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Alveolar echinococcosis in humans: the current situation in Central Europe and the need for countermeasures.

Alveolar echinococcosis (AE) in humans is caused by a larval stage (metacestode) of Echinococcus multilocularis, which exhibits a tumor-like growth, initially in the liver, with the potential to induce serious disease. At the end of the 1980s, E. multilocularis was known to occur in four countries of Central Europe, but has now been identified in ten countries. Red foxes are the principal definitive hosts of E. multilocularis and sources of human infection, but dogs and cats can also be infected. Growing populations of foxes and their increasing immigration to urban areas are new risk factors. Human AE is rare but its potential high fatality rate, considerable costs of treatment and the persisting infection risk should be reasons for health authorities in European countries to establish coordinated systems of surveillance and risk assessment in combination with measures to reduce morbidity and mortality of AE in the human population. Here, J. Eckert and P. Deplazes outline the current epidemiological situation in Central Europe, and discuss options for surveillance, prevention and control.

Animals↗

Cerebral cysticercosis and echinococcosis: a preoperative diagnostic dilemma.

BACKGROUND: Seven cases of neurocysticercosis and three cases of neuroechinococcosis with symptoms of elevated intracranial pressure requiring urgent neurosurgical treatment are described. No neuroradiologic procedure established exact diagnosis preoperatively; this was achieved by pathohistologic analysis of bioptic material. METHODS: Ten patients with duration of clinical symptoms ranging from 1 week to 1 month were operated on at the Department of Neurosurgery of Sestre Milosrdnice University Hospital in Zagreb, Croatia during the period 1988-2000. On receipt, bioptical material was examined pathohistologically at the Ljudevit Jurak Clinical Department of Pathology of the same hospital. We compared our data with facts collected by reviewing the pertinent literature over the past 10 years. RESULTS: The most common localization of parasitic cysts in our study was posterior cranial fossa, i.e., subtentorial, which, according to the literature, is a rare localization. Due to this unusual localization, dominant clinical symptoms included elevated intracranial pressure, requiring urgent surgical removal of parasitic cysts. CONCLUSIONS: With the exception of the epidemiologic aspect, cerebral cysticercosis and echinococcosis are important as a true diagnostic and therapeutic problem. These human parasitic zoonoses are rarely diagnosed preoperatively despite newly developed neuroradiologic and serologic methods, especially in cases of primary appearance in brain when exact diagnosis reveals adequate surgical removal with subsequent complete recovery.

Adult↗

Skin localization of alveolar echinococcosis of the liver.

Alveolar echinococcosis is a rare parasitic disease caused by the intrahepatic growth of Echinococcus multilocularis larvae. Secondary localizations can be observed; pulmonary metastases are the most frequent and are observed in 22% of patients. Other extrahepatic localizations are less frequent. We describe two patients with abdominal skin involvement. To our knowledge, this has never before been reported. In both patients, the liver lesion was located in the left lobe, and larvae probably spread to the skin via the falciform ligament. In one patient albendazole therapy was effective.

Aged↗

The Echinococcus multilocularis 14-3-3 protein protects mice against primary but not secondary alveolar echinococcosis.

Alveolar echinococcosis (AE), caused by the larval stage (metacestode) of the tapeworm Echinococcus multilocularis, exhibits very similar disease characteristics in humans and rodents. Recently, it has been shown that an over-expression of the parasite 14-3-3 protein could be associated to the proliferative growth of the E. multilocularis metacestode. We now demonstrate the expression of this protein at the E. multilocularis oncospheral stage as well. A recombinant E. multilocularis 14-3-3 protein (E14t) was used to vaccinate mice against either primary or secondary experimental E. multilocularis infection in BALB/c mice. Conversely to non-vaccinated but control infected mice, which developed a very weak anti-E14t response during infection, the response elicited in the E14t-vaccinated and subsequently infected animals exhibited a strong reactivity against the parasite 14-3-3 protein. Major differences became apparent between secondarily and primarily infected animals: whereas no protection against secondary infection was achieved by vaccination, vaccinated animals were protected by 97% against challenge primary infection with 2000 E. multilocularis eggs. Consequently, the parasite 14-3-3 molecule appears crucially involved in the early stage of the host-parasite interplay and exhibits potential to be used as target molecule for the development of protective tools against AE.

