Background
Methods
Results
Articles included
Reference | Study design | Study settings Children age | Sample | Study qualitya Study limitations/bias | Type of data |
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Finland
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Heikkinen et al., 2004 [35] | Prospective, observational study of respiratory infections in community-based children. | Community (day care centres, family day care, and schools); | 2,231 child-seasons, | 1b: prospective cohort study; | Resource use, absenteeism |
382 episodes of culture-confirmed influenza were documented | |||||
Only winter months were evaluated. | |||||
Study seasons: 9 October 2000 — 20 May 2001 and 1 October 2001 — 19 May 2002. | ≤ 13 years. | ||||
Follow-up: not specified. | |||||
Heinonen et al., 2010 [42] | Randomised, double-blind, controlled trial comparing oseltamivir with placebo for clinical efficacy in children with influenza. | Community; | 1,185 children were recruited in the community prior to influenza seasons; among those,409 children with fever or respiratory infection who attended the study clinic were randomised to either intervention or placebo; among those,98 (24.7%) children had laboratory-confirmed influenza | 1b: randomised, controlled trial; | Resource use, absenteeism. |
1-3 years | |||||
Not a population- based study;b
| |||||
Broad exclusion criteria prior to enrolment in the trial. | |||||
Study seasons: 2 local influenza circulation seasons (14 January — 9 April 2008 and 7 January — 26 March 2009). | |||||
Follow-up: 21 days. | |||||
France
| |||||
Ploin et al., 2003 [43] | Prospective, observational study in a paediatric ED of a university hospital. | Paediatric ED; | 304 infants consecutively enrolled during influenza peak | 2b: prospective cohort study with poor follow-up; | Resource use, absenteeism |
≤ 11 months. | |||||
99 (33%) with confirmed influenza. | Not a population- based study. | ||||
Study season: 4 weeks of local influenza epidemic peak (weeks 3-6 in 2002). | |||||
Follow-up: 15 days. | |||||
Ploin et al., 2007 [36] | Prospective, observational study in a paediatric ED of a university hospital. | Paediatric ED; | 575 children consecutively enrolled during influenza peak | 2b: prospective cohort study with poor follow-up; | Resource use, absenteeism |
< 36 months. | |||||
283 (49%) with confirmed influenza. | Not a population- based study. | ||||
Study season: 4 weeks of local influenza epidemic peak (weeks 3-6 in 2002). | |||||
Follow-up: 15 days. | |||||
Sanni et al., 2004 [44] | Prospective, observational survey of hospitalised children. | Hospital; | 114 nasal swabs collected; among those – 59 (51.8%) with confirmed influenza. | 1b: prospective cohort study; | Resource use. |
≤ 15 years. | |||||
Not a population- based study. | |||||
Study season: 37 days of local influenza epidemic (1 January — 6 February 2002). | |||||
Follow-up: not specified. | |||||
Germany
| |||||
Ehlken et al., 2005 [45] | Cost-of-illness analysis of a prospective, multi-centre, population-based epidemiological study on the impact of LRTI in children. | Office-based PCP and hospitals; | 3,458 cases with LRTI, including 1,329 office based cases, 2,039 hospitalized cases, and 90 nosocomial cases. | 2c: outcomes research; | Cost (direct and indirect).c
|
Not a population- based study; | |||||
≤ 36 months. | |||||
Limited to children with LRTI; | |||||
Costs were imputed based on existing standards. | |||||
Study period: 2 years (1 November 1999 — 31 October 2001). | |||||
Follow-up: not specified. | |||||
Italy
| |||||
Bosis et al., 2005 [46] | Prospective, observational, single-centre study of children enrolled at an ED, comparing the impact of confirmed influenza and RSV with hMPV. | ED; | All children (n = 1,505) attending the ED on Wednesdays and Sundays. | 1b: prospective cohort study; | Resource use, absenteeism. |
< 15 years. | |||||
Not a population- based study. | |||||
Of these, 1,019 children had evidence of acute respiratory infection. | |||||
Influenza was confirmed by PCR in 230 (15.3%) of total cases; among these, 7 cases were co-infected with RSV or hMPV. | |||||
Study season: 5 months (1 November 2002 — 31 March 2003). | |||||
Follow-up: not specified. | |||||
