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1.
Vaccine ; 36(31): 4701-4707, 2018 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-29937245

RESUMO

The 13-valent conjugate vaccine (PCV13) was recommended for childhood immunization programs in 2010 in Canada and has decreased the incidence of invasive pneumococcal disease (IPD) in children and changed the epidemiology of IPD in adults. This study investigated the epidemiology of IPD in adults 65 years of age and older in Canada. A total of 7282 invasive S. pneumoniae isolated from adults ≥65 years old were serotyped from 2010 to 2016 and antimicrobial susceptibility was performed on 2527 isolates. Serotyping was performed by Quellung reaction using commercial antisera and antimicrobial susceptibilities were determined by broth microdilution. PCV7 serotypes decreased non-significantly from 2010 to 2016 from 9.1% (n = 96) to 6.7% (n = 72) while the additional six PCV13 serotypes declined significantly from 39.5% (n = 418) to 18.6% (n = 201) (p < 0.05). The 23-valent pneumococcal polysaccharide vaccine (PPV23) and non-vaccine (NVT) serotypes increased from 26.3% (n = 278) to 36.2% (n = 393) (p < 0.05), and from 25.1% (n = 266) to 38.4% (n = 416) (p < 0.05), respectively. There were no significant changes in antimicrobial resistance rates from 2011 to 2016: 24.1% of the IPD from adults ≥65 years were resistant to clarithromycin (n = 609), 10.0% to doxycycline (n = 254), 11.8% to penicillin (n = 299), 5.2% to cefuroxime (n = 131), 6.6% to clindamycin (n = 168), 6.0% to trimethoprim-sulfamethoxazole (n = 152), and 0.5% (n = 12) to ceftriaxone. Although overall incidence of IPD in adults ≥65 years has remained relatively constant from 2010 to 2016, childhood PCV13 vaccination programs have been successful in indirectly reducing IPD caused by PCV13 serotypes in adults through herd immunity effects.


Assuntos
Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas/administração & dosagem , Sorogrupo , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Canadá/epidemiologia , Farmacorresistência Bacteriana , Feminino , Humanos , Imunidade Coletiva , Incidência , Masculino , Testes de Sensibilidade Microbiana , Sorotipagem
2.
J Microbiol Methods ; 144: 99-106, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29162393

RESUMO

Serotyping of Streptococcus pneumoniae is important to monitor disease epidemiology and assess the impact of pneumococcal vaccines. Traditionally, the Quellung reaction used serotype-specific antibodies to classify S. pneumoniae based on differences in capsular antigens. More recently, PCR-based serotype deduction relying on serotype-specific capsule biosynthesis genes has been broadly applied for pneumococcal surveillance. However, PCR-based serotyping lacks discrimination for certain S. pneumoniae serotypes, including the differentiation of serotype 22F from 22A, and serotype 33F from 33A and 37. Serotypes 22F and 33F are emerging serotypes that are absent in the currently licensed 13-valent pneumococcal conjugate vaccine, but present in the new candidate 15-valent formulation. This study validated novel PCR reactions to detect and discriminate S. pneumoniae serotypes 22F and 33F. In order to differentiate S. pneumoniae serotypes 22F or 33F from genetically similar serotypes, two novel PCR reactions were designed and validated. The specificity of all PCR targets was evaluated using all 92 different S. pneumoniae serotypes, as well as 32 other streptococci. Reproducibility was evaluated using geographically and genetically diverse strains of S. pneumoniae serotypes 22F and 22A, or serotypes 33F, 33A, and 37 that were previously characterized by reputable reference laboratories. Overall, S. pneumoniae serotypes 22F and 33F could be accurately and reproducibly be detected and discriminated using PCR alone. Such a molecular serotyping approach provides a valuable diagnostic tool that is feasible in any molecular laboratory, to enable pneumococcal serotype surveillance and subsequent assessment of the impact of the new 15-valent candidate pneumococcal vaccine.

