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SUMMARYWeekly (August 2003-December 2008) numbers of five common paediatric diseases and the incidence of respiratory viruses were obtained from a children's hospital in Singapore and correlated with climate data using multivariate time-series techniques. Upper respiratory tract infections were positively correlated with the incidences of influenza A, B, respiratory syncytial virus (RSV) and parainfluenza viruses (types 1-3 combined). Lower respiratory tract infections were positively correlated with only the incidence of RSV. Both upper and lower respiratory tract infections were negatively correlated with relative humidity. Asthma admissions were negatively correlated with maximum temperature and positively correlated with the incidence of influenza B and increasing hours of sunshine. Although sporadic cases of adenovirus infection were identified, not enough cases were available for a more detailed analysis. Gastroenteritis and urinary tract infections, included as control diseases, were not correlated significantly with any climate parameters. These correlations are compatible with current understanding of respiratory virus survival under certain climate conditions and may assist the prediction of disease burdens and hospital resource planning in such tropical environments. [ABSTRACT FROM AUTHOR]

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., (© 2019 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

In the first reported pediatric case series of virologically confirmed Zika virus (ZIKV) infections from Southeast Asia, ZIKV infection was generally mild. Routine screening of children with suspected ZIKV infection for dengue virus coinfection should be considered in dengue-endemic countries., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: We conducted a national point prevalence survey (PPS) to determine the prevalence of healthcare-associated infections (HAIs) and antimicrobial use (AMU) in Singapore acute-care hospitals., Methods: Trained personnel collected HAI, AMU, and baseline hospital- and patient-level data of adult inpatients from 13 private and public acute-care hospitals between July 2015 and February 2016, using the PPS methodology developed by the European Centre for Disease Prevention and Control. Factors independently associated with HAIs were determined using multivariable regression., Results: Of the 5415 patients surveyed, there were 646 patients (11.9%; 95% confidence interval [CI], 11.1%-12.8%) with 727 distinct HAIs, of which 331 (45.5%) were culture positive. The most common HAIs were unspecified clinical sepsis (25.5%) and pneumonia (24.8%). Staphylococcus aureus (12.9%) and Pseudomonas aeruginosa (11.5%) were the most common pathogens implicated in HAIs. Carbapenem nonsusceptibility rates were highest in Acinetobacter species (71.9%) and P. aeruginosa (23.6%). Male sex, increasing age, surgery during current hospitalization, and presence of central venous or urinary catheters were independently associated with HAIs. A total of 2762 (51.0%; 95% CI, 49.7%-52.3%) patients were on 3611 systemic antimicrobial agents; 462 (12.8%) were prescribed for surgical prophylaxis and 2997 (83.0%) were prescribed for treatment. Amoxicillin/clavulanate was the most frequently prescribed (24.6%) antimicrobial agent., Conclusions: This survey suggested a high prevalence of HAIs and AMU in Singapore's acute-care hospitals. While further research is necessary to understand the causes and costs of HAIs and AMU in Singapore, repeated PPSs over the next decade will be useful to gauge progress at controlling HAIs and AMU., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: Enteric fever is a multisystemic infection which largely affects children. This study aimed to analyse the epidemiology, clinical presentation, treatment and outcome of paediatric enteric fever in Singapore., Materials and Methods: A retrospective review of children diagnosed with enteric fever in a tertiary paediatric hospital in Singapore was conducted from January 2006 to January 2012. Patients with positive blood cultures for Salmonella typhi or paratyphi were identified from the microbiology laboratory information system. Data was extracted from their case records., Results: Of 50 enteric fever cases, 86% were due to Salmonella typhi, with 16.3% being multidrug resistant (MDR) strains. Sixty-two percent of S. typhi isolates were of decreased ciprofloxacin susceptibility (DCS). Five cases were both MDR and DCS. The remaining 14% were Salmonella paratyphi A. There were only 3 indigenous cases. Ninety-four percent had travelled to typhoid-endemic countries, 70.2% to the Indian subcontinent and the rest to Indonesia and Malaysia. All patients infected with MDR strains had travelled to the Indian subcontinent. Anaemia was a significant finding in children with typhoid, as compared to paratyphoid fever (P = 0.04). Although all children were previously well, 14% suffered severe complications including shock, pericardial effusion and enterocolitis. None had typhoid vaccination prior to their travel to developing countries., Conclusion: Enteric fever is largely an imported disease in Singapore and has contributed to significant morbidity in children. The use of typhoid vaccine, as well as education on food and water hygiene to children travelling to developing countries, needs to be emphasised.

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.

