ResearchPad - echinococcosis https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Genetic diversity of <i>Echinococcus multilocularis</i> and <i>Echinococcus granulosus sensu lato</i> in Kyrgyzstan: The A2 haplotype of <i>E</i>. <i>multilocularis</i> is the predominant variant infecting humans]]> https://www.researchpad.co/article/elastic_article_13871 Analysis of the genetic variability in Echinococcus species from different endemic countries have contributed to the knowledge in the taxonomy and phylogeography of these parasites. The most important species of this genus, Echinococcus granulosus sensu lato and Echinococcus multilocularis, co-exist in Kyrgyzstan causing serious public health issues. E. granulosus s.l. causes cystic echinococcosis and E. multilocularis is the causative agent of alveolar echinococcosis. The most relevant finding of our study is the identification of the cob/nad2/cox1 A2 haplotype of E. multilocularis as the most commonly found in humans and dogs. However, it remains unknown if this variant of E. multilocularis, based on genetic differences in mitochondrial genes, presents differences in virulence which could have contributed to the emergence of alveolar echinococcosis in Kyrgyzstan. The results also show a number of non-previously described genetic variants of E. multilocularis and E. granulosus s.s.

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<![CDATA[Human Alveolar Echinococcosis, Croatia]]> https://www.researchpad.co/article/N27474fa5-57fc-4427-b408-50eae7c98d24

Alveolar echinococcosis is a parasitic disease caused by the tapeworm larval stage of Echinococcus multilocularis. This zoonotic disease has not been known to occur in Croatia. We report a confirmed case of human alveolar echinococcosis in a patient in Croatia who had never visited a known E. multilocularis–endemic area.

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<![CDATA[Evaluation of direct costs associated with alveolar and cystic echinococcosis in Austria]]> https://www.researchpad.co/article/5c5ca2d2d5eed0c48441eb7a

Background

Cystic echinococcosis (CE) is a globally occurring zoonosis, whereas alveolar echinococcosis (AE) is endemic only in certain parts of the Northern Hemisphere. The socioeconomic impact of human echinococcosis has been shown to be considerable in highly endemic regions. However, detailed data on direct healthcare-related costs associated with CE and AE are scarce for high income countries. The aim of this study was to evaluate direct costs of human disease caused by CE and AE in Austria.

Methods

Clinical data from a registry maintained at a national reference center for echinococcosis at the Medical University of Vienna were obtained for the years 2012–2014. These data were used in conjunction with epidemiological data from Austria’s national disease reporting system and diagnostic reference laboratory for echinococcosis to assess nationwide costs attributable to CE and AE.

Results

In Austria, total modelled direct costs were 486,598€ (95%CI 341,825€ – 631,372€) per year for CE, and 683,824€ (95%CI 469,161€ - 898,486€) for AE. Median costs per patient with AE from diagnosis until the end of a 10-year follow-up period were 30,832€ (25th– 75th percentile: 23,197€ - 31,220€) and 62,777€ (25th– 75th percentile: 60,806€ - 67,867€) for inoperable and operable patients, respectively. Median costs per patients with CE from diagnosis until end of follow-up after 10 years were 16,253€ (25th– 75th percentile: 8,555€ - 24,832€) and 1,786€ (25th– 75th percentile: 736€ - 2,146€) for patients with active and inactive cyst stages, respectively. The first year after inclusion was the most cost-intense year in the observed period, with hospitalizations and albendazole therapy the main contributors to direct costs.

Conclusions

This study provides detailed information on direct healthcare-related costs associated with CE and AE in Austria, which may reflect trends for other high-income countries. Surgery and albendazole therapy, due to surprisingly high drug prices, were identified as important cost-drivers. These data will be important for cost-effectiveness analyses of possible prevention programs.

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<![CDATA[Psychological burden and resilience factors in patients with Alveolar Echinococcosis – A cross-sectional study]]> https://www.researchpad.co/article/5c3d00edd5eed0c484036c02

Background

Alveolar echinococcosis (AE) is a parasitic zoonosis resembling malignancy due to its clinically silent infiltrative growth, predominately in the liver. The comorbid psychological burden and fear of disease progression in AE patients have hardly been examined to date. The aim of this study was to evaluate depression, anxiety, quality of life, and fear of disease progression in AE patients.

