Clostridium difficile infection is the leading cause of health care-associated diarrhea, and the bacterium can also be carried asymptomatically. The objective of this study was to identify host and ...bacterial factors associated with health care-associated acquisition of C. difficile infection and colonization.
We conducted a 15-month prospective study in six Canadian hospitals in Quebec and Ontario. Demographic information, known risk factors, potential confounding factors, and weekly stool samples or rectal swabs were collected. Pulsed-field gel electrophoresis (PFGE) was performed on C. difficile isolates to determine the genotype. Levels of serum antibodies against C. difficile toxins A and B were measured.
A total of 4143 patients were included in the study; 117 (2.8%) and 123 (3.0%) had health care-associated C. difficile infection and colonization, respectively. Older age and use of antibiotics and proton-pump inhibitors were significantly associated with health care-associated C. difficile infection. Hospitalization in the previous 2 months; use of chemotherapy, proton-pump inhibitors, and H(2) blockers; and antibodies against toxin B were associated with health care-associated C. difficile colonization. Among patients with health care-associated C. difficile infection and those with colonization, 62.7% and 36.1%, respectively, had the North American PFGE type 1 (NAP1) strain.
In this study, health care-associated C. difficile infection and colonization were differentially associated with defined host and pathogen variables. The NAP1 strain was predominant among patients with C. difficile infection, whereas asymptomatic patients were more likely to be colonized with other strains. (Funded by the Consortium de Recherche sur le Clostridium difficile.).
Using whole genome sequencing of isolates from a cohort of patients with Clostridium difficile infection (CDI) and colonization, we found that incident CDI cases were more likely to be linked to an ...infected than colonized donor.
Abstract
Background
Whole genome sequencing (WGS) studies can enhance our understanding of the role of patients with asymptomatic Clostridium difficile colonization in transmission.
Methods
Isolates obtained from patients with Clostridium difficile infection (CDI) and colonization identified in a study conducted during 2006-2007 at 6 Canadian hospitals underwent typing by pulsed-field gel electrophoresis, multilocus sequence typing, and WGS. Isolates from incident CDI cases not in the initial study were also sequenced where possible. Ward movement and typing data were combined to identify plausible donors for each CDI case, as defined by shared time and space within predefined limits. Proportions of plausible donors for CDI cases that were colonized, infected, or both were examined.
Results
Five hundred fifty-four isolates were sequenced successfully, 353 from colonized patients and 201 from CDI cases. The NAP1/027/ST1 strain was the most common strain, found in 124 (62%) of infected and 92 (26%) of colonized patients. A donor with a plausible ward link was found for 81 CDI cases (40%) using WGS with a threshold of ≤2 single nucleotide polymorphisms to determine relatedness. Sixty-five (32%) CDI cases could be linked to both infected and colonized donors. Exclusive linkages to infected and colonized donors were found for 28 (14%) and 12 (6%) CDI cases, respectively.
Conclusions
Colonized patients contribute to transmission, but CDI cases are more likely linked to other infected patients than colonized patients in this cohort with high rates of the NAP1/027/ST1 strain, highlighting the importance of local prevalence of virulent strains in determining transmission dynamics.
ObjectivesTo study the association between polypharmacy and the risk of hospitalisation and death in cases of COVID-19 in the population over the age of 65.DesignPopulation-based cohort ...study.SettingQuebec Integrated Chronic Disease Surveillance System, composed of five medico-administrative databases, in the province of Quebec, Canada.Participants32 476 COVID-19 cases aged over 65 whose diagnosis was made between 23 February 2020 and 15 March 2021, and who were covered by the public drug insurance plan (thus excluding those living in long-term care). We counted the number of different medications they claimed between 1 April 2019 and 31 March 2020.Outcome measuresRobust Poisson regression was used to calculate relative risk of hospitalisation and death associated with the use of multiple medications, adjusting for age, sex, chronic conditions, material and social deprivation and living environment.ResultsOf the 32 476 COVID-19 cases included, 10 350 (32%) were hospitalised and 4146 (13%) died. Compared with 0–4 medications, polypharmacy exposure was associated with increased hospitalisations, with relative risks ranging from 1.11 (95% CI 1.04 to 1.19) for those using 5–9 medications to 1.62 (95% CI 1.51 to 1.75) for those using 20+. Similarly, the risk of death increased with the number of medications, from 1.13 (95% CI 0.99 to 1.30) for those using (5–9 medications to 1.97 (95% CI 1.70 to 2.27) (20+). Increased risk was mainly observed in younger groups.ConclusionsPolypharmacy was significantly associated with the risk of hospitalisations and deaths related to COVID-19 in this cohort of older adults. Polypharmacy may represent a marker of vulnerability, especially for younger groups of older adults.
