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OBJECTIVE: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), which is caused primarily by the Canadian methicillin-resistant Staphylococcus aureus-10 (CMRSA-10) strain (also known as the USA300 strain) has emerged rapidly in the United States and is now emerging in Canada. We assessed the prevalence, risk factors, microbiological characteristics and outcomes of CA-MRSA in patients with purulent skin and soft tissue infections (SSTIs) presenting to emergency departments (EDs) in the Greater Toronto Area. METHODS: Patients with Staphylococcus aureus SSTIs who presented to 7 EDs between Mar. 1 and Jun. 30, 2007, were eligible for inclusion in this study. Antimicrobial susceptibilities and molecular characteristics of MRSA strains were identified. Demographic, risk factor and clinical data were collected through telephone interviews. RESULTS: MRSA was isolated from 58 (19%) of 299 eligible patients. CMRSA-10 was identified at 6 of the 7 study sites and accounted for 29 (50%) of all cases of MRSA. Telephone interviews were completed for 161 of the eligible patients. Individuals with CMRSA-10 were younger (median 34 v. 63 yr, p = 0.002), less likely to report recent antibiotic use (22% v. 67%, p = 0.046) or health care-related risk factors (33% v. 72%, p = 0.097) and more likely to report community-related risk factors (56% v. 6%, p = 0.008) than patients with other MRSA strains. CMRSA-10 SSTIs were treated with incision and drainage (1 patient), antibiotic therapy (3 patients) or both (5 patients), and all resolved. CMRSA-10 isolates were susceptible to clindamycin, tetracycline and trimethoprim-sulfamethoxazole. CONCLUSION: CA-MRSA is a significant cause of SSTIs in the Greater Toronto Area, and can affect patients without known community-related risk factors. The changing epidemiology of CA-MRSA necessitates further surveillance to inform prevention strategies and empiric treatment guidelines. [ABSTRACT FROM AUTHOR]

Azithromycin-resistant shigellosis is increasing globally. This retrospective analysis of Shigella flexneri serotype 2a isolates from 2016 to 2018 in Ontario found nearly half were azithromycin (47.7%, 72/151) and ciprofloxacin (50.7%, 77/152) resistant. Moreover, 34.7% (25/72) of azithromycin-resistant isolates were also ciprofloxacin-resistant. Four isolates were ceftriaxone-resistant, although all azithromycin-resistant isolates were ceftriaxone-susceptible. Overall, 83.6% (127/152) of all S. flexneri 2a isolates were recovered from males and 97.2% (70/72) of the azithromycin-resistant cases were males. Among the azithromycin-resistant cases, some (8/72) reported international travel. Phylogenetic analysis of azithromycin-resistant isolates revealed two large male-dominated clusters, and one cluster may have been due to importation of resistant strain. Comparison of plasmids isolated from the clusters in Ontario revealed the presence of incFII plasmid with high percentage of similarity to plasmids present in global outbreaks affecting mostly males including men who have sex with men (MSM). These two large azithromycin-resistant clusters are suggestive of an outbreak among MSM, though disease exposure or sexual orientation of patients was unknown. The presence of plasmid-borne azithromycin resistance in ciprofloxacin-resistant isolates is a public health concern. Antimicrobial surveillance is important for patient management, understanding the spread of novel resistance types in local communities which sometimes is introduced by travel. We found ongoing multidrug-resistant outbreaks spanning multiple years affecting males. Reduction of future outbreaks in high-risk communities like MSM requires consorted information flow between laboratory, public health, and physicians. We impart genomic and antimicrobial characteristics of multidrug S. flexneri 2a which may serve as reference by clinicians and public health.IMPORTANCEOral ciprofloxacin and azithromycin are generally considered as the first-line therapy of shigellosis. Here, we report the emergence and transmission of azithromycin and ciprofloxacin-resistant S. flexneri serotype 2a among male adults in Ontario during 2016-2018. The percentage of azithromycin and ciprofloxacin resistance among S. flexneri 2a is higher compared to previous reports from Canada and United States. Here, we show the genetic basis of the antimicrobial resistance among these unique groups of S. flexneri 2a isolates. We describe a domestically acquired azithromycin-resistant and ciprofloxacin-resistant S. flexneri 2a lineage in Ontario. Combining whole-genome sequencing (WGS) data with travel-associated data helped in understanding dissemination and transmission. We employed WGS, which not only helped us in understanding the genetic-relationship between isolates but also mine information regarding plasmids. In the future, linking WGS, travel-related data, and clinical data can provide enhanced contact tracing and improve public-health management., Competing Interests: The authors declare no conflict of interest.

Azithromycin (AZM) resistance among Shigella is a major public health concern. Here, we investigated the epidemiology of Shigella flexneri serotype 1b recovered during 2016-2018 in Ontario, to describe the prevalence and spread of AZM resistance. We found that 72.3% (47/65) of cases were AZM-resistant (AZM R ), of which 95.7% (45/47) were among males (P < 0.001). Whole-genome based phylogenetic analysis showed three major clusters, and 56.9% of isolates grouped within a single closely-related cluster (0-10 ∆SNP). A single AZM R clonal population was persistent over 3 years and involved 67.9% (36/53) of all male cases, and none reported international travel. In 2018, a different AZM R cluster appeared among adult males not reporting travel. A proportion of isolates (10.7%) with reduced susceptibility to ciprofloxacin (CIP) due to S83L mutation in gyrA were AZM susceptible, and 71.4% reported international travel. Resistance to AZM was due to the acquisition of mph gene-bearing incFII plasmids having > 95% nucleotide similarity to pKSR100. Plasmid-borne resistance limiting treatment options to AZM, ceftriaxone (CRO) and CIP was noted in a single isolate. We characterized AZM R isolates circulating locally among males and found that genomic analysis can support targeted prevention and mitigation strategies against antimicrobial-resistance., (© 2023. Springer Nature Limited.)

Introduction: Population-level surveillance systems have demonstrated reduced transmission of non-SARS-CoV-2 respiratory viruses during the COVID-19 pandemic. In this study, we examined whether this reduction translated to reduced hospital admissions and emergency department (ED) visits associated with influenza, respiratory syncytial virus (RSV), human metapneumovirus, human parainfluenza virus, adenovirus, rhinovirus/enterovirus, and common cold coronavirus in Ontario., Methods: Hospital admissions were identified from the Discharge Abstract Database and exclude elective surgical admissions and non-emergency medical admissions (January 2017-March 2022). Emergency department (ED) visits were identified from the National Ambulatory Care Reporting System. International Classification of Diseases (ICD-10) codes were used to classify hospital visits by virus type (January 2017-May 2022)., Results: At the onset of the COVID-19 pandemic, hospitalizations for all viruses were reduced to near-trough levels. Hospitalizations and ED visits for influenza (9,127/year and 23,061/year, respectively) were nearly absent throughout the pandemic (two influenza seasons; April 2020-March 2022). Hospitalizations and ED visits for RSV (3,765/year and 736/year, respectively) were absent for the first RSV season during the pandemic, but returned for the 2021/2022 season. This resurgence of hospitalizations for RSV occurred earlier in the season than expected, was more likely among younger infants (age ≤6 months), more likely among older children (aged 6.1-24 months), and less likely to comprise of patients residing in higher areas of ethnic diversity (p<0.0001)., Conclusion: During the COVID-19 pandemic, there was a reduced the burden of other respiratory infections on patients and hospitals. The epidemiology of respiratory viruses in the 2022/23 season remains to be seen., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Habbous et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Surveillance of antimicrobial resistance is essential to mitigate its impact on population health and inform local empiric treatment practices. Our aims were to evaluate urine culture specimen susceptibility from a range of diverse settings and describe antibiotic susceptibility across all organisms and compare susceptibilities to that of Escherichia coli alone., Methods: In this descriptive cohort study, we measured the prevalence of organisms in urine culture specimens using linked province-wide administrative databases. Using positive urine cultures collected in Ontario between Jan. 1, 2016, and Dec. 31, 2017, we measured susceptibility to 6 classes of antibiotics using a weighted antibiogram for all organisms compared with E. coli alone., Results: We included 689 497 cultures derived from 569 399 patients and 879 778 test orders for specimens. For all organisms, the rates of susceptibility in the outpatient, inpatient and long-term care settings were 49.3%, 42.8% and 39.2%, respectively, for ampicillin; 83.1%, 72.7% and 69.7%, respectively, for nitrofurantoin; 80.3%, 64.8% and 73.1%, respectively, for trimethoprim-sulfamethoxazole; 87.2%, 74.1% and 66.2%, respectively, for ciprofloxacin; 90.6%, 73.6% and 85.1%, respectively, for aminoglycosides; and 82.6%, 57.5% and 73.5%, respectively, for cefazolin. We found resistance to 3 or more antibiotic classes in 20.6% of episodes for all organisms compared with 14.0% for E. coli alone. The average absolute difference in antibiotic susceptibility between all organisms and E. coli across all drugs was lowest in the outpatient setting (6.2%) and highest in the inpatient setting (14.6%)., Interpretation: In this study, urinary organism prevalence and antimicrobial susceptibility varied across health care settings and patient populations, with implications for both antimicrobial resistance surveillance and clinical decision-making. Weighted antibiograms may be most useful for guiding empiric treatment of urinary infections in inpatient settings where the diversity of infectious organisms is higher than in the community., Competing Interests: Competing interests: None declared., (© 2022 CMA Impact Inc. or its licensors.)

