Risk of tuberculosis after endoscopic resection and gastrectomy in gastric cancer: nationwide population-based matched cohort study.

BACKGROUND: This study aimed to investigate the association between gastrectomy and endoscopic resection for gastric cancer and the subsequent tuberculosis incidence. METHODS: We conducted a nationwide matched cohort study using data from the Korea National Health Insurance Service from 2013 to 2019. We created two cohorts: patients who underwent gastrectomy and those who had endoscopic resection. Each patient was matched 1:1 with an unexposed individual based on index year, age, sex, income, and various comorbidities. The primary outcome was the incidence of tuberculosis during the follow-up period. RESULTS: Our study comprised 90,886 gastrectomy patients and 46,759 endoscopic resection patients. The tuberculosis incidence was significantly higher in the gastrectomy group compared to its matched non-gastrectomy group (IRR 1.69, 95% CI 1.43-1.99, p < .001). In contrast, there was no significant difference in tuberculosis incidence between the endoscopic resection group and its matched non-resection group (IRR 0.95, 95% CI 0.75-1.19, p = 0.627). The Kaplan-Meier cumulative incidence also did not differ between the two groups. However, tuberculosis incidence significantly increased in the first year after endoscopic resection. CONCLUSION: Gastrectomy for gastric cancer is associated with a higher incidence of subsequent tuberculosis, while no significant association was observed for endoscopic resection. However, tuberculosis incidence increases significantly during the first year after endoscopic resection.

Pregnancy and neonatal outcomes in infertile patients with positive tuberculin skin test results.

RESEARCH QUESTION: Do infertile women with positive tuberculin skin test (TST) results have a higher risk of adverse pregnancy outcomes after IVF or intracytoplasmic sperm injection and embryo transfer (ICSI-ET) and does preventive anti-tuberculosis treatment applied to infertile women with positive TST results before IVF/ICSI-ET affect pregnancy and neonatal outcomes? DESIGN: This was a retrospective cohort analysis of 6283 infertile women who underwent IVF/ICSI-ET treatment for the first time at the Reproductive Hospital affiliated to Shandong University from November 2016 to September 2022. None of the participants had prior tuberculosis or active tuberculosis. According to their TST results, 5947 patients who had never received preventive anti-tuberculosis treatment were divided into a TST-positive group (1704 cases) and a TST-negative group (4243 cases). A total of 504 patients with TST (+++) results (using the 20 mm sclerosis threshold) were divided into a treated TST (+++) group (336 cases) and an untreated TST (+++) group (168 cases) according to whether they received preventive anti-tuberculosis treatment before IVF/ICSI-ET. The outcome measures were pregnancy outcomes and neonatal outcomes. RESULTS: There were no significant differences in pregnancy or neonatal outcomes between the TST-positive group and the TST-negative group (P > 0.05). In the TST (+++) group, there were no significant differences in pregnancy or neonatal outcomes between the treated TST (+++) group and the untreated TST (+++) group (P > 0.05). CONCLUSIONS: For infertile women undergoing IVF/ICSI-ET without prior tuberculosis or active tuberculosis, positive TST results and preventive anti-tuberculosis treatments prior to IVF/ICSI-ET do not affect pregnancy or neonatal outcomes.

Surgical Management of Patients With GI Tuberculosis.

