H1N1 and its descendents

Published: October, 2009

Where this pandemic flu came from — and where it might go

In a typical year, about 10% of Americans get the flu. Although many people think of the flu as a mild ailment, each year in the United States a couple of hundred thousand people get sick enough to require hospitalization, and between 20,000 and 40,000 die from the infection.

Already, 2009 is not a typical year. We're in the midst of a flu pandemic caused by a virus that first emerged in Mexico in mid-February. Billions are being spent on preparedness plans. And millions of Americans may line up in the fall to get two kinds of flu vaccines, one for the regular seasonal flu that comes around every winter and another for the pandemic strain.

So far, the 2009 pandemic has been more widespread than lethal. Only about a thousand deaths have been reported worldwide, including about four hundred in the United States, and it didn't get appreciably more deadly during the peak flu season in the Southern Hemisphere in June, July, and August. Flu experts believe the virus has some properties that may make it inherently less pathogenic — that is, less capable of causing serious disease — than other strains.

But we relate all this with fingers crossed — and without a crystal ball. It's difficult to make firm predictions about flu pandemics for a number of reasons. Flu viruses are notorious for being genetically unstable, so the course of a flu pandemic may swerve midstream if the virus that's causing it mutates.

Immune responses are also hard to predict. Part of what makes a pandemic possible is that large numbers of people don't have immunological protection against a new infectious agent. But sometimes a new virus is close enough to those circulating in previous years that many people's immune systems manage to fight off the newcomer.

Public health policy — along with how people react to it — is another wild card. Historians say one reason the 1918–19 flu epidemic was so deadly is that government and public health officials did little and downplayed the danger because they didn't want to panic people. "Worry kills more than the disease" was a catch phrase.

The public health response to this pandemic has gotten pretty high marks for striking the right balance of reasonable warning without fear-mongering. Now it's up to each of us to respond and take the appropriate precautions.

On the surface

Epidemics of respiratory disease came before any understanding of why they occurred. Flu is short for influenza, which is Italian for influence. It was thought that respiratory illness epidemics were due to the cosmic influenza of the heavenly bodies. Other etymologies trace it back to influenza di freddo, or influence of the cold, which is a bit closer to the truth (see sidebar below).

Now, of course, we know influenza is caused by viruses. Scientists have categorized flu viruses into three main groups — A, B, and C. The viruses in the A group are the big troublemakers: common and capable of infecting people, other mammals, and birds. The new pandemic virus — and, indeed, most of the flu viruses you'll ever hear about — is in the A group.

By longstanding convention, flu viruses are further categorized and named by two proteins they brandish on their outer coats. One is hemagglutinin, which latches on to cells and infects them — it's the way the virus gets its foot in the door. The other is neuraminidase, a different surface protein that lets the virus's progeny escape once it has reproduced. Only the initials, H and N, and numbers are used in flu names. Scientists have identified 16 varieties of hemagglutinin and nine varieties of neuraminidase, which makes for 144 possible pairs. To date, only three combinations — H1N1, H2N2, and H3N2 — have been found on viruses that spread from person to person and therefore are capable of causing human epidemics. The virus causing the 2009 pandemic has the H1N1 combination.

A cool virus

Flu viruses are more contagious and more capable of causing severe illness once the air is cool and dry. Because the viruses like chilly weather, the peak flu season in the Northern Hemisphere starts in November and ends in May. In the Southern Hemisphere, the season is May to September, the winter months there. In the tropics, there is no true flu season and, in fact, very little flu at all.

The outbreak in the spring of 2009 may have been milder than feared because it occurred as the weather in the Northern Hemisphere was warming up. And it may not have been as severe in the Southern Hemisphere because relatively few people live in the coldest parts of that hemisphere. H1N1 may bounce back with a vengeance as winter, flu's favorite season, comes to the more populous, northerly half of the globe.

Bird flu takes off

Birds, especially ducks and other waterfowl, are the natural reservoir of the group A flu viruses. For the most part, birds and flu coexist, with the viruses causing the birds little harm as they swap genes and mutate inside the birds' digestive systems.

But occasionally, these bird (or avian) flu viruses change in such a way that they are capable of infecting other species. Researchers now believe that the 1918–19 flu epidemic, which by some estimates killed 40 million people around the world, was caused by an avian flu virus that not only jumped from bird to human, but also adapted to the human respiratory tract, enabling easy person-to-person transmission. This was the original H1N1 virus and the ancestor of so many others to come.

Aside from a 20-year hiatus between 1957 and 1977, different versions of human-adapted H1N1 have been circulating in people ever since. Subsequent flu pandemics (in 1957 and 1968) have been caused by viruses with genes that were a mixture of those from H1N1 and other bird flu viruses.

In 1997, a new avian flu virus, H5N1, emerged in Hong Kong. The outbreak was contained, but until the 2009 pandemic, H5N1 had been the big worry. As a new avian flu virus with which humans have no immunological experience, H5N1 has potential to cause a human pandemic like the one in 1918–19. And it's been lethal, killing over half of the people it has infected. But so far, it's infected only a few hundred people and hasn't been very transmissible from human to human. The "so far" needs to be stressed. H5N1 could change to become contagious. By the same token, the new H1N1, which has been very contagious but not very lethal so far, might undergo a genetic change and become deadly.

