History and epidemiology.
Influenza viruses are normally highly species-specific, meaning that viruses that infect an individual species (humans, certain species of birds, pigs, horses, and seals) stay “true” to that species, and only rarely spill over to cause infection in other species. Since 1959, instances of human infection with an avian infl uenza virus have been documented on only 10 occasions. Of the hundreds of strains of avian infl uenza A viruses, only four are known to have caused human infections: H5N1, H7N3, H7N7, and H9N2. In general, human infection with these viruses has resulted in mild symptoms and very little severe illness, with one notable exception: the highly pathogenic H5N1 virus.
Of all infl uenza viruses that circulate in birds, the H5N1 virus is of greatest present concern for human health for two main reasons. First, the H5N1 virus has caused by far the greatest number of human cases of very severe disease and the greatest number of deaths. It has crossed the species barrier to infect humans on at least three occasions in recent years: in Hong Kong in 1997 (18 cases with six deaths), in Hong Kong in 2003 (two cases with one death) and in the current outbreaks that began in December 2003 and were first recognized in January 2004.
A second implication for human health, of far greater concern, is the risk that the H5N1 virus - if given enough opportunities - will develop the characteristics it needs to start another infl uenza pandemic. The virus has met all prerequisites for the start of a pandemic save one: the ability to spread effi ciently and be sustainable among humans. While H5N1 is presently the virus of greatest concern, the possibility that other avian infl uenza viruses, known to infect humans, might cause a pandemic cannot be ruled out.
The virus can improve its transmissibility among humans via two principal mechanisms. The first is a “reassortment” event, in which genetic material is exchanged between human and avian viruses during co-infection of a human or pig. Reassortment could result in a fully transmissible pandemic virus, characterised by a sudden surge of cases with explosive spread.
The second mechanism is a more gradual process of adaptive mutation, whereby the capability of the virus to bind to human cells increases during subsequent infections of humans. Adaptive mutation, expressed initially as small clusters of human cases with some evidence of human-to-human transmission, would probably give the world some time to take defensive action, if detected suffi ciently early.
During the first documented outbreak of human infections with H5N1, which occurred in Hong Kong in 1997, the 18 human cases coincided with an outbreak of highly pathogenic avian infl uenza, caused by a virtually identical virus, in poultry farms and live markets. Extensive studies of the human cases determined that direct contact with diseased poultry was the source of infection. Studies carried out in family members and social contacts of patients, health workers engaged in their care, and poultry cullers found very limited, if any, evidence of spread of the virus from one person to another. Human infections ceased following the rapid destruction - within three days - of Hong Kong’s entire poultry population, estimated at around 1.5 million birds. Some experts believe that that drastic action may have averted an infl uenza pandemic.
All evidence to date indicates that close contact with dead or sick birds is the principal source of human infection with the H5N1 virus. Especially risky behaviours identified include the slaughtering, defeathering, butchering and preparation for consumption of infected birds.
In a few cases, exposure to chicken faeces when children played in an area frequented by free-ranging poultry is thought to have been the source of infection. Swimming in water bodies where the carcasses of dead infected birds have been discarded or which may have been contaminated by faeces from infected ducks or other birds might be another source of exposure. In some cases, investigations have been unable to identify a plausible exposure source, suggesting that some as yet unknown environmental factor, involving contamination with the virus, may be implicated in a small number of cases. Some explanations that have been put forward include a possible role of peri-domestic birds, such as pigeons, or the use of untreated bird faeces as fertilizer. At present, H5N1 avian infl uenza remains largely a disease of birds. The species barrier is signifi cant: the virus does not easily cross from birds to infect humans. Despite the infection of tens of millions of poultry over large geographical areas since mid-2003, fewer than 200 human cases have been laboratory confi rmed. For unknown reasons, most cases have occurred in rural and periurban households where small fl ocks of poultry are kept. Again for unknown reasons, very few cases have been detected in presumed high-risk groups, such as commercial poultry workers, workers at live poultry markets, cullers, veterinarians, and health staff caring for patients without adequate protective equipment. Also lacking is an explanation for the puzzling concentration of cases in previously healthy children and young adults. Research is urgently needed to better define the exposure circumstances, behaviours, and possible genetic or immunological factors that might enhance the likelihood of human infection.
Assessment of possible cases.
Investigations of all the most recently confi rmed human cases, in China, Indonesia, and Turkey, have identifi ed direct contact with infected birds as the most likely source of exposure. When assessing possible cases, the level of clinical suspicion should be heightened for persons showing infl uenza-like illness, especially with fever and symptoms in the lower respiratory tract, who have a history of close contact with birds in an area where confi rmed outbreaks of highly pathogenic H5N1 avian infl uenza are occurring. Exposure to an environment that may have been contaminated by faeces from infected birds is a second, though less common, source of human infection. To date, not all human cases have arisen from exposure to dead or visibly ill domestic birds. Research published in 2005 has shown that domestic ducks can excrete large quantities of highly pathogenic virus without showing signs of illness. A history of poultry consumption in an affected country is not a risk factor, provided the food was thoroughly cooked and the person was not involved in food preparation. As no effi cient human-to- human transmission of the virus is known to be occurring anywhere, simply travelling to a country with ongoing outbreaks in poultry or sporadic human cases does not place a traveller at enhanced risk of infection, provided the person did not visit live or “wet” poultry markets, farms, or other environments where exposure to diseased birds may have occurred.