BACKGROUND: The Philippines ranks 10th in tuberculosis prevalence worldwide. Aside from pulmonary tuberculosis, GI tuberculosis remains an important cause of morbidity and mortality, particularly in endemic areas. OBJECTIVE: This study aimed to describe the clinicopathologic profile and surgical outcomes of patients with GI tuberculosis. DESIGN: Retrospective descriptive study. SETTING: Department of Surgery at the Philippine General Hospital, Manila, Philippines. PATIENTS: This study included all newly diagnosed cases of GI tuberculosis from January 1, 2009, to December 31, 2019. MAIN OUTCOME MEASURES: Clinical response to surgery. RESULTS: A total of 241 confirmed new cases were managed during an 11-year period. Of these, 208 patients (86.30%) underwent outright surgery, whereas the remaining patients (13.69%) received antituberculous therapy. Fifteen medically managed patients eventually required surgery, bringing the total surgically managed patients to 223. The patients' age ranged from 19 to 72 years, with a 1.9:1 male to female ratio. The most common complaint was abdominal pain. Intestinal obstruction was the most common indication for surgery. A right hemicolectomy was the most often performed procedure, with the ileocecal area as the most frequently involved segment. The most common histopathologic findings were epithelioid granuloma and caseation necrosis. Postoperative length of stay ranged from 0 to 59 days (mean, 7 days). Morbidity rate was 5.38% and mortality rate was 3.14%. Four deaths were operative and resulted from septic shock because of hollow viscus perforation. LIMITATIONS: This study was limited to histopathologic basis for diagnosis. CONCLUSION: The recommended initial therapy for all forms of extrapulmonary tuberculosis is a 6-month regimen of antituberculous therapy unless the organisms are known or suspected to be resistant to first-line drugs. Surgery is reserved for complications of intra-abdominal tuberculosis: obstruction, perforation, or severe bleeding. Timely surgical intervention, coupled with medical management led to the best outcomes for these patients. See Video Abstract at http://links.lww.com/DCR/C56. MANEJO QUIRRGICO DE PACIENTES CON TUBERCULOSIS GASTROINTESTINAL: ANTECEDENTES:Las Filipinas ocupa el décimo lugar en prevalencia de tuberculosis en todo el mundo. Aparte de la tuberculosis pulmonar, la tuberculosis gastrointestinal sigue siendo una causa importante de morbilidad y mortalidad, especialmente en las zonas endémicas.OBJETIVO:Este estudio tuvo como objetivo describir el perfil clinicopatológico y los resultados quirúrgicos de pacientes con tuberculosis gastrointestinal.DISEÑO:Estudio descriptivo retrospectivo.AJUSTE:Departamento de Cirugía del Hospital General de Filipinas, Manila, Filipinas.PACIENTES:Todos los casos de tuberculosis gastrointestinal recién diagnosticados desde el 1 de Enero del 2009 hasta el 31 de Diciembre del 2019.MEDIDAS DE RESULTADO PRINCIPAL:Respuesta clínica a la cirugía.RESULTADOS:Se manejaron un total de 241 casos nuevos confirmados durante un período de 11 años. De estos, 208 (86,30%) pacientes fueron intervenidos directamente quirúrgicamente mientras que el resto recibió tratamiento antituberculoso (13,69%). Quince pacientes manejados médicamente finalmente requirieron cirugía, lo que elevó el total de pacientes manejados quirúrgicamente a 223. Las edades de los pacientes oscilaron entre 19 y 72 años, con una proporción de 1,9: 1 entre hombres y mujeres. La queja más común fue el dolor abdominal. La obstrucción intestinal fue la indicación más frecuente para cirugía. La hemicolectomía derecha fue el procedimiento más realizado, siendo la zona ileocecal el segmento más afectado. Los hallazgos histopatológicos más comunes fueron granuloma epitelioide y necrosis caseosa. La estancia postoperatoria varió de 0 a 59 días (media, 7 días). Las tasas de morbilidad y mortalidad fueron 5,38% y 3,14%, respectivamente. Cuatro fueron muertes operatorias por choque séptico debido a perforación de víscera.LIMITACIONES:Este estudio se limitó a la base histopatológica para el diagnóstico.CONCLUSIÓN:La terapia inicial recomendada para todas las formas de tuberculosis extrapulmonar es un régimen de 6 meses de terapia antituberculosa a menos que se sepa o se sospeche que los organismos son resistentes a los medicamentos de primera línea. La cirugía se reserva para las complicaciones de la tuberculosis intraabdominal, es decir, obstrucción, perforación o hemorragia grave. La intervención quirúrgica oportuna, junto con el manejo médico, condujo a mejores resultados para estos pacientes. Consulte el Resumen del Video en http://links.lww.com/DCR/C56. (Traducción- Dr. Yesenia Rojas-Khalil).

Incidence and risk factors of tuberculosis in patients following gastrectomy or endoscopic submucosal dissection: a cohort analysis of country-level data.

