Utilizing radial endobronchial ultrasound-guided lung biopsy to diagnose pseudotumoral tuberculosis in sputum-negative immunocompetent adults.

Current Concepts in the Management of Tuberculosis

TB OR NOT TB?

“Won’t Get Fooled Again” (by Tuberculosis)

This review highlights important contributions published in Respirology and other reputable respiratory journals in 2011 in four principle respiratory medicine areas, namely pulmonary infections, tuberculosis (TB), pleural diseases and chest imaging/interventional pulmonology. The articles have been selected for their insight, reliability and potential impact on clinical practice. From a total of 111 original articles and 40 review papers published in Respirology that year, 34% and 40%, respectively, were devoted to the earlier topics.

Screening and identification of potential protein biomarkers for evaluating the efficacy of intensive therapy in pulmonary tuberculosis

The aim of our study was to show socio-demographic factors and clinical characteristics in patients with smear negative and smear positive pulmonary tuberculosis. Methodology: The prospective study included all patients with Pulmonary tuberculosis (N = 43) treated at the Pulmonology Department of the Clinical Hospital Center in Kosovska Mitrovica during the study period 2012-2014. Results: 15 (35%) patients were treated for smear negative tuberculosis. Smear positive pulmonary tuberculosis was significantly more common in younger population (p = 0.05), while people above age 50 were equally infected with both smear positive and smear negative pulmonary tuberculosis. In relation to gender, place of residence and marital status there was no difference between the patients. Significantly more patients with smear negative pulmonary tuberculosis had lower level of education (p <0.001). Cough and expectoration were equally frequent. Hemoptysis was more likely in smear positive pulmonary tuberculosis (p = 0.08). Night sweats and exhaustion were equally present in both groups of patients. Anemia was significantly more common at smear negative tuberculosis (p = 0.037) patients. There was no significant difference in the radiographic changes between smear negative tuberculosis and smear positive pulmonary tuberculosis. Concomitant diseases were equally present in both groups of patients, except chronic obstructive pulmonary disease which was more frequent in a group of patients with smear positive tuberculosis. Conclusion: Smear negative pulmonary tuberculosis was present in about one-third of tuberculosis patients and more frequently affected persons above age 50 with lower education. Anemia was widespread in smear negative tuberculosis patients. Hemoptysis and chronic obstructive pulmonary disease were more common at smear positive tuberculosis patients.

Wallgren's tuberculosis (TB) timetable demonstrated co-occurrence of miliary TB and tuberculous meningitis in children. To verify the same in immunocompetent adults, we prospectively evaluated the prevalence and spectrum of central nervous system (CNS) involvement in patients with pulmonary miliary TB. This was a tertiary care, University hospital-based, prospective evaluation performed from December 2018 to June 2020. Newly diagnosed patients with pulmonary miliary TB were subjected to a detailed clinical, laboratory and MRI-based evaluation. All patients received treatment as per WHO guidelines. Out of 342 patients with pulmonary TB, 53 patients met the eligibility criteria. The median age at presentation was 32 y and approximately two-thirds of patients were female. Clinically, only two-fifths of patients had features of CNS involvement. Cerebrospinal fluid (CSF) and imaging abnormalities were noted in 46 patients each. Twelve (23.5%) patients were diagnosed with definite-category tuberculous meningitis. Presence of an infarct significantly correlated with neurological features. Mantoux positivity correlated significantly with the presence of choroid tubercles, CSF changes and brain tuberculomas. This is the first study to endorse Wallgren's observations in immunocompetent adults. A high index of suspicion, even in asymptomatic patients, may uncover tuberculous lesions involving the CNS and guide optimal monitoring of patients.

