Positive Tuberculin Skin Test Results Research Articles

Predictors of positive tuberculin skin test in neonates exposed to pulmonary tuberculosis.

Neonates are at risk of nosocomial tuberculosis (TB) infection from health care workers (HCWs) in neonatal care facilities, which can progress to severe TB diseases. Tuberculin skin test (TST) is commonly used for TB diagnosis, but its accuracy in neonates is influenced by various factors, including bacilli Calmette-Guérin (BCG) vaccination. This study aimed to identify predictors of positive TSTs in neonates exposed to HCWs with pulmonary TB. A retrospective observational study was conducted to compare the frequency of predictors between TST-positive and TST-negative neonates. Demographic, epidemiological, and clinical data of neonates exposed to TB, along with that of HCW and household contacts, were collected retrospectively through contact investigations with the Korean National TB Surveillance System (KNTSS) database. TSTs using 2 tuberculin units of purified protein derivative RT23 were performed on exposed neonates at the end of preventive TB treatment. Firth logistic regression was performed to identify predictors of TST positivity. Contact investigations revealed that 152 neonates and 54 HCWs were exposed to infectious TB index cases in 3 neonatal care facilities. Of 152 exposed neonates, 8 (5.3%) had positive TST results. Age of 6 days or more at the initial exposure is a statistically significant predictor of positive TST (Firth coefficient 2.1, 95% confidence interval 0.3-3.9, P = 0.024); BCG vaccination showed no statistical significance in both univariable and multivariable analysis. Sex, prematurity, exposure duration, duration from initial exposure to contact investigation, and isoniazid preventive treatment duration were not significant predictors. Age at the initial exposure is a significant predictor of positive TST in neonates exposed to active pulmonary TB. Given the complexities of TST interpretation, including false positives due to BCG vaccination, careful risk assessment is necessary for appropriate decision-making and resource allocation in the management of neonatal TB exposure.

Comparison of Tuberculin Skin Testing and Interferon-γ Release Assays in Predicting Tuberculosis Disease

Elimination of tuberculosis (TB) disease in the US hinges on the ability of tests to detect individual risk of developing disease to inform prevention. The relative performance of 3 available TB tests-the tuberculin skin test (TST) and 2 interferon-γ release assays (IGRAs; QuantiFERON-TB Gold In-Tube [QFT-GIT] and SPOT.TB [TSPOT])-in predicting TB disease development in the US remains unknown. To compare the performance of the TST with the QFT-GIT and TSPOT IGRAs in predicting TB disease in high-risk populations. This prospective diagnostic study included participants at high risk of TB infection (TBI) or progression to TB disease at 10 US sites between 2012 and 2020. Participants of any age who had close contact with a case patient with infectious TB, were born in a country with medium or high TB incidence, had traveled recently to a high-incidence country, were living with HIV infection, or were from a population with a high local prevalence were enrolled from July 12, 2012, through May 5, 2017. Participants were assessed for 2 years after enrollment and through registry matches until the study end date (November 15, 2020). Data analysis was performed in June 2023. At enrollment, participants were concurrently tested with 2 IGRAs (QFT-GIT from Qiagen and TSPOT from Oxford Immunotec) and the TST. Participants were classified as case patients with incident TB disease when diagnosed more than 30 days from enrollment. Estimated positive predictive value (PPV) ratios from generalized estimating equation models were used to compare test performance in predicting incident TB. Incremental changes in PPV were estimated to determine whether predictive performance significantly improved with the addition of a second test. Case patients with prevalent TB were examined in sensitivity analysis. A total of 22 020 eligible participants were included in this study. Their median age was 32 (range, 0-102) years, more than half (51.2%) were male, and the median follow-up was 6.4 (range, 0.2-8.3) years. Most participants (82.0%) were born outside the US, and 9.6% were close contacts. Tuberculosis disease was identified in 129 case patients (0.6%): 42 (0.2%) had incident TB and 87 (0.4%) had prevalent TB. The TSPOT and QFT-GIT assays performed significantly better than the TST (PPV ratio, 1.65 [95% CI, 1.35-2.02] and 1.47 [95% CI, 1.22-1.77], respectively). The incremental gain in PPV, given a positive TST result, was statistically significant for positive QFT-GIT and TSPOT results (1.64 [95% CI, 1.40-1.93] and 1.94 [95% CI, 1.65-2.27], respectively). In this diagnostic study assessing predictive value, IGRAs demonstrated superior performance for predicting incident TB compared with the TST. Interferon-γ release assays provided a statistically significant incremental improvement in PPV when a positive TST result was known. These findings suggest that IGRA performance may enhance decisions to treat TBI and prevent TB.

