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
Today, tuberculosis (TB) remains a global public health threat associated with significantly high rates of morbidity and mortality. The World Health Organization's (WHO) Global Tuberculosis Report 2018[1] has repo...Today, tuberculosis (TB) remains a global public health threat associated with significantly high rates of morbidity and mortality. The World Health Organization's (WHO) Global Tuberculosis Report 2018[1] has reported that in 2017, 10.0 million people across the world had developed TB diseases that resulted in an estimated 1.6 million deaths, and 889, 000 people developed TB in China that led to 39, 000 TB-related deaths. Therefore, rapid and accurate detection of Mycobacterium tuberculosis (MTB) is important for initiating early treatment and reducing mortality. Traditional diagnostic methods for pulmonary TB incorporate chest radiography and sputum smear microscopy;however, several cases of tuberculosis go undiagnosed because of the low sensitivity of smear microscopy[2].展开更多
Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of th...Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking.Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns.Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023–1.954;P=0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains.Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.展开更多
Bovine tuberculosis (bTB) is an endemic zoonosis significantly affects animal health in Burkina Faso. The primary causative agent is Mycobacterium tuberculosis (M. tuberculosis) complex, mainly M. bovis. Cattle are co...Bovine tuberculosis (bTB) is an endemic zoonosis significantly affects animal health in Burkina Faso. The primary causative agent is Mycobacterium tuberculosis (M. tuberculosis) complex, mainly M. bovis. Cattle are considered as natural reservoir of M. bovis. However, in Burkina Faso, the circulation of these strains remains poorly understood and documented. This study aimed to identify and characterize Mycobacterium strains from suspected carcasses during routine meat inspection at Bobo-Dioulasso refrigerated slaughterhouse. A prospective cross-sectional study was conducted from January 2021 to December 2022 on cases of seizures linked to suspected bovine tuberculosis. Microbiological and molecular analyzes were used for mycobacterial strain isolation and characterization. Out of 50 samples, 24% tested positive by microscopy and 12% by culture. Molecular analysis identified 6 strains of Mycobacteria, exclusively Mycobacterium bovis specifically the subspecies bovis (Mycobacterium bovis subsp bovis). In conclusion, M. bovis subsp bovis is the primary agent responsible for bovine tuberculosis in Bobo-Dioulasso. Continuous monitoring of mycobacterial strains is therefore necessary for the effective control of this pathology in the local cattle population.展开更多
Tuberculosis (TB) is a serious infectious disease and its control is considered a challenge, particularly among vulnerable populations such as prisoners. The prevalence of TB in prisons is an alarming public health pr...Tuberculosis (TB) is a serious infectious disease and its control is considered a challenge, particularly among vulnerable populations such as prisoners. The prevalence of TB in prisons is an alarming public health problem in many countries. The aim of this study is to describe the epidemiology of tuberculosis and the strategies for controlling this disease in the Chadian prison population. During the course of our study, the prevalence of tuberculosis in prisons was 9.64%. The age group between 55 years and over (43.33%) was the most represented in this study, and all patients were men with a frequency of 62.66%. The cross-tabulation of Culture_7H9G and Culture_7H9P showed that out of our total positive sample, we found a total of 87 positive strains and 63 negative strains. Our study shows that it is essential to know the prevalence of tuberculosis in all the country’s prisons. Indeed, this can serve as an indication of the need for action in prisons to reduce TB rates, in particular by improving the structure of prison environments, diagnosing new cases quickly and accurately, identifying drug-resistant strains and implementing effective, direct treatment observed in people with tuberculosis.展开更多
