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Advances in liver echinococcosis: diagnosis and treatment.

Echinococcosis or hydatid cyst disease is a zoonosis caused by the larval cestode Echinococcus granulosus. It consists of a parasitic tapeworm disease affecting mainly liver. Nevertheless, the disease might well spread to more unusual sites such as lungs and brain. The definitive diagnosis of liver echinococcosis requires a combination of imaging, serologic, and immunologic studies. Despite the fact that a number of scolecoidal agents have been developed against liver hydatid disease, the cornerstone of the definitive treatment remains surgery. Both the classic surgical techniques and the recently developed minimally invasive and laparoscopic methods target the eradication of the disease by simultaneously avoiding perioperative spillage and dissemination or recurrence of echinococcosis. The present article constitutes a review of the biology of the parasite as well as the epidemiology, diagnosis, and therapeutic options of the liver hydatid disease.

Algorithms↗

Reliable serodiagnosis of imported cystic echinococcosis with a commercial indirect hemagglutination assay.

A commercially available indirect hemagglutination assay (IHA) (Echinococcosis Fumouze; Laboratoires Fumouze, Levallois-Perret, France) was evaluated using sera from 52 patients with proven cystic echinococcosis. The specificity was assessed using 247 sera from patients with various parasitic, bacterial, viral, and fungal infectious diseases; sera containing autoimmune antibodies; and sera from healthy blood donors. With a cutoff value for a positive result of 320 (as recommended by the manufacturer), the sensitivity and specificity were 88% and 98.4%; with a cutoff of 160, the sensitivity and specificity were 94% and 95.1%, respectively. The IHA is rapid, easy to perform, and is a very sensitive serodiagnostic test for cystic echinococcosis.

Animals↗

Echinococcosis in Tunisia: a cost analysis.

Echinococcus granulosus infection is a preventable zoonosis of human and veterinary public health importance in Tunisia. We aimed to comprehensively quantify human and animal echinococcosis losses in Tunisia. Itemized cost menus were developed for the health of both domestic animals and humans, and for productivity monetary losses. The incidence and prevalence of the disease in all species were obtained from national and personal reports. The domestic animal and human costs of echinococcosis in Tunisia were estimated using age-stratified rates and losses, productivity losses (including those not formally employed) and Monte Carlo sampling to represent the uncertainty inherent in some epidemiological and economic values. Echinococcosis in Tunisia causes significant direct and indirect losses in both humans and animals of approximately US dollars 10-19 million annually. These estimates are based on numerous methodological improvements over previous studies and are of considerable consequence relative to Tunisia's US dollars 21.2 billion gross domestic product. A cost-benefit analysis of control programmes using the methodological advances presented here and regional comparison to other endemic diseases is warranted. These may provide information to assist policy decision-makers in prioritizing the allocation of scarce resources.

Animals↗

Simultaneous alveolar and cystic echinococcosis of the liver.

Alveolar echinococcosis (AE) and cystic echinococcosis (CE), caused by infection with the larval stages of Echinococcus multilocularis and E. granulosus, respectively, are of major clinical importance. Reports of infection with AE or CE are very common, but instances of simultaneous or dual infection are rare. We report on four cases with mixed AE/CE infections in the liver, diagnosed using retrospective surgical records and active community surveys in southern Ningxia Hui Autonomous Region (NHAR), PR China, a recognized hyperendemic area for echinococcosis.

Adolescent↗

A canine purgation study and risk factor analysis for echinococcosis in a high endemic region of the Tibetan plateau.

