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 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).

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.

Influenza A(H5N1) Virus Infection in a Child With Encephalitis Complicated by Obstructive Hydrocephalus.

A 2-year-old boy with highly pathogenic avian influenza A(H5N1) virus infection with minimal respiratory symptoms developed encephalitis complicated by obstructive hydrocephalus. Viral RNA was detectable in cerebrospinal fluid. The virus belonged to H5N1 clade 2.3.2.1b and had acquired the mammalian adaptation mutation PB2 Q591K.

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.

Efficacy, safety and immunogenicity of a human rotavirus vaccine (RIX4414) in Hong Kong children up to three years of age: a randomized, controlled trial.

BACKGROUND: A phase III, double-blind, randomized, controlled trial was conducted in Hong Kong to evaluate the efficacy, safety and immunogenicity of a human rotavirus vaccine, RIX4414 (Rotarix) against severe rotavirus gastroenteritis in children up to three years of age. METHODS: Healthy infants aged 6-12 weeks were enrolled between 08-December-2003 and 31-August-2005 and received two oral doses of either RIX4414 vaccine (N=1513) or placebo (N=1512) given 2 months apart. Vaccine efficacy was assessed from two weeks post-Dose 2 until the children were two and three years of age. Anti-rotavirus IgA seroconversion rate was calculated pre-vaccination and 1-2 months post-Dose 2 using ELISA (cut-off=20 U/mL) for 100 infants. Safety was assessed until the children were two years of age; serious adverse events (SAEs) were recorded throughout the study period. RESULTS: In children aged two and three years of life, vaccine efficacy against severe rotavirus gastroenteritis was 95.6% (95% CI: 73.1%-99.9%) and 96.1% (95% CI: 76.5%-99.9%), respectively. The seroconversion rate 1-2 months after the second dose of RIX4414 was 97.5% (95% CI: 86.8%-99.9%). At least one SAE was recorded in 439 and 477 infants who were administered RIX4414 and placebo, respectively (p-value=0.130). Six intussusception cases were reported (RIX4414=4; placebo=2) and none was assessed to be vaccine-related. CONCLUSION: RIX4414 was efficacious, immunogenic and safe in the prevention of rotavirus gastroenteritis for at least two years post-vaccination in Hong Kong children.

Histological chorioamnionitis - implication for bacterial colonization, laboratory markers of infection, and early onset sepsis in very-low-birth-weight neonates.

OBJECTIVE: The objective of this study was to evaluate the relationship between histological chorioamnionitis and laboratory markers of infection and congenital sepsis in very-low-birth-weight (VLBW) premature neonates. METHOD: This study is a retrospective review of laboratory results of VLBW neonates with birth weight less than 1500 g in our neonatal intensive care unit (NICU) in the last 5 years. RESULTS: Ninety-nine VLBW neonates had histological chorioamnionitis, and 50 of them further had funisitis. One hundred and sixty-two VLBW neonates did not have chorioamnionitis. The chorioamnionitis group was more likely than the 'no chorioamnionitis' group to have raised C-reactive proteins (23% versus 9.9%; p = 0.006) and neutrophilia (41% versus 4.3%; p < 0.001). White blood cells were more likely to be present in gastric lavage of the former group than the latter group (70% versus 50%; p = 0.002). Ear swab and gastric lavage were more likely to yield positive growth of micro-organisms from the former group than the latter group (34% versus 9.9% and 22% versus 2.7%; p < 0.001 and p < 0.001, respectively). Congenital sepsis proven by positive blood culture was also more likely to occur (3% versus 0%; p = 0.027). Presence of funisitis further increased the likelihood of the above abnormal laboratory results. CONCLUSIONS: Histological chorioamnionitis increases the likelihood of having markers of infection, bacterial colonization, and congenital sepsis. Only 3% of histological chorioamnionitis resulted in congenital sepsis confirmed by blood culture.

Viral load in patients infected with pandemic H1N1 2009 influenza A virus.

Viral shedding profile of infections caused by the pandemic H1N1 2009 influenza A virus has not been reported. The aim of this study was to determine the viral load in different body sites. Viral loads of pandemic H1N1 virus in respiratory specimens, stool, urine, and serum were determined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Respiratory specimens from patients with seasonal influenza were used as historical controls. Initial pre-treatment viral load were compared between these two groups. Serial respiratory specimens from patients with pandemic H1N1 virus infection were obtained for analysis of viral dynamics. Twenty-two pandemic H1N1 cases and 44 seasonal influenza historical controls were included. The mean initial viral load before oseltamivir therapy was 1.84 x 10(8) copies/ml for pandemic H1N1 virus compared with 3.28 x 10(8) copies/ml in seasonal influenza historical controls (P = 0.085). Among patients with pandemic H1N1 virus infection, peak viral load occurred on the day of onset of symptoms, and declined gradually afterwards, with no virus being detectable in respiratory specimens by RT-PCR 8 days and by culture 5 days after the onset of symptoms respectively, except in one patient. Pandemic H1N1 virus was detected in stool and in urine from 4/9 and 1/14 patients, respectively. Viral culture was also positive from the stool sample with the highest viral load. Younger age was associated with prolonged shedding in the respiratory tract and higher viral load in the stool. Data from this quantitative analysis of viral shedding may have implications for formulating infection control measures.

