Know thine enemy

The four WHO Collaborating Centres act as global collection points for influenza virus samples sent from the national laboratories and other diagnostic laboratory or medical facilities in the region. The viruses collected undergo detailed antigenic and genetic characterisation to monitor changes in influenza virus around the world over time. Most of this work involves the seasonal viruses and basically, WHO is watching out for two things - how the virus population as a whole is changing globally from season to season, and anything unusual that needs more thorough analysis.

To measure the seasonal changes in influenza virus, or antigenic drift, samples are compared to a panel of reference strains. Antisera against these reference strains are raised in ferrets, which are the best-established animal model of influenza infection in humans, and then used to test collected samples.

"Antisera are also raised against anything new and interesting as a future reference strain, or more importantly, as a future vaccine strain," Kelso says. "What we really want to know is how far the virus has drifted in antigenicity and genetic profile from what we saw in previous northern and southern hemisphere seasons."

Of course, only a small proportion of the influenza virus out there is being monitored by the WHO efforts. Most people who contract the flu do not seek medical care, and of those that do, only a few are officially reported with appropriate samples sent to the WHO labs. However, according to Kelso, Australia has good systems set up for monitoring influenza-like illness, through hospitals and some GP surveillance networks.

Additionally, the detection of flu is notifiable in all states in Australia except South Australia. In 2007, the Collaborating Centre received about 2600 samples for analysis. These samples came mostly from within Australia, but many samples and virus isolates also arrived from other countries in the region including New Zealand, Malaysia, The Philippines and Macau.

Members of the four WHO Collaborating Centres then meet in Geneva twice a year to review all the data collected over the previous six months and issue a public statement about the latest antigenic trends in influenza virus wear for the following winter. This information is used to recommend virus strains for inclusion in the next seasonal vaccines for the northern and southern hemispheres, respectively.

What follows is then an intensive period of work for all concerned to culture suitable virus by its antigenic properties to include in the vaccin, and then grow enough up in eggs for the relevant companies to produce vaccine and release it into the market. "Even though it is many months between our meeting and the release of the vaccine, it is a very tight timeline that the companies face," she says.

The two A-type viruses circulating in humans at the moment, H1N1 and H3N2, both originated as pandemics and their history is quite interesting. "H1N1 is the progeny of the virus that caused the 1918 influenza pandemic virus, which after the pandemic became established in humans, circulated until the 1930s, and then disappeared," Kelso says.

"It re-emerged in Russia in 1977 and has been circulating in humans ever since. So, it has now drifted a long way from the original pandemic form. It is also only the A viruses that give rise to pandemics from time to time. The B-type viruses are not as variable and are human strains originally."