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Search Results: 1 - 10 of 31348 matches for " Lee Ching Ng "
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Challenges in dengue surveillance and control
Lee Ching Ng
Western Pacific Surveillance and Response , 2011,
Abstract: Globally, the challenge posed by dengue has escalated at an astonishing rate in the last three decades, with no sign of abating. It is estimated that dengue affects at least 50 million – 100 million people every year. With more than 120 dengue-endemic countries, 3.6 billion people are at risk of infection. More than 70% of those at risk reside in the Asia Pacific region, making this region an epicentre of dengue activity.In addition to making a comeback in places such as the Americas and Singapore, where dengue was previously successfully controlled for decades, the virus has also breached the subtropical-temperate barrier as it claims new territories. In the last decade, dengue transmission has extended its reach into places as far north as Nepal, Ningbo in China and France, and as far south as Bueno Aires in Argentina. The Pacific islands, with much lower population densities, have also not been spared, with increasing dengue outbreaks since the 1970s.The direct economic and social impact of dengue on dengue-endemic regions is high,9–12 and the burden in other aspects such as the security of blood supplies is increasingly being recognized. Dengue’s threat to travellers has also been systematically demonstrated by a 2008 study on 6957 travellers who returned ill and sought treatment from EuroTravNet centres. Of those travellers, 1.9% were diagnosed with dengue, and one of the three deaths reported was due to dengue shock syndrome.
Evaluation of Pathogen Reduction Systems to Inactivate Dengue and Chikungunya Viruses in Apheresis Platelets Suspended in Plasma  [PDF]
Li Kiang Tan, Sally Lam, Swee Ling Low, Fang Hui Tan, Lee Ching Ng, Diana Teo
Advances in Infectious Diseases (AID) , 2013, DOI: 10.4236/aid.2013.31001

The risk of blood-borne transmission of infectious diseases has led to an increasing awareness of the need for a safe and effective pathogen reduction technology. This study evaluated the efficacy of 2 pathogen reduction systems to inactivate dengue virus (DENV-2) and chikungunya virus (CHIKV) spiked into apheresis platelets (APLT) concentrates. Double-dose APLT collections (n = 3) were split evenly into two units and spiked with 107 infectious units of DENV-2 or CHIKV. APLTs samples were assayed for viral infectivity before and after Amotosalen photochemical treatment (PCT) or Riboflavin pathogen reduction treatment (PRT). Viral infectivity was determined by plaque assays. Platelet (PLT) count, pH and residual S-59 were measured during the storage of 5 days. Amotosalen PCT showed robust efficacy and complete inactivation of both viruses in APLTs, with up to 3.01 and 3.75 log reductions of DENV-2 and CHIKV respectively. At similar initial concentrations, Riboflavin PRT showed complete inactivation of CHIKV with up to 3.73 log reduction, much higher efficacy than against DENV-2 where a log reduction of up to 1.58 was observed. All post-treated APLTs maintained acceptable PLT yields and quality parameters. This parallel study of 2 pathogen reduction systems demonstrates their efficacy in inactivating or reducing DENV and CHIKV in APLTs and reaffirms the usefulness of pathogen inactivation systems to ensure the safety in PLTs transfusion.

Optimal Lead Time for Dengue Forecast
Yien Ling Hii ,Joacim Rockl?v,Stig Wall,Lee Ching Ng,Choon Siang Tang,Nawi Ng
PLOS Neglected Tropical Diseases , 2012, DOI: 10.1371/journal.pntd.0001848
Abstract: Background A dengue early warning system aims to prevent a dengue outbreak by providing an accurate prediction of a rise in dengue cases and sufficient time to allow timely decisions and preventive measures to be taken by local authorities. This study seeks to identify the optimal lead time for warning of dengue cases in Singapore given the duration required by a local authority to curb an outbreak. Methodology and Findings We developed a Poisson regression model to analyze relative risks of dengue cases as functions of weekly mean temperature and cumulative rainfall with lag times of 1–5 months using spline functions. We examined the duration of vector control and cluster management in dengue clusters > = 10 cases from 2000 to 2010 and used the information as an indicative window of the time required to mitigate an outbreak. Finally, we assessed the gap between forecast and successful control to determine the optimal timing for issuing an early warning in the study area. Our findings show that increasing weekly mean temperature and cumulative rainfall precede risks of increasing dengue cases by 4–20 and 8–20 weeks, respectively. These lag times provided a forecast window of 1–5 months based on the observed weather data. Based on previous vector control operations, the time needed to curb dengue outbreaks ranged from 1–3 months with a median duration of 2 months. Thus, a dengue early warning forecast given 3 months ahead of the onset of a probable epidemic would give local authorities sufficient time to mitigate an outbreak. Conclusions Optimal timing of a dengue forecast increases the functional value of an early warning system and enhances cost-effectiveness of vector control operations in response to forecasted risks. We emphasize the importance of considering the forecast-mitigation gaps in respective study areas when developing a dengue forecasting model.
