scholarly journals Isoniazid Concentration and NAT2 Genotype Predict Risk of Systemic Drug Reactions during 3HP for LTBI

2019 ◽  
Vol 8 (6) ◽  
pp. 812 ◽  
Author(s):  
Meng-Rui Lee ◽  
Hung-Ling Huang ◽  
Shu-Wen Lin ◽  
Meng-Hsuan Cheng ◽  
Ya-Ting Lin ◽  
...  
Keyword(s):  
Latent Tuberculosis ◽  
Clinical Information ◽  
Estimating Equation ◽  
Equation Model ◽  
Candidate Snps ◽  
Drug Reactions ◽  
Nat2 Genotype ◽  
Latent Tb ◽  
Latent Tb Infection ◽  
Systemic Drug

Weekly rifapentine and isoniazid therapy (known as 3HP) for latent tuberculosis infection (LTBI) is increasingly used, but systemic drug reactions (SDR) remain a major concern. Methods: We prospectively recruited two LTBI cohorts who received the 3HP regimen. In the single-nucleotide polymorphism (SNP) cohort, we collected clinical information of SDRs and examined the NAT2, CYP2E1, and AADAC SNPs. In the pharmacokinetic (PK) cohort, we measured plasma drug and metabolite levels at 6 and 24 h after 3HP administration. The generalised estimating equation model was used to identify the factors associated with SDRs. Candidate SNPs predicting SDRs were validated in the PK cohort. A total of 177 participants were recruited into the SNP cohort and 129 into the PK cohort, with 14 (8%) and 13 (10%) in these two cohorts developing SDRs, respectively. In the SNP cohort, NAT2 rs1041983 (TT vs. CC+CT, odds ratio [OR] [95% CI]: 7.00 [2.03–24.1]) and CYP2E1 rs2070673 (AA vs. TT+TA, OR [95% CI]: 3.50 [1.02–12.0]) were associated with SDR development. In the PK cohort, isoniazid level 24 h after 3HP administration (OR [95% CI]: 1.61 [1.15–2.25]) was associated with SDRs. Additionally, the association between the NAT2 SNP and SDRs was validated in the PK cohort (rs1041983 TT vs. CC+CT, OR [95% CI]: 4.43 [1.30–15.1]). Conclusions: Isoniazid played a role in the development of 3HP-related SDRs. This could provide insight for further design of a more optimal regimen for latent TB infection.

scholarly journals Prevalence of latent tuberculosis infection and feasibility of TB preventive therapy among Thai prisoners: a cross-sectional study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sivaporn Gatechompol ◽  
Weerakit Harnpariphan ◽  
Ruamthip Supanan ◽  
Gompol Suwanpimolkul ◽  
Jiratchaya Sophonphan ◽  
...  
Keyword(s):  
Latent Tuberculosis ◽  
Cross Sectional Study ◽  
Preventive Therapy ◽  
Sectional Study ◽  
Cross Sectional ◽  
Ltbi Prevalence ◽  
History Of ◽  
Chest X Ray ◽  
Latent Tb ◽  
Latent Tb Infection

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.

scholarly journals Latent Tuberculosis Infection

2018 ◽  
Vol 4 (1) ◽  
pp. 21 ◽  
Author(s):  
Jean-Pierre Zellweger ◽  
Keyword(s):  
Latent Tuberculosis ◽  
Public Health Problem ◽  
World Health Organisation ◽  
Pulmonary Involvement ◽  
World Health ◽  
Global Public Health ◽  
Expert Interview ◽  
Immunodeficiency Virus ◽  
Latent Tb ◽  
Latent Tb Infection

Tuberculosis (TB) is a major global public health problem and is the leading cause of death linked to a single pathogen, ranking above human immunodeficiency virus (HIV).1 Clinically, TB has been categorised as active disease (patients who are generally symptomatic and may be infectious if pulmonary involvement is present) and latent infection (asymptomatic and not infectious, but at variable risk for progression to active TB disease). It is increasingly being recognised that latent TB infection (LTBI) reflects diverse responses to infection with Mycobacterium tuberculosis and may lead to heterogeneous clinical outcomes. In an expert interview, Jean-Pierre Zellweger discusses the latest World Health Organisation (WHO) guidelines on the management of LTBI.

scholarly journals Effect of isoniazid on antigen-specific interferon-γ secretion in latent tuberculosis

