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      Relevance and acceptability of using the Quantiferon gold test (QGIT) to screen CD4 blood draws for latent TB infection among PLHIV in South Africa: formative qualitative research findings from the TEKO trial

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          Abstract

          Background

          Tuberculosis (TB) is the leading cause of mortality among people living with HIV (PLHIV), despite the availability of effective preventive therapy. The TEKO trial is assessing the impact of using a blood test, Quantiferon-TB Gold In-Tube Test (QGIT), to screen for latent TB compared to the Tuberculin Screening Test (TST) among PLHIV in South Africa.

          Methods

          Fifty-six qualitative interviews were conducted with PLHIV and clinical providers participating in the TEKO trial. We explored TB screening, diagnosis, and treatment guidelines and processes and the use of the QGIT to screen for latent TB infection at the time of CD4 blood draw. Thematic content analysis was conducted.

          Results

          Considerable variability in TB screening procedures was documented due to lack of personnel and clarity regarding current national TB guidelines for PLHIV. Few clinics had started using the TST per national guidelines and many patients had never heard of isoniazid preventive therapy (IPT). Nearly all participants supported the idea of latent TB screening using routine blood drawn for CD4 counts.

          Conclusions

          Findings indicate that screening for latent TB infection using QGIT from blood drawn for CD4 counts among PLHIV is an acceptable approach to increase latent TB detection given the challenges associated with ensuring systematic latent TB screening in overburdened public clinics.

          Trial registration

          The results presented here were from formative research related to the TEKO trial (Identifier NCT02119130, registered 10 April 2014).

          Electronic supplementary material

          The online version of this article (10.1186/s12913-018-3088-8) contains supplementary material, which is available to authorized users.

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          Most cited references4

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          Overcoming health-systems constraints to achieve the Millennium Development Goals.

          Effective interventions exist for many priority health problems in low income countries; prices are falling, and funds are increasing. However, progress towards agreed health goals remains slow. There is increasing consensus that stronger health systems are key to achieving improved health outcomes. There is much less agreement on quite how to strengthen them. Part of the challenge is to get existing and emerging knowledge about more (and less) effective strategies into practice. The evidence base also remains remarkably weak, partly because health-systems research has an image problem. The forthcoming Ministerial Summit on Health Research seeks to help define a learning agenda for health systems, so that by 2015, substantial progress will have been made to reducing the system constraints to achieving the MDGs.
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            Interferon gamma release assays: principles and practice.

            The last decade has witnessed significant advances in mycobacterial genomics and cellular research which have resulted in the development of two new blood tests, the enzyme-linked immunospot assay (ELISpot) (TSPOT.TB, Oxford Immunotec, Oxford, UK) and the enzyme-linked immunosorbent assay (ELISA) (QuantiFERON-TB Gold In-Tube, Cellestis, Carnegie, Australia). These tests, which are collectively known as interferon gamma release assays (IGRAs), detect latent tuberculosis infection (LTBI) by measuring interferon (IFN)-gamma release in response to antigens present in Mycobacterium tuberculosis, but not bacille Calmette-Guerin (BCG) vaccine and most nontuberculous mycobacteria. This is done through enumeration of IFN-gamma-secreting T cells (ELISpot) or by measurement of IFN-gamma concentration (ELISA). The evidence base for these tests has expanded rapidly and now demonstrates that IGRAs are more specific than the tuberculin skin test (TST) as they are not confounded by previous BCG vaccination. In addition, with active tuberculosis (TB) as a surrogate for LTBI, it appears that the ELISA has a similar sensitivity to the TST, whereas the ELISpot is more sensitive. Using degree of exposure to TB as a surrogate for LTBI, both assays correlate at least as well with TB exposure as the TST. Recent longitudinal data have now demonstrated the prognostic power of positive IGRA results in recent contacts for the subsequent progression to active TB. Deployment of IGRAs, driven by new guidelines internationally, will impact on clinical practice in several ways. Their high specificity means that BCG-vaccinated individuals with a false-positive TST will not receive unnecessary preventive treatment, whereas improved sensitivity in individuals with weakened cellular immunity at highest risk of progressing to active TB (for example HIV-positive individuals) enables more reliable targeted testing and treatment of these vulnerable groups. The role of IGRAs in active TB is less clear but they may be useful as adjunctive tests in the diagnostic work-up of an individual with suspected TB. Finally, recent developments and future directions in IGRA development are reviewed. Copyright 2009 Elsevier España, S.L. All rights reserved.
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              Different screening strategies (single or dual) for the diagnosis of suspected latent tuberculosis: a cost effectiveness analysis

