Tuberculosis Testing Research Articles

P-2108. Risk Factors for Indeterminate Tuberculosis (TB) Testing Results Among Immunocompromised Children in an Area of Low TB Endemicity

Abstract Background Tumor necrosis factor α inhibitors (TNFαi) are immunosuppressants used to treat autoimmune (AI) conditions and inflammatory bowel disease (IBD). TNFαi initiation requires tuberculosis infection (TBI) screening, often performed by interferon-γ release assays (IGRA) including the QuantiFERON Gold Plus (QFT) and T-SPOT.TB (T-SPOT). The rate of and risk factors for indeterminate (IND) testing results, as well as the optimal TBI screening assay, among immunocompromised children (ICC) with AI or IBD in an area of low TB endemicity remain poorly defined. We performed a retrospective analysis of QFT testing at our institution to identify rates of and risk factors for IND results. We also prospectively evaluated the performance of QFT versus T-SPOT in an area of low TB endemicity. Methods A retrospective analysis of children (ages 0-21 years) with AI or IBD on immunosuppression cared for at Nationwide Children’s Hospital (NCH) from 1/2010-12/2023 who underwent TBI screening with QFT. Patients were excluded if they had prior TBI, BCG vaccine, and organ or stem cell transplant. Demographic, laboratory results, and medication history were recorded. Prospectively, QFT-eligible patients were consented for concurrent testing utilizing the T-SPOT test, run in parallel. Single variable statistical analysis was performed. Results 662 patients (372 (56.2%) male) had 2011 unique QFT tests performed. 148 patients (22.4%) had a total 191 (9.5%) IND QFT result at any time in the study interval. Younger age, lower absolute lymphocyte counts (ALC), and corticosteroid exposure at testing were observed more frequently in those with IND QFT results [TABLE 1]. At an interim assessment of the prospective study, 117 patients underwent tandem screening by QFT and T-SPOT; 5 total IND results were observed [QFT (n=4), T-SPOT (n=1)] [TABLE 2]. Conclusion Younger age, lower ALC, and corticosteroid exposure at time of testing were observed more frequently in those with IND QFT results. While interim assessment of T-SPOT vs. QFT does not yield a difference, this may be driven by a high proportion of individuals with adequate disease control. Ongoing prospective assessment may better define an optimal screening IGRA assay for TBI among ICC with AI or IBD in an area of low TB endemicity. Disclosures Jennifer L. Dotson, MD, MPH, Pfizer: Grant/Research Support Christopher Ouellette, MD, Oxford Immunotec: Grant/Research Support|UpToDate: Royalties

P-770. Impact of parallel use of low-complexity automated nucleic acid amplification tests and urine lateral flow lipoarabinomannan assays to detect tuberculosis in people living with HIV

Abstract Background Tuberculosis (TB) is the leading cause of death in people living with HIV (PWH). Missed and delayed TB diagnoses in PWH lead to worse outcomes. The World Health Organization (WHO) recommends the use of low-complexity automated nucleic acid amplification tests (LC-aNAAT) as the initial diagnostic test for TB and urine lateral flow lipoarabinomannan assays (LF-LAM) to assist with TB diagnosis in PWH. This systematic review assesses the impact of parallel use of respiratory sample LC-aNAAT and urine LF-LAM in PWH on patient-important outcomes.Table 1.Comparison of mortality in randomized trials evaluating interventions that included respiratory LC-aNAATs and urine LF-LAM in adult inpatients with HIV . Methods We searched multiple databases up to 3 November 2023. Eligible studies were randomized trials that allocated PWH to parallel LC-aNAAT and LF-LAM testing or LC-aNAAT alone or LF-LAM alone. We used a standardized form to extract data on mortality, proportion diagnosed with TB, proportion treated with TB and time to diagnosis and treatment. We assessed study quality using Cochrane Risk of Bias tools. Outcome measurement used random-effects meta-analysis to estimate pooled risk ratios with 95% confidence intervals.Figure 1.Impact of interventions that included respiratory LC-aNAATs and urine LF-LAM on mortality in adult inpatients with HIV Results After 457 articles were screened, three randomized trials were included, all of which were conducted in inpatient settings in sub-Saharan Africa, with 4602 adult participants (Table 1). Risk-of-bias was low. The effect of parallel testing with respiratory LC-aNAAT and urine LF-LAM on mortality in PWH at eight weeks compared to testing with LC-aNAAT alone was uncertain (risk ratio 0.93; 95% CI 0.74 to 1.17) (Figure 2). Parallel testing may increase the proportion of patients with a confirmed TB diagnosis (pooled RR: 3.06, 95% CI 1.82 to 5.16) (Figure 3) and the proportion treated for TB (pooled RR: 1.47, 95% CI 1.25 to 1.73) (Figure 4) compared to LC-aNAAT alone. Time-to-treatment was shorter for the parallel testing group compared to the LC-aNAAT group in two trials and similar in the third.Figure 2.Impact of interventions that included respiratory LC-aNAATs and urine LF-LAM on the proportion of adult inpatients with HIV and with a confirmed tuberculosis diagnosis. Conclusion In inpatient settings, the effect of parallel use of LC-aNAAT and LF-LAM on mortality in PWH at eight weeks was uncertain. Parallel testing may increase the proportion of PWH diagnosed with TB and treated for TB. There was no data on children or outpatient settings. Evidence is limited by heterogeneity in implementation approaches in included trials and contextual differences that included the effects of the COVID pandemic on one trial.Figure 3.Impact of respiratory LC-aNAATs and urine LF-LAM on the proportion of adult inpatients with HIV treated for tuberculosis. Disclosures Laura Olbrich, PHD candidate, Cepheid: received Xpert MTB/Rif ultra cartridges for free Maunank Shah, MD, PhD, Scene Health: Royalties for license