Background: Tuberculous endocarditis is a rare but serious complication of heart valve replacement surgery. We report the case of a 24-year-old patient, who presented with tuberculous endocarditis after mechanical mit...Background: Tuberculous endocarditis is a rare but serious complication of heart valve replacement surgery. We report the case of a 24-year-old patient, who presented with tuberculous endocarditis after mechanical mitral valve replacement, with a favorable clinical course following anti-tuberculosis treatment. Case Presentation: We report a 24-year-old male patient, admitted to the cardiac surgery department of the Fann Hospital (Dakar, Senegal), for the management of severe mixed (rheumatic and endocarditic) mitral insufficiency with associated tricuspid insufficiency. He had a history of recurrent angina and polyarthralgia in childhood, was hospitalized several times for refractory global cardiac decompensation, and for a suspected infective endocarditis a month before his admission. On admission, the clinical examination revealed signs suggestive of mitral and tricuspid insufficiency. Transthoracic echocardiography revealed severe post-endocarditic mitral insufficiency with A3 amputation, highly mobile 15 mm vegetations on the free edge of the large valve, moderate tricuspid insufficiency, and severe pulmonary artery hypertension. Mechanical mitral valve replacement and tricuspid valve annuloplasty using autologous pericardial strip were performed via median sternotomy. After ten days, the patient presented with global cardiac decompensation associated with a clinico-biological infectious syndrome, and tans-oesophageal echography revealed an abscess at the sinotubular junction, communicating with the aorta. A thoraco-abdomino-pelvic CT scan was done, which revealed a bilateral alveolar-interstitial syndrome with mediastinal lymphadenopathy. Anti-tuberculosis treatment with RHZE was initiated for 06 months. The clinical course was favorable. Conclusion: Tuberculous endocarditis in prostheses is a serious complication of heart valve replacement surgery, which may evolve favorably under medical treatment.展开更多
Background: The emergence of multidrug resistant tuberculosis (MDR-TB) and extensively drug- resistant tuberculosis (XDR-TB) has highlighted the need for early accurate detection and drug susceptibility. Objective: Th...Background: The emergence of multidrug resistant tuberculosis (MDR-TB) and extensively drug- resistant tuberculosis (XDR-TB) has highlighted the need for early accurate detection and drug susceptibility. Objective: The purpose of the present study was to evaluate the accuracy of GeneX-pert MTB/RIF assay for the detection of Mycobacterium tuberculosis and rifampicin resistance. Methodology: This cross sectional study was done in the Department of Microbiology at Sir Salimullah Medical College, Dhaka and National Institute of Chest Disease & Hospital (NIDCH), Dhaka during the period of January 2014 to December 2014 for a period of 1 (one) year. Sputum samples from suspected MDR-TB patients were collected by purposive sampling technique from OPD of Sir Salimullah Medical College (SSMC) and NIDCH. Microscopy, liquid culture in liquid MGIT 960 media and GeneXpert MTB/RIF were done for MTB diagnosis and detection of rifampicin resistance. MGIT 960 media were also used for determination of drug resistance. Result: Liquid culture yielded higher growth (68%) from 100 samples while GeneXpert MTB assay showed similar result (67% positive and 33% negative). Drug susceptibility test in MGIT 960 media showed that out of 68 positive cases Rifampicin resistant cases were 15 (22.05%) whereas GeneXpert MTB assay detected 14 (20.89%) were Rifampicin resistant out of 67 MTB positive samples. When compared to liquid culture the calculated sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and accuracy of GeneXpert MTB were 98.52%, 100%, 96.96%, 100% and 99%. Conclusion: GeneXpert MTB/RIF assay is high detection rate of pulmonary tuberculosis and multidrug resistant tuberculosis.展开更多
