European echinococcosis registry: human alveolar echinococcosis, Europe, 1982-2000. (Research).Surveillance for alveolar alveolar /al·ve·o·lar/ (al-ve´o-lar) [L. alveolaris ] pertaining to an alveolus. al·ve·o·lar adj. Relating to an alveolus. echinococcosis Echinococcosis Definition Echinococcosis (Hydatid disease) refers to human infection by the immature (larval) form of tapeworm, Echinococcus. One of three forms of the Echinococcus spp., E. in central Europe Central Europe is the region lying between the variously and vaguely defined areas of Eastern and Western Europe. In addition, Northern, Southern and Southeastern Europe may variously delimit or overlap into Central Europe. was initiated in 1998. On a voluntary basis, 559 patients were reported to the registry. Most cases originated from rural communities in regions from eastern France to western Austria; single cases were reported far away from the disease-"endemic" zone throughout central Europe. Of 210 patients, 61.4% were involved in vocational or part-time farming, gardening, forestry, or hunting. Patients were diagnosed at a mean age of 52.5 years; 78% had symptoms. Alveolar echinococcosis primarily manifested as a liver disease Liver Disease Definition Liver disease is a general term for any damage that reduces the functioning of the liver. Description The liver is a large, solid organ located in the upper right-hand side of the abdomen. . Of the 559 patients, 190 (34%) were already affected by spread of the parasitic larval larval 1. pertaining to larvae. 2. larvate. larval migrans see cutaneous and visceral larva migrans. tissue. Of 408 (73%) patients alive in 2000, 4.9% were cured. The increasing prevalence of Echinococcus multilocularis Echinococcus multilocularis is a cyclophyllid cestode that, like Echinococcus granulosus, produces hydatid disease in many mammals, including rodents and humans. Unlike E. in foxes in rural and urban areas of central Europe and the occurrence of cases outside the alveolar echinococcosis--endemic regions suggest that this disease deserves increased attention. ********** Human alveolar echinococcosis, caused by the metacestode of the fox tapeworm tapeworm, name for the parasitic flatworms forming the class Cestoda. All tapeworms spend the adult phase of their lives as parasites in the gut of a vertebrate animal (called the primary host). Echinococcus multilocularis, is considered to be the most pathogenic zoonosis Zoonosis Definition Zoonosis, also called zoonotic disease refers to diseases that can be passed from animals, whether wild or domesticated, to humans. in temperate and arctic regions of the Northern Hemisphere. Transmission to humans occurs when eggs of the tapeworm, excreted by the final hosts (usually foxes), are accidentally ingested in·gest tr.v. in·gest·ed, in·gest·ing, in·gests 1. To take into the body by the mouth for digestion or absorption. See Synonyms at eat. 2. . The larva's primary target organ target organ n. A tissue or organ that is affected by a specific hormone. target organ, n the organ or body part whose activity levels demonstrate change in the course of biofeedback. is the liver, where it proliferates slowly, but the larva larva, in zoology larva, independent, immature animal that undergoes a profound change, or metamorphosis, to assume the typical adult form. Larvae occur in almost all of the animal phyla; because most are tiny or microscopic, they are rarely seen. also spreads into extrahepatic ex·tra·he·pat·ic adj. Originating or occurring outside the liver. structures and even metastasizes to distant organs. In earlier untreated cohorts, the fatality rate fa·tal·i·ty rate n. See death rate. fatality rate see case fatality rate. exceeded 90% within 10 years (1). The introduction of benzimidazoles for alveolar echinococcosis treatment in 1976 has considerably improved the prognosis (2,3). Long-term follow-up of 117 patients showed that the 5-year actuarial survival rate increased to 88% with this improved management (4). As chemotherapy is parasitostatic only, long-term administration is mandatory for most patients (5,6). Radical surgical excision, the only curative treatment, is feasible in a few select cases (7). In Europe, previous assessments of human cases did not cover all alveolar echinococcosis--endemic areas at comparable periods. In Switzerland, where laboratory-diagnosed alveolar echinococcosis was a reportable disease re·port·a·ble disease n. See notifiable disease. until 1997, the annual incidence ranged from 7.2 to 10.4 (0.10-0.18/100,000) and did not markedly vary during a 36-year period (8). In Austria, an average incidence of 2.5 cases per year corresponded to an incidence of 0.034/100,000 from 1985 to 1999 (9). These low numbers of human infections throughout a whole country failed to alarm public health authorities. However, two findings are beginning to attract more attention: 1) high annual incidence rates occurring regularly in particular regions, e.g., the Swiss Jura (0.74/100,000) (10); and 2) a presumed range extension of the parasite in its sylvatic sylvatic /syl·vat·ic/ (sil-vat´ik) sylvan; pertaining to, located in, or living in the woods. sylvatic found in the woods; occurring in animals of the forest. life cycle. In Europe, the Red Fox (Vulpes vulpes Vulpes vulpes see red fox. ) is the most important final host for E. multilocularis. Reviews based on the data collected during the past decade have shown that the natural range of the parasite extends farther to the east and north in Europe than previously thought (11,12). Defined rural areas have been monitored regularly for many years, and increasing parasite prevalence rates in foxes have been recorded (13). Clusters of high endemicity (60% to 75%) have been found (14). Increasing fox populations have been reported from several European countries (13). Foxes migrating to urban areas are also causing concerns: E. multilocularis prevalence rates of 20% and 48% have been recorded in Stuttgart, Germany (11), and Zurich, Switzerland, respectively (15). Knowledge of the parasite's range and prevalence in animal hosts has thus grown during recent years. However, comprehensive assessments of human alveolar echinococcosis covering the known risk areas across European countries have not been performed. To provide baseline data for future risk calculations and to establish a prospective case retrieval, the European Echinococcosis Registry (EurEchinoReg) created a network of reporting centers in 11 countries of western and central Europe and Turkey. This report provides the status of reporting, origin, and clinical and epidemiologic data of such patients reported to the registry up to the year 2000. Methods Case Retrieval Case detection and data collection have been organized by each participating country according to according to prep. 1. As stated or indicated by; on the authority of: according to historians. 