THE THIN WHITE LINE: the history of a future avian influenza pandemic

Chapter 1: Outbreak

A virus is born

    Three major types of influenza have been categorized since scientists first recognized the disease in the 1930s: A, B and C. Influenza B affects people, mostly children, and changes little from year to year. Influenza C causes only mild infection. Influenza A affects everybody. Pandemic influenza viruses are A-type viruses.
    Type A viruses are further classified according to proteins on their surface——hemagglutinin (H) and neutraminidase (N). Consider a virus as a little spiked ball floating in space searching for respiratory cells to convert into factories to make more virus.
    The H protein’s job is breaking and entering; it helps the virus attach itself to and then penetrate the cell. This accomplished, the virus takes over the cell’s machinery and makes copies of itself. The N protein’s is jail-breaking; it helps free these new virions so they can spread and find other healthy cells to infect.
    Therefore, an influenza virus may be classified as A/H2N1; before H5N1 evolved to become infectious to humans, there were three major Type A viruses circulating worldwide: H1N1, H2N1 and H3N2.
    The word virus is derived from a Latin word meaning “poison.”
    Over time, a population builds up a natural level of immunity to disease. When somebody has a high level of immunity to a virus, his or her immune system’s antibodies recognize the virus and attach to the proteins on its surface, blocking them. The antibodies recognize the virus because of prior infection; if you get the flu, it is unlikely you will suffer from the same type of flu again. One would think that a flu virus would therefore die in a few years after it had run out of hosts, but this doesn’t happen.

In 1997, the avian flu virus H5N1 acquired the ability to infect humans, alarming health systems around the world and resulting in the culling of millions of wild birds and poultry. Here, a man in Germany wearing protective biohazard gear removes feathers from a dead bird for analysis and testing for avian flu. Organizations such as the WHO worried that avian flu could mutate so that it became easily transmissible between humans, triggering a pandemic.(2)

    Influenza survives by constantly evolving and changing. Being unstable and fast reproducing, the virus can mutate quickly, producing new variants. Typically, it evolves one of two ways, antigenic drift or shift.
    Most often, it drifts, staying the same subtype, such as H2N1, but gradually evolving throughout the entire flu season and from year to year. This is why somebody theoretically could catch the same flu strain each year——they had caught and built up immunity to a past form of a flu strain that has since slightly mutated and now evades their immune system; their antibodies simply don’t recognize the modified virus.
    Antigenic drift is an important reason why people must get vaccinated annually instead of once. A single flu shot ideally provides immunity to everything that’s out there at the time. But the flu is a moving target. By the end of the flu season, it has changed into something slightly different. And so every year the vaccine must be updated.
    This situation created a race in which common flu viruses are virtually always one small step ahead of humans. If the flu didn’t stay one step ahead, it would die.
    On the other hand, fortunately for humans, drifting viruses do encounter some level of acquired immunity, which limits their virulence, or deadliness.
    Every 20 to 30 years on average, however, a major mutation occurs, called antigenic shift. These novel viruses are usually zoonoses, infections formally exclusive to animals but mutating such that they can be transmitted to humans. It is believed that all influenza A-type viruses, for example, originated in the digestive tracts of wild birds and subsequently mutated to infect other animals such as pigs and horses as well as humans.
Antigenic shift in influenza strains can occur when a human flu and an animal flu infect the same cells in an animal or human and then swap genetic material, recombining to become an entirely new virus. A pig infected with a human flu virus, for example, might become contaminated by flu-infected droppings from another animal, incubating a new virus that it passes back to a human. If the infected human can then easily pass the novel virus on to other humans, ideal conditions for a pandemic have been achieved.
    For this reason, China, with its high population density in close proximity to animals——one out of every seven people in the world, in fact, lives on small farms in China—has long been considered a likely candidate to produce pandemic influenza. Most new pandemic strains, such as the Hong Kong Flu and Severe Acute Respiratory Syndrome (SARS), originated in Asia. In 1968, when the Hong Kong Flu emerged, 790 million people populated China along with 5.2 million pigs and 12.3 million poultry. In 2012, these populations had swelled to 1.3 billion people, 508 million pigs and 13 billion poultry. (3)
    Zoonotic diseases are the most lethal killers of the microbial world, with such famous diseases as plague, rabies, tuberculosis, anthrax, measles, smallpox, AIDS, SARS and radical new strains of influenza. A major reason they are so severe is because they are entirely new, meaning humans have little or no immunological defense against them.
    As a result, the virus can be highly virulent——particularly among young, healthy people who would normally not be at high risk; pathogenic——able to cause disease; and highly infectious and contagious——able to be passed from person to person.
    Unlike other zoonotic diseases, however, influenza may be particularly deadly and infectious when it emerges, but its rapid mutation also enables it to reach an accommodation with humans, its hosts, over time; deadly new flu strains tend to gradually become milder. This too is a survival technique for the flu; after all, it is not in the virus’ interest to kill its host, but instead to proliferate by being passed on to new hosts.
    The Spanish Flu, for example, started as a major killer. In 1918-19, in fact, it killed between 40 and 100 million people. Today, it is simply another seasonal flu strain that continues to circulate each year.