BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complet...BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complete bone regeneration often remains unachieved,contributing to subsequent orthopedic complications.AIM To investigate the efficacy and safety of pamidronate in promoting bone regeneration following surgical treatment of experimental animal tuberculous osteitis.METHODS A controlled randomized basic study of rabbit femoral tuberculosis induced by Mycobacterium tuberculosis strain H37Rv included surgical removal of infected tissue and implantation of osteoinductive bone grafts with the following animal allocation to one of three groups:(1)Bisphosphonates alone;(2)Bisphosphonates combined with anti-tuberculous therapy;and(3)Anti-tuberculous therapy alone.The control group consisted of animals that received no surgical or medical treatment.Clinical evaluations,biochemical markers,micro-computed tomography imaging,and histomorphometry analyses were conducted at 3 months and 6 months postoperatively.RESULTS Pamidronate treatment significantly reduced early implant resorption,increased osteoblastic activity,improved trabecular bone regeneration,and maintained graft integrity compared to the anti-tuberculous therapy-only group.Histologically,pamidronate led to enhanced vascular remodeling and increased bone matrix formation.Crucially,bisphosphonate therapy demonstrated safety,compatibility with anti-tuberculous medications,and did not exacerbate tuberculous inflammation.Furthermore,micro-computed tomography analysis revealed a significant increase in trabecular thickness and density in pamidronate-treated groups,underscoring the anabolic effects of bisphosphonates.Morphometric evaluation confirmed a marked reduction in osteoclast number and activity at graft interfaces.These combined radiological,histological,and biochemical data collectively demonstrate the efficacy of pamidronate as an adjunctive agent in enhancing bone repair outcomes following surgical intervention for tuberculous osteitis.CONCLUSION A single intravenous dose of pamidronate significantly enhances bone regeneration and prevents implant resorption following surgical treatment of tuberculous osteitis.The following prospective studies are needed.展开更多
Background:Skeletal tuberculosis(TB)remains a persistent clinical and research chal-lenge due to its chronic course,osteolytic destruction,and the limitations of existing animal models,which often require high-level b...Background:Skeletal tuberculosis(TB)remains a persistent clinical and research chal-lenge due to its chronic course,osteolytic destruction,and the limitations of existing animal models,which often require high-level biosafety containment or fail to repli-cate human skeletal pathology.Methods:This study developed a biosafe,accessible,and versatile murine model of skeletal TB using Mycobacterium smegmatis,a fast-growing,nonpathogenic myco-bacterial species with high genomic homology to Mycobacterium tuberculosis.Three infection routes-subperiosteal calvarial injection,intratibial injection,and intra-cardiac inoculation-were systematically evaluated for their ability to induce lo-calized versus disseminated bone infection under standard biosafety level(BSL)-1 conditions.Results:Subperiosteal calvarial and intratibial injection of M.smegmatis induced local-ized bone lesions characterized by osteolysis,sequestrum formation,granulomatous inflammation,and increased osteoclast activity.Intratibial infection additionally trig-gered compartment-specific immune responses,including neutrophil and macrophage expansion,transient B-cell depletion,and activation of interferon-γ^(+)(IFN-γ^(+))T cells,reflecting active immune remodeling at the infection site.Systemic dissemination via intracardiac injection reproducibly generated progressive vertebral and tibial bone destruction with organized granuloma formation and immune cell infiltration but without prominent sequestrum formation.Compared to intratibial infection,intracar-diac delivery exhibited lower intragroup variability and more closely recapitulated the diffuse progression of extrapulmonary skeletal tuberculosis.Conclusions:This M.smegmatis-based murine model provides a straightforward,reliable,and immunopathologically relevant platform for exploring host-pathogen dynamics,immune-driven bone destruction,and early-stage therapeutic testing in skeletal TB,all within standard BSL-1 laboratories.This model fills a critical gap by enabling BSL-1 research into skeletal TB mechanisms and drug development.展开更多
Tuberculosis(TB),one of the oldest infectious diseases caused by Mycobacterium tuberculosis,poses a considerable challenge to global public health.There are approximately 10 million new TB cases worldwide annually,and...Tuberculosis(TB),one of the oldest infectious diseases caused by Mycobacterium tuberculosis,poses a considerable challenge to global public health.There are approximately 10 million new TB cases worldwide annually,and TB claims the lives of nearly 3 million people each year,making it one of the leading causes of death from a single infectious disease[1].China ranks third globally in terms of TB burden,with approximately 733,000 TB cases reported in 2023[2].Based on the ecological model of health determinants developed by Whitehead and Dahlgren,health determinants can be classified into direct causes.展开更多
Objective To determine the proportions of drug-resistant tuberculosis(TB),its trends,and the drug resistance-conferring mutations among patients with pulmonary TB aged 10-24 years in China.Methods The data of patients...Objective To determine the proportions of drug-resistant tuberculosis(TB),its trends,and the drug resistance-conferring mutations among patients with pulmonary TB aged 10-24 years in China.Methods The data of patients with pulmonary TB were retrieved from a national drug-resistant TB survey for analysis.Joinpoint regression software was used to analyze time trends.We also used whole genome sequencing to analyze the lineages and drug resistance-conferring mutations of 621 isolates.Results Among 4,235 patients with pulmonary TB,the proportion of new cases of multidrug-resistant tuberculosis(MDR-TB)was 3.18%(95%confidence interval[CI]:2.37-4.15)for adolescents and 3.76%(95%CI:3.03-4.60)for young adults;for previously treated patients,MDR-TB accounted for 11.25%(95%CI:5.28-20.28)of adolescents and 11.05%(95%CI:6.88-16.55)of young adults.The proportion of patients with MDR-TB remained stable among both new and previously treated patients aged 10-24 years during the study period.Through whole genome sequencing,we found that the most common mutations in the MDR-TB strains were Ser315Thr in the katG gene(71.74%)and Ser450Leu in the rpoB gene(50.00%).Conclusion This study revealed a high proportion of MDR-TB among adolescents and young adults,indicating that urgent and comprehensive measures are needed to reduce the emergence and transmission of drug-resistant TB among this population in China.展开更多
Objective Post tuberculosis lung disease(PTLD)manifests in various forms,including tuberculosisassociated chronic obstructive pulmonary disease(TB-COPD),yet the clinical features of PTLD remain undercharacterized.This...Objective Post tuberculosis lung disease(PTLD)manifests in various forms,including tuberculosisassociated chronic obstructive pulmonary disease(TB-COPD),yet the clinical features of PTLD remain undercharacterized.This study aimed to assess longitudinal changes in lung function over a 5-year period and to identify predictors of airflow obstruction in a cohort of patients treated for active pulmonary TB.Methods Patients with active pulmonary TB were enrolled in this study and were followed during treatment,at treatment completion and five years post-treatment.Assessments included lung function and chest CT,analyzing longitudinal trends and airflow obstruction risk factors.Results Among 53 patients(mean age 36.9±13.9 years;64.2%male),7 patients(13.2%)exhibited airflow obstruction.At the 5-year follow-up,the mean FEV_(1)/FVC declined significantly(76.27%±12.04%vs.80.23%±11.02%,P<0.001)and 9 patients(17.0%)exhibited airflow obstruction.Seven of these patients predominantly showed air trapping consistent with small airway disease on chest CT,aligning with TB-COPD phenotype.Notably,four young-to-middle-aged patients(<60 years old)had persistent obstruction over the five years.Conclusion The initial test revealed that 13.2%of patients presented with airflow obstruction.By the 5-year follow-up,this proportion had increased to 17.0%,with most cases demonstrating imaging findings aligning with TB-COPD,even among younger,non-smoking individuals.These findings emphasize the importance of long-term follow-up and routine lung function assessments in TB survivors.展开更多
