Assessing the Evidence Live Attenuated Influenza Vaccine in Children Younger than 2 Years. A Systematic Review
ABSTRACT Live attenuated influenza vaccine (LAIV) is effective in children but contraindicated in children <2 years of age.
We searched Medline, EMBASE, the Cochrane Library, Web of Science, Scopus, PsycInfo and CINAHL through February 2013 for existing systematic reviews, randomized controlled trials (RCTs) and observational studies (for safety). We included studies enrolling healthy children <2 years of age who received LAIV, compared with placebo or inactivated influenza vaccine (IIV). Data were extracted independently by 2 investigators. The relative risk (RR) was pooled across studies using the random effects model.
We found 7 eligible randomized controlled trials and 2 observational studies. Randomized controlled trials included 6281 children and were at low to moderate risk of bias. LAIV reduced the incidence of influenza compared with placebo (relative risk = 0.36, 95% confidence interval: 0.23-0.58, P < 0.05) with a number needed to vaccinate of 17. LAIV increased the incidence of minor side effects (fever and rhinorrhea). LAIV had a similar effect in preventing influenza (relative risk = 0.76, 95% confidence interval: 0.45-1.30, P > 0.05) compared with inactivated influenza vaccine. There was an increase of hospitalization rate (post hoc analysis) and medical attended wheezing with LAIV.
LAIV is highly effective in children <2 years of age compared with placebo and is as effective to inactivated influenza vaccine. The safety profile of LAIV is reasonable although evidence is sparse. LAIV may be considered as an option in this age group particularly during seasons with vaccine shortage.
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ABSTRACT: No published meta-analyses have assessed efficacy and effectiveness of licensed influenza vaccines in the USA with sensitive and highly specific diagnostic tests to confirm influenza. We searched Medline for randomised controlled trials assessing a relative reduction in influenza risk of all circulating influenza viruses during individual seasons after vaccination (efficacy) and observational studies meeting inclusion criteria (effectiveness). Eligible articles were published between Jan 1, 1967, and Feb 15, 2011, and used RT-PCR or culture for confirmation of influenza. We excluded some studies on the basis of study design and vaccine characteristics. We estimated random-effects pooled efficacy for trivalent inactivated vaccine (TIV) and live attenuated influenza vaccine (LAIV) when data were available for statistical analysis (eg, at least three studies that assessed comparable age groups). We screened 5707 articles and identified 31 eligible studies (17 randomised controlled trials and 14 observational studies). Efficacy of TIV was shown in eight (67%) of the 12 seasons analysed in ten randomised controlled trials (pooled efficacy 59% [95% CI 51-67] in adults aged 18-65 years). No such trials met inclusion criteria for children aged 2-17 years or adults aged 65 years or older. Efficacy of LAIV was shown in nine (75%) of the 12 seasons analysed in ten randomised controlled trials (pooled efficacy 83% [69-91]) in children aged 6 months to 7 years. No such trials met inclusion criteria for children aged 8-17 years. Vaccine effectiveness was variable for seasonal influenza: six (35%) of 17 analyses in nine studies showed significant protection against medically attended influenza in the outpatient or inpatient setting. Median monovalent pandemic H1N1 vaccine effectiveness in five observational studies was 69% (range 60-93). Influenza vaccines can provide moderate protection against virologically confirmed influenza, but such protection is greatly reduced or absent in some seasons. Evidence for protection in adults aged 65 years or older is lacking. LAIVs consistently show highest efficacy in young children (aged 6 months to 7 years). New vaccines with improved clinical efficacy and effectiveness are needed to further reduce influenza-related morbidity and mortality. Alfred P Sloan Foundation.The Lancet Infectious Diseases 09/2012; 12(1):36-44. DOI:10.1016/S1473-3099(11)70295-X · 19.45 Impact Factor
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ABSTRACT: The Strategic Group of Advisory Experts (SAGE) on immunization is an independent advisory committee with a mandate to advise the World Health Organization (WHO) on the development of vaccine and immunization related policies. SAGE working groups are established on a time-limited basis to review and provide evidence-based recommendations, together with their implications, for open deliberation and decision-making by SAGE. In making its recommendations, SAGE takes into consideration: the epidemiologic and clinical characteristics of the disease; vaccine and immunization characteristics; economic analysis; health system considerations; the existence of and interaction with other intervention and control strategies; costing and social impacts; and legal and ethical concerns. Since 1998, WHO has produced evidence-based vaccine position papers for use primarily by national public health officials and immunization programme managers. Since April 2006 all new or updated position papers have been based on SAGE recommendations. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach has been adopted by WHO and, since 2008, GRADE tables that rate the quality of evidence have been produced in support of key recommendations. SAGE previously expressed concern that GRADE was not ideally suited to many immunization-specific issues such as the vaccine population level effect and the inclusion of surveillance system data, particularly for vaccine safety. Extensive productive interactions with various advisory groups including the US Advisory Committee on Immunization Practices, the European Centres for Disease Control, the German Standing Committee on Vaccination (STIKO), WHO's Global Advisory Committee on Vaccine Safety and the GRADE working group resulted in key enhancements to accommodate vaccine-relevant evidence. This facilitated integration and acceptability of the GRADE approach in the development of immunization related SAGE and WHO recommendations. Ongoing utilisation should result in further fine-tuning of the approach to ensure that recommendations are based on the full range of appropriate evidence.Vaccine 03/2012; 31(1). DOI:10.1016/j.vaccine.2012.02.041 · 3.49 Impact Factor
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ABSTRACT: Background. Influenza infection is a major public health burden worldwide. Available vaccines include the inactivated intramuscular trivalent vaccine and, more recently, a live attenuated intranasal vaccine (LAIV). The measure of successful vaccination with the inactivated vaccine is a systemic rise in IgG but for the LAIV no such correlate has been established.Methods. Seventy nine subjects were given the live, attenuated intranasal influenza vaccine FluMist. Blood was collected prior to vaccination and 3 days and 30 days post-vaccine. Nasal wash was collected 3 days and 30 days post-vaccine. Responses were measured systemically and in mucosal secretions for cytokines, cell activation profiles and antibody responses.Results. Only 9% of subjects who received LAIV seroconverted, while 33% of patients developed at least a two-fold increase in influenza specific IgA antibodies in nasal wash. LAIV induced a localized inflammation as suggested by increased expression of interferon response genes in mucosal RNA and increased G-CSF and IP10 in nasal wash. Interestingly, patients who seroconverted had significantly lower pre-vaccine serum G-CSF.Conclusions. Protection by LAIV is likely provided through mucosal IgA and not by increases in systemic IgG. LAIV induces local inflammation. Seroconversion is achieved in a small fraction of subjects with lower serum G-CSF.The Journal of Infectious Diseases 10/2012; DOI:10.1093/infdis/jis641 · 5.78 Impact Factor