TB Test Research Articles

Management of drug-resistant tuberculosis in Indonesia: a four-year cascade of care analysis

In Indonesia, drug resistance testing for TB largely relies on Xpert MTB/RIF, and it is unknown what proportion of drug-resistant (DR) TB is adequately diagnosed and treated. We conducted a cascade of care analysis on a cohort of presumptive rifampicin-resistant (RR) TB patients registered in 2015-2018 in a tertiary hospital in Indonesia. Estimated incidences of (presumptive) DR-TB cases were assumption-based using global reports. Data on diagnosis and consecutive cascades steps, including their timing were collected from national electronic registers, and medical records. We described a secondary cascade for patients receiving treatment not supported by phenotypic drug susceptibility testing (pDST). Factors associated with delay and loss between diagnosis and treatment were identified using logistic regression. Less than a third of estimated incident TB cases at risk of DR-TB were identified as presumptive DR-TB case and tested, and 9.8% (982/10,065) of estimated true DR-TB cases was diagnosed. Of those diagnosed, only 45.1% (443/982) had treatment regimens supported by pDST results, but this did not significantly influence treatment outcomes. Only 25.5% (250/982) of diagnosed patients completed all steps of the cascade including successful treatment. Delays between diagnosis and treatment were substantial, and more common among those referred from a primary healthcare facility, and among those who were employed, living outside of Bandung, and reporting engagement with the private sector. The DR-TB care cascade in this urban setting in Indonesia is characterized by substantial attrition and delays. Strategies to increase access to DR-TB diagnosis accompanied by optimisation of clinical care could substantially improve outcomes and reduce onward transmission. Radboud university medical center and University of Otago.

Negative conversion of T-SPOT results after hemodialysis: case series and literature review

BackgroundLatent tuberculosis infection (LTBI) affects 11.9% of outpatients under maintenance hemodialysis in Japan. In addition, the risk of reactivation of LTBI in hemodialysis patients is up to 10–25 times higher than that in the general population. Therefore, the accurate diagnosis and treatment for LTBI are extremely important. The interferon-γ release assays are widely used for screening LTBI; however, the impact of hemodialysis on the assay results has been uncertain.Case presentationTwenty-seven hemodialysis patients (17 males, 69.9 ± 10.1 year old) were performed T-SPOT®.TB test (T-SPOT) both before and after hemodialysis. In cases where T-SPOT results were different before and after hemodialysis, T-SPOT was re-evaluated in a same manner. As a result, two cases showed consistent T-SPOT diagnostic discrepancy before and after hemodialysis in two measurements. In the first case, T-SPOT was indeterminate/positive before hemodialysis, but changed to negative after hemodialysis. In the second case, T-SPOT was positive before hemodialysis, but changed to indeterminate after hemodialysis.ConclusionsWe experienced the negative conversion of T-SPOT after hemodialysis in cases of LTBI. T-SPOT may show false-negative when measured after hemodialysis due to immunomodulation caused by hemodialysis.

Impact of COVID-19 Pandemic on Tuberculosis Care and Treatment in Puducherry - A Mixed Method Study.

The shift of focus toward pandemic control had an impact on public health issues that need to be addressed. As the impact may vary in the different areas based on COVID-19 cases and strictness of measures to control the disease, studying the local situation and related factors is essential to strengthening the TB program. The objective is to compare the TB care before and during the COVID-19 pandemic and to explore the challenges faced by stakeholders during the pandemic. A mixed method study was conducted in Puducherry with a quantitative phase involving data extraction from the National TB Elimination Programme (NTEP), followed by in-depth interviews to explore the challenges faced by stakeholders. In 2020, there were 67% and 23% reductions in number of presumptive TB case and notified TB cases, respectively, while the decline was lesser in the year 2021 (reduction of 59% and 13%, respectively). The main challenges faced in providing and accessing TB care were social stigma, lockdown restrictions, fear of getting COVID-19, redeployment of staff to COVID-19-related activities and increased COVID-19 workload. There is a need to strengthen active case finding for the missed TB cases through the mobile vans equipped with diagnostics, combined testing for COVID-19 and TB, greater inclusion of private sector and dispensaries as well as community awareness for stigma prevention.

