Positive Tuberculin Skin Test Research Articles

Latent Tuberculosis in Hematopoietic Stem Cell Transplantation: Diagnostic and Therapeutic Strategies to Prevent Disease Activation in an Endemic Population

Introduction Latent tuberculosis infection (LTBI) affects one third of the world population. It is well known that patients with immunodeficiency are at a higher risk of developing active tuberculosis (ATBI). Hematopoietic stem cell transplant (HSCT) recipients have an incidence of ATBI 10 to 40 times greater when compared to the general population, this being related to a higher morbidity and mortality. The aim of this study was to determine the prevalence of LTBI and incidence of ATBI after transplant in recipients and donors of HSCT living in an endemic region. Methods Retrospective single-center study that included all HSCT recipients and donors treated and followed at our Institution between February 2000 and June 2018. LTBI and ATBI were categorized according to WHO definitions. Results A total of 411 patients were included: 125 allogeneic HSCT (allo-HSCT) recipients, 167 autologous HSCT (auto-HSCT) recipients, and 119 HSCT donors. Median age of the group was 34 years (range 11-70) and 59.9% were male (n=246). Baseline diagnoses that led to HSCT were: acute leukemia in 30.9% (n=127), lymphoma in 17.3% (n=71), and monoclonal gammopathy (MG) in 10.7% (n=44) (Figure 1). Allo-HSCT donors were matched related donors (MRD) in 84.8% (n=106), matched unrelated donors (MUD) in 3.2% (n=4), haploidentical in 10.4% (n=13), and umbilical cord in 1.6% (n=2). The source of HSCT was peripheral blood (PB) in 175 patients (59.9%), bone marrow (BM) in 50 patients (17.1%), primed-BM in 65 patients (22.3%), and umbilical cord in 2 patients (0.7%). All patients were evaluated pre-HSCT with tuberculin skin test (TST) and thoracic imaging. LTBI was diagnosed in 109 patients (26.5%): 21%, 20%, and 41.2% of patients were auto-HSCT recipients, allo-HSCT recipients, and allo-donors; respectively. One-hundred and seven patients had a positive TST and two patients presented findings suggestive of LTBI on chest X-ray. Seventy-eight percent of LTBI-HSCT recipients were further evaluated with chest CT (n=29), sputum (n=26), gastric fluid (n=15), and/or urine (n=25) cultures to rule out ATBI according to treating physician's criteria. In contrast, only 42.9% (n=21) of donors were further evaluated with chest CT (n=11), sputum (n=15), gastric fluid (n=2) and/or urine (n=12) cultures. All cultures were negative at follow-up. At LTBI diagnosis 80 patients (73.3%) initiated treatment with isoniazid (INH) 300mg daily for a minimum of 6 months. Treated HSCT recipients represented 91.7% and donors were 51%. Median days of therapy received before HSCT were 76 days (range 0-732) in HSCT recipients and 48 days (range 0-401) in donors. Distribution of cases according to the patient's state of residency, excluding Mexico City, revealed an increase prevalence of cases in the southern border of the country (Figure 2). ATBI incidence at 1 year of follow-up in the cohort was 0%. Only one patient developed a pulmonary mycobacterial-related infection; however, the species identified was M. chelonae. Conclusions To our knowledge, this is the first study that evaluates the prevalence of LTBI among HSCT recipients in a Latin American country where tuberculosis is endemic. We identified a prevalence of LTBI similar to what the WHO estimates; however, the presence of lower rates in recipients compared to donors in our population suggests a negative impact of depressed humoral immunity over the TST diagnostic yield. Interestingly, we do not report any ATBI cases post-transplant; pre-transplant diagnostic strategies, as well as length of treatment may be influencing factors for these outcomes. Collaborative working groups are required to stablish the best diagnostic and therapeutic approach in order to improve ATBI-attributable morbidity and mortality in this vulnerable HSCT-patient population. Disclosures Demichelis: AMGEN: Research Funding, Speakers Bureau; Abbvie: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Shire: Speakers Bureau.

Impact of negative tuberculin skin test on growth among disadvantaged Bangladeshi children.

