Effects of Nonpharmaceutical COVID-19 Interventions on Pediatric Hospitalizations for Other Respiratory Virus Infections, Hong Kong.

To determine the effects of nonpharmaceutical interventions (NPIs) for coronavirus disease on pediatric hospitalizations for infection with respiratory viruses other than severe acute respiratory syndrome coronavirus 2, we analyzed hospital data for 2017-2021. Compared with 2017-2019, age-specific hospitalization rates associated with respiratory viruses greatly decreased in 2020, when NPIs were in place. Also when NPIs were in place, rates of hospitalization decreased among children of all ages for infection with influenza A and B viruses, respiratory syncytial virus, adenovirus, parainfluenza viruses, human metapneumovirus, and rhinovirus/enterovirus. Regression models adjusted for age and seasonality indicated that hospitalization rates for acute febrile illness/respiratory symptoms of any cause were reduced by 76% and by 85%-99% for hospitalization for infection with these viruses. NPIs in Hong Kong were clearly associated with reduced pediatric hospitalizations for respiratory viruses; implementing NPIs and reopening schools were associated with only a small increase in hospitalizations for rhinovirus/enterovirus infections.

Maternal Antibodies Against Influenza in Cord Blood and Protection Against Laboratory-Confirmed Influenza in Infants.

BACKGROUND: Studies that correlate maternal antibodies with protection from influenza A or B virus infection in young infants in areas with prolonged influenza circulation are lacking. METHODS: We conducted a prospective, observational study to evaluate the effects of maternally transferred antibodies against influenza A and B viruses against laboratory-confirmed influenza in a cohort born over 24 months. Cord blood samples were retrieved at birth and infants were actively followed for the first 6 months of life. Nasal swabs were collected and tested for influenza A and B by reverse transcriptase-polymerase chain reaction whenever an illness episode was identified. Cord blood samples were tested by the hemagglutination inhibition (HAI) assay to viruses that circulated during the follow-up period. RESULTS: 1162 infants were born to 1140 recruited women: 1092 (94%) infants completed 6 months of follow-up. Proportions of cord blood with HAI antibody titers ≥40 against A(H1N1), A(H3N2), B/Victoria, and B/Yamagata were 31%, 24%, 31%, and 54%, respectively. Only 4% of women had maternal influenza vaccination. Cord blood antigen-specific HAI titers ≥40 were found to correlate with protection from infection only for influenza B/Yamagata. No influenza B virus infection occurred in infants ≤60 days old. Proportional hazards analysis showed that a cord blood HAI titer of 40 was associated with 83% (95% confidence interval, 44-95%) reduction in the risk of influenza B/Yamagata infections compared with a cord blood titer <10. CONCLUSIONS: We documented that maternal immunity against influenza B/Yamagata was conferred to infants within the first 6 months of life.

Effectiveness of Partial and Full Influenza Vaccination Among Children Aged <9 Years in Hong Kong, 2011-2019.

BACKGROUND: Two doses of influenza vaccination are recommended for previously unvaccinated children aged <9 years, and receipt of 1 dose is sometimes termed "partial vaccination." We assessed the effectiveness of partial and full influenza vaccination in preventing influenza-associated hospitalization among children in Hong Kong. METHODS: Using the test-negative design we enrolled 23 187 children aged <9 years admitted to hospitals with acute respiratory illness from September 2011 through March 2019. Vaccination and influenza status were recorded. Fully vaccinated children included those vaccinated with 2 doses or, if previously vaccinated, those vaccinated with 1 dose. Partially vaccinated children included those who should have received 2 doses but only received 1 dose. We estimated vaccine effectiveness (VE) by using conditional logistic regression models matched on epidemiological week. RESULTS: Overall VE estimates among fully and partially vaccinated children were 73% (95% confidence interval, 69%-77%) and 31% (95% confidence interval, 8%-48%), respectively. A consistently higher VE was observed in children fully vaccinated against each influenza virus type/subtype. The effectiveness of partial vaccination did not vary by age group. CONCLUSIONS: Partial vaccination was significantly less effective than full vaccination. Our study supports the current recommendation of 2 doses of influenza vaccination in previously unvaccinated children <9 years of age.

