skip to primary navigationskip to content

WHO Collaborating Centre

for Modelling, Evolution and Control of Emerging Infectious Diseases

Studying at Cambridge


Influenza H5N1

Risk analysis – how far away are we from an aerosol transmissible A/H5N1 influenza virus?

H5N1 phylogenetic treeProfessor Derek Smith and Dr Colin Russell from the Centre for Pathogen Evolution explain how their research provides insight into the feasibility of  of the H5N1 virus becoming aerosol transmissible.

Since 1997, influenza A(H5N1) virus, or ‘bird flu’, has infected over 1,000 people, killing ~60% of them. However, even with all of these infections the virus has not been seen to transmit between humans – almost all cases have been of individuals in close contact with infected birds. Does this mean the virus is incapable of human to human transmission?

In 2012, two papers by the Fouchier and Kawaoka groups revealed that potentially as few as five mutations (amino acid substitutions) in avian H5N1 were necessary to create a strain of H5N1 that could transmit through the air between ferrets, and thus potentially among humans.

A key question is: could such a virus evolve in nature? If so, how soon would such a virus evolve? We performed an analysis of all the available influenza A(H5N1) virus surveillance data, and found that there are viruses that have recently circulated in birds that might require only three additional substitutions to become mammal-to-mammal transmissible.

We then developed a mathematical model of within-host virus evolution to study factors that could increase and decrease the probability of the remaining substitutions evolving after the virus has infected a mammalian host. Our work suggested that it is possible for a mammal-to-mammal transmissible A(H5N1) virus to evolve within a single mammalian host and highlighted critical areas of research in which more data are needed for further refining this risk assessment, and potentially averting this threat.

This risk analysis was published in Science and used by the WHO and US and Dutch governments in critical security decisions related to the original findings.


Russell CA, Fonville JM, Brown AE, Burke DF, Smith DL, James SL, Herfst S, van Boheemen S, Linster M, Schrauwen EJ, Katzelnick L, Mosterín A, Kuiken T, Maher E, Neumann G, Osterhaus AD, Kawaoka Y, Fouchier RA, Smith DJ. The potential for respiratory droplet-transmissible A/H5N1 influenza virus to evolve in a mammalian host.Science 22 June 2012: Vol. 336 no. 6088 pp. 1541-1547