The Tibetan plateau of western China has been shown to have a very high prevalence of human cystic echinococcosis (CE) caused by Echinococcus granulosus and human alveolar echinococcosis (AE) caused by Echinococcus multilocularis. The domestic dog is suspected to be the primary definitive host for the transmission of both E. granulosus and E. multilocularis to humans in this locality. A purgation study of 371 dogs in Shiqu County, Sichuan Province during 2002-2003 resulted in an E. multilocularis prevalence of 12% and an E. granulosus prevalence of 8%. These crude prevalences were then adjusted, based on the known sensitivity of arecoline purgation for the detection of E. granulosus and a suggested sensitivity for the detection of E. multilocularis. In addition, it was assumed that some immature parasites of either species could be misidentified morphologically and wrongly assigned. This resulted in credible true prevalence intervals of between 13-33% for E. multilocularis and 8-19% for E. granulosus. Prevalences of other intestinal helminthes found on purgation were: Taenia spp. 31%, Dipylidium caninum 1%, and ascarids 8%. Risk factors associated with the acquisition of canine echinococcosis were evaluated based on responses to a questionnaire administered to dog owners. Male dogs were more likely to be infected with Echinococcus spp. than female dogs (P<0.05) and dogs allowed to roam were more likely to be infected with E. multilocularis (P<0.05).

Animals↗

Control of echinococcosis and cysticercosis: a public health challenge to international cooperation in China.

Echinococcosis, both cystic and alveolar, and Taenia solium cysticercosis are the most serious zoonotic cestodoses worldwide. Because of the emerging importance of these diseases in China, several international workshops and meetings were held in this country from 1998 to 2001. Based on round table discussions in Chengdu 2000, the proposal of a strategy to control echinococcosis and cysticercosis has been prepared in China. It includes a comprehensive approach based on a careful analysis of the local situations (particularly concerning the particularities of the cycle, ecology, and ethology of the animal hosts, and behavioral characteristics of the population at risk), the use of newly developed tools both in animals and human (immunology, molecular biology, and imaging), and the association of the traditional control measures (control of slaughtering, antiparasitic treatment and control of the definitive hosts, and health education) with more recent developments such as vaccination of the intermediate hosts. Plans on for the control of echinococcosis and cysticercosis in China are summarized.

Animals↗

A clinical dilemma: cardiac and pericardiac echinococcosis.

BACKGROUND: Cardiac and pericardial echinococcosis as a life-threatening disease may present with a clear picture most of the time, however it may also become a clinical puzzle. METHODS: In the period between 1977 and 1998, 14 patients were operated on with the diagnosis of cardiac and pericardial echinococcosis. Nine patients were operated on with standard cardiopulmonary bypass (CPB) techniques, and the remaining 5 patients were operated on without CPB. Transesophageal echocardiography (TEE) or intraoperative surface echocardiography were used to plan and perform the operation for the late cases. RESULTS: One patient died during the postoperative period due to the rupture of interventricular septum. All other patients survived the perioperative period, received mebendazole treatment, and exhibited no recurrence during the follow-up. CONCLUSIONS: The definitive treatment is the surgical extraction of the cyst. Because the clinical picture may vary according to the number, size, and location of cysts, as well as complications, cardiac echinococcosis should be remembered and included in the differential diagnosis to achieve the treatment. Intraoperative surface echocardiography is of paramount value for diagnosis and planning the management of a successful surgery.

Adolescent↗

Insulin-like growth factors and their binding proteins in the circulation of patients with echinococcosis, trichinellosis and toxoplasmosis.

BACKGROUND: Insulin-like growth factors (IGFs) are polypeptide hormones that play anabolic roles in cellular growth and metabolism. Their activity is regulated by binding proteins (IGFBPs) and degradation mechanisms. The liver is regarded as the main source of circulating forms and the levels change in various disease states. The aim of the study was to explore the effects of parasitic infections on the circulating IGFs and IGFBPs. METHODS: Peptide concentrations in sera of patients with echinococcosis, trichinellosis and toxoplasmosis were measured by radioimmunoassay, while IGFBP patterns were characterised by ligand-affinity blotting and gel chromatography. RESULTS: IGF-I levels were reduced in trichinellosis (p=0.016), with the increased relative amounts of IGFBP-1, -2 and -4. The significantly reduced levels of IGF-I (p<0.001), IGF-II (p=0.017) and IGFBP-3 and the increased presence of IGFBP-2 were found in patients with echinococcosis. CONCLUSIONS: In subjects with trichinellosis probably the combined effects of inadequate nutrition and the immunological response occurred. A possible explanation for the changes found in patients with echinococcosis is that the liver is a frequent target organ for Echinococcus granulosus. Since liver cysts were present in these patients, it can be expected that hepatic injury may affect liver metabolism leading to altered IGF/IGFBP profiles.