Simultaneous diagnosis of tuberculous pleurisy and malignant pleural effusion using metagenomic next-generation sequencing (mNGS)

BackgroundMetagenomic next-generation sequencing (mNGS) has become a powerful tool for pathogen detection, but the value of human sequencing reads generated from it is underestimated.MethodsA total of 138 patients with pleural effusion (PE) were diagnosed with tuberculous pleurisy (TBP, N = 82), malignant pleural effusion (MPE, N = 35), or non-TB infection (N = 21), whose PE samples all underwent mNGS analysis. Clinical TB tests including culture, Acid-Fast Bacillus (AFB) test, Xpert, and T-SPOT, were performed. To utilize mNGS for MPE identification, 25 non-MPE samples (20 TBP and 5 non-TB infection) were randomly selected to set human chromosome copy number baseline and generalized linear modeling was performed using copy number variant (CNV) features of the rest 113 samples (35 MPE and 78 non-MPE).ResultsThe performance of TB detection was compared among five methods. T-SPOT demonstrated the highest sensitivity (61% vs. culture 32%, AFB 12%, Xpert 35%, and mNGS 49%) but with the highest false-positive rate (10%) as well. In contrast, mNGS was able to detect TB-genome in nearly half (40/82) of the PE samples from TBP subgroup, with 100% specificity. To evaluate the performance of using CNV features of the human genome for MPE prediction, we performed the leave-one-out cross-validation (LOOCV) in the subcohort excluding the 25 non-MPE samples for setting copy number standards, which demonstrated 54.1% sensitivity, 80.8% specificity, 71.7% accuracy, and an AUC of 0.851.ConclusionIn summary, we exploited the value of human and non-human sequencing reads generated from mNGS, which showed promising ability in simultaneously detecting TBP and MPE.

B-086 High Precision T Cell Testing Using the T-SPOT Technology: Improved Cell Yields From Lower Volumes of Blood When the T-SPOT Technology is Used With the T-Cell Select Reagent Kit for Cell Isolation

Abstract Background T cells play a critical role in protecting humans from disease, and are a powerful diagnostic tool when used to measure immune responses to infection. However, the use of T cells in a clinical setting has been limited due to challenges associated with T cell testing methodologies. One of the key challenges has been the ability to scale up T cell testing to meet the needs of clinical laboratories. The T-SPOT technology is most widely known for the T-SPOT.TB test, an Interferon-Gamma Release Assay (IGRA) diagnostic test based on the detection of Mycobacterium tuberculosis-specific effector T cells using a single cell resolution platform (ELISPOT). The conventional method of running the T-SPOT.TB test was to use density gradient isolation on 6 mL of whole blood to isolate peripheral blood mononuclear cells (PBMCs) for high precision T cell testing. However, this testing was not accessible to some clinical laboratories due to the hands-on time associated with isolating PBMCs from whole-blood. The T-Cell Select reagent kit was developed to positively select mononuclear cells and enhance cell separation efficiency for the T-SPOT technology. The T-Cell Select reagent kit offers the opportunity to automate the T-SPOT technology which improves scalability and reliability, but it also means that an improved cell yield can be achieved from a lower volume of blood. This makes high precision T cell testing more accessible, whilst maintaining the high sensitivity and specificity of the T-SPOT technology. Methods PBMCs from 242 samples were isolated from 6 mL of whole blood, and were processed according to the T-SPOT.TB test package insert for density gradient isolation. Matched samples were used to isolate PBMCs from 3.5 mL of whole blood using magnetic bead-based positive selection according to the T-Cell Select reagent kit package insert. Results Cell yields were compared using matched samples for density gradient and the T-Cell Select reagent kit isolated cells. Cell count means were 6.6 vs 6.7 × 10^6 cell/mL for the T-Cell Select reagent kit and density gradient isolation methods, respectively. Of the 242 samples tested, two samples had insufficient yields to run the T-SPOT.TB test with the density gradient method, whilst the T-Cell Select reagent kit isolated sufficient numbers from all samples. Results of the T-SPOT.TB test had an overall agreement between the two methods of 97%, negative agreement 99% and positive agreement 94%. Conclusion When used with the T-SPOT technology, the T-Cell Select reagent kit provides an improved cell isolation methodology, requiring up to 50% lower blood volumes, and reducing the hands-on time associated with T cell testing. This makes T cell testing more accessible to labs, meaning that fewer blood samples need to be redrawn due to low cell numbers, providing an advantage in the immunosuppressed.

