PREVENTING PANDEMICS

Because influenza viruses can gene swap so easily, public health officials closely monitor the types of influenza viruses that infect animals. Viruses that infect animals may accumulate mutations or pick up genes that enable them to infect human cells. Severe acute respiratory syndrome (SARS), for example, is a respiratory illness caused by a virus. In 2003, more than 8,000 people worldwide became sick with SARS, according to the World Health Organization (WHO), and 774 died. Experts think the virus jumped from animals to people, although they have not yet determined the identity of the animal host.

They do, however, suspect that the source was a species of bird. Birds are a primary source of potentially pandemic viruses. Wild birds are routinely infected with viruses that live in their gastrointestinal tracts but cause little or no disease in the bird. Sometimes, however, bird flu viruses can jump from wild birds to poultry or other farm animals and become lethal. And since many human populations maintain close contact with poultry, pigs, and other domestic animals, the risk of an animal flu infecting humans is high.

In the 1990s, a lethal strain of the avian flu virus (H5N1) crossed over into humans from domesticated birds, but it was not easily transferred from person to person. However, scientists continue to monitor this bird strain, not only because it can be deadly to the commercial poultry business, but also because the 1918 flu carried a variation of the H5N1 bird flu genes. In fact, most human influenza pandemics have been caused by flu viruses that carry variations of bird flu genes (TABLE 31.1).

FOR COMPARISON Defending Oneself Is a Fact of Life






The adaptive immune system that protects humans and other vertebrates from infection is a relatively recent adaptation. Evidence suggests that adaptive immunity first arose in fishes, some 500 million years ago. The innate immune system, by contrast, is much older and is shared by creatures as diverse as sea sponges, fruit flies, and humans. In fact, all organisms have evolved ways to defend themselves from threats, both large and small.

Sea sponges employ physical and chemical defenses
Bacteria use enzymes to defend against infection

Some organisms are able to repel invaders and predators by physical and chemical means. The invertebrate animals called sea sponges, for example, combine physical defenses with poisonous secretions to ward off danger. An internal support system made of collagen fibers and stiffened with hard spikes called crystalline spicules acts as a physical defense against predators like fish, who may want to take a bite. In order to deter such predators from getting close enough to nibble, sponges also secrete chemicals that are toxic to many potential predators.

Sea stars have innate cellular defenses

Many bacteria are able to protect themselves from a class of viruses known as bacteriophage—”phage” for short. Phage infection causes a bacterial cell to burst, or lyse—a life-ending event for that bacterium. Bacteria defend themselves against phage by producing enzymes that act like scissors, cutting up the DNA that phage inject into the bacterial cell. By destroying the phage DNA, bacteria prevent phage from replicating. A bacterium’s own DNA is protected from these powerful molecular scissors by a mechanism that chemically modifies its DNA, ensuring that it won’t be cut up by these enzymes.

Many invertebrate animals have an innate immune system armed with specialized cells that attack or neutralize invaders. Sea stars are a good example. It has long been known that sea stars very rarely develop bacterial infection. It turns out that their ability to resist bacterial pathogens comes from a class of cells called amoebocytes, which act much like the macrophages of the vertebrate innate immune system. Amoebocytes circulate in the body cavity fluid of sea stars. When bacteria are injected into the body cavity of sea stars, the amoebocytes actively engulf and destroy the bacteria within 10 minutes. This rapid response helps sea stars remain infection free.

Fruit flies have multiple physical, chemical, and cellular defenses

Fruit flies also have several innate defense mechanisms. Phagocytic cells called plasmatocytes act like macrophages, ingesting and destroying foreign cells by phagocytocis. Fruit flies also have cells called lamellocytes, which can coat and essentially wall off foreign objects, such as the eggs of parasitic wasps, which are too big to be phagocytosed. This walling off, or encapsulation, helps destroy the foreign object. Humans carry out a similar process in response to lung infections, such as those caused by tuberculosis. In humans, immune cells surround and wall off the pathogen in a structure called a granuloma.

That many organisms from many different phyla share similar kinds of immune responses is evidence that these defensive strategies evolved early in the history of life and were a crucial part of the organisms’ survival and reproduction.

To help people ward off flu infection, public health officials offer flu shots every year at the beginning of flu season, which typically runs from October to February in the northern hemisphere. A flu shot is a vaccine: a weakened version or part of a flu virus is injected into the body in the hope of generating a primary immune response and memory cells against that strain of virus. However, since influenza viruses mutate so frequently, a yearly flu shot may not protect us from getting the flu the following year. In fact, a flu shot may not confer protection for the duration of a single season. Scientists create a new vaccine each year by tracking which strains of influenza are circulating worldwide and studying the antigens on their surfaces. But their predictions can be wrong. If public health officials decide to vaccinate against a strain of influenza with one variant of hemagglutinin antigen but a strain with a different variant of the antigen strikes, those who are vaccinated may become ill anyway.

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This is one reason why public health officials were so concerned about the 2009 H1N1 influenza virus, or swine flu. H1N1 was a new virus strain that was first detected in people in the United States in April 2009 and became a worldwide pandemic in 2010, the first pandemic in 40 years. It was called swine flu because many of its genes were similar to those in influenza viruses that normally occur in North American pigs. Further study has shown, however, that this new virus is actually a mix of genes from flu viruses that normally circulate in European and Asian pigs, birds, and humans.

There are other reasons for concern. Whereas 90% of deaths from seasonal flu occur in people over 65 years old, H1N1 causes most severe disease in people under 25. The 1918 virus also preferentially affected young people, suggesting that swine flu, like Spanish flu, has the potential to become a more virulent infection that can kill within hours. By the end of the 2009–2010 flu season, a total of 2,125 deaths in the United States were confirmed as influenza deaths. A total of 344 children died, four times higher than in the previous four years.

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In 2009, Kawaoka reported in the journal Nature that the H1N1 virus could replicate in the lungs of mice, ferrets, and monkeys much better than a seasonal flu virus could. That finding “suggests the virus can cause serious respiratory illness in many people,” Kawaoka stated in the paper. He also reported that some people born before 1918 have antibodies to the H1N1 virus, suggesting it shares some antigens in common with the 1918 virus.

Today, scientists have better surveillance, better communication, and can make more informed decisions about whether and how to quarantine groups to prevent a dangerous virus from spreading–even when extensive global travel might enable a new pandemic to spread rapidly.

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The 1918 flu pandemic taught scientists a lot about how viruses can become lethal in a matter of days and demonstrated that developing vaccines can be like taking aim at a moving target. But by finding influenza genes common to strains that mutate less frequently than others, researchers may be able to develop a universal flu vaccine that would be effective over a number of years.

There are now at least two universal flu vaccines that have been shown to provide protection against lethal strains of influenza, including H5N1 and H1N1, in laboratory animals. Some companies are scaling up their vaccine manufacturing efforts, while others are boosting research and development of new universal vaccines. Some researchers are also working on different antiviral drugs to help reduce the impact and spread of the influenza virus. The hope is that such measures will suppress the next big flu outbreak, whenever and wherever it happens.

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