Health and Economic Benefits of Early Vaccination and Nonpharmaceutical Interventions for a Human Influenza A (H7N9) Pandemic: A Modeling Study.
Harvard University, Cambridge, Massachusetts, United StatesAnnals of internal medicine (Impact Factor: 17.81). 05/2014; 160(10):684-94. DOI: 10.7326/M13-2071
Background: Vaccination for the 2009 pandemic did not occur until late in the outbreak, which limited its benefits. Influenza A (H7N9) is causing increasing morbidity and mortality in China, and researchers have modified the A (H5N1) virus to transmit via aerosol, which again heightens concerns about pandemic influenza preparedness. Objective: To determine how quickly vaccination should be completed to reduce infections, deaths, and health care costs in a pandemic with characteristics similar to influenza A (H7N9) and A (H5N1). Design: Dynamic transmission model to estimate health and economic consequences of a severe influenza pandemic in a large metropolitan city. Data Sources: Literature and expert opinion. Target Population: Residents of a U. S. metropolitan city with characteristics similar to New York City. Time Horizon: Lifetime. Perspective: Societal. Intervention: Vaccination of 30% of the population at 4 or 6 months. Outcome Measures: Infections and deaths averted and cost-effectiveness. Results of Base-Case Analysis: In 12 months, 48 254 persons would die. Vaccinating at 9 months would avert 2365 of these deaths. Vaccinating at 6 months would save 5775 additional lives and $51 million at a city level. Accelerating delivery to 4 months would save an additional 5633 lives and $50 million. Results of Sensitivity Analysis: If vaccination were delayed for 9 months, reducing contacts by 8% through nonpharmaceutical interventions would yield a similar reduction in infections and deaths as vaccination at 4 months. Limitation: The model is not designed to evaluate programs targeting specific populations, such as children or persons with comorbid conditions. Conclusion: Vaccination in an influenza A (H7N9) pandemic would need to be completed much faster than in 2009 to substantially reduce morbidity, mortality, and health care costs. Maximizing nonpharmaceutical interventions can substantially mitigate the pandemic until a matched vaccine becomes available.
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ABSTRACT: Entry inhibitors are of particular importance in current efforts to develop a new generation of anti-influenza virus drugs. Here we report certain pentacyclic triterpenes exhibiting conserved structure features and with in vitro anti-influenza virus activity comparable to and even higher than that of oseltamivir. Mechanistic studies indicated that these lead triterpenoids bind tightly to the viral envelope hemagglutinin (HA), disrupting the interaction of HA with the sialic acid receptor and thus the attachment of viruses to host cells. Docking studies suggest that the binding pocket within HA for sialic acid receptor potentially acts as a targeting domain, and this is supported by structure-activity data, sialic acid competition studies and broad anti-influenza spectrum as well as less induction of drug resistance. Our study might establish the importance of triterpenoids for development of entry inhibitors of influenza viruses.
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ABSTRACT: Avian influenza virus (AIV) is an important zoonotic pathogen, resulting in global human morbidity and mortality and substantial economic losses to the poultry industry. Poultry and wild birds have transmitted AIV to humans, most frequently subtypes H5 and H7, but also different strains and subtypes of H6, H9, and H10. Determining which birds are AIV reservoirs can help identify human populations that have a high risk of infection with these viruses due to occupational or recreational exposure to the reservoir species. To assess the prevalence of AIV in tropical birds, from 2010 to 2014, we sampled 40 099 birds at 32 sites in Central Africa (Cameroon, Central African Republic, Congo-Brazzaville, Gabon) and West Africa (Benin, Côte d'Ivoire, Togo). In Central Africa, detection rates by real-time RT–PCR were 16·6% in songbirds (eight passerine families, n = 1257), 16·4% in kingfishers (family Alcedinidae, n = 73), 8·2% in ducks (family Anatidae, n = 564), and 3·65% in chickens (family Phasianidae, n = 1042). Public health authorities should educate human cohorts that have high exposure to these bird populations about AIV and assess their adherence to biosecurity practices, including Cameroonian farmers who raise small backyard flocks.
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