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1.
Can J Microbiol ; 65(11): 823-830, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31295416

RESUMO

This study examined the evolving nature of Bordetella pertussis in Ontario, Canada, by characterizing isolates for their genotypes and expression of pertactin (PRN). From 2009 to 2017, 413 B. pertussis were cultured from pertussis cases at the Public Health Ontario Laboratory. Their genotypes were determined by partial gene sequence analysis of their virulence and (or) vaccine antigens: filamentous haemagglutinin, PRN, fimbriae 3, and pertussis toxin, including the promoter region. Expression of PRN was measured by Western immunoblot. Two predominant genotypes, ST-1 and ST-2, were found throughout the study and were responsible for 47.5% and 46.3% of all case isolates, respectively. The prevalence of ST-1 appeared to fluctuate from 80.3% in 2009 to 20.0% in 2014 and 58.5% in 2017, while the prevalence of ST-2 changed from 18.4% in 2009 to 80.0% in 2014 and 26.2% in 2017. A PRN-deficient strain was first noted in 2011 (16.7%), and its prevalence increased to 70.8% in 2016 but decreased to 46.2% in 2017. More ST-2 (46.6%) than ST-1 (16.8%) strains were associated with PRN deficiency. Newer ST-21 and ST-22 found in 2015-2017 were uniformly PRN deficient. The impact of the evolving nature of B. pertussis on disease epidemiology requires further longitudinal studies.


Assuntos
Proteínas da Membrana Bacteriana Externa/metabolismo , Bordetella pertussis/genética , Bordetella pertussis/isolamento & purificação , Fatores de Virulência de Bordetella/metabolismo , Coqueluche/microbiologia , Proteínas da Membrana Bacteriana Externa/genética , Bordetella pertussis/metabolismo , Genótipo , Humanos , Ontário/epidemiologia , Prevalência , Fatores de Virulência de Bordetella/genética , Coqueluche/epidemiologia
2.
Emerg Infect Dis ; 25(7)2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31215507

RESUMO

Surveys suggest that clinicians diverge from guidelines when treating Mycobacterium avium complex (MAC) pulmonary disease (PD). To determine prescribing patterns, we conducted a cohort study of adults >66 years of age in Ontario, Canada, with MAC or Mycobacterium xenopi PD during 2001-2013. Using linked laboratory and health administrative databases, we studied the first treatment episode (>60 continuous days of >1 of a macrolide, ethambutol, rifamycin, fluoroquinolone, linezolid, inhaled amikacin, or, for M. xenopi, isoniazid). Treatment was prescribed for 24% MAC and 15% of M. xenopi PD patients. Most commonly prescribed was the recommended combination of macrolide, ethambutol, and rifamycin, for 47% of MAC and 36% of M. xenopi PD patients. Among MAC PD patients, 20% received macrolide monotherapy and 33% received regimens associated with emergent macrolide resistance. Although the most commonly prescribed regimen was guidelines-recommended, many regimens prescribed for MAC PD were associated with emergent macrolide resistance.


Assuntos
Antibacterianos , Prescrições de Medicamentos , Complexo Mycobacterium avium , Infecção por Mycobacterium avium-intracellulare/epidemiologia , Padrões de Prática Médica , Tuberculose Pulmonar/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Prescrições de Medicamentos/normas , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , História do Século XXI , Humanos , Masculino , Complexo Mycobacterium avium/efeitos dos fármacos , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/história , Infecção por Mycobacterium avium-intracellulare/microbiologia , Ontário/epidemiologia , Fatores Socioeconômicos , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/história , Tuberculose Pulmonar/microbiologia
3.
Can J Microbiol ; 65(11): 805-813, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31242396

