Paul Van Caeseele

Effect of Influenza Vaccination of Children on Infection Rates in Hutterite Communities: A Randomized Trial

CONTEXT Children and adolescents appear to play an important role in the transmission of influenza. Selectively vaccinating youngsters against influenza may interrupt virus transmission and protect those not immunized. OBJECTIVE To assess whether vaccinating children and adolescents with inactivated influenza vaccine could prevent influenza in other community members. DESIGN, SETTING, AND PARTICIPANTS A cluster randomized trial involving 947 Canadian children and adolescents aged 36 months to 15 years who received study vaccine and 2326 community members who did not receive the study vaccine in 49 Hutterite colonies in Alberta, Saskatchewan, and Manitoba. Follow-up began December 28, 2008, and ended June 23, 2009. INTERVENTION Children were randomly assigned according to community and in a blinded manner to receive standard dosing of either inactivated trivalent influenza vaccine or hepatitis A vaccine, which was used as a control. MAIN OUTCOME MEASURES Confirmed influenza A and B infection using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay and by measuring serum hemagglutination inhibition titers. RESULTS The mean rate of study vaccine coverage among eligible participants was 83% (range, 53%-100%) for the influenza vaccine colonies and 79% (range, 50%-100%) for the hepatitis A vaccine colonies. Among nonrecipients, 39 of 1271 (3.1%) in the influenza vaccine colonies and 80 of 1055 (7.6%) in the hepatitis A vaccine colonies had influenza illness confirmed by RT-PCR, for a protective effectiveness of 61% (95% confidence interval [CI], 8%-83%; P = .03). Among all study participants (those who were and those who were not vaccinated), 80 of 1773 (4.5%) in the influenza vaccine colonies and 159 of 1500 (10.6%) in the hepatitis A vaccine colonies had influenza illness confirmed by RT-PCR for an overall protective effectiveness of 59% (95% CI, 5%-82%; P = .04). No serious vaccine adverse events were observed. CONCLUSION Immunizing children and adolescents with inactivated influenza vaccine significantly protected unimmunized residents of rural communities against influenza. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00877396.

Low 2012–13 Influenza Vaccine Effectiveness Associated with Mutation in the Egg-Adapted H3N2 Vaccine Strain Not Antigenic Drift in Circulating Viruses

Background Influenza vaccine effectiveness (VE) is generally interpreted in the context of vaccine match/mismatch to circulating strains with evolutionary drift in the latter invoked to explain reduced protection. During the 2012–13 season, however, detailed genotypic and phenotypic characterization shows that low VE was instead related to mutations in the egg-adapted H3N2 vaccine strain rather than antigenic drift in circulating viruses. Methods/Findings Component-specific VE against medically-attended, PCR-confirmed influenza was estimated in Canada by test-negative case-control design. Influenza A viruses were characterized genotypically by amino acid (AA) sequencing of established haemagglutinin (HA) antigenic sites and phenotypically through haemagglutination inhibition (HI) assay. H3N2 viruses were characterized in relation to the WHO-recommended, cell-passaged vaccine prototype (A/Victoria/361/2011) as well as the egg-adapted strain as per actually used in vaccine production. Among the total of 1501 participants, influenza virus was detected in 652 (43%). Nearly two-thirds of viruses typed/subtyped were A(H3N2) (394/626; 63%); the remainder were A(H1N1)pdm09 (79/626; 13%), B/Yamagata (98/626; 16%) or B/Victoria (54/626; 9%). Suboptimal VE of 50% (95%CI: 33–63%) overall was driven by predominant H3N2 activity for which VE was 41% (95%CI: 17–59%). All H3N2 field isolates were HI-characterized as well-matched to the WHO-recommended A/Victoria/361/2011 prototype whereas all but one were antigenically distinct from the egg-adapted strain as per actually used in vaccine production. The egg-adapted strain was itself antigenically distinct from the WHO-recommended prototype, and bore three AA mutations at antigenic sites B [H156Q, G186V] and D [S219Y]. Conversely, circulating viruses were identical to the WHO-recommended prototype at these positions with other genetic variation that did not affect antigenicity. VE was 59% (95%CI:16–80%) against A(H1N1)pdm09, 67% (95%CI: 30–85%) against B/Yamagata (vaccine-lineage) and 75% (95%CI: 29–91%) against B/Victoria (non-vaccine-lineage) viruses. Conclusions These findings underscore the need to monitor vaccine viruses as well as circulating strains to explain vaccine performance. Evolutionary drift in circulating viruses cannot be regulated, but influential mutations introduced as part of egg-based vaccine production may be amenable to improvements.