P-2101. Coverage Of The Molecular Diagnostic Technology For Pulmonary Tuberculosis In Bangladesh: Diagnostic Milestone For Control Of Tuberculosis

Abstract Background Provision of early and accurate Tuberculosis (TB) diagnosis is crucial to end TB specially in a densely populated like Bangladesh. Molecular WHO-approved rapid diagnostic tests for TB (mWRDs) can significantly improve identification of undiagnosed TB cases. This study estimates the coverage of mWRDs among the total detected Pulmonary TB (PTB). Methods Monthly programmatic data on nationwide TB diagnosis in Bangladesh using mWRDs were pulled and compiled. Routine programmatic data for TB detection using mWRDs were segregated and compared quarterly for the first three quarter of 2023 to know the percentage of molecular testing coverage among presumptive TB tested and percentage of pulmonary TB notified diagnosed through molecular testing during that time. Results A total of 5,53,172 presumptive cases undergone mWRDs to detect the Mycobacterium Tuberculosis (MTB) and Rifampicin Resistant (RR) cases. Among them, 80,414 (14.54%) cases were detected as MTB including RR. During the 1st, 2nd, and 3rd quarters of 2023, the total number of presumptive tests conducted were 133,845, 175,038, and 244,289, respectively. Among them, the detected TB cases according to each quarter were 15,418 (11.52%), 24,397 (13.94%), and 40,599 (16.62%), respectively (Figure 1). With this data it was obvious that in the 3rd quarter of 2023 the percentage of case detection by mWRDs increased compared to the consecutive previous two quarters. It revealed that, percentage of case detection by mWRDs gradually increased over the time during 1st to 3rd quarter 2023. To assess the coverage of mWRDs, quarterly data was analyzed and compared. It was determined how many TB cases were confirmed using molecular technology (GeneXpert and TrueNat) out of the total number of pulmonary cases over time. The analysis revealed that the quarterly percentage coverage of mWRDs was 26.85%, 42.68%, and 68.89% during the 1st, 2nd, and 3rd quarters, respectively, indicating an increasing trend over time (Figure 2). Conclusion Scaling up the mWRDs as a point of care diagnostic test for presumptive TB cases in resource limited settings would have a significant impact to meet the SDG and End TB strategy for TB detection. Increasing coverage of molecular testing for more PTB case detection is inevitable considering the context of Bangladesh. Disclosures All Authors: No reported disclosures

P-354. Clinical Utility of Tuberculosis Screening Tests After Tuberculosis Exposure at an Infusion Clinic

Abstract Background Tuberculin skin testing (PPD) and interferon gamma release assays (IGRA) facilitate screening of patients exposed to active tuberculosis (TB), but the clinical utility of TB screening tests in determining management of exposed high-risk patients is not well described. Because the sensitivity of TB screening tests is dependent on patient’s immunocompetency, further studies looking at the correlation between exposure, testing, and risk of progression to active TB in immunocompromised patients are needed. This study aims to describe TB testing and TB transmission among a large cohort of immunocompromised patients after a known TB exposure event. Methods Retrospective case series of patients who were exposed to TB as defined by CDC Guidelines, identified through contact tracing reports during exposure period April-July 2019. Local infection control protocol was to assess exposed patients with an IGRA initially, then place a PPD if IGRA was inconclusive. Results During the exposure period, an employee with direct patient care duties at an oncology infusion clinic developed active TB, exposing 443 patients. Of the 443 exposed patients, 57 either passed away prior to testing or declined testing. Of the 386 patients who underwent screening tests, 351 (91%), 23 (6%), and 12 (3%) were IGRA negative, positive, and indeterminate, respectively. Of the 12 IGRA indeterminate patients, 8 (67%) had a negative PPD, 2 (16%) refused PPD testing and a repeat IGRA turned negative, and 2 (16%) passed away without further testing. Of the 23 IGRA positive patients, latent TB infection (LTBI) treatment was given in 16 (70%) patients with 7 patients either declining therapy or passed away. None of the 443 patients developed active TB after a 5 year follow up. Conclusion The results of this study found no TB transmission occurred during a high-risk exposure event involving immunocompromised patients when protocol driven testing, treatment, and follow-up was completed. Although CDC publications report low sensitivities of IGRAs in immunocompromised patients, given the large number of exposed patients, serum testing was a practical choice for initial exposure testing and this study showed successful interventions when paired IGRA-PPD testing was used to risk stratify high-risk patients for LTBI therapy. Disclosures All Authors: No reported disclosures

