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Echinococcosis

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Related Terms
  • Albendazole, cestode, definitive host, echinococcal cyst, echinococcosis, Echinococcus granulosus, Echinococcus multilocularis, EG95, ELISA, EM2, EM18, eosinophilia, hydatid cyst disease, hydatid disease, hydatidosis, immunoelectrophoresis, immunofluorescence, indirect hemagglutination, intermediate host, PAIR, pericystectomy, praziquantel, protoscolice, Western blot, zoonosis, zoonotic disease.

Background
  • Echinococcosis is a parasitic zoonotic disease caused by a specific cestode, the dog tapeworm. Zoonosis, or zoonotic disease, refers to diseases that are transmitted from animals to humans. Cestodes are a class of parasitic flatworms. Echinococcosis is transmitted to humans from animal hosts by a fecal-oral route.
  • There are two forms of echinococcosis: the cystic form, caused primarily by Echinococcus granulosus, and the alveolar form, caused by Echinococcus multilocularis. In the cystic form of echinococcosis, pouch-like structures are formed, while in the alveolar form, the lesions formed resemble little sacs or alveoli similar to the sacs in the lungs. E. granulosus is found in the feces of infected dogs and E. multilocularis in that of foxes, coyotes, wolves, and dogs.
  • E. granulosus is present worldwide, especially in areas where livestock is raised in close proximity to dogs. There are areas in southern South America, northern Africa, Uganda, Kenya, Australia, New Zealand, the Mediterranean coast, the southern part of the former Soviet Union, the Middle East, and southwestern Asia in which echinococcosis is endemic. A disease is said to be endemic in a region if it occurs with predictable regularity, with only relatively minor fluctuations in its frequency over time. It is estimated that 6.6% of the population on the Tibetan Plateau is infected with E. granulosus cysts. E. multilocularis is more common in the Northern Hemisphere.
  • Echinococcosis causes productivity losses in human and domestic animal populations. Infection with E. granulosus is rarely fatal but may cause blindness from an infection of the eye socket or paralysis from brain infection. E. multilocularis infection is fatal if left untreated.
  • The number of human cases diagnosed varies greatly across countries, ranging from one to a few hundred out of 100,000 people. For example, the number of human cases in Greece is 13 out of 100,000.
  • Treatment of echinococcosis is difficult, and a complete cure is not always achieved. Patients may require lifelong medication therapy to keep the infection under control.
  • In view of the inadequacy of treatment options, prevention plays a very important role in reducing the rate of infection. Fencing around vegetable fields, thoroughly washing fallen wild berries before eating, washing hands after handling pets, preventing dogs from consuming infected meat, and treatment of infected dogs may be effective preventive measures.

Signs and symptoms
  • Echinococcal cysts may not be accompanied by any symptoms for a long time and may be discovered only on routine X-ray. The most commonly affected organs are the liver and the lungs, although other areas such as the heart, bones, and central nervous system may be affected. When the liver is infected, pain in the stomach region is the predominant symptom, whereas lung infection may cause coughing, chest pain, and coughing up blood. Echinococcus granulosus infection is rarely fatal, but it may cause blindness from an infection of the eye socket or paralysis from a brain infection.
  • Symptoms of alveolar echinococcal infection appear late in the course of the infection, even up to 10-15 years later. Symptoms may include an enlarged liver that may look like an enlarged abdomen, recurrent jaundice, and bleeding from the gastrointestinal tract. Jaundice is the yellowing of the skin and the whites of the eyes. Infection with E. multilocularis is fatal if left untreated.

