How do we find out about new Flu strains in time to develop new vaccines against them?

How do we find out about new strains in time to develop new vaccines against them?

The World Health Organization, in cooperation with dozens of other national and international health groups, maintains the Global Outbreak Alert and Response program to provide continuous surveillance of infectious disease outbreaks around the world.

This program covers all kinds of infectious disease outbreaks, and there are various specialized surveillance programs, including FluNet, a geographical system that monitors influenza activity. There are 110 National Influenza Centers in 82 countries, and four Collaborating Centers for Reference and Research, including one at the CDC in Atlanta.

Each of the 110 national centers collects information and sends virus isolates to one of the four research centers for strain identification. If ever an argument for international cooperation were needed, the activity of infectious microorganisms provides it: preparing for and responding to epidemic disease can be done effectively only with an internationally organized effort. Viruses are immune to immigration laws.

On the basis of this information, WHO arrives at its conclusions about what should be included in this year’s flu vaccine and then makes its recommendations; individual countries and their vaccine manufacturers are responsible for carrying out the vaccination programs.

In June 2002, for example, the FDA recommended the contents of the 2002–2003 vaccine for the Northern Hemisphere. That winter’s vaccine contained three components: A/New Caledonia/20/99-like (H1N1), A/Moscow/10/99-like (H3N2), and B/Hong Kong/330/01like viruses, because these three types were the most likely to strike that winter. (The name of the city tells you where the virus was first isolated.) The flu vaccine is protective for up to 80 percent of the people who take it and encounter one of these strains. It is, in addition, partially effective for other strains, in that it helps make the disease less severe and less deadly.

The flu is quite contagious and is transmitted from one person to another primarily by coughing and sneezing. Between one and four days pass from the time you’re infected until you begin to show symptoms, two days is about the average incubation period for the flu virus. You can infect others from about one day before symptoms begin until about five days after they start. With children, the period of infectivity can be longer. You’re probably quite familiar with the symptoms. There is an abrupt onset of fever, muscle ache, headache, and malaise. You get a nonproductive (dry) cough, and sometimes a sore throat and a runny nose. The symptoms are difficult to distinguish from the symptoms of other respiratory diseases, and the only sure way of knowing you have the flu is by getting an antigen test or a lab culture done. Most otherwise healthy people don’t bother with this because in a few days they feel better anyway.

There are some antiviral medicines, which we’ll get to in a moment, but their effectiveness is limited. The only really effective treatment is prophylactic, that is, the flu vaccine. If someone tells you, and someone probably already has told you, that he got the flu from the flu vaccine, he is mistaken. You cannot get the flu from the flu vaccine.

There are three different kinds of vaccine. One is prepared from killed (inactivated) virus that has been grown in hen’s eggs and is highly purified; the two others contain no virus at all, only the part of the virus that induces an immune response (these are called the purified-surface-antigen preparation and the subvirion preparation, and sometimes both are referred to as “split virus” preparations).

None of these can cause the flu. This does not mean, however, that you cannot get the flu after you have had the vaccine. The vaccine is, as we said above, about 80 percent effective, and that’s against the viruses it is designed to combat. It’s largely ineffective against other strains. So you might get the flu after you have the vaccine and then mistakenly attribute your flu to the vaccine. You did not, however, get the flu because you had the shot. Very rarely, the inactivated vaccine can cause a fever, but it’s not the flu. For this reason the subvirion and purified-surface-antigen preparations, which are less likely to provoke this reaction, are recommended for children. (In the 2001–2002 season, the only vaccines distributed in the United States were of the split virus type.)

Should you get the flu vaccine this year? The CDC recommends that any person over the age of six months who is at increased risk for complications from the flu should get the shot. This means you should get the flu vaccine if you:

• Are over age 50.
• Are a resident of a nursing home or any other chronic care facility.
• Have a chronic disorder of the pulmonary or cardiovascular system (including asthma).
• Have required regular medical follow-up or hospitalization during the previous year for chronic metabolic diseases (including diabetes), renal dysfunction, hemoglobinopathies, or immunosuppression.
• Are immunocompromised, including immunosuppression by HIV infection or medications.
• Are a child or teenager receiving long-term aspirin therapy, and therefore might be at risk of developing Reye’s syndrome as a complication of the flu.
• Are a woman who will be in the second or third trimester of pregnancy during the flu season.
• Work in a hospital, an outpatient care setting, or as part of an emergency response team.
• Work in a nursing home, an assisted living facility, or other residence for people at high risk.
• Provide home care to people at high risk.
• Have any household members (including children) who are at high risk.

The CDC has this to say about vaccination of pregnant women: “Because currently available influenza vaccine is an inactivated vaccine, many experts consider influenza vaccination safe during any stage of pregnancy. A study of influenza vaccination of more than 2,000 pregnant women demonstrated no adverse fetal effects associated with influenza vaccine.

However, more data are needed. Some experts prefer to administer influenza vaccine during the second trimester to avoid a coincidental association with spontaneous abortion, which is common in the first trimester, and because exposures to vaccines have traditionally been avoided during this time.” (Centers for Disease Control and Prevention. Health Information for International Travel 1999–2000, DHHS, Atlanta, GA.)

There are certain people who should not get the vaccine. The inactivated vaccine should not be given to anyone with a known hypersensitivity to eggs or any other component of the vaccine without first consulting a physician who may recommend you get the shot after desensitization for the allergy. (This does not apply to the split virus vaccines, which have no egg component.) People who have an acute illness with a fever should not get the shot until the fever has abated. But minor illnesses with or without fever, especially among children with mild upper respiratory infections, are not a contraindication for the vaccination.

