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1.
Artigo em Inglês | MEDLINE | ID: mdl-32520212

RESUMO

Drug resistant tuberculosis (DR-TB) is challenging particularly in developing countries. As such, a previous investigation gave the first insight into the mutational status of the Rifampicin Resistance Determining Region (RRDR) of rpoB gene among a restricted number of MTB patients' residents in the Northern Morocco. The purpose of this study was to investigate rpoB mutation types and frequencies associated with resistance to Rifampicin in a larger panel of MTB patients and to evaluate the usefulness of these mutations to improve the diagnosis of resistance to Rifampicin. A panel of 301 consecutive sputum samples belonging to patients suscpected of having TB from Northern Morocco was collected at the Pasteur Institute of Tangier between 2014-2017. Samples were subjected to conventionel microbiological tests. Evaluation of rpoB muational status was assessed by PCR amplification and sequencing of the RRDR of the rpoB gene. DST results showed that 26.4% of strains were MDR. Sequencing results reported single point mutations in 36 of 65 RIFR isolates of which two had two mutations. Aminoacid substitutions in the codon Ser531Leu occurred at the highest frequency (34.46%). Overall, 10 aminoacid substitutions have been registered, and the H526S substitution was reported for the first time. The present study highlighted that resistance to RIF is a reliable marker of MDR-TB, the common mutations successfully detected in the rpoB 531, rpoB526 and rpoB516 codons provide a foundation for the implementation of molecular approaches such as Hain and GeneXpert as a routine tests to detect DR-TB. However, considerable work is still necessary to identify extensive mutations associated with DR-TB.


Assuntos
Antituberculosos/farmacologia , Mutação/genética , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Rifampina/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto , Feminino , Genótipo , Humanos , Masculino , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase
2.
Medicine (Baltimore) ; 99(21): e20012, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481268

RESUMO

INTRODUCTION: Paradoxical reaction in tuberculosis (TB) is defined as the reappearance of general symptoms, aggravation of pre-existing diseases, or appearance of new lesions despite adequate anti-TB therapy. It may result from the hyperactivity of the immune response, resulting in an intense inflammation. There are few cases of vertebral TB reported as paradoxical reaction, mainly among immunocompetents patients. PATIENT CONCERNS: We describe a male immunocompetent patient with confirmed pulmonary and meningeal TB. He was readmitted after 60 days of adequate treatment, with vertebral TB and paravertebral abscess, despite clinical improvement of the other locations. We defined as an uncommon case of a paradoxical reaction, confirmed by nuclear magnetic resonance and molecular rapid test for TB. DIAGNOSIS: Mycobacterium tuberculosis (MTB) was detected in cerebrospinal fluid by molecular rapid test (Gene Xpert MTB/ rifampicina method). Sputum research and culture were positive for the same agent. Lumbosacral spine nuclear magnetic resonance revealed bone destruction from T8 to T11, and a paravertebral collection was found. Gene Xpert MTB/rifampicina and culture were positive for M tuberculosis in the drained material of the paravertebral abscess. INTERVENTIONS: The paravertebral abscess was drainage by tomography-guided. Treatment with 4 anti-TB drugs was extended for 60 days and 2 anti-TB drugs was maintained for 10 months. There was a complete clinical improvement. OUTCOME: After draining the paravertebral abscess, the patient progressively improved and was discharged for outpatient follow-up. He was on antituberculous drugs for 1 year; subsequently, complete resolution of the infection was reported. CONCLUSION: Paradoxical reaction may be a difficult diagnosis in immunocompetent patient. Vertebral TB as a paradoxical reaction is an uncommon presentation. Therapeutic failure or resistance to treatment should be ruled out to confirm the diagnosis of paradoxical reaction.