2. In keeping with: according to instructions. 3. the existing infrastructure of the national health systems and the availability of data sources. In the EurEchinoReg, experts from universities (research units and hospitals) and public health authorities cooperate in eight countries of the European Union European Union (EU), name given since the ratification (Nov., 1993) of the Treaty of European Union, or Maastricht Treaty, to the European Community (Austria, Belgium, France, Germany, Greece, Great Britain Great Britain, officially United Kingdom of Great Britain and Northern Ireland, constitutional monarchy (2005 est. pop. 60,441,000), 94,226 sq mi (244,044 sq km), on the British Isles, off W Europe. The country is often referred to simply as Britain. , Italy, and the Netherlands), and in Switzerland, Poland, the Czech Republic Czech Republic, Czech Česká Republika (2005 est. pop. 10,241,000), republic, 29,677 sq mi (78,864 sq km), central Europe. It is bordered by Slovakia on the east, Austria on the south, Germany on the west, and Poland on the north. , and Turkey. Patient data are stripped of identifiers and sent to two subregistries (the University of Franche-Comte, Besancon, France and the University of Ulm The University of Ulm (German: Universität Ulm) is a public university in the city of Ulm, in the South German state of Baden-Württemberg. The university was founded in 1967 and focuses on natural sciences, medicine and the engineering sciences, mathematics/ economics and , Ulm, Germany), where they are controlled and approved for electronic recording. Case Definition and Period of Inclusion Diagnosis of alveolar echinococcosis is confirmed by 1) positive histopathology his·to·pa·thol·o·gy n. The science concerned with the cytologic and histologic structure of abnormal or diseased tissue. Histopathology The study of diseased tissues at a minute (microscopic) level. , if available and/or 2) typical liver lesion morphology identified by imaging techniques (ultrasound scan ultrasound scan Noun an examination of an internal bodily structure by the use of ultrasonic waves, esp. for diagnosing abnormality in a fetus , computed tomography Computed tomography (CT scan) X rays are aimed at slices of the body (by rotating equipment) and results are assembled with a computer to give a three-dimensional picture of a structure. , and magnetic resonance imaging magnetic resonance imaging (MRI), noninvasive diagnostic technique that uses nuclear magnetic resonance to produce cross-sectional images of organs and other internal body structures. ) with or without the detection of serum antibodies (serology Serology The division of biological science concerned with antigen-antibody reactions in serum. It properly encompasses any of these reactions, but is often used in a limited sense to denote laboratory diagnostic tests, especially for syphilis. ). Positive serologic se·rol·o·gy n. pl. se·rol·o·gies 1. The science that deals with the properties and reactions of serums, especially blood serum. 2. results without suggestive imaging findings or positive histopathology does not qualify for a case definition. The period of inclusion began in 1982, when benzimidazoles, ultrasound, and other imaging techniques (which facilitated diagnosis, treatment, and follow-up) were introduced. The registry includes all confirmed new cases from January 1982 to December 2000, as well as cases with a diagnosis from earlier periods, provided the patients were alive in 1982 and their diagnosis was confirmed with the appropriate techniques in 1982 or later. Case Report Form and Completeness of Registration Patients were asked to allow their nominal registration at their national center, in conformity with the national legislation for data privacy to avoid double registration and to facilitate follow-up. Two questionnaires are used: an epidemiologic part to be answered by the patient and a clinical part to be completed by the reporting physician. In addition to demographic baseline data, we gathered information on year of diagnosis, disease manifestation at the time of the diagnosis, co-existing conditions; diagnostic and therapeutic measures, year of death, presumed cause of death, places of residence, and occupation in agriculture, forestry, and gardening. Data files from the study groups in Austria, France, Germany, and Switzerland were the basis for the European patient registry; additional case files were collected by active case finding and with the help of physicians from hospitals and private practices. Completeness of registration can be assumed: 1) in France, since access to patient files is facilitated by a centralized distribution of albendazole by a few university hospitals; 2) in Austria, since laboratory diagnosis is made in a single institution; and 3) in Switzerland, where alveolar echinococcosis was a reportable disease until 1997; case reports are thus complete from the 1970s until 1997. Underreporting is likely in Germany, where reporting relies entirely on the cooperation of family physicians and clinicians. In Belgium, Greece, and Poland, alveolar echinococcosis seems to be newly emerging, and cases are discussed in the medical community; the cases reported to the registry should reflect the true prevalence in these countries. Data Analysis The combined data sets for all European patients are kept in an Access database (Microsoft Corp., Redmond, WA). Descriptive analyses were made with SAS (1) (SAS Institute Inc., Cary, NC, www.sas.com) A software company that specializes in data warehousing and decision support software based on the SAS System. Founded in 1976, SAS is one of the world's largest privately held software companies. See SAS System. software V8 (SAS Institute SAS Institute Inc., headquartered in Cary, North Carolina, USA, has been a major producer of software since it was founded in 1976 by Anthony Barr, James Goodnight, John Sall and Jane Helwig. , Inc., Cary, NC). The regional distribution of alveolar echinococcosis cases was mapped with the software package RegioGraph 5.1 (GfK MACON AG, Waghausel, Germany). Results Epidemiology The total number of verified alveolar echinococcosis cases reported to the registry was 559; 42.0% were diagnosed in France, 23.6% in Germany, and 21.1% in Switzerland (Table 1). Fifteen patients acquired the infection outside their reporting country, 7 of these cases originated from one of the neighboring countries, 8 were of non-European