In the first half of 2004, an estimated 200 million poultry birds across Asia died or were destroyed in an effort to control a widespread outbreak of avian influenza.1 Though such outbreaks have occurred before, this one, primarily in China and Southeast Asia, demonstrated increased pathogenicity in poultry, increased resistance to environmental controls, and an expanded range of mammalian hosts.
Lest anyone conclude this is a problem affecting only the birds and the people who raise them, clinical and laboratory evidence since 1997 point to a series of human cases of avian flu (TABLE 1), most of which were associated with outbreaks of the disease in poultry.2 The change in characteristics of the current outbreak in birds in Asia combined with increased knowledge of the characteristics of human influenza have many scientists and public health officials increasingly concerned that we may be watching the unfolding of the next great flu pandemic. In this article, I describe how this might happen and what we can attempt to prevent it.
TABLE 1
Avian influenza infection in humans
| Hong Kong (1997): | 18 people hospitalized with 6 deaths |
| China and Hong Kong (1999): | 2 cases in children who recovered |
| Virginia (2002): | 1 person with serologic evidence of avian flu |
| China and Hong Kong (2003): | 2 adults cases with one death |
| Netherlands (2003): | 89 human cases with 1 death; most cases were of conjunctivitis, some with flu symptoms. The antiviral drug oseltamivir was used to help control spread |
| Canada (2004): | Human infections among poultry workers consisting of eye infections |
| Asia (since January 2004): | 55 cases with 42 deaths in Vietnam, Thailand, and Cambodia |
Human influenza pandemics
A flu pandemic is a global outbreak of disease among people after the emergence of a new influenza A virus. Three great pandemics occurred in the 20th century, all spreading worldwide within 1 year.
- Spanish flu (1918–1919): 20 to 50 million people died, more than 500,000 in the US. Nearly half of those dying were young, healthy adults.
- Asian flu (1957–1958): Caused about 70,000 deaths in the US.
- Hong Kong flu (1968–1969): Caused about 34,000 deaths in the US.
Both the Asian and Hong Kong flus resulted from a mixing of a human and avian influenza virus; the Spanish flu may have resulted from a mutation in a purely avian virus.3
How avian influenza viruses spread
Avian influenza A viruses vary greatly, owing to the myriad combinations of their 15 hemagglutinins and 9 neuraminidases. The viruses are widespread in migratory birds and waterfowl and are usually of low pathogenicity. Water birds, in particular, act as hosts for influenza viruses, carrying them in their intestines and then shedding them.
Wild bird hosts do not usually get sick, but they can spread influenza to other birds. For instance, there have been 16 outbreaks of H5 and H7 influenza in US poultry since 1997. Usually, such events are from low-pathogenic avian viruses that cause little illness in affected chickens. When highly pathogenic viruses cause outbreaks, 90% to 100% of affected poultry can die. This has been happening in the current Asian outbreaks.
In the past, isolating poultry, culling (destroying) infected flocks, and vaccinating poultry eventually quelled the outbreaks. Such measures have not worked this time, and scientists think it likely that H5N1 infection among birds has become endemic to the region—ie, Cambodia, China, Indonesia, Malaysia, Thailand, and Vietnam.4
Rethinking how humans become infected
Since humans have distinct receptors for human viruses, as do birds for avian viruses, it was thought that an intermediate host—the pig, with both receptors—was necessary to allow the mixing of the viruses and subsequent human infection with avian influenza. However, recent outbreaks in poultry with proven spread of highly pathogenic virus from chickens directly to humans have challenged this theory (TABLE 1). While the mortality rate so far has been very high, this rate may turn out to be overstated as milder, nonfatal cases of human avian flu are discovered.
New research has raised additional concerns: ducks infected with H5N1 are now shedding virus for longer times while remaining asymptomatic; pigs in China and tigers in Thailand have been infected with H5 virus; and experiments with house cats in the Netherlands have demonstrated they could be infected with H5. These findings are troubling because the reassortment of avian viruses is more likely to occur when they are able to infect multiple species. Moreover, the infection in humans from Vietnam has shown resistance to the older antiviral drugs, amantadine and rimantadine, leaving oseltamivir and zanamivir as the antivirals likely effective against avian influenza A H5N1.4