Experts monitor H5N1 spread and overlap in wild bird flyways

September 2007

TORONTO — For the past several years, H5N1 has been a major concern of public health officials worldwide. Based on past pandemics, experts agree that, although a pandemic of avian influenza is not guaranteed, the effects could be devastating.

“The major concern in public health is whether avian influenza could spread more widely around the world and among humans,” said Thomas C. Quinn, MD, associate director for international research at the National Institute of Allergy and Infectious Disease. “It is an obvious global threat.”

Quinn, who is also the director of the Center for Global Health at Johns Hopkins University, gave a presentation about the spread and the current status of H5N1 at the American Society for Microbiology Conference, held here recently.

“Could H5N1 become a pandemic?” Quinn said. “I don’t know, but we are in phase 3, which means we are seeing a new virus present in humans with little or no spread among humans.”

Quinn noted that in the past three years, 59 countries have reported cases of avian influenza. He said that although there are 16 different subtypes, only three major types have been well-described in humans. Problems arise for potential crossover from birds to humans because in seasonal and pandemic influenza, the virus can undergo antigenic shifts, usually caused by point mutations in the genes. H5N1 is not the only avian influenza strain, which could confound pandemic influenza preparedness planning.

“For the antigenic shift, this is a major change in which you are infected by a new subtype and this is what we fear may become a pandemic,” Quinn said.

History examined

Quinn said experts should look to history and study the 1918 Spanish influenza epidemic to help preparedness efforts against avian influenza.

An estimated 25% to 30% of the world population was affected by the 1918 Spanish influenza epidemic, with an estimated related death toll of 40 million. “The most telling data about what this pandemic did is that it dropped life expectancy in nearly all countries all due to one disease,” Quinn said. “These are historical lessons to keep in the back of your mind when we consider avian influenza.”

According to Quinn, the virus that caused the 1918 pandemic has been recovered and fully sequenced; researchers determined it was a form of avian influenza.

The Spanish influenza pandemic was followed by Asian influenza and Hong Kong influenza in the 1950s and 1960s. All occurred before the advent of antiretrovirals.

Prototype H5N1 vaccines are highly protective in mice, with greater than 80% to 90% protection rates. But the number of people affected in future pandemics will be based on multiple factors, most of which are unknown.

Many experts agree that a pandemic in this century could be much worse than 1918 because of several factors, including the increase in world population and increased potential exposure.

Transportation is also a key concern in avian influenza pandemic spread; air travel has aided global infectious disease spread.

“A prime example is SARS and how rapidly the virus spread; it took four months to circle the globe,” Quinn said. “Estimates today for pandemic influenza would be four days, including the incubation period.”

Flyways, domestic fowl

Most birds infected with avian influenza move along flyways and occasionally intermix with domesticated birds. The flyways are being closely monitored by WHO and CDC.

Quinn showed a time lapse of H5N1 global tracking beginning in 2004. Reported cases of birds with H5N1 began in Southeast Asia and China and then moved to Eastern Europe and Africa. The pattern overlaps the flyways of known migratory birds. The H5N1 spread from east to west usually occur during the cooler months, when most of the birds migrate.

“If you superimpose them, you see how migratory birds have spread H5N1. It didn’t take long, only three or four years,” Quinn said.

In Hong Kong, the first reports of H5N1 were in 1997. At the time, officials culled all chickens and a pandemic was averted. A new strain, H9N2, followed. Then, in 2002, H5N1 made a resurgence with two cases and one fatality. Other strains – including H7N7 and H9N2 – have been reported recently.

“We have tended to focus primarily on H5N1 and this is what the production is being built against at present, however, that does not guarantee that we could not get a pandemic from H9N2, H7N7 or other avian virus strains,” Quinn said.

H5N1 has broken into two clades: clade one, the earliest, and clade two, which is H5N1.

“The interesting thing is that the new vaccines are using clade one as the prototype, but we are not seeing many human cases from clade one anymore,” Quinn said. “The antigenic differences between these clades really do warrant development of a new vaccine as a reference stock for these Indonesian strains and other viruses.”

H5N1 mortality, prevention

As of May 24, there were 306 H5N1 human infections with 185 deaths, representing 65% mortality, in the past four years. Mortality in the 1918 influenza pandemic was 2.5%.

“The mortality rate for H5N1 is exceedingly high,” Quinn said. “In comparison, SARS was 15%.”

More than half of reported H5N1 human cases occurred in 2006. In infected humans, 98% have a history of contact with sick or dead birds. Mortality depends on region as Indonesia has the highest number of reported human H5N1 cases at 96 with 76 fatalities. In Egypt, there are 34 known human cases with 14 fatalities.

“There is no demonstrable evidence of person-to-person transmission at this time, which is good news,” Quinn said.

Control of H5N1 among poultry by culling will be key in reducing the public health threat. Culling should be monitored and compensation for affected poultry farmers should be considered to ensure compliance as a part of pandemic public health measures.

For more information:

• Quinn TC. Avian influenza: Birds of a feather may not flock together. Symposium 319/Y. Presented at: the American Society for Microbiology 107th General Meeting; May 21-25, 2007; Toronto.