Methodology/Principal findings

In a cross-sectional study, n = 57 AE patients were invited to report on depression (PHQ-9), anxiety (GAD-7), somatic symptom load (SSS 8), trauma symptoms (PTSS-10), quality of life (SF-12) and on fear of disease progression (FoP-Q-SF) using validated psychometric instruments. Furthermore, attachment style was assessed (RQ-2). N = 47 patients completed the questionnaires (response rate 82.5%). Depression, anxiety, and somatic symptom load were above norm sample means, while physical quality of life was below norm sample means. Existing traumatic symptoms were comparable to those in cancer patients, while fear of disease progression even exceeded cancer patient scores. Patients with a secure attachment style showed less pronounced psychological burden than patients with other attachment styles. Adequate, guideline-based depression and anxiety treatment was very rarely installed.

Conclusion/Significance

The present study revealed remarkable levels of psychological burden in AE patients. In our study sample, we discovered high depression and anxiety levels, a significant reduction of physical quality of life, and fear of disease progression. These results show how important it is for AE patients to be thoroughly assessed with regard to psychological symptoms and mental disorders so that those in need can receive sufficient psychosocial support and treatment according to official guidelines.

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<![CDATA[The ectodomains of the lymphocyte scavenger receptors CD5 and CD6 interact with tegumental antigens from Echinococcus granulosus sensu lato and protect mice against secondary cystic echinococcosis]]> https://www.researchpad.co/article/5c0ae451d5eed0c4845895e9

Background

Scavenger Receptors (SRs) from the host’s innate immune system are known to bind multiple ligands to promote the removal of non-self or altered-self targets. CD5 and CD6 are two highly homologous class I SRs mainly expressed on all T cells and the B1a cell subset, and involved in the fine tuning of activation and differentiation signals delivered by the antigen-specific receptors (TCR and BCR, respectively), to which they physically associate. Additionally, CD5 and CD6 have been shown to interact with and sense the presence of conserved pathogen-associated structures from bacteria, fungi and/or viruses.

Methodology/Principal findings

We report herein the interaction of CD5 and CD6 lymphocyte surface receptors with Echinococcus granulosus sensu lato (s.l.). Binding studies show that both soluble and membrane-bound forms of CD5 and CD6 bind to intact viable protoscoleces from E. granulosus s.l. through recognition of metaperiodate-resistant tegumental components. Proteomic analyses allowed identification of thioredoxin peroxidase for CD5, and peptidyl-prolyl cis-trans isomerase (cyclophilin) and endophilin B1 (antigen P-29) for CD6, as their potential interactors. Further in vitro assays demonstrate that membrane-bound or soluble CD5 and CD6 forms differentially modulate the pro- and anti-inflammatory cytokine release induced following peritoneal cells exposure to E. granulosus s.l. tegumental components. Importantly, prophylactic infusion of soluble CD5 or CD6 significantly ameliorated the infection outcome in the mouse model of secondary cystic echinococcosis.

Conclusions/Significance

Taken together, the results expand the pathogen binding properties of CD5 and CD6 and provide novel evidence for their therapeutic potential in human cystic echinococcosis.

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<![CDATA[Clinical and Demographic Characteristics of Patients with Urinary Tract Hydatid Disease]]> https://www.researchpad.co/article/5989daf0ab0ee8fa60bc0f7e

Background

Human cystic echinococcosis (CE) is caused by flatworm larvae of Echinococcus granulosus and is endemic in many parts of the world. In humans, CE cysts primarily affect the liver and pulmonary system, but can also affect the renal system. However, the clinical manifestations of renal CE can be subtle, so healthcare professionals often overlook renal CE in differential diagnosis. In this study, we examined the clinical and demographic characteristics of patients with urinary tract CE and analyzed the diagnosis and treatment procedures for this disease.

Methods

The records of 19 consecutive renal CE patients who were admitted to the First Affiliated Hospital of Xinjiang Medical University from January 1983 to April 2011 were retrospectively reviewed. In all cases, CE of the urinary tract was confirmed by pathological examination and visual inspection during surgery.

Results

Fifteen patients were males and 4 were females. The most common symptoms were non-specific lower back pain and percussion tenderness on the kidney region. All patients were followed up for 9–180 months after surgery. None of the patients experienced a recurrence of renal CE, but 4 patients experienced non-renal recurrence of hydatid disease.

