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Phenotypic susceptibility testing of the Mycobacterium tuberculosis complex (MTBC) isolate requires culture growth, which can delay rapid detection of resistant cases. Whole genome sequencing (WGS) and data analysis pipelines can assist in predicting resistance to antimicrobials used in the treatment of tuberculosis (TB). This study compared phenotypic susceptibility testing results and WGS-based predictions of antimicrobial resistance (AMR) to four first-line antimicrobials-isoniazid, rifampin, ethambutol, and pyrazinamide-for MTBC isolates tested between the years 2018-2022. For this 5-year retrospective analysis, the WGS sensitivity for predicting resistance for isoniazid, rifampin, ethambutol, and pyrazinamide using Mykrobe was 86.7%, 100.0%, 100.0%, and 47.8%, respectively, and the specificity was 99.4%, 99.5%, 98.7%, and 99.9%, respectively. The predictive values improved slightly using Mykrobe corrections applied using TB Profiler, i.e., the WGS sensitivity for isoniazid, rifampin, ethambutol, and pyrazinamide was 92.31%, 100%, 100%, and 57.78%, respectively, and the specificity was 99.63%. 99.45%, 98.93%, and 99.93%, respectively. The utilization of WGS-based testing addresses concerns regarding test turnaround time and enables analysis for MTBC member identification, antimicrobial resistance prediction, detection of mixed cultures, and strain genotyping, all through a single laboratory test. WGS enables rapid resistance detection compared to traditional phenotypic susceptibility testing methods using the WHO TB mutation catalog, providing an insight into lesser-known mutations, which should be added to prediction databases as high-confidence mutations are recognized. The WGS-based methods can support TB elimination efforts in Canada and globally by ensuring the early start of appropriate treatment, rapidly limiting the spread of TB outbreaks.
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Antituberculosos , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis , Secuenciación Completa del Genoma , Secuenciación Completa del Genoma/métodos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/efectos de los fármacos , Antituberculosos/farmacología , Humanos , Pruebas de Sensibilidad Microbiana/métodos , Estudios Retrospectivos , Farmacorresistencia Bacteriana/genética , Genoma Bacteriano , Etambutol/farmacología , Isoniazida/farmacología , Pirazinamida/farmacología , Tuberculosis/microbiología , Tuberculosis/tratamiento farmacológico , Rifampin/farmacologíaRESUMEN
Background: Invasive pneumococcal disease (IPD, Streptococcus pneumoniae) has been a nationally notifiable disease in Canada since 2000. The use of conjugate vaccines has caused a shift in the distribution of serotypes over time. This report is a summary of the demographics, serotypes and antimicrobial resistance of IPD isolates collected in Canada in 2021 and 2022. Methods: The National Microbiology Laboratory (NML) of the Public Health Agency of Canada in Winnipeg, Manitoba collaborates with provincial and territorial public health laboratories to conduct national surveillance of IPD. There were 1,999 isolates reported in 2021 and 3,775 isolates in 2022. Serotype was determined by the Quellung reaction or whole-genome sequencing (WGS). Antimicrobial susceptibilities were determined by WGS methods, broth microdilution, or data shared by collaborators in the Canadian Antimicrobial Resistance Alliance program at the University of Manitoba. Population-based IPD incidence rates were obtained through the Canadian Notifiable Disease Surveillance System. Results: The incidence of IPD in Canada was 5.62 cases per 100,000 population in 2021, decreasing from the peak of 10.86 cases per 100,000 population in 2018. Serotypes with increasing trends (p<0.05) between 2018 and 2022 included: 4 (6.1%-12.4%), 9V (1.0%-5.1%) and 12F (4.8%-5.4%). The overall prevalence of PCV13 serotypes increased over the same period (31.2%-41.5%, p<0.05) while the prevalence of non-vaccine types decreased significantly (27.3%-21.5%, p<0.0001). The highest rates of antimicrobial resistance in 2021 and 2022 were seen with clarithromycin (21%, 2021; 24%, 2022) and erythromycin (22%, 2021; 24%, 2022). Multidrug-resistant IPD continued to increase from 2018 to 2022 (6.7%-12.6%, p<0.05). Conclusion: The number of cases of IPD continued to decrease in 2021 in comparison to previous years, however, 2022 saw a return to pre-COVID-19 levels. Disease due to PCV13 serotypes 3, 4, 9V and 19F, as well as non-PCV13 serotypes 12F and 20, is increasing in prevalence. Surveillance of IPD to monitor changing serotype distribution and antimicrobial resistance is essential.