Objective:To analyze the mutation characteristics of inhA and katG genes in isoniazid-resistant Mycobacterium tuberculosis in Xinjiang.Methods:The katG and inhA in 148 strains of isoniazid-resistant Mycobacterium tube...Objective:To analyze the mutation characteristics of inhA and katG genes in isoniazid-resistant Mycobacterium tuberculosis in Xinjiang.Methods:The katG and inhA in 148 strains of isoniazid-resistant Mycobacterium tuberculosis were amplified through fluorescence quantitative PCR,and the amplified products were sequenced and compared.Results:The inhA gene mutation rate of 148 strains of isoniazid-resistant mycobacterium tuberculosis was 13.51%(20/148),among which the inhA gene mutation rate among patients of Han,Uygur,and Kazakh ethnicity were 15.87%,13.21%,and 17.65%,respectively.There was no significant difference in the inhA mutation rate among nationalities(c^(2)=2.897,P>0.05).The mutation rate of the katG gene was 84.46%(125/148),among which the mutation rates of patients of Han,Uyghur,and Kazak ethnicities were 82.54%,84.91%,and 76.47%,respectively.The Hui and other ethnic groups were all affected by the katG gene mutation.There was no significant difference in the mutation rate of the katG gene among different ethnicities(c^(2)=3.772,P>0.05).The mutation rates of the inhA gene in southern Xinjiang,northern Xinjiang,and other provinces were 18.60%,9.28%,and 37.50%,respectively.The mutation rates of the inhA gene in different regions were statistically different(c^(2)=6.381,P<0.05).There was no significant difference in the inhA mutation rate between patients from southern and northern Xinjiang(c^(2)=2.214,P>0.05)and between southern Xinjiang and other provinces(c^(2)=1.424,P>0.05).However,the mutation rate of the inhA gene in patients from other provinces was higher than that in northern Xinjiang(c^(2)=5.539,P<0.05).The mutation rates of the katG gene in southern Xinjiang,northern Xinjiang,and other provinces were 81.40%,87.63%,and 62.50%,respectively.There was no significant difference in the mutation rates of the katG gene among different regions(c^(2)=3.989,P>0.05).Conclusion:katG gene mutation was predominant in isoniazid-resistant tuberculosis patients in Xinjiang Uygur Autonomous Region,and inhA and katG gene mutation were no different among different ethnic groups.展开更多
The aim of this study was to investigate the usefulness of combining profiles obtained by using a line probe assay (LPA) originally intended to characterize the resistance of two major anti-tuberculosis drugs to the a...The aim of this study was to investigate the usefulness of combining profiles obtained by using a line probe assay (LPA) originally intended to characterize the resistance of two major anti-tuberculosis drugs to the association of spoligotyping and MIRU-VNTR, in order to improve its discriminatory power. For this purpose, 74 strains of Mycobacterium tuberculosis belonging to the same cluster after spoligotyping were further typed by using the 24 loci MIRU/VNTR. These strains were then tested by the GenoType MTBDRplus, and profiles obtained were analyzed within previously obtained clusters. The combination of spoligotying and MIRU-VNTR led to the consolidation of 56 of them (75.7%) in 9 clusters. Most of the strains (54, 96.4%) were multidrug resistant (MDR). From the 9 initial clusters, the addition of GenoType MTBDRplus helped to define 26 profiles including 11 unique profiles, and 3 original clusters remained undifferentiated. Results obtained express the relevance of combining this method which improved quite significantly the discriminatory power in typing Mycobacterium tuberculosis.展开更多
Objective Tuberculosis remains a severe public health issue, and the Beijing family of mycobacterium tuberculosis （M. tuberculosis） is widespread in East Asia, especially in some areas in China, like Beijing and Tia...Objective Tuberculosis remains a severe public health issue, and the Beijing family of mycobacterium tuberculosis （M. tuberculosis） is widespread in East Asia, especially in some areas in China, like Beijing and Tianjin. This study aimed at determining the mutation patterns of drug-resistant Beijing strains of M. tuberculosis isolated from Tianjin, China. Methods A total of 822 M. tuberculosis isolates were screened for drug resistance by an absolute concentration method and the genotype was identified by PCR. 169 drug-resistant isolates of the Beijing family were analyzed for the potential mutations in the rpoB, katG, inhA promoter region and in rpsL, rrs and embB genes, which are associated with resistance to rifampin （RFP）, isoniazid （INH）, streptomycin （SM） and ethambutol （EMB） respectively by PCR and DNA sequencing. Results Fifty-eight out of 63 RFP-resistant isolates were found to carry the mutations within the 81-bp RFP resistance determining region （RRDR） of the rpoB gene and the most frequent mutations occurred at codon 531 （44.4%）, 526 （28.6%）, and 516 （7.9%） respectively. 