Publications by authors named "Chee Fu Yung"

64 Publications

Comparative Analysis of Pediatric COVID-19 Infection in Southeast Asia, South Asia, Japan, and China.

Am J Trop Med Hyg 2021 Jun 15. Epub 2021 Jun 15.

Duke-NUS Medical School, Singapore.

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.
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http://dx.doi.org/10.4269/ajtmh.21-0299DOI Listing
June 2021

A Virus-Specific Immune Rheostat in the Immunome of Patients Recovering From Mild COVID-19.

Front Immunol 2021 25;12:674279. Epub 2021 May 25.

Duke-NUS Medical School, Singapore, Singapore.

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) cell recall response that is balanced by the enrichment of a highly specialized regulatory T (T) 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) cells. Overall, these findings pinpoint critical immune effector and regulatory mechanisms essential for a potent, yet harmless resolution of COVID-19 infection.
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http://dx.doi.org/10.3389/fimmu.2021.674279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185226PMC
June 2021

Author Correction: Kawasaki Disease following administration of 13-valent pneumococcal conjugate vaccine in young children.

Sci Rep 2021 Apr 12;11(1):8368. Epub 2021 Apr 12.

Infectious Disease Service, KK Women's and Children's Hospital, 100 Bukit Timah Road, 229899, Singapore, Singapore.

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http://dx.doi.org/10.1038/s41598-021-87465-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041797PMC
April 2021

Impact of COVID-19 on pediatric emergencies and hospitalizations in Singapore.

BMC Pediatr 2020 12 23;20(1):562. Epub 2020 Dec 23.

Duke-NUS Medical School, Singapore, Singapore.

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.
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http://dx.doi.org/10.1186/s12887-020-02469-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755581PMC
December 2020

Optimal Dosing of Meropenem in a Small Cohort of Critically Ill Children Receiving Continuous Renal Replacement Therapy.

J Clin Pharmacol 2021 Jun 12;61(6):744-754. Epub 2021 Jan 12.

Department of Paediatric Subspecialties, Children's Intensive Care Unit, KK Women's and Children's Hospital, Singapore, Singapore.

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 ). 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 target for at least 90% of simulated patients.
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http://dx.doi.org/10.1002/jcph.1798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089047PMC
June 2021

Effectiveness of a Mobile-Based Influenza-Like Illness Surveillance System (FluMob) Among Health Care Workers: Longitudinal Study.

JMIR Mhealth Uhealth 2020 12 7;8(12):e19712. Epub 2020 Dec 7.

National Centre for Infectious Diseases, Singapore, Singapore.

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.
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http://dx.doi.org/10.2196/19712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752531PMC
December 2020

Effectiveness of Palivizumab Against Respiratory Syncytial Virus Hospitalization Among Preterm Infants in a Setting With Year-Round Circulation.

J Infect Dis 2021 Jul;224(2):279-287

Department of Neonatology, KK Women's & Children's Hospital, Singapore.

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.
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http://dx.doi.org/10.1093/infdis/jiaa749DOI Listing
July 2021

Meteorological drivers of respiratory syncytial virus infections in Singapore.

Sci Rep 2020 11 24;10(1):20469. Epub 2020 Nov 24.

Department of Neonatology, KK Women's and Children's Hospital, Singapore, Singapore.

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), 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 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.
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http://dx.doi.org/10.1038/s41598-020-76888-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686497PMC
November 2020

Poor Performance of Masks Secured Using Ear Loops.

Authors:
Chee Fu Yung

JAMA Intern Med 2021 Feb;181(2):294

Infectious Disease Service, KK Women's and Children's Hospital, Singapore.

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http://dx.doi.org/10.1001/jamainternmed.2020.6393DOI Listing
February 2021

Respiratory viral infections in hospitalised paediatric patients in the tropics.

J Paediatr Child Health 2021 04 13;57(4):559-565. Epub 2020 Nov 13.

Department of Infectious Disease, KK Women's and Children's Hospital, Singapore.

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.
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http://dx.doi.org/10.1111/jpc.15267DOI Listing
April 2021

Comparative Analysis of Symptomatic and Asymptomatic SARS-CoV-2 Infection in Children.

Ann Acad Med Singap 2020 Aug;49(8):530-537

Infectious Disease Service, Department of Paediatric Medicine, KK Women's and Children's Hospital, Singapore.

