Influenza and its effects on infants and children

February 2001

---Philip A. Brunell, MD

Until recently, influenza virus has been viewed as a scourge of the elderly, with most efforts directed at preventing morbidity in this age group. Annual epidemics have claimed tens of thousands of lives — mainly in older individuals. Although the effect of influenza virus infection on infants and children has been recognized for many years, unlike in the elderly, it might not produce a unique syndrome and is not the dominant respiratory illness. It is one of many respiratory viruses that affect our patients.

A new class of antiviral drugs, neuraminidase in hib itors (NIs), has been found to be effective in adults and in children. This may make it feasible to offer specific therapy for the treatment of influenza and to decrease the need to use antibacterial drugs, which have become more resistant because of their widespread, and often, inappropriate use. These new antiviral drugs, zanamivir (Relenza, GlaxoSmith Kline) and oseltamivir (Tamiflu, Roche) now are approved for treatment of children older than 12 and 1 year of age, respectively. Both drugs must be used within the first day or so to be efficacious. In clinical trials in children, zanamivir decreased the duration of symptoms by an average of 1.25 days [Pediatr Infect Dis J 000;19:410]. Oseltamivir is approved for prophylaxis in children older than 12. Zanamivir given within 36 hours of the introduction of influenza into a household to children older than 5 years of age is effective in preventing spread to their family members. Those treated had a 2.5 day reduction in symptoms [N Engl J Med 2000;343:1282]. However, this drug has not been approved for prophylaxis in children.

Tests for influenza

The availability of rapid diagnostic office tests, eg, QuickVue Influenza Test (Quidel Corp.) or Zstat Flu (ZymeTx Inc.), should enable one in the office to make a specific diagnosis and prescribe one of the new antiviral drugs. The tests are said to have great specificity and reasonable sensitivity, but evaluation of these tests in children has been difficult to find. To minimize expense, one should test those who are candidates for treatment with the antiviral drugs rather than testing everyone with a respiratory illness. It also has been suggested that at a time when there is a substantial number of positive tests, children with illnesses compatible with influenza might be treated without testing. Ways to track the path of influenza virus are to access the Centers for Disease Control and Prevention's (CDC) influenza page: www.cdc.gov/ncidod/diseases/flu/weekly; call the CDC at (888) 232-3228; or call your local health department.

The NIs cost more than the older antivirals, amantadine and rimantadine (Flumadine, Forest), but they have not been associated with as much resistance or as many adverse reactions. Zanamivir has been reported to reduce air flow and cause brochospasm in some patients with reactive airway disease and should be used with caution in these patients. The NIs are effective against both A and B strains of influenza; the older drugs are effective only against A strains.

We don't have a direct comparison of the newer with the older anti-influenza drugs. However, rimantadine was reported to be superior to acetaminophen in the treatment of influenza A in children [Pediatrics 1987;80:275]. We do not have similar data for the new antiviral drugs. There is also a substantial difference in price between the older and the new drugs and between the antiviral drugs and acetaminophen.

The shortage of influenza vaccine this season has probably done more to stimulate immunization than any organized campaign. In recent years there has been more interest in the immunization of children because of greater appreciation of the morbidity that this virus causes in children. The rate of hospitalization in the very young is second only tothe very old. Even in the absence of complications, influenza is a severe illness. Severe croup can result from influenza virus and bacterial otitis media (OM) is a common complication. Probably the greatest impetus to the immunization of children is the need to prevent illnesses that are likely to keep them from school and day care and their parents from work.

What has been the reticence to recommend routine use of influenza vaccine for children? In contrast to other vaccines, influenza vaccine must be given annually. For children 6 months to 8 years of age, they must receive two doses the first time they receive influenza vaccine. Thus, it adds injections to an already crowded schedule. What is more, it is much less effective than the other routine vaccines. Recent studies in a day care center indicated that its efficacy was only 45% and 31% against influenza B and influenza A(H3N2), respectively [N Engl J Med 2000;284:1677]. Fortunately, the split vaccines, which are used in children, are much less reactive than the older vaccines, which gave this vaccine a bad reputation for reactions. It is prepared in eggs and so it should be used with this in mind. This is particularly important when immunizing children with asthma for whom it is often recommended.

Influenza vaccine capabilities

It is important that parents understand that influenza vaccine protects against influenza and will not prevent or modify most respiratory illnesses that occur during the fall and winter. It will not prevent RSV or the parainfluenza or rhinoviruses that cause similar illnesses. In a study of influenza during an epidemic in a day care center, those immunized did not have a significant decrease in respiratory illness although there was a reduction in influenza [J Infect Dis. 2000;182:1218]. It tends to modify influenza in those who are infected. It has been shown to prevent OM associated with influenza virus infection, as has treatment with oseltamivir. However, this may be one episode in a season in which a child may experience several attacks of OM. Parents must understand that influenza vaccine is not a vaccine against "ear infections."

It is necessary to monitor the changes in the antigen composition of circulating influenza viruses to be certain to match the vaccine with the strain that one anticipates will be the prevalent one in the coming epidemic. This is done by a global surveillance of influenza isolates. The vaccine must match the circulating stain of virus as closely as possible to be effective. To accomplish this, a decision must be made months ahead of the influenza season to enable manufacturers to produce the vaccine in time.

New influenza vaccines

There has been considerable experience with a cold-adapted intranasal influenza vaccine. By growing influenza virus in the laboratory at lower temperatures, it becomes attenuated. In addition, it will grow in the lower temperature of the nose in preference to the lungs and will produce local immunity in the nasal mucosa. This vaccine is in large-scale trials at this time. It has the obvious advantage of not requiring an injection. In addition, it appears to be less restricted in terms of strain specificity. Thus, if the match of the vaccine strain with the circulating strain is not very good, one may still expect to have some protection. There is also a suggestion that protection may extend beyond a single influenza season.

If the intranasal vaccine fulfills its early promise, routine immunization of children against influenza may become a reality. Greater experience with rapid diagnostic tests for influenza and with the NIs in children also may increase our ability to reduce morbidity from influenza in pediatric patients.

See also Pediatric Annals' November 2000 issue on influenza in children.