Influenza Vaccine Effectiveness Against Influenza A(H3N2) Hospitalizations in Children in Hong Kong in a Prolonged Season, 2016/2017.

Background: Influenza A(H3N2) viruses circulated for 12 consecutive months in Hong Kong in 2016-2017, peaking in late June and July 2017. The objective of our study was to estimate the effectiveness of influenza vaccination in preventing hospitalizations in children in Hong Kong. Methods: We conducted a test-negative study between 1 September 2016 and 31 August 2017, enrolling children 6 months to 17 years of age hospitalized for an acute respiratory infection. Influenza was diagnosed by PCR on nasopharyngeal aspirates. Results: We enrolled 5514 children, including 3608 children 6 months to 2 years, 1600 children 3-5 years, and 1206 children 6-17 years of age. Influenza-associated hospitalizations occurred throughout the study year but time of vaccination of these children was also wide spread, from September 2016 to May 2017. Influenza vaccine effectiveness (VE) was 39.7% (95% confidence interval [CI], 14.7%-57.3%) against laboratory-confirmed influenza A(H3N2). In analyses stratified by time since vaccination, the VE against influenza A(H3N2) was 52.8% (95% CI, 17.1%-73.2%) within 3 months of vaccination, and 31.2% (95% CI, -6.6% to 55.6%) 4-6 months after vaccination. Conclusions: Influenza vaccination was effective in preventing hospitalizations in children in Hong Kong.

Interim estimate of influenza vaccine effectiveness in hospitalised children, Hong Kong, 2017/18.

We conducted a hospital-based test-negative study in Hong Kong to estimate influenza vaccine effectiveness (VE) for the winter of 2017/18. The interim analysis included data on 1,078 children admitted between 4 December 2017 and 31 January 2018 with febrile acute respiratory illness and tested for influenza. We estimated influenza VE at 66% (95% confidence interval (CI): 43-79) overall, and 65% (95% CI: 40-80) against influenza B, the dominant virus type (predominantly B/Yamagata).

Population-Based Pediatric Hospitalization Burden of Lineage-Specific Influenza B in Hong Kong, 2004-2014.

BACKGROUND: Influenza B virus has been perceived to cause less disease burden and milder disease compared with influenza A, but recent studies suggest that influenza B does have a significant impact. We aimed to estimate the burden of influenza B virus infections on hospitalizations in Hong Kong, in the context of virus lineage changes over time. METHODS: The pediatric age-specific rates of influenza B hospitalization in Hong Kong for 2004-2014 were estimated based on admissions to 2 hospitals that together catered for 72.5% of all pediatric admissions on Hong Kong Island. Influenza B virus was detected by immunofluorescence and culture on nasopharyngeal aspirates. Lineage typing was performed by real-time reverse-transcription polymerase chain reaction. RESULTS: A total of 5085 children were recruited on 1 designated day each week, year-round during the 11 years, and 221 (4.3%) tested positive for influenza B. Hospitalization rates were highest in children aged 2 to <5 years with year-to-year variation. Victoria-lineage viruses appeared to be associated with a greater fraction of influenza B hospitalizations in children than of influenza B infections in the general community. Influenza B did not cause significant hospitalization in infants <1 year of age. CONCLUSIONS: We report one of the first population-based, age- and lineage-specific studies of pediatric hospitalization for influenza B. We found that changes in lineage were associated with higher hospitalization rates and documented that Victoria lineage viruses were associated with greater pediatric hospitalization burden compared with Yamagata lineage viruses.

Influenza vaccine effectiveness against hospitalizations associated with influenza A(H3N2) in Hong Kong children aged 9 months to 17 years, June-November 2023.