3.
PLoS One ; 12(5): e0178040, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28531208

RESUMO

Since implementation of the 13-valent polyvalent conjugate vaccine (PCV13) in Canada during 2010, the proportion of PCV13 serotypes causing invasive pneumococcal disease (IPD) has declined from 55% (n = 1492) in 2010 to 31% (n = 764) in 2014. A concurrent increase of non-PCV13 serotypes has occurred and 22F has become the most prevalent serotype in Canada increasing from 7% (n = 183) to 11% (n = 283). Core single nucleotide variant phylogenetic analysis was performed on 137 Streptococcus pneumoniae serotype 22F isolates collected across Canada from 2005-2015. Six phylogenetic lineages (n = 117) were identified among a serotype 22F/ST433 clonal complex (CC), including a recently expanding erythromycin-resistant clone. Erythromycin-resistance was observed in 25 isolates possessing ermB, mef or a 23S rRNA A2061G point mutation; 2 penicillin-resistant isolates had recombinant pbp1a, pbp2a and/or pbp2x; 3 tetracycline-resistant isolates contained tetM; and 1 isolate was multidrug-resistant. Virulence factor analysis indicated a high level of homogeneity among the 22F/ST433 clonal complex strains. A group of 6 phylogenetic outlier strains had differing MLST, antimicrobial resistance and molecular profiles suggestive of capsule switching events. While capsule switch events among S. pneumoniae serotype 22F has been observed, increasing prevalence of S. pneumoniae serotype 22F can be attributed to an evolving homogenous clone expanding nationally through local transmission events.


Assuntos
Tipagem Molecular/métodos , Infecções Pneumocócicas/microbiologia , Análise de Sequência de DNA/métodos , Streptococcus pneumoniae/classificação , Canadá , Farmacorresistência Bacteriana , Eritromicina , Genoma Bacteriano , Humanos , Filogenia , Polimorfismo de Nucleotídeo Único , Sorogrupo , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificação
4.
Clin Infect Dis ; 65(1): 37-45, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28510723

RESUMO

Background: Increasing azithromycin usage and resistance in Neisseria gonorrhoeae threatens current dual treatment. Because antimicrobial exposure influences resistance, we analyzed the association between azithromycin exposure and decreased susceptibility of N. gonorrhoeae. Methods: We included N. gonorrhoeae isolates of patients who visited the Amsterdam STI Clinic between 1999 and 2013 (t0), with another clinic visit in the previous 60 days (t-1). Exposure was defined as the prescription of azithromycin at t-1. Using multivariable linear regression, we assessed the association between exposure and azithromycin minimum inhibitory concentration (MIC). Whole genome sequencing (WGS) was performed to produce a phylogeny and identify multilocus sequence types (MLST), N. gonorrhoeae multiantigen sequence types (NG-MAST), and molecular markers of azithromycin resistance. Results: We included 323 isolates; 212 were unexposed to azithromycin, 14 were exposed ≤30 days, and 97 were exposed between 31 and 60 days before isolation. Mean azithromycin MIC was 0.28 mg/L (range, <0.016-24 mg/L). Linear regression adjusted for age, ethnicity, infection site, and calendar year showed a significant association between azithromycin exposure ≤30 days and MIC (ß, 1.00; 95% confidence interval, 0.44-1.56; P = .002). WGS was performed on 31 isolates: 14 unexposed, 14 exposed to azithromycin ≤30 days before isolation, and 3 t-1 isolates. Exposure to azithromycin was significantly associated with A39T or G45D mtrR mutations (P = .046) but not with MLST or NG-MAST types. Conclusions: The results suggest that frequent azithromycin use in populations at high risk of contracting N. gonorrhoeae induces an increase in MIC and may result in resistance.


