Pediatric Echinococcosis

Echinococcosis is the general term used to describe four disease forms caused by the larval stage of Echinococcus tapeworms, the smallest tapeworms in the Taeniidae family. Human echinococcosis is a zoonotic disease that occurs in four clinically well-described forms:

• Cystic echinococcosis, also called hydatid disease or hydatidosis, is caused by infection with Echinococcus granulosus (E. granulosus).

• Alveolar echinococcosis, also called alveolar hydatid echinococcosis is caused by infection with E. multilocularis.

• Polycystic echinococcosis is caused by infection with E. vogeli.

• Unicystic echinococcosis is caused by infection with E. oligarthrus.

Cystic echinococcosis (CE) and alveolar echinococcosis (AE) are the key forms of echinococcosis that are of significant medical and public health concerns for humans.[1]  These disease processes will be the focus of this article.

Cystic echinococcosis (CE) is caused by infection with the larvae of E granulosus. CE is found worldwide and on every continent except Antarctica. Areas of the world with noted prevalence are rural regions of Africa, southern Europe, Asia, the Middle East, Central and South America (especially the countries of Argentina and Uruguay). Cases are rare in North America. The parasite is transmitted to dogs when they eat organs of other animals that contain hydatid cysts. Once ingested by canines, these cysts develop into adult tapeworms. Infected dogs shed tapeworm eggs in their feces, which contaminate the ground. Sheep, cattle, goats, and pigs ingest the E granulosus eggs in the contaminated soil. Once eaten, the eggs hatch and develop into cysts in the animal’s internal organs.[2]  CE is principally maintained in a dog–sheep–dog cycle; however, other domestic animals may be involved, including goats, swine, horses, cattle, camels and yaks.[1]

The most common mode of transmission of E granulosus to humans is via the accidental ingestion of soil, water, or food contaminated by fecal matter from an infected dog. Echinococcus eggs deposited in soil can remain viable for a year. The disease is most commonly found in people who raise sheep, due to the sheep's role as the parasite’s intermediate host and the lives of working dogs that are allowed to eat the offal of infected sheep.[2]

Alveolar echinococcosis (AE) is caused by infection with E multilocularis larvae. AE is found worldwide and is especially prevalent in the northern latitudes of Europe, Asia (China and Russia), and North America.[2] The adult tapeworm is found in foxes, coyotes, and dogs. Infection with the larval stages is transmitted to people through ingestion of food or water contaminated with tapeworm eggs.[2]  AE is typically maintained within a wildlife cycle between foxes, other carnivores and small mammals (mostly rodents); however, domesticated dogs and cats can also be infected.[1]

The Echinococcus tapeworm's life cycle (see image below) involves a definitive host, usually a dog (although foxes and coyotes have also been implicated), and intermediate hosts such as sheep, goats, and swine. The 3-mm to 6-mm adult tapeworm is found in the definitive host's intestines. Eggs are excreted via the feces into the environment. Dogs typically become infected by eating the remains of infected sheep and other livestock.

Diagram of the Echinococcus life cycle, provided by the Centers for Disease Control and Prevention.

Humans are accidental intermediate hosts and are not typically involved in the life cycle of the organism. Infected humans are not contagious to others. Humans become infected through accidental exposure to canine feces. Humans can also become infected by eating food contaminated with tapeworm eggs, which hatch in human small intestine under the influence of gastric and intestinal secretions. Larvae hatched from these eggs can penetrate the small intestine and become widely distributed in the human body. These larvae, then, develop into hydatid cysts. Human disease is usually caused by the mass effect of slow-growing hydatid cysts, although bacterial secondary infection and/or anaphylaxis due to cyst rupture have also been reported.

Hydatid cysts may contain many protoscolices, each with the ability to develop into an adult tapeworm in a definitive host. The definitive host usually becomes infected by ingesting the protoscolices in hydatid cysts from the intermediate host; adult tapeworms only develop in the intestines of the definitive host.

Cystic echinococcosis (CE), also known as hydatid disease, is caused by infection with the larval stage of E granulosus, a ~2-7 millimeter long tapeworm found in dogs (definitive host) and sheep, cattle, goats, and pigs (intermediate hosts). Most infections in humans are asymptomatic; infected humans may remain symptom-free for 20 years.

