Diagnosis Of Latent Tuberculosis Infection Research Articles

Implementation of latent tuberculosis infection screening and treatment among newly arriving immigrants in the Netherlands: A mixed methods pilot evaluation.

IntroductionTo reach pre-elimination levels of tuberculosis (TB) incidence in the Netherlands, prevention of TB among immigrants through diagnosis and treatment of latent TB infection (LTBI) is needed. We studied the feasibility of a LTBI screening and treatment program among newly arriving immigrants for national implementation.MethodsWe used mixed methods to evaluate the implementation of LTBI screening and treatment in five Public Health Services (PHS) among immigrants from countries with a TB incidence >50/100,000 population. We used Poisson regression models with robust variance estimators to assess factors associated with LTBI diagnosis and LTBI treatment initiation and reported reasons for not initiating or completing LTBI treatment. We interviewed five PHS teams using a semi-structured method to identify enhancing and impeding factors for LTBI screening and treatment.ResultsWe screened 566 immigrants; 94 (17%) were diagnosed with LTBI, of whom 49 (52%) initiated and 34 (69%) completed LTBI treatment. LTBI diagnosis was associated with male gender, higher age group, higher TB incidence in the country of origin and lower level of education. Treatment initiation was associated with PHS (ranging from 29% to 86%), lower age group, longer intended duration of stay in the Netherlands, and lower level of education. According to TB physicians, clients and their consulted physicians in the home country lacked awareness about benefits of LTBI treatment. Furthermore, TB physicians questioned the individual and public health benefit of clients who return to their country of origin within the foreseeable future.ConclusionsDoubt of physicians in both host country and country of origin about individual and public health benefits of LTBI screening and treatment of immigrants hampered treatment initiation: the high initiation proportion in one PHS shows that if TB physicians are committed, the LTBI treatment uptake can be higher.

P077 Tuberculosis in inflammatory bowel disease patients from a referral center in Salvador-Bahia, Brazil

BACKGROUND: In the last decade, potent immunosuppressive therapy has become the standard treatment for inflammatory bowel disease (IBD) (1). However, the increasingly use of immunomodulators associated to biological therapy—especially the inhibitors of tumor necrosis factor alpha (TNF-α)—have considerably increased the cases of tuberculosis (TB) in IBD patients (2,3). Meanwhile, Brazil is a high TB burden country, with 87,000 new cases per year, and the state of Bahia reports more than 3,600 new cases annually (4,5). METHODS: Were included IBD patients under treatment followed at a referral center from August 2017 to July 2018. The IBD was diagnosed according to the guideline criteria of was according to the criteria the European Crohn's and Colitis Organizsation. Diagnosis of latent TB infection (LTBI) was based on tuberculin skin test (TST) induration ≥5 mm without evidence of clinically manifested active tuberculosis (TB). The development of active TB, diagnosed during the treatment for inflammatory bowel disease, was based on symptoms, TST, chest X ray and laboratory finding. In addition, Sstatistical analysies was performed using the statistical software package SPSS version 21.0 for Windows. A P-value less than 0.05 was considered statistically significant. RESULTS: Of the 302 patients evaluated, 185 were submitted to screening for LTBI and 24 (12.9%) were positive. Of the total sample, 8 (2.6%) developed active TB during treatment for IBD. Six cases occurred despite theof negative screening for LTBI and 2 cases occurred even after chemoprophylaxis with isoniazid. Among 186 UC patients, 4 (2.1%) developed active TB and all cases were pulmonary TB. Two patients were under azathioprine monotherapy (?) with azathioprine and 2 were using 5-ASA derivatives without immunosuppressant. Among 116 Crohn disease (CD) patients, 4 (3.4%) developed active TB, 2 cases of pulmonary TB and 2 cases of pleural TB. All patients with CD who developed active TB were under anti-TNF therapy, 2 under treatment with infliximab monotherapy and 2 with adalimumab combotherapy associated with azathioprine. In total, 63 (20.9%) patients were under biological therapy. The frequency of active TB disease among patients exposed to anti-TNF when compared to patients not exposed was 6.3% (4/63) and 1.7% (4/239), respectively, and the difference was significant (P = 0.047) between those groups. The median time between initiation of anti-TNF therapy and the diagnosis of TB was 19 months (range: 3.0–45.0). CONCLUSION(S): The frequency of latent TB in our center is comparable to the frequency described in IBD patients from endemic countries. It was observed a high frequency of active TB in IBD patients under anti-TNF therapy from a reference center in Brazil. ACKNOWLEDGMENT: Fellowship Program from University of the State of Bahia (PICIN UNEB).