Diagnostic value of interferon-γ release assay in patients with COPD complicated with pulmonary tuberculosis

BackgroundThe common diagnostic methods for tuberculosis have been showing reduced sensitivity among chronic obstructive pulmonary disease patients. This study was conducted to evaluate and analyse the diagnostic value of an interferon-γ release assay in COPD patients complicated with pulmonary tuberculosis.MethodsA nested case-control study was conducted on 123 COPD patients hospitalized at the Fifth Hospital of Shijiazhuang, Hebei Province, from January 2019 to June 2021. Thirty-one patients with active pulmonary tuberculosis complicated with COPD composed the observation group (Group A), 31 patients with nonactive pulmonary tuberculosis complicated with COPD composed the COPD control group (Group B), and 31 patients with active pulmonary tuberculosis not complicated with COPD composed the non-COPD control group (Group C). An interferon-γ release assay, a purified protein derivative of tuberculin (PPD) test, an anti-tuberculosis antibody test, a test of Mycobacterium tuberculosis by sputum smear microscopy and a test of Mycobacterium tuberculosis by PCR method were used to test patients in each group. The positive detection rates generated from the five test methods were compared and analysed.ResultsIn COPD patients complicated with active pulmonary tuberculosis, the differences in the percentage of patients with positive interferon-γ release between the PPD test, anti-tuberculosis antibody test, Mycobacterium tuberculosis by sputum smear microscopy and PCR test results were statistically significant.ConclusionIn patients with COPD complicated with active pulmonary tuberculosis, the percentage of patients who were positive according to the interferon-γ release assay was higher than that according to the sputum smear microscopy, PCR detection of Mycobacterium tuberculosis in sputum specimen, and detection of anti-tuberculosis antibodies. COPD-related complications did not affect the T-SPOT; the greater the T-SPOT value was, the greater the likelihood of active TB. For patients who are T-SPOT positive but clinically considered to have inactive tuberculosis, regular follow-ups should be performed to observe changes in the patient’s condition.

P0539 Prevalence of QuantiFERON Positivity in Patients with Inflammatory Bowel Disease Eligible for Biological Therapy: Clinical and Demographic Analysis

