Echinococcosis Hydatid Cyst

Back

Practice Essentials

Practice Essentials

Cystic Echincococcosis (CE) is an infection caused by the metacestode of the taenia Echinococcus granulosus.[1, 2]  

The infection causes the formation of Echinococcal or Hydatid cysts in intermediate hosts. Humans are accidental intermediate hosts. The infection disproportionally affects patients in rural, pastoral communities where sheep rearing is practiced. 

The main organs affected by CE are the liver (70-75% of cases),[3] followed by the lungs (10-20% of cases),[4] but any organ can be affected.

Sings and Symptoms

Most cysts (around 70%) stay asymptomatic until found accidentally. Symptomatic cases have features dependent on the size, location and relationship with other organs.

Abdominal CE Patients may present with pain, acute abdomen, jaundice or in very rare instances, features of anaphylactic shock in cases complicated by cyst rupture. Fever due to cyst superinfection may be present, as well as ascites due to portal hypertension. Discharge of cyst membrans or vescicles with urine has been reported in complicated kidney cysts.[5]  

Thoracic CE  In the case of parenchymal CE, patients usually become symptomatic when a bronchial fistula is present and vomica (i.e. coughing up pieces of cyst membranes or vescicles) occurs. Superinfection and abscess formation has also been reported. 

Other localizations Bone CE often presents with pain and neurological symptoms including sensitive or motor deficits and neurological bladder in the most advanced cases. Heart CE can present with embolization. Brain CE can present with seizures or neurological deficit.

Diagnosis

The mainstay of diagnosis for abdominal CE is ultrasound (US), as this technique allows for the use of a WHO-Informal Working Group on Echinococcosis (IWGE) classification for cyst staging. If US expertise is lacking, Magnetic Resonance Imaging (MRI) has been shown to better show stage specific characteristics in patients with liver CE. It is also the imaging method of choice for abdominal cysts not seen by US and for extra-hepatic localizations. CT is still useful for the pre-surgical study of thoracic and liver CE.

Serological assays are available but should not be used as screening tests due to issues with sensitivity in both early and inactive cysts, as well as with issues in cross-reactivity.

Currently, our group endorses the use of at least two first line tests, preferably including an immunoblot. A positive serological case is defined by the positivity of two tests. In one single center experience, western blot had sufficient sensitivity and specificity alone, but an assessment of several serological tests have found variability between different commercial tests. Serology should not be used in the abscence of lesions without imaging characteristics suggestive of CE (eg, isolated hypereosinophilia).

Treatment

 Abdominal CE

Non-complicated liver CE can be managed through a stage-specific approach as per WHO-IWGE recommendations: current expert recommendations use cyst stage to direct towards four options (medical treatment, surgery, percutaneous treatments, watch and wait) (see Management for further details). Complicated liver CE is usually managed surgically, with the potential exception of superinfected cysts with abscess formation. In such cases, percutaneous aspiration can be considered.  Extra-hepatic cysts and peritoneal localizations require individualized management toghether with an expert provider.

Thoracic CE Lung CE cyst have been shown to respond to medical treatment with benzimidazoles, provided that they are of small dimensions (< 5 cm in diameter). Other cysts require an individualized approach to establish indication for surgerey (e.g. small, inactive cysts may be managed by watch and wait in selected cases), but surgery is the main treatment approach. 

Other localizations Other localization of CE require management in conjunction with an expert provider. 

SeeTreatment for further details  

Background

Cystic echinococcosis (CE) is the larval cystic stage (called echinococcal cysts) of a small taeniid-type tapeworm (Echinococcus granulosus) that may cause illness in intermediate hosts, generally herbivorous animals and people who are infected accidentally.[6]  Ultrasonographic (US) appearance of echinococcal cysts is seen in the image below.[7]

WHO Informal Working Group on Echinococcosis standardized ultrasound classification of echinococcal cysts and treatment options.

Three other species are recognized within the genus Echinococcus, and they may also develop in the human host and cause various forms of echinococcosis (hydatidosis). E granulosus is discussed separately from the other 3 species, notably Echinococcus multilocularis, which causes alveolar echinococcosis, because of marked differences in epidemiology, clinical features, diagnosis, and treatment.[8]

In the normal life cycle of Echinococcus species, adult tapeworms (3-6 mm long) inhabit the small intestine of carnivorous definitive hosts, such as dogs, coyotes, or wolves, and echinococcal cyst stages occur in herbivorous intermediate hosts, such as sheep, cattle, and goats.[6, 9, 10]  A number of other suitable intermediate hosts, such as camels, pigs, and horses, are involved in the life cycle in many parts of the world.[6, 9, 10]

In the typical dog-sheep cycle, tapeworm eggs are passed in the feces of an infected dog and may subsequently be ingested by grazing sheep; they hatch into embryos in the intestine, penetrate the intestinal lining, and are then picked up and carried by blood throughout the body to major filtering organs (mainly liver and/or lungs). After the developing embryos localize in a specific organ or site, they transform and develop into larval echinococcal cysts in which numerous tiny tapeworm heads (called protoscolices) are produced via asexual reproduction.[6, 9, 10]

These protoscolices are infective to dogs that may ingest viscera containing echinococcal cysts (with protoscolices inside), mainly because of the habit in endemic countries of feeding dogs viscera of home-slaughtered sheep or other livestock.[6, 9, 10]

Protoscolices attach to the dog's intestinal lining and, in approximately 40-50 days, grow and develop into mature adult tapeworms, once again capable of producing infective eggs to be passed to the outside environment with the dog's feces.

Because humans play the same role of intermediate hosts in the tapeworm life cycle as sheep, humans also become infected by ingesting tapeworm eggs passed from an infected carnivore. This occurs most frequently when individuals handle or contact infected dogs or other infected carnivores or inadvertently ingest food or drink contaminated with fecal material containing tapeworm eggs.[6, 9, 10]

Pathophysiology

In primary CE, metacestodes develop from oncospheres after peroral infection with E granulosus eggs. In secondary echinococcosis, larval tissue proliferates after being spread from the primary site of the metacestode. This can occur by spontaneous trauma such as induced rupture or during medical interventions.