Millions of children are suffering from tuberculosis (TB) worldwide and often end-up with fatal outcome especially in resource-poor settings. Tuberculin skin test (TST) is a conventionally used diagnostic test, less sensitive but highly specific for the diagnosis of clinical TB especially in undernourished children. However, we do not have any data on the role of TST positivity among the children who received nutritional intervention. Our aim was to examine the growth differences between TST-positive and TST-negative undernourished children aged 12 to 18 months who received nutritional intervention prospectively for 90 feeding days. Our further aim was to explore the determinants of TST positivity at enrollment. TB screening as one of the secondary causes of malnutrition was performed on 243 stunted [length for age Z score (LAZ) <-2 standard deviations] or at-risk of stunting (LAZ score between <-1 and -2 standard deviations) children in a community-based intervention study designed to improve their growth parameters. Differences of growth between TST-positives (n = 29) and TST-negatives (n = 214) were compared using paired samples t-test and multivariable linear regression from anthropometric data collected before and after nutritional intervention. Multivariable logistic regression was used to find out possible predictors of TST positivity using baseline sociodemographic data. Of the 243 children screened, 29 (11.9%) were TST-positive and 11 (4.5%) had clinically diagnosed pulmonary TB. Statistically significant improvement of LAZ and weight for age Z-score (WAZ) were observed among the TST-negative participants at the end of intervention period (p = 0.03 for LAZ and p = 0.01 for WAZ). However, we did not find any association between TST status and response to nutritional intervention in our multivariable linear regression models. Our study findings demonstrated a positive impact of nutritional intervention on growth parameters among TST-negative participants.

Performance of a household tuberculosis exposure survey among children in a Latin American setting.

OBJECTIVE: To evaluate the performance of a survey that quantifies the intensity of household tuberculosis (TB) exposure among children.METHODS: Children aged 0-14 years in Lima, Peru, with ≥1 signs and/or symptoms of TB and a history of contact with an adult TB patient were included. The 10-question survey was administered to caregivers and addressed sleep proximity, frequency of exposure, and infectiousness of the contact. Infection status was determined using tuberculin skin tests (TSTs). The exposure scale was evaluated for association with TST positivity using mixed-effects regression analyses.RESULTS: The exposure score was significantly associated with TST positivity (age-adjusted odds ratio [aOR] 1.14, 95%CI 1.02-1.28). We observed a stronger association with TST positivity in children aged ≤5 years; (aOR 1.23, 95%CI 1.07-1.41) and no association in children 6-14 years of age (aOR 0.99, 95%CI 0.82-1.20).CONCLUSION: This survey was easy to use and modestly successful in predicting TST positivity in children aged ≤5 years. It may be a useful resource for clinicians for diagnosing TB in children, and for national TB programs aiming to scale up preventive therapy initiatives.

Factors associated with tuberculosis disease among children who are household contacts of tuberculosis cases in an urban setting in Malaysia

BackgroundWith the rise in prevalence of childhood tuberculosis (TB) globally, contact tracing should be a powerful strategy for early diagnosis and management, especially in children who are household contacts of active TB cases. Here, we aimed to determine the prevalence and factors associated with TB disease in children who are household contacts of TB cases.MethodsWe used a cross-sectional study with data from the Malaysian TB Information System (TBIS) recorded from 1 January 2014 to 31 December 2017. All children aged 0–14 years who were registered in the TBIS with at least one household contact of TB cases were included in the study. Multiple logistic regression analysis was performed to calculate the adjusted odds ratio (adj. OR) and for adjusting the confounding factors.ResultsA total of 2793 children were included in the study. The prevalence of active TB was 1.5% (95% confidence interval [CI]: 1.31, 1.77%). Children aged < 5 years [adj. OR 9.48 (95% CI: 3.41, 26.36) p < 0.001] with positive tuberculin skin test [adj. OR 395.73 (95% CI: 134.17, 1167.13), p < 0.001] and investigation period of > 6 weeks [adj. OR 7.48 (95% CI: 2.88, 19.43), p < 0.001] had significantly higher odds for TB disease.ConclusionsThe prevalence of TB disease in children who were household contacts of TB cases is relatively low. However, contact tracing programmes should not only focus on children aged < 5 years and with positive tuberculin skin test results, but also be empowered to reduce the investigation period.

Transmissibility and potential for disease progression of drug resistant Mycobacterium tuberculosis: prospective cohort study

ObjectiveTo measure the association between phenotypic drug resistance and the risk of tuberculosis infection and disease among household contacts of patients with pulmonary tuberculosis.Setting106 district health centers in Lima, Peru...

