Who Transmits Tuberculosis to Whom: A Cross-Sectional Analysis of a Cohort Study in Lima, Peru.

Rationale: The persistent burden of tuberculosis (TB) disease emphasizes the need to identify individuals with TB for treatment and those at a high risk of incident TB for prevention. Targeting interventions toward those at high risk of developing and transmitting TB is a public health priority. Objectives: We aimed to identify characteristics of individuals involved in TB transmission in a community setting, which may guide the prioritization of targeted interventions. Methods: We collected clinical and sociodemographic data from a cohort of patients with TB in Lima, Peru. We used whole-genome sequencing data to assess the genetic distance between all possible pairs of patients; we considered pairs to be the result of a direct transmission event if they differed by three or fewer SNPs, and we assumed that the first diagnosed patient in a pair was the transmitter and the second was the recipient. We used logistic regression to examine the association between host factors and the likelihood of direct TB transmission. Measurements and Main Results: Analyzing data from 2,518 index patients with TB, we identified 1,447 direct transmission pairs. Regardless of recipient attributes, individuals less than 34 years old, males, and those with a history of incarceration had a higher likelihood of being transmitters in direct transmission pairs. Direct transmission was more likely when both patients were drinkers or smokers. Conclusions: This study identifies men, young adults, former prisoners, alcohol consumers, and smokers as priority groups for targeted interventions. Innovative strategies are needed to extend TB screening to social groups such as young adults and prisoners with limited access to routine preventive care.

T-cell signature cytokines distinguish pulmonary sarcoidosis from pulmonary tuberculosis.

Sarcoidosis is a systemic inflammatory disorder characterized by tissue infiltration due to mononuclear phagocytes and lymphocytes and associated noncaseating granuloma formation. Pulmonary sarcoidosis (PS) shares a number of clinical, radiological, and histopathological characteristics with that of pulmonary tuberculosis (PTB). Due to this, clinicians face issues in differentiating between PS and PTB in a substantial number of cases. There is a lack of any specific biomarker that can diagnose PS distinctively from PTB. We compared T-cell-based signature cytokines in patients with PS and PTB. In this study, we proposed a serum biomarker panel consisting of cytokines from cells: T helper (Th) 1 [interferon-gamma (IFN-γ); tumor necrosis factor-alpha (TNF-α)], Th9 [interleukin (IL)-9], Th17 [IL-17], and T regulatory (Treg) [IL-10; transforming growth factor-beta (TGF-ß)]. We performed the principal component analysis that demonstrated that our serum cytokine panel has a significant predictive ability to differentiate PS from PTB. Our results could aid clinicians to improve the diagnostic workflow for patients with PS in TB endemic settings where the diagnosis between PS and PTB is often ambiguous.

T cells exhaustion, inflammatory and cellular activity markers in PBMCs predict treatment outcome in pulmonary tuberculosis patients.

BACKGROUND: Pulmonary tuberculosis (PTB) is a well-known disease caused by Mycobacterium tuberculosis. Its pathogenesis is premised on evasion of the immune system and dampened immune cells activity. METHODS: Here, the transcription pattern of immune cells exhaustion, inflammatory, and cellular activity markers were examined in peripheral blood mononuclear cells (PBMCs) from PTB patients at various stages of treatment. PBMCs were isolated, and RNA extracted. cDNA synthesis was performed, then amplification of genes of interest. RESULTS: The T cell exhaustion markers (PD-L1, CTLA4, CD244 and LAG3) showed varied levels of expressions when comparing 0 T and 1 T to the other treatment phases, suggesting their potential roles as markers for monitoring TB treatment. IL-2, IFN-g and TNF-a expression at the gene level returned to normal at completion of treatment, while granzyme B levels remained undetectable at the cured stage. At the cured stage, the cellular activity monitors Ki67, CD69, GATA-3, CD8 and CD4 expressions were comparable to the healthy controls. Correlation analysis revealed a significantly strong negative relationship with CD244 expression, particularly between 1 T and 2 T (r = -0.94; p = 0.018), and 3 T (r = -0.95; p = 0.013). Comparing 0 T and 3 T, a genitive correlation existed in PD-L1 (r = -0.74) but statistically not significant, as seen in CTLA4 and LAG-3 expressions. CONCLUSION: Collectively, the findings of the study suggest that T-cells exhaustion marker particularly CD244, inflammatory markers IL-2, IFN-g and TNF-a, and cellular activity indicators such as Ki67, CD69, GATA-3, CD8 and CD4 are promising markers in monitoring the progress of PTB patients during treatment.