Conclusions

Hydatid cysts from E. granulosus are structurally similar in the liver and urinary tract. Thus, the treatment regimen for liver CE developed by the World Health Organization/Informal Working Group on Echinococcosis (WHO/IWGE) could also be used for urinary tract CE. In our patients, the use of ultrasound, computed tomography, serology, and clinical characteristics provided a diagnostic accuracy of 66.7% to 92.3%.

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<![CDATA[Cystic Echinococcosis Epidemiology in Spain Based on Hospitalization Records, 1997-2012]]> https://www.researchpad.co/article/5989dafaab0ee8fa60bc45e9

Background

Cystic echinococcosis (CE) is a parasitic disease caused by the tapeworm Echinococcus granulosus. Although present throughout Europe, deficiencies in the official reporting of CE result in under-reporting and misreporting of this disease, which in turn is reflected in the wrong opinion that CE is not an important health problem. By using an alternative data source, this study aimed at describing the clinical and temporal-spatial characteristics of CE hospitalizations in Spain between 1997 and 2012.

Methodology/Principal Findings

We performed a retrospective descriptive study using the Hospitalization Minimum Data Set (CMBD in Spanish). All CMBD’s hospital discharges with echinococcosis diagnosis placed in first diagnostic position were reviewed. Hospitalization rates were computed and clinical characteristics were described. Spatial and temporal distribution of hospital discharges was also assessed. Between 1997 and 2012, 14,010 hospitalizations with diagnosis of CE were recorded, 55% were men and 67% were aged over 45 years. Pediatric hospitalizations occurred during the whole study period. The 95.2% were discharged at home, and only 1.7% were exitus. The average cost was 8,439.11 €. The hospitalization rate per 100,000 per year showed a decreasing trend during the study period. All the autonomous communities registered discharges, even those considered as non-endemic. Maximum rates were reached by Extremadura, Castilla-Leon and Aragon. Comparison of the CMBD data and the official Compulsory Notifiable Diseases (CND) reports from 2005 to 2012 showed that official data were lower than registered hospitalization discharges.

Conclusions

Hospitalizations distribution was uneven by year and autonomous region. Although CE hospitalization rates have decreased considerably due to the success of control programs, it remains a public health problem due to its severity and economic impact. Therefore, it would be desirable to improve its oversight and surveillance, since officially reported data are underestimating the real burden of CE in Spain.

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<![CDATA[Justified Concern or Exaggerated Fear: The Risk of Anaphylaxis in Percutaneous Treatment of Cystic Echinococcosis—A Systematic Literature Review]]> https://www.researchpad.co/article/5989da71ab0ee8fa60b9513a

Percutaneous treatment (PT) emerged in the mid-1980s as an alternative to surgery for selected cases of abdominal cystic echinococcosis (CE). Despite its efficacy and widespread use, the puncture of echinococcal cysts is still far from being universally accepted. One of the main reasons for this reluctance is the perceived risk of anaphylaxis linked to PTs. To quantify the risk of anaphylactic reactions and lethal anaphylaxis with PT, we systematically searched MEDLINE for publications on PT of CE and reviewed the PT-related complications. After including 124 publications published between 1980 and 2010, we collected a total number of 5943 PT procedures on 5517 hepatic and non-hepatic echinococcal cysts. Overall, two cases of lethal anaphylaxis and 99 reversible anaphylactic reactions were reported. Lethal anaphylaxis occurred in 0.03% of PT procedures, corresponding to 0.04% of treated cysts, while reversible allergic reactions complicated 1.7% of PTs, corresponding to 1.8% of treated echinococcal cysts. Analysis of the literature shows that lethal anaphylaxis related to percutaneous treatment of CE is an extremely rare event and is observed no more frequently than drug-related anaphylactic side effects.

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<![CDATA[The Burden of Zoonoses in Kyrgyzstan: A Systematic Review]]> https://www.researchpad.co/article/5989da65ab0ee8fa60b91a5a

Introduction

Zoonotic disease (ZD) pose a serious threat to human health in low-income countries. In these countries the human burden of disease is often underestimated due to insufficient monitoring because of insufficient funding. Quantification of the impact of zoonoses helps in prioritizing healthcare needs. Kyrgyzstan is a poor, mountainous country with 48% of the population employed in agriculture and one third of the population living below the poverty line.

