Emergence of the Influenza A H5N1 Subtype (1997-2005)
|This page is based on Avian influenza: assessing the pandemic threat published by the World Health Organization. The WHO also publishes Situation Updates on the H5N1 avian influenza.|
Sometime prior to 1997, the H5N1 strain of avian influenza (bird flu) virus began circulating in poultry in parts of Asia. At first, H5N1 caused only mild sickness in poultry, with symptoms that were not detected. Then in 1997 the virus mutated into a highly pathogenic form that could kill chickens within 48 hours. Almost all infected chickens died.
Historically, human infections with avian influenza viruses have been extremely rare. Most caused only mild illness followed by full recovery. H5N1 has been the exception. In the first documented instance of human infection, the virus caused 18 cases and six deaths in Hong Kong in 1997. That coincided with outbreaks of highly pathogenic H5N1 in poultry on farms and in live markets.
Hong Kong immediately destroyed its entire poultry population within three days. Many experts believe that averted a flu pandemic by removing opportunities for further human exposure. The outbreak ended.
Direct Jump to Humans
Influenza viruses can easily swap genetic material when two of them infect the same host. This exchange is called "reassortment." The pandemics of 1957 and 1968 were caused this way.
Prior to 1997, pigs were thought to be the mixing vessel for reassortment of viruses, because the cells of their respiratory tract have receptors for both avian and human influenza viruses. The reassorted virus could then pass from pigs to humans. But in the Hong Kong event, research indicated that the virus jumped directly from birds to humans - direct infection with a purely avian influenza virus. (Most human cases could be traced to direct contact with poultry.) It also meant humans also could serve as the mixing vessel for the exchange of virus genes.
On the encouraging side, the absence of disease in two high-exposure groups – poultry workers and cullers – indicated that H5N1 did not cross easily from birds to humans.
Following the Hong Kong eradication, H5N1 did not appear again until the end of 2003.
Then it suddenly became highly and widely visible.
First Phase: Hundreds of Outbreaks in Asia
On January 5, 2004, Vietnam reported an unusual cluster of severe respiratory disease in 11 previously healthy children hospitalized in Hanoi. Of these patients, 7 had died and 2 were in critical condition.
Concern intensified on January 8, when Vietnam confirmed that highly pathogenic H5N1 had killed large numbers of poultry at two farms.
On January 11-12, the WHO confirmed that three of the children who died in Hanoi were infected with H5N1. Elsewhere, Japan reported a large outbreak of highly pathogenic H5N1 avian influenza at a poultry farm. Within three weeks, Vietnam had more than 400 outbreaks in poultry, affecting at least three million birds.
With the confirmed human cases, the H5N1-infected poultry was now clearly a health threat. Two of the three prerequisites for the start of a pandemic had been met: (1) a new influenza virus subtype had emerged; (2) it infects humans, causing serious illness. Should the virus gain the ability to spread easily and sustainably among humans - the third prerequisite for a pandemic - everyone in the world would be vulnerable. (Even if human-to-human transmission occurs, it might be random and inefficient; the virus must easily and sustainably spread for it to cause a pandemic.) The risk that the H5N1 virus will acquire this ability will persist as long as opportunities for human infections occur. These opportunities, in turn, will persist as long as the virus continues to circulate in birds, and this situation could endure for some years to come.
Among the January cases, two Vietnamese sisters who died from H5N1 were identified as possibly (though inconclusively) the first instance of human-to-human transmission.
Actions were begun to eliminate the virus from its poultry host, including: culling of infected or exposed birds, quarantine and disinfection of farms, control of animal movements, and implementation of strict biosecurity measures on farms.
On January 23, Thailand announced a large outbreak at a poultry farm and its first two human cases of H5N1. During the rest of January, other human cases, most of which were fatal, occurred in Vietnam and Thailand. And Thailand reported 156 outbreaks affecting 11 million birds.
Near the end of January, the situation in poultry exploded. Outbreaks in the Republic of Korea, Vietnam, Japan, and Thailand were followed by reports in Cambodia, Lao People’s Democratic Republic, Indonesia, and China.
The H5N1 outbreaks in poultry were historically unprecedented. Previously, Highly Pathogenic Avian Influenza (HPAI) was considered a rare disease. Never before had HPAI spread so widely and rapidly to cause outbreaks in so many countries at once. Within three months, more than 120 million birds died or were destroyed.
The massive control efforts had an impact and the outbreaks declined sharply during March. Predictably, new human cases dwindled, then ceased. Yet from January through March, Vietnam and Thailand had reported 35 cases, of which 24 were fatal. This outbreak in humans was almost twice the size of that in Hong Kong in 1997 ... and far more deadly.
Second Phase: More Cases - And More Surprises From The Virus
In July, fresh outbreaks were reported in Cambodia, China, Indonesia, Thailand, and Vietnam. In late August, Malaysia reported its first poultry outbreaks. Compared with the first wave, these were much smaller, yet human cases again occurred. In September, Thailand reported its first probable case of human-to-human transmission in a family cluster. That initiated a massive door-to-door search, involving around one million volunteers. They detected no further clusters that suggested continuing transmission.
Since January, there had been 44 cases, with 32 fatal. Two features were striking: the overwhelming concentration of cases in previously healthy children and young adults, and the very high mortality.
Several unusual features suggested the virus may be evolving in ways which increasingly favor the start of a pandemic:
- Evidence strongly indicates that H5N1 is now endemic in parts of Asia, having established a permanent ecological niche in poultry. The risk of further human cases will continue, as will opportunities for a pandemic virus to emerge.
- Studies comparing virus samples over time show that H5N1 has become progressively more pathogenic and is now hardier than in the past, surviving several days longer in the environment.
- Evidence suggests that H5N1 is expanding its mammalian host range. The virus has been shown to cause severe disease and deaths in species not previously considered susceptible to any influenza A virus.
- The highly pathogenic form of H5N1 has been seen in dead migratory birds. Wild waterfowl are the natural reservoir of all influenza A viruses and have historically carried low-pathogenic viruses without showing symptoms or succumbing to disease. Although more evidence is needed, the finding suggests that the role of migratory waterfowl in the evolution and maintenance of highly pathogenic H5N1 may be changing.
- Evidence suggests that domestic ducks are now excreting H5N1 in its highly lethal form without showing signs of illness. This "silent" role of domestic ducks may help explain why some recent human cases cannot be linked to contact with diseased poultry. The ducks were not sick, but were transmitters.
The present concentration of poultry outbreaks in rural areas, where most households maintain free-ranging flocks, is of particular concern, especially as many households depend on these birds for income and food.
Taken together, these changes in the ecology of the disease and behavior of the virus have created multiple opportunities for a pandemic virus to emerge. Thusfar, it has not happened. But, with the virus now endemic, the probability has increased that H5N1 will realize its pandemic potential.
WHO H5N1 avian influenza: timeline [45k .pdf]