We have read the journal's policy and have the following competing interests: DEN has participated on an influenza advisory board for Novartis. RB works with all major manufacturers of influenza vaccines in an advisory capacity, as a researcher on vaccines and as presenter of academic info at conferences, receiving support to travel and attend such conferences. The authors have declared that no other competing interests exist.
Conceived and designed the experiments: KEL HN MAW. Performed the experiments: KEL MW EAB MAW. Analyzed the data: KEL HN EAB MAW. Contributed reagents/materials/analysis tools: KEL HN MW. Wrote the first draft of the manuscript: KEL. Contributed to the writing of the manuscript: MAW. Enrolled patients: MHR FV RB MR PK HY GG DC JA DJ SH WA RM MCha ODS GOE ZN AC JMH DEN RC PN AB AA MvH RO TN MV VM MChi THN AT GRIPP-WG. Agree with the manuscript’s results and conclusions: KEL HN MHR FV RB MR PK HY GG DC JA DJ SRCH WA RM MCha ODS GOE ZN AC JMH DEN RC PN AB AA MvH RO TN MV VM MChi THN AT MW EAB JB HC MAW GRIPP-WG. All authors have read, and confirm that they meet, ICMJE criteria for authorship.
¶ Membership of the GRIPP Working Group is provided in the Acknowledgments.
The global burden of pediatric severe respiratory illness is substantial, and influenza viruses contribute to this burden. Systematic surveillance and testing for influenza among hospitalized children has expanded globally over the past decade. However, only a fraction of the data has been used to estimate influenza burden. In this analysis, we use surveillance data to provide an estimate of influenza-associated hospitalizations among children worldwide.
We aggregated data from a systematic review (
Influenza was associated with 10% (95% CI 8%–11%) of respiratory hospitalizations in children <18 y worldwide, ranging from 5% (95% CI 3%–7%) among children <6 mo to 16% (95% CI 14%–20%) among children 5–17 y. On average, we estimated that influenza results in approximately 374,000 (95% CI 264,000 to 539,000) hospitalizations in children <1 y—of which 228,000 (95% CI 150,000 to 344,000) occur in children <6 mo—and 870,000 (95% CI 610,000 to 1,237,000) hospitalizations in children <5 y annually. Influenza-associated hospitalization rates were more than three times higher in developing countries than in industrialized countries (150/100,000 children/year versus 48/100,000). However, differences in hospitalization practices between settings are an important limitation in interpreting these findings.
Influenza is an important contributor to respiratory hospitalizations among young children worldwide. Increasing influenza vaccination coverage among young children and pregnant women could reduce this burden and protect infants <6 mo.
The substantial global burden of influenza infections in children is revealed by Lafond and colleagues. Children in developing countries are 3 times more likely to be hospitalised and treatments vary. This study highlights the need for vaccination programs in the young.
Acute lower respiratory infections—bacterial and viral infections of the lungs and airways (the tubes that take oxygen-rich air to the lungs)—are major causes of illness and death in children worldwide. Pneumonia (infection of the lungs) alone is responsible for 15% of deaths among children under five years old and kills nearly one million young children every year. Globally, infections with respiratory syncytial virus and with
Annual immunization (vaccination) can reduce an individual’s risk of catching influenza, but before a country implements this preventative measure, policymakers need reliable estimates of the burden of influenza in their country. Although such estimates have been calculated for resource-rich countries with temperate climates, where influenza largely occurs in the winter, few estimates of influenza burden are available for resource-limited countries, which has hampered informed consideration of vaccination for influenza prevention in many settings. Recently, however, there has been a global expansion of systematic surveillance and testing for influenza virus among patients admitted to hospital for severe respiratory infection. Here, the researchers use this expanded surveillance data to provide an estimate of influenza-associated hospitalizations among children worldwide between 1982 and 2012. Specifically, they undertake a systematic review to identify published research articles on influenza-associated respiratory disease in hospitalized children, and, by aggregating the data from these articles with data collected by hospital-based influenza surveillance, they calculate a pooled estimate of the proportion of children hospitalized with respiratory disease who are positive for influenza.
