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Gaps in Study Design for Immune Parameter Research for Latent Tuberculosis Infection: A Systematic Review.

ABSTRACT: Background:Immune parameters (IP) have been extensively studied to distinguish between latent tuberculosis (LTBI) and active tuberculosis (TB). Objective:To determine the IP associated with LTBI, compared to active TB and individuals not infected by M. tuberculosis published in literature. Methods:We conducted a systematic search using Google Scholar and PubMed databases, combining the MeSH terms latent tuberculosis, Mycobacterium tuberculosis, cytokines, and biological markers, with the free terms, biomarkers and cytokines. Spanish, English, and Portuguese articles comparing the concentration of IP associated with LTBI, either in plasma/serum or in vitro, in adults and nonimmunocompromised versus individuals with TB or without M. tuberculosis infection between 2006 July and 2018 July were included. Two blinded reviewers carried out the searches, read the abstracts, and selected the articles for analysis. Participants' information, diagnostic criteria, IP, detection methods, and biases were collected. Results:We analyzed 36 articles (of 637 abstracts) with 93 different biomarkers in different samples. We found 24 parameters that were increased only in active TB (TGF-?, CSF3, CSF2, CCL1 [I-309], IL-7, TGF-?1, CCL3 [MIP-1?], sIL-2R, TNF-?, CCL7 [MCP-3], IFN-?, fractalkine, I-TAG, CCL8 [MCP-2], CCL21 [6Ckine], PDGF, IL-22, VEGF-A, LXA4, PGE2, PGF2?, sCD163, sCD14, and 15-Epi-LXA4), five were elevated in LTBI (IL-5, IL-17F, IL-1, CCL20 [MIP-3?], and ICAM-1), and two substances were increased among uninfected individuals (IL-23 and basic FGF). We found high heterogeneity between studies including failure to account for the time/illness of the individuals studied; varied samples and protocols; different clinical classification of TB; different laboratory methods for IP detection, which in turn leads to variable units of measurement and assay sensitivities; and selection bias regarding TST and booster effect. None of the studies adjusted the analysis for the effect of ethnicity. Conclusions:It is mandatory to harmonize the study of immune parameters for LTBI diagnosis. This systematic review is registered with PROSPERO CRD42017073289.

SUBMITTER: Herrera M

PROVIDER: S-EPMC7191376 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Gaps in Study Design for Immune Parameter Research for Latent Tuberculosis Infection: A Systematic Review.

Herrera Mariana M Vera Cristian C Keynan Yoav Y Rueda Zulma Vanessa ZV

Journal of immunology research 20200421

<h4>Background</h4>Immune parameters (IP) have been extensively studied to distinguish between latent tuberculosis (LTBI) and active tuberculosis (TB).<h4>Objective</h4>To determine the IP associated with LTBI, compared to active TB and individuals not infected by <i>M. tuberculosis</i> published in literature.<h4>Methods</h4>We conducted a systematic search using Google Scholar and PubMed databases, combining the MeSH terms latent tuberculosis, <i>Mycobacterium tuberculosis</i>, cytokines, and ...[more]

PMID: 32377537

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Project description:ContextLatent tuberculosis infection diagnosis and treatment is a strategic priority for eliminating tuberculosis in the U.S. The Centers for Disease Control and Prevention has recommended the short-course regimen of 3-month isoniazid-rifapentine administered by directly observed therapy. However, longer-duration regimens remain the most widely prescribed latent tuberculosis infection treatments. Limitation on adoption of 3-month isoniazid-rifapentine in the U.S. might be because of patients' preference for self-administered therapy, providers' lack of familiarity with 3-month isoniazid-rifapentine, or lack of resources to support directly observed therapy. This review examines the most recent evidence regarding 3-month isoniazid-rifapentine's effectiveness, safety, and treatment completion when directly compared with other latent tuberculosis infection regimens primarily comprising 9-month isoniazid treatment.Evidence acquisitionUsing Community Guide methodology, reviewers identified, evaluated, and summarized available evidence published during January 2006-June 2017. Analysis of the data was completed in 2017.Evidence synthesisThe analysis included 15 unique studies. Three-month isoniazid-rifapentine was determined to be equal to other latent tuberculosis infection regimens in effectiveness (OR=0.89, 95% CI=0.46, 1.70), and has higher treatment completion (87.5%, 95% CI=83.2%, 91.3%) compared with other latent tuberculosis infection regimens (65.9%, 95% CI=53.5%, 77.3%). Three-month isoniazid-rifapentine was associated with similar risk to other latent tuberculosis infection regimens for adverse events (relative risk=0.59, 95% CI=0.23, 1.52); discontinuing treatment because of adverse events (relative risk=0.48, 95% CI=0.17, 1.34); and death (relative risk=0.79, 95% CI=0.56, 1.11).ConclusionsThe 3-month isoniazid-rifapentine regimen is as safe and effective as other recommended latent tuberculosis infection regimens and achieves significantly higher treatment completion rates.

