HOWZAT

The idea of mining survivors’ blood for lifesaving chemicals dates back to 1918, when doctors transfused the blood of flu survivors into new patients. This roughly doubled the chances that the recipient would survive. The technique was also employed on a smaller scale during the Sars outbreak, although success rates are hard to pin down. Latterly, however, the threat from blood-borne diseases such as HIV and hepatitis B dampened enthusiasm for serum therapy. Some British academics are arguing for British laws governing blood products — tightened in the wake of “mad cow” disease — to be relaxed ahead of any flu pandemic.

Simmons has isolated the H5N1-killing antibodies from the blood of four survivors. He says: “We’ve shown that if you give these antibodies to mice before they’re infected,you can protect the animal from what is rapidly lethal.”

The antibodies can quash the strain of H5N1 circulating in Vietnam (this strain is also circulating in Thailand and Cambodia)but are only partially effective against the other major strain of H5N1, which has cornered China, Indonesia, Japan and South Korea. Any mass-produced vaccine using this method would need to contain antibodies to both strains.

The mice are also protected if the antibodies are given 24 hours after infection. The researchers are now trying to gauge how long the delay between infection and immu-nisation can be. The atmosphere in the unit, Simmons says, is one of measured optimism: “It’s difficult to extrapolate from a mouse to a human, so there’s doubt as to what our experiments will mean for people.

“But it’s exciting because although influenza has been a significant disease for decades and the risk of a pandemic is a real one, we have only one or two existing drugs. Our antibodies are another treatment option for H5N1 that can be made on an industrial scale and potentially very cheaply.”

Another of Farrar’s colleagues, Dr Menno de Jong, has been studying the impact of H5N1 on the immune system of patients. He recently reported, in Nature Medicine, that the patients who died displayed a particularly fierce immune response. Flu experts are now wondering whether this ability to provoke an “immune storm” in the lungs accounts for the virus’ deadliness. Immunosuppressants might be another therapeutic prospect.

De Jong, who helped to define the WHO’s diagnostic criteria for H5N1, is now trying to discover whether some individuals are immune to it. Together with health officials in Ho Chi Minh City, he has collected the blood of hundreds of poultry workers and individuals involved with culling infected birds. It has been noted, anecdotally, that no poultry workers or cullers have ever come down with H5N1. The plan is to test the blood for H5N1 antibodies, to see whether these workers actually encounter the virus but don’t succumb to it.

Bleakly, De Jong believes that a human flu pandemic is inevitable, although the culprit may not be H5N1: “If you look at history, every now and then we do get a pandemic. My fear is that there is already a pandemic under way in poultry.” Unlike chickens, ducks and geese can carry H5N1 without ill effect; they are often described as Trojan horses. Influenza researchers would like to see long-term strategic planning for a human pandemic, plus basic research into the H5N1, as a matter of urgency. A vaccine cannot be produced until a pandemic strain emerges (to ensure the best match) but then, production capacity is limited by the fact that the vaccine would need to be cultured in chick eggs (and is thus dependent on egg supply). All the while, H5N1 remains a moving target: it has already diverged into two clades (families), with each family further split into various subtypes.

Farrar says: “I’m not saying we will or won’t have a pandemic, but if we do, then we have to recognise that we don’t have great vaccines, we don’t have the global capacity to produce them, and we have only two drugs (Tamiflu and Relenza), neither of which is brilliant, because you can’t get them directly into the bloodstream. From a public health perspective, that’s not a great position to be in.”

He also points out that while an international effort is called for, “pontificating in Washington or Geneva (the site of WHO’s HQ) or Oxford will get you only so far. It’s local doctors who’ll be seeing patients, who will need to identify what’s going on. If we rely on people flying in from Geneva, we’re stuffed.” The 2003 severe acute respiratory syndrome (Sars) outbreak, which killed 774 people, was popularly viewed as a dress rehearsal for a flu pandemic; alas, it wasn’t a realistic one. Sars sickened people immediately, making victims easily identifiable, and containable, while they were infectious. This allowed a prospective pandemic to be reined in with relative ease (although not before losing the Asian economy an estimated £22 billion; the World Bank reckons a flu pandemic could cost 20 times that).

Human influenza is a stealthier foe, taking around three days to make people ill, thus giving them ample time to infect others. Should H5N1 mutate into a transmissible form, this time lag between infection and the appearance of symptoms may persist. In this case, the likelihood of an H5N1 pandemic depends on how infectious the disease becomes.

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