Influenza-associated illness is an important contributor to febrile convulsions in Danish children

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Summary

Objective

To determine the burden of febrile convulsions attributed to influenza like illness in a western country during ten influenza seasons.

Methods

Based on national Danish registries, we explored the association between influenza like illness (ILI) activity and weekly number of hospital admittances for febrile convulsions in time-series analyses. We included data on 59,870 admissions for febrile convulsions in children between three months and five years of age in the period 1995–2005.

Results

There was a significant relation between ILI-activity and number of children admitted for febrile convulsions with a systematic increase in admissions to pediatric wards about one week before the national surveillance system detected the corresponding rise in ILI-activity. The yearly number of admissions attributable to ILI varied from 11 to 47% of admissions and was highest during influenza epidemics. This was in particular observed in seasons when a new strain of influenza A/H3N2 was circulating. During these epidemics, influenza contributed to 29–47% of admissions.

Conclusions

Influenza like illness is associated with a considerable burden of febrile convulsions in children, most pronounced in years with epidemics. As febrile convulsions are just one of many complications contributing to the burden of influenza in children, this should be taken into consideration when planning a vaccination strategy for preventing influenza-related morbidity in younger children.

Introduction

Morbidity and mortality due to influenza are well recognized among the elderly but in recent years there has been an increasing interest to ascertain the burden of influenza-associated disease among children. The severity and magnitude of seasonal influenza depend on combinations of different factors: waning immunity in the population (or in subgroups of the population), the extent of the viral antigenic drift and the virulence of new virus strains.1 Children have little or no immunity for circulating influenza types and during seasonal influenza epidemics the attack rate in the community is highest among pre-school and school-aged children; during larger epidemics between 30 and 50% of these may be infected.1, 2, 3 Also, infection in children is usually occurring prior to seniors being affected.

Influenza is an important cause of hospitalization among infants and young children. Children without chronic and serious medical conditions have the same risk of admittance as adults in high-risk groups. Many studies have shown different and substantial rates of influenza-related complications in children. Primary influenza pneumonias, super infections such as otitis media, bacterial pneumonia and exacerbation of asthma are among possible complications in children after infection with influenza.4, 5, 6, 7, 8, 9 Neurologic complications including febrile convulsions associated with influenza have mainly been reported from Japan and South East Asia, but only recently addressed in western countries.10, 11 A consensus statement defines febrile convulsion as “an event in infancy or childhood usually occurring between 3 months and 5 years of age associated with a fever, but without evidence of intracranial infection or defined cause for their convulsion”.12 Febrile convulsions can be associated with a fever of any cause, but mainly with upper respiratory tract infections.13, 14

Studies mainly from Asia report that among children admitted for febrile convulsions (FC), most are caused by influenza A; 35–44% during epidemics of influenza. Furthermore, some researchers have suggested that influenza A virus may be neurotropic; this is based on these consistent observations as well as manifestations such as encephalitis and encephalopathy linked to influenza.15, 16, 17, 18, 19, 20, 21, 22, 23

In Europe, the burden of FC associated with influenza is not completely understood. The aim of the present study was to use national Danish surveillance data and the hospital discharge registry to examine the relationship between children’s diagnosis of discharge for FC and activity of influenza like illness (ILI), as well as the impact of changes in circulating influenza types on admissions for FC.

Section snippets

Study population

The Danish National Patient Registry contains data on admittances and discharges from Danish Hospitals, and since 1993 also includes the diagnoses of visits to emergency rooms and outpatient clinics.24 We extracted data from this registry for the period January 2, 1995 to December 31, 2005, applying the International Classification of Diseases (ICD)-10 code for febrile convulsions, R56.0. The data contained information on date of admission and discharge, patient age at admission and gender. The

Results

Approximately 85% of the children were younger than three years of age, and most (56.6%) were boys, Table 1. The weekly number of admissions for FC in children correlated with ILI-activity (p < 0.001). With increasing ILI-activity there were increasing numbers of admittance for FC.

By categorizing the ILI-activity in four categories, Table 2, we found an RR of being admitted of 2.05 if ILI-percentage was above 3%; periods with ILI-activity <1% served as the reference. The correlation between FC

Discussion

Studies primarily from Japan but also other Asian countries, and recently reported in Europe, indicate that infection with influenza virus is an important trigger of FC, including complex febrile convulsions, but also severe convulsions in influenza-verified encephalitis-encephalopathy.10, 11, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 It has been suggested that the rate of complications depends on viral strains. To explore the full picture of complications it is therefore necessary to examine

Conflict of interest

None of the authors have conflict of interest.

Acknowledgments

We thank Bernadette Gergonne for her expertise in Time Series Analysis used in an epidemiological context.

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    Copyright © 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.