Adult↗

Echinococcosis: an emerging or re-emerging zoonosis?

The aim of this review is a critical discussion of factors actually or potentially contributing to persistence or emergence of echinococcosis in humans. Alveolar echinococcosis (AE), a life-threatening infection of humans, is caused by a larval stage of Echinococcus multilocularis. The adult parasite inhabits the intestine of foxes and other carnivores and has a wide distribution in the northern hemisphere (North America and northern and central Eurasia). Recent surveys in central Europe have extended the known geographical occurrence of E. multilocularis in foxes from four countries at the end of the 1980s to at least 11 countries in 1999. Cases of human AE previously regularly reported from only four countries are now recorded from seven countries, but the annual incidences are low. Since adequate information from earlier surveys is not available, it is not possible to conclude if the new findings reflect a recent extension of the parasite's range or just the first identification of hitherto unnoticed endemic areas. Evidence of parasite spreading has been reported from North America and Japan. Factors with the potential of enhancing the infection risk for humans in the future include increasing fox populations and parasite prevalences, progressing invasion of cities by foxes, the establishment of urban cycles of the parasite, and the spill-over of the E. multilocularis infection from wild carnivores to domestic dogs and cats. In view of the potential severity and fatality of AE in humans health authorities should initiate internationally coordinated countermeasures. Although control programmes against human cystic echinococcosis (CE), caused by E. granulosus, have been established in some countries and effective control strategies are available, the parasite has still a wide geographical distribution affecting many countries of all continents. Thus, human CE is persisting in many parts of the world with high incidences, and in some areas it is a re-emerging problem. For example, alarming increases of the number of human cases have been reported from Bulgaria and Kazakhstan, and the People's Republic of China. Progress in control can only be expected if health authorities attribute a higher priority to this disease and if all modern diagnostic and control options (for example vaccination of intermediate host animals) can be used.

Adult↗

[Vaccination against echinococcosis (?)].

Two species of the genus Echinococcus occur sympatrically in central Europe, namely Echinococcus multilocularis, the causative agent of alveolar echinococcosis (AE), and E. granulosus, resulting in cystic echinococcosis (CE) in humans. The endemic area of Europe demonstrates an annual incidence of 0.02 to 1.4 new AE cases per 100000 inhabitants. The importance of the disease refers primarily to the high lethality observed in untreated cases. Therapeutically, radical surgical resection of hepatic lesions followed by continuous benzimidazole-therapy is anticipated. Recently, the strategic control of cystic echinococcosis in humans has considerably been improved by the development of an effective and efficient vaccine that will indirectly prevent humans from infection. The vaccine protects animal intermediate hosts (mainly farm ruminants), thus the lack of hydatid cysts in these animals will prevent dogs to become infected. This on the long-term will result in an abrogation of infection sources (Echinococcus eggs) for humans (and other intermediate hosts). Principally, it has been shown that a similar vaccination is also possible for E. multilocularis. Thus, a 14-3-3 and another Em95-vaccine have successfully been tested in the experimental murine model. As the parasite development mainly focuses on a wildlife cycle (wild rodents), a practical application of the vaccine can hardly be implemented. Nevertheless, AE is a very severe disease in humans, therefore one should discuss about the feasibility and the health-economic impact of large-scale vaccination of humans living in areas of high endemicity and thus being at high infection risk.

Echinococcosis↗

[The computer tomographic diagnosis of echinococcosis (author's transl)].