Objectives: Performance characteristics of SARS-CoV-2 nucleic acid detection assays are understudied within contexts of low pre-test probability, including screening asymptomatic persons without epidemiological links to confirmed cases, or asymptomatic surveillance testing. SARS-CoV-2 detection without symptoms may represent presymptomatic or asymptomatic infection, resolved infection with persistent RNA shedding, or a false-positive test. This study assessed the positive predictive value of SARS-CoV-2 real-time reverse transcription polymerase chain reaction (rRT-PCR) assays by retesting positive specimens from 5 pre-test probability groups ranging from high to low with an alternate assay., Methods: In total, 122 rRT-PCR positive specimens collected from unique patients between March and July 2020 were retested using a laboratory-developed nested RT-PCR assay targeting the RNA-dependent RNA polymerase (RdRp) gene followed by Sanger sequencing., Results: Significantly fewer (15.6%) positive results in the lowest pre-test probability group (facilities with institution-wide screening having ≤3 positive asymptomatic cases) were reproduced with the nested RdRp gene RT-PCR assay than in each of the 4 groups with higher pre-test probability (individual group range, 50.0%-85.0%)., Conclusions: Large-scale SARS-CoV-2 screening testing initiatives among low pre-test probability populations should be evaluated thoroughly prior to implementation given the risk of false-positive results and consequent potential for harm at the individual and population level.

Background: We implemented an opt-out clinic-based intervention pairing syphilis tests with routine human immunodeficiency virus (HIV) viral load testing. The primary objective was to determine the degree to which this intervention increased the detection of early syphilis., Methods: The Enhanced Syphilis Screening Among HIV-Positive Men (ESSAHM) Trial was a stepped wedge cluster-randomized controlled trial involving 4 urban HIV clinics in Ontario, Canada, from 2015 to 2017. The population was HIV-positive adult males. The intervention was standing orders for syphilis serological testing with viral loads, and control was usual practice. We obtained test results via linkage with the centralized provincial laboratory and defined cases using a standardized clinical worksheet and medical record review. We employed a generalized linear mixed model with a logit link to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of the intervention., Results: A total of 3895 men were followed over 7471 person-years. The mean number of syphilis tests increased from 0.53 to 2.02 tests per person per year. There were 217 new diagnoses of syphilis (control, 81; intervention, 136), for which 147 (68%) were cases of early syphilis (control, 61 [75%]; intervention, 86 [63%]). The annualized proportion with newly detected early syphilis increased from 0.009 to 0.032 with implementation of the intervention; the corresponding time-adjusted OR was 1.25 (95% CI, .71-2.20)., Conclusions: The implementation of standing orders for syphilis testing with HIV viral loads was feasible and increased testing, yet produced less-than-expected increases in case detection compared to past uncontrolled pre-post trials., Clinical Trials Registration: NCT02019043., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background and Objectives: We describe the third documented case of autochthonous human babesiosis in Canada and the second in a Canadian blood donor., Materials and Methods: Multiple laboratory investigations were carried out on the donor and the immunocompromised recipient of an associated, potentially infectious red blood cell product., Results: The donor had not travelled except for outdoor exposure in south-eastern Manitoba, followed by illness and hospital admission. The donor had a notable parasitaemia, positive for Babesia microti using whole blood nucleic acid testing (NAT). The recipient was negative for B. microti by both serology and NAT., Conclusion: There was no evidence of transfusion-transmitted babesiosis., (© 2021 International Society of Blood Transfusion.)

The N501Y amino acid mutation caused by a single point substitution A23063T in the spike gene of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is possessed by three variants of concern (VOCs), B.1.1.7, B.1.351, and P.1. A rapid screening tool using this mutation is important for surveillance during the coronavirus disease 2019 (COVID-19) pandemic. We developed and validated a single nucleotide polymorphism real-time reverse transcription PCR assay using allelic discrimination of the spike gene N501Y mutation to screen for potential variants of concern and differentiate them from SARS-CoV-2 lineages without the N501Y mutation. A total of 160 clinical specimens positive for SARS-CoV-2 were characterized as mutant (N501Y) or N501 wild type by Sanger sequencing and were subsequently tested with the N501Y single nucleotide polymorphism real-time reverse transcriptase PCR assay. Our assay, compared to Sanger sequencing for single nucleotide polymorphism detection, demonstrated positive percent agreement of 100% for all 57 specimens displaying the N501Y mutation, which were confirmed by Sanger sequencing to be typed as A23063T, including one specimen with mixed signal for wild type and mutant. Negative percent agreement was 100% in all 103 specimens typed as N501 wild type, with A23063 identified as wild type by Sanger sequencing. The identification of circulating SARS-CoV-2 lineages carrying an N501Y mutation is critical for surveillance purposes. Current identification methods rely primarily on Sanger sequencing or whole-genome sequencing, which are time consuming, labor intensive, and costly. The assay described herein is an efficient tool for high-volume specimen screening for SARS-CoV-2 VOCs and for selecting specimens for confirmatory Sanger or whole-genome sequencing. IMPORTANCE During the coronavirus disease 2019 (COVID-19) pandemic, several variants of concern (VOCs) have been detected, for example, B.1.1.7, B.1.351, P.1, and B.1.617.2. The VOCs pose a threat to public health efforts to control the spread of the virus. As such, surveillance and monitoring of these VOCs is of the utmost importance. Our real-time RT-PCR assay helps with surveillance by providing an easy method to quickly survey SARS-CoV-2 specimens for VOCs carrying the N501Y single nucleotide polymorphism (SNP). Samples that test positive for the N501Y mutation in the spike gene with our assay can be sequenced to identify the lineage. Thus, our assay helps to focus surveillance efforts and decrease turnaround times.

