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.     

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.     

Polycystic echinococcosis in the state of Acre,Brazil: contribution to patient diagnosis,treatment and prognosis

The lack of knowledge regarding polycystic hydatid disease results in delayed or even incorrect diagnosis. The lack of systematic information regarding treatment also makes it difficult to assess the results and prognosis in patients with peritoneal and hepatic lesions caused by Echinococcus vogeli. Here we describe the clinical features of patients, propose a radiological classification protocol and describe a therapeutic option for the treatment of hydatid disease that previously had only been used for cases of cystic echinococcosis (Echinococcus granulosus). A prospective cohort study was initiated in 1999 and by 2009 the study included 60 patients. These patients were classified according to the PNM classification (parasite lesion, neighbouring organ invasion and metastases) and placed in one of three therapeutic modalities: (i) chemotherapy with albendazole at a dose of 10 mg/kg/day, (ii) surgical removal of cysts or (iii) percutaneous puncture of the cysts via puncture, aspiration, injection and re-aspiration (PAIR). The results were stratified according to therapeutic outcome: "cure", "clinical improvement", "no improvement", "death" or "no information". The PNM classification was useful in indicating the appropriate therapy in cases of polycystic hydatid disease. In conclusion, surgical therapy produced the best clinical results of all the therapies studied based on "cure" and "clinical improvement" outcomes. The use of PAIR for treatment requires additional study.     

Recurrent hepatic alveolar echinococcosis: report of the first case in Korea with unproven infection route

Human alveolar echinococcosis (AE), a hepatic disorder that resembles liver cancer, is a highly aggressive and lethal zoonotic infection caused by the larval stage of the fox tapeworm, Echinococcus multilocularis. E. multilocularis is widely distributed in the northern hemisphere; the disease-endemic area stretches from north America through Europe to central and east Asia, including northern parts of Japan, but it has not been reported in Korea. Herein, we represent a first case of AE in Korea. A 41-year-old woman was found to have a large liver mass on routine medical examination. The excised mass showed multinodular, necrotic, and spongiform appearance with small irregular pseudocystic spaces. Microscopically, the mass was composed of chronic granulomatous inflammation with extensive coagulation necrosis and parasite-like structure, which was revealed as parasitic vesicles and laminated layer delineated by periodic acid-Schiff (PAS) stain. Clinical and histologic features were consistent with AE. After 8 years, a new liver mass and multiple metastatic pulmonary nodules were found and the recurred mass showed similar histologic features to the initial mass. She had never visited endemic areas of AE, and thus the exact infection route is unclear.     

Echinococcus multilocularis in the mouse: The in vitro protoscolicidal activity of peritoneal macrophages

Baron R. W. and Tanner C. E. 1977. Echinococcus multilocularis in the mouse: the in vitro protoscolicidal activity of peritoneal macrophages. International Journal for Parasitology7: 489–495. The larvae of Echinococcus multilocularis are susceptible to the protoscolicidal activity of infected A/J mouse peritoneal cells. It is shown that the effector cell in this response is an activated macrophage. Preincubation of protoscolices in ‘immune’ serum increases their susceptibility to the protoscolicidal activity of infected mouse peritoneal cells. Macrophages activated nonspecifically by BCG or Taenia crassiceps infections also exhibit protoscolicidal activity in vitro. The identity of the effector cell was confirmed by scanning electron microscopy. It is shown that ‘immune’ macrophages adhere to and form close cellular contacts with the protoscolex surface. It is concluded that resistance to hydatid infections is mediated by activated macrophages.     

