Diagnosis Of Tuberculosis In Adults Research Articles

High sensitivity of ultrasound for the diagnosis of tuberculosis in adults in South Africa: A proof-of-concept study

There are limited data on the performance characteristics of ultrasound for the diagnosis of pulmonary tuberculosis in both HIV-positive and HIV-negative persons. The objective of this proof-of-concept study was to determine the sensitivity and specificity of ultrasound for the diagnosis of tuberculosis in adults. Comprehensive thoracic and focused abdominal ultrasound examinations were performed by trained radiologists and pulmonologists on adults recruited from a community multimorbidity survey and a primary healthcare clinic in KwaZulu-Natal Province, South Africa. Sputum samples were systematically collected from all participants. Sensitivity and specificity of ultrasound to detect tuberculosis were calculated compared to a reference standard of i) bacteriologically-confirmed tuberculosis, and ii) either bacteriologically-confirmed or radiologic tuberculosis. Among 92 patients (53 [58%] male, mean age 41.9 [standard deviation 13.7] years, 49 [53%] HIV positive), 34 (37%) had bacteriologically-confirmed tuberculosis, 8 (9%) had radiologic tuberculosis with negative bacteriologic studies, and 50 (54%) had no evidence of active tuberculosis. Ultrasound abnormalities on either thoracic or abdominal exams were detected in 31 (91%) participants with bacteriologic tuberculosis and 27 (54%) of those without tuberculosis. Sensitivity and specificity of any ultrasound abnormality for bacteriologically-confirmed tuberculosis were 91% (95% confidence interval [CI] 76%-98%) and 46% (95% CI 32%-61%). Sensitivity and specificity of any ultrasound abnormality for either bacteriologically-confirmed or radiologic tuberculosis were 86% (95% CI 71%-95%) and 46% (95% CI 32%-61%). Overall performance did not appear to differ markedly between participants with and without HIV. A comprehensive ultrasound scanning protocol in adults in a high TB burden setting had high sensitivity but low specificity to identify bacteriologically-confirmed tuberculosis.

Lateral flow urine lipoarabinomannan assay for extrapulmonary tuberculosis diagnosis in adults who are HIV-positive

BackgroundThe diagnosis of extrapulmonary tuberculosis (EPTB) in patients with HIV remains a challenge for clinicians. The World Health Organization recommends the detection of lipoarabinomannan (LAM) for diagnosing pulmonary tuberculosis in patients with HIV. A new generation of urine LAM tests (FujiLAM®) is available. However, studies regarding its accuracy are limited. ObjectiveThis study aimed to evaluate the accuracy of urine LAM tests using FujiLAM® for diagnosing EPTB in patients with HIV. MethodsA cross-sectional study using urine samples of patients at Cipto Mangunkusumo Hospital, Indonesia, was performed from January 2020 to December 2020. Fresh urine was applied to the FujiLAM®. Patients were grouped into definitive, probable, and non-TB groups. The diagnostic accuracy of the urine LAM test was compared with other Mycobacterium tuberculosis specimen gold standard tests. ResultsAmong 62 patients, 16 patients (25.8%) had definitive diagnosis of EPTB. Among those with definitive TB, an urine LAM test yielded a sensitivity of 75% (95% confidence interval [CI]: 47.62-92.73%) and specificity of 73.91% (95% CI: 87-85.73%). Meanwhile, compared with all diagnostic tests (definite + probable TB), FujiLAM® had a sensitivity value of 61% (95% CI 43.36-76.86%) and a specificity value of 92.31% (95% CI 74.87-99.05%). ConclusionThe FujiLAM® test is a feasible method for diagnosing EPTB in patients with HIV.

