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Specimen types and collection methods Specimen integrity is critical to the accuracy of testing. Where the instructions for use do not include a certain specimen type within the intended use, it indicates that the assay manufacturer has not yet validated that specimen type for use with their assay. However, taking whole blood specimens using venepuncture requires technical skill and profciency, with the need for additional processing steps to generate serum/plasma from the venous whole blood, which requires a centrifuge and refrigerated storage facilities. Collection of oral fuid and capillary whole blood is less invasive than venepuncture. However, oral fuid testing is currently limited to serological tests, and may have lower sensitivity than testing performed on capillary whole blood or serum/ plasma specimens. If eluted from the flter paper and used for the the manufacturer has not validated test procedure. Although disclosure to supportive family members and health workers is often benefcial, this must be done only with the consent of the person being tested. Promoting testing awareness Depending on the current levels of knowledge and awareness of hepatitis in different countries and settings, general promotion and awareness campaigns for viral hepatitis testing and where it is available may be necessary. This may include promotion through the mass media, including radio, television, billboards and posters, the Internet and electronic social media. Creating an enabling environment Critical enablers are strategies, activities and approaches (generally outside the purview of the health sector) that are key to the success of health sector interventions. Addressing such critical enablers as reducing stigma and discrimination, empowering the community and reviewing certain national laws, policies and practice can help strengthen interventions to support the uptake of viral hepatitis testing and linkages to prevention, care and treatment. People being tested for hepatitis B or C must give informed consent to be tested and counselled. Verbal consent is suffcient, and they should be informed of the process for testing and of their right to decline. Provision of information about testing and the need for consent can be delivered in a group setting, such as group health education, but clients should give consent in an individual and private manner.

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Physical examination should include evaluation for stigmata of advanced liver disease such as spider angiomata, palmar erythema, splenomegaly, jaundice, or caput medusa. Assessment of liver disease severity Assessment of liver disease severity should be done prior to therapy. Identifying patients with cirrhosis is of particular importance, as the likelihood of response to therapy and post-treatment prognosis are proportional to the stage of fibrosis. The absence of significant fibrosis may also have important implications for the choice or timing of therapy. Assessment of the stage of fibrosis by biopsy is not required in patients with clinical evidence of cirrhosis. Alternative, non-invasive methods can now be used instead of liver biopsy to assess liver disease severity prior to therapy at a safe level of predictability. In case of contradictory results with non-invasive markers, liver biopsy may be indicated. Also, histology may 15 be required in cases of known or suspected mixed etiologies. Avoid hemolysed samples as it may interfere with the ability of tests to accurately test the markers. Hepatitis A Three serological markers are available for the diagnosis of hepatitis A. These are fi Hepatitis A Total(IgG and IgM) antibody fi Hepatitis A IgM fi Hepatitis A IgG 16 Figure 1 Scheme of typical clinical and laboratory features of acute Hepatitis A fi Hepatitis A IgM is generally detectable 5-10 days before onset of symptoms and can persist for upto 6 months. The antigen is detectable even before the liver enzymes elevation and onset of clinical illness. This has no effect on viral replication, in fact such cases are more difficult to treat and have greater risk of turning to cirrhosis. Genotyping and Resistance Testing: fi the genotyping is indicated for detection of mutations that confer resistance to antiviral agents and for epidemiological purpose in case of outbreak investigation. No particular diet has had a major impact on outcomes of patients with acute hepatitis A. Patients rarely require hospitalization except for those who develop acute hepatic failure. While the time course that differentiates acute liver failure from chronic liver failure varies between reports, a commonly used cut-off is an illness duration of <26 weeks. Acute liver failure can be subcategorized based upon how long the patient has been ill and various cutoffs have been used.