16 mutation pattems affecting 12 different codons around the RRDR of rpoB were found. Of 116 INH-resistant isolates, 56 （48.3%） had the mutation of katG 315 （AGC→ACC） （Ser→Thr）, 3 （2.6%） carried S315N （AGC→AAC） and 27 （16.0%） had the mutation of inhA-15A→T. 84 out of 122 SM-resistant isolates （68.9%） displayed mutations at the codons 43 or 88 with AAG→AGG （Lys→Arg） of the rpsL gene and 22 （18.0%） with the mutations at positions 513A→C, 516C→T or 905 A→G in the rrs gene. Of 34 EMB-resistant isolates, 6 had mutation with M306V （ATG→GTG）, 3 with M306I （ATG→ATT）, 1 with M306I （ATG→ATA）, 1 with D328Y （GAT→TAT）, 1 with V348L （GTC→CTC）, and 1 with G406S （GGC→AGC） in the embB gene. Conelusion These novel findings extended our understanding of resistance-related mutations in the Beijing strains of M. tuberculosis and may provide a scientific basis for development of new strategies for diagnosis and control of tuberculosis in China and other countries where Beijing strains are prevalent.展开更多
Objective:To study the effect of immune formulation-assisted conventional therapy on antiinfective ability of multidrug-resistant Mycobacterium tuberculous infection mice.Methods:BALB/c mice were used as experimental ...Objective:To study the effect of immune formulation-assisted conventional therapy on antiinfective ability of multidrug-resistant Mycobacterium tuberculous infection mice.Methods:BALB/c mice were used as experimental animals,multidrug-resistant Mycobacterium tuberculosis infection models were built,randomly divided into model group,moxifloxacin group,thymopentin group and combined treatment group and given corresponding drug intervention,and then colony numbers in the spleen and lung,T lymphocyte subset contents and programmed death-1(PD-1) expression levels in peripheral blood were detected.Results:Colony numbers in lung and spleen of moxifloxacin group and thymopentin group were significantly lower than those of model group and colony numbers in lung and spleen of combined treatment group were significantly lower than those of moxifloxacin group and thymopentin group:contents of CD3^+CD4^+T cells,Thl and Thl7 in peripheral blood of moxifloxacin group and thymopentin group were higher than dtose of model group,and contents of CD3^+CD8^+T cells.Th2 and Treg were lower than those of model group;contents of CD3^+CD4^+T cells.Th 1 and Th 17 in peripheral blood of combined treatment group were higher than those of moxifloxacin group and thymopentin group,and contents of CD3^+CD8^+T cells.Th2 and Treg were lower than those of moxifloxacin group and thymopentin group:PD-I expression levels on T lymphocyte,B lymphocyte and monocyte surface in peripheral blood of moxifloxacin group and thymopentin group were lower than those of model group,and PD-I expression levels on T lymphocyte.B lymphocyte and monocyte surface in peripheral blood of combined treatment group were lower than those of moxifloxacin group and thymopentin group.Conclusions:Immune formulation thymopentin can enhance the anti-infective ability of multidrug-resistant Mycobacterium tuberculosis infection mice,decrease bacterial load in lung and spleen,and enhance immune function.展开更多
Solid organ transplantation(SOT)is the best treatment option for end-stage organ disease.Newer immunosuppressive agents have reduced the incidence of graft rejection but have increased the risk of infection,particular...Solid organ transplantation(SOT)is the best treatment option for end-stage organ disease.Newer immunosuppressive agents have reduced the incidence of graft rejection but have increased the risk of infection,particularly due to the reactivation of latent infections due to opportunistic agents such as Mycobacterium tuberculosis.Active tuberculosis(TB)after SOT is a significant cause of morbidity and mortality.Most cases of posttransplant TB are secondary to reactivation of latent tuberculosis infection(LTBI)due to the effects of long-term immunosuppressive therapy.Risk minimization strategies have been developed to diagnose LTBI and initiate treatment prior to transplantation.Isoniazid with vitamin B6 supplementation is the treatment of choice.However,liver transplantation(LT)candidates and recipients have an increased risk of isoniazid-induced liver toxicity,leading to lower treatment completion rates than in other SOT populations.Fluoroquinolones(FQs)exhibit good in vitro antimycobacterial activity and a lower risk of drug-induced liver injury than isoniazid.In the present review,we highlight the disease burden posed by posttransplant TB and summarize the emerging clinical evidence supporting the use of FQs for the treatment of LTBI in LT recipients and candidates.展开更多
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.
