Avian flu and planning for pandemic

Oct 20 2005

Influenza season is almost upon us. While it is impossible to tell whether we are going to experience a usual flu season -- with one in every five people falling ill -- or whether we are facing a more serious problem such as a dangerous new strain capable of causing a global pandemic, information is important.

Dr. Anne Moscona, an influenza expert, professor of pediatrics, professor of microbiology and immunology, vice chair for research of pediatrics, and attending pediatrician at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, is available to share her knowledge.

Dr. Moscona's authoritative review of antiviral drugs to treat influenza and strategies for combating an influenza pandemic was published in the September 29 New England Journal of Medicine. (Moscona, A. Neuraminidase inhibitors for influenza. New Engl. Jl. Med. 353:1363-1371, 2005)

The Four Drugs to Combat Influenza

There are two categories of drugs and four individual drugs for the treatment or prophylaxis of influenza. The category of adamantanes contains the drugs amantadine and rimantadine, and a newer category of drugs, neuraminidase inhibitors, contains the drugs zanamivir (known commercially as Relenza) and oseltamivir (known commercially as Tamiflu).

Adamantanes interfere with viral uncoating inside the cell. They are cheaper and generally more available than neuraminidase inhibitors, but are only effective against Type-A influenza and are not at all effective against avian flu. Adamantanes can also be toxic to patients and can cause a virus to mutate into a drug-resistant strain, capable of being passed from the infected patient to others.

Neuraminidase inhibitors are a better bet.

The neuraminidase inhibitors zanamivir and oseltamivir, marketed as Relenza and Tamiflu, interfere with the release of influenza virus from infected host cells, a process that prevents infection of new host cells and thereby halts the spread of infection in the respiratory tract.

Neuraminidase inhibitors must be administered early before the virus infects too many cells, but the drugs are highly effective at treating and protecting against all strains of influenza, including avian influenza. In contrast to adamantanes, the neuraminidase inhibitors are associated with very little toxicity and they are far less likely to promote the development of drug-resistant variants or strains. In a pandemic caused by avian influenza, neuraminidase inhibitors would be the only useful drug.

Drugs Are Essential Because Vaccines Are Not Perfect

Each year, health officials create vaccines to match the strains of influenza that are anticipated to surface. However, because it is difficult to anticipate every strain that might surface and because even anticipated strains shift some within each season, vaccines generally cannot provide complete immunity from influenza.

Concerns About H5N1 Viruses and Avian Flu

The H5N1 viruses that have now become endemic in Asian domestic fowl are being spread by wild birds and appear unlikely to be eradicable. In fact, the viruses are expanding to a wider range of bird species, and sporadic bird-to-human infections with high fatality rates continue to occur in Vietnam, Thailand, and Cambodia.

A case of human-to-human infection, where an infected child passed the virus to two close contacts, has also been documented. And, scientists fear that the continued spread of H5N1 viruses amongst fowl will create greater opportunities for bird-to-human transmission, and a greater risk that human-to-human transmission will occur.

Planning for Pandemic

Vaccine is the primary tool for preventing influenza. However, since a vaccine against H5N1 is not yet available (one is under development) and vaccines for other newly arrived strains would require several months of preparation and more time to distribute, the creation and stockpiling of neuraminidase inhibitors is critical.

Neuraminidase inhibitors would have been effective against the virus that caused the 1918 influenza pandemic, and were effective against the avian viruses of 1997 to 1999, and the avian viruses of 2004. The 2004 avian viruses were resistant to adamantanes.

Short Supplies and Uneven Plans

The bad news -- Current supplies of neuraminidase inhibitors are inadequate and there is little capacity to increase production in the time of need. Therefore, it is important that agencies or nations create stockpiles of neuraminidase inhibitors as well as plans to distribute the drugs quickly. Some countries are formulating response plans quickly while others are lagging behind. In the United States, where response to public health crisis is largely handled by individual state agencies, planning has been slow and uneven.

The good news -- In 2005, the tools to detect and diagnose an outbreak, as well as highly effective drugs to treat existing cases and safeguard against others developing, make for a better state of affairs than what was faced during previous influenza pandemics. However, modernity has also created a problem. Individuals can carry and spread influenza before showing any symptoms, and with modern transportation, where much of the world's population can travel literally anywhere within a day, the challenge of controlling an outbreak has increased.

One approach to containing an outbreak is to develop international stockpiles of antiviral drugs managed by the World Health Organization. The drugs would be quickly delivered to the site of an outbreak, administered to infected individuals as well as to those who may have come in contact with them, in an effort to create "rings of prophylaxis" that would contain an outbreak. This method is seen as preferable to other plans such as treating only the recognized cases and health-care workers, or offering drugs prophylactically to those at high risk.