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1.
Int J Infect Dis ; 92: 241-246, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31978580

RESUMO

OBJECTIVES: To compare the prevalence of levofloxacin (LFX) resistance and the population structure of Mycobacterium tuberculosis (MTB) with different mutations conferring LFX resistance between 2005 and 2015. METHODS: A total 542 MTB isolates were randomly selected from pulmonary tuberculosis (TB) patients in 2005 and 2015 and analyzed regarding minimum inhibitory concentrations (MICs) and quinolone resistance-determining regions (QRDR). RESULTS: One hundred and eleven of the 542 MTB isolates analyzed (20.5%) were resistant to LFX. There were 42 and 69 LFX-resistant isolates from 2005 and 2015, respectively, and MIC high-level LFX resistance was significantly higher in 2015 (40.6%, 28/69) than in 2005 (16.7%, 7/42) (p = 0.02). There were 87 (78.4%) mutations of these 111 LFX-resistant isolates. In addition, a significant difference in proportion was observed in the isolates with mutations in codon 90 of the gyrA gene between 2005 and 2015 (11.9% in 2005 versus 29.0% in 2015, p = 0.04). CONCLUSIONS: There was an alarming increase in prevalence of LFX-resistant TB in China between 2005 and 2015. This dynamic change is mostly attributed to the increase in high-level LFX resistance. Moreover, a significant difference was noted in the proportion of LFX-resistant isolates harboring specific mutations within the gyrA gene between 2005 and 2015.


Assuntos
Farmacorresistência Bacteriana , Levofloxacino/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Tuberculose Pulmonar/tratamento farmacológico , Adulto , China/epidemiologia , DNA Girase/genética , Feminino , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Humanos , Levofloxacino/farmacologia , Masculino , Testes de Sensibilidade Microbiana , Mutação , Mycobacterium tuberculosis/isolamento & purificação , Prevalência , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia
2.
Infect Immun ; 88(2)2020 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-31792077

RESUMO

We used a genome-wide screen in N-ethyl-N-nitrosourea (ENU)-mutagenized mice to identify genes in which recessive loss-of-function mutations protect against pathological neuroinflammation. We identified an R367Q mutation in the ZBTB7B (ThPOK) protein in which homozygosity causes protection against experimental cerebral malaria (ECM) caused by infection with Plasmodium berghei ANKA. Zbtb7bR367Q homozygous mice show a defect in the lymphoid compartment expressed as severe reduction in the number of single-positive CD4 T cells in the thymus and in the periphery, reduced brain infiltration of proinflammatory leukocytes in P. berghei ANKA-infected mice, and reduced production of proinflammatory cytokines by primary T cells ex vivo and in vivo Dampening of proinflammatory immune responses in Zbtb7bR367Q mice is concomitant to increased susceptibility to infection with avirulent (Mycobacterium bovis BCG) and virulent (Mycobacterium tuberculosis H37Rv) mycobacteria. The R367Q mutation maps to the first DNA-binding zinc finger domain of ThPOK and causes loss of base contact by R367 in the major groove of the DNA, which is predicted to impair DNA binding. Global immunoprecipitation of ThPOK-containing chromatin complexes coupled to DNA sequencing (ChIP-seq) identified transcriptional networks and candidate genes likely to play key roles in CD4+ CD8+ T cell development and in the expression of lineage-specific functions of these cells. This study highlights ThPOK as a global regulator of immune function in which alterations may affect normal responses to infectious and inflammatory stimuli.


Assuntos
Proteínas de Ligação a DNA/genética , Malária Cerebral/genética , Fatores de Transcrição/genética , Tuberculose Pulmonar/genética , Animais , Encéfalo/microbiologia , Linfócitos T CD4-Positivos/microbiologia , Linfócitos T CD8-Positivos/microbiologia , Citocinas/genética , Feminino , Inflamação/genética , Inflamação/microbiologia , Malária Cerebral/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mycobacterium tuberculosis/patogenicidade , Plasmodium berghei/patogenicidade , Tuberculose Pulmonar/microbiologia , Virulência/genética
3.
Immunology ; 159(1): 121-129, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31606895

RESUMO

The transcription factor hypoxia-inducible factor-1 alpha (HIF-1α) is a key regulator of the response and function of myeloid cells in hypoxic and inflammatory microenvironments. To define the role of HIF-1α in tuberculosis, the progression of aerosol Mycobacterium tuberculosis infection was analysed in mice deficient in HIF-1α in the myeloid lineage (mHIF-1α-/- ). We show that myeloid HIF-1α is not required for the containment of the infection, as both wild-type (WT) and mHIF-1α-/- mice mounted normal Th1 responses and maintained control of bacterial growth throughout infection. However, during chronic infection mHIF-1α-/- mice developed extensive lymphocytic inflammatory involvement of the interstitial lung tissue and died earlier than WT mice. These data support the hypothesis that HIF-1α activity coordinates the response of myeloid cells during M. tuberculosis infection to prevent excessive leucocyte recruitment and immunopathological consequences to the host.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Pulmão/metabolismo , Mycobacterium tuberculosis/crescimento & desenvolvimento , Células Mieloides/metabolismo , Pneumonia/metabolismo , Tuberculose Pulmonar/metabolismo , Animais , Carga Bacteriana , Células Cultivadas , Modelos Animais de Doenças , Progressão da Doença , Interações Hospedeiro-Patógeno , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Pulmão/imunologia , Pulmão/microbiologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mycobacterium tuberculosis/imunologia , Células Mieloides/imunologia , Células Mieloides/microbiologia , Pneumonia/genética , Pneumonia/imunologia , Pneumonia/microbiologia , Transdução de Sinais , Tuberculose Pulmonar/genética , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologia
4.
PLoS Med ; 16(10): e1002961, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31671150