Influence of age, IGRA results, and inflammatory markers on mortality in hospitalized tuberculosis patients

IntroductionTuberculosis (TB) remains a leading cause of death globally. Identifying the factors associated with mortality during hospitalization for TB is crucial for improving patient outcomes. This study aimed to investigate the potential risk factors, including T-SPOT.TB test results and routine laboratory markers of inflammation, associated with death during hospitalization due to TB. MethodsA retrospective analysis was conducted on 244 hospitalized TB patients. Demographic data, clinical characteristics, T-SPOT.TB results, and laboratory parameters were collected. Univariate and multivariate analyses were performed to identify independent risk factors for in-hospital mortality. ResultsAmong the patients, 206 survived and 38 died during hospitalization. Multivariate analysis revealed that age (HR: 1.08, 95% CI: 1.02–1.15, p = 0.001), a negative T-SPOT.TB test result (HR: 4.01, 95% CI: 1.78–9.01, p < 0.001), elevated C-reactive protein (CRP) levels (HR: 1.04, 95% CI: 1.01–1.08, p = 0.007), and increased neutrophil-to-lymphocyte ratio (NLR) (HR: 1.04, 95% CI: 1.00–1.07, p = 0.025) were independent risk factors for mortality. ConclusionsThis study identified age, a negative T-SPOT.TB result, elevated CRP levels, and a high NLR as significant independent risk factors for death in hospitalized TB patients. These findings underscore the importance of these parameters in the risk stratification and management of hospitalized TB patients. Further research is warranted to elucidate the mechanisms behind these associations and to validate these results in different populations.

Use of stool swabs in molecular transport media increases access to Xpert Ultra testing for TB in children.

SETTING: Tertiary level hospital in Lusaka, Zambia.OBJECTIVE: To measure concordance between Xpert® MTB/RIF Ultra (Ultra) results of stool with and without transport media, and compare Ultra results from the two stool processing methods to Ultra and culture results using gastric aspirates (GA).DESIGN: This was a cross-sectional study collecting stool and GA from children 0-5 years presenting with signs and symptoms of TB. Stool was processed for Ultra testing by two methods: the Simple-One-Step (SOS) on an aliquot of stool and PrimeStore® MTM Molecular Transport Medium (PS-MTM) using a stool swab.RESULTS: A total of 114 children (median age: 17 months, IQR 7-30) provided both a stool and a GA sample. Stool Ultra results processed using the PS-MTM method showed high concordance with stool Ultra results processed by the SOS method, with only 1/114 discordant results. Concordance with GA Ultra was high as well, as 9/13 Mycobacterium tuberculosis (MTB) cases detected were identified by all three methods.CONCLUSION: Ultra results from stool swabs collected using PS-MTM were equivalent to results from stool using the SOS method and GA. Given that PS-MTM inactivates MTB and stabilises DNA without cold chain, using it for stool has the potential to increase access to a TB diagnosis for children in underserved areas.

MHealth to improve implementation of TB contact investigation: a case study from Uganda

BackgroundImplementation science offers a systematic approach to adapting innovations and delivery strategies to new contexts but has yet to be widely applied in low- and middle-income countries. The Fogarty Center for Global Health Studies is sponsoring a special series, “Global Implementation Science Case Studies,” to address this gap.MethodsWe developed a case study for this series describing our approach and lessons learned while conducting a prospective, multi-modal study to design, implement, and evaluate an implementation strategy for TB contact investigation in Kampala, Uganda. The study included formative, evaluative, and summative phases that allowed us to develop and test an adapted contact investigation intervention involving home-based sample collection for TB and HIV testing. We concurrently developed a multi-component mHealth implementation strategy involving fingerprint scanning, electronic decision support, and automated reporting of test results via text message. We then conducted a household-randomized, hybrid implementation-effectiveness trial comparing the adapted intervention and implementation strategy to usual care. Our assessment included nested quantitative and qualitative studies to understand the strategy’s acceptability, appropriateness, feasibility, fidelity, and costs. Reflecting on this process with a multi-disciplinary team of implementing researchers and local public health partners, we provide commentary on the previously published studies and how the results influenced the adaptation of international TB contact investigation guidelines to fit the local context.ResultsWhile the trial did not show improvements in contact investigation delivery or public health outcomes, our multi-modal evaluation strategy helped us identify which elements of home-based, mHealth-facilitated contact investigation were feasible, acceptable, and appropriate and which elements reduced its fidelity and sustainability, including high costs. We identified a need for better tools for measuring implementation that are simple, quantitative, and repeatable and for greater attention to ethical issues in implementation science.ConclusionsOverall, a theory-informed, community-engaged approach to implementation offered many learnings and actionable insights for delivering TB contact investigation and using implementation science in low-income countries. Future implementation trials, especially those incorporating mHealth strategies, should apply the learnings from this case study to enhance the rigor, equity, and impact of implementation research in global health settings.

