Tuberculosis of the uterine cervix is grouped under genital tuberculosis. Other sites for genital tuberculosis include the Fallopian tubes and the endometrium. Genital tuberculosis and other types of tuberculosis outs...Tuberculosis of the uterine cervix is grouped under genital tuberculosis. Other sites for genital tuberculosis include the Fallopian tubes and the endometrium. Genital tuberculosis and other types of tuberculosis outside the lungs are referred to as extra-pulmonary tuberculosis (EPTB). Genital tuberculosis presents with unspecific symptoms and signs;and because of this, most often, the diagnosis is made incidentally during investigations for other conditions that present with similar clinical pictures. Therefore, misdiagnosis and wrong treatment are not uncommon. We present a case of tuberculosis of the uterine cervix which was incidentally diagnosed when the patient was being investigated for cervical cancer, and successfully treated with a 6-months rifampicin regimen, 2RHZE/4HRE. Health providers have a duty to highly suspect tuberculosis of the cervix among women who present with abnormal vaginal discharge, abnormal vaginal bleeding and post-coital bleeding especially in countries where HIV and TB are endemic. If properly diagnosed and correctly treated, tuberculosis of the uterine cervix is curable.展开更多
The diagnosis of extra-pulmonary tuberculosis(TB) seems relatively difficult due to the absence of specific symptoms and signs in patients on peritoneal dialysis or hemodialysis.We report four cases of extra-pulmonary...The diagnosis of extra-pulmonary tuberculosis(TB) seems relatively difficult due to the absence of specific symptoms and signs in patients on peritoneal dialysis or hemodialysis.We report four cases of extra-pulmonary tuberculosis on dialysis,with two cases on peritoneal dialysis and two cases on hemodialysis.The presentations,therapy,and outcomes of TB infection in these patients were reviewed.Otherwise,the English literature published in the PubMed database associating extra-pulmonary tuberculosis on dialysis over the last three decades is reviewed.A total of 61 studies containing 70 cases were included.The most common primary disease was diabetic nephropathy(22.86%,16/70).The peritoneum(31.42%,22/70),bone(21.42%,15/70),and lymph node(20%,14/70) were the most frequently infected.Single organ infection was common(90%,63/70).Fever(58.57%,41/70),pain(35.71%,25/70),and enlarged lymph node(20%,14/70) were the most common symptoms.Biopsy(67.14%,47/70) and culture(40%,28/70) provided most reliable methods for clear diagnosis of tuberculosis.The combined treatment of isoniazid,rifampicin,pyrazinamide,and ethambutol(44.29%,31/70) was the most common therapy.The majority of patients improved(82.86%,58/70);however,12 cases got worse(17.14%),with 10 of them dying(14.29%).Physicians should be aware of the non-specific symptoms and location of infection,and consider tuberculosis in their differential diagnoses in dialysis patients presenting with symptoms such as fever,pain,and weight loss.展开更多
Background: Tuberculosis primarily affects lungs, but all organs may be affected. Extra-pulmonary forms of tuberculosis cause a big public health problem as it is diagnosed late. This delay in diagnosis is not only du...Background: Tuberculosis primarily affects lungs, but all organs may be affected. Extra-pulmonary forms of tuberculosis cause a big public health problem as it is diagnosed late. This delay in diagnosis is not only due to the delay in the examination, but also due to difficulties related to extra-pulmonary tuberculosis diagnostic. Aim: To describe the different locations of extra-pulmonary Tuberculosis and its aspects in Togo. Patients and Methods: A retrospective analysis of all extra-pulmonary tuberculosis cases diagnosed by imaging over five years (January 2010 to December 2015) was done. All the cases were confirmed either by direct examination of biological fluids or by histological analysis of biopsy and surgical samples or by culture on specific area. Data were collected from the Department of Radiology, from Microbiology Laboratory of the Pneumo-phthisiology unit and from Pathology Laboratory of Sylvanus Olympio Teaching Hospital of