Recent advances in the immunology and diagnosis of echinococcosis

Echinococcosis is a cosmopolitan zoonosis caused by adult or larval stages of cestodes belonging to the genus Echinococcus (family Taeniidae). The two major species of medical and public health importance are Echinococcus granulosus and Echinococcus multilocularis, which cause cystic echinococcosis and alveolar echinococcosis, respectively. Both cystic echinococcosis and alveolar echinococcosis are serious diseases, the latter especially so, with a high fatality rate and poor prognosis if managed inappropriately. This review highlights recent advances in immunity to infection and vaccination against both parasites in their intermediate and definitive hosts and procedures for diagnosis of cystic echinococcosis and alveolar echinococcosis, including the value of immunodiagnostic and DNA approaches. There is discussion also of progress in genomics and related technologies that is providing valuable insights on the functional biology of the Echinococcus organisms. These studies will underpin future research that will reveal a better understanding of the Echinococcus-host interplay, and suggest new avenues for the identification of additional targets for diagnosis, vaccination and chemotherapy.     

Geographical Detector-based influence factors analysis for Echinococcosis prevalence in Tibet,China

Echinococcosis, caused by genus Echinococcus, is the most pathogenic zoonotic parasitic disease in the world. In Tibet of the People’s Republic of China, echinococcosis refers principally to two types of severe zoonosis, cystic echinococcosis (CE) and alveolar echinococcosis (AE), which place a serious burden on public health and economy in the local community. However, research on the spatial epidemiology of echinococcosis remains inadequate in Tibet, China. Based on the recorded human echinococcosis data, maps of the spatial distribution of human CE and AE prevalence in Tibet were produced at city level and county level respectively, which show that the prevalence of echinococcosis in northern and western Tibet was much higher than that in other regions. We employ a geographical detector to explore the influencing factors for causing CE and AE while sorting information on the maps of disease prevalence and environment factors (e.g. terrain, population, and yak population). The results of our analysis showed that biological factors have the most impact on the prevalence of echinococcosis, of which the yak population contributes the most for CE, while the dog population contributes the most for AE. In addition, the interaction between various factors, as we found out, might further explain the disease prevalence, which indicated that the echinococcosis prevalence is not simply affected by one single factor, but by multiple factors that are correlated with each other complicatedly. Our results will provide an important reference for the evaluation of the echinococcosis risk, control projects, and prevention programs in Tibet.     

Serodiagnosis of Echinococcosis by ELISA Using Cystic Fluid from Uzbekistan Sheep

According to increase of travel, the cases of imported echinococcosis have been increasing in Korea. The present study was undertaken to develop a serodiagnostic system for echinococcosis in Korea. For diagnosis of echinococcosis, the fluid of Echinococcus granulosus hydatid cysts was collected from naturally infected sheep in Uzbekistan. Also serum samples of infected patients who were surgically confirmed were collected in a hospital in Tashkent, Uzbekistan. According to the absorbance of 59 echinococcosis positive and 39 negative control serum samples, the cut-off value was determined as 0.27. The sensitivity and specificity of ELISA with hydatid fluid antigen were 91.5% and 96%, respectively. The antigen cross-reacted with the serum of some cysticercosis or clonorchiasis patients. However, immunoblot analysis on the cystic fluid recognized antigenic proteins of 7-, 16-, and 24-kDa bands in their dominant protein quantity and strong blotting reactivity. In conclusion, the present ELISA system using hydatid cyst fluid antigen from Uzbekistan sheep is sensitive and specific for diagnosis of echinococcosis cases.     

Echinococcosis in China,a Review of the Epidemiology of <Emphasis Type="Italic">Echinococcus</Emphasis> spp.

Cystic echinococcosis (CE) and alveolar echinococcosis (AE) are highly significant infectious diseases occurring worldwide and caused by metacestodes of tapeworms Echinococcus granulosus and E. multilocularis, respectively. Both human CE and AE have highest prevalence rates in western and northwestern China. Livestock is the main intermediate host of E. granulosus, and wild small mammal are the main intermediate hosts of E. multilocularis. Since they range freely in pastoral areas, prey on wild small mammals and offal of livestock after slaughter, and have close relationships with humans, domestic dogs are the most important definitive host of both Echinococcus spp. with the highest risk of transmitting CE and AE to humans. Pastoralism is the occupation with the highest risk of being infected with the both kinds of echinococcosis due to the proximity of livestock, dogs, and wildlife host species. In this review, we summarize the epidemiology of human echinococcosis, the situation of parasite transmission in animal hosts, and possible transmission patterns in China. In addition, human activities and their potential influence on the transmission of echinococcosis are also discussed.     