Tuberculosis(TB)continues to pose a significant threat to global public health,necessitating rapid and precise diagnostic methods and comprehensive detection of antimicrobial resistance(AMR)to facilitate timely clinic...Tuberculosis(TB)continues to pose a significant threat to global public health,necessitating rapid and precise diagnostic methods and comprehensive detection of antimicrobial resistance(AMR)to facilitate timely clinical management.Traditional diagnostic techniques suffer from extended turnaround times and limited ability to comprehensively profile AMR,often resulting in delayed therapeutic interventions.Highthroughput sequencing(HTS)technologies have revolutionized pathogen research by significantly improving diagnostic speed and accuracy.In the context of TB,diverse sequencing strategies and platforms are being employed to fulfill specific research goals,ranging from elucidating the molecular mechanisms underlying AMR to characterizing the genomic diversity among clinical isolates.This review systematically examines current progress in the application of HTS for rapid pathogen identification,comprehensive AMR profiling,epidemiological studies,advances in novel drugs,and vaccine development.Furthermore,we address existing technological limitations and bioinformatics challenges and explore the future directions necessary for effectively integrating HTS-based methodologies into global TB control efforts.展开更多
Objective:Endometrial tuberculosis,which commonly affects women of reproductive age,is a significant cause of intrauterine adhesions(IUA),potentially leading to hypomenorrhea,amenorrhea,and infertility.Hysteroscopic a...Objective:Endometrial tuberculosis,which commonly affects women of reproductive age,is a significant cause of intrauterine adhesions(IUA),potentially leading to hypomenorrhea,amenorrhea,and infertility.Hysteroscopic adhesiolysis is the primary treatment for IUA;however,studies specifically addressing its efficacy in tuberculosisinduced IUA remain scarce.This study aims to evaluate the therapeutic outcomes of hysteroscopic adhesiolysis for IUA caused by endometrial tuberculosis.Methods:This retrospective cohort study included patients diagnosed with tuberculosisinduced IUA who underwent hysteroscopic adhesiolysis at the Third Xiangya Hospital of Central South University between May 2014 and October 2022.Clinical data including age,medical history,adhesion severity,surgical treatment,and reproductive outcomes were analyzed.Results:Among 39 patients identified,2 were lost to follow-up.A total of 37 patients were included,with a follow-up duration ranging from 6 months to 9 years.Hypomenorrhea was reported in 24(64.9%)patients,secondary amenorrhea in 10(27.0%)patients,and normal menstruation in 3(8.1%)patients.Most patients presented with primary infertility(59.5%),and only 2(5.4%)had secondary infertility.The median American Fertility Society(AFS)score at initial assessment was 10(range,8−12);8(21.6%)patients had moderate IUA,and 29(78.4%)had severe IUA.A total of 86 surgical procedures were performed across 37 patients,with 27 patients undergoing 2 or more surgeries.Postoperatively,25(67.6%)patients achieved normalization of the uterine cavity,while 12(32.4%)still had a reduced cavity.Only 7(18.9%)patients had a grossly normal endometrium at the final surgery,all of whom had moderate adhesions at the initial procedure.Menstrual flow returned to normal in 12(32.4%)patients,while 25(67.6%)continued to experience hypomenorrhea.Of 29 patients who attempted in vitro fertilization and embryo transfer(IVF-ET),only 6(20.7%)conceived.Among these,4(13.8%)delivered at term via cesarean section;one case was complicated by postpartum hemorrhage due to uterine atony and another by placental adhesion.Conclusion:Endometrial tuberculosis can lead to severe IUA.Hysteroscopic adhesiolysis facilitates cavity restoration and improvement of menstrual conditions,but the overall reproductive outcomes remain suboptimal.展开更多
BACKGROUND Tuberculosis is among the most devastating infectious diseases worldwide.Spinal tuberculosis is not easy to detect at an early stage,which without effective treatment often leads to spinal deformity and spi...BACKGROUND Tuberculosis is among the most devastating infectious diseases worldwide.Spinal tuberculosis is not easy to detect at an early stage,which without effective treatment often leads to spinal deformity and spinal cord damage which in turn cause complications such as paraplegia and quadriplegia.In this study,we established a model using three concentrations of bacteria and carried out a comprehensive evaluation of the model by imaging,general observations,and histopathological and bacteriological studies.AIM To establish a rabbit model of spinal tuberculosis and examine the effect on the model’s efficacy using different concentrations of Mycobacterium tuberculosis(M.tuberculosis)inoculum.METHODS New Zealand rabbits were randomly divided into experimental,control and blank groups.The experimental and control animals were sensitized with complete Freund′s adjuvant,a hole was drilled beneath the upper endplate of the L6 vertebral body and filled with gelfoam sponge.The experimental group was divided into three subgroups(experimental 1,experimental 2,experimental 3)and infused with M.tuberculosis suspension at various concentrations.The control group was inoculated with saline and the blank group received no treatment.The 12-week post-operative survival rates were 100%,80%and 30%in the experimental groups inoculated with concentrations of 106,107 and 108 CFU/mL bacteria,respectively.RESULTS The survival rate of the control and blank groups was 100%.Vertebral body destruction at 8 weeks in the three experimental groups as determined by X-ray analysis was 33.3%,62.5%and 66.7%,and by computed tomography(CT)and 3-dimensional CT 44.4%,75%and 100%,respectively.At 12 weeks,the figures were 44.4%,75%and 100%by X-ray analysis and 44.4%,100%and 100%by CT and 3-dimensional CT,respectively.All surviving rabbits of the experimental groups had vertebral destruction.The positive bacterial culture rates were 22.2%,75%and 66.7%,respectively,in the experimental groups.After being sensitized with complete Freund's adjuvant,large differences were observed in the extent of spinal tuberculosis after inoculation of the rabbits with different concentrations of H37RV standard M.tuberculosis.CONCLUSION The experimental 1 had a low success rate at establishing an infection.The experimental 3 resulted in high mortality and complication rates.The experimental 2 was optimum for establishing a spinal tuberculosis model based on the high level of symptoms observed and the low rabbit mortality.展开更多
Detection and treatment of drug resistance in extrapulmonary tuberculosis(EPTB)is a major challenge worldwide.Drug resistance in EPTB has not been studied extensively.However,patients with drug-resistant EPTB have bee...Detection and treatment of drug resistance in extrapulmonary tuberculosis(EPTB)is a major challenge worldwide.Drug resistance in EPTB has not been studied extensively.However,patients with drug-resistant EPTB have been reported to have poor outcomes[1].Rifampicin and isoniazid are the cornerstone drugs in the management of EPTB.Resistance in Mycobacterium(M.)tuberculosis to these drugs commonly arises due to mutations in the‘rpoB’gene and‘katG&inhA’genes,which confer resistance to rifampicin and isoniazid,respectively.Treatment outcomes are affected by the presence of these mutations.In addition,anatomical and physiological barriers impede the effective delivery of drugs to the affected extrapulmonary site[1].An analysis of the frequency of mutations in drug resistant M.tuberculosis strains causing EPTB in our region can help identify patterns of drug resistance.This,in turn,can provide inputs that may be used for modifying standard treatment regimens to make them more effective.The present study aims to identify the frequency and pattern of mutations in the‘rpoB’gene and‘katG&inhA’genes in M.tuberculosis strains isolated from EPTB samples.展开更多