RESUMO

BACKGROUND: Whole genome sequencing provides better delineation of transmission clusters in Mycobacterium tuberculosis than traditional methods. However, its ability to reveal individual transmission links within clusters is limited. Here, we used a 2-step approach based on Bayesian transmission reconstruction to (1) identify likely index and missing cases, (2) determine risk factors associated with transmitters, and (3) estimate when transmission happened. METHODS AND FINDINGS: We developed our transmission reconstruction method using genomic and epidemiological data from a population-based study from Valencia Region, Spain. Tuberculosis (TB) incidence during the study period was 8.4 cases per 100,000 people. While the study is ongoing, the sampling frame for this work includes notified TB cases between 1 January 2014 and 31 December 2016. We identified a total of 21 transmission clusters that fulfilled the criteria for analysis. These contained a total of 117 individuals diagnosed with active TB (109 with epidemiological data). Demographic characteristics of the study population were as follows: 80/109 (73%) individuals were Spanish-born, 76/109 (70%) individuals were men, and the mean age was 42.51 years (SD 18.46). We found that 66/109 (61%) TB patients were sputum positive at diagnosis, and 10/109 (9%) were HIV positive. We used the data to reveal individual transmission links, and to identify index cases, missing cases, likely transmitters, and associated transmission risk factors. Our Bayesian inference approach suggests that at least 60% of index cases are likely misidentified by local public health. Our data also suggest that factors associated with likely transmitters are different to those of simply being in a transmission cluster, highlighting the importance of differentiating between these 2 phenomena. Our data suggest that type 2 diabetes mellitus is a risk factor associated with being a transmitter (odds ratio 0.19 [95% CI 0.02-1.10], p < 0.003). Finally, we used the most likely timing for transmission events to study when TB transmission occurred; we identified that 5/14 (35.7%) cases likely transmitted TB well before symptom onset, and these were largely sputum negative at diagnosis. Limited within-cluster diversity does not allow us to extrapolate our findings to the whole TB population in Valencia Region. CONCLUSIONS: In this study, we found that index cases are often misidentified, with downstream consequences for epidemiological investigations because likely transmitters can be missed. Our findings regarding inferred transmission timing suggest that TB transmission can occur before patient symptom onset, suggesting also that TB transmits during sub-clinical disease. This result has direct implications for diagnosing TB and reducing transmission. Overall, we show that a transition to individual-based genomic epidemiology will likely close some of the knowledge gaps in TB transmission and may redirect efforts towards cost-effective contact investigations for improved TB control.


Assuntos
Busca de Comunicante/métodos , Genoma Bacteriano , Mycobacterium tuberculosis/genética , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/transmissão , Sequenciamento Completo do Genoma , Adolescente , Adulto , Idoso , Teorema de Bayes , Biomarcadores , Feminino , Genômica , Soropositividade para HIV/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Filogenia , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Espanha/epidemiologia , Resultado do Tratamento , Tuberculose Pulmonar/epidemiologia , Adulto Jovem
5.
BMC Infect Dis ; 19(1): 923, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666021

RESUMO

BACKGROUND: Pulmonary tuberculosis (TB) with detectable Mycobacterium tuberculosis in the sputum is a major source of transmission. In resource limited TB endemic settings, cure is declared through sputum smear examination for acid fast bacilli without performing culture. This may lead to erroneous treatment outcomes as viable bacteria may be missed due to the low sensitivity of direct smear method. The aim of this study was to investigate if sterilizing cure is achieved among the new pulmonary TB cases declared cured by sputum smear conversion and to evaluate the impact of addition of ethambutol in the continuation phase in achieving it. METHODS: New sputum smear-positive pulmonary TB patients registered at a tertiary care hospital in Pakistan from November 2013 to March 2014 were followed under standard Directly Observed Treatment Short Course strategy for 6 months. Half of these patients received ethambutol in addition to isoniazid and rifampicin in the continuation phase. Sputum specimens were examined on microscopy at 2 months and at the end of treatment. Sputa of patients with negative direct smear examination at the end of treatment were cultured. RESULTS: Among 5746 TB suspects, 1595 were new sputum smear positive pulmonary TB cases, and 533 were registered at our hospital. Among these, 504 converted sputum negative at 2 months and 348 converted at the end of 6 months of treatment and were declared cured. Sputa of 204/348 patients were cultured, and 12/204 (6%) were culture-positive. Culture positivity at 6 months was not associated with bacterial load, smoking, diabetes, presence of cavities, history of contact with TB patients, age, sex, socioeconomic status, or addition of ethambutol in the continuation phase. CONCLUSION: Viable cultivable bacilli were detected in 6% of cured patients, which would have significant impact on the control of TB. This highlights the need for an inexpensive and accurate surrogate marker for culture as it is not feasible to perform culture in routine for monitoring treatment response in the low-resource settings. The treatment outcome did not improve by addition of ethambutol emphasizing the need to find the optimal duration of treatment for individual or carefully selected groups of patients.