Esposito et al., 2005 [47] | Prospective, observational, single-centre study of children admitted to an ED, comparing the impact of confirmed influenza and RSV. | ED; | 1,520 children attending ED for acute conditions other than trauma on Wednesdays and Sundays; | 1b: prospective cohort study; | Resource use, absenteeism |
< 15 years. | |||||
Not a population- based study. | |||||
234 (15.4%) with confirmed influenza. | |||||
Study season: 5 months (1 November 2002 — 31 March 2003). | |||||
Follow-up: not specified. | |||||
Esposito et al., 2011 [37] | Prospective, observational study of children presenting to PCP with ILI | PCP | PCPs continuously followed 21,986 community children | 1b: prospective cohort study with good follow-up | Resource use, absenteeism, cost (direct and indirect) |
< 14 years | |||||
6,988 children with ILI presented to PCPs | Costs were imputed based on existing standards | ||||
Study season: 6 months (1 November 2008 —30 April 2009) | 2,143 (30.7%) children had confirmed influenza | ||||
Follow-up: not specified | |||||
Principi et al., 2003 [48] | Prospective, observational, multi-centre study. | ED and PCP; | 3,771 children with ILI; among those | 1b: prospective cohort study; | Resource use, absenteeism |
< 14 years. | |||||
352 (9.3%) with confirmed influenza, including 260 (8.7%) of 2,970 children seen in EDs and 92 (11.5%) of 801 children seen by PCPs | Not a population- based study. | ||||
Principi et al., 2004 [38] | Study season: 6 months (1 November 2001 — 30 April 2002). | ||||
Follow-up: not specified. | |||||
The Netherlands
| |||||
Bueving et al., 2004 [49] | Randomised, double-blind, placebo-controlled trial comparing inactivated vaccine with placebo for clinical efficacy in children with asthma. | Community; | 696 children with asthma enrolled through PCP offices prior to influenza seasons’ start. | 1b: individual randomised, controlled trial; | HRQoL. |
6-18 years. | |||||
Limited to children with asthma. | |||||
Study seasons: 2 influenza seasons (1999 — 2000 and 2000 — 2001). | |||||
Follow-up: not specified. | |||||
Van Der Zalm, et al., 2009 [50] | Prospective birth cohort study, a part of a prospective, ongoing population-based birth cohort study on determinants of wheezing illness. | Community; | 305 healthy full-term infants (2-3 weeks old); | 2b: individual cohort study. | Resource use. |
≤ 1 year. | |||||
668 samples positively tested for any respiratory virus; | |||||
18 (2.7%) samples with influenza virus. | |||||
Study duration: October 2003 — September 2006. | |||||
Follow-up: until infants reached 1 year of age. |
Clinical burden of influenza
Incidence of influenza
Reference | Country | Age | Setting | Study season or period | Influenza rates |
---|---|---|---|---|---|
Community-based estimates
| |||||
Van der Zalm, et al., 2009 [50] | The Netherlands | < 1 year | Community | October 2003 – September 2006. | Prevalence rate: influenza was detected in 2.7% of respiratory samples |
Follow-up: until infants reached 1 year of age. | |||||
Annual incidence rate: 62 per 1,000a
| |||||
Heikkinen et al., 2004 [35] | Finland | ≤ 13 years | Community | 9 October 2000 – 20 May 2001 and 1 October 2001 – 19 May 2002. | Influenza-season incidence rate per 1,000 children: |
All ages combined: 167,b
| |||||
Age < 3 years: 179, | |||||
Age 3-6 years: 175, | |||||
Age 7-13 years: 142. | |||||
Health care setting-based estimates
| |||||
Ploin et al., 2003 [43] | France | 0-11 months | Paediatric ED | 4 weeks of local influenza epidemic peak (weeks 3-6 in 2002) | Prevalence rate: |
Total: 33%, | |||||
Aged 0-2 months: 31%, | |||||
Aged 3-5 months: 27%, | |||||
Aged 6-8 months: 30%, | |||||
Aged 9-11 months: 40%. | |||||
Ploin et al., 2007 [36] | France | < 36 months | Paediatric ED | 4 weeks of local influenza epidemic peak (weeks 3-6 in 2002) | Prevalence rate: 49% |
Ehlken et al., 2005 [45] | Germany | 0-36 months | PCP, paediatric hospital | 1 November 1999 – 31 October 2001. | Annual incidence rate of LRTI associate with influenza: 1.1 per 100 children-years. |
Heinonen et al., 2010 [42] | Finland | 1-3 years (mean age: 2.4 years) | Primary care clinic | Two local influenza circulation seasons: 14 January – 9 April 2008 and 7 January – 26 March 2009. | Prevalence rate: 24.7% of children tested positive for influenza. |
