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Influenza 2



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Influenza continues to have a significant public health impact year after year, but with the exception of the amantadine-like drug rimantadine, there have been no new treatment options for physicians within the last 30 to 40 years. This situation is about to change within the next 24 months when both a new vaccine, the live attenuated vaccine, and a new class of antiviral agents, the neuraminidase inhibitors, will become available for routine clinical use. These new drugs appear to offer two major benefits.

The new vaccine and neuraminidase inhibitors potentially could provide a great clinical benefit. Phase III studies of these drugs in acute, uncomplicated influenza have shown them to be well tolerated and to reduce the duration of symptoms by about one third. Somewhat in contrast to the situation that occurs with amantadine and rimantadine, viruses resistant to the antiviral activity of the neuraminidase inhibitors are rarely, if ever, recovered from treated patients. Furthermore, it is important to recognize that neither of these drugs is intended to replace the influenza vaccine as the prime prevention method. However, the drugs could be used in those rare instances where vaccine is contraindicated or unavailable, or to provide protection in the time between vaccination and the development of antibody, in the same ways that amantadine and rimantadine are used now. Another potential preventative use of these drugs is in the family setting or in institutional outbreaks. Neuraminidase inhibitors would provide protection against both influenza A and B and might be better tolerated than amantadine in this situation.

Furthermore, the early clinical studies of neuraminidase inhibitors have suggested interesting trends toward reduced frequencies of influenza-related complications in treated patients. Since complications of influenza such as bacterial superinfection and, more rarely, viral pneumonia are directly related to reproduction of the virus and damage to respiratory epithelial cells, it is reasonable to think that early antiviral therapy could forestall the development of some of these problems. If studies in high-risk adults (e.g., the elderly or those with chronic cardiopulmonary conditions) confirm an effect of early therapy on complications, the potential usefulness of these drugs will be expanded considerably.

The clinical benefits of acute antiviral treatment of influenza have so far been rather modest although testing to date has largely concentrated on healthy adults who generally recover fairly rapidly without any treatment at all. Even this modest benefit may be significant when one considers the disruption in normal daily activities that a bout of influenza often causes – as suggested by the enormous quantities of over-the-counter cold and flu remedies, many of doubtful effectiveness, consumed by Americans each year. Early treatment could allow adults to return to work or their usual activities that much sooner and, with the increasing recognition of the economic impact of influenza in the workplace, could have substantial economic benefits for the public. If treatment with specific antivirals could simply reduce the amounts of inappropriate antibiotic use for these illnesses, a significant public health benefit would also occur.

Additional public benefits exist in regard to children. The influenza season is typically a busy one at the pediatrician's office. While influenza rarely causes serious morbidity or death in children, it is one of the most common reasons that children are brought to medical attention for feverish illness and is a significant contributor to the development of otitis media. Because young children have had less experience with influenza infection, they are relatively more susceptible to infection than are adults; they tend to shed influenza virus at higher levels and for a longer duration than do their older counterparts and, thus, may represent an even longer window of opportunity for intervention with a well-tolerated and effective antiviral. A more rapid return to school or day care for children could also be of significant benefit to adults.

While one would hope that it won't be another 40 years before the next wave of therapeutic advances in influenza, the current crop of new vaccines and therapies is a very welcome addition. These recent achievements are particularly timely as public health authorities prepare for the next influenza pandemic, which is certainly in our future even if the date of its appearance remains clouded in mystery.