In primary CE, larval cysts may develop in every organ.[11] Most patients (as many as 80%) have single-organ involvement and harbor a solitary cyst.[9, 10]  Approximately two thirds of patients experience liver echinococcosis.[3, 12] The second most common organ involved is the lung.[4, 8]

In each anatomic site, cysts are surrounded by the periparasitic host tissue (pericyst), which encompasses the endocyst of larval origin. Inside the laminated layer, or hyaline membrane, the cyst is covered by a multipotential germinal layer, giving rise to the production of brood capsules and protoscolices. The central cavities of cysts of E granulosus are filled with clear fluid, numerous brood capsules, and protoscolices. In addition, daughter cysts of variable size often are detected. The growth rate of cysts is highly variable and may depend on strain differences. Estimates of the average increase of cyst diameter vary, depending on the target organ and host dependent factors that are not completely studied, although historically a growth of around 1 cm/year has been reported.[13]

The clinical features of cystic echinococcosis are highly variable. The spectrum of symptoms depends on the following:

Epidemiology

Unfortunately, realistic national or international figures do not exist for total numbers of cases of CE. This is largely due to the undereporting of cases, due to the lack of official notification systems in many countries. Even countries that do have notification systems often do not collect data on CE.

When they have reported cases, uneven reporting occurred in different regions of countries. Moreover, the groups most at risk for CE are usually underserved by medical services.[10]  Recently, epidemiological studies carried out with ultrasound have clarified that the disease is severely underreported. Furthermore, the EuropeanRegistry for Cystic Echinococcosis (ERCE) has gathered a number of cases superior to those present in the ECDC reporting systems for a consistent number of years.[15, 16, 17]

United States

In the United States, transmission of E granulosus in the dog-sheep cycle is known to occur most frequently in several western states, including California, Arizona, New Mexico, and Utah. In Arizona and New Mexico, cystic echinococcosis is known to occur in American Indians belonging to the Zuni, Navajo, and Santo Domingo tribes, whose members live in close proximity to their animals, kill many of their own animals each year, and generally have limited knowledge concerning the life cycle and transmissibility of the parasite. In the United States, Utah has had the highest number of surgical cases of those states involved, with approximately 45 cases from 1944-1994.[18]

International

E granulosus is a cosmopolitan parasite, and endemic regions exist in each continent. Considerable public health problems occur in many areas, including countries of Central America and South America, Western and Southern/Southeastern Europe, the Middle East and North Africa, some sub-Saharan countries, Russia and adjacent countries, and China. Annual incidence rates of diagnosed human cases per 100,000 inhabitants vary widely, from less than 1 case per 100,000 to high levels. For example, rates in the indicated regions are as follows:

Greece - 13 cases per 100,000 persons

Rural regions of Uruguay - 75 cases per 100,000 persons

Rural regions of Argentina - 143 cases per 100,000 persons in Rio Negro province

Parts of Xinjiang province of China - 197 cases per 100,000 persons Parts of the Turkana district of Kenya - 220 cases per 100,000 persons

CE causes not only illness but also productivity losses in human and agricultural animal population, and it can have large societal impacts on endemic areas. Research is ongoing to evaluate the burden of disease, including nonmonetary costs.[18, 19]  

Prognosis

Prognosis generally is good but it depends on the cyst location. For instance, neither surgery nor medical therapy is generally effective for bone, especially spinal, CE. Surgery to treat cardiac cysts can be risky, and there is very little experience with the use of albendazole in this site.

Sometimes after removal of a cyst, one or more new cysts may develop at a different site. A hypothesis for this is that the growth of some cysts may be inhibited by the presence of the cyst that has been removed.

Patient Education

Patient education should include the followoing:

 

History

Months or years may pass before an individual exhibits any signs or symptoms of infection with the cystic larval stages.

During the natural course of infection, the fate of E granulosus cysts is variable. Some cysts may grow to a certain size and then persist without noticeable change for many years. Other cysts may rupture spontaneously or collapse and completely disappear.[20, 21, 22]

Spontaneous or traumatic cyst rupture and spillage of viable parasitic tissue during interventional procedures may result in secondary CE. Cysts may rupture into the peritoneal or pleural cavity, the pericardium, the bile ducts, the gastrointestinal tract, or even blood vessels, leading to extraordinary manifestations and severe complications.[23, 24]

Usually, cysts do not induce clinical symptoms before they have reached a size sufficient to exert pressure on adjacent organs. After a variable incubation period, infections may become symptomatic if cysts are growing and exerting pressure on adjacent tissue and inducing other pathologic findings.[25]  Sudden symptomatology usually is due to spontaneous or traumatic cyst rupture.

Physical

The presentation of human echinococcosis is protean.[25, 26, 27, 28]  Patients come to the clinician's attention for different reasons, such as when a large cyst has some mechanical effect on organ function or rupture of a cyst causes acute hypersensitivity reactions. The cyst may also be discovered accidentally during radiographic examination, body scanning, surgery, or for other clinical reasons.[14, 25]

Common chief symptoms are upper abdominal discomfort and pain, poor appetite, and a self-diagnosed mass in the abdomen. Physical findings are hepatomegaly, a palpable mass if on the surface of the liver or other organs, and abdominal distention. If cysts in the lung rupture into the bronchi, intense cough may develop, followed by vomiting of hydatid material and cystic membranes.[25, 26, 27, 28]

Liver findings may include the following[3, 12] :

Heart findings may include the following:

Complications

Several complications are possible depending on cyst size, location, and relation with other organs. Abdominal cysts may rupture, both spontaneously or as a consequence of percutaneous treatment or surgical intervention, although iatrogenic rupture is a rare instance.[34]  When an echinococcal cysts rupture, protoscoleces have the chance to spread in the peritoneum or pleura and cause secondary CE, whereas if the spread occurs in a blood vessel this can cause hematogenous spread of the disease (secondary CE) or thromboembolism. Rupture in the bronchi manifests with the presence of vomica (ie, the expulsion of cyst fragments with cough).[26, 27, 28, 34]

Approach Considerations

CE is mainly diagnosed through the use of imaging: ultrasound, MRI and CT-scan have been shown to be able to evidentiate the features of CE with decreasing specificity. Serology plays a largely ancillary role at present, and serological tests should be relied upon for their negative predictive value rather than for their ability to confirm a CE diagnosis. Both molecular techniques and antigen detection are not used in clinical practice currently. Laboratory studies are often aspecific, as eosinophilia may be present in complicated cysts but is not frequent in CE patients.