Assuntos
Antituberculosos/uso terapêutico , Etambutol/uso terapêutico , Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Adolescente , Adulto , Idoso , Carga Bacteriana , Testes Diagnósticos de Rotina , Quimioterapia Combinada , Feminino , Humanos , Isoniazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Paquistão , Rifampina/uso terapêutico , Resultado do Tratamento , Tuberculose Pulmonar/diagnóstico por imagem , Adulto Jovem
6.
BMC Infect Dis ; 19(1): 993, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752713

RESUMO

BACKGROUND: The goal of this study was to further investigate the clinical effectiveness of the T-SPOT.TB test in diagnosing tuberculosis (TB), including the effects of T-SPOT.TB test on evaluating diverse TB types and locations. METHODS: We collected 20,332 specimens from patients suspected to have TB. Afterwards, we performed an integrative analysis of T-SPOT.TB results and clinical diagnoses, and evaluated the composition ratio and positive detection rate of the T-SPOT.TB test in various age groups, sample types, and hospital departments. In addition, we compared the spot number and composition rate between latent TB infection (LTBI), active TB infection, and old TB infection groups. The active TB group was then further divided into pulmonary TB (PTB), pulmonary and extrapulmonary TB (PETB), and extrapulmonary TB (EPTB) subgroups, and we evaluated whether there were statistical differences in spot number and composition rate between subgroups. RESULTS: Positive results from the T-SPOT.TB test were found across different age groups, specimen types, and hospital departments. Elderly patient groups, pleural effusion samples, and thoracic surgery departments showed the highest rates of positivity. There were no statistically significant differences in spot number of CFP-10 and ESAT-6 wells between disease groups or active TB subgroups. The composition rate, however, was significantly different when ESAT-6 and CFP-10 wells were double-positive. The spot number and composition rate were statistically different between the three disease groups, but showed no significant differences between the three subgroups of active TB. CONCLUSIONS: The results of T-SPOT. TB test showed differences in LTBI, active TB and old TB. Additionally, a higher spot number level was observed in the active TB group.


Assuntos
Testes Diagnósticos de Rotina/métodos , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Interferon gama/sangue , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Resultado do Tratamento , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/microbiologia , Adulto Jovem
7.
BMC Infect Dis ; 19(1): 909, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664931

RESUMO

BACKGROUND: Disseminated nontuberculous mycobacteria (NTM) infections occur mostly in immunocompromised patients. Therefore, it is difficult to diagnose disseminated NTM infections in patients without history of immunocompromised diseases or using immunosuppressant. Patients with anti-interferon-γ (IFN-γ) autoantibodies are vulnerable to intracellular infections, such as disseminated NTM. Currently, there is no widely used and efficient technique for the detection of anti-IFN-γ autoantibodies. Herein, we report a case of an apparently healthy patient with disseminated Mycobacterium avium complex (MAC) infection who tested positive for anti-IFN-γ autoantibodies. CASE PRESENTATION: A 64-year-old non-immunocompromised and apparently healthy Asian male presented to the emergency department with complaints of progressive chest pain for about 6 months and weight loss. A bulging tumour was found in the anterior chest wall. Chest computed tomography showed a lung mass over the right lower lobe and an osteolytic lesion with a soft tissue component at the sternum. Sonography-guided biopsies for the osteolytic lesion and sputum culture confirmed the presence of disseminated MAC infection. In addition, positive test result of anti-IFN-γ autoantibodies was noted. The patient was prescribed antibiotics. The lesions over the right lower lobe and sternum attenuated following the antibiotic treatment. CONCLUSION: Detection of anti-IFN-γ autoantibodies is important among previously healthy people with disseminated NTM infection. Presence of anti-IFN-γ autoantibodies may suggest a high risk of severe intracellular infection, such as disseminated NTM infection.


Assuntos
Autoanticorpos/análise , Interferon gama/imunologia , Neoplasias Pulmonares/diagnóstico , Infecções por Micobactéria não Tuberculosa/diagnóstico por imagem , Complexo Mycobacterium avium , Tuberculose Pulmonar/diagnóstico por imagem , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Biópsia/métodos , Diagnóstico Diferencial , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Micobactéria não Tuberculosa/tratamento farmacológico , Infecções por Micobactéria não Tuberculosa/microbiologia , Infecções por Micobactéria não Tuberculosa/patologia , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Escarro/microbiologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia
8.
BMJ ; 367: l5894, 2019 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-31649017

