Tuberculin Skin Test Induration Research Articles

Attenuated tuberculin skin test responses associated with Mycobacterium intracellulare sputum colonization in an adolescent TB prevalence survey in Western Kenya

IntroductionExposure to Non-tuberculous Mycobacteria (NTM) varies regionally and may partly explain the disparate outcomes of BCG vaccination and tuberculosis (TB) susceptibility. MethodsWe examined NTM sputum colonization, associations with clinical characteristics, and tuberculin skin test (TST) responses in an adolescent TB prevalence survey. ResultsAmong 5004 adolescents screened, 2281 (45.5 %) were evaluated further. TB and NTM prevalence rates were 0.3 % and 8.0 %, respectively. Among 418 NTM isolates, 103 were unidentifiable, and 315 (75 %) comprised 15 species, the most frequent being M. intracellulare (MAC) (108, 26 %), M. scrofulaceum (96, 23 %) and M. fortuitum (51, 12 %). “NTM colonized” adolescents had less frequent chronic cough and night sweats (adjusted odds ratio [aOR] 0.62, 95 % confidence interval [CI] 0.44-0.87and aOR 0.61, CI 0.42–0.89 respectively), and lower TST induration (median 11 mm (interquartile range [IQR] 0–16) vs 13 mm (IQR 6–17; p = 0.006)) when compared to “NTM not colonized” participants. MAC, but not M. scrofulaceum or M. fortuitum, was associated with decreased TST induration (median 7.5 mm (IQR 0–15) vs 13 mm (IQR 6–17) among “MAC colonized” vs “not colonized”, p = 0.001). ConclusionWe observed high NTM prevalence rates with species-specific associations with TST induration, consistent with a model of species-dependent heterologous immunity among mycobacteria.

Diagnostic performance of a novel ESAT6-CFP10 skin test for tuberculosis infection in school tuberculosis outbreak in China.

The ESAT6-CFP10 (EC) skin test is recommended by the World Health Organization for latent tuberculosis infection (LTBI). However, it is still unknown how the EC skin test performs in students during a school tuberculosis outbreak. We conducted an epidemiological investigation to assess the performance of the EC skin test in this high-risk population. A total of 9 active student patients were confirmed in the same class as the index case, with an incidence rate of 18.0% (9/50). Among the 50 close contacts, 14 (28%) were over 15 years old and had a chest X-ray (CXR), and none of them had abnormal CXR findings. The rates of positive tuberculin skin test (TST) ≥ 5 mm and < 10 mm, ≥ 10 mm and < 15 mm, and ≥ 15 mm were 12.0% (6/50), 16.0% (8/50), and 10.0% (5/50), respectively. On the second screening, 44 students with the same class as the index case had the EC skin test, of which 31 (70.5%) had positive EC tests. All patients had negative sputum smear results, of whom 4 (44.4%) had positive Xpert results; three had a TST induration diameter between 5 mm and 10 mm, but all of them had an EC diameter > 15 mm; 5 (55.6%) had abnormal CXR results, but all the confirmed patients had abnormal CT results; Except for four cases that were diagnosed by Xpert, the remaining five were confirmed by CT scan. The novel EC skin test performed well in students during the school tuberculosis outbreak. In some special conditions, such as when the index case is bacteriologically positive for tuberculosis and the rate of LTBI is higher than the average for the local same-age group, secondary screening is recommended 2-3 months after the first screening. Furthermore, we cannot ignore the role of CT in the diagnosis of early student tuberculosis.

How useful is the tuberculin skin test for the detection of active tuberculosis: Assessing diagnostic accuracy metrics and selection of best cut-off value through a large Tunisian multicenter case-control study

Background and aim: During the past decade, the frequency of extrapulmonary forms of tuberculosis (TB) has increased. These forms are often miss-diagnosed. This statement of the TB epidemiological profile modification, conduct us to reflect about the utility of the Tuberculin Skin Test (TST) in active TB detection. This study aimed to evaluate the diagnostic accuracy performance of the TST for active tuberculosis detection. Methods: This was a case-control, multicenter study conducted in 11 anti-TB centers in Tunisia (June-November2014). The cases were adults aged between 18 and 55 years with newly diagnosed and confirmed tuberculosis. Controls were free from tuberculosis. A data collection sheet was filled out and a TST was performed for each participant. Diagnostic accuracy measures of TST were estimated using Receiver Operating Curve (ROC) curve and Area Under Curve (AUC) to estimate sensitivity and specificity of a determined cut-off point. Results: Overall, 1050 patients were enrolled, composed of 336 cases and 714 controls. The mean age was 38.3±11.8 years for cases and 33.6±11 years for controls. The mean diameter of the TST induration was significantly higher among cases than controls (13.7mm vs.6.2mm; p=10-6). AUC was 0.789 [95% CI: 0.758-0.819; p=0.01], corresponding to a moderate discriminating performance for this test. The most discriminative cut-off value of the TST, which was associated with the best sensitivity (73.7%) and specificity (76.6%) couple was ≥ 11 mm with a Youden index of 0.503. Positive and Negative predictive values were 3.11% and 99.52%, respectively. Conclusions: TST could be a useful tool used for active tuberculosis detection, with a moderate global performance and accepted sensitivity and specificity at the cut-off point of 11 mm. However, it cannot be considered as a gold standard test due to its multiple disadvantages.

