Displaying publications 41 - 60 of 111 in total

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  1. Young KI, Mundis S, Widen SG, Wood TG, Tesh RB, Cardosa J, et al.
    Parasit Vectors, 2017 Aug 31;10(1):406.
    PMID: 28859676 DOI: 10.1186/s13071-017-2341-z
    BACKGROUND: Mosquito-borne dengue virus (DENV) is maintained in a sylvatic, enzootic cycle of transmission between canopy-dwelling non-human primates and Aedes mosquitoes in Borneo. Sylvatic DENV can spill over into humans living in proximity to forest foci of transmission, in some cases resulting in severe dengue disease. The most likely vectors of such spillover (bridge vectors) in Borneo are Ae. albopictus and Ae. niveus. Borneo is currently experiencing extensive forest clearance. To gauge the effect of this change in forest cover on the likelihood of sylvatic DENV spillover, it is first necessary to characterize the distribution of bridge vectors in different land cover types. In the current study, we hypothesized that Ae. niveus and Ae. albopictus would show significantly different distributions in different land cover types; specifically, we predicted that Ae. niveus would be most abundant in forests whereas Ae. albopictus would have a more even distribution in the landscape.

    RESULTS: Mosquitoes were collected from a total of 15 sites using gravid traps and a backpack aspirator around Kampong Puruh Karu, Sarawak, Malaysian Borneo, where sylvatic DENV spillover has been documented. A total of 2447 mosquitoes comprising 10 genera and 4 species of Aedes, were collected over the three years, 2013, 2014 and 2016, in the three major land cover types in the area, homestead, agriculture and forest. Mosquitoes were identified morphologically, pooled by species and gender, homogenized, and subject to DNA barcoding of each Aedes species and to arbovirus screening. As predicted, Ae. niveus was found almost exclusively in forests whereas Ae. albopictus was collected in all land cover types. Aedes albopictus was significantly (P = 0.04) more abundant in agricultural fields than forests. Sylvatic DENV was not detected in any Aedes mosquito pools, however genomes of 14 viruses were detected using next generation sequencing.

    CONCLUSIONS: Land cover type affects the abundance and distribution of the most likely bridge vectors of sylvatic DENV in Malaysia Borneo. Conversion of forests to agriculture will likely decrease the range and abundance of Ae. niveus but enhance the abundance of Ae. albopictus.