Assuntos
Antituberculosos/efeitos adversos , Imunocompetência/efeitos dos fármacos , Tuberculose Meníngea/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose da Coluna Vertebral/etiologia , Adulto , Antituberculosos/administração & dosagem , Antituberculosos/uso terapêutico , Humanos , Imagem por Ressonância Magnética , Masculino , Mycobacterium tuberculosis/isolamento & purificação , Sacro/diagnóstico por imagem , Sacro/patologia , Tuberculose Meníngea/complicações , Tuberculose Pulmonar/classificação , Tuberculose da Coluna Vertebral/líquido cefalorraquidiano
4.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(5): 764-769, 2020 May 10.
Artigo em Chinês | MEDLINE | ID: mdl-32447922

RESUMO

Objective: To investigate the drugs-sensitivity spectrum of multidrug-resistant tuberculosis (MDR-TB) in China and provide a scientific evidence for the drug selection in clinical therapy and the control of MDR-TB. Methods: A total of 167 strains of MDR-TB were included in this study. Every strain was genotyped by lysX gene sequencing and their sensitivity to 13 different anti-TB drugs was tested by using MicroDST(TM) and BACTEC(TM) MGIT 960(TM) liquid-culturing method. The association between drug resistance and genotypes as well as cross drug resistance was also analyzed. The results were analyzed by means of the comparison of enumeration data between two groups with χ(2) test. Results: The overall resistance rate of 167 MDR-TB strains to 11 anti-TB drugs, except isoniazide and rifampicin, was 95.81%, the rates of pre-extensive drug-resistance (pre-XDR) and extensive drug-resistance were 31.14%(52/167) and 6.59% (11/167), respectively. The streptomycin resistance rate of Beijing genotypes was significantly higher than that of the non-Beijing genotypes ( χ(2)=30.682, P<0.05), while the pre-XDR proportion in Beijing genotypes was lower than that in non-Beijing genotypes (χ(2)=5.332, P<0.05). The resistance rates of Ofloxacin and Pyrazinamide in the modern Beijing genotype were significantly higher than those in classical ones (χ(2)=4.105 and χ(2)=3.912, P<0.05). In addition, the cross-resistance rate to rifampicin and rifabutin was 86.23%. A significant difference in drug-resistance rate to rifabutin was seen among groups with different levels of rifampicin resistance (χ(2)=45.912, P<0.05). There was positive correlation not only between ofloxac resistance and moxifloxac resistance, but also between amikacin resistance and kanamycin resistance, with the coefficient of 0.87 and 0.91, respectively. Conclusions: In this study, we observed that there were high incidences of the resistance to 11 anti-TB drugs in 167 clinical MDR-TB strains and the cross resistance phenomena between drugs of the same type were quite serious. The majority of MDR-TB strains belonged to Beijing genotype, which was highly associated with streptomycin resistance.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos , China , Humanos , Testes de Sensibilidade Microbiana
5.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(5): 770-775, 2020 May 10.
Artigo em Chinês | MEDLINE | ID: mdl-32447923

RESUMO

Objective: To analyze the resistance mutational profiles of multi-drug resistant Mycobacterium tuberculosis in China and the correlation between major mutation types and genotypes based on the whole-genome sequencing data. Methods: Search and download of the genome-wide sequencing data of M. tuberculosis published in China by August 2019 on NCBI database were conducted. Mutation frequency of drug resistance-related gene loci based on whole-genome sequencing was used to predict the molecular susceptibility of strains, and the correlation between mutation types and genotypes was analyzed. Results: According to the results of molecular resistance and susceptibility profiles, 1 024 MDR strains were identified from 2 019 M. tuberculosis strains. The major mutation types of resistance-related genes to common drugs were katG S315T (73.2%, isoniazid), rpoB S450L (63.1%, rifampicin), rpsL K43R (70.0%, streptomycin), embB M306V (37.4%, ethambutol), pncA_promoter T (-11)C (7.9%, pyrazinamide), gyrA A90V (32.3%, fluoroquinolones), rrs A1401G (67.7%, second-line injection drugs), fabG1_promoter C (-15) T (87.0%, Ethionamide), folC I43T (30.4%, P-aminosalicylic acid). Among them, the frequencies of katG S315T, embB M306V, rpsL K43R, gyrA A90V in lineage 2 were significantly higher than those in lineage 4, and folC I43T was only found in lineage 2. The proportion of katG S315T was significantly higher in the ancient Beijing genotype compared to the modern genotype, in contrast, the proportion of rpsL K43R was significantly higher in modern Beijing genotype, the differences were significant (all P<0.05). Conclusions: The results showed the main mutation types of resistance-related genes of MDR strains to many commonly used anti-tuberculosis drugs in China based on whole-genome sequencing, providing a basis for the development of sensitive and specific rapid molecular detection methods. At the same time, it was also found that the major mutation types of MDR-related genes were related to the genotype of the strains.