Abstract Background Inflammatory Bowel Disease (IBD), when treated with biological therapies, increases the risk of infections such as tuberculosis (TB). QuantiFERON-TB Gold (QFT) is a diagnostic tool used to detect latent tuberculosis (LTBI) in immunosuppressed patients. Evaluating the prevalence of QFT positivity in IBD patients who are eligible for biological therapies is of utmost importance. Understanding the prevalence of latent TB in this population will help in implementing better preventive and therapeutic strategies. Methods A cross-sectional and relational study was conducted at the Inflammatory Bowel Disease Clinic of the General Hospital of Mexico “Dr. Eduardo Liceaga,” involving 67 patients diagnosed with IBD and candidates for biological therapy. Clinical and demographic characteristics of each patient were collected, including QuantiFERON-TB Gold (QFTB) results. All patients underwent bacilloscopy, culture, and CRP testing for tuberculosis. For statistical analysis, measures of central tendency (mean and standard deviation) were used for continuous variables, while frequencies and percentages were used for categorical variables. Comparisons between groups were performed using Student’s t-tests for continuous variables and chi-square tests for categorical variables. The analysis was conducted using SPSS statistical software, version 29. Results Of the 67 patients with IBD included in the study, 26.86% tested positive for QFTB. Significant differences were observed in the age at diagnosis (45 ± 16.59 years in positives vs. 35.16 ± 14.64 years in negatives, p < 0.05) and the duration of the disease (12 ± 0.73 months in positives vs. 36 ± 0.64 months in negatives, p < 0.05). Additionally, a higher prevalence of arthralgia was noted in the positive group (61.1% vs. 38.8%, p < 0.05). No significant differences were found in gender, age, type of diagnosis (UC vs. CD), or clinical CRP course of the disease between the groups. All patients underwent bacilloscopy, culture, and testing for tuberculosis, all of which were negative. Patients who began advanced therapies received prophylactic antituberculous treatment. Table 1 shows the clinical and demographic characteristics of the patients included in the study. Conclusion This study found a 26.86% prevalence of QuantiFERON positivity in patients with IBD. The results provide crucial data on the demographic and clinical characteristics of this population, highlighting the importance of latent tuberculosis detection and the implementation of antituberculous prophylaxis before initiating biological therapies. These measures are essential to prevent TB reactivation and improve the clinical management of patients with IBD. References Vajravelu RK, Osterman MT, Aberra FN, Roy JA, Lichtenstein GR, Mamtani R, Goldberg DS, Lewis JD, Scott FI. Indeterminate QuantiFERON-TB Gold Increases Likelihood of Inflammatory Bowel Disease Treatment Delay and Hospitalization. Inflamm Bowel Dis. 2017 Dec 19;24(1):217-226. doi: 10.1093/ibd/izx019. PMID: 29272482; PMCID: PMC7007987. Lai HC, Chang CH, Cheng KS, Chen TW, Tsai YY, Chou JW. QuantiFERON-TB Gold Test Conversion Is Associated with Active Tuberculosis Development in Inflammatory Bowel Disease Patients Treated with Biological Agents: An Experience of a Medical Center in Taiwan. Gastroenterol Res Pract. 2019 Nov 3;2019:7132875. doi: 10.1155/2019/7132875. PMID: 31781198; PMCID: PMC6875270. Calzada-Hernández J, Anton-López J, Bou-Torrent R, Iglesias-Jiménez E, Ricart-Campos S, Martín de Carpi J; Carmen García de Vicuña Muñoz de la Nava; Torrente-Segarra V, Sánchez-Manubens J, Giménez-Roca C, Rozas-Quesada L, Juncosa-Morros MT, Fortuny C, Noguera-Julian A. Tuberculosis in pediatric patients treated with anti-TNFα drugs: a cohort study. Pediatr Rheumatol Online J. 2015 Dec 3;13:54. doi: 10.1186/s12969-015-0054-4. PMID: 26635208; PMCID: PMC4669612. Calzada-Hernández J, Anton J, Martín de Carpi J, López-Montesinos B, Calvo I, Donat E, Núñez E, Blasco Alonso J, Mellado MJ, Baquero-Artigao F, Leis R, Vegas-Álvarez AM, Medrano San Ildefonso M, Pinedo-Gago MDC, Eizaguirre FJ, Tagarro A, Camacho-Lovillo M, Pérez-Gorricho B, Gavilán-Martín C, Guillén S, Sevilla-Pérez B, Peña-Quintana L, Mesa-Del-Castillo P, Fortuny C, Tebruegge M, Noguera-Julian A. Dual latent tuberculosis screening with tuberculin skin tests and QuantiFERON-TB assays before TNF-α inhibitor initiation in children in Spain. Eur J Pediatr. 2023 Jan;182(1):307-317. doi: 10.1007/s00431-022-04640-3. Epub 2022 Nov 5. PMID: 36335186; PMCID: PMC9829583.

Performance evaluation of the LIOFeron®TB/LTBI IGRA for screening of paediatric LTBI and tuberculosis

Purpose: High-accuracy diagnostic screening tests for Mycobacterium tuberculosis (MTB) infection are required, primarily to detect patients with latent infections (LTBIs) in order to avoid their progression to active tuberculosis disease. The performance of the novel IGRA LIOFeron®TB/LTBI was evaluated in children. The originality of this test is the new MTB antigen contained (l-alanine dehydrogenase), identified as a tool to differentiate active TB from LTBI infection. Methods: From March 2022 to November 2023, a population of 90 children was enrolled and grouped into healthy, active TB or LTBI individuals, based on diagnostic guidelines. The blood of all these participants was tested with LIOFeron®TB/LTBI assay in comparison to diagnosis, as gold standard, and to the current used IGRA QuantiFERON®-TB Gold Plus. Results: The two assays demonstrated an excellent concordance of their results with patients’ diagnosis of MTB infection. The performance of LIOFeron®TB/LTBI assay in terms of accuracy of MTB infection diagnosis was high at ROC analysis (AUC = 0.997), and the test showed 100% sensitivity in LTBI detection. The QuantiFERON®-TB Gold Plus sensitivity for LTBI detection was 85.7%. Conclusions: Based on the obtained results, the LIOFeron®TB/LTBI assay appears to be a promising test for TB and LTBI screening among paediatric patients.What is known:• The detection of LTBI in children, exposed to MTB infections, followed by appropriate treatment, has a pivotal role in reducing tuberculosis burden.• IGRA tests are easy-to-use methods for helping large TB screening in paediatrics.What is new:• The LIOFeron®TB/LTBI performance evaluation showed 100% of sensitivity in the detection of LTBI patients.• The LIOFeron®TB/LTBI assay might be useful for the detection of LTBI and active tuberculosis paediatric patients.