Lomé. Results: A total of 83 cases of extra-pulmonary Tuberculosis had been taken into account: 45 men and 38 women, with a maximum number of cases (66.3%) in the age group between 20 to 40 years old. An HIV infection was known in 51 patients (61.4%). Pulmonary damage was associated in 21 patients (25.3%). A total of 116 extra-pulmonary tuberculosis locations were recorded. Damages were pleural in 37.1% (43), ganglion in 24.1% (28), osteo-articular in 15.5% (18), abdominal in 12.9% (15), military represented 8.6% (10), a case of testicular damage, and a case of mammary tuberculosis. Conclusion: The medical scanning based on conventional radiography, ultrasonography and TDM is indispensable for the diagnosis and the care taking of extra-pulmonary tuberculosis since some locations may be confused with many other diseases and lead to misdiagnosis errors and delay the treatment.展开更多
Primate sanctuaries across Africa play a pivotal role in the rescue and rehabilitation of confiscated and rescued wild primates, many of whom have had extensive contact with humans prior to their arrival and throughou...Primate sanctuaries across Africa play a pivotal role in the rescue and rehabilitation of confiscated and rescued wild primates, many of whom have had extensive contact with humans prior to their arrival and throughout the rehabilitation process, heightening the risk of disease transmission. While tuberculosis is not naturally occurring in free-living chimpanzees, it has been extensively observed in captive primates that have been in close proximity to humans or other captive primates infected with Mycobacterium tuberculosis. This case report delves into an outbreak of extra-pulmonary tuberculosis among juvenile chimpanzees within a sanctuary, detailing the associated diagnostic challenges and treatment approaches. The five cases had close contact with a caregiver infected with tuberculosis, subsequently transmitting the infection to other in-contact chimpanzees. Prolonged treatment, employing the human protocol of quadri-therapy (rifampicin, isoniazid, pyrazinamide, and ethambutol), followed by bi-therapy (rifampicin and isoniazid), resulted in complete resolution for all five cases. These cases underscore the critical importance of maintaining high levels of biosecurity, implementing effective quarantine measures, and adhering to strict hygiene practices when working with non-human primates.展开更多
Introduction: Tuberculosis is an infectious disease that mainly affects the lung. Extrapulmonary localizations are a reason for hospitalization in our health facilities. The objective of this study was to describe the...Introduction: Tuberculosis is an infectious disease that mainly affects the lung. Extrapulmonary localizations are a reason for hospitalization in our health facilities. The objective of this study was to describe the epidemiological, clinical, paraclinical and evolutionary aspects of extra pulmonary tuberculosis (EPT) at the Abass Ndao Hospital Center. Patients and Methods: This was a descriptive cross-sectional study conducted over a period of 11 years (January 1, 2010 to December 30, 2021). All patients with extrapulmonary tuberculosis hospitalized in the department of internal medicine during the recruitment period were included. Results: Fifty-two (52) patients were collected. The year 2019 recorded the most cases 23.08% (n = 20). The mean age of the patients was 40.56 ± 18.24 years. The age group 20 - 34 years 42.31% (n = 22) was the most represented. Females were in the majority 61.54% (n = 32) with a sex ratio (M/F) was 0.63. Housewives were in the majority 40.38% (n = 21). 60.87% of the cases (n = 14) came from a health facility. 38.46% of the cases had been infected. 