332,751 research outputs found

    Benefit of viral load testing for confirmation of immunological failure in HIV patients treated in rural Malawi.

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    Objective  Viral load testing is used in the HIV programme of Chiradzulu, Malawi, to confirm the diagnosis of immunological failure to prevent unnecessary switching to second-line therapy. Our objective was to quantify the benefit of this strategy for management of treatment failure in a large decentralized HIV programme in Africa. Methods  Retrospective analysis of monitoring data from adults treated with first-line antiretroviral regimens for >1 year and meeting the WHO immunological failure criteria in an HIV programme in rural Malawi. The positive predictive value of using immunological failure criteria to diagnose virological failure (viral load >5000 copies/ml) was estimated. Results  Of the 227 patients with immunological failure (185 confirmed with a repeat CD4 measurement), 155 (68.2%) had confirmatory viral load testing. Forty-four (28.4%) had viral load >5000 copies/ml and 57 (36.8%) >1000 copies/ml. Positive predictive value was 28.4% (95% CI 21.4-36.2%). Repeat CD4 count testing showed that 41% of patients initially diagnosed with immunological failure did no longer meet failure criteria. Conclusions  Our results support the need for confirming all cases of immunological failure with viral load testing before switching to second-line ART to optimize the use of resources in developing countries

    Modelling Immunological Memory

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    Accurate immunological models offer the possibility of performing highthroughput experiments in silico that can predict, or at least suggest, in vivo phenomena. In this chapter, we compare various models of immunological memory. We first validate an experimental immunological simulator, developed by the authors, by simulating several theories of immunological memory with known results. We then use the same system to evaluate the predicted effects of a theory of immunological memory. The resulting model has not been explored before in artificial immune systems research, and we compare the simulated in silico output with in vivo measurements. Although the theory appears valid, we suggest that there are a common set of reasons why immunological memory models are a useful support tool; not conclusive in themselves

    The role of targeted viral load testing in diagnosing virological failure in children on antiretroviral therapy with immunological failure.

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    Objectives  To determine the improvement in positive predictive value of immunological failure criteria for identifying virological failure in HIV-infected children on antiretroviral therapy (ART) when a single targeted viral load measurement is performed in children identified as having immunological failure. Methods  Analysis of data from children (<16 years at ART initiation) at South African ART sites at which CD4 count/per cent and HIV-RNA monitoring are performed 6-monthly. Immunological failure was defined according to both WHO 2010 and United States Department of Health and Human Services (DHHS) 2008 criteria. Confirmed virological failure was defined as HIV-RNA >5000 copies/ml on two consecutive occasions <365 days apart in a child on ART for ≥18 months. Results  Among 2798 children on ART for ≥18 months [median (IQR) age 50 (21-84) months at ART initiation], the cumulative probability of confirmed virological failure by 42 months on ART was 6.3%. Using targeted viral load after meeting DHHS immunological failure criteria rather than DHHS immunological failure criteria alone increased positive predictive value from 28% to 82%. Targeted viral load improved the positive predictive value of WHO 2010 criteria for identifying confirmed virological failure from 49% to 82%. Conclusion  The addition of a single viral load measurement in children identified as failing immunologically will prevent most switches to second-line treatment in virologically suppressed children

    Evaluation of Clinical and Immunological Markers for predicting Virological Failure in a HIV/AIDS treatment cohort in Busia, Kenya

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    In resource-limited settings where viral load (VL) monitoring is scarce or unavailable, clinicians must use immunological and clinical criteria to define HIV virological treatment failure. This study examined the performance of World Health Organization (WHO) clinical and immunological failure criteria in predicting virological failure in HIV patients receiving antiretroviral therapy (ART)

    Methods for microbiological and immunological studies of space flight crews

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    Systematic laboratory procedures compiled as an outgrowth of a joint U.S./U.S.S.R. microbiological-immunological experiment performed during the Apollo-Soyuz Test Project space flight are presented. Included are mutually compatible methods for the identification of aerobic and microaerophilic bacteria, yeast and yeastlike microorganisms, and filamentous fungi; methods for the bacteriophage typing of Staphylococcus aureus; and methods for determining the sensitivity of S. aureus to antibiotics. Immunological methods using blood and immunological and biochemical methods using salivary parotid fluid are also described. Formulas for media and laboratory reagents used are listed

