When drift becomes shift, a pandemic strain emerges

Well in the morning . . . dead by nightfall

In addition to antigenic drift, which is seen to some extent in a typical flu season, influenza type A viruses can undergo a more dramatic and abrupt type of antigenic change called antigenic shift, explains a draft pandemic response plan developed by advisors and officials at the National Vaccine Program Office of the Centers for Disease Control and Prevention.

Antigenic shift occurs when viruses belonging to a new influenza A subtype bearing either a novel hemagglutinin or neuraminidase proteins begin circulating among people. Antigenic shift may be the result of an exchange of genetic material between two different influenza viruses or changes in an influenza virus that previously infected only animals that allows the virus to be transmitted to people. When antigenic shift does occur, a large proportion, or even all, of the world’s population would not have antibody against the new virus.

If the new virus can cause disease in people and can be transmitted easily from person to person, a pandemic can occur. "Pandemic’ technically means that there is a new influenza A virus against which the human population does not have immunity and that spreads globally," says Carolyn Bridges, MD, a medical epidemiologist in the influenza branch at the CDC. "You have to have a new subtype of influenza A that the population does not have any antibody to. It has to be one that is easily transmitted from person to person and be pathogenic."

According to the draft plan, influenza pandemics have been recognized since the 1500s. During this century, pandemics occurred in 1918, 1957, and 1968, causing widespread illness, death, and social disruption. The 1918-1919 Spanish influenza pandemic is the catastrophe against which all modern pandemics are measured. In addition to millions of deaths, 20% to 40% of the worldwide population became severely ill. There were approximately 20 million deaths worldwide, including 500,000 deaths in the United States. This virus was especially quick to kill. Many people who felt well in the morning became sick by noon and were dead by nightfall. Those who did not succumb to the disease within the first few days often died of complications of the flu caused by bacterial illnesses such as pneumonia, the draft states.

While the 1918 pandemic was first detected in the United States, its geographic origin remains unclear, Bridges says. However, the 1957 and 1968 pandemics appeared to have begun in China or elsewhere in Asia, Bridges notes. Some have hypothesized it is the proximity of humans, fowl, and swine — both in rural settings and urban bird markets — that allows intermixing of mutating flu strains in Asia. "Perhaps there is just an increased chance that you are going to have interspecies [mutation] because there is increased contact," she says. "But I don’t think there is some kind of genetic susceptibility in that population for becoming infected with animal viruses."

The question of how serious the next pandemic might be depends in part on how virulent and transmissible the virus is. "Since our world today is vastly more populated than it was during previous pandemics, and people travel the globe with ease, the spread of a next pandemic could be more rapid than that of previous pandemics," the draft guidelines warn.