RESUMO

OBJECTIVE: To measure the association between phenotypic drug resistance and the risk of tuberculosis infection and disease among household contacts of patients with pulmonary tuberculosis. SETTING: 106 district health centers in Lima, Peru between September 2009 and September 2012. DESIGN: Prospective cohort study. PARTICIPANTS: 10 160 household contacts of 3339 index patients with tuberculosis were classified on the basis of the drug resistance profile of the patient: 6189 were exposed to drug susceptible strains of Mycobacterium tuberculosis, 1659 to strains resistant to isoniazid or rifampicin, and 1541 to strains that were multidrug resistant (resistant to isoniazid and rifampicin). MAIN OUTCOME MEASURES: Tuberculosis infection (positive tuberculin skin test) and the incidence of active disease (diagnosed by positive sputum smear or chest radiograph) after 12 months of follow-up. RESULTS: Household contacts exposed to patients with multidrug resistant tuberculosis had an 8% (95% confidence interval 4% to 13%) higher risk of infection by the end of follow-up compared with household contacts of patients with drug sensitive tuberculosis. The relative hazard of incident tuberculosis disease did not differ among household contacts exposed to multidrug resistant tuberculosis and those exposed to drug sensitive tuberculosis (adjusted hazard ratio 1.28, 95% confidence interval 0.9 to 1.83). CONCLUSION: Household contacts of patients with multidrug resistant tuberculosis were at higher risk of tuberculosis infection than contacts exposed to drug sensitive tuberculosis. The risk of developing tuberculosis disease did not differ among contacts in both groups. The evidence invites guideline producers to take action by targeting drug resistant and drug sensitive tuberculosis, such as early detection and effective treatment of infection and disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT00676754.


Assuntos
Tuberculose Resistente a Múltiplos Medicamentos/transmissão , Tuberculose Pulmonar/transmissão , Adolescente , Adulto , Idoso , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Criança , Pré-Escolar , Busca de Comunicante/métodos , Progressão da Doença , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Isoniazida/farmacologia , Isoniazida/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Peru/epidemiologia , Estudos Prospectivos , Rifampina/farmacologia , Rifampina/uso terapêutico , Escarro/microbiologia , Teste Tuberculínico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia , Adulto Jovem
9.
J Med Microbiol ; 68(11): 1622-1628, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31596198

RESUMO

Introduction. Nosocomial transmission of Mycobacterium tuberculosis is an important health issue and the detection of tuberculosis (TB) cases is the main tool for controlling this disease.Aim. We aimed to assess the possible occurrence of nosocomial transmission of M. tuberculosis in a reference hospital for HIV/AIDS patients and evaluate both the performance of the Xpert MTB/RIF (Xpert) platform and drug resistance profiles.Methodology. We evaluated the performance of the Xpert platform. Samples that tested positive on the BACTEC MGIT 320 (MGIT320) platform were submitted for genotyping and drug susceptibility testing.Results. In this study, pulmonary and extrapulmonary samples from 407 patients were evaluated, and among these, 15.5 % were diagnosed with TB by the MGIT320 platform, with a TB/HIV coinfection rate of 52.4 %. The Xpert platform gave positive results for TB for 11 samples with negative results on the MGIT320 platform. In the genotyping results, 53.3 % of the strains clustered; of these strains, half were in two of the four clusters formed, and the patients had visited the hospital on the same day. Drug resistance was observed in 11.7 % of the strains.Conclusion. Putative nosocomial transmission of M. tuberculosis was detected, showing that genotyping is a powerful approach for understanding the dynamics of M. tuberculosis transmission, especially in a high-burden TB and HIV landscape.


Assuntos
Infecções por HIV/complicações , Técnicas de Diagnóstico Molecular/métodos , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Pulmonar/microbiologia , Síndrome de Imunodeficiência Adquirida/complicações , Antibióticos Antituberculose/farmacologia , Técnicas de Laboratório Clínico , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/microbiologia , Estudos Transversais , Farmacorresistência Bacteriana , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Filogenia , Tuberculose , Tuberculose Pulmonar/diagnóstico
10.
Int J Infect Dis ; 89: 122-127, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31639521

RESUMO

OBJECTIVE: To evaluate the utility of a volunteer health development army in conducting population screening for active tuberculosis (TB) in a rural community in southern Ethiopia. METHODS: A population-based cross-sectional survey was conducted in six kebeles (the lowest administrative units). Volunteer women community workers led a symptom screening programme to identify adults ≥15 years of age with TB in the community. Individuals with a cough for ≥2 weeks had spot and morning sputum samples taken, which were examined using acid-fast bacillus (AFB) smear microscopy, culture, and Xpert MTB/RIF. RESULTS: All 24517 adults in the study area had a symptom screen performed; 544 (2.2%) had had a cough for ≥2 weeks. Among those with a positive symptom screen, 13 (2.4%) were positive on sputum AFB smear microscopy, 13 (2.4%) had a positive culture, and 32 (5.8%) had a positive Xpert MTB/RIF test. Overall, 34 TB cases (6%) were identified by culture and/or Xpert, corresponding to a prevalence of 139 per 100000 persons. CONCLUSIONS: This study demonstrated the capability of community health workers (volunteer and paid) to rapidly conduct a large-scale population TB screening evaluation and highlight the high yield of such a programme in detecting previously undiagnosed cases when combined with Xpert MTB/RIF testing. This could be a model to implement in other similar settings.