Forecast of Dengue Incidence Using Temperature and Rainfall
Yien Ling Hii ,Huaiping Zhu,Nawi Ng,Lee Ching Ng,Joacim Rockl?v
PLOS Neglected Tropical Diseases , 2012, DOI: 10.1371/journal.pntd.0001908
Abstract: Introduction An accurate early warning system to predict impending epidemics enhances the effectiveness of preventive measures against dengue fever. The aim of this study was to develop and validate a forecasting model that could predict dengue cases and provide timely early warning in Singapore. Methodology and Principal Findings We developed a time series Poisson multivariate regression model using weekly mean temperature and cumulative rainfall over the period 2000–2010. Weather data were modeled using piecewise linear spline functions. We analyzed various lag times between dengue and weather variables to identify the optimal dengue forecasting period. Autoregression, seasonality and trend were considered in the model. We validated the model by forecasting dengue cases for week 1 of 2011 up to week 16 of 2012 using weather data alone. Model selection and validation were based on Akaike's Information Criterion, standardized Root Mean Square Error, and residuals diagnoses. A Receiver Operating Characteristics curve was used to analyze the sensitivity of the forecast of epidemics. The optimal period for dengue forecast was 16 weeks. Our model forecasted correctly with errors of 0.3 and 0.32 of the standard deviation of reported cases during the model training and validation periods, respectively. It was sensitive enough to distinguish between outbreak and non-outbreak to a 96% (CI = 93–98%) in 2004–2010 and 98% (CI = 95%–100%) in 2011. The model predicted the outbreak in 2011 accurately with less than 3% possibility of false alarm. Significance We have developed a weather-based dengue forecasting model that allows warning 16 weeks in advance of dengue epidemics with high sensitivity and specificity. We demonstrate that models using temperature and rainfall could be simple, precise, and low cost tools for dengue forecasting which could be used to enhance decision making on the timing, scale of vector control operations, and utilization of limited resources.
Use of Saliva for Early Dengue Diagnosis
Grace Yap equal contributor,Bijon Kumar Sil equal contributor,Lee-Ching Ng
PLOS Neglected Tropical Diseases , 2011, DOI: 10.1371/journal.pntd.0001046
Abstract: Background The necessity of a venous blood collection in all dengue diagnostic assays and the high cost of tests that are available for testing during the viraemic period hinder early detection of dengue cases and thus could delay cluster management. This study reports the utility of saliva in an assay that detects dengue virus (DENV)–specific immunoglobulin A (Ig A) early in the phase of a dengue infection. Methods and Findings Using an antigen capture anti-DENV IgA (ACA) ELISA technique, we tested saliva samples collected from dengue-confirmed patients. The sensitivity within 3 days from fever onset was over 36% in primary dengue infections. The performance is markedly better in secondary infections, with 100% sensitivity reported in saliva samples from day 1 after fever onset. Serum and salivary IgA levels showed good correlation (Pearson's r = 0.69, p<0.001). Specificity was found to be 97%. Conclusion Our findings suggest that this technique would be very useful in dengue endemic regions, where the majority of dengue cases are secondary. The ACA-ELISA is easy to perform, cost effective, and especially useful in laboratories without sophisticated equipment. Our findings established the usefulness and reliability of saliva for early dengue diagnosis.