Pregnancy and neonatal outcomes in infertile patients with positive tuberculin skin test results

Research questionDo infertile women with positive tuberculin skin test (TST) results have a higher risk of adverse pregnancy outcomes after IVF or intracytoplasmic sperm injection and embryo transfer (ICSI–ET) and does preventive anti-tuberculosis treatment applied to infertile women with positive TST results before IVF/ICSI–ET affect pregnancy and neonatal outcomes? DesignThis was a retrospective cohort analysis of 6283 infertile women who underwent IVF/ICSI–ET treatment for the first time at the Reproductive Hospital affiliated to Shandong University from November 2016 to September 2022. None of the participants had prior tuberculosis or active tuberculosis. According to their TST results, 5947 patients who had never received preventive anti-tuberculosis treatment were divided into a TST-positive group (1704 cases) and a TST-negative group (4243 cases). A total of 504 patients with TST (+++) results (using the 20 mm sclerosis threshold) were divided into a treated TST (+++) group (336 cases) and an untreated TST (+++) group (168 cases) according to whether they received preventive anti-tuberculosis treatment before IVF/ICSI–ET. The outcome measures were pregnancy outcomes and neonatal outcomes. ResultsThere were no significant differences in pregnancy or neonatal outcomes between the TST-positive group and the TST-negative group (P > 0.05). In the TST (+++) group, there were no significant differences in pregnancy or neonatal outcomes between the treated TST (+++) group and the untreated TST (+++) group (P > 0.05). ConclusionsFor infertile women undergoing IVF/ICSI–ET without prior tuberculosis or active tuberculosis, positive TST results and preventive anti-tuberculosis treatments prior to IVF/ICSI–ET do not affect pregnancy or neonatal outcomes.

Risk of tuberculosis in children with rheumatologic diseases treated with biological agents: A cross-sectional cohort study.

This study aimed to evaluate the risk of tuberculosis (TB) disease in children receiving biological agents for rheumatologic diseases, focusing on appropriate screening tests in a high-priority country for TB control. One hundred nine children (56 females, 53 males; range, 3.4 to 16.2 years) who received any biological agent for rheumatologic diseases for more than two years between May 2012 and October 2021 were included in this retrospective study. Patients were screened for TB infection using tuberculin skin test (TST) or interferon-gamma release assay (IGRA). Following the initial evaluation, patients were clinically examined for TB every three months by a comprehensive medical history and physical examination, and every 12 months using TST or IGRA. At the initiation of the biological agent, the patients' mean age was 12.4±4.5 years. The average follow-up duration was 3.6±1.3 years (range, 2.6 to 10.2 years) for patients treated with biological agents. Each patient had a documented Bacillus Calmette-Guérin vaccination. Before the initiating of therapy, TST was performed alone in 45 (41.3%) patients and in combination with IGRA in 64 (58.7%) patients. In the 64 patients who underwent both TST and IGRA, IGRA revealed nine (14.1%) positive results. Six (66.7%) of these nine patients, however, had negative baseline TST. Four (7.3%) of the 55 individuals whose initial IGRA results were negative also had positive TST results. Overall, no TB disease was observed after a follow-up period. This study reveals that biological agents were not associated with an increased risk of TB disease in closely monitored children. Additionally, the concomitant use of TST and IGRA for screening of TB is reasonable in patients receiving biological agents.