Overview of therapeutic options for cystic echinococcosis

Surgical excision of echinococcal cyst has long been considered the only effective treatment for echinococcosis. However, the remarkable advances in imaging techniques, particularly ultrasound, made during the past 25 years have greatly facilitated diagnosis, treatment and follow-up. Today, chemotherapy and percutaneous treatments have become widely available. A major step forward in management of the disease came in 2001, when the WHO International Working Group on Echinococcosis (WHO-IWGE) came to a consensus by developing a standardized classification of ultrasound images in cystic echinococcosis. Thus, the most appropriate treatment for patients affected by this serious and sometimes life-threatening disease may now be chosen. An overview of the three main therapeutic options for abdominal- and particularly hepatic-cystic echinococcosis is presented, with focus on the indications and contraindications of each one. Data from long-term follow-up studies are also discussed, with emphasis on the resulting stage-specific criteria for treatment.     

超声与CT 在肝脏囊型包虫病与非寄生虫性囊肿鉴别中的比较

目的:分析囊型包虫病的CT以及超声的影像学特征以及联合诊断的效能,以减少对于CL及Ⅰ型包虫囊肿误诊率。方法:回顾性分析自2008年1月～2010年9月在我院行CT和超声检查的包虫病患者22例,肝脏单纯囊肿25例,分析其表现并进行比较。结果:CT检出36个病灶,超声检测出34个病灶,单纯囊肿组和包虫组病灶分布及形态等无明显差别,22例超声显示位于包虫囊肿底部可以随体位运动棘球呦砂样改变,显示囊肿壁不规则增厚3例,病灶周围胆管扩张2例,CT显示包虫囊肿壁钙化5例,病灶周围胆管扩张3例。结论:联合CT和超声学检查可以帮助提高CEI及CL型包虫囊肿的诊断率。     

Echinococcosis: An Economic Evaluation of a Veterinary Public Health Intervention in Rural Canada

Echinococcosis is a rare but endemic condition in people in Canada, caused by a zoonotic cestode for which the source of human infection is ingestion of parasite eggs shed by canids. The objectives of this study were to identify risk factors associated with infection and to measure the cost-utility of introducing an echinococcosis prevention program in a rural area. We analyzed human case reports submitted to the Canadian Institutes for Health Information between 2002 and 2011. Over this 10 year period, there were 48 cases associated with E. granulosus/E. canadensis, 16 with E. multilocularis, and 251 cases of echinococcosis for which species was not identified (total 315 cases). Nationally, annual incidence of echinococcosis was 0.14 cases per 100 000 people, which is likely an underestimate due to under-diagnosis and under-reporting. Risk factors for echinococcosis included female gender, age (>65 years), and residing in one of the northern territories (Nunavut, Yukon, or Northwest Territories). The average cost of treating a case of cystic echinococcosis in Canada was $8,842 CAD. Cost-utility analysis revealed that dosing dogs with praziquantel (a cestocide) at six week intervals to control cystic echinococcosis is not currently cost-effective at a threshold of $20,000-100,000 per Quality Adjusted Life Year (QALY) gained, even in a health region with the highest incidence rate in Canada ($666,978 -755,051 per QALY gained). However, threshold analysis demonstrated that the program may become cost-saving at an echinococcosis incidence of 13-85 cases per 100,000 people and therefore, even one additional CE case in a community of 9000 people could result in the monetary benefits of the program outweighing costs.     

Prevalence and spatial distribution characteristics of human echinococcosis in China