2014 ◽  
Vol 45 (2) ◽  
pp. 473-482 ◽  
Author(s):  
Martha Torres ◽  
Lourdes García-García ◽  
Pablo Cruz-Hervert ◽  
Heinner Guio ◽  
Claudia Carranza ◽  
...  
Keyword(s):  
Latent Tuberculosis ◽  
Peptide Pool ◽  
Interferon Γ ◽  
Treatment Regimes ◽  
Latent Tb ◽  
Ifn Γ ◽  
New Treatment ◽  
Latent Tb Infection ◽  
Culture Filtrate Protein

Treatment of persons with latent tuberculosis (TB) infection at greatest risk of reactivation is an important component of TB control and elimination strategies. Biomarkers evaluating the effectiveness of treatment of latent TB infection have not yet been identified. This information would enhance control efforts and assist the evaluation of new treatment regimes.We designed a two-group, two-arm, randomised clinical study of tuberculin skin test-positive participants: 26 with documented contact with TB patients and 34 with non-documented contact. Participants in each group were randomly assigned to the immediate- or deferred-isoniazid treatment arms. Assays ofin vitrointerferon (IFN)-γ secretion in response to recombinant Rv1737 and overlapping synthetic peptide pools from various groups of immunodominant proteins were performed.During isoniazid therapy, a significant increase from baseline in the proportion of IFN-γ responders to the 10-kDa culture filtrate protein, Rv2031, Rv0849, Rv1986, Rv2659c, Rv2693c and the recombinant Rv1737 protein was observed (p⩽0.05). The peptide pool of Rv0849 and Rv1737 recombinant proteins induced the highest percentage of IFN-γ responders after isoniazid therapy.Thein vitroIFN-γ responses to these proteins might represent useful markers to evaluate changes associated with treatment of latent TB infection.

scholarly journals CD4+ T-cell–independent mechanisms suppress reactivation of latent tuberculosis in a macaque model of HIV coinfection

2016 ◽  
Vol 113 (38) ◽  
pp. E5636-E5644 ◽  
Author(s):  
Taylor W. Foreman ◽  
Smriti Mehra ◽  
Denae N. LoBato ◽  
Adel Malek ◽  
Xavier Alvarez ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Latent Tuberculosis ◽  
Natural Immunity ◽  
Macaque Model ◽  
Hiv Coinfection ◽  
Immunodeficiency Virus ◽  
Latent Tb ◽  
Latent Tb Infection

The synergy between Mycobacterium tuberculosis (Mtb) and HIV in coinfected patients has profoundly impacted global mortality because of tuberculosis (TB) and AIDS. HIV significantly increases rates of reactivation of latent TB infection (LTBI) to active disease, with the decline in CD4+ T cells believed to be the major causality. In this study, nonhuman primates were coinfected with Mtb and simian immunodeficiency virus (SIV), recapitulating human coinfection. A majority of animals exhibited rapid reactivation of Mtb replication, progressing to disseminated TB and increased SIV-associated pathology. Although a severe loss of pulmonary CD4+ T cells was observed in all coinfected macaques, a subpopulation of the animals was still able to prevent reactivation and maintain LTBI. Investigation of pulmonary immune responses and pathology in this cohort demonstrated that increased CD8+ memory T-cell proliferation, higher granzyme B production, and expanded B-cell follicles correlated with protection from reactivation. Our findings reveal mechanisms that control SIV- and TB-associated pathology. These CD4-independent protective immune responses warrant further studies in HIV coinfected humans able to control their TB infection. Moreover, these findings will provide insight into natural immunity to Mtb and will guide development of novel vaccine strategies and immunotherapies.

scholarly journals ID Learning Unit: Understanding Advances in the Treatment of Latent Tuberculosis Infection among People with HIV

2021 ◽  
Author(s):  
Nicky J Mehtani ◽  
Sarah Puryear ◽  
Paul Pham ◽  
Kelly E Dooley ◽  
Maunank Shah
Keyword(s):  
Antiretroviral Therapy ◽  
Drug Interactions ◽  
Latent Tuberculosis Infection ◽  
Modern Art ◽  
Latent Tuberculosis ◽  
Significant Heterogeneity ◽  
Preventative Therapy ◽  
Latent Tb ◽  
Latent Tb Infection ◽  
Current Guidelines

Abstract Tuberculosis remains the leading cause of death among people with HIV (PWH). The diagnosis of latent TB infection (LTBI) and treatment with TB preventative therapy (TPT) can reduce morbidity and mortality in this population. Historically, isoniazid has been recommended for TPT in PWH due to the absence of drug-drug interactions with most antiretroviral therapy (ART). However, newer rifamycin-based regimens are safer, shorter in duration, associated with improved adherence, and may be as or more effective than isoniazid TPT. Current guidelines have significant heterogeneity in their recommendations for TPT regimens and acceptability of drug interactions with modern ART. In this ID learning unit, we review common questions on diagnosis, treatment, and drug interactions related to the management of LTBI among PWH.

