferation, and infiltration into adjacent tissues, resulting in necrosis of surrounding host tissue. Central necrosis of the lesions is frequent, and irregular calcifications are seen in up to 70 percent of cases. Microscopically, the cysts are composed of a thin, laminated layer with minimal or no germinative layer. Brood capsules and protoscolices form in less than 10 percent of these cysts; instead, reproduction occurs by asexual lateral budding.

Question 13

What is the geographical distribution of E. vogeli and E. oligarthrus?

Answer 13

Central and South America.

Question 14

Suggest some methods for decreasing infection rates with Echinococcus.

Answer 14

The likelihood of cystic echinococcosis infection can be reduced by avoiding close contact with dogs. Careful washing of fresh produce can also reduce the likelihood of infection. The life cycle of the parasite can be disrupted by preventing dogs from consuming infected sheep viscera, which generally occurs in settings where dogs reside in close proximity to areas where sheep are slaughtered.

Vaccination of sheep may also be useful for prevention of cystic echinococcosis; intermediate hosts are capable of developing protective immunity.

Question 15

Give a general outline of the clinical manifestations of E. granulosus.

Answer 15

The initial phase of primary infection is always asymptomatic. Many infections are acquired in childhood but do not cause clinical manifestations until adulthood.

The clinical presentation of E. granulosus infection depends upon the site of the cysts and their size. Small and/or calcified cysts may remain asymptomatic indefinitely. However, symptoms due to mass effect within organs, obstruction of blood or lymphatic flow, or complications such as rupture or secondary bacterial infections can result.

Question 16

How fast do E. granulosus cysts grow once they start to?

Answer 16

Cysts typically increase in diameter at a rate of one to five centimeters per year. However, cyst growth rates and time courses are highly variable.

Question 17

Where can E. granulosus cysts be found? Which organs are most common?

Answer 17

Hydatid cysts may be found in almost any site of the body, either from primary inoculation or via secondary spread. The liver is affected in approximately two-thirds of patients, the lungs in approximately 25 percent, and other organs including the brain, muscle, kidneys, bone, heart, and pancreas in a small proportion of patients.

Question 18

In E. granulosus infection, is it more common for patients to present with a single cyst or multiple cysts?

Answer 18

Single-organ involvement occurs in 85 to 90 percent of patients with E. granulosus infection, and only one cyst is observed in more than 70 percent of cases.

Question 19

Describe the clinical manifestations of liver involvement in E. granulosus infection.

Answer 19

E. granulosus infection of the liver frequently produces no symptoms. The right lobe is affected in 60 to 85 percent of cases. Significant symptoms are unusual before the cyst has reached at least 10 cm in diameter. If the cysts become large, hepatomegaly with or without associated right upper quadrant pain, nausea, and vomiting can result
.
E. granulosus cysts can rupture into the biliary tree and produce biliary colic, obstructive jaundice, cholangitis, or pancreatitis.

Pressure or mass effects on the bile ducts, portal and hepatic veins, or on the inferior vena cava can result in cholestasis, portal hypertension, venous obstruction, or the Budd-Chiari syndrome.

Liver cysts can also rupture into the peritoneum, causing peritonitis, or transdiaphragmatically into the pleural space or bronchial tree, causing pulmonary hydatidosis or a bronchial fistula. Secondary bacterial infection of the cysts can result in liver abscesses.

Question 20

Describe the clinical manifestations of lung involvement in E. granulosus infection.

Answer 20

The most common symptoms of pulmonary cystic echinococcosis (CE) described in the literature include cough (53 to 62 percent), chest pain (49 to 91 percent), dyspnea (10 to 70 percent), and hemoptysis (12 to 21 percent). Less frequent symptoms include malaise, nausea and vomiting, and thoracic deformations.

Cysts can break or develop secondary bacterial infection. The presence of these complications changes the clinical presentation, either by causing new symptoms or by increasing the severity of existing symptoms. The principal complication is cyst rupture, with spilling of cyst material containing fragments of larval tissue and protoscolices into the bronchial tree or the pleural cavity. Bronchial tree involvement can lead to cough, chest pain, hemoptysis, or emesis; pleural cavity involvement can cause pneumothorax, pleural effusion, or empyema. Secondary bacterial infection of the cyst can manifest as a pulmonary abscess with poorly defined margins.

Approximately 60 percent of pulmonary hydatid disease affects the right lung, and 50 to 60 percent of cases involve the lower lobes. Multiple cysts are common. Approximately 20 percent of patients with lung cysts also have liver cysts.

