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Background: The use of a squalene-containing (AS03) pandemic vaccine for high-risk groups in England allowed vaccine effectiveness (VE) of such novel oil-in-water adjuvanted vaccine to be evaluated.Methods: Cases of laboratory-confirmed pandemic (H1N1)2009 influenza in England between November 2009 and January 2010 were followed up for history of pandemic (H1N1)2009 or 2009/10 seasonal influenza vaccination and relevant comorbidities. Controls were patients similarly tested but negative for the virus. We estimated pandemic (H1N1)2009 VE from the relative reduction in the odds of confirmed pandemic (H1N1)2009 infection between vaccinated and unvaccinated individuals after adjustment for confounders.Results: A total of 933 cases and 1220 controls were analyzed. VE from ≥ 14 days was 62% (95% CI 33% to 78%) with protection from 7 to 13 days post-vaccination (59%, 95% CI 12% to 81%). VE from ≥ 14 days differed by age (P = .03) being 77% (11% to 94%) in children <10 years, 100% (80% to 100%) in 10-24-year olds, 22% (-153% to 76%) in 25-49-year olds, and 41% (-71% to 80%) in 50-plus-year-olds.Conclusion: Use of oil-in-water adjuvant contributed to a high VE with reduced antigen dosage in children and young adults. Our VE estimate supports the serological correlates of protection used for licensure in these age groups. However, the immunological basis of disappointing VE in older adults merits investigation. [ABSTRACT FROM AUTHOR]

Aim: Continuous monitoring of blood culture (BC) systems allows rapid detection of microbial growth. We aimed to determine differences in time to positivity (TTP) in BACTEC BC between organisms and whether a 36-h period was sufficient to detect all relevant pathogenic bacteria for children admitted to a tertiary care paediatric hospital., Methods: This was a retrospective audit of positive aerobic (AE) and anaerobic (AN) BC from paediatric inpatients with available TTP from 1 August 2016 to 2 January 2019. First positive BC per bacteraemia episode was analysed., Results: Overall, 649 BC were positive, of which 480 first positive BC were analysed: 246 AE (51.3%) only, 216 paired (45%) (108 AE and 108 AN) and 18 AN (3.8%) only. There were 372 episodes of bacteraemia in 340 patients. Median age was 19 months (interquartile range (IQR): 1.25-60). Median TTP for AE and AN cultures was 13.20 (IQR: 9.84-18.48) and 13.92 h (IQR: 10.32-17.04), respectively. Organisms were GNR 49.7%, GPC 29.6%, contaminants 14.5%, mixed 3.0%, other 2.4% and yeast 0.8%. Streptococcus agalactiae had the fastest median TTP in AE and AN cultures, followed by Escherichia coli (AE 8.88 vs. 10.20 h). For paired AE and AN cultures, TTP was faster for AE versus AN cultures (13.36 vs. 14.52 h, P = 0.001). A 36-h cut-off time captured 97.7% AE BC and 99.1% AN BC with pathogens, and 86.5% AE BC and 91.7% AN BC with contaminants, respectively., Conclusions: GNR were the commonest pathogens in paediatric BC and faster growth was detected in AE versus AN cultures. By 36 h, >97.7% of BC were positive for pathogens versus 86.5% for contaminants., (© 2024 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background: Hybrid immunity to SARS-CoV-2, resulting from both vaccination and natural infection, remains insufficiently understood in paediatric populations, despite increasing rates of breakthrough infections among vaccinated children., Methods: We conducted a prospective longitudinal study to investigate the magnitude, specificity, and cytokine profile of antigen-specific T cell responses elicited by breakthrough SARS-CoV-2 infection in a cohort of mRNA-vaccinated children (n = 29) aged 5-11. This longitudinal analysis involved six distinct time points spanning a 16-month period post-vaccination, during which we analysed a total of 159 blood samples. All children who were followed for at least 12 months (n = 26) experienced a breakthrough infection. We conducted cytokine release assays using minimal blood samples, and we verified the cellular origin of these responses through intracellular cytokine staining., Findings: After breakthrough infection, children who had received mRNA vaccines showed enhanced Th1 responses specific to Spike peptides. Additionally, their Spike-specific T cells exhibited a distinctive enrichment of CD4+ IFN-γ+IL10+ cells, a characteristic akin to adults with hybrid immunity. Importantly, vaccination did not impede the development of multi-specific T cell responses targeting Membrane, Nucleoprotein, and ORF3a/7/8 antigens., Interpretation: Children, previously primed with a Spike-based mRNA vaccine and experiencing either symptomatic or asymptomatic breakthrough infection, retained the ability to enhance and diversify Th1/IL-10 antigen-specific T cell responses against multiple SARS-CoV-2 proteins. These findings mirror characteristics associated with hybrid cellular immunity in adults, known to confer resistance against severe COVID-19., Funding: This study was funded by the National Medical Research Council (NMRC) Singapore (COVID19RF-0019, MOH-000019, MOH-000535, OFLCG19May-0034 and MOH-OFYIRG19nov-0002)., Competing Interests: Declaration of interests MQ: none; SH: none; SKH: none; JZ: none; CWT: none; CYC: none; JGL: none; LW: none; AB and NLB: report a pending patent for a method to monitor virus-specific T cells in biological samples and are co-founders of T Cell Diagnostic (TCD) Ltd., a biotech company developing T cell diagnostic for viral infections. CFY: reports honoraria and funding to attend conferences from Sanofi, Pfizer and Takeda., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In studies of infectious disease prevention, the level of protective efficacy of medicinal products such as vaccines and prophylactic drugs tends to vary over time. Many products require administration of multiple doses at scheduled times, as opposed to one-off or continual intervention. Accurate information on the trajectory of the level of protective efficacy over time facilitates informed clinical recommendations and implementation strategies, for example, with respect to the timing of administration of the doses. Based on concepts from pharmacokinetic and pharmacodynamic modeling, we propose a non-linear function for modeling the trajectory after each dose. The cumulative effect of multiple doses of the products is captured by an additive series of the function. The model has the advantages of parsimony and interpretability, while remaining flexible in capturing features of the trajectories. We incorporate this series into the Andersen-Gill model for analysis of recurrent event time data and compare it with alternative parametric and non-parametric functions. We use data on clinical malaria disease episodes from a trial of four doses of an anti-malarial drug combination for chemoprevention to illustrate, and evaluate the performance of the methods using simulation. The proposed method out-performed the alternatives in the analysis of real data in terms of Akaike and Bayesian Information Criterion. It also accurately captured the features of the protective efficacy trajectory such as the area under curve in simulations. The proposed method has strong potential to enhance the evaluation of disease prevention measures and improve their implementation strategies., (© 2024 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.)