Diagnosis
  • Diagnosis of echinococcosis involves lab tests, imaging, and serology. Serological tests involve the identification of antibodies in the serum, the fluid part of blood. Lab tests may reveal eosinophilia, defined as an increase in eosinophils, a type of white blood cell, which is observed in less than 25% of cases.
  • Imaging: X-rays may prove useful in detecting liver cysts with calcification and lung cysts, but their sensitivity is low. Calcification is a process in which calcium accumulates in soft tissue, causing it to harden. Ultrasound is the method of choice to detect the parasites and to determine the stage of Echinococcus granulosus infection. Staging refers to identifying how widespread the infection is (whether it is restricted to the liver or involved in the adjacent organs). Staging information may also help inform treatment options.
  • Magnetic resonance imaging (MRI) and computed tomography (CT) define the morphology of the cysts. MRI is imaging by computer using a strong magnetic field and radio frequencies. Alveolar echinococcosis may look like grapes or a honeycomb on an MRI scan. Cystic echinococcosis is characterized by numerous "daughter" cysts within a larger cyst, with calcification visible on a CT scan. A daughter cyst is a smaller cyst that develops from a large cyst. In fact, alveolar echinococcosis gets its name from its resemblance to little sacs or alveoli. The CT scan is also useful to determine the effectiveness of therapy. Calcification of the rim of the lesion reveals parasite degeneration.
  • Serological tests: Serological tests include enzyme-linked immunosorbent assay (ELISA), indirect hemagglutination, immunofluorescence, immunoelectrophoresis, and Western blot, which are explained below. These tests may be used to confirm a diagnosis in the setting of typical symptoms and suspicious radiological findings. Most of these methods make use of antigens to detect echinococcus-specific antibodies. Antigens are substances that prompt an immune response when introduced into the body. Antibodies are proteins produced by the body in response to antigens.
  • ELISA is a diagnostic tool that detects the presence of an antigen or antibody in a sample. ELISA is currently the most sensitive and specific technique available for diagnosing echinococcosis. Sensitivity refers to the probability of a test to correctly identify antigens and antibodies present in extremely small quantities. Specificity refers to the ability to distinguish specific antigens and antibodies from other antigens and antibodies. ELISA is positive in more than 90% of cases of echinococcosis, but it may also be positive in other tapeworm infections. E. multilocularis-specific antigen, called Em2, is 95% successful in distinguishing between E. multilocularis and E. granulosus. The sensitivity and specificity increases to 97% and 99%, respectively, with the use of recombinant E.multilocularis antigen. Recombinant antigen refers to antigen produced by genetic engineering.
  • Indirect hemagglutination and indirect fluorescent antibody tests are two other simple and easy-to-use serological tests to detect echinococcal infections. The indirect hemagglutination test is a technique in which antigens are adsorbed, or attracted and retained, onto red blood cell surfaces; the red blood cells then agglutinate (adhere to each other) in the presence of specific antisera that contain the specific antibodies. The indirect fluorescent antibody test detects antibodies to specific antigens using the fluorescent antibody technique. This technique makes use of an antibody tied to a fluorescent dye to detect an antigen. However, E. multilocularis and E.granulosus share some common antigens, so differentiation by these techniques may be difficult. Test sensitivity is generally higher for E. multilocularis if species-specific antigens are used.
  • The Western blot technique is a diagnostic method to detect proteins in a tissue extract. Here, it uses extracts from E. multilocularis as well as E. granulosus, or E. multilocularis alone. For the latter, sensitivity is excellent, at 97%, and it may distinguish between the two species in 76% of cases. However, cross-reaction with neurocysticercosis may occur, necessitating the use of species-specific antigens in patients with neurological disorders. A cross-reaction is a reaction between an antigen and an antibody that was developed to react against another antigen. Neurocysticercosis refers to a parasitic infection of the brain caused by pork tapeworm.

Complications
  • Cyst rupture may cause allergic reaction, coughing, coughing up blood, and spread of the infection to multiple organs. The bile duct, a tube through which bile, a digestive fluid, passes in and out of the liver, may get obstructed or infected. The bile duct may also form a biliary fistula, an unnatural opening that forms between the bile duct and another organ or between the bile duct and the outside of the body. Bacterial superinfection is another hazard. A superinfection is a new infection in addition to the one already present. Echinococcus multilocularis infection may cause abnormal liver function and permanent liver scarring, known as cirrhosis.