21.74% (n = 9) were smokers. The reasons for consultation were dominated by fever (67.44%), AEG (62.79%) and cough (41.86%). Eighteen patients (40.91%) had fever. The mean time to consultation was 77.37 ± 90.3 days with extremes of 3 and 365 days. The median was 45 days. More than half of the patients 61.90% (n = 26) had anemia. Positive retroviral serology was noted in 21.43% of cases. All patients had a CRP greater than 6. More than half of the patients 51.92% (n = 27) had multifocal tuberculosis. The peritoneum 44.23% (n = 23) was the main organ affected. The average hospital stay was 9.8 ± 4.9 days with extremes of 1 and 19 days. All patients had received the protocol in force at the national level. Death was noted in 4 patients (9.52%). Conclusion: EPT is characterized in our context by a notorious diagnostic difficulty due to the multiplicity of clinical presentations, the complexity of explorations, and the problems of differential diagnosis notably with other granulomatosis, systemic lupus and cancers. This difficulty is reflected in the low rate of diagnosis with a paraclinical argument of certainty and in the long diagnostic delays.展开更多
<b>Background: </b>Many inflammatory cells, cytokines, acute phase reactants as well as platelets are recruited in the battle against the invading mycobacterium. As a result, alterations in the hematologic...<b>Background: </b>Many inflammatory cells, cytokines, acute phase reactants as well as platelets are recruited in the battle against the invading mycobacterium. As a result, alterations in the hematologic profile of infected patients are anticipated.<b> Objectives: </b>The primary objective was to investigate the various hematologic characteristics of patients with active tuberculosis. The secondary objective was to study the correlation between such hematologic characteristics and the type of tuberculosis including pulmonary, extra-pulmonary, and disseminated. <b>Methods: </b>This was a retrospective, descriptive study investigating the hematological findings in adult patients (aged 18 years or older) with active, bacteriologically-confirmed tuberculosis infection. <b>Results: </b>Among the 605 confirmed active tuberculosis cases, 465 (78.8%) were pulmonary, 104 (17.6%) extra-pulmonary, and 21 (3.6%) disseminated type. The mean age at diagnosis was 33.4 ± 11.4 years and males constituted 80.2% of cases. Peripheral leukocytosis was observed in 177 (30.1%) and leukopenia in 7 (1.2%) (Pulmonary type of tuberculosis was significantly associated with leukocytosis (P = 0.000)). Neutrophilia, lymphocytosis, monocytosis, eosinophilia, and basophilia were observed in 15.3%, 3.1%, 10.4%, 6.3% and 4.7% respectively. Thrombocytopenia and thrombocytosis were observed in 3.9% and 26.7% respectively. Anemia was observed in 44.8% of all cases with 4.4% had severe anemia and 60.3% had anemia of chronic diseases. Erythrocyte sedimentation rate was high in 77.2% of cases and ≥100 mm/hr in 5%. C-reactive protein was high in 93.4% and it exceeded 40 mg/L in 69.3%. <b>Conclusion: </b>There is a wide range of variability in the leukocyte and differential leukocyte abnormalities observed in patients with active tuberculosis. Leukocytosis can be seen in one-third of patients with pulmonary tuberculosis. Anemia of chronic diseases is the most common type of anemia observed in tuberculosis patients. Erythrocyte sedimentation rate and C-reactive protein are elevated in the majority of patients with active tuberculosis. Levels of the sedimentation rate can be useful indices to determine the extent of the disease.展开更多
Despite the efforts made to fight the tuberculosis, <i><i><span style="font-family:Verdana;">Mycobacterium tuberculosis</span></i><span style="font-family:Verdana;"...Despite the efforts made to fight the tuberculosis, <i><i><span style="font-family:Verdana;">Mycobacterium tuberculosis</span></i><span style="font-family:Verdana;"></span></i> still remains a public health problem, particularly for low-income countries. According to the World Health Organization data, our country, Mali has detected only half of the 10,385 cases of tuberculosis expected for 2014 for a population of 17,309,000 inhabitants. The objective of this present work was to describe the different clinical aspects and the epidemiology of tuberculosis at Hospital Sominé Dolo <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">in</span></span></span><span><span><span style="font-family:;" "=""><span style="font-family:Verdana;"> Mopti. We performed a retro-prospective and descriptive of tuberculosis cases diagnosed in our department of medicine between May 2016 and August 2018. A total of 96 tuberculosis cases were recorded, <i></i></span><i><i><span style="font-family:Verdana;">i.e</span></i><span style="font-family:Verdana;">.