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

12 May 2009

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

  • David

    Getting these initial attack rates is quite interesting. One thing I have not yet seen estimated are attack rates for HP H5N1. I know they are extremely low but I would like to see an estimation from someone/organization with boots on the gound in a impacted area.

    Also, I noticed on CDC's FluView site that they showed the number of viruses isolated during testing. Clearly, the new H1N1 strain had as many – if not more – positive results than the perviously circulating H1N1 strain (for week 17). At what point will we simply see the new strain become the dominating strain circulating in communities around the US?

  • cvarona

    The article discuss the following sources of bias on the estimates of the case fatality ratio : underestimate the denominator by detecting only the most severe cases; underestimate the numerator by right censoring or underestimate the old deaths associated to influenza; or overestimate the true deaths caused by the novel virus.
    But what about the antiviral use? Or changes in the virulence of the virus as we suspect occurs in the 1918 pandemia?

  • Marie

    Here's a Woods Hole press release that might explain the cluster of deaths in Mexico. Very interesting, either way!

    http://www.mbl.edu/news/press_releases/2009_pr_
    Scientists Link Influenza A (H1N1) Susceptibility to Common Levels of Arsenic Exposure

    MBL, WOODS HOLE, MA—”The ability to mount an immune response to influenza A (H1N1) infection is significantly compromised by a low level of arsenic exposure that commonly occurs through drinking contaminated well water, scientists at the Marine Biological Laboratory (MBL) and Dartmouth Medical School have found.

    Joshua Hamilton, the MBL's Chief Academic and Scientific Officer and a senior scientist in the MBL's Bay Paul Center; graduate student Courtney Kozul of Dartmouth Medical School, where the work was conducted; and their colleagues report their findings this week in the journal Environmental Health Perspectives.

    “When a normal person or mouse is infected with the flu, they immediately develop an immune response,” says Hamilton, in which immune cells rush to the lungs and produce chemicals that help fight the infection. However, in mice that had ingested 100 ppb (parts per billion) arsenic in their drinking water for five weeks, the immune response to H1N1 infection was initially feeble, and when a response finally did kick in days later, it was “too robust and too late,” Hamilton says. “There was a massive infiltration of immune cells to the lungs and a massive inflammatory response, which led to bleeding and damage in the lung.” Morbidity over the course of the infection was significantly higher for the arsenic-exposed animals than the normal animals.

    Respiratory infections with influenza A virus are a worldwide health concern and are responsible for 36,000 deaths annually. The recent outbreak of the influenza A H1N1 substrain (“swine flu”)–which is the same virus that Hamilton and his colleagues used in their arsenic study–to date has killed 72 people in Mexico and 6 in the United States.

    “One thing that did strike us, when we heard about the recent H1N1 outbreak, is Mexico has large areas of very high arsenic in their well water, including the areas where the flu first cropped up. We don't know that the Mexicans who got the flu were drinking high levels of arsenic, but it's an intriguing notion that this may have contributed,” Hamilton says.”
    ———————————————-

    Whole article here:
    http://www.mbl.edu/news/press_releases/pdf/h1n1

  • Marie

    Here's a Woods Hole press release that might explain the cluster of deaths in Mexico. Very interesting, either way!

    http://www.mbl.edu/news/press_releases/2009_pr_
    Scientists Link Influenza A (H1N1) Susceptibility to Common Levels of Arsenic Exposure

    MBL, WOODS HOLE, MA—”The ability to mount an immune response to influenza A (H1N1) infection is significantly compromised by a low level of arsenic exposure that commonly occurs through drinking contaminated well water, scientists at the Marine Biological Laboratory (MBL) and Dartmouth Medical School have found.

    Joshua Hamilton, the MBL's Chief Academic and Scientific Officer and a senior scientist in the MBL's Bay Paul Center; graduate student Courtney Kozul of Dartmouth Medical School, where the work was conducted; and their colleagues report their findings this week in the journal Environmental Health Perspectives.

    “When a normal person or mouse is infected with the flu, they immediately develop an immune response,” says Hamilton, in which immune cells rush to the lungs and produce chemicals that help fight the infection. However, in mice that had ingested 100 ppb (parts per billion) arsenic in their drinking water for five weeks, the immune response to H1N1 infection was initially feeble, and when a response finally did kick in days later, it was “too robust and too late,” Hamilton says. “There was a massive infiltration of immune cells to the lungs and a massive inflammatory response, which led to bleeding and damage in the lung.” Morbidity over the course of the infection was significantly higher for the arsenic-exposed animals than the normal animals.

    Respiratory infections with influenza A virus are a worldwide health concern and are responsible for 36,000 deaths annually. The recent outbreak of the influenza A H1N1 substrain (“swine flu”)–which is the same virus that Hamilton and his colleagues used in their arsenic study–to date has killed 72 people in Mexico and 6 in the United States.

    “One thing that did strike us, when we heard about the recent H1N1 outbreak, is Mexico has large areas of very high arsenic in their well water, including the areas where the flu first cropped up. We don't know that the Mexicans who got the flu were drinking high levels of arsenic, but it's an intriguing notion that this may have contributed,” Hamilton says.”
    ———————————————-

    Whole article here:
    http://www.mbl.edu/news/press_releases/pdf/h1n1

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