Impact of COVID-19 pandemic on carbapenem-resistant Enterobacterales incidence in the South-East Asia region: an observational study.

The COVID-19 pandemic led to an initial increase in the incidence of carbapenem-resistant Enterobacterales (CRE) from clinical cultures in South-East Asia hospitals, which was unsustained as the pandemic progressed. Conversely, there was a decrease in CRE incidence from surveillance cultures and overall combined incidence. Further studies are needed for future pandemic preparedness.

Whole genome sequencing reveals hidden transmission of carbapenemase-producing Enterobacterales.

Carbapenemase-producing Enterobacterales (CPE) infection control practices are based on the paradigm that detected carriers in the hospital transmit to other patients who stay in the same ward. The role of plasmid-mediated transmission at population level remains largely unknown. In this retrospective cohort study over 4.7 years involving all multi-disciplinary public hospitals in Singapore, we analysed 779 patients who acquired CPE (1215 CPE isolates) detected by clinical or surveillance cultures. 42.0% met putative clonal transmission criteria, 44.8% met putative plasmid-mediated transmission criteria and 13.2% were unlinked. Only putative clonal transmissions associated with direct ward contact decreased in the second half of the study. Both putative clonal and plasmid-mediated transmission associated with indirect (no temporal overlap in patients' admission period) ward and hospital contact did not decrease during the study period. Indirect ward and hospital contact were identified as independent risk factors associated with clonal transmission. In conclusion, undetected CPE reservoirs continue to evade hospital infection prevention measures. New measures are needed to address plasmid-mediated transmission, which accounted for 50% of CPE dissemination.

Characterisation of Salmonella Enteritidis ST11 and ST1925 Associated with Human Intestinal and Extra-Intestinal Infections in Singapore.

Salmonella Enteritidis is a major foodborne pathogen worldwide. In this study, a total of 276 S. enteritidis isolates, collected between 2016 and 2017 from human, food and farm/slaughterhouse samples, were studied to enhance the understanding of the epidemiology of human salmonellosis in Singapore. Results showed all 276 isolates belonged either to ST1925 (70.3%) or ST11 (29.7%), with ST11 being significantly more frequent in extra-intestinal isolates and chicken isolates. Food isolates, most of which were from poultry, showed the highest prevalence of resistance (33-37%) against beta-lactams or beta-lactams/beta-lactamase inhibitor combination (ampicillin, piperacillin and ampicillin/sulbactam). The analysis showed the detection of genes associated with resistance to aminoglycoside genes (99.6%), tetracycline (55.1%), and beta-lactams (14.9%) of all isolates. Nine types of plasmids were found in 266 isolates; the most common incompatibility group profiles were IncFIB(S)-IncFII(S)-IncX1 (72.2%) and IncFIB(S)-IncFII(S) (15.8%). Most plasmid harbouring isolates from chicken (63.6%, 14/22) and from human (73.8%, 175/237) shared the same plasmid profile (IncFIB(S)-IncFII(S)-IncX1). SNP analysis showed clustering of several isolates from poultry food products and human isolates, suggesting phylogenetic relatedness among these isolates. Lastly, this study provides important epidemiological insights on the application of phenotypic and next-generation sequencing (NGS) tools for improved food safety and public health surveillance and outbreak investigation of S.enteritidis.

Clinical profile of children with parechovirus meningitis in Singapore.

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/mm3, with a median of 3 cells/mm3 [interquartile range (IQR) 1-6 cells/mm3]. 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).

Ovarian biomarkers predict controlled ovarian stimulation for in vitro fertilisation treatment in Singapore.

INTRODUCTION: Ovarian biomarkers have been shown to predict responses to controlled ovarian hyperstimulation (COH) during in vitro fertilisation (IVF) in predominantly Caucasian populations, with limited studies performed in Southeast Asian women in Singapore. METHODS: We evaluated the performance of serum anti-Müllerian hormone (AMH), follicle-stimulating hormone and oestradiol levels, antral follicle count (AFC), body mass index, ovarian volume, and age to establish thresholds for the prediction of poor (< 4 oocytes retrieved) and excessive responses (> 19 oocytes retrieved) in 263 women undergoing COH. Univariate and multivariate logistic regression analysis and receiver operating characteristic curves were used to calculate probabilities for poor and excessive responders to COH. RESULTS: 36 (13.7%) and 50 (19.0%) women had poor and excessive response to COH, respectively. An AMH value of 0.69 ng/mL predicted poor ovarian response with positive likelihood ratio (LR) of 2.94, compared to an AFC of ≤ 5 when the positive LR is 2.36. Conversely, an AMH value of ≥ 3.06 ng/mL predicted excessive ovarian response with positive LR of 2.24, compared to an AFC cut-off of ≥ 12 with positive LR of 1.93. CONCLUSION: AMH levels and AFC are equivalent in the prediction of both poor and excessive ovarian response in women undergoing IVF. Our study highlights the importance of establishing population-specific cut-off biomarker values so that protocols can be tailored to optimise IVF treatment.

