Fatal cases of influenza a in childhood

Abstract

Background: In the northern hemisphere winter of 2003-04 antigenic variant strains (A/Fujian/411/02 -like) of influenza A H3N2 emerged. Circulation of these strains in the UK was accompanied by an unusually high number of laboratory confirmed influenza associated fatalities in children. This study was carried out to better understand risk factors associated with fatal cases of influenza in children.

Methodology/principal findings: Case histories, autopsy reports and death registration certificates for seventeen fatal cases of laboratory confirmed influenza in children were analyzed. None had a recognized pre-existing risk factor for severe influenza and none had been vaccinated. Three cases had evidence of significant bacterial co-infection. Influenza strains recovered from fatal cases were antigenically similar to those circulating in the community. A comparison of protective antibody titres in age stratified cohort sera taken before and after winter 2003-04 showed that young children had the highest attack rate during this season (21% difference, 95% confidence interval from 0.09 to 0.33, p = 0.0009). Clinical incidences of influenza-like illness (ILI) in young age groups were shown to be highest only in the years when novel antigenic drift variants emerged.

Conclusions/significance: This work presents a rare insight into fatal influenza H3N2 in healthy children. It confirms that circulating seasonal influenza A H3N2 strains can cause severe disease and death in children in the apparent absence of associated bacterial infection or predisposing risk factors. This adds to the body of evidence demonstrating the burden of severe illness due to seasonal influenza A in childhood.

Figure 1. Age-distribution of seroconversion to influenza virus in 2003 and 2004.

Charts show the proportion of sera from the summers of 2003 (clear bars) and 2004 (filled bars) that gave a HI titre above 1/40 for each age group against A/Wyoming/3/03 (antigenically equivalent to A/Fujian/411/02), together with the 95% confidence interval (error bars). Asterisks denote statistical significance (*p<0·05; **p<0·01). A total of 882 and 799 serum samples were tested for 2003 and 2004 respectively, each in duplicate, together with control ferret sera.

Figure 2. Clinical incidence rate of influenza-like illness (ILI) per 100,000 population recorded by the Royal College of General Practitioners Weekly Returns Service.

Weekly incidence rate of ILI presented for all-age, 0–4 and 5–14 years age groups. Vertical shaded bars represent defined periods of influenza virus circulation derived from laboratory reports. Arrows indicate those years in which a new variant was introduced into the community (1. A/Wuhan/359/95; 2. A/Sydney/5/97; 3. A/Fujian/411/02).

Figure 3. Clinical incidence rate of influenza-like illness (ILI) by age group expressed as a factor of the all-age incidence rate.

Mean weekly incidence rates of ILI during influenza virus active weeks were calculated for winters: A) 1995/96 (A/Wuhan/359/95); B) 1997/98 (A/Sydney/5/97); C) 1999/00 (no new variant); and D) 2003/04 (A/Fujian/411/02).