Latent Tuberculosis Cases Research Articles

RATE OF INFECTION (TUBERCULOSIS) IN BRAZILIANS IBD PRIVATE PATIENTS: FOLLOW-UP 15 YEARS.

Latent tuberculosis (LTB) is a condition where the patient is infected with Mycobacterium tuberculosis but does not develop active TB. There's a possibility of tuberculosis (TB) activation following the introduction of anti-TNFs. To assess the risk of biological therapy inducing LTB during inflammatory bowel diseases (IBD) treatment over 15 years in a high-risk area in Brazil. A retrospective study of an IBD patients' database was carried out in a private reference clinic in Brazil. All patients underwent TST testing and chest X-ray prior to treatment, and once a year after starting it. Patients were classified according to the Montreal stratification and risk factors were considered for developing TB. Among the analyzed factors, age and gender were risk factors for LTB. DC (B2 and P) and UC (E2) patients showed a higher number of LTB cases with statistical significance, what was also observed for adalimumab and infliximab users, compared to other medications, and time of exposure to them favored it significantly. Other factors such as enclosed working environment have been reported as risk. The risk of biological therapy causing LTB is real, so patients with IBD should be continually monitored. This study reveals that the longer the exposure to anti-TNFs, the greater the risk. •Rate of infection (tuberculosis) in Brazilians IBD private patients: follow-up 15 years. •Patients treated with immunosuppressants and/or anti-TNFs have a higher risk of developing opportunistic infections, among them the most common is latent tuberculosis or even active tuberculosis. •Similar risks may be noted in patients with inflammatory bowel diseases (IBDs). •This study reveals that the longer the exposure to anti-TNFs, the greater the risk for de IBD patients. •The study demonstrated the importance of monitoring these patients permanently and continuously.

Short-term risk and long-term incidence rate of infection and malignancy with IL-17 and IL-23 inhibitors in adult patients with psoriasis and psoriatic arthritis: a systematic review and meta-analysis.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022363127.

Dynamics of the Main Indicators of Tuberculosis Epidemiology in Bukovina, the Influence of the COVID-19 Pandemic and Wartime Conditions

According to the WHO, Ukraine is one of the 27 countries in the world where 85 % of the incidence of tuberculosis (TB) is concentrated, and it ranks 4th in the world in terms of its prevalence. Objective — to analyze the regional epidemiological characteristics of TB in the Chernivtsi region under the influence of unfavorable socio-economic factors. Materials and methods. The medical records of all newly diagnosed tuberculosis cases registered at the Chernivtsi Regional Clinical Tuberculosis Dispensary from January 2021 to December 2022 were analyzed. Statistical processing of the data obtained during the research was conducted using the IBM SPSS Statistics v26.0 program. Results and discussion. Tuberculosis incidence among the adult population has significantly increased. The lockdown situation caused by the COVID-19 pandemic and the conditions of martial law have had a negative impact on TB prevalence. An analysis of TB prevalence in Bukovina revealed a decrease of this indicator by 25.9 % in 2020 compared to 2019, by 1.5 % in 2021 compared to 2020, but there was a substantial increase of 16.1 % in 2022. Conclusions. In the Chernivtsi region, from 2019 to 2022, there has been a noticeable trend of a significant decrease in the incidence rate of tuberculosis, both during this period and in the conditions of martial law, aligning with the national trend. Due to the onset of the COVID-19 pandemic caused by SARS-CoV-2, the number of newly diagnosed TB cases decreased in 2020 compared to 2019, which led to the accumulation of undiagnosed and latent TB cases, which were detected more, in late stages and in more severe forms and showed an indicative probable increase in the number of active cases in 2022. The mortality rate in Bukovina was 4.7 per 100,000 population in 2021, and 4.4 per 100,000 population in 2022, i. e. it shows a downward tendency under the negative influence of socio-economic factors.

Prevalence of latent tuberculosis infection in household contacts of pulmonary tuberculosis, time to treat.