14-3-3 Proteins↗

Veterinary aspects of alveolar echinococcosis--a zoonosis of public health significance.

Human alveolar echinococcosis (AE), caused by the metacestode stage of Echinococcus multilocularis, is a serious zoonosis which caused up to 100% lethality in untreated patients before the 1970s, when modern methods of treatment were not yet established. AE occurs in large areas of the northern hemisphere mostly with low country-wide prevalences, but high prevalences of up to 4% have been reported from small population groups in highly endemic foci, e.g. from China. AE includes many veterinary aspects which are the topic of this review. Recent studies have shown that E. multilocularis has a wider geographic range than previously anticipated. There is evidence for growing populations of red foxes (Vulpes vulpes) in some areas, for increasing invasion of cities by foxes and also for establishment of the parasite cycle in urban areas. These and other factors may lead to an increased infection risk for humans. Significant progress has been made in the development of sensitive and specific new techniques for the intra vitam and post mortem diagnosis of intestinal E. multilocularis infection in definitive hosts, notably the detection of coproantigen by enzyme-linked immunosorbent assay and of copro-DNA by PCR. Both tests can also be used for the identification of E. multilocularis in faecal samples collected in the environment. Recommendations are given for chemotherapy and chemoprophylaxis of the intestinal infection in definitive hosts. In recent years, infections with the metacestode stage of E. multilocularis have not only been diagnosed in humans in several regions, including at least eight countries in central Europe, but also in animal species which do not play a role in the transmission cycle (wild and domestic pigs, dogs etc.). From 1987 to 2000 our group in Zurich has diagnosed 10 cases of AE in dogs and 15 in captive monkeys. In 2 dogs, concurrent infections of the intestine and of the liver with adult and larval stages of E. multilocularis, respectively, were observed for the first time. Clinical data are presented, and methods of diagnosis and treatment (surgery, chemotherapy) are described. Furthermore, small liver lesions caused by E. multilocularis were diagnosed in 10% of 90 slaughter pigs, and 2.9% of 522 breeding sows had specific serum antibodies against parasite antigens. In view of the unpredictable epidemiological situation, all possible measures for preventing E. multilocularis infections in humans and in domestic animals should be initiated by the veterinary and health authorities.

Animals↗

Cystic echinococcosis in Algeria: cattle act as reservoirs of a sheep strain and may contribute to human contamination.

In Algeria, cystic echinococcosis (CE) is a serious economic and public health problem. The common sheep/dog cycle is usually considered as the major source of human contamination. But to date the main strain of Echinococcus granulosus involved in the human contamination and the role of other hosts are still unknown. This paper reports an original work performed in northern Algeria combining field observations and molecular analysis. In a first step, examination of 6237 carcasses in slaughterhouses showed high infection and fertility rates in cattle and dromedaries. Then, in a second step, we used a molecular biology approach to identify the E. granulosus strain(s) involved. Forty-six samples from various origins were collected. They were analysed using comparison of PCR-amplified DNA sequences with one genomic (BG 1/3) and two mitochondrial (COI and NDI) targets. Results show the presence of a "sheep" strain of E. granulosus in North Algeria circulating between cattle and ovines and infectious to humans, whereas in South Algeria, a "camel" strain and a "sheep" strain were found to circulate in camels and in sheep, respectively. This study also reports an ambiguous genotype which resembled the "sheep" strain genotype (Gl) on the basis of the partial COI gene sequence, whereas on the basis of the partial NDI gene sequence, it was similar either to the "sheep" strain (Gl) or to the "camel" strain (G6). Besides its basic interest, our study confirms the role of other hosts (mainly cattle) in leading to transmission to humans and suggests that control measures should not only target sheep.

Algeria↗

Canine echinococcosis: an alternative for surveillance epidemiology.