Assuntos
Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia , Adolescente , Adulto , Agentes Comunitários de Saúde/estatística & dados numéricos , Estudos Transversais , Etiópia/epidemiologia , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Prevalência , Sensibilidade e Especificidade , Escarro/microbiologia , Tuberculose Pulmonar/microbiologia , Adulto Jovem
11.
Medicine (Baltimore) ; 98(39): e17378, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574888

RESUMO

RATIONALE: Pulmonary tuberculosis and lung adenocarcinoma are highly prevalent pulmonary diseases associated with high mortality. However, the coexistence of lung cancer and pulmonary tuberculosis is rare. Further, the morphological features of lung cancer with coexisting pulmonary tuberculosis are similar to that of lung cancer without pulmonary tuberculosis, even though the lesion is predominantly cavity. For these reasons, the diagnosis in patients with coexisting lung cancer and pulmonary tuberculosis could be delayed until the advanced stage, and therefore, prognosis in these patients is worse compared with that of lung cancer patients without coexisting pulmonary tuberculosis. Therefore, early diagnosis of the condition is essential for initiating timely and suitable treatment. PATIENT CONCERNS: A 67-year-old man was detected abnormal finding on chest CT performed outside the hospital during health screening without significant symptom. DIAGNOSES: Chest CT revealed a 3.2, irregular, enhancing cavitary mass in right lower lobe of lung and PET-CT revealed significant uptake of 18 FDG by the cavitary mass, which was suggestive of lung cancer. Pathology results confirmed a diagnosis of coexisting lung adenocarcinoma and tuberculosis. INTERVENTIONS AND OUTCOME: The patient underwent a right lower lobectomy. No significant complications occurred in a 24 month post-surgery follow-up period LESSONS:: Although rare, the coexistence of lung adenocarcinoma and tuberculosis within a single lesion can occur. Therefore, early diagnosis of such a lesion is essential to improve the prognosis in affected patients.


Assuntos
Adenocarcinoma de Pulmão/microbiologia , Neoplasias Pulmonares/microbiologia , Tuberculose Pulmonar/microbiologia , Idoso , Humanos , Pulmão/microbiologia , Masculino , Tuberculose Pulmonar/complicações
12.
BMC Infect Dis ; 19(1): 819, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533664

RESUMO

BACKGROUND: Reports on the worldwide ascending trend of pulmonary nontuberculous mycobacteria (NTM) isolation rates and their effective role in respiratory tract infections are compelling. However, as yet, there are no such data relating to Tunisia. METHODS: Here we carried out a retrospective review of mycobacterial cultures originating from Northern Tunisia, which have been processed in the laboratory of mycobacteria of the Institut Pasteur de Tunis, during the time period 2002-2016. All pulmonary NTM (PNTM) isolates available for culture were characterized phenotypically and their taxonomic status was further established based on polymorphisms in rpoB, 16S rRNA, hsp65, and sodA DNA gene sequences. RESULTS: Of the 10,466 specimens collected from HIV-negative Tunisian patients with presumptive clinical pulmonary TB, 60 (0.6%) yielded PNTM isolates. An overall annual PNTM isolation prevalence of 0.2/100,000 was estimated. As far as could be ascertained, this isolation rate accounts amongst the lowest reported hitherto throughout the world. Among the 30 NTM isolates that were available for culture, 27 (90.0%) have been identified to the species level. The most commonly encountered species was Mycobacterium kansasii (23.3%) subtype 1. Strikingly, all M. kansasii cases were male patients originating from Bizerte, an industrialized region particularly known for iron industry. The remaining NTM species were M. fortuitum (16.6%), M. novocastrense (16.6%), M. chelonae (10.0%), M. gordonae (6.6%), M. gadium (6.6%), M. peregrinum (3.3%), M. porcinum (3.3%), and M. flavescens (3.3%). There were no bacteria of the M. avium complex, the most frequently isolated NTM globally, and the main driver of the rise of NTM-lung diseases. CONCLUSIONS: This study uncovered an exceptional low prevalence of PNTM isolation among HIV-negative TB suspects in Northern Tunisia, suggesting a very low burden of NTM pulmonary disease. However, the frequent isolation of M. kansasii subtype 1, the most pathogenic subtype, particularly from the industrialized region of Bizerte, strongly suggests its effective involvement in a typical pulmonary disease.