Heterologous Sinovac-CoronaVac booster(s) in 12-17-year-olds who had a moderate/severe reaction to Pfizer-BNT162b2 mRNA vaccine was found to safe with no serious adverse events reported. In those primed with 1 dose of Pfizer-BNT162b2 vaccine, subsequent boosters with 2 doses of Sinovac-CoronaVac vaccines achieved neutralizing antibody levels which were comparable to those who had received 2 doses of Pfizer-BNT162b2 vaccines followed by 1 dose of Sinovac-CoronaVac vaccination. Adolescents with 1 Pfizer-BNT162b2 followed by 2 Sinovac-CoronaVac vaccines developed T-cell responses against broad peptides including membrane, nucleoprotein 1 and 2 but levels were highest for Spike protein and lasted until day 150 post-vaccination., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Chia-Yin CHong reports financial support was provided by Government of Singapore Ministry of Health. Chee-Fu Yung reports financial support was provided by National Medical Research Council.]., (Copyright © 2024. Published by Elsevier India Pvt Ltd.)

Background and Aims: There is a paucity of information on remdesivir (RDV) use in severe pediatric coronavirus disease 2019 (COVID-19). We aimed to explore the effectiveness of RDV as the cumulative proportion of pediatric COVID-19 patients deescalated from Day 5 of high dependency or intensive care unit (HD/ICU)., Methods: All children ≤18 years admitted to Singapore's largest pediatric hospital from January 1, 2020 to March 18, 2022 were reviewed retrospectively. Patients were included if they were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on reverse transcriptase polymerase chain reaction, required oxygen, and HD/ICU care. The characteristics and outcomes of those who received RDV or not (no-RDV) were compared., Results: We reviewed 15 children with a median age of 2.5 years (interquartile range [IQR]: 0.8-11.0), of which 7 (46.7%) received RDV. There was no difference in cumulative proportion of children deescalated from Day 5 of HD/ICU care in the RDV versus the no-RDV group (5/7, 70% vs. 7/8, 87.5%, p  = 0.57). The RDV versus no-RDV group had higher disease severity, that is, WHO Ordinal Scale scores (median 6, IQR: 5-7 vs. 5, IQR: 4-5, p  = 0.03), higher procalcitonin levels (ug/L) (median 4.31, IQR: 0.8-24.2 vs. 0.12, IQR: 0.09-0.26, p  = 0.02), and longer HD/ICU care days (median 5, IQR: 4-9, vs. 1, IQR: 1-4, p  = 0.01). There was no significant difference in hospitalization days. There were no adverse events directly attributable to RDV. None died from COVID-19 infection., Conclusion: Our observational analysis was unable to detect any clear benefit of RDV in terms of reducing duration in HD/ICU. RDV was well-tolerated in children with severe COVID-19., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Importance: Literature on vaccine effectiveness of SARS-CoV-2 messenger RNA (mRNA) vaccines for children younger than 5 years is limited., Objective: To report the effectiveness of monovalent mRNA vaccines against SARS-CoV-2 infection among Singaporean children aged 1 through 4 years during a COVID-19 pandemic wave of the Omicron XBB variant., Design, Setting, and Participants: This was a population-based cohort study, conducted over a 6-month study period from October 1, 2022, through March 31, 2023, after the implementation of community vaccination among all Singaporean children aged 1 through 4 years. The study period was dominated by the Omicron XBB subvariant., Exposure: Receipt of SARS-CoV-2 mRNA vaccines., Main Outcome Measure: Vaccine effectiveness against confirmed SARS-CoV-2 infection. The adjusted incidence rate ratio for confirmed infections using Poisson regression was reported, with the reference group being those who were unvaccinated. Analyses were stratified by prior documented SARS-CoV-2 infection., Results: A total of 121 628 children (median [IQR] age, 3.1 [2.2-3.9] years; 61 925 male [50.9%]) were included in the study, contributing 21 015 956 person-days of observation. The majority of children (11 294 of 11 705 [96.5%]) received the mRNA-1273 COVID-19 vaccine (Moderna). Vaccine effectiveness against confirmed infection was 45.2% (95% CI, 24.7%-60.2%) in partially vaccinated, infection-naive children and 63.3% (95% CI, 40.6%-77.3%) in fully vaccinated, infection-naive children compared with the unvaccinated group. Among previously infected children, vaccine effectiveness against reinfections in those with at least 1 vaccine dose was estimated at 74.6% (95% CI, 38.7%-89.5%)., Conclusions and Relevance: Study results suggest that completion of a primary mRNA vaccine series provided protection against SARS-CoV-2 infection in children aged 1 through 4 years. Although incidence of hospitalization and severe illness is low in this age group, there is potential benefit of vaccination in preventing infection and potential sequelae.

Multiple Omicron sub-lineages have emerged, with Omicron XBB and XBB.1.5 subvariants becoming the dominant variants globally at the time of this study. The key feature of new variants is their ability to escape humoral immunity despite the fact that there are limited genetic changes from their preceding variants. This raises the question of whether Omicron should be regarded as a separate serotype from viruses serologically clustered with the ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Here, we present cross-neutralization data based on a pseudovirus neutralization test using convalescent sera from naïve individuals who had recovered from primary infection by SARS-CoV-1 and SARS-CoV-2 strains/variants including the ancestral virus and variants Beta, Delta, Omicron BA.1, Omicron BA.2 and Omicron BA.5. The results revealed no significant cross-neutralization in any of the three-way testing for SARS-CoV-1, ancestral SARS-CoV-2 and SARS-CoV-2 Omicron subvariants. The data argue for the assignment of three distinct serotypes for the currently known human-infecting SARS-related coronaviruses., Competing Interests: DECLARATION OF COMPETING INTERESTS The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Importance: Infants younger than 6 months are at risk of severe SARS-CoV-2 infection. Data are lacking on the optimum timing for maternal vaccination and estimated effectiveness against Omicron variants, including XBB, for infants., Objective: To investigate maternal vaccination against Omicron variants, including XBB, and the association of vaccination timing during pregnancy vs prior to pregnancy and risks of SARS-CoV-2 infection among infants aged 6 months or younger., Design, Setting, and Participants: This population-based cohort study was conducted between January 1, 2022, and March 31, 2023. Singapore's national dataset was used to study infants born at greater than 32 weeks' gestation between January 1, 2022, and September 30, 2022. The study included infants whose parents had a confirmed SARS-CoV-2 infection from the date of birth up to 6 months of age. Of 21 609 infants born during this period, 7292 (33.7%) had at least 1 parent infected with SARS-CoV-2 before the age of 7 months. Statistical analysis was performed from April to July 2023., Exposure: Infants' mothers were unvaccinated, vaccinated prior to pregnancy, or vaccinated with a messenger RNA (mRNA) SARS-CoV-2 vaccine during pregnancy., Main Outcome and Measure: Infants were considered infected if they had a positive polymerase chain reaction test., Results: Among 7292 infants included in this study, 4522 (62.0%) had mothers who were Chinese, 527 (7.2%) had mothers who were Indian, 2007 (27.5%) had mothers who were Malay, and 236 (3.2%) had mothers who were other ethnicity; 6809 infants (93.4%) were born at full term, and 1272 infants (17.4%) were infected during the study period. There were 7120 infants (97.6%) born to mothers who had been fully vaccinated or boosted as of 14 days prior to delivery. The crude incidence rate was 174.3 per 100 000 person-days among infants born to mothers who were unvaccinated, 122.2 per 100 000 person-days among infants born to mothers who were vaccinated before pregnancy, and 128.5 per 100 000 person-days among infants born to mothers who were vaccinated during pregnancy. The estimated vaccine effectiveness (VE) was 41.5% (95% CI, 22.8% to 55.7%) among infants born to mothers vaccinated during pregnancy. Infants of mothers who received vaccination prior to pregnancy did not have a lower risk for infection (estimated VE, 15.4% [95% CI, -17.6% to 39.1%]). A lower risk for Omicron XBB infection was only observed among mothers vaccinated with the third (booster) dose antenatally (estimated VE, 76.7% [95% CI, 12.8% to 93.8%])., Conclusions and Relevance: In this population-based cohort study, maternal mRNA vaccination was associated with a lower risk of Omicron SARS-CoV-2 infection among infants up to 6 months of age only if the vaccine was given during the antenatal period. These findings suggest that mRNA vaccination during pregnancy may be needed for lower risk of SARS-CoV-2 infection among newborns.