The essential activities for programmes of cystic echinococcosis control are the census of all dogs from the program and identification of parasitised animals. Currently, in South America evaluations and epidemiological surveillance are based on the administration of arecoline hydrobromide. This method has the disadvantage of increasing environmental pollution and risk for operators and owners of treated dogs. A genus-specific ELISA capture method has been employed for recently issued faeces and the confirmation of positive examination was performed by dog autopsies. Our work presents an alternative method based on collection of dry field-dispersed faeces, followed by serological diagnosis by Copro-ELISA and confirmation by Copro-Western blot. If Copro-ELISA were used to define positive samples of dry faeces, the Copro-Western blot assay would provide 70% sensitivity and 100% specificity. Global efficiency of the system using dry faeces would reach 76%, allowing epidemiological surveillance to be oriented to analysis of surface units instead of dog as measurement unit.

Animals↗

Hepatic alveolar echinococcosis: MRI findings.

The purpose of this study was to describe the magnetic resonance imaging (MRI) appearance of hepatic alveolar echinococcosis (HAE) on T(1)-weighted, T(2)-weighted and postgadolinium images. A total of 13 lesions were demonstrated in 13 patients. All patients underwent MR examination at 1 T imager. MR examinations included precontrast T(1)-weighted breathing averaged spin echo (SE), breath-hold spoiled gradient echo, T(2)-weighted TSE sequences with and without fat suppression, and T(1)-weighted breath-hold spoiled gradient echo (SGE) sequence following i.v. after gadolinium administration. All lesions were confirmed with histopathology. HAE hepatic lesions revealed geographic patterns of variable signal intensities on noncontrast T(1)- and T(2)-weighted images. Slightly hyperintense, iso- and hypointense signal on T(1)-weighted images corresponded to calcified regions, which appeared hypo-isointense signal on T(2)-weighted images. Necrotic areas were hypointense signal on T(1)-weighted and hyperintense signal on T(2)-weighted images. On postgadolinium images, lesions did not reveal enhancement. Dilatation of intrahepatic bile ducts distal to HAE abscesses were observed in five patients and portal vein invasion or compression was observed in four patients, lobar atrophy of the liver was coexistent finding in cases with portal vein compression. The MRI appearance of HAE abscesses included large irregularly marginated masses with heterogenous signal on T(1)- and T(2)-weighted images and lack of enhancement with gadolinium.

Adult↗

Karyological and dental identification of Microtus limnophilus in a large focus of alveolar echinococcosis (Gansu, China).

A study of voles (Arvicolidae, Rodentia) from Gansu (China) designed to identify a potential host of Echinococcus multilocularis, responsible for human alveolar echinococcosis, leads to a general analysis of Microtus limnophilus population karyotypes, M1 of M. oeconomus populations from all of Eurasia and of M. limnophilus of Mongolia. The Microtus of Gansu belonging to the nominal subspecies M. limnophilus limnophilus (2n = 38; NF = 58) differs markedly in size and shape of M1 from the M. limnophilus of Mongolia, which must therefore be considered as a new subspecies M. limnophilus of malygini nov. ssp. (2n = 38; NF = 60) and the M. oeconomus of Mongolia should be ranked as M. oeconomus kharanurensis nov. ssp. (2n = 30; NF = 60).

Animals↗

MRI findings of hepatic alveolar echinococcosis.

Diagnosis of liver infestation by alveolar echinococcosis (AE) is based on serologic, sonographic and computed tomography (CT) findings. Experience with magnetic resonance imaging (MRI) demonstrates that features of this disease are limited. CT and MRI findings of 14 cases with hepatic AE were compared in this report. We have described the MRI appearance of hepatic AE, which exhibits variable signal intensities on T1- and T2-weighted images. Fibrous and parasitic tissue showed low signal both on T1- and, generally, on T2-weighted images. In a few cases, a high signal on T2-weighted images may be observed, due either to central necrotic zones or to small peripheral cyst. MRI than by CT was more easily identified central necrosis. However, MRI seemed to be less effective than CT in allowing us to reach a positive diagnosis, due to its inability to show microcalcifications. In addition, MRI may not reveal small lesions. In most cases, T1-weighted images revealed more clearly than CT did the margins of the lesions and the hepatic extension, especially to hepatic veins, vena cava and perihepatic spaces.

Adult↗

Double aldehyde stabilisation of erythrocytes in the indirect hemagglutination for echinococcosis.

