This study aims to systematically compare the clinical characteristics of tuberculosis (TB) and nontuberculous mycobacterial (NTM) diseases in AIDS patients,and to identify independent predictors for differential diagnosis. Clinical data of AIDS patients co-infected with TB or NTM at Shanghai Public Health Clinical Center (January 2019 - January 2024) were retrospectively analyzed. Univariate comparisons were performed using t-test, Mann-Whitney U test, χ2 or Fisher's exact test, with Bonferroni correction for multiple comparisons. Multivariate binary logistic regression (Enter method) was used to adjust for age, gender, CD4+ T-cell count, C-reactive protein (CRP), procalcitonin, neutrophil count, miliary nodules, and superficial lymphadenopathy. A total of 494 patients were included (AIDS/TB: 206, AIDS/NTM: 288). The predominant NTM species was Mycobacterium avium (68.2%), followed by Mycobacterium kansasii (13.6%) and Mycobacterium intracellulare (10.9%). After Bonferroni correction, AIDS/NTM patients had significantly higher rates of Pneumocystis jirovecii pneumonia, cytomegalovirus infection, and progressive multifocal leukoencephalopathy (all P < 0.0083). Among clinical symptoms, only enlarged lymph nodes remained significantly more common in the TB group after correction (P = 0.002). Multivariate analysis showed that male gender (adjusted OR for NTM vs. TB = 0.451, 95% CI: 0.208-0.979, P = 0.044), higher CD4+ count (per 10 cells/μL: OR = 0.98, 95% CI: 0.96-0.99, P = 0.005), higher CRP (per 10 mg/L: OR = 0.90, 95% CI: 0.86-0.95, P < 0.001), higher neutrophil count (OR = 0.903 per 1 × 10(Akokuebere et al., 20249)/L, 95% CI: 0.836-0.976, P = 0.010), presence of miliary nodules (OR = 0.079, 95% CI: 0.027-0.233, P < 0.001), and presence of superficial lymphadenopathy (OR = 0.565, 95% CI: 0.327-0.977, P = 0.041) were independently associated with lower odds of NTM disease (i.e., associated with TB). Imaging revealed that only miliary nodules remained significantly more common in TB after Bonferroni correction (P < 0.001). While AIDS/TB and AIDS/NTM share many clinical similarities, the presence of miliary nodules, superficial lymphadenopathy, higher inflammatory markers (CRP, neutrophils), higher CD4+ count, and male gender favor TB. These findings can assist clinicians in differentiating the two infections when rapid microbiological results are unavailable. The high prevalence of Mycobacterium avium (68.2%) suggests that empirical therapy for suspected NTM in severely immunocompromised AIDS patients in Shanghai should cover the Mycobacterium avium complex (MAC). Prospective multicenter studies with pre-specified outcomes are needed to validate our findings.
Tuberculosis remains one of the primary infectious diseases in Bangladesh that affects both adults and children. Poor diagnostic criteria and insufficient reporting, especially of pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) in children, limit the prevalence estimation, resulting in insufficient preventive strategies. This systematic review and meta-analysis aim to estimate the pooled proportions of PTB and EPTB among pediatric and adult diagnosed tuberculosis cases in Bangladesh, and to summarize the associated factors. We searched PubMed, Scopus, Cochrane Library, and BanglaJOL to retrieve articles published between January 1, 2000, and May 31, 2025. Eligible studies included retrospective studies that reported PTB and/or EPTB prevalence in pediatrics (<18 years) or adults (≥18 years) diagnosed tuberculosis cases in Bangladesh. We used the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies to assess the quality of the studies. Random-effects models estimated pooled proportions and I2, τ2, Cochran's Q, and meta-regression assessed heterogeneity. Subgroup analyses compared proportion by age group. Eleven studies (6 pediatrics, 5 adults) met the eligibility criteria. In patients with tuberculosis, the overall pooled proportion across all ages was 44.4% for PTB (95% CI: 35.9-53.3%; I2 = 93%) and 47.1% for EPTB (95% CI: 34.0-60.7%; I2 = 95%). Among pediatric populations, the pooled proportion of PTB was 44.5% (95% CI: 35.9-53.4%; I2 = 76%), while EPTB accounted for 55.5% (95% CI: 46.6-64.1%; I2 = 77%). In adults, PTB proportion was 44.2% (95% CI: 28.8-61.2%; I2 = 97%), and EPTB proportion was 37.4% (95% CI: 17.0-63.6%; I2 = 97%). Subgroup analysis revealed no significant difference in the proportions of PTB and EPTB between pediatric and adult groups. The most notable reported associations with PTB and EPTB in pediatrics included young age, exposure to tuberculosis patients, and male sex and, in adults, elderly age, female sex, low socioeconomic status, low education level, and comorbidities. Findings suggest a high proportion of PTB and EPTB in diagnosed tuberculosis cases in Bangladesh, with a relatively higher proportion of EPTB in children than adults. Key associated factors included exposure to tuberculosis patients, sex, low socioeconomic status, and other related comorbidities. Strengthening diagnostic capacity, expanding contact tracing, and addressing the associated factors through targeted public health interventions are necessary to enhance tuberculosis control efforts.
