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  1. Sofosbuvir as treatment against dengue?
    Gan CS, Lim SK, Chee CF, Yusof R, Heh CH
    Chem Biol Drug Des, 2018 02;91(2):448-455.
    PMID: 28834304 DOI: 10.1111/cbdd.13091
    Dengvaxia® (CTD-TDV), the only licensed tetravalent dengue vaccine by Sanofi Pasteur, was made available since 2015. However, administration of CTD-TDV, in general, has not received the prequalification recommendation from the World Health Organization. Having a universal antidengue agent for treatment will therefore beneficial. Accordingly, the development of nucleoside inhibitors specific to dengue viral polymerase that perturb dengue infection has been studied by many. Alternatively, we have used a marketed anti-HCV prodrug sofosbuvir to study its in silico and in vitro effects against dengue. As a result, the active metabolite of sofosbuvir (GS-461203) was predicted to bind to the catalytic motif (Gly-Asp-Asp) of dengue viral polymerase with binding affinity of -6.9 kcal/mol. Furthermore, sofosbuvir demonstrated excellent in vitro viral inhibition with an EC90 of 0.4 μm. In addition, this study demonstrated the requirement of specific liver enzymes to activate the prodrug into GS-461203 to exert its antidengue potential. All in all, sofosbuvir should be subjected to in-depth studies to provide information of its efficacy toward dengue and its lead potential as DENV polymerase inhibitor in human subjects. In conclusion, we have expended the potential of the clinically available drug sofosbuvir as treatment for dengue.
    Matched MeSH terms: Dengue/therapy*
  2. Fulltext Dengue and acute kidney injury: A need for aggressive maneuvers
    Mallhi TH, Khan AH, Khan YH, Adnan AS, Sarriff A
    Saudi J Kidney Dis Transpl, 2017 5 26;28(3):667-669.
    PMID: 28540914 DOI: 10.4103/1319-2442.206453
    Matched MeSH terms: Dengue*
  3. Antiviral actions of flavanoid-derived compounds on dengue virus type-2
    Muhamad M, Kee LY, Rahman NA, Yusof R
    Int J Biol Sci, 2010 May 23;6(3):294-302.
    PMID: 20567498
    Dengue viruses, mosquito-borne members of the Flaviviridae family, are the causative agents of dengue fever and its associated complications, dengue haemorrhagic fever and dengue shock syndrome. To date, more than 2.5 billion people in over 100 countries are at risk of infection, and approximately 20 million infections were reported annually. There is currently no treatment or vaccine available for dengue infection. This study employed a whole-cell organism model or in vitro methods to study the inhibitory property of the flavanoid-derived compounds against DENV2 activity. Results showed that at concentration not exceeding the maximum non-toxic dose (MNTD), these compounds completely prevented DENV2 infection in HepG2 cells as indicated by the absence of cytophatic effects. The in vitro antiviral activity assessed in HepG2 cells employing virus inhibition assay showed high inhibitory activity in a dose dependent manner. At concentration below MNTD, compounds exhibited inhibitory activity against DENV2 with a range of potency strengths of 72% to 100%. The plaque forming unit per ml (pfu/ml) was reduced prominently with a maximum reduction of 98% when the infected HepG2 cells were treated with the highest non-toxic dose of compounds. The highly potent activity of the compounds against DENV2 infection strongly suggests their potential as a lead antiviral agent for dengue.
    Matched MeSH terms: Dengue/drug therapy*; Dengue/immunology; Dengue Virus/drug effects*; Dengue Virus/immunology; Severe Dengue/drug therapy
  4. Association of dengue serotypes and its complications: a retrospective cohort study
    Lau Q, Lee ZM, Shunmugarajoo A, Tan CY, Azmel A, Yap SY
    Med J Malaysia, 2023 May;78(3):372-378.
    PMID: 37271848
    INTRODUCTION: Dengue fever is an arthropod-borne disease and has a wide clinical spectrum. It is hypothesised that dengue serotypes could be a possible factor for such phenomena and therefore be a possible predictor for the development of severe dengue.