BackgroundEchinococcosis is a zoonotic parasitic disease caused by larval stages of cestodes belonging to the genus Echinococcus. The infection affects people’s health and safety as well as agropastoral sector. In China, human echinococcosis is a major public health burden, especially in western China. Echinococcosis affects people health as well as agricultural and pastoral economy. Therefore, it is important to understand the prevalence status and spatial distribution of human echinococcosis in order to advance our knowledge of basic information for prevention and control measures reinforcement.MethodsReport data on echinococcosis were collected in 370 counties in China in 2018 and were used to assess prevalence and spatial distribution. SPSS 21.0 was used to obtain the prevalence rate for CE and AE. For statistical analyses and mapping, all data were processed using SPSS 21.0 and ArcGIS 10.4, respectively. Chi-square test and Exact probability method were used to assess spatial autocorrelation and spatial clustering.ResultsA total of 47,278 cases of echinococcosis were recorded in 2018 in 370 endemic counties in China. The prevalence rate of human echinococcosis was 10.57 per 10,000. Analysis of the disease prevalence showed obvious spatial positive autocorrelation in globle spatial autocorrelation with two aggregation modes in local spatial autocorrelation, namely high-high and low-high aggregation areas. The high-high gathering areas were mainly concentrated in northern Tibet, western Qinghai, and Ganzi in the Tibetan Autonomous Region and in Sichuan. The low-high clusters were concentrated in Gamba, Kangma and Yadong counties of Tibet. In addition, spatial scanning analysis revealed two spatial clusters. One type of spatial clusters included 71 counties in Tibet Autonomous Region, 22 counties in Qinghai, 11 counties in Sichuan, three counties in Xinjiang Uygur Autonomous Region, two counties in Yunnan, and one county in Gansu. In the second category, six types of spatial clusters were observed in the counties of Xinjiang Uygur Autonomous Region, and the Qinghai, Gansu, and Sichuan Provinces.ConclusionThis study showed a serious prevalence of human echinococcosis with obvious spatial aggregation of the disease prevalence in China. The Qinghai-Tibet Plateau is the "hot spot" area of human echinococcosis in China. Findings from this study indicate that there is an urgent need of joint strategies to strengthen efforts for the prevention and control of echinococcosis in China, especially in the Qinghai-Tibet Plateau.     

Immunodiagnostic tests for hydatidosis in sheep: an evaluation of double diffusion, immunoelectrophoresis, indirect hemagglutination, and intradermal tests

Immunoelectrophoresis (IEP), double diffusion (DD5), indirect hemagglutination (IHA), and intradermal (ID) tests were evaluated to determine their ability to detect echinococcosis in sheep. Four sheep were infected per os with approximately 4,00, 1-wk-old eggs of Echinococcus gradulosus; four more sheep were similarly infected with approximately 3,000 1-wk-old eggs of Taenia hydatigena, and two additional sheep were used as uninfected controls. Blood samples were collected from each sheep prior to infection, at 2 and 4 wk postinoculation, and monthly thereafter for 1 yr. Serum from each blood sample was tested by IEP and DD5 for antiantigen "5" activity and by IHA for Echinococcus-specific hemagglutination activity. Following the last blood collection, an ID test for echinococcosis was performed on each sheep, after which all sheep were necropsied, and the type, location, and size of all larval tapeworms recorded. The DD5 test was found to be more sensitive and at least as specific as IEP in detecting echinococcosis in sheep. The IHA test approached the specificity and sensitivity pattern of DD5 and IEP if a titer of greater than or equal to 1:1,024 was considered positive. The ID test supported DD5 and IEP results but demonstrated a lack of specifiity. Necropsy data verified that all sheep were infected according to the experimental design. We conclude that DD5 reliably detects echinococcosis in experimentally infected sheep, and that further research is warranted to evaluate this test for detecting echinococcosis in naturally infected sheep.     

Impact of Increased Economic Burden Due to Human Echinococcosis in an Underdeveloped Rural Community of the People's Republic of China

Background

Ningxia is located in western People''s Republic of China, which is hyperendemic for human cystic echinococcosis (CE) throughout the entire area with alveolar echinococcosis (AE) hyperendemic in the south. This is in part due to its underdeveloped economy. Despite the recent rapid growth in P.R. China''s economy, medical expenditure for hospitalization of echinococcosis cases has become one of the major poverty generators in rural Ningxia, resulting in a significant social problem.

Methodology/Principal Findings

We reviewed the 2000 inpatient records with liver CE in surgical departments of hospitals from north, central and south Ningxia for the period 1996–2002. We carried out an analysis of health care expenditure of inpatient treatment in public hospitals, and examined the financial inequalities relating to human echinococcosis and the variation in per capita income between various socioeconomic groups with different levels of gross domestic product for different years. Hospital charges for Yinchuan, NHAR''s capital city in the north, increased approximately 35-fold more than the annual income of rural farmers with the result that they preferred to seek health care in local county hospitals, despite higher quality and more efficient treatment and diagnosis available in the city. Household income levels thus strongly influenced the choice of health care provider and the additional expense impeded access of poor people to better quality treatment.

Conclusions/Significance

Information on socioeconomic problems arising from echinococcosis, which adds considerably to the burden on patient families and communities, needs to be collected as a prerequisite for developing policies to tackle the disease in rural Ningxia.     