RESUMO

In the post-Haemophilus influenzae serotype b (Hib) vaccine era, invasive H. influenzae serotype a (Hia) disease emerged in Canadian First Nation, Inuit, and Alaskan Indigenous populations. Previous studies by our group found a high incidence of invasive Hia disease in northwestern Ontario. We retrospectively reviewed 24 cases (4 pediatric and 20 adult) of invasive H. influenzae disease hospitalized at the northwestern Ontario regional hospital between August 2011 and June 2018. The objectives were to further document the changing epidemiology of invasive H. influenzae disease in the region and to discuss potential control measures. Twenty-two H. influenzae isolates were serotyped and characterized using molecular-biological methods. Of the serotyped cases, there were 2 Hib, 9 Hia, and 11 non-typeable (NTHi). All Hia isolates belonged to the most common sequence types (ST) found in Canada (ST-23 and ST-929); 8 out of 9 were pan susceptible to antibiotics. One (11%) of 9 Hia and 5 (45%) of 11 NTHi cases were fatal. Our data on the consistent presence of serious invasive H. influenzae disease, with 41% prevalence of Hia (9 out of 22 serotyped isolates) and 50% prevalence of NTHi strains (11 out of 22), emphasize the importance of continued surveillance of H. influenzae in the post-Hib vaccine era and are critical information to inform potential vaccine development.


Assuntos
Infecções por Haemophilus/microbiologia , Vacinas Anti-Haemophilus/administração & dosagem , Haemophilus influenzae/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Pré-Escolar , Monitoramento Epidemiológico , Infecções por Haemophilus/epidemiologia , Infecções por Haemophilus/imunologia , Infecções por Haemophilus/prevenção & controle , Vacinas Anti-Haemophilus/imunologia , Haemophilus influenzae/classificação , Haemophilus influenzae/genética , Haemophilus influenzae/imunologia , Humanos , Incidência , Lactente , Pessoa de Meia-Idade , Ontário/epidemiologia , Estudos Retrospectivos , Sorogrupo , Vacinação , Adulto Jovem
4.
PLoS One ; 14(4): e0214870, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30943250

RESUMO

OBJECTIVES: Compare the molecular epidemiology of tuberculosis (TB) between two large Canadian provinces-Ontario and British Columbia (BC)-to identify genotypic clusters within and across both provinces, allowing for an improved understanding of genotype data and providing context to more accurately identify clusters representing local transmission. DESIGN: We compared 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) genotyping for 3,314 Ontario and 1,602 BC clinical Mycobacterium tuberculosis isolates collected from 2008 through 2014. Laboratory data for each isolate was linked to case-level records to obtain clinical and demographic data. RESULTS: The demographic characteristics of persons with TB varied between provinces, most notably in the proportion of persons born outside Canada, which was reflected in the large number of unique genotypes (n = 3,461). The proportion of clustered isolates was significantly higher in BC. Substantial clustering amongst non-Lineage 4 TB strains was observed within and across the provinces. Only two large clusters (≥10 cases/cluster) representing within province transmission had interprovincial genotype matches. CONCLUSION: We recommend expanding analysis of shared genotypes to include neighbouring jurisdictions, and implementing whole genome sequencing to improve identification of TB transmission, recognize outbreaks, and monitor changing trends in TB epidemiology.


Assuntos
Mycobacterium tuberculosis/genética , Tuberculose/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Técnicas de Tipagem Bacteriana , Colúmbia Britânica/epidemiologia , Criança , Pré-Escolar , Feminino , Técnicas de Genotipagem , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Ontário/epidemiologia , Tuberculose/transmissão , Sequenciamento Completo do Genoma , Adulto Jovem
5.
Vaccine ; 37(19): 2617-2623, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30967309