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., (©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Melioidosis, caused by Burkholderia pseudomallei, is endemic in Singapore and can present as localized or disseminated disease., Methods: Demographic data, clinical features, investigation results, treatments, and outcomes in patients aged <16 years diagnosed with melioidosis at KK Women's and Children's Hospital between January 2002 and January 2014 were retrospectively reviewed. Data for patients with primary skin disease and those with other organ involvement were compared., Results: Seventeen children were diagnosed with melioidosis. Their median age was 12.5 years (range: 2-15 years). Nine (53%) patients presented with localized cutaneous melioidosis and five (29%) with localized lymphadenitis, pneumonia, or septic arthritis. The remaining three (18%) patients had melioidosis sepsis; two of these patients died from septic shock. Treatment included an initial 1-2 weeks of IV antibiotics followed by 3-6 months of oral combination antibiotics. All cases of localized cutaneous disease resolved completely with no recurrences. Three (60%) of the five patients with localized involvement of other organ systems achieved complete resolution of disease, and the remaining two were lost from follow-up., Conclusions: Although uncommon, melioidosis can occur in children living in endemic regions. Patients with localized skin disease have good outcomes with no recurrences. Systemic disease can be fatal, especially in the presence of underlying immunodeficiency. Diagnosis requires a high index of suspicion, and treatment requires prolonged combination antibiotic therapy., (© 2015 The International Society of Dermatology.)

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.

Background: Human adenoviruses (HAdVs) can cause a variety of human illnesses, with associated temporal and geographic changes in disease incidence. We report the emergence of an outbreak of HAdV infections in Singapore, presumably caused by a change of the predominating type to HAdV-7. We examined the clinical features of children admitted with HAdV infection to 1 institution and the risk factors for severe infection., Materials and Methods: This is a retrospective case-control study of all HAdV-infected children admitted during weeks 1 to 19 in 2013, as identified from laboratory records. A descriptive retrospective analysis of epidemiology, clinical data and the outcome of these children was also performed. Patients with severe infections were defined as cases, those with non-severe infections as controls, and the 2 groups were compared to find possible independent risk factors., Results: Eighty-five patients with HAdV infection were studied, including 11 (12.9%) cases and 74 (87.1%) controls. Binary logistic regression showed that cases were more likely to be <2 years old (adjusted OR 10.6, 95% CI, 1.8 to 63.2) and to have significant comorbidities (adjusted OR 19.9, 95% CI, 3.4 to 116.1) compared to controls. The predominant type in 2013 was HAdV-7, which differed from 2011 and 2012, when HAdV-3 was more common. There was a trend towards pneumonia being more common in patients infected with HAdV-7 than in patients infected with other types, although this did not reach statistical significance (OR 2.8, 95% CI, 0.9 to 8.7)., Conclusion: The emergence of HAdV-7 in a population where other HAdV types had circulated previously may have caused the outbreak in Singapore, and this was associated with more serious infections in children. Young age (<2 years) and significant comorbidities were associated with more severe HAdV infection.

