Routinized Syphilis Screening Among Men Living With Human Immunodeficiency Virus: A Stepped Wedge Cluster Randomized Controlled Trial.

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.

Babesia microti in a Canadian blood donor and lookback in a red blood cell recipient.

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.

SARS-CoV-2 Seroprevalence Survey Estimates Are Affected by Anti-Nucleocapsid Antibody Decline.

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.

Genomic Epidemiology of Carbapenemase-Producing Enterobacterales at a Hospital System in Toronto, Ontario, Canada, 2007 to 2018.

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.

Patient perspectives on the implementation of routinised syphilis screening with HIV viral load testing: Qualitative process evaluation of the Enhanced Syphilis Screening Among HIV-positive Men trial.

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.

Assessment of population infection with SARS-CoV-2 in Ontario, Canada, March to June 2020.

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.

Importation of Extensively Drug-Resistant Salmonella enterica Serovar Typhi Cases in Ontario, Canada.

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.

Use of Whole Genome Sequencing for the Molecular Comparison of Neisseria gonorrhoeae Isolates With Decreased Susceptibility to Extended Spectrum Cephalosporins From 2 Geographically Different Regions in America.

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.

Serosorting and recreational drug use are risk factors for diagnosis of genital infection with chlamydia and gonorrhoea among HIV-positive men who have sex with men: results from a clinical cohort in Ontario, Canada.

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.

High incidence of diagnosis with syphilis co-infection among men who have sex with men in an HIV cohort in Ontario, Canada.

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.

Hepatitis C virus seroconversion among HIV-positive men who have sex with men with no history of injection drug use: Results from a clinical HIV cohort.

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.

HISTORIQUE: Sur la scène internationale, il apparaît de plus en plus clairement que le virus de l'hépatite C (VHC) peut être transmis sexuellement entre hommes positifs au VIH ayant des relations sexuelles avec des hommes (HARSAH). OBJECTIF: Rendre compte de la première estimation canadienne de la séro-incidence de VHC entre 2000 et 2010 et de ses facteurs de risque chez les HARSAH positifs au VIH sans antécédents connus de consommation de drogues injectables. MÉTHODOLOGIE: Les chercheurs ont analysé les données de l'Ontario HIV Treatment Network Cohort Study, une cohorte continue de personnes soignées pour le VIH en Ontario. Ils ont tiré les données de dossiers médicaux, d'entrevues et de liens entre les dossiers et les laboratoires provinciaux de santé publique. Ils ont restreint l'analyse à 1 534 HARSAH qui ne déclaraient pas consommer de drogues injectables et qui avaient subi au moins deux tests d'anticorps du VHC, dont le premier était négatif (suivi médian de 6,1 années-personne [AP]; somme de 9 987 AP). RÉSULTATS: De 2000 à 2010, les chercheurs ont observé 51 cas de séroconversion au VHC, pour une incidence globale de 5,1 cas sur 1 000 AP (95 % IC 3,9 à 6,7). L'incidence annuelle variait entre 1,6 et 8,9 cas sur 1 000 AP, sans preuve statistique de tendance temporelle. Le risque de séroconversion était élevé chez les hommes qui n'avaient jamais eu la syphilis (RR rajusté 2,5 [95 % IC 1,1 à 5,5) et chez les hommes qui avaient eu une infection aiguë par la syphilis dans les 18 mois précédents (RR rajusté 2,8 [95 % IC 1,0 à 7,9]). Le risque était plus faible chez les hommes qui avaient entrepris un traitement anti-rétroviral (RR rajusté 0,49 [95 % IC 0,25 à 0,95]). L'âge, l'ethnie, la région, la numération des cellules CD4 et la charge virale du VIH n'avaient pas d'effet statistiquement significatif. CONCLUSIONS: D'après ces observations, il serait judicieux de procéder au dépistage périodique du VHC chez les HARSAH positifs au VIH de l'Ontario. De prochaines recherches devraient viser à établir si la syphilis est un simple marqueur de comportements ou de réseaux sexuels à haut risque ou si elle potentialise la transmission sexuelle du VHC chez les personnes atteintes du VIH.

Azithromycin resistance is coevolving with reduced susceptibility to cephalosporins in Neisseria gonorrhoeae in Ontario, Canada.

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.

Determination of vancomycin pharmacokinetics in neonates to develop practical initial dosing recommendations.

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.

Modest rise in chlamydia and gonorrhoea testing did not increase case detection in a clinical HIV cohort in Ontario, Canada.

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.

Patterns of syphilis testing in a large cohort of HIV patients in Ontario, Canada, 2000-2009.

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.

Neisseria gonorrhoeae treatment failure and susceptibility to cefixime in Toronto, Canada.

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.

Changes in hospitalizations and emergency department respiratory viral diagnosis trends before and during the COVID-19 pandemic in Ontario, Canada.

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.

Whole genome sequencing of increased number of azithromycin-resistant Shigella flexneri 1b isolates in Ontario.

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 (AZMR), 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 AZMR 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 AZMR 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 AZMR isolates circulating locally among males and found that genomic analysis can support targeted prevention and mitigation strategies against antimicrobial-resistance.

Escherichia coli O104:H4 infections and international travel.

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.

Estimation of the burden of disease and costs of genital Chlamydia trachomatis infection in Canada.

BACKGROUND: Rates of Chlamydia trachomatis (CT) infection in Canada have been increasing since the mid-1990s. We sought to estimate the burden of CT in this population. METHODS: We developed an age- and sex-structured mathematical model parameterized to reproduce trends in CT prevalence between 1991 and 2009 in the Canadian population aged 10 to 39 years. Costs were identified, measured, and valued using a modified societal perspective and converted to year 2009 Canadian dollars. Cost-effectiveness of the implemented policy of enhanced screening for asymptomatic infections was estimated by comparison with model-projected trends in the absence of increased screening. Main outcome measures were current net cost and burden of illness attributable to CT infection, and incremental cost-effectiveness ratios. RESULTS: Under base case model assumptions, there was a trend of increasing detection of CT cases (due to increases in screening), despite an underlying stabilization of actual CT infections. Average estimated costs associated with CT infection over this period were $51.4 million per year. Costs of screening and treatment of asymptomatic infections as a proportion of total CT costs were estimated to have increased over time, whereas costs of long-term sequelae associated with untreated infections declined over the same period. Compared with no change in screening, enhanced screening was estimated to be highly cost-effective, with an incremental cost-effectiveness ratio of $2910 per quality-adjusted life year. CONCLUSIONS: Despite increases in screening, the economic burden of CT in Canada remains high. Further investigation of trends in chlamydia-associated complications is required to better understand the impact of screening on incidence.