TB Test Research Articles

Online Survey on the Acceptance of Latent Tuberculosis Testing and Isoniazid Preventive Therapy among Healthcare Workers in Nigeria

Background: Healthcare workers in Nigeria are exposed to myriads of occupational risks including workplace acquired infections such as tuberculosis. Methods: This study was a cross-sectional survey and used google form to administer the questionnaire via social media networks. Descriptive statistical methods were used to summarize data on socio-demographic characteristics and responses to questions, Microsoft excel and SPSS version 20.0 for statistical analysis of data summarized as categorical variables, frequency (n) and percentages (%). Results: About six out of ten of the participants believed that they could be severely ill if they got tuberculosis. Majority of respondents 413 (89.2%) reported acceptance of latent TB testing while 87.7% agreed to take Isoniazid treatment if they test positive for LTBI. The occupational risk group was found to be less likely to accept LTBI testing. Also, respondents from the Northeast (OR = 4.225; 95% CI = 1.216-14.688; p value = 0.023) and southeast (OR = 4.494; 95% CI = 1.382-14.609; p value = 0.012) were four times more likely to accept isoniazid preventive treatment respectively. Participants who held that tuberculosis is a serious disease were more likely to accept isoniazid preventive treatment (OR = 2.220; 95% CI = 1.100-4.480 p value = 0.026). The majority of the HCW (56%) in the study never get tested for LTBI. Conclusion: the majority of the healthcare workers in this study showed that TB is a dangerous disease and agreed to get regular testing and isoniazid therapy to prevent tuberculosis.

Exhaled breath analysis: A promising triage test for tuberculosis in young children

The diagnosis of paediatric pulmonary tuberculosis is difficult, especially in young infants who cannot expectorate sputum spontaneously. Breath testing has shown promise in diagnosing respiratory tract infections, but data on paediatric tuberculosis are limited.We performed a prospective cross-sectional study in Kenya in children younger than five years with symptoms of tuberculosis. We analysed exhaled breath with a hand-held battery-powered nose device. For data analysis, machine learning was applied using samples classified as positive (microbiologically confirmed) or negative (unlikely tuberculosis) to assess diagnostic accuracy.Breath analysis was performed in 118 children. The area under the curve of the optimal model was 0.73. At a sensitivity of 86 % (CI 62–96 %), this resulted in a specificity of 42 % (95 % CI 30–55 %).Exhaled breath analysis shows promise as a triage test for TB in young children, although the WHO target product characteristics were not met.

Progress in programmatic management of drug-resistant TB, WHO Eastern Mediterranean Region, 2018-2023

<sec><title>BACKGROUND</title>Since 2012, WHO has supported countries in scaling up programmatic management of drug-resistant tuberculosis (PMDT). We assessed progress and challenges to formulate recommendations for improvement.</sec><sec><title>METHODS</title>We reviewed the regional Green Light Committee (rGLC)mission reports and analysed data to describe the progression of programme indicators.</sec><sec><title>RESULTS</title>The proportion of TB patients initially tested using Xpert MTB/RIF rose from 5% in 2017 to 54% in 2022. Testing for rifampicin-resistant TB (RR-TB) increased from 4% in 2015 to 68% in 2022 among new patients and from 17% in 2015 to 94% in 2022 among those previously treated. Consequently, in 2021–2022, the number of multidrug-resistant (MDR)/RR-TB patients diagnosed increased by 29% and 84% of them were treated, accounting for 22% of estimated cases. By 2023, fourteen countries had implemented all-oral regimens, with three initiating the 6-month bedaquiline, pretomanid, linezolid, and moxifloxacin regimen (BPaL(M)). MDR/RR-TB treatment success increased from 64% in 2017 to 73% in 2020.</sec><sec><title>CONCLUSIONS</title>Eastern Mediterranean Region countries progressed in PMDT using Xpert MTB/RIF, increased diagnosis and treatment of MDR/RR-TB patients using all-oral regimens, and improved treatment success. They must now enhance diagnostic capacity using WHO-recommended diagnostics, decentralise services while integrating them into primary health care, and prioritise the BPaL(M) regimen.</sec>

Diagnostic accuracy of an exhaled breath test for TB in hospitalized patients with cough or risk.