Prevalence of extra-pulmonary tuberculosis in Africa: A systematic review and meta-analysis.

OBJECTIVE: The burden of extra-pulmonary tuberculosis (EPTB) is not well quantified in TB endemic countries such as those in sub-Saharan Africa. This study aimed to quantify that burden via a systematic review of the prevalence of EPTB in African countries. METHODS: Studies were retrieved by searching five databases; 105 studies published between 1990 and 2023 were included. The studies described the prevalence of EPTB among the general population (4 studies), TB patients (68) and patients with other conditions, including HIV (15), meningitis (3), renal failure (3) and other comorbidities, some of which are cancer (12). Due to the low number of studies reporting EPTB in patients with conditions other than TB, the meta-analysis was performed on studies reporting on EPTB among TB patients (68 studies). Meta-analysis was performed on the 68 studies (271,073 participants) using a random-effects model to estimate the pooled prevalence of EPTB. Meta-regression was used to explore possible explanations for heterogeneity according to regions and time periods. RESULTS: The pooled prevalence of EPTB among TB patients was 26% (95% CI 23-29%). There was substantial heterogeneity of prevalence for the five African regions. The Eastern region had the highest prevalence of 32% (95% CI 28-37%) and the lowest in Western Africa, 16% (95% CI 10-24%). There was no significant difference in the prevalence of EPTB between the 3 eleven-year time periods. CONCLUSIONS: Our systematic review and meta-analysis give insight into the burden of EPTB in Africa. This review could inform clinical and programmatic practices-a higher suspicion index for clinicians and more effort for better services. This could contribute to efforts aiming to end TB, which have historically been focused on PTB.Coordinated efforts that target both EPTB and PTB are needed.

Efficacy and tolerability of a 4-month ofloxacin-containing regimen compared to a 6-month regimen in the treatment of patients with superficial lymph node tuberculosis: a randomized trial.

BACKGROUND: Tuberculosis (TB) lymphadenitis is the most common form of extra-pulmonary TB, and the treatment duration is six months. This non-inferiority based randomized clinical trial in South India evaluated the efficacy and safety of a four-month ofloxacin containing regimen in tuberculosis lymphadenitis (TBL) patients. METHODS: New, adult, HIV-negative, microbiologically and or histopathologically confirmed superficial lymph node TB patients were randomized to either four-month oflaxacin containing test regimen [ofloxacin (O), isoniazid (H), rifampicin (R), pyrazinamide (Z) -2RHZO daily/ 2RHO thrice-weekly] or a six-month thrice-weekly control regimen (2HRZ, ethambutol/4RH). The treatment was directly observed. Clinical progress was monitored monthly during and up to 12 months post-treatment, and thereafter every three months up to 24 months. The primary outcome was determined by response at the end of treatment and TB recurrence during the 24 months post-treatment. RESULTS: Of the 302 patients randomized, 298 (98.7%) were eligible for modified intention-to-treat (ITT) analysis and 294 (97%) for per-protocol (PP) analysis. The TB recurrence-free favourable response in the PP analysis was 94.0% (95% CI: 90.1-97.8) and 94.5% (95% CI: 90.8-98.2) in the test and control regimen respectively, while in the ITT analysis, it was 92.7% and 93.2%. The TB recurrence-free favourable response in the test regimen was non-inferior to the control regimen 0.5% (95% CI: -4.8-5.9) in the PP analysis based on the 6% non-inferiority margin. Treatment was modified for drug toxicity in two patients in the test regimen, while one patient had a paradoxical reaction. CONCLUSION: The 4-month ofloxacin containing regimen was found to be non-inferior and as safe as the 6-month thrice-weekly control regimen.