RESUMO

BACKGROUND: Resurgences of pertussis have occurred in several high-income countries, often linked to waning of immunity from acellular pertussis vaccines. The degree of waning observed has varied by study design and setting. In Ontario, pertussis has not shown a substantial resurgence in the past decade. The routine immunization schedule comprises three priming doses in infancy, toddler and pre-school doses, and an adolescent dose at 14-16 years of age. METHODS: We estimated pertussis vaccine effectiveness (VE) through a case-control study of 1335 cases statutorily reported to public health in Ontario and occurring between January 1, 2009 and March 31, 2015, compared with 5340 randomly selected population controls, frequency-matched by age, primary-care provider and year of diagnosis. Pertussis cases met provincial confirmed or probable case definitions. We used multivariable logistic regression to estimate crude and adjusted odds ratios (aOR). RESULTS: VE against pertussis was sustained between 92% (95% confidence interval (95%CI) 88-95%) in 2-3 year olds and 90% (95%CI: 80-95%) in 8-9 year olds, but fell rapidly to 49% (95%CI: 2-73%) in children 12-13 years of age. VE following the teenage booster given at 14-16 years in Ontario reached 76% (95%CI: 52-88%) in 14-16 year olds and 78% (95%CI: -31 to 96%) in those 16-22 years old. For children who were up-to-date with the immunization schedule, VE declined from 87% (95%CI: 84-90%) during the first year to 74% (95%CI: 63-82%) after 8 or more years following their last dose of immunization. CONCLUSIONS: VE is high during the first decade of life but then falls rapidly. Protection is not fully restored by the teenage booster. Our findings are consistent with the localized outbreaks we observe in high school children and underline the importance of additional policies to protect infants.

6.
Zoonoses Public Health ; 66(1): 164-168, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30144283

RESUMO

In July 2015, a cluster of five suspect cases of clinically diagnosed Mycobacterium marinum (M. marinum) skin infections were reported to the Haliburton, Kawartha, Pine Ridge District Health Unit (HKPRDHU), Ontario, Canada, with two additional cases subsequently identified through case finding. All seven cases presented with cutaneous lesions located on the finger, hand and/or elbow regions typical of M. marinum infection. Specimens were collected by skin biopsy for two of the seven cases; both cases tested positive for M. marinum by molecular detection (hsp65 gene amplification and sequencing), and one was confirmed positive for M. marinum by culture. All seven cases reported handling raw shrimp from an aquaculture facility in the Health Unit's jurisdiction. M. marinum is not a reportable disease in Ontario, and there are no known previous reports of a cluster of M. marinum reported in Ontario, Canada. A cluster investigation working group was struck that included representation from various agencies including Public Health Ontario (PHO), Public Health Ontario Laboratories (PHOL), Ontario Ministry of Agriculture and Rural Affairs (OMAFRA) and the two health units involved in case investigations. Several public health and aquaculture farming recommendations were made to mitigate further risks associated with handling of raw shrimp from the facility. Several challenges were faced during the investigation process. The paper discusses these challenges and public health recommendations made in order to mitigate occupational and public health risks related to the hazard identified.


Assuntos
Infecções por Micobactéria não Tuberculosa/microbiologia , Mycobacterium marinum/isolamento & purificação , Dermatopatias Bacterianas/microbiologia , Adulto , Idoso , Animais , Aquicultura , Análise por Conglomerados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Micobactéria não Tuberculosa/epidemiologia , Ontário/epidemiologia , Dermatopatias Bacterianas/epidemiologia , Zoonoses
7.
J Antimicrob Chemother ; 74(1): 22-28, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30295754

RESUMO

Objectives: Neisseria meningitidis is rarely penicillin resistant. We describe WGS analysis of a penicillin-resistant N. meningitidis collected from a case of invasive meningococcal disease. Methods: Serogrouping, serotyping and serosubtyping were performed with specific antibodies. ß-Lactamase was detected by nitrocefin. MICs were determined by Etest and agar dilution. Sequencing of N. meningitidis genomes was done on the Illumina MiSeq platform and genome data were analysed using the Bacterial Isolate Genome Sequence Database (BIGSdb) on the PubMLST Neisseria website (https://pubmlst.org/neisseria/). Transformation was used to confirm the genetic basis of the penicillin resistance. Results: An N. meningitidis blood isolate from a female patient in her mid-50s with a painful and septic left shoulder was found to have penicillin MIC values of 3-12 mg/L. The isolate was typed as Y: 14, 19: P1.- and ST3587, and was weakly ß-lactamase positive. WGS analysis identified a full-length copy of the ß-lactamase gene blaROB-1, which was contained on a 1719 bp insert with a G + C content of 41.7% (versus a G + C content of N. meningitidis of 51.7%), suggesting that the blaROB-1 gene came from a different bacterial species. A GenBank analysis of the blaROB-1 gene insert found 99.77% identity with a DNA segment found in plasmid pB1000' from Haemophilus influenzae. Transformation of a penicillin-susceptible strain with the blaROB-1 gene conferred ß-lactamase activity and penicillin resistance. Conclusions: N. meningitidis serogroup Y, ST3587 can carry and express the blaROB-1 gene, leading to penicillin resistance. It is highly likely that the N. meningitidis isolate acquired the blaROB-1 gene from H. influenzae.