Tuberculosis(TB)remains a critical global health challenge,with 10.8 million new cases and over 1.25 million deaths reported annually,disproportionately affecting low-income regions.Despite its use,the Bacillus Calmet...Tuberculosis(TB)remains a critical global health challenge,with 10.8 million new cases and over 1.25 million deaths reported annually,disproportionately affecting low-income regions.Despite its use,the Bacillus Calmette-Guérin(BCG)vaccine provides limited protection against adult pulmonary TB,necessitating novel solutions.The messenger RNA(mRNA)vaccine technology,proven effective in combating coronavirus disease 2019,offers significant promise for TB prevention.These vaccines elicit robust immune responses by encoding antigens that stimulate humoral and cell-mediated immunity,essential for combating mycobacterium TB.Unlike traditional methods,mRNA vaccines are highly adaptable,scalable,and capable of targeting emerging strains.Preclinical studies highlight the enhanced efficacy of mRNA TB vaccines over BCG,demonstrating their ability to reduce bacterial burdens and generate memory T-cell responses critical for long-term protection.However,challenges persist,including mRNA instability,cold-chain storage needs,and mycobacterium’s complex immune evasion strategies.Innovative solutions,such as lipid nanoparticle delivery systems and selfamplifying mRNA platforms,are being developed to address these barriers.The initiation of clinical trials,notably BioNTech’s BNT164,marks a pivotal advancement in TB vaccine development.These trials focus on safety,immuno genicity,and efficacy,particularly in regions with high TB prevalence.While logistical and financial hurdles remain,mRNA vaccines hold transformative potential to bridge critical gaps in TB prevention.Their adaptability extends to tackling co-infections like human immunodeficiency virus,further amplifying their impact on global health.By integrating mRNA vaccines into existing TB control strategies,these advancements could revolutionize prevention efforts,especially in regions where current solutions fall short.Continued innovation and investment are crucial to harnessing the full potential of mRNA vaccines,positioning them as a cornerstone in the fight against TB and its global eradication.展开更多
Chronic obstructive pulmonary disease(COPD)and respiratory tuberculosis are important respiratory problems.Meeting together,these diseases can mutually worsen the severity of clinical manifestations and negatively aff...Chronic obstructive pulmonary disease(COPD)and respiratory tuberculosis are important respiratory problems.Meeting together,these diseases can mutually worsen the severity of clinical manifestations and negatively affect prognosis.COPD and tuberculosis share a number of common risk factors and pathogenetic mechanisms involving various immune and non-immune cells.Inflammation,hypoxia,oxidative stress,and lung tissue remodeling play an important role in the comorbid course of COPD and respiratory tuberculosis.These mechanisms are of diagnostic interest and are promising therapeutic targets.Thus,the aim of the current review is to discuss the mechanisms of the comorbid course of chronic obstructive pulmonary disease and respiratory tuberculosis.展开更多
BACKGROUND Due to low bacteria count and high likelihood of having extrapulmonary tuberculosis(TB)among patients with advanced human immunodeficiency virus(HIV)disease,the World Health Organization(WHO)recommended the...BACKGROUND Due to low bacteria count and high likelihood of having extrapulmonary tuberculosis(TB)among patients with advanced human immunodeficiency virus(HIV)disease,the World Health Organization(WHO)recommended the use of urine lateral flow urine lipoarabinomannan(LF-LAM)or sputum-Xpert to screen for TB.AIM To estimate pooled prevalence of TB screening uptake,TB diagnosis,TB treatment initiation and mortality among patients with advanced HIV disease in Africa.METHODS PubMed,Cochrane Library and EMBASE were searched for articles published between January 2011 and December 2024.TB screening uptake was defined as percentage of patients with advanced HIV disease(CD4≤200 cells/mm3 or WHO stage III/IV)who tested for TB.Using random effects models,we computed the pooled estimate of TB screening uptake,TB prevalence,TB treatment initiation and mortality and their corresponding 95%CIs.Stratified analysis to compare uptake of TB testing and TB prevalence between children vs adults and multisite vs single site studies was performed.RESULTS A total of nineteen studies with 16065 people with advanced HIV disease were analyzed.The pooled prevalence of TB screening uptake was 64.6%(95%CI:49.2–80.1).The pooled prevalence of TB was 29.4%(95%CI:22.0–36.8),and TB treatment initiation was 77.9%(95%CI:63.9–91.8),and mortality was 19.5%(95%CI:8.9–30.0).The pooled prevalence of TB testing uptake was significantly lower among children compared to adults(28.2%vs 66.4%,P=0.003)and lower for multi-sites compared to single site studies(58.8%vs 82.9%,P=0.002).The pooled prevalence of TB was significantly lower among children compared to adults(24.2%vs 27.6%,P=0.012)and higher among studies that involved multi vs single sites(30.0%vs 21.9%,P=0.001).CONCLUSION Four in ten people with advanced HIV disease were not screened for TB as recommended by the WHO,indicating significant gaps in identifying patients with TB.Excluding patients with evidence of TB is critical to avoid exposing them to subtherapeutic levels of anti TB treatment.展开更多
Objective:To assess aptamer-based assays for diagnosing latent tuberculosis infection(LTBI).Methods:Literature from Medline,ScienceDirect,and Scopus,covering publications from January 1,2012,to December 31,2023,was ex...Objective:To assess aptamer-based assays for diagnosing latent tuberculosis infection(LTBI).Methods:Literature from Medline,ScienceDirect,and Scopus,covering publications from January 1,2012,to December 31,2023,was examined.This review evaluates different aptamers,biomarkers,sample types,sample sizes,reference assays,and the assays'sensitivity and specificity.By using the Quality Assessment of Diagnostic Accuracy Studies 2,the risk of bias in each study was evaluated.Results:Aptamer-based assays generally showed a sensitivity of 90%(95%CI:75%-100%)and specificity of 90%(95%CI:50%-100%),where optical aptasensor showed the highest sensitivity and specificity at 100%.Serum samples were frequently used to enhance antigen detectability,improving the assay’s performance.Meanwhile,HspX was the most studied biomarker,followed by MPT64,and IFN-γ.Conclusions:Aptamer-based assays could be reliable alternatives to current LTBI detection methods,but further research is needed to validate their clinical efficacy.展开更多
Mycobacterium tuberculosis(Mtb)employs multiple mechanisms,such as phagocytosis and autophagy,to evade innate immune clearance and establish infection.In the present study,we identified the ESX-1 secretion-associated ...Mycobacterium tuberculosis(Mtb)employs multiple mechanisms,such as phagocytosis and autophagy,to evade innate immune clearance and establish infection.In the present study,we identified the ESX-1 secretion-associated protein EspL,which promotes Mtb survival by inhibiting phagosome maturation and autophagy initiation.EspL knockout decreased Mtb intracellular survival,while EspL overexpression increased bacterial survival by interfering with phagocytosis and autophagy.EspL interacts with ULK1 and promotes its phosphorylation at Ser^(757),leading to the inhibition of autophagy initiation.Additionally,overexpression of EspL reduced antigen presentation and T-cell responses both in vitro and in vivo.Our findings revealed that EspL interferes with autophagy and antigen presenta-tion by suppressing ULK1 activation.These insights provide a novel understanding of Mtb pathogenicity.展开更多