Using predefined search criteria, the researchers identified 108 published research articles that provided information on influenza-associated respiratory illness among hospitalized children. In addition, the Global Respiratory Hospitalizations–Influenza Proportion Positive (GRIPP) working group provided 37 hospital-based influenza surveillance datasets. By aggregating the data from these sources using a statistical approach called meta-analysis, the researchers calculated that, overall, influenza was associated with 9.5% of hospitalizations for severe respiratory infection among children under 18 years old worldwide, ranging from 4.8% among children under six months old to 16.4% among children aged 5–17 years. The researchers also calculated that, on average over the study period, influenza resulted in about 374,000 hospitalizations annually among children under one year old (including 228,000 hospitalizations among children less than six months old) and nearly one million hospitalizations annually among children under five years old. Finally, the researchers calculated that influenza-associated hospitalization rates among children under five years old over the study period were more than three times higher in resource-limited countries than in industrialized countries (150 and 48 hospitalizations, respectively, per 100,000 children per year).
Differences in hospitalization practices, in applications of case definitions, and in influenza testing protocols between settings may affect the accuracy of these findings. Specifically, the approach taken by the researchers may mean that their estimate of the total burden of severe respiratory disease due to influenza is an underestimate of the true situation. Even so, these findings suggest that influenza is an important contributor to hospitalizations for severe respiratory illness among children worldwide. Increasing influenza vaccination coverage among young children and pregnant women could, therefore, reduce the contribution that influenza makes to hospitalizations for respiratory infections among children. Importantly, the estimates of the burden of influenza provided by these findings can now be used by countries considering influenza vaccination programs for children and/or pregnant women to help them investigate the possible health and cost implications of such programs and should also stimulate further research into the development of effective influenza vaccines for young children.
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Influenza virus infections are a substantial contributor to respiratory morbidity and mortality, with the highest burden of severe disease experienced by those aged <5 y and ≥65 y [
In the last 10 y, however, the global expansion of influenza surveillance and laboratory capacity for influenza testing by reverse transcription PCR has led to dramatic increases in testing in settings with previously sparse data. Many countries worldwide now perform hospital-based influenza surveillance among patients hospitalized with severe acute respiratory illness (SARI) [
We aimed to update the previous influenza burden estimates in young children, making full use of updated and expanded surveillance data from the past decade (2003–2012), both before and after the 2009 pandemic influenza emergence. We further aimed to extend previous studies by providing global estimates of the prevalence of influenza among acute lower respiratory infection (ALRI) hospitalizations among both younger (<5 y) and older (5–17 y) children.
We aggregated data from all eligible published etiologic studies of influenza-associated respiratory illness among hospitalized children, which we supplemented with data from a working group of inpatient surveillance systems worldwide. We then calculated a final pooled estimate of the proportion of tested samples that were positive for influenza by reverse transcription PCR among children aged <18 y (referred to as proportion or percent positive), using age-group-specific random-effects log-binomial regression models. Finally, we applied the aggregate pooled proportion positive among children <1 and <5 y to age-specific denominators of global hospitalizations for ALRI among these two age groups [
We searched nine online databases (PubMed, Embase, Web of Science, CINAHL [Cumulative Index to Nursing and Allied Health Literature], IndMed, LILACS [Literatura Latino-Americana e do Caribe em Ciências da Saúde], WHOLIS [WHO Library Database], CNKI [China National Knowledge Infrastructure], and the Global Health Database) to identify articles published from 1 January 1996 to 1 June 2012. The search was conducted with no language restrictions, and full search terms are provided in
Identified articles were screened by two independent reviewers (two from K. E. L., M. W., E. A.-B., M.-A. W., P. Glew, S. Mei, Z. Suizan) for inclusion in the analysis, and duplicates were removed. The inclusion criteria were as follows: (1) original study with human participants, (2) laboratory testing for influenza, with description of the type of diagnostic method used, (3) minimum of 12 mo of continuous surveillance, (4) specified case definition (such as ALRI, SARI, or acute respiratory illness) or other clear criteria for specimen collection and testing, (5) hospitalized patients (excluding nosocomial infections), (6) number of enrolled cases from whom clinical specimens were collected and found positive was provided, and (7) minimum of 50 children (<18 y or “pediatric” as defined by authors) tested for influenza, in order to screen out small, potentially unreliable studies from the study dataset. For title and abstracts that met these criteria, full-text articles were obtained and re-screened. Full-text articles written in languages other than English were screened twice by co-investigators who could read the relevant language. Any discrepancies were discussed and resolved by reviewers. Independent screening was concordant for 92% of full-text articles, with 100% concordance after joint discussion of discrepancies.
