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Search Results: 1 - 10 of 31381 matches for " Lee-Ching Ng "
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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.
Simple Clinical and Laboratory Predictors of Chikungunya versus Dengue Infections in Adults
Vernon J. Lee ,Angela Chow,Xiaohui Zheng,Luis R. Carrasco,Alex R. Cook,David C. Lye,Lee-Ching Ng,Yee-Sin Leo
PLOS Neglected Tropical Diseases , 2012, DOI: 10.1371/journal.pntd.0001786
Abstract: Background Dengue and chikungunya are co-circulating vector-borne diseases with substantial overlap in clinical presentations. It is important to differentiate between them during first presentation as their management, especially for dengue hemorrhagic fever (DHF), is different. This study compares their clinical presentation in Singapore adults to derive predictors to assist doctors in diagnostic decision-making. Methods We compared 117 patients with chikungunya infection diagnosed with reverse transcription-polymerase chain reaction (RT-PCR) with 917 dengue RT-PCR-positive adult patients (including 55 with DHF). We compared dengue fever (DF), DHF, and chikungunya infections by evaluating clinical characteristics of dengue and chikungunya; developing classification tools via multivariate logistic regression models and classification trees of disease etiology using clinical and laboratory factors; and assessing the time course of several clinical variables. Findings At first presentation to hospital, significantly more chikungunya patients had myalgia or arthralgia, and fewer had a sore throat, cough (for DF), nausea, vomiting, diarrhea, abdominal pain, anorexia or tachycardia than DF or DHF patients. From the decision trees, platelets <118×109/L was the only distinguishing feature for DF versus chikungunya with an overall correct classification of 89%. For DHF versus chikungunya using platelets <100×109/L and the presence of bleeding, the overall correct classification was 98%. The time course analysis supported platelet count as the key distinguishing variable. Interpretation There is substantial overlap in clinical presentation between dengue and chikungunya infections, but simple clinical and laboratory variables can predict these infections at presentation for appropriate management.
Evaluation of Chikungunya Diagnostic Assays: Differences in Sensitivity of Serology Assays in Two Independent Outbreaks
Grace Yap,Kwoon-Yong Pok,Yee-Ling Lai,Hapuarachchige-Chanditha Hapuarachchi,Angela Chow,Yee-Sin Leo,Li-Kiang Tan,Lee-Ching Ng
PLOS Neglected Tropical Diseases , 2010, DOI: 10.1371/journal.pntd.0000753
Abstract: Background The sensitivity and specificity of two in-house MAC-ELISA assays were tested and compared with the performance of commercially-available CTK lateral flow rapid test and EUROIMMUN IFA assays for the detection of anti-Chikungunya virus (CHIKV) IgM. Each MAC-ELISA assay used a whole virus-based antigen derived from genetically distinct CHIKV strains involved in two chikungunya disease outbreaks in Singapore (2008); a January outbreak strain with alanine at amino acid residue 226 of the E1 glycoprotein (CHIKV-A226) and a May-to-September outbreak strain that possessed valine at the same residue (CHIKV-226V). We report differences in IgM detection efficacy of different assays between the two outbreaks. The sensitivities of two PCR protocols were also tested. Methods and Findings For sera from January outbreak, the average detection threshold of CTK lateral flow test, MAC-ELISAs and EUROIMMUN IFA assays was 3.75, 4.38 and 4.88 days post fever onset respectively. In contrast, IgM detection using CTK lateral flow test was delayed to more than 7 days after fever onset in the second outbreak sera. However, MAC-ELISA using CHIKV-226V detected IgM in the second outbreak sera 3.96 days after fever onset, which was approximately one day earlier compared to the same assay using CHIKV-A226 (4.86 days). Specificity was 100% for both commercial assays, and 95.6% for the in-house MAC-ELISAs. For sensitivity determination of the PCR protocols, the probe-based real time RT-PCR method was found to be 10 times more sensitive than one based on SYBR Green. Conclusion Our findings suggested that the two strains of CHIKV using variants A226 and 226V resulted in variation in sensitivities of the assays evaluated. We postulated that the observed difference in antigen efficacy could be due to the amino acid substitution differences in viral E1 and E2 envelope proteins, especially the E1-A226V substitution. This evaluation demonstrates the importance of appraisal of different diagnostic assays before their application in clinical and operational settings.