BACKGROUND Tuberculosis(TB)remains a global health concern despite decreasing incidence.Delayed TB diagnosis can exacerbate patient outcomes and lead to broader public health issues such as mass infections.Differentia...BACKGROUND Tuberculosis(TB)remains a global health concern despite decreasing incidence.Delayed TB diagnosis can exacerbate patient outcomes and lead to broader public health issues such as mass infections.Differentiation between TB and bacterial pneumonia is often complicated by variable clinical and radiological manifestations of TB,leading to diagnostic delays.CASE SUMMARY An 89-year-old,Japanese male patient with a history of diabetes mellitus,hypertension,and hypothyroidism presented with right-sided chest pain.Based on the elevated inflammatory response,right pleural effusion,and infiltrating shadow in the lung field,the diagnosis of right pleurisy was made and the antibiotic,ampicillin/sulbactam,was administered.The patient’s condition,inflammatory reaction,and right pleural effusion temporarily improved.However,persistent low-grade fever and malaise prompted further evaluation,revealing repeated right pleural effusion and inflammatory response.A right thoracentesis was performed;the patient was diagnosed with tuberculous pleurisy as a result of exudative effusion with lymphocyte predominance,elevated adenosine deaminase levels,and positive Mycobacterium TB polymerase chain reaction test.Anti-TB treatment,including isoniazid,rifampicin,and ethambutol was initiated,leading to significant clinical improvement.The patient successfully completed a 12-month course of TB therapy without recurrence or deterioration.CONCLUSION There are cases of TB wherein temporary improvement apparently could be shown through treatment with antimicrobial agents other than anti-TB drugs,necessitating careful evaluation in atypical cases of bacterial pneumonia.展开更多
BACKGROUND Tuberculosis(TB)is a common infection causing huge morbidity and mortality to mankind.The analytical methods used in diagnosing TB are not sensitive in paucibacillary infections and also require trained tec...BACKGROUND Tuberculosis(TB)is a common infection causing huge morbidity and mortality to mankind.The analytical methods used in diagnosing TB are not sensitive in paucibacillary infections and also require trained technical personnel.MicroRNAs are stable in serum and other body fluids,and hold great potential in the diagnosis of TB.AIM To analyze the dysregulated microRNA profiles among patients with cavitatory and non-cavitatory pulmonary TB.METHODS The prospective study will be conducted in a tertiary care center in India.Adult patients with newly diagnosed pulmonary TB will be included.There will be two groups:Patients with sputum positive pulmonary TB with cavity and without cavity(group1),and apparently healthy individuals(group 2).The participants will undergo sputum examination,Xpert Mycobacterium TB complex/resistance to rifampin(Mtb/RIF)assay,chest X-ray,and blood investigations and serum microRNA detection.Ethics approval has been obtained.Written informed consent will be obtained.Appropriate statistical analyses will be used.RESULTS MicroRNAs will be correlated with sputum positivity,Xpert Mtb/RIF assay,radiological involvement,inflammatory markers,and course of the disease among cases and controls.CONCLUSION MicroRNAs could serve as potential diagnostic biomarkers in diagnostically challenging TB patients.展开更多
BACKGROUND India has the highest tuberculosis(TB)burden in the world.Of the estimated annual 10 million TB cases,features of extra pulmonary TB are evident in up to 45%.Urogenital TB(UGTB)accounts for approximately 20...BACKGROUND India has the highest tuberculosis(TB)burden in the world.Of the estimated annual 10 million TB cases,features of extra pulmonary TB are evident in up to 45%.Urogenital TB(UGTB)accounts for approximately 20%of those cases.The lack of non-sputum based diagnostic tools continue to hinder efforts to reduce the burden of UGTB.MicroRNAs(miRNAs)play a crucial role in biological pathways and can be used as a potential biomarker for TB.We evaluated urinary extracellular vesicles(uEVs)as non-invasive source to explore miRNAs with biomarker potential for UGTB.AIM To evaluate the potential of miRNA-155-5p,miRNA-26a-5p and miRNA-29a-3p in uEVs to diagnose UGTB in adults.METHODS uEV characterization was done using nanoparticle tracking analysis and flow cytometry.Quantitative reverse transcriptase polymerase chain reaction(qRTPCR)for urinary uEV-miRNAs were carried out in samples from patients with suspected UGTB,or Urinary tract infections[UTI,disease controls(DC)]and healthy controls(HCs)(n=20/group).U6 was used to normalize the qRT-PCR data.Receivers operating characteristic curves was used to calculate the diagnostic accuracy of uEV-miRNAs to differentiate UGTB from controls(DC and HCs).RESULTS uEVs from UGTB or UTI patients had higher mean size,and also lower proportion of CD63 positive vesicles as compared to HC’s uEVs.Between UTI and UGTB,the mean size of uEVs was significantly higher in UTI cases.qRT-PCR analysis revealed a significantly lower abundance of miRNA-155-5p and miRNA-26a-5p in uEVs from UGTB relative to UTI(P value=0.004)and HC(P value=0.009)respectively n=20/group).While,miRNA-29a-3p was higher in abundance in both UGTB and HCs’uEV,relative to uEVs from UTI cases(P values=0.004 and 0.002 respectively,n=20/group).Moreover,miRNA-155-5p[area under curve(AUC)=0.88,P≤0.0001]and miRNA-29a-3p(AUC=0.76,P value=0.005)had optimal diagnostic accuracy to differentiate UGTB from DC(n=20/groups)with a likelihood ratio of 5.2 and 4.3,respectively through receivers operating characteristic curve.While,miRNA-155-5p(AUC=0.68,P value=0.05)and miRNA-26a-5p(AUC=0.78,P value=0.002)had optimal diagnostic accuracy to differentiate UGTB from HCs with a likelihood ratio of>2.CONCLUSION The differential expression of uEV-miRNAs,miRNA-155-5p and miRNA-29a-3p in UTGB and UTI cases hold promise in the specific diagnosis of UGTB.Further studies in large cohort are,however,needed to confirm the diagnostic accuracy of these uEV-miRNAs.展开更多
BACKGROUND Pancreatic tuberculosis(TB)is a rare clinical condition that is frequently misdia-gnosed.A definitive diagnosis is often established through surgical biopsy.CASE SUMMARY We report a previously healthy 21-ye...BACKGROUND Pancreatic tuberculosis(TB)is a rare clinical condition that is frequently misdia-gnosed.A definitive diagnosis is often established through surgical biopsy.CASE SUMMARY We report a previously healthy 21-year-old male who presented with epigastric pain and fever.Initially diagnosed with a pancreatic abscess and duodenal bulb perforation,the patient declined surgical intervention and was subsequently re-ferred to our hospital.Abdominal computed tomography and endoscopy revea-led a duodenal bulb perforation,esophageal and duodenal ulcers,and a mass in the pancreatic head.Endoscopic ultrasound with fine-needle aspiration identified a hypoechoic mass suggestive of TB.Cytological and histopathological analysis confirmed the diagnosis.The patient was diagnosed with primary pancreatic TB and started on anti-TB therapy.At the 1-year follow-up,the pancreatic mass had markedly regressed,and the patient had fully recovered with complete symptom resolution.CONCLUSION Pancreatic TB should be included in differential diagnosis;prompt endoscopic ul-trasound-fine-needle aspiration and therapy enable recovery.展开更多
Tuberculosis(TB)remained the first leading cause of death from a single infectious agent worldwide in 2023,resulting in nearly twice as many deaths as those caused by the human immunodeficiency virus/acquired immune d...Tuberculosis(TB)remained the first leading cause of death from a single infectious agent worldwide in 2023,resulting in nearly twice as many deaths as those caused by the human immunodeficiency virus/acquired immune deficiency syndrome.An estimated 10.8 million TB cases were reported globally in 2023,with approximately 1.25 million associated deaths.In China,which ranks third in the global TB burden,there were approximately 741,000 new cases and 25,000 deaths in 2023^([1]).TB poses a significant threat to human health worldwide.展开更多
There is a bidirectional association between type II diabetes mellitus(T2DM)and pulmonary tuberculosis(PTB),with each enhancing the risk of the other,thus increasing the burden of both drug-sensitive and drug-resistan...There is a bidirectional association between type II diabetes mellitus(T2DM)and pulmonary tuberculosis(PTB),with each enhancing the risk of the other,thus increasing the burden of both drug-sensitive and drug-resistant forms of the disease.This dual burden also has a detrimental impact on patient's mental health.Although several recommendations have been made for bidirectional screening of diabetes and tuberculosis,implementation remains poor,resulting in increased morbidity and mortality among patients with this comorbidity.Mental health is often neglected,as clinical outcomes receive disproportionate focus,with limited attention to patients’social and psychological well-being.According to the World Health Organization,health is defined as a state of physical,mental,and social well-being,and not merely the absence of disease or infirmity.The aim of this mini-review is to highlight the intersection of PTB and T2DM,specifically discussing the mental health outcomes of the co-burden.展开更多
基金Supported by Russian Science Foundation Grant,No.24-15-00185.