origin. During the reporting period, the number of new cases varied from year to year. From 1981 to 2000, a peak incidence of 36 was noted in 1988; aside from this 1 year, reports ranged from 15 to 27 patients. A total of 258 patients were male (46.2%) and 301 female (53.8%) (gender ratio 1:1.2). The median age at first diagnosis was 56 (mean 52.5, range 5-86 years) and was almost equal in men and women (Figure 1). The proportion of patients <20 years old was 2.1% (12/559); 88 (15.7%) were >69 years of age. For four patients (0.7%), the year of birth was missing. Three of the four children in this case series, ages 5 and 7 when diagnosed, had severe organ damage; two were immunocompromised immunocompromised /im·mu·no·com·pro·mised/ (-kom´pro-mizd) having the immune response attenuated by administration of immunosuppressive drugs, by irradiation, by malnutrition, or by certain disease processes (e.g., cancer). . [FIGURE 1 OMITTED] Information on potential risk factors was available for 210 (37.6%) patients from Austria, Germany, Greece, and France (Table 2), including 97 men and 113 women. Of these, 21.9% were farmers. In addition, of all the patients engaged in other professions (including housewives and students), 46.2% regularly farmed, gardened, or performed related activities as a pastime. Of all pensioners and unemployed patients, 62.2% also gardened, farmed, or the like. Most patients (70.5%) owned or formerly kept dogs and cats. Among these pet owners, 105 persons also actively farmed or gardened. Only 15 patients (7.1%) did not farm, garden, or own pets. Geographic Distribution Figure 2 gives the residence at the time of diagnosis or at the time of the last medical report for 532 alveolar echinococcosis patients; cases were autochthonous autochthonous /au·toch·tho·nous/ (aw-tok´thah-nus) 1. originating in the same area in which it is found. 2. denoting a tissue graft to a new site on the same individual. from the countries represented on the map. The patient from Greece lived in Macedonia. Data were unavailable for 18 patients. [FIGURE 2 OMITTED] Most residences were clustered in defined regions: central France, French Jura and Savoy, Swiss Jura and northeastern Switzerland, southern Germany The term Southern Germany (German: Süddeutschland) is used to describe a region in the south of Germany. The exact area defined by the term is not constant, but it usually includes Bavaria, Baden-Württemberg, and the southern part of Hesse. , and western Austria. Single cases were identified in Belgium, the northern regions of France France is divided into 26 regions or régions (in French), of which 21 are in continental metropolitan France, one is the island of Corsica, and four lie overseas. Régions in mainland France are further subdivided in between 1 and 8 départements. , Germany, and Poland, and northeastern Austria. For the period 1980-1999, a total of 201 cases were reported from Turkey; all originated from the Asian part of the country, mostly from eastern Anatolia. However, the aggregated data (reviewed by Altintas et al. [16]) could not be combined with the detailed datasets from western and central Europe. No autochthonous cases were reported from the Netherlands, the Netherlands, The officially Kingdom of The Netherlands byname Holland Country, northwestern Europe. Area: 16,034 sq mi (41,528 sq km). Population (2005 est.): 16,300,000. Capital: Amsterdam. Seat of government: The Hague. Most of the people are Dutch. Czech Republic, the Slovak Republic, Italy, or the U.K. Clinical Data Table 3 lists the main diagnostic procedures, conducted within a time span of 6 months after initial examination, which led to the diagnosis of alveolar echinococcosis. A total of 53.5% of diagnoses were definitely confirmed by positive histopathology; 38.5% were ascertained by imaging techniques combined with serology, or imaging alone, when obtaining tissue specimens for analysis was not possible. Information on diagnostic procedures was missing for 7.7% of the patients. In 397 (71.0%) of the 559 cases, the diagnosis was made after the patients reported symptoms; 66 (11.8%) cases were disclosed by chance in the course of a general medical checkup check·up n. 1. An examination or inspection. 2. A general physical examination. checkup See Yearly checkup. or an examination related to other diseases; and 18 (3.2%) cases were found during studies that screened for alveolar echinococcosis. Data on these circumstances were not available for 78 (14%) of 559 patients. The primary infection site was the liver for almost all patients, and primary extrahepatic lesions without any involvement of the liver were diagnosed in 13 patients (Table 4). At first diagnosis, the liver was the only affected organ for 351 (62.8%) of 559 patients. Damage to the liver included single or multiple lesions in one or more segments of one or both liver lobes, the hilus hilus /hi·lus/ (hi´lus) pl. hi´li [L.] hilum. hilus (hī´lus), n region, the intrahepatic portal vein portal vein n. A wide short vein that is formed by the superior mesenteric and splenic veins behind the pancreas, ascends in front of the inferior vena cava, and divides into right and left branches that ramify within the liver. , hepatic vein hepatic vein n. Any of the veins that carry from the liver the blood collected from the hepatic artery and portal vein and that terminate in three large veins, designated right, middle, and left, that open into the inferior vena cava below the diaphragm. , or bile duct bile duct or biliary duct n. Any of the excretory ducts in the liver that convey bile between the liver and the intestine, including the hepatic, cystic, and common bile ducts. Also called gall duct. bile duct 1. . Approximately one third (34%) of the patients (190/559) were already affected by a spread of the larval tissue either in continuum into neighboring organs, by the formation of distant metastases Metastasis (plural, metastases) A tumor growth or deposit that has spread via lymph or blood to an area of the body remote from the primary tumor. Mentioned in: Malignant Melanoma , or both. Specific details of organ damage were available for 178 of 190 patients. The organs most frequently affected by continuous growth were the diaphragm (59 patients), kidneys or adrenal glands Adrenal glands The two glands that are located on top of the kidneys. These glands secrete several hormones, including the glucocorticoids which, among other things, influence the way the immune system works, and the mineralocorticoids, which affect retention of (26 patients), and lungs and pleura pleura (pl r`ə), membranous lining of the upper body cavity and covering for the lungs. (15 patients).
