This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (162)  • Contact me when this article is cited  Related Content  • Related articles  • Similar articles in JAMA  Topic Collections  • Randomized Controlled Trial  • Alert me on articles by topic

A Randomized Controlled Trial

Kristin L. Nichol, MD, MPH; Paul M. Mendelman, MD; Kenneth P. Mallon, MS, MHS; Lisa A. Jackson, MD, MPH; Geoffrey J. Gorse, MD; Robert B. Belshe, MD; W. Paul Glezen, MD; Janet Wittes, PhD; for the Live Attenuated Influenza Virus Vaccine in Healthy Adults Trial Group

JAMA. 1999;282:137-144.

Context  Influenza virus is a major cause of illness, disruption to daily life, and increased use of health care in all age groups.

Objective  To assess the safety and effectiveness of intranasally administered trivalent, live, attenuated influenza virus (LAIV) vaccine for reducing illness, absenteeism, and health care use among healthy, working adults.

Design  Randomized, double-blind, placebo-controlled trial conducted from September 1997 through March 1998.

Setting  Thirteen centers across the United States.

Participants  A total of 4561 healthy, working adults aged 18 to 64 years recruited through health insurance plans, at work sites, and from the general population.

Intervention  Participants were randomized 2:1 to receive intranasally administered trivalent LAIV vaccine (n=3041) or placebo (n=1520) in the fall of 1997.

Main Outcome Measures  Episodes of febrile illness, severe febrile illness, febrile upper respiratory tract illness, work loss, and health care use during the peak and total influenza outbreak periods, and adverse events.

Results  Recipients of LAIV vaccine were as likely to experience 1 or more febrile illnesses as placebo recipients during peak outbreak periods (13.2% for vaccine vs 14.6% for placebo; P=.19). However, vaccination significantly reduced the numbers of severe febrile illnesses (18.8% reduction; 95% confidence interval [CI], 7.4%-28.8%) and febrile upper respiratory tract illnesses (23.6% reduction; 95% CI, 12.7%-33.2%). Vaccination also led to fewer days of illness across all illness syndromes (22.9% reduction for febrile illnesses; 27.3% reduction for severe febrile illnesses), fewer days of work lost (17.9% reduction for severe febrile illnesses; 28.4% reduction for febrile upper respiratory tract illnesses), and fewer days with health care provider visits (24.8% reduction for severe febrile illnesses; 40.9% reduction for febrile upper respiratory tract illnesses). Use of prescription antibiotics and over-the-counter medications was also reduced across all illness syndromes. Vaccine recipients were more likely to experience runny nose or sore throat during the first 7 days after vaccination, but serious adverse events between the groups were not significantly different. The match between the type A(H3N2) vaccine strain and the predominant circulating virus strain (A/Sydney/05/97[H3N2]) for the 1997-1998 season was poor, suggesting that LAIV provided substantial cross-protection against this variant influenza A virus strain.

Conclusion  Intranasal trivalent LAIV vaccine was safe and effective in healthy, working adults in a year in which a drifted influenza A virus predominated.

Author Affiliations: Medicine Service, VA Medical Center, and the University of Minnesota, Minneapolis (Dr Nichol); Aviron, Mountain View, Calif (Dr Mendelman and Mr Mallon); Immunization Studies Program, Center for Health Studies, Group Health Cooperative and Department of Epidemiology, University of Washington, Seattle (Dr Jackson); Medicine Service, VA Medical Center (Dr Gorse), and Department of Medicine, St Louis University (Drs Gorse and Belshe), St Louis, Mo; Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Tex (Dr Glezen); and Statistics Collaborative, Washington, DC (Dr Wittes).

RELATED ARTICLES

Intranasal Influenza Vaccine: Adding to the Armamentarium for Influenza Control
Gregory A. Poland and Robert Couch
JAMA. 1999;282(2):182-184.
EXTRACT | FULL TEXT  

July 14, 1999
JAMA. 1999;282(2):201-202.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Adverse events associated with intranasal influenza vaccine in the United States
Vasu et al.
Therapeutic Advances in Respiratory Disease 2008;2:193-198.
ABSTRACT  

Correlation of Cellular Immune Responses with Protection against Culture-Confirmed Influenza Virus in Young Children
Forrest et al.
CVI 2008;15:1042-1053.
ABSTRACT | FULL TEXT  

Update on the Management of COPD
Celli
Chest 2008;133:1451-1462.
ABSTRACT | FULL TEXT  

Safety and Immunogenicity of Concurrent Administration of Live Attenuated Influenza Vaccine With Measles-Mumps-Rubella and Varicella Vaccines to Infants 12 to 15 Months of Age
Nolan et al.
Pediatrics 2008;121:508-516.
ABSTRACT | FULL TEXT  

Safety and Tolerability of Cold-Adapted Influenza Vaccine, Trivalent, in Infants Younger Than 6 Months of Age
Vesikari et al.
Pediatrics 2008;121:e568-e573.
ABSTRACT | FULL TEXT  

Comparative Immunogenicities of Frozen and Refrigerated Formulations of Live Attenuated Influenza Vaccine in Healthy Subjects
Block et al.
Antimicrob. Agents Chemother. 2007;51:4001-4008.
ABSTRACT | FULL TEXT  

Comparison of the Influenza Virus-Specific Effector and Memory B-Cell Responses to Immunization of Children and Adults with Live Attenuated or Inactivated Influenza Virus Vaccines
Sasaki et al.
J. Virol. 2007;81:215-228.
ABSTRACT | FULL TEXT  

Prevention of Antigenically Drifted Influenza by Inactivated and Live Attenuated Vaccines
Ohmit et al.
NEJM 2006;355:2513-2522.
ABSTRACT | FULL TEXT  