1377. Use of Interferon-Gamma Release Assays (IGRAs) Reduced Latent Tuberculosis Infection (LTBI) Diagnosis in Refugee and Immigrant Children

BackgroundFor foreign-born children from countries with high tuberculosis (TB) burden, positive tuberculin skin test (TST) results, associated with Bacillus Calmette Guerin (BCG) vaccination, paradoxically increase the risk for overdiagnosis and overtreatment of latent TB infection (LTBI) during immigration. The higher specificity of interferon-gamma release assays, such as QuantiFERON-TB (QFT), may help distinguish LTBI from positive TSTs due to BCG or non-TB Mycobacteria. However, data on QFT usage in pediatric populations, particularly refugee and immigrant children, are sparse. Our objective was to assess the impact of QFT on LTBI diagnosis and treatment in the vulnerable child refugee and immigrant population.MethodsWe initiated a retrospective study of children (≤15 years) seen in Santa Clara County Refugee/Immigrant Clinic for post-immigration TB re-evaluation in 2017. We collected information from the Electronic Disease Notification system and post-immigration clinic records, including laboratory studies, imaging, and clinical impression. The primary outcome was post-immigration LTBI diagnosis in patients with positive pre-immigration TB screening. Patients with prior active TB or LTBI treatment were excluded.Results102/135 clinic encounters examined to date were post-immigration encounters. Median age was 9 years (range 14mo to 15y). Most (82.5%) were from Asia, primarily the Philippines (n = 48), Afghanistan (n = 10), Iran (n = 9), and Vietnam (n = 8). Sixty-six (64.7%) had documented BCG vaccination. Among 102 encounters, 71 (69.6%) were of children diagnosed pre-immigration with LTBI based on positive TST and normal chest radiograph. After post-immigration evaluation with retesting by QFT, 13/71 (18%) were diagnosed with LTBI (Table 1). There were no active TB cases among 102 patients, though long-term follow-up varied (mean 5.5 ± 6.5 months).ConclusionQFT use for post-immigration LTBI re-evaluation reduced LTBI diagnosis by 82% in children as young as 2 years old. Preliminary data suggest the preferential use of QFT over TST in non-United States-born children, in accordance with new California Department of Public Health TB screening recommendations for children ≥2 years, could reduce unnecessary diagnosis and treatment of LTBI in refugee and immigrant children. Disclosures All authors: No reported disclosures.

Should isoniazid prophylaxis be prescribed to the patients under tumor necrosis factor-alpha antagonists independent of tuberculin skin test?

Introduction The aim of this study was to present the follow-up results of 110 patients who were given anti-tumor necrosis factor alpha (TNF-α) therapy for rheumatic and dermatologic diseases in a country with a high rates of active and latent tuberculosis bacillus infection. Material and Methods Between February 2008 and January 2015, 110 cases in the age range of 23–77 who are using anti-TNF-α were included in the study retro-prospectively. Results 52.7% of them (n = 58) were male. The most common diagnoses were rheumatoid arthritis (42.7%) and ankylosing spondylitis (38.2%). Most frequently given treatment were infliximab 37.3% and etanercept 30.9%, respectively. The 65 patients whose first tuberculin skin test (TST) value “5 mm and above” was started daily 300 mg INH prophylaxis for 9 months but 3 patients had not been started because of refusing treatment. In only one case chemoprophylaxis has had to be interrupted because of high liver function test due to the INH prophylaxis. TST conversion was observed in 14 patients. Further follow-up, it was observed that 4 patients had TST's positivity. Isoniazide (INH) prophylaxis was started these 18 patients (42.9%). Although INH prophylaxis has been given in two patients, they developed active tuberculosis in follow-up. Conclusion Considering the INH resistance in our country, all patients especially the ones with residual lesion and history of previous exposure, should be followed up closely during the anti-TNF-α treatment.

Prevalence of Tuberculosis in Children After Natural Disasters, Bohol, Philippines.

In 2013, a severe earthquake and typhoon affected Bohol, Philippines. To assess the postdisaster risk for emergence of Mycobacterium tuberculosis infection in children, we conducted a cross-sectional multistage cluster study to estimate the prevalence of tuberculin skin test (TST) positivity and tuberculosis (TB) in children from 200 villages in heavily affected and less affected disaster areas. Of the 5,476 children we enrolled, 355 were TST-positive (weighted prevalence 6.4%); 16 children had active TB. Fourteen (7%) villages had >20% TST-positive prevalence. Although prevalence did not differ significantly between heavily affected and less affected areas, living in a shelter with >25 persons approached significance. TST positivity was independently associated with older age, prior TB treatment, known contact with a person with TB, and living on a geographically isolated island. We found a high TST-positive prevalence, suggesting that national programs should consider the differential vulnerability of children and the role of geographically isolated communities in TB emergence.

