Containment of a Southeast Asian outbreak of avian influenza in humans may be possible

Aug 3 2005

Though quick to caution about the many things that could go wrong, researchers say that it may be possible to contain a Southeast Asian outbreak of avian influenza in humans, buying precious time for the production of a vaccine.

Using a computer model to simulate an outbreak in a rural Southeast Asian population, the scientists have shown how a combination of strategies, including targeted administration of antivirals, quarantine and prevaccination - even with a poorly effective vaccine - could potentially contain an outbreak in Southeast Asia under many circumstances.

The study, by Ira Longini of Emory University and colleagues, will be published online by the journal Science, at the Science Express website, on Thursday, 4 August.

"Our findings indicate that we have reason to be somewhat hopeful. If - or, more likely, when - an outbreak occurs in humans, there is a chance of containing it and preventing a pandemic. However, it will require a serious effort, with major planning and coordination, and there is no guarantee of success," said coauthor Elizabeth Halloran of Emory University.

"Early intervention could at least slow the pandemic, helping to reduce morbidity until a well-matched vaccine could be produced," she said.

The danger of avian flu is that the virus could develop into a new strain that could be transmitted among humans. The virus might mutate, or it might jump over to a human already infected with the flu and then mix, or "reassort," with the human flu virus. Because humans would have little or no immune protection against this strain, it could potentially cause a massive pandemic.

"There were three influenza pandemics in the 20th century alone. The threat of another pandemic, related to avian influenza, is real and very serious. Fortunately, as the new study shows, for the first time in human history, we have a chance of stopping the spread of a new influenza strain at the source through good surveillance and aggressive use of public health measures," said Katrina Kelner, Deputy Editor, Life Sciences, at Science.

A rural Southeast Asian population is a likely place for the new strain to emerge, so Longini and his colleagues based their model on the Thai 2000 census and a previous study of the social networks in the Nang Rong District in rural Thailand.

With this information, they simulated a population of 500,000 in which individuals mixed in a variety of settings, including households, household clusters, preschool groups, schools, workplaces, and a hospital. Social settings for casual contacts, such as might take place in markets, shops, and temples, were also included.

Using the model, the researchers analyzed how the disease, starting with a single case, would spread through the population in a variety of different scenarios.

They found that targeted use of antiviral drugs could be effective for containment as long as the intervention occurred within 21 days and the virus' reproductive number (which represents the average number of people within a population someone with the disease is able to infect) had a relatively moderate value of roughly 1.6.

A process of administering antiviral drugs to the people in the same mixing groups as the infected person, called TAP for "targeted antiviral prophylaxis," could contain the outbreak as long as it reached 80 percent of the people targeted. A related strategy, GTAP, for "geographically targeted antiviral prophylaxis," which targets people within a certain geographic range of the initial case, produced similar results as long as it achieved coverage of 90 percent.

Vaccination before the outbreak, even with a vaccine that is poorly matched to the actual virus strain, increased the effectiveness of TAP and GTAP.

For even higher viral reproductive numbers, household quarantines would also be necessary to contain the virus. A combination of TAP, prevaccination and quarantine could contain strains with a reproductive number around 2.4. A value of 2.4 is relatively contagious, though some other viruses such as measles are substantially higher. In all cases, early intervention would be essential.

The authors note in their study that the current World Health Organization stockpile of antivirals for avian flu could probably be sufficient to help contain a pandemic in a population like the one in the model, if the stockpile were deployed within two to three weeks of detection.

As part of their study, the researchers consulted with Thai ministry of health officials and concluded that public health workers may decide that TAP, rather than GTAP, is the more realistic strategy, given their resources.

This research effort is part of a network called MIDAS (Models for Infectious Disease Agents Study), supported by the National Institute of General Medical Sciences. A related paper from another group of MIDAS researchers is being published simultaneously in the journal Nature.

http://www.aaas.org/