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Scientists trying to gauge the severity of the threat of a swine influenza pandemic face many important knowledge gaps.

Even the death toll from the outbreak, which is thought to have begun more than a month ago in Mexico, and has now spread to several continents, is open to question. Some 150 people have died in Mexico but the number of cases, dead or alive, that have actually been confirmed in the laboratory is much lower at 26 — which means there is little data available for scientists attempting to assess the virus.

Similarly little is known about the epidemiology of the virus. Yesterday (27 April) the WHO increased its influenza pandemic alert level from phase 3 to phase 4, indicating that they believe 'sustained' human-to-human transmission is occurring. But there is much more to learn about how the virus is transmitted.

"We don't really know the mortality rate, we don't really know which age groups are affected," says Sandra Mounier-Jack, lecturer in health policy and expert in pandemic preparedness at the London School of Hygiene and Tropical Medicine.

"We don't know the cause of death — I think that's really important, what are people dying of? Until we have more epidemiological information it's very difficult to make any kind of judgement [about pandemic potential]."

Jonathan Read, lecturer in infectious diseases at the University of Liverpool, says: "One of the key things from an epidemiological viewpoint would be how many cases we've actually got of this and how quickly they're building up or not. From that you can work out some key epidemiological parameters and get some estimate of whether a pandemic — or a large epidemic — is likely or not."

He told SciDev.Net that there is a parameter known as R0, "which encapsulates how transmissible a disease can be between individuals. The higher that number is, the harder it is to control the disease." Finding out the R0 will help to assess how serious the threat from swine influenza is, he says.

Keiji Fukuda, assistant director-general for Health Security and Environment at the WHO said at a press briefing yesterday that the WHO is working hard to document how transmissible the disease is, among other factors such as the virus's incubation period — how long symptoms appear after a person is infected. "We have a minimal amount of data about some of the factors," he said.

There is also conflicting data about the severity of the disease. No one outside Mexico has died, and most cases outside the country have been mild and easily treatable with antiviral drugs.

"There's no good explanation [for why people are dying in Mexico and not anywhere else] although there are very few confirmed cases outside of Mexico yet so we need to be cautious about extrapolating that," says Read.

It could be that there simply aren't enough cases outside Mexico for the virus' ability to kill people to have been manifested.

Another possibility put forward by scientists is that, in Mexico, victims are dying of secondary infections because the healthcare system is not reaching them in time and there is widespread antibiotic resistance.

It is even possible that the virus is gradually adapting to its human hosts and becoming less dangerous as it passes from person to person. Fukuda, however, has rejected this theory on the basis that all samples of the virus examined so far have been very similar.

"What we need to know is why we're seeing a different disease spectrum in Mexico than we're seeing [in the United States]. As we continue to look I expect that we will see additional cases and I expect that the spectrum of disease will expand," Richard Besser, the acting head of the US Centers for Disease Control and Prevention, told a press briefing yesterday.

There are also reports that most of the deaths in Mexico have been in young to middle-aged adults —  all of those who have died were aged between 20 and 50, Health Minister Jose Angel Cordova told the BBC.

This is a hallmark of the 1918 flu pandemic, says Read. "The thinking is that if you've got a fit, active immune system it goes over the top in trying to fight the disease and that's what causes most of the disease symptoms and causes a build-up of too much fluid in the lungs."

Even the genetic makeup of the virus is under debate. Scientists agree that it is a H1N1 virus — named because of the types of haemagglutinin and neuraminidase proteins that it possesses. According to some analyses it is made up of an assortment of human, swine and avian influenza genetic material, while the WHO is saying it is made up of largely swine influenza genes.

"By and large when you analyse this virus it is a swine influenza virus," said Fukuda. "I appreciate the difficulty of keeping all of this straight but these are new viruses — they're new for pigs and they're new for people."


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