Evaluation of Prenatal Hepatitis C Virus Prevalence Using Universal Screening, and Linkage to Care in a Real-World Setting in Ontario.

OBJECTIVES: International infectious disease/obstetrical societies have recently recommended universal hepatitis C virus (HCV) prenatal screening and these same recommendations are forthcoming in Canada. At present, there is no formal analysis of universal HCV screening or linkage to care of pregnant people in Ontario. The objectives of our study were to determine the seroprevalence of HCV using 2 different methods to evaluate universal screening, as well as identify opportunities that may improve linkage to care. METHODS: To assess seroprevalence in a large urban area, we aimed to test 12 000 de-identified samples submitted for prenatal HIV testing in the catchment area of Toronto Public Health for HCV antibodies. Then, to assess the seroprevalence as well as the operational impact and follow-up in a real-world setting, we completed a Quality Improvement Project (QIP) for 1 year at a large tertiary care obstetrical centre in London, Ontario. RESULTS: From 2019 to 2021, 11 999 de-identified samples were screened from Toronto with a seroprevalence of 0.40 (95% CI 0.29-0.53). In London, 5771 people were screened in 2021 with a seroprevalence of 0.55% (95% CI 0.38-0.78). Taken together, those aged 26-35 years had the highest positivity; in the QIP, 9% had no documented risk factor, and 59% of individuals were not linked to the next step in HCV care. CONCLUSIONS: HCV prenatal seroprevalence in Ontario is comparable to hepatitis B virus, and ∼15-30-fold higher than HIV. Diagnosis in pregnancy is critical to facilitate referrals for treatment between pregnancies and could increase screening among children born to positive women.

Divergent SARS-CoV-2 variant emerges in white-tailed deer with deer-to-human transmission.

Wildlife reservoirs of broad-host-range viruses have the potential to enable evolution of viral variants that can emerge to infect humans. In North America, there is phylogenomic evidence of continual transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from humans to white-tailed deer (Odocoileus virginianus) through unknown means, but no evidence of transmission from deer to humans. We carried out an observational surveillance study in Ontario, Canada during November and December 2021 (n = 300 deer) and identified a highly divergent lineage of SARS-CoV-2 in white-tailed deer (B.1.641). This lineage is one of the most divergent SARS-CoV-2 lineages identified so far, with 76 mutations (including 37 previously associated with non-human mammalian hosts). From a set of five complete and two partial deer-derived viral genomes we applied phylogenomic, recombination, selection and mutation spectrum analyses, which provided evidence for evolution and transmission in deer and a shared ancestry with mink-derived virus. Our analysis also revealed an epidemiologically linked human infection. Taken together, our findings provide evidence for sustained evolution of SARS-CoV-2 in white-tailed deer and of deer-to-human transmission.

Prevalence and Mortality Associated with Bloodstream Organisms: a Population-Wide Retrospective Cohort Study.

Bloodstream infections (BSIs) represent a substantial mortality risk, yet most studies are limited to select pathogens or populations. The aim of this study was to describe the population-wide prevalence of BSIs and examine the associated mortality risk for the responsible microorganisms. We conducted a population-wide retrospective cohort study of BSIs in Ontario in 2017. Blood culture data was collected from almost all microbiology laboratories in Ontario and linked to data sets of patient characteristics. For each organism, we determined the prevalence and crude mortality risk, and using logistic regression models, the adjusted odds of 30-day mortality was calculated relative to patients with negative blood cultures and matched patients without blood culture testing. From 531,065 blood cultures, we identified 22,935 positive BSI episodes in 19,326 patients, for an incidence of 150 per 100,000 population. The most frequently isolated organisms were Escherichia coli, Staphylococcus aureus, coagulase-negative staphylococci, Klebsiella species, and Enterococcus species with 40.2, 22.4, 12.1, 11.1, and 7.1 episodes per 100,000 population respectively. BSI episodes were associated with 17.0% mortality at 30 days. Compared to patients with negative cultures, the adjusted 30-day mortality risk for positive BSIs was 1.47 (95% confidence interval (CI), 1.41 to 1.54) and compared to matched patients without blood culture testing was 2.62 (95% CI, 2.52 to 2.73). Clostridium species were associated with the highest adjusted odds of mortality compared to that of negative cultures (adjusted odds ratio, 5.81; 95% CI, 4.00 to 8.44). Among high incidence pathogens, Staphylococcus aureus had the highest odds ratio of mortality (adjusted odds ratio, 2.14; 95% CI, 1.94 to 2.36). BSIs are associated with increased mortality risk, varying across organisms.