MEDIASTINAL TB PRESENTING AS RIGHT MIDDLE LOBE SYNDROME WITH PIGMENTED AIRWAYS ON BRONCHOSCOPY

SESSION TITLE: Monday Fellow Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Mediastinal tuberculous lymphadenitis (MTLD) is an uncommon manifestation of tuberculosis (TB). We describe a case of MTLD in an adult with a recent history of pleurisy, presenting as right middle lobe syndrome, found to have black mucosal discoloration on bronchoscopy. CASE PRESENTATION: A 60-year-old Afghan female was evaluated for chronic cough. She previously immigrated from Pakistan, at which time she was evaluated for a pleural effusion and positive tuberculin skin test (20mm). Thoracentesis revealed a lymphocytic effusion, normal glucose, low ADA, and negative AFB. She did not complete an isoniazid course, yet her effusion resolved. Two years later, she presented with 2 months of cough, rare hemoptysis, fatigue, night sweats, and dyspnea. She was frail, nontoxic, with a dry cough and coarse right parasternal breath sounds. CT chest showed calcified hilar and mediastinal lymphadenopathy with right middle lobe atelectasis [Figure 1]. Bronchoscopy revealed black mucosal plaques [Figure 2], with a nodular bronchus intermedius lesion obstructing the middle lobe [Figure 3]. Biopsy showed plasma cells, eosinophils, and basement membrane thickening; no malignancy or granulomas. Bronchoalveolar lavage (BAL) and stains for acid-fast and fungal organisms were all negative. She was started on isoniazid and rifampin, with marked improvement at 1 month; CT chest at 2 months showed increased right middle lobe aeration [Figure 4]. She was diagnosed with culture-negative TB, treated with 9-months of therapy. DISCUSSION: Pleurisy is common in primary TB, and often resolves spontaneously1, but one-third have reactivation2. Lymphadenopathy is characteristic of primary disease, but isolated MTLD is unusual in post-primary TB3. Yield of sputum, BAL, and transbronchial biopsy is low in MTLD due to microorganism burden4. EBUS can aid in diagnosis in 42-85%, and mediastinoscopy is an option if benefit outweighs risk5. In a patient with compatible clinical picture, culture-negative TB may be diagnosed after demonstrating response to therapy6. Black airway pigmentation is nonspecific, seen in malignancy, anthracosis, soot, and infections such as Aspergillus and Mycobacterium tuberculosis7. Mechanism is not fully understood, but may reflect rupture of lymph nodes with pigment-laden macrophages into bronchial mucosa7. Despite treatment, it is often irreversible. CONCLUSIONS: MTLD is uncommon in post-primary TB, and diagnosis is difficult due to atypical imaging findings and low organism burden. When traditional methods for diagnosis fail, procedures such as EBUS may increase diagnostic yield. Black mucosal changes can be suggestive of TB. If clinical and radiographic findings are consistent, culture-negative TB may be diagnosed based on response to antimycobacterial therapy. Reference #1: Jeon D. Tuberculous pleurisy: an update. Tuberc Respir Dis (Seoul). 2014;76(4):153-9. Reference #2: Valdés L, Álvarez D, San José E, et al. Tuberculous Pleurisy: A Study of 254 Patients. Arch Intern Med.1998;158(18):2017–2021. https://doi.org/10.1001/archinte.158.18.2017 Reference #3: Kim J, Jang Y, Kim Yo, et. Al. Mediastinal Tuberculous Lymphadenitis Diagnosed by Endosonographic Fine Needle Aspiration. Korean J Gastroenterol. 2016 Dec 25; 68 (6): 312-316. DISCLOSURES: No relevant relationships by richard blinkhorn, source=Web Response No relevant relationships by Hau Chieng, source=Web Response No relevant relationships by Shannon Murawski, source=Web Response

High tuberculosis burden among HIV-infected populations in Thailand due to a low-sensitivity tuberculin skin test

The current Thai guideline recommends that among people living with HIV, isoniazid preventive therapy (IPT) should be given to those with a positive tuberculin skin test (TST). We conducted a case-control study, nested within a cohort study, in Chiang Rai Province in Thailand to determine the role of TST in predicting the development of active tuberculosis (TB) within the following 2 years. Comparison between participants with CD4+ counts <50cells/mm3 to those with CD4+ ≥200cells/mm3 revealed that TST results were less sensitive (7.7% vs 50.0%) and had a lower negative predictive value (73.1% vs 97.3%) in those with a CD4+ count <50cells/mm3. In people with HIV, using a positive TST result as a criterion for initiating IPT inadvertently decreases the benefits of IPT, especially among those with low CD4+ counts.