P016 To rescreen or not to rescreen, that is the question: an evaluation of practice of rescreening for infections when switching advanced therapies in rheumatology patients

Abstract Background/Aims The 2018 British Society for Rheumatology guidelines mandate pre-treatment screening for infections (including tuberculosis [TB], viral hepatitis and HIV) in patients prior to treatment initiation with advanced therapies. It is increasingly common for patients to switch advanced therapies due to inefficacy or intolerance. There is no established guideline stipulating the frequency of rescreening patients for infections when switching advanced therapies. Rescreening is expensive and can delay the prescribing process. This audit reviewed the current practice at a single tertiary rheumatology centre. Methods A retrospective case note analysis of 100 consecutive patients who underwent biologic switch between April 2021 to March 2022 was included. Data extraction included patient demographics, rheumatic diagnosis, drug exposures, co-morbidities including past infections and rescreening tests were undertaken (including T-SPOT.TB, chest X-ray and serological tests for hepatitis B, C and HIV). Results The median age of this cohort (64 female, 36 male) was 53 (IQR 41 - 60). The most common diagnosis was rheumatoid arthritis (n = 62), followed by psoriatic arthritis (n = 27) and ankylosing spondylitis (n = 7). Seven patients were identified as high-risk individuals: two patients with hepatitis B, one with latent TB, one with previous positive TSPOT.TB and three with underlying lung diseases. 69 patients were partially rescreened for infections and 21 patients had a complete re-screen including chest X-ray, TSPOT.TB, HIV serology, HBsAg, Anti-HbC and Anti HCV. 31 patients did not have any re-screening tests when switching to a different biological drug. The range since the previous pre-advanced therapy screening was between 6 months and 5 years. There was no significant difference in the rate of rescreening investigations between those who switched drugs within the same class, versus those switching drug classes (p = 0.874). No new infections, active or latent, were identified on rescreening. The total cost involved in rescreening this cohort of patients was estimated at £5930. Conclusion Our audit data showed that rescreening for infections at 18 months or less has a low yield for identifying new incident infections. The decision to rescreen patients was primarily driven by the clinician’s judgement. It is pertinent to standardise the practice by establishing an evidence-based guideline based on a robust risk assessment which may then lead to long-term cost-savings. Disclosure A. Masood: None. Y. Xiang: None. S. Rose-Hartwell: None. S. Subesinghe: None.

Bidirectional screening and testing for TB and COVID-19 among outpatient department attendees: outcome of an initial intervention in Ghana

BackgroundTuberculosis (TB) remains a major public health threat in Ghana. The impact of COVID-19 resulted in a 15% decline of TB case notification in 2020 compared to 2019. To mitigate the impact on TB services, the Ghana National Tuberculosis Programme (NTP) introduced the bidirectional screening and testing for TB and COVID-19 in 2021.ObjectiveTo evaluate the yield of bidirectional screening and testing for TB and COVID-19 among facility attendees in the Greater Accra region.MethodWe used secondary data obtained from the initial implementation stage of the bidirectional testing for TB and COVID-19 among COVID-19 and/or TB presumed cases in five health facilities in the Greater Accra Region from January to March 2021. To mitigate the impact of COVID-19 on TB services and accelerate TB case detection, the NTP of Ghana introduced bidirectional screening and testing for TB and COVID-19 in Greater Accra Region before scaling up at national level.ResultsA total of 208 presumed TB or COVID-19 cases were identified: 113 were tested for COVID-19 only, and 94 were tested for both TB and COVID-19, 1 was tested for TB only. Among presumed cases tested for COVID-19, 9.7% (95% CI, 5.6-13.7%) were tested positive. Whilst among the total presumed tested for TB, 13.7% (95% CI, 6.8-20.6%) were confirmed to have TB. Among the total 94 presumed cases tested for both TB and COVID-19, 11.7% (95% CI, 5.2-18.2%) were confirmed to have TB and 13.8% (95% CI, 6.9-20.8%) participants were COVID-19 positive and one participant (1.1%) had both COVID-19 and TB.ConclusionBidirectional screening and testing for TB and COVID-19 shows significant potential for improving overall case detection for the two diseases. The bidirectional screening and testing could be applicable to address a similar respiratory epidemic in the future that might have a masking effect on the response to TB disease.

