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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 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.)

The fight against hand, foot, and mouth disease (HFMD) remains an arduous challenge without existing point-of-care (POC) diagnostic platforms for accurate diagnosis and prompt case quarantine. Hence, the purpose of this salivary biomarker discovery study is to set the fundamentals for the realization of POC diagnostics for HFMD. Whole salivary proteome profiling was performed on the saliva obtained from children with HFMD and healthy children, using a reductive dimethylation chemical labeling method coupled with high-resolution mass spectrometry-based quantitative proteomics technology. We identified 19 upregulated (fold change = 1.5-5.8) and 51 downregulated proteins (fold change = 0.1-0.6) in the saliva samples of HFMD patients in comparison to that of healthy volunteers. Four upregulated protein candidates were selected for dot blot-based validation assay, based on novelty as biomarkers and exclusions in oral diseases and cancers. Salivary legumain was validated in the Singapore (n = 43 healthy, 28 HFMD cases) and Taiwan (n = 60 healthy, 47 HFMD cases) cohorts with an area under the receiver operating characteristic curve of 0.7583 and 0.8028, respectively. This study demonstrates the feasibility of a broad-spectrum HFMD POC diagnostic test based on legumain, a virus-specific host systemic signature, in saliva., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

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.)

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.

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.

Human parechovirus (HPeV) is one of the most common causes of aseptic meningitis in children worldwide. This study aims to review the epidemiology, clinical presentation, and cerebrospinal fluid (CSF) findings in HPeV meningitis and compare these with Enterovirus (EV) meningitis. This is a retrospective study of children aged ≤ 1 year admitted for HPeV meningitis between November 2015 and July 2017, with positive CSF HPeV PCR and negative blood and CSF bacterial cultures. The clinical findings were compared with a historical cohort of children with EV meningitis admitted between July 2008 and July 2011. There were 71 children with HPeV meningitis, aged between 2 and 127 days, with the majority (96%) being ≤ 90 days old. The most common symptoms reported were poor feeding (42%), tachycardia out of proportion to fever (27%), and lethargy (20%). Only 2 patients (3%) had CSF pleocytosis. Cerebral spinal fluid white blood cell counts ranged from 0 to 28 cells/mm 3 , with a median of 3 cells/mm 3 [interquartile range (IQR) 1-6 cells/mm 3 ]. When compared to our historical cohort of EV meningitis ≤ 90 days old, children with HPeV meningitis ≤ 90 days old were less likely to have CSF pleocytosis (OR 0.008, 95% CI 0.001-0.057). HPeV and EV meningitis are known to cause sepsis-like illness in infants < 90 days old. This study further supports this, with the requirement for fluid bolus therapy for tachycardia or poor perfusion noted to be higher in children with HPeV meningitis ≤ 90 days old (OR 6.3, 95% CI 2.7-14.2)., (© 2021. Journal of NeuroVirology, Inc.)

Background: Osteomyelitis in immunocompromised children can present differently from immunocompetent children and can cause devastating sequelae if treated inadequately. We aim to review the aetiology, clinical profile, treatment and outcomes of immunocompromised children with osteomyelitis., Methods: Retrospective review of all immunocompromised children aged < 16 years and neonates admitted with osteomyelitis in our hospital between January 2000 and January 2017, and referred to the Paediatric Infectious Disease Service., Results: Fourteen patients were identified. There were 10 boys (71%), and the median age at admission was 70.5 months (inter-quartile range: 12.3-135.0 months). Causal organisms included, two were Staphylococcus aureus, two were Mycobacterium bovis (BCG), and one each was Mycobacterium tuberculosis, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Burkholderia pseudomallei and Rhizopus sp. One patient had both Clostridium tertium and Clostridium difficile isolated. Treatment involved appropriate antimicrobials for a duration ranging from 6 weeks to 1 year, and surgery in 11 patients (79%). Wherever possible, the patients received treatment for their underlying immunodeficiency. For outcomes, only three patients (21%) recovered completely. Five patients (36%) had poor bone growth, one patient had recurrent discharge from the bone and one patient had palliative care for underlying osteosarcoma., Conclusions: Although uncommon, osteomyelitis in immunocompromised children and neonates can be caused by unusual pathogens, and can occur with devastating effects. Treatment involves prolonged administration of antibiotics and surgery. Immune recovery also seems to be an important factor in bone healing., (© 2021. The Author(s).)

