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Article ; Online: Blood pressure trend in hospitalized adult dengue patients.

Wesley Yeung / David Chien Boon Lye / Tun-Linn Thein / Yirong Chen / Yee-Sin Leo

PLoS ONE, Vol 15, Iss 7, p e

2020 Volume 0235166

Abstract: BACKGROUND:Monitoring of blood pressure is an important part of management of dengue illness. Large scale studies of temporal trend of blood pressure in adult dengue are lacking. In this study, we examined the differences in time trend of systolic (SBP) ... ...

Abstract	BACKGROUND:Monitoring of blood pressure is an important part of management of dengue illness. Large scale studies of temporal trend of blood pressure in adult dengue are lacking. In this study, we examined the differences in time trend of systolic (SBP) and diastolic blood pressure (DBP) in patients with and without severe dengue (SD), dengue hemorrhagic fever (DHF) and pre-existing hypertension, and elderly versus non-elderly patients. METHODS:We studied a retrospective cohort from 2005 to 2008 of 6,070 hospitalized adult dengue patients confirmed by polymerase chain reaction or clinical criteria plus positive dengue serology. Dengue severity was defined according to World Health Organization 1997 and 2009 guidelines. We used Bayesian hierarchical Markov models to compare the daily mean SBP and DBP between different subgroups. Analysis was conducted by day of defervescence (denoted as day 0), and day of illness onset (denoted as day 1) respectively. RESULTS:SBP decreased to a nadir during the critical phase before defervescence and was significantly lower for patients with SD or DHF, compared with patients without SD or DHF. DBP increased marginally more for patients with SD or DHF in the critical phase before defervescence. By day of defervescence, comparison of patients with and without SD showed significant difference in SBP from day -6 to day +6, except days +1, +3 and +5, and similarly in DBP except days 0, and +4 to +6. Comparison of patients with and without DHF showed significant difference in SBP from day -6 to day -1, but for DBP, significant difference was noted from day -6 to day +6, except day -2 to day 0. By day of illness, SBP differed significantly between patients with and without SD from illness days 1 to 10, and DBP from illness days 7 to 12. Between patients with and without DHF, SBP differed significantly on illness days 1, 2, 4 to 7, while DBP from days 7 to 12. On analysis by days of defervescence or by days of illness, elderly patients and those with hypertension showed consistently ...
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A nonstructural protein 1 capture enzyme-linked immunosorbent assay specific for dengue viruses.

Pei-Yin Lim / Appanna Ramapraba / Thomas Loy / Angeline Rouers / Tun-Linn Thein / Yee-Sin Leo / Dennis R Burton / Katja Fink / Cheng-I Wang

PLoS ONE, Vol 18, Iss 5, p e

2023 Volume 0285878

Abstract: Dengue non-structural protein (NS1) is an important diagnostic marker during the acute phase of infection. Because NS1 is partially conserved across the flaviviruses, a highly specific DENV NS-1 diagnostic test is needed to differentiate dengue infection ...

Abstract	Dengue non-structural protein (NS1) is an important diagnostic marker during the acute phase of infection. Because NS1 is partially conserved across the flaviviruses, a highly specific DENV NS-1 diagnostic test is needed to differentiate dengue infection from Zika virus (ZIKV) infection. In this study, we characterized three newly isolated antibodies against NS1 (A2, D6 and D8) from a dengue-infected patient and a previously published human anti-NS1 antibody (Den3). All four antibodies recognized multimeric forms of NS1 from different serotypes. A2 bound to NS1 from DENV-1, -2, and -3, D6 bound to NS1 from DENV-1, -2, and -4, and D8 and Den3 interacted with NS1 from all four dengue serotypes. Using a competition ELISA, we found that A2 and D6 bound to overlapping epitopes on NS1 whereas D8 recognized an epitope distinct from A2 and D6. In addition, we developed a capture ELISA that specifically detected NS1 from dengue viruses, but not ZIKV, using Den3 as the capture antibody and D8 as the detecting antibody. This assay detected NS1 from all the tested dengue virus strains and dengue-infected patients. In conclusion, we established a dengue-specific capture ELISA using human antibodies against NS1. This assay has the potential to be developed as a point-of-care diagnostic tool.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Differentiating coronavirus disease 2019 (COVID-19) from influenza and dengue

Tun-Linn Thein / Li Wei Ang / Barnaby Edward Young / Mark I-Cheng Chen / Yee-Sin Leo / David Chien Boon Lye

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 9

Abstract: Abstract The novel coronavirus disease 2019 (COVID-19) presents with non-specific clinical features. This may result in misdiagnosis or delayed diagnosis, and lead to further transmission in the community. We aimed to derive early predictors to ... ...

