Genotypic and phenotypic drug resistance patterns of Mycobacterium tuberculosis isolated from presumptive pulmonary tuberculosis patients in Ethiopia: A multicenter study.

BACKGROUND: The emergence of drug-resistant tuberculosis (DR-TB) has been a major obstacle to global tuberculosis control programs, especially in developing countries, including Ethiopia. This study investigated drug resistance patterns and associated mutations of Mycobacterium tuberculosis Complex (MTBC) isolates from the Amhara, Gambella, and Benishangul-Gumuz regions of Ethiopia. METHODS: A cross-sectional study was conducted using 128 MTBC isolates obtained from patients with presumptive tuberculosis (TB). Phenotypic (BACTEC MGIT 960) and genotypic (MTBDRplus and MTBDRsl assays) methods were used for drug susceptibility testing. Data were entered into Epi-info and analyzed using SPSS version 25. Frequencies and proportions were determined to describe drug resistance levels and associated mutations. RESULTS: Of the 127 isolates recovered, 100 (78.7%) were susceptible to four first-line anti-TB drugs. Any drug resistance, polydrug resistance, and multi-drug resistance (MDR) were detected in 21.3% (27), 15.7% (20), and 15% (19) of the isolates, respectively, by phenotypic and/or genotypic methods. Mono-resistance was observed for Isoniazid (INH) (2, 1.6%) and Streptomycin (STR) (2, 1.6%). There were two genotypically discordant RIF-resistant cases and one INH-resistant case. One case of pre-extensively drug-resistant TB (pre-XDR-TB) and one case of extensively drug-resistant TB (XDR-TB) were identified. The most frequent gene mutations associated with INH and rifampicin (RIF) resistance were observed in the katG MUT1 (S315T1) (20, 76.9%) and rpoB (S531L) (10, 52.6%) genes, respectively. Two MDR-TB isolates were resistant to second-line drugs; one had a mutation in the gyrA MUT1 gene, and the other had missing gyrA WT1, gyrA WT3, and rrs WT1 genes without any mutation. CONCLUSIONS: The detection of a significant proportion of DR-TB cases in this study suggests that DR-TB is a major public health problem in Ethiopia. Thus, we recommend the early detection and treatment of DR-TB and universal full first-line drug-susceptibility testing in routine system.

Risk factors of adult isoniazid-resistant and rifampicin-susceptible tuberculosis in Nanjing, 2019-2021.

INTRODUCTION: This study aimed to analyze the risk factors associated with isoniazid-resistant and rifampicin-susceptible tuberculosis (Hr-TB) in adults. METHOD: The clinical data of 1,844 adult inpatients diagnosed with culture-positive pulmonary tuberculosis (PTB) in Nanjing Second Hospital from January 2019 and December 2021 were collected. All culture positive strain from the patient specimens underwent drug susceptibility testing (DST). Among them, 166 patients with Hr-TB were categorized as the Hr-TB group, while the remaining 1,678 patients were classified as having drug-susceptible tuberculosis (DS-TB). Hierarchical logistic regression was employed for multivariate analysis to identify variables associated with Hr-TB. RESULTS: Multivariate logistic regression analysis revealed that individuals with diabetes mellitus (DM) (OR 1.472, 95% CI 1.037-2.088, p = 0.030) and a history of previous tuberculosis treatment (OR 2.913, 95% CI 1.971-4.306, p = 0.000) were at higher risk of developing adult Hr-TB, with this risk being more pronounced in male patients. Within the cohort, 1,640 patients were newly treated, and among them, DM (OR 1.662, 95% CI 1.123-2.461, p = 0.011) was identified as risk factors for Hr-TB. CONCLUSIONS: Diabetes mellitus is a risk factor for Hr-TB in adults, and the contribution of diabetes as a risk factor was more pronounced in the newly treatment or male subgroup. And previous TB treatment history is also a risk factor for Hr-TB in adults.

Subclinical tuberculosis: a meta-analysis of prevalence and scoping review of definitions, prevalence and clinical characteristics.