Metastases occurred mainly in the lungs (39 patients), brain (17
patients), and spleen (10 patients).At the time of reporting, 267 (47.8%) of the 559 patients had undergone surgery and received benzimidazoles; 200 (35.8%) were treated with these drugs alone, and 48 (8.6%) by surgery alone. A total of 29 patients (5.2%) underwent liver transplantation Liver Transplantation Definition Liver transplantation is a surgery that removes a diseased liver and replace it with a healthy donor liver. Purpose The liver is the body's principle chemical factory. . Twenty-two patients (3.9%) had not received any treatment during the time between diagnosis and notification; another 13 (2.3%) had apparently had inadequate treatment. For 9 patients (1.6%) the chosen treatment options were not specified. By December 2000, 73.0% of the patients were alive, 21.3% had died, and 5.7% were lost to follow-up (Table 5). Of the patients still alive, disease activity was assessed at their last clinical examination as follows: cured (20 patients, 4.9%); stable or regressive (226 patients, 55.4%); or progression, sequelae sequelae Clinical medicine The consequences of a particular condition or therapeutic intervention , or complications caused by larval growth or occurring after intervention (43 patients, 10.5%). An assessment was not provided for 119 patients (29.2%); many of them had been diagnosed recently, and treatment had just begun. Death was definitely associated with alveolar echinococcosis in 13 (10.9%) of the 119 cases; in 15 cases (12.6%) death was probably related to this disease. In 20 patients (16.8%), death was definitely independent of the diagnosis of alveolar echinococcosis. No assessment was available for 71 patients (59.7%). Discussion In 1998, the EurEchinoReg network initiated the assessment of human alveolar echinococcosis across European borders. The reasons for promoting concerted efforts to survey a disease thought to be rare in Europe were as follows: 1) the disease is one of the most aggressive chronic liver diseases, 2) comprehensive assessments of human cases covering all known risk areas were not available, 3) the routes of transmission to humans are still hypothetical, and 4) the range of the parasite in its life cycle seems to have extended, posing threats in previously unaffected areas. The assessment included patients from former clinical studies and cases identified by active case finding. Nine European countries reported on 559 patients; cases were autochthonous from seven of these countries. The median numbers per year did not vary during two decades (24 in 1980s; 22 in 1990s). Underreporting from previous years was responsible for a seemingly increasing incidence in Germany; underreporting since 1998 explains a decline in Switzerland. High numbers in France in the mid-1980s could be an effect of mass screenings performed at that time in alveolar echinococcosis--endemic areas, which may have raised awareness of the disease. In the past, the number of verified and published cases from Europe (Austria, France, Germany, and Switzerland) amounted to 844 cases or 10.6 cases per year (published between 1900 and 1980) (17). The patient numbers from our report reflect what is probably an optimal detection rate owing to owing to prep. Because of; on account of: I couldn't attend, owing to illness. owing to prep → debido a, por causa de improved technology. Thus, low but constant incidence is characteristic of the occurrence of human alveolar echinococcosis in Europe today Europe Today is a daily radio news show on the BBC World Service about public affairs throughout Europe. It is presented by Audrey Carville at 17:00 GMT every weekday. External links
In this parasitic infection, a long incubation period incubation period n. 1. See latent period. 2. See incubative stage. Incubation period seems to precede diagnosis. Albeit difficult to prove, the initial asymptomatic period is assumed to last 5-15 years (1). (This conclusion is derived from the small proportion of patients <20 years old at diagnosis [2.1% in this report]). Determining the time and place of infection is difficult. Assuming that in humans, who are unsuitable hosts for E. multilocularis, repeated or long-term exposure is required before an infection becomes established, these conditions are more likely to be met by outdoor activities close to the place of residence than by travels to alveolar echinococcosis--endemic areas. We therefore assume that for most cases, the place of residence is most likely the area of infection. A complete documentation of all the places where the patients had lived during their lives was available for approximately 30%. Mobility of this patient subgroup was low, in conjunction with long-term farming. The distribution of alveolar echinococcosis in Europe shows a core area with a high density of cases and border areas with clusters of a few patients or single cases. The core area covers large parts of the classic alveolar echinococcosis--endemic regions in Austria, France, Germany, and Switzerland, including those where the index cases from each of these countries have been identified since 1855 (17). In these areas, recent screening studies have detected not only a small number of manifest diseases but also self-cured infections (aborted lesions, first described by Rausch et al. [18]), and seropositivity Seropositivity is the presence of a certain antibody in a blood sample. A patient with seropositivity for a particular antigen or agent is termed seropositive. rates of up to 2% (14,19,20). Fifteen persons with aborted hepatic lesions (lesions with characteristic calcification calcification /cal·ci·fi·ca·tion/ (kal?si-fi-ka´shun) the deposit of calcium salts in a tissue. dystrophic calcification ) and positive serologic results were reported to the registry but were excluded from this analysis, since a definite diagnosis based on histopathologic or molecular findings had not been provided, Together with a persistent E. multilocularis seroprevalence seroprevalence Immunology The proportion of a population that is seropositive–ie, has been exposed to a particular pathogen or immunogen; the seropositivity of a population is calculated as the number of individuals who produce a particular antibody divided , such reports point to a manifest infection pressure in the core area. In the core area, a consistently high prevalence of E. multilocularis in foxes has been reported, e.g., >50% in southwestern Germany (11), 44% in western Bavaria (21), 65% in eastern France (13), and 35% in western Austria (9). In the border area with less frequent and more dispersed human cases, fewer investigations have been undertaken to establish parasite prevalence, and the figures determined rely on low numbers of examined foxes. The prevalence was generally low, e.g., 13% in northern Germany Northern Germany is the geographic area in the north of Germany. The native German concept of northern Germany is called Norddeutschland. Northern German States Norddeutschland is the geographic area of five German states:
Whether low parasite prevalence exerts an infection pressure relevant for transmission to humans remains questionable. Recent investigations have shown that foci of high prevalence can persist, even for long periods, in regions where the overall infection rates in foxes are low (e.g., foci of 25% in areas with 5% in eastern Germany Eastern Germany refers to:
prep. Without consideration of; regardless of. irrespective of preposition despite the magnitude of prevalence rates. This view is the basis for the current concept of a continuous distribution of the parasite in Europe from central France to Poland. Future studies should, therefore, address the redefinition of risk areas for alveolar echinococcosis and the population at risk. Transmission of the parasite to humans occurs rarely, and individual risk factors for human disease are not well understood. In Europe, only one case-control study case-control study, n an investigation employing an epidemiologic approach in which previously existing incidents of a medical condition are used in lieu of gathering new information from a randomized population. has been published; this study included 21 patients and 84 controls from Austria (25). A high association of the disease was found with cat ownership and hunting, but because of the low case number the study was of limited power. Farming did not seem to have an impact on infection risk. In China, a population-based study showed that farming was the most important risk factor (26). In Alaska, dog ownership was found to be associated with the disease (19 patients, 38 controls) (27). None of these studies found an association of the disease with a history of picking and eating wild berries and mushrooms or raw produce from unfenced gardens. Also, neither fox hunters in China (26) nor trappers in South Dakota South Dakota (dəkō`tə), state in the N central United States. It is bordered by North Dakota (N), Minnesota and Iowa (E), Nebraska (S), and Wyoming and Montana (W). , United States United States, officially United States of America, republic (2005 est. pop. 295,734,000), 3,539,227 sq mi (9,166,598 sq km), North America. The United States is the world's third largest country in population and the fourth largest country in area. , are affected by the disease (28). The records of 210 patients from the European registry data show that 21.9% were farmers; another 39.5% were engaged in farming, gardening, hunting, or working in forestry as a pastime; 70.5% of all patients kept dogs or cats. These data point to a high frequency of putative exposure, but the lack of a comparison group does not allow an evaluation of the risk potential of these activities. These activities may be characteristic of most people in rural communities in Europe. For Europe, the questions of how risk behavior can be defined and how exposure can best be prevented are, therefore, still unanswered. Within the last 20 years, major improvements have been made in the diagnosis and treatment of alveolar echinococcosis. Definite diagnosis by histopathology was available in 53.3% of this case series; the remaining cases were ascertained by imaging with or without specific serology. At diagnosis, 34% of the patients were already affected by advanced larval growth; when the parasitic tissue does not affect important organs or vessels, it may go unnoticed for prolonged periods. This fact may also explain a diagnosis late in a patient's life. In Europe, the mean age at diagnosis was slightly higher than in non-Caucasian populations, i.e., in Hokkaido, Japan (48.7 years) (29), or in China (35.7 years) (30). Immunodeficiencies, e.g. HIV HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. infection (31) or immunosuppressive therapy Immunosuppressive therapy Medical treatment in which the immune system is purposefully thwarted. Such treatment is necessary, for example, to prevent organ rejection in transplant cases. after liver transplantation (32), may possibly accelerate the manifestation of alveolar echinococcosis. Chemotherapy with benzimidazoles was the only treatment for one third of the registered patients; complete cure after surgery and adjuvant chemotherapy Adjuvant chemotherapy Treatment of the tumor with drugs after surgery to kill as many of the remaining cancer cells as possible. Mentioned in: Neuroblastoma was achieved in only 4.9%. For most patients, stability can be achieved with long-term chemotherapy, with or without surgery or interventional radiology interventional radiology Imaging A subspecialty of radiology that provides Diagnostic information–eg, CT-guided 'skinny' needle biopsies and dye injection for analysis of various lumina and tracts–eg, arteriography, cholangiography, antegrade , but the disorder remains chronic. This report is the first collection of data on human alveolar echinococcosis in Europe. Our study confirms that an infection with this parasite is still dangerous. A low annual incidence persists in the previously known foci. However, case reports from regions remote from the core area indicate that the disease is spreading. We therefore recommend that the occurrence of this potentially reemerging zoonosis should be continuously monitored in western and central Europe.
Table 1. Number of patients with alveolar echinococcosis, Europe
Reporting country
Yr of first diagnosis Austria Belgium France Germany
Until 1980 8 0 23 30
1981-1985 12 0 60 11
1986-1990 11 0 80 17
1991-1995 13 0 40 26
1996-2000 10 3 32 48
Total no. of patients (b) 54(1) 3 235 132(6)
Reporting country
Yr of first diagnosis Great Britain Netherlands Switzerland
Until 1980 0 0 43
1981-1985 0 0 29
1986-1990 0 0 17
1991-1995 0 0 16
1996-2000 1 1 13
Total no. of patients (b) 1(1) 1(1) 118(6)
Reporting country
Yr of first diagnosis Poland Greece Total (a)
Until 1980 0 0 104
1981-1985 0 0 112
1986-1990 2 0 127
1991-1995 6 0 101
1996-2000 6 1 115
Total no. of patients (b) 14 1 559
(a) Status of notification to the European
Echinococcosis Registry as of August 2001.