Introduction: In this study, a comparison of clinical, epidemiological and laboratory parameters between symptomatic and asymptomatic children with SARS-CoV-2 infection was performed.

Materials And Methods: Data from all children with laboratory confirmed SARS-CoV-2 infection admitted to KK Women's and Children's Hospital (KKH), Singapore, from January to May 2020 were analysed.

Results: Of the 39 COVID-19 children included, 38.5% were asymptomatic. Household transmission accounted for 95% of cases. The presenting symptoms of symptomatic children were low-grade fever (54.2%), rhinorrhoea (45.8%), sore throat (25%), diarrhoea (12.5%) and acute olfactory dysfunction (5.4%). Children of Chinese ethnicity (37.5% vs 6.7%), complete blood count (45.8% vs 6.7%) and liver enzyme abnormalities (25% vs 7.7%) were more common in symptomatic versus asymptomatic children. All children had a mild disease course and none required oxygen supplementation or intensive care.

Conclusions: The high proportion of asymptomatic infected children coupled with household transmission as the main source of paediatric COVID-19 infection underscores the importance of early screening and isolation of children upon detection of an index case of COVID-19 in a household. Symptomatic children were more likely to have abnormal laboratory parameters but they did not have a poorer outcome compared to asymptomatic cases.
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August 2020

Epidemiologic trends in Kawasaki disease during coronavirus disease-19 in Singapore.

J Pediatr 2020 Jul 24. Epub 2020 Jul 24.

KK Women's and Children's Hospital, Department of Paediatrics, Infectious Disease Service, Singapore.

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http://dx.doi.org/10.1016/j.jpeds.2020.07.063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380241PMC
July 2020

Successful containment of horizontal enterovirus infection in a neonatal unit in Singapore through diagnosis by polymerase chain reaction (PCR) and direct sequence analysis.

J Infect Public Health 2020 Oct 9;13(10):1556-1561. Epub 2020 Jul 9.

Department of Neonatology, KK Women's and Children's Hospital, Singapore; Duke-National University of Singapore Graduate Medical School, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Lee Kong Chian School of Medicine, National Technological University, Singapore.

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.
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http://dx.doi.org/10.1016/j.jiph.2020.06.029DOI Listing
October 2020

Household Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 from Adults to Children.

J Pediatr 2020 Oct 4;225:249-251. Epub 2020 Jul 4.

Department of Pediatrics, Infectious Disease Service, KK Women's and Children's Hospital, Singapore; Duke-NUS Medical School, Singapore; Lee Kong Chian School of Medicine, Imperial College London, Nanyang Technological University, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Knowledge of transmission dynamics of severe acute respiratory syndrome coronavirus 2 from adults to children in household settings is limited. We found an attack rate among 213 children in 137 households to be 6.1% in households with confirmed adult 2019 novel coronavirus disease index case(s). Transmission from adult to child occurred in only 5.2% of households. Young children <5 years old were at lowest risk of infection (1.3%). Children were most likely to be infected if the household index case was the mother.
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http://dx.doi.org/10.1016/j.jpeds.2020.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334921PMC
October 2020

Novel Coronavirus 2019 Transmission Risk in Educational Settings.

Clin Infect Dis 2021 03;72(6):1055-1058

Duke-National University of Singapore Medical School, Singapore.

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.
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http://dx.doi.org/10.1093/cid/ciaa794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337629PMC
March 2021

Burden and Cost of Hospitalization for Respiratory Syncytial Virus in Young Children, Singapore.

Emerg Infect Dis 2020 07;26(7):1489-1496

Respiratory syncytial virus (RSV) is the most common cause of pediatric acute lower respiratory tract infection worldwide. Detailed data on the health and economic burden of RSV disease are lacking from tropical settings with year-round RSV transmission. We developed a statistical and economic model to estimate the annual incidence and healthcare cost of medically attended RSV disease among young children in Singapore, using Monte Carlo simulation to account for uncertainty in model parameters. RSV accounted for 708 hospitalizations in children <6 months of age (33.5/1,000 child-years) and 1,096 in children 6-29 months of age (13.2/1,000 child-years). The cost of hospitalization was SGD 5.7 million (US $4.3 million) at 2014 prices; patients bore 60% of the cost. RSV-associated disease burden in tropical settings in Asia is high and comparable to other settings. Further work incorporating efficacy data from ongoing vaccine trials will help to determine the potential cost-effectiveness of different vaccination strategies.
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http://dx.doi.org/10.3201/eid2607.190539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323550PMC
July 2020

DISSEMINATED BACILLUS-CALMETTE-GUÉRIN INFECTIONS AND PRIMARY IMMUNODEFICIENCY DISORDERS IN SINGAPORE: A SINGLE CENTER 15-YEAR RETROSPECTIVE REVIEW.

