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PEDIATRICS Vol. 110 No. 4 October 2002, pp. 662-672

Safety of the Trivalent, Cold-Adapted Influenza Vaccine in Preschool-Aged Children

Pedro A. Piedra, MD^*,Dagger;, Lihan Yan, MS, Karen Kotloff, MD^||, Ken Zangwill, MD^¶, David I. Bernstein, MD^#, James King, MD^||, John Treanor, MD^**, Flor Munoz, MD^*,, Mark Wolff, PhD, Iksung Cho, MS, Paul M. Mendelman, MD, Julie Cordova, BS and Robert B. Belshe, MD

^* Department of Molecular Virology and Microbiology
Pediatrics, Baylor College of Medicine, Houston, Texas
EMMES Corporation, Potomac, Maryland
^|| Center for Vaccine Development, University of Maryland, Baltimore, Maryland
^¶ Kaiser-UCLA Vaccine Program and Department of Pediatrics, Harbor-University of California Los Angeles Medical Center, Los Angeles, California
^# Department of Medicine, Department of Pediatrics, Children’s Hospital Medical Center, Cincinnati, Ohio
^** University of Rochester, Rochester, New York
Aviron, Mountain View, California
Department of Medicine, Saint Louis University, St Louis, Missouri

--> Objective. To provide additional information on the safety of trivalent, cold-adapted influenza vaccine (CAIV-T) in children.

Methods. Children 15 to 71 months of age were enrolled in a multicenter, prospective, randomized, double-blind, and placebo-controlled trial to receive by nasal spray CAIV-T or placebo. In year 1 (1996–1997), 1314 were enrolled in the 2-dose cohort and 288 were enrolled in the 1-dose cohort. In year 2 (1997–1998), 1358 of the original participants received 1 dose of vaccine or placebo according to their original treatment group assignment. In year 3 (1998–1999) and year 4, the trial continued as an open-label safety trial of CAIV-T. A total of 642 and 549 children enrolled in years 3 and 4, respectively, received their third and fourth sequential annual doses of CAIV-T. Measured were 1) the occurrence of specific respiratory, gastrointestinal and systemic symptoms, unexpected symptoms (not specified in the diary card), and use of medications within the first 10 days after vaccination; 2) the occurrence of an acute illness and use of medication within 11 to 42 days after vaccination; and 3) the occurrence of serious adverse events within 42 days after vaccination.

Results. The adjusted odd ratios of specific respiratory and gastrointestinal symptoms during the 10 days after vaccination were determined in years 1 and 2. Runny nose or nasal congestion, vomiting, muscle aches, and fever were significantly associated with the first dose of CAIV-T. With the second dose, runny nose was the only symptom that was associated with CAIV-T. In year 2, CAIV-T did not cause excess in any of the specific respiratory and gastrointestinal symptoms. In years 3 and 4, specific respiratory and gastrointestinal symptoms were comparable to that observed in year 2. A CAIV-T–associated symptom was most likely to occur on day 2 with the first dose of vaccine. The occurrence of unexpected symptoms was primarily of the gastrointestinal system. Approximately 6% of CAIV-T and 3.6% of placebo recipients had a gastrointestinal symptom. CAIV-T seemed to be associated with a mild excess in abdominal pain and vomiting only with the first vaccine dose. A statistically significant increase in the use of analgesics/antipyretics was detected only with the first dose in CAIV-T vaccinees compared with placebo recipients (23.5% vs 16.6%). Between days 11 and 42, CAIV-T use was not associated with an excess of illness, otitis media, or use of medication. None of the 6 serious adverse events in CAIV-T recipients in years 1 to 4 was attributed to the vaccine.

Conclusions. CAIV-T was safe in children. Mild respiratory, gastrointestinal, and systemic symptoms of short duration were observed in a minority of children and primarily with the first vaccine dose. Sequential annual doses of CAIV-T were well tolerated.

Key Words: trivalent • cold-adapted influenza vaccine • safety • preschool-aged children

Abbreviations: IIV-T, trivalent inactivated influenza vaccine • CAIV-T, trivalent, cold-adapted influenza vaccine • PD-OM, physician-diagnosed otitis media • PD-FOM, physician-diagnosed febrile otitis media • PD-LRTI, physician-diagnosed lower respiratory tract illness • SAE, serious adverse event • COSTART, Coding Symbols for Thesaurus of Adverse Reaction Terms

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Received for publication Jul 18, 2002; Accepted Apr 12, 2002.

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