Publications by authors named "Koh Cheng Thoon"

89 Publications

SpiroBooth-innovation to mitigate COVID-19 risk in the lung function laboratory.

Pediatr Pulmonol 2021 Jul 22. Epub 2021 Jul 22.

Paediatric Respiratory Medicine, KK Women's and Children's Hospital, Singapore.

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http://dx.doi.org/10.1002/ppul.25580DOI Listing
July 2021

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

Patient, staff empowerment and hand hygiene bundle improved and sustained hand hygiene in hospital wards.

J Paediatr Child Health 2021 Apr 28. Epub 2021 Apr 28.

Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Aim: We piloted a hand hygiene (HH) project in a ward, focusing on World Health Organization moments 1 and 4. Our aim was to design highly reliable interventions to achieve >90% compliance.

Methods: Baseline HH compliance was 57 and 67% for moments 1, 4, respectively, in 2015. After the pilot ward showed sustained improvement, we launched the 'HH bundle' throughout the hospital. This included: (i) appointment of HH champions; (ii) verbal/visual bedside reminders; (iii) patient empowerment; (iv) hand moisturisers; (v) tagging near-empty handrub (HR) bottles. Other hospital-wide initiatives included: (vi) Smartphone application for auditing; (vii) 'Speak up for Patient Safety' Campaign in 2017 for staff empowerment; (viii) making HH a key performance indicator.

Results: Overall HH compliance increased from a baseline median of 79.6-92.6% in end-2019. Moments 1 and 4 improved from 71 to 92.7% and from 77.6 to 93.2%, respectively. Combined HR and hand wash consumption increased from a baseline median of 82.6 ml/patient day (PD) to 109.2 mL/PD. Health-care-associated rotavirus infections decreased from a baseline median of 4.5 per 10 000 PDs to 1.5 per 10 000 PDs over time.

Conclusions: The 'HH Bundle' of appointing HH champions, active reminders and feedback, patient education and empowerment, availability of hand moisturisers, tagging near-empty hand rub bottles together with hospital-wide initiatives including financial incentives and the 'Speak Up for Patient Safety' campaign successfully improved the overall HH compliance to >90%. These interventions were highly reliable, sustained over 4 years and also reduced health-care-associated rotavirus infection rates.
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http://dx.doi.org/10.1111/jpc.15526DOI Listing
April 2021

A practical approach to defining aerosol-generating procedures.

Infect Control Hosp Epidemiol 2021 Apr 19:1-2. Epub 2021 Apr 19.

Division of Infectious Diseases, National University Hospital of Singapore, Singapore.

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http://dx.doi.org/10.1017/ice.2021.184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138870PMC
April 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

Paediatric emergency department attendances during COVID-19 and SARS in Singapore.

Ann Acad Med Singap 2021 02;50(2):126-134

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

Introduction: We evaluated the impact of public health measures on paediatric emergency department attendances during the COVID-19 and severe acute respiratory syndrome (SARS) outbreaks in Singapore.

Methods: Between 1 January 2020 and 31 July 2020, we retrospectively reviewed paediatric emergency department attendances and admissions in a tertiary paediatric hospital in Singapore before and after a national lockdown to combat the spread of COVID-19 in Singapore. Hospital attendances and admissions were compared with data from a corresponding period in 2019 (1 January 2019 to 31 July 2019), as well as during and after the SARS outbreak (1 January 2003 to 31 December 2004).

Results: Compared with a corresponding non-outbreak period, emergency department attendances decreased in line with nationwide public health measures during the COVID-19 and SARS outbreaks (2020 and 2003 respectively), before increasing gradually following lifting of restrictions, albeit not to recorded levels before these outbreaks. During the COVID-19 outbreak, mean daily attendances decreased by 40%, from 458 per day in January-July 2019, to 274 per day in January-July 2020. The absolute number of hospital inpatient admissions decreased by 37% from January-July 2019 (19,629) to January-July 2020 (12,304). The proportion of emergency department attendances requiring admission remained similar: 20% in January-July 2019 and 21% in January-July 2020.

Conclusion: Nationwide public health measures in Singapore have had an impact on paediatric emergency department attendances and hospital inpatient admissions. Data from this study could inform planning and resource allocation for emergency departments in Singapore and internationally.
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February 2021

Validation of self-collected buccal swab and saliva as a diagnostic tool for COVID-19.

Int J Infect Dis 2021 Mar 2;104:255-261. Epub 2021 Jan 2.