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The criteria for hypersplenism autoimmune haemolytic anaemia or thrombocytopenia, the are as under: respective blood cell counts are increased following 1. Splenic destruction of one or more of the cell types in the as under: peripheral blood causing anaemia, leucopenia, thrombo1. Red cells: There is appearance of target cells in the blood cytopenia, or pancytopenia. Splenectomy is followed by improvement in the severity shows increased resistance to haemolysis. There is shift-to-left of the myeloid medulla composed of onion skin-like concentrically arranged cells with appearance of some myelocytes. Platelets: Within hours after splenectomy, there is rise in Thymocytes are predominantly present in the cortex. These cells include immature T lymphocytes in the cortex and mature T lymphocytes in the medulla. The most common cause of splenic rupture or laceration is the main function of the thymus is in the cell-mediated blunt trauma. Nonimmunity by T-cells and by secretion of thymic hormones traumatic or spontaneous rupture occurs in an enlarged such as thymopoietin and thymosin-fi1. In acute Thymic lesions are associated with diverse conditions infections, the spleen can enlarge rapidly to 2 to 3 times its which may be immunologic, haematologic or neoplastic. Some of the other common causes of involvement in myasthenia gravis is discussed in spontaneous splenic rupture are splenomegaly due to chronic Chapter 28. Sometimes Thymic hypoplasia and agenesis are acquired and congenital fragments of splenic tissue are autotransplanted within the disorders respectively in which the gland is either unusually peritoneal cavity and grow into tiny spleens there (splenosis). Acquired hypoplasia occurs as an Primary tumours of the spleen are extremely rare. The ageing phenomenon or may occur in the young due to severe only notable benign tumours are haemangiomas and stress, malnutrition, irradiation, therapy with cytotoxic drugs lymphangioma, while examples of primary malignant and glucocorticoids. Enlargement of the thymus or failure to involute produces Secondary tumours occur late in the course of disease thymic hyperplasia. Hyperplasia is usually associated with and represent haematogenous dissemination of the appearance of lymphoid follicles in the medulla of the thymus malignant tumour. Splenic metastases appear as multiple and is called thymic follicular hyperplasia.

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Inputs and assumptions used was no evidence of this type for the sub-systems relating in economic evaluations can also vary widely. There is scope for harmonization between European While covering more sub-systems, the level of evidence countries in terms of the process and methods for for reports and non-systematic reviews was inherently developing recommendations, including sharing of lower, with most references to health system factors resources such as systematic reviews (to avoid duplicated being based on expert opinion, either the opinion of the effort) and agreeing common definitions. This would authors themselves or surveys of individual experts on have many direct benefits, especially for families moving vaccination, rather than observational or interventional between countries, as well as indirect ones, such as studies. Moreover, the limited information about study or reducing the scope for those opposed to immunization article references provided in the non-systematic reviews to portray differences negatively. Common European made it more difficult to assess their particular relevance guidelines can be established (72) and, unlike across to this review. Broader review articles could fill the gaps where evidence from outcomes, such as economic analysis in immunization literature reviews and reports was not available. While that the information provided in reviews was generally these analyses can assist modelling future effects of the opinion of the author(s), with occasional reference to vaccines, comparing different strategies, identifying the literature, and did not add much to the information critical input parameter, estimating budget impact and found in the systematic reviews, non-systematic reviews cost-effectiveness, appraisals are generally informal and reports. Given the general nature of this data and and without the use of cost effectiveness thresholds or the availability of evidence from systematic reviews multiple-criteria decision making (36, 37). Systematic and reports we did not extract any data about the and harmonized development of recommendations characteristics of the articles. Employing lay workers for the purposes of recommendations are likely to remain due to varying improving coverage (28) or implementing programmes national or regional priorities, systems and finance across within the school system are examples of this, although Europe. Funding Registering the population Funding mechanisms for vaccination vary across Europe Ideally immunization registers should collect data on and across vaccination types, including out-of-pocket, vaccines, generate reminders/recall notices, provide publicly funded, official health insurance and employer official vaccination forms on request, allow coverage funding, either in full or in part. Recommendations assessments, be established from birth, linked to health that are not accompanied by the necessary funding may outcomes (to monitor long term impact and performance), not achieve adequate uptake but different countries in protect data, allow data sharing and be standardized, such Europe will have different public health priorities (14). However, not only the ability to fund vaccination programmes (including do some countries lag behind in terms of establishing capacity, identification of and response to inequalities such comprehensive information systems, there are also in uptake, monitoring and investment, as well as unit certain under-vaccinated population groups. Roma, vaccination costs) can be frustrated by financial crises, migrants and refugees) that have restricted access to although at such times concerted efforts to maintain healthcare and these groups also tend to be those who vaccination coverage are most important (75). Some may be excluded from medical and population registers countries, such as those in Southern Europe with fewer due to high mobility/migration, lack of appropriate resources available, may also be more sensitive to changes information, fear of legal consequences, economic in funding than other high-income countries where environment and insufficient coordination among public parental hesitancy is more of an issue in vaccine refusal health authorities (39, 40). Enacting legislation Vaccination programmes can be mandatory, based on Monitoring public attitudes recommendations alone, or a mix of both (77). This is essentially a political decision, reflecting views about There are challenges in terms of vaccination coverage the relationship between the individual and the state. This includes both disease outbreaks and this will depend on context, while comparisons are general issues with achieving target coverage rates.

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