BACKGROUND: This scoping review aimed to characterise definitions used to describe subclinical tuberculosis (TB), estimate the prevalence in different populations and describe the clinical characteristics and treatment outcomes in the scientific literature. METHODS: A systematic literature search was conducted using PubMed. We included studies published in English between January 1990 and August 2022 that defined "subclinical" or "asymptomatic" pulmonary TB disease, regardless of age, HIV status and comorbidities. We estimated the weighted pooled proportions of subclinical TB using a random-effects model by World Health Organization reported TB incidence, populations and settings. We also pooled the proportion of subclinical TB according to definitions described in published prevalence surveys. RESULTS: We identified 29 prevalence surveys and 71 other studies. Prevalence survey data (2002-2022) using "absence of cough of any duration" criteria reported higher subclinical TB prevalence than those using the stricter "completely asymptomatic" threshold. Prevalence estimates overlap in studies using other symptoms and cough duration. Subclinical TB in studies was commonly defined as asymptomatic TB disease. Higher prevalence was reported in high TB burden areas, community settings and immunocompetent populations. People with subclinical TB showed less extensive radiographic abnormalities, higher treatment success rates and lower mortality, although studies were few. CONCLUSION: A substantial proportion of TB is subclinical. However, prevalence estimates were highly heterogeneous between settings. Most published studies incompletely characterised the phenotype of people with subclinical TB. Standardised definitions and diagnostic criteria are needed to characterise this phenotype. Further research is required to enhance case finding, screening, diagnostics and treatment options for subclinical TB.

The potential association between metabolic disorders and pulmonary tuberculosis: a Mendelian randomization study.

BACKGROUND: Metabolic disorders (MetDs) have been demonstrated to be closely linked to numerous diseases. However, the precise association between MetDs and pulmonary tuberculosis (PTB) remains poorly understood. METHOD: Summary statistics for exposure and outcomes from genome-wide association studies (GWASs) for exposures and outcomes were obtained from the BioBank Japan Project (BBJ) Gene-exposure dataset. The 14 clinical factors were categorized into three groups: metabolic laboratory markers, blood pressure, and the MetS diagnostic factors. The causal relationship between metabolic factors and PTB were analyzed using two-sample Mendelian Randomization (MR). Additionally, the direct effects on the risk of PTB were investigated through multivariable MR. The primary method employed was the inverse variance-weighted (IVW) model. The sensitivity of this MR analysis was evaluated using MR-Egger regression and the MR-PRESSO global test. RESULTS: According to the two-sample MR, HDL-C, HbA1c, TP, and DM were positively correlated with the incidence of active TB. According to the multivariable MR, HDL-C (IVW: OR 2.798, 95% CI 1.484-5.274, P = 0.001), LDL (IVW: OR 4.027, 95% CI 1.140-14.219, P = 0.03) and TG (IVW: OR 2.548, 95% CI 1.269-5.115, P = 0.009) were positively correlated with the occurrence of PTB. TC (OR 0.131, 95% CI 0.028-0.607, P = 0.009) was negatively correlated with the occurrence of PTB. We selected BMI, DM, HDL-C, SBP, and TG as the diagnostic factors for metabolic syndrome. DM (IVW, OR 1.219, 95% CI 1.040-1.429 P = 0.014) and HDL-C (IVW, OR 1.380, 95% CI 1.035-1.841, P = 0.028) were directly correlated with the occurrence of PTB. CONCLUSIONS: This MR study demonstrated that metabolic disorders, mainly hyperglycemia, and dyslipidemia, are associated with the incidence of active pulmonary tuberculosis.

Predictors of positive tuberculin skin test in neonates exposed to pulmonary tuberculosis.