Treatment of latent pulmonary tuberculosis (TB) in household contacts has been included in the National Tuberculosis Elimination Program to achieve the target of TB elimination by the Government of India by 2025. However, there are no clear estimates of the prevalence of latent TB among the contacts that could suggest the impact of this intervention. The study was conducted to determine the prevalence of and factors predicting latent TB among household contacts with pulmonary TB. All microbiologically confirmed pulmonary TB patients registered between January 2020 and July 2021 and their household contacts were enrolled. All contacts underwent Mantoux testing to determine the prevalence of latent TB. All symptomatic patients also underwent chest radiographs and sputum examinations to diagnose active pulmonary TB. Thereafter, different demographic and clinical factors were evaluated to find predictors of latent TB using a logistic regression model. A total of 118 pulmonary TB cases and their 330 household contacts were enrolled. The prevalence of latent TB and active TB among the contacts was found to be 26.36% and 3.03%, respectively. The female gender of index TB cases was independently associated with a high proportion of latent TB cases in the family (adjusted odds ratio 2.32; 95% confidence interval 1.07-5.05; p=0.03). Neither the higher sputum smear positivity nor the severity of the chest radiograph of index TB cases had any association with the number of contacts being diagnosed as latent TB or active TB. The results showed a significant prevalence of latent TB among household contacts with pulmonary TB. The severity of the disease in the index patient had no association with the prevalence of latent TB.

CT in the detection of latent tuberculosis: a systematic review

To evaluate the use of computed tomography (CT) and low-dose CT in the detection of latent tuberculosis (TB). A systematic search of literature in adherence with the PRISMA guidelines was carried out. Quality assessment of the included studies was conducted. The search strategy identified a total of 4,621 studies. Sixteen studies were considered eligible and included in the review. There was high heterogeneity among all studies. CT was identified as much more sensitive for the detection of latent TB in all studies despite chest radiography often being recommended in guidelines to assess patients for latent TB. Low-dose CT showed promising results in four of the studies; however, these results were limited due to small sample sizes. CT is much superior to chest radiography consistently identifying additional cases of latent TB. There are limited high-quality publications available using low-dose CT but findings thus far suggest low-dose CT could be used as an alternative to standard-dose CT for the detection of latent TB. It is recommended that a randomised controlled trial investigating low-dose CT should be carried out.

Country-specific lockdown measures in response to the COVID-19 pandemic and its impact on tuberculosis control: a global study.

ABSTRACTThe objective of this study was to describe country-specific lockdown measures and tuberculosis indicators collected during the first year of the COVID-19 pandemic. Data on lockdown/social restrictions (compulsory face masks and hand hygiene; international and local travel restrictions; restrictions to family visits, and school closures) were collected from 24 countries spanning five continents. The majority of the countries implemented multiple lockdowns with partial or full reopening. There was an overall decrease in active tuberculosis, drug-resistant tuberculosis, and latent tuberculosis cases. Although national lockdowns were effective in containing COVID-19 cases, several indicators of tuberculosis were affected during the pandemic.

Application of optimal control to tuberculosis model with parameter estimations: Bayesian approach

In this paper, one-strain tuberculosis (TB) model with two control mechanisms, education campaigns and chemoprophylaxis of TB-infected patients, was studied to determine their effects on the reduction of latent and active TB cases. In the case of analysis, boundedness and positivity of the model solutions were carried out to determine the biological feasibility of the study. Besides, the calibration of the parameters by utilizing the identifiability technique through the Markov chain Monte Carlo (MCMC) was thoroughly analysed. The optimum conditions for controlling TB were derived from the Pontryagin Maximum Principle. The numerical simulations were carried out using the forward-back sweep method with the help of the Runge-Kutta fourth-order numerical schemes. Simulation results showed that the education campaigns strategy is more effective in reducing TB infections than the chemoprophylaxis of TB-infected individuals. The combination of the two control strategies reduces a significant number of infections than when each strategy is used on its own. To minimize the transmission of TB from the community, we recommend the education campaigns strategy be a focal point and treatment of latent TB to be paired with the treatment of active TB cases.
 Keywords: Tuberculosis, Education campaigns, Chemoprophylaxis, MCMC

Frequency Distribution and Risk Factors for Latent Tuberculosis in Contact Persons: Cologne 2012-2016