scholarly journals “If I’ve got latent TB, I would like to get rid of it”: Derivation of the CARD (Constraints, Actions, Risks, and Desires) Framework informed by South African healthcare worker perspectives on latent tuberculosis treatment

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0254211
Author(s):  
Ruvandhi R. Nathavitharana ◽  
Ananja van der Westhuizen ◽  
Helene-Mari van der Westhuizen ◽  
Hridesh Mishra ◽  
Annalean Sampson ◽  
...  
Keyword(s):  
South African ◽  
Latent Tuberculosis ◽  
Transmission Risk ◽  
Administrative Leadership ◽  
Open Coding ◽  
High Risk Populations ◽  
Latent Tb ◽  
Latent Tb Infection ◽  
Infrastructural Support ◽  
Ltbi Testing

Background Healthcare workers (HWs) have at least twice the risk of tuberculosis (TB) compared to the general population. There is growing emphasis on latent TB infection (LTBI) in high-risk populations. Yet we know little about HWs’ perspectives of LTBI testing and treatment to inform implementation in high-incidence settings. We developed a qualitative networked approach to analyze HWs’ perspectives on LTBI testing and treatment. Methods We conducted 22 in-depth interviews with nurse and physician stakeholders, who had been recruited as part of a larger study evaluating TB transmission risk in HWs at Tygerberg Hospital, Cape Town, South Africa. We performed open coding to identify emergent themes and selective coding to identify relevant text citations. We used thematic analysis to inductively derive the CARD (Constraints, Actions, Risks, Desires) framework. Results All HWs desired to avoid developing TB but few felt this was actionable. Despite LTBI knowledge gaps, safety and cost concerns, most HWs reported hypothetical willingness to take LTBI treatment. The CARD framework showed that desire and action related to LTBI testing and treatment was clearly framed by the interactions between constraints, administrative action, and risk. The surprise HWs described on receiving a negative LTBI (Quantiferon-Plus) result suggests LTBI testing may recalibrate HWs’ perceptions regarding the futility of actions to reduce their TB risk. Conclusions LTBI testing and treatment are acceptable to HWs and could counteract the perceived inevitability of occupational TB infection that currently may limit risk reduction action. This should be coupled with administrative leadership and infrastructural support. The CARD analytic framework is a helpful tool for implementation scientists to understand current practices within complex health systems. Application of CARD could facilitate the development of contextually-relevant interventions to address important public health problems such as occupational TB.

scholarly journals Interferon Gamma Release Assay After BCG Vaccination Among Newborns and Family Members Living in an Overcrowded Area in Jakarta, Indonesia

2020 ◽  
Author(s):  
Francisca Srioetami Tanoerahar ◽  
Indri Rooslamiati ◽  
Natalie Kipuw ◽  
Hadiyanto ◽  
Soegianto Ali ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Family Members ◽  
Latent Tuberculosis ◽  
Interferon Gamma Release Assay ◽  
Pulmonary Tb ◽  
Bcg Vaccination ◽  
Release Assay ◽  
Latent Tb ◽  
Poor Area ◽  
Latent Tb Infection

Abstract IntroductionActive tuberculosis (TB) patient is a potential source of Mycobacterium tuberculosis transmission in an overcrowded and poor area. Family members living in the same house may have been infected or latent tuberculosis infection (LTBI) may develop. The aim of the study was to explore LTBI among newborns and their family members living in an overcrowded area in Jakarta, Indonesia. MethodsA prospective analytical study was conducted among newborns from October 2016 to March 2017. Interferon gamma release assay (IGRA) was examined before BCG vaccination and after 12 weeks. In parallel, TB active case finding was performed among family members of the newborns.ResultsOf 135 newborns, only 117 (86.7%) came for BCG vaccination. Of 346 family members screened, 8 (2.3%) were detected as untreated active pulmonary TB, confirmed by positive sputum and/or MTB culture. Family members living in the same house with active TB individuals (p=0.011, OR 2.69) as well as being males (p = 0.025; OR 1.68) had a significant higher risk of having a positive IGRA. ConclusionsUntreated pulmonary TB infection in overcrowded areas infects the surrounding neighbors, resulting in latent TB infection. An active program for detecting pulmonary TB cases and preventive measures need to be taken seriously to contain the potential spreading of the infection.

