The identification and characterization of new immunogenic egg components: implications for evaluation and control of the immunopathogenic T cell response in schistosomiasis

In schistosomiasis, granuloma formation to parasite eggs signals the beginning of a chronic and potentially life-threatening disease. Granulomas are strictly mediated by CD4+ T helper (Th) cells specific for egg antigens; however, the number and identity of these T cell-sensitizing molecules are largely unknown. We have used monoclonal T cell reagents derived from egg-sensitized individuals as probes to track down, isolate and positively identify several egg antigens; this approach implicitly assures that the molecules of interest are T cell immunogens and, hence, potentially pathogenic. The best studied and most abundant egg component is the Sm-p40 antigen. Sm-p40 and its peptide 234-246 elicit a strikingly immunodominant Th-1-polarized response in C3H and CBA mice, which are H-2k strains characterized by severe egg-induced immunopathology. Two additional recently described T cell-sensitizing egg antigens are Schistosoma mansoni phosphoenolpyruvate carboxykinase (Sm-PEPCK) and thioredoxin peroxidase-1 (Sm-TPx-1). In contrast to Sm-p40, both of these molecules induce a more balanced Th-1/Th-2 response, and are relatively stronger antigens in C57BL/6 mice, which develop smaller egg granulomas. Importantly, Sm-p40 and Sm-PEPCK have demonstrated immunogenicity in humans. The findings in the murine model introduce the important notion that egg antigens can vary significantly in immunogenicity according to the host's genetic background. A better knowledge of the principal immunogenic egg components is necessary to determine whether the immune responses to certain antigens can serve as indicators or predictors of the form and severity of clinical disease, and to ascertain whether such responses can be manipulated for the purpose of reducing pathology.

Draft Health and Personal Social Services (Quality, Improvement and Regulation) Order (PDF 56 KB)

Explanatory Memorandum

The Health and Personal Social Services (Quality, Improvement and Regulation) NI Order 2003 (PDF 178 KB)

Draft Statutory Instruments

Report to the Minister for Health from the Health Insurance Authority (Redacted) on an evaluation and analysis of returns for 1 July 2012 to 30 June 2013 including advice on risk equalisation credits

Report to the Minister for Health from the Health Insurance Authority (Redacted) on an evaluation and analysis of returns for 1 July 2012 to 30 June 2013 including advice on risk equalisation credits Click here to download PDF 11MB

HIA Report to the Minister for Health on an evaluation and analysis of returns for 1 July 2011 to 30 June 2012 including advice

HIA Report to the Minister for Health The Department of health requested that the Health Insurance Authority provide a report to the Minister ‘in anticipation of the enactment of the health Insurance (Amendment) Bill 2012.” Click here to download PDF 8.87MB The Health Insurance (Amendment) Bill 2012 Link to the Minister’s Second Stage Speech to the Dáil on 14 November 2012          

Introduction to Evaluation and Health Economics

A video summary by Orla Doyle

Serological diagnosis of Chagas disease: evaluation and characterisation of a low cost antigen with high sensitivity and specificity

In spite of evident progress in the serology of Chagas disease, the requirement for new diagnostic antigens persists. We have evaluated different antigens obtained from Trypanosoma cruzi grown in medium rich in nutrients or under nutrient stress, autoclaved or sonicated and fractionated by differential centrifugation. The resulting antigens were evaluated for diagnosis of Chagas disease using ELISA. Immunofluorescence of the parasites demonstrated that nutrient stress induced changes in the distribution and density of antigens recognised by a pool of sera from experimentally infected mice. When evaluated using ELISA, it was evident that most fractions had good sensitivity but poor specificity. Surprisingly, the best specificity and sensitivity was observed with parasites cultured under nutrient stress and autoclaved. Furthermore this antigen had low cross reactivity with sera from other parasitic diseases, Leishmaniasis in particular. Western blot analysis demonstrated that autoclaving seems to non-specifically eliminate cross-reactive antigens. In conclusion, autoclaving epimastigotes of T. cruzi, after nutrient stress, allowed us to obtain an antigen that could be used in the serological diagnosis of Chagas disease.

Immunologic evaluation and validation of methods using synthetic peptides derived from Mycobacterium tuberculosis for the diagnosis of tuberculosis infection

The goal of this study was to demonstrate the usefulness of an enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of pulmonary tuberculosis (PTB) and extrapulmonary TB (EPTB). This assay used 20 amino acid-long, non-overlapped synthetic peptides that spanned the complete Mycobacterium tuberculosis ESAT-6 and Ag85A sequences. The validation cohort consisted of 1,102 individuals who were grouped into the following five diagnostic groups: 455 patients with PTB, 60 patients with EPTB, 40 individuals with non-EPTB, 33 individuals with leprosy and 514 healthy controls. For the PTB group, two ESAT-6 peptides (12033 and 12034) had the highest sensitivity levels of 96.9% and 96.2%, respectively, and an Ag85A-peptide (29878) was the most specific (97.4%) in the PTB groups. For the EPTB group, two Ag85A peptides (11005 and 11006) were observed to have a sensitivity of 98.3% and an Ag85A-peptide (29878) was also the most specific (96.4%). When combinations of peptides were used, such as 12033 and 12034 or 11005 and 11006, 99.5% and 100% sensitivities in the PTB and EPTB groups were observed, respectively. In conclusion, for a cohort that consists entirely of individuals from Venezuela, a multi-antigen immunoassay using highly sensitive ESAT-6 and Ag85A peptides alone and in combination could be used to more rapidly diagnose PTB and EPTB infection.

Quality uncertainty and allocation of decision rights in the European protected designation of origin

The paper considers some issue in the governance of the European Protected Designation of Origin (PDO). The PDO systems are the outcomes of both farmers and consumers expectations and connect the valorisation of the agricultural and rural resources of given territories to the quality of typical products. A critical point in the governance of the PDO systems is represented by the connection between the quality strategies and the uncertainty. The paper argues that the PDO systems can be thought of as strictly coordinated subsystems in which the ex post governance play a critical role in coping with quality uncertainty. The study suggests that the society's inducements given raise to complex organizational systems in which the allocation of decision rights to PDO collective organizations play a major role. The empirical analysis is carried out by examining ten Italian PDO systems in order to identify the decision rights allocated.

Sales restriction, quality selection and the mode of competition

A regulator imposing “sales restrictions” on firms competing in oligopolistic markets may enhance quality provision by the firms. Moreover, for most restrictions levels, the impact on quality selection is invariant to the mode of competition

Semantic web adoption: online tools for web evaluation and metadata extraction

This work briefly analyses the difficulties to adopt the Semantic Web, and in particular proposes systems to know the present level of migration to the different technologies that make up the Semantic Web. It focuses on the presentation and description of two tools, DigiDocSpider and DigiDocMetaEdit, designed with the aim of verifYing, evaluating, and promoting its implementation.