Standard weight-based dosing of first-line anti-tuberculosis drugs does not consistently achieve therapeutic plasma concentrations in all patients. Inadequate drug exposure may contribute to poor treatment response, particularly in extrapulmonary and disseminated tuberculosis, where pharmacokinetic variability is more pronounced. Therapeutic drug monitoring (TDM) offers a strategy to individualize dosing and optimize plasma drug concentrations. This observational analytical study enrolled 100 patients with pulmonary, extrapulmonary, or disseminated tuberculosis, of whom 84 with complete TDM data were included in the final analysis. All patients received standard weight-based doses of rifampicin, isoniazid, and pyrazinamide. Plasma drug concentrations were measured after two weeks of anti-tuberculosis therapy (steady state) at 2 and 4 h following supervised drug administration. Patients with subtherapeutic concentrations underwent TDM-guided dose modification, followed by repeat plasma sampling at identical post-dose time points. Plasma drug concentrations before and after dose modification were compared, including subgroup analysis by acetylator status. Among the 84 patients, 27.4% (n = 23) had pulmonary tuberculosis, 58.3% (n = 49) extrapulmonary tuberculosis, and 14.3% (n = 12) disseminated disease. At baseline, subtherapeutic 2-hour plasma concentrations were observed in 67.9% (57/84) for rifampicin and 61.9% (52/84) for isoniazid, while 11.9% (10/84) had subtherapeutic pyrazinamide levels. Following TDM-guided dose modification, median rifampicin concentrations increased from 5.9 mg/L (IQR 4.8-6.6) to 15.1 mg/L (IQR 13.7-16.8), and median isoniazid concentrations from 2.3 mg/L (IQR 1.9-2.6) to 6.2 mg/L (IQR 5.3-6.9) (p < 0.001 for both). Subtherapeutic exposure declined to 7.1% for rifampicin and 9.5% for isoniazid. Fast acetylators had significantly lower baseline isoniazid concentrations but showed marked improvement after dose escalation. Subtherapeutic plasma concentrations of rifampicin and isoniazid are highly prevalent in patients with pulmonary, extrapulmonary, and disseminated tuberculosis receiving standard weight-based dosing. TDM-guided dose modification results in significant and clinically meaningful improvements in drug exposure. Selective incorporation of TDM into routine tuberculosis care may facilitate precision dosing, particularly in patients with extrapulmonary disease or suspected pharmacokinetic variability.
Diagnosis of pulmonary tuberculosis (PTB) among people living with HIV (PLHIV) remains challenging, particularly in high TB/HIV burden settings. We evaluated serum biomarkers associated with active PTB and their relationship with TB-related clinical characteristics among hospitalized PLHIV in Uganda. We analysed archived serum samples from adult PLHIV (n = 60) categorized into three groups (20 each): (i) sputum culture and/or GeneXpert-confirmed PTB (active PTB), (ii) presumptive TB with negative TB culture/GeneXpert (symptomatic PTB-negative), and (iii) asymptomatic PLHIV attending routine HIV care (asymptomatic PLHIV controls). Inflammatory biomarkers including C-reactive protein (CRP) and leptin as well as immune activation markers (interferon gamma-induced protein 10 -IP-10 and β2-microglobulin) were quantified using enzyme-linked immunosorbent assay and Bio-Plex Pro assays. Biomarker levels were compared between active PTB and TB-negative groups. Logistic regression identified biomarkers independent associations with active PTB and Spearman rank correlation assessed biomarkers correlations with TB-related clinical characteristics among active PTB participants. Median serum concentrations of IP-10 (19,566 pg/mL; p = 0.001), β2-microglobulin (33.9 ng/mL; p = 0.023), and CRP (1.77 mg/dL; p = 0.05) were significantly higher among active PTB participants compared to symptomatic PTB-negatives and asymptomatic PLHIV controls. Conversely, leptin levels were significantly lower in the active PTB (35.0 pg/mL) than in asymptomatic PLHIV controls (102.4 pg /mL; p = 0.001). IP-10 (adjusted odds ratio-aOR 2.74; 95% CI: 1.54-4.88; p < 0.001) and β2-microglobulin (aOR 2.09; 95% CI: 1.13-3.86; p = 0.019) were the strongest independent predictors of active PTB. Biomarker concentrations did not correlate significantly with TB-related clinical characteristics. IP-10, β2-microglobulin, and CRP were elevated in PLHIV with active PTB, whereas leptin levels were reduced. These biomarkers did not correlate with clinical characteristics. Our findings show that serum biomarkers may aid in identifying PTB among hospitalized PLHIV but with limited value in assessing clinical presentation. Further research is warranted to rigorously evaluate their diagnostic performance in both simple and combined biomarkers models and to evaluate their point-of-care utility for TB screening and timely treatment initiation in hospitalized PLHIV.