Thin-Section CT 12 Months After the Diagnosis of Severe Acute Respiratory Syndrome in Pediatric Patients.

OBJECTIVE: The objective of our study was to report the thin-section CT findings 12 months after the diagnosis of severe acute respiratory syndrome (SARS) in pediatric patients who had recovered clinically but had persistent abnormal CT findings 6 months after the diagnosis. The clinical data for these patients were correlated to identify risk factors that might increase the likelihood of the development of CT abnormalities. SUBJECTS AND METHODS: The study involved an extended 12-month thin-section CT follow-up of 16 of 47 pediatrics patients with SARS coronavirus-associated pneumonia proven serologically (21 girls and 26 boys; age range, 1.5-17 years; median age, 13.6 years). Patients' clinical information, the extent of radiographic opacification during the acute phase of illness, and conventional pulmonary function test results on follow-up were obtained for correlation. The clinical parameters were compared with other pediatric SARS patients who had normal CT findings at the 6-month follow-up. RESULTS: Fifteen patients still had abnormal CT findings 12 months after diagnosis, all of whom were older than 10 years (age range, 10-17 years). In seven patients with previous residual ground-glass opacification at the 6-month follow-up, two showed persistent changes and three had a reticular pattern in the area of the previously detected abnormality, whereas two showed complete resolution. The extent of air trapping remained similar to that at the 6-month follow-up in nine of 11 patients while two showed a slight increase in the same segments. Parenchymal scars remained unchanged from the 6- to 12-month follow-up in all six patients with that finding. None of our patients showed any evidence of bronchiectasis or bronchial wall thickening. Lymphopenia (p = 0.03), extent of radiographic opacification at acute illness (p = 0.047), and duration of use of ribavirin (p = 0.03) were significant risk factors in predicting whether abnormal CT features persisted 12 months after diagnosis. CONCLUSION: We found that 32% of the children (15/47) affected with SARS showed thin-section CT abnormalities up to 12 months after diagnosis despite clinical remission and unremarkable pulmonary function assessment. Persistent CT abnormalities are more likely to develop in patients who are older and who present with more severe disease. The CT changes in children with SARS are, however, minor.

Cytotoxic therapy for severe avian influenza A (H5N1) infection.

The mortality rate in documented avian influenza A virus subtype H5N1 infection is still high, which is currently reported by WHO at about 50%. Post-mortem analyses in affected patients have revealed haemophagocytosis similar to that found in patients with haemophagocytic lymphohistiocytosis (HLH); such haemophagocytosis could be a very prominent post-mortem feature in H5N1 infection. There are also clinical similarities between H5N1 infection and HLH, such as massive hypercytokinaemia, cytopenia, and acute encephalitis. Importantly, patients with another severe viral infection that may be complicated by secondary HLH, severe Epstein-Barr-virus-associated HLH, have significantly better survival if specific HLH therapy (including the cytotoxic and pro-apoptotic drug etoposide) is initiated early, with survival reported to rise from about 50% to 90%. With this notable improvement in survival, specific HLH treatment, including cytotoxic therapy, could be considered in patients with severe avian influenza A infection complicated by secondary HLH.

Pustulo-vesicular skin eruption in a child with probable Kawasaki disease.

We report the association of painful pustulo-vesicular skin rash with Kawasaki disease. The initial clinical presentation of our patient mimicked chickenpox infection, and the diagnosis was based on the characteristic clinicopathological features and the exclusion of other causes of pustulo-vesicular eruption.

Diarrhoea as the presenting sign in an adolescent suffering from severe acute respiratory syndrome.

UNLABELLED: Patients with severe acute respiratory syndrome (SARS) may present with extra-pulmonary symptoms. We report a 16-year-old adolescent with SARS who presented with diarrhoea. Treatment directed against SARS was prompted by an epidemiological link and the clinical picture as the disease evolved. This atypical presentation posed a diagnostic challenge for physicians. CONCLUSION: Proper disposal of patient excreta is important to prevent the spread of severe acute respiratory syndrome.

Severe acute respiratory syndrome among children.

