Increased Extent of and Risk Factors for Pandemic (H1N1) 2009 and Seasonal Influenza among Children, Israel

During the pandemic (H1N1) 2009 outbreak in Israel, incidence rates among children were 2× higher than that of the previous 4 influenza seasons; hospitalization rates were 5× higher. Children hospitalized for pandemic (H1N1) 2009 were older and had more underlying chronic diseases than those hospitalized for seasonal influenza.

W e compared the extent and pattern of pandemic (H1N1) 2009 with the previous 4 infl uenza seasons (2005-2009) among Israel's child population, both for community-based surveillance and pediatric hospitalizations. We also sought a possible association between the pandemic waves and schools closure. The study was approved by the Institutional Review Board Committee of Hadassah Medical Center.

The Study
Israel's Center for Disease Control seasonal infl uenza surveillance system operated throughout our 5-year study. The system is based primarily on 1) anonymous patient visits for infl uenza-like illnesses (ILI) to Maccabi Community Clinics, Israel's second largest health maintenance organization, insuring ≈1 of every 4 Israelis; and 2) nasopharyngeal swabs from sample ILI patients at designated sentinel clinics countrywide. ILI was defi ned as fever (>37.8°C) with >1 of the following: cough, coryza, sore throat, or myalgia. Swab samples were tested for infl uenza viruses at the Health Ministry's Central Virology Laboratory (1) by using multiplex real-time reverse transcription PCR (RT-PCR) (TaqMan chemistry quantitative RT-PCR) (2). ILI rates constituted 3 escalating waves of infection, all at times atypical for seasonal infl uenza ( Figure 1). The fi rst peaked early August (week 32). Israel's schools close July/August, but children stay together in summer frameworks during July. Wave  Israel identifi ed its fi rst pediatric pandemic (H1N1) 2009 cases in June 2009 (week 24) and recorded local transmission the following week ( Figure 2). During weeks 28-43, the weekly percentage of positive infl uenza samples among children was 40%-60%, peaking at We compared hospitalization of children with laboratory-confi rmed infl uenza infection during the pandemic with the previous 4 infl uenza seasons in the pediatric departments of Hadassah's 2 hospitals in Jerusalem. These departments provide primary medical care for ≈250,000 children (1 of every 10 children in Israel), as well as tertiary care for chronic diseases. We performed our study at these hospitals because respiratory specimens were routinely taken year-round for laboratory confi rmation from all children with suspected infl uenza or respiratory virus infection during the 5-year study. Direct immunofl uorescence assay was used at Hadassah in previous years for detection of infl uenza and other respiratory viruses and multiplex real-time PCR (TaqMan chemistry quantitative RT-PCR) for detection of infl uenza viruses during the pandemic.
Findings from pandemic (H1N1) 2009 were retrospectively compared with those from previous infl uenza seasons. In previous shorter infl uenza A/B seasons, fewer children were hospitalized; none were treated with antiviral agents, and statistically signifi cant differences included age, underlying chronic diseases, underlying chronic lung disease, and neonatal fever as the initial symptom ( Table 2). No signifi cant differences were found regarding history of prematurity (<33 weeks), weight percentile, pediatric intensive care unit admission, evidence of pneumonia, oxygen saturation <90%, and leukopenia. In previous seasons, 6 nosocomial infl uenza infections and 2 co-infections with respiratory syncytial virus were reported; none were seen for pandemic (H1N1) 2009.

Conclusions
Children, mainly those 5-10 years of age, were affected by pandemic (H1N1) 2009 markedly more so than by seasonal infl uenza, similar to results reported from the United States, Spain, and Switzerland (3)(4)(5)(6). During the 1918 Spanish infl uenza pandemic, the highest incidence rates were among older children (7). In our study, hospitalized children infected with pandemic (H1N1) 2009 were older, and fi ndings were compatible with reports from several other countries (8,9), but Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 17, No. 9, September 2011  fi ndings were unlike those from Argentina, where 60% were infants (9). The age of children who died in Israel also underlines the impact on older children, as reported elsewhere (10,11). Although pandemic (H1N1) 2009 virus may cause severe, life-threatening disease in previously healthy children of all ages (12), the children we studied had signifi cantly more underlying chronic diseases than did children hospitalized for seasonal infl uenza (13). We, like others (3), found no increase in pneumonia or pediatric intensive care unit admissions caused by pandemic (H1N1) 2009. However, this fi nding could be because antiviral therapy was administered during the pandemic but not in previous years; 98/127 (77.2%) of children hospitalized for pandemic (H1N1) 2009 received oseltamivir ( Table 2).
The nationwide pandemic (H1N1) 2009 infl uenza mortality rate in Israel is similar to that reported for the United Kingdom (14) but cannot be compared with previous years because laboratory data are lacking and there was no requirement to report the death of children >12 months of age. Our study is limited in that it was retrospective. During the pandemic, parents were advised not to attend the clinic for mild disease, although anxiety may have increased visits. There may have been differences between diagnoses of ILI among different Maccabi physicians. The 2 hospitals studied, which represented 10% of hospitalized children, were selected not as nationally representative but because of the feasibility of viral diagnosis since 2005. Infl uenza detection during the pandemic in patients hospitalized at Hadassah was based on PCR; immunofl uorescent antibody assay was used for previous seasons.
Awareness that pandemic infl uenza may have unique clinical characteristics, risk factors, and increased incidence, mainly among children 5-18 years of age, is advocated. Because school opening in late summer 2009 triggered the wave of pandemic (H1N1) 2009 infl uenza (15), closing or delaying opening schools until vaccine is available should be considered among mitigation strategies in future infl uenza pandemics, especially for more virulent viruses.