T-SPOT®.TB test and clinical risk scoring for diagnosis of latent tuberculosis infection among Thai healthcare workers.

Screening for latent tuberculosis infection (LTBI) is important to identify healthcare workers (HCWs) benefiting from preventive therapy. Interferon-gamma release assays (IGRAs) are sensitive and specific tests for LTBI diagnosis. However, in settings where IGRAs are not available, clinical risk assessment may be used as an alternative to diagnose LTBI. A cross-sectional study was conducted among HCWs of a tertiary-care university hospital in Thailand. All HCWs underwent T-SPOT®.TB test (T-SPOT) and assessment of LTBI clinical risks. Clinical risks associated with T-SPOT positivity were determined by multivariable logistic regression analysis and were given scores accordingly. The performance of the clinical risk scoring was evaluated in comparison to T-SPOT. Among 140 enrolled HCWs, 125 (89%) were females, the median age was 27 years and 23 (16%) had T-SPOT positivity. Independent factors associated with T-SPOT positivity were age ≥30 years (adjusted odds ratio [aOR] 3.95; P=0.002), working duration ≥60 months (aOR 3.75, P=0.004) and frequency of TB contact ≥6 times (aOR 8.83, P=0.005). The study's clinical risk scoring had the area under the curve by receiver operating curve analysis of 0.76 (P<0.001) using T-SPOT positivity as a reference standard. The score of ≥3 had the best performance in diagnosing LTBI with sensitivity, specificity, positive predictive value and negative predictive value of 70%, 71%, 32% and 92%, respectively. In this setting where LTBI was prevalent among HCWs but IGRAs are not widely available, the clinical risk scoring may be used as an alternative to diagnose LTBI in HCWs.

DIAGNOSTIC VALUE OF SPECIFIC IMMUNE COMPLEXES IN DETECTION OF ACTIVE TUBERCULOSIS INFECTION

The diagnostic of tuberculosis infection, including the use of immunological methods, evolved significant changes. The introduction of new diagnostic tests allowed to improve the diagnosis of latent tuberculosis infection (LTI). However, the positive results of immunological tests in both tuberculosis patients and in those with LTI do not allow to divide these conditions, which requires the development and implementation of new diagnostic approaches. Materials and methods . A prospective study with a survey of two groups of patients was conducted: group I (n=50) - patients with verified pulmonary tuberculosis, MBT (+); group II (n =15) – subjects with LTI and control group – healthy subjects (n=14). The examination complex included clinical, radiological, bacteriological, immunological (Mantoux test with 2 TU, T-SPOT.TB, QFT and Diaskintest) methods. Immune complexes were determined in all patients and healthy individuals by the method of dynamic light scattering after the in vitro addition of specific antigens - peptides ESAT-6 and SFP-10. Results . The obtained data demonstrate the low informativeness of the clinical method in the diagnostic of pulmonary tuberculosis. In the presence of characteristic X-ray changes, bacteriological verification of tuberculosis was obtained only in 46% of cases. The use of various immunological tests allows to obtain positive test results in 84-90% of cases simultaneously with the 100% of the positive results in subjects with LTI. Determination of specific immune complexes by the method of dynamic light scattering allows to determine the activity of tuberculosis infection in 100 % of cases and to identify a high-risk group for the development of active tuberculosis in people with latent tuberculosis infection. Conclusions : the obtained data can be applied not only in the diagnosis of active tuberculosis in the absence of diagnosis verification, but also allow to identify a high-risk group for the development of the disease in people with latent tuberculosis infection.

Screening and treatment for tuberculosis in a cohort of unaccompanied minor refugees in Berlin, Germany.

