Think prevention, then treatment for influenza

February 2003

NEW YORK CITY — Managing influenza cases this winter can be a lot simpler with proper diagnosis, prophylaxis and treatment as necessary.

Studies have shown that approximately 40% of children get sick with influenza each winter. Although, depending on the severity of the circulating influenza virus and whether it matches the virus in the vaccine, that number can vary greatly.

Children are a very efficient harbinger of influenza viruses during the winter months and so become epicenters of disease transmission. According to Kenneth Zangwill, MD, associate professor of pediatrics at the Harbor-University of California, Los Angeles, Medical Center, influenza, which spreads through the air but can also live on fomites for 24 to 36 hours, usually starts in school children, spreads to families and into the community.

“If children are efficient transmitters of influenza throughout the community – and they are, particularly school-aged children 5 to 15 years old – and 40% are becoming infected even if they do not have classical influenza, then the likelihood of transmission is significant,” said Zangwill here at the Infectious Diseases in Children Symposium New York.

Influenza is especially prevalent during school months. Full-blown outbreaks of disease are often preceded by a spike in school absenteeism. In past years, pediatricians have been faced with dealing with influenza outbreaks after they occur.

This season the CDC and AAP, for the first time, encouraged vaccination of children against influenza.

According to Zangwill, pediatricians should use the vaccine whenever possible, but they should not forget the full armamentarium of effective antivirals they have for prophylaxis and treatment. Though far from perfect, studies have shown antivirals to be highly effective in reducing symptoms and unnecessary antibiotic use.

Typically atypical

Typical influenza is anything but a typical disease. In actuality, influenza virus can cause a spectrum of nonspecific clinical signs and symptoms. Disease is often marked by upper respiratory illness, croup or laryngitis and bronchiolitis.

Influenza can mimic any number of other viruses that are prominent in the winter months, making a differential that much more difficult to make.

Rapid tests are available and should be considered, said Zangwill, especially since clinical symptoms are only about 75% to 80% accurate in an influenza diagnosis. “Not all antigen tests detect both influenza A and B, but all are relatively specific and sensitive,” he said.

Once the diagnosis is made, treatment should consist of antivirals, said Zangwill. Older antivirals like amantadine, which can be used as treatment in children as young as 1 year and rimantadine (Flumadine, Forest), which is approved for children age 12 and older, are cost-beneficial and effective in treating influenza A virus.

The older antivirals work by inhibiting the M2 protein ion channel, a component of influenza that assists in replication inside the host cell. However, the M2 channel is a feature only present in influenza A viruses, so older antivirals are not effective against influenza B.

In 1999, the FDA approved two new antiviral drugs. Zanamivir (Relenza, GlaxoSmithKline), is approved to treat both influenza A and B in children as young as age 7 and oseltamivir (Tamiflu, Roche) is approved for treatment in children as young as 1.

Antivirals typically reduce influenza symptoms and duration of fever by about a day. Antiviral use has also been associated with a 30% reduction in antibiotic use and a 44% lowered incidence of acute otitis media. Newer antivirals are more expensive than older ones.

Zangwill said antivirals are cost-beneficial and effective, but come with one important caveat. “All four antivirals are effective, but you have to use them early,” he said. “If you don’t use these drugs within the first couple of days, you shouldn’t bother.”

Antiviral drugs are also useful prophylactically. Amantadine and rimantadine are approved for prophylaxis in children as young as 1 year and oseltamivir is approved down to age 13.

Antivirals can be used as a substitute for children who have contraindications to the vaccine or for high-risk children at the time of vaccination during the flu season while immunity is developing.

Underused vaccine

The influenza vaccine story is well known by now: an effective vaccine that is sorely underused. Under old CDC guidelines for influenza vaccine use, all individuals at high risk for complications from influenza were indicated for vaccination as were all individuals older than 50.

That strategy produced poor results, with just 25% of asthmatic children vaccinated in 2000 and just 10% of pregnant women vaccinated against influenza in 1999. So, to reverse the trend, the CDC opted for age-based recommendations instead.

This year, the Advisory Committee on Immunization Practices and the AAP Committee on Infectious Diseases both encouraged influenza vaccination for all children 6 to 23 months of age with an eye toward making a full recommendation in years to come.

An FDA advisory panel recently recommended the cold-adapted influenza vaccine (CAIV, FluMist, MedImmune-Wyeth) for approval for children older than age 5.

The arrival of the CAIV has been anticipated for some time, as the nasal administration will help reduce the shot burden on young children. The nasal flu vaccine may confer local, mucosal immunity in the nose in addition to systemic immunity, supplying additional protection against the influenza virus.

Until CAIV reaches final approval, pediatricians should continue to encourage parents to get their child vaccinated with the inactivated influenza vaccine, said Zangwill.

For more information:

• Zangwill K. Influenza: new strategies for an old disease. Presented at the Infectious Diseases in Children East Symposium. Nov. 11-14, 2002. New York, New York.