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

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.

Seroprevalence of vaccine-preventable diseases among children and adolescents in Singapore: Results from the National Paediatric Seroprevalence Survey 2018.

OBJECTIVES: The Ministry of Health (MOH), Singapore, conducted the National Paediatric Seroprevalence Survey 2018 (NPSS 2018) to estimate the latest immunity levels against measles, rubella, varicella, diphtheria, tetanus and hepatitis B, and the seroprevalence of chronic hepatitis B virus (HBV) carriage in children and adolescents in Singapore. METHODS: The survey involved prospective collection of residual sera from 1,200 children and adolescents aged 1-17 years in two public acute hospitals. Enzyme-linked immunosorbent assays (EIA) or plague reduction neutralisation tests (PRNT) were used to determine the seroprevalence of the vaccine-preventable diseases. RESULTS: Overall prevalence of measles and rubella antibodies among Singaporean children and adolescents aged 1-17 years were 98.2% (95% CI: 91.2-98.8%) and 94.8% (95% CI: 93.4-95.9%) respectively. 97.1% (95% CI: 96.0-97.9%) of subjects had at least basic protection against diphtheria, while 89.3% (95% CI: 87.5-91.0%) were protected against tetanus. The prevalence of chronic HBV carriage was 0.4% (95% CI: 0.2-1.0%), while 45.7% (95% CI: 42.9-48.5%) were immune against HBV. The seroprevalence for varicella antibodies was 52.9% (95% CI: 50.1-55.7%). Concordance between vaccination status and seroprevalence was observed for measles, rubella, diphtheria and tetanus. CONCLUSION: Singapore's children and adolescents are well-protected against measles, rubella, diphtheria and tetanus. Continual efforts in ensuring high vaccination coverage should be sustained.

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

Salmonella in Retail Food and Wild Birds in Singapore-Prevalence, Antimicrobial Resistance, and Sequence Types.

Non-typhoidal salmonellosis is a leading cause of foodborne zoonosis. To better understand the epidemiology of human salmonellosis, this study aimed to determine the prevalence, antimicrobial resistance and sequence types of Salmonella in retail food and wild birds (proximity to humans) in Singapore. We analyzed 21,428 cooked and ready-to-eat food and 1,510 residual faecal samples of wild birds collected during 2010-2015. Thirty-two Salmonella isolates from food and wild birds were subjected to disc diffusion and multi-locus sequence typing (MLST). Salmonella was isolated from 0.08% (17/21,428) of food and 0.99% (15/1510) of wild birds. None of the isolates from wild birds (n = 15) exhibited phenotypic resistance, while the isolates from food (47.1%, 8/17) showed a high prevalence of phenotypic resistance to, at least, one antimicrobial. These findings suggested that the avian Salmonella isolates had been subjected to less antimicrobial selection pressure than those from food samples. MLST revealed specific sequence types found in both food and wild birds. The study can guide future studies with whole-genome analysis on a larger number of isolates from various sectors for public health measures.

Antecedent Carbapenem Exposure as a Risk Factor for Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae and Carbapenemase-Producing Enterobacteriaceae.

Carbapenem-resistant Enterobacteriaceae (CRE) can be mechanistically classified into carbapenemase-producing Enterobacteriaceae (CPE) and non-carbapenemase-producing carbapenem nonsusceptible Enterobacteriaceae (NCPCRE). We sought to investigate the effect of antecedent carbapenem exposure as a risk factor for NCPCRE versus CPE. Among all patients with CRE colonization and infection, we conducted a case-control study comparing patients with NCPCRE (cases) and patients with CPE (controls). The presence of carbapenemases was investigated with phenotypic tests followed by PCR for predominant carbapenemase genes. We included 843 unique patients with first-episode CRE, including 387 (45.9%) NCPCRE and 456 (54.1%) CPE. The resistance genes detected in CPEs were blaNDM (42.8%), blaKPC (38.4%), and blaOXA-48-like (12.1%). After adjusting for confounders and clustering at the institutional level, the odds of prior 30-day carbapenem exposure was three times higher among NCPCRE than CPE patients (adjusted odds ratio [aOR], 3.48; 95% confidence interval [CI], 2.39 to 5.09; P < 0.001). The odds of prior carbapenem exposure and NCPCRE detection persisted in stratified analyses by Enterobacteriaceae species (Klebsiella pneumoniae and Escherichia coli) and carbapenemase gene (blaNDM and blaKPC). CPE was associated with male gender (aOR, 1.45; 95% CI, 1.07 to 1.97; P = 0.02), intensive care unit stay (aOR, 1.84; 95% CI, 1.24 to 2.74; P = 0.003), and hospitalization in the preceding 1 year (aOR, 1.42; 95% CI, 1.01 to 2.02; P = 0.05). In a large nationwide study, antecedent carbapenem exposure was a significant risk factor for NCPCRE versus CPE, suggesting a differential effect of antibiotic selection pressure.

Burden, Etiology, and Risk Factors of Respiratory Virus Infections Among Symptomatic Preterm Infants in the Tropics: A Retrospective Single-Center Cohort Study.

