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1.
Nat Commun ; 12(1): 2716, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976135

RESUMO

Polyclonal infections occur when at least two unrelated strains of the same pathogen are detected in an individual. This has been linked to worse clinical outcomes in tuberculosis, as undetected strains with different antibiotic resistance profiles can lead to treatment failure. Here, we examine the amount of polyclonal infections in sputum and surgical resections from patients with tuberculosis in the country of Georgia. For this purpose, we sequence and analyse the genomes of Mycobacterium tuberculosis isolated from the samples, acquired through an observational clinical study (NCT02715271). Access to the lung enhanced the detection of multiple strains (40% of surgery cases) as opposed to just using a sputum sample (0-5% in the general population). We show that polyclonal infections often involve genetically distant strains and can be associated with reversion of the patient's drug susceptibility profile over time. In addition, we find different patterns of genetic diversity within lesions and across patients, including mutational signatures known to be associated with oxidative damage; this suggests that reactive oxygen species may be acting as a selective pressure in the granuloma environment. Our results support the idea that the magnitude of polyclonal infections in high-burden tuberculosis settings is underestimated when only testing sputum samples.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Genoma Bacteriano , Granuloma/patologia , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/patologia , Tuberculose Pulmonar/patologia , Antituberculosos/uso terapêutico , Biópsia , Células Clonais , Estudos de Coortes , Variação Genética , República da Geórgia , Granuloma/tratamento farmacológico , Granuloma/microbiologia , Granuloma/cirurgia , Humanos , Pulmão/microbiologia , Pulmão/patologia , Pulmão/cirurgia , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/patogenicidade , Espécies Reativas de Oxigênio/metabolismo , Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/cirurgia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/cirurgia
3.
Int J Tuberc Lung Dis ; 25(5): 395-399, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33977908

RESUMO

BACKGROUND: Treatment outcomes in multidrug-resistant TB (MDR-TB) patients are suboptimal in several low-incidence countries.METHODS: The primary outcome measure was the proportion of successfully treated patients in Italy during an 18-year period. Secondary outcomes were treatment outcomes in certain drug-containing regimens and the possibility for the WHO shorter MDR-TB regimen.RESULTS: In the 191 patients included (median age at admission: 33 years; 67.5% male, following drug-resistance patterns were found: MDR-TB in 68.6%, pre-extensively drug-resistant TB (pre-XDR-TB) in 30.4% and XDR-TB in 1.1% patients. The most frequently prescribed drugs were fluoroquinolones in 84.6% cases, amikacin in 48.7%, linezolid in 34.6% and meropenem/clavulanic acid in 29.5%. The median duration of treatment was 18 months. Treatment success was achieved in 71.2% patients, of whom, 44% were cured and 27.2% completed treatment. Treatment success rates did not statistically differ between the MDR- (68.8%) and pre-XDR-TB (77.6%) groups (P = 0.26). Treatment success rates had large variability between North and South of Italy (81.3% vs. 53.3%). Only 22.5% of the cases would have been eligible for shorter MDR-TB regimensCONCLUSION: Our study highlights variability in treatment outcomes in MDR- and pre-XDR-TB patients. Study findings confirmed the potential utility of linezolid and, for patients with limited oral options, meropenem/clavulanic acid and amikacin.


Assuntos
Tuberculose Extensivamente Resistente a Medicamentos , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/uso terapêutico , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/epidemiologia , Feminino , Humanos , Itália/epidemiologia , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
4.
Stud Health Technol Inform ; 281: 512-513, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34042626

RESUMO

In this study, an attempt has been made to differentiate Drug Resistant Tuberculosis (DR-TB) in chest X-rays using projection profiling and mediastinal features. DR-TB is a condition which is non-responsive to at least one of anti-TB drugs. Mediastinum variations can be considered as significant image biomarkers for detection of DR-TB. Images are obtained from a public database and are contrast enhanced using coherence filtering. Projection profiling is used to obtain the feature lines from which the mediastinal and thoracic indices are computed. Classification of Drug Sensitive (DS-TB) and DR-TB is performed using three classifiers. Results show that the mediastinal features are found to be statistically significant. Support vector machine with quadratic kernel is able to provide better classification performance values of greater than 93%. Hence, the automated analysis of mediastinum could be clinically significant in differentiation of DR-TB.


