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Objective: To date, the burden of childhood spinal TB in China has not been estimated, and current treatment is hindered by a lack of evidence. This study aimed to review our experience of childhood spinal TB.Methods: We reviewed the medical records of paediatric patients (≤15 years) admitted for spinal TB (confirmed or possible) at Shandong Provincial Chest Hospital from January 2006 to December 2019. Demographic, clinical, laboratory and radiological data were collected from medical records and analysed retrospectively.Results: Seventy-two patients were diagnosed with spinal TB. 45 were male (62.5%), and 27 female (37.5%), with a mean age of 8.42 ± 4.47 (SD) years. During this 14-year period, the overall prevalence of spinal TB among childhood TB was 4.5%. T-SPOT.TB, AFB smear, mycobacterial culture, TB RT-PCR and biopsies were positive in 29.6%, 14.3%, 23.3%, 43.8% and 88.5% of assayed patients, respectively. The overall surgical rate of the studied patients was 40.3%. The requirement of surgery in childhood spinal TB was associated with pulmonary TB (OR = 4.000, 95% CI: 1.197, 13.367).Conclusion: Spinal TB in children cannot be neglected. It remains a severe problem to public health, and more attention should be paid to initiating treatment early. [ABSTRACT FROM AUTHOR]

Tuberculous meningitis (TBM) remains a serious disease for children and its risk factors of poor outcome remain unclear. Therefore, a retrospective study was conducted aiming to investigate the risk factors associated with poor outcome of childhood TBM. Between January 2006 and December 2019, consecutive children patients (≤ 15 years old) who had a diagnosis of TBM were included for the analysis. The demographic, clinical, laboratory, and radiographic data were collected from the electronic medical records retrospectively. Poor outcome was defined as death or transfer to a higher-level hospital. Patients were then divided into good and poor outcome groups. Subsequently, risk factors for poor outcome were estimated using univariate and multivariate logistic regression analysis. A total of 149 children with TBM was enrolled, twenty-two patients suffered poor outcome, including 16 transfers to a higher-level hospital and 6 deaths, and the remaining 127 patients were classified as good outcome group. Further multivariate analysis revealed that coma (age- and sex-adjusted OR = 6.425, 95% CI: 1.743, 23.676; P < 0.01) and cerebrospinal fluid (CSF) protein (> 1188.3 mg/L; age- and sex-adjusted OR = 4.680, 95% CI: 1.469, 14.902; P < 0.01) were associated with the poor outcome of childhood TBM. Childhood TBM remains to have a high mortality rate in China. High CSF protein and coma were identified as risk factors for poor outcome of childhood TBM. Hence, more attention is required to be paid to suspected patients with such characteristics, thus facilitating access to optimum treatment. [ABSTRACT FROM AUTHOR]

Background. In China, the prevalence of tuberculosis (TB) diseases and epidemiological trends in the TB forms among children are still unclear; a retrospective study was conducted aiming to assess it. Methods. Between January 2007 and September 2020, 1577 consecutive childhood TB patients (aged ≤ 15 years) were included in the study. Data, including demographic information and underlying diseases, were collected from medical records. Then, patients were categorized and reported according to the anatomical site of TB disease. To analyze the epidemiological trends in the proportion of each form of TB disease, a linear-by-linear association was used, and a P value of <0.05 was considered to indicate that a significant change had occurred in the proportion of TB disease over the studied period. Results. During the fourteen-year study period, a total of 1577 children patients were enrolled, including 954 boys (60.5%) and 623 girls (39.5%), with a mean age of 9.26 ± 5.18 years. Among the studied patients, 810 (51.4%) patients have pulmonary TB, 1137 (72.1%) have extrapulmonary TB, 372 (23.6%) have both conditions, and another 765 (48.5%) extrapulmonary cases presented in isolated form. Pleural TB (29.0%) and tuberculous lymphadenitis (23.7%) were the most frequent two forms of childhood TB. In addition, during the past decade, the proportions of pulmonary TB, pleural TB, and tuberculous lymphadenitis showed an increasing trend (all P < 0.05). However, no significant trends in the proportions of other forms of TB disease, such as extrapulmonary TB (P > 0.05), tuberculous meningitis (P > 0.05), endobronchial TB (P > 0.05), and disseminated TB (P > 0.05), were found. Conclusion. Our findings suggest that childhood TB is facing new challenges, and the policy should be adjusted timely to fit the real situation. [ABSTRACT FROM AUTHOR]