Question 21

Mention the clinical manifestations of E. granulosus infection in the following:

• Heart
• CNS
• Kidneys
• Bones
• Eyes
• Subcutaneous tissue

Answer 21

Involvement of organs outside of the liver or lung is unusual but can lead to significant morbidity and mortality.
●Infection of the heart can result in mechanical rupture with widespread dissemination or pericardial tamponade.
●Central nervous system involvement can lead to seizures or signs of raised intracranial pressure; infection of the spinal cord can result in spinal cord compression.
●Cysts in the kidney can cause hematuria or flank pain. Immune complex-mediated disease, glomerulonephritis leading to the nephrotic syndrome, and secondary amyloidosis have also been described.
●Bone cysts are usually asymptomatic until a pathologic fracture develops; the spine, pelvis, and long bones are most frequently affected.
●Ocular cysts also occur.
●Subcutaneous cyst has been described.

Question 22

What are the clinical manifestations associated with E. granulosus cyst rupture?

Answer 22

Fever and acute hypersensitivity reactions, including anaphylaxis, may be the principal manifestations of cyst rupture. Hypersensitivity reactions are related to the release of antigenic material and secondary immunologic reactions.

Question 23

What are the outcomes like with E. granulosus infection?

Answer 23

The outcome of infection varies with the stage of the disease.

Approximately 15 percent of patients had undergone surgery 10 to 12 years after the initial diagnosis. Among patients who did not undergo surgery, 75 percent remained asymptomatic; 57 percent did not have a change in the size of the cyst by imaging.

Calcification usually requires 5 to 10 years to develop and occurs most commonly with hepatic cysts but rarely with pulmonary or bone cysts. Total calcification of the cyst wall suggests that the cyst may be nonviable.

Question 24

Comment briefly on the intra- and extra-hepatic clinical manifestations of E. multilocularis.

Answer 24

Infection due to E. multilocularis is usually symptomatic, although the clinical manifestations are frequently nonspecific. The most common presenting complaints include malaise, weight loss, and right upper quadrant discomfort due to hepatomegaly. Cholestatic jaundice, cholangitis, portal hypertension, and the Budd-Chiari syndrome can also occur. The clinical presentation may mimic that of hepatocellular carcinoma.

Extrahepatic primary disease is very rare (1 percent of cases). Immunodeficiency, such as HIV or transplantation, may accelerate the manifestations of alveolar echinococcosis.

Question 25

What are the outcomes like with E. multilocularis infection?

Answer 25

If left untreated, more than 90 percent of patients will die within 10 years of the onset of clinical symptoms, and virtually 100 percent will die by 15 years. Since treatment with albendazole has been introduced, the prognosis has improved considerably. Of 117 patients from France who underwent long-term follow-up, the actuarial survival rate was 88 percent.

Question 26

How does one approach the diagnosis of Echinococcus infection?

Answer 26

Both cystic and alveolar Echinococcus may be diagnosed with a combination of imaging and serology.

Question 27

What do routine lab investigations show for E. granulosus?

Answer 27

Nonspecific leukopenia or thrombocytopenia, mild eosinophilia, and nonspecific liver function abnormalities may be observed but are not diagnostic. Eosinophilia is observed in fewer than 15 percent of cases and generally occurs only if there is leakage of antigenic material.

Question 28

Outline the approach to imaging used for e. granulosus infection.

Answer 28

Hydatid cysts may be visualized and evaluated with ultrasonography, computed tomography (CT), or magnetic resonance imaging (MRI). Ultrasonography is employed most widely because it is easy to perform and relatively inexpensive.

However, CT or MRI may be useful for circumstances in which greater anatomic detail is needed.

Question 29

Discuss the use of ultrasound in the diagnosis of E. granulosus infection. Cover:

• Sensitivity and specificity
• Suggestive findings
• The WHO classification
• Lung cysts

Answer 29

The sensitivity of ultrasonography for evaluation of Echinococcus is 90 to 95 percent.

The most common appearance on ultrasound is an anechoic, smooth, round cyst, which can be difficult to distinguish from a benign cyst. Shifting the patient’s position during ultrasonography may demonstrate “hydatid sand,” which consists predominantly of hooklets and scolexes from the protoscolices. Hydatid disease is probable in the setting of hydatid sand, inner cyst wall infoldings, and separation of the hydatid membrane from the wall of the cyst observed on ultrasound.