Introduction: Information on the quality of health of children and younger persons (CYPs) after SARS-COV-2 infection remains scarce, especially from Asia. In this study, we utilised an online survey to investigate Long COVID prevalence in CYPs in Singapore., Method: The study was an anonymised online survey of physical and functional symptoms, made available from 14 October 2022 to 15 January 2023. Caregivers of CYPs aged 0 to 18 years were invited to complete the survey on behalf of their CYPs. Participants provided demographic information and their history of SARS-CoV-2 infection status to allow classification into cases and controls for analysis., Results: A total of 640 completed responses were analysed, 471 (73.6%) were cases and 169 (26.4%) were controls. The prevalence of Long COVID ≥3 months post-infection was 16.8%. This decreased to 8.7% ≥6 months post-infection. Cases had higher odds of developing Long COVID (odds ratio [OR] 2.42, 95% confidence interval [CI] 1.31-4.74). The most common symptoms of Long COVID were persistent cough (7.4%), nasal congestion (7.6%) and fatigue (3.0%). Male gender was significantly associated with higher odds of Long COVID (adjusted OR 1.71 [1.04-2.83]). Vaccinated CYPs had lower odds of Long COVID but this was not statically significant (adjusted OR 0.65, 95% CI 0.34-1.25)., Conclusion: About 1 in 6 CYPs in Singapore developed Long COVID with persistence of 1 or more symptoms ≥3 months post-infection, and approximately half will recover by 6 months. Male gender was associated with higher odds of Long COVID, and vaccination could potentially be protective against Long COVID in CYPs., Competing Interests: The authors have no conflict of interest to disclose.

There is little information on BNT162b2 vaccine-induced variant-specific immunogenicity, safety data and dynamics of breakthrough infections in pediatric populations. We addressed these questions using a prospective two dose BNT162b2 (10 mcg) vaccination cohort study of healthy children 5-11 years in Singapore. Follow up included blood samples at scheduled visits, daily vaccination symptom diary and confirmation of SARS-CoV-2 infection. Surrogate virus neutralization test (sVNT) and spike-specific T cell responses against SARS-CoV-2 variants were performed. The mean age of 127 participants was 8.27 years (SD 1.95) and 51.2% were males. The median sVNT level against original variant after 1 dose and 2 dose vaccination was 61.4% and 95.1% respectively (p < 0.0001). Neutralizing antibodies against the Omicron variant was the lowest, median 22.4% (IQR 16.5-30.8). However, T cell IFN-γ cytokine response against Omicron variant was high and remained so about 4 months after vaccination. Fever rate increased significantly from 4% (dose 1) to 11.5% (dose 2). The risk of Omicron breakthrough infection decreased by 7.8% for every 1% increase in sVNT inhibition level measured after dose 2 vaccination. BNT162b2 vaccines were safe, induced good T cell responses but poor neutralizing antibodies against Omicron in children. Low neutralizing antibody levels post-vaccination was predictive of subsequent breakthrough infection., (© 2023. Springer Nature Limited.)

Background: Information on variant-specific vaccine protection and the effect of previous infection variant is scarce in children. We aimed to ascertain the level of protection conferred by BNT162b2 COVID-19 vaccination against omicron variant infection (BA.4 or BA.5, and XBB) in a previously infected national paediatric cohort. We also explored the association between sequence of previous infection (variant) and vaccination on protection., Methods: We did a retrospective, population-based cohort study using the national databases of all confirmed SARS-CoV-2 infections, vaccines administered, and demographic records maintained by the Ministry of Health, Singapore. The study cohort consisted of children aged 5-11 years and adolescents aged 12-17 years who had a previous SARS-CoV-2 infection from Jan 1, 2020, to Dec 15, 2022. People who were infected during the pre-delta period or were immunocompromised (received three vaccination doses [children 5-11 years old] and four vaccinations doses [adolescents 12-17 years old]) were excluded. Those who had multiple episodes of infection before the study start date, were not vaccinated before infection but completed three doses, received bivalent mRNA vaccine, or received non-mRNA vaccine doses were also excluded. All SARS-CoV-2 infections confirmed by reverse transcriptase polymerase chain reaction or rapid antigen testing were grouped into delta, BA.1, BA.2, BA.4 or BA.5, or XBB variants using a combination of whole-genome sequencing, S-gene target failure results, and imputation. For BA.4 or BA.5, the study outcome period was June 1-Sept 30, 2022, and for XBB variants the outcome period was Oct 18-Dec 15, 2022. Incidence rate ratios between vaccinated and unvaccinated were derived using adjusted Poisson regressions and vaccine effectiveness was estimated as (1-risk ratio) × 100%., Findings: 135 197 people aged 5-17 years (79 332 children and 55 865 adolescents) were included in the cohort for the vaccine effectiveness analysis against omicron BA.4 or BA.5, and 164 704 people aged 5-17 years (97 235 children and 67 469 adolescents) were included for the analysis against omicron XBB. Approximately 47% of participants were female and 53% were male. Among those previously infected, vaccine effectiveness against BA.4 or BA.5 infection in fully vaccinated children (two doses) was 74·0% (95% CI 67·7-79·1) and in adolescents (three doses) was 85·7% (80·2-89·6). Against XBB, protection conferred with full vaccination was lower at 62·8% (95% CI 42·3-76·0) in children and 47·9% (20·2-66·1) in adolescents. In children, receipt of two-dose vaccination before first SARS-CoV-2 infection provided them with the highest protection against subsequent BA.4 or BA.5 infection at 85·3% (95% CI 80·2-89·1); however, this was not shown to be the case for adolescents. First infection variant had an effect on vaccine effectiveness against omicron BA.4 or BA.5 reinfection in the following descending order: BA.2 conferred the highest protection (92·3% [95% CI 88·9-94·7] in children and 96·4% [93·5-98·0] in adolescents) followed by BA.1 (81·9% [75·9-86·4] in children and 95·0% [91·6-97·0] in adolescents), and delta which conferred the lowest protection (51·9% [5·3-75·6] in children and 77·5% [63·9-86·0] in adolescents)., Interpretation: In previously infected children and adolescents, BNT162b2 vaccination provided additional protection against omicron BA.4 or BA.5 and XBB variants compared with those who remained unvaccinated. Hybrid immunity against XBB was lower than against BA.4 or BA.5, especially in adolescents. Early vaccination of previously uninfected children before their first SARS-CoV-2 exposure could potentially strengthen population immunity resilience against future variants., Funding: None., Competing Interests: Declaration of interests CFY declares funding to attend conferences and honorarium from Sanofi, Pfizer, and Takeda, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aim: Actinomycosis is a rare subacute to chronic granulomatous infection which can mimic other infectious or malignant diseases. This study examined the epidemiology and treatment outcome of actinomycosis in children., Methods: A retrospective study on children admitted for actinomycosis in a tertiary paediatric hospital in Singapore, from January 2004 to December 2020. Clinical profile, therapeutic interventions and outcomes were examined., Results: A total of 10 patients were identified; 7 were female. The median age at first presentation was 9.8 years (range 4.7-15.7). The most common presenting symptom was fever (n = 6, 60%), followed by facial or neck swelling (n = 3, 30%) and ear pain (n = 3, 30%). Actinomycosis occurred predominantly in the orocervicofacial region (n = 6, 60%). Four patients (40%) had preceding dental infections in the form of dental caries or gingivitis. One patient had poorly controlled insulin-dependent diabetes mellitus. Actinomycosis was confirmed via culture in four patients, histopathology in four patients and both methods in two patients. All except one patient (n = 9, 90%) underwent surgical procedures. All patients received ampicillin or amoxicillin/clavulanate or other beta-lactams, for a median duration of 6.5 months (range 1.5-14). Complications included osteomyelitis (n = 4, 40%), mastoiditis (n = 2, 20%), brain abscess (n = 1, 10%) and recurrent neck abscess (n = 1, 10%). There was no mortality and all patients achieved complete resolution., Conclusions: Paediatric actinomycosis was rare in our 16-year review, but had a high complication rate. It can occur in immunocompetent patients, and dental infection was the predominant risk factor identified. Prognosis was excellent after surgical intervention and appropriate antimicrobial therapy., (© 2023 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Protective efficacy of vaccines and pharmaceutical products for prevention of infectious diseases usually vary over time. Information on the trajectory of the level of protection is valuable. We consider a parsimonious, non-linear and non-monotonic function for modelling time-varying intervention effects and compare it with several alternatives. The cumulative effects of multiple doses of intervention over time can be captured by an additive series of the function. We apply it to the Andersen-Gill model for analysis of recurrent time-to-event data. We re-analyze data from a trial of intermittent preventive treatment for malaria to illustrate and evaluate the method by simulation.