BACKGROUND: Gastric cancer adversely affects nutrition and immunity, while increasing the risk of tuberculosis (TB). This study investigated the incidence and risk factors for TB in gastric cancer patients who had undergone gastrectomy or endoscopic submucosal dissection (ESD). METHODS: This retrospective cohort study was conducted using Korean national insurance claims data. We defined three study groups (total gastrectomy, subtotal gastrectomy, and ESD) of patients diagnosed with gastric cancer plus a cancer-free control group. The latent TB infection (LTBI) screening status, TB incidence, and potential confounders in each cohort were analyzed, and the risk of TB was analyzed using a Cox proportional hazard model. RESULTS: LTBI tests were performed in less than 1% of all patients, and the TB incidence rates were 473.8, 287.4, 199.4, 111.1 events/100,000 person-years in the total gastrectomy, subtotal gastrectomy, ESD, and control cohorts, respectively. Compared to the control cohort, the total gastrectomy cohort showed the highest hazard ratio (HR) for TB incidence (HR: 2.896, 95% CI: 2.559-2.337), while the ESD cohort showed a significantly increased risk (HR: 1.578, 95% CI: 1.957-1.980). Age, body mass index, and lack of exercise were risk factors in all cohorts. Comorbidities were also considered risk factors, depending on the cohort type. CONCLUSIONS: Patients who underwent gastrectomy or ESD had an increased risk of TB, and this risk was correlated with the scope of gastrectomy. Considering the low rate of LTBI diagnostic tests and increased risk of TB in the study cohorts, more specific and practical guidelines for TB management are required for gastric cancer patients.

The association between air pollutants, meteorological factors and tuberculosis cases in Beijing, China: A seven-year time series study.

BACKGROUND: Tuberculosis (TB) is a severe public health problem globally. Previous studies have revealed insufficient and inconsistent associations between air pollutants, meteorological factors and TB cases. Yet few studies have examined the associations between air pollutants, meteorological factors and TB cases in Beijing. OBJECTIVE: The purpose of this study was to explore the impact of air pollutants and meteorological factors on TB in Beijing, and to provide novel insights into public health managers to formulate control strategies of TB. METHODS: Data on the daily case of TB in Beijing during 2014-2020 were obtained from Chinese tuberculosis information management system. Concurrent data on the daily PM10, PM2.5, SO2, NO2, CO and O3, were obtained from the online publication platform of the Chinese National Environmental Monitoring Center. Daily average temperature, average wind speed, relative humidity, sunshine duration and total precipitation were collected from the China Meteorological Science Data Sharing Service System. A distributed lag non-linear model was fitted to identify the non-linear exposure-response relationship and the lag effects between air pollutions, meteorological factors and TB cases in Beijing. RESULTS: In the single-factor model, the excess risk (ER) of TB was significantly positively associated with every 10 µg/m3 increase in NO2 in lag 1 week (ER: 1.3%; 95% confidence interval [CI]: 0.4%, 2.3%) and every 0.1 m/s increase in average wind speed in lag 5 weeks (ER: 0.3%; 95% CI: 0.1%, 0.5%), and was negatively associated with every 10 µg/m3 increase in O3 in lag 1 week (ER: -1.2%; 95% CI: -1.8%, -0.5%), every 5 °C increase in average temperature (ER: -1.7%; 95% CI: -2.9%, -0.4%) and every 10% increase in average relative humidity (ER: -0.4%; 95% CI: -0.8%, -0.1%) in lag 10 weeks, respectively. In the multi-factor model, the lag effects between TB cases and air pollutants, meteorological factors were similar. The subgroup analysis suggests that the effects of NO2, O3, average wind speed and relative humidity on TB were greater in male or labor age subgroup, while the effect of CO was greater in the elderly. In addition, no significant associations were found between PM2.5, SO2, sunshine duration and TB cases. CONCLUSION: Our findings provide a better understanding of air pollutants and meteorological factors driving tuberculosis occurrence in Beijing, which enhances the capacity of public health manager to target early warning and disease control policy-making.

Risk factors for the development of tuberculosis among the pediatric population: a systematic review and meta-analysis.