Assuntos
Tuberculose Resistente a Múltiplos Medicamentos , Gerenciamento de Dados , Bases de Dados Factuais , Humanos , Máquina de Vetores de Suporte , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico por imagem , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Raios X
5.
J Pak Med Assoc ; 71(3): 912-915, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34057947

RESUMO

OBJECTIVE: To explore the burden of drug-resistant tuberculosis in Khyber Pakhtunkhwa, Pakistan. METHODS: The cross-sectional study was conducted from March 1, 2016, to February 28, 2017, at the Khyber Pakhtunkhwa Tuberculosis Reference Laboratory, Hayatabad Medical Complex, Peshawar, Pakistan, and comprised referred suspected tuberculosis patient samples. Drug Susceptibility testing on all Mycobacterium tuberculosis complex strains was performed and data was subjected to statistical analysis. RESULTS: Of the 8220 samples, 4230 (51.5%) were related to females and 3990 (48.5%) to males. Also, 1978 (24%) were related to patients aged 15-24 years. Of the total, 1351 (16.5%) samples were positive on culture. Drug susceptibility testing showed 525 (39%) samples to be resistant to at least one of the first- and second-line drugs. Among the culture-positive cases, 5 (0.4%) were extensively drug-resistant, 62 (4.6%) multi-drug resistant, 243 (18%) polyresistant, 215 (16%) monoresistant and 826 (61%) were pan-sensitive. CONCLUSIONS: Drug-resistant tuberculosis in newly-diagnosed tuberculosis patients was alarmingly high in Khyber Pakhtunkhwa region.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Estudos Transversais , Farmacorresistência Bacteriana , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Mutação , Paquistão/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
6.
Pan Afr Med J ; 38: 203, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995809

RESUMO

Introduction: the emergence of HIV/TB co-infection has changed the global health landscape globally, particularly in sub-Saharan Africa and Asia with a high prevalence rate. It has further worsened and compound patient diagnosis, treatment/management approach and infection control. Rifampicin resistance TB (RR-TB) is a good indicator of treatment failure and infection control in the community. This study determines the prevalence of RR-TB among HIV/TB coinfected patients in Benue State, Nigeria. Methods: the case-control study was carried out at Federal Medical Centre, Makurdi and General Hospital, Otupko, between January 2017 and February 2018. One thousand and ten suspected tuberculosis and HIV patients were enrolled in the study, diagnosed according to WHO guidelines. Sputum samples were collected and then analyzed by acid-fast bacilli smear test and GeneXpert MTB/RIF assay. Results: overall prevalence of tuberculosis by acid-fast test was 74 (7.3%), 171 (16.93%) by GeneXpert assay and 2.18% by RR-TB test respectively. Significant difference was observed between the detection technique and demographic variables, high prevalence among urban patient compared to rural (8.85%vs 5.40%; X2= 4.38; P = 0.036) and ethnic background of the patients (X2= 23.21; P = 0.000) by acid fast test. With GeneXpert, high prevalence recorded among patient within age-group15-45years (X2= 8.01; P = 0.046) and ethnic group (X2= 6.30; P = 0.044). The occurrence of HIV/TB co-infection was less associated with Idoma ethnic group (COR; 0.440; 95% C.I; 0.246 - 0.786). Conclusion: the relatively high prevalence of HIV/TB co-infection and RR-TB is a tremendous public health threat, considering society's attendant implication. Further surveillance studies are needed to evaluate the situation in Benue State better.