Methodology/Principal Findings

We have assessed the burden of zoonoses in Kyrgyzstan by conducting a systematic review. We have used the collected data to estimate the burden of ZDs and addressed the underestimation in officially reported disease incidence. The estimated incidences of the ZDs were used to calculate incidence-based Disability Adjusted Life Years (DALYs). This standardized health gap measure enhances comparability between injuries and diseases. The combined burden for alveolar echinococcosis, cystic echinococcosis, brucellosis, campylobacteriosis, congenital toxoplasmosis, non-typhoidal salmonellosis and rabies in Kyrgyzstan in 2013 was 35,209 DALYs [95% Uncertainty interval (UI):13,413–83,777]; 576 deaths [95% UI: 279–1,168] were attributed to these infections. We estimate a combined median incidence of ZDs of 141,583 cases [95% UI: 33,912–250,924] in 2013. The highest burden was caused by non-typhoidal Salmonella and Echinococcus multilocularis, respectively 14,792 DALYs [95% UI: 3,966–41,532] and 11,915 DALYs [95% UI: 4,705–27,114] per year.

Conclusion/Significance

The health impact of zoonoses in Kyrgyzstan is substantial, comparable to that of HIV. Community-based surveillance studies and hospital-based registration of all occurrences of zoonoses would increase the accuracy of the estimates.

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<![CDATA[Potential Risk Factors Associated with Human Cystic Echinococcosis: Systematic Review and Meta-analysis]]> https://www.researchpad.co/article/5989da20ab0ee8fa60b7ec3b

Background

Scientific literature on cystic echinococcosis (CE) reporting data on risk factors is limited and to the best of our knowledge, no global evaluation of human CE risk factors has to date been performed. This systematic review (SR) summarizes available data on statistically relevant potential risk factors (PRFs) associated with human CE.

Methodology/Principal Findings

Database searches identified 1,367 papers, of which thirty-seven were eligible for inclusion. Of these, eight and twenty-nine were case-control and cross-sectional studies, respectively. Among the eligible papers, twenty-one were included in the meta-analyses. Pooled odds ratio (OR) were used as a measure of effect and separately analysed for the two study designs. PRFs derived from case-control studies that were significantly associated with higher odds of outcome were “dog free to roam” (OR 5.23; 95% CI 2.45–11.14), “feeding dogs with viscera” (OR 4.69; 95% CI 3.02–7.29), “slaughter at home” (OR 4.67; 95% CI 2.02–10.78) or at “slaughterhouses” (OR 2.7; 95% CI 1.15–6.3), “dog ownership” (OR 3.54; 95% CI 1.27–9.85), “living in rural areas” (OR 1.83; 95% CI 1.16–2.9) and “low income” (OR 1.68; 95% CI 1.02–2.76). Statistically significant PRFs from cross-sectional studies with higher odds of outcome were “age >16 years” (OR 6.08; 95% CI 4.05–9.13), “living in rural areas” (OR 2.26; 95% CI 1.41–3.61), “being female” (OR 1.38; 95% CI 1.06–1.8) and “dog ownership” (OR 1.37; 95% CI 1.01–1.86).

Conclusions/Significance

Living in endemic rural areas, in which free roaming dogs have access to offal and being a dog-owner, seem to be among the most significant PRFs for acquiring this parasitic infection. Results of data analysed here may contribute to our understanding of the PRFs for CE and may potentially be useful in planning community interventions aimed at controlling CE in endemic areas.

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<![CDATA[Characterisation of Antigen B Protein Species Present in the Hydatid Cyst Fluid of Echinococcus canadensis G7 Genotype]]> https://www.researchpad.co/article/5989db53ab0ee8fa60bdce70