Background: The current group B streptococcal (GBS) preventive measures had reduced invasive GBS early onset disease (EOD) incidences worldwide, but the late onset disease (LOD) incidences had remained unchanged. Administration of a safe and effective GBS vaccine in addition to the current strategies were thought to be the next steps in reducing the incidences of invasive GBS infection especially LOD. In this study, we aimed to examine the causative GBS serotypes in invasive GBS disease, determine the incidences of EOD and LOD, and compare the risk factors between EOD and LOD., Methods: A retrospective study of infants ≤ 90-day-old over an 8-year period (2010-2017). The incidences of EOD and LOD were obtained by using patients with EOD and LOD who were born in our institution as the numerator and the live births in our institution per year of the study period as the denominator. Available GBS isolates were serotyped by the National Public Health Laboratory using capsular serotyping methods. The risk factors of EOD and LOD were compared., Results: A total of 71 infants were identified; 16 (22.5%) and 55 (77.5%) of them had EOD and LOD, respectively. Serotype III (n = 42, 71.2%) was the most common serotype amongst the 59 isolates available for serotyping. Serotypes Ia, Ib, II, III, and V accounted for 98.3% (n = 58) of the invasive GBS diseases. The overall incidence was 0.42 per 1000 live births. The mean incidences of EOD and LOD were 0.13 per 1000 live births and 0.29 per 1000 live births, respectively. On multivariate analysis, risk factors for LOD as compared to EOD were: Chinese ethnicity (OR 27.1, 95% CI 3.0-243.1, p = 0.003) and negative/unknown maternal GBS status (OR 20.0, 95% CI 2.0-250.0, p = 0.012). Prematurity and intrapartum risk factors (peripartum maternal pyrexia, prolonged rupture of membrane) of EOD were not associated with LOD., Conclusions: The LOD incidence had remained higher than EOD incidence in our cohort. A GBS vaccine that covers the major causative serotypes found in our cohort can potentially reduce the overall GBS disease burden in the country., (© 2021. The Author(s).)

Aim: Evaluation of hearing outcome in children following non-polio enteroviral meningitis (EVM)., Methods: We reviewed hearing outcome of children, aged ≤15 years, with EVM managed at our institution over a 4-year period from July 2008 to July 2011 and January-December 2015. Children with concomitant bacterial infections, and those who required intensive care, or with a prior history of hearing impairment or immunodeficiency were excluded. Data on demographics, medical history, presentation and outcome of hearing screen were collected. The children attended post-meningitis review and hearing screen utilising transient-evoked otoacoustic emission testing at 8-10 weeks. Children who failed the transient-evoked otoacoustic emission testing and those with caregiver concerns were referred to otolaryngology for comprehensive audiologic evaluation., Results: The study cohort consisted of 179 children, aged from 3 days to 15 years, of whom 158 (89%) were younger than 90 days of age. Eleven were preterm infants. A total of 158 children had received intravenous gentamicin at 5-7.5 mg/kg/day for a median duration of 2 days. All 179 study participants were found to have good hearing post EVM., Conclusion: Hearing outcome in children recovering from EVM is good., (© 2021 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

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.)

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.)

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.