Assuntos
Antituberculosos/farmacologia , Infecções por HIV/complicações , Rifampina/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose/epidemiologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Coinfecção , Feminino , Infecções por HIV/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Prevalência , População Rural/estatística & dados numéricos , Escarro/microbiologia , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , População Urbana/estatística & dados numéricos , Adulto Jovem
7.
Pan Afr Med J ; 38: 229, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34046134

RESUMO

Introduction: in Cameroon patients with multidrug/rifampicin resistant pulmonary tuberculosis (MDR/RR-PTB) are treated with a 9-11 month standardised shorter treatment regimen. Despite its effectiveness, factors associated with the occurrence of an unfavourable treatment outcome in this group of patients are not known. Determine the incidence and identify factors associated with an unfavourable treatment outcome among patients with rifampicin resistant pulmonary tuberculosis (RR-PTB) in Yaoundé. Methods: we conducted a retrospective record review of all consecutive patients with bacteriologically confirmed RR-PTB followed up at the specialised MDR/RR-TB treatment centre of the Jamot Hospital in Yaoundé (JHY) from January 2013 to November 2019. A patient was classified as having an unfavourable outcome if he/she had treatment failure, died or was lost to follow-up during the course of treatment. Results: a total of 242 RR-PTB patients with a mean age of 35.59 ± 12.02 years including 144 (59.5%) males were registered. Forty-nine (49) of the 242 patients had an unfavourable treatment outcome giving a cumulative incidence of 20.20% (95% confidence interval (95% CI): 15.40-25.90%). Multivariable analysis revealed that patients with an unfavourable outcome were more likely to be males (odds ratio (OR): 2.94; 95% CI: 1.24-7.00, p= 0.015), HIV infected (OR: 2.67; 95% CI: 1.17-6.06, p = 0.019), and have a baseline haemoglobin level ≤ 10g/dl (OR: 2.87; 95% CI: 1.25-6.58, p = 0.013). Conclusion: the rate of an unfavourable treatment outcome among patients with RR-PTB at the specialised MDR/RR-TB treatment centre of the JHY is relatively high. The male sex, HIV infection and moderate to severe anaemia are independent factors associated with an unfavourable treatment outcome.


Assuntos
Antituberculosos/administração & dosagem , Rifampina/administração & dosagem , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Anemia/epidemiologia , Camarões/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rifampina/farmacologia , Fatores de Risco , Fatores Sexuais , Falha de Tratamento , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Pulmonar/microbiologia , Adulto Jovem
8.
Artigo em Inglês | MEDLINE | ID: mdl-33925705

RESUMO

Uzbekistan has a high burden of drug-resistant tuberculosis (TB). Although conventional treatment for multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) has been available since 2013, there has been no systematic documentation about its use and effectiveness. We therefore documented at national level the trends, characteristics, and outcomes of patients with drug-resistant TB enrolled for treatment from 2013-2018 and assessed risk factors for unfavorable treatment outcomes (death, failure, loss to follow-up, treatment continuation, change to XDR-TB regimen) in patients treated in Tashkent city from 2016-2017. This was a cohort study using secondary aggregate and individual patient data. Between 2013 and 2018, MDR-TB numbers were stable between 2347 and 2653 per annum, while XDR-TB numbers increased from 33 to 433 per annum. At national level, treatment success (cured and treatment completed) for MDR-TB decreased annually from 63% to 57%, while treatment success for XDR-TB increased annually from 24% to 57%. On multivariable analysis, risk factors for unfavorable outcomes, death, and loss to follow-up in drug-resistant TB patients treated in Tashkent city included XDR-TB, male sex, increasing age, previous TB treatment, alcohol abuse, and associated comorbidities (cardiovascular and liver disease, diabetes, and HIV/AIDS). Reasons for these findings and programmatic implications are discussed.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/uso terapêutico , Estudos de Coortes , Humanos , Masculino , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Uzbequistão/epidemiologia
11.
BMC Infect Dis ; 21(1): 394, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33926375