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Background: Invasive group A streptococcal (iGAS, Streptococcus pyogenes) disease has been a nationally notifiable disease in Canada since 2000. This report summarizes the demographics, emm types, and antimicrobial resistance of iGAS isolates collected in Canada in 2021 and 2022. Methods: The Public Health Agency of Canada's National Microbiology Laboratory collaborates with provincial and territorial public health laboratories to conduct national surveillance of invasive S. pyogenes. Emm typing was performed using the Centers for Disease Control and Prevention emm sequencing protocol or extracted from whole-genome sequencing data. Antimicrobial susceptibilities were determined using Kirby-Bauer disk diffusion according to Clinical and Laboratory Standards Institute guidelines or predicted from whole-genome sequencing data based on the presence of resistance determinants. Results: Overall, the incidence of iGAS disease in Canada was 5.56 cases per 100,000 population in 2021, decreasing from the peak of 8.6 cases per 100,000 population in 2018. A total of 2,630 iGAS isolates were collected during 2022, representing an increase from 2021 (n=2,179). In particular, there was a large increase in isolates collected from October to December 2022. The most predominant emm type overall in 2021 and 2022 was emm49, at 21.5% (n=468) and 16.9% (n=444), respectively, representing a significant increase in prevalence since 2018 (p<0.0001). The former most prevalent type, emm1, increased from 0.5% (n=10) in 2021 to 4.8% (n=125) in 2022; similarly, emm12 increased from 1.0% (n=22) in 2021 to 5.8% (n=151) in 2022. These two types together accounted for almost 25% of isolates collected in late 2022 (October to December). Antimicrobial resistance rates in 2021 and 2022 included: 14.9%/14.1% erythromycin resistance, 4.8%/3.0% clindamycin resistance, and <1% chloramphenicol resistance. Conclusion: The increase of iGAS isolates collected in Canada is an important public health concern. Continued surveillance of iGAS is critical to monitor expanding emm types and antimicrobial resistance patterns.
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The International Circumpolar Surveillance (ICS) program is a population-based surveillance network for invasive bacterial diseases throughout Arctic countries and territories. The ICS quality control program for Streptococcus pneumoniae serotyping and antimicrobial susceptibility testing has been ongoing since 1999. Current participating laboratories include the Provincial Laboratory for Public Health in Edmonton, Alberta; Laboratoire de santé publique du Québec in Sainte-Anne-de-Bellevue, Québec; the Centers for Disease Control's Arctic Investigations Program in Anchorage, Alaska; the Neisseria and Streptococcus Reference Laboratory at Statens Serum Institut in Copenhagen, Denmark; the Department of Clinical Microbiology, Landspitali in Reykjavik, Iceland; and Public Health Agency of Canada's National Microbiology Laboratory in Winnipeg, Manitoba. From 2009 to 2020, 140 isolates of S. pneumoniae were distributed among the six laboratories as part of the quality control program. Overall serotype concordance was 96.9%, with 99.3% concordance to pool level. All participating laboratories had individual concordance rates >92% for serotype and >97% for pool. Overall concordance by modal minimum inhibitory concentration (MIC) for testing done by broth microdilution or Etest was 99.1%, and >98% for all antimicrobials tested. Categorical concordance was >98% by both CLSI and EUCAST criteria. For two laboratories performing disc diffusion, rates of concordance by modal MIC were >97% for most antimicrobials, except chloramphenicol (>93%) and trimethoprim/sulfamethoxazole (>88%). Data collected from 12 years of the ICS quality control program for S. pneumoniae demonstrate excellent (≥95%) overall concordance for serotype and antimicrobial susceptibility testing results across six laboratories. IMPORTANCE: Arctic populations experience several social and physical challenges that lead to the increased spread and incidence of invasive diseases. The International Circumpolar Surveillance (ICS) program was developed to monitor five invasive bacterial diseases in Arctic countries and territories. Each ICS organism has a corresponding interlaboratory quality control (QC) program for laboratory-based typing, to ensure the technical precision and accuracy of reference testing services for these regions, and identify and correct potential problems. Here, we describe the results of the ICS Streptococcus pneumoniae QC program, from 2009 to 2020. Excellent overall concordance was achieved for serotype and antimicrobial susceptibility testing results across six laboratories. Ongoing participation in these QC programs ensures the continuation of quality surveillance systems within Arctic populations that experience health disparities.