Int J Infect Dis 2020 Aug 2;97:117-125. Epub 2020 Jun 2.

Infectious Disease Service, Department of Pediatric Medicine, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore 117597, Singapore; Duke-National University of Singapore Medical School, 8 College Road, Singapore 169857, Singapore; Lee Kong Chian School of Medicine, National Technological University, 59 Nanyang Drive, Experimental Medicine Building, Singapore 636921, Singapore.

Background: Disseminated Bacillus Calmette-Guérin (BCG) disease (BCGosis) is a classical feature of children with primary immunodeficiency disorders (PIDs).

Methods: A 15-year retrospective review was conducted in KK Women's and Children's Hospital in Singapore, from January 2003 to October 2017.

Results: Ten patients were identified, the majority male (60.0%). The median age at presentation of symptoms of BCG infections was 3.8 (0.8 - 7.4) months. All the patients had likely underlying PIDS - four with Severe Combined Immunodeficiency (SCID), three with Mendelian Susceptibility to Mycobacterial Diseases (MSMD), one with Anhidrotic Ectodermal Dysplasia with Primary Immunodeficiency (EDA-ID), one with combined immunodeficiency (CID), and one with STAT-1 gain-of-function mutation. Definitive BCGosis was confirmed in all patients by the identification of Mycobacterium bovis subsp BCG from microbiological cultures. The susceptibility profiles of Mycobacterium bovis subsp BCG are as follows: Rifampicin (88.9%), Isoniazid (44.47%), Ethambutol (100.0%), Streptomycin (100.0%), Kanamycin (100.0%), Ethionamide (25.0%), and Ofloxacin (100.0%). Four patients (40.0%) received a three-drug regimen. Five patients (50.0%) underwent hematopoietic stem cell transplant (HSCT), of which three (60%) have recovered. Overall mortality was 50.0%.

Conclusion: Disseminated BCG disease (BCGosis) should prompt immunology evaluation to determine the diagnosis of the immune defect. A three-drug regimen is adequate for treatment if the patient undergoes early HSCT.
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http://dx.doi.org/10.1016/j.ijid.2020.05.117DOI Listing
August 2020

Clinical Utility of Buccal Swabs for Severe Acute Respiratory Syndrome Coronavirus 2 Detection in Coronavirus Disease 2019-Infected Children.

J Pediatric Infect Dis Soc 2020 Jul;9(3):370-372

Infectious Disease Service, Department of Pediatrics, KK Women's and Children's Hospital, Singapore.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected from at least 1 buccal specimen in 9 of 11 coronavirus disease 2019 (COVID-19)-infected children (81.8%). Viral loads in buccal specimens were substantially lower than those in nasopharyngeal specimens. Buccal swabs are not good as COVID-19 screening specimens in children.
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http://dx.doi.org/10.1093/jpids/piaa068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313923PMC
July 2020

Universal Face Masking Reduces Respiratory Viral Infections Among Inpatient Very-Low-Birthweight Neonatal Infants.

Clin Infect Dis 2020 12;71(11):2958-2961

Department of Neonatology, KK Women's & Children's Hospital, Singapore.

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.
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http://dx.doi.org/10.1093/cid/ciaa555DOI Listing
December 2020

Epidemiology of Adenovirus Infections and Outcomes of Cidofovir Treatment in Severely Ill Children.

Pediatr Infect Dis J 2020 10;39(10):907-913

Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.

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.
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http://dx.doi.org/10.1097/INF.0000000000002726DOI Listing
October 2020

Statistical inference in matched case-control studies of recurrent events.

Int J Epidemiol 2020 06;49(3):996-1006

Medical Research Council Unit The Gambia at London School of Hygiene & Tropical Medicine, PO Box 273, Fajara, The Gambia.