Molecular characterization of two hantavirus strains from different rattus species in Singapore
Patrik Johansson, Grace Yap, Hwee-Teng Low, Chern-Chiang Siew, Relus Kek, Lee-Ching Ng, G?ran Bucht
Virology Journal , 2010, DOI: 10.1186/1743-422x-7-15
Abstract: Pan-hanta RT-PCR performed on samples of Rattus norvegicus and Rattus tanezumi indicated that 27 (2.24%) of the animals were positive. sequence analysis of the S and M segments established that two different hantavirus strains circulate in the rodent population of Singapore. Notably, the hantavirus strains found in Rattus norvegicus clusters with other Asian Seoul virus sequences, while the virus strains found in Rattus tanezumi had the highest sequence similarity to the Serang virus from Rattus tanezumi in Indonesia, followed by Cambodian hantavirus isolates and the Thailand virus isolated from Bandicota indica.Sequence analysis of the S and M segments of hantavirus strains found in Rattus norvegicus (Seoul virus strain Singapore) and Rattus tanezumi (Serang virus strain Jurong TJK/06) revealed that two genetically different hantavirus strains were found in rodents of Singapore. Evidently, together with Serang, Cambodian and Thailand virus the Jurong virus forms a distinct phylogroup. Interestingly, these highly similar virus strains have been identified in different rodent hosts. Further studies are underway to analyze the public health significance of finding hantavirus strains in Singapore rodents.The hantavirus genus in the Bunyaviridae family contains several important human pathogens that are prevalent worldwide. This group of viruses includes the etiological agents of hemorrhagic fever with renal syndrome (HFRS), largely seen in Europe and Asia, and hantaviruses causing (cardio) pulmonary syndrome (HCPS) in the Americas. The clinical severity of hantavirus infections ranges from asymptomatic infections to fulminate hemorrhagic shock and death. Hantaan virus (HTNV) and Dobrava viruses (DOBV) are causative agents of severe forms of HFRS and mortality rates of up to 15% have been reported. About 20 - 30% of HTNV infected patients develop hemorrhages [1,2].Hantaviruses are enveloped and contain genomes composed of three negative-stranded RNA segments; small (S),
Aedes (Stegomyia) albopictus (Skuse): A Potential Vector of Zika Virus in Singapore
Pei-Sze Jeslyn Wong,Mei-zhi Irene Li,Chee-Seng Chong,Lee-Ching Ng,Cheong-Huat Tan
PLOS Neglected Tropical Diseases , 2013, DOI: 10.1371/journal.pntd.0002348
Abstract: Background Zika virus (ZIKV) is a little known arbovirus until it caused a major outbreak in the Pacific Island of Yap in 2007. Although the virus has a wide geographic distribution, most of the known vectors are sylvatic Aedes mosquitoes from Africa where the virus was first isolated. Presently, Ae. aegypti is the only known vector to transmit the virus outside the African continent, though Ae. albopictus has long been a suspected vector. Currently, Ae. albopictus has been shown capable of transmitting more than 20 arboviruses and its notoriety as an important vector came to light during the recent chikungunya pandemic. The vulnerability of Singapore to emerging infectious arboviruses has stimulated our interest to determine the competence of local Ae. albopictus to transmit ZIKV. Methodology/Principal Findings To determine the competence of Ae. albopictus to ZIKV, we orally infected local mosquito strains to a Ugandan strain virus. Fully engorged mosquitoes were maintained in an environmental chamber set at 29°C and 80–85%RH. Twelve mosquitoes were then sampled daily from day one to seven and on day 10 and 14 post infection (pi). Zika virus titre in the midgut and salivary glands of each mosquito were determined using tissue culture infectious dose50 assay, while transmissibility of the virus was determined by detecting viral antigen in the mosquito saliva by qRT-PCR. High dissemination and transmission rate of ZIKV were observed. By day 7-pi, all mosquitoes have disseminated infection and 73% of these mosquitoes have ZIKV in their saliva. By day 10-pi, all mosquitoes were potentially infectious. Conclusions/Significance The study highlighted the potential of Ae. albopictus to transmit ZIKV and the possibility that the virus could be established locally. Nonetheless, the threat of ZIKV can be mitigated by existing dengue and chikungunya control program being implemented in Singapore.