In late spring 2009, concern was raised in Canada that prior vaccination with the 2008-09 trivalent inactivated influenza vaccine (TIV) was associated with increased risk of pandemic influenza A ...(H1N1) (pH1N1) illness. Several epidemiologic investigations were conducted through the summer to assess this putative association.
(1) test-negative case-control design based on Canada's sentinel vaccine effectiveness monitoring system in British Columbia, Alberta, Ontario, and Quebec; (2) conventional case-control design using population controls in Quebec; (3) test-negative case-control design in Ontario; and (4) prospective household transmission (cohort) study in Quebec. Logistic regression was used to estimate odds ratios for TIV effect on community- or hospital-based laboratory-confirmed seasonal or pH1N1 influenza cases compared to controls with restriction, stratification, and adjustment for covariates including combinations of age, sex, comorbidity, timeliness of medical visit, prior physician visits, and/or health care worker (HCW) status. For the prospective study risk ratios were computed. Based on the sentinel study of 672 cases and 857 controls, 2008-09 TIV was associated with statistically significant protection against seasonal influenza (odds ratio 0.44, 95% CI 0.33-0.59). In contrast, estimates from the sentinel and three other observational studies, involving a total of 1,226 laboratory-confirmed pH1N1 cases and 1,505 controls, indicated that prior receipt of 2008-09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring-summer 2009, with estimated risk or odds ratios ranging from 1.4 to 2.5. Risk of pH1N1 hospitalization was not further increased among vaccinated people when comparing hospitalized to community cases.
Prior receipt of 2008-09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring-summer 2009 in Canada. The occurrence of bias (selection, information) or confounding cannot be ruled out. Further experimental and epidemiological assessment is warranted. Possible biological mechanisms and immunoepidemiologic implications are considered.
Objectives
In Quebec, three pneumococcal conjugate vaccines (PCV) were used sequentially starting in December 2004. The objective of the study was to investigate the association between exposure to ...different PCV regimens and hospitalizations for lower respiratory tract infection (LRTI).
Methods
Records with a main diagnosis of LRTI in children born in 2000–2012 and observed up to their second birthday were extracted from the provincial hospital administrative database. Main vaccine regimen in different birth cohorts was derived from the Quebec City Immunization Registry. Hospital admission risk was analyzed by Poisson regression models adjusting for age, season of birth, ambient air temperature, circulation of respiratory viruses, and the weekly hospital admission rate for all other causes excluding LRTI to control for temporal changes in hospital admission practices.
Results
In univariate analyses, hospitalizations for LRTI, pneumonia, and bronchiolitis were less frequent in cohorts exposed to PCVs than in unvaccinated cohorts with no difference between PCV regimens. For pneumonia, the difference in cumulative incidence was 16% (13%; 18%). In multivariate analyses, exposure to any PCV schedule was associated with a lower although statistically non-significant hospitalization risk for pneumonia as compared with unvaccinated cohorts. Again, differences between PCV regimens were minimal.
Conclusions
Interpretation of results of this ecological study should be made with care as many factors could influence hospitalizations for respiratory infection in young children. Results are compatible with a modest effect of PCVs in reducing hospitalizations for pneumonia in children. No substantial differences between various PCV schedules were observed.