<sec><title>INTRODUCTION</title>Closing the TB diagnostic gap is an urgent priority, for which non-sputum-based tests are needed. We evaluated the diagnostic accuracy of Aeonose, an exhaled breath test (EBT), as a TB triage test.</sec><sec><title>METHODS</title>Patients with cough or TB risk factors admitted to a tertiary hospital in Lima, Peru, were prospectively enrolled and underwent EBT. We evaluated EBT sensitivity and specificity for diagnosing pulmonary TB using culture and Xpert as primary and secondary reference standards and conducted stratified analyses based on risk factors.</sec><sec><title>RESULTS</title>EBT sensitivity was 85% (95% CI 72.9-93.4), and specificity was 51% (95% CI 46.0-56.6) in the training cohort (n = 417). EBT sensitivity was 70% (95% CI 47.1-86.8), and specificity was 54% (95% CI 44.8-63.6) in the validation cohort (n = 139) using the culture reference standard, with higher sensitivity (78%) when using the Xpert reference standard (n = 156). Sensitivity (60%) and specificity (48%) were lower when patients with prior TB were included. In a subset of participants randomly selected for interviews, 94% (15/16) preferred EBT to sputum-based testing.</sec><sec><title>CONCLUSIONS</title>EBT had moderate sensitivity and low specificity as a TB triage test in this hospitalised cohort with cough or risk factors. Diagnostic accuracy was lower in people with prior TB.</sec>.

Why CBNAAT not called as gold standard test for TB?

Why CBNAAT not called as gold standard test for TB?

Blood RNA signatures outperform CRP triage of tuberculosis lymphadenitis and pericarditis.

Limited data are available on the diagnostic accuracy of blood RNA biomarker signatures for extrapulmonary TB (EPTB). We addressed this question among people investigated for TB lymphadenitis and TB pericarditis, in Cape Town, South Africa. We enrolled 440 consecutive adults referred to a hospital for invasive sampling for presumptive TB lymphadenitis (n=300) or presumptive TB pericarditis (n=140). Samples from the site of disease underwent culture and/or molecular testing for Mycobacterium tuberculosis complex (Mtb). Discrimination of patients with and without TB defined by microbiology or cytology reference standards was evaluated using seven previously reported blood RNA signatures by area under the receiver-operating characteristic curve (AUROC) and sensitivity/specificity at predefined thresholds, benchmarked against blood C-reactive protein (CRP) and the World Health Organization (WHO) target product profile (TPP) for a TB triage test. Decision curve analysis (DCA) was used to evaluate the clinical utility of the best performing blood RNA signature and CRP. Data from 374 patients for whom results were available from at least one microbiological test from the site of disease, and blood CRP and RNA measurements, were included. Using microbiological results as the reference standard in the primary analysis (N=204 with TB), performance was similar across lymphadenitis and pericarditis patients. In the pooled analysis of both cohorts, all RNA signatures had comparable discrimination with AUROC point estimates ranging 0.77-0.82, superior to that of CRP (0.61, 95% confidence interval 0.56-0.67). The best performing signature (Roe3) achieved an AUROC of 0.82 (0.77-0.86). At a predefined threshold of 2 standard deviations (Z2) above the mean of a healthy reference control group, this signature achieved 78% (72-83%) sensitivity and 69% (62-75%) specificity. In this setting, DCA revealed that Roe3 offered greater net benefit than other approaches for services aiming to reduce the number needed to investigate with confirmatory testing to <4 to identify each case of TB. RNA biomarkers show better accuracy and clinical utility than CRP to trigger confirmatory TB testing in patients with TB lymphadenitis and TB pericarditis, but still fall short of the WHO TPP for TB triage tests. South African MRC, EDCTP2, NIH/NIAID, Wellcome Trust, NIHR, Royal College of Physicians London. Evidence before this study: Blood RNA biomarker signatures and CRP measurements have emerged as potential triage tests for TB, but evidence is mostly limited to their performance in pulmonary TB. Microbiological diagnosis of extrapulmonary TB (EPTB) is made challenging by the need for invasive sampling to obtain tissue from the site of disease. This is compounded by lower sensitivity of confirmatory molecular tests for EPTB compared to their performance in pulmonary disease. We performed a systematic review of diagnostic accuracy studies of blood RNA biomarkers or CRP measurements for EPTB, which could mitigate the need for site-of-disease sampling for the diagnosis of TB. We searched PubMed up to 1 st August 2023, using the following criteria: "extrapulmonary [title/abstract] AND tuberculosis [title/abstract] AND biomarker [title/abstract]". Although extrapulmonary TB was included in several studies, none focused specifically on EPTB or included an adequate number of EPTB cases to provide precise estimates of test accuracy. Added value of this study: To the best of our knowledge, we report the first diagnostic accuracy study of blood RNA biomarkers and CRP for TB among people with EPTB syndromes. We examined the performance of seven previously identified blood RNA biomarkers as triage tests for TB lymphadenitis and TB pericarditis compared to a microbiology reference standard among people referred to hospital for invasive sampling in a high TB and HIV prevalence setting. Multiple blood RNA biomarkers showed comparable diagnostic accuracy to that previously reported for pulmonary TB in both EPTB disease cohorts, irrespective of HIV status. All seven blood RNA biomarkers showed superior diagnostic accuracy to CRP for both lymphadenitis and pericarditis, but failed to meet the combined >90% sensitivity and >70% specificity recommended for a blood-based diagnostic triage test by WHO. Nonetheless, in decision curve analysis, an approach of using the best performing blood RNA biomarker to trigger confirmatory microbiological testing showed superior clinical utility in clinical services seeking to reduce the number needed to test (using invasive confirmatory testing) to less than 4 for each EPTB case detected. If acceptable to undertake invasive testing in more than 4 people for each true case detected, then a test-all approach will provide greater net benefit in this TB/HIV hyperendemic setting.Implications of all the available evidence: Blood RNA biomarkers show some potential as diagnostic triage tests for TB lymphadenitis and TB pericarditis, but do not provide the level of accuracy for blood-based triage tests recommended by WHO for community-based tests. CRP has inferior diagnostic accuracy to blood RNA biomarkers and cannot be recommended for diagnostic triage among people with EPTB syndromes referred for invasive sampling.