Determining the Need for Additional Testing With Quantiferon TB Gold in Patients With Positive Tuberculin Skin Tests and a History of BCG Vaccination.

To determine if the QuantiFERON-TB Gold (QFT) testing can be obviated for the diagnosis of latent tuberculosis infection (LTBI) in patients with a positive tuberculin skin test (TST) and a history of Bacillus Calmette-Guerin (BCG)vaccination by identifying high-risk features in patients with positive TST and a history of BCG vaccination who are associated with positive QFT. Retrospective chart review was done for 76 adult patients by dividing them into two groups. Group 1 consisted of true positive TST patients who had BCG vaccination and were positive for QFT. Group 2 consisted of false positive TST patients who had BCG vaccination but were negative for QFT. The two groups were compared to determine if the high-risk features of TST induration diameter of 15mm and more, TST induration of 20mm and more, recent immigration to the US, the advanced age of more than 65 years, country of origin with high TB burden, known exposure to active TB, and smoking history were more prevalent in Group 1 compared to Group 2. Group 1 had 23 patients and Group 2 had 53 patients. Group 1 had a higher prevalence of patients with PPD induration of more than 10mm than Group 2, which was statistically significant with a P value of 0.03. Other risk factors of advanced age, exposure to active TB and smoking did not show statistically significant differences between Groups 1 and 2. Conclusion:This study also confirms that if the TST induration is more than 10mm in patients with a history of BCG vaccination, the TST induration is likely because of LTBI and is less likely because of cross-reaction with BCG vaccination.

Contribution of remote M.tuberculosis infection to tuberculosis disease: A 30-year population study.

The importance of remote infection with M.tuberculosis as a cause of tuberculosis disease (TB) is unclear, with limited evidence of impact on TB rates beyond 10 years. Our objective was to assess rates of tuberculosis over 30 years by M.tuberculosis infection status at baseline in Karonga District, Northern Malawi. Population-based surveys of tuberculin skin testing (TST) from the 1980s were linked with follow-up and TB surveillance in Karonga district. We compared rates of microbiologically-confirmed TB by baseline TST induration <5mm (no evidence of M.tuberculosis infection) and those with baseline TST >17mm (evidence of M.tuberculosis infection), using hazard ratios by time since baseline and attributable risk percent. The attributable risk percent was calculated to estimate the proportion of TB in those infected that can be attributed to that prior infection. We analysed whole genome sequences of M.tuberculosis strains to identify recent transmission. Over 412,959 person-years, 208 incident TB episodes were recorded. Compared to the small induration group, rates of TB were much higher in the first two years in the large induration group, and remained higher to 20 years: age, sex and area-adjusted hazard ratios (HR) 2-9 years post-TST 4.27 (95%CI 2.56-7.11); 10-19 years after TST 2.15 (1.10-4.21); ≥20 years post-TST 1.88 (0.76-4.65). The attributable risk percent of remote infection was 76.6% (60.9-85.9) 2-9 years post-TST, and 53.5% (9.1-76.2) 10-19 years post-TST. Individuals with large TST indurations had higher rates of unique-strain TB (HR adjusted for age, sex and area = HR 6.56 (95% CI 1.96-22.99)), suggesting disease following remote infection, but not of linked-strain TB (recent transmission). M.tuberculosis infection can increase the risk of TB far beyond 10 years, accounting for a substantial proportion of TB occurring among those remotely infected.

Contact Investigations With a Single Tuberculin Skin Test on Infants Exposed to Tuberculosis in a Postpartum Care Center During the Neonatal Period.

