- [Show abstract] [Hide abstract] ABSTRACT: Objectives Owing to gene transposition and plasmid conjugation, New Delhi metallo-β-lactamase (NDM) is typically identified among varied Enterobacteriaceae species and STs. We used WGS to characterize the chromosomal and plasmid molecular epidemiology of NDM transmission involving four institutions in Singapore. Methods Thirty-three Enterobacteriaceae isolates (collection years 2010–14) were sequenced using short-read sequencing-by-synthesis and analysed. Long-read single molecule, real-time sequencing (SMRTS) was used to characterize genetically a novel plasmid pSg1-NDM carried on Klebsiella pneumoniae ST147. Results In 20 (61%) isolates, blaNDM was located on the pNDM-ECS01 plasmid in the background of multiple bacterial STs, including eight K. pneumoniae STs and five Escherichia coli STs. In six (18%) isolates, a novel blaNDM-positive plasmid, pSg1-NDM, was found only in K. pneumoniae ST147. The pSg1-NDM–K. pneumoniae ST147 clone (Sg1-NDM) was fully sequenced using SMRTS. pSg1-NDM, a 90 103 bp IncR plasmid, carried genes responsible for resistance to six classes of antimicrobials. A large portion of pSg1-NDM had no significant homology to any known plasmids in GenBank. pSg1-NDM had no conjugative transfer region. Combined chromosomal–plasmid phylogenetic analysis revealed five clusters of clonal bacterial NDM-positive plasmid transmission, of which two were inter-institution clusters. The largest inter-institution cluster involved six K. pneumoniae ST147-pSg1-NDM isolates. Fifteen patients were involved in transmission clusters, of which four had ward contact, six had hospital contact and five had an unknown transmission link. Conclusions A combined sequencing-by-synthesis and SMRTS approach can determine effectively the transmission clusters of blaNDM and genetically characterize novel plasmids. Plasmid molecular epidemiology is important to understanding NDM spread as blaNDM-positive plasmids can conjugate extensively across species and STs.
- [Show abstract] [Hide abstract] ABSTRACT: Introduction: Determining the optimal time to vaccinate is important for influenza vaccination programmes. Here, we assessed the temporal characteristics of influenza epidemics in the Northern and Southern hemispheres and in the tropics, and discuss their implications for vaccination programmes. Methods: This was a retrospective analysis of surveillance data between 2000 and 2014 from the Global Influenza B Study database. The seasonal peak of influenza was defined as the week with the most reported cases (overall, A, and B) in the season. The duration of seasonal activity was assessed using the maximum proportion of influenza cases during three consecutive months and the minimum number of months with ≥80% of cases in the season. We also assessed whether co-circulation of A and B virus types affected the duration of influenza epidemics. Results: 212 influenza seasons and 571,907 cases were included from 30 countries. In tropical countries, the seasonal influenza activity lasted longer and the peaks of influenza A and B coincided less frequently than in temperate countries. Temporal characteristics of influenza epidemics were heterogeneous in the tropics, with distinct seasonal epidemics observed only in some countries. Seasons with co-circulation of influenza A and B were longer than influenza A seasons, especially in the tropics. Discussion: Our findings show that influenza seasonality is less well defined in the tropics than in temperate regions. This has important implications for vaccination programmes in these countries. High-quality influenza surveillance systems are needed in the tropics to enable decisions about when to vaccinate.
Dataset: S1 File
- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: Studies of influenza-associated hospitalizations in tropical settings are lacking. To increase understanding of the effect of influenza in Singapore, we estimated the age-specific influenza-associated hospitalizations for pneumonia and influenza during 2004-2008 and 2010-2012. The rate of hospitalization was 28.3/100,000 person-years during 2004-2008 and 29.6/100,000 person-years during 2010-2012. The age-specific influenza-associated hospitalization rates followed a J-shaped pattern: rates in persons >75 years of age and in children <6 months of age were >47 times and >26 times higher, respectively, than those for persons 25-44 years of age. Across all ages during these 2 study periods, ≈12% of the hospitalizations for pneumonia and influenza were attributable to influenza. The rates and proportions of hospitalizations for influenza, particularly among the very young and the elderly, are considerable in Singapore and highlight the importance of vaccination in protecting populations at risk.
