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To analyze the clinical features, epidemiological characteristics, risk factors, and complication characteristics of pulmonary tuberculosis (PTB) combined with extrapulmonary tuberculosis (EPTB) in elderly patients (aged > 60 years). Clinical data were collected from pathogen positive elderly patients with PTB hospitalized in a teaching hospital in Zhejiang from 2017 to 2023. We retrospectively analyzed the risk factors for complications of EPTB in elderly patients with PTB by univariate and multivariate logistic regression models. We also described the characteristics of complications in PTB with EPTB. A total of 781 PTB elderly patients were enrolled, of whom 86 (11.01%) had complicated EPTB. The most commonly invasive sites for EPTB were thoracic spine (17.53%), cervical lymph nodes (13.40%), and meninges (12.37%). 60 < aged < 80 years (OR = 2.876, 95%CI 1.290–6.412; P  = 0.010), anaemia (OR = 2.212, 95%CI 1.135–3.967; P  = 0.018) and osteoporosis (OR = 4.925, 95%CI 1.501–16.160; P  = 0.009) were the independent risk factors for PTB with EPTB infection. PTB with EPTB had a higher proportion of multiple serous cavity effusion (19.8% vs. 12.2%) and longer hospitalisation (17 vs. 15, P  = 0.004). 60 < aged < 80 years, anaemia and osteoporosis were found to be independent risk factors for PTB with EPTB in elderly patients. We compared the epidemiological and clinical characteristics of PTB with EPTB. These results are important for improving the diagnosis of EPTB, reducing complications, and improving prognosis.

Extra-pulmonary TB (EPTB) is difficult to diagnose due to paucibacillary nature of disease. Current study evaluated accuracy of Truenat MTB and MTB-Rif Dx (TN), for detection of  Mycobacterium tuberculosis  and resistance to rifampicin. Samples were collected from 2103 treatment naive adults with presumptive EPTB, and tested by smear microscopy, liquid culture (LC) (MGIT-960) and GeneXpert MTB/RIF (GX) (Microbiological Reference Standards, MRS). TN results were compared to MRS and Composite Reference Standards (CRS, Microbiology, histopathology, radiology, clinical features prompting decision to treat, response to treatment). CRS grouped patients into 551 confirmed, 1096 unconfirmed, and 409 as unlikely TB. TN sensitivity and specificity was 73.7% and 90.4% against GX. Against LC, Overall sensitivity of GX was 67.6%, while that of TN was 62.3%. Highest sensitivity by TN was observed in pus samples (89%) and highest specificity (92%) in CSF samples, similar to GX. TN sensitivity was better in fluid and biopsy samples and slightly inferior for lymph node aspirates compared to GX. TN sensitivity for RIF resistance detection was slightly superior to GX. TN and GX results were further compared to Clinical Reference Standards. TN detected 170 TB patients initiated on treatment missed by GX, while GX detected 113 such patients missed by TN. Of 124 samples with RIF resistance discordance between GX and TN, GX reported 103/124 as sensitive, 3/124 as indeterminate and 18 as resistant (13/18 samples had low/very low DNA load) while TN reported RIF resistance indeterminate in 103/111 low/very low DNA load samples. Due to paucibacillary nature of EPTB samples, culture yield was poor and phenotypic drug susceptibility testing failed to resolve the discordance. The study establishes TN at par with GX and can be utilized for quick and accurate diagnosis of EPTB.

Tuberculosis (TB) is a significant global public health concern. The incidence of extrapulmonary tuberculosis (EPTB) is increasing; however, comprehensive data on its epidemiological and clinical characteristics remain limited, especially among populations who are co-infected with human immunodeficiency virus (HIV) or hepatitis C virus (HCV). This study aimed to assess the incidence and predictors of EPTB in patients co-infected with HIV or HCV in Egypt. We conducted a retrospective cohort study on patients infected with TB who are treated in Egyptian chest hospitals from January 1 to December 31, 2023. Patients were categorized into pulmonary TB (PTB) and EPTB. Clinical data, including HIV or HCV co-infection status, were analyzed to identify risk factors and comorbidities associated with EPTB. Multilevel logistic regression was employed to examine predictors of EPTB. Among 7,245 TB patients, 42.5% were diagnosed with EPTB. Determinant of EPTB were HIV-positive (OR = 0.46, 95% CI: 0.30–0.71, p  < 0.001), being male (OR = 0.31, 95% CI: 0.27–0.35, p  < 0.001 ), age (particularly children under 5 years) (OR = 4.75, 95% CI: 2.29–9.84, p  < 0.001 ), urban residency (OR = 1.05, 95% CI: 0.87–1.27, p  < 0.05), and comorbidities (OR = 0.59, 95% CI: 0.35–0.98, p  < 0.05). The most common sites for EPTB were the lymph nodes (27.10%) and pleural cavity/effusion (24.60%). EPTB represents a substantial proportion of TB cases in Egypt, particularly among younger individuals and females. Despite the low percentage of HIV or HCV co-infection in EPTB cases, further analysis and diagnostic testing of undiagnosed patients are required. These findings underscore the need for targeted interventions and comprehensive care models for TB patients, especially in the context of HIV co-infection.