RATIONALE: Pseudotumoral tuberculosis (TB), an uncommon malignancy-mimicking form of pulmonary TB, often causes diagnostic delays, especially in patients without TB history or immunosuppression. In TB-endemic areas, reliance on negative sputum culture or GeneXpert results—even from fibro aspiration—can lead to misdiagnosis. A comprehensive approach, including biopsy and radiologic assessment, is crucial for accurate diagnosis. This study evaluates the diagnostic yield of various modalities, describes key clinical, radiologic, and bronchoscopic features, and underscores the need to consider TB in the differential diagnosis of pulmonary masses. METHODS: This retrospective study included 35 patients diagnosed with pseudotumoral TB, 82% of whom presented with isolated pulmonary involvement. Demographics, clinical presentations, radiologic and bronchoscopic findings, diagnostic methods used, and treatment outcomes were analyzed. Patients underwent diagnostic evaluation with sputum analysis (culture and GeneXpert), bronchial biopsy, bronchial aspiration, and CT-guided biopsy, with each modality's observed diagnostic contribution documented to assess utility within this population. RESULTS: The clinical presentation was largely nonspecific, with 62-79% of patients presenting with symptoms like dyspnea, cough, and weight loss, while fever was observed in only 44%. This frequent absence of fever contributes to an initial misdiagnosis as malignancy. Radiologically, 55% of cases displayed nodules or masses, while 45% showed lung consolidations; 76% had accompanying micronodules, and 51% presented multiple lymphadenopathies. This typical CT pattern, particularly prevalent among HIV-positive patients (38%) who showed increased mediastinal lymphadenopathy, suggests distinguishing features in pseudotumoral TB.Sputum studies, performed in 55% of patients, yielded no positive results, indicating limited sensitivity in pseudotumoral presentations. Bronchial biopsy, bronchial aspiration, and CT-guided biopsy were the primary methods for definitive TB confirmation. Notably, diagnostic delays were more significant in non-HIV patients, suggesting that systematic bronchial biopsy or aspiration may be warranted in all patients with pulmonary masses from TB-endemic areas, regardless of HIV status. Following TB treatment, 70% of patients reported symptom resolution, and 48% showed partial or complete regression of the pseudotumoral mass. CONCLUSIONS: Our findings underscore the need to systematically include TB in the differential diagnosis of pulmonary masses in patients from TB-endemic regions, irrespective of HIV status or prior TB history. Radiologic findings of mass-like lesions with micronodules and lymphadenopathy, especially in non-HIV cases, should prompt consideration of bronchial biopsy when initial sputum results are negative. By minimizing diagnostic delays and supporting TB elimination efforts, these findings aim to reduce TB-related morbidity and mortality and prevent unnecessary invasive surgical procedures through earlier case detection in atypical presentations.

Pujari, Sanjay; Gugale, Piyush; Shah, Darshan; Patel, Divya; Gaikwad, Sunil; Desouza, Clyde; Atre, Ashish Author Information

BackgroundIn patients with HIV and tuberculosis (TB) in resource-constrained settings, smear-negative disease has been associated with higher mortality than smear-positive disease. Higher reported mortality may be due to misdiagnosis, diagnostic delays, or because smear-negative disease indicates more advanced immune suppression.MethodsWe analyzed culture-confirmed, pulmonary TB among patients with TB and HIV in the United States from 1993–2008 to calculate prevalence ratios (PRs) for smear-negative disease by demographic and clinical characteristics. Allowing two years for treatment outcome to be reported, we determined hazard ratios (HRs) for survival by smear status, adjusted for significant covariates on patients before 2006.ResultsAmong 16,710 cases with sputum smear results, 6,739 (39%) were sputum smear-negative and 9,971 (58%) were sputum smear-positive. The prevalence of smear-negative disease was lower in male patients (PR: 0.89, 95% confidence interval [CI]: 0.86–0.93) and in those who were homeless (PR: 0.92, CI: 0.87–0.97) or used alcohol excessively (PR: 0.91, CI: 0.87–0.95), and higher in persons diagnosed while incarcerated (PR: 1.20, CI: 1.13–1.27). Patients with smear-negative disease had better survival compared to patients with smear-positive disease, both before (HR: 0.82, CI: 0.75–0.90) and after (HR: 0.81, CI: 0.71–0.92) the introduction of combination anti-retroviral therapy.ConclusionsIn the United States, smear-negative pulmonary TB in patients with HIV was not associated with higher mortality, in contrast to what has been documented in high TB burden settings. Smear-negative TB can be routinely and definitively diagnosed in the United States, whereas high-burden countries often rely solely on AFB-smear microscopy. This difference could contribute to diagnostic and treatment delays in high-burden countries, possibly resulting in higher mortality.

