Swine flu is viral respiratory disease mainly of poultry and certain other bird species, including migratory water birds, some imported pet birds, and ostriches, that can be transmitted directly to humans. The first known cases in humans were reported in 1997, when an outbreak in poultry in Hong Kong led to severe illness in 18 people, a third of whom died. Symptoms of bird flu in humans resemble those of the human variety of influenza and include fever, sore throat, cough, headache, and muscle aches, which appear following an incubation period of several days. . Between 2003 and late 2005, outbreaks of the most deadly variety of bird flu occurred among poultry in Cambodia, China, Indonesia, Japan, Kazakhstan, Laos, Malaysia, Romania, Russia, South Korea, Thailand, Turkey, and Vietnam. Hundreds of millions of birds in those countries died from the disease or were killed in attempts to control the epidemics. From 2003 through January 2009, 397 people were reported to have been infected with bird flu, and slightly less than two-thirds of them died. The majority of human infections and deaths occurred in China, Egypt, Indonesia, Thailand, and Vietnam. Poultry-associated human infection with a less severe form of the disease was reported in the Netherlands. Bird flu in avian species occurs in two forms, one mild and the other highly virulent and contagious; the latter form has been termed fowl plague. Mutation of the virus causing the mild form is believed to have given rise to the virus causing the severe form. The infectious agents of bird flu are any of several subtypes of type A orthomyxovirus. Other subtypes of this virus are responsible for most cases of human influenza and for the great influenza pandemics of the past Genetic analysis suggests that the influenza A subtypes that afflict mainly no avian animals, including humans, pigs, whales, and horses, derive at least partially from bird flu subtypes. All the subtypes are distinguished on the basis of variations in two proteins found on the surface of the viral particle hemagglutinin (H) and neuraminidase (N). The 1997 bird flu outbreak in Hong Kong was found to be caused byH5N1. This subtype, first identified in terns in South Africa in 1961, has been responsible for nearly all laboratory-confirmed bird flu infections in humans and for the most devastating outbreaks in poultry. Other bird flu subtypes recognized to cause disease in birds and humans are H7N2, H7N3, H7N7, and H9N2. The H5N1 virus, however, appears resistant to at least two of the drugs, amantadine and rimantadine.