scholarly journals Latent tuberculosis and COVID-19 disease

2021 ◽  
Vol 4 (3) ◽  
pp. e26
Author(s):  
Sruthi Sekaran ◽  
◽  
Ravi Pankajbhai Jagani ◽  
Madeeha Subhan Waleed ◽  
Claudia Samanta Villa Celi ◽  
...  
Keyword(s):  
Latent Tuberculosis ◽  
The Other ◽  
Latent Form ◽  
The World ◽  
Latent Tb ◽  
Immunocompromised State ◽  
Latent Tb Infection ◽  
The Individual ◽  
Available Information ◽  
Healthy Immune System

Since the start of the COVID-19 pandemic in 2020, there has been chaos in the world. With the COVID-19 cases rising, many other medical diseases have been ignored and not prioritized. One of these crucial diseases is Tuberculosis (TB). TB is a highly infectious bacterial respiratory disease. Every year there are millions of cases that are registered all around the world. TB is seen in two forms, an active and a latent form. In both of the states, the individual with TB is immunocompromised. This is of great importance, as COVID-19 is known to readily infect individuals in an immunocompromised state more than those with a healthy immune system. Although a little investigation about coexisting infections with COVID-19 and TB is conducted, it is important to consider many factors that can be beneficial to help treat these patients with both conditions effectively and promptly. A few of these factors are pathophysiological relation, diagnostic measurements, effects of each condition on the other, and approaches to treatment. Through a literature review of available information, we summarized the knowledge regarding the correlation between Latent TB infection and COVID-19 infection. The main objective of this publication is to provide a brief overview of how the two conditions overlap with one another. The article also provides a clinical review of how to approach these two conditions in a scenario where an individual is found to be infected with both Latent TB and COVID-19.

The Diagnostic Value of Blood and Urine IP-10 Test in Children Having Active Tuberculosis or Latent Tuberculosis Infection

2021 ◽  
Author(s):  
Salim Can ◽  
Ayse Sahin ◽  
Nazan Dalgic ◽  
Deniz Aygün
Keyword(s):  
Pediatric Patients ◽  
Latent Tuberculosis ◽  
Diagnostic Value ◽  
Active Tuberculosis ◽  
Control Group ◽  
Healthy Children ◽  
Combined Use ◽  
Latent Tb ◽  
Inducible Protein ◽  
Latent Tb Infection

Abstract Objective This study aimed to investigate interferon-gamma-inducible protein-10 (IP-10) values in serum and urine in pediatric patients in the diagnosis of active tuberculosis (TB) or latent TB infection (LTBI). It also aimed to investigate whether it can be used as a biomarker to distinguish between active TB and LTBI. Methods Our study comprised active TB (25 patients), LTBI (25 patients), and the “infected” group (50 patients) formed by combining the two groups. As the control group, 37 healthy children were included in the study. TB skin test, plasma IP-10, and urine IP-10 measurements were performed in all patients included in the study. An additional QuantiFERON-TB Gold In-Tube (QFT-GIT) test was performed on patients evaluated as active TB or LTBI. Results Plasma IP-10 levels of the patients in the active TB, LTBI, and the “infected” groups were significantly higher than the control group (p = 0.022, p = 0.028, and p = 0.007, respectively). Urine IP-10 was successful in distinguishing the active TB and “infected” groups from the control group (p = 0.007 and p = 0.047, respectively). Also, in the combined use of the tests, when QFT-GIT and urine IP-10 were positive together, active TB and LTBI could be distinguished (p = 0.044). Urine IP-10 levels were found to be significantly higher in those with pulmonary TB than those with extrapulmonary TB (p = 0.012). Conclusion Our findings suggest that IP-10 can be used as a useful biomarker in the diagnosis of active TB in children.

scholarly journals Recent Progress in Diagnosis Methods for Latent Tuberculosis Infection and Its Clinical Applications

2015 ◽  
Vol 4 (3) ◽  
pp. 69-74
Author(s):  
Ling Zhou
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Recent Progress ◽  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
Interferon Γ ◽  
Clinical Applications ◽  
Active Tuberculosis ◽  
Advantages And Disadvantages ◽  
Latent Tb ◽  
Latent Tb Infection

AbstractMost people with latentMycobacterium tuberculosisinfection can partly develop active tuberculosis (TB). Therefore, diagnosis of this condition bears significance in early TB prevention. To date, the main methods for diagnosis of latent TB infection (LTBI) include tuberculin skin test and interferon γ release test. These two methods feature their own advantages and disadvantages. Although new diagnostic markers continually emerge, no uniform diagnostic criteria are available for TB detection. This study summarizes several methods for diagnosis of LTBI and new related markers and their application value in clinical practice.

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