    METHOD: A retrospective cohort study was done to explore the association between dengue serotypes and the various complications. All patients who underwent dengue serotyping from 1st January to 31st December 2018 in Tengku Ampuan Rahimah Hospital were selected. Serotypes were randomly done for admitted dengue patients. Notes were then retrieved for data collection. Secondary outcomes like length of stay and highest lactate level were also studied. Data analysis was done using SPSS version 20.

    RESULT: A total of 193 patient records were included in the analysis. Chi-square test for independence indicated that the proportion of dengue complications between male and female were significantly different (χ2(1) = 11.37, p = 0.001). Dengue serotype was not associated with the development of dengue complications, total number of dengue complications, length of admission, lactate level and survival among the serotypes. Results of the binary logistic regression showed that men have thrice the odds (AOR = 3.3, 95% CI: 1.6 6.7) for developing dengue complications. One patient was found to be co-infected with serotype 2 and 3.

    CONCLUSION: Our study did not reveal any association between the different dengue virus serotypes and its complications. Therefore, all dengue infection should be approached with equal meticulousness. There are possibilities that apart from serotype, dengue genotype and lineage would determine clinical outcome. However, more studies are required to study such associations.

    Matched MeSH terms: Severe Dengue*
  5. Phytochemical profiling of the essential oils from three Curcuma species and their in vitro and in silico dengue protease inhibition activity
    Jani NA, Maarof NI, Zahari MMFM, Jamil M, Zakaria II, Mohamad Zobir SZ, et al.
    Nat Prod Res, 2024 Mar;38(6):926-932.
    PMID: 37144399 DOI: 10.1080/14786419.2023.2208256
    The chemical compositions, in vitro and in silico anti-dengue activity of the essential oils of the rhizomes of Curcuma longa Linn., C. aeruginosa Roxb., and C. xanthorrhiza Roxb. had been investigated. The C. longa oil was mainly composed of ar-turmerone (54.0%) and curlone (17.7%), while the C. aeruginosa oil was rich in curzerenone (23.4%), 1,8-cineole (21.2%), and camphor (7.1%). Xanthorrhizol (21.6%), β-curcumene (19.5%), ar-curcumene (14.2%), and camphor (9.2%) were the major compounds in the C. xanthorrhiza oil. Among the oils, the C. longa oil was found to be the most active NSB-NS3 protease inhibitor (IC50 1.98 μg/mL). PLS biplot disclosed that the essential oils were classified into three separated clusters based on their characteristic chemical compositions, with C. longa positioned closest to the in vitro anti-dengue activity. Four compounds from the C. longa oil have both hydrogen and hydrophobic bonds that could be responsible for the DENV-2 NS2B-NS3 inhibitory effect.
    Matched MeSH terms: Dengue*
  6. Fulltext Meta-Analysis of Dengue Severity during Infection by Different Dengue Virus Serotypes in Primary and Secondary Infections
    Soo KM, Khalid B, Ching SM, Chee HY
    PLoS One, 2016;11(5):e0154760.
    PMID: 27213782 DOI: 10.1371/journal.pone.0154760
    INTRODUCTION: Dengue virus (DENV) infection is currently a major cause of morbidity and mortality in the world; it has become more common and virulent over the past half-century and has gained much attention. Thus, this review compared the percentage of severe cases of both primary and secondary infections with different serotypes of dengue virus.

    METHODS: Data related to the number of cases involving dengue fever (DF), dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) or severe dengue infections caused by different serotypes of dengue virus were obtained by using the SCOPUS, the PUBMED and the OVID search engines with the keywords "(dengue* OR dengue virus*) AND (severe dengue* OR severity of illness index* OR severity* OR DF* OR DHF* OR DSS*) AND (serotypes* OR serogroup*)", according to the MESH terms suggested by PUBMED and OVID.