Background: Haemophilus influenzae type b (Hib) conjugate vaccines have significantly limited Hib's disease impact in every country where it was introduced. We previously estimated invasive Hib disease incidence in Singapore at ∼4.4 per 100,000 children <5 years (from 1994 to 2003, period 1), but the vaccine was not included in the national childhood immunization schedule until May 2013 (although it was available privately). The current study aims to describe changes in Hib disease incidence and vaccine coverage prior to the introduction of the vaccine., Methodology: We retrospectively reviewed all invasive Hib cases from January 2004 to December 2012 (period 2) and estimated population-based incidence rates. Vaccine coverage was estimated from vaccine sales for 1994-2003, and from National Immunisation Registry for 2004-2010., Results: There were 8 cases of invasive Hib disease in period 2, of whom 5 were <5 years. Invasive Hib incidence for period 2 was 0.57 per 100,000 children <5 years, representing an 86.4% reduction compared to period 1 (rate ratio 0.14, 95% confidence interval 0.06-0.26). However, for the later part of period 2 (2008-2012), incidence was 0.2 per 100,000 children <5 years; this represented a 95% reduction from period 1 (rate ratio 0.05, 95% confidence interval 0.01-0.18). Between periods 1 and 2, national Hib vaccine coverage rose from 22% to >80%, with >99% of children receiving combination Hib-containing vaccines., Conclusions: Childhood invasive Hib disease has nearly disappeared from Singapore, despite the absence of universal mass vaccination. We believe this is likely due to excellent uptake of combination vaccines., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: This study aims to determine the incidence, trends of systemic candidiasis and meningitis in extremely low birthweight (ELBW) neonates (<1000 gms) despite the routine use of topical miconazole prophylaxis and to compare the risk factors, adverse outcomes and comorbidities with controls., Materials and Methods: Retrospective cohort study of ELBW neonates with systemic candidiasis and meningitis over an 11-year period (1997 to 2007). Matched case control analyses were performed to determine the risk factors and comorbidities which were severe intraventricular haemorrhage (IVH), severe retinopathy of prematurity (ROP), patent ductus arteriosus (PDA) requiring treatment, necrotising enterocolitis (NEC), chronic lung disease (CLD) and cholestatic jaundice. Mortality and end organ involvement secondary to systemic candidiasis were identified as adverse outcomes., Results: Of the 757 ELBW neonates, 51 (6.7%) had evidence of systemic candidiasis with a significant 3-fold increase in trend noted in 2007 as compared against 1997 (12.1% vs 3.8%) (RR 1.2, 95% CI, 1.06 to 1.36, P <0.001). This corresponds to a significant increasing trend of preceding or co-existent bacterial blood stream infections (BSI) in neonates with systemic candidiasis (0% in 1997 vs 7.1% in 2007, RR 1.40, 95% CI, 1.04 to 1.25, P = 0.005). On logistic regression analysis, decreasing gestational age was an independent risk factor for systemic candidiasis (OR 2.0, 95% CI, 1.52 to 2.63, P <0.001). Candida meningitis was detected in 4/38 (10.5%) and end organ involvement in 17 (33%). The organisms isolated were Candida parapsilosis 31 (61%), Candida albicans 17 (33%) and Candida glabrata 3 (5.8%). Significantly higher mortality was seen in cases when compared to controls 10/51 (19.6%) vs 76/706 (10.7%) (OR 2.02, 95% CI, 1.02 to 4.40, P <0.001)., Conclusion: Increasing trend in the incidence of systemic candidiasis despite routine use of topical miconazole prophylaxis is of concern and future studies comparing the use of systemic fl uconazole versus oral nystatin may need to be considered.

A prospective cross-sectional study was performed to determine the continuing shift in the molecular epidemiology of meticillin-resistant Staphylococcus aureus (MRSA) in Singapore. In total, 666 MRSA isolates from screening cultures performed between 7 and 20 January 2013 were obtained from all seven public sector hospitals in Singapore and were subjected to molecular typing using multilocus variable-number tandem-repeat fingerprinting with confirmatory multilocus sequencing typing for clustered isolates. Isolates were also tested for the presence of the orfX-ACME insert and the high-level mupirocin resistance gene ileS-2. The major circulating clones in Singaporean hospitals were ST22 (63.2%), ST45 (18.9%) and ST239 (10.7%). The orfX-ACME insert was only found in ST239 isolates (31/71, 43.7%), but ileS-2 was found in 207 (31.1%) of the MRSA isolates, varying between 10.0% and 47.8% among the hospitals. In conclusion, the molecular epidemiology of MRSA in Singaporean hospitals has continued to change, with ST45 now replacing ST239 in addition to the ongoing replacement of the latter by ST22. Although a greater proportion of ST239 isolates carry the orfX-ACME insert, the actual clinical impact may be marginal as ST239 MRSA continues to decline. Finally, high-level mupirocin resistance rates are remarkably high in local healthcare-associated MRSA, with implications for MRSA decolonisation and infection prevention. Further surveillance is required to monitor the changing epidemiological trends., (Copyright © 2013 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

Background: Human metapneumovirus (HMPV) is now a major cause of lower respiratory infection in children. Although primary isolation of HMPV has been achieved in several different cell lines, the low level of virus replication and the subsequent recovery of low levels of infectious HMPV have hampered biochemical studies on the virus. These experimental methodologies usually require higher levels of biological material that can be achieved following HMPV infection. In this study we demonstrate that expression of the HMPV F, G and M proteins in mammalian cells leads to HMPV virus-like particles (VLP) formation. This experimental strategy will serve as a model system to allow the process of HMPV virus assembly to be examined., Methods: The HMPV F, G and M proteins were expressed in mammalian cell lines. Protein cross-linking studies, sucrose gradient centrifugation and in situ imaging was used to examine interactions between the virus proteins. VLP formation was examined using sucrose density gradient centrifugation and electron microscopy analysis., Results: Analysis of cells co-expressing the F, G and M proteins demonstrated that these proteins interacted. Furthermore, in cells co-expression the three HMPV proteins the formation VLPs was observed. Image analysis revealed the VLPs had a similar morphology to the filamentous virus morphology that we observed on HMPV-infected cells. The capacity of each protein to initiate VLP formation was examined using a VLP formation assay. Individual expression of each virus protein showed that the G protein was able to form VLPs in the absence of the other virus proteins. Furthermore, co-expression of the G protein with either the M or F proteins facilitated their incorporation into the VLP fraction., Conclusion: Co-expression of the F, G and M proteins leads to the formation of VLPs, and that incorporation of the F and M proteins into VLPs is facilitated by their interaction with the G protein. Our data suggests that the G protein plays a central role in VLP formation, and further suggests that the G protein may also play a role in the recruitment of the F and M proteins to sites of virus particle formation during HMPV infection.