Background: Clinical utility of universal antigen rapid test (ART) in the pediatric setting is unknown. We aimed to assess the performance and utility of universal ART in hospitalized children (≥5-year-old) to prevent nosocomial COVID-19 transmission., Methods: Cross-sectional study involving all hospitalized pediatric patients aged ≥5-year-old from 2 periods during Omicron wave. Clinical data, ART and polymerase chain reaction test results were collected., Results: A total of 444 patients were included from the 2 study periods, and 416 patients (93.7%) had concordant results between ART and polymerase chain reaction. The overall sensitivity and specificity of ART were 83.3% (95% CI: 75.2-89.3) and 97.5% (95% CI: 95.0-98.8), respectively. Negative predictive values of ART between the Omicron emergence and Omicron peak periods for a probable case group were 71.4% and 66.7%, respectively, and for a suspect case group 91.4% and 75.0%, respectively. Negative predictive values for an unlikely case group was >95% in both periods. Positive predictive value of ART was >85% for probable and suspect case groups in both periods. Seventy-five percent of patients (n = 15) who were incorrectly classified as SARS-CoV-2 negative by ART had potentially viable virus. No large nosocomial transmission clusters were detected., Conclusions: Universal ART screening may limit nosocomial outbreaks in hospitalized children. The performance can be optimized by considering clinical symptoms, exposure and periods within COVID waves., (Copyright © 2022 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Poliomyelitis, or polio, is a highly infectious disease and can result in permanent flaccid paralysis of the limbs. Singapore was certified polio-free by the World Health Organization (WHO) on 29 October 2000, together with 36 other countries in the Western Pacific Region. The last imported case of polio in Singapore was in 2006. Fortunately, polio is vaccine-preventable-the world saw the global eradication of wild poliovirus types 2 and 3 achieved in 2015 and 2019, respectively. However, in late 2022, a resurgence of paralytic polio cases from vaccine-derived poliovirus (VDPV) was detected in countries like Israel and the US (specifically, New York); VDPV was also detected during routine sewage water surveillance with no paralysis cases in London, UK. Without global eradication, there is a risk of re-infection from importation and spread of wild poliovirus or VDPV, or new emergence and circulation of VDPV. During the COVID-19 pandemic, worldwide routine childhood vaccination coverage fell by 5% to 81% in 2020-2021. Fortunately, Singapore has maintained a constantly high vaccination coverage of 96% among 1-year-old children as recorded in 2021. All countries must ensure high poliovirus vaccination coverage in their population to eradicate poliovirus globally, and appropriate interventions must be taken to rectify this if the coverage falters. In 2020, WHO approved the emergency use listing of a novel oral polio vaccine type 2 for countries experiencing circulating VDPV type 2 outbreaks. Environmental and wastewater surveillance should be implemented to allow early detection of "silent" poliovirus transmission in the population, instead of relying on clinical surveillance of acute flaccid paralysis based on case definition alone.

Pertussis vaccination (Tdap -Tetanus-diphtheria-acellular pertussis) for pregnant women has been recommended since November 2017 in Singapore. In this prospective test-negative case-control study from 2018 to 2019, we aimed to evaluate vaccine effectiveness (VE) against pertussis infection and pertussis-related intensive care unit (ICU) admission according to Tdap (Tetanus-diphtheria-acellular pertussis) during pregnancy and/or infant pertussis vaccination. A total of 58 children (26 cases, 32 controls) were recruited with 4 ICU admissions. The median age was 3 months (interquartile range [IQR] 1.50-4.56 months). Overall, 25.9 % of mothers had received antenatal Tdap vaccination and 43.1 % of infants received pertussis vaccination, majority only 1 dose. Tdap in pregnancy alone without infant vaccine or with 0-1 infant dose had a VE of 97.62 % (95 % confidence interval [CI] 53.25-99.88 %), 98.17 % (95 %CI 66.61-99.9 %) respectively, against pertussis infection and 71.9 % (95 %CI 0.0-98.64), 75.86 % (95 % CI 0.0-98.78) respectively, against ICU admissions. Conclusion: Maternal Tdap vaccination was highly protective against infant pertussis and should be routinely recommended for all pregnant women., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Multisystem inflammatory syndrome in children (MIS-C) is a rare inflammatory syndrome with multisystem involvement affecting children exposed to COVID-19. This condition is rarely reported in East Asia and was not detected in Singapore until 2021. We present 12 cases of MIS-C diagnosed in KK Women's and Children's Hospital (KKH) from October 2021 to December 2021., Method: We conducted an observational study on cases fulfilling the Singapore Ministry of Health criteria for MIS-C from January 2020 to December 2021 in KKH. Medical records were reviewed to obtain information on clinical presentation, disease course, treatment received and outcomes., Results: In the 12 cases detected, the median age was 7.50 years (interquartile range 4.00-9.25); 8 were male. All patients had mucocutaneous symptoms similar to Kawasaki disease. Other commonly involved systems were: haematological (coagulopathy 100%, lymphopaenia 91.70% and thrombocytopaenia 75.00%), gastrointestinal (75.00%) and cardiovascular (83.30%). Six patients (50.00%) had shock and were admitted to the intensive care unit. The majority of patients received treatment within 2 days of hospitalisation with intravenous immunoglobulin (IVIg) and steroids. All survived; the majority had normal echocardiograms and no long-term organ sequelae at 6 months post-discharge., Conclusion: MIS-C emerged in Singapore as the incidence of COVID-19 in the community increased in 2021. The clinical presentation of our patients is similar to earlier reports, with some significant differences from Kawasaki disease. Multidisciplinary management, timely diagnosis, and early initiation of treatment with IVIg and steroids likely contributed to comparatively good outcomes. Our cases highlight the need for continued awareness of MIS-C among physicians, and surveillance of its incidence, short- and long-term outcomes.