Cloning,expression, and protective immunity in mice of a gene encoding the diagnostic antigen P-29 of Echinococcus granulosus

Taeniid tapeworm Echinococcus granulosus is the causative agent of Echinococcosis, an important zoonosis with worldwide distribution. In this study, a diagnostic antigen P-29 was cloned from E. granulosus and expressed in Escherichia coil Sequence analysis showed that EgP-29 contains 717-bp open reading frame and encodes a protein of 238 amino acid residues with a predicted molecular weight of 27.1 kDa. The recombinant EgP-29 （rEgP-29） could be recognized with antimice sera in Western blotting. The specific antibody was detected by enzyme-linked immunosorbent assay. Mice vaccinated with rEgP-29 and challenged intrapero itoneally with E. granulosus protoscoleces revealed sig- nificant protective immunity of 96.6% （P〈0.05）, compared with the control group. Thus, rEgP-29 protein is a promising candidate for an effective vaccine to prevent secondary echinococcosis.     

Development of an injectable formulation of albendazole and in vivo evaluation of its efficacy against Echinococcus multilocularis metacestode

The loading of poly (D,L-lactide) nanoparticles with ABZ has led us to evaluate the potential of this new colloidal drug delivery system against E. multilocularis, using a murine model of hepatic alveolar echinococcosis. ABZ-loaded nanoparticles had a monodisperse size distribution between 100 and 150 nm. The efficiency of drug loading to nanoparticles was over 97%. In vitro, at an ABZ concentration of 1.0 μg ml⁻¹, the formulation had no toxicity for peritoneal macrophages harvested from uninfected mice, In vivo, the ABZ-loaded nanoparticles exhibited no signs of toxicity at any of the doses tested. Intravenous injections of 6 mg kg⁻¹ of bound ABZ to infected mice had an equivalent antiparasitic effect on the metacestode growth to that of a treatment with 1500 mg kg⁻¹ of orally administered free ABZ. The parasite hepatic superficial size as well as the peritoneal metastatic burden was significantly reduced by these 2 courses of treatment, as compared to those of untreated mice. Our results should encourage further study in order to explain the absence of dose-dependent efficacy of ABZ-loaded nanoparticles demonstrated in the present study.     

Coproantigen detection in dogs experimentally and naturally infected with Echinococcus granulosus by a monoclonal antibody-based enzyme-linked immunosorbent assay

A sandwich ELISA for the detection of Echinococcus granulosus coproantigen in formalin and heat-treated faecal supernatants of dogs was developed. The assay used affinity-purified polyclonal antibodies obtained from rabbits hyperimmunised with E. granulosus excretory/secretory antigens and biotiaylated monoclonal antibody EmA9 produced against adult E. multilocularis somatic extract. The test was sensitive to 7 ng and 2.3 ng of E. granulosus protein and carbohydrate/ml of faecal supernatant, respectively. Thirteen helminth-free dogs were infected with different amounts of E. granulosus protoscoleces and the presence of coproantigen was monitored during the prepatent period until day 35 post-infection, when they were necropsied. Faecal antigen levels started to rise above the normal range between days 10 and 20 post-infection, and typically peaked at the end of the experiment. All the dogs, bearing from 3 to 67 700 worms, showed positive values in the ELISA during the prepatent period. One dog experimentally infected with Taenia hydatigena metacestode and harbouring three worms, tested positive only after the prepatent period at day 52. The test was applied to 98 stray dogs. The ELISA detected all of four dogs naturally infected with E. granulosus, two dogs with patent infections of T. hydatigena and two dogs with no cestode infections, sbowing a sensitivity of 100% and a specificity of 96%.     

Recent advances in biosensors for diagnosis of celiac disease: A review

Celiac disease (CD) is an intestinal issue activated by the inappropriate immune reaction towards gluten protein of wheat, rye, barley, oats, and autoantigen, tissue transglutaminase. Regardless of the accessibility of immunochemical conventions for research facility analysis of CD, there is as yet a need of speedier, less expensive, and simpler devices for diagnosing CD. This review concentrates on progresses in biosensors for diagnosing CD in perspective of the scaled down hardware, multianalyte discovery and low sample volume necessity. Various recently developed biosensors in this field are presented.     

Assessment of the epidemiological status of Echinococcus multilocularis in foxes in France using ELISA coprotests on fox faeces collected in the field.