Introduction: Singapore had its first case of pandemic influenza A (H1N1) 2009 on 26 May 2009. As of 3 August 2009, 440 children with confirmed H1N1were admitted to KK Women's and Children's Hospital (KKH)., Materials and Methods: This is a retrospective case control study of children admitted from 26 May 2009 to 19 July 2009 with H1N1infection. Cases and controls were first differentiated by whether they were complicated or non-complicated in nature, and subsequently analysed with regards to possible independent risk factors., Results: We analysed 143 admitted children; 48 cases and 95 controls (1: 2 ratio). Significant comorbidity was found in 20.3% (n = 29) of patients with the majority having asthma (n = 18, 12.6 %) followed by obesity (n = 7, 4.9%). Binary logistic regression analysis showed risk factors for complicated disease were comorbidity (adjusted OR 6.0, 95% CI, 2.5 to 14.6, P < 0.0001) and age <2 years (adjusted OR 9.8, 95% CI, 2.4 to 40, P = 0.001). Age less than 5 years was not found to be a risk factor., Conclusion: In the early stages of an evolving influenza epidemic when oseltamivir stocks are low, oseltamivir treatment for influenza can be streamlined and offered to those at highest risk who are under 2 years old or have significant comorbidity to prevent complicated disease.

Background: Schools are important foci of influenza transmission and potential targets for surveillance and interventions. We compared several school-based influenza monitoring systems with clinic-based influenza-like illness (ILI) surveillance, and assessed the variation in illness rates between and within schools., Methods: During the initial wave of pandemic H1N1 (pdmH1N1) infections from June to Sept 2009 in Singapore, we collected data on nation-wide laboratory confirmed cases (Sch-LCC) and daily temperature monitoring (Sch-DTM), and teacher-led febrile respiratory illness reporting in 6 sentinel schools (Sch-FRI). Comparisons were made against age-stratified clinic-based influenza-like illness (ILI) data from 23 primary care clinics (GP-ILI) and proportions of ILI testing positive for pdmH1N1 (Lab-ILI) by computing the fraction of cumulative incidence occurring by epidemiological week 30 (when GP-ILI incidence peaked); and cumulative incidence rates between school-based indicators and sero-epidemiological pdmH1N1 incidence (estimated from changes in prevalence of A/California/7/2009 H1N1 hemagglutination inhibition titers ≥ 40 between pre-epidemic and post-epidemic sera). Variation in Sch-FRI rates in the 6 schools was also investigated through a Bayesian hierarchical model., Results: By week 30, for primary and secondary school children respectively, 63% and 79% of incidence for Sch-LCC had occurred, compared with 50% and 52% for GP-ILI data, and 48% and 53% for Sch-FRI. There were 1,187 notified cases and 7,588 episodes in the Sch-LCC and Sch-DTM systems; given school enrollment of 485,723 children, this represented 0.24 cases and 1.6 episodes per 100 children respectively. Mean Sch-FRI rate was 28.8 per 100 children (95% CI: 27.7 to 29.9) in the 6 schools. We estimate from serology that 41.8% (95% CI: 30.2% to 55.9%) of primary and 43.2% (95% CI: 28.2% to 60.8%) of secondary school-aged children were infected. Sch-FRI rates were similar across the 6 schools (23 to 34 episodes per 100 children), but there was widespread variation by classrooms; in the hierarchical model, omitting age and school effects was inconsequential but neglecting classroom level effects led to highly significant reductions in goodness of fit., Conclusions: Epidemic curves from Sch-FRI were comparable to GP-ILI data, and Sch-FRI detected substantially more infections than Sch-LCC and Sch-DTM. Variability in classroom attack rates suggests localized class-room transmission.

