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Human cystic echinococcosis in Kyrgystan: an epidemiological study.

Human cystic echinococcosis (CE), caused by Echinococcus granulosus, is an emerging disease in central Asia. This study examined official data on the incidence of CE between 1991 and 2000 and studied routine hospital records in the main surgical hospitals in Bishkek, Kyrgystan, between 1990 and 2000. In addition, a cross-sectional ultrasound study of a rural population was undertaken in northern Kyrgystan. The results of this study have indicated that the annual incidence of CE over the whole of Kyrgystan has increased from 5.4 cases per 100,000 in 1991 to 18 cases per 100,000 in 2000. Likewise, hospital admissions in Bishkek, due to CE, have increased from an estimated 21 cases in 1990 to approximately 127 and 124 in 1998 and 1999, respectively. Similarly, paediatric cases have increased from 2 in 1990 to 82 in 2000. There was no obvious association with occupation of affected adults although a disproportionate number of hospital cases were registered as unemployed compared to the general population. Whilst there was no gender difference in hospital admissions amongst children, men were more likely to undergo hospital treatment than women. Fifty percent of cysts were recorded as hepatic cysts with forty seven percent recorded as pulmonary cysts. Analysis of the data suggests that the likelihood of an affected patient having a hepatic cyst decreased with age. The results of the cross-sectional study indicated that 20 of 1486 subjects (1.35%) examined by ultrasound had an abdominal hydatid cyst. By extrapolating the ratio of pulmonary to hepatic cysts recorded in the hospital population and adjusting for age it is possible that as much as 3.4% of the rural population may have sub-clinical CE. Analysis of the possible risk factors in the cross-sectional study revealed that subjects who had CE were less likely to use well water as their water supply than non-infected subjects.

Adult↗

Overview of the epidemiological situation on echinococcosis in the Mediterranean region.

Cystic echinococcosis due to its considerable morbidity rates, in the populations of the Mediterranean region, give rise to high economic losses both in the public health sector and the animal production industry. Medium to high infection rates in man are recorded in most of the Mediterranean countries. Public awareness of hydatid disease is rather low in most of these countries. Difficulties in early diagnosis, the prevalent occurrence in rural areas with weak systems of health care, the favourable conditions created by man, as well as the climatic and ecological ones, are factors contributing to the prevalence of the infection. Small, ill-equipped and unsupervised slaughter-houses, illegal slaughtering, high population of stray dogs, etc., are known to be the main sources of infection. Echinococcus granulosus is the species present in nearly all countries of the regions while E. multilocularis infection is limited to a few of them. Accurate data on the incidence of human hydatid disease in the region are not available as it is notifiable in only a few countries.

Animals↗

Hydatidosis-echinococcosis in Greece.

Hydatidosis/echinococcosis (Echinococcus granulosus infection) is considered to be a serious problem for both public health and the livestock economy in Greece. The present paper reviews and summarizes all data available on this disease since 1970. The disease was widely prevalent long before the 1970s. At that time the annual surgical incidence rate was 12.9 per 100000 inhabitants. As a result of the seriousness of the disease, the Greek Department of Veterinary Services initiated an anti-echinococcosis campaign in 1984. When the program started, the prevalence of infection in farm animals was 82% in cattle, 80% in sheep, 24% in goats and 5% in pigs. Data obtained in a survey in Northern Greece in 1994, recorded the prevalence of CE as 100% in sheep, 56.6% in cattle, 15.4% in goats and 9.3% in pigs; sheep had not only more cysts but significantly higher rates of fertile cysts (e.g. contained viable protoscolices) than intermediate host species examined. Serologic surveys (specific IgG) in humans carried out between 1988 and 1999 had shown seroprevalence up to 29%. Surveillance in livestock species, since 1998, carried out as part of an European Union (E.U.) project, have documented the prevalences of CE in sheep (31.3%), in goats (10.3%), in pigs (0.6%) and in cattle (0%). The official campaign against this zoonosis in Greece is ongoing. It is concluded that since hydatidosis/echinococcosis is still present, surveillance and intervention measures should be continued to track the course of the infection and to eliminate risk to humans.

Animals↗

Retrospective surgical incidence and case distribution of cystic echinococcosis in Jordan between 1994 and 2000.