(b) Includes 15 non-autochthonous cases (in parentheses); 7 of them
originated from neighboring countries, 3 from Turkey, 3 from the Newly
Independent States, 1 from Kazakhstan, and 1 from Afghanistan.
Table 2. Possible exposure risks assessed for 210 patients with
alveolar echinococcosis
Activity in agriculture,
gardening, forestry,
hunting
Occupation N (%) Yes No Missing
Farmers 46 (21.9) 46 0 0
Nonfarmers (a) 119 (56.7) 55 56 8
Occupation not specified,
including unemployed and
pensioners 45 (21.4) 28 13 4
Total 210 (100.0) 129 69 12
Ownership of dogs, cats,
or both
Occupation Yes No Missing
Farmers 39 2 5
Nonfarmers (a) 80 13 26
Occupation not specified,
including unemployed and
pensioners 29 6 10
Total 148 21 41
(a) For example, tailors, hairdressers, cooks, nurses, drivers,
teachers, students, and housewives.
Table 3. Diagnostic procedures to ascertain the diagnosis
of alveolar echinococcosis (a)
Histopathology (b) Imaging (c) Serology (d) No. of patients (%)
+ + + 176 (31.5)
+ + - 48 (8.6)
+ - + 19 (3.4)
+ - - 56 (10.0)
Subtotal 299 (53.5)
- + + 192 (34.3)
- + - 25 (4.5)
Subtotal 217 (38.8)
Data not available 43 (7.7)
Total 559 (100.0)
(a) All documented techniques, applied during 6 months after initial
examination. +, positive result in the respective tests/examinations;
-, negative result, tests/examinations not done, or data not available.
(b) Examination of liver tissue samples carried out on material removed
by surgery, diagnostic laparoscopy, or, in rare instances, by fine
needle biopsy.
(c) Comprised one or several examinations, i.e., ultrasound, computed
tomography (CT), or magnetic resonance imagry (MRI) of the abdomen.
In some cases, X-ray, CT, or MRI were available on brain, chest, or
other organs.
(d) Included screening methods using different crude antigen
preparations in indirect hemagglutination or enzyme-linked immunosorbent
assays (ELISA). In addition, purified and recombinant antigen
preparations such as Em2+, Em10 or Em18 were used in ELISA, Western
blot, or both.
Table 4. Location of the primary lesions at first diagnosis in
alveolar echinococcosis
Primary infection site No. of patients
Liver 541 (96.8%)
Spleen, peritoneum, lung, vertebra,
brain, kidneys, heart 13 (2.3%)
Data not available 5 (0.9%)
Total 559
Table 5. Vital status of patients with alveolar echinococcosis,
as of December 2000
No. of patients
Interval between
Yr of first Lost to diagnosis and
diagnosis Alive follow-up Deceased death (yrs)
Until 1980 63 4 37 4-29
1981-1985 73 11 28 <1-14
1986-1990 84 9 34 <1-10
1991-1995 85 6 10 1-4
1996-2000 103 2 10 <1-1
Total 408 32 119
Acknowledgments We thank the hospital and clinic physicians who informed the registry about alveolar echinococcosis cases; students who searched for and extracted data from case report forms; and Alain Gerard, Jacques Beytout, Jerome Watelet, and Thierry Saurin, who made the patients' files available in Nancy, Clermont-Ferrand, and Lyon, France. The pilot phase received financial support of the European Commission, Directorate General V (SOC 97 20239805F01). In Germany, the registry work was additionally financed by the University of Ulm, the Paul-Ehrlich-Gesellschaft e.V., and GlaxoSmithKline GmbH&Co. KG, Munich. In Switzerland, the registry was financed in part by the Swiss National Science Foundation The Swiss National Science Foundation is a science research support organization mandated by the Swiss Federal Government. The SNSF was established in 1952 as a foundation under private law. Its secretariat is based in Berne. , Janssen Pharmaceutica Janssen Pharmaceutica, is a pharmaceutical company based in Beerse, Belgium, was established in 1953 by Dr. Paul Janssen. It was created not as a subsidiary of a chemical factory but solely with the aim of conducting pharmacological research. , Berse, Belgium, the Echinococcosis Foundation in Zurich, and a number of private sponsors. In France, the study received support from the Conseil Regional de Franche Comte (1) The European Echinococcosis Registry (EurEchinoReg) is a surveillance network for human alveolar echinococcosis coordinated by D.A. Vuitton (France) and P. Kern (Germany). Registration of human cases is organized by H. Auer (Austria), Y. Carlier (Belgium), L. Kolarova (Czech Republic), K. Bardonnet (France), P. Kern (Germany), P.S. Craig (Great Britain), I. Prousalidis (Greece), A. Siracusano (Italy), J. van der Giessen (Netherlands), Z. Pawlowski (Poland), E. Renner, R.W. Ammann (Switzerland), and N. Altintas (Turkey). References (1.) Ammann RW, Eckert J. Cestodes. Echinococcus Echinococcus /Echi·no·coc·cus/ (e-ki?no-kok´us) a genus of small tapeworms, including E. granulo´sus, usually parasitic in dogs and wolves, whose larvae (hydatids) may develop in mammals, forming hydatid tumors or cysts chiefly in . Gastroenterol Clin North Am 1996;25:655-89. (2.) Schantz PM, Van den Bossche H, Eckert J. Chemotherapy for larval echinococcosis in animals and humans: report of a workshop. Zeitschrift fur Parasitenkunde 1982;67:5-26. (3.) Wilson JF, Rausch RL, McMahon