Assuntos
Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos , China , Resistência a Medicamentos , Estudo de Associação Genômica Ampla , Humanos , Testes de Sensibilidade Microbiana , Mutação
6.
BMC Infect Dis ; 20(1): 344, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404119

RESUMO

BACKGROUND: The burden of drug resistant tuberculosis in Africa is largely driven by the emergence and spread of multidrug resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis strains. MDR-TB is defined as resistance to isoniazid and rifampicin, while XDR-TB is defined as MDR-TB with added resistance to any of the second line injectable drugs and any fluoroquinolone. The highest burden of drug resistant TB is seen in countries further experiencing an HIV epidemic. The molecular mechanisms of drug resistance as well as the evolution of drug resistant TB strains have been widely studied using various genotyping tools. The study aimed to analyse the drug resistant lineages in circulation and transmission dynamics of these lineages in Africa by describing outbreaks, nosocomial transmission and migration. Viewed as a whole, this can give a better insight into the transmission dynamics of drug resistant TB in Africa. METHODS: A systematic review was performed on peer reviewed original research extracted from PubMed reporting on the lineages associated with drug resistant TB from African countries, and their association with outbreaks, nosocomial transmission and migration. The search terms "Tuberculosis AND drug resistance AND Africa AND (spoligotyping OR molecular epidemiology OR IS6110 OR MIRU OR DNA fingerprinting OR RFLP OR VNTR OR WGS)" were used to identify relevant articles reporting the molecular epidemiology of drug resistant TB in Africa. RESULTS: Diverse genotypes are associated with drug resistant TB in Africa, with variations in strain predominance within the continent. Lineage 4 predominates across Africa demonstrating the ability of "modern strains" to adapt and spread easily. Most studies under review reported primary drug resistance as the predominant type of transmission. Drug resistant TB strains are associated with community and nosocomial outbreaks involving MDR- and XDR-TB strains. The under-use of molecular epidemiological tools is of concern, resulting in gaps in knowledge of the transmission dynamics of drug resistant TB on the continent. CONCLUSIONS: Genetic diversity of M. tuberculosis strains has been demonstrated across Africa implying that diverse genotypes are driving the epidemiology of drug resistant TB across the continent.


Assuntos
Epidemias , Tuberculose Extensivamente Resistente a Medicamentos/epidemiologia , Tuberculose Extensivamente Resistente a Medicamentos/transmissão , Epidemiologia Molecular/métodos , Mycobacterium tuberculosis/genética , África/epidemiologia , Antituberculosos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/microbiologia , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Polimorfismo de Fragmento de Restrição
7.
Cancer Radiother ; 24(4): 335-339, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32444284

RESUMO

Hodgkin lymphoma (HL) is a disease characterized by a high curability rate, and the treatment benefit-risk balance must be carefully addressed to achieve complete disease control with low risk of long-term toxicities. Most patients are treated with a combination of chemotherapy and radiotherapy, after disease staging and response to treatment evaluated by FDG PET/CT. We report the case of a 28-year-old patient concomitantly diagnosed of a Hodgkin lymphoma and active tuberculosis. Initial staging was difficult due to pulmonary and abdominal tuberculosis localization that induced FDG PET/CT hypermetabolism. Anti-tuberculosis treatment was first started, allowing secondary an early accurate Hodgkin lymphoma staging by FDG PET/CT. The patient was then treated by chemotherapy and radiotherapy. Helical TomoTherapy® was used with involved site (IS) irradiation volume was performed to decrease the high doses to organs-at-risk (OAR), especially lungs in this context of tuberculosis.