</span></i> 4.6% and 1.0% for hospitalizations and consultations patterns, respectively. The median of age was 41 with extremes from 5 to 80 years. The age group [31</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span><span><span style="font-family:;" "=""><span style="font-family:Verdana;">40 years] was the most affected with 20.8%. Men and women were affected in identical proportions, <i></i></span><i><i><span style="font-family:Verdana;">i.e</span></i><span style="font-family:Verdana;">.</span></i> 50%. Pulmonary locations were the most frequent with 55.2%. Pleural tuberculosis was far the most frequent of the extra-pulmonary forms with 24.0% followed by the peritoneal and bone localization with 6.3% each. The majority of patients were followed on an outpatient basis, <i></i></span><i><i><span style="font-family:Verdana;">i.e</span></i><span style="font-family:Verdana;">.</span></i> 90.6%. The disease lethality was 7.3%. Our data show that the cases of extra</span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">pulmonary tuberculosis are in an increasing proportion and their diagnosis confirmation remains difficult in our context.</span></span></span>展开更多
Objective: With scant studies in the literature, little is known about the risk factors for tuberculosis in patients with dermatomyositis/polymyositis. Therefore, the aim of the present study was to analyze the predic...Objective: With scant studies in the literature, little is known about the risk factors for tuberculosis in patients with dermatomyositis/polymyositis. Therefore, the aim of the present study was to analyze the predictive factors for tuberculosis development in dermatomyositis/polymyositis. Methods: This single-center, retrospective, cohort study initially included 290 patients with dermatomyositis/polymyositis, from 2002 to 2016. Tuberculosis (pulmonary and/or extra-pulmonary) was confirmed after dermatomyositis/polymyositis diagnosis in 12 patients (4.1%) (Tuberculosis+ group). For the control group (Tuberculosis−), 24 patients without tuberculosis were arbitrarily selected in the same period and matched for age, ethnicity, gender, age at disease diagnosis, disease duration and type (dermatomyositis or polymyositis). Results: Tuberculosis occurred for a median of 16 months after dermatomyositis/polymyositis diagnosis. Clinical, laboratory and treatment features were similar in Tuberculosis+ and Tuberculosis−groups (P > 0.05). However, previous pulmonary fibrosis in dermatomyositis/polymyositis was more prevalent in the Tuberculosis+ group (41.7 vs. 8.3%;P = 0.029). Moreover, on a multivariate logistic regression model, pulmonary fibrosis was significantly associated with Tuberculosis (Odds ratio: 9.59, 95% confidence interval: 1.17 - 78.82). Tuberculosis affected 3 dermatomyositis cases for every 1 polymyositis case, with predominantly pulmonary followed by extra-pulmonary involvement (pleura, cutaneous, muscular, joint, soft tissue and hematologic). Two or more sites were affected in 41.7% of cases. Conclusions: Previous pulmonary fibrosis in dermatomyositis/polymyositis was a predictive factor associated with tuberculosis development. Further studies are needed to confirm these results.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
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
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
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 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
To assess the effectiveness of vaccination in contaminated environments,this study introduces a modeling framework that encompasses two transmission routes,namely direct human-to-human contact and indirect human-to-en...To assess the effectiveness of vaccination in contaminated environments,this study introduces a modeling framework that encompasses two transmission routes,namely direct human-to-human contact and indirect human-to-environment contact,as well as the implementation of new M72/AS01_(E)vaccine.Motivated by this,a coupled age-structured tuberculosis(TB)model is proposed.Its well-posedness requirement is verified using the integrated semigroup theory.Furthermore,this study presents a comprehensive analysis of threshold dynamics associated with the proposed model.Specifically,the global stability of the disease-free and positive steady states is demonstrated by employing Lyapunov functionals.Lastly,the effects of the vaccination with M72/AS01_(E)and contaminated environments on TB control are numerically simulated.Experimental results indicate that high concentrations of Mycobacterium tuberculosis in contaminated environments may somewhat impede TB control efforts,but that large-scale deployment of new vaccine could significantly reduce the prevalence of TB.