Screening for latent tuberculosis in patients with inflammatory bowel disease under antitumor necrosis factor: data from a Portuguese center

Portugal is one of the countries with the highest tuberculosis (TB) burden in the European Union. Patients who are receiving antitumor necrosis factor (TNF) treatment should be screened and treated for latent tuberculosis infection (LTBI). This study aimed to evaluate the prevalence of LTBI and the number of active TB cases in patients with inflammatory bowel disease (IBD) treated with anti-TNF agents. This was a retrospective study from a Portuguese center that included patients with IBD who started anti-TNF treatment between 2013 and 2017. LTBI screening was considered positive in case of positive tuberculin skin test, positive/indeterminate interferon gamma release test, or history of exposure to TB irrespective of the results of the screening. One hundred and seventeen patients were included, 56% female, mean age 40 years; 91% had Crohn's disease; infliximab was initiated in 79%, adalimumab in 21%, and golimumab in 1%. Of these, 37 (32%) presented LTBI - tuberculin skin test was positive in 18 (49%) patients; interferon gamma release test was positive in 14 (38%) patients and undetermined in seven (19%); and there was a history of exposure in 12 (32%) patients. All patients screened with LTBI were on isoniazid for 9 months. During follow-up (mean 21.6 months), one patient under infliximab developed pleural TB 5 years after receiving treatment with isoniazid. None of the patients with negative LTBI screening developed active TB. In this sample of patients with IBD, the prevalence of LTBI before starting anti-TNF treatment was significant (32%), but only one patient had active TB after LTBI treatment.

Estimating the annual risk of infection with Mycobacterium tuberculosis among adolescents in Western Kenya in preparation for TB vaccine trials

BackgroundAdolescents are a prime target group for tuberculosis (TB) vaccine trials that include prevention of infection (POI). The BCG vaccine is given at birth and does not prevent TB infection. TB infection, a critical endpoint for POI vaccine trials would need to be documented to estimate sample sizes in target populations.MethodsAdolescents aged 12–18 years of age were enrolled in an area under continuous demographic surveillance. A tuberculin skin test (TST) survey was conducted as part of a study on TB prevalence and incidence. All adolescents got TSTs at enrolment and returned after 72 h for reading. A TST of ≥10 mm if HIV negative or ≥ 5 mm if HIV positive, was considered positive.ResultsOf 4808 adolescents returning for TST readings (96% of those enrolled), mean age was 14.4 (SD 1.9), 4518(94%) were enrolled in school and 21(0.4%) gave a previous history of tuberculosis. Among adolescents with TST reactivity, the mean TST induration was 13.2 mm (SD 5.4). The overall prevalence of latent TB infection was 1544/4808 (32.1, 95% CI 29.2–35.1) with a corresponding annual risk of TB infection (ARTI) of 2.6% (95% CI 2.2–3.1). Risk factors for a positive TST included being male (OR 1.3, 95% CI 1.2,1.5), history of having a household TB contact (OR 1.5, 95% CI 1.2,1.8), having a BCG scar (OR 1.5,95% CI 1.2,1.8), living in a rural area (OR 1.4, 95% CI 1.1,1.9), and being out of school (OR 1.8, 95% CI 1.4,2.3).ConclusionWe conclude that the high TB transmission rates we found in this study, suggest that adolescents in this region may be an appropriate target group for TB vaccine trials including TB vaccine trials aiming to prevent infection.

Evaluation of Clinical and Laboratory Characteristics of Children with Pulmonary and Extrapulmonary Tuberculosis.

Background and objective: Tuberculosis (TB) is an important public health problem in both developing and developed countries. Childhood TB is also an important epidemiological indicator in terms of forming the future TB pool. The diagnosis of TB is difficult in children due to the lack of a standard clinical and radiological description. We aimed to evaluate and compare the clinical, laboratory, and radiologic findings of childhood pulmonary and extrapulmonary TB. Material and Methods: The medical records of patients hospitalized with the diagnosis of pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) between December 2007 and December 2017 were evaluated retrospectively. Results: There were 163 patients diagnosed with TB with 94 females (57.7%) and 69 males (42.3%). Seventy-three patients (44.8%) had PTB, 71 (43.6%) patients had EPTB, and 19 patients (11.7%) had both PTB and EPTB, called as disseminated TB. Ninety-six (58.9%) patients had tuberculin skin test (TST) positivity and 64 patients (39.3%) had interferon-gamma release assay (IGRA) positivity. Acid-resistant bacteria were observed in 34 (20.9%) body fluid samples and culture positivity was observed in 33 (20.2%) samples. Comparison of PTB, EPTB, and disseminated TB revealed that low socioeconomic status, TB contact, and low body weight were more common in disseminated TB, and TST positivity was more common in PTB. Conclusion: Malnutrition, low socioeconomic status, and TB contact were important diagnostic variables in our study and all three parameters were more common in disseminated TB. Tuberculosis should be considered in patients admitted with different complaints and signs in populations with high TB incidence and low socioeconomic status.

