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Search Results: 1 - 10 of 4325 matches for " Yee-Sin Leo "
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Implications of Discordance in World Health Organization 1997 and 2009 Dengue Classifications in Adult Dengue
Victor C. Gan, David C. Lye, Tun L. Thein, Frederico Dimatatac, Adriana S. Tan, Yee-Sin Leo
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0060946
Abstract: Background Revised dengue guidelines were published by the World Health Organization (WHO) in 2009 addressing severe dengue cases not classified by dengue hemorrhagic fever (DHF) and shock syndrome (DSS). Methods and Principal Findings We conducted a retrospective cohort study to compare WHO 2009 and 1997 classifications using 1278 adult dengue cases confirmed by polymerase chain reaction assay from Singapore epidemics in 2004 and 2007 (predominantly serotype 1 and 2 respectively).DHF occurred in 14.3%, DSS 2.7% and severe dengue 16.0%. The two WHO dengue classifications were discordant in defining severe disease (p<0.001). Five DSS patients (15%) were classified as non-severe dengue without warning signs. Of severe dengue patients, 107 did not fulfil DHF criteria. Of these, 14.9% had self-resolving isolated elevated aminotransferases, 18.7% gastrointestinal bleeding without hemodynamic compromise and 56.1% plasma leakage with isolated tachycardia. We compared both guidelines against requirement for intensive care including the single death in this series: all six had severe dengue; only four had DHF as two lacked bleeding manifestations but had plasma leakage. Increasing length of hospitalization was noted among severe cases with both classifications but the trend was only statistically significant for WHO 2009. Length of hospitalization was significantly longer for severe plasma leakage compared with severe bleeding or organ impairment. Requirement for hospitalization increased using WHO 2009 from 17.0% to 51.3%. Conclusions While the WHO 2009 dengue classification is clinically useful, we propose retaining criteria for plasma leakage and hemodynamic compromise from WHO 1997, and refining definitions of severe bleeding and organ impairment to improve clinical relevance having found that differences in these accounted for the discordance between classifications. Findings from our retrospective study may be limited by the study site - a tertiary referral center in a hyperendemic country - and should be evaluated in a wider range of geographic settings.
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.
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.
Confirmed adult dengue deaths in Singapore: 5-year multi-center retrospective study
Yee-Sin Leo, Tun L Thein, Dale A Fisher, Jenny G Low, Helen M Oh, Rajmohan L Narayanan, Victor C Gan, Vernon J Lee, David C Lye
BMC Infectious Diseases , 2011, DOI: 10.1186/1471-2334-11-123
Abstract: We conducted a multi-center retrospective chart review of all confirmed adult dengue deaths in Singapore from 1 January 2004 to 31 December 2008.Of 28 adult dengue deaths, median age was 59 years. Male gender comprised 67.9% and co-morbidities existed in 75%. From illness onset, patients presented for admission at a median of 4 days and death occurred at a median of 12 days. Intensive care admission was required in 71.4%. Probable dengue was diagnosed in 32.1% by WHO 1997 criteria and 78.6% by WHO 2009. The earliest warning sign was persistent vomiting at a median of 1.5 days. Hematocrit change ≥20% concurrent with platelet count <20 × 10^9/L was associated with the shortest interval to death at a median of 3 days. Only 35.7% of death cases fulfilled DHF criteria by WHO 1997 versus severe dengue in 100.0% by WHO 2009 criteria. Deaths were due to shock and organ failure. Acute renal impairment occurred in 71.4%, impaired consciousness 57.1% and severe hepatitis 53.6%.In our adult fatal dengue cohort, WHO 2009 criteria had higher sensitivity in diagnosing probable dengue and severe dengue compared with WHO 1997. As warning signs, persistent vomiting occurred early and hematocrit change ≥20% concurrent with platelet count <20 × 10^9/L preceded death most closely.Dengue is the most important arthropod-borne viral disease in humans. The World Health Organization (WHO) has estimated that 1.8 billion people, or more than 70% of the global at-risk population, live in the WHO Southeast Asia and the Western Pacific regions which account for nearly 75% of current global disease burden from dengue [1]. Singapore, a developed island city-state in Southeast Asia has experienced resurgent dengue epidemics since the 1990s after previous decades of vector control effectively reduced the Aedes house index [2]. In addition, dengue infections in Singapore in recent years have shifted from primarily a childhood disease to that of adults [2]. With this resurgence, the classification of d