Background: Lyme disease (caused by Borrelia burgdorferi ) is an infectious disease transmitted to humans by a bite from infected blacklegged ticks ( Ixodes scapularis ) in eastern North America. Lyme disease can be prevented if antibiotic prophylaxis is given to a patient within 72 hours of a blacklegged tick bite. Therefore, recognizing a blacklegged tick could facilitate the management of Lyme disease. Methods: In this work, we build an automated detection tool that can differentiate blacklegged ticks from other tick species using advanced computer vision approaches in real-time. Specially, we use convolution neural network models, trained end-to-end, to classify tick species. Also, advanced knowledge transfer techniques are adopted to improve the performance of convolution neural network models. Results: Our best convolution neural network model achieves 92% accuracy on unseen tick species. Conclusion: Our proposed vision-based approach simplifies tick identification and contributes to the emerging work on public health surveillance of ticks and tick-borne diseases. In addition, it can be integrated with the geography of exposure and potentially be leveraged to inform the risk of Lyme disease infection. This is the first report of using deep learning technologies to classify ticks, providing the basis for automation of tick surveillance, and advancing tick-borne disease ecology and risk management.

BackgroundSerosurveys for SARS-CoV-2 aim to estimate the proportion of the population that has been infected.AimThis observational study assesses the seroprevalence of SARS-CoV-2 antibodies in Ontario, Canada during the first pandemic wave.MethodsUsing an orthogonal approach, we tested 8,902 residual specimens from the Public Health Ontario laboratory over three time periods during March-June 2020 and stratified results by age group, sex and region. We adjusted for antibody test sensitivity/specificity and compared with reported PCR-confirmed COVID-19 cases.ResultsAdjusted seroprevalence was 0.5% (95% confidence interval (CI): 0.1-1.5) from 27 March-30 April, 1.5% (95% CI: 0.7-2.2) from 26-31 May, and 1.1% (95% CI: 0.8-1.3) from 5-30 June 2020. Adjusted estimates were highest in individuals aged ≥ 60 years in March-April (1.3%; 95% CI: 0.2-4.6), in those aged 20-59 years in May (2.1%; 95% CI: 0.8-3.4) and in those aged ≥ 60 years in June (1.6%; 95% CI: 1.1-2.1). Regional seroprevalence varied, and was highest for Toronto in March-April (0.9%; 95% CI: 0.1-3.1), for Toronto in May (3.2%; 95% CI: 1.0-5.3) and for Toronto (1.5%; 95% CI: 0.9-2.1) and Central East in June (1.5%; 95% CI: 1.0-2.0). We estimate that COVID-19 cases detected by PCR in Ontario underestimated SARS-CoV-2 infections by a factor of 4.9.ConclusionsOur results indicate low population seroprevalence in Ontario, suggesting that public health measures were effective at limiting the spread of SARS-CoV-2 during the first pandemic wave.

At a hospital system (H1) in Ontario, Canada, we investigated whether whole-genome sequencing (WGS) altered initial epidemiological interpretation of carbapenemase-producing Enterobacterales (CPE) transmission. We included patients with CPE colonization/infection identified by population-based surveillance from October 2007 to August 2018 who received health care at H1 in the year before/after CPE detection. H1 reported epidemiological transmission clusters. We combined single nucleotide variant (SNV) analysis, plasmid characterization, and epidemiological data. Eighty-five patients were included. H1 identified 7 epidemiological transmission clusters, namely, A to G, involving 24/85 (28%) patients. SNV analysis confirmed transmission clusters C, D, and G and identified two additional cases belonging to cluster A. One was a travel-related case that was the likely index case (0 to 6 SNVs from other isolates); this case stayed on the same unit as the initially presumed index case 4 months prior to detection of the initially presumed index case on another unit. The second additional case occupied a room previously occupied by 5 cluster A cases. Plasmid sequence analysis excluded a case from cluster A and identified clusters E and F as possibly two parts of a single cluster. SNV analysis also identified a case without direct epidemiologic links that was 18 to 21 SNVs away from cluster B, suggesting possible undetected interhospital transmission. SNV and plasmid sequence analysis identified cases belonging to transmission clusters that conventional epidemiology missed and excluded other cases. Implementation of routine WGS to complement epidemiological transmission investigations has the potential to improve prevention and control of CPE in hospitals.

Accurate SARS-CoV-2 diagnosis is essential to guide prevention and control of COVID-19. Here we examine SARS-CoV-2 molecular-based test performance characteristics and summarize case-level data related to COVID-19 diagnosis. From January 11 through April 22, 2020, Public Health Ontario conducted SARS-CoV-2 testing of 86,942 specimens collected from 80,354 individuals, primarily using real-time reverse-transcription polymerase chain reaction (rRT-PCR) methods. We analyzed test results across specimen types and for individuals with multiple same-day and multi-day collected specimens. Nasopharyngeal compared to throat swabs had a higher positivity (8.8% vs. 4.8%) and an adjusted estimate 2.9 Ct lower (SE = 0.5, p<0.001). Same-day specimens showed high concordance (98.8%), and the median Ct of multi-day specimens increased over time. Symptomatic cases had rRT-PCR results with an adjusted estimate 3.0 Ct (SE = 0.5, p<0.001) lower than asymptomatic/pre-symptomatic cases. Overall test sensitivity was 84.6%, with a negative predictive value of 95.5%. Molecular testing is the mainstay of SARS-CoV-2 diagnosis and testing protocols will continue to be dynamic and iteratively modified as more is learned about this emerging pathogen., Competing Interests: The authors have declared that no competing interests exist.

Background: Syphilis infections have been on the rise, affecting men living with HIV in urban centres disproportionately. Since individuals in HIV care undergo routine blood testing, HIV clinics provide practical opportunities to conduct regular and frequent syphilis testing. Following the implementation of a routine syphilis testing intervention in HIV outpatient clinics, we conducted a qualitative process evaluation of patient experiences to measure patient acceptability, barriers to implementation, and facilitators of successful uptake., Methods: Upon completion of the trial, which took place at four HIV outpatient clinics in Toronto and Ottawa, Canada, we recruited male patients attending these clinics from November 2017 to April 2018. Interviews were conducted on-site and were audio-recorded and transcribed verbatim. All participants provided written informed consent. Interview data were analyzed using grounded theory, assessing qualitative modulators of effective uptake of routinised syphilis testing., Results: A total of 21 male patients were interviewed. Overall, interviewees found the clinical intervention acceptable, endorsing the practice of routinising syphilis testing alongside regular viral load bloodwork. Some men preferred, based on their self-assessment of syphilis risk, to opt out of testing; we considered this as a potential barrier to uptake of population-wide routinised syphilis testing. Interviewees also identified multiple facilitators of successful uptake, including the de-stigmatising of STI testing as a consequence of the universal nature of routinised testing. Participants recommended a routinised syphilis screening intervention to give patients peace of mind surrounding their sexual health. Participants identified HIV care clinics as comfortable and efficient locations to offer testing., Conclusions: Overall, most men were in support of implementing routinised syphilis testing as part of standard HIV care. From the patient perspective, HIV care clinics are convenient places to be tested for syphilis, and the routine approach was viewed to have a de-stigmatisng effect on syphilis testing., Trial Registration: ClinicalTrials.gov NCT02019043; registered December 23, 2013.

Background: Travel-related dissemination of SARS-CoV-2 continues to contribute to the global pandemic. A novel SARS-CoV-2 lineage (B.1.177) reportedly arose in Spain in the summer of 2020, with subsequent spread across Europe linked to travel by infected individuals. Surveillance and monitoring through the use of whole genome sequencing (WGS) offers insights into the global and local movement of pathogens such as SARS-CoV-2 and can detect introductions of novel variants., Methods: We analysed the genomes of SARS-CoV-2 sequenced for surveillance purposes from specimens received by Public Health Ontario (Sept 6 - Oct 10, 2020), collected from individuals in eastern Ontario, which comprised the study sample. Taxonomic lineages were identified using pangolin (v2.08) and phylogenetic analysis incorporated publicly available genomes covering the same time period as the study sample. Epidemiological data collected from laboratory requisitions and standard reportable disease case investigation was integrated into the analysis., Results: Genomic surveillance identified a COVID-19 case with SARS-CoV-2 lineage B.1.177 from an individual in eastern Ontario in late September, 2020. The individual had recently returned from Europe. Genomic analysis with publicly available data indicate the most closely related genomes to this specimen were from Southern Europe. Genomic surveillance did not identify further cases with this lineage., Conclusions: Genomic surveillance allowed for early detection of a novel SARS-CoV-2 lineage in Ontario which was deemed to be travel related. This type of genomic-based surveillance is a key tool to measure the effectiveness of public health measures such as mandatory self-isolation for returned travellers, aimed at preventing onward transmission of newly introduced lineages of SARS-CoV-2., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Author(s). Published by Elsevier Ltd.)