A retrospective follow-up study on the surgical incidence of cystic echinococcosis (CE) was carried out in major governmental, military and private hospitals throughout Jordan between 1994 and 2000. A total of 472 cases were recorded over the 7-year period and an overall mean annual surgical incidence (MASI) of 2.3 per 100,000 inhabitants was estimated. The highest number of surgical cases was recorded in hospitals of the middle region of the country. The highest MASI (3.6 per 100,000) was found in the southern region while the lowest (1.4 per 100,000) was in the northern region of the country. Taking into consideration the population size and the origin of surgically confirmed cases of each region, a relative surgical index (RSI) was calculated at which the highest (RSI=3.4) was among cases originated from the southern region and the lowest (RSI=0.7) was among those originated from the middle region of Jordan. The northern region and desert areas (badia) showed comparable RSI at 1.0 and 1.1, respectively. Males younger than 15 years of age showed significantly higher surgical incidence than females of comparable age at a ratio of 1.6:1, whereas the number of female cases of different age groups over 15 years of age was consistently higher than that of males at a ratio of 1.25-2.5:1.0. The liver was the primary site of cyst development in 69.4% of the cases and the lung involvement accounted for 13.3% of the cases. Diagnosis of CE in Jordan relies mostly on imaging methods with serological techniques being rarely used for diagnosis. The frequency of CE recurrence was 27.5% of the cases, which may be attributed to the low use of chemotherapeutic antihelminthics among surgically treated cases.

Adolescent↗

T-lymphocyte cytokine mRNA expression in cystic echinococcosis.

In the present study we investigated cytokine mRNA expression by peripheral blood mononuclear cells (PBMC) from patients with cystic echinococcosis (CE) after stimulation with different antigens. By using reverse transcriptase polymerase chain reaction (RT-PCR) we could demonstrate that restimulation with crude Echinococcus granulosus antigen (Eg-Ag) induced or enhanced Th2 cytokine mRNA expression, especially IL-5 (by using antigen from sheep cyst fluid) in 23 out of 26 investigated CE patients and IL-10 (by using antigen from camel cyst fluid) in 10 out of 10 investigated CE patients. In contrast, IL-5 mRNA expression was absent in PBMC of healthy controls after Eg-Ag stimulation. To determine the specificity of this reaction we stimulated PBMC from 11 CE patients with crude Echinococcus multilocularis antigen (Em-Ag) and PBMC from 8 CE patients with Toxocara canis antigen (Tc-Ag). We found that the PBMC of patients showed a similar mRNA cytokine pattern on stimulation with Em-Ag when compared with Eg-Ag stimulation. The cytokine mRNA pattern on stimulation with Tc-Ag, however, resembled the cytokine mRNA pattern of unstimulated PBMC. Furthermore, the stimulation of PBMC with crude Mycobacterium tuberculosis antigen (H37Ra) and purified protein derivative (PPD) of M. tuberculosis revealed distinct IL-5 mRNA expression in all investigated CE patients, whereas in healthy controls IL-5 mRNA expression was very weak or totally absent. Thus, our results indicate an induction of Th2 cytokine mRNA expression in CE patients, which is frequently observed in parasite infections. Interestingly, this response persists after stimulation with tuberculosis antigens, which normally induce Th1 response.

Adolescent↗

Albendazole in treatment of human cystic echinococcosis: 12 years of experience.

This review paper examines the evidence from published and previously unpublished sources for the efficacy and safety of albendazole (ABZ) obtained in the last 12 years. Benzimidazole treatment alone is not ideal, requiring prolonged administration over many weeks, with an unpredictable outcome in terms of response rates in individuals. However, studies have shown that treatment with albendazole in E. granulosus infection can result in an apparent cure in up to 30% of cases, with a further 40-50% showing objective evidence of response when followed in the short term. Some studies have demonstrated that even patients who do not show obvious initial evidence of response may be found to be cured when followed up over several years. Duration of therapy and dose are also important, and with ABZ, efficacy seems to increase with exposure up to 3 months in the commoner cyst sites. Formal dose ranging and minimal effective dose studies have not been performed, but the current dose of 800 mg daily appears to be adequate. The issue of cyclical versus continuous treatment still has to be resolved. Data on ABZ safety has been accumulated over the past 12 years of marketing. The profile shows that liver function abnormalities are common although rarely treatment limiting, while occasional hematological changes affecting the white cells may be more serious. The safety data supplies the rationale for monitoring of patients during treatment. On balance ABZ has been shown to be a useful advance in the management of cystic echinococcosis both when used as sole treatment or as an adjunct to surgery or other treatments.

Albendazole↗

Principles of the surgical approach in human liver cystic echinococcosis.