BACKGROUND: Neonates are at risk of nosocomial tuberculosis (TB) infection from health care workers (HCWs) in neonatal care facilities, which can progress to severe TB diseases. Tuberculin skin test (TST) is commonly used for TB diagnosis, but its accuracy in neonates is influenced by various factors, including bacilli Calmette-Guérin (BCG) vaccination. This study aimed to identify predictors of positive TSTs in neonates exposed to HCWs with pulmonary TB. METHODS: A retrospective observational study was conducted to compare the frequency of predictors between TST-positive and TST-negative neonates. Demographic, epidemiological, and clinical data of neonates exposed to TB, along with that of HCW and household contacts, were collected retrospectively through contact investigations with the Korean National TB Surveillance System (KNTSS) database. TSTs using 2 tuberculin units of purified protein derivative RT23 were performed on exposed neonates at the end of preventive TB treatment. Firth logistic regression was performed to identify predictors of TST positivity. RESULTS: Contact investigations revealed that 152 neonates and 54 HCWs were exposed to infectious TB index cases in 3 neonatal care facilities. Of 152 exposed neonates, 8 (5.3%) had positive TST results. Age of 6 days or more at the initial exposure is a statistically significant predictor of positive TST (Firth coefficient 2.1, 95% confidence interval 0.3-3.9, P = 0.024); BCG vaccination showed no statistical significance in both univariable and multivariable analysis. Sex, prematurity, exposure duration, duration from initial exposure to contact investigation, and isoniazid preventive treatment duration were not significant predictors. CONCLUSION: Age at the initial exposure is a significant predictor of positive TST in neonates exposed to active pulmonary TB. Given the complexities of TST interpretation, including false positives due to BCG vaccination, careful risk assessment is necessary for appropriate decision-making and resource allocation in the management of neonatal TB exposure.

Two Difficult Pandemics: Tuberculosis and COVID-19.

BACKGROUND: The coinfection of Mycobacterium tuberculosis and SARS-CoV-2 is called tuberculosis and COVID-19 coinfection (TB-COVID-19). We aimed to share the clinical, radiological, and laboratory findings and treatment processes of our patients with TB-COVID-19 coinfection in our tertiary reference hospital. METHODS: Patients aged 18 years and over and hospitalized in the tuberculosis service between March 2020 and September 2022 were included. All coinfected patients whose COVID-19 polymerase chain reaction results were positive while receiving tuberculosis treatment or who were diagnosed with tuberculosis while receiving treatment for COVID-19 were included. RESULTS: The number of patients was 39; 61.6% of males; the mean age was 52 ± 17.1 years; 20% were foreign nationals; 92.5% were Asian; 69.5% had a bacteriological diagnosis; 84.6% had pulmonary tuberculosis; 10% had received antituberculosis treatment before; and 87.5% were sensitive to the first-line antituberculosis drugs. The most common comorbidities were diabetes and hypertension. 87.5% of the patients were diagnosed with tuberculosis and were superinfected with COVID-19 while receiving tuberculosis treatment. 49.5% of patients had received at least one dose of COVID-19 vaccine. The most common presenting symptom was cough and sputum; the prominent laboratory parameter was C-reactive protein increase, and thorax computed tomography finding was consolidation, tree-in-bud, and cavitation. While 45.9% of the patients were still under treatment, 1 (2.5%) patient also resulted in mortality. CONCLUSION: In this study, attention was drawn to two infectious diseases seen with respiratory tract symptoms. The mortality rate was found to be low. Neither disease was found to be a factor aggravating the course of each other.

Pulmonary tuberculosis epidemiology and genetics in Kazakhstan.

Background: Tuberculosis (TB) is a major public health emergency in many countries, including Kazakhstan. Despite the decline in the incidence rate and having one of the highest treatment effectiveness in the world, the incidence rate of TB remains high in Kazakhstan. Social and environmental factors along with host genetics contribute to pulmonary tuberculosis (PTB) incidence. Due to the high incidence rate of TB in Kazakhstan, our research aimed to study the epidemiology and genetics of PTB in Kazakhstan. Materials and methods: 1,555 participants were recruited to the case-control study. The epidemiology data was taken during an interview. Polymorphisms of selected genes were determined by real-time PCR using pre-designed TaqMan probes. Results: Epidemiological risk factors like diabetes (χ2 = 57.71, p < 0.001), unemployment (χ2 = 81.1, p < 0.001), and underweight-ranged BMI (<18.49, χ2 = 206.39, p < 0.001) were significantly associated with PTB. VDR FokI (rs2228570) and VDR BsmI (rs1544410) polymorphisms were associated with an increased risk of PTB. A/A genotype of the TLR8 gene (rs3764880) showed a significant association with an increased risk of PTB in Asians and Asian males. The G allele of the rs2278589 polymorphism of the MARCO gene increases PTB susceptibility in Asians and Asian females. VDR BsmI (rs1544410) polymorphism was significantly associated with PTB in Asian females. A significant association between VDR ApaI polymorphism and PTB susceptibility in the Caucasian population of Kazakhstan was found. Conclusion: This is the first study that evaluated the epidemiology and genetics of PTB in Kazakhstan on a relatively large cohort. Social and environmental risk factors play a crucial role in TB incidence in Kazakhstan. Underweight BMI (<18.49 kg/m2), diabetes, and unemployment showed a statistically significant association with PTB in our study group. FokI (rs2228570) and BsmI (rs1544410) polymorphisms of the VDR gene can be used as possible biomarkers of PTB in Asian males. rs2278589 polymorphism of the MARCO gene may act as a potential biomarker of PTB in Kazakhs. BsmI polymorphism of the VDR gene and rs2278589 polymorphism of the MARCO gene can be used as possible biomarkers of PTB risk in Asian females as well as VDR ApaI polymorphism in Caucasians.