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
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
Among critically ill patients,severe pulmonary and extrapulmonary tuberculosis has high morbidity and mortality.Yet,it is a diagnostic challenge given its nonspecific clinical symptoms and signs in early stages of the...Among critically ill patients,severe pulmonary and extrapulmonary tuberculosis has high morbidity and mortality.Yet,it is a diagnostic challenge given its nonspecific clinical symptoms and signs in early stages of the disease.In addition,management of severe pulmonary and extrapulmonary tuberculosis is complicated given the high risk of drug-drug interactions,drug-disease interactions,and adverse drug reactions.To help clinicians acquire an up-to-date approach to severe tuberculosis,this paper will provide a narrative review of contemporary diagnosis and management of severe pulmonary and extrapulmonary tuberculosis in critically ill patients.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
文摘Tuberculosis of the uterine cervix is grouped under genital tuberculosis. Other sites for genital tuberculosis include the Fallopian tubes and the endometrium. Genital tuberculosis and other types of tuberculosis outside the lungs are referred to as extra-pulmonary tuberculosis (EPTB). Genital tuberculosis presents with unspecific symptoms and signs;and because of this, most often, the diagnosis is made incidentally during investigations for other conditions that present with similar clinical pictures. Therefore, misdiagnosis and wrong treatment are not uncommon. We present a case of tuberculosis of the uterine cervix which was incidentally diagnosed when the patient was being investigated for cervical cancer, and successfully treated with a 6-months rifampicin regimen, 2RHZE/4HRE. Health providers have a duty to highly suspect tuberculosis of the cervix among women who present with abnormal vaginal discharge, abnormal vaginal bleeding and post-coital bleeding especially in countries where HIV and TB are endemic. If properly diagnosed and correctly treated, tuberculosis of the uterine cervix is curable.
文摘The diagnosis of extra-pulmonary tuberculosis(TB) seems relatively difficult due to the absence of specific symptoms and signs in patients on peritoneal dialysis or hemodialysis.We report four cases of extra-pulmonary tuberculosis on dialysis,with two cases on peritoneal dialysis and two cases on hemodialysis.The presentations,therapy,and outcomes of TB infection in these patients were reviewed.Otherwise,the English literature published in the PubMed database associating extra-pulmonary tuberculosis on dialysis over the last three decades is reviewed.A total of 61 studies containing 70 cases were included.The most common primary disease was diabetic nephropathy(22.86%,16/70).The peritoneum(31.42%,22/70),bone(21.42%,15/70),and lymph node(20%,14/70) were the most frequently infected.Single organ infection was common(90%,63/70).Fever(58.57%,41/70),pain(35.71%,25/70),and enlarged lymph node(20%,14/70) were the most common symptoms.Biopsy(67.14%,47/70) and culture(40%,28/70) provided most reliable methods for clear diagnosis of tuberculosis.The combined treatment of isoniazid,rifampicin,pyrazinamide,and ethambutol(44.29%,31/70) was the most common therapy.The majority of patients improved(82.86%,58/70);however,12 cases got worse(17.14%),with 10 of them dying(14.29%).Physicians should be aware of the non-specific symptoms and location of infection,and consider tuberculosis in their differential diagnoses in dialysis patients presenting with symptoms such as fever,pain,and weight loss.