文摘BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complete bone regeneration often remains unachieved,contributing to subsequent orthopedic complications.AIM To investigate the efficacy and safety of pamidronate in promoting bone regeneration following surgical treatment of experimental animal tuberculous osteitis.METHODS A controlled randomized basic study of rabbit femoral tuberculosis induced by Mycobacterium tuberculosis strain H37Rv included surgical removal of infected tissue and implantation of osteoinductive bone grafts with the following animal allocation to one of three groups:(1)Bisphosphonates alone;(2)Bisphosphonates combined with anti-tuberculous therapy;and(3)Anti-tuberculous therapy alone.The control group consisted of animals that received no surgical or medical treatment.Clinical evaluations,biochemical markers,micro-computed tomography imaging,and histomorphometry analyses were conducted at 3 months and 6 months postoperatively.RESULTS Pamidronate treatment significantly reduced early implant resorption,increased osteoblastic activity,improved trabecular bone regeneration,and maintained graft integrity compared to the anti-tuberculous therapy-only group.Histologically,pamidronate led to enhanced vascular remodeling and increased bone matrix formation.Crucially,bisphosphonate therapy demonstrated safety,compatibility with anti-tuberculous medications,and did not exacerbate tuberculous inflammation.Furthermore,micro-computed tomography analysis revealed a significant increase in trabecular thickness and density in pamidronate-treated groups,underscoring the anabolic effects of bisphosphonates.Morphometric evaluation confirmed a marked reduction in osteoclast number and activity at graft interfaces.These combined radiological,histological,and biochemical data collectively demonstrate the efficacy of pamidronate as an adjunctive agent in enhancing bone repair outcomes following surgical intervention for tuberculous osteitis.CONCLUSION A single intravenous dose of pamidronate significantly enhances bone regeneration and prevents implant resorption following surgical treatment of tuberculous osteitis.The following prospective studies are needed.
基金Southwest Hospital Boqing Innovation Fund,Grant/Award Number:2024BQCXJJ-9Fundings for Young Investigators of PLA,Grant/Award Number:2022-JCJQ-QT-004+3 种基金NSFC Key Projects of the Regional Innovation and Development Joint Fund,Grant/Award Number:U23A20413China Postdoctoral Science Foundation,Grant/Award Number:2023M744280National Natural Science Foundation of China,Grant/Award Number:82103778,82172449 and 82172489Southwest Hospital Postdoctoral Starting Fund,Grant/Award Number:5175ZA36BP。
文摘Background:Skeletal tuberculosis(TB)remains a persistent clinical and research chal-lenge due to its chronic course,osteolytic destruction,and the limitations of existing animal models,which often require high-level biosafety containment or fail to repli-cate human skeletal pathology.Methods:This study developed a biosafe,accessible,and versatile murine model of skeletal TB using Mycobacterium smegmatis,a fast-growing,nonpathogenic myco-bacterial species with high genomic homology to Mycobacterium tuberculosis.Three infection routes-subperiosteal calvarial injection,intratibial injection,and intra-cardiac inoculation-were systematically evaluated for their ability to induce lo-calized versus disseminated bone infection under standard biosafety level(BSL)-1 conditions.Results:Subperiosteal calvarial and intratibial injection of M.smegmatis induced local-ized bone lesions characterized by osteolysis,sequestrum formation,granulomatous inflammation,and increased osteoclast activity.Intratibial infection additionally trig-gered compartment-specific immune responses,including neutrophil and macrophage expansion,transient B-cell depletion,and activation of interferon-γ^(+)(IFN-γ^(+))T cells,reflecting active immune remodeling at the infection site.Systemic dissemination via intracardiac injection reproducibly generated progressive vertebral and tibial bone destruction with organized granuloma formation and immune cell infiltration but without prominent sequestrum formation.Compared to intratibial infection,intracar-diac delivery exhibited lower intragroup variability and more closely recapitulated the diffuse progression of extrapulmonary skeletal tuberculosis.Conclusions:This M.smegmatis-based murine model provides a straightforward,reliable,and immunopathologically relevant platform for exploring host-pathogen dynamics,immune-driven bone destruction,and early-stage therapeutic testing in skeletal TB,all within standard BSL-1 laboratories.This model fills a critical gap by enabling BSL-1 research into skeletal TB mechanisms and drug development.
基金supported by the National Natural Science Foundation of China(82574173,82003516)Jiangsu Provincial Natural Science Foundation(BK20251958)+2 种基金Jiangsu Provincial Medical Key Discipline(ZDXK202250)Top Talent Awards Project Fund(RDF-TP-0023,RDF-TP-0030)Postgraduate Research Fund(PGRS2112022)at Xi'an Jiaotong-Liverpool University.
文摘Tuberculosis(TB),one of the oldest infectious diseases caused by Mycobacterium tuberculosis,poses a considerable challenge to global public health.There are approximately 10 million new TB cases worldwide annually,and TB claims the lives of nearly 3 million people each year,making it one of the leading causes of death from a single infectious disease[1].China ranks third globally in terms of TB burden,with approximately 733,000 TB cases reported in 2023[2].Based on the ecological model of health determinants developed by Whitehead and Dahlgren,health determinants can be classified into direct causes.
基金funded by the National Key Research and Development Program of China(grant number 2022YFC2305204).
文摘Objective To determine the proportions of drug-resistant tuberculosis(TB),its trends,and the drug resistance-conferring mutations among patients with pulmonary TB aged 10-24 years in China.Methods The data of patients with pulmonary TB were retrieved from a national drug-resistant TB survey for analysis.Joinpoint regression software was used to analyze time trends.We also used whole genome sequencing to analyze the lineages and drug resistance-conferring mutations of 621 isolates.Results Among 4,235 patients with pulmonary TB,the proportion of new cases of multidrug-resistant tuberculosis(MDR-TB)was 3.18%(95%confidence interval[CI]:2.37-4.15)for adolescents and 3.76%(95%CI:3.03-4.60)for young adults;for previously treated patients,MDR-TB accounted for 11.25%(95%CI:5.28-20.28)of adolescents and 11.05%(95%CI:6.88-16.55)of young adults.The proportion of patients with MDR-TB remained stable among both new and previously treated patients aged 10-24 years during the study period.Through whole genome sequencing,we found that the most common mutations in the MDR-TB strains were Ser315Thr in the katG gene(71.74%)and Ser450Leu in the rpoB gene(50.00%).Conclusion This study revealed a high proportion of MDR-TB among adolescents and young adults,indicating that urgent and comprehensive measures are needed to reduce the emergence and transmission of drug-resistant TB among this population in China.
基金supported by the National Science and Technology Major Project for the Prevention and Control of Emerging and Major Infectious Diseases[2025ZD01908702]Peking University Medicine Fund of Fostering Young Scholars’Scientific&Technological innovation[BMU2024YFJHP014]supported by Fundamental Research Funds for the Central Universities+1 种基金Key Clinical Projects of Peking University Third Hospital[BYSYZD2022014]Peking University Third Hospital[2025024].
