Quantifying viral pandemic potential from experimental transmission studies

Abstract

In an effort to avert future pandemics, surveillance studies aimed at identifying zoonotic viruses at high risk of spilling over into humans act to monitor the viral chatter at the animal-human interface. These studies are hampered, however, by the diversity of zoonotic viruses and the limited tools available to assess pandemic risk. Methods currently in use include the characterization of candidate viruses using in vitro laboratory assays and experimental transmission studies in animal models. However, transmission experiments yield relatively low-resolution outputs that are not immediately translatable to projections of viral dynamics at the level of a host population. To address this gap, we present an analytical framework to extend the use of measurements from experimental transmission studies to generate more quantitative risk assessments. Specifically, we use within-host viral titer data from index and contact animals to estimate parameters relevant to transmission, including an estimate of transmissibility. We then extended this model to estimate epidemiological parameters, such as the basic reproductive number and generation interval. To illustrate these approaches, we present them in the context of two influenza A virus (IAV) ferret transmission experiments: one using influenza A/California/07/2009 (Cal/2009) and one using influenza A/Hong Kong/1/1968 (Hong Kong/1968). Despite estimating broadly similar transmissibilities for Cal/2009 and Hong Kong/1968, we conclude that Cal/2009 has a higher pandemic potential. This difference in pandemic potential seems to be primarily driven by its more robust within-host replication. Our results critically depend on several assumptions, namely that the within-host viral dynamics in humans and those in the model animal used (here, ferrets) share quantitative similarities and that viral transmissibility between model animals reflects viral transmissibility between humans. The methods we present to assess relative pandemic risk across viral isolates can be used to improve quantitative risk assessment of other emerging viruses of pandemic concern. Author summaryPandemic viruses often originate in animal reservoirs. Surveillance studies at the animal-human interface try to identify which of the many viruses circulating in animals could cause a pandemic in humans. Experimental transmission studies in animal models are one such method used to characterize potential pandemic viruses. However, only simple outcomes usually get reported from these experiments, such as the fraction of animals that become infected in such an experiment. Here, we develop a framework to extract more information from these experiments. Specifically, we use data on the virus population within infected ferrets to extrapolate information about transmission. We then simulate many transmission events to estimate epidemiological parameters commonly used in public health to quantify pandemic potential. Our methods therefore allow us to use commonly gathered data from experimental transmission studies to estimate epidemic dynamics in humans. This set of methods can be used to compare the relative pandemic risk of animal viruses before they emerge in humans.