The relationship between vitamin D receptor gene variations and other risk factors in pulmonary tuberculosis remains unclear, largely due to the complex interplay of genetic and environmental factors. The purpose of this study was to investigate how TaqI gene polymorphism and vitamin D deficiency affect the risk of developing pulmonary tuberculosis. A hospital-based case-control study of 70 pulmonary tuberculosis patients and 70 age- and sex-matched healthy controls was conducted. Serum 25-hydroxyvitamin D levels were measured using ELISA to assess vitamin D status. Genomic DNA was extracted from peripheral blood samples, and VDR TaqI polymorphism was analyzed using PCR-RFLP. Data were analyzed using independent t-tests, chi-square tests, and multivariable logistic regression to calculate adjusted odds ratios at a 95% confidence level. Our analysis showed that the TaqI-tt genotype (OR = 2.19; 95% CI = 1.21-4.06; P = 0.022) and t allele (OR = 1.66; 95% CI: 1.02-2.70; P = 0.038) are considerably higher in patients than controls. Our study also identified vitamin D deficiency, which was found to be considerably greater in patients than controls (OR = 5.14; 95% CI: 2.49-10.58; P < 0.001), indicating that it is a major risk factor for the onset of pulmonary tuberculosis. The TaqI gene of the tt genotype and the t allele have been linked to an increased risk of developing pulmonary tuberculosis. Moreover, vitamin D deficiency is a risk factor for the occurrence of pulmonary tuberculosis.
This study aims to evaluate the clinical value and safety of hand-drawn mapping for bronchoscopic navigation combined with radial probe endobronchial ultrasound (RP-EBUS) in the diagnosis of primary peripheral sputum smear-negative pulmonary tuberculosis (SNPTB). Patients suspected of having peripheral-type primary SNPTB, who were admitted to Southeast University Zhongda Hospital from 2021 to 2024, were retrospectively analyzed. Patients were divided into two groups. The sensitivity, specificity, diagnostic accuracy rate, and area under the receiver-operating characteristic (ROC) curve were evaluated with different diagnostic methods. A total of 212 patients were enrolled, including 149 in the SNPTB group and 63 in the non-SNPTB group. The success rate of ultrasound bronchoscopy exploration is 90.6 %. The sensitivity, specificity, diagnostic accuracy, and AUC value of bronchoscopy guided by hand-drawn mapping were 92.6 %, 95.2 %, 93.4 %, and 0.939, respectively, which were superior to those of T-SPOT detection (P < 0.05). Among the various sampling methods, EBUS-guided bronchoalveolar lavage fluid metagenomic next-generation sequencing (EBUS-BALF mNGS) demonstrated the highest sensitivity (86.6 %), positive predictive value (89.6 %), and AUC (0.917). For peripheral SNPTB, the combination of hand-drawn navigation and RP-EBUS is both safe and effective. EBUS-BALF mNGS demonstrated the highest diagnostic efficiency. When radial ultrasound detects hypoechoic areas of the lesion, it is recommended to perform BALF mNGS. Conversely, in solid lesions, the negative rate of BALF mNGS is relatively high, and combining mNGS with biopsy is recommended to further improve diagnostic efficiency.
