New approaches in latent TB infection detection and management

Abstract Background Prisons are considered as major reservoirs for tuberculosis. Preventive therapy for latent TB infection (LTBI) is an adjunctive strategy to control TB. However, LTBI data in Thai prisoners is limited. This study assessed the prevalence of LTBI and feasibility of isoniazid preventive therapy (IPT). Methods A cross-sectional study was conducted among prisoners in Klong Prem Central Prison, Bangkok. Participants were screened for active TB by questionnaire and chest X-ray. LTBI was evaluated by Tuberculin skin test (TST) and QuantiFERON-TB Gold Plus (QFTP) among subgroup. Participants with positive TST or QFTP were considered to have LTBI. Participants with LTBI were offered IPT. Results From August 2018–November 2019, 1002 participants were analyzed. All participants were male with a median age of 38 (IQR 32–50) years. LTBI identified by either TST/QFTP was present in 466 (46.5%) participants. TST was positive in 359 (36%) participants. In the subgroup of 294 participants who had both TST and QFTP results, 181/294 (61.6%) tested positive by QFTP. Agreement between TST and QFTP was 55.1% (Kappa = 0.17). The risk factors associated with LTBI were previous incarceration (aOR 1.53, 95%CI, 1.16–2.01, p = 0.002), history of prior active TB (aOR 3.02, 95%CI, 1.74–5.24, p < 0.001) and duration of incarceration ≥10 years (aOR 1.86, 95%CI, 1.24–2.79, p = 0.003). Majority of LTBI participants (82%) agreed to take IPT. Three hundred and 56 (93%) participants completed treatment whereas 27 (7%) participants discontinued IPT due to the side effects of INH. Conclusion This is the first study to evaluate the prevalence of LTBI and feasibility of IPT among Thai prisoners. LTBI prevalence in male prisoners in Thailand is high. LTBI screening and treatment should be implemented together with other preventive components.

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Ex vivo mRNA expression of toll-like receptors during latent tuberculosis infection

BMC Immunology ◽

10.1186/s12865-021-00400-4 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Birhan Alemnew ◽

Soren T. Hoff ◽

Tamrat Abebe ◽

Markos Abebe ◽

Abraham Aseffa ◽

...

Keyword(s):

Mrna Expression ◽

Expression Patterns ◽

Fold Change ◽

Mrna Levels ◽

Healthy Children ◽

Toll Like Receptors ◽

Relative Expression ◽

Latently Infected ◽

Latent Tb ◽

Latent Tb Infection

Abstract Background Understanding immune mechanisms, particularly the role of innate immune markers during latent TB infection remains elusive. The main objective of this study was to evaluate mRNA gene expression patterns of toll-like receptors (TLRs) as correlates of immunity during latent TB infection and further infer their roles as potential diagnostic biomarkers. Methods Messenger RNA (mRNA) levels were analysed in a total of 64 samples collected from apparently healthy children and adolescents latently infected with tuberculosis (n = 32) or non-infected (n = 32). Relative expression in peripheral blood of selected genes encoding TLRs (TLR-1, TLR-2, TLR-4, TLR-6 and TLR-9) was determined with a quantitative real-time polymerase chain reaction (qRT-PCR) using specific primers and florescent labelled probes and a comparative threshold cycle method to define fold change. Data were analysed using Graph-Pad Prism 7.01 for Windows and a p-value less than 0.05 was considered statistically significant. Results An increased mean fold change in the relative expression of TLR-2 and TLR-6 mRNA was observed in LTBI groups relative to non-LTBI groups (p < 0.05), whereas a slight fold decrease was observed for TLR-1 gene. Conclusions An increased mRNA expression of TLR-2 and TLR-6 was observed in latently infected individuals relative to those non-infected, possibly indicating the roles these biomarkers play in sustenance of the steady state interaction between the dormant TB bacilli and host immunity.

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Upregulation of PD-1 expression on circulating CD8+ but not CD4+ T cells is associated with tuberculosis infection in health care workers

BMC Immunology ◽

10.1186/s12865-021-00433-9 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Cui-lin Shi ◽

Jian-ping Zhang ◽

Ping Xu ◽

Jin Li ◽

Jie Shen ◽

...