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Antibacterianos , Pruebas de Sensibilidad Microbiana , Infecciones Neumocócicas , Control de Calidad , Streptococcus pneumoniae , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/clasificación , Streptococcus pneumoniae/aislamiento & purificación , Humanos , Pruebas de Sensibilidad Microbiana/normas , Infecciones Neumocócicas/microbiología , Regiones Árticas , Antibacterianos/farmacología , Laboratorios/normas , Serotipificación , Alaska/epidemiología , Serogrupo , Monitoreo EpidemiológicoRESUMEN
Epidemiologic research on zoonotic tuberculosis historically used Mycobacterium bovis as a surrogate measure, however, increased reports of human tuberculosis caused by other animal-associated Mycobacterium tuberculosis complex members like Mycobacterium orygis necessitates their inclusion. We performed a retrospective cohort study including persons infected with any animal-lineage M. tuberculosis complex species in Alberta, Canada, from January 1995 to July 2021, identifying 42 patients (20 M. bovis, 21 M. orygis, one M. caprae). Demographic, epidemiologic and clinical characteristics were compared against persons with culture-confirmed M. tuberculosis infection. The proportion of culture-positive infections caused by M. orygis increased continuously from 2016-2020. Significantly more females at a higher median age were impacted by M. orygis, with all patients originating from South Asia. M. bovis caused significantly more extra-pulmonary disease, and disproportionately impacted young females, particularly those pregnant or post-partum. All infections were acquired abroad. These findings can aid in developing targeted public health interventions.
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BACKGROUND: Subclinical pulmonary tuberculosis (PTB) is an asymptomatic disease state between established TB infection and symptomatic (clinical) TB disease. It is present in 20-25% of PTB patients in high-income countries. Mycobacterium tuberculosis complex (MTBC) genetic heterogeneity, and differential host immunological responses, have been implicated in its pathogenesis. METHODS: To determine the association between MTBC lineage and PTB disease phenotype, we used two retrospective cohorts of PTB patients in Canada and two independent lineage attribution methods (DNA fingerprinting and genome sequencing). The first cohort, Cohort 1, consisted of consecutively diagnosed PTB patients between 2014 and 2020. The second, Cohort 2, consisted of newly-arrived foreign-born PTB patients who either were or were not referred for post-landing medical surveillance between 2004 and 2017. Univariable and multivariable logistic regression models were sequentially fitted to both cohorts, adjusting for age, sex, disease type, drug resistance and HIV. Evolution of radiographic features was correlated to lineage in Cohort 2. FINDINGS: Cohort 1 and 2 included 874 (209 subclinical) and 111 (44 subclinical) patients, respectively. In both cohorts, subclinical patients were more likely than clinical patients to have relapse/retreatment disease, be smear-negative, have longer times-to-culture positivity and to harbor an ancestral MTBC lineage (Indo-Oceanic or Mycobacterium africanum). Relapse/retreatment disease and ancestral MTBC lineage were independent predictors of subclinical disease (ORs and 95% CIs in Cohort 1, 1.85 [1.07,3.28], p < 0.029 and 2.30 [1.66,3.18], p < 0.001, respectively, and Cohort 2, 5.74 [1.37-24.06], p < 0.017 and 3.21 (1.29,7.97], p < 0.012, respectively). The geographic distribution of Indo-Oceanic strains causing subclinical disease was uneven. Non-progressive lung disease was more common in patients infected with ancestral than modern lineages in Cohort 2, 56.0% vs 25.4%, p < 0.005. INTERPRETATION: MTBC lineage is a strong predictor of PTB disease phenotype. The genetic drivers of this association, and the relative contribution of other explanatory variables, are unknown.