WHO categories CE1 and CE2 are active cysts. Type CE1 is unilocular, and type CE2 is multilocular with daughter cysts. Class CE3 consists of cysts that are thought to be degenerating (transitional group). There are two types of CE3: CE3a, featuring the “water-lily” sign for floating membranes, and CE3b, which is predominantly solid with daughter cysts. Classes CE4 and CE5 are considered inactive. By ultrasonography, they are echogenic with increasing degrees of calcification and are nearly always nonviable.

Lung cysts may be single or multiple, usually do not calcify, rarely lead to daughter cyst formation, and may contain air if the cyst has ruptured.

Question 30

Comment on the use of CT in the diagnosis of E. granulosus infection.

Answer 30

Many reports suggest that CT has higher overall sensitivity than ultrasonography (95 to 100 percent). CT is the best mode for determining the number, size, and anatomic location of the cysts and is better than ultrasound for detection of extrahepatic cysts. CT may also be used for monitoring lesions during therapy and to detect recurrences.

Question 31

Comment on the use of MRI in the diagnosis of E. granulosus infection.

Answer 31

MRI has no major advantage over CT for evaluation of abdominal or pulmonary hydatid cysts, except in defining changes in the intra- and extrahepatic venous system.

Both CT and MRI are useful in diagnosing echinococcal infection in other sites such as in the brain.

Question 32

Besides US, CT and MRI, which other imaging modalities might be required in the diagnosis/management of E. granulosus infection?

Answer 32

Other imaging techniques such as cholangiography may be indicated to diagnose biliary involvement, particularly in patients with cholestatic jaundice. Endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography (MRCP) is frequently performed in patients with liver cysts prior to intervention to ascertain potential involvement of the biliary system and to guide the treatment approach.

Question 33

Comment on the use of serology in the diagnosis of E. granulosus infection. Cover:

• Use of tests for screening and confirmation.
• Sensitivity and specificity of above
• Interpretation of above, including comments on false negatives and false-positives.

Answer 33

Serology is useful for primary diagnosis and for follow-up after treatment. Antibody detection is more sensitive than antigen detection for diagnosis of E. granulosus.

There are a host of tests available. ELISA appears to be the most sensitive and specific of the available assays.

The utility of serology can be improved by using a combination of tests or sequential testing. A highly sensitive assay, usually an ELISA or indirect hemagglutination test, is commonly used as an initial screen, followed by a highly specific immunoblot or gel diffusion assay for confirmation.

The dot-ELISA has a reported sensitivity of 88 to 96 percent and a specificity of 90 to 98 percent. The sensitivity in immunoblot and gel diffusion assays is approximately 90 percent with a specificity of 97 to 100 percent.

A negative serologic test generally does not rule out echinococcosis. Overall, approximately 85 to 95 percent of liver cysts and 65 percent of lung cysts are associated with positive serology, although this varies with the specific serologic test used and cyst activity. The likelihood of false-negative results is variable depending on the site of the lesion and the integrity and viability of the cyst. False-positive reactions are more likely in the presence of other helminth infections (such as Taenia saginata, Taenia solium, and particularly neurocysticercosis), cancer, and immune disorders.

Question 34

What do routine lab investigations show for E. multilocularis infection?

Answer 34

Nonspecific leukopenia or thrombocytopenia, mild eosinophilia, and nonspecific liver function abnormalities may be detected but are not diagnostic. Hypergammaglobulinemia and elevated serum IgE levels are present in more than 50 percent of cases.

Question 35

Comment on the use of imaging in the diagnosis of E. multilocularis infection.

Answer 35

The diagnosis of E. multilocularis is generally made by imaging techniques in conjunction with serology. On ultrasound or CT, the lesions usually have an irregular contour with no well-defined wall, central necrosis, and irregular intralesional and wall calcifications. They may be difficult to distinguish from a tumor, but the patient’s overall condition is usually better than would be expected for a malignancy.

Question 36

Discuss the use of serology in the diagnosis of E. multilocularis infection.

• Cover the common antigen test used and include its sensitivity and specificity
• Mention their status following treatment/recurrence.
• Mention the most sensitive antibodies for monitoring treatment success.

Answer 36

Serologic tests are more reliable for diagnosis of E. multilocularis infection than for E. granulosus infection; sensitivity and specificity rates are 95 to 100 percent. A specific E. multilocularis antigen such as the affinity purified Em2 antigen from AE metacestodes is often used; the Em2-ELISA can discriminate between E. granulosus and E. multilocularis in 95 percent of cases. Serology usually remains positive indefinitely; following complete surgical resection, serology may normalize within a few years. The Em2-ELISA frequently becomes negative within four years of surgery and becomes positive again in the setting of a recurrence.