Background: In a previous study covering the period 1998-2004, we estimated the incidence of invasive pneumococcal disease (IPD) in Singapore to be 13.6 per 10(5) children aged <5 years, and determined that the 7-valent pneumococcal conjugate vaccine (PCV-7) would provide 78.1% serotype coverage for children aged <5 years. In the present study we sought to determine whether incidence and serotype trends have changed and to estimate pneumococcal vaccine coverage., Methods: We retrospectively reviewed IPD cases from 2005 to 2010 and calculated separate serotype proportions and population-based incidence rates for 2005-2007 (early PCV period) and 2008-2010 (late PCV period). PCV-7 coverage was obtained from the National Immunisation Registry, and patients with PCV-7 vaccine-type IPD (VT IPD) and non-vaccine-type IPD (non-VT IPD) were compared., Results: One hundred and eighteen patients, with a mean age of 46 months, were identified during 2005-2010. The incidence rate of IPD increased to 14.8 (for 2005-2007) and 15.2 (for 2008-2010) per 10(5) children <5 years, despite a gradual increase in PCV-7 coverage to approximately 45% of the birth cohort receiving one or more doses of PCV-7. Although IPD due to serotypes 6B and 19A increased, there was a concomitant reduction in other serotypes. Coverage by PCV-7 progressively declined from 78.6% in 2005-2007 to 64.4% in 2008-2010 for children aged <5 years., Conclusions: Although population coverage with PCV-7 has risen, it remains suboptimal and the incidence of IPD remains unchanged. Furthermore, significant serotype changes (especially increases in 19A) have occurred. We need to adopt newer PCVs with broader serotype coverage and increase the number of children vaccinated as a matter of urgency., (Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Vancomycin-resistant enterococci (VRE) have emerged as one of the major nosocomial antimicrobial-resistant pathogens globally. In this article, we describe the epidemiology of VRE in Singaporean public hospitals in the 5 years following the major local VRE outbreak in 2005., Materials and Methods: A passive laboratory surveillance programme identified non-duplicate VRE isolates from 7 hospitals from 2006 to 2010. Descriptive statistics and time-series analysis was performed on all clinical VRE isolates for each individual hospital as well as for the combined dataset., Results: There were a total of 418 VRE isolates over 5 years, of which 102 isolates (24.4%) were from clinical cultures. Between 0.4% and 0.7% of all clinical enterococcal isolates were resistant to vancomycin. The overall incidence-density of VRE did not change over time in Singapore despite 2 separate outbreaks in tertiary hospitals in 2009 and 2010. Incidence-density of clinical VRE cases fell in 2 secondary hospitals, while another 2 hospitals experienced no significant VRE infections after 2008., Conclusion: The prevalence of VRE clinical isolates remains low in Singaporean public sector hospitals. However, the presence of at least 2 outbreaks in separate hospitals over the past 5 years indicates the need for continued vigilance in order to prevent any further increase in VRE prevalence locally.

Background: Clostridium difficile is the major cause of pseudomembranous colitis associated with antibiotic use, and the spread of the hypervirulent epidemic ribotype 027/NAP-1 strain across hospitals worldwide has re-focused attention on this nosocomial pathogen. The overall incidence and trend of C. difficile-associated disease (CDAD) in Singapore is unknown, and a surveillance program to determine these via formal laboratory-based reporting was established., Findings: Laboratory and pharmacy data were collated from one tertiary and two secondary hospitals on a quarterly basis between 2006 and 2008. All hospitals tested for C. difficile using Immunocard Toxins A&B (Meridian Bioscience Inc., Cincinnati, OH) during this period. Duplicate positive C. difficile results within a 14-day period were removed. The CDAD results were compared with trends in hospital-based prescription of major classes of antibiotics.Overall CDAD incidence-density decreased from 5.16 (95%CI: 4.73 - 5.62) cases per 10,000 inpatient-days in 2006 to 2.99 (95%CI: 2.67 to 3.33) cases per 10,000 inpatient-days in 2008 (p < 0.001), while overall rates for C. difficile testing increased significantly (p < 0.001) within the same period. These trends were mirrored at the individual hospital level. Evaluation of antibiotic prescription data at all hospitals showed increasing use of carbapenems and fluoroquinolones, while cephalosporin and clindamycin prescription remained stable., Conclusions: Our results demonstrate a real decline of CDAD rates in three large local hospitals. The cause is unclear and is not associated with improved infection control measures or reduction in antibiotic prescription. Lack of C. difficile stool cultures as part of routine testing precluded determination of the decline of a major clone as a potential explanation. For more accurate epidemiological trending of CDAD and early detection of epidemic clones, data collection will have to be expanded and resources set in place for reference laboratory culture and typing.