Finger printing-RFLP analysis of chromosomal IS6110 insertion sequence and PCR diagnosis of pulmonary tuberculosis, isolated from patients in El Hajeb region of Morocco.

Tuberculosis (TB) is one of the contagious diseases caused by M. tuberculosis (MTB) bacteria. Prompt diagnosis is one of the active solutions to control the spread of this infection. Besides, a targeted, specific and non-complex diagnosis can prove promising in this type of epidemic. This study was designed to compare the efficiencies of a diagnosis by Ziehl-Neelsen staining (ZN) and by the polymerase chain reaction (PCR) technique. Samples presented smear-positive pulmonary TB were subjected to Chromosomal restriction fragment length polymorphism of IS6110 (IS6110-RFLP) for fingerprinting profile determination. The results showed that out of 100 sputum samples of suspected case, 53 were positive. Numbers of positive individuals for tuberculosis obtained by the different diagnostic techniques, to know, (ZN staining; culture and PCR) were respectively: 6, 25 and 22. Chromosomal RFLP fingerprinting profile revealed the presence of five different genotypes obtained from seven tested isolates. These results suggest that molecular techniques are alternative tool for fast and specific diagnosis of pulmonary MTB from sputum.

Timely Pulmonary Tuberculosis Diagnosis Based on the Epidemiological Disease Spectrum: Population-Based Prospective Cohort Study in the Republic of Korea.

BACKGROUND: Timely pulmonary tuberculosis (PTB) diagnosis is a global health priority for interrupting transmission and optimizing treatment outcomes. The traditional dichotomous time-divided approach for addressing time delays in diagnosis has limited clinical application because the time delay significantly varies depending on each community in question. OBJECTIVE: We aimed to reevaluate the diagnosis time delay based on the PTB disease spectrum using a novel scoring system that was applied at the national level in the Republic of Korea. METHODS: The Pulmonary Tuberculosis Spectrum Score (PTBSS) was developed based on previously published proposals related to the disease spectrum, and its validity was assessed by examining both all-cause and PTB-related mortality. In our analysis, we integrated the PTBSS into the Korea Tuberculosis Cohort Registry. We evaluated various time delays, including patient, health care, and overall delays, and their system-associated variables in line with each PTBSS. Furthermore, we reclassified the scores into distinct categories of mild (PTBSS=0-1), moderate (PBTBSS=2-3), and severe (PBTBSS=4-6) using a multivariate regression approach. RESULTS: Among the 14,031 Korean patients with active PTB whose data were analyzed from 2018 to 2020, 37% (n=5191), 38% (n=5328), and 25% (n=3512) were classified as having a mild, moderate, and severe disease status, respectively, according to the PTBSS. This classification can therefore reflect the disease spectrum of PTB by considering the correlation of the score with mortality. The time delay patterns differed according to the PTBSS. In health care delays according to the PTBSS, greater PTB disease progression was associated with a shorter diagnosis period, since the condition is microbiologically easy to diagnose. However, with respect to patient delays, the change in elapsed time showed a U-shaped pattern as PTB progressed. This means that a remarkable patient delay in the real-world setting might occur at both apical ends of the spectrum (ie, in both mild and severe cases of PTB). Independent risk factors for a severe PTB pattern were age (adjusted odds ratio 1.014) and male sex (adjusted odds ratio 1.422), whereas no significant risk factor was found for mild PTB. CONCLUSIONS: Timely PTB diagnosis should be accomplished. This can be improved with use of the PTBSS, a simple and intuitive scoring system, which can be more helpful in clinical and public health applications compared to the traditional dichotomous time-only approach.