There is a lack of objective tools for monitoring treatment response in extrapulmonary tuberculosis (EPTB). This study aimed to explore the utility of inflammatory biomarkers from the dry blood spots (DBS) as a tool for monitoring treatment response in EPTB. In a prospective cohort study, 40 inflammatory biomarkers were investigated in DBS samples from 105 EPTB cases using a Luminex platform. The samples were taken before, and, at the end of the 2nd and 6th months of treatment. A total of 11 inflammatory host biomarkers changed significantly with treatment in all EPTB patients. CXCL9/MIG, CCL20, CCL23, CXCL10/IP-10, CXCL1, CXCL2, and CXCL8 significantly declined in our cohort of EPTB (48 TB pleuritis and 57 TB lymphadenitis) patients at both time points. A biosignature consisting of MIG, CCL23, and CXCL2, corresponded with the treatment response in 81% of patients in the 2nd month and 79% of patients at the end of treatment. MIG, CCL23, IP-10, and CXCL2 changed significantly with treatment in all patients including those showing partial clinical response at the 2nd month of treatment. The changes in the levels of inflammatory biomarkers in the DBS correspond with the treatment success and can be developed as a routine test in low-resource settings.

Background The clinical presentation of extrapulmonary tuberculosis (EPTB) is atypical and it is easily confused with other diseases such as common infections, making prompt diagnosis a great challenge. This study aimed to evaluate the accuracy of targeted nanopore sequencing (TNS) in the diagnosis of EPTB. The diagnostic accuracy of TNS using different types of extrapulmonary specimens was also evaluated. Methods We reviewed the clinical data of patients with suspected EPTB for whom TNS was conducted and who were hospitalized at our center. The true positive, false positive, false negative, and true negative values were determined. Indices of diagnostic accuracy were computed, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) for TNS and acid-fast bacilli (AFB) culture, and compared with those from clinical diagnosis. Results 149 patients were included in the analysis. The overall sensitivity, specificity, PPV, NPV, and AUC of TNS for the diagnosis of EPTB were 86.4%, 87.5%, 97.3%, 55.3%, and 0.87, respectively. For diagnosis by AFB culture, these values were 25.6%, 100.0%, 100.0%, 20.5%, and 0.63, respectively. The most common specimens used were lymph node tissue, cerebrospinal fluid, pleural effusion, and pleural tissue. The diagnostic accuracy of TNS using all types of extrapulmonary specimens was good. Conclusions TNS demonstrates good diagnostic accuracy in the rapid diagnosis of EPTB and this was true across different types of extrapulmonary specimens.

The burden of extrapulmonary tuberculosis (EPTB) has gradually increased in recent years, but not enough epidemiological data is available from central Guangxi. To better understand the epidemiology of EPTB in central Guangxi and identify risk factors associated with them, we retrospectively investigated the epidemiology of tuberculosis (TB), especially EPTB, among patients admitted to the Chest Hospital of Guangxi Zhuang Autonomous Region between 2016 and 2021. We excluded those infected with both pulmonary tuberculosis (PTB) and EPTB, reported the proportion and incidence of PTB or EPTB, and compared the demographic characteristics and risk factors of EPTB and PTB cases using univariate and multivariate logistic regression models. Among 30,893 TB patients, 67.25% (20,774) had PTB and 32.75% (10,119) had EPTB. Among EPTB, pleural, skeletal, lymphatic, pericardial, meningeal, genitourinary, intestinal, and peritoneal TB accounted for 49.44%, 27.20%, 8.55%, 4.39%, 3.36%, 1.48%, 0.87%, and 0.79%, respectively. Patients who were younger (age < 25), from rural areas, Zhuang and other ethnic groups, and diagnosed with anemia and HIV infection were more likely to develop EPTB. However, patients with diabetes and COPD were less likely to have EPTB. From 2016 to 2021, the proportion of PTB cases decreased from 69.73 to 64.07%. The percentage of EPTB cases increased from 30.27 to 35.93%, with the largest increase in skeletal TB from 21.48 to 34.13%. The epidemiology and risk factors of EPTB in central Guangxi are different from those of PTB. The incidence of EPTB is increasing and further studies are needed to determine the reasons for it.