Comparison of Two Interferon-Gamma Release Assays for Pediatric Tuberculosis Infection.

Identifying tuberculosis infection (TBI) using interferon-gamma release assays (IGRAs) is a primary component of clinical and public health efforts to prevent pediatric tuberculosis (TB). Pediatric data comparing the 2 IGRAs in the United States are very limited. We compared the performance of the 2 IGRAs among a large pediatric cohort tested for TBI and assessed whether discordance might be due to quantitative results close to test cutoff values. Children aged 0-15 years with both T-SPOT.TB (T-SPOT) and QuantiFERON-TB Gold In-Tube (QFT-GIT) tests were identified from a US multicenter study enrolling people at elevated risk of TBI or progression to TB disease. Results were compared using McNemar's Chi-square tests with stratification by age category and testing reason. Percent agreement and kappa statistics were also calculated. We characterized quantitative test results among children with discordant QFT-GIT-positive/T-SPOT-negative results. Among 3793 children, a higher number had positive QFT-GIT than T-SPOT (10.1% vs 7.4%, P < .001). This difference was noted for all age categories except <2 years, and for children with close-contact and non-close contact test indications. Among discordant QFT-GIT-positive/T-SPOT-negative children, lowering the positive threshold for T-SPOT to include borderline spot counts (5-7) did not eliminate the discordance, nor were QFT-GIT antigen-minus-nil results concentrated in the range just above the standard cutoff of 0.35 IU/mL. In a large pediatric cohort tested for TBI, QFT-GIT had a higher proportion of positive results than T-SPOT, and discordance was not related to quantitative results close to the established diagnostic cutoffs.

The Challenge of Urogenital Tuberculosis Diagnosis in Elderly Patients

Recurrent urinary tract infections (UTIs) in elderly patients with comorbidities can present diagnostic challenges. Extrapulmonary tuberculosis, particularly urogenital tuberculosis, is a rare but important cause of persistent genitourinary symptoms. We describe the case of an 83-year-old female with hypertension, diabetes, chronic kidney disease, and obesity who was repeatedly hospitalized for UTIs. In December 2023, she presented with progressive weakness, suprapubic pain, and altered urine despite prior antibiotic treatment. Imaging showed important bilateral pyelocalyceal dilation. She was diagnosed with urinary retention and remained catheterized. In February 2024, the patient was readmitted with multi-organ dysfunction, and Mycobacterium tuberculosis was eventually isolated from a urine culture. Despite being referred for treatment, the patient died. This case emphasizes: 1) the need to consider urogenital tuberculosis in elderly patients with recurrent UTIs, particularly in regions where tuberculosis is prevalent; 2) the importance of early diagnosis for appropriate and timely treatment, fundamental for a favorable outcome of a treatable disease. This case highlights the importance of implementing structured diagnostic protocols and educational initiatives to raise awareness of urogenital tuberculosis in elderly patients. Clinicians should prioritize early use of diagnostic tools like urine cultures for Mycobacterium tuberculosis and nucleic acid amplification tests, particularly in high-risk populations, to mitigate diagnostic delays and improve patient outcomes.

Cervical Tuberculosis Mimicking Cervical Cancer in a Postmenopausal Woman: A Case Report

Cervical tuberculosis is a rare form of genital tuberculosis. A case of a 73-year-old woman who presented with cervical wall thickening on magnetic resonance imaging, suggesting an invasive malignant neoplasm, is documented. Cervical cone excision was performed for histopathological study. Microscopy showed epithelioid granulomas, without appreciable caseous necrosis, in the wall of the uterine cervix, associated with erosion of the overlying cervical mucosa. Histochemical stains for microorganisms (Ziehl–Neelsen, Grocott, and Warthin–Starry) were negative. Immunohistochemistry for Treponema pallidum revealed scarce, spiral-shaped bacilli, which raised the diagnostic possibility of secondary syphilis. The serological study for syphilis was negative, however. Polymerase chain reaction (PCR) tests for Mycobacterium tuberculosis and Treponema pallidum were performed in the formaldehyde-fixed, paraffin embedded tissue and resulted positive for Mycobacterium tuberculosis and negative for Treponema pallidum, confirming the diagnosis of cervical tuberculosis. Our objective was to report a rare case of cervical tuberculosis, discussing the advantages and limitations of complementary techniques used in the pathological diagnosis of infectious agents and highlighting diagnostic pitfalls. In conclusion, correct microbiological diagnosis requires the implementation of integrated workflows employing complementary techniques in a multidisciplinary setting to improve the accuracy of histopathological examination in infectious diseases.