Prevalence of pulmonary tuberculosis and HIV infections and risk factors associated to tuberculosis in detained persons in Antananarivo, Madagascar.

The incidence rate of tuberculosis in prisons is estimated to be 8 times greater than that in the general population in Madagascar. Our objectives were to estimate the prevalence of pulmonary tuberculosis and HIV infection among prisoners and to identify risk factors associated with tuberculosis. We conducted a cross-sectional study at the central prison of Antananarivo from March to July 2021. Individual male and female inmates aged ≥ 13 years who had lived in the prison for at least three months prior to the study period were included as participants. Acid-fast bacilli detection by microscopy and/or culture, an intradermal tuberculin test, a chest X-ray, and a rapid diagnostic orientation test for HIV were performed. Among 748 participants, 4 (0.5%) were confirmed to have pulmonary tuberculosis. Overall, 14 (1.9%) patients had "confirmed" or "probable" tuberculosis [0.90-2.84, 95% CI]. The proportion of participants with latent tuberculosis infection was 69.6% (517/743) based on a positive tuberculin test without clinical symptoms or radiography images indicating tuberculosis. Out of 745 HIV screening tests, three showed reactive results (0.4%). Age (OR = 4.4, 95% CI [1.4-14.0]) and prior tuberculosis treatment (or episodes) were found to be associated with confirmed and probable tuberculosis.

Sociodemographic and clinical risk factors associated with in-hospital tuberculosis mortality in Türkiye, 2008-2018.

Introduction: Tuberculosis (TB) is an infectious disease that can be fatal if left untreated or poorly treated, and it is associated with many morbidities. Deaths may provide better understanding of the associated factors and help guide interventions to reduce mortality. In this study, it was aimed to reveal some of the features that predict hospital mortality in patients with TB and to present some alarming findings for clinicians. Materials and Methods: Patients who had been hospitalized with the diagnosis of TB between January 2008 and December 2018 were included and analyzed retrospectively. In-hospital mortality because of any TB disease after the initiation of treatment in patients admitted to the TB Ward and the primary cause of mortality were taken as endpoint. Result: A total of 1321 patients with a mean age of 50.1 years were examined. Total mortality was 39.4% (521 deaths) and 13.1% were in-hospital deaths (173 deaths). Of the deaths, 61.8% (n= 107) occurred during the first month after TB treatment were started. On univariate analysis, age over 48.5 years, Charlson comorbidity index, extension of radiological involvement, hypoalbuminemia and lymphopenia were most predictive variables with higher odds ratios (respectively, p<0.001 for all). Conclusions: In-hospital tuberculosis disease mortality is related with older age, cavitary or extensive pulmonary involvement, low albumin levels, unemployment, cigarette smoking and especially those with concomitant malignancy and chronic pulmonary disease.

[Spatial-temporal distribution characteristics of etiologically positive pulmonary tuberculosis in Jiangsu Province from 2011 to 2021].