Spatial-temporal distribution characteristics of pulmonary tuberculosis in eastern China from 2011 to 2021.

China is still among the 30 high-burden tuberculosis (TB) countries in the world. Few studies have described the spatial epidemiological characteristics of pulmonary TB (PTB) in Jiangsu Province. The registered incidence data of PTB patients in 95 counties of Jiangsu Province from 2011 to 2021 were collected from the Tuberculosis Management Information System. Three-dimensional spatial trends, spatial autocorrelation, and spatial-temporal scan analysis were conducted to explore the spatial clustering pattern of PTB. From 2011 to 2021, a total of 347,495 newly diagnosed PTB cases were registered. The registered incidence rate of PTB decreased from 49.78/100,000 in 2011 to 26.49/100,000 in 2021, exhibiting a steady downward trend (χ2 = 414.22, P < 0.001). The average annual registered incidence rate of PTB was higher in the central and northern regions. Moran's I indices of the registered incidence of PTB were all >0 (P< 0.05) except in 2016, indicating a positive spatial correlation overall. Local autocorrelation analysis showed that 'high-high' clusters were mainly distributed in northern Jiangsu, and 'low-low' clusters were mainly concentrated in southern Jiangsu. The results of this study assist in identifying settings and locations of high TB risk and inform policy-making for PTB control and prevention.

Correlation between a low serum free triiodothyronine level and mortality of severe pulmonary tuberculosis patients.

BACKGROUND: This study aimed to assess the relationship between a low serum free triiodothyronine (FT3) level and the mortality of severe pulmonary tuberculosis (TB) patients. METHODS: We performed a retrospective study and reviewed the medical records of patients with severe pulmonary TB between January 2016 and June 2022. The patient demographics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, survival or death at 28 and 90 days after hospital admission, and serum FT3 level were recorded. Bivariate regression analysis was performed to study the relationship between mortality and the FT3 level. The Kaplan-Meier method and the log-rank test were used to compare the survival rates between patients with different serum FT3 levels. RESULTS: Our study included 495 severe pulmonary TB patients, with 383 (77.4%) patients having a low serum FT3 level. The low-serum FT3 group had high 28-day and 90-day mortalities. The patients who had died by 28 or 90 days after hospital admission had a low FT3 level. Survival analysis showed that the patients with a low serum FT3 level had a low probability of survival at 28 days and at 90 days after hospital admission. CONCLUSION: The serum FT3 level was correlated with the 28-day and 90-day mortalities in patients with severe pulmonary TB. The serum FT3 level should be monitored in these patients to help manage their disease.

Treatment outcomes of retreated patients with isoniazid/rifampicin resistant pulmonary tuberculosis.

BACKGROUND: About 8% of TB cases worldwide are estimated to have rifampicin-susceptible, isoniazid-resistant tuberculosis (Hr-TB), ranging from 5 to 11% regions. However, Hr-TB has not received much attention while comparing to be given high priority to the management of rifampicin-resistant tuberculosis (RR-TB). This study aimed to compare the differences of treatment effects for Hr-TB and RR-TB, so as to intensify the treatment and management of Hr-TB. METHODS: A retrospective study was used to collect bacteriologically positive retreated patients with isoniazid/rifampicin resistant pulmonary tuberculosis, who were conducted at 29 tuberculosis control institutions in China from July 2009 to June 2021. We assessed effectiveness and safety of retreated patients with isoniazid/ rifampicin resistant pulmonary tuberculosis. RESULTS: A total of 147 with either positive smear or cultures were enrolled, and 80 cases were in Hr-TB group and 67 cases were in RR-TB group. There was no significant difference in terms of age, sex, body mass, type of retreatment and comorbid diabetes between the two groups (P > 0.05). The rate of number of lesions involving lung fields ≥ 3 in Hr-TB group 75.9% (60/79) was significantly higher than RR-TB group 56.7% (38/67) (χ2 = 6.077, P = 0.014). There was no statistically significant difference (P = 0.166) with regard to the treatment outcomes of the two groups, the cure rates were 54.7% (41/75) and 53.6% (30/56), respectively, and the failure rate in Hr-TB group 22.7% (17/75) was 10% higher than RR-TB group 10.7% (6/56). The rate of negative sputum smear at the end of the second month (65.7%) in the Hr-TB group was significantly lower than that in the RR-TB group (85.7%) (P = 0.025). There were no significant differences in the incidences of serious adverse reactions and chest X-ray changes between the two groups (P > 0.05). During the 5-year follow-up, recurrence in the Hr-TB group (7 cases, 14.9%) was no significantly lower than that in the RR-TB group (4 cases, 11.8%) (P = 0.754). CONCLUSION: The treatment of retreated Hr-TB patients was difficult and could be statistically similar or considerably worse than RR-TB. It's urgent to conduct further evaluation of the treatment status quo to guide the guideline development and clinical practice of Hr-TB patients.