Assuntos
Doenças do Colo/tratamento farmacológico , Doença de Hodgkin/terapia , Tuberculose Gastrointestinal/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antituberculosos/uso terapêutico , Bleomicina/administração & dosagem , Doenças do Colo/complicações , Doenças do Colo/diagnóstico por imagem , Doenças do Colo/metabolismo , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Doença de Hodgkin/complicações , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/metabolismo , Humanos , Pulmão , Linfonodos/diagnóstico por imagem , Linfonodos/metabolismo , Masculino , Órgãos em Risco , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Radioterapia de Intensidade Modulada , Medição de Risco , Tomografia Computadorizada por Raios X , Tuberculose Gastrointestinal/complicações , Tuberculose Gastrointestinal/diagnóstico por imagem , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/diagnóstico por imagem , Vimblastina/administração & dosagem
8.
BMC Infect Dis ; 20(1): 365, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32448204

RESUMO

BACKGROUND: Mycobacterium fortuitum complex is a group of rapidly growing nontuberculous mycobacteria (NTM) associated with skin and soft-tissue infections after surgery or trauma. Treatment of NTM is challenging, due to resistance to multiple antimycobacterial agents. Bedaquiline is a diarylquinoline that inhibits mycobacterial ATP-synthase. The drug has recently been approved for the treatment of multidrug-resistant tuberculosis and evidence of its in vitro efficacy against NTM, including Mycobacterium fortuitum complex, has been published. CASE PRESENTATION: A 20-year-old Caucasian woman with chronic skin and soft tissue infection in the lower leg following a traffic accident in Vietnam underwent a tedious journey of healthcare visits, hospital admissions, empiric antimicrobial treatments, surgical debridement and plastic reconstruction before definite diagnosis of Mycobacterium fortuitum complex-infection was established by culture from a tissue biopsy and targeted antimycobacterial therapy was administered. Histopathological examination revealed granulomatous purulent inflammation, which strongly supported the diagnosis. Genotypic identification was performed and broth microdilution for susceptibility testing showed macrolide resistance. Five weeks of induction treatment with intravenous amikacin, imipenem / cilastin, and oral levofloxacin was administered, followed by all-oral treatment with bedaquiline combined with levofloxacin for four months, which was well-tolerated and led to persistent healing with scars but without signs of residual infection. CONCLUSIONS: Bedaquiline is a promising novel agent for NTM treatment, although clinical data are limited and trials evaluating efficacy, safety, and resistance of bedaquiline are required. To our knowledge, this is the first reported case of successful in vivo use of bedaquiline for a skin and soft tissue infection caused by Mycobacterium fortuitum complex.


Assuntos
Antituberculosos/uso terapêutico , Diarilquinolinas/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Mycobacterium fortuitum/efeitos dos fármacos , Dermatopatias Bacterianas/tratamento farmacológico , Pele/lesões , Infecções dos Tecidos Moles/tratamento farmacológico , Amicacina/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Humanos , Imipenem/uso terapêutico , Levofloxacino/uso terapêutico , Macrolídeos/efeitos adversos , Macrolídeos/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium fortuitum/genética , Lesões dos Tecidos Moles/microbiologia , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Vietnã , Adulto Jovem
9.
BMC Infect Dis ; 20(1): 318, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32357835

RESUMO

BACKGROUND: Sichuan is a province located in southwestern China, which have a higher incidence of tuberculosis (TB). This study aimed to analyze the epidemiological and clinical characteristics, as well as drug resistance in culture-confirmed children with Tuberculosis meningitis (TBM) in Southwest of China. METHODS: We performed a retrospective study on children (< 14 years old) with cerebrospinal fluid (CSF) culture-confirmed TBM between January 2013 and December 2018 at Public Health Clinical Center of Chengdu (PHCCC). Mycobacterium tuberculosis (MTB) drug sensitivity testing (DST) was performed using the MicroDST™ method. The age, gender, family history of tuberculosis, status of Bacillus Calmette-Guérin (BCG) vaccination, residential areas information, clinical, laboratory, and radiological features were recorded. Data were analyzed using SPSS Statistics Client 25.0, and the change in drug resistance rate was examined using the Cruskal-Wallis test. RESULTS: Among 319 patients clinically diagnosed with TBM, 42 (13.2%) were Mycobacterial culture positive. Their median age was nine years, and the distribution was equal among female and male patients. Among 42 patients who were enrolled in the study, 1/42 (2.38%) passed away. Children with TBM were concentrated in the minority areas of western Sichuan, where 34/42 (81.0%) patients with TBM belonged to ethnic minorities, and only 2/42 (4.76%) received BCG vaccination in the past. Chest X-rays changes were observed in all patients. Fever and headache were the most common presenting symptom. Thirty-five (83.3%) patients suffered from neck stiffness, and 30/42 (71.4%) had high CSF pressure. DST results showed that the resistance rate was high; resistance to any anti-tuberculosis drug (ATD) was observed in 13 (31.0%) patient isolates, while multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) were found in 2 (4.8%) and 1 (2.4%) patients, respectively. CONCLUSIONS: TBM among children in Southwest China was mainly concentrated in the minority areas of western Sichuan and more than 95% of patients did not receive BCG vaccination at birth. The most common symptoms were fever, headache, and neck stiffness and all patients had positive chest X-ray findings. In addition, high rates of drug resistance were found.