Objective: To analyze the spatial-temporal distribution of etiologically positive pulmonary tuberculosis (PTB) at the county (city, district) unit in Jiangsu Province from 2011 to 2021 to provide evidence for the implementation and adjustment of prevention and control strategies of PTB in Jiangsu Province. Methods: The registration data of etiologically positive PTB patients in Jiangsu Province from 2011 to 2021 were collected from the Tuberculosis Management Information System in the China Information System of Disease Control and Prevention. Data on the permanent population were from the statistical yearbook of each county (city, district) in Jiangsu Province. Geoda 1.18.0 software was used to analyze the global and local spatial autocorrelation and explore the spatial clustering. SaTScan 10.1 software was used to analyze the spatial-temporal clusters, and ArcGIS 10.7 software was used to visualize the spatial-temporal clusters. Results: A total of 128 240 etiological positive PTB cases were registered in Jiangsu Province from 2011 to 2021, with an average annual registration rate of 13.99/100 000. The registration rate showed an overall upward trend (trend χ2=63.49, P<0.001) after 2017, and the etiologically positive rate showed an overall upward trend (trend χ2=3 710.86, P<0.001). The annual Moran's I values ranged from 0.107 to 0.343, which showed a spatial clustering distribution. The results of local spatial autocorrelation analysis showed that there were "high-high" clustering areas in Jiangsu Province each year, showing a dynamic distribution, and most of the areas were distributed in the central and southern regions of Jiangsu Province, with the largest number (7) in 2015 and the smallest number (1) in 2011. A total of 4 spatial-temporal clustering areas were explored by spatial-temporal scanning analysis (all P<0.001), among which the first-level clustering area covered 3 counties (cities, districts), namely Changshu, Taicang, and Xiangcheng District of Suzhou, and the clustering time was from 2011 to 2015. The secondary clustering areas covered 24 counties (cities, districts), mainly covering Jiangsu's central and northern regions, such as Huai'an, Suqian, and Yancheng. The third-level clustering areas covered 26 counties (cities, districts); the fourth-level clustering area was the Gaochun District of Nanjing, with the clustering period from 2017 to 2021. Conclusions: From 2011 to 2021, the etiologically positive PTB registration rate at the county (city, district) level in Jiangsu Province had obvious spatial-temporal clustering characteristics. The clustering areas included the northern areas with relatively backward economies and the southern areas with better economic development. Multiple measures should be taken to prevent and control PTB according to the specific situation in different regions.

Tuberculosis treatment during the COVID-19 pandemic: actions offered and case profile.

OBJECTIVE: To analyze the association between the provision of tuberculosis treatment actions and the sociodemographic and clinical characteristics of cases during the COVID-19 pandemic. METHOD: Cross-sectional study conducted with data from secondary sources of 134 tuberculosis cases that underwent treatment in 2020 in the city of Pelotas, RS, Brazil. Data were analyzed using descriptive statistics, Chi-square test, and Fisher's exact test. RESULTS: The least frequently offered actions in the period were: three or more control smear microscopies (12.7%), smear microscopy at the end of treatment (16.7%), chest X-ray at sixth month (48.5%) and sputum culture (49%). The number of medical and nursing consultations did not reach six in 52.9% and 83.3% of cases, respectively. The lower offer of treatment actions was associated with: retreatment (p<0.001); comorbidities (p=0.023); HIV infection (p<0.001); mental disorder (p=0.013); illicit substance use (p=0.018); normal chest X-ray (p=0.024); and special treatment regimen (p=0.009). CONCLUSION: After the COVID-19 pandemic, it is essential to invest in cases follow-up, especially those undergoing retreatment, with comorbidities, drug use, normal chest X-ray results, and special treatment regimens.

Characteristics of TB cases without documented sputum culture in the United States, 2011-2021.

Culture-based diagnostics are the gold standard for diagnosing pulmonary TB (PTB). We characterized culture practices by comparing cases with documented sputum culture to those without.Using multivariable logistic regression, we examined associations between PTB case characteristics and no documented sputum culture reported to the U.S. National TB Surveillance System during 2011-2021.Among 69,538 PTB cases analyzed, no sputum culture attempt was documented for 5,869 (8%). Non-sputum culture specimens were documented for 54%, 80%, and 89% of cases without documented sputum culture attempts among persons aged <15 years, 15-64, and 65+ years, respectively; bronchial fluid and lung tissue were common non-sputum specimens among cases in persons >15 years old. Having no documented sputum culture was associated with age <15 years (aOR 23.84, 99% CI 20.09-28.27) or ≥65 years (aOR 1.22, 99% CI 1.07-1.39), culture of a non-sputum specimen (aOR 6.57, 99% CI 5.93-7.28), residence in a long-term care facility (aOR 1.58, 99% CI 1.23-2.01), and receiving TB care outside of a health department (aOR 1.79, 99% CI 1.61-1.98).Inability to obtain sputum from children and higher diagnostic suspicion for disease processes that require tissue-based diagnostics could explain these findings..