Pediatric tuberculosis is a major cause of mortality and morbidity in children due to high transmission, poor diagnostic tools, and various respiratory diseases mimicking TB. Identifying risk factors will provide evidence for clinicians to strongly relate their diagnosis to the associated pathology. Studies were retrieved from PubMed, Embase, and Google Scholar, systematically reviewed, and meta-analyzed for various risk factors and their association with pediatric TB. Meta-analysis depicted that four out of eleven risk factors were significant-contact with known TB cases (OR 6.42 [3.85,10.71]), exposure to smoke (OR 2.61 [1.24, 5.51]), overcrowding in the houses (OR 2.29 [1.04, 5.03]), and, poor household conditions (OR 2.65 [1.38, 5.09]). Although significant odds ratio estimates were obtained, we observed heterogeneity in the studies included.    Conclusion: The study findings demand the constant screening of risk factors such as contact with known TB cases, exposure to smoke, overcrowding, and, poor household conditions for the development of pediatric TB. What is Known: • Knowledge of the risk factors of a disease is of utmost importance in the planning and institution of its control measures. Well-established risk factors in the occurrence of TB in the pediatric group are HIV positivity, older age and close contact with a known case of TB. What is New: • In addition to what is already known; this review and meta-analysis has identified exposure to indoor smoking, overcrowding and poor household conditions as important risk factors for developing pediatric TB. • Implications of the study: The findings highlight that in addition to routine contact screening for the pediatric group, the children living in poor household conditions and getting exposed to passive indoor smoking demand more attention to prevent the development of pediatric TB.

Association of air pollutants and meteorological factors with tuberculosis: a national multicenter ecological study in China.

The impact of weather variability and air pollutants on tuberculosis (TB) has been a research hotspot. Previous studies have mostly been limited to a certain area or with a small sample size of cases, and multi-scale systematic studies are lacking. In this study, 14,816,329 TB cases were collected from 31 provinces in China between 2004 and 2018 to estimate the association between TB risk and meteorological factors and air pollutants using a two-stage time-series analysis. The impact and lagged time of meteorological factors and air pollutants on TB risk varied greatly in different provinces and regions. Overall cumulative exposure-response summary associations across 31 provinces suggested that high monthly mean relative humidity (RH) (66.8-82.4%, percentile56-100 (P56-100)), rainfall (316.5-331.1 mm, P96-100), PM2.5 exposure concentration (93.3-145.0 µg/m3, P58-100), and low monthly mean wind speed (1.6-2.1 m/s, P0-38) increased the risk of TB incidence, with a relative risk (RR) of 1.10 (95% CI: 1.04-1.16), 1.10 (95% CI: 1.03-1.16), 2.08 (95% CI: 1.18-3.65), and 2.06 (95% CI: 1.27-3.33), and attributable risk percent (AR%) of 9%, 9%, 52%, and 51%, respectively. Conversely, high monthly average wind speed (2.3-2.9 m/s, P54-100) and mean temperature (20.2-25.3 °C, P79-96), and low monthly average rainfall (2.4-25.2 mm, P0-7) and concentration of SO2 (8.1-21.2 µg/m3, P0-16) exposure decreased the risk of TB incidence, with an overall cumulative RR of 0.92 (95% CI: 0.87-0.98), 0.74 (95% CI: 0.59-0.94), 0.87 (95% CI: 0.79-0.95), and 0.72 (95% CI: 0.56-0.93), respectively. Our study provided insights into future planning of public health interventions for TB.

Screening for Latent Tuberculosis Infection in Adults: US Preventive Services Task Force Recommendation Statement.

Importance: In the US, tuberculosis remains an important preventable disease, including active tuberculosis, which may be infectious, and latent tuberculosis infection (LTBI), which is asymptomatic and not infectious but can later progress to active disease. The precise prevalence rate of LTBI in the US is difficult to determine; however, estimated prevalence is about 5.0%, or up to 13 million persons. Incidence of tuberculosis varies by geography and living accommodations, suggesting an association with social determinants of health. Objective: To update its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review on LTBI screening and treatment in asymptomatic adults seen in primary care, as well as the accuracy of LTBI screening tests. Population: Asymptomatic adults 18 years or older at increased risk for tuberculosis. Evidence Assessment: The USPSTF concludes with moderate certainty that there is a moderate net benefit in preventing active tuberculosis disease by screening for LTBI in persons at increased risk for tuberculosis infection. Recommendation: The USPSTF recommends screening for LTBI in populations at increased risk. (B recommendation).

Ambient PM2.5 exposures could increase risk of tuberculosis recurrence.

