Influenza A pandemics of the 20th century with special reference to 1918: virology, pathology and epidemiology

Influenza A virus initiated worldwide epidemics (pandemics) in 1918, 1957, 1968 and 1977. A revised calculation of the 1918-1919 pandemic estimates th at 40 million persons died and 500 million were infected. The mortalities i n 1957 and 1968 were nearly 6 million. Biological and genetic characteristi cs of the causative agents of the more recent pandemics, have been well stu died but little is known about the causative agent of the Great Pandemic in 1918. Genetic characterisation of the 1918 virus has been achieved by sour cing virus RNA from formalin fixed lung samples or by exhuming frozen victi ms of the outbreak from Arctic regions. Initial analysis of the HA gene fro m two USA sources indicates a virus related to swine and human influenza wi th no base insertion at the HA1-HA2 cleavage junction which, at least in av ian influenza A, characterises high virulence. Important unanswered questio ns are whether the 1918 virus spread pantropically perhaps to include the b rain and hence cause encephalitis including the later lethargic forms, or w hether infection was confined to the respiratory tract. Re-examination of r eports of respiratory disease in England and France in 1916-1917 may indica te a non-Spanish origin of the pandemic and a period of 2 years for the vir us to be seeded worldwide. In contrast the other two pandemic viruses in 19 57 and 1968 appeared to originate in Asia. New anti-neuraminidase drugs in conjunction with amantadine and novel developments with influenza vaccines would be expected to ameliorate the disease in a future pandemic. Copyright (C) 2000 John Wiley & Sons, Ltd.