Assuntos
Infecções por Micobactéria não Tuberculosa/diagnóstico , Micobactérias não Tuberculosas/isolamento & purificação , Tuberculose Pulmonar/diagnóstico , Adulto , Líquido da Lavagem Broncoalveolar/microbiologia , Feminino , Humanos , Masculino , Infecções por Micobactéria não Tuberculosa/epidemiologia , Infecções por Micobactéria não Tuberculosa/microbiologia , Micobactérias não Tuberculosas/classificação , Micobactérias não Tuberculosas/genética , Filogenia , Prevalência , RNA Ribossômico 16S/química , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Estudos Retrospectivos , Escarro/microbiologia , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia , Tunísia/epidemiologia
13.
J Pak Med Assoc ; 69(9): 1273-1278, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31511711

RESUMO

OBJECTIVE: To evaluate the sensitivity, specificity, positive predictive and negative predictive values of Xpert mycobacterium tuberculosis and resistance to rifampicin by comparing it with acid-fast bacilli smear and culture in suspected tuberculosis patients. METHODS: The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised patient data from January 2013 to December 2016. Data related to children with clinical suspicion of pulmonary and extra-pulmonary tuberculosis based on Modified Kenneth Jones criteria, aged 1 month to 18 years whose samples (respiratory or non-respiratory) were sent for Xpert mycobacterium tuberculosis and resistance to rifampicin and acid-fast bacilli smear and culture con currently. Analysis was carried out by STATA 12 and Med Calc softwares . RESULTS: Of the 91 cases, 50(54.9%) related to females. The overall median age of the patients was 12.5 years (interquartile range: 8 years). Overall, 42(46.2%) cases had extra-pulmonary tuberculosis. The Xpert test had 66.7% sensitivity compared to smear microscopy 47.6%. Overall sensitivity, specificity, positive predictive value and negative predictive value were 95.7%, 72%, 51.2% and 98.3% respectively when the two tests were compared. CONCLUSIONS: Xpert mycobacterium tuberculosis was found to be more sensitive than acid-fast bacilli smear and culture in both pulmonary and extra-pulmonar y tuberculosis in children.


Assuntos
Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose/diagnóstico , Adolescente , Antibióticos Antituberculose , Criança , Pré-Escolar , Técnicas de Cultura , Farmacorresistência Bacteriana/genética , Feminino , Humanos , Lactente , Masculino , Mycobacterium tuberculosis/crescimento & desenvolvimento , Técnicas de Amplificação de Ácido Nucleico , Paquistão , Estudos Retrospectivos , Rifampina , Sensibilidade e Especificidade , Centros de Atenção Terciária , Tuberculose/microbiologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia
14.
Int J Mycobacteriol ; 8(3): 237-243, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31512599

RESUMO

Background: Extrapulmonary tuberculosis (EPTB), accounting for 10%-20% of all cases of tuberculosis (TB), is known to be determined by host immunity. However, the contribution of bacterial factors to the development of EPTB has not been studied extensively. Mycolic acids are predominant lipids constituting the cell wall of Mycobacterium tuberculosis, and keto-mycolic acid is involved in the synthesis of foamy macrophages that facilitate persistence of mycobacteria. Hence, the present study was performed to gain an insight into variable expression of mycolic acids in clinical isolates of M. tuberculosis under stress. Methods: Pansusceptible clinical isolates of M. tuberculosis from patients with lymph node TB (LNTB) (n = 10) and pulmonary TB (PTB) (n = 10) were subjected to sodium dodecyl sulfate (SDS) stress, and the expression of mycolic acid and its biosynthetic genes was compared. Any bias arising due to the genotype of the clinical isolates was ruled out by performing single-nucleotide polymorphism cluster grouping (SCG), wherein no significant difference was observed between the SCG of LNTB or PTB isolates. Results: The expression of α-mycolic acid during the exposure to SDS was high in 7/10 (70%) LNTB and 6/10 (60%) PTB isolates. Methoxy mycolic acid showed an increased expression in 7/10 (70%) LNTB isolates and 4/10 (40%) PTB isolates. Increased expression of keto-mycolic acid on exposure with SDS was observed in 8/10 (80%) M. tuberculosis LNTB and 3/10 (30%) PTB isolates. Similarly, the mycolic acid synthesis gene, fas, was upregulated more in LNTB isolates than PTB isolates in vitro and ex vivo. SCG 3a was the most common SCG observed in 40% (8/20) of the isolates, followed by SCG 3b in 30% (6/20) of the isolates. There was no significant difference between the SCG of LNTB or PTB isolates. Conclusion: The higher expression of keto-mycolic acid in LNTB as against PTB isolates may indicate better survival in LNTB isolates in the presence of stress.


Assuntos
Expressão Gênica/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Ácidos Micólicos/metabolismo , Proteínas de Bactérias/genética , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Dodecilsulfato de Sódio/farmacologia , Estresse Fisiológico , Células THP-1 , Tuberculose dos Linfonodos/microbiologia , Tuberculose Pulmonar/microbiologia
15.
Emerg Microbes Infect ; 8(1): 1361-1369, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31522608

RESUMO

Rapid and simple-to-use diagnostic methods for tuberculosis are urgently needed. Recent development has unveiled the diagnostic power of the CRISPR system in the detection of viral infections. However, its potential use in detecting the Mycobacterium tuberculosis complex (MTB) remained unexplored. We developed a rapid CRISPR-based assay for TB detection and conducted a retrospective cohort study of 179 patients to evaluate the CRISPR-MTB test for identifying MTB in various forms of direct clinical samples. Its diagnostic performance was compared, in parallel with culture and the GeneXpert MTB/RIF assay (Xpert). The CRISPR-MTB test is highly sensitive with a near single-copy sensitivity, demands less sample input and offers shorter turnaround time than Xpert. When evaluated in the clinical cohort of both pulmonary and extra-pulmonary tuberculosis, the CRISPR-MTB test exhibited an overall improved sensitivity over both culture (79% vs 33%) and Xpert (79% vs 66%), without comprise in specificity (62/63, 98%). The CRISPR-MTB test exhibits an improved overall diagnostic performance over culture and Xpert across a variety of sample types, and offers great potential as a new diagnostic technique for both pulmonary and extra-pulmonary tuberculosis.


Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Técnicas de Diagnóstico Molecular , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Pulmonar/diagnóstico , Tuberculose/diagnóstico , Humanos , Mycobacterium tuberculosis/genética , Kit de Reagentes para Diagnóstico/normas , Estudos Retrospectivos , Sensibilidade e Especificidade , Escarro/microbiologia , Tuberculose/microbiologia , Tuberculose Pulmonar/microbiologia
16.
Medicine (Baltimore) ; 98(34): e16921, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441875

RESUMO

Pulmonary tuberculosis (PTB) continues to be one of the significant public health threats with significant morbidity and mortality. The present study was aimed to assess the clinical characteristics and chest computed tomography (CT) findings of smear-positive and smear-negative PTB in hospitalized adult patients.Hospitalized adult patients diagnosed with PTB by positive Mycobacterium tuberculosis growth on acid-fast bacilli culture from bronchial aspiration or sputum from 2015 to 2017 were reviewed. Only the patients who had chest CT within 14 days of the diagnosis of PTB were included. Medical records and CT images were analyzed.A total of 189 patients was enrolled. The median age was 62 years, and there were 118 males (62.4%). More than half of the patients had underlying chronic medical conditions (55.5%). The most common CT finding was nodular lesions (96.8%). The patients were categorized in 2 groups of smear-positive (n = 94, 49.7%) and smear-negative (n = 95, 50.3%). Between 2 groups, there was no difference in underlying medical conditions. However, there were more lesions of cavity, consolidation, bronchiectasis, upper lobe involvement, multiple lobe involvement, and lymphadenopathy in the smear-positive group. A predictive model for smear-positive tuberculosis was created based on the comparison analysis that had an area of 0.724 under the receiver operating characteristic curve. In a multivariate logistic regression analysis, CT findings of consolidation (odds ratio [OR] 2.521, 95% confidence interval [CI] 1.175-5.408, P = .02), lymphadenopathy (OR 1.947, 95% CI 1.025-3.696, P = .04), and multi-lobe involvement (OR 2.795, 95% CI 1.084-7.205, P = .03) were associated with smear-positive PTB.PTB patients who have chest CT findings of cavity, consolidation, bronchiectasis, upper lobe involvement, multiple lobe involvement, and lymphadenopathy may be at higher risk for smear-positive TB. A predictive model may be helpful for further assessment.


Assuntos
Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Tomografia Computadorizada por Raios X/métodos , Tuberculose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/microbiologia , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos
17.
Indian J Tuberc ; 66(3): 353-357, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31439179

RESUMO

BACKGROUND: Several determinants are responsible for different incidences of smear positive pulmonary tuberculosis (TB). The main determinants are cigarette smoking and diabetes mellitus. The aim of this study is to determine the effect of these risk factors effect modifiers in TB/gender association. METHODOLOGY: In this retrospective cohort, relative risk of gender in developing smear positive TB as well as its interaction with smoking and diabetes mellitus were investigated. RESULTS: Of 1243 smear positive TB cases, 63.2% were male. Prevalences of diabetes mellitus among men and women TB cases were 9.2% and 22.9% respectively (p<0.001). Frequency of cigarette smoking among men was significantly higher than that in women (61.7% vs. 7.6% respectively, p<0.001). Male gender, increased the risk of developing smear positive TB as of 98% and 5% in smokers and non-smokers respectively (p=0.001), indicating an interaction between gender and smoking in the effect on TB. In addition, male gender increased the risk of TB as of 13% and 34% in patients with and without diabetes mellitus respectively (p=0.300) indicating no interaction between gender and diabetes mellitus on TB incidence. CONCLUSION: Our study showed that cigarette smoking is a determinant factor for gender differences in TB incidence but diabetes mellitus does not affect the association between TB and gender.


Assuntos
Diabetes Mellitus Tipo 2 , Identidade de Gênero , Fumar , Tuberculose Pulmonar/epidemiologia , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Incidência , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Escarro/microbiologia , Tuberculose Pulmonar/etiologia , Tuberculose Pulmonar/microbiologia , Adulto Jovem
18.
Braz J Infect Dis ; 23(4): 246-253, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31421107