Analysis on time delay of tuberculosis among adolescents and young adults in Eastern China.

Background: Tuberculosis (TB) is recognized as a significant global public health concern. Still, there remains a dearth of comprehensive evaluation regarding the specific indicators and their influencing factors of delay for adolescents and young adults. Methods: All notified pulmonary TB (PTB) patients in Jiaxing City were collected between 2005 and 2022 from China's TB Information Management System. Logistic regression models were conducted to ascertain the factors that influenced patient and health system delays for PTB cases, respectively. Furthermore, the impact of the COVID-19 pandemic on local delays has been explored. Results: From January 1, 2005 to December 31, 2022, a total of 5,282 PTB cases were notified in Jiaxing City, including 1,678 adolescents and 3,604 young adults. For patient delay, female (AOR: 1.18, 95%CI: 1.05-1.32), PTB complicated with extra-pulmonary TB (AOR: 1.70, 95% CI: 1.28-2.26), passive case finding (AOR: 1.46, 95% CI: 1.07-1.98) and retreatment (AOR: 1.52, 95% CI: 1.11-2.09) showed a higher risk of delay. For health system delay, minorities (AOR: 0.69, 95% CI: 0.53-0.90) and non-students (AOR: 0.83, 95% CI: 0.71-0.98) experienced a lower delay. Referral (AOR: 1.46, 95% CI: 1.29-1.65) had a higher health system delay compared with clinical consultation. Furthermore, county hospitals (AOR: 1.47, 95% CI: 1.32-1.65) and etiological positive results (AOR: 1.46, 95% CI: 1.30-1.63) were associated with comparatively high odds of patient delay. Contrarily, county hospitals (AOR: 0.88, 95% CI: 0.78-1.00) and etiological positive results (AOR: 0.67, 95% CI: 0.59-0.74) experienced a lower health system delay. Besides, the median of patient delay, health system delay, and total delay during the COVID-19 pandemic were significantly lower than that before. Conclusion: In general, there has been a noteworthy decline in the notification rate of PTB among adolescents and young adults in Jiaxing City while the declining trend was not obvious in patient delay, health system delay, and total delay, respectively. It also found factors such as gender, case-finding method, and the hospital level might influence the times of seeking health care and diagnosis in health agencies. These findings will provide valuable insights for refining preventive and treatment strategies for TB among adolescents and young adults.

Risk factors for pulmonary tuberculosis recurrence, relapse and reinfection: a systematic review and meta-analysis.

BACKGROUND: The rate of pulmonary tuberculosis (TB) recurrence is substantial. Identifying risk factors can support the development of prevention strategies. METHODS: We retrieved studies published between 1 January 1980 and 31 December 2022 that assessed factors associated with undifferentiated TB recurrence, relapse or reinfection. For factors reported in at least four studies, we performed random-effects meta-analysis to estimate a pooled relative risk (RR). We assessed heterogeneity, risk of publication bias and certainty of evidence. RESULTS: We included 85 studies in the review; 81 documented risk factors for undifferentiated recurrence, 17 for relapse and 10 for reinfection. The scope for meta-analyses was limited given the wide variety of factors studied, inconsistency in control for confounding and the fact that only few studies employed molecular genotyping. Factors that significantly contributed to moderately or strongly increased pooled risk and scored at least moderate certainty of evidence were: for undifferentiated recurrence, multidrug resistance (MDR) (RR 3.49; 95% CI 1.86 to 6.53) and fixed-dose combination TB drugs (RR 2.29; 95% CI 1.10 to 4.75) in the previous episode; for relapse, none; and for reinfection, HIV infection (RR 4.65; 95% CI 1.71 to 12.65). Low adherence to treatment increased the pooled risk of recurrence 3.3-fold (95% CI 2.37 to 4.62), but the certainty of evidence was weak. CONCLUSION: This review emphasises the need for standardising methods for TB recurrence research. Actively pursuing MDR prevention, facilitating retention in treatment and providing integrated care for patients with HIV could curb recurrence rates. The use of fixed-dose combinations of TB drugs under field conditions merits further attention. PROSPERO REGISTRATION NUMBER: CRD42018077867.

