Title:
Estimation of outbreak severity and transmissibility: Influenza A(H1N1)pdm09 in households.

Abstract:
When an outbreak of a novel pathogen occurs, some of the most pressing questions from a public-health point of view relate to its transmissibility, and the probabilities of different clinical outcomes following infection, to allow an informed response. Estimates of these quantities are often based on household data due to the high potential for transmission in this setting, but typically a rich spectrum of individual-level outcomes (from uninfected to serious illness) are simplified to binary data (infected or not). We address the added benefit from retaining the heterogeneous outcome information in the case of the 2009-10 influenza pandemic, which posed particular problems for estimation of key epidemiological characteristics due to its relatively mild nature and hence low case ascertainment rates.
We use mathematical models of within-household transmission and case ascertainment, together with Bayesian statistics to estimate transmission probabilities stratified by household size, the variability of infectiousness of cases, and a set of probabilities describing case ascertainment. This novel approach was applied to data we collected from the early "containment phase" stage of the epidemic in Birmingham, England. We also conducted a comprehensive review of studies of household transmission of influenza A(H1N1)pdm09.
We find large variability in the published estimates of within-household transmissibility of influenza A(H1N1)pdm09 in both model-based studies and those reporting secondary attack rates, finding that these estimates are very sensitive to how an infected case is defined. In particular, we find that reliance on laboratory confirmation alone underestimates the true number of cases, while utilising the heterogeneous range of outcomes (based on case definitions) for household infections allows a far more comprehensive pattern of transmission to be elucidated.
Differences in household sizes and how cases are defined could account for an appreciable proportion of the reported variability of within-household transmissibility of influenza A(H1N1)pdm09. Retaining and statistically analysing the full spectrum of individual-level outcomes (based on case definitions) rather than taking a potentially arbitrary threshold for infection, provides much-needed additional information. In a future pandemic, our approach could be used as a real-time analysis tool to infer the true number of cases, within-household transmission rates and levels of case ascertainment.