As part of tuberculosis control and the WHO end-TB strategy, contact persons of tuberculosis patients in Germany are examined for a possible infection with latent tuberculosis (LTBI). Activation of LTBI contributes a considerable proportion of newly reported tuberculosis cases in low-incidence countries such as Germany. Therefore, the aim is to detect cases of LTBI and, through chemopreventive treatment of these cases, prevent future, post-primary, active tuberculosis.In Germany, the rate of LTBI among contact persons of people diagnosed with active tuberculosis is not systematically recorded. The aim of the present work was to close this data gap for Cologne, a major city in Germany with a TB incidence of around 9/100,000 in the past years. The study further aimed to describe risk factors for LTBI and to reevaluate the standard inclusion criteria for contact investigation for tuberculosis under routine conditions in Germany. For the period 07/2012 to 12/2016, the retrospective cohort study examined the rate of LTBI diagnoses among contact persons of those with pulmonary tuberculosis notified at the Cologne public health department, as well as factors that increase the LTBI infection risk of contact persons. The diagnosis of latent tuberculosis was made when the interferon-gamma release assay (IGRA) was positive and there were no signs of active tuberculosis. The study included contact persons who cumulatively had a previously defined minimum total contact time with a tuberculosis patient, who were at least 5 years old at the time of the study and who were registered in Cologne. Statistical evaluation was carried out descriptively as absolute and relative frequency with a significance level of p ≤ 0.05. The analytical evaluation was carried out with univariate and multivariate logistic regression. Of a total of 3862 IGRA examinations among contact persons, 2834 cases met the inclusion criteria. A median of seven contact persons per index patient was reported. 12.5 % ​​of the study group tested positive for LTBI. In contact persons of microscopically open index patients, the positivity rate was 11.4 %, in culturally open but microscopically negative index patients, it was 14.3 %. Factors associated with a higher risk of LTBI included male sex (OR = 1.95), age ≥ 50 years (OR = 1.8) and household exposure (OR = 2.37). Using the German standard criteria, the positivity rate of IGRA testing and the diagnosis of LTBI among contacts in the present study was 12.5 %, which is lower than in other similar studies. Factors identified in the cohort for an increased risk of LTBI confirm known constellations. The significantly higher positivity rate among contact persons of microscopically negative but culturally positive index patients (p = 0.033) underscores the need to conduct a detailed contact examination of individuals of this group as well.

A Tuberculose pulmonar, em lactente jovem, diagnosticada pela avaliação de contato - Relato de caso

The purpose of this report is to emphasize the importance of tuberculosis (TB) contacts evaluation in order to detect cases of latent tuberculosis infection (LTBI) and active TB. This case reports a two-month-old infant diagnosed with pulmonary TB with a bacilliferous mother whose diagnosis of TB occurred in the second week of puerperium. The correct evaluation of the child allowed the early diagnosis and treatment of pulmonary TB, avoiding its evolution to severe forms of the disease (miliary TB and meningoencephalitis) and its sequelae or deadly outcome.

Variations in Antimicrobial Activities of Human Monocyte-Derived Macrophage and Their Associations With Tuberculosis Clinical Manifestations.

Macrophages play a significant role in preventing infection through antimicrobial activities, particularly acidification, and proteolysis. Mycobacterium tuberculosis (Mtb) infection can lead to diverse outcomes, from latent asymptomatic infection to active disease involving multiple organs. Monocyte-derived macrophage is one of the main cell types accumulating in lungs following Mtb infection. The variation of intracellular activities of monocyte-derived macrophages in humans and the influence of these activities on the tuberculosis (TB) spectrum are not well understood. By exploiting ligand-specific bead-based assays, we investigated macrophage antimicrobial activities real-time in healthy volunteers (n = 53) with 35 cases of latent TB (LTB), and those with active TB (ATB), and either pulmonary TB (PTB, n = 70) or TB meningitis (TBM, n = 77). We found wide person-to-person variations in acidification and proteolytic activities in response to both non-immunogenic IgG and pathogenic ligands comprising trehalose 6,6'−dimycolate (TDM) from Mtb or β-glucan from Saccharamyces cerevisiase. The variation in the macrophage activities remained similar regardless of stimuli; however, IgG induced stronger acidification activity than immunogenic ligands TDM (P = 10−5, 3 × 10−5 and 0.01 at 30, 60, and 90 min) and β-glucan (P = 10−4, 3 × 10−4 and 0.04 at 30, 60, and 90 min). Variation in proteolysis activity was slightly higher in LTB than in ATB (CV = 40% in LTB vs. 29% in ATB, P = 0.03). There was no difference in measured antimicrobial activities in response to TDM and bacterial killing in macrophages from LTB and ATB, or from PTB and TBM. Our results indicate that antimicrobial activities of monocyte-derived macrophages vary among individuals and show immunological dependence, but suggest these activities cannot be solely responsible for the control of bacterial replication or dissemination in TB.