Pigs mix it up

The H1N1 avian flu virus that found a new home in the human respiratory tract in 1918 also set up shop that year in the airways of pigs. For the next six decades or so, "classical," swine-adapted H1N1 virus circulated in pigs in this country, with only occasional infection of people, although pig-to-person transmission probably happens more often than recognized because the symptoms of swine and regular flu are similar.

Pigs have been described as natural mixing vessels for flu viruses because they are easily infected with both avian- and human-adapted viruses. A new "triple reassortant" virus that combines genetic elements of the avian, human, and swine viruses has been circulating in pigs in the United States since about 1999. Pigs in Europe and China have been infected with a different virus — swine-adapted of avian origin — since about 1979.

The new H1N1 flu virus seems to be a mixture of some genes from the triple reassortant virus and some from the Eurasian swine-avian one.

The last major swine flu outbreak occurred in 1976 among soldiers at Fort Dix in New Jersey. Federal health officials organized a mass vaccination campaign that came under sharp criticism for two reasons. First, the vaccine was found to create a small risk (1 in 100,000 people vaccinated) for Guillain-Barré syndrome, an autoimmune disorder that attacks the nervous system. More importantly, the outbreak hadn't spread outside of New Jersey before the vaccination campaign began. By contrast, the current H1N1 swine flu has already spread around the world — and is likely to surge in winter.

So very typical

American and Mexican officials started to investigate the new flu outbreak in mid-April 2009, but there's now epidemiological data suggesting that a spike in flulike illness occurred two months earlier. The novel virus had spread to over 40 countries by the end of May, and the World Health Organization (WHO) declared it a pandemic in June.

Pandemic has technical WHO definition, and the word has scary connotations, but the plainer meaning is an epidemic (which is any unusual increase in a disease) with wide geographic spread. It doesn't necessarily mean a disease is dire or deadly.

Symptoms of this pandemic flu are like those of the regular flu: cough, fever, muscle aches, sore throat, and so on. Nausea and vomiting may be a bit more common, fever a little less. So if you get the flu come fall or winter, it may be hard to tell just by symptoms if you've been infected by one of the regular seasonal flu viruses currently in circulation or the new pandemic H1N1 virus.

The pandemic flu also seems to be transmitted in much the same way as garden-variety flu: infected people expel the virus in respiratory droplets when they cough or sneeze. The prevention recommendations for the 2009 flu season are pretty much the same as those for any other (see sidebar on tips).

One big difference between the regular seasonal flu and the pandemic flu is that the pandemic flu seems to be hitting younger people, pregnant women, and obese individuals harder than the regular flu does. Younger people may be more vulnerable than older people because older people might have some immunity to the new virus "left over" from exposure to similar H1N1 viruses that circulated years ago.

Before the flu season started, federal officials were confident that there would eventually be enough vaccine against the pandemic flu to go around, but they took the precaution of prioritizing who should get it first. The people at the front of the queue include pregnant women, children and young adults ages six months to 24, people who take care of infants younger than six months, adults ages 25 to 64 with chronic health conditions, and health care workers. Priority for the regular flu shot, in 2009 and in the past, goes to older adults because that's the population most likely to die from seasonal flu and related lung infections.

Six flu-fighting tips

  1. Get vaccinated.

  2. Don't shake hands.

  3. Wash your hands often.

  4. Cough and sneeze into your sleeve or into a tissue. Deposit the tissue in a wastebasket or toilet.

  5. Stay home if you have flulike symptoms.

  6. Stock up on supplies (canned food, bottled water, some medicines) in case of closings and social-distancing restrictions.

No replay...we hope

The trajectory of flu pandemic is uncertain. But there were several reasons to be cautiously optimistic that we won't have a replay of 1918–19. People are healthier and better nourished than they used to be. Today we have vaccines to prevent flu infection, and antiviral drugs — oseltamivir (Tamiflu) and zanamivir (Relenza) — to treat it. Antibiotics have made it easier to combat the bacterial lung infections that "pile on" after a flu infection. And the public health system, while not perfect, is vastly superior to the one that existed then.

Three nonsurprises

This flu season may hold many surprises, but here are three distinct possibilities:

Flu-related school closings. Flu spreads through social contact. It doesn't have to be intimate: someone coughing or sneezing can easily spread the germ to others in the same room. Social distancing is a control strategy aimed at breaking up the social networks through which disease spreads. Because school-age children are major transmitters of flu viruses, school closings are a useful social-distancing tactic. Federal officials issued guidelines in the summer of 2009 designed to keep the number of closings to a minimum. Still, we wouldn't be surprised to see quite a few if the pandemic takes off.

Vaccine shortage — or maybe a surplus. Flu vaccine is still made by growing the virus in eggs. Late in summer 2009, manufacturers were having difficulty getting a good yield of pandemic vaccine. Despite government assurances, shortages looked to be a real possibility. But if the pandemic virus doesn't become widespread, the government may wind up with surplus vaccine as people decide vaccination isn't necessary.

The El-blow-kerchief — yours for $9.99! The crook of the elbow is fast replacing the hands and the handkerchief as the best place to block a cough or sneeze. Even during the summer people seemed to be getting into the elbow-first habit. Maybe someone will design an El-blow-kerchief. In the meantime, the sleeve will have to do.

Look for updates on this flu story at www.health.harvard.edu/healthextra.

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