BACKGROUND: The effect of ambient PM2.5 on the incidence of tuberculosis (TB) has been investigated in epidemiological studies. However, they did not separately study new and relapsed TB infection and focused on relatively short-term effects of PM2.5. In this regard, we examined the associations of long-term PM2.5 exposures with both new and relapsed TB incidences in South Korea, where the disease burden of TB is greatest among high-income countries. METHODS: An area-level ecological study of 250 districts was conducted from 2015 to 2019. Age- and sex-standardized TB incidence ratios for each district and year were used as outcome variables, and their associations with PM2.5 concentrations for one to five-year average were examined. Negative binomial regression models incorporating spatiotemporal autocorrelation were employed using integrated nested Laplace approximations. Stratified analyses were conducted by type of TB (total, new, and relapsed cases). RESULTS: Districts with higher PM2.5 concentrations tended to have significantly higher TB recurrence rate. The relative risks per 10 µg/m3 PM2.5 increase were 1.218 (95% credible interval 1.051-1.411), 1.260 (1.039-1.527) and 1.473 (1.015-2.137) using the two, three and five-year average PM2.5 exposures, respectively. CONCLUSIONS: The results imply that interventions for reducing air pollution might help prevent TB recurrence.

The Intestinal Commensal, Bacteroides fragilis, Modulates Host Responses to Viral Infection and Therapy: Lessons for Exploration during Mycobacterium tuberculosis Infection.

The gut microbiota has emerged as a critical player in host health. Bacteroides fragilis is a prominent member of the gut microbiota within the phyla Bacteroidetes. This commensal bacterium produces unique capsular polysaccharides processed by antigen-presenting cells and activates CD4+ T cells to secrete inflammatory cytokines. Indeed, due to their immunomodulatory functions, B. fragilis and its capsular polysaccharide-A (PSA) are arguably the most explored single commensal microbiota/symbiotic factor. B. fragilis/PSA has been shown to protect against colitis, encephalomyelitis, colorectal cancer, pulmonary inflammation, and asthma. Here, we review recent data on the immunomodulatory role of B. fragilis/PSA during viral infections and therapy, B. fragilis PSA's dual ability to mediate pro-and anti-inflammatory processes, and the potential for exploring this unique characteristic during intracellular bacterial infections such as with Mycobacterium tuberculosis. We also discuss the protective roles of single commensal-derived probiotic species, including B. fragilis in lung inflammation and respiratory infections that may provide essential cues for possible exploration of microbiota based/augmented therapies in tuberculosis (TB). Available data on the relationship between B. fragilis/PSA, the immune system, and disease suggest clinical relevance for developing B. fragilis into a next-generation probiotic or, possibly, the engineering of PSA into a potent carbohydrate-based vaccine.

Activated Phosphoinositide 3-Kinase δ Syndrome: a Large Pediatric Cohort from a Single Center in China.

PURPOSE: Activated phosphoinositide 3-kinase δ syndrome (APDS) is a primary immunodeficiency first described in 2013, which is caused by gain-of-function mutations in PIK3CD or PIK3R1, and characterized by recurrent respiratory tract infections, lymphoproliferation, herpesvirus infection, autoimmunity, and enteropathy. We sought to review the clinical phenotypes, immunological characteristics, treatment, and prognosis of APDS in a large genetically defined Chinese pediatric cohort. METHODS: Clinical records, radiology examinations, and laboratory investigations of 40 APDS patients were reviewed. Patients were contacted via phone call to follow up their current situation. RESULTS: Sinopulmonary infections and lymphoproliferation were the most common complications in this cohort. Three (10.3%) and five (12.5%) patients suffered localized BCG-induced granulomatous inflammation and tuberculosis infection, respectively. Twenty-seven patients (67.5%) were affected by autoimmunity, while malignancy (7.5%) was relatively rare to be seen. Most patients in our cohort took a combined treatment of anti-infection prophylaxis, immunoglobulin replacement, and immunosuppressive therapy such as glucocorticoid or rapamycin administration. Twelve patients underwent hematopoietic stem cell transplantation (HSCT) and had a satisfying prognosis. CONCLUSION: Clinical spectrum of APDS is heterogeneous. This cohort's high incidence of localized BCG-induced granulomatous inflammation and tuberculosis indicates Mycobacterial susceptibility in APDS patients. Rapamycin is effective in improving lymphoproliferation and cytopenia. HSCT is an option for those who have severe complications and poor response to other treatments.

Drug-level change and optimal dose adjustment of tacrolimus with the use of rifabutin for treating mycobacterial disease in solid organ transplant recipients.