A test negative study was carried out from 13 June through to 15 November 2023 enrolling 3183 children hospitalized with acute respiratory illness in Hong Kong. Influenza A and B viruses were detected in 528 (16.6%) children, among which 419 (79.4%) were influenza A(H3N2). The overall vaccine effectiveness against hospitalization associated with any influenza virus infection was estimated as 22.4% (95% CI: -11.7%, 46.1%), and against influenza A(H3N2) specifically was 14.3% (95% CI: -29.2%, 43.2%). Despite the moderate to low VE estimated here, which could be a result of waning immunity and antigenic drift, influenza vaccination remains an important approach to reduce the impact of influenza in children.

Influenza Vaccine Effectiveness Against Influenza-Associated Hospitalization in Hong Kong Children Aged 9 Months to 17 Years, March-June 2023.

In March-June 2023, we conducted a test-negative study in 1671 children who were hospitalized with acute respiratory illness in Hong Kong. Two hundred and eighty-six children (17.2%) were tested positive for influenza virus including 188 with A(H1N1). We estimated influenza vaccine effectiveness against influenza-associated hospitalization as 69.6% (95% confidence interval: 49.3%, 81.7%).

Influenza vaccine effectiveness against influenza-associated hospitalization in children in Hong Kong, 2010-2020.

BACKGROUND: Influenza virus infections can cause hospitalizations in children, and annual vaccination of children can provide protection against influenza. METHODS: We analyzed a test-negative design study with data spanning from 2010/11 through 2019/20 to evaluate influenza vaccine effectiveness (VE) against influenza hospitalization in children by age group, influenza type/subtype and time period within each season. We enrolled children admitted to hospital with acute febrile respiratory illnesses. Nasopharyngeal aspirates were tested by culture and/or RT-PCR to determine influenza status, and vaccination status was obtained by interviewing parents or legal guardians and was verified where possible. VE was estimated by conditional logistic regression model adjusting for sex, age and age-squared, matching on week. RESULTS: Influenza seasons in Hong Kong are prolonged with influenza-associated hospitalizations occurring in almost every month of the year during the study period. Influenza vaccination was effective in preventing influenza-associated hospitalizations in children of all ages. Influenza VE was higher in younger children than in older children, and higher against hospitalization due to influenza A(H1N1)pdm09 than A(H3N2) and B. CONCLUSIONS: The childhood influenza vaccination program in Hong Kong has prevented influenza-associated hospitalizations particularly in younger children. Our findings support the use of influenza vaccines in children as an effective approach to influenza control and prevention.

Influenza vaccination effectiveness in preventing influenza hospitalization in children, Hong Kong, winter 2019/20.

The winter influenza season 2019/20 in Hong Kong was predominated by influenza A(H1N1)pdm09. We analysed an on-going test-negative design study consisting of 1227 children admitted for febrile acute respiratory illness from 3 November 2019 (week 45) to 21 March 2020 (week 12). We estimated influenza vaccine effectiveness of 65% (95% CI: 46 - 78) against hospitalization due to influenza A and B combined, and 74% (95% CI: 54 - 85) against hospitalization due to influenza A(H1N1)pdm09.

Effectiveness of influenza vaccination on influenza-associated hospitalisations over time among children in Hong Kong: a test-negative case-control study.

