Burden of Severe Illness Associated With Laboratory-Confirmed Influenza in Adults Aged 50-64 Years, 2010-2011 to 2016-2017.

Background: Understanding the burden of influenza is necessary to optimize recommendations for influenza vaccination. We describe the epidemiology of severe influenza in 50- to 64-year-old residents of metropolitan Toronto and Peel region, Canada, over 7 influenza seasons. Methods: Prospective population-based surveillance for hospitalization associated with laboratory-confirmed influenza was conducted from September 2010 to August 2017. Conditions increasing risk of influenza complications were as defined by Canada's National Advisory Committee on Immunization. Age-specific prevalence of medical conditions was estimated using Ontario health administrative data. Population rates were estimated using Statistics Canada data. Results: Over 7 seasons, 1228 hospitalizations occurred in patients aged 50-64 years: 40% due to A(H3N2), 30% A(H1N1), and 22% influenza B. The average annual hospitalization rate was 15.6, 20.9, and 33.2 per 100 000 in patients aged 50-54, 55-59, and 60-64 years, respectively; average annual mortality was 0.9/100 000. Overall, 33% of patients had received current season influenza vaccine; 963 (86%) had ≥1 underlying condition increasing influenza complication risk. The most common underlying medical conditions were chronic lung disease (38%) and diabetes mellitus (31%); 25% of patients were immunocompromised. The average annual hospitalization rate was 6.1/100 000 in those without and 41/100 000 in those with any underlying condition, and highest in those with renal disease or immunocompromise (138 and 281 per 100 000, respectively). The case fatality rate in hospitalized patients was 4.4%; median length of stay was 4 days (interquartile range, 2-8 days). Conclusions: The burden of severe influenza in 50- to 64-year-olds remains significant despite our universal publicly funded vaccination program. These data may assist in improving estimates of the cost-effectiveness of new strategies to reduce this burden.

Canada-Wide Epidemic of emm74 Group A Streptococcus Invasive Disease.

BACKGROUND: The number of invasive group A Streptococcus (iGAS) infections due to hitherto extremely rare type emm74 strains has increased in several Canadian provinces since late 2015. We hypothesized that the cases recorded in the different provinces are linked and caused by strains of an emm74 clone that recently emerged and expanded explosively. METHODS: We analyzed both active and passive surveillance data for iGAS infections and used whole-genome sequencing to investigate the phylogenetic relationships of the emm74 strains responsible for these invasive infections country-wide. RESULTS: Genome analysis showed that highly clonal emm74 strains, genetically different from emm74 organisms previously circulating in Canada, were responsible for a country-wide epidemic of >160 invasive disease cases. The emerging clone belonged to multilocus sequence typing ST120. The analysis also revealed dissemination patterns of emm74 subclonal lineages across Canadian provinces. Clinical data analysis indicated that the emm74 epidemic disproportionally affected middle-aged or older male individuals. Homelessness, alcohol abuse, and intravenous drug usage were significantly associated with invasive emm74 infections. CONCLUSIONS: In a period of 20 months, an emm74 GAS clone emerged and rapidly spread across several Canadian provinces located more than 4500 km apart, causing invasive infections primarily among disadvantaged persons.

Prevalence of vancomycin-variable Enterococcus faecium (VVE) among vanA-positive sterile site isolates and patient factors associated with VVE bacteremia.

Vancomycin-variable enterococci (VVE) are vanA-positive, vancomycin-susceptible enterococci with the ability to revert to a vancomycin-resistant phenotype on exposure to vancomycin. We sought to assess the prevalence of VVE and to determine clinical characteristics of patients infected with VVE. We prospectively collected Enterococcus faecium sterile site isolates from Toronto Invasive Bacterial Diseases Network hospitals from January 2015 to June 2016 and calculated VVE (defined as vanA-positive, vancomycin-susceptible isolates) prevalence among vanA-containing isolates. We performed chart reviews of VVE and vancomycin-resistant E. faecium (VRE) bacteremias identified from January 2012 to June 2016, and on a random sample of patients with bacteremia due to vanA/vanB-negative, vancomycin-susceptible enterococci (VSE) from January 2015 to June 2016. Clinical characteristics were compared and factors associated with mortality assessed. Because of the potential reversion from VVE to VRE, pulsed-field gel electrophoresis (PFGE) was performed for strains causing breakthrough bacteremia in order to identify relatedness among strains with different phenotypic resistance within the same patient. VVE comprised 47% (18/38) of vanA-positive isolates. The charts of 36 VRE, 25 VVE, and 79 VSE patients were reviewed. Central venous catheter associated bacteremia was more common in VVE (44%) and VRE patients (57%) than in VSE patients (28%) (P = 0.01). The Pitt bacteremia (OR 1.3, P = 0.002) and the Charlson score (OR 1.2, P = 0.008) were the only independent mortality predictors. PFGE of strains causing breakthrough bacteremia showed high within-patient clonality, irrespective of vanA-positivity or vancomycin-susceptibility. A substantial proportion of vanA-positive isolates are VVE and are therefore not detected with conventional selective culture methods. Bacteremia sources of patients with VVE are similar to those infected with VRE. We detected no association between VVE and 30-day mortality or breakthrough bacteremia.