The study evaluated tuberculosis specific antigen (TB-SA) antibody in lymphocyte supernatant (ALS) assay for diagnosis of pulmonary tuberculosis (PTB). The mean concentration of TB-SA ALS in PTB patients was significantly higher than that of two control groups (non-PTB patients and healthy subjects, P < 0.001). The area under the curve of the ALS assay were 0.960 (0.904–0.988, PTB vs healthy subjects), and were 0.822 (0.739–0.887, PTB vs Non-PTB patients), respectively. Our data indicated the ALS assay for TB-SA can be used as a screening test and is a useful adjunct to current tests for diagnosis of PTB. [ABSTRACT FROM AUTHOR]

Background: The actual positive rate of interferon gamma release assays (IGRAs) in patients with nontuberculous mycobacteria (NTM) infections remains unclear. This review and meta-analysis present the prevalence of positive IGRAs (T-SPOT.TB and QuantiFERON [QFT] tests) among patients infected with NTM isolates (with or without ESAT-6/CFP-10). Methods: Several databases, including PubMed, Scopus, Embase, and Web of Science were searched (until June 18th, 2022). Studies that had the following data were included: (1) results of T-SPOT.TB, QuantiFERON (QFT) test, or both, (2) NTM species, and (3) NTM diseases, or NTM colonization. The metaprop command that incorporates a Freeman-Tukey double arcsine transformation is used for pooling proportions. Results: A total of 11 articles (n = 929) were deemed eligible for inclusion. Meta-analysis identified that the overall pooled positive and indeterminate rates of IGRA results in patients with NTM infections was 16% and 5%, respectively. Subgroup analysis showed that the positive rate of IGRAs in patients infected with NTM (without ESAT-6/CFP-10) was 7% (95% CI, 1%-18%), and 44% (95%CI, 22%-68%) in patients infected with NTM (with ESAT-6/CFP-10). In addition, the indeterminate rate of QFT (7%, 95% CI: 4%-12%) was higher than that of T-SPOT.TB (0%; 95% CI, 0%-2%) among the overall population with NTM infections. Conclusions: The IGRAs have a moderate positive rate for the diagnosis of NTM (expressing ESAT-6/CFP-10) infections, and a significant indeterminate rate is observed among the overall population infected with NTM. However, these findings should be interpreted with caution because of the high heterogeneity among studies. [ABSTRACT FROM AUTHOR]

Aim: Until now, the performance of interferon-γ release assay (IGRA) and Mantoux tests remains unclear in infant tuberculous meningitis (TBM). Therefore, a systematic review is performed to evaluate the sensitivity of IGRA and Mantoux tests for the diagnosis of infant TBM in low and intermediate tuberculosis (TB) burden countries, while following PRISMA. Methods: Several databases, including PubMed, EBSCO, Embase, Scopus, Web of Science, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials, were searched. Articles describing the results of IGRA or Mantoux tests among infant TBM were included for analysis. Data, such as age, sex, Mantoux test or IGRA, and cerebrospinal fluid (CSF) microbiological examinations (such as acid-fast bacilli (AFB) smear, TB PCR, and TB culture), were extracted from each study. Results: A total of 31 articles were enrolled for further analysis, including 48 cases. The mean age was 9.4 ± 5.8 months and boys accounted for 57.1% of infants (24/42). Mantoux test was positive in 57.4% (27/47) of tested infants and IGRA was positive in 77.8% (7/9) of infants. In addition, among the infants with confirmed TB, 18 (52.9%, 18/34) of them have positive Mantoux responses and 7 (20.0%, 7/35) have positive IGRA results. Conclusions: In low or intermediate TB burden countries, the Mantoux test has a poor performance for diagnosing TBM among infants, and IGRAs appear to have a moderate sensitivity for the diagnosis of infant TBM. [ABSTRACT FROM AUTHOR]