Tuberculosis (TB) exposure in congregate settings related to neonates is a serious medical and social issue. TB exposure happens during the neonatal period, but contact investigations for exposed infants are usually conducted after the neonatal period. Generally, recommendations for screening and managing close contact are different for neonates and children. Thus, there are challenges in contact investigations. We aimed to report contact investigations with a single tuberculin skin test (TST) on infants exposed to infectious TB in a postpartum care center. The index case was a healthcare worker with active pulmonary TB: sputum acid-fast bacilli smear negative, culture positive, and no cavitary lesion. All exposed infants underwent medical examinations and chest X-ray. After TB disease was ruled out, contacts received window period prophylaxis with isoniazid (INH) until three months after the last exposure. TST was performed only once after completing the prophylaxis. A total of 288 infants were selected as high-priority contacts. At the initial contact investigation, the age of infants ranged from 8 to 114 days. None of these exposed infants had TB disease. The prevalence of latent TB infection (LTBI) was 25.3% (73/288; 95% confidence interval [CI], 20.7-30.7). There were no serious adverse events related to the window period prophylaxis or LTBI treatment with INH. During the 1-year follow-up period, no infants progressed to overt TB disease. The size of TST induration in infants vaccinated with percutaneous Bacillus Calmette-Guérin (BCG) vaccine was significantly larger than that of infants vaccinated with intradermal BCG vaccine (median, 8 mm vs. 5 mm; P = 0.002). In multiple logistic regression analysis, independent factors associated with TST positivity (≥ 10 mm induration) were male (adjusted odds ratio [aOR], 2.98; 95% CI, 1.6-5.64), percutaneous BCG vaccination (aOR, 3.30; 95% CI, 1.75-6.48), TST reading between 60 and 72 hours after injecting purified protein derivative (aOR, 2.87; 95% CI, 1.53-5.49), and INH prophylaxis more than four weeks (aOR, 0.49; 95% CI, 0.25-0.94). A single TST at three months after the last TB exposure with INH prophylaxis could be used as a main protocol in contact investigations for infants exposed to infectious TB during the neonatal period in congregate settings in Korea.

Feasibility study of the prevalence of latent tuberculosis infection for Māori in the Waikato region, Aotearoa New Zealand

ObjectiveThis study aimed to assess the feasibility of conducting a representative tuberculin skin test (TST) survey for Māori in Aotearoa New Zealand and to estimate the prevalence of latent tuberculosis (TB) infection. MethodsParticipants were Māori in the Waikato region, recruited by a Māori nurse, through: 1) random household selection from the Electoral Roll; 2) randomly selected prison inmates; and 3) community and health settings. A TB history and symptoms questionnaire was completed, TST performed and investigation of those with TST induration ≥10mm. ResultsRandom household selection was resource intensive and only contributed 14 participants. Repeated random selection of prison lists were required to recruit 207 participants and there were no positive TST cases. Community and health settings yielded the highest participation (n=370) and the three people (0.5%) with TST ≥10mm. Age ≥45 years and history of contact with a TB case were associated with TST induration ≥5mm (n=39; 6.6%). ConclusionsThe community and health settings were the only feasible options for recruitment. The overall prevalence of a positive TST in the study population was low. A 5mm cut‐off may be best to maximise sensitivity for future studies. Implications for public healthA mixture of sample selection processes that are more targeted are needed to identify Māori with latent TB infection.

A CD4+ TNF+ monofunctional memory T-cell response to BCG vaccination is associated with Mycobacterium tuberculosis infection in infants exposed to HIV.

SummaryBackgroundThe immunologic correlates of risk of Mycobacterium tuberculosis (Mtb) infection after BCG vaccination are unknown. The mechanism by which BCG influences the tuberculin skin test (TST) remains poorly understood. We evaluated CD4+ T-cell responses in infants exposed to HIV and uninfected (HEU) who received BCG at birth and examined their role in susceptibility to Mtb infection and influence on TST induration.MethodsHEU infants were enrolled in a randomised clinical trial of isoniazid (INH) to prevent Mtb infection in Kenya. We measured mycobacterial antigen-specific Th1 and Th17 cytokine responses at 6–10 weeks of age prior to INH randomisation and compared responses between Mtb infected and uninfected infants. Outcomes at 14 months of age included TST, QuantiFERON-Plus (QFT-Plus), and ESAT-6/CFP-10-specific non-IFN-γ cytokines measured in QFT-Plus supernatants.FindingsA monofunctional mycobacterial antigen-specific TNF+ CD4+ effector memory (CCR7-CD45RA-) T-cell response at 6–10 weeks of age was associated with Mtb infection at 14 months of age as measured by ESAT-6/CFP-10-specific IFN-γ and non-IFN-γ responses (Odds Ratio 2.26; Confidence Interval 1.27–4.15; P = 0.006). Mycobacterial antigen-specific polyfunctional effector memory Th1 responses at 6–10 weeks positively correlated with TST induration in infants without evidence of Mtb infection at 14 months, an association which was diminished by INH therapy.InterpretationInduction of monofunctional TNF+ CD4+ effector memory T-cell responses may be detrimental in TB vaccine development. This study also provides mechanistic insight into the association of BCG-induced immune responses with TST induration and further evidence that TST-based diagnoses of Mtb infection in infants are imprecise.FundingThrasher Research Fund.