Unveiling Pediatric Neurosarcoidosis Mimicking Central Nervous System Tuberculosis: Diagnostic Challenges.

Neurosarcoidosis is a rare chronic inflammatory disease affecting the nervous system. Owing to its varying manifestations that can mimic other central nervous system infectious or autoimmune diseases, and scarcity of literature, it proves to be a challenging diagnosis. We report two cases of possible neurosarcoidosis in the pediatric age group. Our first patient presented to us with seizures at the age of 13 years, whereas our second patient presented with headaches and vomiting at the age of 10 years. Both patients had elevated cerebrospinal fluid protein levels and leptomeningeal enhancement on magnetic resonance imaging (MRI); however, one patient also had a pituitary lesion. Tests for tuberculosis were negative for both. One of the 2 patients exhibited normal angiotensin-converting enzyme levels at the start of symptoms but later showed raised angiotensin-converting enzyme levels. His diagnosis was delayed as he was treated initially for central nervous system infections. His disease course showed frequent relapses with varying clinical symptoms. After trying steroids and different immunosuppressive agents, he was given a rituximab infusion, and he went into remission. Our cases contribute to the literature for addressing diagnostic and management challenges in children with neurosarcoidosis.

Tuberculosis healthcare service disruptions during the COVID-19 pandemic in Brazil, India and South Africa: A model-based analysis of country-level data.

Tuberculosis (TB) is the leading infectious disease cause of death worldwide. In recent years, stringent measures to contain the spread of SARS-CoV-2 have led to considerable disruptions of healthcare services for TB in many countries. The extent to which these measures have affected TB testing, treatment initiation and outcomes has not been comprehensively assessed. We aimed to estimate TB healthcare service disruptions occurring during the COVID-19 pandemic in Brazil, India, and South Africa. We obtained country-level TB programme and laboratory data and used autoregressive integrated moving average (ARIMA) time-series models to estimate healthcare service disruptions with respect to TB testing, treatment initiation, and treatment outcomes. We quantified disruptions as the percentage difference between TB indicator data observed during the COVID-19 pandemic compared with values for a hypothetical no-COVID scenario, predicted through forecasting of trends during a three-year pre-pandemic period. Annual estimates for 2020-2022 were derived from aggregated monthly data. We estimated that in 2020, the number of bacteriological tests conducted for TB diagnosis was 24.3% (95% uncertainty interval: 8.4%;36.6%) lower in Brazil, 27.8% (19.8;3 4.8%) lower in India, and 32.0% (28.9%;34.9%) lower in South Africa compared with values predicted for the no-COVID scenario. TB treatment initiations were 17.4% (13.9%;20.6%) lower than predicted in Brazil, 43.3% (39.8%;46.4%) in India, and 27.0% (15.2%;36.3%) in South Africa. Reductions in 2021 were less severe compared with 2020. The percentage deaths during TB treatment were 13.7% (8.1%; 19.7%) higher than predicted in Brazil, 1.7% (-8.9%;14.0%) in India and 21.8% (7.4%;39.2%) in South Africa. Our analysis suggests considerable disruptions of TB healthcare services occurred during the early phase of the COVID-19 pandemic in Brazil, India, and South Africa, with at least partial recovery in the following years. Sustained efforts to mitigate the detrimental impact of COVID-19 on TB healthcare services are needed.

Amplification-free detection of Mycobacterium tuberculosis using CRISPR-Cas12a and graphene field-effect transistors.

Current molecular tests for tuberculosis (TB), such as whole genome sequencing and Xpert Mycobacterium tuberculosis/rifampicin resistance assay, exhibit limited sensitivity and necessitate the pre-amplification step of target DNA. This limitation greatly increases detection time and poses an increased risk of infection. Here, we present a graphene field-effect transistor (GFET) based on the CRISPR/Cas system for detecting Mycobacterium tuberculosis. The CRISPR/Cas12a system has the ability to specifically recognize and cleave target DNA. By integrating the system onto the FET platform and utilizing its electrical amplification capability, we achieve rapid and sensitive detection without requiring sample pre-amplification, with a limit of detection (LoD) as low as 2.42 × 10-18 M. Cas12a-GFET devices can differentiate 30 positive cases from 56 serum samples within 5 minutes. These findings highlight its immense potential in future biological analysis and clinical diagnosis.

Performance of three diagnostic tests for tuberculosis among Human Immunodeficiency Virus (HIV) patients presenting to a health facility in an informal urban settlement in Nairobi, Kenya.