Evaluating Latent Tuberculosis Infection Test Performance Using Latent Class Analysis in a TB and HIV Endemic Setting.

Background: Given the lack of a gold standard for latent tuberculosis infection (LTBI) and paucity of performance data from endemic settings, we compared test performance of the tuberculin skin test (TST) and two interferon-gamma-release assays (IGRAs) among health-care workers (HCWs) using latent class analysis. The study was conducted in Cape Town, South Africa, a tuberculosis and human immunodeficiency virus (HIV) endemic setting Methods: 505 HCWs were screened for LTBI using TST, QuantiFERON-gold-in-tube (QFT-GIT) and T-SPOT.TB. A latent class model utilizing prior information on test characteristics was used to estimate test performance. Results: LTBI prevalence (95% credible interval) was 81% (71–88%). TST (10 mm cut-point) had highest sensitivity (93% (90–96%)) but lowest specificity (57%, (43–71%)). QFT-GIT sensitivity was 80% (74–91%) and specificity 96% (94–98%), and for TSPOT.TB, 74% (67–84%) and 96% (89–99%) respectively. Positive predictive values were high for IGRAs (90%) and TST (99%). All tests displayed low negative predictive values (range 47–66%). A composite rule using both TST and QFT-GIT greatly improved negative predictive value to 90% (range 80–97%). Conclusion: In an endemic setting a positive TST or IGRA was highly predictive of LTBI, while a combination of TST and IGRA had high rule-out value. These data inform the utility of LTBI-related immunodiagnostic tests in TB and HIV endemic settings.

Contribution of QuantiFERON-TB Gold-in-Tube to the Diagnosis of Mycobacterium tuberculosis Infection in Young Children in a Low TB Prevalence Country.

Introduction: Interferon Gamma Release Assay (IGRA) has proven to be a useful test to evaluate the immune response to Mycobacterium tuberculosis antigens in children over the age of 5 years as an alternative to tuberculin skin testing (TST). Much less is known about its performance in younger children, who are at higher risk for developing tuberculosis (TB) disease after exposure. We aimed to evaluate the accuracy of using IGRA in TB screening in this population.Methods: Children below the age of 5 years at high risk for TB infection were prospectively enrolled, to compare the performance of TST and the QuantiFERON-TB Gold-In-Tube test (QFT). Children were treated in accordance with the diagnosis made at baseline and followed-up for 12 months.Results: We included a total of 60 children of which 97 blood samples were available for analysis. There was 90.72% agreement between TST and QFT (Kappa test 0.59, moderate agreement). With TST as a reference, the QFT positive predictive value was 0.72 and the negative predictive value 0.93. Discordant results were observed with 6% TST+/QFT– paired tests. When we restricted the comparison of TST and QFT to non-BCG-vaccinated children, the degree of agreement was more substantial (95%, Kappa test 0.75) and the negative predictive value was 0.99. We observed 3% discordant TST–/QFT+ results. All children with active TB disease had concordant positive QFT results, with QFT values above 4.00 IU/ml.Conclusion: In a low TB prevalence country, serial testing of QFT was found to produce a moderate agreement with TST results. False positive QFT results would have been eliminated by using a higher cutoff without misdiagnosing the children with TB disease. Some of the false negative QFT results could be explained by false positive TST results on consecutive testing. For now the most prudent approach would be to consider discordant QFT–/TST+ results as false negative QFT results, taking into account the young age of our population and the potential risk for evolution to active TB disease.

STUDY OF EXUDATIVE PLEURAL EFFUSION IN THE AGE GROUP OF 15-40 YEARS WITH SPECIAL REFERENCE TO ADENOSINE DEAMINASE AND TUBERCULIN SKIN TEST IN THE DIAGNOSIS OF TUBERCULOUS ETIOLOGY