Tuberculosis (TB) remains a major global health challenge, particularly in low-income settings where structural inequities hinder early diagnosis and care. Ethiopia, one of the 30 high TB-burden countries, continues to experience marked geographic disparities. Understanding knowledge, attitudes, and practices (KAP) among affected populations is essential to inform context-specific interventions supporting the End TB Strategy. A cross-sectional KAP survey was conducted in Woliso District (Oromia Region, Ethiopia) between April 2023 and December 2024, including 152 TB index cases and 326 household contacts. A structured, interviewer-administered questionnaire assessed knowledge of TB symptoms, transmission, diagnosis, and perceived barriers to care. Categorical variables were compared using Chi-square or Fisher's exact test, and continuous variables with Mann-Whitney test. Among 478 participants (median age 28 years [IQR 19-40]; 44.1% female), 69.5% lived in rural areas. The main barriers to timely diagnosis were absence of nearby TB diagnostic facilities (13.4%), poor road conditions (6.3%), health system delays (5.9%), and financial constraints for transportation (3.8%). Poor roads and transport costs were reported more often by rural residents (p < 0.05), while absence of nearby TB diagnostic facilities was reported most often by index cases and older subjects (p < 0.05). Recognition of cough lasting >2 weeks (84.3%) and night sweats (65.7%) was common, while hemoptysis (49.6%) and fever (16.1%) were less recognized. Awareness of sputum and X-ray diagnostics was 87.2%, higher among index cases (95.4% vs. 83.4%, p = 0.0005). Although 77.0% considered TB life-threatening, 52.2% believed it was transmissible only through close or bed-sharing contact (p < 0.0001 for rural vs. urban). Older age correlated with better knowledge across most domains (all p < 0.01). Overall, subjects living in rural area had higher scores about barriers for accessing TB care (p = 0.0004) and attitude on TB (p = 0.01), and lower score about knowledge on TB (p = 0.002). While TB knowledge and attitudes were generally high, misconceptions about transmission and persistent structural barriers hinder access to timely diagnosis and care. Expanding community-based diagnostic capacity, improving rural infrastructure, and integrating social protection strategies are key to advancing Ethiopia's progress toward End TB targets.
Vitamin D supplementation as adjunctive therapy in tuberculosis has generated multiple systematic reviews with variable conclusions. The proliferation of syntheses in this field requires comprehensive evaluation to determine the temporal evolution of evidence and its translation into clinical recommendations. To synthesize systematic reviews on vitamin D supplementation in tuberculosis, evaluate the temporal evolution of conclusions, examine heterogeneity in clinical outcomes, and determine the quality of available evidence for clinical practice. An umbrella review was conducted in accordance with PRIOR guidance for overviews of reviews, searching MEDLINE, Embase, Web of Science, and Scopus. Systematic reviews examining vitamin D as adjunctive therapy in tuberculosis were included. Methodological quality was assessed using AMSTAR-2 and ROBIS, and evidence certainty was evaluated with GRADE adapted for umbrella reviews. Overlap among primary randomized trials was quantified using a citation matrix and the corrected covered area (CCA). Nine systematic reviews (2009-2022) were identified, encompassing 300-2991 participants. A citation matrix identified 16 unique primary RCTs and 64 trial occurrences across nine reviews, corresponding to very high overlap (CCA = 37.5%). Meta-analytic findings consistently demonstrated null effects for primary outcomes: culture conversion RR 1.04-1.05, time to conversion HR 1.04-1.15, and mortality without significant differences. Subgroup analyses revealed potential effects in VDR TaqI tt genotype (HR 8.09, 95% CI 1.36-48.01) and multidrug-resistant tuberculosis (RR 2.40, 95% CI 1.11-5.18), although these findings were based on small sample sizes. Safety profiles were favorable with hypercalcemia <2%. Current evidence from overlapping systematic reviews does not support routine vitamin D supplementation as adjunctive therapy to improve tuberculosis treatment outcomes in unselected populations. Signals in VDR TaqI tt genotype carriers and multidrug-resistant tuberculosis remain hypothesis-generating and require prospective validation before clinical translation.