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Mycobacterium tuberculosis , Tuberculosis Pulmonar , Humanos , Mycobacterium tuberculosis/genética , Filogenia , Estudios de Cohortes , Estudios Retrospectivos , Tuberculosis Pulmonar/tratamiento farmacológico , Fenotipo , RecurrenciaRESUMEN
In the province of Alberta, Canada, invasive disease caused by Streptococcus pneumoniae serogroup 20 (serotypes 20A/20B) has been increasing in incidence. Here, we characterize provincial invasive serogroup 20 isolates collected from 1993 to 2019 alongside invasive and non-invasive serogroup 20 isolates from the Global Pneumococcal Sequencing (GPS) Project collected from 1998 to 2015. Trends in clinical metadata and geographic location were evaluated, and serogroup 20 isolate genomes were subjected to molecular sequence typing, virulence and antimicrobial resistance factor mining, phylogenetic analysis and pangenome calculation. Two hundred and seventy-four serogroup 20 isolates from Alberta were sequenced, and analysed along with 95 GPS Project genomes. The majority of invasive Alberta serogroup 20 isolates were identified after 2007 in primarily middle-aged adults and typed predominantly as ST235, a sequence type that was rare among GPS Project isolates. Most Alberta isolates carried a full-length whaF capsular gene, suggestive of serotype 20B. All Alberta and GPS Project genomes carried molecular resistance determinants implicated in fluoroquinolone and macrolide resistance, with a few Alberta isolates exhibiting phenotypic resistance to azithromycin, clindamycin, erythromycin, tetracycline and trimethoprim-sulfamethoxazole, as well as non-susceptibility to tigecycline. All isolates carried multiple virulence factors including those involved in adherence, immune modulation and nutrient uptake, as well as exotoxins and exoenzymes. Phylogenetically, Alberta serogroup 20 isolates clustered with predominantly invasive GPS Project isolates from the USA, Israel, Brazil and Nepal. Overall, this study highlights the increasing incidence of invasive S. pneumoniae serogroup 20 disease in Alberta, Canada, and provides insights into the genetic and clinical characteristics of these isolates within a global context.
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Antibacterianos , Streptococcus pneumoniae , Adulto , Persona de Mediana Edad , Humanos , Alberta/epidemiología , Serogrupo , Streptococcus pneumoniae/genética , Antibacterianos/farmacología , Filogenia , Farmacorresistencia Bacteriana/genética , Macrólidos , GenómicaRESUMEN
A recently described member of the Mycobacterium tuberculosis complex (MTBC) is Mycobacterium orygis, which can cause disease primarily in animals but also in humans. Although M. orygis has been reported from different geographic regions around the world, due to a lack of proper identification techniques, the contribution of this emerging pathogen to the global burden of zoonotic tuberculosis is not fully understood. In the present work, we report single nucleotide polymorphism (SNP) analysis using whole genome sequencing (WGS) that can accurately identify M. orygis and differentiate it from other members of the MTBC species. WGS-based SNP analysis was performed for 61 isolates from different provinces in Canada that were identified as M. orygis. A total of 56 M. orygis sequences from the public databases were also included in the analysis. Several unique SNPs in the gyrB, PPE55, Rv2042c, leuS, mmpL6, and mmpS6 genes were used to determine their effectiveness as genetic markers for the identification of M. orygis. To the best of our knowledge, five of these SNPs, viz., gyrB 277 (AâG), gyrB 1478 (TâC), leuS 1064 (AâT), mmpL6 486 (TâC), and mmpS6 334 (CâG), are reported for the first time in this study. Our results also revealed several SNPs specific to other species within MTBC. The phylogenetic analysis shows that the studied genomes were genetically diverse and clustered with M. orygis sequences of human and animal origin reported from different geographic locations. Therefore, the present study provides a new insight into the high-confidence identification of M. orygis from MTBC species based on WGS data, which can be useful for reference and diagnostic laboratories.