Sheep erythrocytes were stabilised with glutaraldehyde tanned and fixed with formalin in the indirect hemagglutination test (IHA-GF) and sensitised with hydatid antigen for the diagnosis of human cystic echinococcosis (CE). The sensitivity of this method was compared to that prepared with fresh tanned cells (IHA-TA) in 278 sera from hydatid patients. The sensitivity of IHA-GF (87.8%) was higher than that of IHA-TA (85.6%), the difference being insignificant. Higher geometric mean titres were obtained by IHA-GF (1:13300) than by IHA-TA (1:11600). The use of two sorts of aldehydes proved to be a satisfactory method, showing high sensitivity, a very good specificity and some advantages. The sensitised cells retained their diagnostic effectiveness for at least 15-18 months when stored at 4 degrees C. The technique is inexpensive and rapid, allowing the testing of a large number of sera. The method reduces the variation of the results and improves the reproducibility of the test. When the minimal diagnostic titre-1:400 is used the specificity of IHA-GF might increase by 2.9% while the sensitivity might decline by only 1.4%. The IHA-GF demonstrated better immunodiagnostic characteristics than enzyme linked immunosorbent assay (ELISA) and Latex agglutination test (LAT). The IHA-GF should be considered as an useful method in the range of classical diagnosis for the serology of CE. The clinical diagnostic potential should be increased by a combination of at least two tests: IHA-GF and ELISA or LAT.

Animals↗

The development of new foci of echinococcosis in northern Israel: prevalence in domestic animals.

In a survey carried out in 1991-1992 in the town of Yirka in Northern Israel, 49 dogs were examined for Echinococcus granulosus infection and abattoir data, based on organs condemned for the presence of parasites, was collected. The presence of E. granulosus by arecoline test was demonstrated in 7 (14.2%) of the dogs examined, but not parasites were found in the intestines of five stray dogs shot in the area. A survey of sheep slaughtered in the local abattoir during a one-month period revealed Echinococcus cysts in 10% of the 255 animals examined. No Echinococcus parasites were detected in 21 dogs examined 3 months after the initiation of praziquantel treatment. Echinococcosis seems to be a very serious public health problem in Israel and a control programme needs to be given a high priority.

Abattoirs↗

Em18 and Em16, new serologic marker epitopes for alveolar echinococcosis in western blot analysis, are the only two epitopes recognized by commercially available weak positive (cut off) sera for Em2plus-ELISA.

The assay system for antibody responses against Em2, the most specific antigen for serodiagnosis of alveolar echinococcosis (AE), has been established by enzyme-linked immunosorbent assay (ELISA) but not by Western blot assay, since Em2 antigen is not protein but carbohydrate in nature. Recently we reported that previously undescribed protein epitopes, designated Em18 and Em16 due to their molecular weights, were good serologic markers for AE by Western blot analysis. It has been shown that Em18 and Em16 are the only two epitopes recognized by commercially available weak positive (cut off) sera for the Em2plus-ELISA.

Antibodies, Helminth↗

Path analysis: application in an epidemiological study of echinococcosis in New Zealand.

The method of path analysis is described in detail. Application of this analyogical systems is demonstrated using data from an epidemiological study of echinococcosis in New Zealand. The results identified the major causal pathways determining Echinococcus granulosus prevalence in dogs, based on multiple regression analysis of a linear causal model constructed from prior biological and epidemiological knowledge. Only ethnic and sheep husbandry variables had important direct effect on prevalence in the North Island of New Zealand, with some climate factors (maximum temperature and relative humidity) and soil porosity acting indirectly through animal husbandry practices. It is suggested that path analysis, by permitting interaction between epidemiological theory and statistical analysis, provides a valuable additional tool to epidemiologists for the study of causal relationships among variables in multivariates systems.

Animals↗

Population dynamics in echinococcosis and cysticercosis: comparison of the response of Echinococcus granulosus, Taenia hydatigena and T. ovis to control.