              Background Previous health economic studies recommend either a dual screening strategy [tuberculin skin test (TST) followed by interferon-γ-release assay (IGRA)] or a single one [IGRA only] for latent tuberculosis infection (LTBI), the former largely based on claims that it is more cost-effective. We sought to examine that conclusion through the use of a model that accounts for the additional costs of adverse drug reactions and directly compares two commercially available versions of the IGRA: the Quantiferon-TB-Gold-In-Tube (QFT-GIT) and T-SPOT.TB. Methods A LTBI screening model directed at screening contacts was used to perform a cost-effectiveness analysis, from a UK healthcare perspective, taking into account the risk of isoniazid-related hepatotoxicity and post-exposure TB (2 years post contact) using the TST, QFT-GIT and T-SPOT.TB IGRAs. Results Examining costs alone, the TST/IGRA dual screening strategies (TST/T-SPOT.TB and TST/QFT-GIT; £162,387 and £157,048 per 1000 contacts, respectively) cost less than their single strategy counterparts (T-SPOT.TB and QFT-GIT; £203,983 and £202,921 per 1000 contacts) which have higher IGRA test costs and greater numbers of persons undergoing LTBI treatment. However, IGRA alone strategies direct healthcare interventions and costs more accurately to those that are truly infected. Subsequently, less contacts need to be treated to prevent an active case of TB (T-SPOT.TB and QFT-GIT; 61.7 and 69.7 contacts) in IGRA alone strategies. IGRA single strategies also prevent more cases of post-exposure TB. However, this greater effectiveness does not outweigh the lower incremental costs associated with the dual strategies. Consequently, when these costs are combined with effectiveness, the IGRA dual strategies are more cost-effective than their single strategy counterparts. Comparing between the IGRAs, T-SPOT.TB-based strategies (single and dual; £39,712 and £37,206 per active TB case prevented, respectively) were more cost-effective than the QFT-GIT-based strategies (single and dual; £42,051 and £37,699 per active TB case prevented, respectively). Using the TST alone was the least cost-effective (£47,840 per active TB case prevented). Cost effectiveness values were sensitive to changes in LTBI prevalence, IGRA test sensitivities/specificities and IGRA test costs. Conclusion A dual strategy is more cost effective than a single strategy but this conclusion is sensitive to screening test assumptions and LTBI prevalence.
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                Author and article information

                Contributors
                +1 (410) 955 2218 , dkerrig1@jhu.edu
                carrie_tudor@hotmail.com
                Motlhaolengk@phru.co.za
                lebinal@phru.co.za
                qomfuc@phru.co.za
                Ebrahim.Variava@wits.ac.za
                schon2@jhmi.edu
                Neil.Martinson@wits.ac.za
                jgolub@jhmi.edu
                Journal
                BMC Health Serv Res
                BMC Health Serv Res
                BMC Health Services Research
                BioMed Central (London )
                1472-6963
                16 April 2018
                16 April 2018
                2018
                : 18
                : 288
                Affiliations
                [1 ]The Johns Hopkins Bloomberg School of Public Health, Department of Health, Behavior and Society, 624 North Broadway Street, HH257, Baltimore, MD 21205 USA
                [2 ]The Johns Hopkins School of Medicine, Center for Tuberculosis Research, Baltimore, MD USA
                [3 ]ISNI 0000 0004 1937 1135, GRID grid.11951.3d, The University of the Witwatersrand, Perinatal HIV Research Unit, ; Johannesburg, South Africa
                Article
                3088
                10.1186/s12913-018-3088-8
                5902890
                29661197
                c14f7aad-c4d1-4fa3-ac3b-e15a28cea670
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 3 June 2017
                : 3 April 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;
                Award ID: R01AI095041
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Health & Social care
                tb,hiv,qgit,tst,qualitative methods,south africa
                Health & Social care
                tb, hiv, qgit, tst, qualitative methods, south africa

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