Liver CE: All patients with an abdominal cyst suspect for CE should undergo an ultrasound (US) to stage the cyst. If US expertise is not available at the managing center, referral to a physician with experience in the use of the WHO-IWGE classification of CE cysts is advised. If not possible, MRI with contrast enhancement is the radiological technique of choice. 

Abdominal CE: Patients with extra-hepatic cysts should be studied with radiological techniques including the use of contrast enhancement, preferably MRI if the US examination is inconclusive. 

Thoracic CE: Patients with a clinical suspicion of CE should at least umndergo a chest X-ray. CT scan is the most frequently used exam in these patients.

Other localizations US is the method of choice to image cysts when feasible. Otherwise, MRI is required if possible. 

Laboratory Studies

Generally, routine laboratory tests do not show specific results. In patients with rupture of the cyst in the biliary tree, marked and transient elevation of cholestatic enzyme levels occurs, often in association with hyperamylasemia and eosinophilia (up to 60%). In most cases, eosinophilia is limited (< 15%) or absent.

Depending on the test system used and other parameters, approximately 10% of patients with hepatic cysts and 40% with pulmonary cysts do not produce detectable serum IgG antibodies and exhibit false-negative results.

Cysts of the brain or eye and calcified cysts often induce no or low antibody titers.

Children aged 3-15 years may produce minimal serologic reactions.

No standard, highly sensitive, and specific serologic test exists for cystic echinococcosis antibody detection. In specialized laboratories, the arc 5 test or detection of cestode-specific antibodies can be used to exclude cross-reactions caused by noncestode parasites.

For liver cysts, seropositivity is a function of cyst viability, with early CE1 cysts sometimes being seronegative until nonsurgical treatments disrupt the integrity of the cyst (eg, endocyst detachment). Inactive cysts may be seropositive for reasons that are still unknown, generating confusion as to whether treatment is needed.

Other Tests

Endoscopic retrograde cholangiopancreatography may be indicated in patients with cholestatic jaundice. This technique may also be a therapeutic intervention when cysts communicating with the biliary tree can be basketed out.

Procedures

Fine-needle aspiration biopsy of the cyst performed under ultrasonographic guidance, by the transhepatic approach, and under anthelmintic coverage is generally safe and diagnostically useful for differentiation of cystic echinococcosis, malignancy, and abscesses.[35] It may be particularly helpful in cases with no detectable anti-Echinococcus serum antibodies and inconclusive imaging appearance. The hooks are usually numerous and can be found even in bacteriologically infected and/or degenerating cysts. Rostellar hooklets are seen in the image below.



View Image

Viable scolices (note rostellar hooklets).

Imaging Studies

Radiographic examination is useful for cysts in the lungs, bone, and muscle and for detecting calcified cysts.

Ultrasonography is the procedure of choice when making the diagnosis of asymptomatic cystic echinococcosis because it is safe, noninvasive, and relatively inexpensive. Ultrasonography is an imaging technique that uses the reflection of ultrasound waves emitted by a probe on the bodily organs to build images of the organs explored.

Any abnormality can be viewed using ultrasonography from an infinite number of angles and positions. Cysts in every part of the abdomen and in muscles can be imaged with ultrasonography.

Ultrasonography is useful in longitudinal studies, such as monitoring the response of cysts to treatment and recording cyst growth rate.[36]

Ultrasonography has also been used extensively in endemic areas for mass screening, often using portable machines that can work without an electrical distribution system by running on batteries or on a generator.

Many authors consider ultrasonographic mass surveys to be the best way to assess prevalence.

Various classifications exist of the ultrasonographic picture in cystic echinococcosis, the most widely used still being the one proposed by Gharbi in the early 1980s.[37] In 2003, the World Health Organization Informal Working Group on Echinococcosis (WHO-IWGE) proposed a standardized ultrasound classification based on the active-transitional-inactive status of the cyst as suggested by its sonographic appearance.[20]

The standardized classification scheme is intended to promote uniform standards of diagnosis and treatment and may be applied to the clinical treatment of patients as well as to field diagnostic surveys. This classification has important implications for clinical decision-making ad prognosis.[29, 21, 22]  CE1 and CE2 are active cysts containing viable protoscolices. CE3 has been subdivided into CE3a (detached endocyst) and CE3b (predominantly solid with daughter cysts). This subdivision is supported by a recent work that used high-field 1 H magnetic resonance spectroscopy to evaluate ex vivo the metabolic profiles of cyst contents.[23] Another paper has shown that, contrary to what was previously assumed, calcifications are not limited to CE5 cysts, but are present to a various extent in all cystic stages.[24]

Whatever the classification used, general consensus exists about the following:

CT scanning has the advantage of inspecting any organ (lungs cannot be explored with ultrasonography), detecting smaller cysts when located outside the liver, locating cysts precisely, and sometimes differentiating parasitic from nonparasitic cysts. Measurement of cyst density appears to be an additional tool to differentiate parasitic from nonparasitic cysts and for follow-up studies during chemotherapy. However, the cost of CT scanning is prohibitive in several endemic countries.

MRI may have some advantages over CT scanning in the evaluation of postsurgical residual lesions, recurrences, and selected extrahepatic infections, such as cardiac infections.[25] It is superior in identifying changes of the intrahepatic and extrahepatic venous system and in identifying cysto-biliary fistulas.[26]

A 2012 study found that MRI reproduces the ultrasound-defined features of CE better than CT. If ultrasonography cannot be performed owing to cyst location or patient-specific reasons, MRI with heavily T2-weighted series is preferable to CT.[27]

Approach Considerations

For liver cysts, a stage-specific approach should be taken, in which CE1 and CE3a cysts should be treated with either albendazole alone (if < 5 cm in diameter) or percutaneous treatment in association with medical therapy (if cysts are 5-10 cm in diameter). For cysts larger than 10 cm, continuous catheterization may be a viable option. Inactive uncomplicated cysts can be safely managed expectantly, especially if they became spontaneously inactive (ie, as opposed to treatment-induced inactivity).[28, 30, 31, 32, 33]

Medical Care

Two benzimidazolic drugs, mebendazole and albendazole, are the only anthelmintics effective against cystic echinococcosis. Albendazole and mebendazole are well tolerated but show different efficacy.