    RESULTS: Approximately 31 studies encompassing 15,741 cases reporting on the dengue serotypes together with their severity were obtained, and meta-analysis was carried out to analyze the data. This study found that DENV-3 from the Southeast Asia (SEA) region displayed the greatest percentage of severe cases in primary infection (95% confidence interval (CI), 31.22-53.67, 9 studies, n = 598, I2 = 71.53%), whereas DENV-2, DENV-3, and DENV-4 from the SEA region, as well as DENV-2 and DENV-3 from non-SEA regions, exhibited the greatest percentage of severe cases in secondary infection (95% CI, 11.64-80.89, 4-14 studies, n = 668-3,149, I2 = 14.77-96.20%). Moreover, DENV-2 and DENV-4 from the SEA region had been found to be more highly associated with dengue shock syndrome (DSS) (95% CI, 10.47-40.24, 5-8 studies, n = 642-2,530, I2 = 76.93-97.70%), while DENV-3 and DENV-4 from the SEA region were found to be more highly associated with dengue hemorrhagic fever (DHF) (95% CI, 31.86-54.58, 9 studies, n = 674-2,278, I2 = 55.74-88.47%), according to the 1997 WHO dengue classification. Finally, DENV-2 and DENV-4 from the SEA region were discovered to be more highly associated with secondary infection compared to other serotypes (95% CI, 72.01-96.32, 9-12 studies, n = 671-2,863, I2 = 25.01-96.75%).

    CONCLUSION: This study provides evidence that the presence of certain serotypes, including primary infection with DENV-3 from the SEA region and secondary infection with DENV-2, DENV-3, and DENV-4 also from the SEA region, as well as DENV-2 and DENV-3 from non SEA regions, increased the risk of severe dengue infections. Thus, these serotypes are worthy of special consideration when making clinical predictions upon the severity of the infection.

    SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015026093 (http://www.crd.york.ac.uk/PROSPERO).

    Matched MeSH terms: Dengue/virology*; Dengue Virus/classification*; Dengue Virus/genetics; Dengue Virus/immunology; Severe Dengue/virology*
  7. Fulltext A Deep Learning Approach for Dengue Fever Prediction in Malaysia Using LSTM with Spatial Attention
    Majeed MA, Shafri HZM, Zulkafli Z, Wayayok A
    Int J Environ Res Public Health, 2023 Feb 25;20(5).
    PMID: 36901139 DOI: 10.3390/ijerph20054130
    This research aims to predict dengue fever cases in Malaysia using machine learning techniques. A dataset consisting of weekly dengue cases at the state level in Malaysia from 2010 to 2016 was obtained from the Malaysia Open Data website and includes variables such as climate, geography, and demographics. Six different long short-term memory (LSTM) models were developed and compared for dengue prediction in Malaysia: LSTM, stacked LSTM (S-LSTM), LSTM with temporal attention (TA-LSTM), S-LSTM with temporal attention (STA-LSTM), LSTM with spatial attention (SA-LSTM), and S-LSTM with spatial attention (SSA-LSTM). The models were trained and evaluated on a dataset of monthly dengue cases in Malaysia from 2010 to 2016, with the task of predicting the number of dengue cases based on various climate, topographic, demographic, and land-use variables. The SSA-LSTM model, which used both stacked LSTM layers and spatial attention, performed the best, with an average root mean squared error (RMSE) of 3.17 across all lookback periods. When compared to three benchmark models (SVM, DT, ANN), the SSA-LSTM model had a significantly lower average RMSE. The SSA-LSTM model also performed well in different states in Malaysia, with RMSE values ranging from 2.91 to 4.55. When comparing temporal and spatial attention models, the spatial models generally performed better at predicting dengue cases. The SSA-LSTM model was also found to perform well at different prediction horizons, with the lowest RMSE at 4- and 5-month lookback periods. Overall, the results suggest that the SSA-LSTM model is effective at predicting dengue cases in Malaysia.
    Matched MeSH terms: Dengue*
  8. Thrombocytopenia in dengue infection: mechanisms and a potential application
    Khazali AS, Hadrawi WH, Ibrahim F, Othman S, Nor Rashid N
    Expert Rev Mol Med, 2024 Oct 14;26:e26.