RARE PRESENTATION OF DISSEMINATED TB: MULTIPLE RING ENHANCING LESIONS IN BRAIN

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Cerebral tuberculomas is a rare form of extrapulmonary tuberculosis (TB). Due to lack of tests available for confirmatory diagnosis, the diagnosis is difficult. However, missing the diagnosis could lead to catastrophic consequences. Here, we report a case of disseminated tuberculosis presented with multiple ring enhancing lesions in the brain. CASE PRESENTATION: A 75-year-old male presented with progressive generalized weakness associated with fever and chills for 3 weeks. He has a history of bronchial carcinoid tumor status post radiation therapy, Waldenstrom's macroglobulinemia, heart failure with reduced ejection fraction, implantable cardiac defibrillator placement, coronary artery disease, stroke, and type 1 diabetes. He appeared tired with mild symmetrical lower limb weakness, but there were no meningeal signs. CT of head revealed innumerable ring-enhancing lesions in both cerebrum, cerebellum and brainstem. Analysis of cerebrospinal fluid (CSF) showed lymphocyte predominant pleocytosis (WBC of 253/cumm), elevated protein (155 mg/dl) with low glucose ratio (CSF/serum glucose ratio of 0.4). Empirical treatment for meningitis were started, but intermittent spiking fever persisted. Unfortunately, the patient had a cardiac arrest while he was undergoing brain MRI. Postmortem autopsy revealed multiple necrotizing granulomatous nodules with AFB positive bacteria in multiple organs, including brain, lung, liver, spleen, thyroid, pulmonary and extrapulmonary lymph nodes. Mycobacterium tuberculosis complex was isolated from CSF subsequently. A diagnosis of disseminated TB was made. Upon further investigation, the patient did not have exposure history, except for travelling around the globe when he was young. DISCUSSION: The differential of multiple ring-enhancing lesions in the brain is broad, which include neurocysticercosis, toxoplasmosis, cryptococcosis, bacterial abscess, CNS lymphoma and cerebral metastases. Given the complicated medical history of our patient and lack of risk factor for TB, empirical treatment for TB was not given. In such a clinical scenario, a more sensitive test, e.g. nucleic acid amplification (NAA), would be the deciding factor for initiation of therapy. Unfortunately, there is a lack of data to support the use of NAA in patients at risk for cerebral tuberculoma. Future studies would be warranted to explore the use of NAA in the setting of extra-pulmonary tuberculosis. CONCLUSIONS: Disseminated tuberculosis is a lethal disease if missed. However, diagnosis of disseminated tuberculosis remains a huge challenge, especially when pulmonary symptoms are absent. A high index of suspicion is required to diagnose and treat disseminated tuberculosis. More researches are warranted to expedite the diagnosis of TB. REFERENCE #1: Suárez I, Fünger SM, Jung N, et al. Severe disseminated tuberculosis in HIV-negative refugees. Lancet Infect Dis 2019; 19: e352–e359. REFERENCE #2: Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis 2017; 64:e1–33. DISCLOSURES: No relevant relationships by Gin Yi Lee, source=Web Response No relevant relationships by Kaiqing Lin, source=Web Response No relevant relationships by Guangchen Zou, source=Web Response

Effect of Xpert MTB/RIF on clinical outcomes in routine care settings: individual patient data meta-analysis.