Assuntos
Antibacterianos/farmacologia , Azitromicina/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Gonorreia , Neisseria gonorrhoeae/efeitos dos fármacos , Adulto , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Feminino , Genoma Bacteriano/efeitos dos fármacos , Genoma Bacteriano/genética , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Gonorreia/microbiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Estudos Retrospectivos
5.
Clin Infect Dis ; 2017 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-28369420

RESUMO

Background: Increasing azithromycin usage and resistance in Neisseria gonorrhoeae threatens current dual treatment. Because antimicrobial exposure influences resistance, we analysed the association between azithromycin exposure and decreased susceptibility of N. gonorrhoeae. Methods: We included N. gonorrhoeae isolates of patients visiting the Amsterdam STI Clinic between 1999 and 2013 (t0), with another visit in the previous 60 days (t-1). Exposure was defined as the prescription of azithromycin at t-1. We included one isolate per patient. Using multivariable linear regression we assessed the association between exposure and azithromycin minimum inhibitory concentration (MIC). Whole genome sequencing (WGS) was performed to produce a phylogeny, identify multilocus sequence types (MLST), multiantigen sequence types (NG-MAST), and molecular markers of azithromycin resistance. Results: We included 323 isolates: 212 were unexposed to azithromycin, 14 were exposed ≤30 days, and 97 were exposed between 31-60 days before isolation. Mean azithromycin MIC was 0.28 mg/L (range: <0.016-24 mg/L). Linear regression adjusted for age, ethnicity, infection site, and calendar year showed a significant association between azithromycin exposure ≤30 days and MIC (ß: 1.00, 95%-CI: 0.44-1.56, p=0.002). WGS was performed on 31 isolates: 14 unexposed, 14 exposed to azithromycin ≤30 days before isolation, and three t-1 isolates. Exposure to azithromycin was significantly associated with A39T or G45D mtrR mutations (p=0.046), but not with MLST or NG-MAST molecular types. Conclusions: The results suggest that frequent azithromycin use in populations at high risk of contracting N. gonorrhoeae induces an increase in MIC, and may result in resistance.

6.
Vaccine ; 34(6): 846-53, 2016 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-26602266

RESUMO

BACKGROUND: Pneumococcal disease burden is difficult to quantify due to limited data regarding non-bacteremic disease. We assessed serotype-specific differences in pneumococcal disease presentations in adults in Toronto, Canada. METHODS: From 2003 to 2011, population-based surveillance for invasive pneumococcal disease was conducted and respiratory pneumococcal isolates collected in Metropolitan Toronto/Peel Region, Canada. Episodes of care were classified into disease categories. RESULTS: Of 3105 eligible cases of IPD, 2060 cases were bacteremic pneumonia, and 1045 bacteremia without pneumonia. Of 2751 eligible respiratory cases, 1542 (56.0%) were non-bacteremic pneumonia (NBPP), 467 (17.0%) were other acute respiratory infection (oARI), and 742 (27.0%) were isolates representing colonization. Serotypes 3 (11.3%), 19A (8.4%) and 22F (6.2%) were the most common; serotypes 1,5, and 8 were rare. Serotypes 4, 14, 7F, 9V, 12F, 14, 19A and 6C were over-represented in bacteremic disease, and serotypes 3, 6A, 11A, 19F, 23A, 23F, 35B, 35F were more common in NBPP. The proportion of cases due to PCV7 serotypes declined from 48.7% to 8.7% in bacteremic pneumonia, from 35.3% to 10.9% in NBPP, from 34.2% to 7.5% in oARI, and from 38.7% to 12.2% in colonizing isolates. In 2010-2011, PCV13 serotypes accounted for 62.6% of isolates associated with bacteremic pneumonia, 42.0% of bacteremia without pneumonia, 41.1% of NBPP, 25.7% of oARI, and 32.9% of colonizing isolates. CONCLUSIONS: Serotype distributions differ significantly in different presentations of pneumococcal disease. Herd protection due to PCV7 has changed serotype distribution, but PCV13 serotypes remain important in all categories of disease.