Utilities and Limitations of the World Health Organization 2009 Warning Signs for Adult Dengue Severity
Tun-Linn Thein equal contributor ,Victor C. Gan equal contributor,David C. Lye,Chee-Fu Yung,Yee-Sin Leo
PLOS Neglected Tropical Diseases , 2013, DOI: 10.1371/journal.pntd.0002023
Abstract: Background In 2009, the World Health Organization (WHO) proposed seven warning signs (WS) as criteria for hospitalization and predictors of severe dengue (SD). We assessed their performance for predicting dengue hemorrhagic fever (DHF) and SD in adult dengue. Method DHF, WS and SD were defined according to the WHO 1997 and 2009 dengue guidelines. We analyzed the prevalence, sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of WS before DHF and SD onset. Results Of 1507 cases, median age was 35 years (5th–95th percentile, 17–60), illness duration on admission 4 days (5th–95th percentile, 2–6) and length of hospitalization 5 days (5th–95th percentile, 3–7). DHF occurred in 298 (19.5%) and SD in 248 (16.5%). Of these, WS occurred before DHF in 124 and SD in 65 at median of two days before DHF or SD. Three commonest warning signs were lethargy, abdominal pain/tenderness and mucosal bleeding. No single WS alone or combined had Sn >64% in predicting severe disease. Specificity was >90% for both DHF and SD with persistent vomiting, hepatomegaly, hematocrit rise and rapid platelet drop, clinical fluid accumulation, and any 3 or 4 WS. Any one of seven WS had 96% Sn but only 18% Sp for SD. Conclusions No WS was highly sensitive in predicting subsequent DHF or SD in our confirmed adult dengue cohort. Persistent vomiting, hepatomegaly, hematocrit rise and rapid platelet drop, and clinical fluid accumulation, as well as any 3 or 4 WS were highly specific for DHF or SD.
Risk Factors for Fatality among Confirmed Adult Dengue Inpatients in Singapore: A Matched Case-Control Study
Tun-Linn Thein, Yee-Sin Leo, Dale A. Fisher, Jenny G. Low, Helen M. L. Oh, Victor C. Gan, Joshua G. X. Wong, David C. Lye
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0081060
Abstract: Objectives To identify demographic, clinical and laboratory risk factors for death due to dengue fever in adult patients in Singapore. Methods Multi-center retrospective study of hospitalized adult patients with confirmed dengue fever in Singapore between 1 January 2004 and 31 December 2008. Non-fatal controls were selected by matching age and year of infection with fatal cases. World Health Organization 1997, 2009 criteria were applied to define dengue hemorrhagic fever (DHF), warning signs and severe dengue. Statistical significance was assessed by conditional logistic regression modeling. Results Significantly more fatal cases than matched controls had pre-existing co-morbid conditions, and presented with abdominal pain/tenderness. Median pulse rates were significantly higher while myalgia was significantly less frequent in cases. . Fatal cases also had higher leucocyte counts, platelet counts, serum sodium, potassium, urea, creatine and bilirubin levels on admission compared to controls. There was no statistical significant difference between the prevalence of DHF and hematocrit level among cases and controls. Multivariate analysis showed myalgia and leucocyte count at presentation were independent predictors of fatality (adjusted odds ratios 0.09 and 2.94 respectively). None of the controls was admitted to intensive care unit (ICU) or given blood transfusion, while 71.4% and 28.6% of fatal cases received ICU admission and blood transfusion. Conclusions Absence of myalgia and leucocytosis on admission were independently associated with fatality in our matched case-control study. Fatalities were also commonly associated with co-morbidities and clinicians should be alarmed if dengue patients fulfilled severe dengue case definition on admission.