Key data from each eligible article were abstracted by two independent reviewers. Data abstracted included the total number of inpatients tested and total positive for influenza by age group and year, case definition and diagnostic test, WHO region, World Bank income level (low, lower-middle, upper-middle, or high income) [
Data quality for each eligible article was scored using a modified Newcastle–Ottawa checklist for bias assessment [
To supplement data from published studies, we compiled data from surveillance platforms that conducted hospital-based influenza surveillance. We established a working group, the Global Respiratory Hospitalizations–Influenza Proportion Positive (GRIPP) Working Group. To be eligible, surveillance platforms needed to conduct systematic year-round inpatient enrollment, with testing for at least 12 mo and >50 pediatric patients. Forty-eight partners were contacted, of which 37 had eligible data and agreed to participate. Data were collected using a standard format. Variables included the number of persons tested and positive for influenza by calendar year and age group, as well as surveillance system information such as the total number of inpatient sites and case definition used. If surveillance data were also represented in a report identified through the systematic review, the more detailed working group dataset was used, and the published article was excluded as a duplicate source.
We first described the median proportion positive by age group, study duration, calendar year, number tested, diagnostic method, case definition, study population, WHO region, and country income level among all eligible datasets. We found substantial variation by age, diagnostic test, and calendar year. To reduce the influence of data from less reliable diagnostic methods (such as immunofluorescence [low sensitivity] and single serological samples [higher likelihood of false-positive findings]), we restricted the data for the meta-analysis to sites that utilized PCR for diagnosis, which is the accepted diagnostic gold standard. Further, to ensure that pooled estimates reflected seasonal rather than pandemic years, we excluded data from 2009.
Pooled estimates of the proportion of respiratory hospitalizations due to influenza were calculated by mixed regression model for each of the following age groups: <6 mo, <1 y, <2 y, <5 y, 5–17 y, and <18 y. If a dataset used age ranges that did not line up with our definitions, it was included in the smallest range that contained both bounds (e.g., a dataset from children 0–36 mo was included in the <5 y analysis). The same datasets could provide estimates for multiple age groups if they provided number tested and positive for influenza for each age group.
The mixed regression model in SAS version 9.3 (SAS Institute) used a log-linked binomial distribution of input values, and included the number tested and positive for influenza by dataset and calendar year for each age group. If a single dataset provided data by year, then each year was treated as a single observation in the model, and the dataset was defined as a cluster. Random effects were accounted for at the dataset level, irrespective of the number of observations within the dataset.