Tuberculosis versus COVID-19 Mortality: A New Evidence

BACKGROUND: Coronavirus current pandemic (COVID-19) is the striking subject worldwide hitting countries in an unexplained non-universal pattern. Bacillus Calmette–Guérin (BCG) vaccine was an adopted recent justification depending on its non-specific immune activation properties. Still the problem of post-vaccine short duration of protection needs to be solved. The same protective mechanism was identified in active or latent tuberculosis (TB). For each single patient of active TB, there are about nine cases of asymptomatic latent TB apparently normal individuals living within the community without restrictions carrying benefits of immune activation and involved in re-infection cycles in an excellent example of repeated immunity training sessions of the whole community.
 AIM: We aimed to asses the correlation between TB burden and COVID-19 mortality in all affected countries having different BCG vaccination policies.
 METHODS: Publicly available data were extracted for 191 countries including population size, TB estimations, national BCG vaccination policy, the World Health Organization regions and economic classification, and COVID-19 mortality and number of cases. The analysis was performed using Spearman’s correlation test.
 RESULTS: Significant large negative correlation (−0.539, p < 0.001) was found between TB prevalence and COVID-19 mortality rate worldwide. Medium negative significant correlations were found between TB cases and COVID-19 mortality in the high and lower middle-income countries, and those having current BCG vaccination programs (−0.395, p = 0.001, −0.365, p = 0.015, and −0.476, p < 0.001, respectively).
 CONCLUSION: Countries with high TB prevalence have higher chances of protection against COVID-19 mortality through the theory of widely distributed natural immune activation within community. Confounders should be assessed separately.

Proteomic analysis of infected primary human leucocytes revealed PSTK as potential treatment-monitoring marker for active and latent tuberculosis.

Markers for monitoring clearance of Mycobacterium tuberculosis (Mtb) infection during anti-TB drug treatment could facilitate management of tuberculosis (TB) treatment, but are lacking. We aimed to screen for Mtb clearance markers from in-vitro-infected leucocytes and to evaluate these markers in followed-up active TB (ATB) patients and latent TB (LTBI) cases after anti-TB drug treatment. Extracellular proteins from primary leucocytes infected with each of the Mtb lineages (East-Asian, Indo-Oceanic, Euro-American and the laboratory strain H37Rv) were screened as possible clearance markers. Leucocytes infected with Staphylococcus aureus acted as controls. The proteomic analysis was performed using GeLC-MS/MS. Several quantitative and qualitative candidate clearance markers were found. These proteins were suppressed during the infection stage of all Mtb lineages and re-expressed after bacillary clearance. PSTK, FKBP8 and MGMT were common clearance markers among the four Mtb lineages in our model. Only PSTK was a potential clearance marker based on western blot validation analysis from culture supernatants. The PSTK marker was further validated with western blot analysis using serum samples (n = 6) from ATB patients and LTBI cases during anti-TB drug treatment, and from healthy controls (n = 3). Time-dependent increase of PSTK was found both in ATB and LTBI patients during the course of anti-TB drug treatment, but not in healthy controls. We have demonstrated that PSTK is a potential treatment-monitoring marker for active and latent TB.

Diagnostic value of miR-145 and its regulatory role in macrophage immune response in tuberculosis.