Keyword(s):

Health Care ◽

T Cells ◽

T Cell ◽

Health Care Workers ◽

Cd4 T Cells ◽

Receptor Expression ◽

Effector Memory ◽

Care Workers ◽

Latent Tb ◽

Latent Tb Infection

Abstract Background Health care workers (HCWs) are at risk for occupationally acquired Mycobacterium tuberculosis infection and tuberculosis (TB) disease due to repeated exposure to workplace tubercle bacilli. To determine whether continual mycobacterial stimulation correlates with increased expression of inhibitory T cell receptors, here we compared PD-1 receptor expression on surfaces of circulating T cells between naïve (uninfected) HCWs and HCWs with latent TB infection (LTBI). Result Data collected from 133 medical workers who met study selection criteria were included in the final analysis. QuantiFERON-TB Gold In-Tube (QFT-GIT) testing yielded positive results for 32 HCWs, for an overall LTBI rate of 24.1%. Multivariate analysis identified HCW length of service > 15 years as an independent risk factor for a positive QFT-GIT result. In addition, comparisons of blood T cell subgroup profiles between QFT- and QFT+ groups indicated QFT+ subjects possessed greater proportions of mature (TM), transitional memory (TTM) and effector memory (TEM) CD4+ T cell subgroups and lower proportions of naïve T cells (TN). Moreover, the QFT+ group percentage of CD8+ T cells with detectable surface PD-1 was significantly higher than the corresponding percentage for the QFT- group. Meanwhile, no statistical intergroup difference was observed in percentages of CD4+ T cells with detectible surface PD-1. Conclusions Our data demonstrated that upregulated PD-1 expression on circulating CD8+, but not CD4+ T cells, was associated with latent TB infection of HCWs. As compared to other hospitals, occupational TB infection risk in our hospital was substantially mitigated by implementation of multitiered infection control measures.

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806. 2013–2015 Nationwide Tuberculosis Contact Investigation in Childcare Centers and Schools in Korea

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.813 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S289-S289

Author(s):

Woosuck Suh ◽

Jong-Hyun Kim ◽

Ji Hyen Hwang ◽

Sodam Lee ◽

Kang-Hee Lee ◽

...

Keyword(s):

School Setting ◽

Age Groups ◽

Disease Status ◽

Childcare Centers ◽

X Ray ◽

Contact Investigation ◽

Chest X Ray ◽

Latent Tb ◽

The Republic ◽

Latent Tb Infection

Abstract Background The Republic of Korea has the highest incidence rate of tuberculosis (TB) among members of the OECD, reported as 78.8/100,000 population in 2016. In response, a state-run intensive contact investigation for TB is being conducted. More effective TB control requires an epidemiologic emphasis on the diagnosis and treatment of latent TB infections in children and adolescents, compared with other age groups. Here we present an analysis of data from the childcare center and school contact investigation by the Korea Centers for Disease Control and Prevention (CDC) in 2013–2015. Methods Data collected from index patients included age, sex, occupation, disease status, results of AFB smear/culture, and chest x-ray. Data collected from contacts included age, sex, results of serial tuberculin skin test (TST), and chest x-ray. Congregate settings included childcare centers, kindergartens, elementary and secondary schools, and age groups were stratified as follows: 0–4 years, 5–12 years, and 13–18 years. TSTs were considered positive if induration ≥10 mm on the first test (TST1) or demonstrated an increase ≥6 mm over the induration of TST1 on repeat testing after 8 weeks (TST2). Results Of the 197,801 subjects with data collected, 173,998 were eligible and included in our analysis. TST1 results were available for 159,346 (91.6%) and when results were positive, induration was 10–14 mm in 7.6% and ≥15 mm in 1.5%. TST2 results were available for 119,797 (82.7%) of the 144,904 with negative TST1, and conversion rate was 9.0%. Altogether considering TST1 and TST2, 17.3% contacts had latent TB infections. Positive rates of TST significantly decreased with age: 20.3% in 0–4 years, 18.8% in 5–12 years, 17.1% in 13–18 years. Conclusion In this 3-year school-setting contact investigation, 17.3% contacts were diagnosed with latent TB infection, as demonstrated by TST reactions. Positive rates of TST significantly but mildly decreased with age. Disclosures All authors: No reported disclosures.

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Expected background rates of latent TB infection in London inner city schools: lessons from a TB contact investigation exercise in a secondary school

Epidemiology and Infection ◽

10.1017/s0950268818002327 ◽

2018 ◽

Vol 146 (16) ◽

pp. 2102-2106 ◽

Cited By ~ 1

Author(s):

S. Anaraki ◽

A.J. Bell ◽

S. Perkins ◽

S. Murphy ◽

S. Dart ◽

...

Keyword(s):

Contact Tracing ◽

London Borough ◽

Contact Group ◽

Contact Investigation ◽

High Prevalence ◽

Cohort Study Design ◽

Latent Tb ◽

Group 2 ◽

Latent Tb Infection ◽

Group 1

AbstractFollowing an extensive contact tracing exercise at a school in a London borough with one of highest tuberculosis (TB) rates in England, we estimated the background prevalence of latent TB infection to be significantly less than the widely accepted 10%. We screened 271 pupils aged 14–15 years in two groups: 96 pupils in group 1 had significant exposure (>8 h/week in the same room) to a case of infectious TB and 175 in group 2 who had minimal exposure. In group 1, 26% were diagnosed with latent or active TB, compared to 6.3% in group 2. Risk factors for TB infection (e.g. previous exposure or link to high-prevalence communities) were analysed using a cohort study design. In the univariable analysis only being in contact group 1 was statistically significantly associated with being a case (OR 5.25, 95%, P < 0.001). In the multivariable model contact group 1 remained significantly associated with being a case (adjusted OR 4.40, P = 0.001). We concluded that the 6.3% yield of TB infection in contact group 2 is either similar to or higher than the background prevalence rate of latent TB infection (LTBI) in this high TB prevalence London borough. Other parts of England with lower TB prevalence are likely to have even lower LTBI rates.