Academic Program in Obstetrics and Gynaecology, Duke-NUS Medical School, Singapore; Department of Reproductive Medicine, KK Women's and Children's Hospital, 100, Bukit Timah Road, 229899, Singapore. Electronic address:

Background: Effective management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires large-scale testing to identify and isolate infectious carriers. Self-administered buccal swab and saliva collection are convenient, painless, and safe alternatives to the current healthcare worker (HCW)-collected nasopharyngeal swab (NPS).

Methods: A cross-sectional single-centre study was conducted on 42 participants who had tested positive for SARS-CoV-2 via an NPS within the past 7 days. Real-time polymerase chain reaction (RT-PCR) was performed and cycle threshold (Ct) values were obtained for each test. The positive percent agreement (PPA), negative percent agreement (NPA), and overall agreement (OA) were calculated for the saliva samples and buccal swabs, and compared with NPS.

Results: Among the 42 participants, 73.8% (31/42) tested positive by any one of the three tests. With reference to NPS, the saliva test had PPA 66.7%, NPA 91.7%, and OA 69.0%; the buccal swab had PPA 56.7%, NPA 100%, and OA 73.8%.

Conclusion: Self-collected saliva tests and buccal swabs showed only moderate agreement with HCW-collected NPS. Primary screening for SARS-CoV-2 may be performed with a saliva test or buccal swab, with a negative test warranting a confirmatory NPS to avoid false-negatives, minimize discomfort, and reduce the risk of spread to the community and HCWs.
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http://dx.doi.org/10.1016/j.ijid.2020.12.080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833930PMC
March 2021

Pregnancy Outcomes in COVID-19: A Prospective Cohort Study in Singapore.

Ann Acad Med Singap 2020 11;49(11):857-869

Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Introduction: Pregnant women are reported to be at increased risk of severe coronavirus disease 2019 (COVID-19) due to underlying immunosuppression during pregnancy. However, the clinical course of COVID-19 in pregnancy and risk of vertical and horizontal transmission remain relatively unknown. We aim to describe and evaluate outcomes in pregnant women with COVID-19 in Singapore.

Methods: Prospective observational study of 16 pregnant patients admitted for COVID-19 to 4 tertiary hospitals in Singapore. Outcomes included severe disease, pregnancy loss, and vertical and horizontal transmission.

Results: Of the 16 patients, 37.5%, 43.8% and 18.7% were infected in the first, second and third trimesters, respectively. Two gravidas aged ≥35 years (12.5%) developed severe pneumonia; one patient (body mass index 32.9kg/m2) required transfer to intensive care. The median duration of acute infection was 19 days; one patient remained reverse transcription polymerase chain reaction (RT-PCR) positive >11 weeks from diagnosis. There were no maternal mortalities. Five pregnancies produced term live-births while 2 spontaneous miscarriages occurred at 11 and 23 weeks. RT-PCR of breast milk and maternal and neonatal samples taken at birth were negative; placenta and cord histology showed non-specific inflammation; and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulins were elevated in paired maternal and umbilical cord blood (n=5).

Conclusion: The majority of COVID-19 infected pregnant women had mild disease and only 2 women with risk factors (obesity, older age) had severe infection; this represents a slightly higher incidence than observed in age-matched non-pregnant women. Among the women who delivered, there was no definitive evidence of mother-to-child transmission via breast milk or placenta.
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November 2020

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

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

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

Transmission modes of severe acute respiratory syndrome coronavirus 2 and implications on infection control: a review.

Singapore Med J 2020 07 30. Epub 2020 Jul 30.

National Centre for Infectious Diseases, Singapore.

The complete picture of transmission modes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. This review summarises the available evidence of its transmission modes, our preliminary research findings and implications on infection control policy, and outlines future research directions. Environmental contamination has been reported in hospital settings occupied by infected patients, and is higher in the first week of illness. Transmission via environmental surfaces or fomites is likely, but decontamination protocols are effective in minimising this risk. The extent of airborne transmission is also unclear. While several studies have detected SARS-CoV-2 RNA in air samples, none has isolated viable virus in culture. Transmission likely lies on a spectrum between droplet to airborne transmission depending on patient, disease and environmental factors. Singapore's current personal protective equipment and isolation protocols are sufficient to manage this risk.
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http://dx.doi.org/10.11622/smedj.2020114DOI Listing
July 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

Heterozygous missense variant in EIF6 gene: A novel form of Shwachman-Diamond syndrome?

Am J Med Genet A 2020 09 13;182(9):2010-2020. Epub 2020 Jul 13.