Tuberculosis (TB) induced by Mycobacterium tuberculosis (Mtb) is a serious global health burden. This study sought to investigate the expression and diagnostic value of serum miR-145 in TB patients and explore the biological function of miR-145 using macrophages. Serum expression levels of miR-145 were estimated by quantitative real-time PCR. A receiver operating characteristic curve was plotted to evaluate the diagnostic accuracy of miR-145. This study further focused on the effects of miR-145 on cell viability and inflammation in macrophages upon Mtb infection, and explored the potential target gene of miR-145. Serum expression levels of miR-145 were decreased in TB patients, and the upregulated inflammatory cytokines in TB patients were negatively correlated with the serum expression levels of miR-145. miR-145 had considerable diagnostic accuracy in distinguishing of TB patients from healthy individuals and differentiating between active TB cases and latent TB cases. Mtb infection induced an increase in cell viability and inflammatory responses in macrophages, but these promoting effects were rescued by the overexpression of miR-145. CXCL16 was determined as a target gene of miR-145 in macrophages. Overall, this study demonstrated that the decreased serum miR-145 expression serves a candidate diagnostic biomarker in TB patients. The overexpression of miR-145 in macrophages upon Mtb infection can suppress cell viability and infection-induced inflammation via regulating CXCL16, indicating the potential of miR-145 as a therapeutic target of TB.

Cartridge-based nucleic acid amplification test (Xpert Mycobacterium tuberculosis/Rifampicin Assay): An essential molecular diagnostic test for early diagnosis and initiation of treatment in childhood tuberculous meningitis and primary multidrug-resistant cases

Background: Tuberculosis (TB) still remains the major public health threat in India. Early diagnosis, so as to initiate early treatment is a priority as any delay, may complicate the prognosis further leading to the failure of an effective control. India accounts for 6% incidence of pediatric TB cases in a population that has 40% as estimated latent TB cases. Pediatric samples were considered as the key population in the study. TB remains the most common cause of childhood meningitis in high burden countries. India accounted for the highest number of TB deaths among children in the year 2015, followed by Nigeria and China. Of which, tuberculous meningitis (TBM) stands to be the most common cause of morbidity. Extrapulmonary TB accounts for 25% of the total TB cases reported among which the most severe form being TBM. Although severe and difficult to diagnose due to lack of specific tests to get confirmed, cartridge-based nucleic acid amplification test (CBNAAT) is the only solution for microbiological confirmation of the disease for early treatment initiation and reduction of morbidity and mortality. Previously, due to lower case detection rates owing to inadequate diagnostic facilities of higher analytical sensitivity, the mortality and morbidity continued to be in the higher range, and empirical treatment modality was the mainstay till the CBNAATs came into existence. The increase in the case detection for tuberculous meningitis at a manageable stage of the disease would help in decreasing the mortality rates. The study explores the increased case detection rates among pediatric population suffering from tuberculous meningitis from referral units to Intermediate Reference Laboratory (IRL), Kolkata. Cerebrospinal fluid (CSF) from the pediatric patients has not been very difficult procedure though invasive, especially in the pediatric age group, and can be practiced at peripheral unit having CBNAAT facility. Methods: CSF from pediatric patients showing obvious clinical signs of meningitis was collected from tertiary unit linked to IRL, Kolkata, and tested on CBNAAT by Xpert Mycobacterium tuberculosis/ rifampicin (RIF) (Cepheid) along with all the pulmonary and extrapulmonary samples based on the manufacturer's instruction. The data were captured in the Inbuilt software of the GeneXpert MTB/RIF (Xpert) and Genotype MTBDRplus (DRplus) (Cepheid , USA) of the cartridge based nucleic acid amplification test machines automatically during the tests and exported to the Microsoft Excel sheets for further analysis. A defined study design against each and every objective was setup to analyze the effective detection of tuberculous meningitis case and their resistance to RIF along with the other pulmonary and extrapulmonary samples. Results and Conclusions: The study concluded the confirmation of tuberculous meningitis cases by the help of CBNAAT. The detection of microbiologically confirmed TB by these specimens sent from the referral unit linked with IRL, Kolkata, for pulmonary and extrapulmonary cases along with tuberculous meningitis cases is significant and facilitates the early initiation of treatment for TB and more so to those who are newly detected as multidrug-resistant TB especially below the 6 months of age. About 5% prevalence and around 4.9% incidence are an alarming situation in the TB control scenario of West Bengal. The positive case detection among the CSF samples was found to be more in the 0.6–1-year group followed by the age group of 1–5 years. The percentage positivity of CSF is recorded as 2.38%, and the percentage of RIF resistance among positive cases from CSF was found to be 13.79% (n = 28).