Assuntos
Meningite Meningocócica/microbiologia , Neisseria meningitidis/genética , Resistência às Penicilinas , Sequenciamento Completo do Genoma , beta-Lactamases/genética , Composição de Bases , Feminino , Humanos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Neisseria meningitidis/efeitos dos fármacos , Neisseria meningitidis/enzimologia , Neisseria meningitidis/isolamento & purificação , Sorotipagem , Transformação Bacteriana
8.
Diagn Microbiol Infect Dis ; 93(4): 329-333, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30527784

RESUMO

Microscopic examination of the specimen smear for acid fast bacilli (AFB) provides a simple and rapid means of detecting AFB using fluorescent stain methods and remains a valuable diagnostic test used worldwide to identify and manage suspect cases of tuberculosis (TB). Methods to improve AFB smear staining protocols could provide better detection of suspect TB cases. In particular, decreasing background debris may improve the detection of smears with low numbers of bacilli. We assessed staining by the standard rack method compared to bulk container staining using an acetone rinse step to decrease background debris. No cross-contamination was observed in the bulk container staining, and higher accuracy with less reading time was achieved with the acetone rinse. Most importantly, more bacilli were detected per positive smear using the acetone rinse method.


Assuntos
Microscopia de Fluorescência/métodos , Manejo de Espécimes/métodos , Coloração e Rotulagem/métodos , Tuberculose/diagnóstico , Acetona , Corantes Fluorescentes , Humanos , Solventes
9.
PLoS One ; 13(5): e0195984, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29718945

RESUMO

INTRODUCTION: Under-reporting of pertussis cases is a longstanding challenge. We estimated the true number of pertussis cases in Ontario using multiple data sources, and evaluated the completeness of each source. METHODS: We linked data from multiple sources for the period 2009 to 2015: public health reportable disease surveillance data, public health laboratory data, and health administrative data (hospitalizations, emergency department visits, and physician office visits). To estimate the total number of pertussis cases in Ontario, we used a three-source capture-recapture analysis stratified by age (infants, or aged one year and older) and adjusting for dependency between sources. We used the Bayesian Information Criterion to compare models. RESULTS: Using probable and confirmed reported cases, laboratory data, and combined hospitalizations/emergency department visits, the estimated total number of cases during the six-year period amongst infants was 924, compared with 545 unique observed cases from all sources. Using the same sources, the estimated total for those aged 1 year and older was 12,883, compared with 3,304 observed cases from all sources. Only 37% of infants and 11% for those aged 1 year and over admitted to hospital or seen in an emergency department for pertussis were reported to public health. Public health reporting sensitivity varied from 2% to 68% depending on age group and the combination of data sources included. Sensitivity of combined hospitalizations and emergency department visits varied from 37% to 49% and of laboratory data from 1% to 50%. CONCLUSIONS: All data sources contribute cases and are complementary, suggesting that the incidence of pertussis is substantially higher than suggested by routine reports. The sensitivity of different data sources varies. Better case identification is required to improve pertussis control in Ontario.


Assuntos
Imunização/estatística & dados numéricos , Relatório de Pesquisa , Pesquisa/estatística & dados numéricos , Coqueluche/prevenção & controle , Humanos , Lactente , Ontário , Projetos de Pesquisa
10.
Int J Infect Dis ; 69: 55-62, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29414677