IL-1β, IL-6, and RANTES as Biomarkers of Chikungunya Severity
Lisa F. P. Ng, Angela Chow, Yong-Jiang Sun, Dyan J. C. Kwek, Poh-Lian Lim, Frederico Dimatatac, Lee-Ching Ng, Eng-Eong Ooi, Khar-Heng Choo, Zhisheng Her, Philippe Kourilsky, Yee-Sin Leo
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0004261
Abstract: Background Little is known about the immunopathogenesis of Chikungunya virus. Circulating levels of immune mediators and growth factors were analyzed from patients infected during the first Singaporean Chikungunya fever outbreak in early 2008 to establish biomarkers associated with infection and/or disease severity. Methods and Findings Adult patients with laboratory-confirmed Chikungunya fever infection, who were referred to the Communicable Disease Centre/Tan Tock Seng Hospital during the period from January to February 2008, were included in this retrospective study. Plasma fractions were analyzed using a multiplex-microbead immunoassay. Among the patients, the most common clinical features were fever (100%), arthralgia (90%), rash (50%) and conjunctivitis (40%). Profiles of 30 cytokines, chemokines, and growth factors were able to discriminate the clinical forms of Chikungunya from healthy controls, with patients classified as non-severe and severe disease. Levels of 8 plasma cytokines and 4 growth factors were significantly elevated. Statistical analysis showed that an increase in IL-1β, IL-6 and a decrease in RANTES were associated with disease severity. Conclusions This is the first comprehensive report on the production of cytokines, chemokines, and growth factors during acute Chikungunya virus infection. Using these biomarkers, we were able to distinguish between mild disease and more severe forms of Chikungunya fever, thus enabling the identification of patients with poor prognosis and monitoring of the disease.
Diagnosing Dengue at the Point-of-Care: Utility of a Rapid Combined Diagnostic Kit in Singapore
Victor C. Gan, Li-Kiang Tan, David C. Lye, Kwoon-Yong Pok, Shi-Qi Mok, Rachel Choon-Rong Chua, Yee-Sin Leo, Lee-Ching Ng
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0090037
Abstract: WHO recommendations for dengue diagnosis require laboratory facilities. Antibody-based rapid diagnostic tests (RDTs) have performed poorly, and clinical diagnosis remains the mainstay in dengue-endemic countries. We evaluated a combination antigen-antibody RDT for point-of-care testing in a high-prevalence setting. In this prospective cohort study, adults were enrolled from a tertiary infectious disease centre for evaluation of undifferentiated febrile illness from October 2011 to May 2012. SD Bioline Dengue Duo was evaluated at point-of-care against a WHO-based reference standard of viral isolation, RT-PCR, NS1-, IgM-, and IgG-ELISA. 246 adults were enrolled (median age 34 years, range 18–69), of which 197 could be confirmed definitively as either dengue or non-dengue. DENV-2 was the predominant serotype (79.5%) and the ratio of primary to secondary cases was 1:1.1. There were no test failures and minimal interobserver variation with a Fleiss’ kappa of 0.983 (95% CI 0.827–1.00). Overall sensitivity and specificity were 93.9% (95% CI 88.8–96.8%) and 92.0% (95% CI 81.2–96.9%) respectively. Using WHO clinical criteria alone for diagnosis had similar sensitivities (95.9%, 95% CI 91.4–98.1%) and lower specificities (20.0%, 95% CI 11.2–33.0%). No significant difference in performance was found when testing early versus late presenters, primary versus secondary cases, or DENV-1 versus DENV-2 infections. The use of a combination RDT fulfills WHO ASSURED criteria for point-of-care testing and can enhance dengue diagnosis in an endemic setting. This has the potential to markedly improve clinical management of dengue in the field.
The Early Clinical Features of Dengue in Adults: Challenges for Early Clinical Diagnosis
Jenny G. H. Low,Adrian Ong,Li Kiang Tan,Shera Chaterji,Angelia Chow,Wen Yan Lim,Koon Wui Lee,Robert Chua,Choon Rong Chua,Sharon W. S. Tan,Yin Bun Cheung,Martin L. Hibberd,Subhash G. Vasudevan,Lee-Ching Ng,Yee Sin Leo,Eng Eong Ooi
PLOS Neglected Tropical Diseases , 2011, DOI: 10.1371/journal.pntd.0001191
Abstract: Background The emergence of dengue throughout the tropical world is affecting an increasing proportion of adult cases. The clinical features of dengue in different age groups have not been well examined, especially in the context of early clinical diagnosis. Methodology/Principal Findings We structured a prospective study of adults (≥18 years of age) presenting with acute febrile illness within 72 hours from illness onset upon informed consent. Patients were followed up over a 3–4 week period to determine the clinical outcome. A total of 2,129 adults were enrolled in the study, of which 250 (11.7%) had dengue. Differences in the rates of dengue-associated symptoms resulted in high sensitivities when the WHO 1997 or 2009 classification schemes for probable dengue fever were applied to the cohort. However, when the cases were stratified into age groups, fewer older adults reported symptoms such as myalgia, arthralgia, retro-orbital pain and mucosal bleeding, resulting in reduced sensitivity of the WHO classification schemes. On the other hand, the risks of severe dengue and hospitalization were not diminshed in older adults, indicating that this group of patients can benefit from early diagnosis, especially when an antiviral drug becomes available. Our data also suggests that older adults who present with fever and leukopenia should be tested for dengue, even in the absence of other symptoms. Conclusion Early clinical diagnosis based on previously defined symptoms that are associated with dengue, even when used in the schematics of both the WHO 1997 and 2009 classifications, is difficult in older adults.