Background: Influenza can produce significant complications in immunocompromised persons., Methods: We studied the effects of the pandemic (H1N1) 2009 (pH1N1) infection on solid organ transplant recipients in our hospital, with emphasis on clinical information, duration of viral culture positivity, polymerase chain reaction positivity, effects of oseltamivir therapy, and graft status at 6 months of follow-up., Results: Twenty-two cases of pH1N1 infection involving 18 renal, two lung, one heart, and one liver transplant recipients were seen from July 14 to September 8, 2009. Their median age was 50.5 years (range 20-70 years); 64% were women, and median time posttransplant was 40 months (range 6-204 months). Common symptoms were fever (86%), cough (77%), sore throat (55%), phlegm (32%), and myalgia (27%). The median duration of symptoms (n=21) and duration of polymerase chain reaction positivity (n=15) were 7 (range 4-13 days) and 8 days (range 4-16 days), respectively. Mean (± SD) duration of symptom resolution (7.4 ± 3.0 vs. 7.8 ± 3.0 days, P=0.76) and viral culture positivity (5.3 ± 2.8 vs. 4.3 ± 3.2 days, P=0.65) did not differ between those who received a 5-day (n=9) or 10-day (n=12) course of oseltamivir. Five patients (22.7%) developed pneumonia with three needing intensive care. Mortality rate was 4.5% (1/22). At 6 months, three graft rejections involving two renal and one lung developed., Conclusions: Our findings indicate that the pH1N1 infection in solid organ transplant recipients is associated with some degree of morbidity and may affect the function of the transplanted organ. In this nonrandomized comparison, patients treated with 5 days of oseltamivir did not fare worse compared with those who received 10 days.

Various studies have documented a shift in species distribution in Candida bloodstream infections (BSI), but there are little data from Southeast Asia. This study was performed to determine the species epidemiology and antifungal susceptibilities of Candida species BSI in Singapore. Candida spp. from BSI were collected from a tertiary and secondary referral hospital, and an obstetrics/paediatric hospital over a 3-year period. The most common isolates were Candida albicans (36%), Candida tropicalis (27%), Candida glabrata (16%) and Candida parapsilosis (16%). Candida parapsilosis and C. albicans were predominant in the paediatric hospital, and C. albicans and C. tropicalis predominant in the other two institutions. Candida tropicalis temporarily replaced C. albicans as the predominant strain from BSI in 2006. Overall, 87.3% of Candida isolates were susceptible to fluconazole, and 10.4% classified as susceptible-dose-dependent. Fluconazole resistance was detected in C. tropicalis (3.6%), C. parapsilosis (2.1%) and C. glabrata (4.0%). Candida albicans is the predominant species isolated from BSI in Singapore. However, non-albicans species accounted for nearly two-thirds of all cases of candidaemia and the relative increase in C. tropicalis infections deserves further investigation. Resistance to fluconazole was uncommon., (© 2009 Blackwell Verlag GmbH.)

Relatively few international comparisons of the incidence of influenza related to climate parameters have been performed, particularly in the Eastern hemisphere. In this study, the incidence of influenza and climate data such as temperature, relative humidity, and rainfall, from cities at different latitudes with contrasting climates: Singapore, Hong Kong (China), Ulaanbaatar (Mongolia), Vancouver (Canada), and three Australian cities (Brisbane, Melbourne and Sydney) were examined to determine whether there was any overall relationship between the incidence of influenza and climate. Applying time-series analyses to the more comprehensive datasets, it was found that relative humidity was associated with the incidence of influenza A in Singapore, Hong Kong, Brisbane, and Vancouver. In the case of influenza B, the mean temperature was the key climate variable associated with the incidence of influenza in Hong Kong, Brisbane, Melbourne, and Vancouver. Rainfall was not significantly correlated with the incidence of influenza A or B in any of these cities., (© 2010 Wiley-Liss, Inc.)

Introduction: Influenza A H1N1 (2009) pandemic has affected countries worldwide including Singapore. Data on obstetric outcomes of women with H1N1 (2009) in pregnancy are lacking., Materials and Methods: This was an observational study analysing the obstetric outcomes of pregnant women with influenza A H1N1 (2009) infection who had delivered at a viable gestation (24 weeks or more) in our centre., Results: Between 23 June 2009 and 30 September 2009, 235 pregnant women were diagnosed with influenza A H1N1 (2009) at our centre, with 42 having delivered and comprising the study cohort. Median age was 27.5 years (range, 16 to 42). Multiparous women comprised 59.5% (25/42) whilst 40.5% (17/42) were primiparous. In terms of ethnicity, 61.9% were Malays, 26.2% Chinese, 4.8% Indians and 7.1% Others. All women received oseltamivir. All had shown recovery from the acute influenza infection. There were no respiratory complications. Twenty-nine women (69.0%) delivered at term. Twenty-fi ve women (59.5%) had spontaneous labour whilst 15 (35.7%) had labour induction. Two women (4.8%) did not labour. Thirty-six women (85.7%) had vaginal delivery, of whom 3 were instrumental deliveries. Apgar scores of greater than 8 at 1 min and 5 min were documented in babies of 95.2% (40/42) women, respectively. Thirty-two women (76.2%) delivered babies with birthweights greater than 2500 g. Compared with historical data from 2008, the H1N1 cohort had comparable mean birthweight and average gestational age at delivery of 38 weeks., Conclusion: Our study suggested that obstetric outcomes were not adversely affected by influenza A H1N1 (2009) infection.

