Background: Influenza is a common illness in children that often leads to outpatient visits, hospitalizations, secondary bacterial complications, and sometimes death. Oseltamivir (Tamiflu), a neuraminidase inhibitor, is currently the only recommended therapy for the treatment of influenza in children younger than five years. A meta-analysis of the evidence, published in 2009, showed that when oseltamivir was started within 48 hours of the onset of symptoms, it modestly shortened the duration of influenza in children by 0.5 to 1.5 days. Heinonen and colleagues conducted a randomized, double-blind, placebo-controlled trial to evaluate the effectiveness of oseltamivir in reducing the duration of influenza when treatment is started within 24 hours of the onset of symptoms.
The Study: Children one to three years of age were recruited from two influenza seasons (2007 to 2008, and 2008 to 2009) in Turku, Finland. During these seasons, parents were asked to bring their children to the clinic if they had fever or signs of respiratory infection. Eligible participants had a fever for less than 24 hours, and at least one sign or symptom of a respiratory infection or a positive rapid influenza test. Children with a confirmed viral disease other than influenza, a potential bacterial infection, a poorly controlled underlying medical condition, immunosuppression, allergy to oseltamivir, treatment with the study medication in the previous four weeks, or participation in another clinical trial with an investigational drug were excluded.
Participants were randomized to receive placebo or oseltamivir twice daily for five days. Parents were responsible for filling out symptom diaries on days 1 through 21 by recording the child's temperature; the presence and severity of symptoms; the return to normal activities; absences from day care or work; and administration of the study drug, relief medications, or antibiotics. Influenza illness was confirmed with viral culture, and further testing with reverse transcriptase polymerase chain reaction assays was conducted when necessary.
The primary outcome was the development of acute otitis media in children with confirmed influenza. Secondary outcomes were the time to resolution of illness, time to resolution of all symptoms, resolution of fever, absence from day care and work, use of relief medications or antibiotics, incidence of complications other than acute otitis media, and hospitalization. Subgroup analysis was performed depending on whether the patient was found to have influenza A or influenza B.
Results: Of the 408 participants who received an intervention, 203 received oseltamivir and 205 received placebo. Laboratory testing confirmed the presence of influenza in 37 patients in the oseltamivir group and 61 patients in the placebo group.
No significant reductions in otitis media occurrence were observed in any group or subgroup when oseltamivir was started within 24 hours of the onset of symptoms. However, an 85 percent reduction in the development of acute otitis media was found in patients with any type of influenza who were taking oseltamivir and began the medication within 12 hours of the onset of symptoms.
Oseltamivir shortened the duration of illness by 1.4 days in all children and by 3.5 days in those with confirmed influenza A. Oseltamivir also significantly reduced parents' absence from work, children's absence from day care, and the use of antipyretics and analgesics. No child with influenza developed pneumonia or was hospitalized during the study period. Vomiting was the main complication associated with oseltamivir use. Oseltamivir had no notable effect on influenza B infections, possibly because of the small number of patients who had influenza B or because of resistance to the drug.
Conclusion: The authors conclude that initiation of oseltamivir within 24 hours of the onset of influenza symptoms significantly reduces the duration of symptoms, absence from work, absence from day care, and use of antipyretics and analgesics, particularly in children with a confirmed influenza A viral infection. The authors acknowledge that it is challenging to clinically diagnose influenza early enough to initiate treatment within 24 hours, especially because only 25 percent of the study population actually had laboratory-confirmed influenza.