The diagnostic accuracy of oral specimen nucleic acid amplification tests (NAATs) for pulmonary tuberculosis (PTB) remains controversial. We performed a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, including studies that reported the diagnostic yield of NAATs in oral samples for PTB diagnosis. The pooled estimates, including those of sensitivity and specificity, were calculated, and a meta-regression was performed to investigate heterogeneity, which was determined using χ2 and I ² tests. A total of 23 articles were included, and the pooled sensitivity, specificity, and area under the curve of NAATs in oral samples for PTB diagnosis were 50% (95% CI, 37%–63%), 97% (95% CI, 93%–99%), and 0.89 (95% CI, 86%–92%; I 2 = 99%; chi-square, 169.61; P <.001), respectively. Our data demonstrated that NAATs using oral samples have a less satisfactory sensitivity and high specificity for PTB diagnosis. However, due to significant heterogeneity, such as heterogeneity in age, the results should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Background: Until now, the influential factors associated with pleural adenosine deaminase (ADA) activity among children remain unclear. This retrospective study was therefore conducted aiming to investigate the factors associated with negative pleural ADA results in the diagnosis of childhood pleural tuberculosis (TB).Methods: Between January 2006 and December 2019, children patients with definite or possible pleural TB were recruited for potential analysis. Then, patients were stratified into two categories: negative pleural ADA results group (experimental group, ≤40 U/L) and positive pleural ADA results group (control group, > 40 U/L). Univariate and multivariate logistic regression analyses were performed to estimate risk factors for negative pleural ADA results.Results: A total of 84 patients with pleural TB were recruited and subsequently classified as experimental (n = 17) and control groups (n = 67). Multivariate analysis (Hosmer-Lemeshow goodness-of-fit test: χ2 = 1.881, df = 6, P = 0.930) revealed that variables, such as chest pain (age-adjusted OR = 0.0510, 95% CI: 0.004, 0.583), pleural total protein (≤45.3 g/L, age-adjusted OR = 27.7, 95% CI: 2.5, 307.7), pleural lactate dehydrogenase (LDH, ≤505 U/L, age-adjusted OR = 59.9, 95% CI: 4.2, 857.2) and blood urea nitrogen (≤3.2 mmol/L, age-adjusted OR = 32.0, 95% CI: 2.4, 426.9), were associated with negative pleural ADA results when diagnosing childhood pleural TB.Conclusion: Our findings demonstrated that chest pain, pleural total protein, pleural LDH, and blood urea nitrogen were associated with a negative pleural ADA result for the diagnosis of pleural TB among children. When interpreting pleural ADA levels in children with these characteristics, a careful clinical assessment is required for the pleural TB diagnosis. [ABSTRACT FROM AUTHOR]

Pleural effusion (PE) Xpert has limited use in the diagnosis of pleural tuberculosis (TB). However, the diagnostic incremental value of sputum Xpert for pleural TB diagnosis remains unclear. Between March 2018 and October 2019, patients with certain causes (such as TB, malignancy, and pneumonia) of PE were enrolled in our study. Sputum and PE were collected from all patients and sent for acid-fast bacilli smear (Auramine O staining), mycobacterial culture (Lowenstein-Jensen media), and Xpert. The differences in the sensitivities of these TB assays between different groups were examined with the chi-square test. One hundred and twenty-seven PE patients were enrolled in the study and then were divided into pleural TB (n = 104) and other causes of PE (excluding TB, referred as non-pleural TB; n = 23). Compared with PE Xpert (11.5%, 12/104), sputum Xpert has a higher sensitivity of 25.0% (26/104, p =.012 <.05). The combination of sputum and PE has a non-significant higher sensitivity of 31.7% (33/104) than Xpert on sputum (p >.05). Culture using both sputum and PE combined has a high sensitivity of 43.3% (45/104). Compared to PE Xpert, sputum Xpert showed an incremental diagnostic yield in the diagnosis of pleural TB and is expected to speed up the diagnosis of pleural TB. [ABSTRACT FROM AUTHOR]

