No abstract

The transmission of avian H5N1 influenza viruses to 18 humans in Hong Kong in 1997 with six deaths established that avian influenza viruses can transmit to and cause lethal infection in humans. This report characterizes the antigenic and biological properties of the H5N1 influenza viruses isolated from chickens, ducks, and geese from farms and poultry markets in Hong Kong during 1997 and compares them with those of virus isolated from the index human case. Each of the H5N1 viruses from Hong Kong poultry markets that were tested were lethal in chickens, possessed polybasic amino acids at the carboxy-terminus of HA1, and by definition were highly pathogenic in poultry. The available nonpathogenic H5 influenza viruses and the pathogenic H5N1 virus from Hong Kong were analyzed with monoclonal antibodies prepared to A/chicken/Pennsylvania/1370/83 (H5N2). The analysis revealed limited antigenic drift in 15 years and established that monoclonal antibodies are useful reagents for identification and antigenic analysis of avian strains that may transmit to humans in the future. One of the monoclonal antibodies permitted separation of the H5N1 influenza viruses from poultry into two groups that correlated with the presence or absence of a carbohydrate at residue 158 adjacent to the receptor binding site on HA. The H5N1 viruses examined replicated in geese, pigs, rats, and mice, but to only a very limited extent in ducks. It is noteworthy that all infected geese shed virus and that the H5N1 viruses caused disease signs and death in a portion (3 of 16) of the geese, with evidence of systemic spread to the brain. The tropism for geese is unusual and may provide insight into the origin of these viruses. In mice, the H5N1 virus caused lethal pneumonia and spread systemically to the brain. Mice would thus provide an ideal model system for studying immune responses and pathogenesis. Transmission experiments in chickens revealed that the H5N1 viruses are spread by fecal-oral transmission rather than by aerosol, and that the viruses are inactivated by drying of feces at ambient temperature. However, infectivity is maintained for at least 4 days in wet feces at 25 degreesC. There were differences in the morphology of the H5N1 viruses isolated from birds and humans. The perpetuation of H5N1 influenza viruses in the poultry markets in Hong Kong and the transmission of these viruses to humans emphasize the importance of these markets in the epidemiology of influenza. The poultry markets are of critical importance in the perpetuation and transmission of influenza viruses to other avian species and to mammals, including humans.

In 1997, outbreaks of highly pathogenic influenza A (H5N1) among poultry coincided with 18 documented human cases of H5N1 illness. Although exposure to live poultry was associated with human illness, no cases were documented among poultry workers (PWs). To evaluate the potential for avian-to-human transmission of H5N1, a cohort study was conducted among 293 Hong Kong government workers (GWs) who participated in a poultry culling operation and among 1525 PWs. Paired serum samples collected from GWs and single serum samples collected from PWs were considered to be anti-H5 antibody positive if they were positive by both microneutralization and Western blot testing. Among GWs, 3% were seropositive, and 1 seroconversion was documented. Among PWs, approximately 10% had anti-H5 antibody. More-intensive poultry exposure, such as butchering and exposure to ill poultry, was associated with having anti-H5 antibody. These findings suggest an increased risk for avian influenza infection from occupational exposure.

Outbreaks of highly pathogenic avian influenza caused by H5N1 viruses were reported almost simultaneously in eight neighbouring Asian countries between December 2003 and January 2004, with a ninth reporting in August 2004, suggesting that the viruses had spread recently and rapidly. However, they had been detected widely in the region in domestic waterfowl and terrestrial poultry for several years before this, and the absence of widespread disease in the region before 2003, apart from localised outbreaks in the Hong Kong Special Autonomous Region (SAR), is perplexing. Possible explanations include limited virus excretion by domestic waterfowl infected with H5N1, the confusion of avian influenza with other serious endemic diseases, the unsanctioned use of vaccines, and the under-reporting of disease as a result of limited surveillance. There is some evidence that the excretion of the viruses by domestic ducks had increased by early 2004, and there is circumstantial evidence that they can be transmitted by wild birds. The migratory birds from which viruses have been isolated were usually sick or dead, suggesting that they would have had limited potential for carrying the viruses over long distances unless subclinical infections were prevalent. However, there is strong circumstantial evidence that wild birds can become infected from domestic poultry and potentially can exchange viruses when they share the same environment. Nevertheless, there is little reason to believe that wild birds have played a more significant role in spreading disease than trade through live bird markets and movement of domestic waterfowl. Asian H5N1 viruses were first detected in domestic geese in southern China in 1996. By 2000, their host range had extended to domestic ducks, which played a key role in the genesis of the 2003/04 outbreaks. The epidemic was not due to the introduction and spread of a single virus but was caused by multiple viruses which were genotypically linked to the Goose/GD/96 lineage via the haemagglutinin gene. The H5N1 viruses isolated from China, including the Hong Kong SAR, between 1999 and 2004 had a range of genotypes and considerable variability within genotypes. The rising incidence and widespread reporting of disease in 2003/04 can probably be attributed to the increasing spread of the viruses from existing reservoirs of infection in domestic waterfowl and live bird markets leading to greater environmental contamination. When countries in the region started to report disease in December 2003, others were alerted to the risk and disease surveillance and reporting improved. The H5N1 viruses have reportedly been eliminated from three of the nine countries that reported disease in 2003/04, but they could be extremely difficult to eradicate from the remaining countries, owing to the existence of populations and, possibly, production and marketing sectors, in which apparently normal birds harbour the viruses.

No abstract