流感感染剂量可能解释了 1918-1919 年流感大流行的第二波和第三波高死亡率的原因。
Influenza infectious dose may explain the high mortality of the second and third wave of 1918-1919 influenza pandemic.
机构信息
Life and Health Sciences Research Institute, School of Health Sciences, Universidade do Minho, Braga, Portugal.
出版信息
PLoS One. 2010 Jul 26;5(7):e11655. doi: 10.1371/journal.pone.0011655.
BACKGROUND
It is widely accepted that the shift in case-fatality rate between waves during the 1918 influenza pandemic was due to a genetic change in the virus. In animal models, the infectious dose of influenza A virus was associated to the severity of disease which lead us to propose a new hypothesis. We propose that the increase in the case-fatality rate can be explained by the dynamics of disease and by a dose-dependent response mediated by the number of simultaneous contacts a susceptible person has with infectious ones.
METHODS
We used a compartment model with seasonality, waning of immunity and a Holling type II function, to model simultaneous contacts between a susceptible person and infectious ones. In the model, infected persons having mild or severe illness depend both on the proportion of infectious persons in the population and on the level of simultaneous contacts between a susceptible and infectious persons. We further allowed for a high or low rate of waning immunity and volunteer isolation at different times of the epidemic.
RESULTS
In all scenarios, case-fatality rate was low during the first wave (Spring) due to a decrease in the effective reproduction number. The case-fatality rate in the second wave (Autumn) depended on the ratio between the number of severe cases to the number of mild cases since, for each 1000 mild infections only 4 deaths occurred whereas for 1000 severe infections there were 20 deaths. A third wave (late Winter) was dependent on the rate for waning immunity or on the introduction of new susceptible persons in the community. If a group of persons became voluntarily isolated and returned to the community some days latter, new waves occurred. For a fixed number of infected persons the overall case-fatality rate decreased as the number of waves increased. This is explained by the lower proportion of infectious individuals in each wave that prevented an increase in the number of severe infections and thus of the case-fatality rate.
CONCLUSION
The increase on the proportion of infectious persons as a proxy for the increase of the infectious dose a susceptible person is exposed, as the epidemic develops, can explain the shift in case-fatality rate between waves during the 1918 influenza pandemic.
背景
人们普遍认为，1918 年流感大流行期间两次浪潮之间病死率的变化归因于病毒的遗传变化。在动物模型中，流感 A 病毒的感染剂量与疾病的严重程度相关，这使我们提出了一个新的假设。我们假设，病死率的增加可以通过疾病的动态变化和易感者与感染者同时接触的数量的剂量依赖性反应来解释。
方法
我们使用了一个具有季节性、免疫衰减和 Holling 型 II 功能的 compartment 模型，来模拟易感者与感染者之间的同时接触。在该模型中，感染轻度或重度疾病的人既取决于人群中感染人数的比例，也取决于易感者与感染者同时接触的水平。我们还允许在流行的不同时间内具有高或低的免疫衰减率和志愿者隔离。
结果
在所有情况下，由于有效繁殖数的减少，第一波（春季）的病死率都较低。第二波（秋季）的病死率取决于严重病例数与轻度病例数的比例，因为每 1000 例轻度感染中仅发生 4 例死亡，而每 1000 例严重感染中有 20 例死亡。第三波（冬末）取决于免疫衰减率或社区中新的易感者的引入。如果一组人自愿隔离并在几天后返回社区，则会出现新的浪潮。对于固定数量的感染者，随着波数的增加，总体病死率会降低。这是因为在每一波中，传染性个体的比例较低，从而防止了严重感染数量的增加，进而降低了病死率。
结论
随着流行的发展，传染性个体比例的增加可以作为暴露于易感者的感染剂量增加的指标，这可以解释 1918 年流感大流行期间两次浪潮之间病死率的变化。
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