The aim of this study was to compare the expression of peripheral blood T cell subsets, soluble interleukin-2 receptor (sIL-2R) and interferon-gamma (IFN-γ) in patients with retreatment pulmonary tuberculosis, initial treatment pulmonary and extra-pulmonary tuberculosis, and therefore to explore the cellular immune changes and the significance among different types and severity of tuberculosis. A total of 170 patients with tuberculosis in Pulmonary Hospital of Shanghai from December 2009 to January 2011, including 98 males and 72 females, aged from 16 to 70 years (average 40 years), were included in this study. The patients were divided into retreatment pulmonary tuberculosis group (47 cases), initial treatment pulmonary tuberculosis group (62 cases) and initial treatment extra-pulmonary tuberculosis group (61 cases). Furthermore, the 109 patients with pulmonary tuberculosis were divided into different subgroups according to cavity formation and the lung fields involved: patients without lung cavity (52 cases) vs those with lung cavity (57 cases), patients with involvement of 1 - 2 lung fields (48 cases), vs 3 - 4 lung fields (26 cases) and 5 - 6 lung fields (35 cases). Peripheral blood T cell subsets (by flow cytometry doubled-labeled antibody), sIL-2R and IFN-γ (by ELISA) were determined in 170 patients. Differences between means of 2 groups were tested by t test, differences among multiple groups were tested by analysis of variance (ANOVA), and multiple comparisons among multiple groups were tested by LSD-t test or χ² test. Linear regression equation was used to analyze the correlations. The levels of peripheral blood CD₄/CD₈ in patients with retreatment pulmonary tuberculosis and initial treatment extra-pulmonary tuberculosis patients were significantly lower than that in initial treatment pulmonary tuberculosis patients, [(1.7 ± 0.7), (1.6 ± 0.7) and (2.0 ± 0.7) respectively (F = 4.380, P < 0.05)]. The levels of serum sIL-2R in patients with retreatment pulmonary tuberculosis and initial treatment extra-pulmonary tuberculosis were significantly higher than that in initial treatment pulmonary tuberculosis patients [(224 ± 89) pmol/L, (209 ± 98) pmol/L, (167 ± 73) pmol/L, (F = 6.402, P < 0.01)]. The levels of serum IFN-γ in patients with retreatment pulmonary tuberculosis and initial treatment extra-pulmonary tuberculosis were significantly higher than that in initial treatment pulmonary tuberculosis patients [(37 ± 23) ng/L, (37 ± 24) ng/L, (29 ± 16) ng/L, (F = 2.799, P < 0.05)]. The levels of peripheral blood CD₄/CD₈ in initial treatment and retreatment cavity pulmonary tuberculosis patients were lower than that in pulmonary tuberculosis patients without cavity, but the results of sIL-2R and IFN-γ were the opposite [(1.7 ± 0.6) vs (2.0 ± 0.8), (214 ± 93) pmol/L vs (167 ± 68) pmol/L and (38 ± 22) ng/L vs (27 ± 14) ng/L, t = -2.813 to 3.076, P < 0.05 or P < 0.01]. The level of serum sIL-2R was negatively correlated with peripheral blood CD₄/CD₈ level in all the patients (r = -0.380, P < 0.01). Patients with retreatment pulmonary tuberculosis and initial treatment extra-pulmonary tuberculosis had lower cellular immune function as compared to those with initial treatment pulmonary tuberculosis, and the cellular immune function was significantly correlated with the extent and cavity formation of pulmonary lesions.