Background: The concurrent sampling design was developed for case-control studies of recurrent events. It involves matching for time. Standard conditional logistic-regression (CLR) analysis ignores the dependence among recurrent events. Existing methods for clustered observations for CLR do not fit the complex data structure arising from the concurrent sampling design.

Methods: We propose to break the matches, apply unconditional logistic regression with adjustment for time in quintiles and residual time within each quintile, and use a robust standard error for observations clustered within persons. We conducted extensive simulation to evaluate this approach and compared it with methods based on CLR. We analysed data from a study of childhood pneumonia to illustrate the methods.

Results: The proposed method and CLR methods gave very similar point estimates of association and showed little bias. The proposed method produced confidence intervals that achieved the target level of coverage probability, whereas the CLR methods did not, except when disease incidence was low.

Conclusions: The proposed method is suitable for the analysis of case-control studies with recurrent events.
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http://dx.doi.org/10.1093/ije/dyaa012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394959PMC
June 2020

A Well Infant With Coronavirus Disease 2019 With High Viral Load.

Clin Infect Dis 2020 07;71(15):847-849

Infectious Disease Service, Department of Pediatrics, KK Women's and Children's Hospital, Singapore, Singapore.

A well 6-month-old infant with coronavirus disease 2019 (COVID-19) had persistently positive nasopharyngeal swabs up to day 16 of admission. This case highlights the difficulties in establishing the true incidence of COVID-19, as asymptomatic individuals can excrete the virus. These patients may play important roles in human-to-human transmission in the community.
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http://dx.doi.org/10.1093/cid/ciaa201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358675PMC
July 2020

Personal level exposure and hazard potential of particulate matter during haze and non-haze periods in Singapore.

Chemosphere 2020 Mar 18;243:125401. Epub 2019 Nov 18.

KK Women's and Children's Hospital, 229899, Singapore; Duke-NUS Medical School, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address:

Severe haze episodes originating from biomass burning are common in Southeast Asia. However, there is a paucity of data on the personal exposure and characteristics of Particulate Matter (PM) present in ambient air during haze and non-haze periods. Aims of this study were to monitor 24 h ambulatory exposure to PM among school children in Singapore; characterize haze and non-haze PM for their physicochemical properties, cytotoxicity and inflammatory potential, using bronchial epithelial cell culture model (BEAS-2B). Forty-six children had ambulatory PM exposure monitored using portable Aethalometer and their hourly activity recorded. The mean (±SE) PM exposure on a typical school day was 3343 (±174.4) ng/m/min. Higher PM exposure was observed during haze periods and during commuting to and from the school. Characterization of PM collected showed a drastic increase in the proportion of ultrafine particle (UFP) in haze PM. These PM fraction showed higher level of sulphur, potassium and trace metals in comparison to those collected during non-haze periods. Dose dependent increases in abiotic reactive oxygen species generation, activation of NF-κB and cytotoxicity were observed for both haze and non-haze PM. Generally, haze PM induced significantly higher release of IL-6, IL-8 and TNFα by BEAS-2B cells in comparison to non-haze PM. In summary, this study provides experimental evidence for higher PM exposure during haze period which has the potential to elicit oxidative stress and pro-inflammatory cytokine release from airway epithelial cells.
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http://dx.doi.org/10.1016/j.chemosphere.2019.125401DOI Listing
March 2020

Timeliness of Childhood Vaccination Coverage: the Growing Up in Singapore Towards Healthy Outcomes Study.

Prev Sci 2020 04;21(3):283-292

Duke-NUS Medical School, Singapore, 169857, Singapore.