Human bocavirus (HBoV) is a parvovirus, belonging to the genus Bocavirus. The virus was identified recently in Sweden, and has now been detected in several different countries. Although it is associated with lower respiratory tract infections in pediatric patients, the incidence of HBoV infection in a developed country in South East Asia, has not been examined. The objective of this study was to determine the importance of HBoV as a cause of lower respiratory tract infections among children admitted to hospital in Singapore. Five hundred nasopharyngeal swabs were collected from anonymized pediatric patients admitted to the Kandang Kerbau Women's and Children's Hospital for acute respiratory infections. The specimens were tested for the presence of HBoV using polymerase chain reactions. HBoV was detected in 8.0% of the patients tested, and a majority of these HBoV patients exhibited lower respiratory tract infections. A significant level of coinfection with respiratory syncytial viruses and rhinoviruses was also observed in these HBoV patients. The data suggest that HBoV is an important cause of lower respiratory tract infections among children admitted to hospital in Singapore, and is the first study examining the incidence of HBoV infection in a developed country in South East Asia.

Introduction: Worldwide, Candida albicans is the most common Candida species implicated in bloodstream infections. However, the proportion of non-albicans bloodstream infections is increasing. Fluconazole resistance is known to be more common in non-albicans species, but is also reported in C. albicans. This retrospective study was performed to determine the species epidemiology of Candida bloodstream infections in Singapore hospitals, and to perform susceptibility testing to a range of antifungal drugs., Materials and Methods: Candida spp. isolated from bloodstream infections from October 2004 to December 2006 were collected from 3 participating hospitals: a tertiary referral hospital (Singapore General Hospital), a secondary referral hospital (Changi General Hospital) and an obstetrics/paediatric hospital [KK Women's and Children's Hospital (KKWCH)]. Isolate collection was also retrospectively extended to January 2000 for KKWCH because of the limited number of cases from this hospital. Isolates were identified by a common protocol, and antifungal susceptibility testing was performed by microbroth dilution (Sensititre One, Trek Diagnostics, United Kingdom)., Results: The most common isolates were C. albicans (37%), C. tropicalis (27%) and C. glabrata (16%). There were differences in species distribution between institutions, with C. parapsilosis and C. albicans predominant in KKWCH, and C. albicans and C. tropicalis predominant in the other 2 institutions. Fluconazole resistance was detected in 3.2% of all Candida spp., and 85.3% were classified as susceptible. All C. albicans and C. parapsilosis were susceptible to fluconazole and voriconazole, while susceptibility to fluconazole was much more variable for C. glabrata and C. krusei., Conclusion: This study shows that C. albicans remains the predominant Candida species isolated from bloodstream infections in the 3 participating hospitals. However, non-albicans species accounted for nearly two-thirds of all cases of candidaemia. Resistance to fluconazole was uncommon, and was generally confined to C. krusei and C. glabrata.

Introduction: Antibiotic resistance in gram-negative bacilli is an area of increasing importance. This prospective study was performed to survey antibiotic resistance in Escherichia coli (E. coli), Klebsiella spp., Pseudomonas aeruginosa and Acinetobacter spp. over a 1-year period., Materials and Methods: Non-duplicate isolates of E. coli, Klebsiella spp., P. aeruginosa and Acinetobacter spp. were collected from participating Singapore hospitals during defined collection periods in 2006 and 2007. Confirmatory identification and antibiotic susceptibility testing were performed at Changi General Hospital. Minimum inhibitory concentrations (MIC) to a defined panel of antibiotics were determined using microbroth dilution methods. The presence of extended-spectrum beta lactamases and AmpC beta-lactamases in Enterobacteriaceae was determined by phenotypic methods, and susceptibility results were defined using current breakpoints from the Clinical Laboratory Standards Institute (CLSI)., Results: Seven hundred and forty-six gram-negative bacilli were received for testing. Resistance to extended-spectrum cephalosporins was present in a third of Enterobacteriaceae isolates, and extended-spectrum beta-lactamases (ESBL) carriage was present in 19.6% and 30.1% of E. coli and Klebsiella pneumoniae, respectively. AmpC enzymes were also detected in 8.5% and 5.6% of E. coli and K. pneumoniae isolates respectively. All Enterobacteriaceae were susceptible to imipenem and meropenem. The most active antibiotics against P. aeruginosa were amikacin, meropenem and piperacillin-tazobactam. A third of P. aeruginosa showed reduced susceptibility to polymyxin B. Carbapenem resistance was significantly higher in Acinetobacter baumannii (70.5%) than in other Acinetobacter species (25.0%). The most active antibiotic against A. baumannii was polymyxin B., Conclusion: Antibiotic resistance is prevalent in gram-negative bacilli isolated from Singapore hospitals. The MIC testing surveillance programme complemented susceptibility data from wider laboratory-based surveillance, and has revealed emerging mechanisms of antibiotic resistance.