Is the course of COVID-19 associated with tuberculin skin test diameter? A retrospective study.

The pathogenesis of coronavirus disease 2019 (COVID‐19) is still not fully understood. As severe acute respiratory syndrome coronavirus 2 (SARS‐COV‐2) has a similar pathogenetic pathway to Mycobacterium tuberculosis, it has been reported that there may be a relationship between Bacille Calmette–Guérin (BCG) vaccination rate and COVID‐19 severity. This study investigated the relationship between tuberculin skin test (TST) induration diameter and the clinical course of COVID‐19. Of 1963 adult patients who underwent TST, 76 patients with SARS‐COV‐2 infection confirmed by RT‐PCR analysis of respiratory tract samples were included in the study. Relationships between COVID‐19 clinical severity and TST positivity, induration size, and other clinical parameters were analyzed. Of the 76 patients, TST results were negative for 53 patients (69.7%) and positive for 23 patients (30.3%). COVID‐19 severity was mild in 47 patients (61.8%), moderate in 22 patients (28.9%), and severe in seven patients (9.3%). All TST‐positive patients had mild disease. Patients with mild disease had a significantly higher TST positivity rate (p < 0.001) and larger induration diameter (p < 0.001). The area under the receiver operating characteristic (ROC) curve of TST induration size for the differentiation of mild with moderate and severe disease was 0.768 (p < 0.001). The maximum Youden J index value was 0.522 at an induration diameter of 6.5 mm, which had a sensitivity of 66.0% and specificity of 86.2%. COVID‐19 patients with positive TST showed a significantly higher rate of mild disease than those with negative TST. TST positivity is favorably associated with the course of COVID‐19.

Diagnosis and Treatment of Latent Tuberculosis Infection in Kidney and Liver Transplant Recipients in Iranian Candidates for Transplant.

The rates of tuberculosis and its mortality are higher in solid-organ transplant recipients than in the general population. In this study, we compared the rate of active tuberculosis disease conversion in solid organ transplant recipients based on pretransplant tuberculin skin test results and also its association with treatment. This cross-sectional study included kidney/liver transplant recipients who had pretransplant tuberculin skin test indurations of ≥5 mm and who were seen from March 2009 to March 2019 at the Shiraz Nemazi Hospital Transplant Center (Shiraz, Iran). Data were analyzed using SPSS software, and P < .05 was considered significant. Of 6289 solid-organ transplant recipients seen at our center over the 10-year period, 334 recipients (mean age of 46.0 ± 13.8 years; 67.6% men) had tuberculin skin test indurations of ≥5 mm. Of these 334 recipients, 76.3% had kidney transplant, and the remainder had liver transplant. Of patients who received complete treatment for latent tuberculosis, the rate of conversion to active tuberculosis was lower than in those who did not adhere to medication (8.6% vs 43.7%; P < .001). In addition, the rate of active tuberculosis development was higher in patients who had pretransplant tuberculin skin tests results of ≥10 mm compared with those who had results of 5 to 9 mm (15.8% vs 3.4%; P < .001). Latent tuberculosis diagnosis and treatment before solid-organ transplant can reduce active tuberculosis conversion and its associated morbidity and mortality. We recommend modifying the cutoff point considered for tuberculin skin test positivity for solid-organ transplant candidates in Iran to ≥10 mm, although further evaluations are needed.

