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If Asian bird flu mutates into a form that spreads easily between humans, an outbreak of just 40 infected people would be enough to cause a global pandemic. And within a year half of the world’s population would be infected with a mortality rate of 50%, according to two studies released on Wednesday.

And yet, the models show, if targeted action is taken within a critical three-week window, an outbreak could be limited to fewer than 100 individuals within two months.

It represents the first opportunity in history to make use of new knowledge and logistics to prevent a pandemic whose potential loss of life could dwarf the horrific 1918 influenza pandemic. But, the researchers caution, we are currently far from ready to take the necessary action.

“If an outbreak occurred tomorrow, it would be devastating,” warns Neil Ferguson from Imperial College London, UK, who led one of the studies. Nature and Science have released the two studies in tandem. The authors stress that an outbreak is no longer an “if” scenario – they are now talking about “when”.

Hundreds of scenarios

Ferguson’s study, in Nature, modelled the potential spread of a bird flu (H5N1) outbreak throughout Thailand’s 85 million people. Ira Longini’s study, published in Science, focused on the nation’s 500,000-strong Nang Rong region.

The two studies modelled hundreds of scenarios, looking at how the virus could spread person-to-person through different modes of contact, and the effect of various methods of mitigation. For example, simulations were run to model the effects of prophylactic treatment, quarantine, as well as investigating the impact of differing strains and different rates of detection.

The key findings of both studies were in agreement: in order for a nascent pandemic to be controlled there needs to be 3 million courses of oseltamivir (Tamiflu) – the antiviral drug – available for the World Health Organization to mobilise and deploy internationally, immediately. There also needs to be good surveillance systems in place at local level, particularly in at-risk countries in south-east Asia, for fast detection of the virus’s emergence and accurate diagnosis.

The WHO has stockpiled of 120,000 courses of the antiviral drug, far too small a supply to halt an outbreak, the studies warn.

International intervention

The virus needs to be detected within 21 days and before 40 people contract it, the researchers say. Accurate medical diagnosis based on symptoms is key, since by the time results from genetic tests arrive, it will almost certainly be too late. In rural communities with poorly coordinated healthcare provision, swift detection and isolation of cluster groups could prove limited, they add. Likewise, where countries are not immediately open – allowing international intervention in an outbreak – the consequences could be dire. This was what happened during China’s SARS virus outbreak.

Following diagnosis of a cluster of infected individuals, the next and hardest task is to prevent the disease spreading, Ferguson says. This should be done through social distancing methods, such as closing schools, travel restrictions and even quarantine. Each new case must be isolated and treated within two days. Populations in a radius surrounding the cluster should be treated with antivirals.

Even treating these populations with a flu vaccine that has low efficacy against H5N1, would buy some time to allow treatment to work, says Longini at Emory University in Atlanta, Georgia, US.

Passing it on

Underpinning all the simulations in the two studies is an assumption about the virus’s basic reproduction number (R) – the number of people each infected person will infect. The findings are based on each person only infecting up to two others. And yet the R value remains unknown until a new strain emerges.

Ferguson and Longini are fairly confident that they have overestimated the R value. Avian flu has a very low virulence, but the danger is that it could combine with a highly virulent human flu virus or mutate into a virus with a higher R number.

“We’re having to make ‘best guesses’ for many of the assumptions in the study, partly basing it on past pandemics. And we may be wrong,” Ferguson said. “Pandemics are rare – they happen every few decades – but if we do not prepare and do not have enough antivirals stockpiled, or fail to confine the outbreak in the first three weeks, then millions could die.

The WHO welcomed the research which would “help WHO and public health officials in our Member States to improve pandemic influenza preparedness planning”. It added that it had taken steps to provide an international stockpile of antivirals.

Ferguson adds that Roche, the manufacturer of Tamiflu, intends to donate drugs to WHO.

Journal references: Nature (DOI: 10.1038/nature04017) and Science (DOI:10.1126/science1115717)

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