We then applied our pooled proportion positive for influenza viruses to global estimates of the total annual number of hospitalizations for ALRI among children <5 y and <1 y from Nair et al. [
No estimates of the frequency of ALRI among children under 6 mo existed to which we could apply the proportion positive for influenza viruses. Therefore, we calculated an incidence rate ratio of influenza-associated ALRI between children aged 0–5 mo and 6–11 mo, collected as part of a separate study [
The systematic literature search identified 38,006 unique records from the nine scientific literature databases, of which 957 full-text articles were reviewed, and 108 included in the descriptive analysis (
Characteristic | Number (Percent) of Published Studies, |
Number (Percent) of Surveillance Datasets, |
---|---|---|
<6 mo | 13 (12) | 12 (32) |
<1 y | 20 (19) | 23 (62) |
<2 y | 19 (18) | 14 (38) |
<5 y | 45 (42) | 35 (95) |
5–17 y | 9 (8) | 28 (76) |
<18 y | 63 (58) | 33 (89) |
1–2 | 78 (72) | 16 (43) |
3–4 | 19 (18) | 13 (35) |
5+ | 11 (10) | 8 (22) |
Before 2009 | 93 (86) | 12 (32) |
During 2009 (“pandemic”) | 1 (1) | 18 (49) |
After 2009 | 1 (1) | 33 (89) |
50–99 | 10 (9) | 1 (3) |
100–499 | 46 (43) | 9 (24) |
500–999 | 21 (19) | 5 (14) |
1,000+ | 31 (29) | 22 (59) |
PCR only | 30 (28) | 15 (41) |
Immunofluorescence only | 32 (30) | 0 (0) |
Culture only | 3 (3) | 0 (0) |
Multiple diagnostic tests, including PCR | 14 (13) | 22 (59) |
Multiple diagnostic tests, excluding PCR | 25 (23) | 0 (0) |
Other |
4 (4) | 0 (0) |
Acute respiratory infection | 35 (32) | 1 (3) |
ALRI | 36 (33) | 2 (5) |
Pneumonia | 18 (17) | 1 (3) |
SARI | 0 (0) | 31 (84) |
Bronchiolitis | 5 (5) | 0 (0) |
Other |
14 (13) | 2 (5) |
Yes | 7 (6) | 0 (0) |
No | 101 (94) | 37 (100) |
Africa | 10 (9) | 13 (35) |
Americas | 18 (17) | 6 (16) |
Eastern Mediterranean | 2 (2) | 2 (5) |
Europe | 30 (28) | 2 (5) |
Southeast Asia | 11 (10) | 6 (16) |
Western Pacific | 37 (34) | 8 (22) |
Low | 7 (6) | 15 (41) |
Lower-middle | 36 (33) | 15 (41) |
Upper-middle | 20 (19) | 6 (16) |
High | 47 (44) | 1 (3) |
0 | 5 (5) | |
1 | 20 (19) | |
2 | 28 (26) | |
3 | 55 (51) |
*If a dataset used age ranges that did not line up with our definitions, it was included in the smallest range that contained both bounds (e.g., a dataset from children 0–36 mo was included in the <5 y analysis).
**Pandemic defined as calendar year 2009; 13 published articles provided only combined pre-pandemic/pandemic estimates.
†Includes serological ELISA of single or paired sera (
‡Case definitions as defined per individual study criteria.
§Includes acute respiratory infection and/or fever (
ǁDefined as study being designed specifically to target a high-risk population; includes recurrent wheezing/asthma (
The crude median percent of respiratory samples that were influenza positive among patients aged 5–17 y was more than double that among those <5 y (15%, interquartile range [IQR] 10%–22%, versus 6%, IQR 3%–9%,
Characteristic | Number of Studies ( |
Median Number (IQR) | Median Percent Positive (IQR) | ||
---|---|---|---|---|---|
<0.001 | |||||
<6 mo | 25 | 386 (148–1,129) | 17 (3–32) | 4 (1–5) | |
<1 y | 42 | 536 (282–1,812) | 34 (11–58) | 4 (2–7) | |
<2 y | 31 | 506 (145–1,322) | 21 (4–77) | 5 (2–8) | |
<5 y | 80 | 766 (321–1,444) | 42 (18–86) | 6 (3–9) | |
5–17 y | 36 | 243 (90–507) | 27 (14–87) | 15 (10–22) | |
<18 y | 92 | 817 (239–1,524) | 53 (15–110) | 7 (5–12) | |
0.001 | |||||
Surveillance | 37 | 1,159 (469–2,185) | 98 (38–249) | 9 (6–12) | |
Published | 104 | 435 (162–1,063) | 29 (8–66) | 5 (3–9) | |
<0.001 | |||||
Before 2009 | 102 | 454 (170–1,086) | 29 (8–70) | 5 (3–9) | |
During 2009 (“pandemic”) | 19 | 610 (100–1,353) | 56 (8–205) | 13 (6–20) | |