More than half of tuberculosis (TB) detected by community prevalence surveys is classified as asymptomatic. We evaluated yield of symptom and chest radiograph (CXR) screening of TB-exposed household contacts (HHC) in South Africa. Adult volunteers (≥18 years) with household exposure to pulmonary TB patients were enrolled at three sites. Systematic screening of TB symptoms (any duration), CXR (any abnormality), and sputum microscopy, Xpert Ultra, and liquid culture were performed. Serum C-reactive protein (CRP) was measured by multiplex bead array. Prevalent TB was microbiologically-confirmed (Xpert Ultra or culture). Symptomatic and asymptomatic TB were defined as prevalent TB with and without reported symptoms, respectively. Between March 2021 - December 2022, 979 HHC were enrolled; 185 (18.9%) living with HIV and 187 (19.1%) with previous TB. Prevalent TB occurred in 51 (5.2%) and was asymptomatic in 42/51 (82.4%). Only 13/42 (31.0%) asymptomatic TB cases were smear-positive [8/13 (61.5%) graded scanty or 1+]. CRP did not discriminate healthy HHC from those with asymptomatic TB (AUC 0.60; 95%CI 0.47-0.73). An abnormal CXR was observed in 23/41 asymptomatic (sensitivity 56.1%, 95%CI 41.0-70.1%) versus 8/9 symptomatic (sensitivity 88.9%, 95%CI 56.5-98.0%) TB cases. Sensitivity of CXR in combination with symptom screening was 64.0% (32/50, 95%CI 50.1-75.9%) for all prevalent TB. More than 80% of confirmed TB cases among HHC were asymptomatic. CXR screening missed more than 40% of these asymptomatic cases. Community prevalence surveys reliant on symptom- and CXR-based approaches may significantly underestimate the prevalence of asymptomatic TB in endemic countries. Supported by RePORT South Africa through funding from the U.S. National Institutes of Health, CRDF Global, and the South African Medical Research Council. Evidence before this study: World Health Organisation (WHO) guidelines for systematic tuberculosis (TB) screening recommend symptom screening and chest radiography (CXR), based on a Cochrane meta-analysis reporting 70.6% sensitivity (any TB symptom) and 94.7% sensitivity (any CXR abnormality) for bacteriologically-confirmed pulmonary TB. National TB prevalence surveys rely on a positive symptom screen or abnormal CXR to trigger diagnostic sputum testing. This approach to community screening would, by definition, miss asymptomatic TB cases without CXR evidence of disease. We reviewed the reference list of the aforementioned meta-analysis for active case-finding studies of adolescents and adults aged 15 years and older in community and contact-tracing settings. We performed forward citation-tracking and searched reference lists, including studies published in English between Jan 1, 1980, and November 1, 2024. We excluded studies that included children <15 years; or that exclusively enrolled people with additional risk factors (HIV; diabetes; latent TB infection; prior TB). We found 28 studies that performed universal sputum testing for bacteriologically-confirmed pulmonary TB and reported 51.8% (95%CI 49.9-53.7%; I 2 = 89.2%) pooled sensitivity for symptom screening (any symptom; 24 studies, 2,969 TB cases) and 62.4% (95%CI 59.3-65.3%; I 2 = 88.3%) pooled sensitivity for CXR (any abnormality; 10 studies, 1,123 TB cases). Only four studies (145 TB cases) reported accuracy of symptom screening in parallel with chest radiography (pooled sensitivity 67.3%, 95%CI 57.3-75.9%; I 2 = 87.1%), but these studies did not disaggregate symptomatic and asymptomatic disease. Added value of this study: We performed systematic screening using universal sputum microbiological testing of 978 household contacts of pulmonary TB patients in three South African communities and compared symptom (any duration) and CXR (any abnormality) screening approaches against a microbiological reference standard. We detected confirmed pulmonary TB in 5.2% of household contacts, and 82.4% of these TB cases reported no TB symptoms. Asymptomatic TB in household contacts was pauci-bacillary and associated with low serum CRP levels that were indistinguishable from healthy controls, but distinct from symptomatic TB in a comparator group of clinic attendees. Sensitivity of CXR screening for asymptomatic TB was only 56.1%; sensitivity of combined symptom and CXR screening for all TB was marginally higher at 64.0%.Implications of all the available evidence: Our findings from household contacts suggest that symptom- and CXR-based approaches are inadequate for community TB screening in South Africa and do not meet the WHO Target Product Profile for a TB screening test (minimum 90% sensitivity; 70% specificity). National TB Prevalence Surveys that omit universal sputum microbiological testing may significantly underestimate the prevalence of asymptomatic TB in high-burden countries.