Background: The burden of respiratory viral infections (RVIs) among preterm infants in the first few years of life, especially those living in the tropics with year-long transmissions of respiratory viruses, remains unknown. We aimed to describe the clinical epidemiology and associated risk factors for RVIs among symptomatic preterm infants ≤32 weeks up to 2 years of life. Methods: We performed a data linkage analysis of clinical and hospital laboratory databases for preterm infants born at KK Women's and Children's Hospital, Singapore, from 2005 to 2015. RVI episodes during initial admission and subsequent hospital readmissions were included. Results: Of 1854 infants in the study, 270 (14.5%) infants were diagnosed with at least 1 RVI. A total of 285 (85.3%) episodes were diagnosed postdischarge, with the highest risk for RVIs being from 3 to 5 months of age. The incidence of RVI in this population was 116 per 1000 infant-years and respiratory syncytial virus was the main overall causative pathogen. Infants with RVIs were more likely to be born at ≤27 weeks' gestational age (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.2-2.3), to have received postnatal steroids (OR, 1.5; 95% CI, 1.0-2.1), and to be diagnosed with bronchopulmonary dysplasia (OR, 1.7; 95% CI, 1.2-2.4). Conclusions: The burden of RVIs is high in preterm infants in the tropics, affecting >1 of 10 infants born at ≤32 weeks' gestation before 2 years of age. Respiratory syncytial virus was the main causative pathogen identified. Risk factors for RVI included extremely low gestational age, receipt of postnatal steroids, and bronchopulmonary dysplasia.

Cerebrospinal fluid white cell count: discriminatory or otherwise for enteroviral meningitis in infants and young children?

Non-polio enteroviruses (EV) are the most common viruses causing aseptic meningitis in children. We aim to evaluate the cerebrospinal fluid (CSF) characteristics of neonates and children with EV meningitis with a view to determine whether it could be discriminatory or otherwise in making a positive diagnosis. We performed a 3-year (July 2008-July 2011) retrospective study of children ≤16 years, treated at a tertiary children's hospital, with positive CSF EV polymerase chain reaction (PCR) and negative blood and CSF bacterial cultures. A total of 206 children were studied. The median CSF white cell count was 79 cells/mm(3) (range 0-4608 cells/mm(3)). CSF pleocytosis was observed in 99/150 (66%) aged ≤90 days, 3/4 (75%) aged 90 days-1 year, and 49/52 (94%) children ≥3 years. There was a huge variability in CSF pleocytosis in infants ≤90 days, where 34% of them had no pleocytosis, while in 66%, a wide range of pleocytosis that might even suggest bacterial meningitis was noted. CSF red cells were low, and protein or sugar values were not discriminatory. CSF pleocytosis in relation to increasing age was found to be statistically significant (p < 0.001). Early lumbar puncture within 48 h of symptoms and absence of CSF pleocytosis was also statistically significant (p = 0.039). CSF pleocytosis in EV meningitis is commoner in older children. As there was a huge variability in CSF pleocytosis in infants ≤90 days particularly, CSF analysis including EV PCR could avoid unnecessary antibiotic therapy.

A 15-year retrospective analysis of prognostic factors in childhood bacterial meningitis.

AIM: This retrospective chart review aimed to identify factors in childhood bacterial meningitis that predicted disease severity and long-term outcome. METHODS: The study included 112 episodes of microbiologically confirmed bacterial meningitis in children aged three days to 15 years who were admitted to a Singapore hospital from 1998 to 2013. RESULTS: The mortality rate was 6%, and 44% required intensive care unit (ICU) admission. Predictive factors associated with ICU admission included pneumococcal meningitis, with an odds ratio (OR) of 5.2 and 95% confidence interval (CI) of 1.5-18.2, leukopenia (OR 5.6, 95% CI 1.7-17.9) and a cerebrospinal fluid (CSF):serum glucose ratio <0.25 (OR 4.5, 95% CI 1.4-14.4). An initial CSF white blood cell count >1000/mm(3) (OR 0.26, 95% CI 0.086-0.76) was negatively associated with ICU admission. Five years after meningitis, 32% had residual sequelae, and the associated prognostic factors were Haemophilus influenzae type b (Hib) meningitis (OR 29.5, 95% CI 2-429), seizures during their inpatient stay (OR 10.6, 95% CI 1.9-60.2) and septic shock (OR 8.4, 95% CI 1.1-62.1). CONCLUSION: As mortality was low in this bacterial meningitis study, ICU admission was used as a marker of disease severity. These findings underscore the importance of the pneumococcal and Hib meningitis vaccines.

Severe Pediatric Adenovirus 7 Disease in Singapore Linked to Recent Outbreaks across Asia.

During November 2012-July 2013, a marked increase of adenovirus type 7 (Ad7) infections associated with severe disease was documented among pediatric patients in Singapore. Phylogenetic analysis revealed close genetic links with severe Ad7 outbreaks in China, Taiwan, and other parts of Asia.