Factors Associated With 30-Day Mortality Rate in Respiratory Infections Caused by Streptococcus pneumoniae.

In multivariable analysis of associations between initial antibiotic therapy and clinical outcomes in 5005 patients with microbiologically confirmed Streptococcus pneumoniae infections, "discordant" empiric antibiotic therapy was not associated with 30-day mortality rate (hazard ratio, 0.94; 95% confidence interval, .67-1.32).

Association of serotype with respiratory presentations of pneumococcal infection, Ontario, Canada, 2003-2011.

BACKGROUND: Pneumococcal disease burden is difficult to quantify due to limited data regarding non-bacteremic disease. We assessed serotype-specific differences in pneumococcal disease presentations in adults in Toronto, Canada. METHODS: From 2003 to 2011, population-based surveillance for invasive pneumococcal disease was conducted and respiratory pneumococcal isolates collected in Metropolitan Toronto/Peel Region, Canada. Episodes of care were classified into disease categories. RESULTS: Of 3105 eligible cases of IPD, 2060 cases were bacteremic pneumonia, and 1045 bacteremia without pneumonia. Of 2751 eligible respiratory cases, 1542 (56.0%) were non-bacteremic pneumonia (NBPP), 467 (17.0%) were other acute respiratory infection (oARI), and 742 (27.0%) were isolates representing colonization. Serotypes 3 (11.3%), 19A (8.4%) and 22F (6.2%) were the most common; serotypes 1,5, and 8 were rare. Serotypes 4, 14, 7F, 9V, 12F, 14, 19A and 6C were over-represented in bacteremic disease, and serotypes 3, 6A, 11A, 19F, 23A, 23F, 35B, 35F were more common in NBPP. The proportion of cases due to PCV7 serotypes declined from 48.7% to 8.7% in bacteremic pneumonia, from 35.3% to 10.9% in NBPP, from 34.2% to 7.5% in oARI, and from 38.7% to 12.2% in colonizing isolates. In 2010-2011, PCV13 serotypes accounted for 62.6% of isolates associated with bacteremic pneumonia, 42.0% of bacteremia without pneumonia, 41.1% of NBPP, 25.7% of oARI, and 32.9% of colonizing isolates. CONCLUSIONS: Serotype distributions differ significantly in different presentations of pneumococcal disease. Herd protection due to PCV7 has changed serotype distribution, but PCV13 serotypes remain important in all categories of disease.

Pneumococcal vaccination programs and the burden of invasive pneumococcal disease in Ontario, Canada, 1995-2011.

BACKGROUND: In 1995, a publicly funded pneumococcal vaccination program for 23-valent polysaccharide vaccine (PPV23) was introduced in Ontario. Conjugate vaccines were authorized in 2001 (PCV7), 2009 (PCV10) and 2010 (PCV13). METHODS: From 1995-2011, active, population-based surveillance for invasive pneumococcal disease (IPD) was conducted in Metropolitan Toronto and Peel Region, Canada. RESULTS: 6404 IPD cases were included. After PPV23 program implementation in 1995, IPD due to PPV23 strains decreased 49% in older adults prior to PCV7 introduction. Estimated PPV23 efficacy in vaccine eligible adults was 42.2% (95% CI; 28.6-53.2%). IPD incidence due to PCV7 serotypes in children <5 years decreased significantly after PCV7 authorization and before introduction of a publicly funded PCV7 program. Seven years after PCV7 program implementation, the incidence of IPD due to PCV7 serotypes decreased to zero in children and by 88% in adults, however, overall IPD incidence remained unchanged in adults. In 2011, the incidence of IPD was 4.5 per 100,000 in adults aged 15-64 and 19.9 per 100,000 in adults aged over 65 years, with 45 serotypes causing disease. Between 1995 and 2011, the case fatality rate of IPD in adults decreased 2% per year (95% CI, -0.9% to -3.2%). In multivariable analysis, predictors of mortality included older age, chronic conditions, nursing home residence, current smoking, bacteraemia, and illness due to serotypes 3,11A, 19A, and 19F. CONCLUSIONS: While vaccination programs resulted in substantial public health benefits, herd immunity benefits of PCV7 were seen at low pediatric vaccination rates, and the case fatality rate of IPD has decreased, IPD will continue to be a cause of considerable morbidity and mortality in adults.

When should a diagnosis of influenza be considered in adults requiring intensive care unit admission? Results of population-based active surveillance in Toronto.