SummaryBackgroundXpert MTB/RIF, the most widely used automated nucleic acid amplification test for tuberculosis, is available in more than 130 countries. Although diagnostic accuracy is well documented, anticipated improvements in patient outcomes have not been clearly identified. We performed an individual patient data meta-analysis to examine improvements in patient outcomes associated with Xpert MTB/RIF.MethodsWe searched PubMed, Embase, ClinicalTrials.gov, and the Pan African Clinical Trials Registry from inception to Feb 1, 2018, for randomised controlled trials (RCTs) comparing the use of Xpert MTB/RIF with sputum smear microscopy as tests for tuberculosis diagnosis in adults (aged 18 years or older). We excluded studies of patients with extrapulmonary tuberculosis, and studies in which mortality was not assessed. We used a two-stage approach for our primary analysis and a one-stage approach for the sensitivity analysis. To assess the primary outcome of cumulative 6-month all-cause mortality, we first performed logistic regression models (random effects for cluster randomised trials, with robust SEs for multicentre studies) for each trial, and then pooled the odds ratio (OR) estimates by a fixed-effects (inverse variance) or random-effects (Der Simonian Laird) meta-analysis. We adjusted for age and gender, and stratified by HIV status and previous tuberculosis-treatment history. The study protocol has been registered with PROSPERO, number CRD42014013394.FindingsOur search identified 387 studies, of which five RCTs were eligible for analysis. 8567 adult clinic attendees (4490 [63·5%] of 7074 participants for whom data were available were HIV-positive) were tested for tuberculosis with Xpert MTB/RIF (Xpert group) versus sputum smear microscopy (sputum smear group), across five low-income and middle-income countries (South Africa, Brazil, Zimbabwe, Zambia, and Tanzania). The primary outcome (reported in three studies) occurred in 182 (4·5%) of 4050 patients in the Xpert group and 217 (5·3%) of 4093 patients in the smear group (pooled adjusted OR 0·88, 95% CI 0·68–1·14 [p=0·34]; for HIV-positive individuals OR 0·83, 0·65–1·05 [p=0·12]). Kaplan-Meier estimates showed a lower rate of death (12·73 per 100 person-years in the Xpert group vs 16·38 per 100 person-years in the sputum smear group) for HIV-positive patients (hazard ratio 0·76, 95% CI 0·60–0·97; p=0·03). The risk of bias was assessed as reasonable and the statistical heterogeneity across studies was low (I2<20% for the primary outcome).InterpretationDespite individual patient data analysis from five RCTs, we were unable to confidently rule in nor rule out an Xpert MTB/RIF-associated reduction in mortality among outpatients tested for tuberculosis. Reduction in mortality among HIV-positive patients in a secondary analysis suggests the possibility of population-level impact.

Pleural TB Presenting as Acute Respiratory Distress in an HIV-Infected Patient

SESSION TITLE: Fungal Infections 2 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Presented is an atypical case of pleural tuberculosis presenting as acute respiratory distress in an HIV-infected patient. CASE PRESENTATION: A 27 year-old African American male with known HIV presented with 2 days of fever, cough, pleuritic chest pain and worsening dyspnea. On exam, temperature 38.9°C, respiratory rate 30 and SpO2 85% room air which improved to 93% on 7L supplemental oxygen. Chest x-ray (CXR) revealed a large left pleural effusion [Figure 1]. Of note, a CXR 1 week prior was normal. Chest computed tomography was negative for intraparenchymal or cavitary findings. Sputum AFB were negative x3 and quantiFERON was negative. He underwent thoracentesis with removal of 2,300 mL with lymphocyte predominance and elevated total protein 5.1 g/dL. Pleural fluid adenosine deaminase was normal 8.7 U/L. Despite initial improvement symptoms worsened. Repeat CXR demonstrated reaccumulated large pleural effusion and worsening hypoxia. He underwent video-assisted thoroscopic surgery with pleural and lung biopsies. Histology revealed caseating granulomas [Figure 2] consistent with pleural tuberculosis and he was started on appropriate therapy. At the time of submission, mycobacterium cultures had not resulted. DISCUSSION: Incidence of pleural involvement in HIV-infected patients with tuberculosis is estimated at 11% and remains the second most common site of extrapulmonary tuberculosis. Most common symptoms include subacute onset fever, cough and pleuritic chest pain; less commonly dyspnea. The case presented is unique given the rapid onset, reaccumulation and large size of pleural effusion and severity of hypoxic respiratory distress. Pleural biopsy with histologic examination remains the most sensitive test for pleural tuberculosis (estimated 95% sensitivity) and histologic finding of caseating granuloma is virtually diagnostic of pleural disease. CONCLUSIONS: Extrapulmonary tuberculosis is more common in HIV-infected patients. Reference #1: Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Clin Infect Dis. 2017; 64(2):e1-e33. Reference #2: Xuwel G, Heping X. Diagnosis of tuberculosis pleurisy with adenosine deaminase (ADA): a systematic review and meta-analysis. Int J Clin Exp Med. 2014; 7(10):3126-3135. Reference #3: Gopi A, Madhavan S, Sharma S, et al. Diagnosis and treatment of tuberculous pleural effusion in 2006. Chest. 2007; 131(3):880-9. DISCLOSURE: The following authors have nothing to disclose: Craig Schuring, Anthony Mattox, Matt Rudd, Julio Lanfranco No Product/Research Disclosure Information

46-Year-Old Man With Lower Back Pain

46-Year-Old Man With Lower Back Pain

Diagnosis of Tuberculosis in Adults and Children.