RESUMO

Accurate and rapid diagnostic tools are important aspects of managing tuberculosis (TB) cases appropriately. However, the sensitivity and specificity of diagnostic kits based on immune response such as the tuberculin skin test (TST) and interferon gamma release assay (IGRA) are still debated. Thus, the exploration and assessment of specific biomarker-targeted antibodies are needed for the development of an accurate and rapid diagnostic tool. The present study was conducted in patients with a respiratory problem suspected to be TB at Dr. Soetomo Hospital, Surabaya, Indonesia. Among 102 patients tested by GeneXpert and AFB, 59 serum samples were from cases retrospectively determined to have active TB. A total of 102 serum of healthy controls (HC) was also collected. The PPD antigen and the recombinant CFP-10 and ESAT-6 proteins were prepared. Antibody responses against these proteins were evaluated by ELISA. All samples were also screened for the possibility of Mycobacterium avium-intracellulare complex (MAC) infection using Capilla MaC kit. The results showed that TB patients had a significantly higher concentration of IgG antibody in response to PPD than the HC. In addition, the receiver operating characteristic (ROC) curve analysis showed that PPD was acceptable for diagnostic purposes with an AUC value of 0.835 (95% CI 0.770-0.900, p < 0.0001). However, ESAT-6 and CFP-10 had low AUCs, and 32 samples from both groups showed a low concentration of IgA antibody against all antigens. The MAC detection results also showed that the concentration of IgA in the HC group was the highest. The current results indicate that PPD is a better antigen for antibody-based detection of TB than ESAT-6 and CFP-10. Based on the MAC detection assay, 53 people in the HC group were probably infected with rapidly growing nontuberculous mycobacteria (NTM), although antibody response to PPD was low.


Assuntos
Formação de Anticorpos/imunologia , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculina/imunologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Indonésia , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estudos Retrospectivos , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Teste Tuberculínico , Tuberculose Pulmonar/sangue , Adulto Jovem
19.
Braz J Infect Dis ; 23(5): 281-290, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31421108

RESUMO

PURPOSE AND OBJECTIVES: Detection of drug resistance plays a crucial role in tuberculosis (TB) treatment and prevention of Mycobacterium tuberculosis (MTB) transmission. The aim of this study was to determine the levels and patterns of resistance of MTB isolates to two key anti-TB drugs (rifampicin, RIF and isoniazid, INH) and the type of mutations in drug resistance genes (rpoB, katG and inhA) of the isolates at the southern coastal region of Andhra Pradesh, India, using commercially available GenoType MTBDRplus assay under the Revised National TB Control Program. METHODS: GenoType MTBDRplus assay was performed on 2859 sputum smear-positive samples and the mutations in the genes responsible for resistance (rpoB, katG and inhA) were analyzed. RESULTS: Among the line probe assay (LPA) valid isolates (2894), 1990 (68.76%) were drug susceptible, 437 (15.13%) were INH monoresistant, 104 (3.59%) were RIF monoresistant, and 363 (12.54%) were multidrug resistant. Codon 531 of rpoB gene and codon 315 of katG gene were found to have the highest mutation frequency for RIF resistance (270/467; 57.81%) and INH resistance (501/800; 62.62%), respectively. The RIF resistant rpoB mutations observed in the samples were S531L (57.81%), H526Y (8.56%), D516V (6.42%), and H526D (6.20%). Mutations in inhA promoter were found in 24.75% INH resistant isolates with C15T being the most common (85.85%). The turnaround times of the LPA test were from 48 to72h. CONCLUSION: The frequency of mutations in MTB in the coastal region of Andhra Pradesh, India, is similar to that in retreatment cases from most settings, with close to 80% in rpoB codon 516, 526, and 531, and over 80% in codons katG 315 and/or inhA promoter. The increase in INH monoresistance underlines the need for greater enforcement of national TB control programs.


Assuntos
Antibióticos Antituberculose/farmacologia , Mycobacterium tuberculosis/genética , Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Pulmonar/microbiologia , Adulto , Feminino , Genótipo , Humanos , Índia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mutação/genética , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Fatores de Risco , Adulto Jovem
20.
EBioMedicine ; 46: 202-214, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31401197

RESUMO

BACKGROUND: Breath tests may diagnose tuberculosis (TB) through detecting specific volatile organic compounds produced by Mycobacterium tuberculosis or the infected host. METHODS: To estimate the diagnostic accuracy of breath test with electronic-nose and other devices against culture or other tests for TB, we screened multiple databases until January 6, 2019. FINDINGS: We included fourteen studies, with 1715 subjects in the analysis. The pooled sensitivity and specificity of electronic-nose were 0.93 (95% CI 0.82-0.97) and 0.93 (95% CI 0.82-0.97), respectively, and no heterogeneity was found. The sensitivity and specificity of other breath test devices ranged from 0.62 to 1.00, and 0.11 to 0.84, respectively. INTERPRETATION: The low to moderate evidence of these studies shows that breath tests can diagnose TB accurately, however, to give a real-time test result, additional development is needed. Research should also focus on sputum smear negative TB, children, and the positioning of breath testing in the diagnostic work flow. FUNDING: The authors received no specific funding for this work.


Assuntos
Testes Respiratórios/métodos , Tuberculose/diagnóstico , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Testes Respiratórios/instrumentação , Nariz Eletrônico , Feminino , Humanos , Masculino , Mycobacterium tuberculosis/metabolismo , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tuberculose/metabolismo , Tuberculose/microbiologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/metabolismo
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