Abstract	Abstract The novel coronavirus disease 2019 (COVID-19) presents with non-specific clinical features. This may result in misdiagnosis or delayed diagnosis, and lead to further transmission in the community. We aimed to derive early predictors to differentiate COVID-19 from influenza and dengue. The study comprised 126 patients with COVID-19, 171 with influenza and 180 with dengue, who presented within 5 days of symptom onset. All cases were confirmed by reverse transcriptase polymerase chain reaction tests. We used logistic regression models to identify demographics, clinical characteristics and laboratory markers in classifying COVID-19 versus influenza, and COVID-19 versus dengue. The performance of each model was evaluated using receiver operating characteristic (ROC) curves. Shortness of breath was the strongest predictor in the models for differentiating between COVID-19 and influenza, followed by diarrhoea. Higher lymphocyte count was predictive of COVID-19 versus influenza and versus dengue. In the model for differentiating between COVID-19 and dengue, patients with cough and higher platelet count were at increased odds of COVID-19, while headache, joint pain, skin rash and vomiting/nausea were indicative of dengue. The cross-validated area under the ROC curve for all four models was above 0.85. Clinical features and simple laboratory markers for differentiating COVID-19 from influenza and dengue are identified in this study which can be used by primary care physicians in resource limited settings to determine if further investigations or referrals would be required.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Competitive ELISA for a serologic test to detect dengue serotype-specific anti-NS1 IgGs using high-affinity UB-DNA aptamers

Ken-ichiro Matsunaga / Michiko Kimoto / Vanessa Weixun Lim / Tun-Linn Thein / Shawn Vasoo / Yee-Sin Leo / William Sun / Ichiro Hirao

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 18

Abstract: Abstract Serologic tests to detect specific IgGs to antigens related to viral infections are urgently needed for diagnostics and therapeutics. We present a diagnostic method for serotype-specific IgG identification of dengue infection by a competitive ... ...

Abstract	Abstract Serologic tests to detect specific IgGs to antigens related to viral infections are urgently needed for diagnostics and therapeutics. We present a diagnostic method for serotype-specific IgG identification of dengue infection by a competitive enzyme-linked immunosorbent assay (ELISA), using high-affinity unnatural-base-containing DNA (UB-DNA) aptamers that recognize the four categorized serotypes. Using UB-DNA aptamers specific to each serotype of dengue NS1 proteins (DEN-NS1), we developed our aptamer–antibody sandwich ELISA for dengue diagnostics. Furthermore, IgGs highly specific to DEN-NS1 inhibited the serotype-specific NS1 detection, inspiring us to develop the competitive ELISA format for dengue serotype-specific IgG detection. Blood samples from Singaporean patients with primary or secondary dengue infections confirmed the highly specific IgG detection of this format, and the IgG production initially reflected the serotype of the past infection, rather than the recent infection. Using this dengue competitive ELISA format, cross-reactivity tests of 21 plasma samples from Singaporean Zika virus-infected patients revealed two distinct patterns: 8 lacked cross-reactivity, and 13 were positive with unique dengue serotype specificities, indicating previous dengue infection. This antigen-detection ELISA and antibody-detection competitive ELISA combination using the UB-DNA aptamers identifies both past and current viral infections and will facilitate specific medical care and vaccine development for infectious diseases.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Author Correction

Tommy Hing-Cheung Tang / Sylvie Alonso / Lisa Fong-Poh Ng / Tun-Linn Thein / Junxiong Pang / Yee-Sin Leo / David Chien-Boon Lye / Tsin-Wen Yeo

Scientific Reports, Vol 11, Iss 1, Pp 1-

Increased Serum Hyaluronic Acid and Heparan Sulfate in Dengue Fever: Association with Plasma Leakage and Disease Severity

2021 Volume 1

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

Abstract	An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A 15-year review of dengue hospitalizations in Singapore

Li Wei Ang / Tun-Linn Thein / Yixiang Ng / Irving Charles Boudville / Po Ying Chia / Vernon Jian Ming Lee / Yee-Sin Leo

PLoS Neglected Tropical Diseases, Vol 13, Iss 5, p e

Reducing admissions without adverse consequences, 2003 to 2017.

2019 Volume 0007389

Abstract: Objectives Since the 1990s, Singapore has experienced periodic dengue epidemics of increasing frequency and magnitude. In the aftermath of the 2004-2005 dengue epidemic, hospitals refined their admission criteria for dengue cases to right-site dengue ... ...