Selection of the cutoff value of the tuberculin skin test for diagnosing students who need preventive treatment: A school-based cross-sectional study

ObjectiveTuberculosis outbreaks in schools are common in China. This study aimed to introduce and evaluate a new screening process to help control outbreaks.MethodsScreening information of students in three schools with tuberculosis outbreaks was collected. QuantiFERON-TB gold in-tube (QFT) results were used as the reference standard to determine the cutoff value of the tuberculin skin test (TST) for diagnosing students who need to have preventive medication.ResultsA total of 1,232 students and teachers from three different schools that all had more than three student patients with tuberculosis were included in this study. In total, 308 (25.0%) students had an induration diameter ≥10 mm; among students in a class different from the index case, the infection rate was 24.4% (264/1,084), which was lower than the rate among students in the same class (29.7%) (P = 0.157). Students in the same class as the index tuberculosis case had a much higher QFT positivity compared to those in a different class (58.1% vs. 7.7%, P < 0.0001). Diagnostic agreement between TST ≥10 mm and QFT was 36.6%. The diagnostic value reached the highest when the induration diameter of TST was ≥9 mm, with a sensitivity and specificity of 94.1% (95% CI: 89.4%–97.1%) and 27.6% (95% CI: 24.9%–30.4%), respectively. The area under the curve (AUC) was 0.664 (95% CI: 0.637–0.690, P < 0.0001).ConclusionIn tuberculosis outbreaks in schools, if there are three or more cases of students with tuberculosis in a class or if the moderate or strong TST positivity rate is much higher than the normal range in the region, attention should be paid to those with moderately positive TST results. Interferon-gamma release assays (IGRAs) are recommended to be conducted following TST on the day of reading the results, especially among students sharing the same class with the index case. In resource-poor areas lacking IGRAs, the induration diameter of TST can be appropriately reduced from 15 to 9 mm to enhance the sensitivity of TST.

High value of early secretory antigenic target-6 and culture filtrate protein-10 in diagnosis of IgA nephropathy with renal tuberculosis: a retrospective study

BackgroundThis retrospective study aimed to evaluate the diagnostic value of early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) in immunoglobulin A nephropathy (IgAN) associated with renal tuberculosis (RT). MethodsForty patients with IgAN (IgAN group), 32 patients with RT (RT group), and 52 patients with IgAN associated with RT (IgAN + RT group) were retrospectively selected for this study. A tuberculin skin test (TST) was conducted, and Mycobacterium tuberculosis (MTB) antibody levels were measured. Immunohistochemistry and western blotting were used to determine the expression of ESAT-6 and CFP-10 proteins in renal tissues. ResultsThe positive results of TST and levels of serum and urinary MTB antibodies were higher in the RT group than in the IgAN + RT group. The expression levels of ESAT-6 and CFP-10 proteins were the highest in the IgAN + RT group and lowest in the IgAN group. The receiver operating characteristic curves indicated that the area under curve (AUC) value of the ESAT-6 protein for the diagnosis of IgAN associated with RT was 0.907 and the cut-off value of the integral optical density (IOD) was 26.72. Diagnosis based on ESAT-6 protein levels showed 75% sensitivity and 94.2% specificity. The AUC value of the CFP-10 protein for the diagnosis of IgAN associated with RT was 0.8 and the cut-off value of IOD was 25.67. Detection based on CFP-10 protein levels showed 63.9% sensitivity and 84.6% specificity. ConclusionsOur study provides evidence for the potential of ESAT-6 and CFP-10 proteins as candidate markers in the diagnosis of IgAN associated with RT.

Oral Swab Specimens Tested With Xpert MTB/RIF Ultra Assay for Diagnosis of Pulmonary Tuberculosis in Children: A Diagnostic Accuracy Study.