BJ, Schantz PM. Parasiticidal effect of chemotherapy in alveolar hydatid disease B67.7 Alveolar hydatid disease, also known as Alveolar echinococcosis, Echinococcosis Alveolar and Echinococciasis multilocular is a disease that originates from the parasitic flatworm Echinococcus multilocularis. : review of experience with mebendazole and albendazole in Alaskan Eskimos. Clin Infect Dis 1992;15:234-49. (4.) Bresson-Hadni S, Vuitton DA, Bartholomot B, Heyd B, Godart D, Meyer JP, et al. A twenty-year history of alveolar echinococcosis: analysis of a series of 117 patients from eastern France. Eur J Gastroenterol Hepatol 2000;12:327-36. (5.) Ammann RW, Ilitsch N, Marincek B, Freiburghaus AU. Effect of chemotherapy on the larval mass and the long-term course of alveolar echinococcosis. Swiss Echinococcosis Study Group. Hepatology 1994;19:735-42. (6.) Reuter S, Jensen B, Buttenschoen K, Kratzer W, Kern P. Benzimidazoles in the treatment of alveolar echinococcosis: a comparative study and review of the literature. J Antimicrob Chemother 2000;46:451-6. (7.) Ishizu H, Uchino J, Sato N, Aoki S, Suzuki K, Kuribayashi H. Effect of albendazole on recurrent and residual alveolar echinococcosis of the liver after surgery. Hepatology 1997;25:528-31. (8.) Eckert J, Deplazes P. Alveolar echinococcosis in humans: the current situation in Central Europe and the need for countermeasures. Parasitol Today 1999;15:315-9. (9.) Auer H, Aspock H. Human alveolar echinococcosis and cystic echinococcosis in Austria: the recent epidemiological situation. Helminthologia 2001;38:3-14. (10.) Ammann RW, Fleiner Hoffmann A, Eckert J, Schweizerische Echinokokkose-Studiengruppe (SESG SESG Systems Engineering Steering Group SESG Software Engineering Support Group SESG System Engineering Sub-Group ). Schweizerische Studie fur Chemotherapie der alveolairen Echinokokkose--Ruckblick auf ein 20jahriges klinisches Forschungsprojekt. Schweiz Med Wochenschr 1999;129:323-32. (11.) Romig T, Bilger B, Dinkel A, Merli M, Mackenstedt U. Echinococcus multilocularis in animal hosts: new data from western Europe Western Europe The countries of western Europe, especially those that are allied with the United States and Canada in the North Atlantic Treaty Organization (established 1949 and usually known as NATO). . Helminthologia 1999;36:185-91. (12.) Eckert J, Conraths FJ, Tackmann K. Echinococcosis: an emerging or reemerging zoonosis? Int J Parasitol 2000;30:1283-94. (13.) Giraudoux P, Raoul F, Bardonnet K, Vuillaume P, Toumeux F, Cliquet F, et al. Alveolar echinococcosis: characteristics of a possible emergence and new perspectives in epidemiosurveillance. Medicine des Maladies Infectieuses 2001;31:247-56. (14.) Romig T, Kratzer W, Kimmig P, Frosch M, Gaus W, Flegel WA, et al. An epidemiologic survey epidemiologic survey, n See research, epidemiologic survey. of human alveolar echinococcosis in southwestern Germany. Romerstein Study Group. Am J Trop Med Hyg 1999;61:566-73. (15.) Hegglin D, Bontadina F, Gloor S. From the alpine to the urban fox--adaptive behavior of the red fox (Vulpes vulpes). Advances in Ethology ethology, study of animal behavior based on the systematic observation, recording, and analysis of how animals function, with special attention to physiological, ecological, and evolutionary aspects. 1998;33:119. (16.) Altintas N. Cystic and alveolar echinococcosis in Turkey. Ann Trop Med Parasitol 1998;92:637-42. (17.) Fesseler M. Vergleich der Endemiegebiete yon Echinococcus multilocularis und Tollwut in Mitteleuropa [dissertation]. Zurich: Universitat Zurich; 1990. (18.) Rausch RL, Wilson JF, Schantz PM, McMahon BJ. Spontaneous death of Echinococcus multilocularis: cases diagnosed serologically (by Em2 ELISA ELISA (e-li´sah) Enzyme-Linked Immuno-Sorbent Assay; any enzyme immunoassay using an enzyme-labeled immunoreactant and an immunosorbent. ELISA n. ) and clinical significance. Am J Trop Med Hyg 1987;36:576-85. (19.) Gottstein B, Saucy sauc·y adj. sauc·i·er, sauc·i·est 1. a. Impertinent or disrespectful. b. Impertinent in an entertaining way; impossible to repress or control. 2. F, Deplazes P, Reichen J, Demierre G, Busato A, et al. Is high prevalence of Echinococcus multilocularis in wild and domestic animals associated with disease incidence in humans? Emerg Infect Dis 2001;7:408-12. (20.) Bresson-Hadni S, Laplante JJ, Lenys D, Rohmer P, Gottstein B, Jacquier P, et al. Seroepidemiologic screening of Echinococcus multilocularis infection in a European area endemic for alveolar echinococcosis. Am J Trop Med Hyg 1994;51:837-46. (21.) Nothdurft HD, Jelinek T, Mai A, Sigl B, von Sonnenburg F, Loscher T. Epidemiology of alveolar echinococcosis in southern Germany (Bavaria). Infection 1995;23:85-8. (22.) Malczewski A. CE and alveolar echinococcosis in eastern Europe Eastern Europe The countries of eastern Europe, especially those that were allied with the USSR in the Warsaw Pact, which was established in 1955 and dissolved in 1991. . In: Craig P, Pawlowski Z, editors. Cestode cestode: see Platyhelminthes; tapeworm. zoonoses