文摘Objective Post tuberculosis lung disease(PTLD)manifests in various forms,including tuberculosisassociated chronic obstructive pulmonary disease(TB-COPD),yet the clinical features of PTLD remain undercharacterized.This study aimed to assess longitudinal changes in lung function over a 5-year period and to identify predictors of airflow obstruction in a cohort of patients treated for active pulmonary TB.Methods Patients with active pulmonary TB were enrolled in this study and were followed during treatment,at treatment completion and five years post-treatment.Assessments included lung function and chest CT,analyzing longitudinal trends and airflow obstruction risk factors.Results Among 53 patients(mean age 36.9±13.9 years;64.2%male),7 patients(13.2%)exhibited airflow obstruction.At the 5-year follow-up,the mean FEV_(1)/FVC declined significantly(76.27%±12.04%vs.80.23%±11.02%,P<0.001)and 9 patients(17.0%)exhibited airflow obstruction.Seven of these patients predominantly showed air trapping consistent with small airway disease on chest CT,aligning with TB-COPD phenotype.Notably,four young-to-middle-aged patients(<60 years old)had persistent obstruction over the five years.Conclusion The initial test revealed that 13.2%of patients presented with airflow obstruction.By the 5-year follow-up,this proportion had increased to 17.0%,with most cases demonstrating imaging findings aligning with TB-COPD,even among younger,non-smoking individuals.These findings emphasize the importance of long-term follow-up and routine lung function assessments in TB survivors.
基金supported by the CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-038 and 2023-I2M-2-001)the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2019PT310029 and 2023-PT310-04).
文摘Tuberculosis(TB)continues to pose a significant threat to global public health,necessitating rapid and precise diagnostic methods and comprehensive detection of antimicrobial resistance(AMR)to facilitate timely clinical management.Traditional diagnostic techniques suffer from extended turnaround times and limited ability to comprehensively profile AMR,often resulting in delayed therapeutic interventions.Highthroughput sequencing(HTS)technologies have revolutionized pathogen research by significantly improving diagnostic speed and accuracy.In the context of TB,diverse sequencing strategies and platforms are being employed to fulfill specific research goals,ranging from elucidating the molecular mechanisms underlying AMR to characterizing the genomic diversity among clinical isolates.This review systematically examines current progress in the application of HTS for rapid pathogen identification,comprehensive AMR profiling,epidemiological studies,advances in novel drugs,and vaccine development.Furthermore,we address existing technological limitations and bioinformatics challenges and explore the future directions necessary for effectively integrating HTS-based methodologies into global TB control efforts.
基金supported by the Wisdom Accumulation and Talent Cultivation Project of Third Xiangya Hosipital of Central South University,China(YX202112).
文摘Objective:Endometrial tuberculosis,which commonly affects women of reproductive age,is a significant cause of intrauterine adhesions(IUA),potentially leading to hypomenorrhea,amenorrhea,and infertility.Hysteroscopic adhesiolysis is the primary treatment for IUA;however,studies specifically addressing its efficacy in tuberculosisinduced IUA remain scarce.This study aims to evaluate the therapeutic outcomes of hysteroscopic adhesiolysis for IUA caused by endometrial tuberculosis.Methods:This retrospective cohort study included patients diagnosed with tuberculosisinduced IUA who underwent hysteroscopic adhesiolysis at the Third Xiangya Hospital of Central South University between May 2014 and October 2022.Clinical data including age,medical history,adhesion severity,surgical treatment,and reproductive outcomes were analyzed.Results:Among 39 patients identified,2 were lost to follow-up.A total of 37 patients were included,with a follow-up duration ranging from 6 months to 9 years.Hypomenorrhea was reported in 24(64.9%)patients,secondary amenorrhea in 10(27.0%)patients,and normal menstruation in 3(8.1%)patients.Most patients presented with primary infertility(59.5%),and only 2(5.4%)had secondary infertility.The median American Fertility Society(AFS)score at initial assessment was 10(range,8−12);8(21.6%)patients had moderate IUA,and 29(78.4%)had severe IUA.A total of 86 surgical procedures were performed across 37 patients,with 27 patients undergoing 2 or more surgeries.Postoperatively,25(67.6%)patients achieved normalization of the uterine cavity,while 12(32.4%)still had a reduced cavity.Only 7(18.9%)patients had a grossly normal endometrium at the final surgery,all of whom had moderate adhesions at the initial procedure.Menstrual flow returned to normal in 12(32.4%)patients,while 25(67.6%)continued to experience hypomenorrhea.Of 29 patients who attempted in vitro fertilization and embryo transfer(IVF-ET),only 6(20.7%)conceived.Among these,4(13.8%)delivered at term via cesarean section;one case was complicated by postpartum hemorrhage due to uterine atony and another by placental adhesion.Conclusion:Endometrial tuberculosis can lead to severe IUA.Hysteroscopic adhesiolysis facilitates cavity restoration and improvement of menstrual conditions,but the overall reproductive outcomes remain suboptimal.
基金Supported by Lanzhou City Science and Technology Development Guiding Plan Project,No.2023-ZD-170Lanzhou Science and Technology Plan Project,No.2023-2-11High-Level Talent Training Project At the 940th Hospital of the Joint Logistics Force,No.2024-G3-5.
文摘BACKGROUND Tuberculosis is among the most devastating infectious diseases worldwide.Spinal tuberculosis is not easy to detect at an early stage,which without effective treatment often leads to spinal deformity and spinal cord damage which in turn cause complications such as paraplegia and quadriplegia.In this study,we established a model using three concentrations of bacteria and carried out a comprehensive evaluation of the model by imaging,general observations,and histopathological and bacteriological studies.AIM To establish a rabbit model of spinal tuberculosis and examine the effect on the model’s efficacy using different concentrations of Mycobacterium tuberculosis(M.tuberculosis)inoculum.METHODS New Zealand rabbits were randomly divided into experimental,control and blank groups.The experimental and control animals were sensitized with complete Freund′s adjuvant,a hole was drilled beneath the upper endplate of the L6 vertebral body and filled with gelfoam sponge.The experimental group was divided into three subgroups(experimental 1,experimental 2,experimental 3)and infused with M.tuberculosis suspension at various concentrations.The control group was inoculated with saline and the blank group received no treatment.The 12-week post-operative survival rates were 100%,80%and 30%in the experimental groups inoculated with concentrations of 106,107 and 108 CFU/mL bacteria,respectively.RESULTS The survival rate of the control and blank groups was 100%.Vertebral body destruction at 8 weeks in the three experimental groups as determined by X-ray analysis was 33.3%,62.5%and 66.7%,and by computed tomography(CT)and 3-dimensional CT 44.4%,75%and 100%,respectively.At 12 weeks,the figures were 44.4%,75%and 100%by X-ray analysis and 44.4%,100%and 100%by CT and 3-dimensional CT,respectively.All surviving rabbits of the experimental groups had vertebral destruction.The positive bacterial culture rates were 22.2%,75%and 66.7%,respectively,in the experimental groups.After being sensitized with complete Freund's adjuvant,large differences were observed in the extent of spinal tuberculosis after inoculation of the rabbits with different concentrations of H37RV standard M.tuberculosis.CONCLUSION The experimental 1 had a low success rate at establishing an infection.The experimental 3 resulted in high mortality and complication rates.The experimental 2 was optimum for establishing a spinal tuberculosis model based on the high level of symptoms observed and the low rabbit mortality.