1373. Clinical Presentation, Demographics, and Outcomes of Cases of Tuberculosis (TB) at Princess Margaret Hospital, Nassau, The Bahamas 2014–2016

BackgroundTuberculosis (TB) is one of the oldest diseases known to man, yet the world health organization reports that Tuberculosis is one of the top 10 causes of death worldwide. There are various factors that have made the eradication of tuberculosis in the Bahamas difficult such as high rates of HIV infection and immigrants migrating from countries with high TB prevalence. In understanding the epidemiology and risk factors of TB cases in the Bahamas, the development of protocols can improve screening procedures and decrease disease burden.MethodsA retrospective chart review of cases of Tuberculosis diagnosed at the Princess Margaret Hospital, Nassau, Bahamas. 189 cases of active tuberculosis diagnosed between 2014–2016 and all cases were evaluated for demographics, risk factors, clinical manifestation, method of diagnosis, symptoms, and treatment outcomes.ResultsOf the 189 cases of notified tuberculosis between 2014 and 2016, 46 cases were reported in 2014, 60 cases in 2015 and 83 cases in 2016. The mean age was 37.96 (±18.20) years old. 164 (86.8%) presented with symptoms, 19 (10.1%) of cases were diagnosed by routine screening and 6 (3.2%) of cases were diagnosed by contact tracing. 109 (59.9%) were HIV negative and 73 (40.1%) were HIV positive. 144 (76.2%) presented with cough, 84 (44.7%) weight-loss, 80 (42.3%) fever, 44 (23.3%) night sweats, 43 (22.8%) chills, 32 (16.9%) fatigue, and 25 (13.2%) hemoptysis. 126(66.7%) completed the full course of antibiotic therapy, 29(15.3%) patients expired before completing treatment and 18(9.5%) of patients defaulted.ConclusionHIV is a major risk factor for Tuberculosis in the Bahamas and it is advised that all patients diagnosed with TB be tested for HIV. We also advise screening HIV-positive patients for TB. Screening other high-risk groups such as migrant populations would also benefit to reduce the amount of latent TB cases which may progress to active TB. Disclosures All authors: No reported disclosures.

Tuberculosis outbreak among high school students in Novi Pazar, Serbia 2016: a retrospective-cohort study.

Between February and November 2016, 17 tuberculosis (TB) cases were identified among high school students in Novi Pazar, Serbia. The objectives of our study were to describe the outbreak, to identify potential risk factors and to evaluate the applied control measures. The outbreak was described by time, person and place. A retrospective cohort study was conducted. Attack rates, unadjusted relative risks (RR) and 95% confidence intervals (CI) were calculated. Multiple log-binomial regression analysis was performed to calculate adjusted RR. Sixteen of the total 17 cases occurred among grade 3 students, AR 5.5%. Previous TB family history, (RR = 5.29; 95% CI = 1.63-17.12), spending time with a known TB case at school (RR = 5.38; 95% CI = 1.48-19.55) and exposure to secondhand smoke (RR = 3.37; 95% CI = 1.11-10.29) were all significantly and independently associated with the occurrence of TB. Delayed diagnosis and reporting resulted in delayed initiation of the contact investigation and non-identification of latent TB cases probably favored the occurrence of this outbreak in a low incidence country. Public health authorities should consider revising the existing guidelines, promoting inter-sectorial collaboration and increasing awareness of public health professionals.