Human Metapneumovirus Infection in the Canadian Population

ABSTRACT Human metapneumovirus (hMPV), a newly discovered paramyxovirus, has been associated with acute respiratory tract infections (ARIs) ranging from upper ARIs to severe bronchiolitis and pneumonia. Important questions remain on the contribution of hMPV to ARIs and its impact on public health. During the 2001-2002 season, we conducted a collaborative study with four provincial public health laboratories to study the prevalence of this new virus in the Canadian population. A total of 445 specimens were collected from patients of all age groups with ARIs and were tested for the presence of hMPV by reverse transcription-PCR. Of these, 66 (14.8%) tested positive for hMPV. Positive specimens were found in all age groups and in all four provinces studied. Virus activity peaked in February and March. The age range of the patients with hMPV infection was 2 months to 93 years (median age, 25 years), with similar numbers of females (35%) and males (41%). Thirty-three percent (n = 22) of hMPV-infected patients were hospitalized; of these, 27% (n = 6) had rhinitis and pneumonia, 23% (n = 5) had bronchiolitis, and 9% (n = 2) had bronchitis. The hospitalization rates were significantly higher among patients <5 years of age (P = 0.0005) and those >50 years of age (P = 0.0044) than among those 6 to 50 years of age. Phylogenetic analysis of the F gene showed that two hMPV genetic clusters were cocirculating in the 2001-2002 season, and comparison with earlier studies suggests a temporal evolutionary pattern of hMPV isolates. These results provide further evidence of the importance of hMPV in ARIs, particularly in young children and elderly individuals.

Human Coronavirus NL63 Infection in Canada

Abstract The isolation of human coronavirus NL63 (HCoV-NL63) in The Netherlands raised questions about its contribution to respiratory illness. In this study, a total of 525 respiratory specimens, collected in Canada primarily during the winter months of 2001–2002, were tested for HCoV-NL63; 19 tested positive for HCoV-NL63, demonstrating virus activity during January–March 2002. Patients with HCoV-NL63 were 1 month-100 years old (median age, 37 years). The main clinical presentations were fever (15/19), sore throat (5/19), and cough (9/19), and 4 patients were hospitalized. These results provide evidence for the worldwide distribution of HCoV-NL63.

Polymorphisms of the Fimbria fim3 Gene of Bordetella pertussis Strains Isolated in Canada

ABSTRACT The fim genes which code for the fimbria protective antigens present in both the inactivated whole-cell and acellular vaccines were analyzed in 86 Canadian Bordetella pertussis isolates. At least one of the novel mutations identified was found to involve a surface epitope that has been mapped by serum antibodies from infected or vaccinated subjects.

Evaluation of MALDI-TOF mass spectroscopy methods for determination of Escherichia coli pathotypes

It is rapidly becoming apparent that many E. coli pathotypes cause a considerable burden of human disease. Surveillance of these organisms is difficult because there are few or no simple, rapid methods for detecting and differentiating the different pathotypes. MALDI-TOF mass spectroscopy has recently been rapidly and enthusiastically adopted by many clinical laboratories as a diagnostic method because of its high throughput, relatively low cost, and adaptability to the laboratory workflow. To determine whether the method could be adapted for E. coli pathotype differentiation the Bruker Biotyper methodology and a second methodology adapted from the scientific literature were tested on isolates representing eight distinct pathotypes and two other groups of E. coli. A total of 136 isolates was used for this study. Results confirmed that the Bruker Biotyper methodology that included extraction of proteins from bacterial cells was capable of identifying E. coli isolates from all pathotypes to the species level and, furthermore, that the Bruker extraction and MALDI-TOF MS with the evaluation criteria developed in this work was effective for differentiating most pathotypes.