Epidemiological characteristics of the 2005 and 2007 dengue epidemics in Singapore - similarities and distinctions
Teck Siang Ler,Li Wei Ang,Grace Siew Lian Yap,Lee Ching Ng
Western Pacific Surveillance and Response , 2011,
Abstract: Introduction: We investigated the epidemiological features of the 2007 dengue outbreak to determine the factors that could have triggered it two years after the previous large outbreak in 2005.Methods: All laboratory-confirmed cases of dengue reported during the year, as well as entomological and virological data, were analysed.Results: A total of 8826 cases including 24 deaths were reported in 2007, giving an incidence of 192.3 cases per 100 000 residents and a case-fatality rate of 0.27%. The median age of the cases was 37 years (interquartile range 25 to 50), with an age range from two days to 101 years, which was higher than the median age of 31 years (interquartile range 20 to 42), with a range from four days to 98 years, in 2005. The overall Aedes premises index in 2007 was 0.68%, lower than the 1.15% observed in 2005. The predominant dengue serotype in 2007 was dengue virus DENV-2 which re-emerged with a clade replacement in early 2007, and overtook the predominant serotype (DENV-1) of 2005. Seroprevalence studies conducted in the three largest outbreak clusters revealed that 73.2% of residents with recent infection were asymptomatic.Discussion: With the exception of an increase in the median age of the cases, and a change in the predominant dengue serotype, the epidemiological features of the 2007 epidemic were largely similar to those of 2005. Singapore remains vulnerable to major outbreaks of dengue, despite sustained vector control measures to maintain a consistently low Aedes premises index.
Mechanisms of Pyrethroid Resistance in the Dengue Mosquito Vector, Aedes aegypti: Target Site Insensitivity, Penetration, and Metabolism
Shinji Kasai ,Osamu Komagata,Kentaro Itokawa,Toshio Shono,Lee Ching Ng,Mutsuo Kobayashi,Takashi Tomita
PLOS Neglected Tropical Diseases , 2014, DOI: 10.1371/journal.pntd.0002948
Abstract: Aedes aegypti is the major vector of yellow and dengue fevers. After 10 generations of adult selection, an A. aegypti strain (SP) developed 1650-fold resistance to permethrin, which is one of the most widely used pyrethroid insecticides for mosquito control. SP larvae also developed 8790-fold resistance following selection of the adults. Prior to the selections, the frequencies of V1016G and F1534C mutations in domains II and III, respectively, of voltage-sensitive sodium channel (Vssc, the target site of pyrethroid insecticide) were 0.44 and 0.56, respectively. In contrast, only G1016 alleles were present after two permethrin selections, indicating that G1016 can more contribute to the insensitivity of Vssc than C1534. In vivo metabolism studies showed that the SP strain excreted permethrin metabolites more rapidly than a susceptible SMK strain. Pretreatment with piperonyl butoxide caused strong inhibition of excretion of permethrin metabolites, suggesting that cytochrome P450 monooxygenases (P450s) play an important role in resistance development. In vitro metabolism studies also indicated an association of P450s with resistance. Microarray analysis showed that multiple P450 genes were over expressed during the larval and adult stages in the SP strain. Following quantitative real time PCR, we focused on two P450 isoforms, CYP9M6 and CYP6BB2. Transcription levels of these P450s were well correlated with the rate of permethrin excretion and they were certainly capable of detoxifying permethrin to 4′-HO-permethrin. Over expression of CYP9M6 was partially due to gene amplification. There was no significant difference in the rate of permethrin reduction from cuticle between SP and SMK strains.