Factors affecting the incidence of pulmonary tuberculosis based on the GTWR model in China, 2004-2021.

Contra-posing panel data on the incidence of pulmonary tuberculosis (PTB) at the provincial level in China through the years of 2004-2021 and introducing a geographically and temporally weighted regression (GTWR) model were used to explore the effect of various factors on the incidence of PTB from the perspective of spatial heterogeneity. The principal component analysis (PCA) was used to extract the main information from twenty-two indexes under six macro-factors. The main influencing factors were determined by the Spearman correlation and multi-collinearity tests. After fitting different models, the GTWR model was used to analyse and obtain the distribution changes of regression coefficients. Six macro-factors and incidence of PTB were both correlated, and there was no collinearity between the variables. The fitting effect of the GTWR model was better than ordinary least-squares (OLS) and geographically weighted regression (GWR) models. The incidence of PTB in China was mainly affected by six macro-factors, namely medicine and health, transportation, environment, economy, disease, and educational quality. The influence degree showed an unbalanced trend in the spatial and temporal distribution.

Epidemiology of tuberculosis among children in Beijing, China, 2012-2021.

Data on epidemiology trends of paediatric tuberculosis (TB) are limited in China. So, we investigated the clinical and epidemiological profiles in diagnosed TB disease and TB infection patients at Beijing Children's Hospital. Of 3 193 patients, 51.05% had pulmonary TB (PTB) and 15.16% had extrapulmonary TB (EPTB). The most frequent forms of EPTB were TB meningitis (39.05%), pleural TB (29.75%), and disseminated TB (10.33%). PTB patients were significantly younger and associated with higher hospitalization frequency. Children aged 1-4 years exhibited higher risk of PTB and TB meningitis, and children aged 5-12 years had higher risk of EPTB. The proportion of PTB patients increased slightly from 40.9% in 2012 to 65% in 2019, and then decreased to 17.8% in 2021. The percentage of EPTB cases decreased from 18.3% in 2012 to 15.2% in 2019, but increased to 16.4% in 2021. Among EPTB cases, the largest increase was seen in TB meningitis. In conclusion, female and young children had higher risk of PTB in children. TB meningitis was the most frequent forms of EPTB among children, and young children were at high risk of TB meningitis. The distribution of different types of EPTB differed by age.

Diagnostic efficacy of endobronchial ultrasound-guided transbronchoscopic lung biopsy for identifying tuberculous nodules.

