Isabelle Rouleau

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.

Household Transmission of the 2009 Pandemic A/H1N1 Influenza Virus: Elevated Laboratory-Confirmed Secondary Attack Rates and Evidence of Asymptomatic Infections

BACKGROUND Characterizing household transmission of the 2009 pandemic A/H1N1 influenza virus (pH1N1) is critical for the design of effective public health measures to mitigate spread. Our objectives were to estimate the secondary attack rates (SARs), the proportion of asymptomatic infections, and risk factors for pH1N1 transmission within households on the basis of active clinical follow-up and laboratory-confirmed outcomes. METHODS We conducted a prospective observational study during the period May-July 2009 (ie, during the first wave of the pH1N1 pandemic) in Quebec City, Canada. We assessed pH1N1 transmission in 42 households (including 43 primary case patients and 119 contacts). Clinical data were prospectively collected during serial household visits. Secondary case patients were identified by clinical criteria and laboratory diagnostic tests, including serological and molecular methods. RESULTS We identified 53 laboratory-confirmed secondary case patients with pH1N1 virus infection, for an SAR of 45% (95% confidence interval [CI], 35.6%-53.5%). Thirty-four (81%) of the households had ≥1 confirmed secondary case patient. The mean serial interval between onset of primary and confirmed secondary cases was 3.9 days (median interval, 3 days). Influenza-like illness (fever and cough or sore throat) developed in 29% (95% CI, 20.5%-36.7%) of household contacts. Five (9.4%) of secondary case patients were asymptomatic. Young children (<7 years of age) were at highest risk of developing laboratory-confirmed influenza-like illness. Primary case patients with both diarrhea and vomiting were the most likely to transmit pH1N1. CONCLUSION Household transmission of pH1N1 may be substantially greater than previously estimated, especially in association with clinical presentations that include gastrointestinal complaints. Approximately 10% of pH1N1 infections acquired in the household may be asymptomatic.

Importance of viral and bacterial infections in chronic obstructive pulmonary disease exacerbations.

Abstract Background Few studies have evaluated the contribution of both viruses and bacteria in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Objectives This study estimated the burden of both types of pathogens among adults seeking care for an AECOPD during two consecutive winter seasons. Study design Patients 50 years or older who consulted within 10 days of AECOPD onset were eligible. Clinical data were collected on a standardized questionnaire, and nasopharyngeal aspirates (NPA), paired sera, and non-induced sputum were collected. Polymerase chain reaction (PRC) assays were used to identify viral, atypical and bacterial pathogens in NPA specimen. Results Overall, 108 patients with AECOPD were included, 88% of patients were admitted and 2 patients (2%) received intensive care. A third of patients (31%) had evidence of a viral infection, 9% with influenza A, 7% RSV and 7% with PIV-3. One patient was positive for Mycoplasma pneumoniae. Bacterial pathogens were identified in 49% of patients with available sputum, most frequently Staphylococcus aureus, Pseudomonas aeruginosa, and Haemophilus influenzae. Among virus-infected patients, 14 (58%) also had bacteria in their sputum, but co-infected patients did not present with different symptoms than patients with single infections. Conclusions These results suggest that influenza and RSV are frequent contributors of AECOPD, and that coinfection with bacteria does not appear to be more severe among virus-infected patients. Clinicians should be aware that AECOPD may be frequently triggered by viruses, and may consider antivirals and proper infection control measures in appropriate epidemiological setting.

No Evidence of False Reassurance among Women with an Inconclusive BRCA1/2 Genetic Test Result

Background: Little is known about how women who receive an inconclusive result from BRCA1/2 testing interpret their result. Clinical observations suggest that some of them may be falsely reassured and, consequently, may not adhere to recommended surveillance. The purpose of this study is to evaluate whether women with inconclusive BRCA1/2 test results are falsely reassured. Methods: Participants were adult women with a family history suggestive of a germ-line mutation in either the BRCA1 or the BRCA2 gene who underwent genetic testing in the context of the interdisciplinary research program INHERIT BRCAs. Data were collected using selfadministered questionnaires at genetic counseling and 1 month after result disclosure. Reassurance was assessed through indicators of cancer risk perception, cancer worry, relief following result disclosure, painfulness of the test result, and its effect on quality of life. Results: Five-hundred women (105 carriers, 140 noncarriers, and 255 inconclusive) were included in this analysis. Compared to noncarriers, women with inconclusive results had higher cancer risk perception, were more worried about cancer, were less relieved by their test result, and perceived their quality of life as being more adversely affected by it. Conclusion: The differences observed between noncarriers and women who received an inconclusive result run counter to the hypothesis that the latter are falsely reassured following BRCA1/2 testing. For clinicians, our findings show the value of taking precautions to fully explain to women that inconclusive results do not rule out the possibility that they still may face a higher risk of developing breast and/or ovarian cancer. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2862–7)

Contagious period for pandemic (H1N1) 2009.

Most infected persons shed live virus after fever abated.