Ultrasonography (USG) has recently contributed much to the diagnostic of hepatic cystic echinococcosis (CE). The use of portable ultrasonograph allowed us to perform a community survey among 9482 people living in a high risk area for CE in the Florida Department (Uruguay). Positive USG results were found in 123 asymptomatic patients. 48 out of 51 USG positive cases were surgically confirmed and 3 were found to be false positive. The results of this survey allowed us to propose a new classification of the echographic imaging based on the parasite's various evolutive and involutive stages. The Echinococcus granulosus cyst size was compared with the parasite's evolutive stages. The cyst's segmentary topography and the related risk of CE is evaluated. The importance of cystic-biliary communication is pointed out and its rational surgical treatment described. Finally, an algorithm is presented facilitating the choice of a rational treatment.

Adolescent↗

Public health aspects of cystic echinococcosis in the Arab countries.

Human cystic echinococcosis (CE) caused by larval Echinococcus granulosus is a zoonosis of major public health importance throughout the region comprising Arab North Africa and the Middle East. Prevalence rates are determined by epizootiological factors related to the size of stray dog population and its worm burden and to the infection rates in the intermediate host reservoir livestock population. Socio-economic development and socio-cultural practices are considered important determinants in the continued transmission of the disease. The reasons why CE remains a significant public health problem in the region are summarized.

Animals↗

Public health importance of cystic echinococcosis in China.

Cystic echinococcosis has been recorded in 21 out of China's 31 provinces, autonomous regions and municipalities (approximately 87% of territory). It constitutes one of the major public health problems, especially in several northwestern provinces and autonomous regions. This paper reviews the general situation, diagnosis, treatment, education and control programmes and international cooperation. Special attention is given to the Xinjiang, an endemic area about one sixth of the country's area with a human population of approximately 16 million.

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Expression and immunological characterisation of Echinococcus granulosus recombinant antigen B for IgG4 subclass detection in human cystic echinococcosis.

A 165bp DNA fragment derived from the 12 kDa subunit of Echinococcus granulosus antigen B (AgB), a major hydatid cyst fluid antigen was cloned in the pMa1-c2 expression vector. A 52 kDa maltose binding-AgB fusion protein (rAgB.MBP) was produced and inclusion bodies containing the fusion protein were solubilised in urea and affinity purified on an amylose-Sepharose 6B column. The immunogenicity of the purified recombinant antigen for IgG4 antibody detection was tested with human serum using immunoblotting, ELISA and dot-ELISA assays and compared to native AgB. Both recombinant and native AgB preparations were highly reactive for human IgG4 antibodies in serum of cystic echinococcus (CE) patients. Recombinant AgB.MBP (rAgB.MBP) showed approximately 65% sensitivity in detection of IgG4 serum antibodies by ELISA from confirmed CE patients. Cross-reactivity (33%) occurred with alveolar echinococcosis (E. multilocularis) sera but recombinant AgB showed no seroreactivity with sera from other helminth infections tested (schistosomsis, onchocercsis, cysticercosis) or from uninfected individuals residing in CE endemic or non-endemic regions. The serologic sensitivity (63%) for IgG4 antibodies of a native AgB fraction enriched from human hydatid cyst fluid was similar to that for recombinant AgB (65%) though specificity was slightly lower (81%). A dot-ELISA for detection of total IgG, incorporating the rAgB.MBP resulted in 74% sensitivity and 88% specificity for human CE and 93% sensitivity and 65% specificity for native AgB. Recombinant AgB is a potential replacement for native antigens currently being used and could provide a better standardised E. granulosus specific test for clinical confirmation for CE especially for IgG4 antibody detection which appears to be predominantly associated with advanced disease.

Animals↗

Ultrasound imaging in cystic echinococcosis. Proposal of a new sonographic classification.

The ultrasonography permits the study of the natural history of cystic echinococcosis (CE) and evaluation of stages of the parasitic pathology. The evolution of abdominal CE was studied in 54 patients suffering from 97 abdominal cysts treated with albendazole, in 20 patients suffering from 20 hepatic cysts treated with echoguided percutaneous ethanol injection and in 39 patients suffering from 42 abdominal cysts, but left untreated. A new sonographic classification is suggested. Type I: Simple CE; (a) overall echofree; (b) with fine echos. Type II: Multiple CE; (a) multiple contiguous; (b) multiseptated with rosette, honeycomb and wheel-like pattern. Type III: With detachment of endocyst CE; (a) with double layer image; (b) with water-lily sign. Type IV: Mixed type CE; with fluid and solid aspect. Type V: Heterogeneous CE; (a) with ball of wool pattern; (b) with hypoechogenic image. Type VI: Hyperechoic CE; (a) with snow-storm pattern; (b) with dyshomogeneous aspect. Type VII: Calcified CE; (a) with advanced calcification of the layer only; (b) with calcification of overall cyst. This classification appears more appropriate to the natural history of CE and permits a better differential diagnosis and more suitable treatment.