Introduction: Children infected with COVID-19 are susceptible to severe manifestations. We aimed to develop and validate a predictive model for severe/ critical pediatric COVID-19 infection utilizing routinely available hospital level data to ascertain the likelihood of developing severe manifestations., Methods: The predictive model was based on an analysis of registry data from COVID-19 positive patients admitted to five tertiary pediatric hospitals across Asia [Singapore, Malaysia, Indonesia (two centers) and Pakistan]. Independent predictors of severe/critical COVID-19 infection were determined using multivariable logistic regression. A training cohort (n = 802, 70%) was used to develop the prediction model which was then validated in a test cohort (n = 345, 30%). The discriminative ability and performance of this model was assessed by calculating the Area Under the Curve (AUC) and 95% confidence interval (CI) from final Receiver Operating Characteristics Curve (ROC)., Results: A total of 1147 patients were included in this analysis. In the multivariable model, infant age group, presence of comorbidities, fever, vomiting, seizures and higher absolute neutrophil count were associated with an increased risk of developing severe/critical COVID-19 infection. The presence of coryza at presentation, higher hemoglobin and platelet count were associated with a decreased risk of severe/critical COVID-19 infection. The AUC (95%CI) generated for this model from the training and validation cohort were 0.96 (0.94, 0.98) and 0.92 (0.86, 0.97), respectively., Conclusion: This predictive model using clinical history and commonly used laboratory values was valuable in estimating the risk of developing a severe/critical COVID-19 infection in hospitalized children. Further validation is needed to provide more insights into its utility in clinical practice., Competing Interests: The authors have declared that no competing interests exist.

We present a country specific method to calculate the COVID-19 vaccination coverage needed for herd immunity by considering age structure, age group-specific contact patterns, relative infectivity and susceptibility of children to adults, vaccination effectiveness and seroprevalence prior to vaccination. We find that across all six countries, vaccination of adults age 60 and above has little impact on R eff and this is could be due to the smaller number of contacts between this age group and the rest of the population according to the contact matrices used. If R 0 is above 6, herd immunity by vaccine alone is unattainable for most countries either if vaccination is only available for adults or that vaccine effectiveness is lower at 65% against symptomatic infections. In this situation, additional control measures, booster shots, if they improve protection against infection, or the extension of vaccination to children, are required. For a highly transmissible variant with R 0 up to 8, herd immunity is possible for all countries and for all four scenarios of varying relative infectivity and susceptibility of children compared to adults, if vaccine effectiveness is very high at 95% against symptomatic infections and that high vaccination coverage is achieved for both adults and children. In addition, we show that the effective reproduction number will vary between countries even if the same proportion of the population is vaccinated, depending on the demographics, the contact rates and the previous pre-vaccination seroprevalence in the country. This therefore means that care must be taken in extrapolating population level impacts of certain vaccine coverages from one country to another., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0-60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0-60 months for 2019, with focus on overall mortality and narrower infant age groups that are targeted by RSV prophylactics in development., Methods: In this systematic analysis, we expanded our global RSV disease burden dataset by obtaining new data from an updated search for papers published between Jan 1, 2017, and Dec 31, 2020, from MEDLINE, Embase, Global Health, CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang, and ChongqingVIP. We also included unpublished data from RSV GEN collaborators. Eligible studies reported data for children aged 0-60 months with RSV as primary infection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitating hospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or for where RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion in acute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was not clearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or if the report included fewer than 50 cases of acute lower respiratory infection. We applied a generalised linear mixed-effects model (GLMM) to estimate RSV-associated acute lower respiratory infection incidence, hospital admission, and in-hospital mortality both globally and regionally (by country development status and by World Bank Income Classification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through a risk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV community mortality data for estimating overall RSV mortality. This review was registered in PROSPERO (CRD42021252400)., Findings: In addition to 317 studies included in our previous review, we identified and included 113 new eligible studies and unpublished data from 51 studies, for a total of 481 studies. We estimated that globally in 2019, there were 33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range [UR] 25·4-44·6 million), 3·6 million RSV-associated acute lower respiratory infection hospital admissions (2·9-4·6 million), 26 300 RSV-associated acute lower respiratory infection in-hospital deaths (15 100-49 100), and 101 400 RSV-attributable overall deaths (84 500-125 200) in children aged 0-60 months. In infants aged 0-6 months, we estimated that there were 6·6 million RSV-associated acute lower respiratory infection episodes (4·6-9·7 million), 1·4 million RSV-associated acute lower respiratory infection hospital admissions (1·0-2·0 million), 13 300 RSV-associated acute lower respiratory infection in-hospital deaths (6800-28 100), and 45 700 RSV-attributable overall deaths (38 400-55 900). 2·0% of deaths in children aged 0-60 months (UR 1·6-2·4) and 3·6% of deaths in children aged 28 days to 6 months (3·0-4·4) were attributable to RSV. More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% of RSV-attributable deaths across all age bands were in low-income and middle-income countries (LMICs)., Interpretation: RSV contributes substantially to morbidity and mortality burden globally in children aged 0-60 months, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in every 50 deaths in children aged 0-60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisation programmes targeting protection during the first 6 months of life could have a substantial effect on reducing RSV disease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSV burden to older age when these are implemented., Funding: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU)., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

There is a scarcity of population-level data of pediatric COVID-19 infection from Southeast Asia. This study aims to describe and compare epidemiological, clinical, laboratory and outcome data among pediatric COVID-19 cases versus controls in two neighboring countries, Singapore and Malaysia. We used a test-negative case-control study design recruiting all suspected COVID-19 cases (defined by either clinical or epidemiological criteria) from January 2020 to March 2021 admitted to two main pediatric centers in Singapore and Malaysia. Data were collected using a standardized registry (Pediatric Acute and Critical Care COVID-19 Registry of Asia). The primary outcome was laboratory-confirmed COVID-19. Univariate and multivariable logistic regression analysis was used to determine factors associated with COVID-19. This study included 923 children with median age of 4 (interquartile range 2-9) years. Of these, 35.3% were COVID-19 cases. Children with COVID-19 were more likely to be asymptomatic compared with controls (49.4 versus 18.6%; P < 0.0001). They were also less likely to develop respiratory complications, such as bronchitis or pneumonia, or organ dysfunction. Four (1.2%) of our COVID-19 patients required respiratory support compared with 14.2% of controls needing respiratory support. COVID-19 cases tended to have lower neutrophil count but higher hemoglobin compared with controls. There were no reported deaths of COVID-19 infection; in contrast, 0.7% of the control group died. In the multivariable analysis, older age, travel history, and close contact with an infected household member were associated with COVID-19 infection. This study shows that the majority of pediatric COVID-19 cases were of lesser severity compared with other community acquired respiratory infections.