Diagnosis of Tuberculosis in Adults and Children.

Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children.

Individuals infected with Mycobacterium tuberculosis (Mtb) may develop symptoms and signs of disease (tuberculosis disease) or may have no clinical evidence of disease (latent tuberculosis infection [LTBI]). Tuberculosis disease is a leading cause of infectious disease morbidity and mortality worldwide, yet many questions related to its diagnosis remain. A task force supported by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America searched, selected, and synthesized relevant evidence. The evidence was then used as the basis for recommendations about the diagnosis of tuberculosis disease and LTBI in adults and children. The recommendations were formulated, written, and graded using the Grading, Recommendations, Assessment, Development and Evaluation (GRADE) approach. Twenty-three evidence-based recommendations about diagnostic testing for latent tuberculosis infection, pulmonary tuberculosis, and extrapulmonary tuberculosis are provided. Six of the recommendations are strong, whereas the remaining 17 are conditional. These guidelines are not intended to impose a standard of care. They provide the basis for rational decisions in the diagnosis of tuberculosis in the context of the existing evidence. No guidelines can take into account all of the often compelling unique individual clinical circumstances.

Diagnosis of Tuberculosis in Adults and Children

Target Population: Clinicians, laboratory workers, staff in medical offices, academic training programs, medical schools, and others involved in the

Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children.

Individuals infected with Mycobacterium tuberculosis (Mtb) may develop symptoms and signs of disease (tuberculosis disease) or may have no clinical evidence of disease (latent tuberculosis infection [LTBI]). Tuberculosis disease is a leading cause of infectious disease morbidity and mortality worldwide, yet many questions related to its diagnosis remain. A task force supported by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America searched, selected, and synthesized relevant evidence. The evidence was then used as the basis for recommendations about the diagnosis of tuberculosis disease and LTBI in adults and children. The recommendations were formulated, written, and graded using the Grading, Recommendations, Assessment, Development and Evaluation (GRADE) approach. Twenty-three evidence-based recommendations about diagnostic testing for latent tuberculosis infection, pulmonary tuberculosis, and extrapulmonary tuberculosis are provided. Six of the recommendations are strong, whereas the remaining 17 are conditional. These guidelines are not intended to impose a standard of care. They provide the basis for rational decisions in the diagnosis of tuberculosis in the context of the existing evidence. No guidelines can take into account all of the often compelling unique individual clinical circumstances.

The Sensitivity and Specificity of Loop-Mediated Isothermal Amplification (LAMP) Assay for Tuberculosis Diagnosis in Adults with Chronic Cough in Malawi.

BackgroundCurrent tuberculosis diagnostics lack sensitivity, and are expensive. Highly accurate, rapid and cheaper diagnostic tests are required for point of care use in low resource settings with high HIV prevalence.ObjectiveTo investigate the sensitivity and specificity, and cost of loop-mediated isothermal amplification (LAMP) assay for tuberculosis diagnosis in adults with chronic cough compared to Xpert® MTB/RIF, fluorescence smear microscopy.MethodsBetween October 2013 and March 2014, consecutive adults at a primary care clinic were screened for cough, offered HIV testing and assessed for tuberculosis using LAMP, Xpert® MTB/RIF and fluorescence smear microscopy. Sensitivity and specificity (with culture as reference standard), and costs were estimated.ResultsOf 273 adults recruited, 44.3% (121/273) were HIV-positive and 19.4% (53/273) had bacteriogically confirmed tuberculosis. The sensitivity of LAMP compared to culture was 65.0% (95% CI: 48.3% to 79.4%) with 100% (95% CI: 98.0% to 100%) specificity. The sensitivity of Xpert® MTB/RIF (77.5%, 95% CI: 61.5% to 89.2%) was similar to that of LAMP, p = 0.132. The sensitivity of concentrated fluorescence smear microscopy with routine double reading (87.5%, 95% CI: 73.2% to 95.8%) was higher than that of LAMP, p = 0.020. All three tests had high specificity. The lowest cost per test of LAMP was at batch size of 14 samples (US$ 9.98); this was lower than Xpert® MTB/RIF (US$ 13.38) but higher than fluorescence smear microscopy (US$ 0.65).ConclusionThe sensitivity of LAMP was similar to Xpert® MTB/RIF but lower than fluorescence smear microscopy; all three tests had high specificity. These findings support the Malawi policy that recommends a combination of fluorescence smear microscopy and Xpert® MTB/RIF prioritised for people living with HIV, already found to be smear-negative, or being considered for retreatment of tuberculosis.