The computer tomographic appearances and differential diagnosis in 22 patients with echinococcosis are described; of these, twelve were of the cystic and ten of the alveolar type. The computer tomographic appearances are characterised by the presence of daughter cysts (66%) within the sharply demarkated parasitic cyst of water density. In the absence of daughter cysts, a definite aetiological diagnosis cannot be made, although there is a tendency to calcification of the occasionally multiple echinococcus cysts. The computer tomographic appearances of advanced alveolar echinococcosis are characterised by partial collequative necrosis, with calcification around the necrotic areas (90%). The absence of CT evidence of partial necrosis and calcification of the pseudotumour makes it difficult to establish a specific diagnosis. The conclusive and non-invasive character of the procedure and its reproducability makes computer tomography the method of choice for the diagnosis and follow-up of echinococcosis.

Adolescent↗

Primary vertebral echinococcosis: four cases reports and review of literature.

Primary vertebral echinococcosis has been considered to be a hypothetical and exceptional possibility. It affects bones in 1% of reported cases. Spine is involved in 45-50% of these. The disease preferentially affects the thoracic spine. It begins as a single primary cyst containing daughter cysts. We report four cases of primary vertebral echinococcosis, extending into the extradural space without any other primary site of infection. We conclude that primary vertebral echinococcosis, although rare should be considered in destructive lesions of the vertebrae and spine in regions that the disease is endemic. Advanced imaging studies should be performed to diagnose the disease. Early decompressive surgery of the spine, with chemotherapy, is the treatment of choice for these patients.

Adolescent↗

A twenty-year history of alveolar echinococcosis: analysis of a series of 117 patients from eastern France.

OBJECTIVES: Alveolar echinococcosis of the liver is a very rare and severe parasitic disease due to the growth of the larva of Echinococcus multilocularis. The aim of this paper was to describe a 20-year study of the epidemiological, clinical and therapeutic aspects of alveolar echinococcosis in eastern France. DESIGN: One hundred and seventeen consecutive cases, diagnosed and followed in our liver unit, were studied from 1972 to 1993. METHODS: Data from 85 patients followed since 1983 (period B) were compared to data from a first series of 32 patients (period A) collected from 1972 to 1982; 1983 was chosen as the cut-off year because of the numerous changes that occurred in the diagnosis, follow-up and treatment of the disease at this time, in particular the introduction of parasitostatic benzimidazoles. RESULTS: The results of patient follow-up were evaluated in December 1997. The cumulative prevalence was 2.5 per 100,000 persons in period A whereas it reached 6.6 per 100,000 in period B. The annual incidence in period B was 7.3 on average, compared with 2.7 in period A. Twenty-nine per cent of patients from period B were asymptomatic at the time of diagnosis compared with 10% in period A. This change was correlated with less advanced liver lesions, and was related to the extensive use of abdominal ultrasound, and from 1987, serological screening. Curative resections were performed in 24% of the cases in period B versus only 3% in period A. From 1986, liver transplantations were performed in eight patients from period A and 13 patients from period B. In period B, palliative surgery was frequently replaced by radiological non-operative procedures to treat abscesses and jaundice. From 1982, 73 patients received benzimidazoles for a period of time ranging from 4 to 138 months. Stabilization of the lesions was observed in two-thirds of the patients. Episodes of jaundice or digestive haemorrhage due to portal hypertension were 31.5 and 11 times less frequent respectively in patients from period B compared with period A. Actuarial survival at 5 years improved from 67% in period A to 88% in period B in patients of similar age. CONCLUSIONS: Radical changes in the diagnosis and the management of alveolar echinococcosis have occurred during the last decade. Together they have contributed to an improvement in the status of the patients affected by this very severe parasitic disease.

Benzimidazoles↗

Screening of an Echinococcus granulosus cDNA library with IgG4 from patients with cystic echinococcosis identifies a new tegumental protein involved in the immune escape.