Computing metrics to inform selection of candidate areas for a regionalized approach to bovine tuberculosis eradication in Ireland.

We describe the computation of metrics to inform the selection of areas for a regionalised approach to bovine tuberculosis eradication in Ireland. Our aim was not to recommend suitable regions but to elucidate the criteria used in metric selection and comment on the diversity of metric values amongst regions. The 26 counties of Ireland were compared using 20 metrics, grouped into five categories: region size and cattle population, herd fragmentation, cattle movement, bovine TB testing, badger population and control. Fragmentation metrics, measuring the proportion of herds with land in at least two counties, varied considerably by county, from 1% to 24 %. Between 25 % and 92 % of moves into herds came from a different county, illustrating the likely disruption in trade that a regionalized approach could entail. Cattle movement networks were combined with a risk model to calculate the proportion of moves which would be deemed risky under a risk-based trading regime and these results were compared to a more traditional approach based on the herd type and test history of each herd, with many fewer moves potentially restricted using the latter approach. We show how correlation between region size and some of the metrics complicates their interpretation.

Integrating molecular and radiological screening tools during community-based active case-finding for tuberculosis and COVID-19 in southern Africa

ObjectivesTo evaluate diagnostic yield and feasibility of integrating testing for TB and COVID-19 using molecular and radiological screening tools during community-based active case-finding (ACF). MethodsCommunity-based participants with presumed TB and/or COVID-19 were recruited using a mobile clinic. Participants underwent simultaneous point-of-care (POC) testing for TB (sputum; Xpert Ultra) and COVID-19 (nasopharyngeal swabs; Xpert SARS-CoV-2). Sputum culture and SARS-CoV-2 RT-PCR served as reference standards. Participants underwent ultra-portable POC chest radiography with computer-aided detection (CAD). TB infectiousness was evaluated using smear microscopy, cough aerosol sampling studies (CASS), and chest radiographic cavity detection. Feasibility of POC testing was evaluated via user-appraisals. ResultsSix hundred and one participants were enrolled, with 144/601 (24.0%) reporting symptoms suggestive of TB and/or COVID-19. 16/144 (11.1%) participants tested positive for TB, while 10/144 (6.9%) tested positive for COVID-19 (2/144 [1.4%] had concurrent TB/COVID-19). Seven (7/16 [43.8%]) individuals with TB were probably infectious. Test-specific sensitivity and specificity (95% CI) were: Xpert Ultra 75.0% (42.8-94.5) and 96.9% (92.4-99.2); Xpert SARS-CoV-2 66.7% (22.3-95.7) and 97.1% (92.7-99.2). Area under the curve (AUC) for CAD4TB was 0.90 (0.82-0.97). User appraisals indicated POC Xpert to have ‘good’ user-friendliness. ConclusionsIntegrating TB/COVID-19 screening during community-based ACF using POC molecular and radiological tools is feasible, has a high diagnostic yield, and can identity probably infectious persons.