Assuntos
Bacteriemia/epidemiologia , Infecções Pneumocócicas/epidemiologia , Pneumonia Bacteriana/epidemiologia , Streptococcus pneumoniae/classificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Vigilância da População , Sorogrupo , Streptococcus pneumoniae/isolamento & purificação , Adulto Jovem
7.
J Antimicrob Chemother ; 70(7): 1960-4, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25761605

RESUMO

OBJECTIVES: Serotype replacement in Streptococcus pneumoniae following the implementation of a new vaccine has been associated with the emergence of non-vaccine serotypes as prominent causes of invasive pneumococcal disease (IPD). The aim of this study was to characterize specific non-PCV-13 serotypes 15A, 22F, 33F and 35B from IPD, isolated in Canada post-PCV-13 introduction in 2010. METHODS: Of 3802 IPD isolates collected from across Canada in 2011-13, 18.4% were found to be serotypes 15A, 22F, 33F and 35B. These 699 isolates were subjected to antimicrobial susceptibility testing, PFGE, MLST, molecular detection of pneumococcal pili and comparison with Pneumococcal Molecular Epidemiology Network (PMEN) clones. RESULTS: This study demonstrated clonal spread of specific STs, including MDR ST63 and its Sweden(15A)-25-related variants, the increasingly common ST433 and a variant of piliated, penicillin-non-susceptible ST558, related to PMEN clone Utah(35B)-24 (ST377). New STs of serotype 33F were identified. Several potential capsular switching events were identified within these serotypes. CONCLUSIONS: Non-PCV-13 serotype 22F is increasing in Canada through the rapid clonal expansion of ST433. Numerous new STs associated with serotype 33F indicate the potential divergence of the serotype. Serotypes 15A and 35B in Canada are related to international clones of S. pneumoniae.


Assuntos
Farmacorresistência Bacteriana Múltipla , Genótipo , Infecções Pneumocócicas/microbiologia , Sorogrupo , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/efeitos dos fármacos , Fatores de Virulência/genética , Canadá/epidemiologia , Proteínas de Fímbrias/genética , Humanos , Testes de Sensibilidade Microbiana , Tipagem Molecular , Infecções Pneumocócicas/epidemiologia , Vacinas Pneumocócicas/imunologia , Prevalência , Streptococcus pneumoniae/isolamento & purificação , Virulência
8.
Pediatr Infect Dis J ; 33(7): 724-30, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24463806

RESUMO

BACKGROUND: We previously reported serotype-specific trends in pneumococcal nasopharyngeal colonization soon after introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in mid-2002. Our current aim is to describe later trends after PCV7 and early trends after PCV13 vaccine introduction in 2010. METHODS: The Calgary Area Streptococcus pneumoniae Epidemiology Research team conducted 10 point-prevalence surveys of pneumococcal nasopharyngeal colonization in healthy children aged 12 and 18 months and 4.5 years biannually from 2003 to 2005 (previously reported) and annually in 2006, 2010, 2011 and 2012. RESULTS: For surveys conducted during 2010-2012, the proportion colonized was 13.2% compared with 19.9% in surveys conducted during 2003-2006 (P < 0.001). Vaccination with 2 or more doses of PCV7 or PCV13, older age and recent antibiotic use reduced the odds of colonization with any pneumococcus. By 2012, 94% of all isolates were nonvaccine serotypes with 11A, 15A/B/C, 22F, 23A/B and 35B/F representing 75% of all isolates. CONCLUSIONS: Pneumococcal nasopharyngeal colonization has changed profoundly since the introduction of conjugate vaccines and overall colonization by pneumococcus has declined in recent years. By 2012, nonvaccine serotypes have nearly completely replaced vaccine serotypes. The impact on clinical disease remains to be seen.