IntroductionIn 2015, 4062 unaccompanied minor refugees were registered in Berlin, Germany. According to national policies, basic clinical examination and tuberculosis (TB) screening is a prerequisite to admission to permanent accommodation and schooling for every refugee. This article evaluates the use of an interferon-γ-release-assay (IGRA) during the initial examination and TB screening of 970 unaccompanied minor refugees.ResultsIGRA test were obtained during TB screening for 301 (31.0%) of 970 adolescents not previously screened for TB. Positive IGRA results were obtained in 13.9% (42/301). Most of the 42 IGRA-positive refugees originated from Afghanistan or Syria (n?20 and 10 respectively). Two IGRA-positive adolescents were lost to follow-up, 2 were diagnosed with TB and the remaining 38 diagnosed with latent TB infection (LTBI). Demographic features of the 40 patients with positive IGRA result were as follows: 39 male, median age 16.8 years (IQR 16.0–17.2y), none meeting underweight criteria (median BMI 21.3kg/m2). On initial chest X-ray 2/40 participants had signs of active TB, while in 38 active disease was excluded and the diagnosis of latent TB infection (LTBI) made. Active hepatitis B-co-infection was diagnosed in 3/38 patients. All patients with LTBI received Isoniazid and Rifampicin for 3 months without occurrence of severe adverse events. The most frequently observed side effect was transient upper abdominal pain (n = 5). Asymptomatic elevation of liver transaminases was seen in 2 patients. 29 patients completed treatment with no signs of TB disease at the end of chemoprevention and 9 were lost to follow up.ConclusionScreening for TB infection in minor refugees was feasible in our setting with a relatively high rate of TB infection detected. Chemopreventive treatment was tolerated well regardless of underlying hepatitis-B-status. Minor refugees migrating to Germany should be screened for TB infection, instead of TB disease only, regardless of the background TB incidence.

High rates of indeterminate interferon-gamma release assays for the diagnosis of latent tuberculosis infection in liver transplantation candidates.

Screening for latent tuberculosis infection (LTBI) is recommended prior to solid organ transplantation. Interferon-gamma release assays (IGRAs) are the most widely used test for LTBI screening; however, assessment of IGRA performance in patients with end-stage liver disease is limited. The purpose of this study was to evaluate the prevalence and predictors of indeterminate (INDT) IGRA results in liver transplantation candidates. Between March 2011 and May 2018, we retrospectively analyzed 155 patients undergoing liver transplantation assessment, who underwent IGRA testing (Quantiferon-TB Gold, QFT-G) to exclude LTBI. Characteristics of patients, including age, gender, etiology of liver disease, MELD score, and absolute lymphocyte counts, were compared by QFT-G result (determinate vs INDT). Of the 155 patients screened, the rate of positive, negative, and INDT results were 5.2%, 69.8%, and 25%, respectively. The only variable independently associated with an indeterminate test on multivariate analysis was MELD score (odds ratio=1.07, 95% CI=1.01-1.14 per unit increase; P=0.014). In 95% of INDT tests, both TB antigen tube and the positive control tube were negative and repeat testing gave the same indeterminate result, suggestive of anergy rather than laboratory error. Our study suggests a high rate of INDT IGRA results during screening of liver transplant candidates for LTBI, associated with severity of liver disease and anergy. Because of the high rate of INDT QFT-G testing in this setting, individualized risk assessment is required including a thorough assessment of clinical risk factors and knowledge of local TB prevalence.

Screening for infectious diseases in newly arrived asymptomatic immigrants in southern Italy.