Background: A tubercular pleural effusion can either be a sequel to a primary infection acquired 3 to 6 month previously or represent reactivation tuberculousis.&#x0D; Two different pathogenic mechanism can lead to tuberculous pleural effusion. By far the more common is the entry of only a few M. tuberculosis into the pleural space; in the presence of specific cell mediated immunity, tubercle bacilli provoke an intense hypersensitivity reaction and outpouring of fluid. Chest radiograph may or may not reveal associated parenchymal involvement. In the second variety, a subpleural caseous focus or cavity rupture into the pleural space and results in a pleural effusion. In this case chest radiograph nearly always shows parenchymal abnormalities.&#x0D; A definitive diagnosis of TBPE can be difficult to make because of the low sensitivity and / or specificity of noninvasive traditional diagnostic tools.&#x0D; In most series of patients with TBPE the result of pleural fluid staining for acid fast bacilli are virtually always negative and pleural fluid cultures are positive for mycobacteria in &lt;35% of cases. Without underlying lung parenchymal lesion sputum examination may be positive in 4% to 11% of patient with TBPE. On the other hand, pleural biopsy specimen will demonstrate granulomatous pleuritis in 50% to 80% of patients.&#x0D; This study was taken whether pleural fluid ADA and tuberculin skin test has any role in the diagnosis of tubercular pleural effusion.&#x0D; Methods and Materials: In the present study 120 cases of exudative pleural effusion in the age group of 15-40 years of varying etiology are taken who attended the pulmonary medicine department of Burdwan Medical College and Hospital.&#x0D; The study was conducted the period of March 2017 to February 2018 apart from relevant history taking a detail clinical examination, full investigation were done to reach a complete and final diagnosis.&#x0D; Result: In our study 120 patient of aged 15-40 years were taken. Different aetiological groups and there frequency as diagnosed by various mean were Tuberculous – 85%, Paraneumonic effusion – 10 %, Malignant effusion – 10%.&#x0D; There was male preponderance in all groups of pleural effusion. History of contact was present in 34 % cases of tuberculous effusion. Sputum for AFB was found 10.78% cases of tuberculous effusion. These patients also had pulmonary lesions. 80.39% cases of tuberculous effusion had pale yellow coloured effusion but 13.72 % cases had haemorrhagic fluid. 66.66% malignant effusion had haemorrhagic fluid and 33.37% of malignant effusion had pale yellow coloured fluid. Pleural fluid for malignant cell was positively 66.67% of malignant effusion. Pleural fluid for Z-N stain detect 1.96% cases tubercle bacilli in TBPE group. Plural biopsy was found positive in 68.18% cases of TBPE and 60% cases of MPE.&#x0D; Pleural fluid ADA level was significantly higher (P&lt;0.001) in patients of tuberculous effusion than non-tuberculous effusion. Taking a cut off value of 70 U/L sensitivity and specificity is 95.09% and 33.33%. But when parapneumonic effusion was excluded, the specificity increases. Lymphocytic pleural effusion below the age group of 40 years with cut off value of ADA &lt;40 U/L can be used as a screening test for malignant effusion.&#x0D; In TBPE tuberculin skin test was positive in 74.50% cases. Taking a cut off value of 10 mm or more induration of tuberculin skin test, "P" value is less than 0.001. Sensitivity and specificity of tuberculin skin test in tuberculous pleural effusion is 74.50% and 50%.&#x0D; If we compare the efficacy of ADA &gt; 70 U/L and tuberculin skin test positivity to diagnose tuberculous pleural effusion the former is superior statistically to the later (P value is less than 0.01) specificity of tuberculin skin test is low because it may be positive with infection with NTM and prior BCG vaccination.&#x0D; Conclusion: Maximum incidence of tuberculous pleural effusion occurs in the age group of 20-30 years. Malignant pleural effusion is less likely below the age group of 30 years.&#x0D; Increased ADA level &gt;70 U/L in pleural fluid is a sensitive, minimally invasive, cost effective, easy method for diagnosis of tuberculous pleural effusion.&#x0D; Lower level of pleural fluid ADA level (&lt;40 U /L) is a sensitive, specific, minimally invasive, cost effective easy method for suspecting malignant effusion. Its value is much more important when younger patients (&lt;40 years of age) present with malignant effusion, especially so when the pleural fluid is also appeared pale yellow. A low ADA level will guide us to look for malignancy in this age group.&#x0D; Tuberculin skin testing with intermediate strength PPD has a high sensitivity in patients with pleural tuberculosis. It was seen negative in 1/3rd cases of TBPE. This negative tuberculin skin test in TBPE may be due to recent tuberculous infection or may be due to sequestration of PPD reactive T-lymphocytes in the pleural space or patient may be anergic. Our study is insufficient to comment this negative result. More precise study need to comment.

Radiological Signs of Latent Tuberculosis on Chest Radiography: A Systematic Review and Meta-Analysis.