Mycobacterium tuberculosis Infections in Solid Organ Transplantation

Background:One-third of tuberculosis (TB) cases are missed each year and delays in the diagnosis of TB are hampering the whole cascade of care. Early chest X-ray (CXR) in patients with cough irrespective of duration may reduce TB diagnostic and treatment delays and increase the number of TB patients put into TB care. We aimed to evaluate the impact of CXR on delay in the diagnosis of pulmonary tuberculosis (PTB) among people with cough of any duration.Methods:A facility-based cross-sectional study was conducted in four selected health facilities from two regions and two city administrations of Ethiopia. Patients who sought health care were screened for cough of any duration, and those with cough underwent CXR for PTB and their sputum specimens were tested for microbiological confirmation. Delays were followed up and calculated using median and inter-quartile range (IQR) to summarize (first onset of cough to first facility visit, ≥15 days), diagnosis delay (first facility visit to date of PTB diagnosis, >7 days), and total delay (first onset of cough to date of PTB diagnosis, >21 days). Kruskal–Wallis and Mann–Witney tests were used to compare the delays among independent variables.Results:A total of 309 PTB cases were consecutively diagnosed of 1853 presumptive TB cases recruited in the study that were identified from 2647 people who reported cough of any duration. The median (IQR) of patient delay, diagnosis delay, and the total delay was 30 (16–44), 1 (0–3), and 31 (19–48) days, respectively. Patients’ delay contributed a great role in the total delay, 201/209 (96.2%). Median diagnosis delay was higher among those that visited health center, diagnosed at a facility that had no Xpert mycobacterium tuberculosis (MTB)/RIF assay, radiologist, or CXR (P < 0.05). Factors associated with patients delay were history of previous TB treatment (adjusted prevalence ratio [aPR] = 0.79, 95% confidence interval [CI]: 0.63–0.99) and history of weight loss (aPR = 1.12; 95% CI: 1.0–1.25). Early CXR screening for cough of <2 weeks duration significantly reduced the patients’ delay and thus the total delay, but not diagnostic delay alone.Conclusion:Early screening using CXR minimized delays in the diagnosis of PTB among people with cough of any duration. Patients’ delay was largest and contributed great role in the delay of TB cases. Screening by cough of any duration and/or CXR among people seeking healthcare along with ensuring the availability of Xpert MTB/RIF assay and skilled human power at primary healthcare facilities are important to reduce patient and diagnostic delays of PTB in Ethiopia.

BACKGROUND AND OBJECTIVES:There are few reports of cutaneous tuberculosis with immunosuppressed states such as HIV, use of immunosuppressants or malignancy. Diagnosis is thus difficult and despite scientific advances such as polymerase chain reaction, it is frequently missed. Although rare, given its worldwide prevalence and the rising incidence of HIV, it is important for clinicians to recognize the variants and promptly treat the patient.DESIGN AND SETTING:Retrospective study of all cases of cutaneous tuberculosis diagnosed from October 2007 to November 2009 at an outpatient clinic of a tertiary-care hospital in northern India.METHODS:We collected information on the clinical form of disease, histopathology and HIV concurrence rates and looked for differences in presentation between mmunocompetent and immunocompromised states. We also looked for differences and HIV concurrence between immunocompetent and immunocomprised patients. Diagnosis was based on clinical, histopathological and microbiological tests for tuberculosis and a test for HIV.RESULTS:The overall incidence of cutaneous tuberculosis was 0.7% (131 of 18720 outpatients). HIV concurrence was 9.1% (12 cases) of all cutaneous tuberculosis cases. Most common variants seen were scrofuloderma (36.5%), lupus vulgaris (31%), tuberculosis verruca cutis (12.9%), lichen scrofulosorum (11.4%), papulonecrotic tuberculids (3.8%), erythema nodosum (2.2%) and erythema induratum of Bazin (1.5%).CONCLUSIONS:Cutaneous tuberculosis rates were slightly higher in our study than in other studies from India. HIV co-infection rates were similar to those in other studies. Many atypical morphological forms and presentations were observed in HIV co-infected patients. Due to the varied clinical presentations, physician awareness and a high index of suspicion are necessary to diagnose cutaneous forms of tuberculosis.