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Mycobacterium tuberculosis , Mycobacterium , Tuberculosis , Animales , Humanos , Filogenia , Tuberculosis/diagnóstico , Tuberculosis/microbiología , Secuenciación Completa del Genoma , Polimorfismo de Nucleótido Simple , Mycobacterium tuberculosis/genéticaRESUMEN
BACKGROUND: A 4-month-old infant hospitalized since birth received multiple blood transfusions. In March 2022, Plasmodium falciparum was confirmed with nucleic acid testing. As the mother was assessed as unlikely to be the source of infection, the blood operator initiated a traceback investigation for a potential blood donor source. The patient had received 13 red blood cell (RBC) transfusions (aliquoted from 11 donors), 4 apheresis platelet (PLT) transfusions and 16 buffy coat pooled PLT transfusions. The blood operator medical team developed a supplementary malaria infection risk questionnaire to identify donors at highest risk of life-time malaria infection, based on birthplace, residence, or travel in malaria-endemic regions. RESULTS: With 79 donors initially implicated, initial focus was on donors of RBC components. The 11 RBC donors were contacted and assessed using the supplementary questionnaire. Three donors, all of whom met current malaria-related donor eligibility criteria, were deemed high risk of prior malaria infection. These donors consented to P. falciparum serology and nucleic acid testing (NAT). One donor who was born and had resided in an endemic West African country for 14 years, was positive for P. falciparum by serology (indirect fluorescent antibody test) and NAT-(Ct ≥32). Lookback of this donor's transfused fresh co-components and prior donation identified no other malaria cases. CONCLUSION: This was a probable transfusion-transmitted malaria (TTM) case from an eligible donor who in retrospect was found to have unrecognized, asymptomatic, semi-immune malaria infection, and who was potentially infectious. Blood donor lack of recall of prior malaria infection does not negate the risk of TTM from those who have lived in malaria-endemic countries.
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Malaria Falciparum , Malaria , Ácidos Nucleicos , Humanos , Lactante , Canadá , Transfusión Sanguínea , Malaria Falciparum/epidemiología , Donantes de Sangre , Infecciones AsintomáticasRESUMEN
Non-cystic fibrosis bronchiectasis (NCFB) is a chronic respiratory disease resulting in chronic cough, thick sputum, and lower airway microbial colonization, akin to patients with cystic fibrosis (CF). NCFB is a common, yet under recognized entity which inflicts significant morbidity and mortality particularly to older individuals, with a rising prevalence in the developed world. Given that sputum cultures are a non-invasive method to characterize the lower airway microbiota in NCFB patients, for which pathogenic organisms are associated with worsened outcomes, we sought to characterize the microbiological pattern and clinical outcomes associated with sputum culture in a cohort of NCFB patients from Western Canada. A total of 20 subjects were prospectively recruited from various bronchiectasis clinics across the Greater Edmonton area. A retrospective chart review and a symptoms questionnaire was performed, gathering information not limited to symptoms, comorbidities, exacerbations, hospitalizations, sputum production, and sputum culture results over the prior 5 years. Subjects reported frequent hospitalization alongside a significant burden of symptoms. A large majority of sputum cultures grew pathogenic organisms such as Haemophilus influenzae and Pseudomonas aeruginosa. We also note the considerable waste and inefficiency associated with sputum cultures, outlining areas for which this important diagnostic modality can be improved. Accurate characterization of the airway microbiota alongside efficient delivery of health services are key to ensuring the proper treatment of individuals with NCFB, given their high disease burden and frequent hospitalization.
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Bronquiectasia , Fibrosis Quística , Infecciones por Pseudomonas , Humanos , Estudios Retrospectivos , Alberta/epidemiología , Esputo/microbiología , Bronquiectasia/complicaciones , Fibrosis Quística/complicaciones , Fibrosis Quística/tratamiento farmacológico , Fibrosis , Pseudomonas aeruginosa , Antibacterianos/uso terapéutico , Infecciones por Pseudomonas/tratamiento farmacológicoRESUMEN
Invasive Group B Streptococcus (GBS) can infect pregnant women, neonates, and older adults. Invasive GBS serotype VIII is infrequent in Alberta; however, cases have increased in recent years. Here, genomic analysis was used to characterize fourteen adult invasive serotype VIII isolates from 2009 to 2021. Trends in descriptive clinical data and antimicrobial susceptibility results were evaluated for invasive serotype VIII isolates from Alberta. Isolate genomes were sequenced and subjected to molecular sequence typing, virulence and antimicrobial resistance gene identification, phylogenetic analysis, and pangenome determination. Multilocus sequencing typing identified eight ST42 (Clonal Complex; CC19), four ST1 (CC1), and two ST2 (CC1) profiles. Isolates were susceptible to penicillin, erythromycin, chloramphenicol, and clindamycin, apart from one isolate that displayed erythromycin and inducible clindamycin resistance. All isolates carried genes for peptide antibiotic resistance, three isolates for tetracycline resistance, and one for macrolide, lincosamide, and streptogramin resistance. All genomes carried targets currently being considered for protein-based vaccines (e.g., pili and/or Alpha family proteins). Overall, invasive GBS serotype VIII is emerging in Alberta, primarily due to ST42. Characterization and continued surveillance of serotype VIII will be important for outbreak prevention, informing vaccine development, and contributing to our understanding of the global epidemiology of this rare serotype.