Field Performance of a Rapid Diagnostic Test for Influenza in an Ambulatory Setting

ABSTRACT Provided test characteristics are adequate, point-of-care rapid antigen detection tests for influenza could improve the timeliness and appropriateness of clinical decisions. Our objective was to estimate the field sensitivity and specificity of the Quidel QuickVue Influenza A+B test in an ambulatory setting. The sensitivity and specificity of the Quidel QuickVue test was evaluated against reverse-transcriptase PCR (RT-PCR) on nasopharyngeal specimens collected over two consecutive influenza seasons from ambulatory patients consulting for influenza-like illness (ILI) within 7 days of ILI onset. A total of 491 patients with ILI (180 in 2006 to 2007 and 311 in 2007 to 2008) provided specimens that were tested both by PCR and by the Quidel QuickVue test. Among the 267 patients positive by PCR (55%), 52 were also positive by the QuickVue test, for an overall sensitivity of 19.5% (95% confidence interval [95% CI], 14.7% to 24.2%). Among the 221 PCR-negative patients, 2 were positive for influenza B virus by the rapid test (<1%), for an overall specificity of 99.1% (95% CI, 97.9 to 100%). The field sensitivity of the test varied little with the age or gender of the patient, immunization status, delay since the onset of symptoms, or influenza season. The sensitivity of the test was slightly but nonsignificantly higher for influenza B virus (23%) than for influenza A virus (18%). Despite its high specificity, the low sensitivity of the Quidel QuickVue Influenza A+B test is too poor to direct clinical decisions for ambulatory patients with ILI. Negative results cannot rule out the diagnosis of influenza, and in that context, this test is of questionable utility for routine application in the clinical setting.

Mid-Season Estimates of Influenza Vaccine Effectiveness against Influenza A(H3N2) Hospitalization in the Elderly in Quebec, Canada, January 2015.

Background 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. Methods 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. Results 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%). Conclusion 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.

Increased risk of anaphylaxis following administration of 2009 AS03-adjuvanted monovalent pandemic A/H1N1 (H1N1pdm09) vaccine.

BACKGROUND Anaphylaxis after trivalent influenza vaccination is typically reported at a rate of <1 per million doses. In Quebec, Canada, anaphylaxis following administration of the monovalent AS03-adjuvanted H1N1pdm09 vaccine was reported through passive surveillance at a rate of 8 per million doses administered. This was 20 times higher than the reporting rate for non-adjuvanted trivalent vaccines administered during the six previous seasons. However, adequate estimation of the incidence of anaphylaxis is hindered by wide variations in definitions and diagnosis. METHODS Using the Brighton collaboration case definition of anaphylaxis, all cases with allergic symptoms (AS) reported to public health were reviewed to estimate the incidence of anaphylaxis following AS03-adjuvanted H1N1pdm09 vaccine. RESULTS Among 752 reports of allergic symptoms, 33 were initially reported as anaphylaxis of which 20/33 (60%) met the Brighton definition (19/20 with certainty levels 1 or 2). A total of 38 additional cases with onset within 1h of vaccination also met the Brighton definition of anaphylaxis (27 (71%) with certainty levels 1 or 2). The 58 cases meeting Brighton Level 1 or 2 criteria for anaphylaxis represent a 75% increase over the 33 passively reported and an incidence of 13 per million doses administered. CONCLUSION A substantial number of patients with early-onset allergic symptoms met the most specific levels of the Brighton case definition but were not reported as anaphylaxis. Based on this specific case definition, the incidence of anaphylaxis after AS03-adjuvanted H1N1pdm09 vaccine substantially exceeded that reported with seasonal influenza vaccines, a signal that warrants better understanding.

Use of Dietary Supplements Among Women at High Risk of Hereditary Breast and Ovarian Cancer (HBOC) Tested for Cancer Susceptibility

Abstract: Although use of dietary supplements among women with breast cancer is high, use among women at high risk of hereditary breast and ovarian cancer (HBOC) is unknown. This study assesses the prevalence of use of dietary supplements and identifies characteristics associated with use among women at high risk of HBOC who underwent genetic testing for cancer susceptibility. Participants were 303 women who underwent BRCA1/2 testing as part of Interdisciplinary Health Research International Team on Breast Cancer Susceptibility. Dietary supplements use was measured 12 mo post-disclosure. Potential determinants of use included personal cancer history, test result, psychological distress, cancer genetics knowledge, and health-related behaviors. Globally, 51% of participants used at least one dietary supplement. Calcium (26%), multivitamins (17%), vitamins D (14%), E (12%), and C (10%) were most frequently reported. Women ≥ 50 yr were more likely to be using dietary supplements (P < 0.0001). Women with an inconclusive test result were more likely to use mineral supplements than noncarriers [odds ratio (OR) = 2.6; 95% confidence interval (CI) = 1.3-5.3]. Cigarette smoking was negatively associated with use of vitamin supplements (OR = 0.3; 95% CI = 0.1-0.7). Use of dietary supplements among women at high risk of HBOC who underwent BRCA1/2 testing is as frequent as use among patients with other types of tumors or use among individuals from the general population.

Comparison of trip characteristics of children and adults with travel-acquired hepatitis A infection.

We compared the trip characteristics of 84 child and 99 adult cases with travel-acquired hepatitis A (HA). Most pediatric cases had traveled in Asia for more than 30 days and had stayed and eaten most of their meals in the homes of friends and relatives in a country where they had not been born. In contrast, the adults with travel-acquired HA had visited Latin America or the Caribbean for 14 days or less and had stayed primarily in hotels. Specific public health interventions should be undertaken to prevent HA in traveling children.