Abstract	Objectives Since the 1990s, Singapore has experienced periodic dengue epidemics of increasing frequency and magnitude. In the aftermath of the 2004-2005 dengue epidemic, hospitals refined their admission criteria for dengue cases to right-site dengue case management and reduce the burden of healthcare utilization and negative outcomes. In this study, we describe the national trends of hospital admissions for dengue and disease severity in terms of length of stay (LOS), admission to the intensive care unit (ICU) and death in hospital, and case fatality rate (CFR) in Singapore. Methods We conducted a retrospective study of notified cases and laboratory confirmed dengue patients admitted to all public and private hospitals between 2003 and 2017. Case notifications for dengue and hospitalization records were extracted from national databases. Results The proportion of dengue cases hospitalized was lower in recent years; 28.9% in the 2013-2014 epidemic, compared to 93.2% in the 2004-2005 epidemic, and 58.1% in the 2007 epidemic. Median LOS remained stable over the years; overall LOS was 3 to 4 days and ICU stay was 2 to 3 days. Less than 2% of hospitalized patients were admitted to the ICU. Overall CFR was low and remained below 0.5%. The proportions of dengue cases hospitalized and patients admitted to the ICU were highest in the elderly aged 65 years and older. Conclusions While the proportion of dengue cases hospitalized saw a drastic decline due to more selective admission criteria, there was no concomitant increase in adverse outcomes, suggesting that admission criteria were appropriate to focus on severe dengue cases. Further studies are needed to optimize dengue management in older adults who are more likely to be hospitalized with greater disease severity, given the higher proportions of hospitalizations and severe disease among older adults.
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
Language	English
Publishing date	2019-05-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Significance of Prolonged and Saddleback Fever in Hospitalised Adult Dengue.

Deborah Hl Ng / Joshua Gx Wong / Tun-Linn Thein / Yee-Sin Leo / David C Lye

PLoS ONE, Vol 11, Iss 12, p e

2016 Volume 0167025

Abstract: Dengue fever is gaining importance in Singapore with an increase in the number of cases and mortality in recent years. Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in ... ...

Abstract	Dengue fever is gaining importance in Singapore with an increase in the number of cases and mortality in recent years. Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. This study aims to examine the prevalence of prolonged and saddleback fever in dengue as well as their associations with dengue severity. A total of 2843 polymerase-chain reaction (PCR) confirmed dengue patients admitted to Tan Tock Seng Hospital from 2004 to 2008 were included in the study. Sixty-nine percent of them were male with a median age of 34 years. Prolonged fever (fever > 7 days duration) was present in 572 (20.1%) of patients. Dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and severe dengue (SD) were significantly more likely to occur in patients with prolonged fever. Mucosal bleeding, anorexia, diarrhea, abdominal pain, nausea or vomiting, lethargy, rash, clinical fluid accumulation, hepatomegaly, nosocomial infection, leukopenia, higher neutrophil count, higher hematocrit, higher alanine transaminase (ALT) and aspartate transaminase (AST), higher creatinine, lower protein and prolonged activated partial thromboplastin time (APTT) were significantly associated with prolonged fever but not platelet count or prothrombin time (PT). Saddleback fever was present in 165 (5.8%). Although DHF and SD were more likely to occur in patients in those with saddleback fever, DSS was not. Compared with prolonged fever, saddleback fever did not show many significant associations except for diarrhea, abdominal pain, clinical fluid accumulation, hematocrit and platelet change, and lower systolic blood pressure. This study demonstrates that prolonged fever may be associated with various warning signs and more severe forms of dengue (SD, DSS, DHF), while saddleback fever showed associations with DHF and SD but not DSS. The presence of prolonged or saddleback fever in dengue patients should therefore prompt detailed evaluation for complications of dengue, as well as early investigation to evaluate for development of nosocomial infection.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Identifying Adult Dengue Patients at Low Risk for Clinically Significant Bleeding.

Joshua G X Wong / Tun Linn Thein / Yee-Sin Leo / Junxiong Pang / David C Lye

PLoS ONE, Vol 11, Iss 2, p e

2016 Volume 0148579

Abstract: BACKGROUND:Clinically significant bleeding is important for subsequent optimal case management in dengue patients, but most studies have focused on dengue severity as an outcome. Our study objective was to identify differences in admission parameters ... ...