Assuntos
Tuberculose Extensivamente Resistente a Medicamentos/diagnóstico , Tuberculose Extensivamente Resistente a Medicamentos/epidemiologia , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Meníngea/diagnóstico , Tuberculose Meníngea/epidemiologia , Adolescente , Antituberculosos/uso terapêutico , Vacina BCG , Criança , Pré-Escolar , China/epidemiologia , Tuberculose Extensivamente Resistente a Medicamentos/líquido cefalorraquidiano , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Feminino , Humanos , Incidência , Lactente , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Tuberculose Meníngea/líquido cefalorraquidiano , Tuberculose Meníngea/tratamento farmacológico , Vacinação
10.
BMC Infect Dis ; 20(1): 321, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32370734

RESUMO

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening disorder characterized by an exacerbated but ineffective inflammatory response, which can be classified as primary and secondary HLH. HLH associated with Mycobacterium tuberculosis is uncommon. This case report accounted an immunocompetent patient who was confirmed to be Mycobacterium infection, or rather, highly suspected tuberculosis (TB) associated HLH, with a favorable outcome. CASE PRESENTATION: A 36-year-old man presented with persistent fever, pancytopenia, and hyperferritinemia. A bone marrow smear demonstrated hemophagocytosis, and pathological examination of lung biopsy was positive for acid-fast bacilli, which established the diagnosis of Mycobacterium infection and HLH. Then the patient treated successfully with anti-TB therapy, along with 8 weeks of etoposide. CONCLUSION: This case emphasizes that HLH should be kept in mind when clinicians encounter a patient with severe infection presenting with pancytopenia and hyperferritinemia. Given the high mortality, early diagnosis and appropriate therapy can provide patients with a favorable prognosis.


Assuntos
Antituberculosos/uso terapêutico , Etoposídeo/uso terapêutico , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Mycobacterium tuberculosis/isolamento & purificação , Inibidores da Topoisomerase II/uso terapêutico , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Adulto , Biópsia , Diagnóstico Precoce , Ferritinas/sangue , Seguimentos , Humanos , Hospedeiro Imunocomprometido , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/microbiologia , Masculino , Pancitopenia , Resultado do Tratamento , Tuberculose/diagnóstico , Tuberculose/microbiologia
11.
Mem Inst Oswaldo Cruz ; 115: e200055, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401997

RESUMO

BACKGROUND Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis, and the number of new cases of multidrug resistant TB (MDR-TB), pre extensively drug-resistant TB (pre-XDR-TB) and extensively drug-resistant TB (XDR-TB) has increased considerably worldwide. OBJECTIVES Herein, using 156 M. tuberculosis isolates from 106 patients previously classified as MDR or pre-XDR or XDR isolates, we investigated the genetic mutation profiles associated with phenotypic resistances in patients with MDR-TB, pre-XDR-TB and XDR-TB, treatment outcomes and resistance evolution. METHODS Molecular analyses were performed by partial sequencing of the rpoB, katG, gyrA, gyrB, rrs genes and analysis of the fabG-inhA promoter region. Clinical, epidemiologic and demographic data were obtained from the TB Notification database system of São Paulo (TB-WEB) and the Information System for Special Tuberculosis Treatments (SITE-TB). FINDINGS Drug resistance was attributed to previously known mutations and a novel Asp449Val mutation in gyrB was observed in four isolates from the same patient. Ten patients had more than one isolate evaluated and eight of these patients displayed resistance progression. MAIN CONCLUSIONS The present study is the first to report the frequency of mutations related to second-line drug resistance in MDR-TB, pre-XDR-TB and XDR-TB isolates. The results could lead to the improvement of available technologies for the rapid detection of drug resistant TB.