The worldwide problem of chronic Echinococcus granulosus disease calls for new parasite-derived immunomodulatory molecules. By screening an E. granulosus cDNA library with IgG4 from patients with active cystic echinococcosis, we identified a cDNA that encodes a predicted partial protein that immunofluorescence studies localized in the protoscolex tegument and on the germinal layer of cyst wall. We named this protein EgTeg because the 105 amino acid sequence scored highest against a family of Schistosoma tegumental proteins. Evaluating the role of EgTeg in the human early inflammatory response we found that EgTeg significantly inhibited polymorphonuclear cell (PMN) chemotaxis. Cytometric analysis of intracellular cytokines disclosed a significantly higher percentage of cells producing IL-4 than IFN-gamma (P = 0.001, Student's t-test) in T lymphocytes from patients with cystic echinococcosis stimulated with EgTeg. EgTeg induced weak Th1-dependent proliferation in 42% of patients' peripheral blood mononuclear cells. In immunoblotting (IB) analysis of total IgG and IgG subclass responses to EgTeg in patients with cystic echinococcosis, patients with other parasitoses, patients with cystic lesions and healthy controls, total IgG specific to EgTeg yielded high sensitivity (73%) but low specificity (44%) precluding its use in immunodiagnosis. Conversely, IgG4 specific to EgTeg gave acceptable sensitivity (65%) and high specificity (89%) suggesting its use in immunodiagnosis to confirm ultrasound documented cysts suggestive of E. granulosus. Because the new tegumental antigen EgTeg inhibits chemotaxis, induces IL-4-positive T lymphocytes and noncomplement fixing antibodies (IgG4) it is an immunomodulatory molecule associated with chronic infection.

Amino Acid Sequence↗

HLA and alveolar echinococcosis.

Evidence in animal intermediate hosts that susceptibility to larval infection with Echinococcus multilocularis is restricted to individual host factors prompted us to investigate the susceptibility markers in humans. Because antigens of the extracellular parasite E. multilocularis are possibly presented by MHC molecules in a restricted way, we speculated that MHC polymorphism may influence resistance of the host towards infection and course of disease. We studied HLA-A, -B, -DRB1, -DQB1 and -DPB1 polymorphism in 151 patients with alveolar echinococcosis. Patients with an observation period of more than 2 years were grouped according to the clinical follow-up into cured (no recurrence following surgery) patients and patients with regressive or progressive forms of disease during benzimidazole chemotherapy. By comparing phenotypic frequency between patients with alveolar echinococcosis and healthy controls, HLA-DRB1*11 was associated with a reduced risk for disease development (odds ratio=0.55, 95% confidence interval=0.34-0.88; P=0.01). HLA-DQB1*02 was more frequent in patients with progressive disease when compared with patients with regressive disease (54.3% vs 28.3%, P=0.02). The result suggests that HLA-DRB1*11 might confer protection against alveolar echinococcosis and that HLA-DQB1*02 may indicate a risk for progressive disease development. The findings may facilitate the search for immunodominant T-cell epitopes of E. multilocularis.

Animals↗

Cystic echinococcosis in a Jordanian patient: albendazole in a short-term immigrant.

With an ever increasing number of international travelers, physicians should be aware of the diseases that have rarely been encountered in their home countries. Cystic echinococcosis (CE) caused by Echinococcus granulosus is seldom seen in Japan despite frequent occurrence of the other type of echinococcosis, alveolar echinococcosis (AE) caused by E. multilocularis, in its northern parts. However, CE is prevalent in many parts of the world including the United Kingdom, Mediterranean basin, Middle East, South America, and Australia, and is supposed to be resurgent in several parts of the world. The disease is acquired by the oral ingestion of the eggs of E. granulosus passed into the feces of several definitive host animals carrying tapeworms, mostly dogs. These definitive hosts are infected by cannibalizing intermediate host animals including sheep and cattle whose livers and/or lungs are affected by cystic lesions that contain protoscoleces. In endemic areas the diagnosis of CE is not considered to be complicated; typical morphological features composed of cysts as revealed by ultrasonography and/or computerized tomography (CT) scan. The diagnosis is also aided by serological methods detecting serum antibodies. However, imaging procedures show a variety of features that could often lead to misdiagnosis as other diseases. Moreover, serological assays are sometimes difficult to interpret because of their incomplete sensitivities and specificities. Hence, a comprehensive understanding of a spectrum of imaging features and the application of serological methods with better sensitivities and specificities are indispensable. The mainstay of treatment of the disease is still surgical removal of cysts that has the potential to lead to a complete cure. Recently, the less invasive method PAIR (Puncture of cysts percutaneously, Aspiration of fluid, Introduction of protoscolicidal agent, and Reaspiration) was introduced with considerable success, and could be a promising alternative to surgery. Lastly, medical treatment with oral mebendazole or albendazole, especially the latter, can be beneficial not only as a adjunctive to surgery or PAIR, but as a sole treatment in cases in which invasive methods are not indicated. Here we report a Jordanian patient with CE whose diagnosis was substantiated by a novel immunoblot assay and who showed a rapid improvement during albendazole therapy.