The aim of this study was to estimate the relevance of Echinococcus multilocularis coproantigen detection in fox faeces collected in the field to identify different levels of endemicity for Echinococcus multilocularis on a large scale (n×10 km²). Six study sites were selected in a high endemicity area and two study sites in a low endemicity area in eastern France on the basis of landscape composition. Sampling was undertaken in the winters of 1996–97, 1997–98 and 1998–99. At each site, (i) necropsy and intestine examination was undertaken on a sample of shot foxes (total number of foxes, 222), and (ii) fox faeces were collected in the field along road verges, and scored for degradation status (total number of faeces, 625). Fox faeces were also sampled in a control area (n=30) in western France in the summer of 1998. Intestines were examined according to the sedimentation method. Echinococcus multilocularis coproantigens were detected by using two ELISA tests: EM-ELISA and EmA9-ELISA. The necropsy prevalence in high and low endemicity areas was 63.3% and 19.4%, respectively, and the distribution of adult worms in the fox population was highly overdispersed (75.5% of the total biomass was harboured by 11.6% of foxes). Using the two ELISA tests, there was no difference in the detection of E. multilocularis coproantigens in field faeces, regardless of the degradation status. The medians of EM- and EmA9-ELISA OD values of field faeces in high endemicity area were significantly higher than in low endemicity area (P<0.001 for both ELISA). The distribution of EM-ELISA OD values in low endemicity area was significantly higher (P=0.002) than in the control area. Moreover, for the two ELISA, the observed ELISA OD value distributions in high endemicity area, low endemicity area and control area seemed representative of the distribution of adult worms in fox populations. These results indicate that E. multilocularis coproantigen detection in field faeces could serve for large-scale surveillance, as an alternative to necropsy.     

幽门螺杆菌诊断的最新进展

幽门螺杆菌(Helicobacter pylori,H. pylori)是一种常见的引起多种胃肠道疾病的病原体。临床中通常利用具有不同灵敏度和特异性的侵入性或非侵入性诊断方法来检测H. pylori的感染。目前,诊断H. pylori的方法包括尿素呼气试验、粪便抗原试验、血清学、内镜检查、胃活检组织学、快速尿素酶试验、培养、分子生物学方法等。在实际临床实践中,考虑不同的医疗条件、医生的专业水平、检测成本、敏感性和特异性等多方面因素,如何合理地选择一种或多种方法来诊断H. pylori感染进而指导临床预防和治疗,是一项重要的临床研究课题。本文将对H. pylori感染诊断方法的最新进展、不同方法的优缺点以及其在临床实践中的应用作一综述。     

Recent advances and hurdles in melanoma immunotherapy

Worldwide incidence of malignant melanoma has been constantly increasing during the last years. Surgical excision is effective when primary tumours are thin. At later disease stages patients often succumb, due to failure of metastasis control. Therefore, great efforts have been made to develop improved strategies to treat metastatic melanoma patients. In the search for novel treatments during the last two decades, immunotherapy has occupied a prominent place. Numerous early phase immunotherapy clinical trials, generally involving small numbers of patients each time, have been reported: significant tumour‐specific immune responses could often be measured in patients upon treatments. However, clinical responses remain at a dismal low rate. In some anecdotal cases, objective clinical benefit was more frequently observed among immune responders than immune non‐responders. This clearly calls for a better understanding of protective immunity against tumours as well as the cross talk taking place between tumours and the immune system. Here we discuss advances and limitations of specific immunotherapy against human melanoma in the light of the literature from the last 5 yr.     

Serological and Molecular Characteristics of the First Korean Case of Echinococcus multilocularis

In December 2011, we reported an autochthonous case of Echinococcus multilocularis infection in a 42-year-old woman in Korea. The diagnosis was based on histopathological findings of the surgically resected liver cyst. In the present study, we evaluated the serological and molecular characteristics of this Korean E. multilocularis case. The patient''s serum strongly reacted with affinity-purified native Em18 and recombinant Em18 antigens (specific for E. multilocularis) but negative for recombinant antigen B8/1 (reactive for Echinococcus granulosus). In immunoaffinity chromatography, the serum also strongly reacted with E. multilocularis and only weakly positive for E. granulosus. We determined the whole nucleotide sequence of cox1 (1,608 bp) using the paraffin-embedded cystic tissue which was compared with E. multilocularis isolates from China, Japan, Kazakhstan, Austria, France, and Slovakia. The Korean case showed 99.8-99.9% similarity with isolates from Asia (the highest similarity with an isolate from Sichuan, China), whereas the similarity with European isolates ranged from 99.5 to 99.6%.     