Microbiologic diagnosis of childhood tuberculosis may be difficult. Oral swab specimens are a potential noninvasive alternative to sputum specimens for diagnosis. This was a prospective diagnostic accuracy study of oral swab specimens (buccal and tongue) for pulmonary tuberculosis diagnosis in children (aged ≤ 15 years) in 2 South African hospital sites. Children with cough of any duration as well as a positive tuberculin skin test result, tuberculosis contact, loss of weight, or chest radiograph suggestive of pulmonary tuberculosis were enrolled. Two induced sputum specimens were tested with Xpert MTB/RIF (or Xpert MTB/RIF Ultra) assay and liquid culture. Oral swab specimens were obtained before sputum specimens, frozen, and later tested with Xpert MTB/RIF Ultra. Children were classified as microbiologically confirmed tuberculosis, unconfirmed tuberculosis (receipt of tuberculosis treatment), or unlikely tuberculosis according to National Institutes of Health consensus definitions based on sputum microbiologic results. Among 291 participants (median age [interquartile range], 32 [14-73] months), 57 (20%) had human immunodeficiency virus (HIV), and 87 (30%) were malnourished; 90 (31%) had confirmed pulmonary tuberculosis (rifampicin resistant in 6 [7%] ), 157 (54%), unconfirmed pulmonary tuberculosis, and 44 (15%), unlikely tuberculosis. A single oral swab specimen was obtained from 126 (43%) of the participants (tongue in 96 and buccal in 30) and 2 swab specimens from 165 (57%) (tongue in 110 and buccal in 55). Sensitivity was low (22% [95% confidence interval, 15%-32%]) for all swab specimens combined (with confirmed pulmonary tuberculosis as reference), but specificity was high (100% [91%-100%]). The highest sensitivity was 33% (95% confidence interval, 15%-58%) among participants with HIV. The overall yield was 6.9% with 1 oral swab specimen and 7.2% with 2. Use of the Xpert MTB/RIF Ultra assay with oral swab specimens provides poor yield for microbiologic pulmonary tuberculosis confirmation in children.

The challenge of minimizing tuberculosis burden in people living with HIV in the Asia Pacific.

The challenge of minimizing tuberculosis burden in people living with HIV in the Asia Pacific.

Prediction Tool to Identify Children at Highest Risk of Tuberculosis Disease Progression Among Those Exposed at Home.

BackgroundThere is a dearth of research to understand which children, among those who are exposed at home to tuberculosis (TB), are at the highest risk of TB disease, to tailor care. We sought to identify predictors of TB progression in children.MethodsWe conducted a prospective cohort study of children living with adults with pulmonary TB in Lima, Peru (2009–2012). We applied classification and regression tree analysis to examine potential predictors of incident TB disease during 12 months in 3 age groups (0–4, 5–9, and 10–14 years). We calculated the relative risk (RR) for top predictors in each age group.ResultsAmong 4545 children 0–14 years old, 156 (3.4%) were diagnosed with TB within 1 year of household exposure to TB (3.4%, 2.3%, and 4.7% in children 0–4, 5–9, and 10–14 years old, respectively). The most important predictor of TB was having a positive tuberculin skin test (TST) result, with RRs of 6.6 (95% CI, 4.0–10.7), 6.6 (95% CI, 3.2–13.6), and 5.2 (95% CI, 3.0–9.0) in the age groups 0–4, 5–9, and 10–14 years, respectively. In young children with a positive TST, not using isoniazid preventive treatment further increased risk of disease (RR, 12.2 [95% CI, 3.8–39.2]).ConclusionsWe present a tool that identifies child household contacts at high risk of TB disease progression based on data collected during contact tracing. In addition to the use of TB preventive therapy for all children exposed at home to TB, those children at highest risk of progressing to TB disease may benefit from more frequent follow-up.

Mültecilerin kabulünden sonra bir referans çocuk hastanesinde çocukluk çağı tüberkülozu

Aim: We aimed to evaluate epidemiologic, clinical, laboratory, microbiologic features, treatment and outcomes of pediatric tuberculosis (TB) patients also to draw attention to immigrant patients.&#x0D; Material- Methods: We retrospectively conducted the medical records of children below 18 years of age with TB between January 2015 and September 2016. &#x0D; Results: A total of 20 TB patients (35% were Syrian refugees, total 65% female) with a median age of 135.5±52.6 months were evaluated. Fourteen (70%) patients were adolescent. The history of contact with an active TB disease patient was found in seven (35%) patients. Four (20%) patients had no complaint at admission whereas the most common symptom was prolonged cough &gt; 2 weeks. Fifteen (75%) patients had a Bacillus Calmette–Guérin scar on the left shoulder. A total of 16 (80%) patients had a positive tuberculin skin test (TST) result. Microbiological confirmation was provided in four (20%) patients totally. The most common chest X-ray findings on admission were hilar lymphadenopathy. Ten (50%) patients had normal chest X-ray and were diagosed with abnormal thorax tomography findings. All of the patients were treated succesfully except one Syrian patients with miliary TB who died.&#x0D; Conclusion: Microbiological confirmation of childhood TB may be absent and the diagnosis can be confirmed in the light of contact history, positive TST reaction, compatible symtomps and radiological evidence. Particular attention might be paid to Syrian refugees, taking into epidemiological characteristics of TB disease and the density of immigrants in the place we live in.