RESUMO

BACKGROUND: Whole-genome sequencing has shown that the Mycobacterium tuberculosis infection process can be more heterogeneous than previously thought. Compartmentalized infections, exogenous reinfections, and microevolution are manifestations of this clonal complexity. The analysis of the mechanisms causing the microevolution -the genetic variability of M. tuberculosis at short time scales- of a parental strain into clonal variants with a patient is a relevant issue that has not been yet completely addressed. To our knowledge, a whole genome sequence microevolution analysis in a single patient with inadequate adherence to treatment has not been previously reported. CASE PRESENTATION: In this work, we applied whole genome sequencing analysis for a more in-depth analysis of the microevolution of a parental Mycobacterium tuberculosis strain into clonal variants within a patient with poor treatment compliance in Argentina. We analyzed the whole-genome sequence of 8 consecutive Mycobacterium tuberculosis isolates obtained from a patient within 57-months of intermittent therapy. Nineteen mutations (9 short-term, 10 fixed variants) emerged, most of them associated with drug resistance. The first isolate was already resistant to isoniazid, rifampicin, and streptomycin, thereafter the strain developed resistance to fluoroquinolones and pyrazinamide. Surprisingly, isolates remained susceptible to the pro-drug ethionamide after acquiring a frameshift mutation in ethA, a gene required for its activation. We also found a novel variant, (T-54G), in the 5' untranslated region of whiB7 (T-54G), a region allegedly related to kanamycin resistance. Notably, discrepancies between canonical and phage-based susceptibility testing to kanamycin were previously found for the isolate harboring this mutation. In our patient, microevolution was mainly driven by drug selective pressure. Rare short-term mutations fixed together with resistance-conferring mutations during therapy. CONCLUSIONS: This report highlights the relevance of whole-genome sequencing analysis in the clinic for characterization of pre-XDR and MDR resistance profile, particularly in patients with incomplete and/or intermittent treatment.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Argentina , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Feminino , Humanos , Isoniazida/uso terapêutico , Adesão à Medicação , Testes de Sensibilidade Microbiana , Mutação , Mycobacterium tuberculosis/isolamento & purificação , Filogenia , Pirazinamida/uso terapêutico , Rifampina/uso terapêutico , Estreptomicina/farmacologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Sequenciamento Completo do Genoma
12.
Artigo em Inglês | MEDLINE | ID: mdl-33799350

RESUMO

Tuberculosis patients "resistant to isoniazid and susceptible to rifampicin (Hr-TB)" remain neglected, despite a high burden and poor outcomes. The World Health Organization (WHO) recommends a 6 month regimen consisting of levofloxacin, rifampicin, ethambutol, and pyrazinamide (LRZE) to treat Hr-TB. In contrast, Uzbekistan uses a 9 month regimen (LRZE plus a second-line injectable in the first 3 months). We aimed to assess the treatment outcomes of this novel regimen among Hr-TB patients treated in two regions of Uzbekistan (Fergana and Bukhara) in 2017-2018. We conducted a cohort study involving secondary analysis of routine surveillance data. Of 132 Hr-TB patients, 105 (80%) were successfully treated. Death was the predominant unsuccessful outcome (13, 10%) followed by "treatment failure" (10, 8%) and "lost to follow-up" (4, 2%). High treatment success is an indicator of the potential effectiveness of the novel regimen and adds to the limited global evidence on this issue. However, the sample size was small and there was no comparison group. Since the study was conducted in two regions of Uzbekistan only, the findings have limited generalizability. We recommend future research using an adequate sample size and an appropriate study design (randomized controlled trial or prospective cohort with a control group receiving the WHO-recommended regimen).


Assuntos
Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Antituberculosos/uso terapêutico , Estudos de Coortes , Humanos , Isoniazida/uso terapêutico , Estudos Prospectivos , Rifampina/uso terapêutico , Resultado do Tratamento , Tuberculose/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Uzbequistão/epidemiologia
13.
BMC Infect Dis ; 21(1): 346, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849486