Introduction: Influenza vaccine has been shown to be highly effective in temperate regions with well-defined seasonal influenza. Healthcare workers (HCWs) are advised to receive regular influenza vaccination to protect themselves and their patients. However, there are limited data on the efficacy of influenza vaccine in HCWs in the tropics., Materials and Methods: In this observational, investigator blinded cohort study, bi-monthly questionnaires recording influenza-like illness (ILI) episodes and medical leave were administered to 541 HCWs at the Singapore National University Hospital and KK Women's and Children's Hospital from 2004 to 2005. ILI was defined according to a standard symptom score., Results: Baseline characteristics were comparable in both the vaccinated and non-vaccinated groups. Overall, the relative risk of self-reported ILI in vaccinated HCWs was 1.13 [95% confidence interval (CI), 0.98-1.13; P=0.107]; medical leave taken was lower in the vaccinated group [mean 0.26+/-0.6 days per visit, compared with 0.30+/-0.5 days in the non-vaccinated group (P=0.40)]. Because of the reported Northern Hemisphere 2003/04 vaccine mismatch, we stratified the cohort and determined that the group which received a matched vaccine had a relative risk of ILI of 0.49 (95% CI, 0.37-0.66; P<0.001), achieving a vaccine efficacy of 51%. Mean medical leave decreased significantly in HCWs who received the matched vaccine, compared with those who did not receive vaccination (0.13+/-0.3 vs 0.30+/-0.5; P<0.001) and with HCWs vaccinated with mismatched strains (0.13+/-0.3 vs 0.39+/-0.9; P=0.01)., Conclusions: A well-matched influenza vaccine is effective in preventing ILI and reducing sickness absence in healthcare workers in tropical settings. Efforts need to be made to increase influenza vaccination rates and to improve the currently available vaccines.

Four hundred specimens were collected from pediatric patients hospitalized in Singapore; 21 of these specimens tested positive for human metapneumovirus (HMPV), with the A2 genotype predominating. A 5% infection rate was estimated, suggesting that HMPV is a significant cause of morbidity among the pediatric population of Singapore.

The aim of this study was to determine the extent of EMRSA-15 spread in hospitals in Singapore. Molecular analysis of 197 non-duplicate meticillin-resistant Staphylococcus aureus (MRSA) isolates collected from five acute care public hospitals in Singapore in May 2005 revealed that 66 (33.5%) were EMRSA-15 while 121 (61.4%) belonged to the endemic multidrug-resistant ST239 clone. Median and mode vancomycin MIC for both major clones of health-care-associated MRSA were relatively high at 2.0 microg ml-1. Subsequent laboratory surveillance data collected from the first half of 2006 confirmed increasing numbers of the EMRSA-15 clone--ranging from 25.0 to 66.1% of all MRSA isolated in local hospitals--replacing the ST239 clone island-wide.

A 78-year-old retired pig farmer developed brucellosis and died of liver failure >20 years after her last exposure to infected livestock. This is an exceptionally long incubation period for this infection, which usually presents within weeks of exposure.

Nocardia, a gram positive variably acid-fast aerobic bacterium is an opportunistic pathogen in immunocompromised hosts. We present 5 cases of nocardiosis in patients with systemic lupus erythematosus. We emphasize the clinical features, radiologic findings, and antibiotic sensitivity. Lung involvement was the predominant manifestation; others include brain abscess, retinitis, thyroiditis, and diaphragmatic infiltration. We describe the first cases of pulmonary nocardiosis presenting as pneumothorax and the use of fine needle aspiration cytology in diagnosing nocardial thyroiditis.

We studied the clinical spectrum, serotypes and antimicrobial resistance of Haemophilus influenzae received by our laboratory. The majority of cases involved the elderly (more than 60 years old) and children under the age of 5 years. Most infections involved the respiratory tract and were caused by non-serotypable strains. Invasive infections (meningitis, septic arthritis and bacteraemia) were infrequent and were caused by both type b and non-serotypable strains. The estimated incidence of invasive Haemophilus influenzae type b disease in children under the age of 5 years is at most 5 per 100 000 a year. Resistance to ampicillin (40.5%) and trimethoprim-sulfa (37.7%) was high and would affect the choice of antimicrobials used for treating Haemophilus influenzae infections.