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

Shwachman-Diamond syndrome (SDS) is a rare multisystem ribosomal biogenesis disorder characterized by exocrine pancreatic insufficiency, hematologic abnormalities and bony abnormalities. About 90% of patients have biallelic mutations in SBDS gene. Three additional genes-EFL1, DNAJC21 and SRP54 have been reported in association with a SDS phenotype. However, the cause remains unknown for ~10% of patients. Herein, we report a 6-year-old Chinese boy, who presented in the neonatal period with pancytopenia, liver transaminitis with hepatosplenomegaly and developmental delay, and subsequently developed pancreatic insufficiency complicated by malabsorption and poor growth. Exome sequencing identified a novel de novo heterozygous variant in EIF6 (c.182G>T, p.Arg61Leu). EIF6 protein inhibits ribosomal maturation and is removed in the late steps of ribosomal maturation by SBDS and EFL1 protein. Given the interaction of EIF6 with SBDS and EFL1, we postulate heterozygous variants in EIF6 as a novel cause of Shwachman-Diamond-like phenotype. We compared the phenotype of our patient with those in patients with mutation in SBDS, EFL1, DNAJC21, and SRP54 genes to support this association. Identification of more cases of this novel phenotype would strengthen the association with the genetic etiology.
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http://dx.doi.org/10.1002/ajmg.a.61758DOI Listing
September 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

Management of HIV-positive pregnant women: a Singapore experience.

Singapore Med J 2020 Apr 3. Epub 2020 Apr 3.

Department of Obstetrics and Gynaecology, KK Women’s and Children’s Hospital, Singapore

Introduction: Perinatal transmission remains one of the important causes of the transmission of the human immunodeficiency virus (HIV). Over the years, with better knowledge and awareness of HIV, the perinatal transmission rate has been significantly reduced. We previously reported on the pregnancy outcomes of HIV-positive mothers from 1997 to 2007 in our institution. This paper aims to review standards of care of HIV-positive pregnant women since then.

Methods: A retrospective study reviewed 84 HIV-positive women who delivered in a tertiary centre from January 2008 to December 2015. Patient demographics and antenatal, intrapartum, postnatal and immediate neonatal data were analysed.

Results: There were a total of 97 deliveries with 98 neonates. 12 women delivered more than once and there was one set of twins. Mean maternal age at diagnosis of HIV was 27.8 years. Of the study population, 63.1% of women were non-Singaporeans. 56 women were known to have HIV on presentation and 90.7% were on antiretroviral therapy during pregnancy. 88.7% of the women received intrapartum intravenous zidovudine, and 93.1% of women with detectable and 58.7% with undetectable viral load underwent Caesarean sections. All neonates were HIV-negative.

Conclusion: Having high standards of care for HIV-positive women has successfully reduced our perinatal transmission rate to zero.
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http://dx.doi.org/10.11622/smedj.2020048DOI Listing
April 2020

Critical illness epidemiology and mortality risk in pediatric oncology.

Pediatr Blood Cancer 2020 06 18;67(6):e28242. Epub 2020 Mar 18.

Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Objective: Pediatric oncology patients admitted to the pediatric intensive care unit (PICU) are at high risk of mortality. This study aims to describe the epidemiology of and the risk factors for mortality in these patients.

Study Design: This is a retrospective cohort study including all consecutive PICU oncology admissions from 2011 to 2017. Demographic and clinical risk factors between survivors and nonsurvivors were compared. Both univariate and multivariate Cox proportional hazard regression models were used to quantify the association between 60-day mortality and admission categories, accounting for other covariates (Pediatric Risk Of Mortality [PRISM] III score and previous bacteremia).

Main Outcome Measures: The primary outcome was 60-day mortality.

Results: The median (interquartile range) age and PRISM III scores of pediatric oncology patients admitted to the PICU were 7 (3, 12) years and 3 (0, 5), respectively. The most common underlying oncological diagnoses were brain tumors (73/200 [36.5%]) and acute lymphoblastic leukemia (36/200 [18.0%]). Emergency admissions accounted for approximately half of all admissions (108/200 [54.0%]), including cardiovascular (24/108 [22.2%]), neurology (24/108 [22.2%]), respiratory (22/108 [20.4%]), and "other" indications (38/108 [35.2%]). The overall 60-day mortality was 35 of 200 (17.5%). Independent risk factors for mortality were emergency respiratory and neurology categories of admission (adjusted hazard ratio[aHR]: 5.62, 95% confidence interval [95% CI]: 1.57, 20.19; P = .008 and aHR: 6.96, 95% CI: 2.04, 23.75; P = .002, respectively) and previous bacteremia (aHR: 3.37, 95% CI: 1.57, 7.20; P = .002).

Conclusion: Emergency respiratory and neurology admissions and previous bacteremia were independent risk factors for 60-day mortality for pediatric oncological patients admitted to the PICU.
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http://dx.doi.org/10.1002/pbc.28242DOI Listing
June 2020
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