People who slowly metabolize isoniazid are at increased risk of drug-induced liver injury (DILI) and interruption of tuberculosis treatment. We hypothesized that immediate identification of slow acetylators among patients with DILI will facilitate rapid and safe reintroduction of isoniazid. Between 2021 and 2023, at our tuberculosis referral centre in The Netherlands, we evaluated an isoniazid acetylator status-guided rapid reintroduction of anti-tuberculous drugs in a cohort of patients with DILI. Patients' acetylator status was determined by phenotyping after a single dose of isoniazid, regardless of liver function abnormalities. In total, 49 tuberculosis patients underwent Therapeutic Drug Monitoring (TDM) from 2021 to 2023, with 67% being slow acetylators as assessed by phenotyping. Out of 10 patients with DILI, 8 were slow acetylators, and the total exposure to isoniazid (AUC0-24h) inversely correlated with the days until onset of hepatotoxicity in those patients (R = -0.84, p = 0.002). Six out of ten patients with DILI received a single dose of isoniazid for phenotyping, five of whom appeared to be slow acetylators. These slow acetylators were restarted at a lower dose of isoniazid. The phenotyping strategy led to a shorter total treatment duration compared to current guidelines for DILI. However, we also propose an even more optimized strategy, in which fewer than 14 days of therapy are ultimately missed, which could further reduce the total treatment duration by more than a month. In tuberculosis patients with DILI, assessment of isoniazid acetylator status can guide rapid reintroduction of isoniazid. Combined with AUC0-24h measurement through TDM, this approach supports appropriate dosing and may help shorten total treatment duration.
Latent tuberculosis infection (LTBI) remains a critical reservoir for the global tuberculosis (TB) epidemic, particularly in South Asia, where high population density and socioeconomic disparities amplify its burden. However, LTBI epidemiological trajectories and long-term forecasts have received limited attention. This study characterizes LTBI prevalence trends in South Asia from 1990 to 2021 and forecasts prevalence to 2050 to inform targeted interventions. We analysed age-standardised LTBI prevalence rates (ASPR per 100 000 population) from the Global Burden of Disease Study 2021 for five high-burden South Asian countries (Bangladesh, Bhutan, India, Nepal, Pakistan) from 1990 to 2021, stratified by sex. Joinpoint regression identified temporal inflection points and calculated average annual percent change (AAPC) and segment-specific annual percent changes (APC) with 95% confidence intervals. Auto-ARIMA models, selected by minimised Akaike Information Criterion with first differencing for stationarity, generated projections up to 2050 with 95% prediction intervals (PI) based on 1000 bootstrap simulations. Negative point forecasts were interpreted as signals of potential near-elimination, with lower bounds truncated at zero. From 1990 to 2021, Bangladesh (AAPC -3.55%, 95% CI -3.61 to -3.49), Bhutan (-3.38%, -3.45 to -3.32), Nepal (-2.17%, -2.31 to -2.06), and Pakistan (-2.53%, -2.64 to -2.42) achieved steep declines. India showed only modest reduction (AAPC -0.76%, -0.93 to -0.59) with a significant resurgence during 2015-2019 (APC + 1.20%, +1.05 to +1.39). Sex-specific patterns revealed steeper declines among females in Nepal, Bangladesh, and Bhutan, but a more pronounced resurgence among Indian females (+1.32%) than males (+1.09%). Auto-ARIMA projections to 2050 indicate continued rapid declines in Bangladesh, Bhutan, Nepal, and Pakistan, with point estimates falling below 5000 per 100 000 (many strata reaching zero) by mid-century. India's ASPR remains essentially stable at approximately 26,300-26,400 per 100 000 through 2050. Regional aggregation masks this heterogeneity, projecting only marginal decline (ASPR 23,283 in 2021 to 23,085 in 2050; 95% PI 12,554-33,616). Wide prediction intervals beyond 2035 highlight substantial long-horizon uncertainty. Four of five high-burden South Asian countries are on trajectories compatible with very low LTBI prevalence or pre-elimination by 2050, driven by strong primary-healthcare integration and community engagement. India's persistently high burden, explained by massive scale, urban transmission hotspots, internal migration, and a large multidrug-resistant reservoir, will continue to dominate regional and global metrics unless transformative interventions are implemented. The extraordinarily wide 2050 prediction intervals underscore that favourable outcomes are plausible but not inevitable; achieving them will require sustained political commitment, equitable financing, and accelerated deployment of new tools (shorter preventive regimens, TB vaccines). Targeted, gender-responsive, and adaptive strategies are essential for South Asia to meet, and in several countries exceed, WHO End TB Strategy milestones.