Surgical intervention use is common in the management of childhood pleural tuberculosis (TB), however, its associated risk factors remain unclear. Between January 2006 and December 2019, consecutive children patients (≤ 15 years old) who had a diagnosis of pleural TB were included for the analysis. Surgical intervention was defined as debridement (such as breaking loculations), decortication, and thoracic surgery (such as lobectomy or segmental resection). Patients undergoing surgery were included as surgical group, without surgery were classified as non-surgical group, surgical risk factors were then estimated. Univariate and multivariate logistic regression analysis were performed to evaluate the risk factors for surgical interventions. A total of 154 children diagnosed as pleural TB (definite, 123 cases; possible, 31 cases) were included in our study. Of them, 29 patients (18.8%) were classified as surgical group and 125 patients (81.2%) were classified as non-surgical group. Surgical treatments were analyzed in 29 (18.8%) patients, including debridement (n = 4), decortication (n = 21), and thoracic surgery (n = 4). Further multivariate analysis revealed that empyema (age- and sex-adjusted OR = 27.3, 95% CI 8.6, 87.1; P < 0.001) and frequency of hospitalization (age- and sex-adjusted OR = 1.53, 95% CI 1.11, 2.11; P < 0.01) were associated with the use of surgical interventions in children with pleural TB. In China, surgical interventions are still required in a significant proportion of children with pleural TB, and the surgical risk is found to be associated with the frequency of hospitalization and empyema. These findings may be helpful to improve the management of children with pleural TB and minimize the risk of poor outcomes. [ABSTRACT FROM AUTHOR]

Background: Delay in diagnosis and treatment worsens the disease and clinical outcomes, which further enhances the transmission of tuberculosis (TB) in the community. Therefore, this study aims to assess treatment delay and its associated factors among childhood pleural TB patients in China.Methods: Between January 2006 and December 2019, consecutive patients aged ≤15 years with definite or possible pleural TB were included for analysis. Treatment delay duration was defined as the time interval from the onset of symptoms to treatment initiation and was stratified into two categories: < 30 days, ≥30 days (median delay day is 30 days). The electronic medical records of children were reviewed to obtain demographic characteristics, clinical characteristics, laboratory examinations, and radiographic findings. Univariate and multivariate logistic regressions were used to explore the factors associated with treatment delay in patients.Results: A total of 154 children with pleural TB were included, with a mean age of 12.4 ± 3.3 years. The median treatment delay was 30 days (interquartile range, 10-60 days) and 51.3% (n = 79) of patients underwent a treatment delay. Multivariate analysis revealed that heart rate (≤92 beats/min, age-adjusted OR = 2.503, 95% CI: 1.215, 5.155) and coefficient of variation of red cell distribution width (RDW-CV, ≥12.9%, age-adjusted OR = 4.705, 95% CI: 2.048, 10.811) were significant risk factors for treatment delays in childhood pleural TB.Conclusion: Our findings suggested that a significant treatment delay occurs among children with pleural TB in China. Patients with a low heart rate or a high RDW-CV experienced delays in the initiation of anti-TB therapy. Therefore, well awareness of the associations between clinical characteristics and treatment delay may improve the management of children with pleural TB and enable us to develop preventive strategies to reduce the treatment delay. [ABSTRACT FROM AUTHOR]

Tuberculous empyema (TE) is associated with high mortality and morbidity. In the retrospective cohort study, we aimed to find risk factors for TE among pleural tuberculosis (TB) patients. Between July 2011 and September 2015, all culture-confirmed pleural TB patients (474 cases) were enrolled in our study. Empyema was defined as grossly purulent pleural fluid. Demographic and epidemiological data were collected for further analysis. Multivariate logistic regression analysis was used to evaluate risk factors of TE in pleural TB, age–adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated to show the risk. The mean age was 35.7 ± 18.1 years old, males comprised 79.1% of the participants (375 cases). Forty-seven patients (9.9%) were multidrug-resistant TB (MDR-TB), 29 (6.1%) had retreatment TB, 26 (5.5%) had diabetes mellitus. The percentage of empyema patients was 8.9% (42 cases). Multivariate analysis revealed that male (adjusted OR = 4.431, 95% CI: 1.411, 13.919), pleural adenosine deaminase (ADA, >88 U/L) (adjusted OR = 3.367, 95% CI: 1.533, 7.395) and white blood cell (WBC, >9.52 109/L) (adjusted OR = 5.763, 95% CI: 2.473, 13.431) were significant risk factors for empyema in pleural TB, while pulmonary TB (adjusted OR = 0.155, 95% CI: 0.072, 0.336) was the protective factor for the patients. TE remains a serious threat to public health in China. Male sex is a significant risk factor for TE while the presence of pulmonary TB is protective, and high levels of pleural ADA and WBC count could aid in early diagnosis of TE. This finding would help towards reducing the mortality and morbidity associated with TE. [ABSTRACT FROM AUTHOR]