Adult↗

Echinococcosis.

Echinococcosis is a human disease caused by the larval form of Taenia echinococcus, which lives in the gut of the dog, wild canides and other carnivorous animals which represent the definitive hosts and involves as intermediate hosts both domestic and wild animals. Humans become accidental intermediate hosts by ingesting Taenia eggs. The main species pathogenic for man are E granulosus causing cystic echinococcosis with worldwide distribution and endemic in sheep and cattle breeding countries, and E multilocularis causing alveolar echinococcosis, with preferential distribution in the northern hemisphere. After ingestion of contaminated food, hexacanth embryos migrate by the portal system to liver and later lung, brain and other tissues. Symptoms are related to both cyst location and size. E granulosus infection of the central nervous system (CNS) may be primary or secondary and has been estimated to be low (2%). Sharply demarcated, spherical and intraparenchymal, cysts may reach a large size causing neurological symptoms. Spilling of cyst fluid due to trauma or surgery may trigger anaphylaxis as well as disseminated infection. Host reaction is minimal in the brain but a foreign giant cell reaction may develop. E multilocularis develops within the liver as a rapid invasive pseudomalignant growth and may metastasize to the CNS, where estimated incidence reaches 5%. Hydatid antigens induce an immune reaction in the host which is helpful for the diagnosis. DNA probes and PCR may be applied to differentiate between Echinococcus spp. Although the host develops an immunological protection from reinfection, the parasite evades host immune attack. A wide range of evasion mechanisms have been advanced, including a barrier for host cells due to hydatid cyst laminated cuticle, polyclonal activation of lymphocytes by parasite soluble antigens, and depression of host cell immune responses. Chronic stimulation of the host by cyst fluid antigens leads to increased specific IgG4 production, which might act as blocking antibodies against anaphlaxis suggestive of host response immunomodulation.

Animals↗

Evaluation of an enzyme-linked immunosorbent assay (ELISA) with affinity-purified Em18 and an ELISA with recombinant Em18 for differential diagnosis of alveolar echinococcosis: results of a blind test.

Alveolar echinococcosis (AE) is the most potentially lethal parasitic zoonosis of the nontropical areas in the northern hemisphere, where cystic echinococcosis (CE) is also endemic. Both AE and CE are highly endemic in China, and both serologic detection of echinococcosis, either AE or CE, and differentiation of AE from CE are crucial problems. Evaluation of Western blot analysis (WB) and enzyme-linked immunosorbent assay (ELISA) for the Em18 antigen, using affinity-purified and recombinant Em18, was carried out "blindly" using 60 human sera from patients diagnosed in France. The results were compared with those obtained using a commercially available Echinococcus WB immunoglobulin G (IgG) kit developed in France. The Em18 WB and Echinococcus WB IgG showed very similar results for detection of AE. Both affinity-purified Em18 or a recombinant Em18 WB and Echinococcus WB IgG seem useful for identification of AE, and the latter seems appropriate for both AE and CE, whereas affinity-purified Em18 ELISA and the newly developed recombinant Em18 ELISA appear to be suitable for detection of AE, especially for epidemiological surveys.

Animals↗