TB drug susceptibility testing in high fluoroquinolone resistance settings.

The insurgence of resistance to key drugs of the BPaLM (bedaquiline + pretomanid + moxifloxacin) regimen is a major concern. In settings with widespread resistance to fluoroquinolones (FQs), like Pakistan, new technologies, such as Xpert® MTB/XDR, may ensure drug resistance upfront screening. This study aims to assess MTB/XDR's performance in detecting FQs and isoniazid resistance, proposing a renewed diagnostic algorithm for drug-resistant TB (DR-TB). This cross-sectional prospective study, approved by the local ethical committee, collected samples from people newly and previously diagnosed with TB over 6 months. Xpert® MTB/RIF Ultra, MTB/XDR, Genotype® MTBDRplus, Genotype® MTBDRsl, culture, and phenotypic drug susceptibility testing (pDST) for relevant drugs (including bedaquiline and levofloxacin) were performed. Next-generation sequencing (NGS) resolved discordances between MTB/XDR and pDST results. The analysis showed that MTB/XDR has 91.5% and 88.2% sensitivity and 99.5% and 97.7% specificity in detecting respectively isoniazid (INH) and resistance to FQs, demonstrating that MTB/XDR meets the WHO targets for INH resistance detection at the peripheral level. NGS effectively resolved discordances between MTB/XDR and pDST results. The obtained results allowed designing the proposed diagnostic algorithm for rapid identification of DR-TB, ensuring rapid and equitable access to drug susceptibility testing for TB, ultimately improving TB care and control.

Spiritual Holy Water Sites in Ethiopia: Unrecognized High-Risk Settings for Transmission of Pulmonary Tuberculosis.

Ethiopia is a high-tuberculosis (TB) burden country with 157 new cases per 100,000 people, with 23,800 TB-related deaths in 2020. In Ethiopia, TB patients have different healthcare-seeking behaviors. They frequently visit spiritual places, such as holy water sites (HWSs), to seek treatment for their illness spiritually. This study examined the prevalence of pulmonary TB (PTB) and drug susceptibility profiles of Mycobacterium tuberculosis (MTB) isolates among spiritual HWS attendees in Northwest Ethiopia. A cross-sectional study was conducted from June 2019 to March 2020. Sputum samples were collected, processed, and cultured using Löwenstein-Jensen (LJ) culture medium. Second-generation line probe assays (LPAs), GenoType®MTBDRplus VER2.0 and GenoType®MTBDRsl VER2.0, were used to detect anti-TB drug-resistant isolates. STATA 17 was utilized to perform descriptive statistics, bivariate, and multivariate regression analyses. Of 560 PTB-symptomatic participants, 21.8% ((95% confidence interval (95 CI): 18.4-25.2%)) were culture-positive, resulting in a point prevalence of 1,183/100,000 attendees. Amongst HWS attendees, culture-positive TB occurred most commonly in persons 18-33 years of age (28.5% (95 CI 23.4-34.3%)). Other participant characteristics significantly associated with culture-positive PTB were as follows: rural residents (adjusted odds ratio (aOR) 2.65; 95 CI 1.38-5.10), married participants (aOR 2.43; 95 CI 1.28-4.63), family members >5 per household (aOR 1.84; 95 CI 1.04-3.24), and sharing living space (aOR 10.57; 95 CI 3.60-31.13). Also, among 438 participants followed for 12 months after showing negative TB culture results while at the HWS, 6.8% (95 CI 4.4-9.4%) developed or contracted culture-positive TB post-residency at the HWSs. Of the 122 tested isolates, 20 (16.4%) were isoniazid (INH) and/or rifampicin (RIF) resistant. Multidrug-resistant (MDR) TB was detected in 15 cases (12.3%), five of which were fluoroquinolones (FLQs) resistant. The findings from this study should raise a concern about HWSs as potential high-risk settings for TB transmission. It is recommended that appropriate control measures be instituted that include compulsory TB testing and tightened infection control at HWSs, where an increased risk exists for transmission of TB.

