Influenza symptoms
The presenting symptoms of influenza in children do not differ greatly between clinical settings. In children aged <14 years who were treated as outpatients, fever was very common (affecting 95 %), as were cough and rhinitis (77 and 78 % affected, respectively) but headache (39 %) and myalgia (13 %) were less common [
114]. An earlier prospective study reported a high prevalence of fever, cough and rhinorrhoea (95–96 %) in influenza-infected outpatients <5 years old [
96]. These three symptoms were almost as common in hospital inpatients of the same age, with cough slightly but significantly more common in those >6 months old (94 %) than those up to 5 months old (80 %;
p = 0.01) [
96]. Even in very young hospitalised infants (aged ≤2 months) with confirmed influenza, fever was the main presenting symptom [
101]. Similarly, high rates of fever and cough were reported from a more recent study of hospitalised children and adolescents with H1N1pdm09 influenza [
91]. Studies of hospitalised influenza patients also report neurological symptoms, such as febrile convulsions [
97,
115,
119], although these are often reported as complications of the disease rather than symptoms (see next section). As well as the neurological system, other non-respiratory systems can be commonly affected in influenza: in some epidemics, up to 50 % of children have presented with gastrointestinal symptoms such as vomiting and diarrhoea, particularly those who are admitted to hospital, and affecting children of all age groups [
1,
11,
67,
69,
90,
134]. In a study of children and adolescents hospitalised with laboratory-confirmed influenza, sepsis-like illness was the admission diagnosis for 52 % of those aged <6 months and for up to 16 % of older children [
115].
Differentiating influenza from other respiratory infections on the basis of symptoms alone is challenging, and virological testing is necessary to confirm the diagnosis. A Finnish group who used a matched case-control study in children aged ≤13 years to compare confirmed influenza patients with those who had respiratory symptoms but were influenza-negative found fever to be the only reliable predictor of influenza [
54].
Complications of influenza
Influenza-associated complications contribute significantly to the disease burden in children. Complications are more likely to develop in recognised high-risk groups, including those with co-morbidities [
26,
71] and younger children [
71].
One of the most common complications of seasonal influenza in children is otitis media, which is associated with excess healthcare visits, antibiotic use and surgical procedures, and can lead to hearing loss. Otitis media affected 28 % of under 5 years presenting as outpatients in the US population-based study by Poehling et al. [
96] and occurred in 24 % of young hospitalised children in both a Finnish and a US study [
90,
93]. Infants and young children aged under 2 years old, however, appear to be at higher risk of acute otitis media than older children [
84], which is consistent with the results of the Finnish prospective cohort study that reported a rate of 40 % in children <3 years old in an outpatient setting [
51].
Respiratory tract infections (RTIs) are also frequently encountered as influenza complications. The most important RTI with respect to healthcare burden is pneumonia which is associated with hospitalisation and poorer outcomes. The incidence of pneumonia is high in children admitted to hospital with more severe influenza; in 2,992 hospitalised children and adolescents with seasonal influenza, radiographic evidence of pneumonia was found in 1,072 (36 %) [
30], and recently published studies in European and Asian children suggest a similar rate in hospitalised children with H1N1pdm09 influenza, with estimates ranging from 22 to 43 % [
11,
69,
91,
111], although two groups found the rate to be higher for H1N1pdm09 infections during 2009 than for influenza A infections in previous seasons [
5,
78]. Pneumonia is less common outside the hospital setting: in the Finnish prospective cohort study in outpatients mentioned above, pneumonia was diagnosed in 9 of 370 (2.4 %) children with confirmed influenza, 8 of whom were aged ≤6 years [
51]. In a retrospective study of 936 children aged 0–15 years with confirmed influenza seen as hospital outpatients or inpatients, pneumonia was present in 134 (14 %) children, 66 % of whom were <3 years old [
65]. As with otitis media, infants aged under 2 years appeared to have a higher risk of LRTI than those aged 2–4 years in a 25-year cohort study, although absolute rates were quite low (annual rates per 1,000 children of 11 and 10 in the first and second years of life, respectively, and 4 for those aged 2–4 years) [
84].
Neurological events or disorders are frequently reported as complications of influenza, ranging from febrile convulsions, which typically have a good prognosis, to encephalitis and encephalopathy, which may be fatal.
Japanese and Taiwanese children appear to have a higher vulnerability to CNS complications, although these findings may be the result of more intense surveillance. In 1,000 Japanese patients aged 0–20 years with H1N1pdm09, neurological complications resulted in hospital admission in 255 (25.5 %) patients; the most common events were febrile convulsions (135 children) whereas encephalopathy, mostly mild, was only seen in 12 [
121]. CNS dysfunction occurred in 26 of 84 (31 %) Taiwanese children with seasonal influenza, 60 of whom were aged <5 years; one of the patients had febrile convulsions, but 21 had encephalitis or encephalopathy [
128]. In a recent Israeli study, 14 of 74 (19 %) children aged 0–16 years hospitalised with H1N1pdm09 had CNS complications, but these were mainly mild seizures [
66].
CNS complications were less common in US studies of seasonal and pandemic influenza. In the earlier survey, 72/842 children hospitalised with seasonal influenza (8.6 %) had CNS complications; 56 had seizures (median age, 1.4 years) and 10 (median age, 3.5 years) had mild encephalopathy [
85]. In 307 children aged 1–19 yrs who were hospitalised with H1N1pdm09 infection, 23 (7.5 %) had CNS complications (17 with seizures and 7 with encephalopathy), but 15 patients required monitoring in ICU and three died [
64].
Neurological complications appear to be more common in severely ill children. In a French study of 181 children admitted to hospital with H1N1pdm09, 14 (7.7 %) had CNS dysfunction; of the 14 children (median age, 5.1 years), eight had febrile seizures and three had encephalitis or encephalopathy [
39]. Twenty-four of the 181 children needed admission to ICU, however, including nine of those with CNS complications (38 % of the ICU cohort). In a study of 20 German children aged 0–15 years (median 7.5 years) who were admitted to ICU with severe seasonal influenza infections, encephalitis or encephalopathy occurred in five cases [
120].
Less common complications of influenza include myositis [
16,
57,
66,
90] and myocarditis [
98,
112].