Seasonal transmission potential and activity peaks of the new influenza A(H1N1): a Monte Carlo likelihood analysis based on human mobility
Authors: Balcan Duygu , Hu Hao , Goncalves Bruno , Bajardi Paolo , Poletto Chiara , Ramasco Jose J , Paolotti Daniela , Perra Nicola , Tizzoni Michele , Van den Broeck Wouter , Colizza Vittoria , Vespignani Alessandro 
Published: September 2009

Abstract

Background
On 11 June the World Health Organization officially raised the phase of pandemic alert (with regard to the new H1N1 influenza strain) to level 6. As of 19 July, 137,232 cases of the H1N1 influenza strain have been officially confirmed in 142 different countries, and the pandemic unfolding in the Southern hemisphere is now under scrutiny to gain insights about the next winter wave in the Northern hemisphere. A major challenge is pre-empted by the need to estimate the transmission potential of the virus and to assess its dependence on seasonality aspects in order to be able to use numerical models capable of projecting the spatiotemporal pattern of the pandemic.

Methods
In the present work, we use a global structured metapopulation model integrating mobility and transportation data worldwide. The model considers data on 3,362 subpopulations in 220 different countries and individual mobility across them. The model generates stochastic realizations of the epidemic evolution worldwide considering 6 billion individuals, from which we can gather information such as prevalence, morbidity, number of secondary cases and number and date of imported cases for each subpopulation, all with a time resolution of 1 day. In order to estimate the transmission potential and the relevant model parameters we used the data on the chronology of the 2009 novel influenza A(H1N1). The method is based on the maximum likelihood analysis of the arrival time distribution generated by the model in 12 countries seeded by Mexico by using 1 million computationally simulated epidemics. An extended chronology including 93 countries worldwide seeded before 18 June was used to ascertain the seasonality effects.

Results
We found the best estimate R
0 = 1.75 (95% confidence interval (CI) 1.64 to 1.88) for the basic reproductive number. Correlation analysis allows the selection of the most probable seasonal behavior based on the observed pattern, leading to the identification of plausible scenarios for the future unfolding of the pandemic and the estimate of pandemic activity peaks in the different hemispheres. We provide estimates for the number of hospitalizations and the attack rate for the next wave as well as an extensive sensitivity analysis on the disease parameter values. We also studied the effect of systematic therapeutic use of antiviral drugs on the epidemic timeline.

Conclusion
The analysis shows the potential for an early epidemic peak occurring in October/November in the Northern hemisphere, likely before large-scale vaccination campaigns could be carried out. The baseline results refer to a worst-case scenario in which additional mitigation policies are not considered. We suggest that the planning of additional mitigation policies such as systematic antiviral treatments might be the key to delay the activity peak in order to restore the effectiveness of the vaccination programs.