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Clindamicina , Infecciones Estreptocócicas , Recién Nacido , Humanos , Femenino , Embarazo , Anciano , Serogrupo , Clindamicina/uso terapéutico , Streptococcus agalactiae , Infecciones Estreptocócicas/microbiología , Alberta/epidemiología , Filogenia , Tipificación de Secuencias Multilocus , Farmacorresistencia Bacteriana , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Eritromicina/uso terapéutico , Genómica , Pruebas de Sensibilidad MicrobianaRESUMEN
OBJECTIVES: Relatively little is known about the prevalence, risk factors, and public health consequences of peripheral lymph node (PLN)-associated pulmonary tuberculosis (PTB). METHODS: We developed a 10-year (2010-2019) population-based cohort of PLNTB patients in Canada. We used systematically collected primary source data and expert reader chest radiograph interpretations in a multivariable logistic regression to determine associations between sputum culture positivity and demographic, clinical, and radiographic features. Public health risks were estimated among contacts of PLNTB patients. RESULTS: There were 306 patients with PLNTB, among whom 283 (92.5%) were 15-64 years of age, 159 (52.0%) were female, and 293 (95.8%) were foreign-born. Respiratory symptoms were present in 21.6%, and abnormal chest radiograph in 23.2%. Sputum culture positivity ranged from 12.9% in patients with no symptoms and normal lung parenchyma to 66.7% in patients with both. Respiratory symptoms, abnormal lung parenchyma, and HIV-coinfection (borderline) were independent predictors of sputum culture positivity (odds ratio [OR] 2.24 [95% confidence interval [CI] 1.15-4.39], Pâ¯=â¯0.01, OR 4.78 [95% CI 2.41-9.48], Pâ¯<â¯0.001, and OR 2.54 [95% CI 0.99-6.52], Pâ¯=â¯0.05), respectively. Among contacts of sputum culture-positive PLNTB patients, one secondary case and 16 new infections were identified. CONCLUSION: Isochronous PTB is common in PLNTB patients. Routine screening of PLNTB patients for PTB is strongly recommended.
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Mycobacterium tuberculosis , Tuberculosis Ganglionar , Tuberculosis Pulmonar , Humanos , Femenino , Masculino , Prevalencia , Salud Pública , Tuberculosis Pulmonar/diagnóstico , Factores de Riesgo , Ganglios Linfáticos , EsputoRESUMEN
Tuberculosis is a significant cause of morbidity worldwide and is a priority at the provincial and federal levels in Canada. It is known that tuberculosis transmission networks are complex and span many years as well as different jurisdictions and countries. MIRU-VNTR is a universal tuberculosis genotyping method that utilizes a 24-loci pattern and it has shown promise in identifying inter and intrajurisdictional clusters within Canada. MIRU-VNTR data collected over 10 years from the National Reference Centre for Mycobacteriology (NRCM) were analyzed in this study. Some clusters were unique to a single province/territory, while others spanned multiple provinces and/or territories in Canada. The use of a universal laboratory test can enhance contact tracing, provide geographical information on circulating genotypes, and hence, aid in tuberculosis investigation by public health. The housing of all data on one platform, technical ease of the method, easy exchange of data between jurisdictions, and strong collaboration with laboratories and surveillance units at the provincial and federal levels have the potential to identify possible outbreaks in real time.
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The relationship between increased short-term mortality rates after invasive pneumococcal disease (IPD) has been frequently studied. However, the relationship between IPD and long-term mortality rates is unknown. IPD patients in Alberta, Canada, had clinical data collected that were linked to administrative databases. We used Cox proportional hazards modeling, and the primary outcome was time to all-cause deaths. First IPD events were identified in 4,522 patients, who had a median follow-up of 3.2 years (interquartile range 0.8â9.1 years). Overall all-cause mortality rates were consistently higher among cases than controls at 30 days (adjusted hazard ratio [aHR] 3.75, 95% CI 3.29-4.28), 30â90 days (aHR 1.56, 95% CI 1.27â1.93), and >90 days (aHR 1.43, 95% CI 1.33-1.54). IPD increases risk for short, intermediate, and long-term mortality rates regardless of age, sex, or concurrent conditions. These findings can help clinicians focus on postdischarge patient plans to limit long-term effects after acute IPD infection.