基金supported by the National Science and Technology Major Project [2018ZX10103001]the National Natural Science Foundation of China [8161101571]
文摘Today, tuberculosis (TB) remains a global public health threat associated with significantly high rates of morbidity and mortality. The World Health Organization's (WHO) Global Tuberculosis Report 2018[1] has reported that in 2017, 10.0 million people across the world had developed TB diseases that resulted in an estimated 1.6 million deaths, and 889, 000 people developed TB in China that led to 39, 000 TB-related deaths. Therefore, rapid and accurate detection of Mycobacterium tuberculosis (MTB) is important for initiating early treatment and reducing mortality. Traditional diagnostic methods for pulmonary TB incorporate chest radiography and sputum smear microscopy;however, several cases of tuberculosis go undiagnosed because of the low sensitivity of smear microscopy[2].
基金funded by the National Key R&D Program of China [2022YFC2305200]Natural Science Foundation of Xinjiang Uygur Autonomous Region [2021A01D145 and 2022D01A115]Applied Technology Research and Development Programing Project of Kashgar Prefecture [KS2021031 and KS2021034]。
文摘Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking.Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns.Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023–1.954;P=0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains.Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.
文摘Bovine tuberculosis (bTB) is an endemic zoonosis significantly affects animal health in Burkina Faso. The primary causative agent is Mycobacterium tuberculosis (M. tuberculosis) complex, mainly M. bovis. Cattle are considered as natural reservoir of M. bovis. However, in Burkina Faso, the circulation of these strains remains poorly understood and documented. This study aimed to identify and characterize Mycobacterium strains from suspected carcasses during routine meat inspection at Bobo-Dioulasso refrigerated slaughterhouse. A prospective cross-sectional study was conducted from January 2021 to December 2022 on cases of seizures linked to suspected bovine tuberculosis. Microbiological and molecular analyzes were used for mycobacterial strain isolation and characterization. Out of 50 samples, 24% tested positive by microscopy and 12% by culture. Molecular analysis identified 6 strains of Mycobacteria, exclusively Mycobacterium bovis specifically the subspecies bovis (Mycobacterium bovis subsp bovis). In conclusion, M. bovis subsp bovis is the primary agent responsible for bovine tuberculosis in Bobo-Dioulasso. Continuous monitoring of mycobacterial strains is therefore necessary for the effective control of this pathology in the local cattle population.
文摘Tuberculosis (TB) is a serious infectious disease and its control is considered a challenge, particularly among vulnerable populations such as prisoners. The prevalence of TB in prisons is an alarming public health problem in many countries. The aim of this study is to describe the epidemiology of tuberculosis and the strategies for controlling this disease in the Chadian prison population. During the course of our study, the prevalence of tuberculosis in prisons was 9.64%. The age group between 55 years and over (43.33%) was the most represented in this study, and all patients were men with a frequency of 62.66%. The cross-tabulation of Culture_7H9G and Culture_7H9P showed that out of our total positive sample, we found a total of 87 positive strains and 63 negative strains. Our study shows that it is essential to know the prevalence of tuberculosis in all the country’s prisons. Indeed, this can serve as an indication of the need for action in prisons to reduce TB rates, in particular by improving the structure of prison environments, diagnosing new cases quickly and accurately, identifying drug-resistant strains and implementing effective, direct treatment observed in people with tuberculosis.