Zoonoses Infections of humans caused by the transmission of disease agents that naturally live in animals. People become infected when they unwittingly intrude into the life cycle of the disease agent and become unnatural hosts. : echinococcosis and cysticercosis cysticercosis /cys·ti·cer·co·sis/ (sis?ti-ser-ko´sis) infection with cysticerci. In humans, infection with the larval forms of Taenia solium. cys·ti·cer·co·sis n. . Amsterdam: IOS (1) (Internetwork Operating System) An operating system from Cisco that is the primary control program used in its routers. IOS is widely used and robust system software that supports the common functions of all products under Cisco's CiscoFusion architecture. Press; 2002. p. 81-9. (23.) Theodoropoulos G, Kolitsopoulos A, Archimandritis A, Melissinos K. Echinococcose alveolaire hepatique: trois observations en Grace. La Nouvelle Presse Medicale 1978;7:3056. (24.) Tackmann K, Loschner U, Mix H, Staubach C, Thulke HH, Conraths FJ. Spatial distribution patterns of Echinococcus multilocularis (Leuckart 1863) (Cestoda: Cyclophyllidea: Talveolar echinococcosisniidalveolar echinococcosis) among red foxes in an endemic focus in Brandenburg, Germany. Epidemiol Infect 1998;120:101-9. (25.) Kreidl P, Allersberger F, Judmaier G, Auer H, Aspock H, Hall AJ. Domestic pets as risk factors for alveolar hydatid disease in Austria. Am J Epidemiol 1998;147:978-81. (26.) Craig PS, Giraudoux P, Shi D, Bartholomot B, Barnish G, Delattre P, et al. An epidemiological and ecological study of human alveolar echinococcosis transmission in south Gansu, China. Acta Trop 2000;77:167-77. (27.) Stehr-Green JK, Stehr-Green P, Schantz PM, Wilson JF, Lanier A. Risk factors for infection with Echinococcus multilocularis in Alaska. Am J Trop Med Hyg 1988;38:380-5. (28.) Hildreth MB, Sriram S, Gottstein B, Wilson M, Schantz PM. Failure to identify alveolar echinococcosis in trappers from South Dakota in spite of high prevalence of Echinococcus multilocularis in wild canids. J Parasitol 2000;86:75-7. (29.) Aoki S, Uchino J, Sato N, Takahashi M, Shimamura T, Misawa K. Clinicopathological study on alveolar echinococcosis of the liver. In: Uchino J, Sato N, editors. Alveolar echinococcosis: strategy for eradication of alveolar echinococcosis of the liver. Sapporo, Japan: Fuji Shoin Sapporo; 1996. p. 101-7. (30.) Zhou HX, Chai SX, Craig PS, Delattre P, Quere JP, Raoul F, et al. Epidemiology of alveolar echinococcosis in Xinjiang Uygur Xin·jiang Uy·gur also Sin·kiang Ui·ghur or Sin·kiang Ui·gur An autonomous region of extreme western China. It came under Chinese control in the 16th century and was the site of a conflict between China and the Soviet Union in 1969. autonomous region, China: a preliminary analysis. Ann Trop Med Parasitol 2000;94:715-29. (31.) Sailer Sail´er n. 1. A sailor. 2. A ship or other vessel; - with qualifying words descriptive of speed or manner of sailing; as, a heavy sailer; a fast sailer s>. M, Soelder B, Allerberger F, Zaknun D, Feichtinger H, Gottstein B. Alveolar echinococcosis of the liver in a six-year-old girl with acquired immunodeficiency syndrome acquired immunodeficiency syndrome, see AIDS. . J Pediatr 1997;130:320-3. (32.) Bresson-Hadni S, Koch S, Beurton I, Vuitton DA, Bartholomot B, Hrusovsky S, et al. Primary disease recurrence after liver transplantation for alveolar echinococcosis: long-term evaluation in 15 patients. Hepatology 1999;30:857-64. Address for correspondence: Petra Kern, Dept. for Biometry biometry /bi·om·e·try/ (bi-om´e-tre) the application of statistical methods to biological phenomena. bi·om·e·try n. The statistical analysis of biological data. Also called biometrics. and Medical Documentation, University of Ulm, Schwabstr. 13, D-89075 Ulm, Germany; fax: (0049) 731-5026902; e-mail: echinoreg@medizin.uni-ulm.de Petra Kern, * Karine Bardonnet, ([dagger]) Elisabeth Renner, ([double dagger]) Herbert Auer, ([section]) Zbigniew Pawlowski, ([paragraph]) Rudolf W. Ammann, ([double dagger]) Dominique A. Vuitton, (#) Peter Kern, ** and the European Echinococcosis Registry (1) * University of Ulm, Ulm, Germany; ([dagger]) University Hospital, Besancon, France; ([double dagger]) University Hospital Zurich, Zurich, Switzerland; ([section]) University of Vienna History The University was founded on March 12, 1365 by Duke Rudolph IV and his brothers Albert III and Leopold III, hence the additional name "Alma Mater Rudolphina". After the Charles University in Prague, the University of Vienna is the second oldest university in Central , Vienna, Austria; ([paragraph]) University of Medical Sciences, Poznan, Poland; (#) University of Franche Comte, Besancon, France; and ** University Hospital Ulm, Ulm, Germany Dr. Kern is a research assistant at the Department of Biometry and Medical Documentation at the University of Ulm, Germany. She is responsible for the data collection of human cases of alveolar echinococcosis, data control, and analysis in the European Echinococcosis Registry. |
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