Pharmaceutical Interventions

The following is a brief description of influenza vaccines and antivirals prepared by Dr. Steven Lawrence, Assistant Professor of Medicine at Washington University School of Medicine, and Associate Director of Emergency Response Planning for the Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research.

For additional information, and updates on the latest vaccine and antiviral developments, please visit www.pandemicflu.gov , and the Center for Infectious Disease Research and Policy website at: www.cidrap.umn.edu .

Influenza Vaccines and Antivirals

Influenza virus infections can be treated or prevented (i.e. prophylaxis) with antiviral medications, which are similar to antibiotics that are used for infections caused by bacteria. There are currently four antiviral drugs, from two different drug classes, available for treating influenza.

Amantadine and rimantadine are in the class known as M2 inhibitors. These are old drugs that have been used for many years, particularly for prophylaxis. However, they are limited by a number of side effects, and more recently they are not recommended for use against seasonal influenza because of a high rate of resistance. Some, but not all, strains of H5N1 avian influenza virus are susceptible to these drugs.

The other class of influenza antiviral drugs is the neuraminidase inhibitor class, of which there are two available drugs, oseltamivir (Tamiflu) and zanamivir (Relenza). These drugs are very potent against nearly all strains of seasonal influenza and H5N1 avian influenza. However, higher doses may be necessary when used for H5N1 because the virus is much more virulent.

Oseltamivir is the mainstay for pandemic stockpiling efforts because it has a long shelf life (5 years), it is easier to take for most people because it is a pill, and it gets distributed throughout the entire body. Zanamivir is delivered directly to the lungs by a hand-held inhaler. For the treatment of seasonal influenza, the neuraminidase inhibitors reduce the duration of illness approximately one day and help people to return to work or school more rapidly. They also reduce the chance of serious complications from influenza, including pneumonia and hospitalization.

These drugs are also very useful for completely preventing influenza in exposed persons. However, they are only effective for this prophylaxis while they are being taken; there is no long-lasting protective effect.

For all of the antivirals, early administration is critical. They work best when given immediately after the onset of symptoms, and they are largely ineffective if they are not given within 48 hours.

The only way to give complete protection prior to exposure is through immunization with influenza vaccines. For seasonal influenza there are two different types of vaccines available. The trivalent inactivated vaccine (TIV, aka the “flu shot”) consists of purified, inactive pieces of virus and is injected in the arm. The live attenuated intranasal vaccine (LAIV) consists of a weakened live influenza virus that is delivered by nasal spray. Both types of vaccine protect versus the same three strains of virus (one is an influenza A virus of subtype H3N2, one is an influenza A virus of subtype H1N1, and one is an influenza B virus). However the specific strains are changed each year depending on what are predicted to be the most likely circulating strains.

The vaccines work best in young, healthy individuals, where the risk of getting influenza can be reduced by 70-90%. In people who are at highest risk of complications from influenza, in particular the elderly and those with compromised immune systems, the vaccines are less effective at preventing influenza. However, they do reduce the risk of death in the elderly during influenza season.

The vaccines are well tolerated and do NOT cause influenza.

The most common side effect from TIV is a mildly sore arm. LAIV currently can only be used in individuals aged 5-49 years old with a normal immune system because of the small chance that even the weakened virus used in the vaccine could make an immunocompromised person sick.

The vaccines used each year for seasonal influenza are likely to offer no meaningful protection against H5N1 avian influenza. A separate H5N1 vaccine was approved by the U.S. Food and Drug Administration in April 2007, however it is far from perfect. Because of the ongoing mutations occurring in H5N1 viruses as they spread around the developing world, the approved vaccine is already somewhat obsolete. The current H5N1 vaccine requires two injections over one month, and is likely to prevent H5N1 in less than half of those receiving the vaccine, although it is likely that vaccinated persons who still get infected will have a milder form of the infection. There is extensive research underway to develop better vaccines that will provide protection versus H5N1 and other influenza subtypes that have the potential to cause a pandemic.