GAMBARAN PEMERIKSAAN TES CEPAT MOLEKULER (TCM) GENEXPERT PADA PASIEN DI RUMAH SAKIT UMUM DAERAH PALEMBANG BARI

Background: Tuberculosis is an infectious disease caused by the bacterium Mycobacterium tuberculosis. The diagnosis of pulmonary TB is made based on the clinical picture, physical examination, radiological picture, laboratory examination, and tuberculin test. The pulmonary TB diagnosis currently used routinely in laboratories including hospitals and health centers is bacteriological diagnosis using the rapid molecular test (TCM) technique, while microscopic examination is used as a follow-up examination (monitoring) in patients receiving treatment. TCM examination is a molecular detection method based on nested real-time PCR. The use of TCM is a priority for TB testing because it has several advantages, including: it can diagnose TB and resistance to rifampicin quickly, accurately with high sensitivity, and results can be known in approximately 2 hours.&#x0D; Objectives: The aim of this study is to see the description of TCM examinations in patients at Palembang BARI Regional Hospital based on gender and age groups. Method: This research was conducted at the Palembang BARI Regional General Hospital Laboratory Installation. The samples taken were from patients at the Palembang BARI Regional General Hospital and not referrals from other health service facilities. 50 samples were taken and grouped based on TCM results, gender and age. Result: In grouping based on TCM results, the highest result was negative. In gender grouping, more male patients underwent TCM examinations. In the age grouping, the elderly are more likely to undergo TCM examinations. Conclusion: There are several factors that cause a person to become infected with TB, namely social status, smoking, and having the habit of drinking alcohol.

Missed opportunities for TB diagnostic testing among people living with HIV in Zimbabwe: Cross-sectional analysis of the Zimbabwe Population-based HIV Impact Assessment (ZIMPHIA) survey 2015–16

BackgroundUsing data from the Zimbabwe Population-based HIV Impact Assessment survey 2015–2016, we examined the TB care cascade and factors associated with not receiving TB diagnostic testing among adult PLHIV with TB symptoms. MethodsStatistical Analysis was limited to PLHIV aged 15 years and older in HIV care. Weighted logistic regression with not receiving TB testing as outcome was adjusted for covariates with crude odd ratios (ORs) with p < 0.25. All analyses accounted for multistage survey design. ResultsAmong 3507 adult PLHIV in HIV care, 2288 (59.7 %, 95 % CI:58.1–61.3) were female and 2425 (63.6 %, 95 % CI:61.1–66.1) lived in rural areas. 1197(48.7 %, 95 % CI:46.5–51.0) reported being screened for TB symptoms at their last HIV care visit. In the previous 12 months, 639 (26.0 %, 95 % CI:23.9–28.1) reported having symptoms and of those, 239 (37.8 %, 95 % CI:33.3–42.2) received TB testing. Of PLHIV tested for TB, 36 (49.5 %, 95 % CI:35.0–63.1) were diagnosed with TB; 32 (90.3 %, 95 % CI:78.9–100) of those diagnosed with TB received treatment. Never having used IPT was associated with not receiving TB testing. ConclusionThe results suggest suboptimal utilization of TB screening and diagnostic testing among PLHIV. New approaches are needed to reach opportunities missed in the HIV/TB integrated services.

Community-level variation in TB testing history in Blantyre, Malawi.

SETTING: Equitable access to TB testing is vital for achieving global diagnosis and treatment targets, but access to diagnostic services is often worse in poorer communities. The SCALE (Sustainable Community-wide Active case-finding for Lung hEalth) survey estimated TB prevalence in Blantyre City, Malawi, and recorded previous engagement with TB services.OBJECTIVE: To explore local variation in the prevalence of ever-testing for TB in Blantyre and investigate potential socio-economic drivers.DESIGN: We fit a mixed-effects model to self-reported prior TB testing from survey participants across 72 neighbourhood clusters, adjusted for sex, age and HIV status and with cluster-level random intercepts. We then evaluated to what extent cluster-level variation was explained by two alternate poverty indicators.RESULTS: We observed substantial variation between clusters in previous TB testing, with little correlation between neighbouring clusters. Individuals residing in less affluent households, on average, had lower odds of having undergone prior testing. However, adjusting for poverty did not explain the cluster-level variations observed.CONCLUSION: Despite a decade of increased active case-finding efforts, access to TB testing is inconsistent across the population of Blantyre. This likely reflects health inequities that also apply to TB testing in many other settings, and motivates collection and analysis of TB testing data to identify the drivers behind these inequities.