We analyzed 21 676 residual specimens from Ontario, Canada collected March-August 2020 to investigate the effect of antibody decline on SARS-CoV-2 seroprevalence estimates. Testing specimens orthogonally using Abbott (anti-nucleocapsid) and Ortho (anti-spike) assays, seroprevalence estimates were 0.4%-1.4%, despite ongoing disease activity. The geometric mean concentration (GMC) of antibody-positive specimens decreased over time (P = .015), and GMC of antibody-negative specimens increased over time (P = .0018). Association between the 2 tests decreased each month (P < .001), suggesting anti-nucleocapsid antibody decline. Lowering Abbott antibody index cutoff from 1.4 to 0.7 resulted in a 16% increase in positive specimens., (© Her Majesty the Queen in Right of Canada, as represented by Ontario Agency for Health Protection and Promotion, 2021.)

Background: Hospital drains may be an important reservoir for carbapenemase-producing Enterobacterales (CPE)., Aim: To determine prevalence of CPE in hospital drains exposed to inpatients with CPE, relatedness of drain and patient CPE, and risk factors for drain contamination., Methods: Sink and shower drains in patient rooms and communal shower rooms exposed to 310 inpatients with CPE colonization/infection were cultured at 10 hospitals. Using short- and long-read whole-genome sequencing, inpatient and corresponding drain CPE were compared. Risk factors for drain contamination were assessed using multi-level modelling., Findings: Of 1209 exposed patient room and communal shower room drains, 53 (4%) yielded 62 CPE isolates in seven (70%) hospitals. Of 49 CPE isolates in patient room drains, four (8%) were linked to prior room occupants. Linked drain/room occupant pairs included Citrobacter freundii ST18 isolates separated by eight single nucleotide variants (SNVs), related bla KPC -containing IncN3-type plasmids (different species), related bla KPC-3 -containing IncN-type plasmids (different species), and related bla OXA-48 -containing IncL/M-type plasmids (different species). In one hospital, drain isolates from eight rooms on two units were Enterobacter hormaechei separated by 0-6 SNVs. Shower drains were more likely to be CPE-contaminated than hand hygiene (odds ratio: 3.45; 95% confidence interval: 1.66-7.16) or patient-use (13.0; 4.29-39.1) sink drains. Hand hygiene sink drains were more likely to be CPE-contaminated than patient-use sink drains (3.75; 1.17-12.0)., Conclusion: Drain contamination was uncommon but widely dispersed. Drain CPE unrelated to patient exposure suggests contamination by undetected colonized patients or retrograde (drain-to-drain) contamination. Drain types had different contamination risks., (Copyright © 2020 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

A strain of extensively drug-resistant (XDR) Salmonella enterica serovar Typhi has caused a large ongoing outbreak in Pakistan since 2016. In Ontario, Canada, 10 cases of mainly bloodstream infections ( n  = 9) were identified in patients who traveled to Pakistan. Whole-genome sequencing showed that Canadian cases were genetically related to the Pakistan outbreak strain. The appearance of XDR typhoid cases in Ontario prompted a provincial wide alert to physicians to recommend treatment with carbapenems or azithromycin in suspected typhoid cases with travel history to Pakistan., (© Crown copyright 2020.)

Background: Neisseria gonorrhoeae isolates with reduced susceptibility or resistance to the recommended first-line antimicrobial therapy have been described in several countries. The purpose of this study was to use genome analyses to compare the molecular characteristics of N. gonorrhoeae isolates with decreased susceptibility to extended-spectrum cephalosporin from Ontario, Canada, and Argentina., Methods: A total of 128 N. gonorrhoeae isolates, collected in 2015, were included. The susceptibility to penicillin G, tetracycline, ciprofloxacin, cefixime, ceftriaxone, and azithromycin was determined using the agar dilution method. Isolates were subjected to whole genome sequencing, and an in silico analysis was performed to identify antimicrobial resistance determinants and for genotyping., Results: Decreased susceptibility to extended-spectrum cephalosporin was mainly associated with penA mosaic allele 34.001, together with an mtrR promoter A deletion and porB1b alterations G120K/A121N. N. gonorrhoeae multiantigen sequence typing ST1407 or closely related genotypes were identified circulating in both regions., Conclusions: An international multi-drug resistant clone of N. gonorrhoeae was associated with decreased susceptibility to extended-spectrum cephalosporin (ESC) in 2 different regions in America. Evidence of clonal dissemination of the organism in some regions suggests that the strength of surveillance programs and establishment of collaborative projects are essential.

Background: Incidence of syphilis continues to increase among HIV-positive men who have sex with men (MSM) in Ontario. Our objective was to determine the effect of acute syphilis on virologic failure (VF) among virally suppressed HIV-positive MSM taking antiretroviral therapy (ART) and determine if the relationship is confounded by drug use., Setting: The OHTN Cohort Study is a voluntary cohort of people receiving HIV care in Ontario. Syphilis and viral load (VL) data were retrieved via linkage with the provincial laboratory., Methods: Analyses included 2632 MSM from 2008 to 2015, on ART, with ≥1 questionnaire and 2 consecutive VL of <50 copies per milliliter 6 months apart. VF was defined as (1) VL of ≥1000 copies per milliliter or (2) 2 consecutive VLs of ≥200 copies per milliliter ≥1 month apart. We modeled acute syphilis as a time-varying covariate on VF using Poisson regression. Time-varying drug use was assessed for confounding using an iterative process where potential confounders were removed and then reintroduced into the model. Our model allowed for repeat observations using generalized estimating equations., Results: VF incidence was 3.5 per 100 person-years [95% confidence interval (CI): 3.4 to 4.2]. The rate ratio for VF for acute syphilis was 1.5 (95% CI: 0.9 to 2.4) in the unadjusted model; 1.6 (95% CI: 1.0 to 2.4) in the model adjusted for age, education, region, and income; and 1.2 (95% CI: 0.7 to 1.9) in the final model with additional adjustment for drug use., Conclusions: Acute syphilis was not associated with VF among virologically suppressed MSM on ART. Consequently, ART may still reduce HIV transmission risk to sexual partners.

A curated Web-based user-friendly sequence typing tool based on antimicrobial resistance determinants in Neisseria gonorrhoeae was developed and is publicly accessible (https://ngstar.canada.ca). The N. gonorrhoeae Sequence Typing for Antimicrobial Resistance (NG-STAR) molecular typing scheme uses the DNA sequences of 7 genes ( penA , mtrR , porB , ponA , gyrA , parC , and 23S rRNA) associated with resistance to β-lactam antimicrobials, macrolides, or fluoroquinolones. NG-STAR uses the entire penA sequence, combining the historical nomenclature for penA types I to XXXVIII with novel nucleotide sequence designations; the full mtrR sequence and a portion of its promoter region; portions of ponA , porB , gyrA , and parC ; and 23S rRNA sequences. NG-STAR grouped 768 isolates into 139 sequence types (STs) ( n = 660) consisting of 29 clonal complexes (CCs) having a maximum of a single-locus variation, and 76 NG-STAR STs ( n = 109) were identified as unrelated singletons. NG-STAR had a high Simpson's diversity index value of 96.5% (95% confidence interval [CI] = 0.959 to 0.969). The most common STs were NG-STAR ST-90 ( n = 100; 13.0%), ST-42 and ST-91 ( n = 45; 5.9%), ST-64 ( n = 44; 5.72%), and ST-139 ( n = 42; 5.5%). Decreased susceptibility to azithromycin was associated with NG-STAR ST-58, ST-61, ST-64, ST-79, ST-91, and ST-139 ( n = 156; 92.3%); decreased susceptibility to cephalosporins was associated with NG-STAR ST-90, ST-91, and ST-97 ( n = 162; 94.2%); and ciprofloxacin resistance was associated with NG-STAR ST-26, ST-90, ST-91, ST-97, ST-150, and ST-158 ( n = 196; 98.0%). All isolates of NG-STAR ST-42, ST-43, ST-63, ST-81, and ST-160 ( n = 106) were susceptible to all four antimicrobials. The standardization of nomenclature associated with antimicrobial resistance determinants through an internationally available database will facilitate the monitoring of the global dissemination of antimicrobial-resistant N. gonorrhoeae strains., (© Crown copyright 2017.)