Abstract	BACKGROUND:Clinically significant bleeding is important for subsequent optimal case management in dengue patients, but most studies have focused on dengue severity as an outcome. Our study objective was to identify differences in admission parameters between patients who developed clinically significant bleeding and those that did not. We sought to develop a model for discriminating between these patients. METHODS:We conducted a retrospective study of 4,383 adults aged >18 years who were hospitalized with dengue infection at Tan Tock Seng Hospital, Singapore from 2005 to 2008. Patients were divided into those with clinically significant bleeding (n = 188), and those without (n = 4,195). Demographic, clinical, and laboratory variables on admission were compared between groups to determine factors associated with clinically significant bleeding during hospitalization. RESULTS:On admission, female gender (p<0.001); temperature >38°C (p<0.001); nausea/vomiting (p = 0.009) and abdominal pain/tenderness (p = 0.005); lower systolic blood pressure (p<0.001); higher pulse rate (p<0.001); increased absolute neutrophil count (ANC; p<0.001); reduced absolute lymphocyte count (ALC; p<0.001), haematocrit percentage (p<0.001) and platelet count (p = 0.04), and increased prothrombin time (p = 0.003) were significantly associated with clinically significant bleeding on univariate analysis. Multivariate analysis showed that independent variables in the final model were female gender (aOR 2.85; 95% CI: 1.9-4.33); temperature >38°C (aOR 1.81; 95% CI: 1.27-2.61), nausea/vomiting (aOR 1.39; 95% CI: 0.94-2.12), ANC (aOR 1.3; 95% CI: 1.15-1.46), ALC (aOR 0.4; 95% CI: 0.25-0.64), hematocrit percentage (aOR 0.96; 95% CI: 0.92-1.002) and platelet count (aOR 0.993; 95% CI: 0.988-0.998). At the cutoff of -3.919, the model achieved an AUC of 0.758 (sensitivity:0.87, specificity: 0.38, PPV: 0.06, NPV: 0.98). CONCLUSION:Clinical risk factors associated with clinically significant bleeding were identified. This ...
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Immune cell phenotypes associated with disease severity and long-term neutralizing antibody titers after natural dengue virus infection

Cell Reports Medicine, Vol 2, Iss 5, Pp 100278- (2021)

2021

Abstract: Summary: Prior immunological exposure to dengue virus can be both protective and disease-enhancing during subsequent infections with different dengue virus serotypes. We provide here a systematic, longitudinal analysis of B cell, T cell, and antibody ... ...

Abstract	Summary: Prior immunological exposure to dengue virus can be both protective and disease-enhancing during subsequent infections with different dengue virus serotypes. We provide here a systematic, longitudinal analysis of B cell, T cell, and antibody responses in the same patients. Antibody responses as well as T and B cell activation differentiate primary from secondary responses. Hospitalization is associated with lower frequencies of activated, terminally differentiated T cells and higher percentages of effector memory CD4 T cells. Patients with more severe disease tend to have higher percentages of plasmablasts. This does not translate into long-term antibody titers, since neutralizing titers after 6 months correlate with percentages of specific memory B cells, but not with acute plasmablast activation. Overall, our unbiased analysis reveals associations between cellular profiles and disease severity, opening opportunities to study immunopathology in dengue disease and the potential predictive value of these parameters.
Keywords	dengue ; longitudinal study ; disease severity ; immune cell phenotype ; CyTOF ; neutralizing antibodies ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Single molecule, near full-length genome sequencing of dengue virus

Thiruni N. Adikari / Nasir Riaz / Chathurani Sigera / Preston Leung / Braulio M. Valencia / Kirston Barton / Martin A. Smith / Rowena A. Bull / Hui Li / Fabio Luciani / Praveen Weeratunga / Tun-Linn Thein / Vanessa W. X. Lim / Yee-Sin Leo / Senaka Rajapakse / Katja Fink / Andrew R. Lloyd / Deepika Fernando / Chaturaka Rodrigo

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 12

Abstract: Abstract Current methods for dengue virus (DENV) genome amplification, amplify parts of the genome in at least 5 overlapping segments and then combine the output to characterize a full genome. This process is laborious, costly and requires at least 10 ... ...

Abstract	Abstract Current methods for dengue virus (DENV) genome amplification, amplify parts of the genome in at least 5 overlapping segments and then combine the output to characterize a full genome. This process is laborious, costly and requires at least 10 primers per serotype, thus increasing the likelihood of PCR bias. We introduce an assay to amplify near full-length dengue virus genomes as intact molecules, sequence these amplicons with third generation “nanopore” technology without fragmenting and use the sequence data to differentiate within-host viral variants with a bioinformatics tool (Nano-Q). The new assay successfully generated near full-length amplicons from DENV serotypes 1, 2 and 3 samples which were sequenced with nanopore technology. Consensus DENV sequences generated by nanopore sequencing had over 99.5% pairwise sequence similarity to Illumina generated counterparts provided the coverage was > 100 with both platforms. Maximum likelihood phylogenetic trees generated from nanopore consensus sequences were able to reproduce the exact trees made from Illumina sequencing with a conservative 99% bootstrapping threshold (after 1000 replicates and 10% burn-in). Pairwise genetic distances of within host variants identified from the Nano-Q tool were less than that of between host variants, thus enabling the phylogenetic segregation of variants from the same host.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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