The aetiology of febrile exanthems in children is often difficult to distinguish clinically. A diagnosis of Kawasaki disease (KD) should be considered in infants with exanthematous fever. More perplexing is the increasing incidence of an atypical form of KD. Pathogenesis of KD remains unclear even though an aberrant response of the immune system to an unidentified pathogen is often hypothesised. A 30-fold increase in the incidence of KD in Italy during the SARS-CoV-2 pandemic suggests an immune response to a viral trigger. We report an infant clinically diagnosed with high probability as incomplete KD, who presented with reactivation of the BCG injection site even though fever with rash was only less than 3 days duration. Echocardiography confirmed coronary artery abnormalities and prompt treatment with intravenous immunoglobulin facilitated rapid recovery. Physicians should consider a diagnosis of KD if BCG site reactivation is noted in children presenting with febrile exanthema., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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., (© 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.)

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., (© The Author(s) 2020. 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.)

Aim: Kikuchi-Fujimoto disease (KFD) is an important cause of lymphadenitis in children. The primary aim of this study was to investigate the clinical characteristics of children with KFD and to assess the recurrence of this disease., Methods: This is a retrospective study of patients younger than 18 years old, who were diagnosed with KFD from January 2000 to September 2017 at KK Women's and Children's Hospital. Records of children with a histological diagnosis of KFD from a lymph node biopsy were obtained from the Department of Pathology. Case notes and electronic medical records of the patients were reviewed. Data collected included patient characteristics, symptoms, clinical and laboratory findings, treatment and follow-up., Results: A total of 98 patients were identified. There were 52 boys and 46 girls with a median age of 11.2 years old. Recurrence occurred in 12 (12.2%) patients. One patient developed systemic lupus erythematosus 10 years after diagnosis of KFD. Recurrent cases were more likely to be managed as an inpatient and have fever at presentation of their first episode of KFD., Conclusion: In our study, KFD in children had a higher prevalence among boys, and had a recurrence rate of 12.2%, with 1% of patients developing systemic lupus erythematosus. We recommend that patients be followed up for recurrence and advised to monitor for symptoms of recurrence., (© 2019 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background . Tuberculosis (TB) remains a major cause of mortality and morbidity globally. Pediatric patients are more likely to develop severe disease. Abdominal TB is a rare manifestation of pediatric TB and can present with chronic and nonspecific abdominal symptoms. This study examines the clinical profile of pediatric patients with abdominal TB and treatment outcomes. Method . A retrospective study of patients admitted to a tertiary pediatric hospital in Singapore over 10 years. Clinical characteristics and outcomes were examined. Results. There were 3 male and 3 female patients with mean age of 11.3 years. Household contacts were traced in 3 cases. The most common presenting symptoms were fever, weight loss, and abdominal symptoms such as diarrhea, vomiting, and loss of appetite. Inflammatory markers were raised with mean C-reactive protein (CRP) and erythrocyte sedimentation (ESR) rate at 70.9 mg/L and 90 mm/h respectively. Abdominal imaging showed abnormalities such as splenic foci and thickened bowel wall with significant intraabdominal lymphadenopathy. Mycobacterium tuberculosis was isolated from stool, rectal swabs and intra-adominal specimens. Two patients underwent excisional biopsy of lymph node to obtain diagnosis. Two patients required emergency laparotomy and 1 patient received esophagogastroduodenoscopy and colonoscopy. Four out of the 6 patients had pulmonary involvement. Conclusion . Abdominal TB should be a differential diagnosis in children with chronic abdominal symptoms for at least 8 weeks with anemia, raised ESR and CRP. The gold standard for diagnosis still remains as positive microbiological culture. However, abdominal imaging studies are also vital in obtaining further supportive evidence for chronic infection., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Objectives: Elizabethkingia meningoseptica is a multi-drug-resistant organism that is associated with high mortality and morbidity in newborn and immunocompromised patients. This study aimed to identify the best antimicrobial therapy for treating this infection., Methods: A retrospective descriptive study was conducted from 2010 to 2017 in a tertiary paediatric hospital in Singapore. Paediatric patients aged 0 to 18 years old with a positive culture for E. meningoseptica from any sterile site were identified from the hospital laboratory database. The data collected included clinical characteristics, antimicrobial susceptibility and treatment, and clinical outcomes., Results: Thirteen cases were identified in this study. Combination therapy with piperacillin/tazobactam and trimethoprim/sulfamethoxazole or a fluoroquinolone resulted in a cure rate of 81.8  %. The mortality rate was 15.4  % and neurological morbidity in patients with bacteraemia and meningitis remained high (75 %)., Conclusions: Treatment with combination therapy of piperacillin/tazobactam and trimethoprim/sulfamethoxazole or a fluroquinolone was effective in this study, with low mortality rates being observed.