PRS27 A Systematic Review on the Impact of Digital Health Technologies in Latent Tuberculosis Infection Management

To date, there is no study that has attempted to focus and summarize the role of digital health technologies in improving latent tuberculosis infection (LTBI) care. This review aims to address this gap and determine the impact of digital health technologies on LTBI screening and treatment outcomes. A systematic literature search was performed on six electronic databases from database inception until November 1, 2020. Studies that assessed the clinical use of digital health technologies in LTBI screening and treatment outcomes were eligible to be reviewed. Two investigators independently evaluated and extracted relevant studies. The Cochrane risk of bias tools were used to evaluate the methodological quality of the included studies. Descriptive data were summarized narratively. The effect of digital health technologies on LTBI treatment completion was estimated using random-effects meta-analysis. A total of 4,723 studies were screened, of which eleven eligible articles describing ten unique studies were included in this review. The use of digital health technologies to improve LTBI care includes voice and/or textual reminders, synchronous video call, tele-education and mobile applications to review tuberculin skin test induration. Improvement in LTBI treatment completion was observed with the use of textual reminders in regions with intermediate and high tuberculosis burden in comparison to regions with low tuberculosis burden [risk ratio (RR): 1.20; 95%CI: 0.99 – 1.46 versus RR: 0.97; 95%CI: 0.90 – 1.04, p = 0.04]. Our findings showed limited improvement in LTBI treatment completion with the use of digital health technologies. Nevertheless, digital interactive tools such as synchronous video call could help establish rapport between health care providers and individuals receiving LTBI treatment. As such, barriers to LTBI management could be addressed efficiently, which could in turn improve the quality of LTBI care among those affected.

An outbreak of pulmonary tuberculosis and a follow-up investigation of latent tuberculosis in a high school in an eastern city in China, 2016-2019.

In October 2016, a senior high school student was diagnosed with sputum-smear positive [SS(+)] pulmonary tuberculosis (TB). We conducted an investigation of an outbreak in the school, including among students and teachers diagnosed with latent TB, who we followed until July 2019. We defined latent TB infection (LTBI) as a tuberculin skin test (TST) induration of 15mm or larger; probable TB as a chest radiograph indicative of TB plus productive cough/hemoptysis for at least 2 weeks, or TST induration of 15mm or larger; and confirmed TB as two or more positive sputum smears or one positive sputum smear plus a chest radiograph indicative of TB or culture positive with M. tuberculosis. We conducted mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing based on 24 loci in the isolates. Between October 2016 and July 2019, we identified 52 cases, including nine probable, six confirmed, and 37 LTBI cases. The index case-student had attended school continuously despite having TB symptoms for almost three months before being diagnosed with TB. We obtained three isolates from classmates of the index case in 2016; all had identical MIRU-VNTR alleles with the index case. The LTBI rate was lower among students (7.41%, 30/405) than among teachers (26.92%, 7/26) (rate ratio [RR] = 0.28, 95% confidential interval [CI]: 0.13-0.57). Among the 17 students who had latent TB and refused prophylaxis in October 2016, 23.53% (4/17) became probable/confirmed cases by July 2019. None of the six teachers who also refused prophylaxis became probable or confirmed cases. Of the 176 students who were TST(-) in October 2016, 1.70% (3/176) became probable/confirmed cases, and among the 20 teachers who were TST(-), 1 became a probable case. Delayed diagnosis of TB in the index patient may have contributed to the start of this outbreak; lack of post-exposure chemoprophylaxis facilitated spread of the outbreak. Post-exposure prophylaxis is strongly recommended for all TST-positive students; TST-negative students exposed to an SS(+) case should be followed up regularly so that prophylaxis can be started if LTBI is detected.

A simple protocol for tuberculin skin test reading certification.

Although tuberculosis preventive therapy is one of the cornerstones for eliminating the disease, many barriers exist in the cascade of care for latent tuberculosis infection, including the need to certify healthcare professionals for reading tuberculin skin tests (TST). This paper proposes and evaluates a simple protocol for TST reading training. Primary care workers from different backgrounds received a 2-hour theoretical course, followed by a practical course on bleb reading. Blebs were obtained by injecting saline into sausages and then in volunteers. A certified trainer then evaluated the effectiveness of this protocol by analyzing the trainees' ability to read TST induration in clinical routine, blinded to each other's readings. Interobserver agreement was analyzed using the Bland-Altman test. The trainees' reading accuracy was calculated using two cut-off points - 5 and 10mm - and the effect of the number of readings was analyzed using a linear mixed model. Eleven healthcare workers read 53 saline blebs and 88 TST indurations, with high agreement for TST reading (0.07mm average bias). Sensitivity was 100% (94.6; 100.0) at 5mm cut-off and 87.3% (75.5; 94.7) at 10mm cut-off. The regression model found no effect of the number of readings [coefficient: -0.007 (-0.055; 0.040)]. A simple training protocol for reading TST with saline blebs simulations in sausages and volunteers was sufficient to achieve accurate TST induration readings, with no effect observed for the number of readings. Training with saline blebs injected into voluntary individuals is safer and easier than the traditional method.