文摘Background: Tuberculous endocarditis is a rare but serious complication of heart valve replacement surgery. We report the case of a 24-year-old patient, who presented with tuberculous endocarditis after mechanical mitral valve replacement, with a favorable clinical course following anti-tuberculosis treatment. Case Presentation: We report a 24-year-old male patient, admitted to the cardiac surgery department of the Fann Hospital (Dakar, Senegal), for the management of severe mixed (rheumatic and endocarditic) mitral insufficiency with associated tricuspid insufficiency. He had a history of recurrent angina and polyarthralgia in childhood, was hospitalized several times for refractory global cardiac decompensation, and for a suspected infective endocarditis a month before his admission. On admission, the clinical examination revealed signs suggestive of mitral and tricuspid insufficiency. Transthoracic echocardiography revealed severe post-endocarditic mitral insufficiency with A3 amputation, highly mobile 15 mm vegetations on the free edge of the large valve, moderate tricuspid insufficiency, and severe pulmonary artery hypertension. Mechanical mitral valve replacement and tricuspid valve annuloplasty using autologous pericardial strip were performed via median sternotomy. After ten days, the patient presented with global cardiac decompensation associated with a clinico-biological infectious syndrome, and tans-oesophageal echography revealed an abscess at the sinotubular junction, communicating with the aorta. A thoraco-abdomino-pelvic CT scan was done, which revealed a bilateral alveolar-interstitial syndrome with mediastinal lymphadenopathy. Anti-tuberculosis treatment with RHZE was initiated for 06 months. The clinical course was favorable. Conclusion: Tuberculous endocarditis in prostheses is a serious complication of heart valve replacement surgery, which may evolve favorably under medical treatment.
文摘Background: The emergence of multidrug resistant tuberculosis (MDR-TB) and extensively drug- resistant tuberculosis (XDR-TB) has highlighted the need for early accurate detection and drug susceptibility. Objective: The purpose of the present study was to evaluate the accuracy of GeneX-pert MTB/RIF assay for the detection of Mycobacterium tuberculosis and rifampicin resistance. Methodology: This cross sectional study was done in the Department of Microbiology at Sir Salimullah Medical College, Dhaka and National Institute of Chest Disease & Hospital (NIDCH), Dhaka during the period of January 2014 to December 2014 for a period of 1 (one) year. Sputum samples from suspected MDR-TB patients were collected by purposive sampling technique from OPD of Sir Salimullah Medical College (SSMC) and NIDCH. Microscopy, liquid culture in liquid MGIT 960 media and GeneXpert MTB/RIF were done for MTB diagnosis and detection of rifampicin resistance. MGIT 960 media were also used for determination of drug resistance. Result: Liquid culture yielded higher growth (68%) from 100 samples while GeneXpert MTB assay showed similar result (67% positive and 33% negative). Drug susceptibility test in MGIT 960 media showed that out of 68 positive cases Rifampicin resistant cases were 15 (22.05%) whereas GeneXpert MTB assay detected 14 (20.89%) were Rifampicin resistant out of 67 MTB positive samples. When compared to liquid culture the calculated sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and accuracy of GeneXpert MTB were 98.52%, 100%, 96.96%, 100% and 99%. Conclusion: GeneXpert MTB/RIF assay is high detection rate of pulmonary tuberculosis and multidrug resistant tuberculosis.