Diabetes-related tuberculosis strains from PIMS Hospital Islamabad pulmonology department qualitative, cross-sectional, and observational study

Background: Tuberculosis is one of the most common infectious diseases that patients with DM get because of their weakened immune systems. Objective: The purpose of this study was to identify the prevalence of different types of active tuberculosis among individuals with diabetes. Methodology: The Department of Pulmonology at PIMS Hospital Islamabad, which was done from January 2021 to January 2022, employed cross-sectional, observational, and qualitative techniques studied in this inquiry. Inquiries were conducted in pulmonology department outpatient clinics with patients with diabetes who satisfied the inclusion criteria (cough with or without expectoration, hemoptysis, persistent fever, and unexplained weight loss) (OPDs). All instances of immunological compensation and secondary diabetes, as well as short duration of diabetes, age less than 10 and more than 85, were disregarded. After approval was gained, a comprehensive history, clinical examination, and testing were carried out to investigate the potential of TB. SPSS version 26 was used to import all the data for further analysis. Of of the 545 patients that were questioned, 149 were selected for further TB testing. Just 18 people had active TB, according to the data (12 per cent).

Diagnosis of Chest Wall Tuberculosis Using Fine Needle Aspiration: A Single-Center Experience.

Minimally invasive diagnosis of chest wall tuberculosis remains a challenge. Fine needle aspiration (FNA) is a simple and safe method of sampling. However, previous studies have shown that conventional tuberculosis tests had poor diagnostic performance in the needle aspirates. With the popularization of molecular detection application, the value of FNA in the diagnosis of chest wall tuberculosis needs to be reevaluated. We retrospectively studied patients with suspected chest wall tuberculosis at admission who underwent FNA for diagnosis and reported the diagnostic efficacy of acid-fast bacilli smear, mycobacterial culture, cytology and Xpert MTB/RIF (GeneXpert) when testing FNA specimens. A composite reference standard (CRS) was used as the diagnostic gold standard for this study. Among 89 included FNA specimens, acid-fast bacilli smear, mycobacterial culture, and GeneXpert were positive in 15 (16.85%), 23 (25.8%), and 61 (68.5%), respectively. Thirty-nine (43.8%) had cytologic features suggestive of tuberculosis. According to CRS, 75 (84.3%) cases were categorized as chest wall tuberculosis, 14 (15.7%) were not diagnosed with tuberculosis. Using CRS as the gold standard, acid-fast bacilli smear, mycobacterial culture, cytology and GeneXpert exhibited sensitivity of 20%, 30.7%, 52% and 81.3%, respectively. Specificity in these four tests was found to be 100%. Sensitivity of GeneXpert was significantly higher than that of smear, culture and cytology, X 2=66.3, p<0.001. GeneXpert achieved higher sensitivity as compared to cytology and conventional TB tests in the chest wall FNA specimens. Theimplementation of GeneXpert may increase the diagnostic efficacy of FNA in the diagnosis of chest wall TB.

Prevalence of hepatitis B virus (HBV) and latent tuberculosis co-infection and risk of drug-induced liver injury across two large HBV cohorts in the United States.

The epidemiology of latent tuberculosis and hepatitis B virus (HBV-LTBI) co-infection among U.S. populations is not well studied. We aim to evaluate LTBI testing patterns and LTBI prevalence among two large U.S. cohorts of adults with chronic HBV (CHB). Adults with CHB in the Chronic Hepatitis Cohort Study (CHeCS) and Veterans Affairs national cohort were included in the analyses. Prevalence of HBV-LTBI co-infection was defined as the number of HBV patients with LTBI divided by the number of HBV patients in a cohort. Multivariable logistic regression evaluated odds of HBV-LTBI co-infection among CHB patients who underwent TB testing. Among 6019 CHB patients in the CHeCS cohort (44% female, 47% Asian), 9.1% were tested for TB, among whom 7.7% had HBV-LTBI co-infection. Among HBV-LTBI co-infected patient, only 16.7% (n=7) received LTBI treatment, among whom 28.6% (n=2) developed DILI. Among 12,928 CHB patients in the VA cohort (94% male, 42% African American, 39% non-Hispanic white), 14.7% were tested for TB, among whom 14.5% had HBV-LTBI. Among HBV-LTBI co-infected patient, 18.6% (n=51) received LTBI treatment, among whom 3.9% (n=3) developed DILI. Presence of cirrhosis, race/ethnicity, and country of birth were observed to be associated with odds of HBV-LTBI co-infection among CHB patients who received TB testing. In summary, among two large distinct U.S. cohorts of adults with CHB, testing for LTBI was infrequent despite relatively high prevalence of HBV-LTBI co-infection. Moreover, low rates of LTBI treatment were observed among those with HBV-LTBI co-infection.

Evaluation of the specificity of an intradermal test with recombinant tuberculosis allergen in Bacillus Calmette-Guérin-vaccinated healthy volunteers.