Studies have reported human bocavirus (HBoV) in children with respiratory tract infections (RTIs), but only occasionally in adults. We searched for HBoV DNA in nasopharyngeal aspirates (NPAs) from ...adults with exacerbations of chronic bronchitis or pneumonia, from children hospitalized for acute RTIs, and from asymptomatic children during the winter of 2002-2003 in Canada. HBoV was detected in NPAs of 1 (0.8%) of 126 symptomatic adults, 31 (13.8%) of 225 symptomatic children, and 43 (43%) of 100 asymptomatic children undergoing elective surgery. Another virus was detected in 22 (71%) of the 31 HBoV-positive NPAs from symptomatic children. Two clades of HBoV were identified. The pathogenic role of HBoV in RTIs is uncertain because it was frequently detected in symptomatic and asymptomatic children and was commonly found with other viruses in symptomatic children.
Seasonal variations in Clostridium difficile-associated diarrhea (CDAD), with a higher incidence occurring during winter months, have been reported. Although winter epidemics of respiratory viruses ...may be temporally associated with an increase in CDAD morbidity, we hypothesized that this association is mainly due to increased antibiotic use for respiratory infections. The objective of this study was to evaluate the effect of the two most frequent respiratory viruses (influenza virus and respiratory syncytial virus RSV) and antibiotics prescribed for respiratory infections (fluoroquinolones and macrolides) on the CDAD incidence in hospitals in the province of Québec, Canada. A multivariable Box-Jenkins transfer function model was built to relate monthly CDAD incidence to the monthly percentage of positive tests for influenza virus and RSV and monthly fluoroquinolone and macrolide prescriptions over a 4-year period (January 2005 to December 2008). Analysis showed that temporal variations in CDAD incidence followed temporal variations for influenza virus (P = 0.043), RSV (P = 0.004), and macrolide prescription (P = 0.05) time series with an average delay of 1 month and fluoroquinolone prescription time series with an average delay of 2 months (P = 0.01). We conclude that influenza virus and RSV circulation is independently associated with CDAD incidence after controlling for fluoroquinolone and macrolide use. This association was observed at an aggregated level and may be indicative of other phenomena occurring during wintertime.
We evaluated the percentage of hospitalizations for acute respiratory tract infections in children <3 years of age attributable to human metapneumovirus (HMPV) and other respiratory viruses in a ...prospective study during winter and spring 2002. We used real-time polymerase chain assays and other conventional diagnostic methods to detect HMPV, human respiratory syncytial virus (HRSV), and influenza viruses in nasopharyngeal aspirates of children. HMPV was detected in 12 (6%) of the 208 children hospitalized for acute respiratory tract infections, HRSV in 118 (57%), and influenza A in 49 (24%). Bronchiolitis was diagnosed in 8 (68%) and pneumonitis in 2 (17%) of HMPV-infected children; of those with HRSV infection, pneumonitis was diagnosed in 99 (84%) and bronchiolitis in 30 (25%). None of the HMPV-infected children was admitted to an intensive-care unit, whereas 15% of those with HRSV or influenza A infections were admitted. HMPV is an important cause of illness in young children with a similar, although less severe, clinical presentation to that of HRSV.
The 2014/15 influenza season in Canada was characterized by an early epidemic due to vaccine-mismatched influenza A(H3N2) viruses, disproportionately affecting elderly individuals ≥65-years-old. We ...assessed vaccine effectiveness (VE) against A(H3N2) hospitalization among elderly individuals during the peak weeks of the 2014/15 epidemic in Quebec, Canada.
Nasal specimens and clinical/epidemiological data were collected within 7 days of illness onset from elderly patients admitted with respiratory symptoms to one of four participating hospitals between November 30, 2014 and January 13, 2015. Cases tested RT-PCR positive for influenza A(H3N2) and controls tested negative for any influenza. VE was assessed by test-negative case-control design.
There were 314 participants including 186 cases (62% vaccinated) and 128 controls (59% vaccinated) included in primary VE analysis. Median age was 81.5 years, two-thirds were admitted from the community and 91% had underlying comorbidity. Crude VE against A(H3N2) hospitalization was -17% (95%CI: -86% to 26%), decreasing to -23% (95%CI: -99 to 23%) with adjustment for age and comorbidity, and to -39% (95%CI: -142 to 20%) with additional adjustment for specimen collection interval, calendar time, type of residence and hospital. In sensitivity analyses, VE estimates were improved toward the null with restriction to participants admitted from the community (-2%; 95%CI: -105 to 49%) or with specimen collection ≤4 days since illness onset (- 8%; 95%CI: -104 to 43%) but further from the null with restriction to participants with comorbidity (-51%; 95%CI: -169 to 15%).
