Network Analysis of Global Influenza Spread

Chan J, Holmes A, Rabadan R. Network Analysis of Global Influenza Spread. PLoS Comput Biol, 2010: 6(11): e1001005. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987833/

Abstract

Although vaccines pose the best means of preventing influenza infection, strain selection and optimal implementation remain difficult due to antigenic drift and a lack of understanding global spread. Detecting viral movement by sequence analysis is complicated by skewed geographic and seasonal distributions in viral isolates. We propose a probabilistic method that accounts for sampling bias through spatiotemporal clustering and modeling regional and seasonal transmission as a binomial process. Analysis of H3N2 not only confirmed East-Southeast Asia as a source of new seasonal variants, but also increased the resolution of observed transmission to a country level. H1N1 data revealed similar viral spread from the tropics. Network analysis suggested China and Hong Kong as the origins of new seasonal H3N2 strains and the United States as a region where increased vaccination would maximally disrupt global spread of the virus. These techniques provide a promising methodology for the analysis of any seasonal virus, as well as for the continued surveillance of influenza.

Author Summary

As evidenced by several historic vaccine failures, the design and implementation of the influenza vaccine remains an imperfect science. The virus's rapid rate of evolution makes the selection of representative strains for vaccine composition a difficult process. From a global health viewpoint, how to optimally implement a limited stockpile of vaccines is another fundamental question that remains unanswered. An understanding of how influenza spreads around the world would greatly aid the design and implementation process, but regional and seasonal bias in collected virus samples hampers epidemiologic analysis. Here, we show that it is possible to counter this data bias through probabilistic modeling and represent the global viral spread as a network of seeding events between different regions of the world. On a local scale, our technique can output the most likely origins of a virus circulating in a given location. On a global scale, we can pinpoint regions of the world that would maximally disrupt viral transmission with an increase in vaccine implementation. We demonstrate our method on seasonal H3N2 and H1N1 and foresee similar application to other seasonal viruses, including swine-origin H1N1, once more seasonal data is collected.