The tuberculin skin test has significant limitations for use in individuals vaccinated with BCG. The presence in the genome of Mycobacterium tuberculosis of the RDI region, which is absent in the genome of Mycobacterium bovis BCG and most non-tuberculous mycobacteria, made it possible to develop new skin tests, which include a skin test with a recombinant tuberculosis allergen [RTA (Diaskintest®, JSC Generium, Russia)]. Diaskintest has shown high diagnostic performance in clinical trials and in conditions of high prevalence of tuberculosis infection. In 2021, the Russia was excluded from the WHO list of high TB burden countries, which makes relevant an assessment of the specificity of the RTA test under conditions of low epidemiologic risk for tuberculosis to confirm the high specificity of the test. To assess the specificity of Diaskintest in the regions of the Russian Federation with low epidemiologic risk for tuberculosis. A multicenter, open-label, prospective study was conducted, which included 150 healthy volunteers aged 18-30 years old, vaccinated with BCG, who were not at risk of tuberculosis, from regions with low epidemiologic risk (Oryol region, Ryazan region, and Arkhangelsk region). During the study, 4 visits were scheduled for each participant: [Visit 0 (screening), Visit 1, Visit 2 (in 72 h) and Visit 3 (in 28 days)]. All participants, who excluded active and latent tuberculosis infection, underwent a test with RTA. To assess the safety of RTA tests, all systemic and local adverse events that occurred during 28 days were recorded. The trial was filed in the NIH clinical trials database ClinicalTrials.gov (NCT05203068). In individuals with a negative T-SPOT.TB test, the specificity of the RTA test was 97% (95% CI: 92-99%) with a cut-off of >0 mm. The study findings confirm data 2009: 100.00 (95% CI: 94-100). When evaluating the safety of the RTA test during 28 days of follow-up, the participants did not report local and systemic adverse reactions that had a causal relationship with the RTA test. Diaskintest is highly specific and safe, therefore it is a valuable tool as a screening test for early detection of tuberculosis.

Cross-municipality migration and spread of tuberculosis in South Africa

Human migration facilitates the spread of infectious disease. However, little is known about the contribution of migration to the spread of tuberculosis in South Africa. We analyzed longitudinal data on all tuberculosis test results recorded by South Africa’s National Health Laboratory Service (NHLS), January 2011–July 2017, alongside municipality-level migration flows estimated from the 2016 South African Community Survey. We first assessed migration patterns in people with laboratory-diagnosed tuberculosis and analyzed demographic predictors. We then quantified the impact of cross-municipality migration on tuberculosis incidence in municipality-level regression models. The NHLS database included 921,888 patients with multiple clinic visits with TB tests. Of these, 147,513 (16%) had tests in different municipalities. The median (IQR) distance travelled was 304 (163 to 536) km. Migration was most common at ages 20–39 years and rates were similar for men and women. In municipality-level regression models, each 1% increase in migration-adjusted tuberculosis prevalence was associated with a 0.47% (95% CI: 0.03% to 0.90%) increase in the incidence of drug-susceptible tuberculosis two years later, even after controlling for baseline prevalence. Similar results were found for rifampicin-resistant tuberculosis. Accounting for migration improved our ability to predict future incidence of tuberculosis.

A Comparative study between the two interferon gamma releasing assays in the diagnosis of pulmonary tuberculosis

Objectives: To examine and compare the diagnostic value of Interferon gamma releasing assay (IGRAs) (T- SPOT TB and Qunati FERON Gold in Tube) in the diagnosis of pulmonary tuberculosis.&#x0D; Materials and methods: The study included 40 patients with active pulmonary tuberculosis. They were attendance of Respiratory Health Care Centers in Mosul City for the period from March to December 2013. From each patient a sputum sample was collected and processed for culture on Löwenstein-Jensen (L-J media). Twelve milliliters (ml) of blood from each patients was collected (10 ml collected in heparinised tube for T SPOT TB and 2 ml in QFT-GIT special tubes)&#x0D; Results: From the total 40 patients with positive AFB staining 37 (92.5%) were culture positive. The specificity of both IGRAs were 100% . The sensitivity of T- SPOT TB test was 91.89%, while the QFT-GIT sensitivity was 86.49%. The positive predictive value of both IGRAs was 100%. The negative predictive value of T SPOT TB was 50 %, while that of QFT-GIT was 37.5 %. There was a moderate degree of agreement between the T -SPOT TB and QFT–GIT in (82.5%, k=0.54, 95%CI). The results of the two IGRAs are not affected by BCG vaccination status of TB patients.&#x0D; Conclusions: The IGRAs could provide a supplementary information as part of diagnostic work-up for tuberculosis diagnosis but it is important to note that a negative IGRA does not rule out active TB . Moreover, and of the two IGRAs, QFT GIT is more convenient to adopted for diagnostic use.