Immunodeficiency secondary to anti-interferon-gamma (anti-IFN-γ) autoantibodies was first described in 2004 as an acquired defect in the IFN-γ pathway leading to susceptibility to multiple opportunistic infections, including dimorphic fungi, parasites, and bacteria, especially tuberculosis and non-tuberculous mycobacterium (NTM) species. It has so far only been described in adult patients. We present 2 cases of disseminated NTM infections in otherwise immunocompetent children. A 16-year-old girl with Sweet's syndrome-like neutrophilic dermatosis developed recurrent fever and cervical lymphadenitis secondary to Mycobacterium abscessus. A 10-year-old boy with a history of prolonged fever, aseptic meningitis, aortitis, and arteritis in multiple blood vessels developed thoracic vertebral osteomyelitis secondary to Mycobacterium avium complex. Both patients were found to have positive serum neutralizing anti-IFNγ autoantibodies. Testing for anti-IFNγ autoantibodies should be considered in otherwise healthy immunocompetent hosts with recurrent or disseminated NTM infection. This represents a phenocopy of primary immunodeficiency which has been recently described only in adults. We report the first two cases of this phenomenon to affect children.

In this article, we report a case of tuberculosis spondylodiscitis in a 2-year-old child. Imaging of her spine showed a paraspinal abscess. The diagnosis of spinal tuberculosis remains difficult, and we discuss its salient features and current management within the pediatric population., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Tuberculosis (TB) is a major cause of mortality and morbidity in the world. Each case represents ongoing transmission and has a significant public health burden. We aim to examine the clinical profile of paediatric TB and compare pulmonary TB (PTB) with extrapulmonary TB (EPTB) in Singapore., Methods: A retrospective study of patients admitted to KK Women's and Children's Hospital, Singapore from January 2008 to September 2017 with active TB was undertaken. The clinical characteristics and outcomes of patients with PTB and EPTB were compared., Results: Seventy-five patients were diagnosed as having active TB (49 (65%) with PTB and 26 (35%) with EPTB). Patients with EPTB were more likely than those with PTB to be younger (median age 5.1 (IQR 1.2-10.2) years vs 10.1 (IQR 3.5-13.5) years), immunodeficient (35% vs 6%), with a lower haemoglobin count (median 11.2 (IQR 10.2-11.9) g/dL vs 12.0 (IQR 10.5-13.9) g/dL), lower recovery rate (27% vs 57%) and required longer duration of treatment (median 12 (IQR 9-12) months vs 6 (IQR 6-9) months). Common clinical presentations of both PTB and EPTB were significant fever (27%), cough (33%) and weight loss (32%). Overall mortality was 8% with septic shock responsible for three of the six deaths., Conclusion: EPTB is more common in the younger age group and is associated with a lower recovery rate., Competing Interests: Competing interests: None declared.