Albendazole is significantly more effective than mebendazole in the treatment of liver cysts. Benzimidazole treatment alone requires prolonged administration over many weeks, with an unpredictable outcome in terms of response rates in individuals.[34]

Treatment with albendazole in E granulosus infection can result in an apparent cure in as many as 30% of patients, with a further 40-50% of patients showing objective evidence of response when observed short term. Patients who do not show obvious initial evidence of response may be found to be cured when observed over several years.

Duration of therapy and doses are important. Albendazole efficacy increases with courses of up to 3 months in the more common cyst sites.

Patients once received these drugs in cycles of 4 weeks separated by 1-2 weeks without drugs. This regimen no longer is advocated given the parasitostatic activity of benzimidazoles and their safety as shown by cumulative data from several retrospective studies. Continuous treatment is preferred and has been administered for periods of up to 2 years without significant side effects.[29, 38]  The safety profile shows that liver function abnormalities are common, although they rarely limit treatment, while occasional hematologic changes affecting white cells may be more serious. The safety data supply the rationale for monitoring patients during treatment.

Overall, albendazole has been demonstrated to be a useful advance in the management of cystic echinococcosis when used as sole treatment or as an adjunct to surgery or other treatments.

Praziquantel has recently been suggested, administered additionally once per week in a dose of 40 mg/kg during treatment with albendazole. However, available data are limited.[39]

Radiation therapy

A 2013 case report described a patient with sternal CE that was successfully treated with radiation therapy after multiple surgical procedures and medical treatment had failed.[40] However, a recent editorial on the subject concluded that “in light of existing data, radiotherapy cannot be advocated as an alternative to surgery in osseous echinococcosis where complete excision of the affected bone is possible, and thus potentially curative. In fact, radiotherapy has to be regarded as contraindicated in such cases.”[41]

Surgical Care

Surgery was the only treatment available before the introduction of anthelmintic drugs. It is considered the first choice of treatment for echinococcosis but is associated with considerable mortality (up to 2% in some series, increasing with second and further operations), morbidity,[42] and recurrence rates (2-25%). Given the more frequent detection of early and asymptomatic E granulosus liver lesions, a widened indication for chemotherapy exists.

Several procedures have been described for the treatment of hepatic echinococcal cysts, ranging from simple puncture to liver resection and transplantation, although the most commonly used technique is total or partial cystopericystectomy.

Usually, radical surgery (total pericystectomy or partial hepatectomy) is indicated for liver cysts. Conservative surgery (open endocystectomy with or without omentoplasty) or palliative surgery (simple tube drainage of infected cysts or communicating cysts) is also an option. More radical interventions have higher intraoperative risks but less numerous relapses. With the inclusion of chemotherapy prior to or after surgery, less-aggressive surgery may be possible.

Surgery for pulmonary cysts includes extrusion of cysts using Barrett technique (intact endocystectomy without preliminary aspiration), pericystectomy, and lobectomy.[43]

Peripheral and unilobar echinococcal cysts, regardless of how complicated they are, can be treated with laparoscopic surgery using partial cystopericystectomy and drainage. When surgery cannot be avoided, presurgical use of albendazole reduces risk for recurrence and facilitates surgery by reducing intracystic pressure.

Surgery is the treatment of choice for spinal echinococcosis, with decompression of a compromised spinal cord and stabilization of a compromised spinal column being the two primary tasks. However, the existing data on follow-up of spinal CE cases is largely insufficient to judge the long-term outcome of surgery.[44]

Percutaneous treatment

Minimally invasive treatment is discussed below.

The puncture of echinococcal cysts has long been discouraged because of risks of anaphylactic shock and spillage of the fluid; however, as experience with ultrasonography-guided interventional techniques has increased since the early 1980s, an increasing number of articles have reported its effectiveness and safety in treating abdominal, especially liver, echinococcal cysts. A recent systematic review of the literature found that the overall fatality rate due to lethal anaphylaxis from puncture of echinococcal cysts is 0.03% (2 in 5943 procedures) for procedures and 0.04% (2 in 5517 cysts) for cysts, respectively.[35]

One study of 446 patients who were treated surgically for cystic echinococcosis (CE) found an increased incidence in anaphylatic shock in younger patients (P< 0.001) and in patients with pulmonary cysts. The authors suggest taking precautions such as reducing intracystic pressure, preventing antigen from contacting other tissues where it might trigger anaphylaxis, and resecting the cyst completely when feasible.[45]

Under albendazole coverage, cysts are punctured under ultrasonographic or CT guidance either with a needle or with a catheter according to their size. The presence of an anesthesiologist who intervenes in case of allergic manifestations or anaphylactic shock is mandatory. Usually, a small quantity of fluid is first aspirated and examined by light microscope to observe for the presence of viable protoscolices. If they are present, the cyst is aspirated completely.

At this point, exclude possible connections of the cyst with the biliary tree by means of injection of contrast medium in the cavity. If no connections are evident, a scolecoidal agent, usually hypertonic sodium chloride solution or ethanol, is injected and left for a variable period (usually 5-30 min) and then reaspirated. The destruction of protoscolices can be observed in fluid sample aspirated after the injection of a scolecoidal agent. This sequence is termed PAIR (puncture, aspiration, injection, reaspiration). As happens with drug therapy, positive responses include both a decrease in cyst size and a progressive change in echo pattern (generally solidification).[46, 47, 48]

From a diagnostic standpoint, PAIR is the only method that helps provide a direct diagnosis of the parasitic nature of the cysts. Neither imaging modalities nor serology is sufficient to exclude the diagnosis. PAIR is an effective alternative to chemotherapy alone because it has a higher efficacy and avoids the problem of drug resistance. It also shortens the time of treatment and final recovery. PAIR is a valuable alternative to surgery in terms of cost containment and hospitalization time.[49, 50, 51, 52, 53, 54] In types I and II (Gharbi classification), CE1 and CE3a (WHO-IWGE classification) echinococcal cysts with no or incomplete response to therapy, PAIR is an effective therapeutic tool in the management of human cystic echinococcosis.

