Section of Virology, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom.
PLoS One. 2012;7(8):e43303. doi: 10.1371/journal.pone.0043303. Epub 2012 Aug 29.
During the early phase of the 2009 influenza pandemic, attempts were made to contain the spread of the virus. Success of reactive control measures may be compromised if the proportion of transmission that occurs before overt clinical symptoms develop is high. In this study we investigated the timing of transmission of an early prototypic strain of pandemic H1N1 2009 influenza virus in the ferret model. Ferrets are the only animal model in which this can be assessed because they display typical influenza-like clinical signs including fever and sneezing after infection. We assessed transmission from infected animals to sentinels that were placed either in direct contact or in adjacent cages, the latter reflecting the respiratory droplet (RD) transmission route. We found that pre-symptomatic influenza transmission occurred via both contact and respiratory droplet exposure before the earliest clinical sign, fever, developed. Three of 3 animals exposed in direct contact between day 1 and 2 after infection of the donor animals became infected, and 2/3 of the animals exposed at this time period by the RD route acquired the infection, with the third animal becoming seropositive indicating either a low level infection or significant exposure. Moreover, this efficient transmission did not temporally correlate with respiratory symptoms, such as coughs and sneezes, but rather with the peak viral titre in the nose. Indeed respiratory droplet transmission did not occur late in infection, even though this was when sneezing and coughing were most apparent. None of the 3 animals exposed at this time by the RD route became infected and these animals remained seronegative at the end of the experiment. These data have important implications for pandemic planning strategies and suggest that successful containment is highly unlikely for a human-adapted influenza virus that transmits efficiently within a population.
在 2009 年流感大流行的早期阶段，人们曾试图控制病毒的传播。如果在明显的临床症状出现之前发生的传播比例较高，那么反应性控制措施的成功可能会受到影响。在这项研究中，我们调查了在雪貂模型中，早期原型大流行 H1N1 2009 流感病毒传播的时间。雪貂是唯一可以评估这种情况的动物模型，因为它们在感染后会表现出典型的流感样临床症状，包括发烧和打喷嚏。我们评估了来自感染动物的传播情况，这些动物被放置在直接接触或相邻笼子中，后者反映了呼吸道飞沫（RD）传播途径。我们发现，在出现最早的临床症状（发烧）之前，通过接触和呼吸道飞沫暴露，在出现症状前就已经发生了流感传播。在供体动物感染后第 1 天至第 2 天期间，3 只直接接触的动物中有 3 只被感染，在这个时间通过 RD 途径暴露的 2/3 动物也被感染，第 3 只动物血清阳性表明感染程度较低或暴露程度较大。此外，这种高效的传播与呼吸道症状（如咳嗽和打喷嚏）没有时间相关性，而是与鼻腔中的病毒载量峰值相关。实际上，即使在打喷嚏和咳嗽最明显的时候，RD 传播也不会在感染后期发生。在 RD 途径暴露的 3 只动物中，没有一只在这个时候被感染，这些动物在实验结束时仍保持血清阴性。这些数据对大流行规划策略具有重要意义，表明对于在人群中高效传播的人类适应流感病毒，成功控制的可能性非常小。