    PMID: 39397710 DOI: 10.1017/erm.2024.18
    Thrombocytopenia is a common symptom and one of the warning signs of dengue virus (DENV) infection. Platelet depletion is critical as it may lead to other severe dengue symptoms. Understanding the molecular events of this condition during dengue infection is challenging because of the multifaceted factors involved in DENV infection and the dynamics of the disease progression. Platelet levels depend on the balance between platelet production and platelet consumption or clearance. Megakaryopoiesis and thrombopoiesis, two interdependent processes in platelet production, are hampered during dengue infection. Conversely, platelet elimination via platelet activation, apoptosis and clearance processes are elevated. Together, these anomalies contribute to thrombocytopenia in dengue patients. Targeting the molecular events of dengue-mediated thrombocytopenia shows great potential but still requires further investigation. Nonetheless, the application of new knowledge in this field, such as immature platelet fraction analysis, may facilitate physicians in monitoring the progression of the disease.
    Matched MeSH terms: Dengue Virus*
  9. Fulltext Understanding antibody-dependent enhancement in dengue: Are afucosylated IgG1s a concern?
    Teo A, Tan HD, Loy T, Chia PY, Chua CLL
    PLoS Pathog, 2023 Mar;19(3):e1011223.
    PMID: 36996026 DOI: 10.1371/journal.ppat.1011223
    Matched MeSH terms: Dengue*
  10. Fulltext Comparing the usefulness of the 1997 and 2009 WHO dengue case classification: a systematic literature review
    Horstick O, Jaenisch T, Martinez E, Kroeger A, See LL, Farrar J, et al.
    Am J Trop Med Hyg, 2014 Sep;91(3):621-34.
    PMID: 24957540 DOI: 10.4269/ajtmh.13-0676
    The 1997 and 2009 WHO dengue case classifications were compared in a systematic review with 12 eligible studies (4 prospective). Ten expert opinion articles were used for discussion. For the 2009 WHO classification studies show: when determining severe dengue sensitivity ranges between 59-98% (88%/98%: prospective studies), specificity between 41-99% (99%: prospective study) - comparing the 1997 WHO classification: sensitivity 24.8-89.9% (24.8%/74%: prospective studies), specificity: 25%/100% (100%: prospective study). The application of the 2009 WHO classification is easy, however for (non-severe) dengue there may be a risk of monitoring increased case numbers. Warning signs validation studies are needed. For epidemiological/pathogenesis research use of the 2009 WHO classification, opinion papers show that ease of application, increased sensitivity (severe dengue) and international comparability are advantageous; 3 severe dengue criteria (severe plasma leakage, severe bleeding, severe organ manifestation) are useful research endpoints. The 2009 WHO classification has clear advantages for clinical use, use in epidemiology is promising and research use may at least not be a disadvantage.
    Matched MeSH terms: Dengue/classification*; Dengue/diagnosis; Dengue/virology; Severe Dengue/classification; Severe Dengue/diagnosis; Severe Dengue/virology
  11. Micro-anatomical changes in major blood vessel caused by dengue virus (serotype 2) infection
    Priya SP, Sakinah S, Ling MP, Chee HY, Higuchi A, Hamat RA, et al.
    Acta Trop, 2017 Jul;171:213-219.
    PMID: 28427958 DOI: 10.1016/j.actatropica.2017.04.010
    Dengue virus (DENV) has emerged as a major economic concern in developing countries, with 2.5 billion people believed to be at risk. Vascular endothelial cells (ECs) lining the circulatory system from heart to end vessels perform crucial functions in the human body, by aiding gas exchange in lungs, gaseous, nutritional and its waste exchange in all tissues, including the blood brain barrier, filtration of fluid in the glomeruli, neutrophil recruitment, hormone trafficking, as well as maintenance of blood vessel tone and hemostasis. These functions can be deregulated during DENV infection. In this study, BALB/c mice infected with DENV serotype 2 were analyzed histologically for changes in major blood vessels in response to DENV infection. In the uninfected mouse model, blood vessels showed normal architecture with intact endothelial monolayer, tunica media, and tunica adventitia. In the infected mouse model, DENV distorted the endothelium lining and disturbed the smooth muscle, elastic laminae and their supporting tissues causing vascular structural disarrangement. This may explain the severe pathological illness in DENV-infected individuals. The overall DENV-induced damages on the endothelial and it's supporting tissues and the dysregulated immune reactions initiated by the host were discussed.
