ETIDIOH - NEW

  Abstract Intercontinental spread of highly pathogenic avian influenza A(H5N1) viruses poses significant pandemic risks and necessitates strong protective countermeasures . We evaluated the therapeutic efficacy of the neuraminidase inhibitor oseltamivir , the polymerase inhibitors baloxavir and favipiravir , and an ion-channel blocker amantadine , against severe influenza A( H5N1 ) virus infection in female BALB/c mice . Baloxavir (≥10 mg/kg, 1 dose) fully protected mice from death , significantly reduced virus respiratory replication, and prevented neuroinvasion . Oseltamivir (≥100 mg/kg/day for 5 days) provided limited survival benefits , reduced lung titers but failed to prevent viral neuroinvasion . Favipiravir (≥100 mg/kg/day for 5 days) provided partial protection , although did not reduce viral titers in lungs and brain . Amantadine provided no benefits . Although all drugs inhibited A(H5N1) viruses in vitro, in vivo correlations did not extend beyond baloxavir . Our result...

  Highlights •  Global Health Impact : Improved influenza vaccines have the potential to avert between 6.6 and 18 billion additional influenza cases, prevent 2.3 to 6.2 million additional deaths, and save 21 to 57 million disability-adjusted life years (DALYs) globally beyond those averted by current seasonal influenza vaccines •  Cost-Effectiveness : Depending on the price, coverage, and vaccine characteristics, improved influenza vaccines could be cost-effective in 9 to 48 % of countries, offering substantial global economic value under most scenarios •  Financial Viability : The development and commercialization of improved influenza vaccines present a robust financial value proposition, with positive net present value (NPV) across all vaccine profiles •  Policy and Decision Making : Vaccine efficacy, duration of protection, and breadth of protection are key factors influencing the adoption of improved influenza vaccines in national immunization programs •...