    Matched MeSH terms: Severe Dengue/epidemiology; Severe Dengue/transmission; Severe Dengue/virology
  2. Nealon J, Taurel AF, Capeding MR, Tran NH, Hadinegoro SR, Chotpitayasunondh T, et al.
    PLoS Negl Trop Dis, 2016 Aug;10(8):e0004918.
    PMID: 27532617 DOI: 10.1371/journal.pntd.0004918
    Dengue incidence has increased globally, but empirical burden estimates are scarce. Prospective methods are best-able to capture all severities of disease. CYD14 was an observer-blinded dengue vaccine study conducted in children 2-14 years of age in Indonesia, Malaysia, Thailand, the Philippines, and Vietnam. The control group received no vaccine and resembled a prospective, observational study. We calculated the rates of dengue according to different laboratory or clinical criteria to make inferences about dengue burden, and compared with rates reported in the passive surveillance systems to calculate expansion factors which describe under-reporting. Over 6,933 person-years of observation in the control group there were 319 virologically confirmed dengue cases, a crude attack rate of 4.6%/year. Of these, 92 cases (28.8%) were clinically diagnosed as dengue fever or dengue hemorrhagic fever by investigators and 227 were not, indicating that most symptomatic disease fails to satisfy existing case definitions. When examining different case definitions, there was an inverse relationship between clinical severity and observed incidence rates. CYD14's active surveillance system captured a greater proportion of symptomatic dengue than national passive surveillance systems, giving rise to expansion factors ranging from 0.5 to 31.7. This analysis showed substantial, unpredictable and variable under-reporting of symptomatic dengue, even within a controlled clinical trial environment, and emphasizes that burden estimates are highly sensitive to case definitions. These data will assist in generating disease burden estimates and have important policy implications when considering the introduction and health economics of dengue prevention and control interventions.
    Matched MeSH terms: Severe Dengue/epidemiology*; Severe Dengue/prevention & control*; Severe Dengue/virology
  3. Sam SS, Omar SF, Teoh BT, Abd-Jamil J, AbuBakar S
    PLoS Negl Trop Dis, 2013;7(5):e2194.
    PMID: 23658849 DOI: 10.1371/journal.pntd.0002194
    Dengue is a mosquito-borne viral disease endemic in many countries in the tropics and sub-tropics. The disease affects mainly children, but in recent years it is becoming more of an adult disease. Malaysia experienced a large dengue outbreak in 2006 to 2007, involving mostly adults, with a high number of deaths.
    Matched MeSH terms: Severe Dengue/mortality*; Severe Dengue/epidemiology*
  4. Mallhi TH, Sarriff A, Adnan AS, Khan YH, Hamzah AA, Jummaat F, et al.
    J Coll Physicians Surg Pak, 2015 Nov;25(11):828-34.
    PMID: 26577971 DOI: 11.2015/JCPSP.828834
    Dengue Viral Infection (DVI) imperils an estimated 2.5 billion people living in tropical and subtropical regions. World Health Organization (2011) guidelines also classified dengue as 'Expanded Dengue Syndrome' to incorporate wide spectrum of unusual manifestations of dengue infection affecting various organ systems - including liver, kidney, heart and brain. Renal involvements are least appreciated area of dengue infection, therefore, we systematically reviewed studies describing renal disorders in dengue infection, with emphasis on Acute Kidney Injury (AKI). The purpose of current review is to underscore clinicians’attention to this neglected intricacy of DVI. It suggests that dengue induced renal involvements vary from glomerulonephritis, nephrotic range proteinuria and AKI. We observed great disparity in incidence of AKI among dengue patients, based upon criteria used to define AKI. AKI among dengue patients was found to be associated with significant morbidity, mortality and longer hospitalization, adding financial burden to patients and healthcare system. Additionally, we identified several predictors of AKI in dengue patients including old age, obesity, severe dengue infection and concurrent bacterial or viral infection. Direct viral injury and deposition of antigen-antibody complex in glomerulus were found to be possible causes of renal disorders in dengue infection. Prior knowledge of clinico-laboratory characteristics and risk factors with early detection of AKI by using appropriate criteria would not only reduce morbidity and mortality but also decrease burden to patients and healthcare system.
    Matched MeSH terms: Severe Dengue/complications*; Severe Dengue/mortality*
  5. Ahmad R, Ismail A, Saat Z, Lim LH
    PMID: 9322296
    Mosquito adults and larvae were collected from dengue high risk areas and transported to the laboratory for identification. Identified mosquitos were pooled according to the species, date and locality and stored at -70 degrees C. A total of 1,385 pools of Aedes albopictus and 267 pools of Ae. Aegypti were collected from major towns in 12 states in Peninsular Malaysia. Virus isolation was carried out using cell culture (C6/36 clone) of Ae. albopictus and detection of dengue virus by the peroxidase anti-peroxidase staining. All positive isolations were further re-confirmed by the reverse transcriptase-polymerase chain reaction (RT-PCR). Most of the pools were negative with PAP staining and RT-PCR. However, 11 mosquito pools were positive with PAP staining. On the other hand, samples from Terengganu, Pulau Pinang and Johor were positive using both methods.
    Matched MeSH terms: Severe Dengue/transmission*; Severe Dengue/virology
  6. Lum LC, Abdel-Latif Mel-A, Goh AY, Chan PW, Lam SK
    J Pediatr, 2003 Nov;143(5):682-4.
    PMID: 14615749
    We compared 53 patients with Dengue shock syndrome (DSS) who received preventive transfusions with 53 who did not. Significant differences in the development of pulmonary edema and length of hospitalization (P
    Matched MeSH terms: Severe Dengue/complications; Severe Dengue/prevention & control*
  7. Md-Sani SS, Md-Noor J, Han WH, Gan SP, Rani NS, Tan HL, et al.
    BMC Infect Dis, 2018 05 21;18(1):232.
    PMID: 29783955 DOI: 10.1186/s12879-018-3141-6
    BACKGROUND: Increasing incidence of dengue cases in Malaysia over the last few years has been paralleled by increased deaths. Mortality prediction models will therefore be useful in clinical management. The aim of this study is to identify factors at diagnosis of severe dengue that predicts mortality and assess predictive models based on these identified factors.