B超在肝囊型包虫病诊断中的临床价值与意义

目的：评价B超在肝囊型包虫病诊断中的价值与临床意义。方法：回顾性分析我院2000年12月至2011年12月收治的接受B超检查和手术治疗的332肝囊型包虫病例的临床资料。结果：332例肝囊型包虫病患者中,303例经过手术证实;肝囊型包虫病的B超分型可分为单发单囊型、多发单囊型、多子囊型、破裂感染型和坏死钙化型。单发单囊型患者以低年龄组多发,而高年龄组较少;破裂感染型以高年龄组多发;坏死钙化型病人共3例年龄均在60岁以上;破裂感染型占各型中病例数最多。结论：B型超声检查是肝囊型包虫病的主要检查方法,可确定包虫病的分型,了解包虫囊肿的部位、数目、大小和结构,为术前诊断、手术定位、观察治疗效果提供参考依据。     

An Imported Case of Echinococcosis of the Liver in a Korean Who Traveled to Western and Central Europe

Echinococcus granulosus, an intestinal tapeworm of dogs and other canids, infects humans in its larval stage and causes human echinococcosis or hydatid disease. In the Republic of Korea, 31 parasite-proven human echinococcosis cases have been reported, most of which were imported from the Middle East. We recently examined a 61-year-old Korean man who had a large cystic mass in his liver. ELISA was negative for tissue parasitic infections, including echinococcosis, cysticercosis, paragonimiasis, and sparganosis. The patient underwent surgery to remove the cyst, and the resected cyst was processed histopathologically for microscopic examinations. In sectioned cyst tissue, necrotizing protoscolices with disintegrated hooklets of E. granulosus were found. In some areas, only freed, fragmented hooklets were detected. The patient had traveled to western and central Europe in 1996, and had no other history of overseas travel. We report our patient as a hepatic echinococcosis case which was probably imported from Europe.     

Spinal Cystic Echinococcosis – A Systematic Analysis and Review of the Literature: Part 2. Treatment,Follow-up and Outcome

Bone involvement in human cystic echinococcosis (CE) is rare, but affects the spine in approximately 50% of cases. Despite significant advances in diagnostic imaging techniques, surgical treatment and introduction of pharmacological therapy, spinal echinococcosis remains associated with a high degree of morbidity, disability and mortality.We systematically reviewed the published literature of the last five decades to update and summarize the currently existing data on treatment, follow-up and outcome of spinal CE.     

Serologic and molecular diagnosis of zoonotic larval cestode infections

Neurocysticercosis, cystic echinococcosis and alveolar echinococcosis are the three major zoonotic larval cestodiases worldwide and threatening human life. Early therapeutic treatment based on early differential diagnosis at the early stage of infection and epidemiological surveillance with the expectation for control and prevention are the keys for improvement of quality of human life. Recent advances in (1). differential serodiagnosis of these three diseases, (2). molecular identification of human taeniid species and (3). polymorphism of mitochodrial DNA highly informative for future molecular epidemiology are reviewed in this article.     

Evaluation of fecal immunoassays for canine Echinococcus infection in China

Human echinococcosis is present worldwide but it is in China that disease prevalence is the highest. In western China, especially in the Tibetan Plateau, the burden of echinococcosis is the most important. Dogs are a major definitive host of Echinococcus and monitoring the presence of Echinococcus worms in dogs is therefore essential to efficiently control the disease. Detection kits based on three different technologies including sandwich ELISA, (indirect) ELISA, and gold immunodiffusion, are currently marketed and used in China. The objective of this work was to assess the efficacy of these kits, in particular with respect to sensitivity and specificity. Four fecal antigen detection kits for canine infection reflecting the three technologies were obtained from companies and tested in parallel on 220 fecal samples. The results indicate that the performance is lower than expected, in particular in terms of sensitivity. The best results were obtained with the sandwich ELISA technology. The gold immunofiltration yielded the poorest results. In all cases, further development is needed to improve the performance of these kits which are key components for the control of echinococcosis.     

The value of ultrasonography alone in screening surveys of cystic echinococcosis in children in Turkey

A total of 1205 primary school children were examined for cystic echinococcosis in five villages of Manisa, Turkey, to evaluate the efficacy of diagnostic methods of this infection in community-based screening surveys. Six hundred and thirty children from three villages, examined by a portable ultrasound scanner, chest microfilm and serological methods (ELISA, indirect hemagglutination) in our previous study, were designated as Study Group 1; and 575 children, from two adjacent villages, examined by ultrasonography alone in the present study, were designated as Study Group 2. In Study Group 1, hepatic cystic echinococcosis was detected in two cases (0.3%) by ultrasonography, while 43 (8.9%) and 49 (10.1%) cases were found to be positive for cystic echinococcosis by ELISA and indirect hemagglutination, respectively. Three of 575 children (0.5%) were diagnosed with cystic echinococcosis (two hepatic and one renal involvement) by ultrasonography alone in Study Group 2; and lung lesions were later detected in both cases with liver involvement by chest radiography.