Integrated Sentinel Surveillance Linking Genetic, Antigenic, and Epidemiologic Monitoring of Influenza Vaccine-Virus Relatedness and Effectiveness During the 2013-2014 Influenza Season.

BACKGROUND Canadas Sentinel Physician Surveillance Network links genetic, antigenic, and vaccine effectiveness (VE) measures in an integrated platform of influenza monitoring, described here for the 2013-2014 influenza season of resurgent A(H1N1)pdm09 and late-season type B activity. METHODS VE was estimated as [1 - odds ratio] × 100% and compared vaccination status between individuals who tested positive (cases) and those who tested negative (controls) for influenza virus. Vaccine-virus relatedness was assessed by genomic sequence analysis and hemagglutination inhibition assays. RESULTS Analyses included 1037 controls (of whom 33% were vaccinated) and 663 cases (of whom 14% were vaccinated). A total of 415 cases tested positive for A(H1N1)pdm09 virus, 15 tested positive for A(H3N2) virus, 191 tested positive for B/Yamagata-lineage virus, 6 tested positive for B/Victoria-lineage virus, and 36 tested positive for viruses of unknown subtype or lineage. A(H1N1)pdm09 viruses belonged to clade 6B, distinguished by a K163Q substitution, but remained antigenically similar to the A/California/07/2009-like vaccine strain, with an adjusted VE of 71% (95% confidence interval [CI], 58%-80%). Most B/Yamagata-lineage viruses (83%) clustered phylogenetically with the prior (ie, 2012-2013) seasons B/Wisconsin/01/2010-like clade 3 vaccine strain, while only 17% clustered with the current (ie, 2013-2014) seasons B/Massachusetts/02/2012-like clade 2 vaccine strain. The adjusted VE for B/Yamagata-lineage virus was 73% (95% CI, 57%-84%), with a lower VE obtained after partial calendar-time adjustment for clade-mismatched B/Wisconsin/01/2010-like virus (VE, 63%; 95% CI, 41%-77%), compared with that for clade-matched B/Massachusetts/02/2012-like virus (VE, 88%; 95% CI, 48%-97%). No A(H3N2) viruses clustered with the A/Texas/50/2012-like clade 3C.1 vaccine strain, and more than half were antigenically mismatched, but sparse data did not support VE estimation. CONCLUSIONS VE corresponded with antigenically conserved A(H1N1)pdm09 and lineage-matched B/Yamagata viruses with clade-level variation. Surveillance linking genotypic, phenotypic, and epidemiologic measures of vaccine-virus relatedness and effectiveness could better inform predictions of vaccine performance and reformulation.

Effectiveness of the pandemic H1N1 influenza vaccines against laboratory-confirmed H1N1 infections: population-based case-control study.

BACKGROUND Excellent immune responses following 1 or 2 doses of the monovalent inactivated pandemic H1N1 vaccines have been documented, but the effectiveness of these vaccines against laboratory-confirmed H1N1 infections in the general population is not clear. We evaluated the effectiveness of the pandemic H1N1 and seasonal trivalent influenza vaccines (TIV) used during the 2009 mass vaccination campaign in Manitoba (Canada) in preventing laboratory-confirmed H1N1 infections. METHODS A population-based case-control study using data from Cadham Provincial Laboratory (CPL) and the Manitoba Immunization Monitoring System (MIMS). All Manitoba residents ≥6 months of age who had a respiratory specimen tested at CPL for H1N1 were included in the study. Cases were individuals who tested positive for pandemic H1N1 influenza A by reverse transcriptase-PCR (N=1435). Controls were individuals who tested negative for both influenza A and B (N=2309). Information on receipt of TIV or H1N1 vaccine was obtained by record linkage with MIMS, the population-based province-wide immunization registry. RESULTS Overall, the adjuvanted H1N1 vaccine was 86% (95%CI 75-93%) effective in preventing laboratory-confirmed H1N1 infections when vaccination occurred ≥14 days before testing. Effectiveness seemed lower among older (≥50 years) individuals [51% (-51 to 84%)] and among those with immunocompromising conditions [67% (-13 to 90%)]. There was also evidence that the H1N1 vaccine might be less effective among those who had received the 2009/10 TIV. DISCUSSION The adjuvanted H1N1 vaccine used during Manitobas H1N1 mass vaccination campaign was highly effective against laboratory-confirmed pandemic H1N1 infection, especially among children and younger adults.