- [Show abstract] [Hide abstract] ABSTRACT: Patients with neutropenic fever after 4-7 days of broad-spectrum antibiotics are given antifungals empirically. This strategy may lead to over-treatment. Patients with hematological malignancies undergoing intensive chemotherapy or hematopoietic stem cell transplantation were randomized to two arms. Patients in the 'preemptive' arm had regular galactomannan (GM) assays, and received caspofungin, amphotericin or voriconazole (CAV) for persistent febrile neutropenia if they had two positive GM results, or a positive GM result and a computed tomography (CT) of the thorax suggestive of invasive pulmonary aspergillosis (IPA). Patients in the 'empirical' arm received CAV in accordance with established guidelines. Of 27 episodes in the preemptive arm, two cases of IPA were picked up by monitoring. In six episodes, CAV was started despite persistently negative GM readings. One additional patient received CAV for a false-positive GM. Of 25 episodes in the empirical arm, CAV was started empirically in 10, one of whom had CT features of IPA. By intent-to-treat and evaluable-episode analyses, respectively, the preemptive approach saved 11% and 14% of patients from empirical antifungals. Twelve-week survival was 85.2% in the preemptive arm and 84% in the empirical arm. A preemptive approach may reduce empirical antifungal use without compromising survival in persistently febrile neutropenic patients.
- [Show abstract] [Hide abstract] ABSTRACT: To the Editor: In the past few years, several publications have reported that Internet search queries may usefully supplement other, traditional surveillance programs for infectious diseases (1-3). The philanthropic arm of Google offers Flu Trends, a site that provides up-to-date estimates of influenza activity in 20 countries of the Pacific Rim and Europe (4) by using data mining techniques to find good predictors of historic influenza indicators (1).
Dataset: Video S3[Show abstract] [Hide abstract] ABSTRACT: Animation of forecast proportion of population infected or recovered, including those not seeking medical attention. Note the change in scale on the y-axis. (0.50 MB SWF)
- [Show abstract] [Hide abstract] ABSTRACT: Reporting of influenza-like illness (ILI) from general practice/family doctor (GPFD) clinics is an accurate indicator of real-time epidemic activity and requires little effort to set up, making it suitable for developing countries currently experiencing the influenza A (H1N1-2009) pandemic or preparing for subsequent epidemic waves. We established a network of GPFDs in Singapore. Participating GPFDs submitted returns via facsimile or e-mail on their work days using a simple, standard data collection format, capturing: gender; year of birth; "ethnicity"; residential status; body temperature (degrees C); and treatment (antiviral or not); for all cases with a clinical diagnosis of an acute respiratory illness (ARI). The operational definition of ILI in this study was an ARI with fever of 37.8 degrees C or more. The data were processed daily by the study co-ordinator and fed into a stochastic model of disease dynamics, which was refitted daily using particle filtering, with data and forecasts uploaded to a website which could be publicly accessed. Twenty-three GPFD clinics agreed to participate. Data collection started on 2009-06-26 and lasted for the duration of the epidemic. The epidemic appeared to have peaked around 2009-08-03 and the ILI rates had returned to baseline levels by the time of writing. This real-time surveillance system is able to show the progress of an epidemic and indicates when the peak is reached. The resulting information can be used to form forecasts, including how soon the epidemic wave will end and when a second wave will appear if at all.
Dataset: Video S1[Show abstract] [Hide abstract] ABSTRACT: Animation of forecast average ILI per GPFD per day. Note the change in scale on the y-axis. (0.81 MB SWF)
Dataset: Video S2[Show abstract] [Hide abstract] ABSTRACT: Animation of forecast total nationwide ILI cases seeking medical attention. The day of week effect has been removed for clarity by treating all days as being Mondays. Note the change in scale on the y-axis. (0.48 MB SWF)
Dataset: Figure S1
- [Show abstract] [Hide abstract] ABSTRACT: The antimicrobial activities of tetracycline, mupirocin, and fusidic acid are tested in combination with Epicatechin Gallate (ECG), and Ethyl Gallate (EG) using 2 Methicillin resistant (MRSA) and 2 Methicillin sensitive (MSSA) strains of Staphylococcus aureus. Sub-inhibitory concentration of EG at 256 mg l-1 is found to be synergistic when used in combination with tetracycline, mupirocin, and fusidic acid; and a sub-inhibitory concentration of ECG at 32 mg l-1 is found to be synergistic with tetracycline in all the four Staphylococcus aureus strains tested. The synergistic combinations reduce the MICs of all the above three antibiotics by 4 fold. Combining ECG at 32 mg l-1 with mupirocin, reduces the MIC of mupirocin by four fold in MSSA C1 strain. 74 per cent of the combinations show consistent results in both time-kill assay and checkerboard method. The identified combinations may lead towards novel therapeutic interventions for treating MRSA infections.