The larva of cestodes belonging to the Echinococcus granulosus sensu lato (s.l.) complex causes cystic echinococcosis (CE). It is a globally distributed zoonosis with significant economic and public health impact. The most immunogenic and specific Echinococcus-genus antigen for human CE diagnosis is antigen B (AgB), an abundant lipoprotein of the hydatid cyst fluid (HF). The AgB protein moiety (apolipoprotein) is encoded by five genes (AgB1-AgB5), which generate mature 8 kDa proteins (AgB8/1-AgB8/5). These genes seem to be differentially expressed among Echinococcus species. Since AgB immunogenicity lies on its protein moiety, differences in AgB expression within E. granulosus s.l. complex might have diagnostic and epidemiological relevance for discriminating the contribution of distinct species to human CE. Interestingly, AgB2 was proposed as a pseudogene in E. canadensis, which is the second most common cause of human CE, but proteomic studies for verifying it have not been performed yet. Herein, we analysed the protein and lipid composition of AgB obtained from fertile HF of swine origin (E. canadensis G7 genotype). AgB apolipoproteins were identified and quantified using mass spectrometry tools. Results showed that AgB8/1 was the major protein component, representing 71% of total AgB apolipoproteins, followed by AgB8/4 (15.5%), AgB8/3 (13.2%) and AgB8/5 (0.3%). AgB8/2 was not detected. As a methodological control, a parallel analysis detected all AgB apolipoproteins in bovine fertile HF (G1/3/5 genotypes). Overall, E. canadensis AgB comprised mostly AgB8/1 together with a heterogeneous mixture of lipids, and AgB8/2 was not detected despite using high sensitivity proteomic techniques. This endorses genomic data supporting that AgB2 behaves as a pseudogene in G7 genotype. Since recombinant AgB8/2 has been found to be diagnostically valuable for human CE, our findings indicate that its use as antigen in immunoassays could contribute to false negative results in areas where E. canadensis circulates. Furthermore, the presence of anti-AgB8/2 antibodies in serum may represent a useful parameter to rule out E. canadensis infection when human CE is diagnosed.

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<![CDATA[A Research Agenda for Helminth Diseases of Humans: Diagnostics for Control and Elimination Programmes]]> https://www.researchpad.co/article/5989db07ab0ee8fa60bc89fa

Diagnostic tools appropriate for undertaking interventions to control helminth infections are key to their success. Many diagnostic tests for helminth infection have unsatisfactory performance characteristics and are not well suited for use in the parasite control programmes that are being increasingly implemented. Although the application of modern laboratory research techniques to improve diagnostics for helminth infection has resulted in some technical advances, uptake has not been uniform. Frequently, pilot or proof of concept studies of promising diagnostic technologies have not been followed by much needed product development, and in many settings diagnosis continues to rely on insensitive and unsatisfactory parasitological or serodiagnostic techniques. In contrast, PCR-based xenomonitoring of arthropod vectors, and use of parasite recombinant proteins as reagents for serodiagnostic tests, have resulted in critical advances in the control of specific helminth parasites. The Disease Reference Group on Helminths Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR) was given the mandate to review helminthiases research and identify research priorities and gaps. In this review, the diagnostic technologies relevant to control of helminth infections, either available or in development, are reviewed. Critical gaps are identified and opportunities to improve needed technologies are discussed.

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<![CDATA[Human cystic echinococcosis in Morocco: Ultrasound screening in the Mid Atlas through an Italian-Moroccan partnership]]> https://www.researchpad.co/article/5989db53ab0ee8fa60bdcf3c

Background

Cystic echinococcosis (CE) is a neglected parasitic zoonosis with considerable socioeconomic impact on affected pastoral communities. CE is endemic throughout the Mediterranean, including Morocco, where the Mid Atlas is the most prevalent area for both human and animal infection. The highest hospital annual incidence of human CE is recorded in the provinces of Ifrane and El Hajeb. However, hospital-based statistics likely underestimate the real prevalence of infection, as a proportion of cases never reach medical attention or official records.

Methodology/Principal findings

In 2012, a project on clinical management of CE in Morocco was launched with the aims of estimating the prevalence of human abdominal CE in selected rural communes of the above mentioned provinces using ultrasound (US) screening and training local physicians to implement US-based focused assessment and rational clinical management of CE according to the WHO-IWGE Expert Consensus. A total of 5367 people received abdominal US during four campaigns in April-May 2014. During the campaigns, 24 local general practitioners received >24 hours of hands-on training and 143 health education sessions were organized for local communities. We found an overall CE prevalence of 1.9%, with significantly higher values in the rural communes of Ifrane than El Hajeb (2.6% vs 1.3%; p<0.001). CE cysts were predominantly in inactive stage, especially in older age groups. However, active cysts were present also in adults, indicating acquisition of infection at all ages. Province of residence was the only risk factor consistently associated with CE infection.