Antibiotic susceptibility of urine culture specimens in Ontario: a population-based cohort study.

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.

Exploring the reasons for low pertussis vaccine effectiveness in Ontario, Canada, 2006-2008: a Canadian Immunization Research Network study.

OBJECTIVES: Although pertussis vaccines have been widely used for many decades, a burden of illness persists. Resurgences in Ontario, Canada, have not been substantial in the past decade, but an outbreak of pertussis occurred in Toronto between 1 October 2005 and 31 March 2006. Previous Ontario studies found high vaccine effectiveness (VE) in the initial years post-immunization. In order to explore the impact of outbreaks and external factors on VE, we investigated pertussis VE during the period 2006-2008. METHODS: We assessed pertussis VE using a frequency-matched case-control study for the period 1 March 2006 to 31 December 2008. We used logistic regression to estimate VE by age, time since last vaccination, and vaccination status according to the Ontario recommended schedule. We compared analyses including and excluding cases from Toronto, and to two recent Ontario pertussis VE studies. RESULTS: We included 1797 confirmed cases and 7188 matched controls. Most cases were under 4 years of age during the study period. Pertussis VE was 3.8% (95% CI: - 21.0, 24.0) in the period 15-364 days following the last pertussis vaccine dose, and increased with increasing time since vaccination. Pertussis VE in the first 15-364 days excluding Toronto increased to 57.1% (95% CI: 26.0, 75.1), but the trend of increasing VE with time since vaccination persisted. Although VE was higher in older (6-11 years) than younger (0-5 years) children, it was lower at 12-13 years than after 14 years. CONCLUSION: VE was lower in comparison with other studies conducted in Ontario, particularly in younger children. Various factors occurring during the study period may have influenced the results, including clinical testing of asymptomatic contacts, laboratory testing and methods and reporting practice, and a sensitive case definition. Further studies are needed to optimize methods for measuring VE to inform pertussis vaccine policy.

RéSUMé: OBJECTIFS: Bien que les vaccins anticoquelucheux soient couramment utilisés depuis des dizaines d'années, la charge de morbidité de la coqueluche persiste. Sa réapparition en Ontario, au Canada, a été modérée au cours des 10 dernières années, mais une éclosion de coqueluche s'est produite à Toronto entre le 1er octobre 2005 et le 31 mars 2006. Des études antérieures menées en Ontario ont fait état d'une efficacité vaccinale (EV) élevée dans les premières années qui suivent l'immunisation. Pour explorer l'impact des éclosions et des facteurs externes sur l'EV, nous avons étudié l'efficacité des vaccins anticoquelucheux pour la période 2006-2008. MéTHODE: Nous avons évalué l'efficacité des vaccins anticoquelucheux à l'aide d'une étude cas-témoins assortie par fréquence pour la période du 1er mars 2006 au 31 décembre 2008. Nous avons procédé par régression logistique pour estimer l'EV selon l'âge, le temps écoulé depuis la dernière vaccination et le statut vaccinal d'après le calendrier recommandé en Ontario. Nous avons comparé les analyses en incluant et en excluant les cas de Toronto et par rapport à deux récentes études ontariennes sur l'efficacité des vaccins anticoquelucheux. RéSULTATS: Nous avons inclus 1 797 cas confirmés et 7 188 témoins assortis. La plupart des cas avaient moins de 4 ans durant la période de l'étude. L'efficacité des vaccins anticoquelucheux était de 3,8 % (IC de 95 % : -21,0, 24,0) au cours des 15 à 364 jours suivant la dernière dose de vaccin anticoquelucheux et augmentait avec le temps après la vaccination. En excluant Toronto, l'efficacité des vaccins anticoquelucheux au cours des 15 à 364 premiers jours passait à 57,1 % (IC de 95 % : 26,0, 75,1), mais la tendance d'augmentation de l'EV avec le temps après la vaccination était toujours présente. Bien que l'EV ait été supérieure chez les enfants plus vieux (6 à 11 ans) que chez les plus jeunes (0 à 5 ans), elle était plus faible chez les 12-13 ans qu'après 14 ans. CONCLUSION: Nous avons observé une EV plus faible que dans d'autres études menées en Ontario, surtout chez les jeunes enfants. Divers facteurs survenus durant la période de l'étude pourraient en avoir influencé les résultats, dont les tests cliniques menés sur les contacts asymptomatiques, les épreuves et les méthodes de laboratoire, les pratiques de déclaration et l'usage d'une définition de cas sensible. D'autres études sont nécessaires pour optimiser la méthode de mesure de l'EV afin d'éclairer la politique vaccinale contre la coqueluche.

