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本文引用的文献

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Effect of an asparagine-to-serine mutation at position 294 in neuraminidase on the pathogenicity of highly pathogenic H5N1 influenza A virus.位置 294 的天冬酰胺到丝氨酸突变对高致病性 H5N1 流感 A 病毒致病性的影响。
J Virol. 2011 May;85(10):4667-72. doi: 10.1128/JVI.00047-11. Epub 2011 Mar 2.
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Viremia associated with fatal outcomes in ferrets infected with avian H5N1 influenza virus.感染禽流感 H5N1 病毒的雪貂中与致死结局相关的病毒血症。
PLoS One. 2010 Aug 12;5(8):e12099. doi: 10.1371/journal.pone.0012099.
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Development of a dose-response model for SARS coronavirus.严重急性呼吸综合征冠状病毒剂量反应模型的建立。
Risk Anal. 2010 Jul;30(7):1129-38. doi: 10.1111/j.1539-6924.2010.01427.x. Epub 2010 May 20.
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Severity of pneumonia due to new H1N1 influenza virus in ferrets is intermediate between that due to seasonal H1N1 virus and highly pathogenic avian influenza H5N1 virus.雪貂感染新型 H1N1 流感病毒所致肺炎的严重程度介於季节性 H1N1 病毒和高致病性禽流感 H5N1 病毒之间。
J Infect Dis. 2010 Apr 1;201(7):993-9. doi: 10.1086/651132.
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H5N1 influenza viruses: outbreaks and biological properties.H5N1 流感病毒：疫情爆发和生物学特性。
Cell Res. 2010 Jan;20(1):51-61. doi: 10.1038/cr.2009.124. Epub 2009 Nov 3.
6
Use of animal models to understand the pandemic potential of highly pathogenic avian influenza viruses.利用动物模型了解高致病性禽流感病毒的大流行潜力。
Adv Virus Res. 2009;73:55-97. doi: 10.1016/S0065-3527(09)73002-7.
7
Relative contributions of four exposure pathways to influenza infection risk.四种暴露途径对流感感染风险的相对贡献。
Risk Anal. 2009 Sep;29(9):1292-303. doi: 10.1111/j.1539-6924.2009.01253.x. Epub 2009 Jun 24.
8
Clinical features of human influenza A (H5N1) infection in Vietnam: 2004-2006.越南2004 - 2006年甲型H5N1流感病毒人间感染的临床特征
Clin Infect Dis. 2009 Jun 15;48(12):1639-46. doi: 10.1086/599031.
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Incorporating time postinoculation into a dose-response model of Yersinia pestis in mice.将接种后时间纳入小鼠中鼠疫耶尔森氏菌的剂量反应模型。
J Appl Microbiol. 2009 Sep;107(3):727-35. doi: 10.1111/j.1365-2672.2009.04248.x. Epub 2009 Mar 18.
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Time-dose-response models for microbial risk assessment.用于微生物风险评估的时间-剂量-反应模型。
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高致病性禽流感（H5N1）病毒感染的剂量-反应时间建模。

Dose-response time modelling for highly pathogenic avian influenza A (H5N1) virus infection.

机构信息

Department of Soil, Water and Environmental Science, The University of Arizona, Tucson, AZ 85721, USA.

出版信息

Lett Appl Microbiol. 2011 Oct;53(4):438-44. doi: 10.1111/j.1472-765X.2011.03128.x. Epub 2011 Aug 25.

DOI:10.1111/j.1472-765X.2011.03128.x
PMID:21790679
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7197897/
Abstract

AIMS

To develop time-dependent dose-response models for highly pathogenic avian influenza A (HPAI) of the H5N1 subtype virus.

METHODS AND RESULTS

A total of four candidate time-dependent dose-response models were fitted to four survival data sets for animals (mice or ferrets) exposed to graded doses of HPAI H5N1 virus using the maximum-likelihood estimation. A beta-Poisson dose-response model with the N(50) parameter modified by an exponential-inverse-power time dependency or an exponential dose-response model with the k parameter modified by an exponential-inverse time dependency provided a statistically adequate fit to the observed survival data.

CONCLUSIONS

We have successfully developed the time-dependent dose-response models to describe the mortality of animals exposed to an HPAI H5N1 virus. The developed model describes the mortality over time and represents observed experimental responses accurately.

SIGNIFICANCE AND IMPACT OF THE STUDY

This is the first study describing time-dependent dose-response models for HPAI H5N1 virus. The developed models will be a useful tool for estimating the mortality of HPAI H5N1 virus, which may depend on time postexposure, for the preparation of a future influenza pandemic caused by this lethal virus.

摘要

目的

开发高致病性禽流感（HPAI）H5N1 亚型病毒的时变剂量反应模型。

方法和结果

使用最大似然估计，将四个候选的时变剂量反应模型拟合到四个动物（小鼠或雪貂）暴露于不同剂量 HPAI H5N1 病毒的生存数据集中。N(50)参数通过指数倒数幂时间依赖性修正的β-泊松剂量反应模型或 k 参数通过指数倒数时间依赖性修正的指数剂量反应模型为观察到的生存数据提供了统计学上的充分拟合。

结论

我们成功地开发了时变剂量反应模型来描述暴露于高致病性禽流感 H5N1 病毒的动物的死亡率。所开发的模型描述了随时间的死亡率，并准确地代表了观察到的实验反应。

研究的意义和影响

这是第一项描述高致病性禽流感 H5N1 病毒的时变剂量反应模型的研究。所开发的模型将是一种有用的工具，可以估计由这种致命病毒引起的未来流感大流行期间，暴露后时间依赖的高致病性禽流感 H5N1 病毒的死亡率。