These tests may not be readily available and may be found only in specialized centers.

Clinical recurrence is frequently associated with rising serologic titers. IgG1 and IgG4 antibodies are the most sensitive isotypes for monitoring success of therapy.

Question 37

Comment on the use of cyst aspiration or biopsy in the diagnosis of Echinococcus infection.

Answer 37

In the absence of a positive serologic test, percutaneous aspiration or biopsy may be required to confirm the diagnosis by demonstrating the presence of protoscolices, hooklets, or hydatid membranes. Percutaneous aspiration of liver cyst contents is associated with very low rates of complications, but this method of diagnosis is generally reserved for situations when other diagnostic methods are inconclusive because of the potential for anaphylaxis and secondary spread of the infection.

If aspiration is required, it should be performed under ultrasound or CT guidance; complications can be minimized by concurrent administration of albendazole and praziquantel.

Question 38

Comment on the use of PCR techniques in the diagnosis of Echinococcus infection.

Answer 38

Polymerase chain reaction techniques are limited to research settings but may play a diagnostic role in the future.

Question 39

Which conditions should be considered in the differential diagnosis of cystic echinococcosis?

Answer 39

In general, any mass occupying lesion may clinically resemble an echinococcal cyst. The differential diagnosis of cystic echinococcosis includes:
●Simple benign cyst 
●Hemangioma 
●Hepatocellular carcinoma 
●Abscess 
●Tuberculosis

Question 40

Which conditions should be considered in the differential diagnosis of alveolar echinococcosis?

Answer 40

●Cirrhosis

●Malignancy (hepatocellular carcinoma or liver metastases).

Question 41

Give a broad overview of the treatment components for E. granulosus infection.

Answer 41

Management options for cystic echinococcosis (CE) include surgery, percutaneous management, drug therapy, and observation.

Question 42

Describe the management of E. granulosus according to the WHO Classification.

Answer 42

In general, clinical approach depends on the World Health Organization (WHO) diagnostic classification. Stage CE1 and CE3a cysts have a single compartment; such cysts that are <5 cm may be treated with albendazole alone. In settings where albendazole treatment with follow-up monitoring is not feasible, definitive management with percutaneous treatment via puncture, aspiration, injection, and reaspiration (PAIR) is an acceptable alternative approach. Stage CE1 and CE3a cysts that are >5 cm may be treated with albendazole in combination with PAIR. In situations where albendazole treatment is not feasible, percutaneous treatment with PAIR (in the absence of adjunctive drug therapy) is an acceptable alternative approach.

Stage CE2 and CE3b cysts have many compartments that require individual puncture; patients with such cysts commonly relapse after PAIR. Therefore, management of these cysts requires either modified catheterization technique (eg, non-PAIR percutaneous therapy) or surgery (with adjunctive drug therapy). The optimal choice between these approaches is uncertain and further study is needed.

Stages CE4 and CE5 are inactive cysts that may be managed with observation.

Question 43

Give an overview of the indications for surgery in the management of E. granulosus.

Answer 43

• Surgery is the treatment of choice for management of complicated cysts (eg, rupture cyst, cysts with biliary fistulae, cysts compressing vital structures, cysts with secondary infection or hemorrhage).
• Surgery is also warranted for management of cysts with many daughter vesicles that are not suitable for percutaneous treatment (eg, WHO stage CE2 and CE3b).
• Other indications for surgery include cyst diameter >10 cm, superficial cyst at risk of rupture due to trauma, and extrahepatic disease (lung, bone, brain, kidney, or other site).
• Surgery is also appropriate in settings where percutaneous treatment is not available.

Question 44

Comment on the use adjunctive medications for surgery in E. granulosus infection.

Answer 44

Adjunctive drug therapy should be administered to minimize risk of secondary echinococcosis from seeding of protoscolices in the abdominal cavity in the event of fluid spillage. Albendazole is generally administered beginning one week prior to surgery and continued for at least four weeks postoperatively. Some use praziquantel in addition to albendazole, although there is no clear evidence regarding its efficacy.

Question 45

What are the outcomes like with surgery?

Answer 45

Surgery may cure the patient, but morbidity, mortality, and relapse rates can vary widely.

Question 46

What complications are associated with surgery?