Project description:BackgroundIn countries with low tuberculosis (TB) incidence, immigrants from higher incidence countries represent the major pool of individuals with latent TB infection (LTBI). The antenatal period represents an opportunity for immigrant women to access the medical system, and hence for potential screening and treatment of LTBI. However, such screening and treatment during pregnancy remains controversial.ObjectivesIn order to further understand the prevalence, natural history, screening and management of LTBI in pregnancy, we conducted a systematic literature review addressing the screening and treatment of LTBI, in pregnant women without known HIV infection.MethodsA systematic review of 4 databases (Embase, Embase Classic, Medline, Cochrane Library) covering articles published from January 1st 1980 to April 30th 2014. Articles in English, French or Spanish with relevant information on prevalence, natural history, screening tools, screening strategies and treatment of LTBI during pregnancy were eligible for inclusion. Articles were excluded if (1) Full text was not available (2) they were case series or case studies (3) they focused exclusively on prevalence, diagnosis and treatment of active TB (4) the study population was exclusively HIV-infected.ResultsOf 4,193 titles initially identified, 208 abstracts were eligible for review. Of these, 30 articles qualified for full text review and 22 were retained: 3 cohort studies, 2 case-control studies, and 17 cross-sectional studies. In the USA, the estimated prevalence of LTBI ranged from 14 to 48% in women tested, and tuberculin skin test (TST) positivity was associated with ethnicity. One study suggested that incidence of active TB was significantly increased during the 180 days postpartum (Incidence rate ratio, 1.95 (95% CI 1.24-3.07). There was a high level of adherence with both skin testing (between 90-100%) and chest radiography (93-100%.). In three studies from low incidence settings, concordance between TST and an interferon-gamma release assay was 77, 88 and 91% with kappa values ranging from 0.26 to 0.45. In low incidence settings, an IGRA may be more specific and less sensitive than TST, and results do not appear to be altered by pregnancy. The proportion of women who attended follow-up visits after positive tuberculin tests varied from 14 to 69%, while 5 to 42% of those who attended follow-up visits completed a minimum of 6 months of isoniazid treatment. One study raised the possibility of an association of pregnancy/post-partum state with INH hepatitis (risk ratio 2,5, 95% CI 0.8-8.2) and fatal hepatotoxicity (rate ratio 4.0, 95% CI 0.2-258). One study deemed INH safe during breastfeeding based on peak concentrations in plasma and breast milk after INH administration.ConclusionPregnancy is an opportunity to screen for LTBI. Interferon-gamma release assays are likely comparable to tuberculin skin tests and may be used during pregnancy. Efforts should be made to improve adherence with follow-up and treatment post-partum. Further data are needed with respect to safety and feasibility of antepartum INH therapy, and with respect to alternative treatment regimens.

Project description:BackgroundTuberculosis (TB) is a serious public health concern around the world including Asia. TB burden is high in Asian countries and significant population harbor latent tuberculosis infection(LTBI).AimThis systematic review and meta-analysis aims to evaluate the prevalence of LTBI in Asian countries.MethodWe performed a systematic literature search on PubMed, Embase, and ScienceDirect to identify relevant articles published between January 1, 2005, and January 1, 2023 investigating the overall prevalence of latent TB among people of Asia. Subgroup analysis was done for Asian subregions during the study period of 2011 to 2016 and 2017 to 2023, for tuberculin skin test (TST) and interferon gamma release assay (IGRA), respectively, as well as for QuantiFERON-TB (QFT) and TSPOT TB tests. Der Simonian and Laird's random-effects model was used to pool the prevalence of LTBI found using TST and IGRA.ResultA total of 15 studies were included after a systematic search from standard electronic databases. The analysis showed that the prevalence of latent TB in Asia was 21% (95% confidence interval [CI]: 19%-23%) and 36% (95% CI: 12%-59%) according to IGRAs and TSTs (cut off 10 mm) results, respectively. Based on IGRA, the prevalence of latent TB was 20% (95% CI: 13%-25%) in 2011 to 2016 and 21% (95% CI: 18%-24%) in 2017 to 2023. Using QFT, the prevalence was 19% (95% CI: 17%-22%) and using TSPOT, the prevalence was 26% (95% CI: 21%-31%). According to the United Nations division of Asia, the prevalence was higher for the Southern region and least for the Western region using TST and higher in the South-Eastern region and least in the Western region using the IGRA test.ConclusionAlmost a quarter of the Asian population has LTBI. Its diagnosis often poses a diagnostic challenge due to the unavailability of standard test in certain areas. Given this prevalence, a mass screening program is suggested with the available standard test and public awareness along with anti-TB regimen should be considered for individuals who test positive. However, for it to be implemented effectively, we need to take the affordability, availability, and cost-effectiveness of such interventions into account.