OBJECTIVE: To study the epidemiologic, clinical, laboratory, and radiologic features, prognostic indicators, and short-term to medium-term outcomes for children with severe acute respiratory syndrome (SARS) and to validate the performance characteristics of a clinical case definition, calculated with respect to SARS-associated coronavirus (SARS-CoV) seroconversion. METHODS: Children <18 years of age, from a single-site outbreak, who satisfied a clinical case definition for SARS, with subsequent serologic confirmation, were treated according to a standard protocol and prospectively monitored. RESULTS: Forty-four children were included. The median age was 12 years. Forty-two children (95.5%) demonstrated an epidemiologic link. Fever, cough, malaise, coryza, sputum production, headache, myalgia, lymphopenia, and elevated lactate dehydrogenase levels were common presenting features. Radiographic findings were nonspecific, but high-resolution computed tomography of the thorax was an early diagnostic aid. A specific reverse transcription-polymerase chain reaction assay for SARS-CoV yielded positive results for <50% of children. Of 9 children who developed hypoxemia, 8 were treated with methylprednisolone. Of 5 children who received intensive care, 3 required assisted ventilation. All children recovered, and serious adverse events in response to treatment were not observed. The outcomes at 3 to 6 months after disease onset, including exercise tolerance, pulmonary functions, and psychologic status, were favorable. An age of >12 years was associated with methylprednisolone therapy for severe illness. After exclusion of the only infant, an age of >12 years was associated with oxygen requirements. Sore throat, high neutrophil count at presentation, and peak neutrophilia were independent factors predicting severe illness. The clinical case definition demonstrated good sensitivity, specificity, and positive and negative predictive values (97.8%, 92.7%, 88%, and 98.7%, respectively) for diagnostic accuracy. CONCLUSIONS: Children are susceptible to SARS-CoV infection. Teenagers resemble adults with respect to disease progression and may develop severe illness. The short-term to medium-term outcomes are good. Sore throat and initial and peak neutrophilia seem to be predictors of severe illness. Our clinical case definition performed well in the epidemic.

Epidemiologic linkage and public health implication of a cluster of severe acute respiratory syndrome in an extended family.

Severe acute respiratory syndrome (SARS) is highly contagious. Mandatory home confinement of 10 days has generally been recommended to quarantine close contacts of SARS cases. We report the epidemiologic linkage of SARS within an extended family. The estimated incubation period was beyond 10 days in some of the affected members. One child was identified as the source of SARS transmission to another household.

Severe acute respiratory syndrome can be mild in children.

A 13-year-old boy contracted severe acute respiratory syndrome (SARS). The clinical course was mild, and no specific treatment was given. His recovery was spontaneous and complete. SARS in children can be a mild and self-limiting disease. The use of the World Health Organization/Centers for Disease Control and Prevention case definitions may not be adequate for the diagnosis of SARS in children.

Severe acute respiratory syndrome (SARS): chest radiographic features in children.

BACKGROUND: Severe acute respiratory syndrome (SARS) is a recently recognized condition of viral origin associated with substantial morbidity and mortality rates in adults. Little information is available on its radiologic manifestations in children. OBJECTIVE: The goal of this study was to characterize the radiographic presentation of children with SARS. MATERIALS AND METHODS: We abstracted data (n=62) on the radiologic appearance and course of SARS in pediatric patients with suspect (n=25) or probable (n=37) SARS, diagnosed in five hospital sites located in three cities: Toronto, Singapore, and Hong Kong. Available chest radiographs and thoracic CTs were reviewed for the presence of the following radiographic findings: airspace disease, air bronchograms, airways inflammation and peribronchial thickening, interstitial disease, pleural effusion, and hilar adenopathy. RESULTS: A total of 62 patients (suspect=25, probable=37) were evaluated for SARS. Patient ages ranged from 5.5 months to 17 years and 11.5 months (average, 6 years and 10 months) with a female-to-male ratio of 32:30. Forty-one patients (66.1%) were in close contact with other probable, suspect, or quarantined cases; 10 patients (16.1%) had recently traveled to WHO-designated affected areas within 10 days; and 7 patients (11.2%) were transferred from other hospitals that had SARS patients. Three patients, who did not have close/hospital contact or travel history to affected areas, were classified as SARS cases based on their clinical signs and symptoms and on the fact that they were living in an endemic area. The most prominent clinical presentations were fever, with a temperature over 38 degrees C (100%), cough (62.9%), rhinorrhea (22.6%), myalgia (17.7%), chills (14.5%), and headache (11.3%). Other findings included sore throat (9.7%), gastrointestinal symptoms (9.7%), rigor (8.1%), and lethargy (6.5%). In general, fever and cough were the most common clinical presentations amongst younger pediatric SARS cases (age<10 years), whereas, in addition to these symptoms, headache, myalgia, sore throat, chills, and/or rigor were common in older patients (age>/=10 years). The chest radiographs of 35.5% of patients were normal. The most prominent radiological findings that were observed in the remaining patients were areas of consolidation (45.2%), often peripheral with multifocal lesions in 22.6%. Peribronchial thickening was noted on chest radiographs of 14.5% of patients. Pleural effusion was observed only in one patient (age 17 years and 11.5 months), whereas interstitial disease was not observed in any patient. CONCLUSION: In pediatric cases, SARS manifests with nonspecific radiographic features making radiological differentiation difficult, especially from other commonly encountered childhood respiratory viral illnesses causing airspace disease. The radiographic presentation of suspected SARS cases ranged from normal to mild perihilar peribronchial thickening. The radiographic presentations, as expected, were relatively more pronounced in the SARS probable cases.