Urine lipoarabinomannan testing for diagnosis of pulmonary tuberculosis in children: a prospective study.

SummaryBackgroundUrine tests for mycobacterial lipoarabinomannan might be useful for point-of-care diagnosis of tuberculosis in adults with advanced HIV infection, but have not been assessed in children. We assessed the accuracy of urine lipoarabinomannan testing for the diagnosis of pulmonary tuberculosis in HIV-positive and HIV-negative children.MethodsWe prospectively recruited children (aged ≤15 years) who presented with suspected tuberculosis at a primary health-care clinic and paediatric referral hospital in South Africa, between March 1, 2009, and April 30, 2012. We assessed the diagnostic accuracy of urine lipoarabinomannan testing with lateral flow assay and ELISA, with mycobacterial culture of two induced sputum samples as the reference standard. Positive cultures were identified by acid-fast staining and tested to confirm Mycobacterium tuberculosis and establish susceptibility to rifampicin and isoniazid.Findings535 children (median age 42·5 months, IQR 19·1–66·3) had urine and two induced specimens available for testing. 89 (17%) had culture-confirmed tuberculosis and 106 (20%) had HIV. The lateral flow lipoarabinomannan test showed poor accuracy against the reference standard, with sensitivity of 48·3% (95% CI 37·6–59·2), specificity of 60·8% (56·1–65·3), and an area under the receiver operating characteristic curve of 0·53 (0·46–0·60) for children without HIV and 0·64 (0·51–0·76) for children with HIV. ELISA had poor sensitivity in children without HIV (sensitivity 3·0%, 95% CI 0·4–10·5) and children with HIV (0%, 0·0–14·3); overall specificity was 95·7% (93·4–97·4).InterpretationUrine lipoarabinomannan tests have insufficient sensitivity and specificity to diagnose HIV-positive and HIV-negative children with tuberculosis and should not be used in this patient population.FundingUS National Institutes of Health, the National Health Laboratory Services Research Trust, the Medical Research Council of South Africa, and the Wellcome Trust.

Examination of Acid-Fast Bacilli in Sputum Using Modified Light Microscope with Homemade Light Emitting Diode Additional Attachment

Typical clinical symptoms and chest X-ray is a marker of Tuberculosis (TB) sufferers. However, the diagnosis of TB in adults should be supported by microscopic examination. Currently, Bacilli microscopic examination of acid-fast bacilli (AFB) in sputum by Ziehl-Neelsen (ZN) coloring is the most widely used. However, for reasons of convenience, especially for laboratories with a considerable amount of smear samples, and due to higher sensitivity compared with ZN staining, the World Health Organization (WHO) has recommended the use of auramine-O-staining (fluorochrome staining), which is visualized by light emitting diode (LED) fluorescence microscopy. The aim of this study was to evaluate the performance of modified light microscope with homemade LED additional attachment for examination of AFB in sputum using auramine-O-staining method. We compared the sensitivity and specificity of 2 kinds of AFB in sputum methods: ZN and fluorochrome, using culture on Lowenstein-Jensen media as the gold standard. The results showed auramine-O-staining gives more proportion of positive findings (81%) compared to the ZN method (70%). These results demonstrated that the sensitivity of auramine-O-staining was higher than ZN, however it gives more potential false positive results than ZN. The sensitivity of auramine-O-staining in detecting AFB in sputum was 100% while the specificity was 88%.