After 2009 | 34 | 707 (291–1,289) | 64 (20–118) | 9 (5–11) | |
0.001 | |||||
PCR only | 44 | 701 (270–983) | 40 (25–67) | 7 (5–10) | |
Immunofluorescence only | 32 | 486 (185–1,654) | 17 (8–78) | 3 (2–6) | |
Culture only | 3 | 302 (68–838) | 39 (5–204) | 13 (7–24) | |
Multiple diagnostic tests, including PCR | 36 | 497 (185–1,167) | 39 (18–88) | 9 (8–10) | |
Multiple diagnostic tests, excluding PCR | 22 | 1,047 (224–2,073) | 64 (15–170) | 8 (5–12) | |
Other | 4 | 211 (143–1,389) | 31 (7–75) | 6 (4–13) | |
0.14 | |||||
Acute respiratory infection | 33 | 958 (415–1,429) | 51 (18–88) | 5 (3–10) | |
ALRI | 37 | 516 (186–1,234) | 32 (17–77) | 6 (3–9) | |
Pneumonia | 19 | 136 (99–627) | 12 (5–32) | 7 (5–9) | |
SARI | 31 | 1,159 (469–1,960) | 91 (38–249) | 8 (5–12) | |
Bronchiolitis | 5 | 142 (118–170) | 8 (3–8) | 6 (3–16) | |
Other | 16 | 278 (158–851) | 29 (8–60) | 7 (5–12) | |
0.98 | |||||
No | 134 | 701 (196–1,369) | 39 (14–84) | 6 (4–10) | |
Yes | 7 | 132 (119–293) | 9 (7–20) | 8 (2–9) | |
0.08 | |||||
Low | 22 | 806 (387–1,256) | 51 (34–108) | 7 (4–9) | |
Lower-middle | 49 | 808 (263–1,960) | 52 (29–117) | 8 (4–13) | |
Upper-middle | 25 | 455 (184–1,429) | 18 (9–70) | 5 (2–9) | |
High | 45 | 415 (143–1,031) | 18 (7–66) | 5 (5–7) | |
0.55 | |||||
Africa | 23 | 817 (202–1,159) | 45 (16–91) | 7 (4–9) | |
Americas | 24 | 299 (132–1,521) | 17 (8–51) | 5 (3–9) | |
Eastern Mediterranean | 4 | 1,223 (534–1,621) | 40 (21–141) | 8 (3–14) | |
Europe | 31 | 415 (142–916) | 14 (7–66) | 5 (3–7) | |
Southeast Asia | 17 | 263 (186–627) | 29 (7–62) | 9 (5–14) | |
Western Pacific | 42 | 1,051 (412–2,077) | 67 (39–98) | 7 (4–11) |
Four eligible articles provided data for influenza A only and were excluded from the overall positive analyses.
*Non-parametric comparisons conducted by Kruskal–Wallis/Wilcoxon rank-sum test. Age-based comparison conducted only between the <5 y and 5–17 y age groups.
**Age groups include datasets that include a subset within the given range, but are non-duplicative, e.g., “<5 y” includes datasets of children 0–36 mo as well as datasets of children 0–59 mo, but does not include datasets of children <1 y or <2 y.
†Pandemic defined as calendar year 2009.
‡Defined as study being designed specifically to target a high-risk population; includes recurrent wheezing/asthma (
Due to steady increases in year-round hospital-based influenza surveillance over the past decade, the number of available datasets substantially increased from 2006 (
Data are for years with more than one dataset providing testing results by virus subtype. Unsubtyped influenza A viruses are included in influenza A totals, but not shown separately. Boxplot excludes outside values.
The pooled meta-analyses with only PCR-confirmed data included 63 datasets, each with 1 to 6 y of data, from 41 countries. The pooled percent positive for influenza among children hospitalized with respiratory illness varied from 4.8% (95% CI 3.3%–6.9%) among those <6 mo to 16.4% (95% CI 13.6%–19.8%) among those 5–17 y, and was 9.5% (95% CI 8.1%–11.0%) overall among children <18 y. Among children <5 y, the pooled estimate was 7.4% (95% CI 6.2%–8.8%). For this age group, we also stratified the pooled estimate by region and country development status. We found the highest percent positive in Southeast Asia (8.5%, 95% CI 6.7%–10.8%) and the lowest in the Americas (4.6%, 95% CI 2.8%–7.4%), and the percent positive was lower in industrialized countries (5.9%, 95% CI 4.6%–7.5%) than in developing countries (7.7%, 95% CI 6.4%–9.3%), although these differences were not statistically significant. There were no significant differences by country income status. Post hoc sensitivity analysis of the effect of outliers (>95th percentile values) on the global estimates showed no difference.