Indications, Interpretation and Clinical Consequences of Tuberculin Skin Tests in Resource Limited Settings

Objective: to evaluate the policy of TST testing in Suriname. As there is no gold standard to diagnose latent tuberculosis infection (LTBI), the tuberculin skin test (TST) is used to diagnose LTBI. However, internationally, the cut-off values of the TST are not uniform and depend on local tuberculosis (TB) epidemiology and guidelines for test initiation. In Suriname, where currently several indications exist for TSTs, cut-off values are set at 5 mm or 10 mm, depending on the age and/or medical history of the patient. LTBI classification is performed by pulmonologists primarily based on the American Thoracic Society targeted TB testing guidelines. Method: retrospective analysis of outpatient TST data between 2011 and 2019 from Suriname’s sole pulmonary medicine clinic. Result: 1373 patients were evaluated. 590 patients were from the screening group of whom 253 had a positive TST result, 46 of whom were classified as LTBI. In the contact tracing group of 649 patients, 616 had a positive TST, 352 of whom were classified as LTBI. In the medical condition group of 134 patients, 96 had a positive TST, 38 of whom were classified as LTBI. Eventually, positive TST results were found for 965 tested patients: 436 patients were classified as LTBI and 529 non-LTBI patients were not prescribed chemoprophylaxis. None of the non-LTBI TST-positive patients were diagnosed with active TB, including 174 patients with a TST result of 15 mm or greater and in need of IPT, but not prescribed by judgement of the pulmonologist or because of loss to follow-up. Conclusion: the overrepresentation of positive TST results in Suriname is attributable to stringent cut-off values, especially among patients who do not disclose TB risk factors. In our opinion the TST cut-off value for such patients in Suriname and other similar settings could be set at 15 mm. We also promote that for all patients with a TST result of 15 mm or greater, offering IPT should be considered (after excluding active TB).

Presumed tuberculous sclerokeratouveitis in immunocompetent South African patients.

Ocular tuberculosis remains a diagnostic challenge since its clinical presentation is so variable. We describe the clinical characteristics of patients presenting with sclerokeratouveitis secondary to presumed Mycobacterium tuberculosis infection. Retrospective analysis of 14 patients presenting with sclerokeratouveitis to Tygerberg Hospital. All patients underwent: (1) detailed ophthalmological evaluation, (2) tuberculin skin test (TST), (3) chest X-ray to assess for systemic disease, and (4) laboratory investigations to exclude other causes of ocular inflammation. Tuberculous sclerokeratouveitis was diagnosed if: (1) clinical findings showed scleritis with adjacent peripheral keratitis and anterior uveitis, (2) TST was positive, (3) other causes of sclerokeratouveitis were excluded, and (4) positive response to tuberculosis treatment without adjunctive anti-inflammatory agents was noted. Seventeen eyes were included. Mean age was 29.1 ± 12.1 years. All patients were females with no history of previous/current pulmonary tuberculosis. Only one patient was HIV positive, but virologically suppressed. All patients had a strongly positive TST result. Scleral involvement was nodular in four patients and diffuse in ten. Corneal involvement manifested as ill-defined peripheral stromal opacities adjacent to the area of scleritis with deep corneal stromal vessels. Corneal sensation was decreased in all involved eyes. All patients responded to tuberculosis treatment with complete resolution of the sclerokeratouveitis. In our highly endemic area, tuberculous sclerokeratouveitis is seen in young, immunocompetent patients, and responds well to tuberculosis treatment without concurrent immunosuppression. Decreased corneal sensation may lead to an incorrect diagnosis of herpetic infection if a high index of suspicion is not maintained for ocular tuberculosis.