CE is characterized by harmful, slowly enlarging cysts that grow in the liver, lungs, and other organs, often for years going unnoticed and neglected.[2] Less frequently, cysts develop in the bones, kidneys, spleen, muscles, CNS and eyes.[1] In CE, the liver is involved in two-thirds of cases; in the remaining one-third of cases, other sites of involvement, in descending order of frequency, are the lung, spleen, skin, muscle, kidney, retroperitoneum, bone, heart, and brain. Compared with adults who have CE, children are more likely to present with multiple cysts and multiple organ involvement, particularly in the lungs.[3, 4]

Alveolar echinococcosis (AE) disease is caused by infection with the larval stage of E multilocularis, a ~1-4 millimeter long tapeworm found in foxes, coyotes, and dogs (definitive hosts). Small rodents are intermediate hosts for E. multilocularis. Although cases of AE in animals in endemic areas are relatively common, human cases are rare. Parasitic tumors can form in the liver (primary location), lungs, brain, and other organs. If left untreated, AE can be fatal.[1, 2]

United States data

Echinococcosis is rare. Indigenous cases have been reported in Minnesota and among Native Americans in western Alaska. Imported cases are uncommon.[5]

International data

Human infection rates are generally highest in areas that practice poor sanitation methods for sheep raising, particularly in common areas with dogs. Dogs in these areas may become infected by eating the entrails of infected butchered sheep or other herded animals. Humans then become accidentally infected when they ingest Echinococcus eggs via soil, water, or food contaminated by fecal matter from an infected dog. Human infection rates are also high in areas where intestines are ingested as part of the diet.

Echinococcosis has been reported in Manitoba and Saskatchewan, Canada.[6] Outside North America, incidence rates vary considerably, from less than 1 case per 100,000 people in many parts of the world, to 13 cases per 100,000 people in Greece, 143 cases per 100,000 people in Argentina, 197 cases per 100,000 people in the Xinjiang province of China, and 220 cases per 100,000 people in Kenya's Turkana District. Echinococcosis is endemic in sub-Saharan Africa.[7] Of those cases occurring in Europe, one-half of the cases occur in France.[8]

The high incidence rate reported in the Turkana District of Kenya is attributed to cultural practices. For tribe members who eat canine intestine, disease transmission likely occurs when infected intestine is not thoroughly cooked. In tribes communities who do not bury their dead; carnivores may become the direct intermediate host after eating human remains.

A new swine Echinococcus tapeworm, E canadensis G7, appears to be present in Austria,[8] where human echinococcosis cases are becoming more common.[9]

Morbidity/mortality

Most human infection is asymptomatic. Death may occur from hydatid rupture, which can cause anaphylactic shock and/or lead to bacterial infection. The mass effect of slow-growing hydatid cysts into the tissue space of vital organs can also be fatal.

Sex- and age-related demographics

Males and females are equally affected.[10]

Most patients infected by E granulosus (CE) are 21-50 years of age. Patients infected by E multilocularis (AE) are typically older, 31-80 years of age.

Patients with echinococcosis often remain asymptomatic for many years. This asymptomatic incubation period can last many years until hydatid cysts grow to a size that triggers clinical signs. For CE, 20 years has been the reported time frame for asymptomatic incubation. For AE, 5 to 15 years is cited.

Routine imaging may incidentally reveal echinococcosis’ hydatid cysts.

Echinococcosis can present as non-specific clinical signs such as anorexia, weight loss and weakness. Other clinical indicators depend on the location of the hydatid(s) and the pressure they exert on the surrounding tissues.[1]

Hepatic involvement causes abdominal pain, anorexia, nausea and vomiting. An abdominal mass may be palpated and/or biliary obstruction can occur. Patients with pulmonary involvement may have respiratory symptoms such as chronic cough, chest pain and shortness of breath. The bodily locations of hydatid cysts determines the presence of other symptoms. Clinical manifestations occur very early in nervous system infection.[11, 1]  In bone infections, necrosis may occur and produce thin and fragile bones, that can serve as nidi for spontaneous fracture. Secondary bacterial infections may occur due to pyogenic abscess formation within the cyst. Cyst leakage or rupture may cause an allergic response, such as urticaria.  

• Anaphylaxis

• Fever

• Asthma

• Acute Urticaria

AE is characterized by the slow development of a primary tumor-like lesion usually located in the liver. This lesion can resemble a hepatic neoplasm, with local destruction, to hepatic tissue and cause biliary obstruction. Clinical signs include weight loss, abdominal pain, general malaise and clinical indicators of hepatic failure. Larval metastases may spread either to organs adjacent to the liver (eg, the spleen) or to more distant organ locations, such as the brain and lungs. Spread of the parasite occurs via the circulatory and lymphatic systems. If left untreated, AE is progressive and fatal.[1]

Ultrasonography, chest radiography, CT scans, or MRI are imaging modalities that can detect findings suggestive of echinococcosis, especially in those patients with reported epidemiological risk factors. Serologic tests are then used to help confirm the diagnosis. If radiologic studies and epidemiology suggest echinococcosis, consider further evaluation when serology test results are negative.