Finally, by applying the age-specific pooled proportion to a denominator of global hospitalized ALRI episodes, we estimated the absolute number of influenza-associated hospitalizations among children <5 y to be 870,000 (95% CI 610,000 to 1,237,000), for a per capita rate of 135/100,000 children/year (95% CI 95–193) (
Characteristic | Pooled Percent Positive (95% CI) | Hospitalized ALRI Episodes (Thousands) |
Global Influenza-Associated Hospitalizations (Thousands) |
Influenza-Associated Hospitalizations per 100,000 Children | |
---|---|---|---|---|---|
<6 mo | 15 (14) | 4.8 (3.3–6.9) | — | — | — |
<1 y | 26 (21) | 6.1 (5.1–7.4) | 6,136 (5,168–7,287) | 374 (264–539) | 284 (200–409) |
<2 y | 23 (18) | 7.1 (6.1–8.4) | — | — | — |
<5 y | 48 (35) | 7.4 (6.2–8.8) | 11,751 (9,837–12,054) | 870 (610–1,237) | 135 (95–193) |
5–17 y | 27 (22) | 16.4 (13.6–19.8) | — | — | — |
<18 y | 42 (32) | 9.5 (8.1–11.0) | — | — | — |
Industrialized | 7 (4) | 5.9 (4.6–7.5) | 551 (408–745) | 33 (19–56) | 48 (28–81) |
Developing | 41 (31) | 7.7 (6.4–9.3) | 11,200 (9,429–13,309) | 862 (603–1,238) | 150 (105–216) |
Africa | 16 (13) | 8.2 (6.4–10.6) | 3,084 (1,985–4,791) | 253 (127–508) | 174 (87–349) |
Americas | 7 (5) | 4.6 (2.8–7.4) | 1,333 (920–1,934) | 61 (26–143) | 79 (33–185) |
Eastern Mediterranean | 1 (1) | 7.4 (NA) | 889 (628–1,258) | 66 (46–93)† | 95 (67–135) |
Europe | 5 (4) | 7.1 (1.5–32.7) | 402 (252–642) | 29 (4–210) | 53 (7–387) |
Southeast Asia | 7 (4) | 8.5 (6.7–10.8) | 3,274 (2,008–5,341) | 278 (135–577) | 157 (76–326) |
Western Pacific | 12 (8) | 8.5 (6.8–10.6) | 2,143 (1,660–2,764) | 182 (113–293) | 153 (95–246) |
*Determined as described by Nair et al. [
**Point estimates and confidence intervals were calculated as products of point estimates, lower bounds, and upper bounds (respectively) of pooled percent influenza positive and total hospitalized ALRI episodes.
†Since 95% CI was not calculable on the percentage influenza positive in the Eastern Mediterranean region, variance in this region’s disease burden estimates was derived only from the 95% CI of hospitalized ALRI episodes.
NA, not applicable.
The incidence of influenza-associated ALRI among children 0–5 mo was approximately 1.6 times higher than that of children 6–11 mo. Applying this rate ratio to the total influenza-associated hospitalizations for children <1 y, we estimate 228,000 (95% CI 150,000 to 344,000) influenza-associated hospitalizations per year among children aged less than 6 mo.
We used influenza surveillance data from 350 sites in 60 countries to estimate that 10% of global respiratory hospitalizations in children under 18 y worldwide were associated with influenza. This proportion increased by age, with the highest percentage found among school-aged children (5–17 y). We further estimated that influenza causes approximately 374,000 respiratory hospitalizations per year in children <1 y of age (including 270,000 among those less than 6 mo) and 870,000 respiratory hospitalizations per year in children <5 y of age, with the greatest impact in developing countries.