Studies investigating timeliness for childhood vaccination are limited especially in Asia. We examined the timeliness of vaccine administration and associated factors among infant and young children in Singapore. A total of 782 children born between November 2009 and July 2011 from a prospective cohort in Singapore were studied. Vaccination records from birth to 24 months of age were obtained from the National Immunization Registry of Singapore. Multivariable logistic regression models were performed. By 2 years of age, 92.8% of children in our cohort experienced a delay in receiving 1 or more vaccine doses according to the recommended national immunization schedule. When vaccinations were reviewed by series for each vaccine, 15.6% received all vaccine series outside the recommended age ranges. Factors associated with receiving vaccination series outside the recommended ages included maternal aged ≤ 35 years (OR 2.00; 95% CI 1.09, 3.66), Malay (1.71; 1.01, 2.89) or Indian ethnicity (2.06; 1.19, 3.59), low monthly household income (1.91; 1.14, 3.18), having at least four children (3.46; 1.62, 7.38) and private (3.42; 1.80, 6.48) and multiple vaccination providers (3.91; 1.23, 12.48). These findings show an unacceptably high proportion of children experienced a delay in the receipt of their vaccinations. The identification of several demographic, socioeconomic, health-seeking behavioural and vaccine provider factors provides opportunities for targeted interventions to enhance the timeliness of childhood vaccination in Singapore.
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http://dx.doi.org/10.1007/s11121-019-01078-2DOI Listing
April 2020

Epstein-Barr Virus Seroprevalence and Force of Infection in a Multiethnic Pediatric Cohort, Singapore.

Pediatr Infect Dis J 2019 12;38(12):1173-1176

Department of Laboratory Medicine, National University Hospital, Singapore.

Background: Epstein-Barr virus (EBV) spreads through bodily fluids, especially saliva, and can cause infectious mononucleosis. EBV immunity and infection status can be assessed by testing EBV viral capsid antigen and nuclear antigen (EBNA) antibodies in blood. In this study, we investigated the seroprevalence and force of infection (FOI) of EBV antibodies among children and young people in 3 ethnic groups in Singapore.

Methods: Eight hundred ninety-six residual serum samples at a tertiary hospital were tested for viral capsid antigen (IgG and IgM) and EBNA IgG antibodies using Abbott Architect assays. We calculated the EBV seroprevalence using catalytic models to estimate the EBV force of infection from age-stratified seroprevalence data, both overall and by ethnic group.

Results: Overall seropositivity was 68.3% (n = 612). Seropositivity was higher in Malays (81.8%) compared with both Chinese (64.2%) and Indians (58.4%). EBV FOI was consistently higher in Malays, with an estimated annual rate of seroconversion of 25% in children 1 year, of age compared with 14% among Chinese and Indians at the same age.

Conclusions: The seroprevalence patterns of EBV antibodies in the Chinese and Indian, but not Malay children in Singapore by 19 years of age resemble those previously reported in developed countries. Ideally, any future EBV vaccination strategy would need to target infants <1 year of age for maximum population benefit.
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http://dx.doi.org/10.1097/INF.0000000000002484DOI Listing
December 2019

The burden and clinical manifestation of hospitalized influenza among different pediatric age-groups in the tropics.

Influenza Other Respir Viruses 2020 01 13;14(1):46-54. Epub 2019 Oct 13.

Infectious Diseases, Department of Paediatrics, KK Women's and Children's Hospital, Singapore.

Introduction: In tropical Singapore, influenza occurs all year-round. This study of influenza-confirmed hospitalized pediatric patients compared clinical characteristics and complications by age-group and differences between influenza A and B.

Methods: This was a retrospective study of pediatric inpatients from January 2013 to December 2014. Patients were grouped into: <6 months, 6 months to <5 years, 5- to <10-year and ≥10 years. Complications were classified into neurologic, pulmonary, and other. We also calculated the incidence of hospitalized influenza cases per 100 000 age-related population.

Results: There were a total of 1272 patients with a median age of 37 months. The highest hospitalization rates were in the <6 months age-group. Majority (75.2%) had no comorbidity; 25.6% had complications: neurologic 11.9%, pulmonary 9.6%, other 4.1%. Patients with other complications were older, male, and had the highest influenza B rates and the longest length of stay. Influenza A comprised 76.9% of cases and had higher complication rates especially neurologic, compared to influenza B. Influenza B patients were older and were more likely to develop other complications. The 6-month to <5-year-age-group had the highest complication rate (30.6%), especially neurologic. However, ≥10 years old had the highest other complications, ICU/ high-dependency admissions and influenza B Victoria rates.

Conclusions: Infants <6 months had the highest hospitalization rates for influenza. The 6-month to <5-year-age-group had the highest complication rate especially neurologic. Influenza A patients were younger, had higher seizure rates and complications compared to influenza B.
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http://dx.doi.org/10.1111/irv.12692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928028PMC
January 2020
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