Background: The utility of determining maternal-neonatal surface colonization as detected by standard microbiological cultures around the time of birth is unclear. The aim of this study is to evaluate the association between maternal and neonatal surface colonization at birth and neonatal early onset sepsis (EOS)., Objective: To investigate the association of white matter hyperintensities (WMHs) present in the brain with AD CSF biomarker levels., Methods: We conducted a case-control study of newborns admitted to the neonatal department of a referral women's and children's hospital from 2009 to 2017. Cases were infants with blood-culture-confirmed EOS (<3 days of life), and controls were infants without EOS randomly chosen based on the cases' date of birth. Maternal genitourinary and neonatal ear swab cultures were used to determine bacterial surface colonization status., Results: Fifty-one infants were diagnosed with EOS during the study period, where Escherichia coli (45%), and Group B Streptococcus (23%) accounted for 68% of infecting organisms. Compared to infants without EOS, those infected were more likely to have surface colonization of the mothers (60% vs 40%, p = 0.048) and infants (90% vs 11%, p < 0.001). In univariate analysis, chorioamnionitis [7.1 (95% CI 2.9, 16.8)], small-for-gestational-age [OR 0.08 (95% CI 0.02, 0.4)], exposure to antibiotics around time of birth [2.3 (95% CI 1.0, 5.1)], maternal surface colonization [2.2 (95% CI 1.0, 4.9)] and neonatal surface colonization [23.5 (95% CI 7.3, 76.1)] were significantly associated with EOS. Adjusting for potential confounders, neonatal colonization remained significantly associated with neonatal EOS [AOR 15.0 (95% CI 3.5, 64.2), p < 0.001]., Conclusion: In our setting with predominant Gram-negative EOS, neonatal colonization but not maternal colonization was significantly associated with EOS in the newborn.

Kawasaki disease (KD, typical/atypical/partial) admissions (n = 644) were surveyed from 2017 to 2020 and compared to urinary tract infection (UTI) admissions and COVID-19 in 2020. KD admissions decreased by 27% and median KD age decreased in 2020, whereas UTI admissions remained steady. KD admissions showed a seasonality with a peak in April and nadir in February-March. All KD/KD-related pediatric intensive care unit cases tested negative for COVID-19, and no multisystem inflammatory syndrome in children was found., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The year-round respiratory syncytial virus (RSV) circulation in tropical regions leads to different transmission patterns and burden of disease among infants born very preterm., Methods: We conducted a retrospective cohort study to estimate the effectiveness of palivizumab in preventing RSV hospitalization at 6 and 12 months after discharge, among infants born at <32 weeks' gestation in our tropical setting., Results: A total of 109 infants (26.3%) received palivizumab at discharge, of 415 who were eligible. All patients received ≥4 doses, with 105 infants (96.3%) completing 5 doses. Within 1 year after discharge, there were 35 RSV-associated admissions (3 [2.8%] in the palivizumab vs 32 [10.5%] in the nonpalivizumab group; P = .02). After adjustment for confounders, the effectiveness of palivizumab against RSV hospitalization was estimated to be 90% (95% confidence interval, 10%-99%) up to 6 months after discharge. The median time to RSV hospitalization was shorter in the nonpalivizumab than in the palivizumab group (median [range], 155 [15-358] vs 287 [145-359] days, respectively; P = .11). Five infants (14.3%), all from the nonpalivizumab group, required admission to the intensive care unit., Conclusions: In our setting with year-round RSV circulation, palivizumab prophylaxis was effective in reducing RSV hospitalization among high-risk preterm infants of <32 weeks' gestation within the initial 6 months after discharge., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

There is a scarcity of data regarding coronavirus disease 2019 (COVID-19) infection in children from southeast and south Asia. This study aims to identify risk factors for severe COVID-19 disease among children in the region. This is an observational study of children with COVID-19 infection in hospitals contributing data to the Pediatric Acute and Critical Care COVID-19 Registry of Asia. Laboratory-confirmed COVID-19 cases were included in this registry. The primary outcome was severity of COVID-19 infection as defined by the World Health Organization (WHO) (mild, moderate, severe, or critical). Epidemiology, clinical and laboratory features, and outcomes of children with COVID-19 are described. Univariate and multivariable logistic regression models were used to identify risk factors for severe/critical disease. A total of 260 COVID-19 cases from eight hospitals across seven countries (China, Japan, Singapore, Malaysia, Indonesia, India, and Pakistan) were included. The common clinical manifestations were similar across countries: fever (64%), cough (39%), and coryza (23%). Approximately 40% of children were asymptomatic, and overall mortality was 2.3%, with all deaths reported from India and Pakistan. Using the multivariable model, the infant age group, presence of comorbidities, and cough on presentation were associated with severe/critical COVID-19. This epidemiological study of pediatric COVID-19 infection demonstrated similar clinical presentations of COVID-19 in children across Asia. Risk factors for severe disease in children were age younger than 12 months, presence of comorbidities, and cough at presentation. Further studies are needed to determine whether differences in mortality are the result of genetic factors, cultural practices, or environmental exposures.

Severe sepsis is an important cause of mortality and morbidity in critically ill children. Meropenem is a broad-spectrum antibiotic commonly used to treat sepsis. Current meropenem dosage recommendations for children on continuous renal replacement therapy are extrapolated from pharmacokinetic (PK) studies done in adults. Our study aims to determine the optimal dosing in critically ill septic children receiving continuous renal replacement therapy. A prospective single-center PK study was performed in 9 children in the intensive care unit on continuous renal replacement therapy. Meropenem concentrations were measured from blood and effluent fluid samples. A population PK model was developed using nonlinear mixed-effects modeling software (NONMEM, AstraZeneca UK Ltd, Cheshire, UK). Monte Carlo simulations were performed. The PK/pharmacodynamic target aimed for plasma concentrations above minimum inhibitory concentration of 4 mg/L for 100% of dosing interval (100%ƒ T>MIC ). A 2-compartment model best characterized meropenem PK. Mean (range) clearance and elimination half-life was 0.091 L/h/kg (0.04-0.157) and 3.9 hours (2.1-7.5), respectively. Dosing of 40 mg/kg/dose every 12 hours over 30 minutes achieved PK/PD target in only 32% while 20 mg/kg every 8 hours over 4 hours or 40 mg/kg every 8 hours over 2 hours achieved 100% ƒ T>MIC target for at least 90% of simulated patients., (© 2020, The American College of Clinical Pharmacology.)