Utility of the Interferon-Gamma Release Assay for Latent Tuberculosis Infection Screening among Indian Health-Care Workers.

Background:The utility of interferon-gamma release assays (IGRAs) for latent tuberculosis infection (LTBI) screening among health-care workers (HCWs) in low- and middle-income countries (LMICs) remains unclear.Methods:This was a prospective cohort study among HCW trainees undergoing annual LTBI screening via tuberculin skin test (TST) and QuantiFERON® TB Gold Test-in-tube (QFT-GIT) in Pune, India. TST induration ≥ 10 mm and QFT-GIT ≥ 0.35 IU/ml were considered positive. Test concordance was evaluated at entry among the entire cohort and at 1 year among baseline TST-negative participants with follow-up testing. Overall test agreement was evaluated at both timepoints using the kappa statistic: fair (k < 0.40), good (0.41 ≥ k ≤0.60), or strong (k > 0.60).Results:Of 200 participants, prevalent LTBI was detected in 42 (21%) via TST and 45 (23%) via QFT-GIT; QFT-GIT was positive in 27/42 (64%) TST-positive and 18/158 (11%) TST-negative trainees. Annual TST conversion was 28% (40/142) and included 11 trainees with baseline TST-/IGRA+; QFT-GIT was positive in 17/40 (43%) TST-positive and 5/102 (5%) TST-negative trainees. Overall test concordance was 84% (k = 0.52; 95% confidence interval [CI]: 0.38–0.66) and 80% (k = 0.44; 95% CI: 0.29–0.59) at baseline and 12 months, respectively.Conclusions:We observed good overall agreement between TST and QFT-GIT, and QFT-GIT detected additional LTBI cases among TST-negative trainees with possible early detection of LTBI conversion. Overall, our results support the use of IGRA for annual LTBI screening among HCWs in a high burden LMIC setting.

DETERMINING THE NEED FOR ADDITIONAL TESTING WITH QUANTIFERON TB GOLD IN PATIENTS WITH POSITIVE TUBERCULIN SKIN TEST AND HISTORY OF BCG VACCINATION

SESSION TITLE: Chest Infections Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: The tuberculin skin test (TST) has been the traditional method for the diagnosis of latent tuberculosis infection (LTBI) for many years. However recently Quantiferon TB gold (QFT) has become the definitive means of diagnosis of LTBI. However QFT is a more expensive test with needs for special equipment and skilled personnel. The purpose of this study is to determine which patient characteristics in patients with positive TST and previous history of BCG vaccination are associated with positive QFT so that we can eliminate the need for additional QTB testing in this patient population. We hypothesize that in patients with high risk features of TST induration diameter of 20mm and more, recent immigration to the USA, advanced age, country of origin with high endemicity, known exposure to active tuberculosis (TB) and smoking history, a positive TST likely expresses true exposure and less likely represents cross reactivity from positive BCG. METHODS: Retrospective chart review was done on adult patients who were referred to our pulmonary clinic with positive TST from January 2014 until December 2019. Patient data was extracted from medical records. The patients were divided into 2 groups. Group 1 consisted of true positive TST patients who had BCG vaccination and were positive for QFT. Group 2 consisted of false positive TST patients who had BCG vaccination but were negative for QFT. The 2 groups were compared with each other to determine if the high risk features were more prevalent in Group 1 compared to Group 2. RESULTS: In total 76 patients met the criteria for our study. Group 1 had 23 patients and Group 2 had 53 patients. The results showed that Group 1 had a higher prevalence of patients with advanced age (4.2%) compared to Group 2 (3%). Patients with exposure to active TB were more prevalent in Group 1(8.3%) compared to Group 2(5.3). However patients with smoking history were more prevalent in Group 2(11.1%) compared to Group 1(4.2%).The above differences were not statistically significant. Patients with TST induration of 20mm and more were more prevalent in Group 1 (60.9%) compared to Group 1(37.7%).The P value in this category alone was trending towards significance with a value of 0.06. Both Group 1 & 2 had equal distribution of patients with recent immigration (16.7%). Patients from Mexico constituted the single largest number of patients in both Group 1(54.2%) & in Group 2 ( 27.7%). CONCLUSIONS: High risk features of large TST size, recent immigration to USA, advanced age, country of origin with high endemicity, known exposure to active TB patients and smoking history does not indicate that positive TST expresses true exposure. Therefore QFT is still needed for definitive confirmation of LTBI. CLINICAL IMPLICATIONS: QFT is a superior testing study than TST for confirmation of LTBI. Hence patients with positive TST must undergo QFT testing to confirm the diagnosis of LTBI. DISCLOSURES: No relevant relationships by Antony Arumairaj, source=Web Response No relevant relationships by Imnett Habtes, source=Web Response No relevant relationships by Hansang Park, source=Web Response No relevant relationships by Fernando Quesada, source=Web Response