Treatment
  • Uncomplicated E. granulosus infestation is treated with puncture, aspiration, injection, and reaspiration (PAIR). In this procedure, the cysts are punctured with a needle and the contents removed, or aspirated, under the guidance of ultrasound or computed tomography (CT) scan. Ultrasound is a test similar to an X-ray but which instead uses sound waves. A CT scan is radiography, in which a three-dimensional image of a body structure is constructed by computer from a series of cross-sectional images made along an axis. This scan is examined for the presence of protoscolices, and, if confirmed, the cyst is completely aspirated. An agent that kills scolices, a scolicidal agent, usually alcohol or very concentrated saline, is then injected into the cyst. Scolices are the heads of cestodes that attach to the host's intestine. After a few minutes, the contents are aspirated again. Antiparasitic drugs are then given to prevent development of secondary echinococcosis in the abdominal cavity from the spillage of fluid.
  • Antiparasitic drugs such as albendazole given for 1-6 months may also be used in treatment. This drug alone may cure as many as 30-70% of echinococcosis cases. Complicated cases may be treated with pericystectomy, a surgical procedure to remove the cysts along with the surrounding fibrous tissue. Albendazole or praziquantel is prescribed for several weeks before and after the surgery. Praziquantel is an antiparasitic drug used to treat flatworms.
  • E. multilocularis lesions are removed surgically and the patient is prescribed albendazole for a period of at least two years after removal.
  • Albendazole, an antiparasitic drug, should be used with caution in patients with liver damage and should not be used in pregnant women. It should also be avoided in patients allergic to the class of drugs called benzimidazoles, which includes albendazole.
  • Praziquantel, an antiparasitic drug, should be avoided in patients with severe liver impairment and in nursing mothers. Because the drug may cause dizziness, patients should be cautious while driving or operating machinery.

Integrative therapies
  • Note: There is a lack of scientific evidence for the effect of integrative therapies on the prevention or treatment of echinococcus granulosus and echinococcus multilocularis. The therapies below have been studied for their effect on parasitic infections in general. They should be used only under the supervision of a qualified healthcare provider and should not be used in replacement of other proven therapies.
  • Unclear or conflicting scientific evidence:
  • Corydalis: Corydalis may be helpful in the treatment of infections caused by the parasite Echinococcus granulosus caused by the hydatid worm. More studies are needed to confirm the antiparasitic effects of corydalis.
  • Corydalis is generally considered to be safe. Avoid if allergic or sensitive to corydalis. Avoid if taking sedative or hypnotic drugs, drugs that treat abnormal heart rhythms (including bepridil), pain relievers, or anticancer drugs. Avoid if pregnant or breastfeeding.
  • Oregano: Early research shows that taking oregano by mouth may help treat parasites. Further research is needed to confirm these results.
  • Research suggests that oregano is well tolerated in recommended doses. Avoid if allergic or hypersensitive to oregano. Use caution if allergic or hypersensitive to other herbs from the Lamiaceae family, including hyssop, basil, marjoram, mint, sage and lavender. Use caution with diabetes and bleeding disorders. Pregnant or breastfeeding women should not consume oregano at doses above those normally found in food.
  • Zinc: In a few studies, patients with cutaneous leishmaniasis were injected with zinc sulfate under the skin. Zinc may decrease the severity of infection and reinfection of S. mansoni but does not seem to prevent initial infection. More research is necessary. The effects of zinc on the rate of parasitic reinfestation have been examined in children. No significant effect of zinc treatment was found. Recent data suggest that supplementation with zinc and vitamin A may favorably alter the infection rate and duration among children. Due to conflicting results in this area, more research is needed before zinc can be recommended for the treatment of parasites.
  • Zinc (zinc sulfate, zinc acetate, zinc glycine, zinc oxide, zinc chelate, and zinc gluconate) is generally considered safe when taken in the recommended dosages. Avoid zinc chloride, as studies have not been done on its safety or effectiveness. While zinc appears safe during pregnancy in amounts lower than the established upper intake level, caution should be used, as studies cannot rule out the possibility of harm to the fetus.

