title: A parsimonious hypothesis to the cause of influenza lethality and its variations in 1918-1919 and 2009.
abstract: Current explanations to the high 1918-1919 mortality involve either a higher pathogenicity of the virus or bacterial super-infection in the absence of adequate therapeutic resources. However, neither of these hypotheses accounts for the age-distribution of severe cases and deaths, or for the geographic and other variations in rates and explosiveness of mortality during the Pandemic. It will be shown here that, alternatively, the epidemiology of the influenza lethality could be completely explained by a combination of two determinants: (1) acquired immune-differentiation of birth-cohorts, within populations, through developmental epigenetic adaptation (and selection) secondary to maternal or early-life episodes of influenza infection and (2) a triggering context - emergence of a new sub-type/strain, and its co-circulation (competition?) with seasonal viruses immunologically related to ones that had circulated in the past and primed particular population birth-cohorts. This article (1) presents age, geographic, and temporal variations in 1918-1919 and 2009 influenza severity, (2) presents and discusses ecologic evidence in favor of the hypothesis to influenza lethality advanced here, (3) suggests biologic mechanisms capable of explaining it, (4) retrospectively, proposes co-circulation between the Pandemic and a 1918 seasonal (H3?) influenza virus as the context for the increased lethality during the second wave of the 1918 Pandemic, and (5) predicts an increase in influenza severity in the northern hemisphere as the 2009-2010 season advances and H3 circulation increases.
authors: Department of Social Medicine, School of Medicine, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600, 4/420 Porto Alegre, 90035-003 Rio Grande do Sul, Brazil. miazambuja@terra.com.br
authors: M I
authors: MI
authors: Azambuja
mesh_terms: D017677:Age Distribution; D004196:Disease Outbreaks; D006801:Humans; D007252:Influenza Vaccines / Q000627:therapeutic use*; D007251:Influenza, Human / Q000150:complications* / Q000453:epidemiology / Q000401:mortality*; D018448:Models, Immunological; D009975:Orthomyxoviridae / Q000276:immunology; D012621:Seasons
chemical_list: D007252:Influenza Vaccines