Patient and provider determinants of breast cancer screening among Ontario women aged 40-49: a population-based retrospective cohort study.

PURPOSE: Canadian breast cancer screening guidelines state that mammography screening for women 40-49 should be individualized based on risk assessment and preferences. This retrospective cohort study describes the frequency of screening in women aged 40-49 and identifies patient and provider-level associations with screening. METHODS: Administrative databases were linked. The overall cohort included Ontario women aged 40-49 between April 1, 2009 and March 31, 2019. Subgroups were created: the "screen" group included women who received a mammogram defined as screening (using a set of exclusion criteria) and the "routine screen" group included women with three or more screening mammograms. A multivariable multilevel logistic regression model accounting for patient and provider characteristics was fit to determine characteristics associated with routine screening. The intracluster correlation co-efficient was used to quantify the degree of variation across providers. RESULTS: Of approximately 2 million eligible women, there were 532,596 (25.5%) in the screen group and 90,651 (4.3%) the routine screen group. There was an average of 0.30 and 0.52 screening mammograms per woman year, in the screen and routine screen groups, respectively. Routine screening was associated with periodic health exams (OR 1.21, 95% CI 1.20-1.22), receiving pap smears (OR 1.38, 95% CI 1.37-1.39), and fee-for-service models of care (OR 1.32, 95% CI 1.27-1.36). Over 20% of the variation in screening was due to systematic between-provider differences. CONCLUSIONS: Approximately 4.3% of women aged 40-49 in Ontario received routine breast cancer screening with substantial variation across providers. Routine screening is associated with periodic health examinations, receipt of pap smears, and fee-for-service models of care.

The Benefits and Harms of Antibiotic Prophylaxis for Urinary Tract Infection in Older Adults.

BACKGROUND: The role of antibiotics in preventing urinary tract infection (UTI) in older adults is unknown. We sought to quantify the benefits and risks of antibiotic prophylaxis among older adults. METHODS: We conducted a matched cohort study comparing older adults (≥66 years) receiving antibiotic prophylaxis, defined as antibiotic treatment for ≥30 days starting within 30 days of a positive culture, with patients with positive urine cultures who received antibiotic treatment but did not receive prophylaxis. We matched each prophylaxis recipient to 10 nonrecipients based on organism, number of positive cultures, and propensity score. Outcomes included (1) emergency department (ED) visit or hospitalization for UTI, sepsis, or bloodstream infection within 1 year; (2) acquisition of antibiotic resistance in urinary tract pathogens; and (3) antibiotic-related complications. RESULTS: Overall, 4.7% (151/3190) of UTI prophylaxis patients and 3.6% (n = 1092/30 542) of controls required an ED visit or hospitalization for UTI, sepsis, or bloodstream infection (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.12-1.57). Acquisition of antibiotic resistance to any urinary antibiotic (HR, 1.31; 95% CI, 1.18-1.44) and to the specific prophylaxis agent (HR, 2.01; 95% CI, 1.80-2.24) was higher in patients receiving prophylaxis. While the overall risk of antibiotic-related complications was similar between groups (HR, 1.08; 95% CI, .94-1.22), the risk of Clostridioidesdifficile and general medication adverse events was higher in prophylaxis recipients (HR [95% CI], 1.56 [1.05-2.23] and 1.62 [1.11-2.29], respectively). CONCLUSIONS: Among older adults with UTI, the harms of long-term antibiotic prophylaxis may outweigh their benefits.