RESUMO

OBJECTIVES: This study was performed to analyze the Canadian invasive serogroup W Neisseria meningitidis (MenW) sequence type 11 (ST-11) clonal complex (CC) isolates by whole genome typing and to compare Canadian isolates with similar isolates from elsewhere. METHODS: Whole genome typing of 30 MenW ST-11 CC, 20 meningococcal group C (MenC) ST-11 CC, and 31 MenW ST-22 CC isolates was performed on the Bacterial Isolate Genome Sequence database platform. Canadian MenW ST-11 CC isolates were compared with the 2000 MenW Hajj outbreak strain, as well as with MenW ST-11 CC from other countries. RESULTS: Whole genome typing showed that the Canadian MenW ST-11 CC isolates were distinct from the traditional MenW ST-22 CC; they were not capsule-switched contemporary MenC strains that incorporated MenW capsules. While some recent MenW disease cases in Canada were caused by MenW ST-11 CC isolates showing relatedness to the 2000 MenW Hajj strain, many were non-Hajj isolates similar to current MenW ST-11 isolates found globally. Geographical and temporal variations in genotypes and surface protein antigen genes were found among the MenW ST-11 CC isolates. CONCLUSIONS: The current MenW ST-11 isolates did not arise by capsule switching from contemporary MenC ST-11 isolates. Both the Hajj-related and non-Hajj MenW ST-11 CC strains were associated with invasive meningococcal disease in Canada.


Assuntos
Técnicas de Tipagem Bacteriana , Infecções Meningocócicas/diagnóstico , Infecções Meningocócicas/epidemiologia , Neisseria meningitidis Sorogrupo C/genética , Neisseria meningitidis/genética , Adesinas Bacterianas/genética , Alelos , Antígenos de Bactérias/genética , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Bactérias/genética , Canadá/epidemiologia , Surtos de Doenças , Técnicas de Genotipagem , Humanos , Neisseria meningitidis/isolamento & purificação , Neisseria meningitidis Sorogrupo C/isolamento & purificação , Filogenia , Porinas/genética , Análise de Sequência de DNA , Sorogrupo
11.
Lung ; 196(2): 213-217, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29349535

RESUMO

Mycobacterium xenopi is responsible for pulmonary disease (PD) in Europe and Canada. Despite its high prevalence and increasing clinical importance, little is known about the genetic diversity of M. xenopi. Through a prospective study for M. xenopi strain type and the relation to clinical phenotype, 39 patients with M. xenopi PD were analyzed. Our study demonstrated that sequence type (ST) 5 was dominant in Ontario among 15 distinct STs and caused PD in people even without underlying lung disease, whereas disease due to non-ST5 was found almost exclusively in patients with underlying lung disease.


Assuntos
DNA Bacteriano/genética , Pulmão/microbiologia , Infecções por Micobactéria não Tuberculosa/microbiologia , Mycobacterium xenopi/genética , Infecções Respiratórias/microbiologia , Idoso , Idoso de 80 Anos ou mais , Técnicas Bacteriológicas , Comorbidade , Feminino , Genótipo , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Tipagem de Sequências Multilocus , Infecções por Micobactéria não Tuberculosa/diagnóstico , Infecções por Micobactéria não Tuberculosa/epidemiologia , Infecções por Micobactéria não Tuberculosa/fisiopatologia , Mycobacterium xenopi/patogenicidade , Ontário/epidemiologia , Fenótipo , Prognóstico , Estudos Prospectivos , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/fisiopatologia , Fatores de Risco
12.
CMAJ Open ; 5(4): E872-E877, 2017 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-29269437

RESUMO

BACKGROUND: There is mounting evidence that the recent resurgence of pertussis in many countries is in part related to the acellular vaccine, which has been administered in Canada since 1997. This vaccine elicits a different cell-mediated immune response than the previously used whole-cell vaccine, and its effectiveness wanes over time. The aim of this study is to understand the immunological, demographic and clinical factors that mediate protection from pertussis on exposure. METHODS: This is a household case-control study protocol. Following notification of an index case in a household, a study team will conduct a home visit to collect data and biological specimens. The study team will return to the household 8 weeks from the onset of illness in the index case. The Th1, Th2 and Th17 responses, cytokine expression, IgG subclass, blood cell counts and presence of Bordetella pertussis will be determined. We will use laboratory and statistical analyses to determine immunological differences between contacts who are infected with B. pertussis and contacts who remain healthy, and to determine which clinical and demographic covariates are associated with a reduced risk of infection. INTERPRETATION: The results of this study will be essential for understanding the immune response required for protection from infection with B. pertussis and will contribute to our understanding of the shortcomings of the current vaccine.