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Infecciones Neumocócicas , Streptococcus pneumoniae , Adulto , Cuidados Posteriores , Alberta/epidemiología , Humanos , Alta del Paciente , Infecciones Neumocócicas/epidemiología , Vacunas NeumococicasRESUMEN
We describe a case of Bartonella quintana endocarditis in an 11-year-old child from Northern Manitoba, Canada. This case demonstrates the neglected endemicity of B. quintana in Northern Canada and highlights the need for improved case finding and elucidation of specific risk factors for B. quintana infection in the Canadian North. Considering B. quintana's predominant transmission via body lice ectoparasitosis, we hypothesize that B. quintana's endemicity in Northern Canada is linked to inadequate access to suitable housing and running water among remote communities in the Canadian North.
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Bartonella quintana , Endocarditis , Pediculus , Fiebre de las Trincheras , Animales , Bartonella quintana/genética , Canadá , Niño , Humanos , ManitobaRESUMEN
BACKGROUND: Pneumonia from SARS-CoV-2 is difficult to distinguish from other viral and bacterial etiologies. Broad-spectrum antimicrobials are frequently prescribed to patients hospitalized with COVID-19 which potentially acts as a catalyst for the development of antimicrobial resistance (AMR). OBJECTIVES: We conducted a systematic review and meta-analysis during the first 18 months of the pandemic to quantify the prevalence and types of resistant co-infecting organisms in patients with COVID-19 and explore differences across hospital and geographic settings. METHODS: We searched MEDLINE, Embase, Web of Science (BioSIS), and Scopus from November 1, 2019 to May 28, 2021 to identify relevant articles pertaining to resistant co-infections in patients with laboratory confirmed SARS-CoV-2. Patient- and study-level analyses were conducted. We calculated pooled prevalence estimates of co-infection with resistant bacterial or fungal organisms using random effects models. Stratified meta-analysis by hospital and geographic setting was also performed to elucidate any differences. RESULTS: Of 1331 articles identified, 38 met inclusion criteria. A total of 1959 unique isolates were identified with 29% (569) resistant organisms identified. Co-infection with resistant bacterial or fungal organisms ranged from 0.2 to 100% among included studies. Pooled prevalence of co-infection with resistant bacterial and fungal organisms was 24% (95% CI 8-40%; n = 25 studies: I2 = 99%) and 0.3% (95% CI 0.1-0.6%; n = 8 studies: I2 = 78%), respectively. Among multi-drug resistant organisms, methicillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and multi-drug resistant Candida auris were most commonly reported. Stratified analyses found higher proportions of AMR outside of Europe and in ICU settings, though these results were not statistically significant. Patient-level analysis demonstrated > 50% (n = 58) mortality, whereby all but 6 patients were infected with a resistant organism. CONCLUSIONS: During the first 18 months of the pandemic, AMR prevalence was high in COVID-19 patients and varied by hospital and geography although there was substantial heterogeneity. Given the variation in patient populations within these studies, clinical settings, practice patterns, and definitions of AMR, further research is warranted to quantify AMR in COVID-19 patients to improve surveillance programs, infection prevention and control practices and antimicrobial stewardship programs globally.
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Bacterias/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológico , COVID-19/complicaciones , Farmacorresistencia Bacteriana , Farmacorresistencia Fúngica , Micosis/tratamiento farmacológico , Antibacterianos/farmacología , Antifúngicos/farmacología , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Infecciones Bacterianas/etiología , Infecciones Bacterianas/microbiología , COVID-19/virología , Hongos/clasificación , Hongos/efectos de los fármacos , Hongos/genética , Hongos/aislamiento & purificación , Humanos , Micosis/etiología , Micosis/microbiología , SARS-CoV-2/fisiologíaRESUMEN
BACKGROUND: Invasive pneumococcal disease due to Streptococcus pneumoniae can cause mortality and severe morbidity due to sepsis, meningitis and pneumonia, particularly in young children and the elderly. Recurrent invasive pneumococcal disease is rare yet serious sequelae of invasive pneumococcal disease that is associated with the immunocompromised and leads to a high mortality rate. METHOD: This retrospective study reviewed recurrent invasive pneumococcal disease cases from the Canadian Immunization Monitoring Program, ACTive (IMPACT) between 1991 and 2019, an active network for surveillance of vaccine-preventable diseases and adverse events following immunization for children ages 0-16 years. Data were collected from 12 pediatric tertiary care hospitals across all 3 eras of public pneumococcal conjugate vaccine implementation in Canada. RESULTS: The survival rate within our cohort of 180 recurrent invasive pneumococcal disease cases was 98.3%. A decrease of 26.4% in recurrent invasive pneumococcal disease due to vaccine serotypes was observed with pneumococcal vaccine introduction. There was also a 69.0% increase in the rate of vaccination in children with preexisting medical conditions compared with their healthy peers. CONCLUSION: The decrease in recurrent invasive pneumococcal disease due to vaccine-covered serotypes has been offset by an increase of non-vaccine serotypes in this sample of Canadian children.
