Detecting Emerging Transmissibility of Avian Influenza Virus in Human Households

Michiel van Boven1,2*, Marion Koopmans3, miRNA Du Ry van Beest Holle3, Adam Meijer3, Don Klinkenberg1, Christl A. Donnelly4, Hans (J. A. P.) Heesterbeek1

1 Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands, 2 Animal Sciences Group, Wageningen University and Research Centre, Lelystad, The Netherlands, 3 Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands, 4 Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom

Accumulating infections of highly pathogenic H5N1 avian influenza in humans underlines the need to track the ability of these viruses to spread among humans. A human-transmissible avian influenza virus is expected to cause clusters of infections in humans living in close contact. Therefore, epidemiological analysis of infection clusters in human households is of key importance. Infection clusters may arise from transmission events from (i) the animal reservoir, (ii) humans who were infected by animals (primary human-to-human transmission), or (iii) humans who were infected by humans (secondary human-to-human transmission). Here we propose a method of analysing household infection data to detect changes in the transmissibility of avian influenza viruses in humans at an early stage. The method is applied to an outbreak of H7N7 avian influenza virus in The Netherlands that was the cause of more than 30 human-to-human transmission events. The analyses indicate that secondary human-to-human transmission is plausible for the Dutch household infection data. Based on the estimates of the within-household transmission parameters, we evaluate the effectiveness of antiviral prophylaxis, and conclude that it is unlikely that all household infections can be prevented with current antiviral drugs. We discuss the applicability of our method for the detection of emerging human-to-human transmission of avian influenza viruses in particular, and for the analysis of within-household infection data in general.

Received: March 26, 2007; Accepted: June 6, 2007; Published: July 27, 2007

 Figure 1.Maximum Likelihood Estimates of the Transmission Rate Parameters for the Model 3A (Top Panel) and Model 3B (Bottom Panel) Described in the Text (Black Dots), with Contours of the 90%, 95%, and 99% Confidence Areas

The maximum likelihood parameter estimates of models that exclude secondary human-to-human transmission (β*₂₂ = 0, models 1A and 1B), and that assume equal primary and secondary human-to-human transmission (β*₂₂ = β*₂₁, models 2A and 2B), are also indicated (grey dots).