New Flu Season Begins as Chance of Pandemic Looms

Global surveillance is a critical part of vaccine development

Scientists around the world are working to develop a vaccine against bird flu. (©AP/WWP)

By Cheryl Pellerin
Washington File Staff Writer

This is part one in a series of articles on human and avian flu and vaccines.

Washington – Scientists around the world are working to develop a human vaccine against the H5N1 strain of bird flu that has moved steadily westward since its 2003 appearance in Asia, but experts are not sure how well such a vaccine will work if a pandemic strikes.

The problem is that flu viruses, including the avian influenza virus, mutate so rapidly that a vaccine created one year is not effective the next year.

“That is a bit of a concern,” says Andrew Pekosz, assistant professor of molecular microbiology at the Washington University School of Medicine in Missouri.

“Because these viruses are changing on a yearly basis,” he added, “we certainly can’t expect that a virus generated from last year’s H5N1 strain will crossreact with next year’s H5N1.”

So far, the World Health Organization (WHO) has confirmed 117 human cases of H5N1 infection in four Asian nations, resulting in at least 60 deaths. Because access to medical care is poor in some rural areas and cases may go undiagnosed, the human count could be higher. (See related article.)

Since the first confirmed appearance of the H5N1 in European flocks October 13, concern and vigilance has been heightened in many more capitals. Although outbreaks have been confirmed among birds in several countries, no human cases have appeared in Europe as of October 19.

In the meantime, flu season is beginning in the Northern Hemisphere and health officials are advising the elderly and other vulnerable groups to roll up their sleeves for the annual flu vaccine shot.

The talk of vaccines, amid confusion about a possible bird flu pandemic, is raising questions about the differences between human flu and avian flu and how people best can protect themselves against the coming threat, which the WHO conservatively estimates could cause 2 million to 8 million deaths.

HEMAGGLUTININ AND NEURAMINIDASE

There are three kinds of flu viruses – influenza types A, B and C. Influenza A viruses mutate much more rapidly than influenza types B and C.

Influenza A viruses infect people, birds, pigs, horses, seals, whales and other animals, but wild birds are their natural hosts.

Because of their ability to mutate, influenza A viruses are divided into subtypes based on two proteins on the virus surface – hemagglutinin (HA) and neuraminidase (NA). Influenza A subtypes are named according to their HA and NA surface proteins. The  letters H and N in subtype names like H5N1 refer to these proteins -- this flu subtype has an HA 5 (H5) protein and an NA 1 (N1) protein.

There are 16 HA subtypes and nine NA subtypes, so many combinations of H and N proteins can occur. This makes it critical for flu experts to track continually the viruses in circulation, so annual flu vaccines can contain and protect against the most current strains.

Only certain influenza A subtypes – H1N1, H1N2, and H3N2 – generally circulate in the human population. Other subtypes are found most commonly in other animal species. H7N7 and H3N8 viruses, for example, cause illness in horses.

It is likely that some genetic parts of the current human influenza A viruses originally came from birds, according to the U.S. Centers for Disease Control and Prevention (CDC).

There are no subtypes for influenza B and C because these subtypes do not change as frequently as influenza A.

Influenza B viruses usually are found only in people; the viruses can cause human epidemics – which affect many individuals in an area at the same time – but have not caused pandemics – epidemics that cover a wide geographic area and affect a large proportion of the population.

Influenza type C viruses cause mild illness in people and do not cause epidemics or pandemics.

BIRD FLU AND PEOPLE

Influenza A viruses are the only subtypes that affect both birds and humans.

Wild birds, the natural hosts for all influenza A virus subtypes, usually do not become sick when infected with flu virus.

But domestic poultry, like turkeys, ducks and chickens, can become very sick and die from bird flu, and some avian viruses can cause serious disease and death in wild birds.

Influenza A viruses usually seen in one species sometimes can cross over and infect another species. Avian flu viruses can be transmitted to people directly from birds, their blood, their feces, virus-contaminated environments or through an intermediate host, such as a pig.

Transmission by these means will not trigger a pandemic. To cause a pandemic among people, H5N1 would have to mutate in such a way that it could be transmitted easily from person to person. H5 viruses usually do not infect people, so there is little or no immune protection against these viruses in the human population.

Vaccines are the best way to prevent any sort of flu. Developing an annual flu vaccine is a complex, international, yearlong process that starts with disease surveillance.

GLOBAL FLU SURVEILLANCE

Surveillance is the close observation of someone or something – in this case, influenza. Because viruses do not respect national boundaries, such surveillance is international and is coordinated by the WHO Global Influenza Surveillance Network, established in 1952.

The WHO network is made up of four collaborating centers – in the United States, Australia, Japan and the United Kingdom – and 112 institutions in 83 countries that are called WHO National Influenza Centers.

The national influenza centers collect specimens in their countries and isolate and scientifically characterize the viruses.

The centers then ship the newly isolated strains to WHO collaborating centers for more scientific and genetic analysis. WHO flu experts use this analysis to recommend the formulation of each year’s flu vaccines for the Northern and Southern Hemispheres, then prepare and distribute the candidate vaccine strain to manufacturers.

The WHO Influenza Surveillance Network serves also as a global alert mechanism for the emergence of influenza viruses with pandemic potential, like the H5N1 bird flu strain.

According to a 2004 U.S. National Academy of Science publication, The Threat of Pandemic Influenza: Are We Ready?, this network is strong in Western countries, sufficient in Eastern Europe and the Middle East, but “riddled with strategic gaps in Africa as well as in Asia.”

LOCAL FLU SURVEILLANCE

In the United States, the CDC is one of the four WHO collaborating centers. As part of its local surveillance process, the Influenza Branch collects and reports information on flu activity in the United States each week from October through May.

The U.S. flu surveillance system has seven components that tell CDC when and where flu activity is occurring, which flu viruses are circulating, how the flu viruses are changing, where flu-related illness is occurring and the effect of flu in U.S. deaths.

The surveillance system includes reports from more than 120 laboratories, 2,000 “sentinel” health care providers, vital statistics offices in 122 cities, research and health care personnel at specific surveillance sites, and flu surveillance coordinators and state epidemiologists from all state health departments.

All flu activity reporting by states and health care providers in the United States is voluntary.

Such surveillance is critical to keep up with mutating influenza A viruses and ensures sure each year’s flu vaccine protects against the currently circulating strains.

For more information on U.S. and international efforts to combat avian influenza, see Bird Flu.

This is part one of a series on human and avian flu and vaccines. Part two describes the process of flu vaccine development and manufacture and discusses evolving trends in flu vaccine production.