Follow-up: 21 days. | |||||
Esposito et al., 2011 [37] | Italy | < 14 years | PCP (with community “base”) | 1 November 2008 – 30 April 2009. | Influenza-season incidence rate: 96.4 per 1,000 children. |
Principi et al., 2003 [48] | Italy | < 14 years | PCP and ED | 1 November 2001 – 30 April 2002. | Prevalence rate: 9.3%, (virology or PCR), |
Principi et al., 2004 [38] | Including: | ||||
8.7% of children seen in EDs and | |||||
11.5% of children seen by PCPs. | |||||
Bosis et al., 2005 [46] | Italy | < 15 years | ED | 1 November 2002 – 31 March 2003. | Prevalence rate; 15.3% (by PCR). |
Esposito et al., 2005 [47] | Italy | < 15 years | ED | 1 November 2002 – 31 March 2003. | Prevalence rate: 15.4% (by PCR). |
Sanni et al., 2004 [44] | France | ≤ 15 years | Hospital | 37 days of local influenza epidemic (1 January – 6 February 2002) | Prevalence rate: |
Total: 51.8%, | |||||
Aged 0-1 year: 42.4%, | |||||
Aged > 1 and ≤ 3 years: 68.9%, | |||||
Aged > 3 and ≤ 5 years: 41.2%, | |||||
Aged > 5 and ≤15 years: 36.8%. |
Complications of influenza
Economic burden
Health care resource use
Costs
Reference, country, and study period | Population | Costs |
---|---|---|
Ehlken et al., 2005 [45], | 3,458 children aged 0-36 months, with LRTI. |
Mean (SD) costs (in 2002 euros) per community-acquired, office-based case of confirmed influenza: |
Germany, | Setting: 11 office-based paediatricians and 5 hospitals. | Total cost: €223 (€280) |
Influenza season: 1999 — 2001. | Direct medical cost: €66 (€24) | |
Direct non-medical cost: €12 (€10) | ||
Indirect cost: €145 (€266) | ||
Mean (SD) costs (in 2002 euros) per community-acquired, hospitalised case of confirmed influenza: | ||
Total cost: €2,597 (€1,214) | ||
Direct medical cost: €2,428 (€1,200) | ||
Direct non-medical cost: €58 (€75) | ||
Indirect cost: €110 (€249) | ||
Median (95% CI) annual economic burden (in 2002 euros) due to confirmed influenza: | ||
Community-acquired office-based cases: NA | ||
Community-acquired, hospitalised cases: | ||
Median: €7,530,105 (€5,547,410-€10,011,705) | ||
Nosocomial cases: NA | ||
Esposito et al., 2011 [37], | 6,988 children aged < 14 years with ILI. |
Mean (SD) costs (in 2008 euros) of influenza in influenza-positive and influenza-negative children and their households, until resolution of illness: |
Italy, | Confirmed influenza cases: 2,143 (30.7%). | |
Influenza season: November 2008 — April 2009. | Total: €131.70 (€71.40); €89.40 (€65.20); P < 0.001 | |
Setting: ED at a university hospital. | ||
Paediatric examinations: €33.00 (€4.00); €30.60 (€4.20) | ||
Antibiotics: €3.70 (€4.30); €4.40 (€4.90) | ||
Antipyretics: €2.40 (€2.00); €1.90 (€1.40) | ||
Hospitalisation: €22.40 (€238.10); €22.50 (€251.00) | ||
Working days lost by mothers: €47.90 (€90.10); €26.70 (€89.90); P < 0.05 | ||
Working days lost by fathers: €22.30 (€89.70); €3.30 (€39.90); P < 0.05 | ||
Mean (SD) costs of influenza in influenza-positive children with influenza A or influenza B and their households, until resolution of illness: | ||
Total: €142.60 (€74.30); €72.80 (€53.30); P < 0.001 | ||
Paediatric examinations: €33.30 (€4.60); €30.90 (€3.40) | ||
Antibiotics: €3.70 (€3.30); €3.40 (€3.10) | ||
Antipyretics: €2.50 (€2.10); €2.00 (€1.90) | ||
Hospitalisation: €22.40 (€243.40); €14.20 (€216.70) | ||
Working days lost by mothers: €54.40 (€94.80); €16.60 (€61.40); P < 0.05 | ||
Working days lost by fathers: €26.30 (€97.70); €5.70 (€33.30); P < 0.05 | ||
Mean (SD) cost of influenza in influenza-positive children of different age groups (<2 years, 2-5 years, and 6-13 years) and their households, until resolution of illness:
| ||
Total: €153.20 (€72.80)a; €148.10 (€83.10)a; €73.90 (€41.90) | ||
Paediatric examinations: €33.50 (€5.60); €32.90 (€4.20); €33.00 (€2.50) | ||
Antibiotics: €3.20 (€3.90); €4.00 (€4.60); €3.30 (€3.90) | ||
Antipyretics: €2.40 (€1.90); €2.30 (€2.20); €2.10 (€2.50) | ||
Hospitalisation: €40.80 (€238.80); €23.90 (€268.90); €11.50 (€153.40) | ||
Working days lost by mothers: €46.70 (€96.40)a; €55.60 (€106.70)a; €19.80 (€49.60) | ||
Working days lost by fathers: €26.60 (€90.40)a; €29.40 (€111.40)a; €4.20 (€39.10) |