Assuntos
Antituberculosos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Mutação/genética , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adolescente , Adulto , Brasil , Tuberculose Extensivamente Resistente a Medicamentos/microbiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Fatores Socioeconômicos , Adulto Jovem
12.
Mem Inst Oswaldo Cruz ; 115: e190407, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32321155

RESUMO

BACKGROUND: Early diagnosis of tuberculosis (TB) and identification of strains of Mycobacterium tuberculosis resistant to anti-TB drugs are considered the main factors for disease control. OBJECTIVES: To standardise a real-time polymerase chain reaction (qPCR) assay technique and apply it to identify mutations involved in M. tuberculosis resistance to Isoniazid (INH) directly in Ziehl-Neelsen (ZN) stained slides. METHODS: Were analysed 55 independent DNA samples extracted from clinical isolates of M. tuberculosis by sequencing. For application in TB diagnosis resistance, 59 ZN-stained slides were used. The sensitivity, specificity and Kappa index, with a 95% confidence interval (CI95%), were determined. FINDINGS: The agreement between the tests was, for the katG target, the Kappa index of 0.89 (CI95%: 0.7-1.0). The sensitivity and specificity were 97.6% (CI95%: 87.7-99.9) and 91.7% (CI95%: 61.5-99.5), respectively. For inhA, the Kappa index was 0.92 (CI95%: 0.8-1.0), the sensitivity and specificity were 94.4% (CI95%: 72.7-99.8) and 97.3% (CI95%: 85.8-99.9), respectively. The use of ZN-stained slides for drug-resistant TB detection showed significant results when compared to other standard tests for drug resistance. MAIN CONCLUSIONS: qPCR genotyping proved to be an efficient method to detect genes that confer M. tuberculosis resistance to INH. Thus, qPCR genotyping may be an alternative instead of sequencing.


Assuntos
Antituberculosos/farmacologia , Farmacorresistência Bacteriana/genética , Marcadores Genéticos/genética , Isoniazida/farmacologia , Mutação/genética , Mycobacterium tuberculosis/genética , DNA Bacteriano/genética , Genótipo , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade
13.
Monaldi Arch Chest Dis ; 90(1)2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32231347

RESUMO

Drug-resistant tuberculosis (DR-TB) is a global challenge and a major contributor of death from anti-microbial resistance. With the main aim to determine factors contributing to treatment outcomes observed among DR-TB patients in the countries in Eastern Europe and Central Asia (EECA), a multi-method study was conducted in: Azerbaijan, Belarus, Romania, Tajikistan and Ukraine. Both quantitative and qualitative methodologies were used for data collection and analysis. The quantitative approaches included a desk review of documents related to the DR-TB responses and an analysis of clinical records of DR-TB patients in selected health facilities of the five countries. Qualitative methods included in-depth interviews with national TB programme (NTP) managers, other healthcare providers and non-governmental organizations (NGOs) workers, as well as interviews and Focus Group Discussions (FGDs) with DR-TB patients. The desk review of 38 reports identified as the main challenges to address DR-TB financial and/or management issues and adverse events of the medicines. The most common recommendations related to treatment outcome focussed on general programme management, treatment regimen composition, clinical management and social support for the patients. In all the five countries the NTPs still have a vertical structure. Some integration into the primary health care system (PHC) already exists but further involvement of PHC facilities is feasible and recommended. Interviews with stakeholders indicated that alcoholism and homelessness and a lack of appropriate response to these issues remain as major challenges for a sub-set of patients. Civil society groups, NGOs and communities are substantially engaged in providing different services to DR-TB patients, especially in Ukraine, Romania and Tajikistan. Data from clinical records of 212 patients revealed that independent risk factors for unfavourable treatment outcome (death, loss to follow-up, failure) were culture-positivity at two months of treatment, history of treatment with second-line drugs and homelessness. More powerful, less toxic and shorter oral treatment regimens as well as comprehensive patient support are needed to improve treatment outcome of patients with DR-TB.