Assuntos
Portador Sadio/epidemiologia , Nasofaringe/microbiologia , Infecções Pneumocócicas/epidemiologia , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/isolamento & purificação , Canadá/epidemiologia , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Vacinas Pneumocócicas/administração & dosagem , Prevalência , Sorogrupo
9.
Can J Microbiol ; 59(12): 778-88, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24313450

RESUMO

The introduction of the 7-valent pneumococcal vaccine (PCV7) in Canada was very effective in reducing invasive pneumococcal disease (IPD) in children; however, increases of non-PCV7 serotypes have subsequently offset some of these reductions. A 13-valent pneumococcal vaccine (PCV13) targeting additional serotypes was implemented between 2010 and 2011, and in 2012 changes in the incidence of disease and the distribution of IPD serotypes began to emerge. The incidence of IPD in children <5 years of age declined from 18.0 to 14.2 cases per 100 000 population between 2010 and 2012; however, the incidence in ages ≥5 years remained relatively unchanged over the 3-year period, at about 9.7 cases per 100 000 population. From 2010 to 2012, PCV13 serotypes declined significantly from 66% (224/339) to 41% (101/244, p < 0.001) in children <5 years of age, and from 54% (1262/2360) to 43% (1006/2353, p < 0.001) in children ≥5 years of age. Serotypes 19A, 7F, 3, and 22F were the most common serotypes in 2012, with 19A decreasing from 19% (521/2727) to 14% (364/2620, p < 0.001), 7F decreasing from 14% (389/2727) to 12% (323/2620, p = 0.04), and 22F increasing from 7% (185/2727) to 11% (279/2620, p < 0.001) since 2010. Serotype 3 increased from 7% (23/339) to 10% (24/244) in <5-year-olds (p = 0.22) over the 3-year period. The highest rates of antimicrobial resistance were observed with clarithromycin (23%), penicillin using meningitis breakpoints (12%), clindamycin (8%), and trimethoprim-sulfamethoxazole (6%). Shifts in the distribution of IPD serotypes and reductions in the incidence of disease suggest that current immunization programs in Canada are effective in reducing the burden of IPD in children. While we acknowledge the limited data on the effectiveness of the PCV13 vaccine, to our knowledge, this study represents one of the first descriptions of the potential impact of the PCV13 vaccine in the Canadian population. Continued surveillance will be important to recognize replacement serotypes, to determine the extent of herd immunity effects in nonpaediatric populations, and to assess the overall effectiveness of PCV13 in reducing IPD in Canada.


Assuntos
Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/classificação , Adolescente , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Canadá/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/microbiologia , Sorotipagem , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/isolamento & purificação , Vacinação , Adulto Jovem
10.
Can J Microbiol ; 58(8): 1008-17, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22827750

RESUMO

A baseline serotype distribution was established by age and region for 2058 invasive Streptococcus pneumoniae isolates collected during the implementation period of the 13-valent pneumococcal conjugate vaccine (PCV13) program in many parts of Canada in 2010. Serotypes 19A, 7F, and 3 were the most prevalent in all age groups, accounting for 57% in <2 year olds, 62% in 2-4 year olds, 45% in 5-14 year olds, 44% in 15-49 year olds, 41% in 50-64 year olds, and 36% in ≥65 year olds. Serotype 19A was most predominant in Western and Central Canada representing 15% and 22%, respectively, of the isolates from those regions, whereas 7F was most common in Eastern Canada with 20% of the isolates. Other prevalent serotypes include 15A, 23B, 12F, 22F, and 6C. PCV13 serotypes represented 65% of the pneumococci isolated from <2 year olds, 71% of 2-4 year olds, 61% of 5-14 year olds, 60% of 15-49 year olds, 53% of 50-64 year olds, and 49% of the ≥65 year olds. Continued monitoring of invasive pneumococcal serotypes in Canada is important to identify epidemiological trends and assess the impact of the newly introduced PCV13 vaccine on public health.


Assuntos
Infecções Pneumocócicas/microbiologia , Adolescente , Adulto , Idoso , Canadá/epidemiologia , Criança , Pré-Escolar , Humanos , Lactente , Pessoa de Meia-Idade , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Prevalência , Sorotipagem , Streptococcus pneumoniae/classificação , Adulto Jovem
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