Project description:IntroductionAchieving tuberculosis (TB) elimination in low TB incidence countries requires identification and treatment of individuals at risk for latent TB infection (LTBI). Persons travelling to high TB incidence countries are potentially at risk for TB exposure. This systematic review and meta-analysis estimates incident LTBI and active TB among individuals travelling from low to higher TB incidence countries.MethodsFive electronic databases were searched from inception to 18 February 2020. We identified incident LTBI and active TB among individuals travelling from low (<10 cases/100 000 population) to intermediate (10-100/100 000) or high (>100/100 000) TB incidence countries. We conducted a meta-analysis and meta-regression using a random effects model of log-transformed proportions (cumulative incidence). Subgroup analyses investigated the impact of travel duration, travel purpose and TB incidence in the destination country.ResultsOur search identified 799 studies, 120 underwent full-text review, and 10 studies were included. These studies included 1 154 673 travellers observed between 1994 and 2013, comprising 443 health care workers (HCW), 1 068 636 military personnel and 85 594 general travellers/volunteers. We did not identify any studies that estimated incidence of LTBI or active TB among people travelling to visit friends and relatives (VFRs). The overall cumulative incidence of LTBI was 2.3%, with considerable heterogeneity. Among individuals travelling for a mean/median of up to 6 months, HCWs had the highest cumulative incidence of LTBI (4.3%), whereas the risk was lower for military (2.5%) and general travellers/volunteers (1.6%). Meta-regression did not identify a difference in incident LTBI based on travel duration and TB incidence in the destination country. Five studies reported cases of active TB, with an overall pooled estimate of 120.7 cases per 100 000 travellers.ConclusionsWe found that travelling HCWs were at highest risk of developing LTBI. Individual risk activities and travel purpose were most associated with risk of TB infection acquired during travel.

Project description:Despite the availability of three network meta-analyses (NMA) examining the efficacy, treatment completion, and adverse events associated with all latent tuberculosis infection (LTBI) treatments, there is currently no evidence to support the notion that the benefits of these treatments outweigh the potential risks. This NMA aimed to conduct a comprehensive comparison and update of the efficacy, treatment completion rates and adverse events associated with recommended treatment options for LTBI for individuals with confirmed LTBI, as outlined in the 2020 World Health Organization (WHO) Consolidated Guidelines for TB preventive treatment. A comprehensive search of the MEDLINE and Scopus databases was conducted until April 2023. The NMA was applied to estimate the risk difference and corresponding 95% confidence interval (CI) using a combination of direct and indirect evidence. The risk-benefit assessment was employed to evaluate the feasibility of the extra benefits in relation to the extra risks. The primary outcomes of interest in this study were active TB disease, completion rates, and adverse events. The meta-analysis incorporated data from 15 studies, which collectively demonstrated that the administration of a placebo resulted in a significant increase in the risk of developing TB disease by 1.279%, compared to the daily intake of isoniazid for 6 months (6H). Furthermore, treatment completion rates were significantly higher when using isoniazid plus rifapentine weekly for 3 months (3HP) and rifampicin daily for 4 months (4R), as compared to 6H. Considering adverse events, the combination of 3HP, 4R, and isoniazid administered daily for 9 months (referred to as 9H) significantly decreased adverse events by 4.53% in comparison to 6H. The risk-benefit assessment showed that alternative treatment regimens (9H, 4R, 3HR and 3HP) had a lower incidence of adverse events, while demonstrating a higher efficacy in preventing TB, as compared to 6H. This review indicates that there were no significant differences observed among various active treatment options in terms of their efficacy in preventing active TB. Moreover, completion rates were higher in 3HP and 4R, and a reduction in adverse events was observed in 3HP, 4R, and 9H.

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Gaps in Study Design for Immune Parameter Research for Latent Tuberculosis Infection: A Systematic Review.

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Gaps in Study Design for Immune Parameter Research for Latent Tuberculosis Infection: A Systematic Review.

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