Assuntos
Antituberculosos/administração & dosagem , Assistência à Saúde , Tuberculose Resistente a Múltiplos Medicamentos/terapia , Alcoolismo , Ásia/epidemiologia , Europa Oriental/epidemiologia , Pessoas em Situação de Rua , Humanos , Atenção Primária à Saúde , Fatores de Risco , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
14.
Zhonghua Jie He He Hu Xi Za Zhi ; 43(4): 356-361, 2020 Apr 12.
Artigo em Chinês | MEDLINE | ID: mdl-32294818

RESUMO

Objective: To explore the prevalence risk factors of Beijing genotype Mycobacterium tuberculosis (MTB) in Beijing and its correlation with second-line anti tuberculosis drug resistance. Methods: A total of 1 140 clinical MTB positive strains were collected from various districts in Beijing, and the drug sensitivity was detected by proportion method. Beijing genotype and non Beijing genotype MTB were identified by the method of Spoligotyping. Using SPSS 22.0 statistical software, chi square test or Fisher exact probability test was used to analyze the experimental data. Results: Among 1 140 MTB clinical isolates, 941 (82.5%) were Beijing genotype MTB, 199 were non Beijing genotype MTB. There were 663 males (70.5%) in Beijing genotype and 124 males (62.3%) in non Beijing genotype strains. There were significant differences in the proportion of males between the two genotypes [P=0.021, OR (95% CI):1.442 (1.048-1.985)]. There were 441 floating population (46.9%) in Beijing genotype MTB and 78 floating population (39.2%) in non Beijing genotype MTB. There was a significant difference in the proportion of floating population between the two genotypes [P=0.048,OR (95%CI):1.368(1.001-1.869)]. There were 129 patients (13.7%) aged 65 or older in Beijing genotype MTB, 40 patients (20.1%) aged 65 or older in non Beijing genotype MTB. The difference was statistically significant [P=0.021, or (95% CI): 0.631 (0.426-0.936)]. The resistance drug rates of Levofloxacin (Lfx), Amikacin (Am), Capreomycin (Cm), Para-aminosalicylic (PAS) in Beijing genotypes were 5.5% (52/941), 1.3% (12/941), 3.2% (30/941) and 3.0% (28/941), respectively, and those of non Beijing genotypes were 10.6% (21/199), 8.5% (17/199, 12.6% (25/199) and 11.6% (23/199), the difference was statistically significant (all P<0.05). There were 58 (6.2%) multidrug-resistant (MDR) strains in Beijing genotype MTB and 19 (9.5%) multidrug-resistant strains in non Beijing genotype. There was no significant difference in the proportion of MDR strains between Beijing genotype and non Beijing genotype (P>0.05). Conclusions: Beijing genotype MTB is widespread in Beijing and has a higher proportion in male population and floating population. Compared with non Beijing genotype, Beijing genotype MTB has a lower resistance rate to Lfx, Am, Cm and PAS, and there is no significant difference in the proportion of MDR-TB patients between the two genotypes.


Assuntos
Antituberculosos/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/genética , Tuberculose Pulmonar/tratamento farmacológico , Idoso , Antituberculosos/farmacologia , China/epidemiologia , DNA Bacteriano/genética , Farmacorresistência Bacteriana Múltipla/genética , Genótipo , Humanos , Masculino , Mycobacterium tuberculosis/isolamento & purificação , Prevalência , Tuberculose Pulmonar/epidemiologia
16.
Science ; 368(6496): 1211-1219, 2020 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-32327601

RESUMO

The arabinosyltransferases EmbA, EmbB, and EmbC are involved in Mycobacterium tuberculosis cell wall synthesis and are recognized as targets for the anti-tuberculosis drug ethambutol. In this study, we determined cryo-electron microscopy and x-ray crystal structures of mycobacterial EmbA-EmbB and EmbC-EmbC complexes in the presence of their glycosyl donor and acceptor substrates and with ethambutol. These structures show how the donor and acceptor substrates bind in the active site and how ethambutol inhibits arabinosyltransferases by binding to the same site as both substrates in EmbB and EmbC. Most drug-resistant mutations are located near the ethambutol binding site. Collectively, our work provides a structural basis for understanding the biochemical function and inhibition of arabinosyltransferases and the development of new anti-tuberculosis agents.