Cellular Immune Responses in Children and Adults Receiving Inactivated or Live Attenuated Influenza Vaccines
He et al.
J. Virol. 2006;80:11756-11766.
ABSTRACT | FULL TEXT  

Safety, Efficacy, and Effectiveness of Cold-Adapted Influenza Vaccine-Trivalent Against Community-Acquired, Culture-Confirmed Influenza in Young Children Attending Day Care
Vesikari et al.
Pediatrics 2006;118:2298-2312.
ABSTRACT | FULL TEXT  

Double-blind peer reviewed paper The role of healthcare workers in influenza prevention: Part one
Chalmers
British Journal of Infection Control 2006;7:16-20.
ABSTRACT  

Chronic Obstructive Pulmonary Disease: From Unjustified Nihilism to Evidence-based Optimism.
Celli
Proc Am Thorac Soc 2006;3:58-65.
ABSTRACT | FULL TEXT  

Guidelines for the management of adult lower respiratory tract infections
Woodhead et al.
Eur Respir J 2005;26:1138-1180.
ABSTRACT | FULL TEXT  

Trivalent Intranasal Influenza Vaccine, Live
McCarthy and Kockler
The Annals of Pharmacotherapy 2004;38:2086-2093.
ABSTRACT | FULL TEXT  

Prevention of influenza in the general population: recommendation statement from the Canadian Task Force on Preventive Health Care
Langley et al.
CMAJ 2004;171:1169-1170.
FULL TEXT  

Prevention of influenza in the general population
Langley and Faughnan
CMAJ 2004;171:1213-1222.
ABSTRACT | FULL TEXT  

Practical Considerations to Influenza Vaccination
Musana et al.
Clin Med Res 2004;2:256-259.
FULL TEXT  

Generation of Influenza A Virus NS2 (NEP) Mutants with an Altered Nuclear Export Signal Sequence
Iwatsuki-Horimoto et al.
J. Virol. 2004;78:10149-10155.
ABSTRACT | FULL TEXT  

Every Nose Counts: A New Influenza Vaccine for All Healthy Schoolchildren?
Gaglani and Herschler
CLIN PEDIATR 2004;43:35-41.
ABSTRACT  

Direct and Total Effectiveness of the Intranasal, Live-Attenuated, Trivalent Cold-Adapted Influenza Virus Vaccine Against the 2000-2001 Influenza A(H1N1) and B Epidemic in Healthy Children
Gaglani et al.
Arch Pediatr Adolesc Med 2004;158:65-73.
ABSTRACT | FULL TEXT  

Invited Commentary: Use of Selective Viral Cultures to Adjust Nonvirologic Endpoints in Studies of Influenza Vaccine Efficacy
Monto
Am J Epidemiol 2003;158:312-315.
FULL TEXT  

Influenza Burden of Illness: Estimates From a National Prospective Survey of Household Contacts in France
Carrat et al.
Arch Intern Med 2002;162:1842-1848.
ABSTRACT | FULL TEXT  

Science, medicine, and the future: New vaccine development
Poland et al.
BMJ 2002;324:1315-1319.
FULL TEXT  

The Safety of Inactivated Influenza Vaccine in Adults and Children with Asthma
The American Lung Association Asthma Clinical Rese
NEJM 2001;345:1529-1536.
ABSTRACT | FULL TEXT  

Influenza Vaccination for Healthy Young Adults
Ahmed et al.
NEJM 2001;345:1543-1547.
FULL TEXT  

Active Immunization in the United States: Developments over the Past Decade
Dennehy
Clin. Microbiol. Rev. 2001;14:872-908.
ABSTRACT | FULL TEXT  

Using Validation Sets for Outcomes and Exposure to Infection in Vaccine Field Studies
Halloran and Longini
Am J Epidemiol 2001;154:391-398.
ABSTRACT | FULL TEXT  

Prevention of influenza and pneumococcal pneumonia in Canadian long-term care facilities: How are we doing?
Stevenson et al.
CMAJ 2001;164:1413-1419.
ABSTRACT | FULL TEXT  

Immunoglobulin A (IgA) Responses and IgE-Associated Inflammation along the Respiratory Tract after Mucosal but Not Systemic Immunization
Hodge et al.
Infect. Immun. 2001;69:2328-2338.
ABSTRACT | FULL TEXT  

Influenza Vaccine for Healthy Working Adults
Nichol et al.
JAMA 2001;285:290-292.
FULL TEXT  

Prevention and Treatment of Influenza
Couch
NEJM 2000;343:1778-1787.
FULL TEXT  

Influenza
Cifu and Levinson
JAMA 2000;284:2847-2849.
FULL TEXT  

Preventing Influenza in Healthy Adults: The Evolving Story
Monto
JAMA 2000;284:1699-1701.
FULL TEXT  

Intranasal, live, attenuated influenza virus vaccine reduced severe febrile illness in healthy adults
Bender
Evid. Based Med. 2000;5:44-44.
FULL TEXT  

Vaccines in the 21st century
Liu
BMJ 1999;319:1301-1301.
FULL TEXT  

Influenza Prevention and Treatment: Current Practices and New Horizons
Belshe
ANN INTERN MED 1999;131:621-623.
FULL TEXT  

Live Intranasal Influenza Vaccine Protects Healthy Adults
JWatch Infect. Diseases 1999;1999:13-13.
FULL TEXT  

Intranasal Flu Vaccine Effective in Adults
JWatch General 1999;1999:3-3.
FULL TEXT  

Intranasal Influenza Vaccine: Adding to the Armamentarium for Influenza Control
Poland and Couch
JAMA 1999;282:182-184.
FULL TEXT