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Live Attenuated Versus Inactivated Influenza Vaccine in Hutterite Children: A Cluster Randomized Blinded TrialLive Attenuated Versus Inactivated Influenza Vaccine in Hutterite Children ONLINE FIRST

Mark Loeb, MD; Margaret L. Russell, MD, PhD; Vanessa Manning, BSc; Kevin Fonseca, PhD; David J.D. Earn, PhD; Gregory Horsman, MD; Khami Chokani, MD; Mark Vooght, MD; Lorne Babiuk, PhD; Lisa Schwartz, PhD; Binod Neupane, PhD; Pardeep Singh, BSc; Stephen D. Walter, PhD; and Eleanor Pullenayegum, PhD
[+] Article, Author, and Disclosure Information

This article was published at www.annals.org on 16 August 2016.


From McMaster University, Hamilton, Ontario; University of Calgary, Calgary, Alberta; Saskatchewan Disease Control Laboratory, Regina, Saskatchewan; Prince Albert Parkland Health Region, Prince Albert, Saskatchewan; Five Hills Health Region, Moose Jaw, Saskatchewan; and Hospital for Sick Children, Toronto, Ontario, Canada.

Acknowledgment: The authors thank members of the data monitoring and safety board, including Carolyn Bridges, MD, Chair (Centers for Disease Control and Prevention, Atlanta, Georgia); John Koval, PhD (University of Western Ontario, London, Ontario, Canada); and Patricia Parkin, MD (Hospital for Sick Children, Toronto, Ontario, Canada). Next, they thank Melissa Naylor (research coordinator), Jen Newton (research laboratory manager), Sasha Eskandarian (research program manager), Caralyn Kelly-Stradiotto (research coordinator), and all at McMaster University. Then, they thank the vaccination nurses and surveillance study staff. Finally, they thank Kanti Pabbaraju, MSc, Sallene Wong, BSc, Clara Soyoon Lee, and Brittany Williamson (Provincial Laboratory for Public Health, Calgary, Alberta, Canada); and Nick Antonishyn, PhD, and Ryan McDonald, PhD (Saskatchewan Disease Control Laboratory, Regina, Saskatchewan, Canada).

Grant Support: By the Canadian Institutes of Health Research (grant 123266), Public Health Agency of Canada, and Canadian Institutes of Health Research Influenza Research Network.

Disclosures: Dr. Loeb reports grants from the Canadian Institute of Health Research, World Health Organization, and National Institutes of Health and personal fees from Sanofi Pasteur, AstraZeneca, and Novartis Vaccines and Diagnostics outside the submitted work. Dr. Schwartz reports honorarium from the Canadian Agency for Drugs and Technologies in Health outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-0513.

Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.

Reproducible Research Statement:Study protocol: See the Supplement. Statistical code: Available from Dr. Loeb (e-mail, loebm@mcmaster.ca). Data set: Not available.

Requests for Single Reprints: Mark Loeb, MD, McMaster University, Michael G. DeGroote Center for Learning, Room 3200, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada; e-mail, loebm@mcmaster.ca.

Current Author Addresses: Dr. Loeb, Ms. Manning, and Mr. Singh: McMaster University, Michael G. DeGroote Center for Learning, Room 3200, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada.

Dr. Russell: Department of Community Health Sciences, Cumming School of Medicine, The University of Calgary, 3280 Hospital Drive Northwest, Calgary, Alberta T2N 4Z6, Canada.

Dr. Fonseca: Provincial Laboratory for Public Health, 3030 Hospital Drive Northwest, Calgary, Alberta T2N 4W4, Canada.

Dr. Earn: Department of Mathematics and Statistics, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada.

Dr. Horsman: Saskatchewan Disease Control Laboratory, 5 Research Drive, Regina, Saskatchewan S4S 0A4, Canada.

Dr. Chokani: Prince Albert Parkland Health Region, 1521 6th Avenue West, Prince Albert, Saskatchewan S6V 5K1, Canada.

Dr. Vooght: Five Hills Health Region, 107-110 Ominica Street West, Moose Jaw, Saskatchewan S6H 6V2, Canada.

Dr. Babiuk: University of Alberta, 2-51 South Academic Building, Edmonton, Alberta T6G 2G7, Canada.

Dr. Schwartz: Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main Street West, CRL-224, Hamilton, Ontario L8S 4K1, Canada.

Dr. Neupane: Department of Clinical Epidemiology and Biostatistics, McMaster University, Michael G. DeGroote Center for Learning, Room 3202, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada.

Dr. Walter: Department of Clinical Epidemiology and Biostatistics, McMaster University, Communications Research Laboratory, Room 233, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada.

Dr. Pullenayegum: Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.

Author Contributions: Conception and design: M. Loeb, M.L. Russell, K. Chokani, L. Babiuk, L. Schwartz.

Analysis and interpretation of the data: M. Loeb, M.L. Russell, L. Babiuk, L. Schwartz, B. Neupane, P. Singh, S.D. Walter, E. Pullenayegum.

Drafting of the article: M. Loeb, M.L. Russell, K. Fonseca, L. Schwartz, S.D. Walter.

Critical revision of the article for important intellectual content: M. Loeb, M.L. Russell, K. Chokani, M. Vooght, B. Neupane, E. Pullenayegum.

Final approval of the article: M. Loeb, M.L. Russell, V. Manning, K. Fonseca, G. Horsman, K. Chokani, M. Vooght, L. Babiuk, L. Schwartz, S.D. Walter, E. Pullenayegum.

Provision of study materials or patients: G. Horsman, K. Chokani.

Statistical expertise: M. Loeb, B. Neupane, S.D. Walter, E. Pullenayegum.

Obtaining of funding: M. Loeb, M.L. Russell, L. Babiuk.

Administrative, technical, or logistic support: M. Loeb, V. Manning, K. Fonseca, K. Chokani, M. Vooght, L. Babiuk.

Collection and assembly of data: M. Loeb, M.L. Russell, V. Manning, K. Chokani, L. Babiuk, P. Singh.


Ann Intern Med. Published online 16 August 2016 doi:10.7326/M16-0513
© 2016 American College of Physicians
Text Size: A A A

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.

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.

Figures

Grahic Jump Location
Figure.

Study flow of diagram of study participants.

IIV = inactivated influenza vaccine; LAIV = live attenuated influenza vaccine.

* 199 persons in a year-1 colony did not participate in year 2 and were replaced by 306 persons from a new colony.

† 178 persons in a year-1 colony did not participate in year 2 and were replaced by 359 persons from a new colony.‡ 99 persons in a year-2 colony did not participate in year 3 and were replaced by 252 persons from a new colony.

§ 71 persons in a year-2 colony did not participate in year 3 and were replaced by 257 persons from 1 new colony and new enrollees from other colonies; 102 persons from year 1 reenrolled.

Grahic Jump Location
Grahic Jump Location
Appendix Figure.

Epidemic curves of laboratory-confirmed influenza by week for each intervention group.

Green and white bars indicate influenza A and B viruses, respectively. IIV = inactivated influenza vaccine; LAIV = live attenuated influenza vaccine; RT-PCR = reverse transcriptase polymerase chain reaction. Top. Influenza season 1. Middle. Influenza season 2. Bottom. Influenza season 3.

Grahic Jump Location

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