Screenings for infectious diseases in asymptomatic immigrants currently takes place when receiving new arrivals. We describe the frequency of infections in a cohort of newly arrived asymptomatic immigrants in Southern Italy. We studied a cohort of 238 Sub-Saharan African and Asian men hosted at a reception centre (CARA) in Foggia between January and December 2015. The tuberculin skin test for diagnosis of latent tuberculosis infection (LTBI) and serology/virology testing for HBV, HCV, HIV were performed. From this cohort, 205 individuals agreed to be tested for serological/virological markers only, while 82 agreed to be tested for LTBI only; 49 people agreed to have both tests. Among those tested for virological markers, 23/205 (11.2%) were HBsAg positive; 12/23 (52.2%) individuals had chronic active hepatitis; 77/205 (37.6%) individuals had only anti-HBc positivity. HCV infection was present in 8/205 (3.9%) individuals, and chronic HCV infection, was diagnosed in only two people. Only 2/205 (1.0%) individuals presented with anti-HIV and HIV-RNA positivity. We found LTBI in 29.6% of TB-tested individuals. Asymptomatic immigrants are at increased risk for some infections, mainly HBV and tuberculosis.

Positivity rate of interferon-γ release assays for estimating the prevalence of latent tuberculosis infection in renal transplant recipients in Japan

Renal transplant recipients are at increased risk of reactivating latent tuberculosis infection (LTBI) and developing active tuberculosis. QuantiFERON®-TB Gold Plus (QFT-Plus) has two TB-specific antigens tubes (TB1 and TB2). TB1 elicits CD4 T-cell response, and TB2 elicits both CD4 and CD8 T-cells responses, with expected increased sensitivity.The aim of this study was to estimate the prevalence of LTBI in renal transplant recipients in Japan. We conducted a cross-sectional study by using two interferon-γ release assays (IGRAs), QFT-Plus and T-SPOT®.TB (TSPOT).One hundred thirty-five recipients were prospectively enrolled. The median age was 49 years (range: 20 to 79). The positivity rates of QFT-Plus and TSPOT were 5.9% (95%CI 3.0–11.3) and 3.7% (95%CI 1.6–8.4), respectively, with no significant difference. The concordance rate was 95.5% (κ coefficient, 0.76). Age of 60 years and higher was related to the higher positivity rate in both QFT-Plus and TSPOT. The positivity rates of TB1 and TB2 were 5.1% (95%CI 2.5–10.2) and 5.9% (95%CI 3.0–11.2), respectively, with no significant difference. The concordance rate was 99.3% (κ coefficient, 0.93). TB2 did not show a higher positivity rate compared with TB1.The estimated prevalence of LTBI by using the both IGRAs was 3.7–5.9% in renal transplant recipients. These results were equivalent to the IGRAs positivity rate in the general Japanese population, even under the condition of immunosuppressive therapy. In consideration of the higher risk of developing active TB from LTBI, we can use both IGRAs as acceptable tools for LTBI diagnosis in renal transplant recipients.

Bioinformatics analysis of microRNA expression between patients with and without latent tuberculosis infections.

Tuberculosis (TB) is a globally prevalent infectious disease. The mechanisms of latent TB infection (LTBI) remain to be fully elucidated and may provide novel approaches for diagnosis. As therapeutic targets and molecular diagnostic markers, microRNAs (miRs) have been studied and utilized in various diseases. In the present study, the differentially expressed miRs (DEMs) in LTBI were screened and analyzed to determine the underlying mechanisms and identify potential biomarkers, thereby contributing to the diagnosis of LTBI. The GSE25435 and GSE29190 datasets from Gene Expression Omnibus were selected for analysis. The 2 datasets were analyzed individually using the Bioconductor package to screen the DEMs with specific cut-off criteria [P<0.01 and |log (fold change)|≥1]. Target gene prediction and interaction network construction were performed using Targetscan, the Search Tool for the Retrieval of Interacting Genes and Proteins and Cytoscape individually, and were merged using the latter tool. The hub genes were finally selected based on their degree of connectivity (DC). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the KEGG and GENCLIP. A total of 144 DEMs were identified from the 2 datasets. By exploring the overlapping miRs in the two datasets, Homo sapiens (hsa)-miR-29a and hsa-miR-15b were identified to be decreased, while hsa-miR-576-5p, hsa-miR-500 and hsa-miR-155 were identified to be upregulated. hsa-miR-500a-3p and hsa-miR-29a-3p, as well as 4 genes, namely cell division cycle (CDC)42, actin α1, skeletal muscle (ACTA1), phosphatase and tensin homolog (PTEN) and fos proto-oncogene (FOS), were selected as the key factors in this regulatory network. A total of 9 signaling pathways, including phosphoinositide-3 kinase (PI3K)/AKT and 11 biological processes, were identified to be associated with LTBI. In conclusion, the present analysis identified hsa-miR-500a-3p and hsa-miR-29a-3p, as well as CDC42, ACTA1, PTEN and FOS, as the most promising biomarkers and therapeutic candidates for LTBI. The PI3K/AKT signaling pathway is the key signaling pathway implicated in LTBI, and an in-depth investigation of the efficiency of PI3K/AKT signaling inhibitors may be used to prevent a chronic state of infection in LTBI.