Although we did not identify any significant trends in the overall proportion positive by WHO region in the crude analysis, the final pooled estimates among children <5 y from the Americas differed from the global estimates (4.6%, 95% CI 2.8%–7.4%, versus 7.4%, 95% CI 6.2%–8.8%). This lower percentage positive for influenza may be related to the use of influenza vaccine in the region, which has been on the rise since 2004 [
Our findings on influenza burden among children <5 y are consistent with a previously published estimate using fewer datasets and a different methodological approach [
Other pathogens, particularly
Our finding of an increased impact among children of pandemic influenza compared to seasonal influenza (median estimate percent positive of 13% among children of all age groups in 2009 compared to 5% before 2009 and 9% after 2009) confirms previous findings of the effect of the pandemic on ALRI hospitalizations worldwide. In the United States, a 5-fold rise was reported in the rate of laboratory-confirmed influenza hospitalizations among children 5–17 y of age during the 2009–2010 influenza pandemic compared to non-pandemic influenza seasons [
Several important limitations should be considered when interpreting our findings. Differences in hospitalization practices, applications of case definitions, influenza testing practices (including sampling method), and factors such as time from symptom onset to specimen collection could make detection of influenza more or less likely and therefore bias the percent positive outcome. Our estimate of the burden of severe respiratory illness due to influenza is an underestimate of total burden for several reasons. First, our approach does not allow estimation of severe respiratory illness in individuals who did not present to hospital, which is particularly a problem in resource-limited settings with poor health care access, where hospitalization rates may be driven by proximity to a health care facility, limiting the generalizability of hospital-based burden estimates. Second, individuals with influenza virus may have stopped shedding by the time they presented to hospital and were tested, resulting in an underestimation of the true percent positive. Lastly, we assumed that influenza virus detected in individuals hospitalized for respiratory disease was causal for the hospitalization episode. While influenza is rarely found in well individuals [
Additionally, year-by-year variability of influenza percent positive and external factors, such as co-infections and vaccination coverage, may affect influenza positivity. This year-by-year variability is better captured in the GRIPP data than in the published data, which was often not analyzable by both year and age group. Data from 2010 onward also include influenza A(H1N1)pdm09, which may have had a greater impact on immunologically naïve children, compared to other influenza viruses, during this period, resulting in an overestimate of annual influenza burden. This may be particularly the case during 2010, when WHO officially transitioned from pandemic to post-pandemic phase, especially in settings such as West Africa, where influenza A(H1N1)pdm09 only began circulating in 2010 [
Our findings expand knowledge of the impact of severe influenza among children <1 and <5 y, and create an evidence base for both younger (<6 mo) and older (5–17 y) children, for whom, to our knowledge, no global estimates of influenza disease burden have been published to date. Countries considering possible influenza vaccination programs for children and/or pregnant women can use our estimates as inputs for vaccine impact and cost–benefit models. Our data may also stimulate further research into the development of effective influenza vaccines for young children. Several recent changes have made influenza vaccination a more realistic goal in settings that have not previously considered influenza vaccination programs, including 2012 WHO recommendations identifying pregnant women as the most important target group for influenza vaccination [
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The authors thank the influenza surveillance teams at each of the collaborating institutions for generating the data used in this analysis. We also thank colleagues at the Stephen B. Thacker CDC Library for assistance in accessing articles for the literature searches.