RESUMO

BACKGROUNDS: The laboratory plays a critical role in tuberculosis (TB) control by providing testing for diagnosis, treatment monitoring, and surveillance at each level of the health care system. Weak accessibility to TB diagnosric services still represents a big concern in many limited resources' countries. Here we report the experience of Burkina Faso in implementing a comprehensive intervention packages to strengthen TB laboratory capacity and diagnostic accessibility. METHODS: The intervention lasted from October 2016 to December 2018 and focused on two main areas: i) development of strategic documents and policies; ii) implementation of TB diagnostic technology. National TB laboratory data were collected between 2016 and 2018 and evaluated according to five programmatic TB laboratory indicators: i) Percentage of notified new and relapse TB cases with bacteriological confirmation; ii) Percentage of notified new and relapse TB cases tested by Xpert MTB/RIF; iii) Percentage of notified, bacteriologically confirmed TB cases with a drug susceptibility testing (DST) result for rifampin; iv) Percentage of notified MDR-TB cases on the estimated number of MDR-TB cases; v) The ration between the number of smear microscopy and Xpert MTB/RIF tests. We compared these indicators between a 1 year (2016-2017) and 2 years (2016-2018) timeframe. RESULTS: From 2016 to 2018, the percentage of bacteriologically confirmed cases increased from 67 to 71%. The percentage of new and relapse TB cases notified tested by Xpert MTB/RIF increased from 18% in 2016 to 46% in 2018 and the percentage of bacteriologically confirmed cases with an available DST result for rifampicin increased from 27% in 2016 to 66% in 2018.. The percentage of notified MDR-TB cases on the estimated number of MDR-TB cases in 2018 increased from 43% in 2016 to 78% in 2018. In 2018, the ratio between the number of smear microscopy and Xpert MTB/RIF tests decreased from 53% in 2016 to 21% in 2018. CONCLUSION: We demonstrated that the implementation of a comprehensive package of laboratory strengthening interventions led to a significant improvement of all indicators. External technical assistance played a key role in speeding up the TB laboratory system improvement process.


Assuntos
Laboratórios , Tuberculose/diagnóstico , Antibióticos Antituberculose/farmacologia , Antibióticos Antituberculose/uso terapêutico , Burkina Faso , Humanos , Cooperação Internacional , Laboratórios/normas , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/efeitos dos fármacos , Kit de Reagentes para Diagnóstico , Recidiva , Rifampina/farmacologia , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
14.
BMJ Open ; 11(4): e043685, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795303

RESUMO

OBJECTIVE: This study aimed to investigate the spatial distribution of drug-resistant tuberculosis (DR-TB) in Hunan province, China. METHODS: An ecological study was conducted using DR-TB data collected from the Tuberculosis Control Institute of Hunan Province between 2012 and 2018. Spatial clustering of DR-TB was explored using the Getis-Ord statistic. A Poisson regression model was fitted with a conditional autoregressive prior structure, and with posterior parameters estimated using a Bayesian Markov chain Monte Carlo simulation, to quantify associations with possible risk factors and identify clusters of high DR-TB risk. RESULTS: A total of 2649 DR-TB patients were reported to Hunan TB Control Institute between 2012 and 2018. The majority of the patients were male (74.8%, n=1983) and had a history of TB treatment (88.53%, n=2345). The proportion of extensively DR-TB among all DR-TB was 3.3% (95% CI 2.7% to 4.1%), which increased from 2.8% in 2012 to 4.4% in 2018. Of 1287 DR-TB patients with registered treatment outcomes, 434 (33.8%) were cured, 198 (15.3%) completed treatment, 92 (7.1%) died, 108 (8.3%) had treatment failure and 455 (35.3%) were lost to follow-up. Half (50.9%, n=655) had poor treatment outcomes. The annual cumulative incidence rate of notified DR-TB increased over time from 0.25 per 100 000 people in 2012 to 0.83 per 100 000 people in 2018. Substantial spatial heterogeneity was observed, and hotspots were detected in counties located in the North and East parts of Hunan province. The cumulative incidence of notified DR-TB was significantly associated with urban communities. CONCLUSION: The annual incidence of notified DR-TB increased over time in Hunan province. Spatial clustering of DR-TB was detected and significantly associated with urbanisation. This finding suggests that targeting interventions to the highest risk areas and population groups would be effective in reducing the burden and ongoing transmission of DR-TB.