    METHOD: This is a retrospective cohort study of confirmed severe dengue patients that were admitted in 2014 to Hospital Kuala Lumpur. Data on baseline characteristics, clinical parameters, and laboratory findings at diagnosis of severe dengue were collected. The outcome of interest is death among patients diagnosed with severe dengue.

    RESULTS: There were 199 patients with severe dengue included in the study. Multivariate analysis found lethargy, OR 3.84 (95% CI 1.23-12.03); bleeding, OR 8.88 (95% CI 2.91-27.15); pulse rate, OR 1.04 (95% CI 1.01-1.07); serum bicarbonate, OR 0.79 (95% CI 0.70-0.89) and serum lactate OR 1.27 (95% CI 1.09-1.47), to be statistically significant predictors of death. The regression equation to our model with the highest AUROC, 83.5 (95% CI 72.4-94.6), is: Log odds of death amongst severe dengue cases = - 1.021 - 0.220(Serum bicarbonate) + 0.001(ALT) + 0.067(Age) - 0.190(Gender).

    CONCLUSION: This study showed that a large proportion of severe dengue occurred early, whilst patients were still febrile. The best prediction model to predict death at recognition of severe dengue is a model that incorporates serum bicarbonate and ALT levels.

    Matched MeSH terms: Severe Dengue/diagnosis; Severe Dengue/mortality*
  8. Kumarasamy V, Chua SK, Hassan Z, Wahab AH, Chem YK, Mohamad M, et al.
    Singapore Med J, 2007 Jul;48(7):669-73.
    PMID: 17609831
    INTRODUCTION: The aim of this report is to establish an accurate diagnosis of acute dengue virus infection early, in order to provide timely information for the management of patients and early public health control of dengue outbreak.
    METHODS: 224 serum samples from patients with a clinical diagnosis of acute dengue infection, which were subsequently confirmed by laboratory tests, were used to evaluate the performance of a commercially-available dengue NS1 antigen-capture ELISA kit.
    RESULTS: The dengue NS1 antigen-capture ELISA gave an overall sensitivity rate of 93.3 percent (209/224). The sensitivity rate was significantly higher in acute primary dengue (97.4 percent) than in acute secondary dengue (68.8 percent). In comparison, the virus isolation gave an overall positive isolation rate of 64.7 percent, with a positive rate of 70.8 percent and 28.1 percent, for acute primary dengue and acute secondary dengue, respectively. Molecular detection of dengue RNA by RT-PCR gave an overall positive detection rate of 63.4 percent, with a positive rate of 62.5 percent and 68.8 percent, for acute primary dengue and acute secondary dengue, respectively. Of the 224 acute serum samples from patients with laboratory-confirmed acute dengue infection, dengue IgM was detected in 88 specimens, comprising 68 acute primary dengue specimens and 20 acute secondary dengue specimens. NS1 antigen-capture ELISA kit gave an overall sensitivity rate of 88.6 percent in the presence of anti-dengue IgM and 96.3 percent in the absence of anti-dengue IgM.
    CONCLUSION: Of the 224 acute serum samples, the sample ages of 166 acute serum samples are known. The positive detection rate of dengue NS1 antigen-capture ELISA, on the whole, was higher than the other three established diagnostic test methods for laboratory diagnosis of acute dengue infection.
    Matched MeSH terms: Severe Dengue/diagnosis*; Severe Dengue/immunology
  9. Kamil SM, Mohamad NH, Narazah MY, Khan FA
    Singapore Med J, 2006 Apr;47(4):332-4.
    PMID: 16572249
    We describe a case of dengue haemorrhagic fever with prolonged thrombocytopaenia. A 22-year-old Malay man with no prior illness presented with a history of fever and generalised macular rash of four days duration. Initial work-up suggested the diagnosis of dengue haemorrhagic fever based on thrombocytopaenia and positive dengue serology. Patient recovered from acute illness by day ten, and was discharged from the hospital with improving platelet count. He was then noted to have declining platelet count on follow-up and required another hospital admission on day 19 of his illness because of declining platelet count. The patient remained hospitalised till day 44 of his illness and managed with repeated platelet transfusion and supportive care till he recovered spontaneously.