Eosinophilic bronchiectasis is defined by a blood eosinophil count (BEC) ≥300 cells/µL, but blood eosinophils imperfectly reflect airway eosinophilic inflammation. Here, we investigated the relationship between eosinophilic airway inflammation, blood eosinophils and clinical severity in bronchiectasis and explored the phenotype associated with eosinophilic bronchiectasis. Sputum from 180 patients with stable CT-confirmed bronchiectasis was utilised to investigate airway levels of eosinophil proteins (eosinophil peroxidase (EPX), eosinophil derived-neurotoxin (EDN), eosinophil cationic protein (ECP), major basic protein (MBP) and Galectin-10 (Gal-10)) using a novel stable isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. To profile eosinophilic bronchiectasis, a nested analysis of patients with BEC <150 cells/µL (n=52) and ≥300 cells/µL (n=49) was conducted. Sputum concentrations of Gal-10, ECP and EDN were weakly but significantly associated with radiological severity, FEV1 and sputum culture positivity for Pseudomonas aeruginosa. Airway eosinophil protein concentrations did not associate with exacerbation frequency. Total eosinophil protein concentration moderately correlated with BECs (r=0.33 95% CI 0.14 to 0.49, p=0.0007). Nested analysis revealed increased sputum PCR-positivity for P. aeruginosa (26.7% vs 7.7%, p=0.033) and an increased frequency of patients showing signs of Aspergillus sensitisation (defined as Aspergillus-specific IgE titres >0.35 kUA/L, 24.5% vs 3.8%) in eosinophilic bronchiectasis. Sputum inflammatory biomarkers and clinical parameters did not differ between groups. LC-MS/MS can detect eosinophilic inflammation within bronchiectasis sputum. Weak associations between elevated airway eosinophil proteins, bronchiectasis severity and P. aeruginosa infection were observed. Direct measurement of eosinophilic airway inflammation provides additional information in addition to BECs. Eosinophilic bronchiectasis associated with P. aeruginosa infection and Aspergillus sensitisation.
HIV coinfection and multidrug-resistant tuberculosis (MDR-TB) pose a major public health challenge in sub-Saharan Africa, where high HIV prevalence promotes tuberculosis progression and complicates its management. In people living with HIV (PLHIV), profound immunosuppression leads to atypical clinical presentations, low bacillary load, and increased diagnostic difficulty. Despite advances such as the introduction of the GeneXpert test and all-oral treatments such as the BPaL regimen, access to these tools remains uneven, exacerbating diagnostic delays and mortality. Drug interactions between antiretrovirals and second-line antituberculosis drugs, as well as the toxicity of prolonged regimens, further complicate clinical management. Mortality among coinfected patients remains high, sometimes exceeding 40%, particularly in the absence of early diagnosis and adequate treatment. Improved early detection, integration of HIV/MDR-TB care and accessibility to innovative treatments are essential to change the trajectory of this dual epidemic in the region.
Non-tuberculous mycobacteria (NTM) increasingly recognized as clinically relevant pathogens, particularly in immunocompromised individuals and patients with structural lung disease. Despite their growing clinical impact, real-world data on NTM infections in Europe remain limited. We conducted a retrospective cohort study in adults diagnosed with NTM infections at a 1700-bed tertiary care hospital in Italy between 2015 and 2024. Data were collected on demographics, comorbidities, radiological and microbiological findings, treatment regimens, and outcomes. Multivariable Cox regression analyses were performed to identify factors associated with treatment failure, overall mortality, and NTM-attributable mortality. Among 149 treated patients (median age: 68 years; 60.4% female), the most prevalent species were Mycobacterium avium (38.9%), M. intracellulare (29.5%), and M. kansasii (8.7%). Pulmonary disease was observed in 87.9%, with radiologic findings commonly including nodules (67.8%) and bronchiectasis (64.6%). Clinical cure was achieved in 52.3%, while 47.7% experienced treatment failure. The relapse rate was 9.4%. All-cause and NTM-attributable mortality were 14.8% and 4.7%, respectively. Treatment failure was significantly associated with cavitary disease. Attributable mortality was independently associated with older age, , previous tuberculosis, cancer, autoimmune disorders, and use of nebulized amikacin. NTM infections remain challenging to manage, particularly among patients with comorbidities and immunosuppression. Our findings highlight the need for individualized care strategies, multidisciplinary approach, improved diagnostics, and enhanced surveillance of NTM infections in Europe.