The absence of an accurate reference test complicates the evaluation of tuberculosis (TB) diagnostic tests among people living with Human Immunodeficiency Virus (PLWHIV). The objective of this study was to estimate (using Bayesian latent class models [BLCM]) the sensitivity (Se), specificity (Sp) and negative and positive predictive values (NPV and PPV) of sputum smear microscopy (SSM), Xpert Ultra and lipoarabinomannan antigen (LAM) tests for TB among PLWHIV in Nairobi, Kenya. This cross-sectional study enrolled a total of 190 patients aged ≥ 18 years with presumptive TB seeking treatment at the Kibra Community Health Center Comprehensive Care Centre (CCC) clinic between September 2022 and March 2023. The diagnostic data obtained from the three tests were analysed using a BLCM framework to derive accuracy estimates of the three diagnostic tests. The Xpert Ultra assay registered a higher Se (85.0; 95% PCI [41.4-99.4]) compared to LAM (26.8; 95% PCI [4.7-67.6]) and SSM (56.7 [16.4-97.4]). However, SSM had the highest Sp (99.6; 95% PCI [97.7-100.0]). The Xpert Ultra assay yielded the highest overall combination of Se and Sp at 80.8% (95% PCI [37.0-96.5]). On predictive values, SSM recorded the highest PPV at 84.5% (95% PCI [38.4-99.4]). Nonetheless, all the tests exhibited noticeably high NPVs (>96%). The Xpert Ultra assay recorded the highest Se of the three tests. Nevertheless, the SSM test registered the highest Sp and correspondingly the highest PPV. On NPVs, the tests had similar estimates. Consequently, a two-test serial testing strategy, entailing an initial screening with the more sensitive Xpert Ultra assay followed by retesting of any positives with the more specific SSM test, could be most optimal in this low-burden TB setting.

Stool processing methods for Xpert Ultra testing in childhood tuberculosis: A prospective, multi-country accuracy study.

Centrifuge-free processing methods support stool Xpert Ultra testing for childhood tuberculosis (TB), but there are limited data on their accuracy, acceptability and usability. We conducted a prospective evaluation of stool Xpert Ultra in India, South Africa, and Uganda with three methods: Stool Processing Kit (SPK), Simple One-Step (SOS), and Optimized Sucrose Flotation (OSF). Children <15 years old with presumptive TB had respiratory specimen testing with Xpert Ultra and culture. Stool was tested using Xpert Ultra after processing with each method. We compared the accuracy of each method to a microbiological reference standard (MRS) and a composite reference standard (CRS). We surveyed the laboratory staff to assess acceptability and usability of the methods. We included 607 children, of whom the median age was 3.5 years (IQR 1.3-7), 48% were female, and 15.5% were HIV positive. Against the MRS, the sensitivities of SPK, SOS and OSF were 36.9% (95% CI 28.6-45.8), 38.6% (95% CI 17.2-51), and 31.3% (95% CI 20.2-44.1), respectively. The specificities of SPK, SOS and OSF were 98.2% (95% CI 96.4-99.3), 97.3% (95% CI 93.7-99.1) and 97.1% (95% CI 93.3-99), respectively. Laboratory staff reported that the methods were acceptable and usable, but SOS was most feasible to implement in a peripheral facility. Sensitivity increased among children who were culture-positive (55-77.3%) and was low (13-16.7%) against the CRS. Stool processing methods for Xpert Ultra were acceptable, usable, and performed similarly, with highest sensitivity among children with culture-positive TB.

Pediatric Tuberculosis Characteristic in West Nusa Tenggara Regional General Hospital During COVID-19 Pandemic 2019-2021

Tuberculosis (TB) infection is still an important health problem worldwide, especially in children. The Coronavirus Disease (COVID-19) pandemic has affected the priority of healthcare including TB services. Many health services reported a significant decrease in TB detection, notification, treatment and prevention due to COVID-19 policies. Therefore, we conducted a study to determine the characteristics of pediatric TB patients in West Nusa Tenggara Province General Hospital during COVID-19 pandemic. This study was a retrospective study using registry data from the Pediatric Respirology Division, Department of Child Health, West Nusa Tenggara Province General Hospital from March 2019 to December 2021. Of 225 children with TB disease, there were 66.2% outpatient and 33.8% inpatient. Thirty point seven percents (69/225) were in ages group 5 to 11 years old and mostly were males (69.8%). West Lombok Regency was the district with highest number of subjects (37.3%). Majority of subjects were visited in March-December 2019, nearly before pandemic. Polymerase Chain Reaction (PCR) test for TB were performed in 172 (76.5%) subjects and showed positive result in 22/172 (9.8%). Most of them were pulmonary TB (72.9%) and 9.8% bacteriologically confirmed. Only 4 (1.8%) of children were died. Pulmonary TB is the most common TB disease among pediatric TB patients in this study. During study period, the number of hospital visit was decreased due to COVID-19 policies. This findings can guided healthcare providers to improve detection, treatment and prevention of TB disease post COVID-19 pandemic.

Diagnostic value of SAT-TB in smear-negative pulmonary tuberculosis: A diagnostic accuracy study.