Factors associated with false-negative for T-SPOT.TB in patients with TB disease

BACKGROUND:: T-SPOT.TB is an adjunctive diagnostic tool that is used for detecting TB disease. However, in some patients with TB disease, a false-negative result can occur. This study aims to determine the factors that are associated with false-negative T-SPOT.TB results in TB disease.METHODS:: We retrospectively enrolled 210 patients who were diagnosed with TB disease and underwent T-SPOT.TB testing between July 2014 and July 2020 at Ramathibodi Hospital Bangkok, Thailand. Clinical characteristics, laboratory findings and radiographic findings were compared between the false-negative and true-positive T-SPOT.TB groups.RESULTS:: Among 210 patients with TB disease, 144 patients had pulmonary TB, 44 patients had extrapulmonary TB and 22 patients had concomitant pulmonary and extrapulmonary TB. There were 100 male and 110 female patients, with a mean age of 54.1 ± 17.5 years. Ninety patients (42.9%) had false-negative T-SPOT.TB results. Multivariate analysis showed that increased age was significantly associated with false-negative T-SPOT.TB (OR 1.025, 95% CI 1.008-1.043, P = 0.006). Those aged ≥55 years had 1.8 times higher false-negative T-SPOT.TB rate than the younger group (age ≥55 years: 64.4% vs. age <55 years: 35.6%; P = 0.001).CONCLUSION:: Advanced age, particularly age ≥55 years, was a significant factor that related with false-negative T-SPOT.TB results in TB disease.

Frequency of Newly Diagnosis Patients of T2DM and COPD in the Department of Pulmonology at HMC Hospital Peshawar a Qualitative, Cross-Sectional, and Observational Study

Background: Since the immune system weakens in people with DM, Tuberculosis is one of the most prevalent infectious diseases . Objective: This study aimed to determine the prevalence of various forms of active Tuberculosis among people with diabetes. Methodology: This Cross-sectional, observational, and qualitative methods were use din this investigation. Patients with diabetes whom et the inclusion criteria (cough with or without expectoration, hemoptysis, persistent fever, and unexplained weight loss) were questioned in one of three pulmonology department outpatient clinics (OPDs). The short duration of diabetes, ageless than ten and more than 85 years, and all cases of immune compensation and secondary diabetes were excluded. When looking in to the possibility of TB, a thorough history, clinical exam, and tests were performed once permission was obtained. All of the information was loaded into SPSS version 24 for further analysis As a result, 151 people were chosen for further testing for TB out of a total of 550 patients questioned. Active TB was found in just 19 individuals (13percent).The mean age was5 2.03±10.01,the male-to-female ratio was01.08:01.04,and the mean duration of diabetes observed was 10.04years. All were type 2 diabetics exception which turned out to be type 01. Out of the total cases of Tuberculosis, 54% were determined to be pulmonary cases and45% were extrapulmonary cases. Pulmonary cancer had an 11% primary rate, an 18% secondary rate, and a 6% milliary rate. Smear positivity was identified in 57% of patients, and multidrug-resistant Tuberculosis was discovered in 21%, about twice the rate seen in non-diabetic cases. Results: As a result, 151 people were chosen for further testing for TB, and 550 patients were questioned. Active TB was found in just 19 individuals (13 per cent). The mean age was 52.03 ±10.01, the male-to-femaleratiowas01.08:01.04,and the mean duration of diabetes observed was 10.04 years. All were type 2 diabetics except one which turned out to be type 01. Out of the total cases of Tuberculosis, 54% were determined to be pulmonary cases and 45% were extra pulmonary cases. Pulmonary cancer had an11%primary rate,and 18% secondary rate, and a 6%milliaryrate.Smear positivity was identified in 57% of patients, and multidrug-resistant Tuberculosis was discovered in 21%,about twice the rate seen in non diabetic cases. Conclusion: Tuberculosis frequency is more prevalent in people with diabetes than in the general population. Extrapulmonary Tuberculosis occurs more often in people with diabetes compared to those without the disease. Diabetics should be screened more often for the illness so that MDR-TB doesn't spread and become a major public health issue in this underdeveloped nation. Keywords: Diabetes, pulmonary Tuberculosis, extra-pulmonary Tuberculosis, tuberculosis variants, drug-resistant Tuberculosis

The integration of tuberculosis and HIV testing on GeneXpert can substantially improve access and same-day diagnosis and benefit tuberculosis programmes: A diagnostic network optimization analysis in Zambia.