Objectives: Rates of chlamydia and gonorrhoea have been rising in urban centres in Canada, particularly among HIV-positive men who have sex with men (MSM). Our objective was to identify behavioural risk factors for diagnosis with chlamydia and gonorrhoea in this population, with a focus on the HIV status of sexual partners., Methods: The OHTN Cohort Study follows people in HIV care across Ontario. We restricted the analysis to 1997 MSM who completed questionnaires in 2010-2013 at one of seven clinics that submit all chlamydia and gonorrhoea tests to the provincial public health laboratory; we obtained test results via record linkage. We estimated cumulative incidences using Kaplan-Meier methods and identified risk factors for diagnosis of a composite outcome (chlamydia or gonorrhoea infection) using Cox regression., Results: At follow-up, there were 74 new chlamydia/gonorrhoea diagnoses with a 12-month cumulative incidence of 1.7% (95% CI 1.1% to 2.2%). Risk factors for chlamydia/gonorrhoea diagnosis were: 5+ HIV-positive partners (HR=3.3, 95% CI 1.4 to 7.8; reference=none) and recreational drug use (HR=2.2, 95% CI 1.2 to 3.9)., Conclusions: Heightened risks with recreational drug use and multiple HIV-positive partners suggest that chlamydia/gonorrhoea may have achieved high prevalence in certain sexual networks among HIV-positive MSM. Interventions to promote safer sex and timely testing among MSM are needed., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: The current syphilis epidemic among urban men who have sex with men (MSM) has serious implications for those co-infected with human immunodeficiency virus (HIV). Routine and frequent syphilis screening has the potential to ensure early detection and treatment, minimize disease burden, and help control the ongoing spread of syphilis and HIV. We aim to enhance syphilis screening among HIV-positive men by conducting a clinic-based intervention that incorporates opt-out syphilis testing into routine HIV laboratory evaluation for this population. Trial objectives are to determine the degree to which the intervention (1) increases the detection rate of untreated syphilis, (2) increases screening coverage, (3) increases screening frequency, and (4) reaches men at highest risk according to sexual behaviors., Methods/design: The trial is a pragmatic, stepped wedge cluster-randomized controlled trial that introduces the intervention stepwise across four urban HIV clinics in Ontario, Canada. The intervention includes standing orders for syphilis serological testing whenever a male in HIV care undergoes HIV viral load testing, which typically occurs every 3-6 months. The control condition is the maintenance of current, provider-initiated syphilis testing practice. Approximately 3100 HIV-positive men will be followed over 30 months. Test results will be obtained from the centralized provincial laboratory in Ontario and will be supplemented by a standardized clinical worksheet and medical chart review at the clinics. Detailed clinical, psychosocial, and behavioral data is available for a subset of men receiving HIV care who are also participants of the province-wide Ontario HIV Treatment Network Cohort Study. Process evaluation plans include audit and feedback of compliance of the participating centers to identify potential barriers to the introduction of this type of practice into routine care. Health economic components include evaluation of the impact and cost-effectiveness of the intervention., Discussion: This trial will be the first of its kind in Canada and will provide evidence regarding the feasibility, clinical effectiveness, and cost-effectiveness of a clinic-based intervention to improve syphilis screening among HIV-positive men. Involvement of knowledge users in all stages of trial design, conduct, and analysis will facilitate scale-up should the intervention be effective., Trial Registration: ClinicalTrials.gov NCT02019043.

A total of 219 clinical isolates of Campylobacter spp. including 180 Campylobacter jejuni and 39 Campylobacter coli were assessed for in vitro antimicrobial susceptibility. Resistance among C. coli was higher for ciprofloxacin (41% versus 30.80%), erythromycin (12.80% versus 3.90%) and lower for tetracycline (53.80% versus 64.60%) compared to C. jejuni., (Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.)

Background: The re-emergence of syphilis among HIV-positive gay and other men who have sex with men (MSM) requires vigilance. We estimated incidence of and risk factors for first and subsequent syphilis diagnoses among MSM in HIV care in Ontario, Canada., Methods: We analyzed data from 2,280 MSM under follow-up from 2006 to 2010 in the Ontario HIV Treatment Network Cohort Study (OCS), a multi-site clinical cohort. We obtained syphilis serology results via record linkage with the provincial public health laboratory. Rates were calculated using Poisson regression., Results: First syphilis diagnoses occurred at a rate of 2.0 per 100 person-years (95 % CI 1.7, 2.4; 121 cases) whereas the re-diagnosis rate was 7.5 per 100 person-years (95 % CI 6.3, 8.8; 136 cases). We observed higher rates over time and among men who were aged <30 years, receiving care in the two largest urban centers, or had a previous syphilis diagnosis. Syphilis diagnosis was less common among Indigenous men, men with higher CD4 cell counts, and, for first diagnoses only, among men with less than high school education., Conclusions: Compared to reported cases in the general male population, incidence of a new syphilis diagnosis was over 300 times greater among HIV-positive MSM but year-to-year changes reflected provincial trends. Re-diagnosis was common, suggesting treatment failure or re-infection. Novel syphilis control efforts are needed among HIV-positive MSM.