Early diagnosis of smear-negative childhood pulmonary tuberculosis and its substantial yield in gastric lavage/aspirates through cartridge-based nucleic acid amplification test (Xpert Mycobacterium tuberculosis/rifampicin assay)

Introduction: Tuberculosis (TB) still remains the major public health threat in India. Early diagnosis is a priority as any delay may complicate the prognosis further leading to the failure of an effective control. India accounts for 6% incidence of pediatric TB cases in a population that has 40% as estimated latent TB cases. Gastric Lavage /aspirates were taken under study for pediatric patients as key population. Collection of sputum samples from the pediatric patients has been very difficult. The most common implementation of cartridge-based nucleic acid amplification tests (CBNAATs) in diagnosis of pediatric TB has augmented the detection rates. As a mandate for universal drug sensitivity, testing of smear-negative pediatric samples is set as a priority. The program included the smear-negative pulmonary samples contributing to high yield after sputum includes induced sputum, bronchoalveolar lavage, gastric aspirate, and gastric lavage. The study involves an analysis probing into the percentage contribution of these samples and the substantial yields of gastric lavage among these samples. Methods: Pulmonary pediatric samples were tested on CBNAAT by Xpert Mycobacterium tuberculosis/rifampicin (RIF) (Cepheid) based on the manufacturer's instruction. All necessary aseptic measures were taken. The data were captured in the Xpert software automatically during the tests and exported to the Microsoft Excel sheets for further analysis. A defined study design against each and every objective was set up. Results: From earlier studies, it was found that a point prevalence of 6%–7% of pediatric TB exists among the tested specimens every quarter. The periodic prevalence was found to be 5%, and the incidence rates ranged from 4.5% to 5%. RIF resistance detection showing a seasonal variation ranged from 13% to 15% among the CBNAAT-positive cases. Conclusions: The study concluded that more skilled collection centers for biological specimens are required to address the undetected pulmonary TB cases among the pediatric age group, especially below 6 months of age. About 5% prevalence and around 4.9% incidence is an alarming situation in the TB control scenario of West Bengal. Gastric lavage showed a major detection in children aged below 6 months of whom collecting sputum samples were difficult. This prompted suboptimal detection levels due to the dearth of sample collection modalities at the peripheries.

807. A Risk-Stratified Approach to Healthcare-Associated Tuberculosis Exposures Following the “Stone in the Pond” Principle

BackgroundLarge-scale tuberculosis (TB) exposure investigations cause anxiety to healthcare personnel (HCP) and patients, in addition to being resource and time intensive. TB contact tracing in England and Singapore follow the “stone in the pond” principle. We propose a similar risk-stratified approach to TB exposure investigations in an area of low incidence.MethodsThis retrospective study was conducted at a 1,541 bed academic medical center in New Haven, CT between January 14 and 11, 2017. Microbiology records, patient charts, and infection prevention databases were reviewed to find TB exposures. A scoring system adapted from CDC’s “Guidelines for the Investigation of Contacts of Persons with Infectious Tuberculosis” was developed to predict infectivity (two points for laryngeal TB, one point each for: cavitary TB, ≥1 positive respiratory acid fast bacilli smear or Xpert MTB/RIF, multi-drug-resistant (MDR) TB, foreign-born status, immunocompromised status, cough/hemoptysis, or procedure associated with positive TB culture). Using the “stone in the pond” principle, contacts were graded based on the type of exposure (Figure 1). Based on high, medium, and low risk, our new risk-stratified approach was applied to contact tracing.ResultsDuring the study period, 17 of 29 patients with pulmonary TB led to exposures. A subset of seven TB patients with complete exposure data was selected for further analysis. The original exposure investigations led to contact tracing of 586 HCP and 72 patients. No active or latent TB cases were identified among these exposed contacts. Using our scoring system, these seven patients were categorized into three high, two medium, and two low infectivity risk groups. On applying our new risk-stratified approach, contact tracing could be reduced by 42% and 84% for medium and low-risk exposures, respectively, by excluding these HCP groups from investigation (Figure 2).ConclusionWe recommend a risk-stratified approach to healthcare-associated TB exposure investigations similar to the “stone in the pond” principle, based on index patient’s infectivity risk and type of exposure. This has potential to optimize resources and possibly reduce anxiety in medium and low-risk TB exposures in an area of low TB incidence. Disclosures All authors: No reported disclosures.

B cells response directed against Cut4 and CFP21 lipolytic enzymes in active and latent tuberculosis infections.