基金Xinjiang Uygur Autonomous Region Health Youth Medical Science and Technology Talents Special Project(Project number:WJW-202116)。
文摘Objective:To analyze the mutation characteristics of inhA and katG genes in isoniazid-resistant Mycobacterium tuberculosis in Xinjiang.Methods:The katG and inhA in 148 strains of isoniazid-resistant Mycobacterium tuberculosis were amplified through fluorescence quantitative PCR,and the amplified products were sequenced and compared.Results:The inhA gene mutation rate of 148 strains of isoniazid-resistant mycobacterium tuberculosis was 13.51%(20/148),among which the inhA gene mutation rate among patients of Han,Uygur,and Kazakh ethnicity were 15.87%,13.21%,and 17.65%,respectively.There was no significant difference in the inhA mutation rate among nationalities(c^(2)=2.897,P>0.05).The mutation rate of the katG gene was 84.46%(125/148),among which the mutation rates of patients of Han,Uyghur,and Kazak ethnicities were 82.54%,84.91%,and 76.47%,respectively.The Hui and other ethnic groups were all affected by the katG gene mutation.There was no significant difference in the mutation rate of the katG gene among different ethnicities(c^(2)=3.772,P>0.05).The mutation rates of the inhA gene in southern Xinjiang,northern Xinjiang,and other provinces were 18.60%,9.28%,and 37.50%,respectively.The mutation rates of the inhA gene in different regions were statistically different(c^(2)=6.381,P<0.05).There was no significant difference in the inhA mutation rate between patients from southern and northern Xinjiang(c^(2)=2.214,P>0.05)and between southern Xinjiang and other provinces(c^(2)=1.424,P>0.05).However,the mutation rate of the inhA gene in patients from other provinces was higher than that in northern Xinjiang(c^(2)=5.539,P<0.05).The mutation rates of the katG gene in southern Xinjiang,northern Xinjiang,and other provinces were 81.40%,87.63%,and 62.50%,respectively.There was no significant difference in the mutation rates of the katG gene among different regions(c^(2)=3.989,P>0.05).Conclusion:katG gene mutation was predominant in isoniazid-resistant tuberculosis patients in Xinjiang Uygur Autonomous Region,and inhA and katG gene mutation were no different among different ethnic groups.
基金the support of the European Respiratory Society,Fellowship STRTF 413-2011.
文摘The aim of this study was to investigate the usefulness of combining profiles obtained by using a line probe assay (LPA) originally intended to characterize the resistance of two major anti-tuberculosis drugs to the association of spoligotyping and MIRU-VNTR, in order to improve its discriminatory power. For this purpose, 74 strains of Mycobacterium tuberculosis belonging to the same cluster after spoligotyping were further typed by using the 24 loci MIRU/VNTR. These strains were then tested by the GenoType MTBDRplus, and profiles obtained were analyzed within previously obtained clusters. The combination of spoligotying and MIRU-VNTR led to the consolidation of 56 of them (75.7%) in 9 clusters. Most of the strains (54, 96.4%) were multidrug resistant (MDR). From the 9 initial clusters, the addition of GenoType MTBDRplus helped to define 26 profiles including 11 unique profiles, and 3 original clusters remained undifferentiated. Results obtained express the relevance of combining this method which improved quite significantly the discriminatory power in typing Mycobacterium tuberculosis.
基金supported by National Science Key Grant(2008ZX10003-009).
文摘Objective Tuberculosis remains a severe public health issue, and the Beijing family of mycobacterium tuberculosis （M. tuberculosis） is widespread in East Asia, especially in some areas in China, like Beijing and Tianjin. This study aimed at determining the mutation patterns of drug-resistant Beijing strains of M. tuberculosis isolated from Tianjin, China. Methods A total of 822 M. tuberculosis isolates were screened for drug resistance by an absolute concentration method and the genotype was identified by PCR. 169 drug-resistant isolates of the Beijing family were analyzed for the potential mutations in the rpoB, katG, inhA promoter region and in rpsL, rrs and embB genes, which are associated with resistance to rifampin （RFP）, isoniazid （INH）, streptomycin （SM） and ethambutol （EMB） respectively by PCR and DNA sequencing. Results Fifty-eight out of 63 RFP-resistant isolates were found to carry the mutations within the 81-bp RFP resistance determining region （RRDR） of the rpoB gene and the most frequent mutations occurred at codon 531 （44.4%）, 526 （28.6%）, and 516 （7.9%） respectively. 16 mutation pattems affecting 12 different codons around the RRDR of rpoB were found. Of 116 INH-resistant isolates, 56 （48.3%） had the mutation of katG 315 （AGC→ACC） （Ser→Thr）, 3 （2.6%） carried S315N （AGC→AAC） and 27 （16.0%） had the mutation of inhA-15A→T. 84 out of 122 SM-resistant isolates （68.9%） displayed mutations at the codons 43 or 88 with AAG→AGG （Lys→Arg） of the rpsL gene and 22 （18.0%） with the mutations at positions 513A→C, 516C→T or 905 A→G in the rrs gene. Of 34 EMB-resistant isolates, 6 had mutation with M306V （ATG→GTG）, 3 with M306I （ATG→ATT）, 1 with M306I （ATG→ATA）, 1 with D328Y （GAT→TAT）, 1 with V348L （GTC→CTC）, and 1 with G406S （GGC→AGC） in the embB gene. Conelusion These novel findings extended our understanding of resistance-related mutations in the Beijing strains of M. tuberculosis and may provide a scientific basis for development of new strategies for diagnosis and control of tuberculosis in China and other countries where Beijing strains are prevalent.