Assuntos
Antituberculosos/química , Parede Celular/enzimologia , Etambutol/química , Mycobacterium tuberculosis/enzimologia , Pentosiltransferases/química , Microscopia Crioeletrônica , Farmacorresistência Bacteriana Múltipla , Conformação Proteica
18.
An Bras Dermatol ; 95(3): 343-346, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32303434

RESUMO

Cutaneous tuberculosis is a rare extrapulmonary manifestation of tuberculosis which, like disseminated tuberculosis, commonly occurs in immunocompromised patients. Poncet reactive arthritis is a seronegative arthritis affecting patients with extrapulmonary tuberculosis, which is uncommon even in endemic countries. We report a previously healthy 23-year-old male patient with watery diarrhea associated with erythematous ulcers on the lower limbs and oligoarthritis of the hands. Histopathological examination of the skin showed epithelioid granulomatous process with palisade granulomas and central caseous necrosis. AFB screening by Ziehl-Neelsen staining showed intact bacilli, the culture was positive for Mycobacterium tuberculosis, and colonoscopy revealed multiple shallow ulcers. Disseminated tuberculosis associated with reactive Poncet arthritis was diagnosed, with an improvement of the clinical and skin condition after appropriate treatment.


Assuntos
Artrite Reativa/imunologia , Imunocompetência , Hospedeiro Imunocomprometido , Tuberculose Cutânea/imunologia , Tuberculose Cutânea/patologia , Antituberculosos/uso terapêutico , Etambutol/uso terapêutico , Humanos , Isoniazida/uso terapêutico , Masculino , Mycobacterium tuberculosis/isolamento & purificação , Pirazinamida/uso terapêutico , Rifampina/uso terapêutico , Úlcera Cutânea/tratamento farmacológico , Úlcera Cutânea/imunologia , Úlcera Cutânea/patologia , Resultado do Tratamento , Tuberculose Cutânea/tratamento farmacológico , Adulto Jovem
19.
Ann Palliat Med ; 9(2): 375-387, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32233632

RESUMO

BACKGROUND: This study aimed to develop and evaluate a sustained drug delivery system for the treatment of osteoarticular tuberculosis (TB) to address the issues surrounding low drug concentration in lesions and bone defects or nonunion after debridement. METHODS: The effects of rifapentine on the proliferation and cell cycle of bone marrow mesenchymal stem cells (BMSCs) were evaluated by Cell Counting Kit-8 (CCK-8) and flow cytometry. Rifapentine polylactic acid (PLA) sustained-release microspheres (RPSMs) were prepared through the double emulsion solvent evaporation method and investigated the antibacterial activity in vitro. In this study, two sustained drug delivery systems were prepared by integrating RPSMs and BMSCs into hydroxyapatite/ß-tricalcium phosphate (HA/ß-TCP) or allogeneic bone. We evaluated these drug delivery systems for dynamics of drug release and osteogenic ability by in vitro release test, alkaline phosphatase (ALP) and alizarin red staining, and real-time PCR. RESULTS: The results showed that rifapentine concentrations up to 45.0 µg/mL had no effect on cell proliferation and cell cycle. The encapsulation and drug loading efficiency of the fabricated RPSMs were 78.11%±1.16% and 35.57%±0.85%, respectively. The RPSMs had uniform particle size distribution and a long-term anti-bacterium effect. The HA/ß-TCP-implanted drug delivery system was found to be more effective in reducing the burst release and having a longer duration of sustained release and retention compared to allogeneic bone. The ALP and alizarin red staining and real-time PCR results showed that it had excellent osteoconductive and osteoinductive properties. CONCLUSIONS: In conclusion, the sustained drug delivery system with HA/ß-TCP as scaffold material represents a potential new strategy for TB infections and bone defects.


Assuntos
Antituberculosos/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Rifampina/análogos & derivados , Tuberculose Osteoarticular/tratamento farmacológico , Animais , Diferenciação Celular , Proliferação de Células , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos , Citometria de Fluxo , Osteogênese/efeitos dos fármacos , Coelhos , Rifampina/farmacologia
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