Prevalence of and risk factors associated with latent tuberculosis infection in a Latin American region

Tuberculosis (TB) represents a health problem in Colombia, and its control is focused on the search for contacts and treatment of TB cases underscoring the role of latent tuberculosis infection (LTBI) as a reservoir of Mycobacterium tuberculosis. The burden of LTBI in Colombia is unknown. We aimed to estimate the prevalence of LTBI and identify the associated risk factors. In this cross-sectional study, we recruited participants from four health care centers in Cali, Colombia. The participants were eligible if they were aged between 14 and 70 years, and all participants answered a survey evaluating their medical history and sociodemographic and lifestyle factors. LTBI status was based on tuberculin skin test (TST) positivity using two thresholds: ≥10 mm (TST-10) and ≥15 mm (TST-15). The magnitude of the associations between independent factors and dependent outcomes (LTBI status and TST induration) were evaluated by logistic regression and generalized linear models, respectively. A total of 589 individuals were included with TST positivity rates of 25.3% (TST-10) and 13.2% (TST-15). Logistic regression showed that being between age 40 and 69 years (OR = 7.28, 95% CI [1.62–32.7]), being male (OR = 1.71, 95% CI [1.04–2.84]), being employed (OR = 1.56, 95% CI [1.02–2.38]), and having a low intake of alcohol (OR = 2.40, 95% CI [1.13–5.11]) were risk factors for TST positivity, while living in the north zone (OR = 0.32, 95% CI [0.18–0.55]), living in the suburb zone (OR = 0.28, 95% CI [0.15–0.52]) and having a secondary education (OR = 0.49 95% CI [0.29–0.83]) lowered the risk of TST positivity. The generalized linear model showed that the previous predictors, as well as a low body mass index, had an effect on TST reaction size. The LTBI prevalence found in the population was moderate, reflecting the continuous transmission of M. tuberculosis. Social factors seem to play a decisive role in the risk of LTBI. Employed males, who are over 40 years of age, are overweight, have a lower level of education and have a low intake of alcohol (50–100 mL, once/week) should be a priority group for prophylactic treatment as a strategy for TB control in this city.

The reliability of tuberculin skin test in the diagnosis of latent tuberculosis infection in psoriasis patients: A case-control study.

Tuberculin skin test (TST), which is used in the diagnosis of latent tuberculosis infection, may cause Koebner's phenomenon and false-positive results in psoriasis patients. The purpose of this study is to compare TST with QuantiFERON-TB Gold Plus (QFT-plus) test in psoriasis patients and to determine the effects of psoriasis on TST results. Ninety-two psoriasis patients and 30 control subjects were included in the study. QFT-plus test, TST, and prick test to distinguish the increase of induration because of the skin trauma were performed on both groups. The demographics, risk factors for latent tuberculosis infection, BCG vaccination history, Koebner's history, psoriasis severity, and treatment history of the patients were recorded. The effects of these variables on test results were investigated by comparing those with control group. The criteria of National Tuberculosis Diagnosis and Treatment Guidelines were used in the evaluation of test results, and threshold value of positivity for TST was taken as 10 mm in BCG-vaccinated patients who are planned to start biological treatment. Prick test results were negative in the control group. There was no significant relation between the results of prick test and TST induration diameters in the patient group. Although TST positivity was significantly higher in patients (62%) compared with control group (33%), QFT-plus test results were not statistically different between two groups. Agreement between two tests was determined to be low in patient group with 48% (K = 0.1), and it was determined to be moderate with 77% in control group (K = 0.4). QFT-plus test was found to be negative in 46 of 57 TST-positive patients (80.7%) in patient group. It was determined in both groups that vaccination did not have any effect on test results. When threshold value was lowered to 5 mm in patient group without considering BCG reaction, the number of TST-positive patients increased from 57 to 65. Mean TST induration diameter was 10 mm and 14 mm in cases with mild and moderate to severe clinical manifestation, respectively (P = .04). However, no effect of disease period and treatment was determined on both test results. TST positivity was higher in psoriasis patients compared with control group. It was considered due to the increased reaction of the skin to mycobacterial antigens rather than the Koebner's response. Although TST results were not affected by BCG, it was concluded that a 10-mm threshold value of positivity was a suitable approach in order to reduce the number of patients receiving unnecessary preventive treatment in patients who are considered to initiate biologic agents. Furthermore, it was also concluded that QFT-plus test may be preferred in psoriasis patients since it is applied in vitro and its specificity is higher and not affected by disease severity.