文摘Background: Tuberculosis primarily affects lungs, but all organs may be affected. Extra-pulmonary forms of tuberculosis cause a big public health problem as it is diagnosed late. This delay in diagnosis is not only due to the delay in the examination, but also due to difficulties related to extra-pulmonary tuberculosis diagnostic. Aim: To describe the different locations of extra-pulmonary Tuberculosis and its aspects in Togo. Patients and Methods: A retrospective analysis of all extra-pulmonary tuberculosis cases diagnosed by imaging over five years (January 2010 to December 2015) was done. All the cases were confirmed either by direct examination of biological fluids or by histological analysis of biopsy and surgical samples or by culture on specific area. Data were collected from the Department of Radiology, from Microbiology Laboratory of the Pneumo-phthisiology unit and from Pathology Laboratory of Sylvanus Olympio Teaching Hospital of Lomé. Results: A total of 83 cases of extra-pulmonary Tuberculosis had been taken into account: 45 men and 38 women, with a maximum number of cases (66.3%) in the age group between 20 to 40 years old. An HIV infection was known in 51 patients (61.4%). Pulmonary damage was associated in 21 patients (25.3%). A total of 116 extra-pulmonary tuberculosis locations were recorded. Damages were pleural in 37.1% (43), ganglion in 24.1% (28), osteo-articular in 15.5% (18), abdominal in 12.9% (15), military represented 8.6% (10), a case of testicular damage, and a case of mammary tuberculosis. Conclusion: The medical scanning based on conventional radiography, ultrasonography and TDM is indispensable for the diagnosis and the care taking of extra-pulmonary tuberculosis since some locations may be confused with many other diseases and lead to misdiagnosis errors and delay the treatment.
文摘Primate sanctuaries across Africa play a pivotal role in the rescue and rehabilitation of confiscated and rescued wild primates, many of whom have had extensive contact with humans prior to their arrival and throughout the rehabilitation process, heightening the risk of disease transmission. While tuberculosis is not naturally occurring in free-living chimpanzees, it has been extensively observed in captive primates that have been in close proximity to humans or other captive primates infected with Mycobacterium tuberculosis. This case report delves into an outbreak of extra-pulmonary tuberculosis among juvenile chimpanzees within a sanctuary, detailing the associated diagnostic challenges and treatment approaches. The five cases had close contact with a caregiver infected with tuberculosis, subsequently transmitting the infection to other in-contact chimpanzees. Prolonged treatment, employing the human protocol of quadri-therapy (rifampicin, isoniazid, pyrazinamide, and ethambutol), followed by bi-therapy (rifampicin and isoniazid), resulted in complete resolution for all five cases. These cases underscore the critical importance of maintaining high levels of biosecurity, implementing effective quarantine measures, and adhering to strict hygiene practices when working with non-human primates.
文摘Introduction: Tuberculosis is an infectious disease that mainly affects the lung. Extrapulmonary localizations are a reason for hospitalization in our health facilities. The objective of this study was to describe the epidemiological, clinical, paraclinical and evolutionary aspects of extra pulmonary tuberculosis (EPT) at the Abass Ndao Hospital Center. Patients and Methods: This was a descriptive cross-sectional study conducted over a period of 11 years (January 1, 2010 to December 30, 2021). All patients with extrapulmonary tuberculosis hospitalized in the department of internal medicine during the recruitment period were included. Results: Fifty-two (52) patients were collected. The year 2019 recorded the most cases 23.08% (n = 20). The mean age of the patients was 40.56 ± 18.24 years. The age group 20 - 34 years 42.31% (n = 22) was the most represented. Females were in the majority 61.54% (n = 32) with a sex ratio (M/F) was 0.63. Housewives were in the majority 40.38% (n = 21). 60.87% of the cases (n = 14) came from a health facility. 38.46% of the cases had been infected. 21.74% (n = 9) were smokers. The reasons for consultation were dominated by fever (67.44%), AEG (62.79%) and cough (41.86%). Eighteen patients (40.91%) had fever. The mean time to consultation was 77.37 ± 90.3 days with extremes of 3 and 365 days. The median was 45 days. More than half of the patients 61.90% (n = 26) had anemia. Positive retroviral serology was noted in 21.43% of cases. All patients had a CRP greater than 6. More than half of the patients 51.92% (n = 27) had multifocal tuberculosis. The peritoneum 44.23% (n = 23) was the main organ affected. The average hospital stay was 9.8 ± 4.9 days with extremes of 1 and 19 days. All patients had received the protocol in force at the national level. Death was noted in 4 patients (9.52%). Conclusion: EPT is characterized in our context by a notorious diagnostic difficulty due to the multiplicity of clinical presentations, the complexity of explorations, and the problems of differential diagnosis notably with other granulomatosis, systemic lupus and cancers. This difficulty is reflected in the low rate of diagnosis with a paraclinical argument of certainty and in the long diagnostic delays.
