The recently licensed quadrivalent seasonal influenza vaccine (QIV) may provide better protection than the traditional trivalent influenza vaccine (TIV) as it includes one more influenza B strain. We developed a Monte Carlo simulation model to determine the economic value of a QIV compared to the TIV for 10 influenza seasons (1999-2009). The addition of the influenza B strain to convert the TIV into a QIV could result in substantial cost savings to society (median of $3.1 billion) and third party payers (median of $292 million), even when the cost of QIV is significantly higher.
"Reed et al.  and Lee et al. , respectively evaluated the relative public health and economic impact of IIV4 compared to IIV3 on the US population. The researchers concluded that IIV4 can offer a health and economic benefit over IIV3 even if IIV4 was priced at a moderate premium . These studies, however, were not age stratified and it was not clear what the impact would be on US seniors. "
[Show abstract][Hide abstract] ABSTRACT: Objectives:
Seniors are particularly vulnerable to complications resulting from influenza infection. Numerous influenza vaccines are available to immunize US seniors, and practitioners must decide which product to use. Options include trivalent and quadrivalent standard-dose inactivated influenza vaccines (IIV3 and IIV4 respectively), as well as a high-dose IIV3 (HD). Our research examines the public health impact, budget impact, and cost-utility of HD versus IIV3 and IIV4 for immunization of US seniors 65 years of age and older.
Our model was based on US influenza-related health outcome data. Health care costs and vaccine prices were obtained from the Centers for Medicare and Medicaid Services. Efficacies of IIV3 and IIV4 were estimated from various meta-analyses of IIV3 efficacy. The results of a head-to-head randomized controlled trial of HD vs. IIV3 were used to estimate relative efficacy of HD. Conservatively, herd protection was not considered.
Compared to IIV3, HD would avert 195,958 cases of influenza, 22,567 influenza-related hospitalizations, and 5423 influenza-related deaths among US seniors. HD generates 29,023 more Quality Adjusted Life Years (QALYs) and a net societal budget impact of $154 million. The Incremental Cost Effectiveness Ratio (ICER) for this comparison is $5299/QALY. 71% of the probabilistic sensitivity analysis (PSA) simulations were <$100,000/QALY. Compared to IIV4, HD would avert 169,257 cases of influenza, 21,222 hospitalizations and 5212 deaths. HD generates 27,718 more QALYs and a net societal budget impact of -$17 million and as such dominates IIV4. For this comparison, 81% of PSA simulations were <$100,000/QALY.
HD is expected to achieve significant reductions in influenza-related morbidity and mortality. Further, HD is a cost effective alternative to both IIV3 and IIV4 in seniors. Our conclusions were robust in the face of sensitivity analyses.
"Concern, however, has been growing, as two lineages of influenza B (Yamagata and Victoria) have been co-circulating in the human population [7,9]. This has led to a novel formulation of a quadrivalent vaccine: against two strains of influenza A and two strains of influenza B [10,11], rather than the previous trivalent vaccine. "
[Show abstract][Hide abstract] ABSTRACT: Influenza B and C are single-stranded RNA viruses that cause yearly epidemics and infections. Knowledge of RNA secondary structure generated by influenza B and C will be helpful in further understanding the role of RNA structure in the progression of influenza infection.
All available protein-coding sequences for influenza B and C were analyzed for regions with high potential for functional RNA secondary structure. On the basis of conserved RNA secondary structure with predicted high thermodynamic stability, putative structures were identified that contain splice sites in segment 8 of influenza B and segments 6 and 7 of influenza C. The sequence in segment 6 also contains three unused AUG start codon sites that are sequestered within a hairpin structure.
When added to previous studies on influenza A, the results suggest that influenza splicing may share common structural strategies for regulation of splicing. In particular, influenza 3[prime] splice sites are predicted to form secondary structures that can switch conformation to regulate splicing. Thus, these RNA structures present attractive targets for therapeutics aimed at targeting one or the other conformation.
BMC Research Notes 01/2014; 7(1):22. DOI:10.1186/1756-0500-7-22
"Influenza B also differs from influenza A by having a lower mutation rate and fewer antigenic serotypes . Though its lack of antigenic diversity bars pandemic outbreaks, influenza B contributes to seasonal occurrences of influenza, which can result in serious infections costing thousands of lives and billions of dollars [4,5]. Influenza B has been of increasing concern lately, due to the rise in circulation of two distinct lineages of the virus: Victoria and Yamagata, which stimulated the recent switch from a trivalent vaccine (against one influenza B and two influenza A serotypes) to a quadrivalent vaccine including both influenza B serotypes [6,7]. The viral genome is comprised of eight negative sense, or (−)RNA, segments. "
[Show abstract][Hide abstract] ABSTRACT: Influenza A virus contributes to seasonal epidemics and pandemics and contains Global Ordered RNA structure (GORS) in the nucleoprotein (NP), non-structural (NS), PB2, and M segments. A related virus, influenza B, is also a major annual public health threat, but unlike influenza A is very selective to human hosts. This study extends the search for GORS to influenza B.
A survey of all available influenza B sequences reveals GORS in the (+) and (--)RNAs of the NP, NS, PB2, and PB1 gene segments. The results are similar to influenza A, except GORS is observed for the M1 segment of influenza A but not for PB1. In general, the folding free energies of human-specific influenza B RNA segments are less stable than allowable by the encoded amino acid sequence. This is consistent with findings in influenza A, where human-specific influenza RNA folds are less stable than avian and swine strains.
These results reveal fundamental molecular similarities and differences between Influenza A and B and suggest a rational basis for choosing segments to target with therapeutics and for viral attenuation for live vaccines by altering RNA folding stability.
BMC Research Notes 08/2013; 6(1):330. DOI:10.1186/1756-0500-6-330
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