Khwaja Mir Islam Saeed (Afghanistan National Public Health Institute, Ministry of Public Health, Kabul, Afghanistan); Yolanda Cardoso (National Institute of Public Health, Luanda, Angola); Gulam Khandaker (National Centre for Immunisation Research and Surveillance, The Children’s Hospital at Westmead, Westmead, New South Wales, Australia); Abdullah Al Mamun, W. Abdullah Brooks (International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh); Katharine Sturm-Ramirez (Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, US; International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh); Borann Sar (Centers for Disease Control and Prevention, Phnom Penh, Cambodia); Zhibin Peng, Hui Jiang, Luzhao Feng (Division of Infectious Disease, Key Laboratory of Surveillance and Early-warning on Infectious Disease, Chinese Centre for Disease Control and Prevention, Beijing, China); Kadjo Hervé Albéric Adje (Pasteur Institut of Côte d’Ivoire, Abidjan, Côte d’Ivoire); Edith Nkwembe (Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of Congo); Gelila Demissie (Ethiopian Public Health Institute, Addis Ababa, Ethiopia); Momodou Jasseh (Medical Research Council Unit, Fajara, The Gambia); Rafal Tokarz (Center for Infection and Immunity, Columbia University, New York, New York, US); Michael Adjabeng (Ghana Health Service, Accra, Ghana); Shobha Broor, Sanjay K. Rai (All India Institute of Medical Sciences, Delhi, India); Renu B. Lal, Siddhartha Saha (Influenza Program, Centers for Disease Control and Prevention, New Delhi, India); Vivi Setiawaty (National Institute of Health Research and Development, Jakarta, Indonesia); James A. Berkley (Centre for Geographic Medicine Research Coast, Kilifi, Kenya; Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, UK,); Joshua Mott (Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, US; Centers for Disease Control and Prevention, Nairobi, Kenya); Henry Njuguna (Centers for Disease Control and Prevention, Nairobi, Kenya); Maurice Ope (Ministry of Public Health and Sanitation, Nairobi, Kenya); Kaliya Kasymbekova (Ministry of Health, Bishkek, Kyrgyzstan); Darouny Phonekeo (National Center for Laboratory and Epidemiology, Vientiane, Lao People’s Democratic Republic); Norosoa Harline Razanajatovo (National Influenza Centre, Virology Unit, Institut Pasteur of Madagascar, Antananarivo, Madagascar); Saray Aranda-Romo (Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico); Anna Roca (Medical Research Council Unit, Fajara, The Gambia; Barcelona Centre for International Health Research [CRESIB], Hospital Clínic/IDIBAPS, Universitat de Barcelona, Barcelona, Spain; Centro de Investigação em Saúde da Manhiça, Ministerio de Saúde, Maputo, Mozambique); Veronica Eder (National Centre for Public Health, Chisinau, Republic of Moldova); Alexanderyn Burmaa (National Influenza Center, Ulaanbaatar, Mongolia); Ibrahim Dalhatu (Centers for Disease Control and Prevention, Abuja, Nigeria); Maria Agueda Cabello (Ministerio de Salud Publica y Bienestar Social, Asunción, Paraguay); Marilla Lucero (Research Institute for Tropical Medicine, Manila, Philippines); Joseph Rukelibuga (Ministry of Health, Kigali, Rwanda; Centers for Disease Control and Prevention, Kigali, Rwanda); Cheryl Cohen (National Institute for Communicable Diseases, Johannesburg, South Africa); Stefano Tempia, Adam L. Cohen (Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, US); Elibariki Mwakapeje (Ministry of Health, Dar es Salaam, Tanzania); Busarawan Sriwanthana, (National Institute of Health, Ministry of Public Health, Nonthaburi, Thailand); Henry C. Baggett (National Institute of Health, Ministry of Public Health, Nonthaburi, Thailand; International Emerging Infections Program, Global Disease Detection Regional Center, Thailand MOPH–U.S. CDC Collaboration, Nonthaburi, Thailand); Sonja J. Olsen (Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, US; Influenza Program, Thailand MOPH–U.S. CDC Collaboration, Nonthaburi, Thailand); Eric A. F. Simoes (University of Colorado Denver and Children’s Hospital Colorado, Denver, Colorado, US); James Kile (Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, US); Mwaka Monze (Virology Laboratory, University Teaching Hospital, Lusaka, Zambia); Ndahwouh Talla Nzussouo (Ghana Detachment, US Naval Medical Research Unit No. 3, Accra, Ghana); Alexey Wilfrido Clara (Central American Regional Office, Centers for Disease Control and Prevention, Guatemala City, Guatemala); Ann Moen, Paul Gargiullo, Patrick Glew (Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, US); Shang Mei, Zhou Suizan (Center for Disease Control and Prevention, Beijing, China).
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
acute lower respiratory infection
Global Respiratory Hospitalizations–Influenza Proportion Positive
interquartile range
respiratory syncytial virus
severe acute respiratory illness