    Matched MeSH terms: Dengue/pathology*; Dengue/virology*; Dengue Virus/classification*
  12. [Laboratory diagnosis and molecular tracing of dengue bordline cases in Henan Province, 2017]
    Du YH, Li Y, Wang RL, Wang HF, Su J, Xu BL, et al.
    Zhonghua Yu Fang Yi Xue Za Zhi, 2018 Nov 06;52(11):1164-1167.
    PMID: 30419702 DOI: 10.3760/cma.j.issn.0253-9624.2018.11.013
    Objective: To confirm the laboratory diagnosis of dengue bordline cases reported in Henan Province and trace its origin from molecular level in 2017. Methods: The study samples were blood samples (3-5 ml), which came from 8 suspected cases of dengue fever reported in the 2017 direct reporting system of Henan provincial infectious disease monitoring network. Meanwhile, case investigation was conducted according to National dengue fever surveillance programme. Serum were separated from blood samples and tested for Dengue NS1 antigen, IgM & IgG antibodies, and dengue RNA. According to dengue diagnosis criteria, confirmed cases were identified by testing results. Samples carried dengue RNA performed for real-time PCR genotyping and amplification of E gene. Then, the amplicons were sequenced and homological and phylogenetic analyses were constructed. Results: 8 serum samples of suspected dengue cases were collected in Henan Province, 2017. Six of them were diagnosed as dengue confirmed cases. All the dengue confirmed cases belonged to outside imported cases, 5 of them were positive by dengue RNA testing. Genotyping results showed there were 1 DENV1 case, 2 DENV2 cases and 2 DENV3 cases. A DENV2 case and a DENV3 case of this study were traced its origin successfully. The sequence of Pakistan imported DENV2 case belongs to cosmopolitan genotype, which was the most consistent with Pakistan's DENV2 KJ010186 in 2013 (identity 99.0%). The sequence of Malaysia imported DENV3 case belongs to genotype I, which was the most consistent with Singapore's DENV3 KX224276 in 2014(identity 99.0%). Conclusion: The laboratory diagnosis and molecular traceability of dengue cases in Henan Province in 2017 confirmed that all cases were imported and did not cause local epidemics.
    Matched MeSH terms: Dengue/diagnosis*; Dengue Virus/genetics*; Dengue Virus/isolation & purification
  13. Fulltext Assessing weather effects on dengue disease in Malaysia
    Cheong YL, Burkart K, Leitão PJ, Lakes T
    Int J Environ Res Public Health, 2013 Nov 26;10(12):6319-34.
    PMID: 24287855 DOI: 10.3390/ijerph10126319
    The number of dengue cases has been increasing on a global level in recent years, and particularly so in Malaysia, yet little is known about the effects of weather for identifying the short-term risk of dengue for the population. The aim of this paper is to estimate the weather effects on dengue disease accounting for non-linear temporal effects in Selangor, Kuala Lumpur and Putrajaya, Malaysia, from 2008 to 2010. We selected the weather parameters with a Poisson generalized additive model, and then assessed the effects of minimum temperature, bi-weekly accumulated rainfall and wind speed on dengue cases using a distributed non-linear lag model while adjusting for trend, day-of-week and week of the year. We found that the relative risk of dengue cases is positively associated with increased minimum temperature at a cumulative percentage change of 11.92% (95% CI: 4.41-32.19), from 25.4 °C to 26.5 °C, with the highest effect delayed by 51 days. Increasing bi-weekly accumulated rainfall had a positively strong effect on dengue cases at a cumulative percentage change of 21.45% (95% CI: 8.96, 51.37), from 215 mm to 302 mm, with the highest effect delayed by 26-28 days. The wind speed is negatively associated with dengue cases. The estimated lagged effects can be adapted in the dengue early warning system to assist in vector control and prevention plan.