Conclusions/Significance

Our results show a high prevalence and on-going, likely environmental transmission of CE in the investigated provinces of Morocco, supporting the implementation of control activities in the area by national health authorities and encouraging the acceptance and divulgation of diagnosis and treatment algorithms based on imaging for CE at both national and local level.

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<![CDATA[ESCDL-1, a new cell line derived from chicken embryonic stem cells, supports efficient replication of Mardiviruses]]> https://www.researchpad.co/article/5989db52ab0ee8fa60bdc52c

Marek’s disease virus is the etiological agent of a major lymphoproliferative disorder in poultry and the prototype of the Mardivirus genus. Primary avian somatic cells are currently used for virus replication and vaccine production, but they are largely refractory to any genetic modification compatible with the preservation of intact viral susceptibility. We explored the concept of induction of viral replication permissiveness in an established pluripotent chicken embryonic stem cell-line (cES) in order to derive a new fully susceptible cell-line. Chicken ES cells were not permissive for Mardivirus infection, but as soon as differentiation was triggered, replication of Marek’s disease virus was detected. From a panel of cyto-differentiating agents, hexamethylene bis (acetamide) (HMBA) was found to be the most efficient regarding the induction of permissiveness. These initial findings prompted us to analyse the effect of HMBA on gene expression, to derive a new mesenchymal cell line, the so-called ESCDL-1, and monitor its susceptibility for Mardivirus replication. All Mardiviruses tested so far replicated equally well on primary embryonic skin cells and on ESCDL-1, and the latter showed no variation related to its passage number in its permissiveness for virus infection. Viral morphogenesis studies confirmed efficient multiplication with, as in other in vitro models, no extra-cellular virus production. We could show that ESCDL-1 can be transfected to express a transgene and subsequently cloned without any loss in permissiveness. Consequently, ESCDL-1 was genetically modified to complement viral gene deletions thus yielding stable trans-complementing cell lines. We herein claim that derivation of stable differentiated cell-lines from cES cell lines might be an alternative solution to the cultivation of primary cells for virology studies.

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<![CDATA[Comparison of the Diagnostic Accuracy of Three Rapid Tests for the Serodiagnosis of Hepatic Cystic Echinococcosis in Humans]]> https://www.researchpad.co/article/5989da82ab0ee8fa60b9b2d3

Background

The diagnosis of cystic echinococcosis (CE) is based primarily on imaging, in particular with ultrasound for abdominal CE, complemented by serology when imaging results are unclear. In rural endemic areas, where expertise in ultrasound may be scant and conventional serology techniques are unavailable due to lack of laboratory equipment, Rapid Diagnostic Tests (RDTs) are appealing.

Methodology/Principal Findings

We evaluated the diagnostic accuracy of 3 commercial RDTs for the diagnosis of hepatic CE. Sera from 59 patients with single hepatic CE cysts in well-defined ultrasound stages (gold standard) and 25 patients with non-parasitic cysts were analyzed by RDTs VIRapid HYDATIDOSIS (Vircell, Spain), Echinococcus DIGFA (Unibiotest, China), ADAMU-CE (ICST, Japan), and by RIDASCREEN Echinococcus IgG ELISA (R-Biopharm, Germany). Sensitivity, specificity and ROC curves were compared with McNemar and t-test. For VIRapid and DIGFA, correlation between semiquantitative results and ELISA OD values were evaluated by Spearman’s coefficient. Reproducibility was assessed on 16 randomly selected sera with Cohen’s Kappa coefficient. Sensitivity and Specificity of VIRapid (74%, 96%) and ADAMU-CE (57%, 100%) did not differ from ELISA (69%, 96%) while DIGFA (72%, 72%) did (p = 0.045). ADAMU-CE was significantly less sensitive in the diagnosis of active cysts (p = 0.019) while DIGFA was significantly less specific (p = 0.014) compared to ELISA. All tests were poorly sensitive in diagnosing inactive cysts (33.3% ELISA and ADAMU-CE, 42.8% DIGFA, 47.6% VIRapid). The reproducibility of all RDTs was good-very good. Band intensity of VIRapid and DIGFA correlated with ELISA OD values (r = 0.76 and r = 0.79 respectively, p<0.001).