文摘<b>Background: </b>Many inflammatory cells, cytokines, acute phase reactants as well as platelets are recruited in the battle against the invading mycobacterium. As a result, alterations in the hematologic profile of infected patients are anticipated.<b> Objectives: </b>The primary objective was to investigate the various hematologic characteristics of patients with active tuberculosis. The secondary objective was to study the correlation between such hematologic characteristics and the type of tuberculosis including pulmonary, extra-pulmonary, and disseminated. <b>Methods: </b>This was a retrospective, descriptive study investigating the hematological findings in adult patients (aged 18 years or older) with active, bacteriologically-confirmed tuberculosis infection. <b>Results: </b>Among the 605 confirmed active tuberculosis cases, 465 (78.8%) were pulmonary, 104 (17.6%) extra-pulmonary, and 21 (3.6%) disseminated type. The mean age at diagnosis was 33.4 ± 11.4 years and males constituted 80.2% of cases. Peripheral leukocytosis was observed in 177 (30.1%) and leukopenia in 7 (1.2%) (Pulmonary type of tuberculosis was significantly associated with leukocytosis (P = 0.000)). Neutrophilia, lymphocytosis, monocytosis, eosinophilia, and basophilia were observed in 15.3%, 3.1%, 10.4%, 6.3% and 4.7% respectively. Thrombocytopenia and thrombocytosis were observed in 3.9% and 26.7% respectively. Anemia was observed in 44.8% of all cases with 4.4% had severe anemia and 60.3% had anemia of chronic diseases. Erythrocyte sedimentation rate was high in 77.2% of cases and ≥100 mm/hr in 5%. C-reactive protein was high in 93.4% and it exceeded 40 mg/L in 69.3%. <b>Conclusion: </b>There is a wide range of variability in the leukocyte and differential leukocyte abnormalities observed in patients with active tuberculosis. Leukocytosis can be seen in one-third of patients with pulmonary tuberculosis. Anemia of chronic diseases is the most common type of anemia observed in tuberculosis patients. Erythrocyte sedimentation rate and C-reactive protein are elevated in the majority of patients with active tuberculosis. Levels of the sedimentation rate can be useful indices to determine the extent of the disease.
文摘Despite the efforts made to fight the tuberculosis, <i><i><span style="font-family:Verdana;">Mycobacterium tuberculosis</span></i><span style="font-family:Verdana;"></span></i> still remains a public health problem, particularly for low-income countries. According to the World Health Organization data, our country, Mali has detected only half of the 10,385 cases of tuberculosis expected for 2014 for a population of 17,309,000 inhabitants. The objective of this present work was to describe the different clinical aspects and the epidemiology of tuberculosis at Hospital Sominé Dolo <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">in</span></span></span><span><span><span style="font-family:;" "=""><span style="font-family:Verdana;"> Mopti. We performed a retro-prospective and descriptive of tuberculosis cases diagnosed in our department of medicine between May 2016 and August 2018. A total of 96 tuberculosis cases were recorded, <i></i></span><i><i><span style="font-family:Verdana;">i.e</span></i><span style="font-family:Verdana;">.</span></i> 4.6% and 1.0% for hospitalizations and consultations patterns, respectively. The median of age was 41 with extremes from 5 to 80 years. The age group [31</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span><span><span style="font-family:;" "=""><span style="font-family:Verdana;">40 years] was the most affected with 20.8%. Men and women were affected in identical proportions, <i></i></span><i><i><span style="font-family:Verdana;">i.e</span></i><span style="font-family:Verdana;">.</span></i> 50%. Pulmonary locations were the most frequent with 55.2%. Pleural tuberculosis was far the most frequent of the extra-pulmonary forms with 24.0% followed by the peritoneal and bone localization with 6.3% each. The majority of patients were followed on an outpatient basis, <i></i></span><i><i><span style="font-family:Verdana;">i.e</span></i><span style="font-family:Verdana;">.</span></i> 90.6%. The disease lethality was 7.3%. Our data show that the cases of extra</span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">pulmonary tuberculosis are in an increasing proportion and their diagnosis confirmation remains difficult in our context.</span></span></span>
基金This work was supported by:Federico Foundation and FundacaoFaculdade de Medicina to S.K.S.