BACKGROUND: Microbiological diagnosis of pulmonary tuberculosis (PTB) is hampered by a low pathogen burden, low compliance and unreliable sputum sampling. Although endobronchial ultrasound-guided transbronchoscopic lung biopsy (EBUS-TBLB) has been found to be useful for the assessment of intrapulmonary nodules in adults, few data are available for the clinical diagnosis of pulmonary tuberculosis. Here, we evaluated EBUS-TBLB as a diagnostic procedure in adult patients with radiologically suspected intrapulmonary tuberculous nodules. METHODS: This was a retrospective analysis of patients admitted with pulmonary nodules between January 2022 and January 2023 at Hangzhou Red Cross Hospital. All patients underwent EBUS-TBLB, and lung biopsy samples were obtained during hospitalization. All samples were tested for Mycobacterium tuberculosis using acid‒fast smears, Bactec MGIT 960, Xpert MTB/RIF, next-generation sequencing (NGS), and DNA (TB‒DNA) and RNA (TB‒RNA). The concordance between different diagnostic methods and clinical diagnosis was analysed via kappa concordance analysis. The diagnostic efficacy of different diagnostic methods for PTB was analysed via ROC curve. RESULTS: A total of 107 patients were included in this study. Among them, 86 patients were diagnosed by EBUS-TBLB, and the overall diagnostic rate was 80.37%. In addition, 102 enrolled patients had benign lesions, and only 5 were diagnosed with lung tumours. Univariate analysis revealed that the diagnostic rate of EBUS-TBLB in pulmonary nodules was related to the location of the probe. The consistency analysis and ROC curve analysis revealed that NGS had the highest concordance with the clinical diagnosis results (agreement = 78.50%, κ = 0.558) and had the highest diagnostic efficacy for PTB (AUC = 0.778). In addition, Xpert MTB/RIF + NGS had the highest concordance with the clinical diagnosis results (agreement = 84.11%, κ = 0.667) and had the highest efficacy in the diagnosis of PTB (AUC = 0.826). CONCLUSION: EBUS-TBLB is a sensitive and safe method for the diagnosis of pathological pulmonary nodules. Xpert MTB/RIF combined with NGS had the highest diagnostic efficacy and can be used in the initial diagnosis of PTB.

Relationship of neutrophil lymphocyte ratio, monocyte lymphocyte ratio and neutrophil monocyte ratio with treatment response in pulmonary tuberculosis patients during intensive phase treatment.

OBJECTIVE: To determine the relationship of Neutrophil Lymphocyte Ratio (NLR), Monocyte Lymphocyte Ratio (MLR), and Neutrophil Monocyte Ratio (NMR) with treatment response in Pulmonary Tuberculosis (PTB) patients during intensive phase treatment (IPT). METHODS: This analytical cross-sectional study was conducted at Ojha Institute of Chest Diseases (OICD), Dow University of Health Sciences, from February to December 2021. 100 patients were enrolled using purposive sampling technique. Both male and female of age 18 and above, rifampicin sensitive newly diagnosed cases of PTB by Acid Fast Bacilli (AFB) microscopy and Gene Xpert MTB/RIF were included. SPSS version 26 was used to analyze data. Numerical data was expressed in median and interquartile range and categorical data was expressed in frequencies and percentages. RESULTS: Out of total 100 patients, 81% (n = 81) showed treatment response with negative AFB Sputum Smear Microscopy (SSM) after 2nd month. Out of 81% (n = 81) of the patients who achieved treatment response, 83.9% (n = 68) also had decreased NLR, 85.2% (n = 69) had decreased MLR and 83.9% (n = 68) had decreased NMR from baseline. However 19% (n = 19) did not achieved treatment response with positive AFB SSM after 2nd month of ATT (Anti tuberculosis treatment), among them 10.52% (n = 2) were INH resistant with no decrease in all the ratios after 2nd month. CONCLUSION: Leukocyte ratios decreased significantly from baseline as PTB was treated in patients who achieved treatment response with negative AFB SSM after two months of ATT and hence these ratios could be used as markers to monitor the treatment response.

The burden and natural history of cardiac pathology at TB diagnosis in a high-HIV prevalence district in Zambia: protocol for the TB-Heart study.

