Influenza Surveillance Among Hospitalized Children in Shenzhen Children’s Hospital, 2012-2016

Objective: Influenza is one of the most important causes of hospitalization and death in children. The current monitoring of influenza in China is mainly conducted on outpatients with mild signs of influenza. To fill the gap in monitoring inpatients of severe influenza, we carried out routine influenza surveillance in hospitalized children with lower respiratory infection (LRI) in Shenzhen Children’s Hospital.


Introduction
Influenza is an acute respiratory tract infection caused by an influenza virus. Highly contagious, it spreads rapidly and widely and exhibits seasonal changes in infection rates. The influenza virus is one of the major causes of acute respiratory tract infection in the world. In non-pandemic situations, annual flu epidemics are not only serious threats to susceptible people, but also have important effects on public health [1]. Children are the most susceptible group and the most likely to spread the infection. During annual flu seasons, the illness mainly occurs in children, especially schoolchildren aged 5-17 [2]. Since the 2009 H1N1 pandemic, there have been a large number of influenza A (H1N1)-related deaths reported [3][4][5][6]. China is recognized as a flu-prone country. Herein, influenza surveillance among Chinese pediatric patients will contribute not only to the understanding of the trends of influenza in China but also to the understanding of the clinical characteristics of children with flu infection. Importantly, it will provides scientific evidence to support further studies. Current surveillance projects in China focus mainly on outpatients with mild flu-like symptoms, and there is a dearth of data on severe and critically ill hospitalized children. Since January 2012, we have conducted a routine 2009 H1N1 influenza A testing on children hospitalized in Shenzhen Children's Hospital for lower respiratory tract infection.

Case Cohort
A total of 28,883 children were selected from 2012-2016. They were hospitalized in Shenzhen Children's Hospital due to lower respiratory tract infections. 18,216 were male and 10,667 female.
They ranged in age from 1 month to 14 years.

Methods
After admission, a throat swab specimen was collected from each child and sent to the virus laboratory for influenza A virus antigen detection. The colloidal gold test was used per the manufacturer's instructions. A color change in a specific zone was considered positive. All deaths were tested for influenza A nucleic acid. SPSS 16.0 software was used for data analysis. Descriptive statistics were used to analyze influenza epidemic data. Age distribution was analyzed. Count data are expressed in (%). Intergroup comparison was performed using Chi-square test (χ2) and P<0.05 was considered statistically significant.

Detection of Respiratory Tract Influenza A Virus
From January 2012 to December 2016, a total of 28,883 specimens were tested and 1117 (3.87%) were found to be positive.

Age Distribution
The following were the detection rates for different age groups: 3.48% (179/5143) for age 0-6 months, 3.25% (308/9473) for  However, the flu activity peaked mainly in spring during our 5-year surveillance. Based on the data in our hospital, H1N1 influenza A positive rate was highest among children 4-6 years old. A similar age distribution has been observed among children in Hebei Province, which showed the highest detection rate in the 4-6 and the 7-14-year-old groups. Children in these age groups are mainly preschool and school-age children. They lack immunity to influenza and tendency to stay in crowded places for long periods of time are two main factors that cause the flu to spread among these high-risk population. Therefore, it is of great significance to develop strategies for the prevention and control of influenza. Schoolteachers and staff need to increase their knowledge and awareness of importance of flu prevention and improve their abilities to deal with emergency situations. Parents also need to be educated about preventing the spread of the flu.

Influenza-associated Deaths in Critically ILL Children
Pneumonia is the most common complication of influenza. It can be primary viral pneumonia or secondary bacterial infection.
A few severe cases can quickly deteriorate in a short term, with respiratory failure, respiratory distress syndrome and even neurological complications such as encephalitis or encephalopathy.
These severe complications are the main causes of influenza-induced death [10][11][12]. Based on the data from multi-center studies in China, 49 (6%) hospitalized children developed encephalopathy and encephalitis as the complications of 2009 H1N1 Influenza and 13 deaths (13/49, 26.5%) occurred. It has been suggested that H1N1 flu-induced encephalopathy or encephalitis is also one of the major causes of child deaths in our country [13]. Of the 7 deaths observed in our surveillance, 3 were children who died from acute necrotizing encephalopathy and 2 cases died from secondary bacterial infection, which is basically consistent with domestic report. It is suggested that H1N1 flu can cause serious harm during both pandemic and non-endemic periods and herein should be given more attention.
Early recognized risk factors for influenza complications are: children under 5 years of age and the elderly over 65 years of age, obesity, pregnant women and perinatal women, previous underlying disease. Subsequent studies have shown that nosocomial influenza a virus infection, delayed treatment, and admission to the PICU were independent risk factors for influenza death [14][15].A recent meta-analysis indicated that the previously recognized risk factors for influenza-related complications, including pregnancy and ethnicity, had a low level of evidence and could not be confirmed as high risk factors, requiring further confirmation and research [16].
In the current study, 3 out of the 7 deaths were associated with underlying diseases, which suggested that patients with chronic diseases or cancers were more likely develop critical illness. In addition, 6 out of the 7 deaths in this study occurred in the spring

Conclusion
In Shenzhen, the high incidence of influenza is identified in the spring. After the global pandemic of influenza A H1N1, the flu remains an important cause of childhood hospitalization and death.
The main causes of death in children are influenza-associated acute necrotizing encephalopathy and secondary severe bacterial infection.