Interferon-γ Release Assays for Active Pulmonary Tuberculosis Diagnosis in Adults in Low- and Middle-Income Countries: Systematic Review and Meta-analysis

The diagnostic value of interferon-γ release assays (IGRAs) for active tuberculosis in low- and middle-income countries is unclear. We searched multiple databases for studies published through May 2010 that evaluated the diagnostic performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB (T-SPOT) among adults with suspected active pulmonary tuberculosis or patients with confirmed cases in low- and middle-income countries. We summarized test performance characteristics with use of forest plots, hierarchical summary receiver operating characteristic (HSROC) curves, and bivariate random effects models. Our search identified 789 citations, of which 27 observational studies (17 QFT-GIT and 10 T-SPOT) evaluating 590 human immunodeficiency virus (HIV)-uninfected and 844 HIV-infected individuals met inclusion criteria. Among HIV-infected patients, HSROC/bivariate pooled sensitivity estimates (highest quality data) were 76% (95% confidence interval [CI], 45%-92%) for T-SPOT and 60% (95% CI, 34%-82%) for QFT-GIT. HSROC/bivariate pooled specificity estimates were low for both IGRA platforms among all participants (T-SPOT, 61% [95% CI, 40%-79%]; QFT-GIT, 52% [95% CI, 41%-62%]) and among HIV-infected persons (T-SPOT, 52% [95% CI, 40%-63%]; QFT-GIT, 50% [95% CI, 35%-65%]). There was no consistent evidence that either IGRA was more sensitive than the tuberculin skin test for active tuberculosis diagnosis. In low- and middle-income countries, neither the tuberculin skin test nor IGRAs have value for active tuberculosis diagnosis in adults, especially in the context of HIV coinfection.

Pediatric Tuberculosis: Global Overview and Challenges

Tuberculosis (TB) is among the top 10 causes of death among children worldwide; however, children with TB are given low priority in most national health programs and are neglected in this epidemic. Recent technological advancements in diagnosis of TB in adults have not been validated in children. Similarly, trials of new drugs and development of pediatric formulations of standard first- and second-line drugs are lagging behind. Among human immunodeficiency virus (HIV)-coinfected children, the optimal timing for highly active antiretroviral therapy initiation and drug combinations that have minimal interactions with anti-TB drugs need further study. Although bacille Calmette-Guérin vaccine, the only vaccine available for TB, protects against disseminated and severe forms of the disease in young children, its safety in the HIV-infected population has been questioned. Multicentric trials are urgently required to help develop improved diagnostic strategies and formulate shorter, more effective, safe, and evidence-based regimens for treatment and prevention of drug-susceptible and drug-resistant TB.

Diagnosis of tuberculosis by polymerase chain reaction

For the diagnosis of extrapulmonary tuberculosis in adults and all forms of tubercular infections in children, microscopic and cultural techniques have been shown to be inadequate. Many serological techniques have been employed for non culture diagnosis of tuberculosis. Early promising results have repeatedly given way to subsequent findings of non-specificity. Major mycobacterial antigens have been shown to be heat shock proteins which are highly conserved in nature. DNA probes for tuberculosis are specific but have a sensitivity equivalent to AFB smear examination. Polymerase Chain Reaction (PCR) with its ability to selectively amplify DNA fragments of interest offers a potentially powerful technique for the rapid, specific and sensitive diagnosis of tuberculosis. Samples from partially treated patients could be culture negative but can be detected by PCR.

Definitions and Diagnostic Standards in the Diagnosis of Pulmonary Tuberculosis in Adults

Definitions and Diagnostic Standards in the Diagnosis of Pulmonary Tuberculosis in Adults

Do's and Don'ts in the Diagnosis of Early Pulmonary Tuberculosis in Adults and Children

Do's and Don'ts in the Diagnosis of Early Pulmonary Tuberculosis in Adults and Children