BACKGROUND: Tuberculosis (TB) continues to be a major cause of death across sub-Saharan Africa (SSA). In parallel, non-communicable disease and especially cardiovascular disease (CVD) burden has increased substantially in the region. Cardiac manifestations of TB are well-recognised but the extent to which they co-exist with pulmonary TB (PTB) has not been systematically evaluated. The aim of this study is to improve understanding of the burden of cardiac pathology in PTB in those living with and without HIV in a high-burden setting. METHODS: This is a cross-sectional and natural history study to evaluate the burden and natural history of cardiac pathology in participants with PTB in Lusaka, Zambia, a high burden setting for TB and HIV. Participants with PTB, with and without HIV will be consecutively recruited alongside age- and sex-matched TB-uninfected comparators on a 2:1 basis. Participants will undergo baseline assessments to collect clinical, socio-demographic, functional, laboratory and TB disease impact data followed by point-of-care and standard echocardiography. Participants with PTB will undergo further repeat clinical and functional examination at two- and six months follow-up. Those with cardiac pathology at baseline will undergo repeat echocardiography at six months. DISCUSSION: The outcomes of the study are to a) determine the burden of cardiac pathology at TB diagnosis, b) describe its association with patient-defining risk factors and biochemical markers of cardiac injury and stretch and c) describe the natural history of cardiac pathology during the course of TB treatment.

Nanopore sequencing for smear-negative pulmonary tuberculosis-a multicentre prospective study in China.

PURPOSE: In this prospective study, the diagnosis accuracy of nanopore sequencing-based Mycobacterium tuberculosis (MTB) detection was determined through examining bronchoalveolar lavage fluid (BALF) samples from pulmonary tuberculosis (PTB) -suspected patients. Compared the diagnostic performance of nanopore sequencing, mycobacterial growth indicator tube (MGIT) culture and Xpert MTB/rifampin resistance (MTB/RIF) assays. METHODS: Specimens collected from suspected PTB cases across China from September 2021 to April 2022 were tested then assay diagnostic accuracy rates were compared. RESULTS: Among the 111 suspected PTB cases that were ultimately diagnosed as PTB, the diagnostic rate of nanopore sequencing was statistically significant different from other assays (P < 0.05). Fleiss' kappa values of 0.219 and 0.303 indicated fair consistency levels between MTB detection results obtained using nanopore sequencing versus other assays, respectively. Respective PTB diagnostic sensitivity rates of MGIT culture, Xpert MTB/RIF and nanopore sequencing of 36.11%, 40.28% and 83.33% indicated superior sensitivity of nanopore sequencing. Analysis of area under the curve (AUC), Youden's index and accuracy values and the negative predictive value (NPV) indicated superior MTB detection performance for nanopore sequencing (with Xpert MTB/RIF ranking second), while the PTB diagnostic accuracy rate of nanopore sequencing exceeded corresponding rates of the other methods. CONCLUSIONS: In comparison with MGIT culture and Xpert MTB/RIF assays, BALF's nanopore sequencing provided superior MTB detection sensitivity and thus is suitable for testing of sputum-scarce suspected PTB cases. However, negative results obtained using these assays should be confirmed based on additional evidence before ruling out a PTB diagnosis.

Association between STAT4 gene polymorphism and susceptibility to pulmonary tuberculosis in the Moldavian population.

Signal transducer and activator of transcription 4 (STAT4) plays a crucial role in the host immune response against Mycobacterium tuberculosis. This study investigates the association between STAT4 gene polymorphisms and pulmonary tuberculosis (TB) risk in the Moldavian population. A total of 272 TB patients and 251 community-matched controls underwent screening for functional single-nucleotide polymorphisms (SNPs) rs897200 and rs7574865 in the STAT4 gene. The minor T allele and the TT/CT genotype of rs897200 demonstrated a significant association with reduced pulmonary TB risk (allelic model: adjusted OR = .74, p = .025; log-additive model: adjusted OR = .72, p = .02; and dominant model: adjusted OR = .65, p = .023), indicating a protective effect. Similar associations, characterized by an even more pronounced reduction in risk, were observed among females and late-onset TB patients (>44 years). No significant associations were found for rs7574865. In addition, a combined genotype analysis incorporating 43 SNPs from our previous studies revealed potential associations, such as STAT4 rs897200 CT with IFNG rs2430561 AA (adjusted OR = .36, p = .0025) and STAT4 rs897200 CT with TNFA rs1800629 GA (adjusted OR = .33, p = .0012). This study emphasizes the significant association of STAT4 rs897200 with pulmonary TB risk in the Moldavian population, underscoring its role in the disease development.