BACKGROUND: The protection conferred by influenza vaccination is generally thought to last less than a year, necessitating annual revaccination. However, the speed with which influenza vaccine effectiveness might decline during a year is unknown, which is of particular importance for locations with year-round influenza activity. We aimed to assess how influenza vaccine effectiveness changes by time intervals between vaccination and admission to hospital, taking advantage of almost year-round circulation of influenza in Hong Kong. METHODS: In this test-negative case-control study, we analysed vaccine effectiveness in children (aged 6 months to 17 years) who were admitted to hospital in Hong Kong over 5 consecutive years (2012-17). We included those who were admitted to general wards in four public hospitals in Hong Kong with a fever (≥38°C) and any respiratory symptom, such as runny nose, cough, or sore throat. We used direct immunofluorescence assay and reverse transcription PCR to detect influenza virus infection, and recorded children's influenza immunisation history. We compared characteristics of positive cases and negative controls and examined how vaccine effectiveness changed by time between vaccination and admission to hospital with regression analyses. FINDINGS: Between Sept 1, 2012, and Aug 31, 2017, we enrolled 15 695 children hospitalised for respiratory infections, including 2500 (15·9%) who tested positive for influenza A or B and 13 195 (84·1%) who tested negative. 159 (6·4%) influenza-positive cases and 1445 (11·0%) influenza-negative cases had been vaccinated. Most vaccinations were done by December of each influenza vaccination season. Influenza-related admissions to hospital occurred year-round, with peaks in January through March in most years and a large summer peak in 2016; pooled vaccine effectiveness for children of all ages was 79% (95% CI 42-92) for September to December, 67% (57-74) for January to April, and 43% (25-57) for May to August. Vaccine effectiveness against influenza A or B was estimated as 79% (95% CI 64-88) within 0·5-2 months of vaccination, 60% (46-71) within >2-4 months, 57% (39-70) within >4-6 months, and 45% (22-61) within >6-9 months. In separate analyses by type and subtype, we estimated that vaccine effectiveness declined by 2-5 percentage points per month. INTERPRETATION: Influenza vaccine effectiveness decreased during the 9 months after vaccination in children in Hong Kong. Our findings confirm the importance of annual vaccination in children. Influenza vaccines that provide broader and longer-lasting protection are needed to provide year-round protection in regions with irregular influenza seasonality or lengthy periods of influenza activity. FUNDING: Health and Medical Research Fund, Hong Kong and the Research Grants Council, Hong Kong.

Interim estimates of the effectiveness of influenza vaccination against influenza-associated hospitalization in children in Hong Kong, 2015-16.

From 1 September 2015 through 31 January 2016, we enrolled 2068 children 6 months to 17 years of age admitted to hospital with a febrile acute respiratory infection in our test-negative study. Information on receipt of 2015-16 northern hemisphere inactivated influenza vaccination was elicited from parents or legal guardians. Using conditional logistic regression adjusting for age and matching on calendar time, we estimated influenza vaccine effectiveness against hospitalization with influenza A or B to be 79.2% (95% confidence interval: 42.0%-92.4%). Annual influenza vaccination should be more widely used in children in Hong Kong.

Hospital-based vaccine effectiveness against influenza B lineages, Hong Kong, 2009-14.

BACKGROUND: We estimated vaccine effectiveness (VE) against pediatric influenza B hospitalizations in Hong Kong year round between November 2001 and October 2014. METHODS: We conducted a test-negative year-round study, enrolling children 6 months to 17 years of age admitted to two hospitals in Hong Kong with a febrile acute respiratory infection. Children were tested for influenza A and B. Conditional logistic regression was used to estimate overall and lineage-specific vaccine effectiveness comparing influenza vaccination history of the trivalent influenza vaccine (TIV) among patients testing positive for influenza B versus negative for influenza A and B, adjusting for age and sex and matching by calendar week of recruitment. RESULTS: Of the 6013 children included in the analysis, 262 tested positive for influenza B. Vaccination coverage was low: 6.5% in the influenza B positive children when compared with 8.8% in children who tested negative for both influenza A and B (p=0.248). Overall, VE was 47.6% (95% CI: 10.0, 69.4%) against influenza B hospitalization despite variable co-circulation of both lineages in all years. VE for Victoria-like virus calculated from 3 years when the vaccine was lineage-matched was 59.1% (95% CI: 6.2, 82.2%). Lineage-matched VE for Yamagata-like virus was -8.8% (95% CI: -215.4, 62.5%) in a clade mismatch season. With wide confidence intervals, we were unable to demonstrate cross-lineage protection: VE against the mismatched B/Yamagata-like virus was 9.5% (95% CI: -240.4, 76.0%) in 2011/12 and against mismatched B/Victoria-like virus in 2013/14 was 42.7% (95% CI: -368.6, 93.0%). CONCLUSIONS: TIV conferred an overall VE of 47.6% (95% CI: 10.0, 69.4%) against influenza B hospitalization in children despite variable co-circulation of both lineages in all years. Lineage-matched VE for Yamagata-like virus was poor and may be related to clade mismatch. Cross-lineage protection was not observed.