Temporal dynamics of the early immune response following Mycobacterium bovis infection of cattle

Bovine tuberculosis is an infectious disease of global significance that remains endemic in many countries. Mycobacterium bovis infection in cattle is characterized by a cell-mediated immune response (CMI) that precedes humoral responses, however the timing and trajectories of CMI and antibody responses determined by newer generation assays remain undefined. Here we used defined-antigen interferon-gamma release assays (IGRA) and an eleven-antigen multiplex ELISA (Enferplex TB test) alongside traditional tuberculin-based IGRA and IDEXX M. bovis antibody tests to assess immune trajectories following experimental M. bovis infection of cattle. The results show CMI responses developed as early as two-weeks post-infection, with all infected cattle testing positive three weeks post-infection. Interestingly, 6 of 8 infected animals were serologically positive with the Enferplex TB assay as early as 4 weeks post-infection. As expected, application of the tuberculin skin test enhanced subsequent serological reactivity. Infrequent M. bovis faecal shedding was observed but was uncorrelated with observed immune trajectories. Together, the results show that early antibody responses to M. bovis infection are detectable in some individuals and highlight an urgent need to identify biomarkers that better predict infection outcomes, particularly for application in low-and-middle income countries where test-and-slaughter based control methods are largely unfeasible.

Transcriptional profiling of human peripheral blood mononuclear cells in household contacts of pulmonary tuberculosis patients provides insights into mechanisms of Mycobacterium tuberculosis control and elimination

ABSTRACT Household contacts (HHCs) of patients with active tuberculosis (ATB) are at higher risk of Mycobacterium tuberculosis (M. tuberculosis) infection. However, the immune factors responsible for different defense responses in HHCs are unknown. Hence, we aimed to evaluate transcriptome signatures in human peripheral blood mononuclear cells (PBMCs) of HHCs to aid risk stratification. We recruited 112 HHCs of ATB patients and followed them for 6 years. Among the HHCs, only 2 developed ATB, while the remaining HHCs were classified into three groups: (1) HHC-1 group (n = 23): HHCs with consistently positive T-SPOT.TB test, negative chest radiograph, and no clinical symptoms or evidence of ATB during the 6-year follow-up period; (2) HHC-2 group (n = 15): HHCs with an initial positive T-SPOT result that later became negative without evidence of ATB; (3) HHC-3 group (n = 14): HHCs with a consistently negative T-SPOT.TB test and no clinical or radiological evidence of ATB. HHC-2 and HHC-3 were combined as HHC-23 group for analysis. RNA sequencing (RNA-seq) in PBMCs, with and without purified protein derivative (PPD) stimulation, identified significant differences in gene signatures between HHC-1 and HHC-23. Gene ontology analysis revealed functions related to bacterial pathogens, leukocyte chemotaxis, and inflammatory and cytokine responses. Modules associated with clinical features in the HHC-23 group were linked to the IL-17 signaling pathway, ferroptosis, complement and coagulation cascades, and the TNF signaling pathway. Validation using real-time PCR confirmed key genes like ATG-7, CXCL-3, and TNFRSF1B associated with infection outcomes in HHCs. Our research enhances understanding of disease mechanisms in HHCs. HHCs with persistent latent tuberculosis infection (HHC-1) showed significantly different gene expression compared to HHCs with no M. tuberculosis infection (HHC-23). These findings can help identify HHCs at risk of developing ATB and guide targeted public health interventions.

