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.
Med Hypotheses. 2010 Apr;74(4):681-4. doi: 10.1016/j.mehy.2009.10.050. Epub 2009 Dec 4.
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.
目前对于 1918-1919 年高死亡率的解释要么涉及病毒的更高致病性，要么涉及在缺乏足够治疗资源的情况下细菌的超级感染。然而，这些假设都无法解释严重病例和死亡的年龄分布，也无法解释大流行期间死亡率的地理和其他变化以及爆发的速度。本文将表明，相反，流感致死率的流行病学可以通过两个决定因素的组合来完全解释：（1）通过母体或生命早期流感感染的发育表观遗传适应（和选择），在人群内使出生队列获得免疫分化；（2）触发环境——新亚型/菌株的出现及其与过去流行的免疫相关的季节性病毒共同循环（竞争？），并使特定人群的出生队列处于免疫致敏状态。本文（1）提出了 1918-1919 年和 2009 年流感严重性的年龄、地理和时间变化，（2）提出并讨论了支持这里提出的流感致死率假设的生态学证据，（3）提出了能够解释它的生物学机制，（4）回顾性地提出大流行期间第二波增加的致死率的背景是大流行期间与 1918 年季节性（H3？）流感病毒的共同循环，以及（5）预测随着 2009-2010 季节的推进和 H3 循环的增加，北半球流感严重程度的增加。
