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Originally published in Science Express on 11 May 2009
Science 19 June 2009:
Vol. 324. no. 5934, pp. 1557 - 1561
DOI: 10.1126/science.1176062
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Reports

Pandemic Potential of a Strain of Influenza A (H1N1): Early Findings

Christophe Fraser1,*, Christl A. Donnelly1,*, Simon Cauchemez1, William P. Hanage1, Maria D. Van Kerkhove1, T. Déirdre Hollingsworth1, Jamie Griffin1, Rebecca F. Baggaley1, Helen E. Jenkins1, Emily J. Lyons1, Thibaut Jombart1, Wes R. Hinsley1, Nicholas C. Grassly1, Francois Balloux1, Azra C. Ghani1, Neil M. Ferguson1,{dagger}, Andrew Rambaut2, Oliver G. Pybus3, Hugo Lopez-Gatell4, Celia M. Alpuche-Aranda5, Ietza Bojorquez Chapela4, Ethel Palacios Zavala4, Dulce Ma. Espejo Guevara6, Francesco Checchi7, Erika Garcia7, Stephane Hugonnet7, Cathy Roth7 and The WHO Rapid Pandemic Assessment Collaboration{ddagger}

1 MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, Faculty of Medicine, Norfolk Place, London W2 1PG, UK.
2 Institute of Evolutionary Biology, University of Edinburgh, Ashworth Laboratories, Edinburgh EH9 3JT, UK.
3 Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK.
4 Directorate General of Epidemiology, FCO. De P. Miranda, 177 5th Floor, Mexico City, 01480, Mexico.
5 National Institute of Epidemiological Diagnosis and Reference, Prolongación Carpio No. 470 (3° piso), Col Santo Tomás, México City, C.P. 11340, Mexico.
6 Secretaría de Salud - Servicios de Salud de Veracruz Soconusco No. 36, Colonia Aguacatal, C.P. 910 Xalapa, Veracruz, México State.
7 World Health Organization.


Figure 1
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  		Fig. 1. (A). The number of passengers flying out of Mexico by actual destination and the number of confirmed cases as reported on 30 April 2009. (B) The number of cases exported to country j as reported on 30 April 2009 as a function of the estimated average number of foreign travelers in Mexico from country j on any given day in March or April. Black circles: minimal number based on one exposure per epidemiological cluster; filled red circles, total number of confirmed cases. (C) Mean assumed generation time distribution (red) and 100 illustrative draws from the prior distribution, and (D) corresponding posterior distribution of R0 estimates for a stochastic model of an epidemic within Mexico with travelers infected at a rate proportional to the estimated density of travelers per local resident. The two bar charts correspond to a 7-day delay between infection and confirmation (blue) and no delay (orange) in cases among travelers. (E) Number of acute respiratory infection cases per 100,000 inhabitants by state as reported on 5 May 2009 (1), demonstrating spatial distribution of disease within Mexico.

 

Figure 3
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  		Fig. 3. Results of a detailed investigation into an outbreak in the village of La Gloria. (A) The time series of cases based on repeat rounds of investigation into the outbreak, and the best fit of an age-stratified transmission model (see Table 2 for estimates). The graph also shows the best fit of a model where the generation time is constrained to be consistent with earlier estimates for influenza (2.6 days), which does not fit significantly worse than the unconstrained best fit (see Table 2 legend). (B) Observed (bars) and fitted (using best fit, circles) age-specific attack rates; (C) best fit and constrained estimate of the generation time distribution.

 

Figure 2
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  		Fig. 2. (A) Starting from publicly available HA viral sequences, a posterior distribution of the estimated TMRCA was derived using a Bayesian coalescent model, which assumes exponential population growth (coded in BEAST 1.4), with the date of the first known human case highlighted. Details of the BEAST analysis and parameter estimates are presented in (8). Posterior distribution of the doubling time of the epidemic (B) and of R0 (C). The bar charts show the results obtained from the first 11 sequences available on 2 May 2009 (orange) and from an updated analysis with 23 epidemiologically unlinked sequences available on 7 May 2009 (blue). The differences in estimates arise due to some sequences in the smaller sample being from epidemiological clusters, highlighting the importance of careful sampling.

 

Figure 4
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  		Fig. 4. (A) Time course of the Mexican epidemic with (B) the posterior estimates (median and 95% CrI) of the reproduction number over time obtained under Poisson and negative binomial models from the analysis of confirmed cases. The estimate of the negative binomial dispersion parameter k is for a low-to-moderate overdispersion, but this is enough to greatly increase the uncertainty in R(t).

 

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