Challenges in Dengue Fever in the Elderly: Atypical Presentation and Risk of Severe Dengue and Hospita-Acquired Infection
Emily K. Rowe ,Yee-Sin Leo,Joshua G. X. Wong,Tun-Linn Thein,Victor C. Gan,Linda K. Lee,David C. Lye
PLOS Neglected Tropical Diseases , 2014, DOI: 10.1371/journal.pntd.0002777
Abstract: Background/methods To better understand dengue fever in the elderly, we compared clinical features, World Health Organization (WHO) dengue classification and outcomes between adult (<60) and elderly (≥60) dengue patients. We explored the impact of co-morbidity and hospital-acquired infection (HAI) on clinical outcomes in the elderly. All patients managed at the Communicable Disease Centre, Singapore, between 2005 and 2008 with positive dengue polymerase chain reaction (PCR) or who fulfilled WHO 1997 or 2009 probable dengue criteria with positive dengue IgM were included. Results Of the 6989 cases, 295 (4.4%) were elderly. PCR was positive in 29%. The elderly suffered more severe disease with more dengue haemorrhagic fever (DHF) (29.2% vs. 21.4%) and severe dengue (SD) (20.3% vs. 14.6%) (p<0.05). Classic dengue symptoms were more common in the adult group. The elderly were less likely to fulfill WHO 1997 (93.6% vs. 96.4%) (p = 0.014), but not WHO 2009 probable dengue (75.3% vs. 71.5%). Time to dengue diagnosis was similar. There was no significant difference in the frequency of warning signs between the two groups, but the elderly were more likely to have hepatomegaly (p = 0.006) and malaise/lethargy (p = 0.033) while the adults had significantly more mucosal bleeding (p<0.001). Intensive care admission occurred in 15 and death in three, with no age difference. Notably, the elderly stayed in hospital longer (median 5 vs. 4 days), and suffered more pneumonia (3.8% vs. 0.7%) and urinary infection (1.9% vs. 0.3%) (p = 0.003). Predictors of excess length of stay were age (adjusted odds ratio [aOR] 2.01, 95% confidence interval [CI] 1.37–2.88), critical illness (aOR 5.13, 95%CI 2.59–9.75), HAI (aOR 12.06, 95%CI 7.39–19.9), Charlson score (aOR 6.9, 95%CI 2.02–22.56) and severe dengue (DHF/dengue shock syndrome/SD) (aOR 2.24, 95%CI 1.83–2.74). Conclusion Elderly dengue patients present atypically and are at higher risk of DHF, SD and HAI. Aside from dengue severity, age, co-morbidity and HAI were associated with longer hospital stay.
Predictive Value of Proteinuria in Adult Dengue Severity
Farhad F. Vasanwala equal contributor,Tun-Linn Thein equal contributor,Yee-Sin Leo ,Victor C. Gan,Ying Hao,Linda K. Lee,David C. Lye
PLOS Neglected Tropical Diseases , 2014, DOI: 10.1371/journal.pntd.0002712
Abstract: Background Dengue is an important viral infection with different presentations. Predicting disease severity is important in triaging patients requiring hospital care. We aim to study the value of proteinuria in predicting the development of dengue hemorrhagic fever (DHF), utility of urine dipstick test as a rapid prognostic tool. Methodology and principal findings Adult patients with undifferentiated fever (n = 293) were prospectively enrolled at the Infectious Disease Research Clinic at Tan Tock Seng Hospital, Singapore from January to August 2012. Dengue infection was confirmed in 168 (57%) by dengue RT-PCR or NS1 antigen detection. Dengue cases had median fever duration of 6 days at enrolment. DHF was diagnosed in 34 cases according to the WHO 1997 guideline. Dengue fever (DF) patients were predominantly younger and were mostly seen in the outpatient setting with higher platelet level. Compared to DF, DHF cases had significantly higher peak urine protein creatinine ratio (UPCR) during clinical course (26 vs. 40 mg/mmol; p<0.001). We obtained a UPCR cut-off value of 29 mg/mmol based on maximum AUC in ROC curves of peak UPCR for DF versus DHF, corresponding to 76% sensitivity and 60% specificity. Multivariate analysis with other readily available clinical and laboratory variables increased the AUC to 0.91 with 92% sensitivity and 80% specificity. Neither urine dipstick at initial presentation nor peak urine dipstick value during the entire illness was able to discriminate between DF and DHF. Conclusions Proteinuria measured by a laboratory-based UPCR test may be sensitive and specific in prognosticating adult dengue patients.
Self-Reported Pain Intensity with the Numeric Reporting Scale in Adult Dengue
Joshua G. X. Wong, Victor C. Gan, Ee-Ling Ng, Yee-Sin Leo, Siew-Pang Chan, Robin Choo, David C. Lye
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0096514
Abstract: Background Pain is a prominent feature of acute dengue as well as a clinical criterion in World Health Organization guidelines in diagnosing dengue. We conducted a prospective cohort study to compare levels of pain during acute dengue between different ethnicities and dengue severity. Methods Demographic, clinical and laboratory data were collected. Data on self-reported pain was collected using the 11-point Numerical Rating Scale. Generalized structural equation models were built to predict progression to severe disease. Results A total of 499 laboratory confirmed dengue patients were recruited in the Prospective Adult Dengue Study at Tan Tock Seng Hospital, Singapore. We found no statistically significant differences between pain score with age, gender, ethnicity or the presence of co-morbidity. Pain score was not predictive of dengue severity but highly correlated to patients’ day of illness. Prevalence of abdominal pain in our cohort was 19%. There was no difference in abdominal pain score between grades of dengue severity. Conclusion Dengue is a painful disease. Patients suffer more pain at the earlier phase of illness. However, pain score cannot be used to predict a patient’s progression to severe disease.
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.
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