Assuntos
Tuberculose Resistente a Múltiplos Medicamentos , Teorema de Bayes , China/epidemiologia , Análise por Conglomerados , Feminino , Humanos , Incidência , Masculino , Análise Espacial , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
15.
BMJ Open ; 11(4): e047023, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33846156

RESUMO

OBJECTIVES: To examine changes in the screening, diagnosis, treatment and management of drug-resistant tuberculosis (DRTB) patients, and investigate the impacts of DRTB-related policies on patients of different demographic and socioeconomic characteristics. DESIGN: A retrospective cohort study using registry data, plus a survey on DRTB-related policies. SETTING: All prefecture-level Centres for Disease Control in Zhejiang Province, China. MAIN OUTCOME MEASURES: Alongside the care cascade, we examined: (1) reported number of presumptive DRTB patients; (2) percentage of presumptive patients with drug susceptibility testing (DST) records; (3) percentage of DRTB/rifampicin-resistant (RR) patients registered; (4) percentage of RR/multidrug-resistant TB (MDRTB) patients that received anti-DRTB treatment; and (5) percentage of RR/MDRTB patients cured/completed treatment among those treated. Multivariate logistic regressions were conducted to explore the impacts of DRTB policies after adjusting for other factors. RESULTS: The number of reported presumptive DRTB patients and the percentage with DST records largely increased during 2015-2018, and the percentage of registered patients who received anti-DRTB treatment also increased from 59.0% to 86.5%. Patients under the policies of equipping GeneXpert plus expanded criteria for DST had a higher likelihood of being registered compared with no GeneXpert (adjusted OR (aOR)=2.57, 95% CI: 1.20 to 5.51), while for treatment initiation the association was only significant when further expanding the registration criteria (aOR=2.38, 95% CI: 1.19 to 4.79). Patients with registered residence inside Zhejiang were more likely to be registered (aOR=1.96, 95% CI: 1.52 to 2.52), treated (aOR=3.83, 95% CI: 2.78 to 5.28) and complete treatment (aOR=1.92, 95% CI: 1.03 to 3.59) compared with those outside. CONCLUSION: The policy changes on DST and registration have effectively improved DRTB case finding and care. Nevertheless, challenges remain in servicing vulnerable groups such as migrants and improving equity in the access to TB care. Future policies should provide comprehensive support for migrants to complete treatment at their current place of residence.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/uso terapêutico , China/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Políticas , Estudos Retrospectivos , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
16.
BMJ Open ; 11(4): e044096, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858870

RESUMO

OBJECTIVES: We aim to define the burden of rifampicin monoresistant tuberculosis (TB) at a tertiary care centre in northern India as well as determine the second-line drug susceptibilities (SL-DST) in a subset of patients. METHODS: A total of 3045 pulmonary (n=1883) and extrapulmonary (n=1162) samples from likely patients with TB were subjected to microscopy, culture and the Xpert MTB/RIF assay from March 2017 to June 2019. SL-DST testing by line probe assay version 2 for fluoroquinolones (FQs) and second-line injectable drugs were performed on 62 samples. RESULTS: Out of 3045 samples processed in our laboratory during the study period, 36.1% (1101/3045) were positive for Mycobacterium tuberculosis complex (MTBC) and 21.6% were rifampicin monoresistant (223/1032). The rate of rifampicin resistance in pulmonary samples was 23.5% (166/706) and in extrapulmonary cases, it was 17.4% (57/326). Out of 62 cases included for second-line testing, 48 were resistant to FQs (77.4%) while 11 were extensively drug resistant. CONCLUSIONS: India urgently needs to arrest an emerging multidrug-resistant TB epidemic with associated resistance to FQs. A robust surveillance system is needed to execute the National Strategic Plan for 2017-2025.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Estudos de Coortes , Farmacorresistência Bacteriana , Humanos , Índia/epidemiologia , Testes de Sensibilidade Microbiana , Estudos Prospectivos , Sensibilidade e Especificidade , Centros de Atenção Terciária , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-33924701