    Matched MeSH terms: Dengue/epidemiology*; Dengue/virology; Dengue Virus/physiology*
  14. A dot enzyme immunoassay for dengue 3 virus: comparison with the haemagglutination inhibition test
    Cardosa MJ, Noor Sham S, Tio PH, Lim SS
    Southeast Asian J Trop Med Public Health, 1988 Dec;19(4):591-4.
    PMID: 3238470
    A dot enzyme immunoassay (DEIA) was used to determine the levels of antibody to dengue 3 virus in the acute and convalescent sera of febrile patients with a clinical diagnosis of dengue fever or dengue haemorrhagic fever. The antibody titres were compared with titres determined by the haemagglutination inhibition (HI) test. The results of the study showed that, besides being more simple to perform, the DEIA is in order of magnitude more sensitive than the HI test. Furthermore, the data suggest that it is possible to use a single dilution as a cutoff point to predict with reasonable accuracy, if a patient has had a recent dengue infection. The DEIA test for antibodies to dengue virus is an appropriate technology highly suitable for rapid diagnosis and surveillance in developing countries.
    Matched MeSH terms: Dengue/diagnosis*; Dengue/microbiology; Dengue Virus/isolation & purification*
  15. Development of a dot enzyme immunoassay for dengue 3: a sensitive method for the detection of antidengue antibodies
    Cardosa MJ, Hooi TP, Shaari NS
    J Virol Methods, 1988 Oct;22(1):81-8.
    PMID: 3058737
    Partially purified DEN3 virus was used as antigen in a sensitive dot enzyme immunoassay (DEIA) for the detection of antibodies to flavivirus antigens. We describe here the method used to prepare and optimise the antigen-bearing nitrocellulose membranes and present the results obtained from screening 20 acute phase sera from patients shown to have had recent dengue infections by the haemagglutination inhibition (HI) test. Sixteen pairs of acute and convalescent sera from dengue-negative patients had no detectable antibody to dengue virus by HI. These were shown to have no antibody detectable by DEIA. Sera positive for dengue antibodies by HI had DEIA titers ranging from 10 to several thousand times greater than the titers detected by HI.
    Matched MeSH terms: Dengue/diagnosis; Dengue/immunology; Dengue Virus/immunology*
  16. Fulltext Isolation of ancestral sylvatic dengue virus type 1, Malaysia
    Teoh BT, Sam SS, Abd-Jamil J, AbuBakar S
    Emerg Infect Dis, 2010 Nov;16(11):1783-5.
    PMID: 21029545 DOI: 10.3201/eid1611.100721
    Ancestral sylvatic dengue virus type 1, which was isolated from a monkey in 1972, was isolated from a patient with dengue fever in Malaysia. The virus is neutralized by serum of patients with endemic DENV-1 infection. Rare isolation of this virus suggests a limited spillover infection from an otherwise restricted sylvatic cycle.
    Matched MeSH terms: Dengue/epidemiology*; Dengue Virus/classification*; Dengue Virus/genetics*
  17. Fulltext Dot enzyme immunoassay: an alternative diagnostic aid for dengue fever and dengue haemorrhagic fever
    Cardosa MJ, Tio PH
    Bull World Health Organ, 1991;69(6):741-5.
    PMID: 1786623
    A dot enzyme immunoassay (DEIA) for the detection of antibodies to dengue virus was tested for use as a tool in the presumptive diagnosis of dengue fever and dengue haemorrhagic fever. Paired sera from the following groups of patients were tested using the DEIA and the haemagglutination inhibition (HI) test: those with primary dengue fever; those experiencing a second dengue infection; and febrile patients who did not have dengue. The data obtained show that the DEIA can be effectively used at a serum dilution of 1:1000 to confirm presumptive recent dengue in patients with a second dengue infection. However, demonstration of seroconversion proved necessary for patients with primary dengue. At a serum dilution of 1:1000 the DEIA has a specificity of 97.3%. The role of this simple and rapid test in improving the effectivity of programmes for the control of dengue virus infection is discussed.
    Matched MeSH terms: Dengue/diagnosis*; Dengue/immunology; Dengue Virus/immunology*
  18. Tropical medicine. Surprising new dengue virus throws a spanner in disease control efforts
    Normile D
    Science, 2013 Oct 25;342(6157):415.