Increasing evidence shows that CE2 cysts (multivesiculated, type I in Gharbi classification) and CE3b (predominantly solid with daughter vesicles)[29] tend to relapse after PAIR,[55] so other percutaneous treatments should be adopted, if indicated, for this type of cyst.

Reserve PAIR for use in highly specialized centers where teams are well prepared to deal with possible complications.

Some authors have treated CE2 and CE3b cysts with large-bore catheters, but studies on larger cohorts of patients are needed to conclude that this method is efficacious.[56, 57]

A 2017 retrospective study showed that percutaneous aspiration without injection of scolicidal agents but in combination with long-term albendazole administration is probably as effective as, simpler than, and safer than percutaneous treatments with injection of scolicidal agents.[58]

Consultations

Consult a surgeon to discuss the opportunity of surgical intervention.

Consult a radiologist for injection of contrast medium in the cyst after fluid aspiration if PAIR is scheduled. Contrast injection in the cyst allows the physician to exclude connections of the cyst with the biliary tree. Contact of scolecoidal agents, such as alcohol and hypertonic sodium chloride solution, with the biliary epithelium may lead to cholangitis. Attempts to inject albendazole directly into the cysts have yielded interesting results in animal studies but are still methodologically weak in human studies. Most recently, a glucose solution as a scolecoidal agent has been used with good results in vitro.[59] Studies in vivo should confirm the safety of this approach before it can be applied to humans.

Consult an anesthesiologist for assistance in case of anaphylactic shock or anaphylactoid reactions if PAIR is scheduled.

Prevention

In endemic areas, distribution of educational material in elementary schools regarding modes of transmission of the disease is helpful to increase knowledge about the nature and transmissibility of cystic echinococcosis.

Educational material should include information about proper disposal of sheep viscera in abattoirs and proximity to dogs and sources of transmission.

Further Outpatient Care

During treatment of patients discharged on benzimidazoles, monitor aminotransferases, WBC, RBC, and hemoglobin monthly.

Evaluate patients for ultrasonographic appearance modifications and changes in serology titers after 3 months of treatment and then for several years (at least 5).

Further Inpatient Care

Reevaluate patients for symptom resolution and determination of cure.

Medication Summary

Albendazole and mebendazole are the only anthelmintics effective against cystic echinococcosis. Albendazole is the drug of choice against this disease because its degree of systemic absorption and penetration into hydatid cysts is superior to that of mebendazole. Albendazole in combination with percutaneous aspiration or PAIR therapy can lead to a reduction in cyst size, and, in one study, it improved efficacy over albendazole alone against hepatic hydatid cysts.[49] When surgery cannot be avoided, presurgical use of albendazole in echinococcus infestations reduced risk of recurrence and/or facilitated surgery by reducing intracystic pressure.

Treatment of echinococcosis for patients weighing more than 60 kg is albendazole administered PO with meals in a dose of 400 mg twice daily for 28 days. A dose of 15 mg/kg of body weight daily in 2 divided doses (not to exceed total daily dose of 800 mg) has been suggested for patients weighing less than 60 kg. For cystic echinococcosis, the 28-day course may be repeated after 14 days without treatment to a total of 3 treatment cycles.

Albendazole (Albenza)

Clinical Context:  Decreases ATP production in worm, causing energy depletion, immobilization, and, finally, death. To avoid inflammatory response in CNS, patient must also take anticonvulsants and high-dose glucocorticoids.

Mebendazole (Vermox)

Clinical Context:  Causes worm death by selectively and irreversibly blocking uptake of glucose and other nutrients in susceptible adult intestine where helminths dwell.

Class Summary

Parasite biochemical pathways are sufficiently different from the human host to allow selective interference by chemotherapeutic agents in relatively small doses.

Author

Enrico Brunetti, MD, Associate Professor, Department of Infectious Diseases, Division of Infectious and Tropical Diseases, University of Pavia, Italy; Staff Physician, Department of Infectious Diseases, IRCCS S Matteo Hospital Foundation, Pavia, Italy

Disclosure: Nothing to disclose.

Coauthor(s)

Tommaso Manciulli, MD, PhD, Research Fellow, Department of Clinical, Surgical, Diagnostics and Paediatric Sciences, University of Pavia, Italy

Disclosure: Nothing to disclose.

Specialty Editors

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

Disclosure: Received salary from Medscape for employment. for: Medscape.

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

Disclosure: Nothing to disclose.

Chief Editor

Pranatharthi Haran Chandrasekar, MBBS, MD, Professor, Chief of Infectious Disease, Department of Internal Medicine, Wayne State University School of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Carlo Filice, MD, Chief of Ultrasound Unit, Adjunct Professor, Department of Internal Medicine, Division of Infectious and Tropical Diseases, IRCCS S Matteo Hospital, University of Pavia, Italy

Disclosure: Nothing to disclose.

Mark R Wallace, MD, FACP, FIDSA, Infectious Disease Physician, Skagit Valley Hospital, Skagit Regional Health

Disclosure: Nothing to disclose.

