Rodica Gilca

Host and Pathogen Factors for Clostridium difficile Infection and Colonization

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.).

Human Metapneumovirus Infections in Hospitalized Children

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.

Association between the 2008-09 seasonal influenza vaccine and pandemic H1N1 illness during Spring-Summer 2009: four observational studies from Canada.

BACKGROUND 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. METHODS AND FINDINGS STUDIES INCLUDED (1) test-negative case-control design based on Canadas 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. CONCLUSIONS 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.

Human bocavirus infections in hospitalized children and adults.

The pathogenic role of this virus in infected children is unclear.

Distribution and Clinical Impact of Human Respiratory Syncytial Virus Genotypes in Hospitalized Children over 2 Winter Seasons

Sequencing studies of the glycoprotein G gene were performed in human respiratory syncytial virus (hRSV) strains detected by reverse-transcription polymerase chain reaction directly from nasopharyngeal aspirates of hospitalized children < or =3 years old over 2 winters. Clinical data were compared between 106 children infected with group A hRSV (96 GA2 genotypes) and 94 children infected with hRSV group B (62 GB3 genotypes). A severity index was defined by assigning 1 point each for the use of >30% supplemental oxygen, admission to an intensive-care unit, and duration of hospital stay of >5 days. Group A and genotype GA2 strains were associated with greater severity of hRSV disease than were group B strains.

Risk factors for hospitalization and severe outcomes of 2009 pandemic H1N1 influenza in Quebec, Canada.

Please cite this paper as: Gilca et al. (2011) Risk Factors for Hospitalization and Severe Outcomes of 2009 Pandemic H1N1 Influenza in Quebec, Canada. Influenza and Other Respiratory Viruses 5(4), 247–255

The Need for Validation of Statistical Methods for Estimating Respiratory Virus–Attributable Hospitalization

Public policy regarding influenza has been based largely on the burden of hospitalization estimated through ecologic studies applying increasingly sophisticated statistical methods to administrative databases. None are known to have been validated by observational studies. The authors illustrated how 6 commonly applied statistical methods estimate virus-attributable hospitalization of children 6-23 months of age and compared the estimates with results obtained from a prospective study using virologic assessment. The proportions of pneumonia and influenza and of bronchiolitis hospitalizations attributable to respiratory syncytial virus and/or influenza were derived by using Serfling regression, periseason differences, Poisson regression with log link, negative binomial regression with identity link, and a Box-Jenkins transfer function. No method provided accurate or consistent estimates for both viruses and outcomes. Virus-attributable hospitalization estimates varied widely between statistical methods and between seasons, with greater between-season variation for admissions attributed to influenza compared with respiratory syncytial virus. Sophistication of statistical methods may have been interpreted as assurance that results are more accurate. Without validation against epidemiologic data, with viral etiology confirmed in individual patients, the accuracy of statistical methods in ecologic studies is simply not known. Until these methods are validated, their methodological limitations should be made explicit and proxy estimates used cautiously in guiding public policy.

Epidemiological patterns and hospital characteristics associated with increased incidence of Clostridium difficile infection in Quebec, Canada, 1998-2006.

OBJECTIVE To explore epidemiological patterns of the incidence of Clostridium difficile infection (CDI) and hospital characteristics associated with increased incidence during nonepidemic and epidemic years. DESIGN Retrospective and prospective ecological study. SETTING Eighty-three acute care hospitals participating in CDI surveillance in the province of Quebec, Canada. METHODS A Serfling-type regression model applied to data obtained from an administrative database (1998-2006) and prospective Quebec CDI surveillance (2004-2006) was used to calculate expected CDI baseline incidence and to detect incidence exceeding the defined epidemic threshold at the provincial and hospital level. Multivariable Poisson regression was used to determine hospital characteristics associated with increased incidence during nonepidemic (1998-2001) and epidemic (2003-2005) periods. RESULTS During the study period (1998-2006), 4,525,847 discharges, including 45,508 with a CDI in any diagnosis field, were reported by 83 hospitals. During 1998-2001, the average Quebec incidence of CDI was 10,304 cases in 1,775,822 discharges (5.8 cases per 1,000 discharges) and presented a pattern of seasonality, with similar patterns at the hospital level for some hospitals. The Quebec epidemic started in October-November 2002 and peaked in March 2004 at 845 cases in 40,852 discharges (20.7 cases per 1,000 discharges). In multivariable analysis, higher incidence was associated with location in Montreal and surrounding regions, greater hospital size, larger proportion of hospitalized elderly patients, longer length of stay, and greater proportion of comorbidities in patients, whereas teaching profile was associated with decreased incidence during both nonepidemic and epidemic periods. The effect of geographical location on incidence was greater during the epidemic. CONCLUSION Baseline incidence from nonepidemic years and hospital characteristics associated with CDI incidence should be taken into account when estimating the efficacy of interventions.

Seasonal Variations in Clostridium difficile Infections Are Associated with Influenza and Respiratory Syncytial Virus Activity Independently of Antibiotic Prescriptions: a Time Series Analysis in Québec, Canada

ABSTRACT 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.

Antibody persistence and response to 2010–2011 trivalent influenza vaccine one year after a single dose of 2009 AS03-adjuvanted pandemic H1N1 vaccine in children

BACKGROUND In 2009, several countries used the ASO3-adjuvanted pandemic A/H1N1 vaccine. We assessed the persistence of antibody and the priming induced by a single paediatric dose of this vaccine in children. METHODS Children aged 15-120 months vaccinated one year before with the ASO3-adjuvanted monovalent pandemic vaccine were tested for the presence of antibody against 2010-2011 TIV components (A/California/7/2009(H1N1), A/Wisconsin/15/2009 (H3N2 A/Perth/16/2009-like) and B/Brisbane/60/2008) before and 21-28 days after each dose of 2010-2011 TIV. Hemagglutination-inhibition (HAI) assay was used. Children received one or two doses of 2010-2011 TIV at 21-28 days interval in relation with their previous immunization status. RESULTS The results of 128 children were included in the ATP analysis. Before the 2010-2011 TIV administration, 46% of children showed sero-protection to the A/California/7/2009(H1N1) strain (HAI titre ≥40) with lower rates of sero-protection to the H3N2A/Perth/16/2009 (37%) and B/Brisbane/60/2008 (19%). After the first dose of 2010-2011 TIV, 98%, 75%, and 57% of vaccinees attained a sero-protective titre to A/California/7/2009(H1N1), A/Perth/16/2009(H3N2), and B/Brisbane/60/2008 strain, respectively. The youngest age group showed significantly lower antibody response to the influenza B component compared to the older age groups after the first dose of vaccine. Among vaccinees who received the second dose of TIV, 96% and 87% had a sero-protective titre to H3N2A/Perth/16/2009 and B/Brisbane/60/2008, respectively. The 2010-2011 TIV was well tolerated. CONCLUSIONS We found substantial persistence of antibody to the A/California/7/2009 strain one year after a single paediatric dose of AS03-adjuvanted pandemic vaccine and a seroprotective level of antibody to this strain in virtually all children who received one year later a single dose of the 2010-2011 TIV. In contrast, two doses of the 2010-2011 TIV were necessary to induce an adequate immune response to the A/Perth/16/2009(H3N2) and B/Brisbane/60/2008 strains in children previously naïve to seasonal vaccine.