Conclusions/Significance

RDTs may be useful in resource-poor settings to complement ultrasound diagnosis of CE in uncertain cases. VIRapid test appears to perform best among the examined kits, but all tests are poorly sensitive in the presence of inactive cysts, which may pose problems with accurate diagnosis.

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<![CDATA[Identification of Thioredoxin Glutathione Reductase Inhibitors That Kill Cestode and Trematode Parasites]]> https://www.researchpad.co/article/5989db46ab0ee8fa60bd8b1e

Parasitic flatworms are responsible for serious infectious diseases that affect humans as well as livestock animals in vast regions of the world. Yet, the drug armamentarium available for treatment of these infections is limited: praziquantel is the single drug currently available for 200 million people infected with Schistosoma spp. and there is justified concern about emergence of drug resistance. Thioredoxin glutathione reductase (TGR) is an essential core enzyme for redox homeostasis in flatworm parasites. In this work, we searched for flatworm TGR inhibitors testing compounds belonging to various families known to inhibit thioredoxin reductase or TGR and also additional electrophilic compounds. Several furoxans and one thiadiazole potently inhibited TGRs from both classes of parasitic flatworms: cestoda (tapeworms) and trematoda (flukes), while several benzofuroxans and a quinoxaline moderately inhibited TGRs. Remarkably, five active compounds from diverse families possessed a phenylsulfonyl group, strongly suggesting that this moiety is a new pharmacophore. The most active inhibitors were further characterized and displayed slow and nearly irreversible binding to TGR. These compounds efficiently killed Echinococcus granulosus larval worms and Fasciola hepatica newly excysted juveniles in vitro at a 20 µM concentration. Our results support the concept that the redox metabolism of flatworm parasites is precarious and particularly susceptible to destabilization, show that furoxans can be used to target both flukes and tapeworms, and identified phenylsulfonyl as a new drug-hit moiety for both classes of flatworm parasites.

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<![CDATA[Screening of the Open Source Malaria Box Reveals an Early Lead Compound for the Treatment of Alveolar Echinococcosis]]> https://www.researchpad.co/article/5989da28ab0ee8fa60b8185c

The metacestode (larval) stage of the tapeworm Echinococcus multilocularis causes alveolar echinococcosis (AE), a very severe and in many cases incurable disease. To date, benzimidazoles such as albendazole and mebendazole are the only approved chemotherapeutical treatment options. Benzimidazoles inhibit metacestode proliferation, but do not act parasiticidal. Thus, benzimidazoles have to be taken a lifelong, can cause adverse side effects such as hepatotoxicity, and are ineffective in some patients. We here describe a newly developed screening cascade for the evaluation of the in vitro efficacy of new compounds that includes assessment of parasiticidal activity. The Malaria Box from Medicines for Malaria Venture (MMV), comprised of 400 commercially available chemicals that show in vitro activity against Plasmodium falciparum, was repurposed. Primary screening was carried out at 10 μM by employing the previously described PGI assay, and resulted in the identification of 24 compounds that caused physical damage in metacestodes. Seven out of these 24 drugs were also active at 1 μM. Dose-response assays revealed that only 2 compounds, namely MMV665807 and MMV665794, exhibited an EC50 value below 5 μM. Assessments using human foreskin fibroblasts and Reuber rat hepatoma cells showed that the salicylanilide MMV665807 was less toxic for these two mammalian cell lines than for metacestodes. The parasiticidal activity of MMV665807 was then confirmed using isolated germinal layer cell cultures as well as metacestode vesicles by employing viability assays, and its effect on metacestodes was morphologically evaluated by electron microscopy. However, both oral and intraperitoneal application of MMV665807 to mice experimentally infected with E. multilocularis metacestodes did not result in any reduction of the parasite load.