Background Worldwide, tuberculosis (TB) is among the most common causes of death. To our knowledge, there has been no study showing the prevalence of EPTB in Khuzestan province. Therefore, the objective of this research was to investigate the prevalence of EPTB in patients with or without pulmonary TB in different cities of Khuzestan province from 2002 to 2023. Additionally, the correlation between patient’s gender, and age groups with the disease was also investigated. Methods In this retrospective study, the existing records in Tuberculosis Regional Reference Laboratory of Khuzestan province related to patients were used. The research was carried out by investigating the archive information in 19 years (from 1st January 2002 to December 30, 2023). All confirmed cases of EPTB and simultaneous EPTB and PTB, based on laboratory results and medical examination were included in the study. Patients with incomplete information and military TB were excluded from the study. Information collected from patients includes age, gender, involved organ, place of residence, and year of disease. Results A total of 12,900 EPTB-related medical records were extracted from Tuberculosis Regional Reference Laboratories in southwest Iran, Ahvaz. After excluding records, 12,836 clinically diagnosed or laboratory-confirmed tuberculosis patients were included in this study, including 5991 patients with simultaneous PTB and EPTB, and 6845 patients with EPTB only. The mean age of male EPTB patients was 37.5 years (SD ± 14.6), while the mean age of male patients with simultaneous PTB and EPTB was 45.8 years (SD ± 15.3). The mean age of female patients with EPTB only, and with simultaneous PTB and EPTB was 31.2 years (SD ± 12.6), and 31.5 years respectively. Discussion tuberculosis is a systemic disease with different clinical manifestations. This study described different epidemiologic patterns of concurrent EPTB. The proportion of different types of EPTB was simultaneously determined for a group of hospitalized patients and shown to be different with gender and age. This study will likely increase clinicians’ awareness of the disease and help them better address diagnostic challenges and improve treatment outcomes for patients with EPTB.

Background We aimed to assess serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations in extrapulmonary tuberculosis (EPTB) patients and to evaluate the effect of vitamin D3 supplementation on their treatment course. Methods Serum 25(OH)D3concentrations were measured in 47 newly diagnosed EPTB patients and 42 controls. Vitamin D-deficient EPTB patients were randomly assigned to receive 50,000 IU of vitamin D3 (cholecalciferol) orally once a week for 6 weeks (total 300,000 IU), followed by maintenance doses of 1000 IU a day besides anti-TB drugs or the first line anti-TB treatment only. Follow up serum 25(OH)D3 concentrations were measured after 3 months of starting vitamin D3 supplementation. Both groups were evaluated for clinical, laboratory, and radiological outcomes after treatment. Results Serum 25(OH)D3 concentrations were significantly lower among TB cases (17.1 ± 5.5 nmol/L) compared to healthy controls (51.8 ± 27.3 nmol/L), and vitamin D deficiency was observed in all EPTB patients ( n  = 47). Patients in VD3 supplementation group had significantly higher weight gain and serum albumin level at 2 months and end of treatment, higher hemoglobin concentration at the end of treatment, significantly lower CRP and ESR at 2 months and at the end of treatment. In cases with TB pleurisy, a significant higher rate of full resolution of pleural fluid after 6 months of anti-TB treatment and shorter treatment duration were noted compared to the other group. Conclusions Vitamin D deficiency is prevalent in EPTB patients, in whom, vitamin D supplementation is a useful adjunctive therapy to anti-TB drugs and improves treatment course.

This study aimed to explore the accuracy of third-generation nanopore sequencing to diagnose extrapulmonary tuberculosis (EPTB). Samples were collected from the lesions of 67 patients with suspected EPTB admitted between April 2022 and August 2023. Nanopore sequencing, acid-fast bacilli (AFB) staining, DNA testing, and X-pert and mycobacterial cultures were performed. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operating characteristic curve (AUC) were calculated for different diagnostic methods, and their diagnostic accuracies were compared. Nanopore sequencing demonstrated the highest correct diagnosis rate among 50 positive EPTB cases, independently diagnosing 19 positive cases missed by conventional methods. Its sensitivity (62.00%), specificity (94.10%), PPV (96.90%), NPV (45.70%) and AUC (0.781, 95% CI: 0.67-0.89) were superior to those of conventional methods, such as AFB staining, DNA testing, X-pert, and solid culture, indicating its significantly efficient advantage in EPTB detection. Nanopore sequencing technology significantly outperforms conventional methods such as AFB staining, DNA testing, X-pert, and mycobacterial culture to diagnose EPTB, promising to improve the diagnosis of EPTB.

The incidence of extrapulmonary tuberculosis (EPTB) in low- and middle-income countries, as well as, high-income countries has increased over the last two decades. The acid-fast bacillus (AFB) smear test is easy to perform and cost-effective with a quick turnaround time but the test has low sensitivity. Culture remains the gold standard for detecting TB; however, it has low sensitivity and slow bacterial growth patterns, as it may take up to 6 to 8 weeks to grow. Therefore, a rapid detection tool is crucial for the early initiation of treatment and ensuring an improved therapeutic outcome. Here, the Xpert Ultra system was developed as a nucleic acid amplification technique to accelerate the detection of MTB in paucibacillary clinical samples and endorsed by the World Health Organization. From March 2020 to August 2021, Xpert Ultra was evaluated for its sensitivity and specificity against EPTB and compared with those of the routinely used Xpert, culture, and AFB tests in 845 clinical samples in Saudi Arabia. The results indicate the overall sensitivity and specificity of Xpert Ultra to be 91% and 95%, respectively, compared with the Xpert (82% and 99%, respectively) and AFB smear (18% and 100%, respectively) tests. The results also indicated that despite the low microbial loads that were categorized as trace, very low, or low on Xpert Ultra, yet, complete detection was achieved with some sample types (i.e., 100% detection). Consequently, Xpert Ultra has great potential to replace conventional diagnostic approaches as a standard detection method for EPTB.