Enhancements in the diagnostic capabilities using host biomarkers are currently much needed where sensitivity and specificity issues plague the diagnosis of Hand, Foot and Mouth Disease (HFMD) in pediatrics clinical samples. We investigated miRNome profiles of HFMD saliva samples against healthy children and developed miRNA-based diagnosis models. Our 6-miRNA scoring model predicted HFMD with an overall accuracy of 85.11% in the training set and 92.86% in the blinded test set of Singapore cohort. Blinded evaluation of the model in Taiwan HFMD cases resulted in 77.08% accuracy with the 6-miRNA model and 68.75% with the 4-miRNA model. The strongest predictor of HFMD in all of the panels, hsa-miR-221 was found to be consistently and significantly downregulated in all of our HFMD cohorts. This is the first study to prove that HFMD infection could be diagnosed by circulating miRNAs in patient's saliva. Moreover, this study also serves as a stepping stone towards the future development of other infectious disease diagnosis workflows using novel biomarkers., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Hand, foot and mouth disease (HFMD) is a prevalent contagious childhood disease typically associated with fever, oral lesions and limb exanthema. While HFMD is caused by a plethora of serotypes of viruses under the genus Enterovirus within the Picornaviridae family, Coxsackievirus A16 (CV-A16) and Enterovirus 71 (EV-A71) are considered the main etiological agents. In recent years however, other viruses have also been isolated in considerable numbers from infected individuals in many regions, joining the legion commonly associated with HFMD. The present study investigated the cytokine and chemokine profiles of HFMD patients from Singapore and Malaysia for the first time. Comparative cohort studies of EV-A71-associated HFMD cases revealed that the Malaysia cohort had a distinct profile from the Singapore cohort, and this could be partly attributed by different EV-A71 genotypes. As the isolation of CV-A6, instead of CV-A16, had become prevalent in the Singapore cohort, it was also of particular interest to study the differential cytokine and chemokine profiles. Our data revealed that overlapping as well as unique profiles exist between the two major causative clinical isolates in the Singapore cohort. Having a better understanding of the respective immunological profiles could be useful for more accurate HFMD diagnosis, which is imperative for disease transmission control until multi-valent vaccines and/or broad-spectrum anti-viral drugs become available.

This is a case report of a 12-year-old returned traveler with typhoid and scrub typhus coinfection. The diagnosis of typhoid was made early with blood cultures and Widal Weil Felix serology. Persistent fever despite appropriate antibiotics for typhoid fever prompted a search for concomitant infection, which led to the diagnosis of scrub typhus confirmed by Orientia tsutsugamushi serology. The patient was given doxycycline with good clinical response. Scrub typhus infection should be an early consideration in the differential diagnoses of fever in a returned traveler from regions where it is endemic. Coinfections should be taken into consideration particularly when fever or symptoms persist despite adequate therapy for a previously identified microorganism., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Antimicrobial stewardship programs (ASPs) aim to improve appropriate antimicrobial use. However, concerns of the negative consequences from accepting ASP interventions exist, particularly when deescalation or discontinuation of broad-spectrum antibiotics is recommended. Hence, we sought to evaluate the impact on clinical outcomes when ASP interventions for inappropriate carbapenem use were accepted or rejected by primary providers. We retrospectively reviewed all carbapenem prescriptions deemed inappropriate according to institutional guidelines with ASP interventions between July 2011 and December 2014. Intervention acceptance and outcomes, including carbapenem utilization, length of stay, hospitalization charges, 30-day readmission, and mortality rates were reviewed. Data were analyzed in two groups, one in which physicians accepted all interventions ("accepted") and one in which interventions were rejected ("rejected"). A total of 158 ASP interventions were made. These included carbapenem discontinuation (35%), change to narrower-spectrum antibiotic (32%), dose optimization (17%), further investigations (including imaging and procalcitonin) (11%), infectious diseases referral (3%), antibiotic discontinuation (other than carbapenem) (1%), and source control (1%). Of 220 unique patients, carbapenem use was inappropriate in 101 (45.9%) patients. A significant reduction in carbapenem utilization was observed in the accepted group versus rejected group (median defined daily doses, 0.224 versus 0.668 per 1,000 patient-days, respectively; P < 0.001). There was a significant reduction in 30-day mortality in the accepted (none) versus rejected group (10 deaths, P = 0.015), but there were no differences in length of stay, hospitalization charge, or 30-day readmission rates. Hypotension was independently associated with mortality in multivariate analysis (odds ratio, 5.25; 95% confidence interval, 1.34 to 20.6). In our institution, acceptance of carbapenem ASP interventions did not compromise patient safety in terms of clinical outcomes while reducing consumption., (Copyright © 2017 American Society for Microbiology.)

Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.