No firm figures exist for the total number of influenza victims who died in the worldwide pandemic of 1918-1919. At best they are measured as "many millions." The flu dead outnumbered those who fell in the battlefields of World War I, which raged from 1914 through 1918.
Flu sidestepped World War II (1939-1945), again outstripping those soldiers who succumbed to combat.
Three journals have documented the avian flu threat: The New York Times, dated Feb. 5, 2004, devoted nearly a full page to its story headlined "As bird flu spreads, global health weaknesses are exposed."
Sciencexpress of the same date carries a Research Article titled "The structure and receptor-binding properties of the 1918 influenza hemagglutinin." Its senior author is John Skehel, of Britain's National Institute for Medical Research in London. A New York Times sidebar bylined Lawrence Altman is headed "Vaccines for humans clears hurdle as bird flu expands." More to the point, and days earlier, is a brief commentary in The Lancet (Jan. 24, 2004) bearing the foreboding headline "Avian influenza: The threat looms."
That editorial leads off, "Five human deaths have been reported in Vietnam up to Jan. 20, 2004. The disease," it explained, "is caused by influenza virus Type A and infects many animal species. A highly pathogenic avian influenza," the editorial continues, "is caused by subtypes H5 and H7. [H is the hemagglutinin protein on the virus surface.] Wild birds are thought to be the reservoir for the virus, which infects humans via live-poultry markets, common in southeast Asia."
Commenting on the implications for a widespread human outbreak of avian influenza, the editorial concludes: "The possibility of a human pandemic with a highly pathogenic avian influenza virus must be taken very seriously, indeed. With the latest outbreak in birds in Vietnam, teams from [World Health Organization], the U.S Centers for Disease Control and Prevention and the United Nations Food and Agriculture Organization were quickly in country. One thing is clear," The Lancet article pointed out. "Given that all new infectious diseases of human beings to emerge in the past 20 years have had an animal source, veterinary science and animal husbandry are as important for disease control as clinical medicine.
"In 1997," the commentary continued, "18 people in Hong Kong were admitted to a hospital with H5N1 [N is the neuraminidase surface protein] infection, and six died. In 2003, two Hong Kong residents, after returning from China, developed bird flu influenza, and one died. In the same year, avian influenza, another virulent subtype, broke out in the poultry industry in the Netherlands, and a veterinarian died. The main response to outbreaks of avian influenza is mass culling of poultry, which is now under way in Vietnam. In the 1997 outbreak in Hong Kong, 1.4 million chickens and other poultry - the entire stock - were destroyed. The 1999 outbreak saw another 1.25 million birds culled."
Human-To-Human Infection Feared
"What if bird influenza, with its high virulence, becomes transmissible between human beings?" The Lancet asked rhetorically. "Such a catastrophe has yet to occur, but is one of the major fears of infectious disease experts throughout the world. Until the 1997 outbreak in Hong Kong, it had been thought that the avian transmission to human beings would require an intermediate such as the pig, whose respiratory epithelium shares sialic acid isoforms with both birds and humans. The prospect of a worldwide pandemic is massively frightening!
"Vaccination against the avian subtypes cannot be an option," the commentary noted, "because they are rapidly lethal to chick embryos, which culture vaccines. Plasmid reverse-genetic technology can be used to make influenza vaccines, but they have to be studied in clinical trials. Antiviral drugs are expensive and not effective enough. And the coronavirus quarantine measures used to control [severe acute respiratory syndrome] are unlikely to control influenza."
The Lancet observed in a separate article that "similar questions can be asked about a pandemic of influenza that is probably imminent."
Human Remains Preserved In Alaska Permafrost
The Lancet, in a "Rapid review" separate from its other commentary, noted that "live-animal, so-called wet markets' provide a source of vertebrate and invertebrate animals for customers in tropical and subtropical regions of the world. Wet markets sell live poultry, fish, reptiles and mammals of every kind - mostly chicken, pigeon, quail, ducks, geese and a wide range of exotic wild-caught and farm-raised fowl are usually separated from markets selling fish or red-meat animals. But the stalls can be near each other with no physical separation protecting from infection."
Two studies of the "Spanish flu" virus that killed millions of people in the 1918-1919 pandemic have been published in Science, one on Feb. 5, 2004. Its title: "Structure of human H1 hemagglutinin precursor from the extinct 1918 influenza virus." Its lead authors are at the Scripps Research Institute in La Jolla, Calif.; Mount Sinai School of Medicine in New York; and the Armed Institute of Pathology in Washington.
They suggest that excavating human remains in the frozen Alaska permafrost "may help explain what made the virus so lethal. The evidence suggests," they added, that the virus may have been derived from an avian virus, and retained some key characteristics of its avian precursor that caught the human immune system off guard. That archeological data have allowed the Science co-authors to reconstruct certain proteins, such as the "hemagglutinin membrane glycoprotein." That molecule, known as "HA," controls the first stages of infection, in which HA binds to a particular receptor on the host cell.
Results reveal that the 1918 viral HA has structural features previously seen in avian influenza viruses. "In particular," the Science report notes, "the receptor's binding site contains the amino acids of the avian virus, but positions them in a way that enables them to interact with human proteins, allowing the virus to be transmitted in the human population."