Antibiotic susceptibility reporting and association with antibiotic prescribing: a cohort study.

OBJECTIVE: Selective reporting of antibiotic susceptibility test results may help guide appropriate antibiotic prescribing, particularly for urinary tract infections. Our objective was to describe laboratory urine culture susceptibility reporting practices and to estimate their impact on antibiotic prescribing in outpatients. METHODS: We examined all positive urine cultures with Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis associated with an antibiotic prescription among outpatients over 65 years of age in Ontario, Canada from 2014 through 2017. We evaluated antibiotic prescribing in the empirical window (1-3 days before culture result) and in the directed window (0-5 days after culture result). Unadjusted and adjusted odds ratios were reported to estimate the association between reporting and prescribing. RESULTS: In total 113 780 eligible urine cultures from 48 laboratories were included in the study cohort. Susceptibility reporting practices were highly variable between laboratories, with a range across antibiotics from norfloxacin (n = 5/48, 10.4% reporting) to nitrofurantoin (n = 40/48, 83.3% reporting). Reporting antibiotic susceptibility was associated with increased odds of prescribing that antibiotic in the directed window (aOR 2.98, 95%CI 2.07-4.28). At the laboratory level, the proportion of urine cultures reporting specific antibiotic susceptibility results was also associated with an increase in prescribing of that antibiotic in the empirical window (adjusted OR 1.23, 95%CI 1.13-1.33, per 25% increase in reporting). CONCLUSIONS: Laboratory reporting of antibiotic susceptibility results for urine cultures is associated with empirical and directed prescribing of the reported antibiotics. Laboratories can play an important role in guiding appropriate antibiotic selection for urinary indications.

A Call for Caution in Use of Pertussis Vaccine Effectiveness Studies to Estimate Waning Immunity: A Canadian Immunization Research Network Study.

BACKGROUND: Vaccine effectiveness (VE) studies provide essential evidence on waning vaccine-derived immunity, a major threat to pertussis control. We evaluated how study design affects estimates by comparing 2 case-control studies conducted in Ontario, Canada. METHODS: We compared results from a test-negative design (TND) with a frequency-matched design (FMD) case-control study using pertussis cases from 2005-2015. In the first study, we identified test-negative controls from the public health laboratory that diagnosed cases and, in the second, randomly selected controls from patients attending the same physicians that reported cases, frequency matched on age and year. We compared characteristics of cases and controls using standardized differences. RESULTS: In both designs, VE estimates for the early years postimmunization were consistent with clinical trials (TND, 84%; FMD, 89% at 1-3 years postvaccination) but diverged as time since last vaccination increased (TND, 41%; FMD, 74% by 8 years postvaccination). Overall, we observed lower VE and faster waning in the TND than the FMD. In the TND but not FMD, controls differed from cases in important confounders, being younger, having more comorbidities, and higher healthcare use. Differences between the controls of each design were greater than differences between cases. TND controls were more likely to be unvaccinated or incompletely vaccinated than FMD controls (P < .001). CONCLUSIONS: The FMD adjusted better for healthcare-seeking behavior than the TND. Duration of protection from pertussis vaccines is unclear because estimates vary by study design. Caution should be exercised by experts, researchers, and decision makers when evaluating evidence on optimal timing of boosters.

Prenatal hepatitis B screening, and hepatitis B burden among children, in Ontario: a descriptive study.

