Avian Influenza – The Next Pandemic?

1Departments of Pathology and Laboratory Medicine, Medicine, and Microbiology and Infectious Diseases, Centre for Antimicrobial Resistance, University of Calgary, Calgary, Alberta; 2Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia Correspondence: Dr JM Conly, Foothills Medical Centre, 1403-29 Street South, Calgary, Alberta T2N 2T9. Telephone 403-944-8222, fax 403-944-1095, e-mail jconly@ucalgary.ca Avian influenza (AI) strains affecting humans were first reported in Hong Kong during the 1997 influenza season. These strains were shown to be derived from avian sources without genetic reassortment between avian and human influenza viruses (1-3). The first AI A strain (H5N1) affected 18 humans and was associated with six deaths during the 1997 to 1998 influenza season. A case-control study (4) identified recent exposure to live poultry as an important risk factor for infection with H5N1. Furthermore, cohort studies (5,6) suggested that human-to-human transmission of the H5N1 virus was limited. Three additional cases of confirmed H5N1 influenza occurred in Hong Kong in February 2003, causing two deaths (7). From late 2003 to February 2004, outbreaks of H5N1 infection in poultry were detected in a number of Asian countries, notably Vietnam, Thailand, Cambodia, China, Indonesia, Japan, Laos and the Republic of Korea (8). These poultry outbreaks have been unpredictable and unprecedented in their scope, with wide geographical spread and severe economic consequences for the affected countries. More than one-half of the aforementioned countries experienced highly pathogenic AI in fowl for the first time in their respective histories. The poultry outbreak in 2004 also affected humans, resulting in the largest recorded human outbreak of H5N1 influenza to date (34 officially reported cases, 23 of which were fatal) (9). Although no human cases had been reported since the winter of 2003/2004, the World Health Organization reported three fatal human cases of laboratory-confirmed AI in Vietnam in August 2004, with H5N1 identified as the etiological agent (10). In addition, the AI A H9N2 virus was isolated for the first time in two young, hospitalized children in Hong Kong, in March 1999 (11,12). The children were unrelated, hospitalized at different facilities, did not have any known contact with or link to each other and had not travelled outside Hong Kong. Both children had uncomplicated, febrile, upper respiratory tract illness. Evidence for five additional human infections attributable to the H9N2 influenza virus was reported from the Guangdong province of China in 1998 (13). The presence of the H9N2 antibody from persons in mainland China and poultry workers in Hong Kong (13,14) suggests that additional unrecognized human H9N2 infections have occurred. Another strain, AI H7N7, has been isolated in humans on three separate occasions since 1980. The majority of these patients developed conjunctivitis after contact with harbour seals, ducks or chickens. In addition, an outbreak of AI H7N7 in the Netherlands was associated with the death of a veterinarian in April 2003. This outbreak was also associated with mild illness in 83 humans, the majority of whom had conjunctivitis (although seven exhibited respiratory symptoms). Mild cases of infection due to an H9N2 strain occurred in children in Hong Kong in 1999 (two cases) and in mid-December 2003 (one case). Given the repeated occurrences of human AI in Asia and Europe, it was considered timely to review the current taxonomy and epidemiology of AI, and the risks these strains pose to the human population. Influenza A and B are the two types of influenza viruses responsible for human epidemic disease. Influenza type C viruses cause mild illness in humans and do not appear to cause epidemics or pandemics. Influenza A viruses are found in many different animal species, including humans, ducks, chickens, pigs, whales, horses and seals, whereas influenza B viruses circulate widely only among humans. Influenza A viruses are divided into subtypes based on two antigens (hemagglutinin [H] and neuraminidase [N]) on the surface of the virus, whereas influenza B and C viruses are not classified according to subtype. There are 15 different hemagglutinin subtypes and nine different neuraminidase subtypes identified to date, all of which have been found among influenza A viruses in wild birds. The hemagglutinin acts as a site of attachment of the virus to host cells to initiate infection and also to erythrocytes, from which its name originally was derived (15). Hemagglutinin contains common and strain-specific antigens and demonstrates antigenic variation. The neuraminidase antigen contains subtype-specific antigens, and also demonstrates antigenic variation between subtypes. Neuraminidase is a surface glycoprotein possessing enzymatic activity essential for viral replication in influenza A and influenza B viruses. Neuraminidase allows the release of newly produced virions from infected host cells, prevents the formation of viral aggregates after release from the host cells and prevents viral inactivation by respiratory mucous (16,17). It is thought that this enzyme may also promote viral penetration into respiratory epithelial cells, and may contribute to the pathogenicity of the virus by promoting the production of pro-inflammatory cytokines such as interleukin-1 and tumour necrosis factor from macrophages (18-20).