Population-based incidence of community-acquired pneumonia hospitalization in Hong Kong children younger than 5 years before universal conjugate pneumococcal immunization.

OBJECTIVES: We sought to document the incidence of pediatric hospitalization for bacterial pneumonia before universal childhood conjugate pneumococcal vaccination using two different methods of diagnosis. METHODS: By following the World Health Organization (WHO) chest radiography (CXR) protocol, two radiologists independently read the CXRs of a cohort of systematically recruited children younger than 5 years. The children had acute respiratory infections and were admitted to one of two hospitals that care for 72.5% of all pediatric admissions on Hong Kong Island. Medical records were reviewed for clinical manifestation and to identify bacterial pneumonia diagnosed by pediatricians. RESULTS: In children younger than 5 years, the incidences of bacterial pneumonia, as diagnosed by pediatricians and by the WHO CXR standard, were 775.7 per 100,000 population [95% confidence interval (CI, 591.8-998.3)] and 439.5 per 100,000 population (95% CI, 304.6-614.5), respectively. The study period was from 2002 to 2004. CONCLUSION: This study provided a reliable baseline estimate of the hospitalization burden of pneumococcal pneumonia in Hong Kong children before the advent of universal conjugate pneumococcal vaccination.

The effectiveness of influenza vaccination in preventing hospitalizations in children in Hong Kong, 2009-2013.

BACKGROUND: Influenza vaccination is widely recommended every year to protect individuals against influenza virus infection and illness. There are few published estimates of influenza vaccine effectiveness against hospitalization in children or from subtropical regions. METHODS: We conducted a test-negative year-round study between October 2009 and September 2013, recruiting children 6 months to 17 years of age admitted to two hospitals in Hong Kong with a febrile acute respiratory infection. Cases were tested for influenza A and B and conditional logistic regression was used to estimate vaccine effectiveness comparing influenza vaccination history of the trivalent influenza vaccine (TIV) among patients testing positive versus negative for influenza, adjusting for age and sex and matching by calendar week of recruitment. RESULTS: Overall vaccine effectiveness against hospitalization with laboratory-confirmed influenza A and B was estimated to be 61.7% (95% CI: 43.0%, 74.2%). The estimated vaccine effectiveness against A(H3N2) was 36.6% (95% CI: -25.5%, 67.9%) compared to 71.5% (95% CI: 39.4%, 86.6%) for A(H1N1)pdm09 and 68.8% (95% CI: 41.6%, 83.3%) for B. CONCLUSIONS: Vaccine effectiveness against hospitalization in children varied from year to year, but was moderate to high overall even in an area with influenza activity throughout the year.

A robust parameter estimation method for estimating disease burden of respiratory viruses.

BACKGROUND: Poisson model has been widely applied to estimate the disease burden of influenza, but there has been little success in providing reliable estimates for other respiratory viruses. METHODS: We compared the estimates of excess hospitalization rates derived from the Poisson models with different combinations of inference methods and virus proxies respectively, with the aim to determine the optimal modeling approach. These models were validated by comparing the estimates of excess hospitalization attributable to respiratory viruses with the observed rates of laboratory confirmed paediatric hospitalization for acute respiratory infections obtained from a population based study. RESULTS: The Bayesian inference method generally outperformed the classical likelihood estimation, particularly for RSV and parainfluenza, in terms of providing estimates closer to the observed hospitalization rates. Compared to the other proxy variables, age-specific positive counts provided better estimates for influenza, RSV and parainfluenza, regardless of inference methods. The Bayesian inference combined with age-specific positive counts also provided valid and reliable estimates for excess hospitalization associated with multiple respiratory viruses in both the 2009 H1N1 pandemic and interpandemic period. CONCLUSIONS: Poisson models using the Bayesian inference method and virus proxies of age-specific positive counts should be considered in disease burden studies on multiple respiratory viruses.