13.
Emerg Infect Dis ; 23(11): 1898-1901, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29048292

RESUMO

In Ontario, Canada, during 1998-2010, nontuberculous mycobacteria (NTM) from pulmonary sites comprised 96% of species/patient combinations isolated; annual rates of isolation and cases increased steadily. NTM isolates from nonpulmonary sites comprised 4% of species/patient combinations; annual rates and cases were temporally stable. NTM increases were driven exclusively by pulmonary isolates and disease.


Assuntos
Infecções por Micobactéria não Tuberculosa/epidemiologia , Micobactérias não Tuberculosas/isolamento & purificação , Humanos , Pulmão/microbiologia , Infecções por Micobactéria não Tuberculosa/microbiologia , Micobactérias não Tuberculosas/classificação , Ontário/epidemiologia , Prevalência , Estudos Retrospectivos
14.
Eur Respir J ; 50(3)2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28931659

RESUMO

Inhaled corticosteroid (ICS) use is associated with an increased risk of pneumonia. This study was performed to determine if ICS use is associated with an increased risk of nontuberculous mycobacterial pulmonary disease (NTM-PD) or tuberculosis (TB).We conducted a population-based nested case-control study using linked laboratory and health administrative databases in Ontario, Canada, including adults aged ≥66 years with treated obstructive lung disease (i.e. asthma, chronic obstructive pulmonary disease (COPD) or asthma-COPD overlap syndrome) between 2001 and 2013. We estimated odds ratios comparing ICS use with nonuse among NTM-PD and TB cases and controls using conditional logistic regression.Among 417 494 older adults with treated obstructive lung disease, we identified 2966 cases of NTM-PD and 327 cases of TB. Current ICS use was associated with NTM-PD compared with nonuse (adjusted OR (aOR) 1.86, 95% CI 1.60-2.15) and was statistically significant for fluticasone (aOR 2.09, 95% CI 1.80-2.43), but not for budesonide (aOR 1.19, 95% CI 0.97-1.45). There was a strong dose-response relationship between incident NTM-PD and cumulative ICS dose over 1 year. There was no significant association between current ICS use and TB (aOR 1.43, 95% CI 0.95-2.16).This study suggests that ICS use is associated with an increased risk of NTM-PD, but not TB.


Assuntos
Corticosteroides/efeitos adversos , Pneumopatias Obstrutivas/complicações , Pneumopatias Obstrutivas/tratamento farmacológico , Infecções por Micobactéria não Tuberculosa/epidemiologia , Tuberculose/epidemiologia , Administração por Inalação , Corticosteroides/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Budesonida/uso terapêutico , Estudos de Casos e Controles , Feminino , Fluticasona/uso terapêutico , Humanos , Modelos Logísticos , Masculino , Infecções por Micobactéria não Tuberculosa/tratamento farmacológico , Infecções por Micobactéria não Tuberculosa/etiologia , Ontário/epidemiologia , Fatores de Risco , Tuberculose/tratamento farmacológico , Tuberculose/etiologia
15.
PLoS One ; 12(6): e0179996, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28650996

RESUMO

Tuberculosis remains one of the most difficult to control infectious diseases in the world. Many different factors contribute to the complexity of this disease. These include the ability of the host to control the infection which may directly relate to nutritional status, presence of co-morbidities and genetic predisposition. Pathogen factors, in particular the ability of different Mycobacterium tuberculosis strains to respond to the harsh environment of the host granuloma, which includes low oxygen and nutrient availability and the presence of damaging radical oxygen and nitrogen species, also play an important role in the success of different strains to cause disease. In this study we evaluated the impact of a naturally occurring 12 gene 15 Kb genomic deletion on the physiology and virulence of M. tuberculosis. The strains denominated ON-A WT (wild type) and ON-A NM (natural mutant) were isolated from a previously reported TB outbreak in an inner city under-housed population in Toronto, Canada. Here we subjected these isogenic strains to transcriptomic (via RNA-seq) and proteomic analyses and identified several gene clusters with differential expression in the natural mutant, including the DosR regulon and the molybdenum cofactor biosynthesis genes, both of which were found in lower abundance in the natural mutant. We also demonstrated lesser virulence of the natural mutant in the guinea pig animal model. Overall, our findings suggest that the ON-A natural mutant is less fit to cause disease, but nevertheless has the potential to cause extended transmission in at-risk populations.