An accurate depiction of the convalescent COVID-19 immunome will help delineate the immunological milieu crucial for disease resolution and protection. Using mass cytometry, we characterized the immune architecture in patients recovering from mild COVID-19. We identified a virus-specific immune rheostat composed of an effector T (T eff ) cell recall response that is balanced by the enrichment of a highly specialized regulatory T (T reg ) cell subset. Both components were reactive against a peptide pool covering the receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein. We also observed expansion of IFNγ + memory CD4 + T cells and virus-specific follicular helper T (T FH ) cells. Overall, these findings pinpoint critical immune effector and regulatory mechanisms essential for a potent, yet harmless resolution of COVID-19 infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yeo, Leong, Tay, Nadua, Anderson, Lim, Ng, Poh, Guo, Yaung, Kumar, Wasser, Hazirah, Sutamam, Chua, Qui, Foo, Gamage, Yeo, Ramakrishna, Arkachaisri, Young, Lye, Wang, Chong, Tan, Li, Kam, Ginhoux, Thoon, Chan, Yung and Albani.)

Aim: Respiratory viruses are a huge disease burden globally. An understanding of the seasonal trends and the ability to predict peak periods of respiratory virus disease incidence is useful for clinical care., Methods: This is a retrospective analysis of paediatric hospitalizations of laboratory-confirmed viral respiratory tract infections in KK Women's and Children's Hospital, Singapore, from 1 January 2011 to 31 December 2016. Standard direct immunofluorescence was used to detect respiratory syncytial virus (RSV), influenza A and B viruses, parainfluenza 1, 2 and 3 viruses, metapneumovirus and adenovirus., Results: A total of 97 840 specimens were analysed with a positive detection rate of 23.8%. RSV made up the largest proportion (42% of the total positive results), predominating between May to September. Influenza A had two peaks, June to July and December to January. Type 3 was the most common parainfluenza virus and showed annually recurring peaks. In contrast, parainfluenza 1 and 2, metapneumovirus and adenovirus had a biennial pattern. The test of seasonality detected identifiable seasonality for RSV and parainfluenza 3 virus., Conclusions: In conclusion, respiratory viruses have different and overlapping seasonality in tropical Singapore. Respiratory virus testing for patients admitted for acute respiratory infection is useful to target antiviral therapies and appropriate infection control practices., (© 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Transmission risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in schools is unknown. Our investigations, especially in preschools, could not detect SARS-CoV-2 transmission despite screening of symptomatic and asymptomatic children. The data suggest that children are not the primary drivers of SARS-CoV-2 transmission in schools and could help inform exit strategies for lifting of lockdowns., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

It is important to understand the temporal trend of the paediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load to estimate the transmission potential of children in schools and communities. We determined the differences in SARS-CoV-2 viral load dynamics between nasopharyngeal samples of infected asymptomatic and symptomatic children. Serial cycle threshold values of SARS-CoV-2 from the nasopharynx of a cohort of infected children were collected for analysis. Among 17 infected children, 10 (58.8%) were symptomatic. Symptomatic children, when compared to asymptomatic children, had higher viral loads (mean cycle threshold on day 7 of illness 28.6 vs. 36.7, P = 0.02). Peak SARS-CoV-2 viral loads occurred around day 2 of illness in infected children. Although we were unable to directly demonstrate infectivity, the detection of significant amount of virus in the upper airway of asymptomatic children suggest that they have the potential to shed and transmit SARS-CoV-2. Our study highlights the importance of contact tracing and screening for SARS-CoV-2 in children with epidemiological risk factors regardless of their symptom status, in order to improve containment of the virus in the community, including educational settings.

We reviewed the impact of a universal face masking policy on respiratory viral infections (RVIs) among admitted very-low-birthweight infants in our neonatal department. There was a significant decrease in RVI incidence, specifically in our step-down level 2 unit, with respiratory syncytial virus and parainfluenza virus being the most common viruses isolated., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Coronavirus disease 2019 (COVID-19) has impacted the provision of health services in all specialties. We aim to study the impact of COVID-19 on the utilization of pediatric hospital services including emergency department (ED) attendances, hospitalizations, diagnostic categories and resource utilization in Singapore., Methods: We performed a retrospective review of ED attendances and hospital admissions among children < 18 years old from January 1st to August 8th 2020 in a major pediatric hospital in Singapore. Data were analyzed in the following time periods: Pre-lockdown (divided by the change in Disease Outbreak Response System Condition (DORSCON) level), during-lockdown and post-lockdown. We presented the data using proportions and percentage change in mean counts per day with the corresponding 95% confidence intervals (CIs)., Results: We attended to 58,367 children with a mean age of 5.1 years (standard deviation, SD 4.6). The mean ED attendance decreased by 331 children/day during lockdown compared to baseline (p < 0.001), attributed largely to a drop in respiratory (% change - 87.9, 95% CI - 89.3 to - 86.3, p < 0.001) and gastrointestinal infections (% change - 72.4, 95%CI - 75.9 to - 68.4, p < 0.001). Trauma-related diagnoses decreased at a slower rate across the same periods (% change - 40.0, 95%CI - 44.3 to - 35.3, p < 0.001). We saw 226 children with child abuse, with a greater proportion of total attendance seen post-lockdown (79, 0.6%) compared to baseline (36, 0.2%) (p < 0.001). In terms of ED resource utilization, there was a decrease in the overall mean number of procedures performed per day during the lockdown compared to baseline, driven largely by a reduction in blood investigations (% change - 73.9, 95%CI - 75.9 to - 71.7, p < 0.001)., Conclusions: We highlighted a significant decrease in infection-related presentations likely attributed to the lockdown and showed that the relative proportion of trauma-related attendances increased. By describing the impact of COVID-19 on health services, we report important trends that may provide guidance when planning resources for future pandemics.

The epidemiological target of lockdowns is to drive down the effective reproduction number (Rt) to less than 1. A key unknown is the duration that lockdowns need to be in place to achieve this and which lockdown measures are effective. Daily number of laboratory confirmed community coronavirus 2019 cases were extracted from regular reports from the Ministry of Health Singapore from 20 March 2020 to 4 May 2020. We generated daily Rt to estimate the time needed for these public health lockdown measures to control the spread of severe acute respiratory syndrome coronavirus 2 as demonstrated by Rt < 1. It took about 14 days of nationwide lockdown for the Rt trend to change and start falling. The upper limit of the 95% confidence interval for time to Rt < 1 was day 15 of lockdown. We have shown that it is possible to start 'bending the Rt curve' about 2 weeks after implementation of specific lockdown measures with strict compliance.