BackgroundBetter understanding of the immune response directed against Mycobacterium tuberculosis (Mtb) is critical for development of vaccine strategies and diagnosis tests. Previous studies suggested that Mtb enzymes involved in lipid metabolism, are associated with persistence and/or reactivation of dormant bacilli.MethodsCirculating antibodies secreting cells (ASCs), memory B cells, and antibodies directed against Cut4 (Rv3452) and CFP21 (Rv1984c) antigens were explored in subjects with either active- or latent-tuberculosis (LTB), and in Mtb-uninfected individuals.ResultsCirculating anti-Cut4 ASCs were detected in 11/14 (78.6%) subjects from the active TB group vs. 4/17 (23.5%) from the LTB group (p = 0.001). Anti-CFP21 ASCs were found in 11/14 (78.6%) active TB vs. in 5/17 (29.4%) LTB cases (p = 0.01). Circulating anti-Cut4 and anti-CFP21 ASCs were not detected in 38 Mtb uninfected controls. Memory B cells directed against either Cut4 or CFP21 were identified in 8/11 (72.7%) and in 9/11 (81.8%) subjects with LTB infection, respectively, and in 2/6 Mtb uninfected individuals (33.3%). High level of anti-Cut4 and anti-CFP21 IgG were observed in active TB cases.ConclusionCirculating IgG SCs directed against Cut4 or CFP21 were mostly detected in patients presenting an active form of the disease, suggesting that TB reactivation triggers an immune response against these two antigens.

Prevalence of rifampicin-resistant pediatric tuberculosis by cartridge-based nucleic acid amplification test at the intermediate reference laboratory under revised national tuberculosis control program India: A multidimensional approach

Background: Tuberculosis (TB) still remains the major public health threat in India. Early diagnosis, so as to initiate early treatment is a priority as any delay, may complicate the prognosis further leading to the failure of an effective control. India accounts for 6% incidence of pediatric TB cases in a population that has 40% as estimated latent TB cases. Implementation of cartridge-based nucleic acid amplification tests (CBNAATs) in diagnosis of pediatric TB has augmented the detection rates. The study involves a retrospective multidimensional analysis of the increased pediatric TB case detection by CBNAAT at the Intermediate Reference laboratory, State TB Demonstration and Training Centre in West Bengal, India. A total of 14,088 samples from pediatric patients coming from all the districts were tested from May 2014 to April 2018. This included pulmonary (sputum, bronchoalveolar lavage, gastric lavage, and gastric aspirate) and extrapulmonary (cerebrospinal fluid [CSF], pus, ascitic fluid, pericardial fluid, lymph node aspirate) samples. Although detection levels showed variation in the nature of the samples, the study explored percentage contribution of the types of samples and the proportion positive rates among them. Percentage-wise propensity with regard to age, clinical presentations, type of samples, and smear result were observed. The predominant geographical location in terms of incidences and periodic prevalence were studied. The resistant cases were retested with line probe assay by MTBDRplus and V2 Hains for concordance analysis. This was done based on the parameters in the erstwhile evaluations. Methods: Pulmonary and extrapulmonary pediatric samples were tested on CBNAAT by Xpert Mycobacterium tuberculosis rifampicin (RIF) (Cepheid) based on the manufacturer's instruction. All necessary aseptic measures were taken. The data were captured in the Xpert software automatically during the tests and exported to the Microsoft Excel sheets for further analysis. A defined study design against each and every objective was set up. Results: It was found that a point prevalence of 6%–7% of pediatric TB exists among the tested specimens every quarter. The periodic prevalence was found to be 5%, the incidence rates ranged from 4.5% to 5%. RIF resistance detection showing a seasonal variation ranged from 13% to 15% among the CBNAAT-positive cases. Gastric lavage showed a major detection in children below 6 months of age of whom collecting sputum samples were difficult. This prompted suboptimal detection levels due to the dearth of sample collection modalities at the peripheries. CSF accounted for 2.37% of positivity. Conclusions: The study concluded that more skilled collection centers for biological specimens are required to address the undetected pulmonary TB cases among the pediatric age group, especially below the 6 months of age. About 5% prevalence and around 4.9% incidence is an alarming situation in the TB control scenario of West Bengal. Focus on the universal drug-susceptibility testing is a prerequisite.