Albendazole↗

Interleukin (IL)-4, IL-10 and IL-12 profile in serum of patients with alveolar echinococcosis.

Alveolar echinococcosis (AE), caused by Echinococcus multilocularis (E.m.), provokes a characteristic immune response. Based mainly on in vitro studies, Th2 dominated immunity is associated with increased susceptibility to disease, while Th1 cell activation is assumed to induce protective immunity. We investigated serum levels of interleukin (IL)4, IL-10, and IL-12 in 40 AE patients and 20 controls to assess Th1/Th2 cell activation in vivo. Significantly higher levels of IL-10 were found in AE patients (P = 0.003) than in controls, with a tendency to higher concentrations in progressive cases. In contrast, IL-4 was only measurable in a minority of patients and controls. IL-12 levels (measured with an ELISA that detects both the p35/p40 heterodimer and free p40) were comparable between AE patients and controls and showed a similar distribution pattern to IL-10 with regard to disease progression. By using an IL-12-ELISA specific for the heterodimer, only minute amounts of IL-12 were detectable in merely a minority of samples. In conclusion, our data are suggestive of Th2 dominated immune response in AE in vivo.

Adult↗

Echinococcosis of the heart: clinical and echocardiographic features in 19 patients.

We describe clinical and echocardiographic features in 19 patients with cardiac echinococcosis. Wide variability in the location and number of cysts inside cardiac cavities, septum, and pericardium is observed. The central role of two-dimensional echocardiography in making the diagnosis is stressed. This report has a significant clinical value in view of the large number of cases of a relatively rare condition.

Adolescent↗

Lack of H-2 gene influence on mouse susceptibility to secondary alveolar echinococcosis.

To determine whether the development of hepatic Echinococcus multilocularis infection is influenced by major histocompatibility-linked genes, metacestode growth and host immune responses were compared in 4 C57BL/10 congenic murine strains of H-2b, H-2d, H-2k and H-2q haplotypes. Although the H-2q strain appeared slightly more resistant than the other strains, the 4 strains of mice developed comparable spleen cell proliferative response and Th1/Th2 cytokine production at 13 weeks p.i. A kinetic analysis, performed in 2 of these congenic strains, showed a similar pattern of parasite growth in these mice and failed to detect any significant difference in the production of parasite-specific IgM, IgG1 and IgG2, antibodies. Consequently, this study indicates that the control of secondary alveolar echinococcosis is not H-2 gene-linked.

Animals↗

Renal echinococcosis: clinical study of 34 cases.

PURPOSE: Hydatid disease, a cyclo-zoonotic parasitic infestation caused by the larval stage of the cestode Echinococcus granulosus, is prevalent worldwide. We reviewed the clinical findings of a large series of renal hydatidosis treated in an endemic area with special emphasis on diagnostic pitfalls. MATERIALS AND METHODS: A retrospective 15-year review in a rural area of central Spain (600,000 population), with a global incidence of hydatidosis of 10 new cases per 100,000 population per year, revealed 34 with renal echinococcosis treated surgically (3 to 4% of officially confirmed cases of hydatidosis). Clinical, radiological and laboratory data were analyzed. RESULTS: Renal hydatid disease mimicked other diseases. The combination of clinical history, imaging studies, and serological and urine investigation yielded a reliable pretreatment diagnosis in only 50% of cases and a presumptive diagnosis in 71%. Among imaging studies computerized tomography was the most valuable diagnostic examination. Moderate eosinophilia was found in half of the cases, while a third had scoleces in the urine. A diagnostic and therapeutic algorithm is presented. CONCLUSIONS: Preoperative diagnosis of renal hydatid disease is difficult even in an endemic zone. Imaging studies are suggestive but usually inconclusive, and the differential diagnosis with a renal tumor or complicated cyst may not be made without surgery. Renal sparing surgery is possible in a significant proportion of cases, particularly when preoperative diagnosis has been considered. Significant surgical morbidity can be expected, and the risk of anaphylaxis and hydatid seeding, although low, should not be overlooked.

Adolescent↗

Cystic echinococcosis in semi-nomadic pastoral communities in north-west China.