Impact of introduction of TB LAM in the TB testing algorithm at Levy Mwanawasa University Teaching Hospital on case detection and notifications

Abstract&#x0D; &#x0D; Introduction&#x0D; TB-LAM tests were introduced in the TB program in Zambia in 2019, to aid in diagnosis of TB. We carried out a study to determine the impact that TB lipoarabinomannan (LAM) test has had on case identification and notification at a tertiary hospital in a city with a high prevalence of HIV. We also compared sensitivity, specificity, positive predictive value and negative predictive of TB LAM tests and X-pert MTB RIF test in HIV positive and HIV negative patients.&#x0D; &#x0D; Method&#x0D; Retrospective analysis of the TB laboratory as well as the TB notification registers to determine the number of TB cases identified by TB LAM and Xpert MTB-RIF. We identified patients who had both TB LAM and X-pert MTB RIF tests to determine sensitivity, specificity, positive and negative predictive values of TB LAM and Xpert MTB RIF, using TB notification and commencement of anti-tuberculosis treatment as the gold standard for comparison. &#x0D; &#x0D; Results&#x0D; Between January 2019 and June 2022, there were a total number of 2353 notified cases of Tuberculosis. A total of 511 cases of Tuberculosis were identified on the basis of positive TB LAM. This accounted for 59% of all bacteriologically confirmed cases of TB. The sensitivity and specificity of TB LAM in diagnosis of TB in the study population was 55.8% and 91.4% respectively. Positive and Negative predictive values for TB LAM were 84.5% and 69.6% respectively. The sensitivity and specificity of Xpert MTB RIF in diagnosis of TB in the study population was 29.2% and 98.2% respectively. Positive and Negative predictive values for Xpert MTB RIF were 93.5% and 60.4% respectively. Positivity yield was higher for TB LAM as compared to Xpert MTB RIF (19% versus 9% in 2019; 36% versus 10% in 2020 and 38% versus 10% in 2021).&#x0D; Conclusion&#x0D; TB LAM identified 59% of all bacteriologically confirmed cases of tuberculosis at Levy Mwanawasa University Teaching Hospital. Contrary to what has been found in other studies, the sensitivity of TB LAM was much higher than that of Xpert MTB RIF. In addition, the sensitivity of TB LAM was higher in HIV negative as compared to HIV positive, which is contrary to what has been established in similar studies.&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D;

1872. Risk factors associated with gaps in screening and testing for latent TB infection in children

Abstract Background Children should be treated for latent TB infection (LTBI) to prevent progression to TB disease, but there are gaps in screening and testing for LTBI. We evaluated demographic and clinical factors associated with LTBI screening and testing at a Federally Qualified Health Center in Oakland, California. Methods We extracted demographic, clinical and note data from the electronic health records of all well-patient visits of children and adolescents 1-19 years old without a history of LTBI or TB disease from 2014 – 2020. Screening was defined as documenting the presence/absence of new TB risk factors, and testing was defined as ordering/completing a tuberculin skin test (TST) or QuantiFERON-TB Gold blood test (Quantiferon Gold). We performed multivariable logistic regression to determine the factors associated with conducting a TB risk assessment, ordering LTBI testing, and completing LTBI testing. Results We evaluated 18,681 visits, of which 38% were age 1 – 4, 50% were female, and 19% preferred a language other than English. Overall, 90% of visits documented a TB risk assessment, of which 8% had a risk factor for TB infection. Only 26% visits with a documented TB risk had a TB test subsequently ordered. 82% of ordered tests were completed. We found that children 1 – 4 years old were more likely to be screened for TB risk factors than adolescents ≥12 years (aOR 7.87, 95% CI 6.77 – 9.13, p &amp;lt; 0.01), but adolescents were more likely to be tested (aOR 1.74, 95% CI 1.12-2.66, p &amp;lt; 0.05). Non-English-speaking patients were more likely to be assessed for TB risk factors and were more likely to have an LTBI test ordered (Table 1). LTBI testing was more likely to be completed in females (aOR 5.08, 95% CI 1.75 – 14.70, p &amp;lt; 0.01) as well as when TST was ordered compared to Quantiferon Gold (aOR 24.15, 95% CI 8.17 – 71.42, p &amp;lt; 0.01). Conclusion Gaps in the LTBI care cascade for children were associated with age, sex and language preference, and interventions are needed to improve LTBI care in these groups. Further efforts are needed to address barriers to Quantiferon Gold completion in children. Disclosures All Authors: No reported disclosures

Factors Influencing the Indeterminate Results in a T-SPOT.TB test: A Matched Case-control Study.