Cryoprobe for Endoscopic Enucleation in Children with Pulmonary Tuberculosis: Effective but Not Without Danger - Case Report and Review of Literature.

INTRODUCTION: Tuberculosis (TB) in children under 15 years often results in airway compression, with bronchus intermedius (BI) being the most common site. Endoscopic enucleations can be used to remove lymph nodes and establish an airway in severe cases. Both rigid and flexible bronchoscopy are suitable, with alligator forceps being preferred for its ability to extract tissue. Recent studies have also explored cryoprobe enucleation. CASE PRESENTATION: An HIV-positive boy with persistent symptoms after 9 months of TB treatment was diagnosed based on his mother's and sister's Xpert MTB/RIF positive status. He was started on 4-drug TB treatment, but the child remained clinically symptomatic with abnormal chest X-ray and unconfirmed TB. Bronchoscopy was performed, revealing complete obstruction of BI due to caseating granulomas causing collapse of the right middle and lower lobes. Cryotherapy was used to recanalize the airway, and follow-up bronchoscopy confirmed patent BI. CONCLUSION: While cryotherapy was effective in the restoration of airway patency in this case, there is a lack of knowledge about its use in children.

Determination of the diagnostic accuracy of nanopore sequencing using bronchoalveolar lavage fluid samples from patients with sputum-scarce pulmonary tuberculosis.

PURPOSE: The early and efficient diagnosis of patients suspected of having pulmonary tuberculosis (PTB) remains challenging. This study aimed to evaluate the accuracy of nanopore sequencing for PTB diagnosis using bronchoalveolar lavage fluid (BALF) samples and compared it with other techniques such as acid-fast bacilli smear, culture, Xpert MTB/RIF, and CapitalBio Mycobacterium reverse transcription-polymerase chain reaction (MTB RT-PCR). METHODS: We retrospectively analyzed the clinical data of 195 patients with suspected PTB who were admitted to our hospital. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC) of these assays were calculated and compared. RESULTS: The overall sensitivity, specificity, PPV, NPV, and AUC of nanopore sequencing were 90.70%, 84.85%, 92.13%, 82.35%, and 0.88; those of acid-fast bacilli smear were 12.40%, 98.48%, 94.12%, 36.52%, and 0.55; those of culture were 36.43%, 100%, 100%, 44.59%, and 0.68; those of Xpert MTB/RIF were 41.09%, 100%, 100%, 46.48%, and 0.71; and those of CapitalBio MTB RT-PCR were 34.88%, 98.48%, 97.83%, 43.62%, and 0.67, respectively. CONCLUSION: The nanopore sequencing assay using BALF samples showed the best diagnostic accuracy for sputum-scarce PTB. Moreover, it can improve the clinical diagnosis of PTB.

Comorbidity increases the risk of pulmonary tuberculosis: a nested case-control study using multi-source big data.

BACKGROUND: Some medical conditions may increase the risk of developing pulmonary tuberculosis (PTB); however, no systematic study on PTB-associated comorbidities and comorbidity clusters has been undertaken. METHODS: A nested case-control study was conducted from 2013 to 2017 using multi-source big data. We defined cases as patients with incident PTB, and we matched each case with four event-free controls using propensity score matching (PSM). Comorbidities diagnosed prior to PTB were defined with the International Classification of Diseases-10 (ICD-10). The longitudinal relationships between multimorbidity burden and PTB were analyzed using a generalized estimating equation. The associations between PTB and 30 comorbidities were examined using conditional logistic regression, and the comorbidity clusters were identified using network analysis. RESULTS: A total of 4265 cases and 17,060 controls were enrolled during the study period. A total of 849 (19.91%) cases and 1141 (6.69%) controls were multimorbid before the index date. Having 1, 2, and ≥ 3 comorbidities was associated with an increased risk of PTB (aOR 2.85-5.16). Fourteen out of thirty comorbidities were significantly associated with PTB (aOR 1.28-7.27), and the associations differed by sex and age. Network analysis identified three major clusters, mainly in the respiratory, circulatory, and endocrine/metabolic systems, in PTB cases. CONCLUSIONS: Certain comorbidities involving multiple systems may significantly increase the risk of PTB. Enhanced awareness and surveillance of comorbidity are warranted to ensure early prevention and timely control of PTB.