Use of IP-10 detection in dried plasma spots for latent tuberculosis infection diagnosis in contacts via mail

The aim of this study was to test the use of IP-10 detection in dried plasma from contact studies individuals (contacts of smear positive patients), by comparing it with IP-10 and IFN-γ detection in direct plasma, to establish IP-10 detection in DPS as a useful assay for LTBI diagnosis. Whole blood samples were collected from 80 subjects: 12 with active tuberculosis (TB), and 68 from contact studies. The amount of IFN-γ produced by sensitized T cells was determined in direct plasma by QuantiFERON Gold In-Tube test. IP-10 levels were determined in direct and dried plasma by an in-house ELISA. For dried plasma IP-10 determination, two 25 µl plasma drops were dried in Whatman903 filter paper and sent by mail to the laboratory. Regarding TB patients, 100.0%, 91.7% and 75.0% were positive for IFN-γ detection and IP-10 detection in direct and dried plasma, respectively. In contacts, 69.1%, 60.3% and 48.5% had positive results after IFN-γ and IP-10 in direct and dried plasma, respectively. The agreement among in vitro tests was substantial and IP-10 levels in direct and dried plasma were strongly correlated (r = 0.897). In conclusion, IP-10 detection in dried plasma is a simple and safe method that would help improve LTBI management.

Enhancing the public health impact of latent tuberculosis infection diagnosis and treatment (ACT4): protocol for a cluster randomised trial

IntroductionTreatment of latent tuberculosis (TB) infection (LTBI) is an important component of the End-TB strategy. However, the number of individuals who successfully complete LTBI treatment remains low as there are...

Latent tuberculosis infection in transplant candidates: a systematic review and meta-analysis on TST and IGRA.

The diagnostic accuracy of interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST) for latent tuberculosis infection (LTBI) in transplant candidates is uncertain. Pubmed, Embase and Cochrane library were searched to identify relevant studies. Quality of included studies was assessed with RevMan5 software (via GUADAS2 checklist). Accuracy measures of IGRAs and TST assays (sensitivity, specificity and others) were pooled with random effects model. Data were analyzed by STATA and Meta-DiSc. Twenty-eight studies were selected for full review, and 16 were included in the final analysis. The pooled sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) for TST were 46% [95% confidence interval (CI) 38-54%], 86% (95% CI 75-93%), 46.3% (95% CI 40-52), 88.7% (95% CI 87-89), 3.3 (95% CI 1.6-6.4), 0.63 (95% CI 0.52-0.77) and 5 (95% CI 2-12), respectively. For QFT-G, the pooled sensitivity, specificity, PPV, NPV, PLR, NLR, and DOR were 58% (95% CI 41-73%), 89% (95% CI 77-95%), 72.7% (95% CI 68-76), 80.6% (95% CI 78-82), 5.3 (95% CI 2.0-14.0), 0.47 (95% CI 0.30-0.75) and 11 (95% CI 3-46), respectively. Likewise, for T-SPOT.TB, the pooled sensitivity, specificity, PPV, NPV, PLR, NLR, and DOR were 55% (95% CI 40-70%), 92% (95% CI 87-95%), 60.4% (95% CI 47-72), 90.2% (95% CI 86-92), 6.7 (95% CI 4.0-11.1), 0.52 (95% CI 0.31-0.85) and 16 (95% CI 7-37), respectively. IGRAs were more sensitive and specific than the TST with regard to the diagnosis of LTBI in the transplant candidates. They have added value and can be complementary to TST.