Prevalence and risk factors for latent tuberculosis infection among household contacts of index cases in two South African provinces: Analysis of baseline data from a cluster-randomised trial.

Household contacts of patients with active pulmonary tuberculosis (TB) often have latent TB infection, and are at risk of progression to disease. We set out to investigate whether index TB case HIV status was linked to a higher probability of latent TB infection among household contacts. Data were collected prospectively from participants in the intervention arm of a household cluster-randomised trial in two South Africa provinces (Mangaung, Free State, and Capricorn, Limpopo). In intervention group households, TB contacts underwent HIV testing and tuberculin skin testing (TST). TST induration was estimated at two cut-offs (≥5mm, ≥10mm). Multilevel Bayesian regression models estimated posterior distributions of the percentage of household contacts with TST induration ≥5mm and ≥10mm by age group, and compared the odds of latent TB infection by key risk factors including HIV status index case age and study province. A total of 2,985 household contacts of 924 index cases were assessed, with most 2,725 (91.3%) undergoing TST. HIV prevalence in household contacts was 14% and 10% in Mangaung and Capricorn respectively. Overall, 16.8% (458/2,725) had TST induration of ≥5mm and 13.1% (359/2,725) ≥10mm. In Mangaung, children aged 0-4 years had a high TST positivity prevalence compared to their peers in Capricorn (22.0% vs. 7.6%, and 20.5% vs. 2.3%, using TST thresholds of ≥5mm and ≥10mm respectively). Compared to contacts from Capricorn, household contacts living in Mangaung were more likely to have TST induration ≥5mm (odds ratio [OR]: 3.08, 95% credibility interval [CI]: 2.13-4.58) and ≥10mm (OR: 4.52, 95% CI: 3.03-6.97). There was a 90% and 92% posterior probability that the odds of TST induration ≥5mm (OR: 0.79, 95% CI: 0.56-1.14) and ≥10mm (OR: 0.77, 95% CI: 0.53-1.10) respectively were lower in household contacts of HIV-positive compared to HIV-negative index cases. High TST induration positivity, especially among young children and people living in Mangaung indicates considerable TB transmission despite high antiretroviral therapy coverage. Household contact of HIV-positive index TB cases were less likely to have evidence of latent TB infection than contacts of HIV-negative index cases.

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...

Risk of infection and disease progression in children exposed to tuberculosis at home, Colombia.

Aim: To assess the risk of tuberculosis (infection and disease) in children less than 15 years’ old who are household contacts of pulmonary tuberculosis patients in three Colombian cities (Medellín, Cali, and Popayán). Methods: A cohort of 1,040 children household contacts of 380 adults with smear-positive pulmonary tuberculosis was followed up for 24 months. Study period 2005-2009. Results: Tuberculin skin test was positive (≥10 mm) in 43.7% (95% CI: 39.2-48.2). Tuberculin skin test positivity was associated with age 10-14 years (Prevalence Ratio -PR= 1.43, 95% CI: 1.1-1.9), having a BCG vaccine scar (PR= 1.52, 95% CI: 1.1-2.1), underweight, closer proximity to the index case and exposure time >3 months. The annual risk of infection (tuberculin skin test induration increase of 6 mm or more per year) was 17% (95% CI: 11.8-22.2) and was associated with a bacillary load of the adult index case (Relative Risk -RR= 2.12, 95% CI: 1.0-4.3). The incidence rate of active tuberculosis was 12.4 cases per 1,000 persons-year. Children <5 years without BCG vaccine scar had a greater risk of developing active disease (Hazard Ratio -HR= 6.00, 95% CI: 1.3-28.3) than those with scar (HR= 1.33, 95% CI: 0.5-3.4). The risk of developing active tuberculosis augmented along with the increase from initial tuberculin skin test (tuberculin skin test 5-9 mm HR= 8.55, 95% CI: 2.5-29.2; tuberculin skin test ≥10 mm HR= 8.16, 95% CI: 2.0-32.9).Conclusions: There is a need for prompt interruption of adult-to-children tuberculosis transmission within households. Conducting proper contact investigation and offering chemoprophylaxis to infected children could reduce tuberculosis transmission.