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      Real-time numerical forecast of global epidemic spreading: case study of 2009 A/H1N1pdm

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          Abstract

          Background

          Mathematical and computational models for infectious diseases are increasingly used to support public-health decisions; however, their reliability is currently under debate. Real-time forecasts of epidemic spread using data-driven models have been hindered by the technical challenges posed by parameter estimation and validation. Data gathered for the 2009 H1N1 influenza crisis represent an unprecedented opportunity to validate real-time model predictions and define the main success criteria for different approaches.

          Methods

          We used the Global Epidemic and Mobility Model to generate stochastic simulations of epidemic spread worldwide, yielding (among other measures) the incidence and seeding events at a daily resolution for 3,362 subpopulations in 220 countries. Using a Monte Carlo Maximum Likelihood analysis, the model provided an estimate of the seasonal transmission potential during the early phase of the H1N1 pandemic and generated ensemble forecasts for the activity peaks in the northern hemisphere in the fall/winter wave. These results were validated against the real-life surveillance data collected in 48 countries, and their robustness assessed by focusing on 1) the peak timing of the pandemic; 2) the level of spatial resolution allowed by the model; and 3) the clinical attack rate and the effectiveness of the vaccine. In addition, we studied the effect of data incompleteness on the prediction reliability.

          Results

          Real-time predictions of the peak timing are found to be in good agreement with the empirical data, showing strong robustness to data that may not be accessible in real time (such as pre-exposure immunity and adherence to vaccination campaigns), but that affect the predictions for the attack rates. The timing and spatial unfolding of the pandemic are critically sensitive to the level of mobility data integrated into the model.

          Conclusions

          Our results show that large-scale models can be used to provide valuable real-time forecasts of influenza spreading, but they require high-performance computing. The quality of the forecast depends on the level of data integration, thus stressing the need for high-quality data in population-based models, and of progressive updates of validated available empirical knowledge to inform these models.

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          Most cited references68

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          Modelling disease outbreaks in realistic urban social networks.

          Most mathematical models for the spread of disease use differential equations based on uniform mixing assumptions or ad hoc models for the contact process. Here we explore the use of dynamic bipartite graphs to model the physical contact patterns that result from movements of individuals between specific locations. The graphs are generated by large-scale individual-based urban traffic simulations built on actual census, land-use and population-mobility data. We find that the contact network among people is a strongly connected small-world-like graph with a well-defined scale for the degree distribution. However, the locations graph is scale-free, which allows highly efficient outbreak detection by placing sensors in the hubs of the locations network. Within this large-scale simulation framework, we then analyse the relative merits of several proposed mitigation strategies for smallpox spread. Our results suggest that outbreaks can be contained by a strategy of targeted vaccination combined with early detection without resorting to mass vaccination of a population.
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            Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus.

            A new pandemic influenza A (H1N1) virus has emerged, causing illness globally, primarily in younger age groups. To assess the level of preexisting immunity in humans and to evaluate seasonal vaccine strategies, we measured the antibody response to the pandemic virus resulting from previous influenza infection or vaccination in different age groups. Using a microneutralization assay, we measured cross-reactive antibodies to pandemic H1N1 virus (2009 H1N1) in stored serum samples from persons who either donated blood or were vaccinated with recent seasonal or 1976 swine influenza vaccines. A total of 4 of 107 persons (4%) who were born after 1980 had preexisting cross-reactive antibody titers of 40 or more against 2009 H1N1, whereas 39 of 115 persons (34%) born before 1950 had titers of 80 or more. Vaccination with seasonal trivalent inactivated influenza vaccines resulted in an increase in the level of cross-reactive antibody to 2009 H1N1 by a factor of four or more in none of 55 children between the ages of 6 months and 9 years, in 12 to 22% of 231 adults between the ages of 18 and 64 years, and in 5% or less of 113 adults 60 years of age or older. Seasonal vaccines that were formulated with adjuvant did not further enhance cross-reactive antibody responses. Vaccination with the A/New Jersey/1976 swine influenza vaccine substantially boosted cross-reactive antibodies to 2009 H1N1 in adults. Vaccination with recent seasonal nonadjuvanted or adjuvanted influenza vaccines induced little or no cross-reactive antibody response to 2009 H1N1 in any age group. Persons under the age of 30 years had little evidence of cross-reactive antibodies to the pandemic virus. However, a proportion of older adults had preexisting cross-reactive antibodies. 2009 Massachusetts Medical Society
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              Mitigation strategies for pandemic influenza in the United States.

              Recent human deaths due to infection by highly pathogenic (H5N1) avian influenza A virus have raised the specter of a devastating pandemic like that of 1917-1918, should this avian virus evolve to become readily transmissible among humans. We introduce and use a large-scale stochastic simulation model to investigate the spread of a pandemic strain of influenza virus through the U.S. population of 281 million individuals for R(0) (the basic reproductive number) from 1.6 to 2.4. We model the impact that a variety of levels and combinations of influenza antiviral agents, vaccines, and modified social mobility (including school closure and travel restrictions) have on the timing and magnitude of this spread. Our simulations demonstrate that, in a highly mobile population, restricting travel after an outbreak is detected is likely to delay slightly the time course of the outbreak without impacting the eventual number ill. For R(0) < 1.9, our model suggests that the rapid production and distribution of vaccines, even if poorly matched to circulating strains, could significantly slow disease spread and limit the number ill to <10% of the population, particularly if children are preferentially vaccinated. Alternatively, the aggressive deployment of several million courses of influenza antiviral agents in a targeted prophylaxis strategy may contain a nascent outbreak with low R(0), provided adequate contact tracing and distribution capacities exist. For higher R(0), we predict that multiple strategies in combination (involving both social and medical interventions) will be required to achieve similar limits on illness rates.
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                Author and article information

                Journal
                BMC Med
                BMC Med
                BMC Medicine
                BioMed Central
                1741-7015
                2012
                13 December 2012
                : 10
                : 165
                Affiliations
                [1 ]Computational Epidemiology Laboratory, Institute for Scientific Interchange (ISI), Torino, Italy
                [2 ]Department of Veterinary Sciences, University of Torino, Italy
                [3 ]INSERM, U707, Paris, France
                [4 ]Instituto de Física Interdisciplinar y Sistemas Complejos IFISC (CSIC-UIB), Palma de Mallorca, Spain
                [5 ]Centre de Physique Théorique (CNRS UMR 6207), Marseille, France
                [6 ]Department of Health Sciences and College of Computer and Information Sciences, Northeastern University, Boston MA 02115 USA
                [7 ]UPMC Université Paris 06, Faculté de Médecine Pierre et Marie Curie, UMR S 707, Paris, France
                [8 ]Institute for Scientific Interchange (ISI), Torino, Italy
                [9 ]Institute for Quantitative Social Sciences at Harvard University, Cambridge MA, 02138 USA
                Article
                1741-7015-10-165
                10.1186/1741-7015-10-165
                3585792
                23237460
                746513ff-e875-48f0-be6f-36b820d10512
                Copyright ©2012 Tizzoni et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 April 2012
                : 13 December 2012
                Categories
                Research Article

                Medicine
                computational epidemiology,h1n1 influenza pandemic,prediction,validation.
                Medicine
                computational epidemiology, h1n1 influenza pandemic, prediction, validation.

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