In order to determine the prevalence of human cystic echinococcosis (CE) in semi-nomadic traditional pastoralist groups in north-west China, 2 large community studies were undertaken in Altai and Tacheng Prefectures in 1990/91 and 1995/96, respectively. The Kekergash community (Altai) comprised mainly ethnic Kazakhs, whereas the Narenhebuke community (Tacheng) comprised mainly Mongolians. Populations were screened for CE by abdominal ultrasound scan (US) and serological tests. The total prevalence of confirmed human CE was higher in Narenhebuke (2.7%, 49/1844) than in Kekergash (0.9%, 17/1861; P < 0.01). Within each community there was no significant difference of CE prevalence between the Kazakh and Mongolian groups, although Han Chinese exhibited twice the rate of CE (4.9%) in Narenhebuke compared to the dominant Mongolian population. For each community, human CE prevalence increased with age and there was a greater risk associated with the practice of home slaughter of livestock. Dogs were screened for Echinococcus granulosus infection and re-infection levels using a highly specific coproantigen test. The proportion of dogs with positive coproantigen tests was significantly higher in Narenhebuke (36.0%, 50/139) compared to Kekergash (17.8%, 16/90). In Narenhebuke the re-infection levels of dogs, as determined by coproantigen positivity, were higher in the winter quarters (49.4%, 39/79) compared to the summer quarters (18.3%, 11/60; P < 0.01). Furthermore, coproantigen re-test positivity was 25% at 3 months and 29.2% at 7 months. Highest dog coproantigen positivity was obtained over the winter period.

Adolescent↗

Classification, follow-up and recurrence of hepatic cystic echinococcosis using ultrasound images.

Ultrasound image and morphological structure of hepatic cystic echinococcosis (CE) were analysed in 277 human cases (385 hepatic hydatid cysts). These included 65 CE cases from community surveys carried out between 1995 and 2000 in 3 countries (China, Mongolia and Jordan) and 212 cases from a clinical hospital survey from Xinjiang, China. A new simplified WHO ultrasound classification for human CE was assessed, and considered useful. It is proposed that type, size and number in particular need to be included in the ultrasound classification of hepatic CE. For comparative purposes 6 categories of type were classified in the study as Type 0 to Type 5 (T0-T5): T0, univesicular without pathognomonic signs; T1, univesicular with pathognomonic signs; T2, cysts with sagging or floating laminated membrane; T3, cysts containing daughter cysts; T4, solid mass or mixed cysts; and T5, cysts with partial or full calcifications. This differs from the WHO classification wherein Type T3 cysts (daughter cysts present) are considered a pathological stage to occur in general prior to the sagging or floating membrane (T2) stage. Recurrent hydatid cysts in the liver were also studied based on morphological structures observed directly from surgical intervention. Case follow-up over 1-5 years since endocystectomy in the community surveys indicated 10% (2/10) recurrence of cysts in the residual surgical cavity. Recurrent CE included 2 (2/4) cases after percutaneous treatment.

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Alveolar echinococcosis: Em2plus-ELISA and Em18-western blots for follow-up after treatment with albendazole.

Eleven cases of alveolar echinococcosis (Echinococcus multilocularis infection) with non-resectable lesions but treated with albendazole for 17 to 69 months were followed-up clinically and serologically for 4.5-11.5 years. Based on the clinical outcome and computerized tomography (CT) scanning, they were divided into 4 groups of 2 cured cases, 5 stabilized cases, 3 cases with recurrences, and one treatment failure. Forty-seven sequentially collected sera from the 11 cases were analysed by sequential enzyme-linked immunosorbent assay (ELISA) using Em2plus antigen (Em2plus-ELISA) and Western blotting to detect antibody response against Em18 (Em18-Western blots). The antibody levels in one of the cured and 2 of the stabilized cases fell below the cut-off level in the Em2plus-ELISA 4.5-6 years after effective treatment, whereas all other cases, including 2 of those with recurrences, showed large reductions initially but increased again during the follow-up period. Em18-Western blots of the 2 cured cases and 2 of the stabilized cases became negative. IgG subclasses with responses against Em18 which fell to zero included IgG1 (2), IgG3 (one) and IgG4 (one). All other cases showed no decrease in antibody response against Em18. There were, in general, reasonably reliable correlations between the success or failure of chemotherapy and antibody responses by Em2plus-ELISA and Em18-Western blots. These results suggest that both Em2plus-ELISA and Em18-Western blot are potentially useful in evaluating and predicting the efficacy of chemotherapy.

Adult↗