Background: Shigellosis is an acute, severe bacterial colitis that, in high-income countries, is typically associated with travel to high-risk regions (Africa, Asia, and Latin America). Since the 1970s, shigellosis has also been reported as a sexually transmitted infection in men who have sex with men (MSM), in whom transmission is an important component of shigellosis epidemiology in high-income nations. We aimed to use sophisticated subtyping and international sampling to determine factors driving shigellosis emergence in MSM linked to an outbreak in the UK., Methods: We did a large-scale, cross-sectional genomic epidemiological study of shigellosis cases collected from 29 countries between December, 1995, and June 8, 2014. Focusing on an ongoing epidemic in the UK, we collected and whole-genome sequenced clinical isolates of Shigella flexneri serotype 3a from high-risk and low-risk regions, including cases associated with travel and sex between men. We examined relationships between geographical, demographic, and clinical patient data with the isolate antimicrobial susceptibility, genetic data, and inferred evolutionary relationships., Findings: We obtained 331 clinical isolates of S flexneri serotype 3a, including 275 from low-risk regions (44 from individuals who travelled to high-risk regions), 52 from high-risk regions, and four outgroup samples (ie, closely related, but genetically distinct isolates used to determine the root of the phylogenetic tree). We identified a recently emerged lineage of S flexneri 3a that has spread intercontinentally in less than 20 years throughout regions traditionally at low risk for shigellosis via sexual transmission in MSM. The lineage had acquired multiple antimicrobial resistance determinants, and prevailing sublineages were strongly associated with resistance to the macrolide azithromycin. Eight (4%) of 206 isolates from the MSM-associated lineage were obtained from patients who had previously provided an isolate; these serial isolations indicated atypical infection patterns (eg, reinfection)., Interpretation: We identified transmission-facilitating behaviours and atypical course(s) of infection as precipitating factors in shigellosis-affected MSM. The intercontinental spread of antimicrobial-resistant shigella through established transmission routes emphasises the need for new approaches to tackle the public health challenge of sexually transmitted infections in MSM., Funding: Wellcome Trust (grant number 098051)., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Internationally, there is a growing recognition that hepatitis C virus (HCV) may be sexually transmitted among HIV-positive men who have sex with men (MSM)., Objective: To report the first Canadian estimate of HCV seroincidence in 2000 to 2010 and its risk factors among HIV-positive MSM with no known history of injection drug use., Methods: Data from the Ontario HIV Treatment Network Cohort Study, an ongoing cohort of individuals in HIV care in Ontario, were analyzed. Data were obtained from medical charts, interviews and record linkage with the provincial public health laboratories. The analysis was restricted to 1534 MSM who did not report injection drug use and had undergone ≥2 HCV antibody tests, of which the first was negative (median 6.1 person-years [PY] of follow-up; sum 9987 PY)., Results: In 2000 to 2010, 51 HCV seroconversions were observed, an overall incidence of 5.1 per 1000 PY (95% CI 3.9 to 6.7). Annual incidence varied from 1.6 to 8.9 per 1000 PY, with no statistical evidence of a temporal trend. Risk for seroconversion was elevated among men who had ever had syphilis (adjusted HR 2.5 [95% CI 1.1 to 5.5) and men who had acute syphilis infection in the previous 18 months (adjusted HR 2.8 [95% CI 1.0 to 7.9]). Risk was lower for men who had initiated antiretroviral treatment (adjusted HR 0.49 [95% CI 0.25 to 0.95]). There were no statistically significant effects of age, ethnicity, region, CD4 cell count or HIV viral load., Conclusions: These findings suggest that periodic HCV rescreening may be appropriate in Ontario among HIV-positive MSM. Future research should seek evidence whether syphilis is simply a marker for high-risk sexual behaviour or networks, or whether it potentiates sexual HCV transmission among individuals with HIV.

Objectives: We described patterns of testing for chlamydia and gonorrhoea infection among persons in specialty HIV care in Ontario, Canada, from 2008 to 2011., Methods: We analysed data from 3165 participants in the OHTN Cohort Study attending one of seven specialty HIV care clinics. We obtained chlamydia and gonorrhoea test results via record linkage with the provincial public health laboratory. We estimated the proportion of participants who underwent testing annually, the positivity rate among those tested and the proportion diagnosed with chlamydia or gonorrhoea among all under observation. We explored risk factors for testing and diagnosis using multiple logistic regression analysis., Results: The proportion tested annually rose from 15.2% (95% CI 13.6% to 16.7%) in 2008 to 27.0% (95% CI 25.3% to 28.6%) in 2011 (p<0.0001). Virtually all were urine-based nucleic acid amplification tests. Testing was more common among men who have sex with men (MSM), younger adults, Toronto residents, persons attending primary care clinics and persons who had tested in the previous year or who had more clinic visits in the current year. We observed a decrease in test positivity rates over time. However, the annual proportion diagnosed remained stable and in 2011 this was 0.97% (95% CI 0.61% to 1.3%) and 0.79% (95% CI 0.46% to 1.1%) for chlamydia and gonorrhoea, respectively. Virtually all cases were among MSM., Conclusions: Chlamydia and gonorrhoea testing increased over time while test positivity rates declined and the overall proportion diagnosed remained stable, suggesting that the modest increase in testing did not improve case detection., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

In Ontario, Canada, the number of Salmonella Enteritidis (SE) cases increased over the years 2005-2010. A population-based case-control study was undertaken from January to August 2011 for the purpose of identifying risk factors for acquiring illness due to SE within Ontario. A total of 199 cases and 241 controls were enrolled. After adjustment for confounders, consuming any poultry meat [adjusted odds ratio (aOR) 2·24, 95% confidence interval (CI) 1·31-3·83], processed chicken (aOR 3·32, 95% CI 1·26-8·76) and not washing hands following handling of raw eggs (OR 2·82, 95% CI 1·48-5·37) were significantly associated with SE infection. The population attributable fraction was 46% for any poultry meat consumption and 10% for processed chicken. Poultry meat continues to be identified as a risk factor for SE illness. Control of SE at source, as well as proper food handling practices, are required to reduce the number of SE cases.

Variability in neonatal vancomycin pharmacokinetics and the lack of consensus for optimal trough concentrations in neonatal intensive care units pose challenges to dosing vancomycin in neonates. Our objective was to determine vancomycin pharmacokinetics in neonates and evaluate dosing regimens to identify whether practical initial recommendations that targeted trough concentrations most commonly used in neonatal intensive care units could be determined. Fifty neonates who received vancomycin with at least one set of steady-state levels were evaluated retrospectively. Mean pharmacokinetic values were determined using first-order pharmacokinetic equations, and Monte Carlo simulation was used to evaluate initial dosing recommendations for target trough concentrations of 15 to 20 mg/liter, 5 to 20 mg/liter, and ≤20 mg/liter. Monte Carlo simulation revealed that dosing by mg/kg of body weight was optimal where intermittent dosing of 9 to 12 mg/kg intravenously (i.v.) every 8 h (q8h) had the highest probability of attaining a target trough concentration of 15 to 20 mg/liter. However, continuous infusion with a loading dose of 10 mg/kg followed by 25 to 30 mg/kg per day infused over 24 h had the best overall probability of target attainment. Initial intermittent dosing of 9 to 15 mg/kg i.v. q12h was optimal for target trough concentrations of 5 to 20 mg/liter and ≤20 mg/liter. In conclusion, we determined that the practical initial vancomycin dose of 10 mg/kg vancomycin i.v. q12h was optimal for vancomycin trough concentrations of either 5 to 20 mg/liter or ≤20 mg/liter and that the same initial dose q8h was optimal for target trough concentrations of 15 to 20 mg/liter. However, due to large interpatient vancomycin pharmacokinetic variability in neonates, monitoring of serum concentrations is recommended when trough concentrations between 15 and 20 mg/liter or 5 and 20 mg/liter are desired.

Azithromycin (AZM) is routinely recommended as a component of dual therapy for gonorrhea in combination with third-generation cephalosporins (3GC). In this study, we examined the prevalence of AZM-resistant (AZM(r)) Neisseria gonorrhoeae from July 2010 to February 2013, assessed the rate of concurrent cephalosporin resistance under the current treatment recommendations, and analyzed the clonal distribution of AZM(r) isolates in Ontario, Canada. Nineteen AZM(r) clinical isolates (one per patient; MIC, ≥2 μg/ml) were included in the study. Susceptibility profiles of these isolates to 11 antibiotics, molecular typing, characterization of macrolide resistance mechanisms, and penicillin-binding protein 2 (PBP2) patterns were determined for all the isolates. Two groups were defined based on AZM(r) level; group A isolates displayed high-level resistance (MIC, ≥2,048 μg/ml) due to mutations (A2143G) in the four copies of the 23S rRNA rrl gene, and group B isolates had moderate resistance to AZM (MICs, 2 to 8 μg/ml, C2599T mutation in the rrl gene), with a subgroup belonging to sequence type 3158 (ST3158) (n = 8), which also showed reduced susceptibility to 3GC (MICs, 0.12 to 0.25 μg/ml, PBP2 pattern XXXIV). This AZM(r) phenotype was not observed in previous provincial surveillance in 2008 (the ST3158 clone was found, with AZM MICs of 0.25 to 0.5 μg/ml associated with mtrR mutations). We hypothesized that the AZM mutant prevention concentration (MPC) in the ST3158 subpopulation we found in 2008 was higher than the MPC in wild-type isolates (AZM MIC, ≤0.031 μg/ml), increasing the chances of additional selection of AZM(r) mutations. Full AZM resistance is now emerging in this clone together with reduced susceptibility to 3GC, threatening the future efficacy of these antibiotics as therapeutic options for treatment of gonorrhea.