Answer 46

Complications include secondary infection of cyst cavity, intraabdominal abscess, biliary fistula, sclerosing cholangitis, and spillage of cyst contents leading to secondary echinococcosis and/or anaphylaxis. Postoperative complications occur in less than 1 percent of cases; recurrent echinococcosis occurs in 2 to 25 percent of cases. These rates depend on the location and size of the cyst and the surgeon’s experience.

Question 47

What are the goals of surgery and which procedure is the best?

Answer 47

The goals of surgical therapy consist of evacuating the cyst and obliterating the residual cavity. Every effort should be made to avoid fluid spillage, which can lead to secondary seeding of infection and/or anaphylaxis. The safest and most effective surgical procedure is uncertain; the relative advantages of the different approaches have not been clearly established. Traditional approaches have included radical resection including pericystectomy or more conservative techniques. Laparoscopic surgery may be an alternative to open surgery in some cases.

Question 48

What is the most commonly used protoscolicidal agent during surgery (when intact cyst excision is not possible)? List some others. Which agent should not be used and why?

Answer 48

The most commonly used protoscolicidal agent is hypertonic saline (20 percent); the solution should be in contact with the germinal layer for at least 15 minutes. Albendazole, ivermectin, and praziquantel solutions have been used as protoscolicidal agents, although their efficacy and safety require further study. Formalin has been associated with sclerosing cholangitis and should not be used.

Question 49

How should a patient be managed who suffers intra-operative cyst spillage?

Answer 49

If spillage does occur, the peritoneum should be washed with hypertonic saline. The patient should be treated with albendazole (three to six months) and a brief course of praziquantel (seven days) should also be administered. The management of anaphylaxis is described separately.

Question 50

What surgical options are available for the management of lung cysts?

Answer 50

Surgical approaches for management of lung cysts include lobectomy, wedge resection, pericystectomy, intact endocystectomy, and capitonnage.

Question 51

Brielfy outline the two percutaneous approaches to the management of E. granulosus infection.

Answer 51

The first approach aims to destroy the germinal layer with scolicidal agents. This is done via the PAIR technique. PAIR is usually effective for definitive treatment of cysts that do not have daughter cysts (eg, WHO stage CE1 and CE3a).

The second approach consists of evacuating the entire cyst with a large-bore catheter. This is generally done for management of cysts that are difficult to drain or tend to relapse after PAIR, such as WHO stage CE2 and CE3b cysts (which may contain daughter cysts).

Question 52

Comment on the use of adjunctive therapy in PAIR.

Answer 52

Adjunctive drug therapy with albendazole or mebendazole should be administered at least four hours prior to PAIR. Albendazole should be continued for one month after the procedure; mebendazole should be continued for three months after the procedure.

Question 53

What are the risks with PAIR?

Answer 53

Risks of PAIR include spillage of cyst contents into the peritoneum (which can lead to secondary echinococcosis, urticaria, and/or anaphylaxis), chemical sclerosing cholangitis, biliary fistula (6 percent), local recurrence (3 percent), and bleeding and infection (4 percent). Fever and urticaria occur in 11 to 13 percent of cases; the risk of anaphylaxis is 0.5 percent and has been reduced with development of fine needles and catheters and advances in imaging techniques.

Question 54

What is the primary antiparasitic agent indicated in the definitive drug management of E. granulosus? What is the alternative?

Answer 54

Albendazole is the primary antiparasitic agent for treatment of E. granulosus. In the absence of albendazole, mebendazole may be used as an alternative therapy; it is less well absorbed than albendazole.

Question 55

Discuss the definitive drug treatment of E. granulosus.

Answer 55

Initial management with drug treatment alone is appropriate for management of small WHO stage CE1 and CE3a cysts (eg cysts with a single compartment and diameter <5 cm). Treatment should be administered without interruption. The optimal duration is uncertain; one to three months may be appropriate, depending clinical factors; up to six months may be required.

Drug treatment alone is usually not effective for treatment of cysts with diameter >5 cm or for treatment of WHO stage CE2 or CE3b cysts (which have multiple compartments). Other circumstances in which drug treatment alone may be warranted include management of multiple liver cysts <5 cm, management of cysts deep in liver parenchyma that are not amenable to percutaneous treatment, and/or peritoneal cysts .

Drug treatment may be appropriate for patients who cannot undergo definitive cyst removal via percutaneous treatment or surgery, although drug treatment alone is generally not sufficient for definitive management in such cases. Drug treatment is also appropriate following spontaneous cyst rupture to reduce the risk of secondary echinococcosis from seeding of protoscolices in the abdominal cavity for one month (albendazole) or three months (mebendazole).