BACKGROUND: Ontario is 1 of 5 provinces that immunize adolescents for hepatitis B virus (HBV), despite the World Health Organization recommendation for universal birth dose vaccination. One rationale for not vaccinating at birth is that universal prenatal screening and related interventions prevent vertical transmission. The aims of our study were to evaluate the uptake and epidemiology of prenatal HBV screening, and to determine the number of children in Ontario with a diagnosis of HBV before adolescent vaccination. METHODS: We extracted data from ICES, Public Health Ontario and Better Outcomes & Registry Network (BORN) Ontario databases. We assessed prenatal screening uptake and prevalence of prenatal hepatitis B surface antigen (HBsAg) from 2012 to 2016, as well as subsequent hepatitis B e-antigen (HBeAg) and HBV DNA testing and percent positivity. We used age and region to subcategorize the results. In a separate unlinked analysis, we evaluated the number of children positive for HBV aged 0-11 years who were born in Ontario from 2003 to 2013. RESULTS: From 2012 to 2016, 93% of pregnant women were screened for HBV, with an HBsAg prevalence of 0.6%. Prevalence of HBsAg increased with age, peaking at older than 45 years at 3%. North Toronto had the highest overall prevalence of 1.5%, whereas northern Ontario had the lowest. Of women who were HBsAg positive, HBeAg and HBV DNA tests were subsequently ordered in 13% and 38%, respectively. Of children born in Ontario between 2003 and 2013, 139 of 23 759 tested positive for HBV. INTERPRETATION: Prenatal HBV screening is not universal and subsequent evaluation is poor, limiting optimal intervention and possibly contributing to some Ontario-born children being given a diagnosis of HBV before age 12 years. These findings underscore the limitations of the province's adolescent vaccination strategy.

Underutilization of nontuberculous mycobacterial drug susceptibility testing in Ontario, Canada, 2010-2015.

Background: Drug susceptibility testing (DST) in nontuberculous mycobacterial pulmonary disease (NTM-PD) is useful for some Mycobacterium species. International guidelines recommend routine use of DST for clinically relevant mycobacteria. DST use and results are poorly studied at the population level. We sought to identify the frequency of DST utilization for nontuberculous mycobacteria (NTMs) and describe the potential relevance of these results in Ontario. Methods: Using public health laboratory data, we performed a population-based retrospective analysis of NTM DST utilization in Ontario from May 2010 to June 2015. We determined the proportion of incident NTM-PD infections for which DST was performed and analyzed minimum inhibitory concentration (MIC) distributions from NTM testing overall, using thresholds recommended by the Clinical and Laboratory Standards Institute. Results: The proportion of incident cases of NTM-PD tested for DST was 6.3% (240/3,806) for Mycobacterium avium complex (MAC), 36.2% (67/185) for M. abscessus, and 1.8% (19/1,057) for M. xenopi. Among specimens from all body sites, MAC resistance to clarithromycin occurred in 8.0% of specimens (21/262) and MAC resistance to amikacin (intravenous, MIC > 64 µg/mL) occurred in 22.6% (19/84). M. abscessus resistance occurred as follows: to amikacin, 3.8% (3/79); cefoxitin, 14.0% (11/79); imipenem, 30.4% (14/46); linezolid, 39.2% (31/79); clarithromycin, 54.2% (13/24); ciprofloxacin, 92.4% (73/79); and moxifloxacin, 91.1% (51/56). M. xenopi analysis was limited by few DST requests and a lack of DST clinical correlation. Conclusions: We found that NTM DST is underutilized in Ontario and observed a very high frequency of amikacin resistance among MAC isolates.