RESUMO

Treatment of drug-resistant tuberculosis is lengthy, insufficiently effective, and toxic. Since 2016, the World Health Organization has recommended shorter treatment regimens (STR). We assessed effectiveness and predictors of drug adverse events (DAE) among patients treated with STR. There were 95 consecutive rifampicin-resistant patients enrolled in STR in Tashkent between June 2018 and September 2019. Of these, 66.3% were successfully treated, 17.9% suffered failed treatment, 7.4% died, 5.3% were lost to follow-up and 3.2% were not evaluated. No recurrence was identified in 54 patients after 12 months of successful treatment completion. There were 47 reported DAE: the incidence rate was 6.15 DAE per 100 person-months-of-treatment. Any DAE was reported in 38 (40%) patients and grade 3/4 DAE were recorded in 21 (22.1%) patients. Median time to DAE was 101 (interquartile range 64-139) days. The most frequently encountered DAE were gastro-intestinal disorders, followed by hepatotoxicity and ototoxicity. The most commonly offending drug inducing DAE was protionamide. The dose was temporarily interrupted in 55.3% of DAE, reduced in 8.5% of DAE and permanently withdrawn in another 8.5% of DAE. HIV status was the only predictor associated with increased hazard of DAE. In Uzbekistan STR showed moderate effectiveness and safety, although treatment failure was high.


Assuntos
Antituberculosos , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/efeitos adversos , Protocolos Clínicos , Humanos , Rifampina/efeitos adversos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Uzbequistão
18.
Artigo em Inglês | MEDLINE | ID: mdl-33921547

RESUMO

Compliance with treatment guidelines is essential to achieve successful outcomes in tuberculosis patients. Thus, we assessed if multidrug-resistant tuberculosis treatment practices from 2012-2018 in Uzbekistan were compliant with national guidelines in terms of regimens prescribed, weight-based drug dosages used, and documentation of treatment changes (such as prolongation of intensive phase, change of drugs, and their reasons) in the treatment card and Consilium form. A total of 1481 patients were included. Of them, only 25% received standardized regimens as per guidelines and the remaining received individualized regimens. There was an increasing trend in using standardized regimens from 2% in 2012 to 44% in 2018. Compliance to recommended weight-based drug dosages was observed in 85% of the patients during the intensive phase and 84% in the continuation phase-ranged 71-91% over the years. Prolongation of the intensive phase was done in 42% of patients. The treatment was changed in 44% of patients during the intensive phase and 34% of patients during the continuation phase. The documentation of treatment changes was suboptimal (42-75%) during the initial years (2012-2014); however, it improved significantly during later years (86-100%). Future research should explore reasons for non-compliance so that the quality of patient care can be improved.


Assuntos
Antituberculosos , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/uso terapêutico , Humanos , Cooperação do Paciente , Políticas , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Uzbequistão/epidemiologia
19.
Wiad Lek ; 74(3 cz 2): 669-673, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33843632

RESUMO

OBJECTIVE: The aim: To analyze molecular epidemiology features of M. tuberculosis in Kyiv oblast; and to identify the safest mode of TB treatment, which will allow clinicians to minimize the risk of drug-resistant strains nosocomial transmission. PATIENTS AND METHODS: Materials and methods: 55 isolates of M. tuberculosis were collected in January-April, 2018 from 31 patients with new cases and 24 patients with re-treatment cases of sputum culture-positive pulmonary TB, in Kyiv oblast, Ukraine. DNA samples extracted from all the isolates were used for 15-loci MIRU-VNTR molecular typing with further M. tuberculosis strains comparison by means of MIRU-VNTRplus web tool (http://www.miru-vntrplus.org). RESULTS: Results: Phylogenetic tree that reflects strains interrelationship reveals four main clusters, the largest of which spans 34 isolates. The presence of two big subclusters with 10 and 7 identical genotypes inside the largest cluster strongly suggests their tight epidemiologic relationship. Smaller clusters consist of five (Harlem), three (URAL), and two unidentified isolates. 10 singletons were detected, among which LAM, URAL and Cameroon lineages were identified; in these cases, epidemiological connection was presumably ruled out. CONCLUSION: Conclusions: High clustering level of isolates of M. tuberculosis suggests possible contact between patients from whom these isolates were obtained. Predominance of Beijing family in the clusters is associated with high DR-TB level, at least in eastern European countries. Similarity of the clusters isolated from different patients in a household or a hospital suggests high probability of recent disease transmission. Clustering genotypes from households and hospital wards can be a surrogate criterion of infection control effectiveness.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Genótipo , Humanos , Repetições Minissatélites , Epidemiologia Molecular , Mycobacterium tuberculosis/genética , Filogenia , Falha de Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Ucrânia
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