References

  1. Almulhim AM, John S. Echinococcus Granulosus. StatPearls. 2023 Jan. [View Abstract]
  2. Huzaifa M, Sharman T. Ecchinococcus. StatPearls. 2023 Jan. [View Abstract]
  3. Bhalla VP, Paul S, Klar E. Hydatid Disease of the Liver. Visc Med. 2023 Oct. 39 (5):112-120. [View Abstract]
  4. Weber TF, Junghanss T, Stojković M. Pulmonary cystic echinococcosis. Curr Opin Infect Dis. 2023 Oct 1. 36 (5):318-325. [View Abstract]
  5. Buscemi C, Randazzo C, Buscemi P, Caldarella R, Lombardo M, Buscemi S. Very Prolonged Treatment with Albendazole of a Case of Disseminated Abdominal Cystic Echinococcosis. Trop Med Infect Dis. 2023 Sep 15. 8 (9):[View Abstract]
  6. Larrieu E, Del Carpio M, Mercapide CH, et al. Programme for ultrasound diagnoses and treatment with albendazole of cystic echinococcosis in asymptomatic carriers: 10 years of follow-up of cases. Acta Trop. 2011 Jan. 117(1):1-5. [View Abstract]
  7. Bouraoui H, Trimeche B, Mahdhaoui A, et al. Echinococcosis of the heart: clinical and echocardiographic features in 12 patients. Acta Cardiol. 2005 Feb. 60(1):39-41. [View Abstract]
  8. Biyik I, Acar S, Ergene O. Left atrial mobile hydatid cyst mimicking left atrial myxoma and mitral stenosis and causing heart failure and arrhythmia. Int J Cardiovasc Imaging. 2007 Apr. 23(2):193-5. [View Abstract]
  9. Tsaroucha AK, Polychronidis AC, Laftsidis PA, Pitiakoudis MS, Fotakis SN, Simopoulos CE. Primary adrenal hydatid cyst: a case report. Acta Chir Iugosl. 2007. 54(2):115-7. [View Abstract]
  10. Tutar N, Cakir B, Geyik E, Tarhan NC, Niron EA. Hydatid cysts in breast: mammography and ultrasound findings. Br J Radiol. 2006 Oct. 79(946):e114-6. [View Abstract]
  11. Aydin Y, Ogul H, Eren S. Hydatid cyst in multiple locations. Br J Hosp Med (Lond). 2023 May 2. 84 (5):1. [View Abstract]
  12. Berto CG, Liou P, Coyle CM, Emond JC. Surgical management of cystic echinococcosis of the liver. Curr Opin Infect Dis. 2023 Oct 1. 36 (5):348-352. [View Abstract]
  13. Türkmen C, Unal SN, Berberoglu K, Genchellac H, Unal Z, Cantez S. Acute pulmonary embolism due to hydatid cyst. Clin Nucl Med. 2004 Nov. 29(11):760-1. [View Abstract]
  14. Yuksel BC, Ozel H, Akin T, Avsar FM, Hengirmen S. Primary hydatid cyst of the breast with elevated CA 19-9 level. Am J Trop Med Hyg. 2005 Aug. 73(2):368-70. [View Abstract]
  15. Pamir MN, Ozduman K, Elmaci I. Spinal hydatid disease. Spinal Cord. 2002 Apr. 40(4):153-60. [View Abstract]
  16. Bulman W, Coyle CM, Brentjens TE, et al. Severe pulmonary hypertension due to chronic echinococcal pulmonary emboli treated with targeted pulmonary vascular therapy and hepatic resection. Chest. 2007 Oct. 132(4):1356-8. [View Abstract]
  17. Bron JL, van Kemenade FJ, Verhoof OJ, Wuisman PI. Long term follow-up of a patient with disseminated spinal hydatidosis. Acta Orthop Belg. 2007 Oct. 73(5):678-82. [View Abstract]
  18. Nagpal V, Kohli K, Chowdhary A, Kumar A, Andley M, Ravi B. Breast lump as a presentation of a hydatid disease. Trop Doct. 2006 Jan. 36(1):57-8. [View Abstract]
  19. Santivanez S, Garcia HH. Pulmonary cystic echinococcosis. Curr Opin Pulm Med. 2010 May. 16(3):257-61. [View Abstract]
  20. WHO Informal Working Group. International classification of ultrasound images in cystic echinococcosis for application in clinical and field epidemiological settings. Acta Trop. 2003 Feb. 85(2):253-61. [View Abstract]
  21. Junghanss T, da Silva AM, Horton J, Chiodini PL, Brunetti E. Clinical management of cystic echinococcosis: state of the art, problems, and perspectives. Am J Trop Med Hyg. 2008 Sep. 79(3):301-11. [View Abstract]
  22. Brunetti E, Junghanss T. Update on cystic hydatid disease. Curr Opin Infect Dis. 2009 Oct. 22(5):497-502. [View Abstract]
  23. Hosch W, Junghanss T, Stojkovic M, et al. Metabolic viability assessment of cystic echinococcosis using high-field 1H MRS of cyst contents. NMR Biomed. 2008 Aug. 21(7):734-54. [View Abstract]
  24. Hosch W, Stojkovic M, Janisch T, Kauffmann GW, Junghanss T. The role of calcification for staging cystic echinococcosis (CE). Eur Radiol. 2007 Oct. 17(10):2538-45. [View Abstract]
  25. Dursun M, Terzibasioglu E, Yilmaz R, et al. Cardiac hydatid disease: CT and MRI findings. AJR Am J Roentgenol. 2008 Jan. 190(1):226-32. [View Abstract]
  26. Hosch W, Stojkovic M, Janisch T, et al. MR imaging for diagnosing cysto-biliary fistulas in cystic echinococcosis. Eur J Radiol. 2008 May. 66(2):262-7. [View Abstract]
  27. Stojkovic M, Rosenberger K, Kauczor HU, Junghanss T, Hosch W. Diagnosing and staging of cystic echinococcosis: how do CT and MRI perform in comparison to ultrasound?. PLoS Negl Trop Dis. 2012. 6(10):e1880. [View Abstract]
  28. Stojkovic M, Rosenberger KD, Steudle F, Junghanss T. Watch and Wait Management of Inactive Cystic Echinococcosis - Does the Path to Inactivity Matter - Analysis of a Prospective Patient Cohort. PLoS Negl Trop Dis. 2016 Feb 24. [View Abstract]
  29. [Guideline] Brunetti E, Kern P, Vuitton DA,. Expert consensus for the diagnosis and treatment of cystic and alveolar echinococcosis in humans. Acta Trop. 2010 Apr. 114(1):1-16. [View Abstract]
  30. Piccoli L, Tamarozzi F, Cattaneo F, Mariconti M, Filice C, Bruno A, et al. Long-term sonographic and serological follow-up of inactive echinococcal cysts of the liver: hints for a "watch-and-wait" approach. PLoS Negl Trop Dis. 2014 Aug. 8 (8):e3057. [View Abstract]
  31. Lissandrin R, Tamarozzi F, Mariconti M, Manciulli T, Brunetti E, Vola A. Watch and Wait Approach for Inactive Echinococcal Cyst of the Liver: An Update. Am J Trop Med Hyg. 2018 Aug. 99 (2):375-379. [View Abstract]
  32. Saidi F, Habibzadeh F. The Non-operative Management of Asymptomatic Liver Hydatids: Ending Echinococcophobia. J Gastrointest Surg. 2018 Mar. 22 (3):486-495. [View Abstract]
  33. Larrieu E, Uchiumi L, Salvitti JC, Sobrino M, Panomarenko O, Tissot H, et al. Epidemiology, diagnosis, treatment and follow-up of cystic echinococcosis in asymptomatic carriers. Trans R Soc Trop Med Hyg. 2018 Nov 9. [View Abstract]
  34. Stojkovic M, Zwahlen M, Teggi A, et al. Treatment response of cystic echinococcosis to benzimidazoles: a systematic review. PLoS Negl Trop Dis. 2009 Sep 29. 3(9):e524. [View Abstract]
  35. Neumayr A, Troia G, de Bernardis C, et al. Justified concern or exaggerated fear: the risk of anaphylaxis in percutaneous treatment of cystic echinococcosis-a systematic literature review. PLoS Negl Trop Dis. 2011 Jun. 5(6):e1154. [View Abstract]
  36. Macpherson CN, Bartholomot B, Frider B. Application of ultrasound in diagnosis, treatment, epidemiology, public health and control of Echinococcus granulosus and E. multilocularis. Parasitology. 2003. 127 Suppl:S21-35. [View Abstract]
  37. Gharbi HA, Hassine W, Brauner MW, Dupuch K. Ultrasound examination of the hydatic liver. Radiology. 1981 May. 139(2):459-63. [View Abstract]
  38. Liu Y, Wang X, Wu J. Continuous long-term albendazole therapy in intraabdominal cystic echinococcosis. Chin Med J (Engl). 2000 Sep. 113(9):827-32. [View Abstract]
  39. Bygott JM, Chiodini PL. Praziquantel: neglected drug? Ineffective treatment? Or therapeutic choice in cystic hydatid disease?. Acta Trop. 2009 Aug. 111(2):95-101. [View Abstract]