    Novel statistical approaches for non-normal censored immunological data: analysis of cytokine and gene expression data

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    Background: For several immune-mediated diseases, immunological analysis will become more complex in the future with datasets in which cytokine and gene expression data play a major role. These data have certain characteristics that require sophisticated statistical analysis such as strategies for non-normal distribution and censoring. Additionally, complex and multiple immunological relationships need to be adjusted for potential confounding and interaction effects. Objective: We aimed to introduce and apply different methods for statistical analysis of non-normal censored cytokine and gene expression data. Furthermore, we assessed the performance and accuracy of a novel regression approach in order to allow adjusting for covariates and potential confounding. Methods: For non-normally distributed censored data traditional means such as the Kaplan-Meier method or the generalized Wilcoxon test are described. In order to adjust for covariates the novel approach named Tobit regression on ranks was introduced. Its performance and accuracy for analysis of non-normal censored cytokine/gene expression data was evaluated by a simulation study and a statistical experiment applying permutation and bootstrapping. Results: If adjustment for covariates is not necessary traditional statistical methods are adequate for non-normal censored data. Comparable with these and appropriate if additional adjustment is required, Tobit regression on ranks is a valid method. Its power, type-I error rate and accuracy were comparable to the classical Tobit regression. Conclusion: Non-normally distributed censored immunological data require appropriate statistical methods. Tobit regression on ranks meets these requirements and can be used for adjustment for covariates and potential confounding in large and complex immunological datasets

    Do we need broad immunological work-up in all patients with CIS?

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    BACKGROUND: The aim of this study was to determine the prevalence of altered immunological tests and their clinical significance in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). ----- PATIENTS AND METHODS: The information was gathered from medical records of patients hospitalized in the Referral Center for Demyelinating Diseases in the 2008-2010 period. All patients had ANA, ENA profile, ANCA, aCl IgG and IgM, C3, C4, CH50, anti-TPO, AST and RF antibodies tested. ----- RESULTS: From 726 patients with CIS that were reviewed, the complete battery of immunological tests was performed in 418 of them (57.6%), representing our cohort. Altered tests were found in 235 patients (56.2%); 73 (17.4%) had positive antinuclear antibodies, 14 (3.3%) had positive ENA, 47 (11.2%) had positive aCl IgG, 83 (19.8%) had positive aCl IgM, and 13 (3.1%) had anti TPO antibodies. We found no correlation between ANA, aCl IgG or IgM positivity (ANA vs aCL IgG p=0.554; ANA vs aCL IgM p=0.19; aCL IgG vs aCL IgM, p=0.155). None of the patients had any clinical manifestations other than MS symptoms. ----- CONCLUSION: These results indicate that significant number of patients with CIS have altered immunological tests but nevertheless none of them had clinical expression of any other autoimmune disease making them clinically insignificant. In conclusion there is no need to perform extensive immunological work-up in all patients with CIS. Contrary, our results argue for more focused testing rather than a battery of screening tests

    Genetic analysis of immunological traits in tilapia

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    The immunological response to handling stress of four tilapia species is evaluated.Polymorphism is examined in genes known to influence immune response in fish

    Screening vaccine formulations for biological activity using fresh human whole blood.

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    Understanding the relevant biological activity of any pharmaceutical formulation destined for human use is crucial. For vaccine-based formulations, activity must reflect the expected immune response, while for non-vaccine therapeutic agents, such as monoclonal antibodies, a lack of immune response to the formulation is desired. During early formulation development, various biochemical and biophysical characteristics can be monitored in a high-throughput screening (HTS) format. However, it remains impractical and arguably unethical to screen samples in this way for immunological functionality in animal models. Furthermore, data for immunological functionality lag formulation design by months, making it cumbersome to relate back to formulations in real-time. It is also likely that animal testing may not accurately reflect the response in humans. For a more effective formulation screen, a human whole blood (hWB) approach can be used to assess immunological functionality. The functional activity relates directly to the human immune response to a complete formulation (adjuvant/antigen) and includes adjuvant response, antigen response, adjuvant-modulated antigen response, stability, and potentially safety. The following commentary discusses the hWB approach as a valuable new tool to de-risk manufacture, formulation design, and clinical progression
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