National cross-sectional cluster survey of tuberculosis prevalence in Timor-Leste: a study protocol.

INTRODUCTION: Timor-Leste has one of the world's highest estimated tuberculosis (TB) incidences, yet the data which informs this estimate is limited and the true burden of TB disease is not known. TB prevalence surveys offer the best means of determining robust estimates of disease burden. This study aims to provide an estimate of the prevalence of bacteriologically confirmed pulmonary TB in Timor-Leste and provide additional insights into diagnostic coverage and health-seeking behaviour of persons with symptoms suggestive of TB. METHODS AND ANALYSIS: A national population-based cross-sectional cluster survey will be conducted in which participants aged 15 years and older will be screened for pulmonary TB using an algorithm consisting of symptom screening and digital X-ray of the chest with computer-aided detection software for X-ray interpretation. Xpert Ultra and liquid culture methods will be used to confirm survey TB cases. Additional data will be collected from persons reporting symptoms suggestive of TB to assess health-seeking behaviour and access to TB diagnosis and care. The survey aims to screen a target sample population of 20 068 people, living within 50 clusters, representing every municipality of Timor-Leste. Bacteriologically confirmed pulmonary TB prevalence will be estimated using WHO-recommended methods. ETHICS AND DISSEMINATION: Research ethics approval has been granted by the human research ethics committee of the Northern Territory, Australia, and the Instituto Nacional da Saúde, Timor-Leste. The results will be published in a peer-reviewed scientific journal and disseminated with relevant stakeholders. TRIAL REGISTRATION NUMBER: ACTRN12623000718640.

Exploring the impact of socioeconomic and natural factors on pulmonary tuberculosis incidence in China (2013-2019) using explainable machine learning: A nationwide study.

Pulmonary tuberculosis (PTB) stands as a significant and prevalent infectious disease in China. Integrating 13 natural and socioeconomic factors, we conduct nine machine learning (ML) models alongside the Tree-Structured Parzen Estimator to predict the monthly PTB incidence rate from 2013 to 2019 in mainland China. With explainable ML techniques, our research highlights that population size, per capita GDP, and PM10 concentration emerge as the primary determinants influencing the PTB incidence rate. We delineate both the independent and interactive impacts of these factors on the PTB incidence rate. Furthermore, crucial thresholds associated with factors influencing the PTB incidence rate are identified. Taking factors that have a positive effect on reducing the incidence rate of PTB as an example, the thresholds at which the effects of factors PM2.5, PM10, O3, and RH on the incidence rate change from increase to decrease are 105.5 µg/m3, 75.5 µg/m3, 90.8 µg/m3, and 72.3 % respectively. Our work will contribute valuable insights for public health interventions.

Using timeliness metrics for household contact tracing and TB preventive therapy in the private sector, India.

Although screening of household contacts (HHCs) of TB patients and provision of TB preventive therapy (TPT) is a key intervention to end the TB epidemic, their implementation globally is dismal. We assessed whether introducing a '7-1-7' timeliness metric was workable for implementing HHC screening among index patients with pulmonary TB diagnosed by private providers in Chennai, India, between November 2022 and March 2023.This was an explanatory mixed-methods study (quantitative-cohort and qualitative-descriptive).There were 263 index patients with 556 HHCs. In 90% of index patients, HHCs were line-listed within 7 days of anti-TB treatment initiation. Screening outcomes were ascertained in 48% of HHCs within 1 day of line-listing. Start of anti-TB treatment, TPT or a decision to receive neither was achieved in 57% of HHC within 7 days of screening. Overall, 24% of screened HHCs in the '7-1-7' period started TPT compared with 16% in a historical control (P < 0.01). Barriers to achieving '7-1-7' included HHC reluctance for evaluation or TPT, refusal of private providers to prescribe TPT and reliance on facility-based screening of HHCs instead of home visits by health workers for screening.Introduction of a timeliness metric is a workable intervention that adds structure to HHC screening and timely management..