Adjuvanted trivalent influenza vaccine versus quadrivalent inactivated influenza vaccine in Hutterite Children: A randomized clinical trial.

BACKGROUND: Children play an important role in the transmission of influenza. The best choice of vaccine to achieve both direct and indirect protection is uncertain. The objective of the study was to test whether vaccinating children with MF59 adjuvanted trivalent influenza vaccine (aTIV) can reduce influenza in children and their extended households compared to inactivated quadrivalent vaccine (QIV). METHODS: We conducted a cluster randomized trial in 42 Hutterite colonies in Alberta and Saskatchewan. Colonies were randomized such that children were assigned in a blinded manner to receive aTIV (0.25 ml of pediatric aTIV for ages 6 months to < 36 months or 0.5 ml for ages ≥ 36 months to 6 years) or 0.5 ml of QIV. Participants included 424 children aged 6 months to 6 years who received the study vaccine and 1246 family cluster members who did not receive the study vaccine. The primary outcome was confirmed influenza A and B infection using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay. An intent to treat analysis was used. Data were collected from January 2017 to June 2019. RESULTS: The mean percentage of children who received study vaccine was 62% for aTIV colonies and 74% for QIV colonies. There were 66 (3.4%) with RT-PCR confirmed influenza A and B in the aTIV colonies (children and family clusters) versus 93 (4.4%) in the QIV colonies, hazard ratio (HR) 0.78 (95 %CI 0.36-1.71). Of these, 48 (2.5%) in the aTIV colonies and 76 (3.6%) in the QIV colonies had influenza A, HR 0.69, (95 %CI 0.29-1.66) while 18 (0.9%) and 17 (0.8%) in the aTIV versus QIV colonies respectively had influenza B, HR 1.22, (95 %CI 0.20-7.41). In children who received study vaccine, there were 5 Influenza A infections in the aTIV colonies (1.1%) compared to 30 (5.8%) in the QIV colonies, relative efficacy of 80%, HR 0.20, (95 %CI 0.06-0.66). Adverse events were significantly more common among children who received aTIV. No serious vaccine adverse events were reported. CONCLUSION: Vaccinating children with aTIV compared to QIV resulted in similar community RT-PCR confirmed influenza illness and led to significant protection against influenza A in children.

Predictors of influenza a molecular viral shedding in Hutterite communities.

BACKGROUND: Patterns of influenza molecular viral shedding following influenza infection have been well established; predictors of viral shedding however remain uncertain. OBJECTIVES: We sought to determine factors associated with peak molecular viral load, duration of shedding, and viral area under the curve (AUC) in children and adult Hutterite colony members with laboratory-confirmed influenza. METHODS: A cohort study was conducted in Hutterite colonies in Alberta, Canada. Flocked nasal swabs were collected during three influenza seasons (2007-2008 to 2009-2010) from both symptomatic and asymptomatic individuals infected with influenza. Samples were tested by real-time reverse-transcription polymerase chain reaction for influenza A and influenza B, and the viral load was determined for influenza A-positive samples. RESULTS: For seasonal H1N1, younger age was associated with a larger AUC, female sex was associated with decreased peak viral load and reduced viral shedding duration, while the presence of comorbidity was associated with increased peak viral load. For H3N2, younger age was associated with increased peak viral load and increased AUC. For pandemic H1N1, younger age was associated with increased peak viral load and increased viral AUC, female sex was associated with reduced peak viral load, while inapparent infection was associated with reduced peak viral load, reduced viral shedding duration, and reduced viral AUC. CONCLUSIONS: Patterns of molecular viral shedding vary by age, sex, comorbidity, and the presence of symptoms. Predictor variables vary by influenza A subtype.

Effect of Influenza Vaccination of Children on Infection Rate in Hutterite Communities: Follow-Up Study of a Randomized Trial.