Comparison between the Interferon γ Release Assay—QuantiFERON Gold Plus (QFT-Plus)—and Tuberculin Skin Test (TST) in the Detection of Tuberculosis Infection in Immunocompromised Children

Background Immunocompromised patients are at a higher risk of having latent tuberculosis infection (LTBI). QuantiFERON-TB Gold Plus (QFT-Plus) has been proven to perform effectively in LTBI detection among immunocompromised adults and can overcome the limitations of the tuberculin skin test (TST). However, the role of QFT-Plus in detecting LTBI in immunocompromised paediatric patients has not been well established. Therefore, the aim of this study was to assess the test agreement between QFT-Plus and the TST in LTBI detection among immunocompromised children. Method In this cross-sectional study, we enrolled immunocompromised paediatric patients, aged between 5 and 18 years, who were treated with corticosteroids and/or chemotherapy from June to November 2019. We categorized them into three groups based on the following diseases: hematologic malignancies and nephrological and immunological diseases. We recorded the patient characteristics and QFT-Plus and TST results, in which the positive result of the TST was induration ≥ 5 mm. Within the same group, comparisons between the two tests were performed using the McNemar test, and results were statistically significant for p values of <0.05. The kappa index was used to assess the agreement between the two test results. Results Among 71 patients (median age: 11.8 years) who underwent TST and QFT-Plus testing, 52% were females, and 69% had a normal nutritional status. Chemotherapy was the most common treatment modality for hematologic malignancy compared to other immunosuppressive treatments. The total number of patients with positive QFT-Plus and TST results was 11/71 (15.5%) and 4/71 (5.6%), respectively, among whom 3/11 patients had positive results in both tests, and one patient with positive TST results exhibited a discrepancy, as this was not followed by positive QFT-Plus results. QFT-Plus generated more positive results than the TST in immunocompromised children (McNemar, p = 0.039 (p < 0.05)). The diagnostic agreement between the tests was fair (K = 0.345, 95% CI: 0.05–0.745). Conclusion QFT-Plus detected LTBI more effectively than the TST in immunocompromised children.

Prevalence of positive TST among healthcare workers in high-burden TB setting in Peru

BackgroundTuberculosis (TB) transmission has long been recognized as an important occupational hazard for healthcare workers (HCWs). HCWs have a 5.8% annual risk of exposure and three times greater risk of developing active TB than the general population.MethodsWe conducted an observational cross-sectional study between September 2014 and March 2015 among HCWs in a high-burden TB setting in Lima to estimate the prevalence of positive Tuberculin Skin Test (TST) and to investigate factors associated with a positive TST.ResultsTwo hundred forty participants were included in the analysis; TST was administered to 190 (79.2%) while the rest were exempt due to a previous positive TST result, history of TB, or test refusal. A positive TST result was found among 56.2% of participants to whom the TST was applied (95% CI: 49.22–63.55%). When considering those who had a previous positive TST result and those with a history of TB, the prevalence of a positive TST result was 64.3% (95% CI: 57.8–70.3%). No significant differences were observed between clinical/paramedical and administrative staff in the health center. The use of N95 masks during work hours was reported by 142 (69.9%) participants. Prevalence ratios (PR) show that workers with more than 120 months as a HCW were 1.44 times more likely to be TST positive. The multivariate analysis found that HCWs with over 10 years of service were 1.52 times more likely to be TST positive.ConclusionThis study supports previous reports that TB infection is an occupational hazard for HCWs. Prevention of TB transmission through control measures, as well as timely diagnosis of LTBI in this particular high-risk group, is critical for individual and public health.

Risk-benefit analysis of tuberculosis infection testing for household contact management in high-burden countries: a mathematical modelling study