Microencapsulated Immunoassays for Detection of Cytokines in Human Blood.

Cytokines are produced by leukocytes in blood and may be used as indicators of malignancies or infections. The objective of this study was to develop a strategy for immunosensing cytokines in whole, unprocessed human blood. Microfluidic droplet generation was employed to fabricate ∼400 μm diameter microcapsules with a hydrogel shell and an aqueous core containing sensing microbeads. The hydrogel shell was composed of poly(ethylene glycol) forming a thin (∼10 μm) immunoisolation layer protecting antibody-modified microbeads inside the capsule from immune cells on the outside. The microbeads were functionalized with antibodies against cytokines of interest: interferon (IFN)-γ and tumor necrosis factor (TNF)-α. While nonfouling, a hydrogel shell was permeable to cytokine molecules; these molecules were captured on microbeads and were detected with fluorescently labeled secondary antibodies. Calibration of encapsulated immunoassays with known concentrations of cytokines revealed a limit of detection of 14.8 and 14.4 pM for IFN-γ and TNF-α, respectively. We also demonstrated the concept of multi-cytokine detection by fabricating distinct populations of capsules carrying either anti-IFN-γ or anti-TNF-α microbeads and dispensing these capsules into a solution containing both cytokine types. Importantly, when placed into whole blood for 16 h, microcapsules were free of leukocytes, effectively protecting sensing beads from the blood components. To further demonstrate utility of this strategy, encapsulated microbeads were used for detection of IFN-γ in blood of patients with latent tuberculosis infection (LTBI) and unexposed healthy controls. When compared to gold standard technology (interferon gamma release assay or IGRA), our encapsulated immunoassay accurately predicted LTBI diagnosis in 11 out of 14 patients. Overall, encapsulation of immunoassays represents a promising strategy for keeping sensing elements operational in a highly fouling complex environment such as blood.

Management of Latent Tuberculosis Infection in Children from Developing Countries.

Tuberculosis (TB), once widely prevalent throughout the world, experienced falling incidence rates in early twentieth century in developed nations, even before the introduction of anti-TB drugs, attributed to improved hygiene and living conditions. Active TB may develop following fresh infection or activation of latent tuberculosis infection (LTBI). LTBI is a state of persistent bacterial viability, however, the host stays asymptomatic and there is no evidence of clinically active tuberculosis. Therefore, treatment of all LTBI is considered as one of the ways to control tuberculosis. Diagnosis of LTBI relies on presence of immune-reactivity to TB antigen and commonly used tests include tuberculin skin test and interferon gamma release assay (IGRA). At present there is no diagnostic test that can identify an individual with LTBI who will progress to develop active disease or remain asymptomatic. Therefore, it is unclear whom to treat. In the current scenario, treatment for LTBI is restricted to high risk groups which include under-5 y contacts of adults with pulmonary TB. Various regimens for treatment of LTBI are evolving and consist of isoniazid (INH) alone for 6-9 mo or combination of INH and rifampicin for 3-4 mo or once a week combination of rifapentin and INH for 3 mo. There is a need for research to identify LTBI, risk factors for progression of LTBI to active disease and a shorter regimen for treatment.

Tuberculin skin test – Outdated or still useful for Latent TB infection screening?

ObjectiveTo make an informed viewpoint on the usefulness of Tuberculin Skin test (TST) compared to Interferon Gamma Release Assays (IGRAs) for diagnosis of Latent TB Infection (LTBI) in different geographical settings. MethodsWe reviewed the current literature on TST compared to IGRA, including national implementation of WHO LTBI recommendations and retrospective data over the past 7 years at the National Institute for Infectious Diseases “L. Spallanzani” as indirect indicator of usage of both tests under actual programmatic conditions. ResultsCurrent national guidelines vary considerably, reflecting the uncertainty and rapidly evolving evidence about the potential use of these tests. Data from Institute “L. Spallanzani” showed IGRA concordance in TST positive subjects only in 54.74% of subjects, while there was strong concordance between two tests in TST negative subjects (93.78%). ConclusionNeither IGRAs nor TST can distinguish active TB from LTBI. TST will continue to be clinically useful in low and high TB endemic areas until more accurate and predictive tests will become available. Clinical judgment remains fundamental in choosing between IGRA/TST tests and interpreting their results.