Our results suggested that serological tests may be beneficial in suspected cases for confirmation and differential diagnosis, but have some drawbacks, such as discrepancy in results and high false seropositivity rates. Chest microfilm is not easy in field studies and exposure to X-ray is undesirable. As a reliable, simple, inexpensive and rapid technique, ultrasonography alone is recommended to be used in community-based screening surveys for cystic echinococcosis with confirmatory tests for suspected cases found during the screening program.     

肝囊型包虫病非手术治疗方法的研究进展

肝囊型包虫病(简称肝包虫病)是一种由细粒棘球蚴感染肝脏引起的人兽共患寄生虫病,严重危害人类以及家畜的健康。近年来,由于该病术后复发率较高且易出现并发症,非手术治疗方法如介入技术、放射治疗以及药物治疗均得到了不断的发展。介入技术对于肝包虫病的治疗是一种比较新颖的方法,其临床应用时间较短,主要包括经皮穿刺治疗、射频消融、门静脉栓塞,以经皮穿刺治疗最为常见。放射治疗肝包虫病尚处于研究阶段,效果尚不完全明确。苯并咪唑类药物及其新剂型、非苯并咪唑类药物如地塞米松等及中草药治疗肝包虫病也均具有各自的优缺点。本文主要对上述非手术治疗方法及优缺点进行了综述。     

A Systematic Review of the Epidemiology of Echinococcosis in Domestic and Wild Animals

Background

Human echinococcosis is a neglected zoonosis caused by parasites of the genus Echinococcus. The most frequent clinical forms of echinococcosis, cystic echinococcosis (CE) and alveolar echinococcosis (AE), are responsible for a substantial health and economic burden, particularly to low-income societies. Quantitative epidemiology can provide important information to improve the understanding of parasite transmission and hence is an important part of efforts to control this disease. The purpose of this review is to give an insight on factors associated with echinococcosis in animal hosts by summarising significant results reported from epidemiological studies identified through a systematic search.

Methodology and Principal Findings

The systematic search was conducted mainly in electronic databases but a few additional records were obtained from other sources. Retrieved entries were examined in order to identify available peer-reviewed epidemiological studies that found significant risk factors for infection using associative statistical methods. One hundred studies met the eligibility criteria and were suitable for data extraction. Epidemiological factors associated with increased risk of E. granulosus infection in dogs included feeding with raw viscera, possibility of scavenging dead animals, lack of anthelmintic treatment and owners'' poor health education and indicators of poverty. Key factors associated with E. granulosus infection in intermediate hosts were related to the hosts'' age and the intensity of environmental contamination with parasite eggs. E. multilocularis transmission dynamics in animal hosts depended on the interaction of several ecological factors, such as hosts'' population densities, host-prey interactions, landscape characteristics, climate conditions and human-related activities.

Conclusions/Significance

Results derived from epidemiological studies provide a better understanding of the behavioural, biological and ecological factors involved in the transmission of this parasite and hence can aid in the design of more effective control strategies.     

A Case of Human Hepatic Alveolar Echinococcosis Accompanied by Lung and Brain Metastases

Alveolar echinococcosis (AE) is considered as a fatal zoonosis caused by the larvae of Echinococcus multilocularis. The lungs and brain are the most common metastatic organs. We report a human case of hepatic alveolar echinococcosis accompanied by lung and brain metastasis. In particular, the patient had a history of tuberculosis and the lung lesions were easily misdiagnosed as lung abscesses. The lesions of liver and lung underwent radical resection and confirmed as alveolar echinococcosis by pathological examination. The patient had no surgical complications after operation and was discharged after symptomatic treatment. Unfortunately, the patient later developed multiple intracerebral AE metastases. We required the patient to take albendazole orally for life and follow up.     

Prevalence of Echinococcosis in Reindeer (Rangifer Tarandus) in Sweden

In Sweden echinococcosis is uncommon in domestic animals. In reindeer in the most northern part of the country echinococcosis was found. Of 1453 pairs of lungs, 23 pairs (1.6 %) were infected with hydatid cysts. These were of two types: typical well-developed hydatid cysts, which were found in nine of the 23 infected lungs, and collapsed hydatid cysts, which were found in 13 of the lungs. In only one lung pair both types of cysts were seen.