The battle against influenza: The role of neuraminidase inhibitors in children.

Abstract

Influenza viruses continue to be a major cause of morbidity and mortality worldwide. During outbreaks of influenza, the highest attack rates are among school-aged children. Secondary spread occurs to adults and other children in the family. The secondary spread is facilitated by viral shedding, which can be quite prolonged in young children (1). In neonates, influenza has been associated with significant morbidity, including a sepsis-like syndrome, apnea and lower respiratory tract disease. Children younger than five years of age have the second highest rates of infection with influenza and hospitalization, which are exceeded only by persons older than 65 years of age (1,2). Increased rates of hospitalization during influenza seasons have been observed among previously healthy infants and young children (3). Besides admissions to hospitals, influenza accounts for a substantial number of outpatient visits and antibiotic prescriptions in children (4,5). Given the burden of influenza infections in children despite the medical community’s best efforts at prevention, treatment strategies are required for certain groups of children, including children at risk of severe complications from influenza. Among the traditional therapeutic agents, only amantadine (Symmetrel, DuPont Pharma, Canada) is approved for treatment in children, and neither amantadine nor rimantadine (Flumadine, Forest Laboratories Inc, USA; not approved for use in Canada) is effective against influenza B. The newly approved neuraminidase inhibitors are active against both influenza A and B (6-8). While the bulk of the evidence for the effectiveness of the neuraminidase inhibitors has been derived from studies in adults and children older than 12 years of age, on-going studies are addressing the role of these agents in the management of influenza infections in young children. INFLUENZA VIRUS NEURAMINIDASE Neuraminidase is a surface glycoprotein that has enzymatic activity essential for the replication of influenza A and B (8). The enzyme catalyses the cleavage of the -ketosidic linkage that exists between a terminal sialic acid, N-acetyl neuraminic acid and an adjacent sugar residue. This action has a number of important effects that enable the spread of the virus within the respiratory tract. These effects include the release of the virus from infected cells, the prevention of viral aggregates after release from host cells, the prevention of viral inactivation and the promotion of viral penetration into respiratory cells.