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Review: Inactivated vaccines provide the greatest protection against influenza in healthy persons

Peter A. Gross, MD
[+] Article and Author Information

Source of funding: Ministry of Defence, UK.

For correspondence: Dr. V. Demicheli, Servizio Sovrazonale di Epidemiologia, Alessandria, Piemonte, Italy. E-mail epidemi@tin.it.


Ann Intern Med. 2002;136(3):103. doi:10.7326/ACPJC-2002-136-3-103
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Question: What is the effectiveness of vaccines in preventing influenza in healthy adults?

Data sources: Studies were identified by searching MEDLINE (1966 to 1997) with the terms influenza, route (oral), route (parenteral), and vaccine; searching EMBASE/Excerpta Medica (1990 to 1997) and the Cochrane Controlled Trials Register; hand searching the journal Vaccine to 1997; scanning the bibliographies of articles; and contacting manufacturers of vaccines and authors of studies in the review.

Study selection: Studies were selected if they were quasirandomized or randomized controlled trials (RCTs) that compared influenza vaccines with placebo, control vaccines, or no intervention or doses or schedules of influenza vaccine in healthy persons 14 to 60 years of age and that assessed protection from exposure to naturally occurring influenza.

Data extraction: Data were extracted on study quality, participant characteristics, intervention, and outcomes. Outcomes included rates of influenza (clinically defined [unspecified], clinically defined on the basis of specific symptoms or signs [specified], and serologically confirmed), hospital admissions, working days lost, and adverse events.

Main results: 20 trials were included (14 RCTs) evaluating 3 types of vaccine: live attenuated aerosol (n = 26 369), inactivated aerosol (n = 1506), and inactivated parenteral (n = 23 628). Live aerosol vaccines were not effective for preventing either type of clinically defined influenza (2 trials). Inactivated vaccines were effective in preventing influenza: Both inactivated aerosol and inactivated parenteral vaccines prevented unspecified clinically defined influenza, and inactivated parenteral vaccines prevented specified clinically defined influenza (Table). Live aerosol and inactivated parenteral vaccines prevented serologically confirmed influenza (Table). No studies of inactivated aerosol reported serologically confirmed influenza. Vaccine and placebo did not differ for working days lost (3 trials), hospitalizations (1 trial), or complications (2 trials). Local tenderness and soreness were increased in patients who received inactivated parenteral vaccine (Table). No increase occurred in systemic myalgia, fever, or fatigue.

Conclusion: Inactivated parenteral vaccines are effective in preventing influenza in healthy adults.

Vaccines vs placebo for preventing influenza in healthy adults at mean 87 days*

OutcomesComparisonsWeighted event ratesNumber of trialsRRR (95% CI)NNT (CI)
CDI unspecifiedIA vs placebo7.2% vs 20%165% (32 to 82)8 (4 to 63)
IP vs placebo17% vs 21%531% (5 to 51)25 (13 to 250)
CDI specifiedIP vs placebo45% vs 53%426% (1 to 45)13 (8 to 29)
SCILA vs placebo0.7% vs 8.5%279% (44 to 92)Not significant
IP vs placebo2.9% vs 8.7%465% (44 to 79)18 (12 to 34)
RRI (CI)NNH (CI)
Local adverse eventsIP vs placebo64% vs 35%4113% (35 to 236)4 (3 to 7)

*CDI = clinically defined influenza; IA = inactivated aerosol vaccine; IP = inactivated parenteral vaccine; LA = live aerosol vaccine; SCI = serologically confirmed influenza. Other abbreviations defined in Glossary; RRR, RRI, NNT, NNH, and CI calculated from data in article using random effects.

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