Accumulation of polymorphonuclear neutrophils (PMN) into the subarachnoidal space is one of the hallmarks of

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The present report explores the role of nitric oxide into the immune response against Neisseria meningitidis serogroup B. Here we show that NO mediates the alphaTNF increase induced by N. meningitidis derived lipopolysaccharides (LPS), at the same time that participates in the bactericidal activity of resting or gammaIFN activated macrophages and plays a role in the specific DTH and IgG response induced by a commercial anti-meningococcal vaccine. Our findings suggest a positive role for NO at the final effector mechanisms and in the early events driving the immunity against N. meningitidis, suggesting also an insight into its role in endotoxic shock.

Objectives: To assess the cost-effectiveness of quadrivalent influenza vaccine (QIV) compared to trivalent vaccine (TIV) in the Italian population aged 65 years or more or at high-risk for influenza. MethOds: A static and multi-cohort Markov model was modified to simulate the disease process of influenza (type A and B) over a lifetime horizon using annual cycles. Several cohorts based on the Italian population (nine different age-groups and two level of risks: high and low) entered the model and could be vaccinated with QIV or TIV. Vaccine coverage rate, epidemiological and demographic estimates were taken from local statistics, surveillance data and Italian published studies, while circulation of type A versus B virus and type of lineage was taken from Euroflu estimates (from 2003-2004 to 2012-2013). Vaccine efficacy against influenza A and B were taken from 2 meta-analyses of clinical trials. Costs and resource use were based on local tariffs and published estimates (price year 2013). Quality of life scores were obtained from a Spanish study, using the EQ-5D questionnaire. The perspective of the National Health Service (NHS) was used and a 3% discount rate was applied to costs and benefits, according to Italian guidelines. To deal with the issue of uncertainty both deterministic and probabilistic sensitivity analyses were conducted. Results: In the basecase, the incremental cost per QALY and per LY saved for QIV versus TIV were € 10,940 and € 9,452, respectively. The most sensitive parameters were vaccine efficacy and probability of circulation of virus A versus B, but the probabilistic analysis showed that at a threshold of € 50,000 per QALY, there was about 90% probability for QIV to be cost-effective. cOnclusiOns: This study suggests that the introduction of QIV at the same level of price of the most recent adjuvated vaccines is likely to be a cost-effective strategy from the perspective of the Italian NHS.