Prevention
  • In view of the inadequate treatment options for Echinococcus, prevention plays a very important role in reducing the rate of infection. Fencing around vegetable fields, thoroughly washing fallen wild berries before eating, washing hands after handling pets, preventing dogs from consuming infected meat, and treatment of infected dogs may be effective preventive measures.

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
  1. Centers for Disease Control and Prevention. .
  2. Chrieki M. Echinococcosis--an emerging parasite in the immigrant population. Am Fam Physician. 2002 Sep 1;66(5):817-20.
  3. Chow C, Gauci CG, Vural G, et al. Echinococcus granulosus: variability of the host-protective EG95 vaccine antigen in G6 and G7 genotypic variants. Exp Parasitol. 2008 Aug;119(4):499-505. Epub 2008 Feb 2.
  4. Dinkel A, Njoroge EM, Zimmermann A, et al. A PCR system for detection of species and genotypes of the Echinococcus granulosus-complex, with reference to the epidemiological situation in eastern Africa. Int J Parasitol. 2004 Apr;34(5):645-53.
  5. Gavidia CM, Gonzalez AE, Zhang W, et al. Diagnosis of cystic echinococcosis, central Peruvian Highlands. Emerg Infect Dis. 2008 Feb;14(2):260-6.
  6. Ito A, Sako Y, Yamasaki H, et al. Development of Em18-immunoblot and Em18-ELISA for specific diagnosis of alveolar echinococcosis. Acta Trop. 2003 Feb;85(2):173-82.
  7. Liance M, Janin V, Bresson-Hadni S, et al. Immunodiagnosis of Echinococcus infections: confirmatory testing and species differentiation by a new commercial Western Blot. J Clin Microbiol. 2000 Oct;38(10):3718-21.
  8. Lightowlers MW, Lawrence SB, Gauci CG, et al. Vaccination against hydatidosis using a defined recombinant antigen. Parasite Immunol. 1996 Sep;18(9):457-62.
  9. Natural Standard: The Authority on Integrative Medicine. .
  10. Petavy AF, Hormaeche C, Lahmar S, et al. An Oral Recombinant Vaccine in Dogs against Echinococcus granulosus, the Causative Agent of Human Hydatid Disease: A Pilot Study. PLoS Negl Trop Dis. 2008 Jan 16;2(1):e125.
  11. Siracusano A, Rigan® R, Ortona E, et al. Immunomodulatory mechanisms during Echinococcus granulosus infection. Exp Parasitol. 2008 Aug;119(4):483-9.
  12. Teke Z, Yagci AB, Atalay AO, et al. Splenic hydatid cyst perforating into the colon manifesting as acute massive lower gastrointestinal bleeding: an unusual presentation of disseminated abdominal echinococcosis. Singapore Med J. 2008 May;49(5):e113-6.
  13. Torgerson PR, Keller K, Magnotta M, et al. The global burden of alveolar echinococcosis. PLoS Negl Trop Dis. 2010 Jun 22;4(6):e722.
  14. World Health Organization. .