The 2014/15 mismatched influenza vaccine provided elderly patients with no cross-protection against hospitalization with the A(H3N2) epidemic strain, reinforcing the need for adjunct protective measures among high-risk individuals and improved vaccine options.
A comprehensive description of the combined effect of SARS-CoV-2 and respiratory viruses other than SARS-CoV-2 (ORVs) on acute respiratory infection (ARI) hospitalizations is lacking.
This study ...aimed to compare the viral etiology of ARI hospitalizations before the pandemic (8 prepandemic influenza seasons, 2012-13 to 2019-20) and during 3 pandemic years (periods of increased SARS-CoV-2 and ORV circulation in 2020-21, 2021-22, and 2022-23) from an active hospital-based surveillance network in Quebec, Canada.
We compared the detection of ORVs and SARS-CoV-2 during 3 pandemic years to that in 8 prepandemic influenza seasons among patients hospitalized with ARI who were tested systematically by the same multiplex polymerase chain reaction (PCR) assay during periods of intense respiratory virus (RV) circulation. The proportions of infections between prepandemic and pandemic years were compared by using appropriate statistical tests.
During prepandemic influenza seasons, overall RV detection was 92.7% (1384/1493) (respiratory syncytial virus RSV: 721/1493, 48.3%; coinfections: 456/1493, 30.5%) in children (<18 years) and 62.8% (2723/4339) (influenza: 1742/4339, 40.1%; coinfections: 264/4339, 6.1%) in adults. Overall RV detection in children was lower during pandemic years but increased from 58.6% (17/29) in 2020-21 (all ORVs; coinfections: 7/29, 24.1%) to 90.3% (308/341) in 2021-22 (ORVs: 278/341, 82%; SARS-CoV-2: 30/341, 8.8%; coinfections: 110/341, 32.3%) and 88.9% (361/406) in 2022-23 (ORVs: 339/406, 84%; SARS-CoV-2: 22/406, 5.4%; coinfections: 128/406, 31.5%). In adults, overall RV detection was also lower during pandemic years but increased from 43.7% (333/762) in 2020-21 (ORVs: 26/762, 3.4%; SARS-CoV-2: 307/762, 40.3%; coinfections: 7/762, 0.9%) to 57.8% (731/1265) in 2021-22 (ORVs: 179/1265, 14.2%; SARS-CoV-2: 552/1265, 43.6%; coinfections: 42/1265, 3.3%) and 50.1% (746/1488) in 2022-23 (ORVs: 409/1488, 27.5%; SARS-CoV-2: 337/1488, 22.6%; coinfections: 36/1488, 2.4%). No influenza or RSV was detected in 2020-21; however, their detection increased in the 2 subsequent years but did not reach prepandemic levels. Compared to the prepandemic period, the peaks of RSV hospitalization shifted in 2021-22 (16 weeks earlier) and 2022-23 (15 weeks earlier). Moreover, the peaks of influenza hospitalization shifted in 2021-22 (17 weeks later) and 2022-23 (4 weeks earlier). Age distribution was different compared to the prepandemic period, especially during the first pandemic year.
Significant shifts in viral etiology, seasonality, and age distribution of ARI hospitalizations occurred during the 3 pandemic years. Changes in age distribution observed in our study may reflect modifications in the landscape of circulating RVs and their contribution to ARI hospitalizations. During the pandemic period, SARS-CoV-2 had a low contribution to pediatric ARI hospitalizations, while it was the main contributor to adult ARI hospitalizations during the first 2 seasons and dropped below ORVs during the third pandemic season. Evolving RVs epidemiology underscores the need for increased scrutiny of ARI hospitalization etiology to inform tailored public health recommendations.
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