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Infecciones Neumocócicas , Adolescente , Anciano , Canadá/epidemiología , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas , Estudios Retrospectivos , Vacunación/efectos adversos , Vacunas ConjugadasRESUMEN
BACKGROUND: Respiratory diphtheria is a potentially fatal toxin-mediated disease that is rare among highly vaccinated populations. Cutaneous infections with toxigenic Corynebacterium diphtheriae are most commonly linked to travel to an endemic region. Corynebacterium ulcerans has emerged as a predominant, locally acquired cause of respiratory and cutaneous diphtheria in Western Europe. Recently, public health agencies from several highly vaccinated regions expanded their guidelines to investigate toxigenic cutaneous diphtheria regardless of travel history. With relatively unknown epidemiology of C diphtheriae in North America, and increasing diphtheria toxin testing over the last decade, this change could lead to substantial increases in public health investigations with unclear benefits. METHODS: This study examined the diagnostic and public health benefits of toxigenic cutaneous diphtheria investigations in the highly vaccinated population of Alberta, Canada, where travel history is not required for cutaneous diphtheria investigations. All C diphtheriae isolates collected between 2010 and 2019 were reviewed for specimen source, toxigenicity, biovar, and associated clinical and public health data. RESULTS: Of these, 5% of C diphtheriae isolates were toxigenic and 82% were isolated from cutaneous sites. Three cases of toxigenic cutaneous disease were identified, none from patients with recent travel. Contact tracing identified asymptomatic C diphtheriae colonization among 0%-26% of close contacts, with identical isolate profiles among colonized contacts and primary cases. CONCLUSIONS: Cutaneous diphtheria in nonendemic regions warrants public health investigation regardless of travel history and overall vaccination levels. This study underscores the importance of including C ulcerans in public health guidelines to assess the overall prevalence and epidemiology of toxigenic corynebacteria.
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Background: Although vaccination against Streptococcus pneumoniae infections (such as invasive pneumococcal disease (IPD)) are available, challenges remain in prevention efforts. Moreover, downstream sequelae in children is relatively unknown. Thus, we aimed to evaluate short and long-term health outcomes among children with IPD. Methods: Analysis of Streptococcus pneumoniae positive isolates from sterile body sites in children (0-17 years) in Alberta (Canada) from 1999 to 2019 was performed retrospectively (n=888). Cases were age and sex-matched to hospitalized population controls. Linkage to administrative health datasets was done to determine comorbidities and healthcare related outcomes. Cox proportional hazards were used to assess differences in time to mortality and hospitalisation between cases and controls in short (<30-day), intermediate (30-90 day), long-term (>90-day) follow-up. Findings: Proportionally more deaths occurred in cases (4.8 deaths/1000 person-years (PY)) than controls (2.7 deaths/1000 PY), leading to a significant adjusted hazard ratio (aHR) of 1.80 (95% CI 1.22-2.64). This increased risk of death was influenced primarily by short-term mortality (319 vs 36 deaths/1000 PY in cases vs controls respectively, aHR 8.78 [95% CI 3.33-23.18]), as no differences were seen in intermediate (14 vs 7 deaths/1000 PY; aHR 2.03, 95% CI 0.41-10.04) or long-term time intervals (2.4 vs 2.3 deaths/1000 PY, aHR 1.03, 95% CI 0.63-1.69). Interpretation: IPD continues to negatively impact survival in children despite vaccination. Although long-term impact on mortality and hospitalisations may not be substantial, the immediate effects of IPD are significant. Funding: This work was supported by grants-in-aid from Pfizer Canada and Wyeth Canada Inc all to GJT.