Causes
  • Cystic echinococcosis is a parasitic infection caused by the dog tapeworm transmitted from dogs to humans. The life cycle of Echinococcus granulosus involves both carnivores and herbivores. The definitive host is the dog. The adult tapeworm lives in the intestine of dogs, specifically the part of the intestine called the jejunum. A definitive host is one in which the parasite develops to a sexually mature stage, the stage at which it is capable of reproduction by the union of male and female sex cells.
  • The adult tapeworm releases eggs in the dog's intestine that are eliminated via the feces, which may then be ingested by sheep, cattle, or humans, which are the intermediate hosts. An intermediate host is one in which the parasite may develop and multiply asexually but not sexually. Asexual reproduction refers to any method of reproduction other than the union of male and female sex cells. An example of asexual reproduction is the formation of protoscolices, or tiny tapeworm heads, produced from the main cyst.
  • The eggs hatch into embryos in the intestine of the intermediate hosts and are carried by the blood to the liver and lungs, where they localize and develop into larval echinococcal cysts. A cyst is a closed cavity lined by epithelium that contains liquid or semisolid material. Protoscolices are then produced in the intermediate hosts, and these are infectious for dogs when they consume the meat of intermediate hosts. The protoscolices develop into adult tapeworms in the dog's intestine within one or two months and again produce eggs to be released in the feces. This process continues until the dog is treated for the infestation.
  • Foxes, coyotes, wolves, and dogs can be definitive hosts for E. multilocularis, and rodents are the intermediate hosts. Humans are an aberrant intermediate host, meaning that they may be infected but do not typically participate in transmission back to a definitive host. The life cycle of E. multilocularis is similar to that of E. granulosus, although the larval development of E. multilocularis in the liver is more aggressive and mimics a cancerous growth. The right lobe of the liver is most commonly involved, but continuous expansion and metastases within the liver cause the infection to spread throughout the organ. Metastasis is a term generally used to describe the spread of cancer from the primary location to other areas, but it is also used to describe the spread of E. multilocularis. The infection may metastasize to the lungs, lymph nodes, bones, or brain.

Risk factors
  • Exposure to infected animals or contaminated food and water is the primary risk factor.
  • Geography is also a factor. Echinococcus granulosus is present worldwide, especially in areas where livestock is raised in close proximity to dogs. There are areas in southern South America, northern Africa, Uganda, Kenya, Australia, New Zealand, the Mediterranean coast, the southern part of the former Soviet Union, the Middle East, and southwestern Asia in which cystic echinococcosis is endemic. A disease is said to be endemic in a region if it occurs with predictable regularity, with only relatively minor fluctuations in its frequency over time. It is estimated that 6.6% of the population on the Tibetan Plateau is infected with E. granulosus cysts. E. multilocularis is more common in the Northern Hemisphere than the Southern.

Types of the disease
  • There are two forms of echinococcosis: the cystic form, caused primarily by Echinococcus granulosus, and the alveolar form, caused by Echinococcus multilocularis. The cystic form refers to the formation of pouch-like structures, and the alveolar form to the lesions that resemble little sacs or alveoli similar to the sacs in the lungs.

Research
  • Polymerase chain reaction (PCR) in combination with specific deoxyribonucleic acid (DNA) probes is expected to simplify diagnosis in the future. PCR is an enzymatic method to make many copies of the two strands of DNA in a particular gene sequence. It is widely used to amplify minute quantities of biologic material to provide adequate specimens for laboratory research. DNA probes are specific DNA sequences that have complementary base pairs to the target DNA sequence. The detection and diagnosis of echinococcal infection utilizing PCR may become rapid, efficient, and accurate, thereby aiding in early detection and treatment of the infection.
  • A specific diagnostic Western blot technique using the Em18 antigen or the Em18 recombinant protein has been developed, but it is not commercially available. A recombinant protein is a protein developed by genetic engineering.
  • A vaccine that prevents the Echinococcus infection in intermediate hosts has been developed. A cloned recombinant antigen (EG95) developed from the echinococcal egg was used to prepare the vaccine. It offered 96-98% protection in sheep exposed to infection with E. granulosus eggs. The same vaccine has been suggested for humans in endemic areas, but its usefulness is questionable. Moreover, trials to test its use in humans are difficult to conduct.

Future research
  • Numerous immunomodulatory molecules are secreted by Echinococcus, which helps the parasite evade destruction by the host's immune system. An immunomodulatory molecule is capable of regulating immune function. These molecules are being characterized to understand the method by which the parasite persists in the host and causes chronic disease.
  • An oral recombinant vaccine in dogs has shown promising results. Recombinant vaccines are those in which genes for specific antigens are inserted into a vector, which is a vehicle used to transfer foreign genetic material to a target cell. The vector expresses the antigen, which is purified and used in the vaccine. The vector used in one study was a live, attenuated (weakened) strain of the bacterium Salmonella enterica serovar Typhimurium, which does not cause disease in its attenuated state. Further research in being carried out on this vaccine.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

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