文摘Detection and treatment of drug resistance in extrapulmonary tuberculosis(EPTB)is a major challenge worldwide.Drug resistance in EPTB has not been studied extensively.However,patients with drug-resistant EPTB have been reported to have poor outcomes[1].Rifampicin and isoniazid are the cornerstone drugs in the management of EPTB.Resistance in Mycobacterium(M.)tuberculosis to these drugs commonly arises due to mutations in the‘rpoB’gene and‘katG&inhA’genes,which confer resistance to rifampicin and isoniazid,respectively.Treatment outcomes are affected by the presence of these mutations.In addition,anatomical and physiological barriers impede the effective delivery of drugs to the affected extrapulmonary site[1].An analysis of the frequency of mutations in drug resistant M.tuberculosis strains causing EPTB in our region can help identify patterns of drug resistance.This,in turn,can provide inputs that may be used for modifying standard treatment regimens to make them more effective.The present study aims to identify the frequency and pattern of mutations in the‘rpoB’gene and‘katG&inhA’genes in M.tuberculosis strains isolated from EPTB samples.
文摘Tuberculosis(TB)remains a critical global health challenge,with 10.8 million new cases and over 1.25 million deaths reported annually,disproportionately affecting low-income regions.Despite its use,the Bacillus Calmette-Guérin(BCG)vaccine provides limited protection against adult pulmonary TB,necessitating novel solutions.The messenger RNA(mRNA)vaccine technology,proven effective in combating coronavirus disease 2019,offers significant promise for TB prevention.These vaccines elicit robust immune responses by encoding antigens that stimulate humoral and cell-mediated immunity,essential for combating mycobacterium TB.Unlike traditional methods,mRNA vaccines are highly adaptable,scalable,and capable of targeting emerging strains.Preclinical studies highlight the enhanced efficacy of mRNA TB vaccines over BCG,demonstrating their ability to reduce bacterial burdens and generate memory T-cell responses critical for long-term protection.However,challenges persist,including mRNA instability,cold-chain storage needs,and mycobacterium’s complex immune evasion strategies.Innovative solutions,such as lipid nanoparticle delivery systems and selfamplifying mRNA platforms,are being developed to address these barriers.The initiation of clinical trials,notably BioNTech’s BNT164,marks a pivotal advancement in TB vaccine development.These trials focus on safety,immuno genicity,and efficacy,particularly in regions with high TB prevalence.While logistical and financial hurdles remain,mRNA vaccines hold transformative potential to bridge critical gaps in TB prevention.Their adaptability extends to tackling co-infections like human immunodeficiency virus,further amplifying their impact on global health.By integrating mRNA vaccines into existing TB control strategies,these advancements could revolutionize prevention efforts,especially in regions where current solutions fall short.Continued innovation and investment are crucial to harnessing the full potential of mRNA vaccines,positioning them as a cornerstone in the fight against TB and its global eradication.
文摘Chronic obstructive pulmonary disease(COPD)and respiratory tuberculosis are important respiratory problems.Meeting together,these diseases can mutually worsen the severity of clinical manifestations and negatively affect prognosis.COPD and tuberculosis share a number of common risk factors and pathogenetic mechanisms involving various immune and non-immune cells.Inflammation,hypoxia,oxidative stress,and lung tissue remodeling play an important role in the comorbid course of COPD and respiratory tuberculosis.These mechanisms are of diagnostic interest and are promising therapeutic targets.Thus,the aim of the current review is to discuss the mechanisms of the comorbid course of chronic obstructive pulmonary disease and respiratory tuberculosis.
文摘BACKGROUND Due to low bacteria count and high likelihood of having extrapulmonary tuberculosis(TB)among patients with advanced human immunodeficiency virus(HIV)disease,the World Health Organization(WHO)recommended the use of urine lateral flow urine lipoarabinomannan(LF-LAM)or sputum-Xpert to screen for TB.AIM To estimate pooled prevalence of TB screening uptake,TB diagnosis,TB treatment initiation and mortality among patients with advanced HIV disease in Africa.METHODS PubMed,Cochrane Library and EMBASE were searched for articles published between January 2011 and December 2024.TB screening uptake was defined as percentage of patients with advanced HIV disease(CD4≤200 cells/mm3 or WHO stage III/IV)who tested for TB.Using random effects models,we computed the pooled estimate of TB screening uptake,TB prevalence,TB treatment initiation and mortality and their corresponding 95%CIs.Stratified analysis to compare uptake of TB testing and TB prevalence between children vs adults and multisite vs single site studies was performed.RESULTS A total of nineteen studies with 16065 people with advanced HIV disease were analyzed.The pooled prevalence of TB screening uptake was 64.6%(95%CI:49.2–80.1).The pooled prevalence of TB was 29.4%(95%CI:22.0–36.8),and TB treatment initiation was 77.9%(95%CI:63.9–91.8),and mortality was 19.5%(95%CI:8.9–30.0).The pooled prevalence of TB testing uptake was significantly lower among children compared to adults(28.2%vs 66.4%,P=0.003)and lower for multi-sites compared to single site studies(58.8%vs 82.9%,P=0.002).The pooled prevalence of TB was significantly lower among children compared to adults(24.2%vs 27.6%,P=0.012)and higher among studies that involved multi vs single sites(30.0%vs 21.9%,P=0.001).CONCLUSION Four in ten people with advanced HIV disease were not screened for TB as recommended by the WHO,indicating significant gaps in identifying patients with TB.Excluding patients with evidence of TB is critical to avoid exposing them to subtherapeutic levels of anti TB treatment.
基金supported by Higher Institution Centre of Excellence(HICoE)Grant(A305-KR-AKH002-0000000278-K134)from the Ministry of Higher Education,Malaysia.
文摘Objective:To assess aptamer-based assays for diagnosing latent tuberculosis infection(LTBI).Methods:Literature from Medline,ScienceDirect,and Scopus,covering publications from January 1,2012,to December 31,2023,was examined.This review evaluates different aptamers,biomarkers,sample types,sample sizes,reference assays,and the assays'sensitivity and specificity.By using the Quality Assessment of Diagnostic Accuracy Studies 2,the risk of bias in each study was evaluated.Results:Aptamer-based assays generally showed a sensitivity of 90%(95%CI:75%-100%)and specificity of 90%(95%CI:50%-100%),where optical aptasensor showed the highest sensitivity and specificity at 100%.Serum samples were frequently used to enhance antigen detectability,improving the assay’s performance.Meanwhile,HspX was the most studied biomarker,followed by MPT64,and IFN-γ.Conclusions:Aptamer-based assays could be reliable alternatives to current LTBI detection methods,but further research is needed to validate their clinical efficacy.
基金supported by the National Natural Science Foundation of China under grant number U21A20259the National Key Research and Development Program of China under grant number 2021YFD1800401.
文摘Mycobacterium tuberculosis(Mtb)employs multiple mechanisms,such as phagocytosis and autophagy,to evade innate immune clearance and establish infection.In the present study,we identified the ESX-1 secretion-associated protein EspL,which promotes Mtb survival by inhibiting phagosome maturation and autophagy initiation.EspL knockout decreased Mtb intracellular survival,while EspL overexpression increased bacterial survival by interfering with phagocytosis and autophagy.EspL interacts with ULK1 and promotes its phosphorylation at Ser^(757),leading to the inhibition of autophagy initiation.Additionally,overexpression of EspL reduced antigen presentation and T-cell responses both in vitro and in vivo.Our findings revealed that EspL interferes with autophagy and antigen presenta-tion by suppressing ULK1 activation.These insights provide a novel understanding of Mtb pathogenicity.