SummaryBackgroundPreventive therapy for tuberculosis reduces the risk of disease in people who have been infected but who are not sick. Countries with a high burden of tuberculosis that are expanding preventive therapy use must decide how tuberculosis infection testing should be used for risk stratification among household contacts of patients with tuberculosis.MethodsWe modelled the risks of tuberculosis disease and severe adverse events, comparing the following two preventive therapy strategies: preventive therapy for all household contacts, or preventive therapy for only household contacts with a positive tuberculin skin test (TST) result. We used data from clinical trials and literature on tuberculosis natural history to model outcomes, assuming different preventive therapy regimens, ages, and TST positivity prevalence.FindingsAssuming 25% prevalence of TST positivity among 1000 household contacts aged 0–17 years, a treat-all approach with isoniazid and rifapentine compared with a treat-TST-only approach led to 13 fewer incident tuberculosis cases (IQR −5 to −18) and four additional severe adverse events (2 to 6). With rifampicin, the difference was 11 fewer incident tuberculosis cases (–3 to −17) and two additional severe adverse events (1 to 3). For adults, a treat-all approach led to fewer incident tuberculosis cases, and additional adverse events increased with age. Assuming 25% prevalence of TST positivity among adult contacts, a treat-all approach would lead to around two fewer tuberculosis cases per 1000 contacts for all regimens; the number of additional severe adverse events ranged from seven (IQR 5 to 8) for 18 to 34-year-olds treated with rifampicin to 63 (50 to 74) for people older than 64 years treated with isoniazid and rifapentine. A rifampicin-only regimen was associated with the fewest additional severe adverse events (seven [IQR 5 to 8] per 1000 adults aged 18–34 years and 35–64 years, and 17 [9 to 23] per 1000 adults older than 64 years).InterpretationBased on the available data, giving preventive therapy to all household contacts would probably reduce the incidence of tuberculosis cases in high-burden settings. Adverse events could be minimised by using non-isoniazid regimens and, in adults older than 18 years, focusing treatment on individuals with a positive infection test.FundingBill & Melinda Gates Foundation, UK Medical Research Council, and UK Department for International Development.

Tuberculosis disease and infection among household contacts of bacteriologically confirmed and non-confirmed tuberculosis patients.

To compare the prevalence of tuberculosis infection and disease in household contacts of patients with bacteriologically confirmed tuberculosis disease and contacts of non-bacteriologically confirmed disease in western Kenya. We enrolled newly diagnosed index patients and their household contacts from March 2014 to June 2016. All contacts were evaluated with a symptom questionnaire, tuberculin skin test (TST) and HIV test. Clinical evaluation and sputum testing were performed for those with symptoms, positive TST result or HIV infection. We enrolled 1155 contacts of 330 index patients with bacteriologically confirmed tuberculosis and 192 contacts of 55 index patients with non-bacteriologically confirmed tuberculosis. 3.5% of contacts of patients with bacteriologically confirmed tuberculosis were diagnosed with tuberculosis, whereas no contacts of index patients with non-bacteriologically confirmed tuberculosis were. Of those diagnosed with tuberculosis disease, 58.5% reported symptoms, 34.1% reported no symptoms but had positive TST results, and 7.3% had neither symptoms nor positive TST but were HIV-positive. Among 872 contacts with a TST result, 50.9% of contacts of index patients with bacteriologically confirmed tuberculosis and 41.0% of contacts of index patients with non-bacteriologically confirmed tuberculosis had a positive result (prevalence ratio=1.16, 95% confidence interval 0.92-1.48). In a high-burden setting, tuberculosis disease was more prevalent among contacts of patients with bacteriologically confirmed tuberculosis than contacts of patients with non-bacteriologically confirmed disease. TST was feasible to perform and helped to detect cases that would have been missed had only symptomatic contacts been evaluated.

Absolute risk of tuberculosis among untreated populations with a positive tuberculin skin test or interferon-gamma release assay result: systematic review and meta-analysis

ObjectiveTo determine the annual rate of tuberculosis development after a positive tuberculin skin test (TST) or interferon-gamma release assay result (IGRA), or both, among untreated populations with characteristics believed to...