ObjectiveCurrent guidelines recommend screening for latent tuberculosis infection (LTBI) with a tuberculin skin test (TST) or interferon gamma release assay (IGRA), or both. Many also recommend chest radiography (CXR), although its added value is uncertain. This systematic review assessed the prevalence of abnormalities suggestive of LTBI on CXR (LTBI-CXR lesions) and evaluated the strength of the association.MethodWe searched 4 databases up to September 2017 and systematically reviewed cross-sectional and cohort studies reporting LTBI-CXR lesions in individuals with a positive TST or IGRA, or both, result. Prevalence estimates were pooled using random effects models and odds ratios (ORs) were used to calculate risk estimates.ResultsIn the 26 included studies, the pooled proportion of individuals with LTBI having LTBI-CXR lesions was 0.15 (95% confidence interval [CI], 0.12–0.18]. In 16 studies that reported on individuals with LTBI and uninfected controls, LTBI-CXR lesions were associated with a positive TST result ≥ 5 mm or ≥ 10 mm (OR, 2.45; 95% CI, 1.00–5.99; and OR, 2.06; 95% CI, 1.38–3.09, respectively) and with a positive QuantiFERON result (OR, 1.99; 95% CI, 1.17–3.39) compared to CXR in uninfected controls. Although few studies reported specified lesions, calcified nodules were most frequently reported in individuals with LTBI (proportion, 0.07; 95% CI, 0.02–0.11).ConclusionsLesions on CXR suggestive of previous infection with Mycobacterium tuberculosis were significantly associated with positive tests for LTBI, although the sensitivity was only 15%. This finding may have added value when detection of past LTBI is important but immunodiagnostic tests may be unreliable.

5-Year Follow-up of Active Tuberculosis Development From Latent Infection in Rural China.

A 5-year follow-up study found declining disease development rates from latent tuberculosis infection. In the latter 3 years, the incidence, per 100 person-years, was 0.26 for interferon-γ release assay positives and 0.19 for tuberculin skin test positives (P = .28). In addition, all round have been checked.

Age-specific prevalence of TB infection among household contacts of pulmonary TB: Is it time for TB preventive therapy?

Household contacts (HHCs) of TB patients are at high risk of developing evidence of latent TB infection (LTBI) and active disease from the index patient. We estimated the age-specific prevalence of LTBI and the force of infection (FI), as a measure of recent transmission, among HHCs of active TB patients. A cross-sectional analysis of HHCs of pulmonary TB patients enrolled in a prospective study, 'CTRIUMPh', was conducted at two sites in India. LTBI was defined as either a positive tuberculin skin test (induration ≥5 mm) or QuantiFERON-Gold in tube test (value ≥0.35 IU/ml) and was stratified by age. FI, which is a measure of recent transmission of infection and calculated using changes in age-specific prevalence rates at specific ages, was calculated. Factors associated with LTBI were determined by logistic regression models. Of 1020 HHCs of 441 adult pulmonary TB cases, there were 566 (55%) females and 289 (28%) children aged ≤15 y. While screening for the study 3% of HHC were diagnosed with active TB. LTBI prevalence among HHCs of pulmonary TB was 47% at <6 y, 53% between 6-14 y and 78% between 15-45 y. FI increased significantly with age, from 0.4 to 1.15 in the HHCs cohort (p=0.05). This study observed an increased prevalence of LTBI and FI among older children and young adults recently exposed to infectious TB in the household. In addition to awareness of coughing etiquette and general hygiene, expanding access to TB preventive therapy to all HHCs, including older children, may be beneficial to achieve TB elimination by 2035.

Tuberculosis Preventive Therapy for Individuals Exposed to Drug-resistant Tuberculosis: Feasibility and Safety of a Community-based Delivery of Fluoroquinolone-containing Preventive Regimen.

Observational studies have demonstrated the effectiveness of a fluoroquinolone-based regimen to treat individuals presumed to be infected with drug-resistant tuberculosis (DR-TB). We sought to assess the feasibility of this approach in an urban setting in South Asia. From February 2016 until March 2017, all household contacts of DR-TB patients enrolled at the Indus Hospital were screened for TB symptoms at home. Children aged 0-17 years, symptomatic adults, and those with an immunocompromising condition (human immunodeficiency virus, diabetes, or malnutrition) were evaluated for TB disease. Contacts diagnosed with TB disease were started on treatment. Contacts without TB disease aged <5 years, contacts aged between 5 and 17 years with either a positive tuberculin skin test or an immunocompromising condition, or contacts aged ≥18 years with an immunocompromising condition were offered 6 months of treatment with a fluoroquinolone. One hundred households with 800 contacts were enrolled: 353 (44.1%) individuals aged ≤17 years with a median age of 19 years (interquartile range, 10-32); 423 (52.9%) were males. In total, 737 (92.1%) individuals were screened, of which 8 were already on treatment for TB (1.1%); another 3 (0.4%) contacts were diagnosed with TB disease and started on treatment. Of 215 eligible for infection treatment, 172 (80.0%) contacts initiated and 121 (70.3%) completed treatment. No TB disease or significant adverse events were observed during 12 months of follow-up. Fluoroquinolone-based treatment for contacts with presumed DR-TB infection is feasible and well tolerated in a high TB burden setting.