BACKGROUND: Little is known about the change in drug level and the need for dose adjustment of calcineurin inhibitor when it is used with rifabutin in solid organ transplant (SOT) recipients. We aimed to analyze whether the drug level of tacrolimus significantly reduced after the use of rifabutin and to assess optimal adjustment of tacrolimus dose in SOT recipients. METHODS: Of the SOT recipients in a tertiary referral center in South Korea in 2000-2019, 50 patients who maintained an unchanged dose of tacrolimus after the use of rifabutin for treating mycobacterial disease were enrolled. Their medical records were reviewed retrospectively. RESULTS: The mean age of the patients was 53.9 ± 11.5 years. The most commonly transplanted organ was the liver (66.0%). The most common indication of rifabutin use was for treating active tuberculosis (78.0%). After rifabutin initiation, the trough level of tacrolimus decreased significantly to the subtherapeutic range in 38 (76.0%) patients. The drug levels of these 38 patients dropped from 7.2 to 3.8 ng/ml (p < .001) after rifabutin treatment. In these patients, the median 1.5-fold increase in the tacrolimus dose was required to restore the drug level to the within-therapeutic range. CONCLUSIONS: These findings indicate that careful tacrolimus drug-level monitoring and dose adjustment are necessary for most SOT recipients when rifabutin is administered for the treatment of mycobacterial disease.

TB in paediatric kidney transplant recipients - A single-centre experience.

BACKGROUND: TB remains a major challenge in transplantation, particularly in endemic countries. This study aimed to describe the incidence, clinical presentation and outcomes of TB in paediatric kidney transplant recipients and to assess the impact of INH prophylaxis. METHODS: Single-centre retrospective descriptive analysis of children who received kidney transplants from 1995 to 2019 was carried out. The cohort was stratified according to receipt of INH prophylaxis which began in 2005. RESULTS: A total of 212 children received a kidney transplant during the study period. Median age at transplantation was 11.2 years (IQR: 2.2-17.9), and 56% were males. TB was diagnosed in 20 (9%) children, with almost two-thirds (n = 12) occurring within the first year. Most infections were pulmonary. The main presenting symptoms included fever (n = 13/20), weight loss (n = 12/20) and cough (n = 10/20). TST was positive in four of 20 children. Coinfection with EBV, CMV or Staph was found in five children. Due to drug interactions, an up to threefold increase in calcineurin inhibitor dose was required to maintain therapeutic blood levels. INH prophylaxis was protective against development of TB (p = .04). Gender, age and type of allograft were not significant risk factors. Graft and patient survival was 100% upon completion of TB treatment. CONCLUSION: Kidney transplant recipients in endemic countries have a high risk of developing TB. Diagnosis remains a challenge. Frequent and meticulous monitoring of immunosuppression drug levels during treatment of TB is required to avoid loss of patient or graft. INH prophylaxis protects against development of TB in this population.

Association between averaged meteorological factors and tuberculosis risk: A systematic review and meta-analysis.

Inconsistencies were discovered in the findings regarding the effects of meteorological factors on tuberculosis (TB). This study conducted a systematic review of published studies on the relationship between TB and meteorological factors and used a meta-analysis to investigate the pooled effects in order to provide evidence for future research and policymakers. The literature search was completed by August 3rd, 2021, using three databases: PubMed, Web of Science and Embase. Relative risks (RRs) in included studies were extracted and all effect estimates were combined together using meta-analysis. Subgroup analyses were carried out based on the resolution of exposure time, regional climate, and national income level. A total of eight studies were included after screening for inclusion and exclusion criteria. Our results show that TB risk was positively correlated with precipitation (RR = 1.32, 95% CI: 1.14, 1.51), while temperature (RR = 1.15, 95% CI: 1.00, 1.32), humidity (RR = 1.05, 95% CI: 0.99, 1.10), air pressure (RR = 0.89, 95% CI: 0.69, 1.14) and sunshine duration (RR = 0.95, 95% CI: 0.80, 1.13) all had no statistically significant correlation. Subgroup analysis shows that quarterly measure resolution, low and middle Human Development Index (HDI) level and subtropical climate increase TB risk not only in precipitation, but also in temperature and humidity. Moreover, less heterogeneity was observed in "high and extremely high" HDI areas and subtropical areas than that in other subgroups (I2 = 0%). Precipitation, a subtropical climate, and a low HDI level are all positive influence factors to tuberculosis. Therefore, residents and public health managers should take precautionary measures ahead of time, especially in extreme weather conditions.