Factors affecting the readiness for hospital discharge of initially treated pulmonary tuberculosis patients in China: a phenomenological study.

BACKGROUND: Despite readiness for hospital discharge widespread popularity since readiness for hospital discharge introduction in 1979 and extensive study, readiness for hospital discharge among pulmonary tuberculosis (PTB) patients has not yet been investigated. Moreover, the factors influencing this process remain unclear. OBJECTIVE: The objective of this study was to investigate the factors influencing readiness for hospital discharge in initially treated PTB patients using the capability, opportunity, motivation-behavior (COM-B) model. METHODS: This phenomenological study was conducted from December 2023 to March 2024. Face-to-face individual interviews were conducted with 18 initially treated patients with PTB according to a semistructured interview guide developed on the basis of the COM-B model. The interview data were subjected to analysis using NVivo 14 software and Colaizzi's method. RESULTS: As a result, 6 themes and 14 subthemes were identified. Physical capability for readiness for hospital discharge (subthemes included poor health status, early acquisition of adequate knowledge about PTB, inadequate knowledge about readiness for hospital discharge), psychological capability for readiness for hospital discharge(subthemes included false perceptions about readiness for hospital discharge, high treatment adherence), physical opportunity for readiness for hospital discharge (subthemes included high continuity of transition healthcare, insufficient financial support, insufficient informational support), social opportunity for readiness for hospital discharge (subthemes included stigmatization, inadequate emotional support), reflective motivation for readiness for hospital discharge (subthemes included lack of reflection on coping with difficulties, intention to develop a readiness for hospital discharge plan), and automatic motivation for readiness for hospital discharge (subthemes included strong desire to be cured, negative emotions). CONCLUSION: We established factors related to readiness for hospital discharge in initially treated PTB patients in terms of capability, opportunity and motivation, which can inform the future development of readiness for hospital discharge plans. To improve patients' readiness for hospital discharge, patients need to be motivated to plan and desire readiness for hospital discharge, patients' knowledge and treatment adherence should be improved, and patients' transition healthcare continuity and emotional support should be focused on. Moreover, the quality of readiness for hospital discharge and discharge education should be assessed in a timely manner to identify impeding factors and provide interventions.

Spatial spillover effect of environmental factors on the tuberculosis occurrence among the elderly: a surveillance analysis for nearly a dozen years in eastern China.

BACKGROUND: In many areas of China, over 30% of tuberculosis cases occur among the elderly. We aimed to investigate the spatial distribution and environmental factors that predicted the occurence of tuberculosis in this group. METHODS: Data were collected on notified pulmonary tuberculosis (PTB) cases aged ≥ 65 years in Zhejiang Province from 2010 to 2021. We performed spatial autocorrelation and spatial-temporal scan statistics to determine the clusters of epidemics. Spatial Durbin Model (SDM) analysis was used to identify significant environmental factors and their spatial spillover effects. RESULTS: 77,405 cases of PTB among the elderly were notified, showing a decreasing trend in the notification rate. Spatial-temporal analysis showed clustering of epidemics in the western area of Zhejiang Province. The results of the SDM indicated that a one-unit increase in PM2.5 led to a 0.396% increase in the local notification rate. The annual mean temperature and precipitation had direct effects and spatial spillover effects on the rate, while complexity of the shape of the greenspace (SHAPE_AM) and SO2 had negative spatial spillover effects. CONCLUSION: Targeted interventions among the elderly in Western Zhejiang may be more efficient than broad, province-wide interventions. Low annual mean temperature and high annual mean precipitation in local and neighboring areas tend to have higher PTB onset among the elderly.