    Matched MeSH terms: Severe Dengue/complications*; Severe Dengue/diagnosis*
  10. Cardosa MJ
    Br Med Bull, 1998;54(2):395-405.
    PMID: 9830205 DOI: 10.1093/oxfordjournals.bmb.a011696
    Dengue virus infection is now a global problem affecting tens of millions of people. The spread of the four dengue virus serotypes had led to increased incidence of dengue haemorrhagic fever (DHF) reported and with 2.5 billion people at risk, efforts towards the development of safe and effective vaccines against dengue must be accelerated. This chapter reviews some of the important lessons of pathogenesis which may be learnt from classical studies in the field and place these in the context of current knowledge about the molecular biology of the virus. The issues which have to be addressed in designing a safe vaccine against dengue are raised and the problems of designing subunit as well as whole virus vaccines are pointed out, particularly with regard to the phenomenon of antibody dependent enhancement and, more generally, the problem of immune potentiation of disease. More efforts must be made to understand the basis of pathogenesis in DHF and in finding out what nature has to teach about protection against and recovery from dengue virus infection.
    Matched MeSH terms: Severe Dengue/immunology; Severe Dengue/prevention & control
  11. Kaur N, Rahim SSSA, Jaimin JJ, Dony JJF, Khoon KT, Ahmed K
    J Physiol Anthropol, 2020 Aug 14;39(1):19.
    PMID: 32795350 DOI: 10.1186/s40101-020-00230-0
    BACKGROUND: Malaysia recorded the highest number of dengue cases between 2014 and 2017. There are 13 states and three federal territories in Malaysia, and each area varies in their prevalence of dengue. Sabah is one of the states situated in Borneo, Malaysia. Although dengue has been increasing for the last several years, no study was being done to understand the burden and serotype distribution of the dengue virus (DENV) in Sabah. Therefore, the present study was carried out to understand the epidemiology of the dengue infection and the factors responsible for severe dengue in Sabah.

    METHODS: Data on dengue infection were extracted from the dengue database of the state of Sabah from 2013 through 2018. DENV NS-1-positive serum samples from multiple sites throughout Sabah were sent to the state public health laboratory, Kota Kinabalu Public Health Laboratory, for serotype determination. The analysis of factors associated with severe dengue was determined from the data of 2018 only.

    RESULTS: In 2013, there were 724 dengue cases; however, from 2014, dengue cases increased exponentially and resulted in 3423 cases in 2018. Increasing dengue cases also led to increased dengue mortality. The number of dengue deaths in 2013 was only five which then gradually increased, and in 2018, 29 patients died. This is an increase of 580% from 2013 to 2018. Deaths were considerably more in the districts of the east coast of Sabah compared with districts in the west coast. During the study period, all DENV serotypes could be identified as serotypes circulating in Sabah. In 2018, the predominant serotype was DENV-3. The monthly peak of dengue infection varied in different years. In the logistic regression analysis, it was identified that children were 6.5 times, patients infected with mixed serotype of DENV were 13 times, and cases from the districts of the east coast were 5.2 times more likely to develop severe dengue.

    CONCLUSIONS: An increasing trend of dengue infection has been observed in Sabah. The burden of dengue, severe dengue, and mortality was noted especially in the districts of the east coast of Sabah. Severe dengue was most likely developed in children, cases from the east coast, and patients infected with mixed serotype of DENV.