Listeria monocytogenes is responsible for severe and often fatal food-borne infections in humans. A collection of 2,421 L. monocytogenes isolates originating from Ontario's food chain between 1993 and 2010, along with Ontario clinical isolates collected from 2004 to 2010, was characterized using an improved multilocus variable-number tandem-repeat analysis (MLVA). The MLVA method was established based on eight primer pairs targeting seven variable-number tandem-repeat (VNTR) loci in two 4-plex fluorescent PCRs. Diversity indices and amplification rates of the individual VNTR loci ranged from 0.38 to 0.92 and from 0.64 to 0.99, respectively. MLVA types and pulsed-field gel electrophoresis (PFGE) patterns were compared using Comparative Partitions analysis involving 336 clinical and 99 food and environmental isolates. The analysis yielded Simpson's diversity index values of 0.998 and 0.992 for MLVA and PFGE, respectively, and adjusted Wallace coefficients of 0.318 when MLVA was used as a primary subtyping method and 0.088 when PFGE was a primary typing method. Statistical data analysis using BioNumerics allowed for identification of at least 8 predominant and persistent L. monocytogenes MLVA types in Ontario's food chain. The MLVA method correctly clustered epidemiologically related outbreak strains and separated unrelated strains in a subset analysis. An MLVA database was established for the 2,421 L. monocytogenes isolates, which allows for comparison of data among historical and new isolates of different sources. The subtyping method coupled with the MLVA database will help in effective monitoring/prevention approaches to identify environmental contamination by pathogenic strains of L. monocytogenes and investigation of outbreaks.

Background: Since 2000, reported syphilis cases increased ten-fold in Canada, particularly among men who have sex with men (MSM) co-infected with HIV. We characterized temporal patterns of of syphilis testing in a large cohort of HIV patients in Ontario, Canada., Methods: We analyzed data from a multi-site cohort of people in HIV care from 2000 to 2009. Data were obtained from medical charts, interviews and record linkage with the syphilis test database at the Public Health Ontario Laboratories. We estimated the proportion that had syphilis testing at least once per year and the period and annual prevalence of reactive tests., Results: Among 4232 participants, the annual proportion tested rose from 2.7% (95%CI 1.9, 3.5) in 2000 to 54.6% (95%CI 52.9, 56.3) in 2009. Testing was most common for participants who were men who have sex with men (MSM), aged <30, recently diagnosed with HIV, were antiretroviral treatment naive, had routine HIV lab testing at least twice in that year, or tested for syphilis in the preceding year. The proportion with at least one reactive test in 2000-09 was 21.0% (95%CI 19.4, 22.7) for MSM, 5.3% (95%CI 3.3, 7.4) for non-MSM males, and 2.6% (95%CI 1.2, 4.0) for women. Among MSM, the annual prevalence of reactive syphilis tests with high RPR titre (≥1:16) peaked at 3.8% in 2009., Conclusions: The burden of syphilis co-infection rose considerably among HIV-positive MSM, such that by 2009, at least 1 in 5 men had laboratory evidence of current or past infection. Interventions may be needed to boost syphilis testing to achieve goals set by guidelines even in settings with universal health care.

Importance: Although cephalosporins are the cornerstone of treatment of Neisseria gonorrhoeae infections, cefixime is the only oral antimicrobial option. Increased minimum inhibitory concentrations (MICs) to cefixime have been identified worldwide and have been associated with reports of clinical failure., Objective: To assess the risk of clinical treatment failure of N. gonorrhoeae infections associated with the use of cefixime., Design, Setting, and Population: A retrospective cohort study of culture-positive N. gonorrhoeae infections at a single sexual health clinic in Toronto, Canada, that routinely performs test of cure. The cohort comprised N. gonorrhoeae culture-positive individuals identified between May 1, 2010, and April 30, 2011, treated with cefixime as recommended by Public Health Agency of Canada guidelines., Main Outcome Measures: Cefixime treatment failure, defined as the repeat isolation of N. gonorrhoeae at the test-of-cure visit identical to the pretreatment isolate by molecular typing and explicit denial of reexposure., Results: There were 291 N. gonorrhoeae culture-positive individuals identified. Of 133 who returned for test of cure, 13 were culture positive; 9 patients were determined to have experienced cefixime treatment failure, involving urethral (n = 4), pharyngeal (n = 2), and rectal (n = 3) sites. The overall rate of clinical treatment failure among those who had a test of cure was 6.77% (95% CI, 3.14%-12.45%; 9/133). The rate of clinical failure associated with a cefixime MIC of 0.12 μg/mL or greater was 25.0% (95% CI, 10.69%-44.87%; 7/28) compared with 1.90% (95% CI, 0.23%-6.71%; 2/105) of infections with cefixime MICs less than 0.12 μg/mL, with a relative risk of 13.13 (95% CI, 2.88-59.72; P < .001)., Conclusion and Relevance: The rate of clinical failure following treatment of N. gonorrhoeae infections with cefixime was relatively high at a Toronto clinic and was associated with elevated MICs.

Most monoclonal antibodies (mAbs) generated from humans infected or vaccinated with the 2009 pandemic H1N1 (pdmH1N1) influenza virus targeted the hemagglutinin (HA) stem. These anti-HA stem mAbs mostly used IGHV1-69 and bound readily to epitopes on the conventional seasonal influenza and pdmH1N1 vaccines. The anti-HA stem mAbs neutralized pdmH1N1, seasonal influenza H1N1 and avian H5N1 influenza viruses by inhibiting HA-mediated fusion of membranes and protected against and treated heterologous lethal infections in mice with H5N1 influenza virus. This demonstrated that therapeutic mAbs could be generated a few months after the new virus emerged. Human immunization with the pdmH1N1 vaccine induced circulating antibodies that when passively transferred, protected mice from lethal, heterologous H5N1 influenza infections. We observed that the dominant heterosubtypic antibody response against the HA stem correlated with the relative absence of memory B cells against the HA head of pdmH1N1, thus enabling the rare heterosubtypic memory B cells induced by seasonal influenza and specific for conserved sites on the HA stem to compete for T-cell help. These results support the notion that broadly protective antibodies against influenza would be induced by successive vaccination with conventional influenza vaccines based on subtypes of HA in viruses not circulating in humans.

We analyzed travel-associated clinical isolates of Escherichia coli O104:H4, including 1 from the 2011 German outbreak and 1 from a patient who returned from the Philippines in 2010, by genome sequencing and optical mapping. Despite extensive genomic similarity between these strains, key differences included the distribution of toxin and antimicrobial drug-resistance determinants.

Escherichia coli O104:H4 was identified as an emerging pathogen during the spring and summer of 2011 and was responsible for a widespread outbreak that resulted in the deaths of 50 people and sickened over 4075. Traditional phenotypic and genotypic assays, such as serotyping, pulsed field gel electrophoresis (PFGE), and multilocus sequence typing (MLST), permit identification and classification of bacterial pathogens, but cannot accurately resolve relationships among genotypically similar but pathotypically different isolates. To understand the evolutionary origins of E. coli O104:H4, we sequenced two strains isolated in Ontario, Canada. One was epidemiologically linked to the 2011 outbreak, and the second, unrelated isolate, was obtained in 2010. MLST analysis indicated that both isolates are of the same sequence type (ST678), but whole-genome sequencing revealed differences in chromosomal and plasmid content. Through comprehensive phylogenetic analysis of five O104:H4 ST678 genomes, we identified 167 genes in three gene clusters that have undergone homologous recombination with distantly related E. coli strains. These recombination events have resulted in unexpectedly high sequence diversity within the same sequence type. Failure to recognize or adjust for homologous recombination can result in phylogenetic incongruence. Understanding the extent of homologous recombination among different strains of the same sequence type may explain the pathotypic differences between the ON2010 and ON2011 strains and help shed new light on the emergence of this new pathogen.