文摘Objective: With scant studies in the literature, little is known about the risk factors for tuberculosis in patients with dermatomyositis/polymyositis. Therefore, the aim of the present study was to analyze the predictive factors for tuberculosis development in dermatomyositis/polymyositis. Methods: This single-center, retrospective, cohort study initially included 290 patients with dermatomyositis/polymyositis, from 2002 to 2016. Tuberculosis (pulmonary and/or extra-pulmonary) was confirmed after dermatomyositis/polymyositis diagnosis in 12 patients (4.1%) (Tuberculosis+ group). For the control group (Tuberculosis−), 24 patients without tuberculosis were arbitrarily selected in the same period and matched for age, ethnicity, gender, age at disease diagnosis, disease duration and type (dermatomyositis or polymyositis). Results: Tuberculosis occurred for a median of 16 months after dermatomyositis/polymyositis diagnosis. Clinical, laboratory and treatment features were similar in Tuberculosis+ and Tuberculosis−groups (P > 0.05). However, previous pulmonary fibrosis in dermatomyositis/polymyositis was more prevalent in the Tuberculosis+ group (41.7 vs. 8.3%;P = 0.029). Moreover, on a multivariate logistic regression model, pulmonary fibrosis was significantly associated with Tuberculosis (Odds ratio: 9.59, 95% confidence interval: 1.17 - 78.82). Tuberculosis affected 3 dermatomyositis cases for every 1 polymyositis case, with predominantly pulmonary followed by extra-pulmonary involvement (pleura, cutaneous, muscular, joint, soft tissue and hematologic). Two or more sites were affected in 41.7% of cases. Conclusions: Previous pulmonary fibrosis in dermatomyositis/polymyositis was a predictive factor associated with tuberculosis development. Further studies are needed to confirm these results.
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 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.
文摘To assess the effectiveness of vaccination in contaminated environments,this study introduces a modeling framework that encompasses two transmission routes,namely direct human-to-human contact and indirect human-to-environment contact,as well as the implementation of new M72/AS01_(E)vaccine.Motivated by this,a coupled age-structured tuberculosis(TB)model is proposed.Its well-posedness requirement is verified using the integrated semigroup theory.Furthermore,this study presents a comprehensive analysis of threshold dynamics associated with the proposed model.Specifically,the global stability of the disease-free and positive steady states is demonstrated by employing Lyapunov functionals.Lastly,the effects of the vaccination with M72/AS01_(E)and contaminated environments on TB control are numerically simulated.Experimental results indicate that high concentrations of Mycobacterium tuberculosis in contaminated environments may somewhat impede TB control efforts,but that large-scale deployment of new vaccine could significantly reduce the prevalence of TB.
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.
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Among critically ill patients,severe pulmonary and extrapulmonary tuberculosis has high morbidity and mortality.Yet,it is a diagnostic challenge given its nonspecific clinical symptoms and signs in early stages of the disease.In addition,management of severe pulmonary and extrapulmonary tuberculosis is complicated given the high risk of drug-drug interactions,drug-disease interactions,and adverse drug reactions.To help clinicians acquire an up-to-date approach to severe tuberculosis,this paper will provide a narrative review of contemporary diagnosis and management of severe pulmonary and extrapulmonary tuberculosis in critically ill patients.
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.