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Diagnosis of Latent TB Infection

Clinical Tuberculosis ◽

10.1201/9781351249980-9 ◽

2020 ◽

pp. 153-171

Author(s):

Ajit Lalvani ◽

Clementine Fraser ◽

Manish Pareek

Keyword(s):

Latent Tb ◽

Latent Tb Infection

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Age-Related Immunoreactivity Profiles to Diverse Mycobacterial Antigens in BCG-Vaccinated Chinese Population

Frontiers in Immunology ◽

10.3389/fimmu.2020.608220 ◽

2021 ◽

Vol 11 ◽

Author(s):

Qing-yuan Yang ◽

Yu-tong Zhang ◽

Jia-ni Xiao ◽

Yu-shuo Liang ◽

Ping Ji ◽

...

Keyword(s):

Elispot Assay ◽

Vaccine Development ◽

Age Related ◽

Healthy Donors ◽

Latent Tb ◽

Latent Tb Infection ◽

Mycobacterial Antigens ◽

Selection Of

Long-term immunoreactivity to mycobacterial antigens in Bovis Calmette-Guérin (BCG)-vaccinated population is not well investigated. Herein, 361 volunteer healthy donors (HDs) with neonatal BCG vaccination from Shanghai region (China) were enrolled. They were subdivided into ESAT-6/CFP10- (E6C10-) and ESAT-6/CFP10+ (E6C10+) groups based on gamma-interferon release assays (IGRAs). Three mycobacterial antigens, including Rv0934, Rv3006, and Rv3841, were subjected to the determination of immunoreactivity by ELISPOT assay. The immunoreactivities to three mycobacterial antigens were firstly compared among TB patients (N=39), E6C10+ HDs (N=78, 21.61% of HDs) and E6C10- HDs (N=283, 78.39% of HDs). It was revealed that Rv3006 was dominant upon M.tb infection, while Rv3841 was likely to be more responsive upon latent TB infection. In E6C10- population, the immunoreactivity to Rv3841 maintained along with aging, whereas those to Rv3006 and Rv0934 attenuated in E6C10- HDs older than 45 years old. Our study implies the shift of dominant antigens at different infection statuses, providing the clues for the selection of mycobacterial antigens in vaccine development and precision revaccination in the future.

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Evaluating the potential costs and impact of digital health technologies for tuberculosis treatment support

European Respiratory Journal ◽

10.1183/13993003.01363-2018 ◽

2018 ◽

Vol 52 (5) ◽

pp. 1801363 ◽

Cited By ~ 11

Author(s):

Ntwali Placide Nsengiyumva ◽

Benjamin Mappin-Kasirer ◽

Olivia Oxlade ◽

Mayara Bastos ◽

Anete Trajman ◽

...

Keyword(s):

Digital Health ◽

Cost Savings ◽

Cost Effective ◽

Multidrug Resistant ◽

Potential Cost ◽

Health Technologies ◽

Life Years ◽

Message Service ◽

Latent Tb ◽

Latent Tb Infection

Ensuring adherence and support during treatment of tuberculosis (TB) is a major public health challenge. Digital health technologies could help improve treatment outcomes. We considered their potential cost and impact on treatment for active or latent TB in Brazil.Decision analysis models simulated two adult cohorts with 1) drug-susceptible active TB, and 2) multidrug-resistant TB, and two cohorts treated with isoniazid for latent TB infection (LTBI): 1) close contacts of persons with active TB, and 2) others newly diagnosed with LTBI. We evaluated four digital support strategies: two different medication monitors, synchronous video-observed therapy (VOT), and two-way short message service (SMS). Comparators were standard directly observed treatment for active TB and self-administered treatment for LTBI. Projected outcomes included costs (2016 US dollars), plus active TB cases and disability-adjusted life years averted among persons with LTBI.For individuals with active TB, medication monitors and VOT are projected to lead to substantial (up to 58%) cost savings, in addition to alleviating inconvenience and cost to patients of supervised treatment visits. For LTBI treatment, SMS and medication monitors are projected to be the most cost-effective interventions. However, all projections are limited by the scarcity of published estimates of clinical effect for the digital technologies.

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