Studies on the specific immunodiagnosis of larval cestode infections of cattle and sheep using antigens purified by affinity chromatography in an enzyme-linked immunosorbent assay (Elisa)

Craig P.S. and Rickard M.D. 1981. Studies on the specific immunodiagnosis of larval cestode infections of cattle and sheep using antigens purified by affinity chromatography in an enzyme-linked immunosorbent assay (ELISA). International Journal for Parasitology11: 441–449. Crude somatic or cyst fluid extracts prepared from Taenia saginata, T. hydatigena or Echinococcus granulosus were partially purified by absorption against homologous and heterologous bovine or ovine antisera on immunoabsorbent affinity columns. Antigens in parasite extracts which were eluted after binding to the homologous anti-parasite antisera (bovine or ovine) coupled to CNBr-activated Sepharose were then passed sequentially through affinity columns containing heterologous anti-parasite Ig and the ‘run-through’ antigens collected. The level of cross reactions to these absorbed antigens, in an enzyme-linked immunosorbent assay (ELISA) using sera from cattle or sheep given heterologous parasite infections (including Fasciola hepatica), were significantly decreased. Absolute specificity was not achieved, and some loss in sensitivity occurred. The absorption of cross-reactive antigen(s) using affinity Chromatographie techniques may be a useful first step in the production of species-specific immunodiagnostic antigens for larval cestode infections.     

Recent advances in the diagnosis and treatment of hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages secreting high amounts of inflammatory cytokines. It is a frequent manifestation in patients with predisposing genetic defects, but can occur secondary to various infectious, malignant, and autoimmune triggers in patients without a known genetic predisposition. Clinical hallmarks are prolonged fever, cytopenias, hepatosplenomegaly, and neurological symptoms, but atypical variants presenting with signs of chronic immunodeficiency are increasingly recognized. Impaired secretion of perforin is a key feature in several genetic forms of the disease, but not required for disease pathogenesis. Despite progress in diagnostics and therapy, mortality of patients with severe HLH is still above 40%. Reference treatment is an etoposide-based protocol, but new approaches are currently explored. Key for a favorable prognosis is the rapid identification of an underlying genetic cause, which has been facilitated by recent immunological and genetic advances. In patients with predisposing genetic disease, hematopoietic stem cell transplantation is performed increasingly with reduced intensity conditioning regimes. Current research aims at a better understanding of disease pathogenesis and evaluation of more targeted approaches to therapy, including anti-cytokine antibodies and gene therapy.     

Recent advances in the biology of IL-1 family cytokines and their potential roles in development of sepsis

The IL-1 family comprises two anti-inflammatory cytokines (IL-37, IL-38), two receptor antagonists (IL-1ra, IL-36ra), and seven ligand agonists (IL-1α, IL-1β, IL-33, IL-36α, IL-36β, IL-36γ). The members of this family exert pleiotropic effects on intercellular signaling, leading to pro- or anti-inflammatory responses. They initiate potent inflammatory and immune responses by binding to specific receptors in the IL-1 receptor family, and their activities are repressed by naturally occurring inhibitors. Various immune cells produce and are regulated by these crucial molecules, which appear to be involved in the pathogenesis of diverse diseases including cancer as well as inflammatory and autoimmune disorders. Recent decades have seen substantial progress in understanding how the IL-1 family contributes to the development of sepsis. In this review, we will briefly introduce the IL-1 family and discuss its critical role in inflammatory and immune responses. The potential significance of IL-1 members in sepsis will also be explored, together with the clinical implications for treating this dangerous condition.