文摘BACKGROUND Tuberculosis(TB)remains a global health concern despite decreasing incidence.Delayed TB diagnosis can exacerbate patient outcomes and lead to broader public health issues such as mass infections.Differentiation between TB and bacterial pneumonia is often complicated by variable clinical and radiological manifestations of TB,leading to diagnostic delays.CASE SUMMARY An 89-year-old,Japanese male patient with a history of diabetes mellitus,hypertension,and hypothyroidism presented with right-sided chest pain.Based on the elevated inflammatory response,right pleural effusion,and infiltrating shadow in the lung field,the diagnosis of right pleurisy was made and the antibiotic,ampicillin/sulbactam,was administered.The patient’s condition,inflammatory reaction,and right pleural effusion temporarily improved.However,persistent low-grade fever and malaise prompted further evaluation,revealing repeated right pleural effusion and inflammatory response.A right thoracentesis was performed;the patient was diagnosed with tuberculous pleurisy as a result of exudative effusion with lymphocyte predominance,elevated adenosine deaminase levels,and positive Mycobacterium TB polymerase chain reaction test.Anti-TB treatment,including isoniazid,rifampicin,and ethambutol was initiated,leading to significant clinical improvement.The patient successfully completed a 12-month course of TB therapy without recurrence or deterioration.CONCLUSION There are cases of TB wherein temporary improvement apparently could be shown through treatment with antimicrobial agents other than anti-TB drugs,necessitating careful evaluation in atypical cases of bacterial pneumonia.
文摘BACKGROUND Tuberculosis(TB)is a common infection causing huge morbidity and mortality to mankind.The analytical methods used in diagnosing TB are not sensitive in paucibacillary infections and also require trained technical personnel.MicroRNAs are stable in serum and other body fluids,and hold great potential in the diagnosis of TB.AIM To analyze the dysregulated microRNA profiles among patients with cavitatory and non-cavitatory pulmonary TB.METHODS The prospective study will be conducted in a tertiary care center in India.Adult patients with newly diagnosed pulmonary TB will be included.There will be two groups:Patients with sputum positive pulmonary TB with cavity and without cavity(group1),and apparently healthy individuals(group 2).The participants will undergo sputum examination,Xpert Mycobacterium TB complex/resistance to rifampin(Mtb/RIF)assay,chest X-ray,and blood investigations and serum microRNA detection.Ethics approval has been obtained.Written informed consent will be obtained.Appropriate statistical analyses will be used.RESULTS MicroRNAs will be correlated with sputum positivity,Xpert Mtb/RIF assay,radiological involvement,inflammatory markers,and course of the disease among cases and controls.CONCLUSION MicroRNAs could serve as potential diagnostic biomarkers in diagnostically challenging TB patients.
基金Supported by the Indian Council of Medical Research,No.Coord/7(1)/CARE-KD/18-NCD-II.
文摘BACKGROUND India has the highest tuberculosis(TB)burden in the world.Of the estimated annual 10 million TB cases,features of extra pulmonary TB are evident in up to 45%.Urogenital TB(UGTB)accounts for approximately 20%of those cases.The lack of non-sputum based diagnostic tools continue to hinder efforts to reduce the burden of UGTB.MicroRNAs(miRNAs)play a crucial role in biological pathways and can be used as a potential biomarker for TB.We evaluated urinary extracellular vesicles(uEVs)as non-invasive source to explore miRNAs with biomarker potential for UGTB.AIM To evaluate the potential of miRNA-155-5p,miRNA-26a-5p and miRNA-29a-3p in uEVs to diagnose UGTB in adults.METHODS uEV characterization was done using nanoparticle tracking analysis and flow cytometry.Quantitative reverse transcriptase polymerase chain reaction(qRTPCR)for urinary uEV-miRNAs were carried out in samples from patients with suspected UGTB,or Urinary tract infections[UTI,disease controls(DC)]and healthy controls(HCs)(n=20/group).U6 was used to normalize the qRT-PCR data.Receivers operating characteristic curves was used to calculate the diagnostic accuracy of uEV-miRNAs to differentiate UGTB from controls(DC and HCs).RESULTS uEVs from UGTB or UTI patients had higher mean size,and also lower proportion of CD63 positive vesicles as compared to HC’s uEVs.Between UTI and UGTB,the mean size of uEVs was significantly higher in UTI cases.qRT-PCR analysis revealed a significantly lower abundance of miRNA-155-5p and miRNA-26a-5p in uEVs from UGTB relative to UTI(P value=0.004)and HC(P value=0.009)respectively n=20/group).While,miRNA-29a-3p was higher in abundance in both UGTB and HCs’uEV,relative to uEVs from UTI cases(P values=0.004 and 0.002 respectively,n=20/group).Moreover,miRNA-155-5p[area under curve(AUC)=0.88,P≤0.0001]and miRNA-29a-3p(AUC=0.76,P value=0.005)had optimal diagnostic accuracy to differentiate UGTB from DC(n=20/groups)with a likelihood ratio of 5.2 and 4.3,respectively through receivers operating characteristic curve.While,miRNA-155-5p(AUC=0.68,P value=0.05)and miRNA-26a-5p(AUC=0.78,P value=0.002)had optimal diagnostic accuracy to differentiate UGTB from HCs with a likelihood ratio of>2.CONCLUSION The differential expression of uEV-miRNAs,miRNA-155-5p and miRNA-29a-3p in UTGB and UTI cases hold promise in the specific diagnosis of UGTB.Further studies in large cohort are,however,needed to confirm the diagnostic accuracy of these uEV-miRNAs.
文摘BACKGROUND Pancreatic tuberculosis(TB)is a rare clinical condition that is frequently misdia-gnosed.A definitive diagnosis is often established through surgical biopsy.CASE SUMMARY We report a previously healthy 21-year-old male who presented with epigastric pain and fever.Initially diagnosed with a pancreatic abscess and duodenal bulb perforation,the patient declined surgical intervention and was subsequently re-ferred to our hospital.Abdominal computed tomography and endoscopy revea-led a duodenal bulb perforation,esophageal and duodenal ulcers,and a mass in the pancreatic head.Endoscopic ultrasound with fine-needle aspiration identified a hypoechoic mass suggestive of TB.Cytological and histopathological analysis confirmed the diagnosis.The patient was diagnosed with primary pancreatic TB and started on anti-TB therapy.At the 1-year follow-up,the pancreatic mass had markedly regressed,and the patient had fully recovered with complete symptom resolution.CONCLUSION Pancreatic TB should be included in differential diagnosis;prompt endoscopic ul-trasound-fine-needle aspiration and therapy enable recovery.
文摘Tuberculosis(TB)remained the first leading cause of death from a single infectious agent worldwide in 2023,resulting in nearly twice as many deaths as those caused by the human immunodeficiency virus/acquired immune deficiency syndrome.An estimated 10.8 million TB cases were reported globally in 2023,with approximately 1.25 million associated deaths.In China,which ranks third in the global TB burden,there were approximately 741,000 new cases and 25,000 deaths in 2023^([1]).TB poses a significant threat to human health worldwide.
文摘There is a bidirectional association between type II diabetes mellitus(T2DM)and pulmonary tuberculosis(PTB),with each enhancing the risk of the other,thus increasing the burden of both drug-sensitive and drug-resistant forms of the disease.This dual burden also has a detrimental impact on patient's mental health.Although several recommendations have been made for bidirectional screening of diabetes and tuberculosis,implementation remains poor,resulting in increased morbidity and mortality among patients with this comorbidity.Mental health is often neglected,as clinical outcomes receive disproportionate focus,with limited attention to patients’social and psychological well-being.According to the World Health Organization,health is defined as a state of physical,mental,and social well-being,and not merely the absence of disease or infirmity.The aim of this mini-review is to highlight the intersection of PTB and T2DM,specifically discussing the mental health outcomes of the co-burden.