Mosquito Cellular Factors and Functions in Mediating the Infectious entry of Chikungunya Virus
Regina Ching Hua Lee,Hapuarachchige Chanditha Hapuarachchi,Karen Caiyun Chen,Khairunnisa' Mohamed Hussain,Huixin Chen,Swee Ling Low,Lee Ching Ng,Raymond Lin,Mary Mah-Lee Ng,Justin Jang Hann Chu
PLOS Neglected Tropical Diseases , 2013, DOI: 10.1371/journal.pntd.0002050
Abstract: Chikungunya virus (CHIKV) is an arthropod-borne virus responsible for recent epidemics in the Asia Pacific regions. A customized gene expression microarray of 18,760 transcripts known to target Aedes mosquito genome was used to identify host genes that are differentially regulated during the infectious entry process of CHIKV infection on C6/36 mosquito cells. Several genes such as epsin I (EPN1), epidermal growth factor receptor pathway substrate 15 (EPS15) and Huntingtin interacting protein I (HIP1) were identified to be differentially expressed during CHIKV infection and known to be involved in clathrin-mediated endocytosis (CME). Transmission electron microscopy analyses further revealed the presence of CHIKV particles within invaginations of the plasma membrane, resembling clathrin-coated pits. Characterization of vesicles involved in the endocytic trafficking processes of CHIKV revealed the translocation of the virus particles to the early endosomes and subsequently to the late endosomes and lysosomes. Treatment with receptor-mediated endocytosis inhibitor, monodansylcadaverine and clathrin-associated drug inhibitors, chlorpromazine and dynasore inhibited CHIKV entry, whereas no inhibition was observed with caveolin-related drug inhibitors. Inhibition of CHIKV entry upon treatment with low-endosomal pH inhibitors indicated that low pH is essential for viral entry processes. CHIKV entry by clathrin-mediated endocytosis was validated via overexpression of a dominant-negative mutant of Eps15, in which infectious entry was reduced, while siRNA-based knockdown of genes associated with CME, low endosomal pH and RAB trafficking proteins exhibited significant levels of CHIKV inhibition. This study revealed, for the first time, that the infectious entry of CHIKV into mosquito cells is mediated by the clathrin-dependent endocytic pathway.
Ultrasensitive cDNA Detection of Dengue Virus RNA Using Electrochemical Nanoporous Membrane-Based Biosensor
Varun Rai, Hapuarachchige C. Hapuarachchi, Lee Ching Ng, Siew Hwa Soh, Yee Sin Leo, Chee-Seng Toh
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0042346
Abstract: A nanoporous alumina membrane-based ultrasensitive DNA biosensor is constructed using 5′-aminated DNA probes immobilized onto the alumina channel walls. Alumina nanoporous membrane-like structure is carved over platinum wire electrode of 76 μm diameter dimension by electrochemical anodization. The hybridization of complementary target DNA with probe DNA molecules attached inside the pores influences the pore size and ionic conductivity. The biosensor demonstrates linear range over 6 order of magnitude with ultrasensitive detection limit of 9.55×10?12 M for the quantification of ss-31 mer DNA sequence. Its applicability is challenged against real time cDNA PCR sample of dengue virus serotype1 derived from asymmetric PCR. Excellent specificity down to one nucleotide mismatch in target DNA sample of DENV3 is also demonstrated.
Oral Susceptibility of Singapore Aedes (Stegomyia) aegypti (Linnaeus) to Zika Virus
MeiZhi Irene Li equal contributor,Pei Sze Jeslyn Wong equal contributor,Lee Ching Ng,Cheong Huat Tan
PLOS Neglected Tropical Diseases , 2012, DOI: 10.1371/journal.pntd.0001792
Abstract: Background Zika virus (ZIKV) is a little known flavivirus that caused a major outbreak in 2007, in the South-western Pacific Island of Yap. It causes dengue-like syndromes but with milder symptoms. In Africa, where it was first isolated, ZIKV is mainly transmitted by sylvatic Aedes mosquitoes. The virus has also been isolated from Ae. aegypti and it is considered to be the vector involved in the urban transmission of the virus. Transmission of the virus by an African strain of Ae. aegypti has also been demonstrated under laboratory conditions. The aim of the present study is to describe the oral susceptibility of a Singapore strain of Ae. aegypti to ZIKV, under conditions that simulate local climate. Methodology/Principal Findings To assess the receptivity of Singapore's Ae. aegypti to the virus, we orally exposed a local mosquito strain to a Ugandan strain of ZIKV. Upon exposure, fully engorged mosquitoes were maintained in an environmental chamber set at 29°C and 70–75% RH. Eight mosquitoes were then sampled daily from day 1 to day 7, and subsequently on days 10 and 14 post exposure (pe). The virus titer of the midgut and salivary glands of each mosquito were determined using a tissue culture infectious dose50 (TCID50) assay. High midgut infection and salivary gland dissemination rates were observed. By day 5 after the infectious blood meal, ZIKV was found in the salivary glands of more than half of the mosquitoes tested (62%); and by day 10, all mosquitoes were potentially infective. Conclusions/Significance This study showed that Singapore's urban Ae. aegypti are susceptible and are potentially capable of transmitting ZIKV. The virus could be established in Singapore should it be introduced. Nevertheless, Singapore's current dengue control strategy is applicable to control ZIKV.
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