The Centers for Disease Control and Prevention in Atlanta, Georgia provides the following types of serologic testing for humans:[12]

• Indirect hemagglutination

• Indirect fluorescent antibody

• Enzyme immunoassay/enzyme-linked immunosorbent assay

Test sensitivities range from 60-95%. Liver cysts are more likely to yield positive serologic test results than pulmonary cysts. Positive test results are less likely with calcified or dead cysts and more likely with ruptured cysts.

False-positive serologic test results may occur in patients with other parasitic infections (e.g. cysticercosis) and in patients diagnosed with cancer or with immune dysfunction.

Antigen testing may be helpful if antibody test results are negative, although this modality is not available in the United States.

Stool evaluation for ova and parasites is generally not useful for diagnosis, but a loop-mediated isothermal amplification method (LAMP) for E. granulosus coprodetection in canines has been described.[13]

Ultrasonography is the imaging study of choice to diagnosis CE and AE. It is a noninvasive diagnostic tool and can ascertain hydatid cyst size. Ultrasonography may reveal irregular, heterogeneous, hypoechoic lesions, and calcified cysts. Ultrasonographic positive findings are then complemented or confirmed with computed tomography (CT) and/or magnetic resonance imaging (MRI). Liver cysts are commonly located in the hepatic right lobe and can be difficult to differentiate from abscesses or neoplasms. Liver cysts may be single or multiple.

Chest radiography may reveal cysts in the pulmonary fields, ranging from 1-20 cm in size. Pulmonary cysts do not calcify and they do not produce daughter cysts. Approximately one-third of patients with a positive finding on chest radiography, have definable hepatic cysts.

Four treatment approaches are utilized to treat cystic echinococcosis (CE):

• Anti-infective drug treatment

• Surgery

• Percutaneous treatment of the hydatid cysts with the PAIR ( P uncture, A spiration, I njection, Re-aspiration) technique
• “Watch and wait”

The treatment approach used is based on the ultrasonographic images of the cyst (along with other imaging studies, if obtained), clinical assessment taking a  stage-specific approach, and health care awareness of available medical infrastructure and human resources.

Preoperative and postoperative albendazole therapy may benefit patients with echinococcosis. As an alternative to surgical management, a randomized controlled study of albendazole in uncomplicated hepatic hydatid disease in adults concluded that 10 mg/kg/d for 3 months without rest periods was effective and could be tried before surgical intervention. In children, the recommended dose is 15 mg/kg/d for 28 days and is repeated, as necessary.

Early diagnosis and radical (tumor-like) surgery followed by anti-infective prophylaxis with albendazole are key treatment approaches for alveolar echinococcosis (AE). If the lesion is confined, radical surgery offers cure. Unfortunately for many patients, the disease is diagnosed at an advanced stage and is not locally confined. Palliative surgery, either with or without prescribed anti-infective treatment, frequently results in disease relapse.[1] The World Health Organization (WHO) recommends postoperative chemotherapy for 2.5 years after radical surgery for treatment of AE.

Inoperable cases can be treated with albendazole or mebendazole.[14] An overall response rate of 55-79% has been documented, with cure in 29% of cases. Albendazole is the drug of choice because of its greater absorption from the GI tract to achieve higher plasma levels. Mebendazole is poorly absorbed and must be taken at higher doses for several months to attain a therapeutic effect. Albendazole is administered in 3 or more cycles of 400-800 mg twice daily for 4 weeks (adult dose), followed by a 2-week period of rest. If response after 3 cycles of albendazole is not evident, subsequent courses are not likely to be beneficial.

Response to anti-infective therapy is best monitored by serial imaging studies. Another treatment option for disseminated AE disease that fails to respond to standard treatment regimens is nitazoxanide with albendazole (with or without praziquantel) for salvage therapy.[15]

Surgery is the treatment of choice for most cases of CE and is usually successful. AE is less amenable to surgery.

Hepatic surgery options include the following:

• Partial hepatic resection

• Pericystectomy

• Cystectomy

In 20% of CE cases, disease recurs despite surgical intervention.

In the past, surgery was the only treatment for removal of echinococcal cysts. Some clinicians have inactivated the fertile cyst with formalin or 30% saline in combination with surgical resection. A potential complication of this procedure is sclerosing cholangitis.