Epidemic of Group A Streptococcus M/emm59 Causing Invasive Disease in Canada

BACKGROUND The incidence of invasive group A Streptococcus (GAS) disease can vary over time and geographic region, possibly reflecting the populations susceptibility to particular strains but also variation in the predominant M/emm types. Canadian surveillance documented an epidemic of an uncommon M/emm59 type from 2006 to 2009. METHODS Invasive GAS isolates are submitted by Public Health Laboratories in Canada to the National Centre for Streptococcus for M/emm typing. Patient age, sex, geographic location, and the anatomical source of isolate are provided with the isolate. When it was recognized that M/emm59 strains were increasing in prevalence, clinical information was collected on M/emm59 cases captured in Alberta and compared with cases of other M/emm types occurring in this province. RESULTS From January 2006 through December 2009, 539 (13.0%) of 4150 invasive GAS cases were identified as M/emm59: 164 from British Columbia, 146 from Alberta, 62 from Saskatchewan, 82 from Manitoba, 68 from Ontario, 14 from Quebec, 1 from New Brunswick, 1 from Newfoundland, 1 from Yukon, and 1 from Nunavut. The predominant clinical presentation was bacteremia (45.0%) followed by cellulitis (41.4%). Compared with concurrent cases of invasive GAS disease caused by all other M/emm types, identified risk factors for M/emm59 disease were alcohol abuse (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.4-3.8), homelessness (OR, 2.0; 95% CI, 1.2-3.4), hepatitis C virus infection (OR, 2.0; 95% CI, 1.1-3.5), and illicit drug use (OR, 1.7; 95% CI, 1.0-3.0). CONCLUSIONS Western Canada has witnessed the rapid emergence of a rare GAS strain causing invasive disease predominately in a select population of disadvantaged persons.

Estimated cumulative incidence of pandemic (H1N1) influenza among pregnant women during the first wave of the 2009 pandemic

Background: Hospitalization and lab confirmed cases of H1N1 have been reported during the first wave of the 2009 pandemic but these are not accurate measures of influenza incidence in the population. We estimated the cumulative incidence of pandemic (H1N1) influenza among pregnant women in the province of Manitoba during the first wave of the 2009 pandemic. Methods: Two panels of stored frozen serum specimens collected for routine prenatal screening were randomly selected for testing before (March 2009, n = 252) and after (August 2009, n = 296) the first wave of the pandemic. A standard hemagglutination inhibition assay was used to detect the presence of IgG antibodies against the pandemic (H1N1) 2009 virus. The cumulative incidence of pandemic (H1N1) influenza was calculated as the difference between the point prevalence rates in the first and second panels. Results: Of the specimens collected in March, 7.1% were positive for the IgG antibodies (serum antibody titre ≥ 1:40). The corresponding prevalence was 15.7% among the specimens collected in August. The difference indicated a cumulative incidence of 8.6% (95% confidence interval [CI] 3.2%–13.7%). The rate differed geographically, the highest being in the northern regions (20.8%, 95% CI 7.9%–31.8%), as compared with 4.0% (95% CI 0.0%–11.9%) in Winnipeg and 8.9% (95% CI 0.0%–18.8%) in the rest of the province. Interpretation: We estimated that the cumulative incidence of pandemic (H1N1) influenza among pregnant women in Manitoba during the first wave of the 2009 pandemic was 8.6%. It was 20.8% in the northern regions of the province.