A comparative study has been made of the progress in the control of ovine echinococcosis caused by Echinococcus granulosus and the ovine cysticercoses caused by Taenia hydatigena and T. ovis in New Zealand. The methods of control included an educational and a dog-dosing programme. In the Styx field trial, the Otago/Southland Surveillance Programme and the national control programme, E. granulosus declined towards extinction. In contrast, this same control effort transformed the cysticercoses from hyper-endemic to endemic status with focal epidemics. In this unstable state, the density-dependent constraint was negligible and superinfection occurred.

Animals↗

Molecular epidemiology of cystic echinococcosis.

Echinococcus granulosus exhibits substantial genetic diversity that has important implications for the design and development of vaccines, diagnostic reagents and drugs effective against this parasite. DNA approaches that have been used for accurate identification of these genetic variants are presented here as is a description of their application in molecular epidemiological surveys of cystic echinococcosis in different geographical settings and host assemblages. The recent publication of the complete sequences of the mitochondrial (mt) genomes of the horse and sheep strains of E. granulosus and of E. multilocularis, and the availability of mt DNA sequences for a number of other E. granulosus genotypes, has provided additional genetic information that can be used for more in depth strain characterization and taxonomic studies of these parasites. This very rich sequence information has provided a solid molecular basis, along with a range of different biological, epidemiological, biochemical and other molecular-genetic criteria, for revising the taxonomy of the genus Echinococcus. This has been a controversial issue for some time. Furthermore, the accumulating genetic data may allow insight to several other unresolved questions such as confirming the occurrence and precise nature of the E. granulosus G9 genotype and its reservoir in Poland, whether it is present elsewhere, why the camel strain (G6 genotype) appears to affect humans in certain geographical areas but not others, more precise delineation of the host and geographic ranges of the genotypes characterised to date, and whether additional genotypes of E. granulosus remain to be identified.

Animals↗

Cystic echinococcosis: analysis of the serological profile related to the risk factors in individuals without ultrasound liver changes living in an endemic area of Tacuarembó, Uruguay.

Cystic echinococcosis (CE) is a high prevalence zoonosis among the rural population of Tacuarembó (Uruguay). The correlation between serological data and the incidence of risk factors was studied in a survey carried out in 1998 among rural communities where 480 individuals were examined by means of abdominal sonography (local prevalence = 0.8%). Serum samples (305) were analysed by ELISA to determine specific IgG against crude antigens from Echinococcus granulosus. A total of 27 individuals exhibiting no detectable changes in abdominal sonographic examination were found to be seropositive ('ultrasound normal group'). Of these individuals 9 were seroreactive against purified antigen B. A significant degree of correlation was found between seroreactivity and the incidence of some risk factors (CE antecedent in the family, P < 0.005 and use of rural water, P < 0.0001) among this group. Follow-up of individuals of the 'ultrasound normal group' was carried out after 2 years to evaluate the implications of this serological reactivity. No predictive value for cyst development was assessed with complementary image study; in contrast transient antibodies were observed with both crude and purified antigen as approximately 60% of individuals became negative when re-sampled.

Adult↗

Genotyping of human cystic echinococcosis in Xinjiang, PR China.

The Xinjiang Uygur Autonomous Region, multi-ethnic province in northwestern China, is one of the most important foci of human cystic echinococcosis (CE) in the world. Two Echinococcus granulosus genotypes (G1 and G6) are known to infect the intermediate hosts in this area but, to date, the source of the human infection remains unclear. The current study aimed to genetically analyse 67 hydatid cysts removed from 47 CE patients for which epidemiological, clinical and serological data were also recorded. Mitochondrial cox 1 gene sequencing suggested that the E. granulosus G1 genotype is the major source of infection (45/47 CE patients). Nevertheless, for the first time in China, 2 patients were found with hydatid cysts of the G6 genotype. In addition, 45 E. granulosus gravid tapeworms, isolated from 13 dogs, were genotyped. The majority of adult worms (42/45) exhibited the G1 genotype, whereas 3 adult tapeworms with the G6 genotype were found in one dog, that also harboured E. granulosus tapeworms of the G1 genotype. This sympatric occurrence of G1 and G6 genotypes of E. granulosus, not only in the same area but also in the same definitive host, raises the interesting question of putative genetic recombination between these E. granulosus genotypes.

Adolescent↗