Many enteric bacteria use bile as an environmental cue to signal resistance and virulence gene expression. Microarray analysis of enterohemorrhagic Escherichia coli O157:H7 (EHEC) treated with bile salts revealed upregulation of genes for an efflux system (acrAB), a two-component signal transduction system (basRS/ pmrAB), and lipid A modification (arnBCADTEF and ugd). Bile salt treatment of EHEC produced a basS-and arnT-dependent resistance to polymyxin.

BackgroundSince the widespread use of Haemophilus influenzae (Hi) type b (Hib) vaccines among children aged <5 years, an increase in invasive non-Hib disease incidence has been reported internationally. We sought to describe the epidemiology of invasive non-Hib disease in Ontario, Canada (population ~13.5 million).MethodsConfirmed invasive non-Hib cases (non-typeable [NTHi] and serotypes a, c, d, e, and f) were obtained from the provincial laboratory data system from 2004–2013. Data were deterministically linked to the provincial reportable disease system to provide further case information. Antibiotic resistance data were analysed separately from 2010–2014. Descriptive analyses included incidence rates, age group, serotype, site of specimen collection and resistance patterns; ethnicity data were not available. Temporal trends were evaluated by Poisson regression and p-values <0.05 were considered significant.ResultsA total of 1307 cases of invasive non-Hib disease were included, increasing from 0.67 cases to 1.60 cases /100,000 from 2004 to 2013. Significant increases in the incidence of NTHi (0.50 to 1.28 cases/100 000 population), Hia (0.02 to 0.08 cases/100, 000) and Hif (0.13 to 0.18 cases/100, 000 population) were seen. Among persons aged 40–64 years, 3 Hi strains significantly increased over time; NTHi (0.22 to 0.99 cases/100, 000), Hia (0.00 to 0.06 cases/100, 000) and Hif (0.05 to 0.21 cases/100, 000). Among persons aged 65–84 years, there was a significant increase of NTHi (1.62 to 3.14 cases/100, 000) and Hia (0.00 to 0.34 cases/100, 000). Among persons aged 85+ years, only NTHi significantly increased from 4.89 to 10.28 cases/100, 000). Antimicrobial resistance (AMR) to ampicillin and clarithromycin was seen in greater than 25% of isolates but AMR did not increase over the duration of this study.ConclusionsThe incidence of invasive non-Hib disease has increased over time; NTHi, Hif and Hia are emerging pathogens, and should be monitored.

NNV has been used in a wide variety of ways in the literature, yet there are no defined thresholds for what is a favourable NNV. Furthermore, the generalizability of the NNV is usually limited. Further work is required to determine the most appropriate use of this measure.

BackgroundInvasive meningococcal disease (IMD) caused by serogroup B is the last major serogroup in Canada to become vaccine-preventable. The anticipated availability of vaccines targeting this serogroup prompted an assessment of the epidemiology of serogroup B disease in Ontario, Canada.MethodsWe retrieved information on confirmed IMD cases reported to Ontario’s reportable disease database between January 1, 2000 and December 31, 2010 and probabilistically-linked these cases to Public Health Ontario Laboratory records. Rates were calculated with denominator data obtained from Statistics Canada. We calculated a crude number needed to vaccinate using the inverse of the infant (<1 year) age-specific incidence multiplied by expected vaccine efficacies between 70% and 80%, and assuming only direct protection (no herd effects).ResultsA total of 259 serogroup B IMD cases were identified in Ontario over the 11-year period. Serogroup B was the most common cause of IMD. Incidence ranged from 0.11 to 0.27/100,000/year, and fluctuated over time. Cases ranged in age from 13 days to 101 years; 21.4% occurred in infants, of which 72.7% were <6 months. Infants had the highest incidence (3.70/100,000). Case-fatality ratio was 10.7% overall. If we assume that all infant cases would be preventable by vaccination, we would need to vaccinate between 33,784 and 38,610 infants to prevent one case of disease.ConclusionsAlthough rare, the proportion of IMD caused by serogroup B has increased and currently causes most IMD in Ontario, with infants having the highest risk of disease. Although serogroup B meningococcal vaccines are highly anticipated, our findings suggest that decisions regarding publicly funding serogroup B meningococcal vaccines will be difficult and may not be based on disease burden alone.

The results of this systematic review delineate both the short- and long-term morbidities that can occur after, and persist beyond, the period of acute illness. A better understanding of the full spectrum of IMD sequelae is critical for assessing the burden of IMD and supporting healthcare planning and decision making in light of new vaccines.

Bordetella pertussis testing performed using real-time polymerase chain reaction (RT-PCR) is interpreted based on a cycle threshold (Ct) value. At Public Health Ontario Laboratories (PHOL), a Ct value <36 is reported as positive, and Ct values ≥36 and <40 are reported as indeterminate. PHOL reported indeterminate results to physicians and public health units until May 2012, after which these results were only reported to physicians. We investigated the association between Ct value and disease symptom and severity to examine the significance of indeterminate results clinically, epidemiologically and for public health reporting. B. pertussis positive and indeterminate RT-PCR results were linked to pertussis cases reported in the provincial Integrated Public Health Information System (iPHIS), using deterministic linkage. Patients with positive RT-PCR results had a lower median age of 10.8 years compared to 12.0 years for patients with indeterminate results (p = 0.24). Hospitalized patients had significantly lower Ct values than non-hospitalized patients (median Ct values of 20.7 vs. 31.6, p<0.001). The proportion of patients reporting the most indicative symptoms of pertussis did not differ between patients with positive vs. indeterminate RT-PCR results. Taking the most indicative symptoms of pertussis as the gold-standard, the positive predictive value of the RT-PCR test was 68.1%. RT-PCR test results should be interpreted in the context of the clinical symptoms, age, vaccination status, prevalence, and other factors. Further information on interpretation of indeterminate RT-PCR results may be needed, and the utility of reporting to public health practitioners should be re-evaluated.

In Canada, measles was eliminated in 1998 and rubella in 2000. Effective measles and rubella surveillance is vital in elimination settings, hinging on reliable laboratory methods. However, low-prevalence settings affect the predictive value of laboratory tests. We conducted an analysis to determine the performance of measles and rubella IgM testing in a jurisdiction where both infections are eliminated.21,299 test results were extracted from the Public Health Ontario Laboratories database and 1,239 reports were extracted from the Ontario Integrated Public Health Information System (iPHIS) from 2008 and 2010 for measles and rubella, respectively, to 2014. Deterministic linkage resulted in 658 linked measles records (2009–2014) and 189 linked rubella records (2010–2014). Sixty-six iPHIS measles entries were classified as confirmed cases, of which 53 linked to laboratory data. Five iPHIS rubella entries were classified as confirmed, all linked to IgM results. The positive predictive value was 17.4% for measles and 3.6% for rubella. Sensitivity was 79.2% for measles and 100.0% for rubella. Specificity was 65.7% for measles and 25.8% for rubella.Our study confirms that a positive IgM alone does not confirm a measles case in elimination settings. This has important implications for countries that are working towards measles and rubella elimination.

Background In contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity. Methods and results CLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia, and Africa in 2009–2010, and followed up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis &gt;50%, proven symptomatic myocardial ischaemia, or prior revascularization procedure. Among 32 694 patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to ∼60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome (cardiovascular death, myocardial infarction, or stroke) with an adjusted hazard ratio of 1.28 (95% confidence interval 1.18, 1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest. Conclusion In patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes. ClinicalTrials identifier ISRCTN43070564