    PMID: 24159024 DOI: 10.1126/science.342.6157.415
    Matched MeSH terms: Dengue/epidemiology*; Dengue/prevention & control*; Dengue/transmission; Dengue Virus/classification*; Dengue Virus/immunology; Dengue Virus/isolation & purification; Dengue Vaccines/immunology*
  19. Clinicians' diagnostic practice of dengue infections
    Ng CF, Lum LC, Ismail NA, Tan LH, Tan CP
    J Clin Virol, 2007 Nov;40(3):202-6.
    PMID: 17928264 DOI: 10.1016/j.jcv.2007.08.017
    BACKGROUND: Difficulties in the classification of dengue infection have been documented. Such difficulties could be due to the low awareness of the World Health Organization diagnostic guidelines among clinicians.
    OBJECTIVE: To study the diagnostic practices of clinicians in classifying patients as dengue fever (DF) or dengue haemorrhagic fever (DHF)/dengue shock syndrome (DSS) at the time of discharge during an outbreak.
    METHODS: A prospective descriptive study of clinical features and disease classification in adult and pediatric dengue patients in the University of Malaya Medical Centre.
    RESULTS: Five hundred and twenty adult and 191 pediatric patients were enrolled. Thrombocytopenia and evidence of plasma leakage were present in 8% of adult and 19% of pediatric patients. Of these, 93% and 49%, respectively, were given the discharge diagnoses of DF instead of DHF/DSS. Hemoconcentration, serous effusion and thrombocytopenia were not recognized in clinicians' discharge diagnosis of DHF/DSS for adult patients. The receiver operating characteristic (ROC) curve suggested a lack of consistency in the use of WHO guidelines in establishing DHF/DSS in adult patients, while implying otherwise for pediatric patients.
    CONCLUSION: DHF/DSS is an under-recognized condition by clinicians managing these patients. This can affect the case fatality rate of DHF/DSS and the economic burden of the disease. The lack of awareness in disease manifestations especially plasma leakage, can lead to delayed recognition of DHF/DSS.
    Study site: Outpatient department and inpatients, adult medical and pediatric wards, University Malaya Medical Center (UMMC), Kuala Lumpur, Malaysia
    Matched MeSH terms: Dengue/classification; Dengue/diagnosis*; Dengue/epidemiology*; Dengue/physiopathology; Severe Dengue/classification; Severe Dengue/diagnosis*; Severe Dengue/epidemiology*; Severe Dengue/physiopathology
  20. Fulltext Senescence affects endothelial cells susceptibility to dengue virus infection
    AbuBakar S, Shu MH, Johari J, Wong PF
    Int J Med Sci, 2014;11(6):538-44.
    PMID: 24782642 DOI: 10.7150/ijms.7896
    Alteration in the endothelium leading to increased vascular permeability contributes to plasma leakage seen in dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). An earlier study showed that senescent endothelial cells (ECs) altered the ECs permeability. Here we investigated the susceptibility of senescing human umbilical vein endothelial cells (HUVECs) to dengue virus infection and determined if dengue virus infection induces HUVECs senescence. Our results suggest that DENV type-2 (DENV-2) foci forming unit (FFU) and extracellular virus RNA copy number were reduced by at least 35% and 85% in infection of the intermediate young and early senescent HUVECs, respectively, in comparison to infection of young HUVECs. No to low infectivity was recovered from infection of late senescent HUVECs. DENV infection also increases the percentage of HUVECs expressing senescence-associated (SA)-β-gal, cells arrested at the G2/M phase or 4N DNA content stage and cells with enlarged morphology, indicative of senescing cells. Alteration of HUVECs morphology was recorded using impedance-based real-time cell analysis system following DENV-2 infection. These results suggest that senescing HUVECs do not support DENV infection and DENV infection induces HUVECs senescence. The finding highlights the possible role of induction of senescence in DENV infection of the endothelial cells.
    Matched MeSH terms: Dengue/virology; Dengue Virus/genetics; Dengue Virus/pathogenicity*; Severe Dengue/virology
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