基金Science and Technology Development Program of Linyi City(No:201113018)
文摘Objective:To study the effect of immune formulation-assisted conventional therapy on antiinfective ability of multidrug-resistant Mycobacterium tuberculous infection mice.Methods:BALB/c mice were used as experimental animals,multidrug-resistant Mycobacterium tuberculosis infection models were built,randomly divided into model group,moxifloxacin group,thymopentin group and combined treatment group and given corresponding drug intervention,and then colony numbers in the spleen and lung,T lymphocyte subset contents and programmed death-1(PD-1) expression levels in peripheral blood were detected.Results:Colony numbers in lung and spleen of moxifloxacin group and thymopentin group were significantly lower than those of model group and colony numbers in lung and spleen of combined treatment group were significantly lower than those of moxifloxacin group and thymopentin group:contents of CD3^+CD4^+T cells,Thl and Thl7 in peripheral blood of moxifloxacin group and thymopentin group were higher than dtose of model group,and contents of CD3^+CD8^+T cells.Th2 and Treg were lower than those of model group;contents of CD3^+CD4^+T cells.Th 1 and Th 17 in peripheral blood of combined treatment group were higher than those of moxifloxacin group and thymopentin group,and contents of CD3^+CD8^+T cells.Th2 and Treg were lower than those of moxifloxacin group and thymopentin group:PD-I expression levels on T lymphocyte,B lymphocyte and monocyte surface in peripheral blood of moxifloxacin group and thymopentin group were lower than those of model group,and PD-I expression levels on T lymphocyte.B lymphocyte and monocyte surface in peripheral blood of combined treatment group were lower than those of moxifloxacin group and thymopentin group.Conclusions:Immune formulation thymopentin can enhance the anti-infective ability of multidrug-resistant Mycobacterium tuberculosis infection mice,decrease bacterial load in lung and spleen,and enhance immune function.
基金“Plan Nacional de I+D+I”Instituto de Salud Carlos III(Fondo de Investigaciones Sanitarias [FIS] PI14/00174)+1 种基金ubdirección General de Redes y Centros de Investigación Cooperativa,Spanish Ministry of Science,Innovation and Universities,Spanish Network for Research in Infectious Diseases(REIPI RD16/0016)cofinanced by the European Development Regional Fund(EDRF)"A way to achieve Europe"
文摘Solid organ transplantation(SOT)is the best treatment option for end-stage organ disease.Newer immunosuppressive agents have reduced the incidence of graft rejection but have increased the risk of infection,particularly due to the reactivation of latent infections due to opportunistic agents such as Mycobacterium tuberculosis.Active tuberculosis(TB)after SOT is a significant cause of morbidity and mortality.Most cases of posttransplant TB are secondary to reactivation of latent tuberculosis infection(LTBI)due to the effects of long-term immunosuppressive therapy.Risk minimization strategies have been developed to diagnose LTBI and initiate treatment prior to transplantation.Isoniazid with vitamin B6 supplementation is the treatment of choice.However,liver transplantation(LT)candidates and recipients have an increased risk of isoniazid-induced liver toxicity,leading to lower treatment completion rates than in other SOT populations.Fluoroquinolones(FQs)exhibit good in vitro antimycobacterial activity and a lower risk of drug-induced liver injury than isoniazid.In the present review,we highlight the disease burden posed by posttransplant TB and summarize the emerging clinical evidence supporting the use of FQs for the treatment of LTBI in LT recipients and candidates.