When should you get the vaccine? The best time is in October or November, but vaccination after December is still a good idea, since the peak of the flu season can be as late as March.

Although flu season is October to March in the northern hemisphere, it isn’t everywhere. In the tropics, it occurs all year round, and in the southern hemisphere the flu season is April through September. If you’re traveling in a large group of people, say on a cruise ship, you can get the flu any time of year, no matter where you are, because there are likely to be fellow travelers who come from parts of the world where the flu virus is currently circulating.

The flu can, at best, mess up your vacation. At worst, it can cause serious complications. It’s best to get the current vaccine if you’re planning a trip. If you weren’t vaccinated in the fall preceding your trip, you should consider getting the shot at least two weeks before you travel, but remember that the availability of the vaccine in the summer is likely to be limited. The benefits of revaccination before travel of people who were vaccinated the previous fall or winter are not known, but current practice is to give high-risk nursing home residents two shots, one in September and one the following January.

There are nasally administered live, attenuated influenza virus vaccines that have been in development in the United States since the 1960s and are presently being used in Russia. These are active viruses that cause minimal symptoms but provoke a protective immune response. Recent studies have found them effective in preventing flu and reducing otitis media in children. These vaccines are not currently available in the United States but may be soon, perhaps even by the time you read this.

There are also some antiviral medicines that are a useful addition to the vaccine in preventing and treating influenza, although they are not a substitute for the vaccine. Amantadine, rimantadine, zanamivir, and oseltamivir have been approved for treatment and prophylaxis of influenza. The drugs have varying side effects and costs. If you take them within two days of the onset of illness, they can reduce the duration of illness by about one day. All four drugs are effective against influenza A. Zanamivir and oseltamivir are somewhat effective against B as well.

These antiviral medications can be useful in special circumstances, such as protecting high-risk people after the flu season has begun, protecting high-risk people who for one reason or another can’t take the vaccine, or protecting the immunocompromised who don’t get a sufficient immune response from the vaccination alone. They also have some prophylactic effect in that they can confer immunity by allowing subclinical illness while the body develops protective antibodies against the virus, and they do not interfere with the immunologic response to the vaccine. All of these drugs have side effects, often much more unpleasant than any side effects of the vaccination. Zanamivir is difficult or impossible for some people to take, it is given as an inhaled powder, and those with asthma or other lung ailments can’t use it.

Antibiotics are of no use in treating influenza and should never be taken for that purpose. Unfortunately, they often are demanded by patients and prescribed by doctors or other health care professionals. In one survey, fully 60 percent of Medicaid patients were prescribed antibiotics for viral illnesses. This is bad practice, if these patients had nothing more than the flu.

The problem is that the symptoms of flu are sometimes very difficult to distinguish from those of bacterial illnesses for which antibiotics are indicated, and sometimes a bacterial illness can accompany the flu, as was frequently the case, with fatal results, in the 1918 pandemic. There are tests that can determine with certainty whether the flu is the cause of the illness, including some that can produce results in as little as 30 minutes. The tests vary in their ability to distinguish different virus types, and the rapid tests are less reliable than the viral culture and blood tests, which take much longer. Information about the exact strain may not be necessary in treating individual cases, but such information is essential for tracking epidemics and developing new vaccines.

Despite considerable knowledge of the genetic structure of the 1918 virus, no one is quite sure why the flu that year was so virulent, and there is still considerable scientific disagreement about where it came from. It is likely that a new surface protein appeared on this virus, one that humans had never encountered before and to which they therefore had no immunity. But there must have been other genetic features of this virus that also contributed, and these remain a mystery, even though complete viral gene sequences of the bug have been developed from the preserved tissue.

So the question arises: Could it happen again? In a sense, it already has happened again, though in not quite so devastating a form. The “Asian flu” of the winter of 1957–1958 killed 70,000 Americans. The 1968–1969 “Hong Kong flu” killed 34,000. The new subtype that appeared that year, called A(H3N2), was milder, perhaps because only the hemagglutinin protein changed, the neuraminidase stayed the same, and therefore people may have had some residual resistance to it.

Still, A(H3N2) has caused 400,000 deaths in the United States since its emergence in 1968, 90 percent of them among people older than 65. In fact, the subtype that caused the 1918 pandemic, A(H1N1) continued to circulate for years, having undergone antigenic drift, and caused a large number of deaths in 1920 (reduced, probably, by greater immunity among the population as well as by the attenuated form of the virus), and then periodic outbreaks until it disappeared in 1957. None of the outbreaks, though, was anywhere near the severity of that of 1918. In 1977 it reappeared, but again without devastating consequences.

In any case, most virologists think that the answer is yes, it could happen again. The reservoir of influenza is believed be wild waterfowl, and the pandemics of 1957 and 1968 were both produced by changes in the surface proteins of an avian strain of the virus.

Such an alteration in the future could produce a pandemic as bad or worse than the 1918 disaster. Of course, circumstances now are a bit different. We have a flu reporting system; we know how to make vaccines against the flu; we have antibiotics to treat the bacterial infections that killed so many in the pandemic of 1918; we even have several antiviral medicines that are helpful.

But we also know that microbes are persistent and very adaptable, and that there is always the possibility that one of them will come up with an answer to the most elaborate defenses we have constructed against it.