Diagnostic network optimization (DNO), a geospatial optimization technique, can improve access to diagnostics and reduce costs through informing policy-makers' decisions on diagnostic network changes. In Zambia, viral load (VL) testing and early infant diagnosis (EID) for HIV has been performed at centralized laboratories, whilst the TB-programme utilizes a decentralized network of GeneXpert platforms. Recently, the World Health Organization (WHO) has recommended point-of-care (POC) EID/VL to increase timely diagnosis. This analysis modelled the impact of integrating EID/VL testing for children and pregnant/breastfeeding-women (priority-HIV) with TB on GeneXpert in Zambia. Using OptiDx, we established the baseline diagnostic network using inputs for testing demand (October 2019-September 2020), referrals, testing sites, testing platforms, and costs for HIV/TB testing (transport, test, device) respectively in Zambia. Next, we integrated priority-HIV testing on GeneXpert platforms, historically only utilized by the TB-programme. 228,265 TB tests were conducted on GeneXpert devices and 167,458 (99%) of priority-HIV tests on centralized devices at baseline, of which 10% were tested onsite at the site of sample collection. With integration, the average distance travelled by priority-HIV tests decreased 10-fold (98km to 10km) and the proportion tested onsite increased (10% to 48%). 52% of EID tests are likely to be processed within the same-day from a baseline of zero. There were also benefits to the TB-programme: the average distance travelled/specimen decreased (11km to 7km), alongside potential savings in GeneXpert device-operating costs (30%) through cost-sharing with the HIV-programme. The total cost of the combined testing programmes reduced marginally by 1% through integration/optimization. DNO can be used to strategically leverage existing capacity to achieve the WHO's recommendation regarding POC VL/EID testing. Through DNO of the Zambian network, we have shown that TB/HIV testing integration can improve the performance of the diagnostic network and increase the proportion of specimens tested closer to the patient whilst not increasing costs.

Discovery of Novel Transketolase Epitopes and the Development of IgG-Based Tuberculosis Serodiagnostics.

Despite advances in rapid molecular techniques for tuberculosis (TB) diagnostics, there is an unmet need for a point-of-care, nonsputum-based test. Previously, through a T7 phage antigen display platform and immunoscreening, we identified that the serum IgGs of active TB patients differentially bind to several antigen-clones and that this immunoreactivity discriminates TB from other respiratory diseases. One of these high-performance clones has some homology to the transketolase of Mycobacterium tuberculosis (M.tb TKT). In this study, we developed a direct enzyme-linked immunosorbent assay (ELISA) detecting IgG against the TKT antigen-clone (TKTμ). Through sequence alignment and in silico analysis, we designed two more peptides with potential antigenicity that correspond to M.tb-specific transketolase (M.tb TKT1 and M.tb TKT3) epitopes. After the development and standardization of a direct peptide ELISA for three peptides, we tested 292 subjects, including TB (n = 101), latent tuberculosis infection (LTBI) (n = 49), healthy controls (n = 66), and sarcoidosis (n = 76). We randomly assigned 60% of the subjects to a training set to create optimal models to distinguish positive TB samples, and the remaining 40% were used to validate the diagnostic power of the IgG-based assays that were developed in the training set. Antibodies against M.tb TKT3 yielded the highest sensitivity (0.845), and these were followed by TKTμ (0.817) and M.tb TKT1 (0.732). The specificities obtained by TKTμ, M.tb TKT3, and M.tb TKT1 on the test sets were 1, 0.95, and 0.875, respectively. The model using TKTμ obtained a perfect positive predictive value (PPV) of 1, and this was followed by M.tb TKT3 (0.968) and M.tb TKT1 (0.912). These results show that IgG antibodies against transketolase can discriminate active TB against LTBI, sarcoidosis, and controls. IMPORTANCE There is an unmet need for a point-of-care, nonsputum-based TB test. Through the immunoscreening of a novel T7 phage library, we identified classifiers that specifically bind to IgGs in active TB sera. We discovered that one of these clones is aligned with Mycobacterium tuberculosis transketolase (TKT). TKT is an essential enzyme for Mycobacterium tuberculosis growth. We designed three TKT epitopes (TKTμ, TKT1, and TKT3) to detect TKT-specific IgGs. After the development and standardization of three different ELISA-utilizing TKT peptides, we tested 292 subjects, including active TB, LTBI, healthy controls, and sarcoidosis. Rigorous statistical analyses using training and validation sets showed that ELISA-based detections of specific IgGs against TKT3 and TKTμ have the greatest sensitivity, specificity, and accuracy to distinguish active TB subjects from others, even LTBI. Our work provides a novel scientific platform from which to further develop a point-of-care test, thereby aiding in faster TB diagnoses.