Population-based hospitalization burden of influenza a virus subtypes and antigenic drift variants in children in Hong Kong (2004-2011).

OBJECTIVES: We aim to document and analyze influenza hospitalization burden in light of antigenic changes in circulating influenza viruses in Hong Kong. METHODS: The pediatric age-specific rates of influenza A hospitalization in Hong Kong for 2004-2011 which encompassed the emergence of H1N1pdm09 were extrapolated from admissions to 2 hospitals that together catered for 72.5% of all pediatric admissions on Hong Kong Island. Influenza A was detected by immunofluorescence, culture and/or PCR on nasopharyngeal aspirates. RESULTS: Influenza A caused high rates of hospitalization in children with year to year fluctuations. The highest hospitalization burden was seen with H1N1pdm09 in 2009. Additional factors affecting hospitalization were the proportion of viral circulation among different subtypes, and antigenic drifts. Taking these into effect, an H3N2 dominated year was not always associated with more hospitalizations than a 'seasonal' H1N1 year. Hospitalization burden was higher in seasons when drifted viruses of H1N1 or H3N2 dominated. No hospitalization was documented in infants <6 months of age during years when an undrifted virus circulated (2006 for H1N1 and 2008 for H3N2) but significant hospitalization was observed with a drifted or shifted virus (2004, 2005, 2007 and 2010 for H3N2, and 2009 for H1N1pdm09). CONCLUSIONS: We documented a consistently high pediatric hospitalization burden of influenza A. Knowledge of antigenic changes and their proportion of circulation aids in the interpretation of impact of the subtypes. Year-to-year variation in hospitalization rates in young infants appeared to correlate with antigenic variation, lending support to the role of protection from maternal antibodies.

The population based socioeconomic burden of pediatric influenza-associated hospitalization in Hong Kong.

We described the monetary and non-monetary cost incurred by children hospitalized for virologically confirmed influenza virus infection in a population-based prospective 3-year study. The mean direct and indirect cost of each child hospitalized was $1217.82 (95% CI, 1111.54-1324.23) and $1328.33 (95% CI, $1136.79-1520.00) for influenza A and B, respectively. School age patients took a mean (SD) of 4.70 (3.05) days and 5.31 (3.62) days of sick leave for influenza A and B infection, respectively. Pediatric influenza A and B hospitalization was associated with 662-1046 days of school absenteeism and 214-336 days of parental work loss per 10,000 population <18 years of age per year. We showed that the cost incurred by hospitalization alone, was comparable to the cost of annual universal pediatric influenza vaccination especially in children 6 months to under 6 years of age and vaccination would result in much larger cost-savings when non-monetary costs are included.

Age-matched comparison of children hospitalized for 2009 pandemic H1N1 influenza with those hospitalized for seasonal H1N1 and H3N2.

BACKGROUND: A wide spectrum of clinical manifestation ranging from deaths to a mild course of disease has been reported in children infected with the 2009 pandemic H1N1 (pH1N1) influenza. METHODOLOGY/MAJOR FINDINGS: We conducted an age-matched control study comparing children hospitalized for pH1N1 with historic controls infected with seasonal H1N1 and H3N2 influenza to correct for the effect of age on disease susceptibility and clinical manifestations. We also compared children with pH1N1 to children concurrently admitted for seasonal influenza during the pandemic period to adjust for differences in health-seeking behavior during the pandemic or other potential bias associated with historic controls. There was no death or intensive care admission. Children with pH1N1 were more likely to have at least one risk condition for influenza, an underlying chronic pulmonary condition, more likely to have asthma exacerbation and to be treated with oseltamivir. There was no difference in other aspects of the clinical course or outcome. CONCLUSION: Disease manifestation of children hospitalized for pH1N1 infection was mild in our patient population.