Historique: Les tests de susceptibilité médicamenteuse (TSM) en cas de pneumopathie à mycobactéries non tuberculeuses (PP-MNT) sont utiles pour certaines espèces de Mycobacterium. Selon les directives internationales, ils sont recommandés systématiquement en présence des mycobactéries appropriés sur le plan clinique. L'utilisation des TSM et leurs résultats sont peu étudiés en population. Les auteurs ont cherché à déterminer la fréquence d'utilisation des TSM en cas de mycobactéries non tuberculeuses (MNT) et ont décrit la pertinence potentielle des résultats en Ontario. Méthodologie: À l'aide de données de laboratoires de santé publique, les auteurs ont réalisé une analyse rétrospective en population de l'utilisation des TSM des MNT en Ontario entre mai 2010 et juin 2015. Ils ont déterminé la proportion de nouveaux cas de PP-MNT qui avaient fait l'objet d'un TSM et analysé la répartition de la concentration minimale inhibitrice (CMI) à partir de l'ensemble des tests de MNT, selon les seuils recommandés par le Clinical and Laboratory Standards Institute. Résultats: La proportion de nouveaux cas de PP-MNT ayant fait l'objet d'un TSM s'élevait à 6,3 % (240 cas sur 3 806) pour le complexe Mycobacterium avium (CMA), 36,2 % (67 cas sur 185) pour le M. abscessus et 1,8 % (19 sur 1 057) pour le M. xenopi. Dans les prélèvements provenant de tous les foyers, les chercheurs ont observé une résistance du CMA à la clarithromycine dans 8,0 % des cas (21 sur 262) et à l'amikacine (par voie intraveineuse, CMI > 64 µg/mL), dans 22,6 % des cas (19 sur 84). La résistance au M. abscessus s'établissait comme suit : à l'amikacine dans 3,8 % des cas (3 sur 79); à la cefoxitine dans 14,0 % des cas (11 sur 79); à l'imipénem dans 30,4 % des cas (14 sur 46); au linézolid dans 39,2 % des cas (31 sur 79); à la clarithromycine, dans 54,2 % des cas (13 sur 24); à la ciprofloxacine dans 92,4 % des cas (73 sur 79) et à la moxifloxacine dans 91,1 % des cas (51 sur 56). L'analyse du M. xenopi était limitée par le peu de demandes de TSM et l'absence de corrélation clinique au TSM. Conclusions: Les TSM des MNT sont sous-utilisées en Ontario et sont liés à une très grande fréquence de résistance des isolats de CMA à l'amikacine.

The direct healthcare costs attributable to West Nile virus illness in Ontario, Canada: a population-based cohort study using laboratory and health administrative data.

BACKGROUND: West Nile virus (WNV) is a mosquito-borne flavivirus, first detected in the Western Hemisphere in 1999 and spread across North America over the next decade. Though endemic in the most populous areas of North America, few studies have estimated the healthcare costs associated with WNV. The objective of this study was to determine direct healthcare costs attributable to WNV illness in Ontario, Canada. METHODS: We conducted a cost-of-illness study on incident laboratory confirmed and probable WNV infected subjects identified from the provincial laboratory database from Jan 1, 2002 through Dec 31, 2012. Infected subjects were linked to health administrative data and matched to uninfected subjects. We used phase-of-care methods to calculate costs for 3 phases of illness: acute infection, continuing care, and final care prior to death. Mean 10-day attributable costs were reported in 2014 Canadian dollars, per capita. Sensitivity analysis was conducted to test the impact of WNV neurologic syndromes on healthcare costs. RESULTS: One thousand five hundred fifty-one laboratory confirmed and probable WNV infected subjects were ascertained; 1540 (99.3%) were matched to uninfected subjects. Mean age of WNV infected subjects was 49.1 ± 18.4 years, 50.5% were female. Mean costs attributable to WNV were $1177 (95% CI: $1001, $1352) for acute infection, $180 (95% CI: $122, $238) for continuing care, $11,614 (95% CI: $5916, $17,313) for final care - acute death, and $3199 (95% CI: $1770, $4627) for final care - late death. Expected 1-year costs were $13,648, adjusted for survival. Three hundred seventeen infected subjects were diagnosed with at least one neurologic syndrome and greatest healthcare costs in acute infection were associated with encephalitis ($4710, 95% CI: $3770, $5650). CONCLUSIONS: WNV is associated with increased healthcare resource utilization across all phases of care. High-quality studies are needed to understand the health system impact of vector-borne diseases and evaluate the cost effectiveness of novel WNV interventions.

The evolving nature of Bordetella pertussis in Ontario, Canada, 2009-2017: strains with shifting genotypes and pertactin deficiency.

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

Prescribing Patterns for Treatment of Mycobacterium avium Complex and M. xenopi Pulmonary Disease in Ontario, Canada, 2001-2013.

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

Cohort profile: Development and profile of a population-based, retrospective cohort of diagnosed people living with HIV in Ontario, Canada (Ontario HIV Laboratory Cohort).