Objective A T-SPOT.TB can yield indeterminate results under two test observation conditions: a high response to the nil in negative control wells (high nil-control) or a low response to the mitogen in positive control wells (low mitogen-control). The most strongly influential factors for these indeterminate results, however, have yet to be identified. Methods From June 1, 2015, to June 30, 2021, we conducted a 1:1 matched case-control, retrospective study. Patients Patients who underwent a T-SPOT.TB test at Chiba University Hospital. Results The study included 5,956 participants. Indeterminate results were found in 63 participants (1.1%), including high nil-control in 37 and low mitogen-control in 26. Human T-cell leukemia virus type 1 (HTLV-1) positivity was the only influencing factor associated with high nil-control (adjusted odds ratio=98.5, 95% confidence interval: 6.59-1480). Conclusion Regarding the indeterminate results, all HTLV-1 positive participants had a high nil response and no low mitogen response. It was suspected that abnormally produced interferon γ caused a nonspecific reaction to the negative control well, resulting in a high nil response. Low mitogen-control, conversely, did not appear to have any statistically significant influential factors.

Abstract 18486: Recurrent Pericarditis Following Atrial Fibrillation Ablation: Unmasking Latent Tuberculosis Infection

Background: Tuberculous pericarditis is rare in the United States but can lead to serious sequelae in the absence of diagnosis and treatment. We report a case of recurrent pericarditis following catheter ablation of atrial fibrillation (AF) due to reactivation of latent TB infection. Case Summary: A 52-year-old male with no past medical history underwent a difficult trans-septal puncture &amp; cryo-balloon PV isolation, complicated by acute pericarditis and pericardial effusion with cardiac tamponade. He underwent pericardiocentesis with removal of 260cc bloody fluid. He had resolution of chest pain with ibuprofen, but experienced recurrence after 3 months and was given a longer NSAID course. Two months later, he presented with chest pain along with night sweats &amp; low-grade fever. He had an elevated C-reactive protein, and echocardiography revealed thickened pericardium &amp; constrictive physiology. He received high-dose aspirin, prednisone, and colchicine for recurrent pericarditis. Extensive Infectious Disease &amp; Rheumatology work-up ruled out autoimmune &amp; viral etiologies but his T-Spot TB test was positive. He denied personal or contact history of TB except travel to Asia 20 years ago. CT scan ruled out pulmonary TB infection. A 6-month course of Rifampin was prescribed. He experienced a 4th episode of pericarditis while tapering off prednisone, and restarted prednisone, Ibuprofen, and colchicine. Additionally, Rilonacept was prescribed. After completing 6-months of Rifampin and Rilonacept, he had significant improvement and no further recurrences on 1 year follow up. Discussion: Pericarditis is a common complication of catheter ablation, often resulting from direct injury. We report a case of recurrent pericarditis, initially believed to be a traumatic complication of AF ablation. However, investigation revealed underlying latent pericardial TB infection. Appropriate treatment led to complete resolution without sequelae.

Relationship between TLR-2 level and clinical or radiological severity on patients with tuberculosis spondylitis in Dr. Wahidin Sudirohusodo hospital Makassar.

Spinal tuberculosis or TB spondylitis is one of the most common types of extra pulmonary tuberculosis, which is about 15% of all cases. It causes severe morbidity, neurological deficits, and severe deformities in the patients. The growth of Mycobacterium tuberculosis in culture specimens obtained from infected tissue is the single gold standard diagnostic test for spinal TB. Toll-like receptor (TLR) is one of the important receptors in the first-line defence system against microbes. TLR-2 and TLR-4 are known to be associated with tuberculosis infection. Based on this background, the researchers were interested in examining the relationship between TLR-2 levels and the clinical and radiological severity of TB spondylitis patients. A cross-sectional study was conducted with patients diagnosed with tuberculosis spondylitis at Dr Wahidin Sudirohusodo Makassar. Patients diagnosed with TB spondylitis confirmed by blood tests, GeneExpert, and magnetic resonance imaging without prior treatment were included. Data analysis were conducted by using descriptive analysis and one-way ANOVA for bivariate analysis. The mean value of TLR2 levels in TB spondylitis patients was 9.1 g/dL. TLR2 levels in paraesthesia were significantly higher than normal (P < .05). Similar trend were analyzed on the motor neurologic status with TLR2 levels in paraparesis were significantly higher than those in normal (P < .05). There is a significant relationship between the TLR2 levels in TB spondylitis and their impaired motor and sensory function. Spinal destruction has been shown to provide significant relationship with TLR2 value in spondylitis TB.