    Matched MeSH terms: Severe Dengue/epidemiology*; Severe Dengue/virology*
  12. Rosenberger KD, Alexander N, Martinez E, Lum LCS, Dempfle CE, Junghanss T, et al.
    PLoS Negl Trop Dis, 2020 Mar;14(3):e0008076.
    PMID: 32130212 DOI: 10.1371/journal.pntd.0008076
    Severe dengue was perceived as one clinical disease entity until the WHO 2009 classification stratified it into severe vascular leakage, severe bleeding, and severe organ dysfunction. The objectives of this study were to investigate the potential use of severe dengue categories as endpoints for intervention research. 271 patients with severe dengue among 1734 confirmed dengue patients were followed prospectively in this hospital-based observational study in Latin America and Asia. We compared the distribution of severe dengue categories according to gender and age (below/above 15y), and determined the relative frequency and the overlap of severe dengue categories in the same patients. In a next step, we extended the analysis to candidate moderate severity categories, based on recently suggested definitions which were adapted for our purposes. Severe vascular leakage occurred in 244 (90%), severe bleeding in 39 (14%), and severe organ dysfunction in 28 (10%) of 271 severe dengue patients. A higher frequency of severe leakage was seen in children or adolescents (<15y) compared to adults. More than 80% of the severe leakage cases, and 30-50% of the cases with severe bleeding or severe organ dysfunction, were defined as severe on the basis of that feature alone. In 136 out of 213 patients with severe leakage alone, neither moderate bleeding manifestation nor hepatic involvement was recorded. On the other hand, moderate leakage manifestations were detected in 4 out of 12 cases that were classified as severe based on bleeding alone. A major proportion of severe dengue patients exhibited clinical manifestations of severe vascular leakage only, which may constitute a useful endpoint for intervention research or pathophysiology studies. Severe bleeding and severe organ manifestation were recorded less frequently and exhibited a higher degree of overlap with severe leakage. Severe bleeding without leakage may be associated with individual predisposition or the presence of comorbidities. More detailed assessments are needed to explore this hypothesis. Candidate moderate disease endpoints were investigated and need to be further validated.
    Matched MeSH terms: Severe Dengue/classification*; Severe Dengue/pathology*
  13. Woon YL, Hor CP, Hussin N, Zakaria A, Goh PP, Cheah WK
    PLoS Negl Trop Dis, 2016 05;10(5):e0004575.
    PMID: 27203726 DOI: 10.1371/journal.pntd.0004575
    BACKGROUND: Dengue infection is the fastest spreading mosquito-borne viral disease, which affects people living in the tropical and subtropical countries. Malaysia had large dengue outbreaks in recent years. We aimed to study the demographics and clinical characteristics associated with dengue deaths in Malaysia.

    METHODS: We conducted a retrospective review on all dengue deaths that occurred nationwide between 1st January 2013 and 31st December 2014. Relevant data were extracted from mortality review reports and investigational forms. These cases were categorized into children (<15 years), adults (15-59 years) and elderly (≥60 years) to compare their clinical characteristics.

    RESULTS: A total of 322 dengue deaths were reviewed. Their mean age was 40.7±19.30 years, half were females and 72.5% were adults. The median durations of first medical contact, and hospitalization were 1 and 3 days, respectively. Diabetes and hypertension were common co-morbidities among adults and elderly. The most common warning signs reported were lethargy and vomiting, with lethargy (p = 0.038) being more common in children, while abdominal pain was observed more often in the adults (p = 0.040). But 22.4% did not have any warning signs. Only 34% were suspected of dengue illness at their initial presentation. More adults developed severe plasma leakage (p = 0.018). More than half (54%) suffered from multi-organ involvement, and 20.2% were free from any organ involvement. Dengue deaths occurred at the median of 3 days post-admission. Dengue shock syndrome (DSS) contributed to more than 70% of dengue deaths, followed by severe organ involvement (69%) and severe bleeding (29.7%).

    CONCLUSION: In Malaysia, dengue deaths occurred primarily in adult patients. DSS was the leading cause of death, regardless of age groups. The atypical presentation and dynamic progression of severe dengue in this cohort prompts early recognition and aggressive intervention to prevent deaths.