BACKGROUND: An earlier cluster randomized controlled trial (RCT) of Hutterite colonies had shown that if more than 80% of children and adolescents were immunized with influenza vaccine there was a statistically significant reduction in laboratory-confirmed influenza among all unimmunized community members. We assessed the impact of this intervention for two additional influenza seasonal periods. METHODS: Follow-up data for two influenza seasonal periods of a cluster randomized trial involving 1053 Canadian children and adolescents aged 36 months to 15 years in Season 2 and 1014 in Season 3 who received the study vaccine, and 2805 community members in Season 2 and 2840 in Season 3 who did not receive the study vaccine. Follow-up for Season 2 began November 18, 2009 and ended April 25, 2010 while Season 3 extended from December 6, 2010 and ended May 27, 2011. Children were randomly assigned in a blinded manner according to community membership to receive either inactivated trivalent influenza vaccine or hepatitis A. The primary outcome was confirmed influenza A and B infection using RT-PCR assay. Due to the outbreak of 2009 H1N1 pandemic, data in Season 2 were excluded for analysis. RESULTS: For an analysis of the combined Season 1 and Season 3 data, among non-recipients (i.e., participants who did not receive study vaccines), 66 of the 2794 (2.4%) participants in the influenza vaccine colonies and 121 of the 2301 (5.3%) participants in the hepatitis A colonies had influenza confirmed by RT-PCR, for a protective effectiveness of 60% (95% CI, 6% to 83%; P = 0.04); among all study participants (i.e., including both those who received study vaccine and those who did not), 125 of the 3806 (3.3%) in the influenza vaccine colonies and 239 of the 3243 (7.4%) in the hepatitis A colonies had influenza confirmed by RT-PCR, for a protective effectiveness of 63% (95% CI, 5% to 85%; P = 0.04). CONCLUSION: Immunizing children and adolescents with inactivated influenza vaccine can offer a protective effect among unimmunized community members for influenza A and B together when considered over multiple years of seasonal influenza. TRIAL REGISTRATION: Clinicaltrials.gov NCT00877396.

Live Attenuated Versus Inactivated Influenza Vaccine in Hutterite Children: A Cluster Randomized Blinded Trial.

BACKGROUND: Whether vaccinating children with intranasal live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in providing both direct protection in vaccinated persons and herd protection in unvaccinated persons is uncertain. Hutterite colonies, where members live in close-knit, small rural communities in which influenza virus infection regularly occurs, offer an opportunity to address this question. OBJECTIVE: To determine whether vaccinating children and adolescents with LAIV provides better community protection than IIV. DESIGN: A cluster randomized blinded trial conducted between October 2012 and May 2015 over 3 influenza seasons. (ClinicalTrials.gov: NCT01653015). SETTING: 52 Hutterite colonies in Alberta and Saskatchewan, Canada. PARTICIPANTS: 1186 Canadian children and adolescents aged 36 months to 15 years who received the study vaccine and 3425 community members who did not. INTERVENTION: Children were randomly assigned according to community in a blinded manner to receive standard dosing of either trivalent LAIV or trivalent IIV. MEASUREMENTS: The primary outcome was reverse transcriptase polymerase chain reaction-confirmed influenza A or B virus in all participants (vaccinated children and persons who did not receive the study vaccine). RESULTS: Mean vaccine coverage among children in the LAIV group was 76.9% versus 72.3% in the IIV group. Influenza virus infection occurred at a rate of 5.3% (295 of 5560 person-years) in the LAIV group versus 5.2% (304 of 5810 person-years) in the IIV group. The hazard ratio comparing LAIV with IIV for influenza A or B virus was 1.03 (95% CI, 0.85 to 1.24). LIMITATION: The study was conducted in Hutterite communities, which may limit generalizability. CONCLUSION: Immunizing children with LAIV does not provide better community protection against influenza than IIV. PRIMARY FUNDING SOURCE: The Canadian Institutes for Health Research.

Characteristics of respiratory viral infections during influenza season in Canadian Hutterite Communities.

OBJECTIVES: To determined the pathogen-specific incidence of respiratory virus infection in Hutterite communities occurring over the 2008-2009 influenza season and assess temporal characteristics of respiratory illness related to infection. METHODS: 3273 participants community members enrolled in a cluster randomized trial of influenza vaccine were studied. RESULTS: One hundred forty-nine participants had laboratory-confirmed influenza, and 595 had at least one episode of laboratory-confirmed respiratory viral infection other than influenza. Entero/rhinovirus had the highest incidence among children<5 years. CONCLUSIONS: A decline in the incidence of infections with age was observed for influenza as well as for most other respiratory viruses.

Human infection with a triple-reassortant swine influenza A(H1N1) virus containing the hemagglutinin and neuraminidase genes of seasonal influenza virus.

A reassortant influenza A(H1N1) virus of swine origin distinct from the pandemic H1N1 2009 strain was isolated from 3 patients, all of whom worked at the same large hog operation in Saskatchewan, Canada. The genomic composition of the isolates has not been previously reported, to our knowledge, and was the product of a genetic reassortment between seasonal H1N1 and triple-reassortant influenza virus that emerged in North American swine during the late 1990s. The neuraminidase and hemagglutinin genes of A/Saskatchewan/5350/2009, A/Saskatchewan/5351/2009, and A/Saskatchewan/5131/2009 were derived from human H1N1 virus and were closely related to those of A/Brisbane/59/2007.

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.