Factors associated with non-initiation of latent tuberculosis treatment among healthcare workers with a positive interferon-gamma releasing assay

Despite widespread use of the interferon-gamma release assay for the diagnosis of latent tuberculosis infection (LTBI), the initiation rate of and factors associated with LTBI treatment among healthcare workers (HCWs) have not been studied in depth. The aim of this study was to evaluate the initiation rate of LTBI treatment and also to identify any factors associated with non-initiation of LTBI treatment among HCWs. A retrospective cohort study of 293 HCWs with LTBI was performed at a teaching hospital in Korea. LTBI was diagnosed using QuantiFERON-TB Gold In-Tube tests (Cellestis Ltd., Carnegie, VIC, Australia). Of the 293 HCWs with LTBI, 189 HCWs (64.5%) visited an outpatient clinic for a medical consultation regarding LTBI treatment. Of these, 128 (67.7%) consented to LTBI treatment for a 43.7% LTBI treatment initiation rate. Upon multivariable analysis, having a liver disease or currently taking hepatotoxic drugs (adjusted odds ratio [OR] = 12.03, 95% confidence interval [CI] = 3.12–46.35), being a physician (adjusted OR = 14.01, 95% CI = 2.82–69.74) and other patient-related HCWs (adjusted OR = 3.58, 95% CI = 1.46–8.78), and years of employment ≥20 years (adjusted OR = 4.77, 95% CI = 1.74–13.12) were independent factors associated with the non-initiation of LTBI treatment. Upon bivariate multivariable analysis, while having a liver disease or currently taking hepatotoxic drugs (adjusted OR = 12.85, 95% CI = 3.06–55.92), being a physician (adjusted OR = 28.43, 95% CI = 4.78–169.28) and other patient-related HCWs (adjusted OR = 4.80, 95% CI = 1.56–14.74), and years of employment ≥20 years (adjusted OR = 4.55, 95% CI = 1.37–15.15) were factors associated with no outpatient clinic visit for a consultation of LTBI treatment, having a liver disease or currently taking hepatotoxic drugs (adjusted OR = 11.76, 95% CI = 2.68–51.73) and years of employment ≥20 years (adjusted OR = 5.29, 95% CI = 1.38–20.19) were factors associated with refusal of LTBI treatment after a consultation. The overall initiation rate of LTBI treatment was suboptimal in HCWs with LTBI diagnosed using an interferon-gamma releasing assay. Having a liver disease or currently taking hepatotoxic drugs, being a physician and other patient-related HCWs, and years of employment ≥20 years were associated with non-initiation of LTBI treatment.

Trend of Mantoux Positivity in a Tertiary Health Institution in Nigeria: A Secondary Data Analysis

Background: Mantoux test is the most widely used screening test that aid diagnosis of latent tuberculosis infection (LTBI) especially in resource poor countries. This study aimed to determine the seven year trend of Mantoux test result at the University of Port Harcourt Teaching Hospital, Rivers State Nigeria. Methods: A secondary data analysis was carried out on abstracted data from 2011 to 2017 in the Mantoux result register. Descriptive statistics was computed for all categorical variables. Chi-square of trend was used to assess significant differences in positivity. P-value less than 0.05 was considered significant. Results: Using a cut-off point of ≥10 mm diameter, a total of 5863 clients were screened for TB. Chi square for trends showed statistical significant decreasing proportion of significant Mantoux reaction status among clients over the study period. Conclusion: The study showed a high prevalence of negative Mantoux reaction compared to positive reaction. Trend analysis showed a notable downward plunge of significant Mantoux positivity. The trend was towards continuous reduction in Mantoux test result positivity suggesting a tailing of LTBI in this region.

Diagnosis and treatment of latent tuberculosis infection in patients undergoing treatment with immunobiologic agents: a four-year experience in an endemic area.