  40. Ulger S, Barut H, Tunc M, Aydin E, Aydinkarahaliloglu E, Gokcek A. Radiation therapy for resistant sternal hydatid disease. Strahlenther Onkol. 2013 Jun. 189(6):508-509. [View Abstract]
  41. Neumayr A. Radiotherapy of osseous echinococcosis: where is the evidence?. Int J Infect Dis. 2015 Jan 10. 33:75-78. [View Abstract]
  42. El Malki HO, El Mejdoubi Y, Souadka A, et al. Predictive factors of deep abdominal complications after operation for hydatid cyst of the liver: 15 years of experience with 672 patients. J Am Coll Surg. 2008 Apr. 206(4):629-37. [View Abstract]
  43. Bagheri R, Haghi SZ, Amini M, Fattahi AS, Noorshafiee S. Pulmonary hydatid cyst: analysis of 1024 cases. Gen Thorac Cardiovasc Surg. 2011 Feb. 59(2):105-9. [View Abstract]
  44. Neumayr A, Tamarozzi F, Goblirsch S, Blum J, Brunetti E. Spinal cystic echinococcosis--a systematic analysis and review of the literature: part 2. Treatment, follow-up and outcome. PLoS Negl Trop Dis. 2013. 7(9):e2458. [View Abstract]
  45. Li Y, Zheng H, Cao X, Liu Z, Chen L. Demographic and clinical characteristics of patients with anaphylactic shock after surgery for cystic echinococcosis. Am J Trop Med Hyg. 2011 Sep. 85(3):452-5. [View Abstract]
  46. Filice C, Pirola F, Brunetti E, Dughetti S, Strosselli M, Foglieni CS. A new therapeutic approach for hydatid liver cysts. Aspiration and alcohol injection under sonographic guidance. Gastroenterology. 1990 May. 98(5 Pt 1):1366-8. [View Abstract]
  47. Paksoy Y, Odev K, Sahin M, Arslan A, Koç O. Percutaneous treatment of liver hydatid cysts: comparison of direct injection of albendazole and hypertonic saline solution. AJR Am J Roentgenol. 2005 Sep. 185(3):727-34. [View Abstract]
  48. Paksoy Y, Odev K, Sahin M, Dik B, Ergül R, Arslan A. Percutaneous sonographically guided treatment of hydatid cysts in sheep: direct injection of mebendazole and albendazole. J Ultrasound Med. 2003 Aug. 22(8):797-803. [View Abstract]
  49. Smego RA Jr, Bhatti S, Khaliq AA, Beg MA. Percutaneous aspiration-injection-reaspiration drainage plus albendazole or mebendazole for hepatic cystic echinococcosis: a meta-analysis. Clin Infect Dis. 2003 Oct 15. 37(8):1073-83. [View Abstract]
  50. Kabaalioglu A, Ceken K, Alimoglu E, Apaydin A. Percutaneous imaging-guided treatment of hydatid liver cysts: do long-term results make it a first choice?. Eur J Radiol. 2006 Jul. 59(1):65-73. [View Abstract]
  51. Khuroo MS, Wani NA, Javid G, et al. Percutaneous drainage compared with surgery for hepatic hydatid cysts. N Engl J Med. 1997 Sep 25. 337(13):881-7. [View Abstract]
  52. Men S, Yucesoy C, Edguer TR, Hekimoglu B. Percutaneous treatment of giant abdominal hydatid cysts: long-term results. Surg Endosc. 2006 Oct. 20(10):1600-6. [View Abstract]
  53. Schipper HG, Laméris JS, van Delden OM, Rauws EA, Kager PA. Percutaneous evacuation (PEVAC) of multivesicular echinococcal cysts with or without cystobiliary fistulas which contain non-drainable material: first results of a modified PAIR method. Gut. 2002 May. 50(5):718-23. [View Abstract]
  54. Ustunsoz B, Ugurel MS, Uzar AI, Duru NK. Percutaneous treatment of hepatic hydatid cyst in pregnancy: long-term results. Arch Gynecol Obstet. 2008 Jun. 277(6):547-50. [View Abstract]
  55. Golemanov B, Grigorov N, Mitova R, et al. Efficacy and safety of PAIR for cystic echinococcosis: experience on a large series of patients from Bulgaria. Am J Trop Med Hyg. 2011 Jan. 84(1):48-51. [View Abstract]
  56. Mohan S, Garg SK, Kathuria M, Baijal SS. Mechanical suction through wide bore catheters for nonsurgical management of Gharbi type III hepatic hydatid cysts. Trop Gastroenterol. 2011 Jul-Sep. 32(3):189-95. [View Abstract]
  57. Yasawy MI, Mohammed AE, Bassam S, Karawi MA, Shariq S. Percutaneous aspiration and drainage with adjuvant medical therapy for treatment of hepatic hydatid cysts. World J Gastroenterol. 2011 Feb 7. 17(5):646-50. [View Abstract]
  58. Firpo G, Vola A, Lissandrin R, Tamarozzi F, Brunetti E. Preliminary Evaluation of Percutaneous Treatment of Echinococcal Cysts without Injection of Scolicidal Agent. Am J Trop Med Hyg. 2017 Dec. 97 (6):1818-1826. [View Abstract]
  59. Hosseini SV, Ghanbarzadeh K, Barzin J, Sadjjadi SM, Tanideh N, Mehrabani D. In vitro protoscolicidal effects of hypertonic glucose on protoscolices of hydatid cyst. Korean J Parasitol. 2006 Sep. 44(3):239-42. [View Abstract]
  60. Brunetti E, Filice C, Meroni V. Comment on percutaneous treatment of liver hydatid cysts. AJR Am J Roentgenol. 2006 Apr. 186(4):1198-9; author reply 1199-200. [View Abstract]
  61. Brunetti E, Gulizia R, Garlaschelli AL, Filice C. Cystic echinococcosis of the liver associated with repeated international travels to endemic areas. J Travel Med. 2005 Jul-Aug. 12(4):225-8. [View Abstract]
  62. Budke CM. Global socioeconomic impact of cystic echinococcosis. Emerg Infect Dis. 2006 Feb. 12(2):296-303. [View Abstract]
  63. Craig PS, McManus DP, Lightowlers MW, Chabalgoity JA, Garcia HH, Gavidia CM. Prevention and control of cystic echinococcosis. Lancet Infect Dis. 2007 Jun. 7(6):385-94. [View Abstract]
  64. Cunha BA. Antibiotic Essentials. Royal Oak, Mich: Physicians Press; 2005.
  65. Eckert J, Deplazes P. Biological, epidemiological, and clinical aspects of echinococcosis, a zoonosis of increasing concern. Clin Microbiol Rev. 2004 Jan. 17(1):107-35. [View Abstract]
  66. Franchi C, Di Vico B, Teggi A. Long-term evaluation of patients with hydatidosis treated with benzimidazole carbamates. Clin Infect Dis. 1999 Aug. 29(2):304-9. [View Abstract]
  67. Kilic M, Yoldas O, Koc M, et al. Can biliary-cyst communication be predicted before surgery for hepatic hydatid disease: does size matter?. Am J Surg. 2008 Nov. 196(5):732-5. [View Abstract]
  68. Macpherson CN, Milner R. Performance characteristics and quality control of community based ultrasound surveys for cystic and alveolar echinococcosis. Acta Trop. 2003 Feb. 85(2):203-9. [View Abstract]
  69. Magistrelli P, Masetti R, Coppola R, Messia A, Nuzzo G, Picciocchi A. Surgical treatment of hydatid disease of the liver. A 20-year experience. Arch Surg. 1991 Apr. 126(4):518-22; discussion 523. [View Abstract]
  70. McManus DP, Zhang W, Li J, Bartley PB. Echinococcosis. Lancet. 2003 Oct 18. 362(9392):1295-304. [View Abstract]
  71. Nasseri-Moghaddam S, Abrishami A, Taefi A, Malekzadeh R. Percutaneous needle aspiration, injection, and re-aspiration with or without benzimidazole coverage for uncomplicated hepatic hydatid cysts. Cochrane Database Syst Rev. 2011. (1):CD003623. [View Abstract]
  72. Rogan MT, Hai WY, Richardson R, Zeyhle E, Craig PS. Hydatid cysts: does every picture tell a story?. Trends Parasitol. 2006 Sep. 22(9):431-8. [View Abstract]
  73. Sayek I, Tirnaksiz MB, Dogan R. Cystic hydatid disease: current trends in diagnosis and management. Surg Today. 2004. 34(12):987-96. [View Abstract]
  74. Men S, Yücesoy C, Edgüer TR, Hekimoğlu B. Percutaneous treatment of giant abdominal hydatid cysts: long-term results. Surg Endosc. 2006 Oct. 20 (10):1600-6. [View Abstract]