Patient perceptions of a tuberculosis testing program provided in the community pharmacy setting

ObjectivesThis study sought to describe patient experiences and perceptions of a public health initiative designed to improve tuberculosis (TB) testing access using the tuberculin skin test (TST) in a community pharmacy setting. Study designThis was a cross-sectional study. MethodsA telephonic survey of patients who had received a TST at one of twelve participating community pharmacies between August 2014 and July 2016 was conducted. The 26-question survey was developed by two pharmacists with expertise in TB management and one pharmacy student. Before administration the survey was peer-reviewed for clarity. Potential study patients were identified through TST records at the study pharmacies. English-speaking patients older than 18 years were eligible for study inclusion. Statistical differences in responses based on location were identified using chi-squared test for frequency comparisons with a P-value of <0.05 to determine statistical significance. ResultsA total of 1709 patients received a TST during the study period, of whom 431 were contacted and 325 participated, meeting the predetermined representative sample needed of 314 patients. The majority of study patients were female (67.1%) and white (81%). The mean age was 36 years (standard deviation = 14.1). A majority (68.3%) lived <5 miles from the TST pharmacy, while 45.2% of those with a primary care provider (PCP) (61.6% of respondents) lived within 5 miles of the PCP's office. Care was accessible and met patients' testing needs. For most patients (84.6%), the initial and follow-up appointments took < 20 min. Follow-up TST reading rate was 98.5%; 4.3% of tests were positive. Positive TST results were associated with use of a small city pharmacy (P = 0.003). Perception differences based on location were identified. ConclusionsUptake of the TST service in the community pharmacy setting was high and patients reported positive experiences.

The use of GeneXpert Mycobacterium tuberculosis/rifampicin assay in diagnosis of pulmonary tuberculosis in children

Introduction Rapid diagno sis of tuberculosis (TB) is essential for early disease management. GeneXpert (GX) test is a novel rapid diagnostic modality. In this study, we aimed to evaluate the diagnostic role of GX test in diagnosing pulmonary tuberculosis (PTB) in children as well as detection of rifampicin (RIF) resistance. Patients and methods This was a cross-sectional study that included 80 patients suspected to have PTB based on clinical data together with at least one of the followings: a positive tuberculin skin test or QuantiFERON-TB Gold In-Tube test result, a positive blood TB PCR result, or a positive Ziehl–Neelsen staining result. Results PTB was more common in older females. Extrapulmonary manifestations and hilar lymphadenopathy were more frequent in younger age. Both positive tuberculin skin test and positive GX were more frequent in older age. Positive GX was found in 30 (37.5%) cases, and RIF resistance was detected in two (6.6%) of them. Positive GX results were more frequent in sputum than gastric aspirate samples. Positive GX results were more frequent with absent Bacillus Calmette–Guerin scar, and with hemoptysis, failure to thrive, cavitary lung lesions, and lower mean hemoglobin. Conclusion GX detects many more cases than blood PCR and Ziehl–Neelsen stain. GX had 70% sensitivity and 95% specificity in diagnosing PTB, with overall diagnostic accuracy of 86.67%, with better performance in older children who could expectorate. RIF resistance was ∼6.6%.

Latent Tuberculosis Infection among Healthcare Students and Postgraduates in a Mediterranean Italian Area: What Correlation with Work Exposure?

Background: Tuberculosis screening is part of the standard protocol for evaluating the risk of infection in healthcare workers. The aim of this study was to evaluate the prevalence of latent tuberculosis infection (LTBI) among students attending various healthcare profession degree courses and postgraduate medical courses at the School of Medicine of the University of Palermo, Italy, and assess the possible professional origin of infection. Methods: In total, 2946 students (2082 undergraduates and 864 postgraduates) took part in a screening program for LTBI between January 2014 to April 2019 using the tuberculin skin test (TST). Students with a positive TST result underwent a Quantiferon-TB test (QFT). Results: Among the 2082 undergraduates, 23 (1.1%) had a positive TST; the result was confirmed with QFT for 13 (0.62%) of them. Among the 864 postgraduate students, 24 (2.78%) had a positive TST and only 18 (2.08%) showed a positive QTF. Latent tuberculosis infections were significantly more frequent among postgraduates than undergraduates (2.08% > 0.62%, p < 0.0001). There was a higher number of subjects previously vaccinated for TB (18.87% > 0.24%, p < 0.0001), and of vaccinated subjects found positive for TST and QTF (66.67% > 7.69%, p = 0.001) in the postgraduate group. Conclusion: Latent TB is relatively low among medical school students in our geographic area. Nevertheless, this infectious disease must be regarded as a re-emerging biohazard for which preventive strategies are required to limit the risk of infection, especially among exposed workers.