Assuntos
Deleção de Genes , Genoma Bacteriano , Mycobacterium tuberculosis/genética , Animais , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/genética , Coenzimas/biossíntese , Coenzimas/genética , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Cobaias , Humanos , Metabolismo dos Lipídeos/genética , Metaloproteínas/biossíntese , Metaloproteínas/genética , Família Multigênica , Mycobacterium tuberculosis/metabolismo , Mycobacterium tuberculosis/patogenicidade , Proteínas Quinases/genética , Proteômica , Pteridinas , Regulon , Tuberculose Pulmonar/microbiologia , Virulência/genética
16.
J Clin Microbiol ; 55(5): 1446-1453, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28228490

RESUMO

Bordetella pertussis is a Gram-negative bacterium that causes respiratory infections in humans. Ongoing molecular surveillance of B. pertussis acellular vaccine (aP) antigens is critical for understanding the interaction between evolutionary pressures, disease pathogenesis, and vaccine effectiveness. Methods currently used to characterize aP components are relatively labor-intensive and low throughput. To address this challenge, we sought to derive aP antigen genotypes from minimally processed short-read whole-genome sequencing data generated from 40 clinical B. pertussis isolates and analyzed using the SRST2 bioinformatic package. SRST2 was able to identify aP antigen genotypes for all antigens with the exception of pertactin, possibly due to low read coverage in GC-rich low-complexity regions of variation. Two main genotypes were observed in addition to a singular third genotype that contained an 84-bp deletion that was identified by SRST2 despite the issues in allele calling. This method has the potential to generate large pools of B. pertussis molecular data that can be linked to clinical and epidemiological information to facilitate research of vaccine effectiveness and disease severity in the context of emerging vaccine antigen-deficient strains.


Assuntos
Bordetella pertussis/genética , Bordetella pertussis/imunologia , Monitoramento Epidemiológico , Genoma Bacteriano/genética , Vacina contra Coqueluche/imunologia , Coqueluche/epidemiologia , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Sequência de Bases , Bordetella pertussis/isolamento & purificação , Criança , Pré-Escolar , DNA Bacteriano/genética , Humanos , Lactente , Ontário , Análise de Sequência de DNA , Coqueluche/microbiologia , Coqueluche/patologia
17.
Emerg Infect Dis ; 23(3): 468-476, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28221106

RESUMO

Survival implications of nontuberculous mycobacterial pulmonary disease (NTM-PD) and NTM pulmonary isolation without disease (NTM-PI) are unclear. To study deaths associated with NTM-PD and NTM-PI and differences in survival between them, we conducted a population-based cohort study of persons with microbiologically defined NTM-PD or NTM-PI diagnosed during 2001-2013 in Ontario, Canada. We used propensity score matching and Cox proportional hazards models to compare survival. Among 9,681 NTM-PD patients and 10,936 NTM-PI patients, 87% and 91%, respectively, were successfully matched with unexposed controls. Both NTM-PD and NTM-PI were associated with higher rates of death for all species combined and for most individual species. Compared with NTM-PI, NTM-PD was associated with higher death rates for all species combined, Mycobacterium avium complex, and M. xenopi. NTM-PD and NTM-PI were significantly associated with death, NTM-PD more so than NTM-PI.