INTRODUCTION: There is a paucity of data about the clinical characteristics that help identify patients at high risk of influenza infection upon ICU admission. We aimed to identify predictors of influenza infection in patients admitted to ICUs during the 2007/2008 and 2008/2009 influenza seasons and the second wave of the 2009 H1N1 influenza pandemic as well as to identify populations with increased likelihood of seasonal and pandemic 2009 influenza (pH1N1) infection. METHODS: Six Toronto acute care hospitals participated in active surveillance for laboratory-confirmed influenza requiring ICU admission during periods of influenza activity from 2007 to 2009. Nasopharyngeal swabs were obtained from patients who presented to our hospitals with acute respiratory or cardiac illness or febrile illness without a clear nonrespiratory aetiology. Predictors of influenza were assessed by multivariable logistic regression analysis and the likelihood of influenza in different populations was calculated. RESULTS: In 5,482 patients, 126 (2.3%) were found to have influenza. Admission temperature ≥38°C (odds ratio (OR) 4.7 for pH1N1, 2.3 for seasonal influenza) and admission diagnosis of pneumonia or respiratory infection (OR 7.3 for pH1N1, 4.2 for seasonal influenza) were independent predictors for influenza. During the peak weeks of influenza seasons, 17% of afebrile patients and 27% of febrile patients with pneumonia or respiratory infection had influenza. During the second wave of the 2009 pandemic, 26% of afebrile patients and 70% of febrile patients with pneumonia or respiratory infection had influenza. CONCLUSIONS: The findings of our study may assist clinicians in decision making regarding optimal management of adult patients admitted to ICUs during future influenza seasons. Influenza testing, empiric antiviral therapy and empiric infection control precautions should be considered in those patients who are admitted during influenza season with a diagnosis of pneumonia or respiratory infection and are either febrile or admitted during weeks of peak influenza activity.

Population-based surveillance for invasive pneumococcal disease in homeless adults in Toronto.

BACKGROUND: Identification of high-risk populations for serious infection due to S. pneumoniae will permit appropriately targeted prevention programs. METHODS: We conducted prospective, population-based surveillance for invasive pneumococcal disease and laboratory confirmed pneumococcal pneumonia in homeless adults in Toronto, a Canadian city with a total population of 2.5 M, from January 1, 2002 to December 31, 2006. RESULTS: We identified 69 cases of invasive pneumococcal disease and 27 cases of laboratory confirmed pneumococcal pneumonia in an estimated population of 5050 homeless adults. The incidence of invasive pneumococcal disease in homeless adults was 273 infections per 100,000 persons per year, compared to 9 per 100,000 persons per year in the general adult population. Homeless persons with invasive pneumococcal disease were younger than other adults (median age 46 years vs 67 years, P<.001), and more likely than other adults to be smokers (95% vs. 31%, P<.001), to abuse alcohol (62% vs 15%, P<.001), and to use intravenous drugs (42% vs 4%, P<.001). Relative to age matched controls, they were more likely to have underlying lung disease (12/69, 17% vs 17/272, 6%, P = .006), but not more likely to be HIV infected (17/69, 25% vs 58/282, 21%, P = .73). The proportion of patients with recurrent disease was five fold higher for homeless than other adults (7/58, 12% vs. 24/943, 2.5%, P<.001). In homeless adults, 28 (32%) of pneumococcal isolates were of serotypes included in the 7-valent conjugate vaccine, 42 (48%) of serotypes included in the 13-valent conjugate vaccine, and 72 (83%) of serotypes included in the 23-valent polysaccharide vaccine. Although no outbreaks of disease were identified in shelters, there was evidence of clustering of serotypes suggestive of transmission of pathogenic strains within the homeless population. CONCLUSIONS: Homeless persons are at high risk of serious pneumococcal infection. Vaccination, physical structure changes or other program to reduce transmission in shelters, harm reduction programs to reduce rates of smoking, alcohol abuse and infection with bloodborne pathogens, and improved treatment programs for HIV infection may all be effective in reducing the risk.

Antiviral therapy and outcomes of influenza requiring hospitalization in Ontario, Canada.

BACKGROUND: We conducted a prospective cohort study to assess the impact of antiviral therapy on outcomes of patients hospitalized with influenza in southern Ontario, Canada. METHODS: Patients admitted to Toronto Invasive Bacterial Diseases Network hospitals with laboratory-confirmed influenza from 1 January 2005 through 31 May 2006 were enrolled in the study. Demographic and medical data were collected by patient and physician interview and chart review. The main outcome evaluated was death within 15 days after symptom onset. RESULTS: Data were available for 512 of 541 eligible patients. There were 185 children (<15 years of age), none of whom died and none of whom were treated with antiviral drugs. The median age of the 327 adults was 77 years (range, 15-98 years), 166 (51%) were male, 245 (75%) had a chronic underlying illness, and 216 (71%) had been vaccinated against influenza. Of the 327 adult patients, 184 (59%) presented to the emergency department within 48 h after symptom onset, 52 (16%) required intensive care unit admission, and 27 (8.3%) died within 15 days after symptom onset. Most patients (292 patients; 89%) received antibacterial therapy; 106 (32%) were prescribed antiviral drugs. Treatment with antiviral drugs active against influenza was associated with a significant reduction in mortality (odds ratio, 0.21; 95% confidence interval, 0.06-0.80; n=100, 260). There was no apparent impact of antiviral therapy on length of stay in survivors. CONCLUSIONS: There is a significant burden of illness attributable to influenza in this highly vaccinated population. Treatment with antiviral drugs was associated with a significant reduction in mortality.