Question 56

What is the mechanism of action of albendazole?

Answer 56

Albendazole inhibits microtubules assembly, leading to impaired glucose absorption and causing glycogen depletion followed by degeneration of the endoplasmic reticulum and mitochondria of the germinal layer, leading to cell death.

Question 57

Comment on the effectiveness of albendazole in E. granulosus infection..

Answer 57

Cumulative experience with albendazole suggests that treatment leads to cyst resolution in up to 30 percent of patients, size reduction in another 30 to 50 percent, and no change in 20 to 40 percent. A lower likelihood of response has been observed in the setting of older patient age and longer duration of infection.

Question 58

What is the typical dose for albendazole in E. granulosus infection.

Answer 58

Albendazole is usually dosed 10 to 15 mg/kg per day in two divided doses; the usual dose for adults is 400 mg twice daily. Absorption is improved by taking albendazole with a fatty meal.

Question 59

Comment on the adverse effects of albendazole and the management thereof.

Answer 59

Albendazole is generally well tolerated. Adverse effects include reversible hepatotoxicity (1 to 5 percent), cytopenia (<1 percent), and alopecia (<1 percent). Increased levels of aminotransferases may occur as a result of drug toxicity or parasite killing. Rarely, agranulocytosis has been reported. Dizziness, headache, vomiting, and rash have also been described. These drugs should not be used in patients with significant underlying liver disease or bone marrow suppression. Laboratory monitoring including blood count and liver function tests should be checked at two-week intervals for the first three months, then monthly.

An increase in aminotransferases that is more than fivefold above the upper limit of normal should prompt discontinuation of albendazole and consideration of alternative treatment approaches such as percutaneous or surgical management. If an alternative therapeutic agent is required, praziquantel may be a reasonable alternative to albendazole.

Question 60

Is albendazole safe in pregnancy?

Answer 60

No and its use should be avoided.

Question 61

When is observation indicated for the management of E. granulosus infection?

Answer 61

Some studies have suggested that, in the absence of complications, inactive liver cysts (eg, WHO stage CE4 and CE5) can be monitored in the absence of treatment. Prospective studies evaluating this approach are needed.

Question 62

How would you monitor a patient who has received therapy for E. granulosus infection? Mention radiological and serological forms of follow-up.

Answer 62

The optimal approach to monitoring is uncertain and must be individualized according to patient characteristics and available resources. Follow-up usually consists of ultrasound or other imaging (CT or magnetic resonance imaging [MRI]) at three- to six-month intervals until the findings are stable, followed by yearly monitoring. Follow-up for up to five years is usually warranted to evaluate for recurrence; in some cases, three years may be sufficient if radiographic findings are stable at 12, 24, and 36 months.

The optimal serologic test for monitoring patients on treatment for hydatid disease is uncertain. Frequently, serologic titers fall one to two years following successful surgery and rise again in the setting of recurrence. However, antibodies may remain elevated even many years after successful cyst removal.

Question 63

In general, is treatment more effective for E. granulosus or E. multilocularis infection?

Answer 63

E. granulosus.

Question 64

Write short notes on the ‘optimal’ therapy of E. multilocularis infection.

Answer 64

In general, the approach to treatment of AE consists of surgery. Infected tissues should be removed as completely as possible, which requires complete excision of parasitic tissue and may also warrant radical resection of host tissue. The feasibility of radical resection depends on the site of the lesion, presence of metastases, patient comorbidities, and available surgical expertise.

In cases that are not amenable to definitive surgery, albendazole should be administered indefinitely to suppress progression of infection. In such cases, albendazole is not curative but can improve quality of life and prolong survival. Survival rates at 15 years of 53 to 80 percent have been observed with palliative albendazole in the absence of surgery

Question 65

Write short notes on the use of albendazole in E. multilocularis infection.

Answer 65

The benefit of routine preoperative albendazole administration is not known. Postoperatively, albendazole (10 to 15 mg/kg per day in two divided doses; usual adult dose 400 mg twice daily) should be administered to reduce the likelihood of relapse, even in cases of apparent cure.

The optimal duration of albendazole is uncertain; in general, at least 2 years of therapy is advisable in conjunction with at least 10 years of follow-up monitoring for recurrence.

Question 66

What local complications might develop after treatment for E. multilocularis?

Answer 66

Local complications may develop that warrant intervention such as stenting, drainage of necrotic liver lesions, or endoscopic sclerosing of esophageal varices.