Entomologic and molecular investigation into Plasmodium vivax transmission in Singapore, 2009
Lee-Ching Ng, Kim-Sung Lee, Cheong-Huat Tan, Peng-Lim Ooi, Sai-Gek Lam-Phua, Raymond Lin, Sook-Cheng Pang, Yee-Ling Lai, Suhana Solhan, Pei-Pei Chan, Kit-Yin Wong, Swee-Tuan Ho, Indra Vythilingam
Malaria Journal , 2010, DOI: 10.1186/1475-2875-9-305
Abstract: Epidemiological, entomological and molecular studies were carried out to investigate the three clusters, namely Mandai-Sungei Kadut, Jurong Island and Sembawang.A total of 29 malaria patients, with no recent travel history, were reported in the three clusters. Molecular analysis based on the msp3α and msp1 genes showed two independent local transmissions: one in Mandai-Sungei Kadut and another in Sembawang. Almost all cases within each cluster were epidemiologically linked. In Jurong Island cluster, epidemiological link remains uncertain, as almost all cases had a unique genetic profile. Only two cases shared a common profile and were found to be linked to the Mandai-Sungei Kadut cluster. Entomological investigation found Anopheles sinensis to be the predominant Anopheline in the two areas where local transmission of P. vivax was confirmed. Anopheles sinensis was found to be attracted to human bait and bites as early as 19:45 hrs. However, all Anopheles mosquitoes caught were negative for sporozoites and oocysts by dissection.Investigation of P. vivax cases from the three cluster areas confirmed the occurrence of local transmission in two areas. Although An. sinensis was the predominant Anopheline found in areas with confirmed transmission, the vector/s responsible for the outbreaks still remains cryptic.Singapore has been certified malaria free since November 1982 by the World Health Organization [1] and despite occasional local transmission, the country has maintained the standing due to its comprehensive system that prevents the re-establishment of malaria viz. vector surveillance and control, early case detection, and aggressive preventive and remedial actions upon detection of cases [2,3]. The incidence of reported malaria declined substantially from 8.0 per 100,000 population in 1977 to 2.0 per 100,000 population in 2007. In recent years, incidence has been maintained at between 2.0 and 2.6 per 100,000 population. Most infections were caused by Plasmodium viva
Description and Prediction of the Development of Metabolic Syndrome: A Longitudinal Analysis Using a Markov Model Approach
Lee-Ching Hwang, Chyi-Huey Bai, San-Lin You, Chien-An Sun, Chien-Jen Chen
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0067436
Abstract: Background Delineating the natural history of metabolic syndrome (MetS) is prerequisite to prevention. This study aimed to build Markov models to simulate each component’s progress and to test the effect of different initial states on the development of MetS. Methods MetS was defined with revised AHA/NHLBI criteria. Each reversible multistate Markov chain consisted of 8 states (no component, five isolated component states, 2-component state, and MetS state). Yearly transition probabilities were calculated from a five-year population-based follow up studywhich enrolled 2,247 individuals with mean aged 32.4 years at study entry. Results In men, high BP or a 2-component state was most likely to initiate the progress of MetS. In women, abdominal obesity or low HDL were the most likely initiators. Metabolic components were likely to occur together. The development of MetS was an increasing monotonic function of time. MetS was estimated to develop within 15 years in 12.7% of young men with no component, and 2 components developed in 16.3%. MetS was estimated to develop in 10.6% of women with at the age of 47, and 2 components developed in 14.3%. MetS was estimated to develop in 24.6% of men and 27.6% of women with abdominal obesity, a rate higher than in individuals initiating with no component. Conclusions This modeling study allows estimation of the natural history of MetS. Men tended to develop this syndrome sooner than women did, i.e., before their fifth decade of life. Individuals with 1 or 2 components showed increased development of MetS.
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