ABSTRACTObjective:To describe the incidence of active tuberculosis and the occurrence of adverse events after isoniazid treatment in patients with latent tuberculosis infection (LTBI) who also had chronic inflammatory diseases and were treated with immunobiologic agents in an endemic area in Brazil. Methods:The diagnosis of LTBI was based on anamnesis, clinical examination, chest X-ray, and a tuberculin skin test (TST). Patients received prophylactic treatment (isoniazid for six months) in accordance with the Brazilian guidelines. Results:A total of 101 patients were evaluated between July of 2011 and July of 2015. Of those, 55 (54.46%) were women (mean age, 53.16 ± 1.76 years) and 46 (45.54%) were men (mean age, 45.39 ± 2.13 years). A total of 79 patients (78.22%) were being treated with immunobiologic agents and 22 (21.78%) were being treated with immunomodulatory or immunosuppressive agents. In the screening for LTBI, 53 patients (52.48%) had a TST induration ≥ 10 mm. Chest X-ray findings consistent with LTBI were observed in 36 patients (35.64%). Isoniazid preventive therapy was effective in 96 (95.05%) of the 101 patients evaluated. It is of note that 84 (83.17%) of the patients experienced no adverse effects from the use of isoniazid and that 83 (98.81%) of those patients completed the prophylactic treatment (p = 0.002). Active tuberculosis was diagnosed in 5 (6.33%) of the 79 patients treated with immunobiologic agents and in 1 (4.55%) of the 22 patients treated with other immunomodulators/immunosuppressants. Conclusions:A six-month course of isoniazid proved to be safe and effective in the treatment of LTBI, which is essential to reducing the risk of developing active tuberculosis.

Comparison of tuberculin skin test and interferon-gamma release assay in the diagnosis of latent tuberculosis infection among indonesian health-care workers

Background: Health-care workers are groups that are close contact with tuberculosis (TB) patients. As an alternative to the tuberculin skin test (TST), there is interferon-gamma release assay (IGRA) for the diagnosis of latent TB infection (LTBI). The objective of this study is to compare TST and IGRA in the diagnosis of LTBI among Indonesian health-care workers. Methods: This study design was a cross-sectional study. TST results are consistent for LTBI if there is induration ≥10 mm in individuals without previous TST, or ≥15 mm in participants with a history of previous TST. Medical history interview, physical examination, chest X-ray, and sputum smear examination were performed to exclude active TB infection. Results: Among 84 healthcare workers, the prevalence of LTBI was 51.2% by IGRA and 29.8% by TST with sufficient agreement (κ = 0.34). Age and low education were significantly correlated with the positive results of IGRA (P

Recent Innovations in Diagnosis and Treatment of Pediatric Tuberculosis.

Tuberculosis is leading cause of global morbidity and mortality and a significant proportion of the burden of disease occurs in children. In the past 5years, a number of innovations have improved the diagnosis and treatment for children with both latent tuberculosis infection and active disease. This review discusses three key areas of innovation. First, we assess utilization and performance of interferon-gamma release assays (IGRAs) in different clinical and epidemiologic scenarios. Recent literature has demonstrated good performance of IGRAs for diagnosis of latent tuberculosis infection, particularly in low-incidence settings such as TB control programs in North America. For high-incidence populations, or when testing is done for possible active TB disease, IGRA performance has some important limitations, but IGRA sensitivity when measured against culture proven disease may be better than earlier studies suggested. The second area of innovation is in increased uptake of nucleic acid amplification (NAA) tests and broader application in non-sputum samples for both pediatric pulmonary and extrapulmonary tuberculosis. Finally, recent studies have provided solid evidence in support of shorter treatment courses for pediatric latent tuberculosis infection, such as 12weeks of weekly isoniazid and rifapentine or 4months daily rifampin, that improve compliance and may reduce resources required for TB control. Many recent innovations in pediatric tuberculosis relate to an improved understanding of how to optimally use existing tests and treatments. Until diagnostic tests and interventions such as vaccination are developed that can dramatically alter the paradigm of pediatric TB management and control, it is important for stakeholders to have a nuanced understanding of tools currently available.