The purpose of this review was to estimate the prevalence of substance use during TB treatment and to synthesize the relationship between substance use and TB care engagement in the African region. Our secondary aim was to identify methods of substance use evaluation. Adhering to the PRISMA method, search strategies for PubMed, Embase and CINAHL were developed to maximize yield. Substance use was defined as use of illicit substances including cannabis and khat/chat. TB care engagement was defined loosely through sub-optimal adherence, missed appointments, treatment interruption and loss to follow up. Peer reviewed research, published in English that evaluated a relationship between substance use and TB care engagement were included. We estimated the pooled prevalence of substance use among people with TB using the meta command in Stata 18. The initial search generated 1311 titles; 18 studies were included spanning six countries. Substance use ranged from 3 to 48% with an estimated pooled prevalence 11.3% across studies. There was conflicting evidence linking substance use and care engagement. While three studies used a validated tool to comprehensively evaluate substance use, most studies used a single indicator (yes/no) to evaluate substance use and did not quantify the frequency of use. We estimated a pooled prevalence of substance use during TB treatment at 11.3%; however, as self-report was used to collect substance use data, desirability bias likely led to an underestimation of the true prevalence. Additional research is warranted to evaluate the true effect of substance use on TB care engagement.
Lung ultrasound (LUS) is increasingly used as a diagnostic tool in respiratory medicine, particularly in resource-limited, tuberculosis (TB)-endemic settings. Sonographic interstitial syndrome (IS), characterized by B-line artefacts, has proven valuable in diagnosing cardiogenic pulmonary edema, pneumonia, and chronic interstitial lung disease. However, in TB-endemic areas, its interpretation remains challenging due to overlapping pathologies. This illustrated review explores the diagnostic and prognostic relevance of IS across three clinical contexts: acute respiratory distress, chronic interstitial lung disease, and pulmonary TB. We review current evidence and discuss illustrative cases from TB-endemic settings to highlight sonographic pattern variations and guide clinicians in recognizing key diagnostic features and common pitfalls. IS, while inherently non-specific, gains diagnostic value when contextualized within the patient's background and within additional sonographic findings such as pleural line abnormalities, consolidations, and altered lung sliding. Specific TB manifestations-including miliary TB, cavitary TB, HIV-associated TB, and post-TB sequelae-demonstrate diverse IS presentations. Accurate interpretation requires understanding disease-specific patterns, using appropriate scanning techniques, and adhering to standardized protocols. Greater awareness of IS variations among clinicians can improve diagnostic accuracy and clinical decision-making in TB-endemic regions.
Medication non-adherence, potentially influenced by psychological and social factors, is a major barrier to effective treatment of tuberculosis. This study aimed to examine the associations between anxiety, depression, and social support with medication adherence. A cross-sectional study was conducted among 215 inpatients at the National Center for Communicable Diseases. Data were collected using Hospital Anxiety and Depression Scale (HADS), Medication Adherence Rating Scale (MARS), Oslo Social Support Scale (OSSS-3). Associations with medication adherence were examined using chi-squared tests and multivariable logistic regression. Among the participants, 53.0% (n = 114) exhibited clinical signs of depression, and 44.2% (n = 95) had borderline or abnormal anxiety. Medication non-adherence was reported in 56.7% of patients. Abnormal anxiety was linked to a threefold higher risk of non-adherence (OR = 3.829, 95% CI = 1.495-9.807, P = 0.005). Poor (OR = 2.769, P = 0.024) and moderate (OR = 2.409, P = 0.043) social support also significantly increased risk. Depression was common but not significantly associated with adherence. Anxiety and social support influence TB patients' adherence with their treatment repertoire. Screening for anxiety and implementing interventions to enhance social and family support may improve adherence and optimize treatment outcomes in this patient population.
Village doctors played a crucial role in tuberculosis (TB) control in China. While scant attention has been paid to village doctors' knowledge of TB preventive treatment (TPT), even less is known about their willingness to receive and manage it. This study assessed their knowledge, acceptance, and willingness to manage TPT via a cross-sectional survey among village doctors in Zhongmu County, Henan. Self-designed questionnaires and interferon-γ release assays (IGRA) were used to assess factors associated with TPT knowledge, acceptance, and management willingness. A total of 496 registered rural doctors were enrolled in this study, IGRA positivity rate was 21.2%, only 32.9% of rural doctors had good knowledge of TPT. Despite the generally low knowledge acquisition, 92.1% of the rural doctors were willing to accept TPT and 93.9% were willing to manage TPT, key concerns included side effects (70.4%), long treatment duration (41.6%), and efficacy doubts (38.3%). Male doctors had significantly higher knowledge scores than females (p < 0.05). Overall, knowledge of latent TB infection and TPT was low, but willingness was high. The IGRA result had no influence on village doctors' knowledge of TPT, acceptance of TPT, or willingness to manage TPT. Education needs to be strengthened, especially for weak knowledge points, to improve prevention and control capacity.
