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Volume 24, Number 6—June 2018

Ferrets as Models for Influenza Virus Transmission Studies and Pandemic Risk Assessments

Jessica A. BelserComments to Author , Wendy Barclay, Ian Barr, Ron A.M. Fouchier, Ryota Matsuyama, Hiroshi Nishiura, Malik Peiris, Charles J. Russell, Kanta Subbarao, Huachen Zhu, and Hui-Ling YenComments to Author 
Author affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA (J.A. Belser); Imperial College, London, UK (W. Barclay); Doherty Institute, Melbourne, Victoria, Australia (I. Barr, K. Subbarao); Erasmus Medical Center, Rotterdam, the Netherlands (R.A.M. Fouchier); Hokkaido University, Sapporo, Japan (R. Matsuyama, H. Nishiura); The University of Hong Kong, Hong Kong, China (M. Peiris, H. Zhu, H.-L. Yen); St. Jude Children's Research Hospital, Memphis, Tennessee, USA (C.J. Russell)

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Table 2

Features that may be conductive to uniform, reproducible risk-assessment transmission setups when using ferrets as models for for influenza virus transmission studies and pandemic risk assessments*

Property Rationale Sample phrasing Perceived importance
Donor:recipient ratio of 1:1
Improved statistical rigor, potential application for meta-analysis, and interpretation of results. The number of donor:recipient pairs housed inside containment with shared ventilation should be reported.
“Inoculated ferrets (n = 3) were each placed in a separate cage; 24 hours later, naïve ferrets (n = 3) were each placed in a different cage adjacent to an inoculated ferret.”
Seronegative ferrets
Prior influenza virus exposure history can be difficult to quantify and control. The methods used for assessing prior exposure should be disclosed.
“Ferrets were serologically negative to currently circulating influenza A (H1N1 and H3N2) and B viruses before challenge, as confirmed by HI assay.”
Harmonization of ventilation and environmental conditions
ACH, directional airflow, cage design, humidity/temperature information are reported concurrent with release of results.
“Ferrets were housed for the duration of the experiment in an environmental chamber with HEPA filtration operating at 20 ACH. Airflow velocity was found to be negligible between donor and recipient cages. Ambient temperature (20°–22°C) and relative humidity (40%) were monitored during the experiment.”
Uniform definition of efficient transmissibility
Virus titers (with detection limit) and seroconversion are both required to demonstrate robust transmission event.
“Virus transmissibility was confirmed by detection of infectious virus and by seroconversion to homologous virus in recipient ferrets.”
Dose, volume, and route of inoculation
Dose of inoculum may affect the transmission kinetics (22). A consensus within the risk-assessment group may be beneficial.
“Ferrets were inoculated by the intranasal route with 106 PFU of virus in a volume of 500 μL”
Application of air sampling device to determine the size and quantity of virus-laden particles in air The results may help correlate and refine the transmission phenotype. “Variables were inclusive of vendor, duration of sampling, specification of collection matrices (buffers, gelatin[s], etc.), specification of virus confirmation via PCR and/or live virus detection, normalization correction of data (if applicable).” Intermediate

*Discussed at workshop held June 22, 2017, ancillary to Transmission of Respiratory Viruses conference held on June 19–21, 2017, in Hong Kong, China (20). ACH, air changes per hour; HEPA, high-efficiency particulate air.

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Page created: May 18, 2018
Page updated: May 18, 2018
Page reviewed: May 18, 2018
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