Background: Existing studies have suggested that internet-based participatory surveillance systems are a valid sentinel for influenza-like illness (ILI) surveillance. However, there is limited scientific knowledge on the effectiveness of mobile-based ILI surveillance systems. Previous studies also adopted a passive surveillance approach and have not fully investigated the effectiveness of the systems and their determinants., Objective: The aim of this study was to assess the efficiency of a mobile-based surveillance system of ILI, termed FluMob, among health care workers using a targeted surveillance approach. Specifically, this study evaluated the effectiveness of the system for ILI surveillance pertaining to its participation engagement and surveillance power. In addition, we aimed to identify the factors that can moderate the effectiveness of the system., Methods: The FluMob system was launched in two large hospitals in Singapore from April 2016 to March 2018. A total of 690 clinical and nonclinical hospital staff participated in the study for 18 months and were prompted via app notifications to submit a survey listing 18 acute respiratory symptoms (eg, fever, cough, sore throat) on a weekly basis. There was a period of study disruption due to maintenance of the system and the end of the participation incentive between May and July of 2017., Results: On average, the individual submission rate was 41.4% (SD 24.3%), with a rate of 51.8% (SD 26.4%) before the study disruption and of 21.5% (SD 30.6%) after the disruption. Multivariable regression analysis showed that the adjusted individual submission rates were higher for participants who were older (<30 years, 31.4% vs 31-40 years, 40.2% [P<.001]; 41-50 years, 46.0% [P<.001]; >50 years, 39.9% [P=.01]), ethnic Chinese (Chinese, 44.4% vs non-Chinese, 34.7%; P<.001), and vaccinated against flu in the past year (vaccinated, 44.6% vs nonvaccinated, 34.4%; P<.001). In addition, the weekly ILI incidence was 1.07% on average. The Pearson correlation coefficient between ILI incidence estimated by FluMob and that reported by Singapore Ministry of Health was 0.04 (P=.75) with all data and was 0.38 (P=.006) including only data collected before the study disruption. Health care workers with higher risks of ILI and influenza such as women, non-Chinese, allied health staff, those who had children in their households, not vaccinated against influenza, and reported allergy demonstrated higher surveillance correlations., Conclusions: Mobile-based ILI surveillance systems among health care workers can be effective. However, proper operation of the mobile system without major disruptions is vital for the engagement of participants and the persistence of surveillance power. Moreover, the effectiveness of the mobile surveillance system can be moderated by participants' characteristics, which highlights the importance of targeted disease surveillance that can reduce the cost of recruitment and engagement., (©May Oo Lwin, Jiahui Lu, Anita Sheldenkar, Chitra Panchapakesan, Yi-Roe Tan, Peiling Yap, Mark I Chen, Vincent TK Chow, Koh Cheng Thoon, Chee Fu Yung, Li Wei Ang, Brenda SP Ang. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 07.12.2020.)

Meteorological drivers are known to affect transmissibility of respiratory viruses including respiratory syncytial virus (RSV), but there are few studies quantifying the role of these drivers. We used daily RSV hospitalization data to estimate the daily effective reproduction number (R t ), a real-time measure of transmissibility, and examined its relationship with environmental drivers in Singapore from 2005 through 2015. We used multivariable regression models to quantify the proportion of the variance in R t explained by each meteorological driver. After constructing a basic model for RSV seasonality, we found that by adding meteorological variables into this model we were able to explain a further 15% of the variance in RSV transmissibility. Lower and higher value of mean temperature, diurnal temperature range (DTR), precipitation and relative humidity were associated with increased RSV transmissibility, while higher value of maximum wind speed was correlated with decreased RSV transmissibility. We found that a number of meteorological drivers were associated with RSV transmissibility. While indoor conditions may differ from ambient outdoor conditions, our findings are indicative of a role of ambient temperature, humidity and wind speed in affecting RSV transmission that could be biological or could reflect indirect effects via the consequences on time spent indoors.

Background: An increase in human adenovirus (HAdV) infections among hospitalized children in Singapore was observed since 2013. Young age (<2 years) and significant comorbidities have been associated with severe HAdV infections which can result in significant morbidity and mortality. Cidofovir (CDV) has been used to treat severe HAdV infections despite limited data and efficacy., Methods: This is a retrospective, observational review of infants and children 1 month to 17 years of age with laboratory-confirmed severe HAdV infection, admitted to a pediatric tertiary care hospital in Singapore between January 2013 and September 2017. Severe infection was defined as requiring intensive care unit or high dependency care at any point during hospital admission. Clinical characteristics, potential risk factors for mortality, as well as the outcome of cases treated with CDV were examined., Results: A total of 1167 children were admitted for HAdV infection, of which 85 (7.3%) were severe. For severe infections, the median age was 1.5 years (interquartile range: 0.72-3.2 years). The majority had comorbidities (69.4%) and presented with pneumonia (32.9%). Genotypes HAdV-7 (29.4%) and HAdV-3 (27.0%) were the most common HAdV genotypes identified. Thirteen (15.3%) patients died. Patients who died had a higher proportion of existing neurologic comorbidity (46.2% vs. 13.9%; P = 0.014) and presentation with pneumonia (69.2% vs. 26.4%; P = 0.008) compared with survivors. Patients who presented with pneumonia had a higher risk of 30-day mortality (odds ratio 4.3, 95% confidence interval: 1.0-28.6; P < 0.05). CDV was administered to 17 (20%) children for mainly viremia (47.1%) and/or pneumonia (41.2%). Mortality rate was 41.2% for severe HAdV cases treated with CDV. A significant proportion of patients who died when compared with recovered patients presented with pneumonia (6 of 7, 85.7% vs 1 of 10, 10%; P = 0.004). All 8 patients who had viremia received CDV and survived., Conclusions: Mortality can be high in pediatric patients with severe HAdV infections. HAdV-7 and HAdV-3 were the most common genotypes identified in our cohort with severe HAdV infection. Pneumonia is a potential risk factor for mortality in severe HAdV infections in our cohort. Early CDV administration may be considered in patients with severe HAdV infection and existing comorbidities but more studies are required.

Background: Enterovirus (EV) outbreaks often coincide with seasonal peaks in the community. However, they may also sporadically occur in neonatal units. Identification of EV infection in neonates can be challenging, as they tend to present with mild or nonspecific symptoms. This study reports an EV outbreak in the Neonatal Unit at KK Women's and Children's Hospital, Singapore., Methods: This is a single-center, retrospective cohort study of neonates who had positive results for EV during the outbreak. Demographic characteristics, clinical presentations and outcomes were analyzed. Control measures used to limit the spread of infection are reported., Results: A total of 7 cases of EV infection were identified. Their median birth weight and gestational age were 1240 g (750 -2890 g) and 28 weeks (26-35 weeks), respectively. Symptoms occurred at a median age of 48 days (9-103 days). All cases presented initially with recurrent apnea and 4 needed assisted ventilator support with CPAP (2) and mechanical ventilation (2). Serious complications occurred in 3 infants (2 with necrotizing enterocolitis and 1 with meningitis) and none died. EV was detected from rectal swabs (n = 6), CSF (n = 2) and nasopharyngeal swabs (n = 2). Viral subtyping uniformly revealed echovirus 25. Surveillance of all exposed infants by nasopharyngeal swabs was implemented, along with strict contact precautions and cohorting measures., Conclusions: Premature infants with EV are more prone to serious complications, which can lead to significant morbidity. Thus, early recognition of symptoms, rapid diagnosis and prompt implementation of infection control measures are key to prevent further spread of infection., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)