Extrapulmonary tuberculosis (EPTB) represents a range of disease manifestations, and is a major contributor to ongoing TB burden in the United States. We examined the incidence, trends and characteristics of EPTB in a high-burden TB county in Northern California. We extracted surveillance data for all TB cases in Alameda County during 2010-2021. TB was classified per national surveillance definitions, and EPTB included any site involvement other than the lung. We determined overall and annual incidence of EPTB in comparison to pulmonary TB (PTB), and assessed trends in incidence using Poisson regression and proportion with Joinpoint regression. We further compared clinical and demographic characteristics by TB site of disease. Of 1,336 TB cases included, 372 (28%) had EPTB disease only. Lymph nodes were the most common site (38.7%), followed by pleura (17.7%), peritoneal (5.4%), and bone (4.8%). From 2010 to 2021, EPTB incidence decreased by 52% from 3.5 to 1.7 cases per 100,000. However, the proportion of TB cases that were extrapulmonary increased from 2015 to 2021 (8.3% annual change, 95% CI 5.2%-14.2%). In comparison to PTB, EPTB case-patients were more likely to be aged < 45 years old, have end-stage renal disease, and pyrazinamide monoresistance, but less likely to have microbiological confirmation. EPTB incidence has decreased over time, but the proportion of EPTB cases increased. Greater awareness of clinical and demographic characteristics of EPTB may guide targeted interventions to support TB elimination.
Pleural tuberculosis is one of the most frequent extrapulmonary manifestations of Mycobacterium tuberculosis infection and is characterized by a pronounced immune-mediated response with a low bacillary burden. Host genetic factors appear to play a central role in its immunopathogenesis. A systematic review was conducted in accordance with PRISMA guidelines and prospectively registered in PROSPERO (CRD420251051395). Searches were performed across MEDLINE/PubMed, Embase, and SciELO databases, covering publications from 1970 to December 2023. The search strategy combined terms related to pleural involvement, tuberculosis, and genetic polymorphisms. Eight studies fulfilled all eligibility criteria. Polymorphisms in genes involved in innate immunity (SLC11A1/NRAMP1, TLR2, TLR4), cytokine regulation (IFN-γ, IL-10), and host lipid metabolism (CYP7A1) were associated with susceptibility patterns and distinct immunological phenotypes in pleural tuberculosis. These findings underscore the multifactorial nature of pleural disease, driven by complex interactions among genetic determinants and immune pathways. Available evidence suggests that pleural tuberculosis reflects genetically mediated amplification of innate and adaptive inflammatory responses, particularly involving macrophage activation pathways and Th1-type cytokine signaling. Integration of genomic, transcriptomic, and immunological data may contribute to improved diagnostic precision, risk stratification, and the development of host-directed biomarkers and personalized therapeutic strategies.
Tuberculosis (TB) is a severe public health issue in prison inmates in Ethiopia since there is no routine screening for TB during prison admission. Also, drug-resistant tuberculosis (DR-TB) is a significant public health problem. Prisons are the most important permissive environments for TB transmission. However, less attention has been given to this segment of the population. Ethiopia's condition is worse because of poor living circumstances and inefficient health care in the prisons. The study determined the pooled prevalence of DR-TB among prisoners in Ethiopia. A systematic search was conducted to retrieve records from databases such as PubMed/MEDLINE, ScienceDirect, Cochrane Library, and Google Scholar. The search did not entail a lower time limit, and articles published up until January 2024 were considered. This study was conducted in accordance with the PRISMA guidelines. The data were extracted using a standardized data extraction format. Meta-analysis was computed using STATA version 16 software. Heterogeneity was assessed by the I^2 and publication bias through a funnel plot. The random-effects meta-analysis model was computed to estimate the pooled prevalence of pulmonary tuberculosis (PTB) and DR-TB among prisoners. Out of 338 records, six cross-sectional studies with 3277 study participants were included in this systematic review and meta-analysis. Of the 3277 study participants included in this study, 5.2% (169) were confirmed positive for PTB. Among 169 PTB cases the pooled prevalence of any DR-TB was 5.0% (95% CI: 2-9%), isoniazid (INH) resistance was 3.0% (95% CI: 0-6%), rifampin (RIF) resistance was 4.0% (95% CI: 0-8%), Multidrug-resistant tuberculosis (MDR-TB) was 3.0% (95% CI 0-6%). This systematic review and meta-analysis study has shown DR-TB in Ethiopian prisoners. These findings suggest the need for attention in prisons to the control of DR-TB in prisoners in Ethiopia.