The impact of climate change on the risk factors for tuberculosis: A systematic review.

BACKGROUND: Tuberculosis (TB) continues to pose a major public health risk in many countries. The current incidence of disease exceeds guidelines proposed by the World Health Organisation and United Nations. Whilst the relationship between climate change and TB has surfaced in recent literature, it remains neglected in global agendas. There is a need to acknowledge TB as a climate-sensitive disease to facilitate its eradication. OBJECTIVE: To review epidemiological and prediction model studies that explore how climate change may affect the risk factors for TB, as outlined in the Global Tuberculosis Report 2021: HIV infection, diabetes mellitus, undernutrition, overcrowding, poverty, and indoor air pollution. METHODS: We conducted a systematic literature search of PubMed, Embase, and Scopus databases to identify studies examining the association between climate variables and the risk factors for TB. Each study that satisfied the inclusion criteria was assessed for quality and ethics. Studies then underwent vote-counting and were categorised based on whether an association was found. RESULTS: 53 studies met inclusion criteria and were included in our review. Vote-counting revealed that two out of two studies found a positive association between the examined climate change proxy and HIV, nine out of twelve studies for diabetes, eight out of seventeen studies for undernutrition, four out of five studies for overcrowding, twelve out of fifteen studies for poverty and one out of three studies for indoor air pollution. DISCUSSION: We found evidence supporting a positive association between climate change and each of the discussed risk factors for TB, excluding indoor air pollution. Our findings suggest that climate change is likely to affect the susceptibility of individuals to TB by increasing the prevalence of its underlying risk factors, particularly in developing countries. This is an evolving field of research that requires further attention in the scientific community.

Molecular and Cellular Mechanisms of M. tuberculosis and SARS-CoV-2 Infections-Unexpected Similarities of Pathogenesis and What to Expect from Co-Infection.

Tuberculosis is still an important medical and social problem. In recent years, great strides have been made in the fight against M. tuberculosis, especially in the Russian Federation. However, the emergence of a new coronavirus infection (COVID-19) has led to the long-term isolation of the population on the one hand and to the relevance of using personal protective equipment on the other. Our knowledge regarding SARS-CoV-2-induced inflammation and tissue destruction is rapidly expanding, while our understanding of the pathology of human pulmonary tuberculosis gained through more the 100 years of research is still limited. This paper reviews the main molecular and cellular differences and similarities caused by M. tuberculosis and SARS-CoV-2 infections, as well as their critical immunological and pathomorphological features. Immune suppression caused by the SARS-CoV-2 virus may result in certain difficulties in the diagnosis and treatment of tuberculosis. Furthermore, long-term lymphopenia, hyperinflammation, lung tissue injury and imbalance in CD4+ T cell subsets associated with COVID-19 could propagate M. tuberculosis infection and disease progression.

miR-495 Regulates Cellular Reactive Oxygen Species Levels by Targeting sod2 To Inhibit Intracellular Survival of Mycobacterium tuberculosis in Macrophages.

Mycobacterium tuberculosis is a chronic infectious disease pathogen. To date, tuberculosis is a major infectious disease that endangers human health. To better prevent and treat tuberculosis, it is important to study the pathogenesis of M. tuberculosis. Based on early-stage laboratory research results, in this study, we verified the upregulation of sod2 in Bacillus Calmette-Guérin (BCG) and H37Rv infection. By detecting BCG/H37Rv intracellular survival in sod2-silenced and sod2-overexpressing macrophages, sod2 was found to promote the intracellular survival of BCG/H37Rv. miR-495 then was determined to be downregulated by BCG/H37Rv. BCG/H37Rv can upregulate sod2 expression by miR-495 to promote the intracellular survival of BCG/H37Rv through a decline in ROS levels. This study provides a theoretical basis for developing new drug targets and treating tuberculosis.

Risk of active tuberculosis infection in kidney transplantation recipients: A matched comparative nationwide cohort study.