Viable scolices (note rostellar hooklets).

WHO Informal Working Group on Echinococcosis standardized ultrasound classification of echinococcal cysts. Image courtesy of World Health Organization (WHO).

CE1 cyst in the right segments of the liver in a young Albanian boy

CE3a echinococcal cyst of the liver. Note the folding endocyst ("waterlily sign") typical of CE3a cysts.

CE3b cyst in the right lobe of the liver. The cyst is predominantly solid with a few daughter cysts

CE4 cyst in the liver. The cyst is completely solid and inactive.

CE3b cyst in the muscles of posterior thigh (scanned with a convex ultrasound probe).

CE4 cysts in the peritoneum in a patient with disseminated echinococcosis (longitudinal scan).

Viable scolices (note rostellar hooklets).

CT scan of peritoneal, disseminated echinococcosis

MR scan of echinococcal cyst in the right psoas muscle, infiltrating the adjacent vertebral body

Ultrasound scan of a CE3b subcutaneous cyst located in the lumbar area. The cyst was the subcutaneous extension of a cyst located in the spine that had been previously operated on.

MR of the spine showing CE involvement of CE3,CE4,CE5 vertebral bodies, spinous processes and subcutaneous tissue (same patient as # )

CT scan showing CE infiltration of vertebral bodies and destruction of left peduncles