Influenza A/Mexico/2009 (H1N1) virulence and transmission

b00528_h1n1_flu_blue_smlThe influenza H1N1 outbreak in Mexico has been analyzed to provide information on the pandemic potential of the new virus strain. The estimates offer some insight into the transmissibility and severity of the virus but must be tempered with the understanding that there are still uncertainties about all aspects of the outbreak.

Influenza incidence is difficult to determine because most infections are not confirmed by laboratory tests. Consequently case estimates play an important role in understanding transmission and spread. In this study, the authors used mathematical models to calculate the number of infections in Mexico based on exportation of the disease by travelers. They estimate that 23,000 infections had occurred in the country by late April. From this number they calculated a case fatality ratio of 0.4%. I note that my own crude calculations yielded a similar number.

To determine the transmissibility of the virus the authors first attempted to pinpoint the start date of the outbreak. One estimate is 15 February 2009 based on the first reported case in La Gloria. But the authors have another method as well:

An alternative approach to estimating the start date of the outbreak is to look at the diversity in the genetic sequences of viral samples collected from confirmed cases, assuming that diversity accumulates according to a molecular clock model.

The authors went on to compare 23 viral HA gene sequences from the Mexican outbreak. Readers of virology blog will understand the reference to a ‘molecular clock’ in the previous paragraph, having read previous posts on the error-prone nature of RNA virus replication. These approaches allow an estimation of the onset of the outbreak in Mexico to 12 January 2009. In other words, an influenza virus with a genome sequence that is the most common ancestor to those represented by the 23 HA gene sequences was circulating in humans in Mexico in January of this year.

The start date of the epidemic and the total number of infections can then be used to calculate the reproductive number, R0. This is the average number of secondary infections that result from one infected host in an otherwise uninfected population. In general, if R0 is less than 1, it is impossible to sustain an epidemic. If R0 is high, an epidemic is almost certain. Very high R0 values are typical of diseases with ‘super-spreaders’, such as the individual who transmitted SARS to others in the Hotel Metropole.

An R0 of 1.4 – 1.6 was calculated for the Mexican outbreak, which means that 14 to 73 generations of human to human transmission took place as of the end of April. This number is higher than observed for seasonal influenza, but in line with estimates from influenza pandemics of 1918, 1957, and 1968.

Fraser, C., Donnelly, C., Cauchemez, S., Hanage, W., Van Kerkhove, M., Hollingsworth, T., Griffin, J., Baggaley, R., Jenkins, H., Lyons, E., Jombart, T., Hinsley, W., Grassly, N., Balloux, F., Ghani, A., Ferguson, N., Rambaut, A., Pybus, O., Lopez-Gatell, H., Apluche-Aranda, C., Chapela, I., Zavala, E., Guevara, D., Checchi, F., Garcia, E., Hugonnet, S., Roth, C., & , . (2009). Pandemic Potential of a Strain of Influenza A (H1N1) : Early Findings Science DOI: 10.1126/science.1176062