PURPOSE: Population-based cohorts of diagnosed people living with HIV (PLWH) are limited worldwide. In Ontario, linked HIV diagnostic and viral load (VL) test databases are centralised and contain laboratory data commonly used to measure engagement in HIV care. We used these linked databases to create a population-based, retrospective cohort of diagnosed PLWH in Ontario, Canada. PARTICIPANTS: A datamart was created by integrating diagnostic and VL databases and linking records at the individual level. These databases contain information on laboratory test results and sociodemographic/clinical information collected on requisition/surveillance forms. Datamart individuals enter our cohort with the first record of a nominal HIV-positive diagnostic test (1985-2015) or VL test (1996-2015), and remain unless administratively lost to follow-up (LTFU; no VL test for >2 years and no VL test in later years). Non-nominal diagnostic tests are excluded as they lack identifying information to permit linkage to other tests. However, individuals diagnosed non-nominally are included in the cohort with record of a VL test. The LTFU rule is applied to indirectly censor for death/out-migration. FINDINGS TO DATE: As of the end of 2015, the datamart contained 40 372 HIV-positive diagnostic tests and 23 851 individuals with ≥1 VL test. Almost half (46.3%) of the diagnostic tests were non-nominal and excluded, although this was lower (~15%) in recent years. Overall, 29 587 individuals have entered the cohort-contributing 229 302 person-years of follow-up since 1996. Between 2000 and 2015, the number of diagnosed PLWH (cohort individuals not LTFU) increased from 8859 to 16 110, and the percent who were aged ≥45 years increased from 29.1% to 62.6%. The percent of diagnosed PLWH who were virally suppressed (<200 copies/mL) increased from 40.7% in 2000 to 79.5% in 2015. FUTURE PLANS: We plan to conduct further analyses of HIV care engagement and link to administrative databases with information on death, migration, physician billing claims and prescriptions. Linkage to other data sources will address cohort limitations and expand research opportunities.

Pertussis vaccine effectiveness in a frequency matched population-based case-control Canadian Immunization Research Network study in Ontario, Canada 2009-2015.

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

Universal genotyping reveals province-level differences in the molecular epidemiology of tuberculosis.

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

Trends in HIV care cascade engagement among diagnosed people living with HIV in Ontario, Canada: A retrospective, population-based cohort study.

BACKGROUND: The HIV cascade is an important framework for assessing systems of care, but population-based assessment is lacking for most jurisdictions worldwide. We measured cascade indicators over time in a population-based cohort of diagnosed people living with HIV (PLWH) in Ontario, Canada. METHODS: We created a retrospective cohort of diagnosed PLWH using a centralized laboratory database with HIV diagnostic and viral load (VL) test records linked at the individual-level. Individuals enter the cohort with record of a nominal HIV-positive diagnostic test or VL test, and remain unless administratively lost to follow-up (LTFU, >2 consecutive years with no VL test and no VL test in later years). We calculated the annual percent of diagnosed PLWH (cohort individuals not LTFU) between 2000 and 2015 who were in care (≥1 VL test), on ART (as documented on VL test requisition) or virally suppressed (<200 copies/ml). We also calculated time from diagnosis to linkage to care and viral suppression among individuals newly diagnosed with HIV. Analyses were stratified by sex and age. Upper/lower bounds were calculated using alternative indicator definitions. RESULTS: The number of diagnosed PLWH increased from 8,859 (8,859-11,389) in 2000 to 16,110 (16,110-17,423) in 2015. Over this 16-year period, the percent of diagnosed PLWH who were: in care increased from 81% (63-81%) to 87% (81-87%), on ART increased from 55% (34-60%) to 81% (70-82%) and virally suppressed increased from 41% (23-46%) to 80% (67-81%). Between 2000 and 2014, the percent of newly diagnosed individuals who linked to care within three months of diagnosis or achieved viral suppression within six months of diagnosis increased from 67% to 82% and from 22% to 42%, respectively. Estimates were generally lower for females and younger individuals. DISCUSSION: HIV cascade indicators among diagnosed PLWH in Ontario improved between 2000 and 2015, but gaps still remain-particularly for younger individuals.