This study aimed to evaluate the diagnostic value of rapid simultaneous RNA amplification and testing for tuberculosis (SAT-TB) in smear-negative pulmonary tuberculosis (PTB). We performed a multicenter prospective analysis of 206 patients with smear-negative suspected PTB between December 2018 and March 2022. We collected sputum or bronchoalveolar lavage fluid (BALF) for simultaneous SAT-TB and Xpert Mycobacterium tuberculosis/rifampin (MTB/RIF) assays. The efficiency of SAT-TB detection was also evaluated. The final analysis included 161 patients with smear-negative suspected PTB, of whom 114 provided sputum specimens and 47 provided BALF specimens. In sputum samples, the area under the curve, sensitivity, and specificity of SAT-TB for diagnosing PTB were 0.75, 50.7%, and 100.0%, respectively, and those of the Xpert MTB/RIF assay were 0.81, 62.3%, and 100.0%, respectively. The kappa coefficient k of the consistency between SAT-TB and Xpert MTB/RIF in sputum specimens was 0.686. In BALF specimens, the area under the curve, sensitivity, and specificity of SAT-TB for diagnosing PTB were 0.79, 57.1%, and 100.0%, respectively, and those of Xpert MTB/RIF were 0.86, 76.2%, and 96.2%, respectively. The kappa coefficient k of the consistency between SAT-TB and Xpert MTB/RIF in BALF specimens was 0.656. The SAT-TB and Xpert MTB/RIF assays were highly consistent in diagnosing smear-negative PTB. It is a valuable method for early detection, prevention, and managing smear-negative PTB suspects. Meanwhile, the detection efficiency and cost-effectiveness of SAT-TB are more suitable for the rapid diagnosis of smear-negative PTB in low- and middle-income countries.

An Evaluation Study on X Ray Screening and Sputum Smear Microscopy as Diagnostic Tests for Tuberculosis Among the Presumptive TB Cases in Rural Area of Thiruvallur District.

An Evaluation Study on X Ray Screening and Sputum Smear Microscopy as Diagnostic Tests for Tuberculosis Among the Presumptive TB Cases in Rural Area of Thiruvallur District.

Ten-year health impact, economic impact and return on investment of the South African molecular diagnostics programme for HIV, tuberculosis and SARS-CoV-2

IntroductionTo ensure there is adequate investment into diagnostics, an understanding of the magnitude of impact and return on investment is necessary. We, therefore, sought to understand the health and economic...

Impact of a multicomponent strategy including decentralized molecular testing for tuberculosis on mortality: planned analysis of a cluster-randomized trial in Uganda

Rapid diagnosis of tuberculosis (TB) is important for improving outcomes and reducing transmission. Previous studies assessing the impact of Xpert MTB/RIF (Xpert), a molecular assay that provides results within 2h, on mortality have been inconclusive. In this planned analysis of a pragmatic cluster-randomized trial in Uganda, we assessed whether a multicomponent strategy, including decentralized Xpert testing, decreased mortality among adults evaluated for TB. Ten community health centers were randomized, using a computer-generated randomization sequence, to the XPEL-TB intervention (on-site Xpert testing plus implementation supports) and ten to routine TB care without any modifications (on-site smear microscopy and referral-based Xpert testing for selected patients). The trial included all adults ( 18 years of age) undergoing evaluation for presumptive TB at each trial health center. All-cause mortality was a secondary outcome of the trial. For this analysis, the primary outcome was the mortality rate (censored at 18 months), and the secondary outcome was the six-month mortality risk. We compared the outcomes between trial arms using cluster-level analyses to account for stratified randomization and patient-level covariates. The trial was registered with the US National Institutes of Health (identifier: NCT03044158) and the Pan African Clinical Trials Registry (identifier: PACTR201610001763265). Vital status was ascertained for 8413 of 9563 (88%) XPEL-TB trial participants who presented at the health centers from October 22, 2018 through February 29, 2020. The adjusted rate ratio (aRR) was 0.77 (95% CI: 0.47-1.28), comparing the intervention (145 deaths/3655 person-years) to routine care (154 deaths/3015 person-years). In sub-group analyses, point estimates for mortality were lower in the intervention arm among people without HIV (aRR=0.50, 95% CI: 0.26-0.96) and among females (aRR=0.64, 95% CI: 0.33-1.23). The mortality risk analysis yielded similar results. Consistent point estimates favoring the intervention in our trial and previous ones suggest that Xpert testing may have an impact on mortality at community health centers. However, the magnitude of effect is small, and statistically significant results are unlikely to be attained within a single trial. Future trials of novel TB diagnostics at community health centers should focus on more proximal outcomes including TB detection and treatment initiation. This work was supported by the National Heart, Lung, and Blood Institute of the US National Institutes of Health under award number R01HL130192.