    TRIAL REGISTRATION: National Medical Research Registry (NMRR, NMRR-14-1374-23352).
    Matched MeSH terms: Severe Dengue/diagnosis; Severe Dengue/mortality*; Severe Dengue/epidemiology*; Severe Dengue/virology
  14. Soe HJ, Manikam R, Raju CS, Khan MA, Sekaran SD
    PLoS One, 2020;15(8):e0237141.
    PMID: 32764789 DOI: 10.1371/journal.pone.0237141
    Severe dengue can be lethal caused by manifestations such as severe bleeding, fluid accumulation and organ impairment. This study aimed to investigate the role of dengue non-structural 1 (NS1) protein and host factors contributing to severe dengue. Electrical cell-substrate impedance sensing system was used to investigate the changes in barrier function of microvascular endothelial cells treated NS1 protein and serum samples from patients with different disease severity. Cytokines and metabolites profiles were assessed using a multiplex cytokine assay and liquid chromatography mass spectrometry respectively. The findings showed that NS1 was able to induce the loss of barrier function in microvascular endothelium in a dose dependent manner, however, the level of NS1 in serum samples did not correlate with the extent of vascular leakage induced. Further assessment of host factors revealed that cytokines such as CCL2, CCL5, CCL20 and CXCL1, as well as adhesion molecule ICAM-1, that are involved in leukocytes infiltration were expressed higher in dengue patients in comparison to healthy individuals. In addition, metabolomics study revealed the presence of deregulated metabolites involved in the phospholipid metabolism pathway in patients with severe manifestations. In conclusion, disease severity in dengue virus infection did not correlate directly with NS1 level, but instead with host factors that are involved in the regulation of junctional integrity and phospholipid metabolism. However, as the studied population was relatively small in this study, these exploratory findings should be confirmed by expanding the sample size using an independent cohort to further establish the significance of this study.
    Matched MeSH terms: Severe Dengue/blood*; Severe Dengue/immunology; Severe Dengue/metabolism; Severe Dengue/pathology
  15. Cardosa J, Ooi MH, Tio PH, Perera D, Holmes EC, Bibi K, et al.
    PLoS Negl Trop Dis, 2009;3(4):e423.
    PMID: 19399166 DOI: 10.1371/journal.pntd.0000423
    Dengue viruses circulate in both human and sylvatic cycles. Although dengue viruses (DENV) infecting humans can cause major epidemics and severe disease, relatively little is known about the epidemiology and etiology of sylvatic dengue viruses. A 20-year-old male developed dengue hemorrhagic fever (DHF) with thrombocytopenia (12,000/ul) and a raised hematocrit (29.5% above baseline) in January 2008 in Malaysia. Dengue virus serotype 2 was isolated from his blood on day 4 of fever. A phylogenetic analysis of the complete genome sequence revealed that this virus was a member of a sylvatic lineage of DENV-2 and most closely related to a virus isolated from a sentinel monkey in Malaysia in 1970. This is the first identification of a sylvatic DENV circulating in Asia since 1975.
    Matched MeSH terms: Severe Dengue/pathology; Severe Dengue/virology*
  16. Fadilah SA, Sahrir S, Raymond AA, Cheong SK, Aziz JA, Sivagengei K
    PMID: 10928365
    Activation of immunoregulatory T lymphocyte subsets has been observed in dengue viral infection, being more evident in dengue hemorrhagic fever (DHF) than in classical dengue fever (DF). There are, however, as yet no well-defined host markers to determine which patients with dengue viral infection will develop severe complications during the acute febrile stage of the disease. A study was performed to compare the cellular immune status in DHF, DF and non-dengue viral infections (NDF) in order to determine the value of these parameters in distinguishing DHF from classic DF and other viral infections during the acute febrile stage of the disease. This study involved 109 febrile patients admitted because of suspected DHF. Fifty patients were serologically confirmed cases of dengue infection, of which 25 had grade 1 or 2 DHF. There was a reduction in total T (CD3), CD4 and