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<![CDATA[A Single Subcutaneous Injection of Cellulose Ethers Administered Long before Infection Confers Sustained Protection against Prion Diseases in Rodents]]> https://www.researchpad.co/article/5989d9f2ab0ee8fa60b6ef6c

Prion diseases are fatal, progressive, neurodegenerative diseases caused by prion accumulation in the brain and lymphoreticular system. Here we report that a single subcutaneous injection of cellulose ethers (CEs), which are commonly used as inactive ingredients in foods and pharmaceuticals, markedly prolonged the lives of mice and hamsters intracerebrally or intraperitoneally infected with the 263K hamster prion. CEs provided sustained protection even when a single injection was given as long as one year before infection. These effects were linked with persistent residues of CEs in various tissues. More effective CEs had less macrophage uptake ratios and hydrophobic modification of CEs abolished the effectiveness. CEs were significantly effective in other prion disease animal models; however, the effects were less remarkable than those observed in the 263K prion-infected animals. The genetic background of the animal model was suggested to influence the effects of CEs. CEs did not modify prion protein expression but inhibited abnormal prion protein formation in vitro and in prion-infected cells. Although the mechanism of CEs in vivo remains to be solved, these findings suggest that they aid in elucidating disease susceptibility and preventing prion diseases.

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<![CDATA[Genetic Characterization of Human-Derived Hydatid Cysts of Echinococcus granulosus Sensu Lato in Heilongjiang Province and the First Report of G7 Genotype of E. canadensis in Humans in China]]> https://www.researchpad.co/article/5989d9f1ab0ee8fa60b6ea99

Cystic echinococcosis (CE) caused by the larval stage of Echinococcus granulosus sensu lato (s.l.) is one of the most important zoonotic parasitic diseases worldwide and 10 genotypes (G1–G10) have been reported. In China, almost all the epidemiological and genotyping studies of E. granulosus s.l. are from the west and northwest pasturing areas. However, in Heilongjiang Province of northeastern China, no molecular information is available on E. granulosus s.l. To understand and to speculate on possible transmission patterns of E. granulosus s.l., we molecularly identified and genotyped 10 hydatid cysts from hepatic CE patients in Heilongjiang Province based on mitochondrial cytochrome c oxidase subunit I (cox1), cytochrome b (cytb) and NADH dehydrogenase subunit 1 (nad1) genes. Two genotypes were identified, G1 genotype (n = 6) and G7 genotype (n = 4). All the six G1 genotype isolates were identical to each other at the cox1 locus; three and two different sequences were obtained at the cytb and nad1 loci, respectively, with two cytb gene sequences not being described previously. G7 genotype isolates were identical to each other at the cox1, cytb and nad1 loci; however, the cytb gene sequence was not described previously. This is the first report of G7 genotype in humans in China. Three new cytb gene sequences from G1 and G7 genotypes might reflect endemic genetic characterizations. Pigs might be the main intermediate hosts of G7 genotype in our investigated area by homology analysis. The results will aid in making more effective control strategies for the prevention of transmission of E. granulosus s.l.

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<![CDATA[Late Cardiac Events after Childhood Cancer: Methodological Aspects of the Pan-European Study PanCareSurFup]]> https://www.researchpad.co/article/5989d9dbab0ee8fa60b678d9

Background and Aim

Childhood cancer survivors are at high risk of long-term adverse effects of cancer and its treatment, including cardiac events. The pan-European PanCareSurFup study determined the incidence and risk factors for cardiac events among childhood cancer survivors. The aim of this article is to describe the methodology of the cardiac cohort and nested case-control study within PanCareSurFup.

Methods

Eight data providers in Europe participating in PanCareSurFup identified and validated symptomatic cardiac events in their cohorts of childhood cancer survivors. Data on symptomatic heart failure, ischemia, pericarditis, valvular disease and arrhythmia were collected and graded according to the Criteria for Adverse Events. Detailed treatment data, data on potential confounders, lifestyle related risk factors and general health problems were collected.

Results

The PanCareSurFup cardiac cohort consisted of 59,915 5-year childhood cancer survivors with malignancies diagnosed between 1940 and 2009 and classified according to the International Classification of Childhood Cancer 3. Different strategies were used to identify cardiac events such as record linkage to population/ hospital or regional based databases, and patient- and general practitioner-based questionnaires.

Conclusion

The cardiac study of the European collaborative research project PanCareSurFup will provide the largest cohort of 5-year childhood cancer survivors with systematically ascertained and validated data on symptomatic cardiac events. The result of this study can provide information to minimize the burden of cardiac events in childhood cancer survivors by tailoring the follow-up of childhood cancer survivors at high risk of cardiac adverse events, transferring this knowledge into evidence-based clinical practice guidelines and providing a platform for future research studies in childhood cancer patients. 

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