Background: Evidence-based priority setting is increasingly important for rationally distributing scarce health resources and for guiding future health research. We sought to quantify the contribution of a wide range of infectious diseases to the overall infectious disease burden in a high-income setting., Methodology/principal Findings: We used health-adjusted life years (HALYs), a composite measure comprising premature mortality and reduced functioning due to disease, to estimate the burden of 51 infectious diseases and associated syndromes in Ontario using 2005-2007 data. Deaths were estimated from vital statistics data and disease incidence was estimated from reportable disease, healthcare utilization, and cancer registry data, supplemented by local modeling studies and national and international epidemiologic studies. The 51 infectious agents and associated syndromes accounted for 729 lost HALYs, 44.2 deaths, and 58,987 incident cases per 100,000 population annually. The most burdensome infectious agents were: hepatitis C virus, Streptococcus pneumoniae, Escherichia coli, human papillomavirus, hepatitis B virus, human immunodeficiency virus, Staphylococcus aureus, influenza virus, Clostridium difficile, and rhinovirus. The top five, ten, and 20 pathogens accounted for 46%, 67%, and 75% of the total infectious disease burden, respectively. Marked sex-specific differences in disease burden were observed for some pathogens. The main limitations of this study were the exclusion of certain infectious diseases due to data availability issues, not considering the impact of co-infections and co-morbidity, and the inability to assess the burden of milder infections that do not result in healthcare utilization., Conclusions/significance: Infectious diseases continue to cause a substantial health burden in high-income settings such as Ontario. Most of this burden is attributable to a relatively small number of infectious agents, for which many effective interventions have been previously identified. Therefore, these findings should be used to guide public health policy, planning, and research.

Surveillance of gonococcal antimicrobial resistance and the molecular characterization of the mechanisms underlying these resistance phenotypes are essential in order to establish correct empirical therapies, as well as to describe the emergence of new mechanisms in local bacterial populations. To address these goals, 149 isolates were collected over a 1-month period (October-November 2008) at the Ontario Public Health Laboratory, Toronto, Canada, and susceptibility profiles (8 antibiotics) were examined. Mutations in previously identified targets or the presence of some enzymes related to resistance (r), nonsusceptibility (ns) (resistant plus intermediate categories), or reduced susceptibility (rs) to the antibiotics tested were also studied. A significant proportion of nonsusceptibility to penicillin (PEN) (89.2%), tetracycline (TET) (72.3%), ciprofloxacin (CIP) (29%), and macrolides (erythromycin [ERY] and azithromycin; 22.3%) was found in these strains. Multidrug resistance was observed in 18.8% of the collection. Although all the strains were susceptible to spectinomycin and extended-spectrum cephalosporins (ESC) (ceftriaxone and cefixime), 9.4% of them displayed reduced susceptibility to extended-spectrum cephalosporins. PBP 2 mosaic structures were found in all of these ESC(rs) isolates. Alterations in the mtrR promoter, MtrR repressor (TET(r), PEN(ns), ESC(rs), and ERY(ns)), porin PIB (TET(r) and PEN(ns)), and ribosomal protein S10 (TET(r)) and double mutations in gyrA and parC quinolone resistance-determining regions (QRDRs) (CIP(r)) were associated with and presumably responsible for the resistance phenotypes observed. This is the first description of ESC(rs) in Canada. The detection of this phenotype indicates a change in the epidemiology of this resistance and highlights the importance of continued surveillance to preserve the last antimicrobial options available.

Two hundred crossbred cattle (Bos indicus x Bos taurus) were supplemented with 2% Tasco (Ascophyllum nodosum) in a commercial finishing facility to evaluate marbling score, USDA quality grade, sensory traits, and retail display shelf life. Treatment animals (n = 100) received a steam-rolled corn (Zea mays)-based diet containing 2% Tasco meal (DM basis), for 14 d beginning at d 45 of the finishing period and again 14 d before slaughter. Control animals (n = 100) received a steam-rolled corn (Zea mays)-based diet without Tasco at identical feeding periods. Carcasses from Tasco-fed cattle exhibited greater marbling scores (P = 0.003) than controls. There were no treatment effects (P > 0.05) on sensory, shear, or purge attributes of striploin or inside round steaks with the exception of inside round steaks from Tasco animals having a greater initial tenderness (P = 0.03) and lower off-flavor score (P = 0.002) than control steaks. The LM samples from Tasco-fed cattle had a greater percentage of ether extractable fat (P = 0.001) and lower percentage of protein (P = 0.001) than controls. Inside round samples from treated animals exhibited a greater percentage of moisture (P = 0.03) than control steaks. Visual lean color of striploin steaks was not affected by Tasco supplementation (P = 0.26); however, steaks from Tasco-treated animals were more uniform and had less discoloration and browning than those from controls (P = 0.005, 0.04, and 0.05, respectively). Inside round visual scores and instrument values reflected similar treatment responses (P < 0.05), with a majority of the effects on muscle redness (CIE a*, hue angle) and measures of discoloration. Tasco steaks were generally more red and less discolored during extended postmortem aging and retail exposure (P < 0.05). The results from this study indicate that short-term supplementation of 2% Tasco meal in feedlot cattle increases carcass quality and prolonged retail shelf life.

Sustainable outdoor pig production requires vegetation that can maintain ground cover, assimilate manure nutrients, and prevent soil erosion. Two experiments were conducted to evaluate the suitability of four forages: alfalfa (Medicago sativa), tall fescue (Festuca arundinacea), white clover (Trifolium repens), and buffalograss (Buchloe dactyloides) for grazing or ground cover in pastures for pigs. Each forage plot covered 7.5 m2, with nine replicates in a randomized block design. In Exp. 1, eight pregnant gilts had free access to all forages during a 2-d adjustment period. Immediately thereafter, pairs of gilts were assigned randomly to one of each of four blocks of the four forages during a 2-d measurement period. The percentage of ground cover for each forage was visually estimated at 0, 24, and 48 h of study. Behavioral data, including walking, eating, grazing, rooting, drinking, standing, lying, and time spent in hut were video-monitored continuously for 48 h. Initial percentage of ground cover was 100% for all species. By 48 h, percentage of ground cover decreased (P < 0.001) for white clover (11.3 +/- 0.88%) and alfalfa (36.3 +/- 0.88%), but not for tall fescue (98.0 +/- 0.88%) or buffalograss (98.0 +/- 0.88%). Gilts spent more (P < 0.01) time grazing white clover (16.3 +/- 1.97 min/d) and alfalfa (11.2 +/- 1.97) than tall fescue (0.8 +/- 1.97) or buffalograss (0.3 +/- 1.97), and rooted more (P < 0.04) white clover than other forages. In Exp. 2, six gilts from the initial group were put on six blocks of the four forages. Each gilt was assigned randomly to three replicates of each forage, including alfalfa, tall fescue, or buffalograss (white clover was excluded because of damage by gilts during Exp. 1), and gilts grazed single forages for 2 d. After this grazing period, the percentage of ground cover was less (P < 0.01) for alfalfa than for buffalograss or tall fescue (37.5 +/- 0.38, 96.7 +/- 0.39, 96.3 +/- 0.39%, respectively). With access to a single forage, pregnant gilts spent more (P < 0.01) time grazing alfalfa (15.8 +/- 2.36 min/d) than buffalograss (1.5 +/- 2.36) or tall fescue (0.7 +/- 2.37). These gilts clearly preferred grazing white clover and alfalfa, and rooting and eating white clover compared with buffalograss or tall fescue. Rates of ground cover loss were less (P < 0.01) for tall fescue and buffalograss than for the more preferred forages. Less preferred forages could have potential as pasture for swine when the primary objective is ground cover maintenance rather than nutrient supply.