Background: Currently, there is limited data on the risk factors associated with treatment delay in tuberculous meningitis (TBM). This study aimed to assess the duration of delay in the treatment TBM and to investigate its determinants.Methods: During the period from September 2009 to February 2016, a retrospective cohort study of consecutive TBM patients admitted to our hospital was conducted to determine the risk factors associated with treatment delay in TBM. Treatment delay duration was defined as the time interval from onset of symptoms (by patient recall) to initiation of treatment and was stratified into two categories: ≤ 20 days, >20 days (median delay day is 20 days). Data collected included demography, comorbidity, cerebrospinal fluid (CSF) examinations and others. Univariable and multivariable logistic regression analysis was used to evaluate the determinants of treatment delay.Results: A total of 161 TBM patients were included in our study, all were confirmed by CSF mycobacterial culture. The median treatment delay for all patients included in the study was 20 days [interquartile range, 14-60 days]. Multivariate analysis revealed that age (≤21 years old, OR = 0.202, 95% CI: 0.079, 0.521), fever (OR = 0.414, 95% CI: 0.180, 0.952), and headache (OR = 0.204, 95% CI: 0.095, 0.442) had significantly lower risk for treatment delay, while multiple healthcare contact (>3 times) (OR = 3.938, 95% CI: 1.326, 11.691) as well as CSF chloride (>111 mmol/L) (OR = 2.479, 95% CI: 1.143, 5.377) had significantly higher risk of the delay.Conclusions: Our findings indicate that multiple healthcare contact and high CSF chloride predict the risk of long delay, while young age, fever and headache are associated with short delay. Maintained focus on awareness of TBM in the population and in healthcare systems, and continuous implementation of diagnostic methods for TBM to detect the disease early, may reduce the mortality and morbidity. [ABSTRACT FROM AUTHOR]

To describe the demographics, clinical characteristics and microbiologic findings of infant (≤2 years old) tuberculosis (TB) in a high TB burden country. Between Feb, 2007 and Jun, 2015, 115 TB infants who admitted to our hospital were enrolled in the study. Their clinicopathological characteristics were reviewed and analyzed. The mean age was 10.1 ± 7.4 (SD) months, and 84 of 115 infants (73.0 %) were males. 23 patients (20.0 %) had isolated pulmonary TB, 18 patients (15.7 %) had pulmonary and extrapulmonary TB (EPTB), the remaining 74 patients (64.4 %) had exclusively EPTB. The most common site of EPTB was lymph node (n = 61), 54 cases were left axillary lymph node involvement. 49 of 51 patients (96.1 %) were validated by pathological examination, 5 of 57 patients (8.8 %) were positive on acid fast bacilli smear, and 27 of 103 patients (26.2 %) were confirmed by mycobacterial culture. 29 of 59 patients (49.2 %) were PPD positive, 14 of 30 patients (46.7 %) were T-SPOT.TB positive. The most common complaints of patients were lymph node swelling (53.0 %), fever (36.5 %), cough (28.7 %) and dyspnea (10.4 %). There was significant difference in the time before hospital admission among different types of tuberculosis (P < 0.01), fever was also a factor influencing the time (P < 0.05). In infants, the sensitivities of routine TB tests were low and emphasize the need for improved diagnostics; EPTB was more common than pulmonary TB, tuberculous lymphadenitis constituted a high proportion of EPTB; there appears to be an association between the incidence of axillary lymph node TB and BCG vaccination among infants in China. [ABSTRACT FROM AUTHOR]

The article offers information on the study related to the evaluation of the double sputum Xpert tests for the diagnosis of pulmonary tuberculosis. It discusses the World Health Organization guidelines to improve the efficiency of Mycobacterium tuberculosis detection in pulmonary tuberculosis. It mentions the potential limitations to the study regarding the small sample size clinical decisions to perform the second Xpert test.