Assuntos
Pneumopatias/microbiologia , Pneumopatias/mortalidade , Infecções por Micobactéria não Tuberculosa/microbiologia , Infecções por Micobactéria não Tuberculosa/mortalidade , Idoso , Feminino , Humanos , Hospedeiro Imunocomprometido , Pneumopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Infecções por Micobactéria não Tuberculosa/epidemiologia , Ontário/epidemiologia , Fatores de Risco
18.
J Antimicrob Chemother ; 72(5): 1314-1319, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28137937

RESUMO

Background: Previously we studied the antibiotic susceptibility of invasive Haemophilus influenzae collected in Canada from 1990 to 2006 and characterized isolates by serotype, MLST and ftsI gene sequencing for significant PBP3 mutations. Objectives: To provide an update based on isolates collected from 2007 to 2014. Methods: A total of 882 case isolates were characterized by serotype using slide agglutination and PCR. MLST was carried out to determine ST. Isolates were tested for ß-lactamase production, presence of significant PBP3 mutations and antibiotic susceptibility by disc diffusion against 14 antibiotics. MIC values of three antibiotics were determined for 316 isolates using microbroth dilution. Results: Non-typeable H. influenzae accounted for 54.6% of the isolates and 45.4% were serotypeable, predominantly type a (23.1%), type b (8.3%) and type f (10.8%). The overall rate of ampicillin resistance due to ß-lactamase production was 16.4% and increased from 13.5% in 2007-10 to 19% in 2011-14. Significant PBP3 mutations were identified in 129 isolates (14.6%) with 23 (2.6%) also producing ß-lactamase. MLST identified related STs (ST-136, ST-14 and ST-367) associated exclusively with genetically ß-lactamase-negative, ampicillin-resistant isolates and confirmed previously reported associations between significant PBP3 mutations and ST. Conclusions: A significant increase in ß-lactamase-producing isolates was observed from 2007 to 2014; the rate of significant PBP3 mutations has increased since previously reported and 52.5% of non-typeable H. influenzae now show resistance markers. Resistance to trimethoprim/sulfamethoxazole was common and no resistance to fluoroquinolones or third-generation cephalosporins was found.


Assuntos
Antibacterianos/farmacologia , Infecções por Haemophilus/microbiologia , Haemophilus influenzae/efeitos dos fármacos , Haemophilus influenzae/genética , Ampicilina/farmacologia , Canadá/epidemiologia , DNA Bacteriano/genética , Genótipo , Infecções por Haemophilus/epidemiologia , Haemophilus influenzae/patogenicidade , Humanos , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Reação em Cadeia da Polimerase , Sorogrupo , Sorotipagem , beta-Lactamases/genética
19.
J Am Med Inform Assoc ; 24(e1): e136-e142, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-27589943

RESUMO

Objective: Develop a tool to disseminate integrated laboratory, clinical, and demographic case data necessary for improved contact tracing and outbreak detection of tuberculosis (TB). Methods: In 2007, the Public Health Ontario Laboratories implemented a universal genotyping program to monitor the spread of TB strains within Ontario. Ontario Universal Typing of TB (OUT-TB) Web utilizes geographic information system (GIS) technology with a relational database platform, allowing TB control staff to visualize genotyping matches and microbiological data within the context of relevant epidemiological and demographic data. Results: OUT-TB Web is currently available to the 8 health units responsible for >85% of Ontario's TB cases and is a valuable tool for TB case investigation. Users identified key features to implement for application enhancements, including an e-mail alert function, customizable heat maps for visualizing TB and drug-resistant cases, socioeconomic map layers, a dashboard providing TB surveillance metrics, and a feature for animating the geographic spread of strains over time. Conclusion: OUT-TB Web has proven to be an award-winning application and a useful tool. Developed and enhanced using regular user feedback, future versions will include additional data sources, enhanced map and line-list filter capabilities, and development of a mobile app.


Assuntos
Surtos de Doenças , Genótipo , Sistemas de Informação Geográfica , Internet , Mycobacterium tuberculosis/genética , Vigilância em Saúde Pública/métodos , Tuberculose/epidemiologia , Humanos , Epidemiologia Molecular , Ontário/epidemiologia , Software , Tuberculose/microbiologia , Interface Usuário-Computador
20.
Nat Genet ; 48(12): 1535-1543, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27798628

RESUMO

Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration.


Assuntos
DNA Bacteriano/análise , Genômica/métodos , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/genética , Polimorfismo Genético/genética , Tuberculose/microbiologia , Genótipo , Saúde Global , Humanos , Mycobacterium tuberculosis/isolamento & purificação , Filogeografia , Tuberculose/genética
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