Large-scale evidence comparing the risk of Mycobacterium tuberculosis (TB) between kidney transplant (KT) recipients and dialysis patients is warranted. This is a nationwide retrospective cohort study based on the claims database of South Korea where a moderate prevalence of TB is reported. We included incident KT recipients from 2011 to 2015 and compared their active TB risks with 1:1 matched dialysis and general population control groups, respectively. The risk of incident active TB was assessed by multivariable Cox regression. Associations between active TB and posttransplant death or death-censored graft failure were investigated. The number of matched subjects included in each of the study groups was 7462. The KT group showed a significantly higher risk of active TB than the general population group (hazard ratio [HR] 3.39 [1.88-6.10]), whereas it showed a similar risk to that of the dialysis group (HR 0.98 [0.73-1.31]). In KT patients, active TB was a significant risk factor for both death (HR 2.33 [1.24-4.39]) and death-censored graft failure (HR 2.26 [1.39-3.67]). Although KT recipients may not have to burden the additional risk of active TB when compared with dialysis patients in recent medicine, active TB should not be overlooked as it is associated with a worse prognosis in posttransplant patients.

Anti-tuberculosis chemotherapy alters TNFR2 expression on CD4+ lymphocytes in both drug-sensitive and -resistant tuberculosis: however, only drug-resistant tuberculosis maintains a pro-inflammatory profile after a long time.

BACKGROUND: Tuberculosis (TB) is an infectious disease. During TB, regulatory T cells (Treg) are related to poor prognosis. However, information about conventional and unconventional Treg (cTreg and uTreg, respectively) is limited. The tumour necrosis factor (TNF) and its receptors (TNFR1 and TNFR2) are necessary for mycobacterial infection, and TNFR2 signalling is required to maintain Treg. METHODS: A blood sample of drug-susceptible (DS-TB) and drug-resistant tuberculosis (DR-TB) patients was obtained before (basal) and after 2 and 6 months of anti-TB therapy. Expression of TNF, TNFR1, and TNFR2 (transmembrane form, tm) on cTreg, uTreg, activated CD4+ (actCD4+), and CD4+ CD25- (CD4+) T cell subpopulations were evaluated. The main objective was to identify immunological changes associated with sensitive/resistant Mtb strains and with the use of anti-TB therapy. RESULTS: We found that after 6 months of anti-TB therapy, both DS- and DR-TB patients have decreased the frequency of cTreg tmTNF+, CD4+ tmTNFR1+ and CD4+ tmTNFR2+. Nevertheless, after 6 months of therapy, only DR-TB patients decreased the frequency of actCD4+ tmTNF+ and actCD4+ tmTNFR2+, exhibited a systemic inflammatory status (high levels of TNF, IFN-γ and IL-12), and their purified CD4+ T cells showed that TNF and TNFR2 are up-regulated at the transcriptional level. Moreover, DS- and DR-TB down-regulated TNFR1 and other proteins associated with Treg (FOXP3 and TGFß1) in response to the anti-TB therapy. CONCLUSION: These results partially explain the differences in the immune response of DS-TB vs DR-TB. The frequency of actCD4+ tmTNFR2+ cells and inflammatory status should be considered in the follow-up of therapy in DR-TB patients.

New management approaches to tuberculosis in people living with HIV.

PURPOSE OF REVIEW: People living with HIV (PLWH) are commonly coinfected with Mycobacterium tuberculosis, particularly in high-transmission resource-limited regions. Despite expanded access to antiretroviral therapy and tuberculosis (TB) treatment, TB remains the leading cause of death among PLWH. This review discusses recent advances in the management of TB in PLWH and examines emerging therapeutic approaches to improve outcomes of HIV-associated TB. RECENT FINDINGS: Three recent key developments have transformed the management of HIV-associated TB. First, the scaling-up of rapid point-of-care urine-based tests for screening and diagnosis of TB in PLWH has facilitated early case detection and treatment. Second, increasing the availability of potent new and repurposed drugs to treat drug-resistant TB has generated optimism about the treatment and outcome of multidrug-resistant and extensively drug-resistant TB. Third, expanded access to the integrase inhibitor dolutegravir to treat HIV in resource-limited regions has simplified the management of TB/HIV coinfected patients and minimized serious adverse events. SUMMARY: While it is unequivocal that substantial progress has been made in early detection and treatment of HIV-associated TB, significant therapeutic challenges persist. To optimize the management and outcomes of TB in HIV, therapeutic approaches that target the pathogen as well as enhance the host response should be explored.