Hope-Simpson R E
J Hyg (Lond). 1979 Aug;83(1):11-26. doi: 10.1017/s002217240002578x.
The antigenic varieties of influenza A virus isolated from 1968 to 1976 in a surveillance of a small, rather remote population were similar to those from England and Wales as a whole, despite frequent antigenic changes during the period. Household studies in the first two H3N2 influenza A epidemics found low attack rates within households, a high proportion (70%) of affected households with only one case of influenza, similar distributions of affected households in the two epidemics by the number of cases of influenza and similar distributions of the influenza cases by the day of their onset in the household outbreak. No serial interval could be demonstrated by cumulating household outbreaks. More than one minor variant was causing influenza contemporaneously in the same villages in several seasons, and different variants were on one occasion found on successive days in bedfellows. The regular occurrence of epidemics in winter was often accompanied by the disappearance of the epidemic variants and their replacement, after a virus-free interval, by new variants. These epidemiological findings seem best interpreted on the following tentative hypothesis. Influenza A sufferers do not transmit the virus during their illness; instead it rapidly becomes latent in their tissues so that they become symptomless carrier-hosts and develop specific immunity. Next season an extraneous seasonally mediated stimulus reactivates the latent virus residues so that the carrier-host becomes briefly infectious, though symptomless. Antigenic drift occurs because particles reconstituted to be identical with the progenitor virus cannot escape the specific immunity it has provoked in the carrier host. He can shed only mutants also determined by the progenitor virus. From the assortment of mutants shed by the carrier-host, his non-immune companions select that (those) which is best fitted to survive, and it rapidly causes influenzal illness. Epidemics consist largely or entirely of such persons sick with influenza caused by reactivated virus caught from symptomless carrier-hosts.
在对一个规模较小且相对偏远的人群进行监测期间(1968年至1976年)分离出的甲型流感病毒抗原变种,与整个英格兰和威尔士的变种相似,尽管在此期间抗原频繁发生变化。在前两次H3N2甲型流感流行期间进行的家庭研究发现,家庭内发病率较低,受影响家庭中70%仅有一例流感病例,两次流行中受影响家庭按流感病例数的分布相似,且家庭暴发中流感病例按发病日的分布也相似。通过累积家庭暴发情况无法证明有连续间隔。在几个季节里,同一个村庄有不止一种 minor 变种同时引发流感,而且有一次在同床者中连续两天发现了不同的变种。冬季流感的定期暴发常常伴随着流行变种的消失,在无病毒间隔期后,被新的变种所取代。这些流行病学发现似乎可以根据以下初步假说来得到最好的解释。甲型流感患者在患病期间不会传播病毒;相反,病毒会在他们的组织中迅速潜伏,使他们成为无症状的携带宿主并产生特异性免疫力。在下个季节,一种由季节介导的外部刺激会重新激活潜伏的病毒残余物,使携带宿主短暂具有传染性,尽管没有症状。抗原漂移的发生是因为重新组装成与亲代病毒相同的颗粒无法逃脱它在携带宿主中引发的特异性免疫。他只能排出同样由亲代病毒决定的突变体。从携带宿主排出的突变体中,他未免疫的同伴选择最适合存活的那种(那些),而它会迅速引发流感疾病。流感流行很大程度上或完全由从无症状携带宿主感染的重新激活病毒引起的流感患者组成。