Alternative methods, such as chemotherapy, cyst puncture, and the PAIR (Puncture, Aspiration, Injection, Re-aspiration) method, are effective treatments for CE. The PAIR method (i.e., puncture the cyst, aspirate fluid, introduce a protoscolicidal agent, then reaspirate) requires concurrent ultrasonographic guidance.[15] Extreme care is essential to prevent spilling hydatid fluid into a body cavity because this may lead to anaphylactic shock. Albendazole therapy may be combined with PAIR from 10 days before to 30 days after the procedure. PAIR is a promising technique, and early large-scale clinical trials have been reassuring.[16]

Surgery remains the most effective treatment approach for hydatid cyst removal and hence, ultimate cure. Some cysts do not cause symptoms and are diagnosed as inactive; these cysts often self-resolve without treatment; hence the “watch and wait” approach.[2]

For hepatic AE, another treatment modality is pericyst radiofrequency ablation.[17] Overall, the treatment of AE is more difficult than for CE and usually requires radical surgery, long-term chemotherapy, or both. Severe cases of AE have led to liver transplantation.[2]

Recommended consultations for patients with echinococcosis include surgeons, infectious diseases specialists, and radiologists with knowledge strength in ultrasonography who have experience in diagnosis and treatment of this parasitic disease.

To prevent repeat infections, instruct patients to wash fruits and vegetables thoroughly and to consume only well-cooked meats.

Albendazole is considered the drug of choice in echinococcosis, although better alternatives are required.[18] Praziquantel should not be used because the drug may aid alveolar hydatid growth.

Class Summary

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

Albendazole (Albenza)

Decreases ATP production in tapeworms, causing energy depletion, immobilization, and death. To avoid inflammatory response in CNS, patient must be started on anticonvulsants and high-dose glucocorticoids. Administer with food to increase absorption.

Patients with echinococcosis who have homogeneously calcified cysts do not usually require surgery and may follow the “watch and wait” treatment approach.

General preventive measures include the following:

• Thoroughly wash all fruits and vegetables before eating.
• Wash hands after handling pets or other canines and before handling food. Teach children early on about the importance of washing their hands to prevent infection.
• Use fences to keep animals away from gardens.
• Use gloves when handling foxes, coyotes, or other wild canines.
• Thoroughly cook meat, especially intestines intended for human consumption.

Prevention programs involve deworming of dogs, improved food inspection, improved slaughterhouse hygiene, and public education campaigns; vaccination of young sheep is currently being evaluated as a possible intervention.[1]

Cystic echinococcosis (CE) is controlled by preventing transmission of the parasite. Prevention measures include limiting the areas where dogs are allowed and preventing animals from consuming meat infected with cysts. These measures can be accomplished in the following ways:

• Prevent dogs from feeding on the carcasses of infected sheep.

• Control stray dog populations.

• Restrict home slaughter of sheep and other livestock.

• No human consumption of food or water possibly contaminated by canine feces.

• Wash hands with soap and warm water after handling dogs.

Surveillance for CE in animals is difficult because this infection is asymptomatic in livestock and dogs. CE is a preventable disease as it involves domestic animal species as definitive and intermediate hosts. Methods to prevent transmission and alleviate the burden of human disease are periodic deworming of dogs, improved hygiene in the slaughtering of livestock and the proper destruction of infected entrails and internal organs. Vaccination of sheep with an E. granulosus recombinant antigen (EG95) offers encouraging prospects for prevention and control. Small-scale EG95 vaccine trials in sheep have indicated high efficacy and safety with vaccinated lambs that are not becoming infected with E. granulosus.

A program that combines vaccination of lambs, deworming of dogs and culling of older sheep could eventually eliminate CE disease in humans.

Alveolar echinococcosis (AE) can be prevented by avoiding human contact with wild animals, such as foxes, coyotes, wild dogs and their feces, and by limiting interaction between dogs and rodents. Preventative measures are cited below:

• Do not allow dogs to feed on rodents and other wild animals.

• Avoid contact with wild animals such as foxes, coyotes and stray dogs.

• Do not encourage wild animals to approach residential housing or for wild animals to be kept as family pets.

• Wash hands with soap and warm water after handling dogs or cats, and before handling food.[2]

AE prevention and control is more complex than for CE as the E. multilocularis lifecycle involves wild animal species as both definitive and intermediate hosts. Regular deworming of domestic carnivores that have access to wild rodents can help reduce the risk of human infection. Culling of foxes and wild free-roaming dogs is possible but inefficient. The deworming of wild and stray definitive hosts with anthelminthic baits resulted in significant reductions in AE cases in Europe and Japan; however, sustainability and cost–benefit effectiveness of this approach are controversial.[1]

Complications include a secondary bacterial or fungal infection[19] at the time of surgical intervention[20] or other complications of cyst rupture.[21]

See the list below:

• Public education about proper sanitation methods, especially sanitary sheep butchering, can dramatically reduce disease transmission.

• Avoid feeding entrails to canines.