CD8 cells in DHF and demonstrated that a low level of CD3, CD4, CD8 and CD5 cells discriminated DHF from DF patients during the febrile stage of the illness. In contrast, B (CD19) cells and natural killer (NK) cells did not appear to be discriminatory in this study. Receiver operating characteristic (ROC) curve analysis showed that a combination of CD3 cell of < or = 45% and CD5 cell of < or = 55% was the best marker to identify DHF patients (sensitivity = 84% and specificity = 52% for CD3 cell of < or = 45%; sensitivity = 92% and specificity = 71% for CD5 cell of < or = 55%). CD4 cell of < or = 25% and CD8 cell < or = 30% were equally good in discriminating DHF from DF patients. On the other hand, the ROC curves indicated no clear difference between the immunoregulatory cell counts in DF from NDF Lymphopenia, atypical lymphocytosis and thrombocytopenia were significantly more evident in dengue compared to non-dengue infection but did not appear to be discriminatory among DHF and DF patients. The reduction in CD3, CD4, CD8, CD5 cells correlated with the degree of thrombocytopenia in DHF (p < 0.05) which suggests that these cells probably participate in a common pathogenetic mechanism.
    Matched MeSH terms: Severe Dengue/diagnosis*; Severe Dengue/immunology
  17. Ibrahim F, Ismail NA, Taib MN, Wan Abas WA
    Physiol Meas, 2004 Jun;25(3):607-15.
    PMID: 15253113 DOI: 10.1088/0967-3334/25/3/002
    This paper describes a model for predicting hemoglobin (Hb) by using bioelectrical impedance analysis (BIA) in dengue patients in the Hospital Universiti Kebangsaan Malaysia (HUKM). Bioelectrical impedance measurements were conducted on 83 (47 males and 36 females) serologically confirmed dengue fever (DF) and dengue hemorrhagic fever (DHF) patients during their hospitalization. The predictive equation for Hb was derived using multivariate analysis. We investigated all the parameters in BIA, patients' symptom and demographic data. In this developed model, four predictors (reactance (XC), sex, weight and vomiting) were found to be the best predictive factors for modeling Hb in dengue patients. However, the model can only explain approximately 42% of the variation in Hb status, thus single frequency bio-impedance stand-alone technique is insufficient to monitor Hb for the DF and DHF patients. Further investigation using multi-frequency BIA is recommended in modeling Hb to achieve the most parsimonious model.
    Matched MeSH terms: Severe Dengue/blood*; Severe Dengue/diagnosis*
  18. Vuong NL, Le Duyen HT, Lam PK, Tam DTH, Vinh Chau NV, Van Kinh N, et al.
    BMC Med, 2020 02 17;18(1):35.
    PMID: 32063229 DOI: 10.1186/s12916-020-1496-1
    BACKGROUND: Dengue infection can cause a wide spectrum of clinical outcomes. The severe clinical manifestations occur sufficiently late in the disease course, during day 4-6 of illness, to allow a window of opportunity for risk stratification. Markers of inflammation may be useful biomarkers. We investigated the value of C-reactive protein (CRP) measured early on illness days 1-3 to predict dengue disease outcome and the difference in CRP levels between dengue and other febrile illnesses (OFI).

    METHOD: We performed a nested case-control study using the clinical data and samples collected from the IDAMS-consortium multi-country study. This was a prospective multi-center observational study that enrolled almost 8000 participants presenting with a dengue-like illness to outpatient facilities in 8 countries across Asia and Latin America. Predefined severity definitions of severe and intermediate dengue were used as the primary outcomes. A total of 281 cases with severe/intermediate dengue were compared to 836 uncomplicated dengue patients as controls (ratio 1:3), and also 394 patients with OFI.

    RESULTS: In patients with confirmed dengue, median (interquartile range) of CRP level within the first 3 days was 30.2 mg/L (12.4-61.2 mg/L) (uncomplicated dengue, 28.6 (10.5-58.9); severe or intermediate dengue, 34.0 (17.4-71.8)). Higher CRP levels in the first 3 days of illness were associated with a higher risk of severe or intermediate outcome (OR 1.17, 95% CI 1.07-1.29), especially in children. Higher CRP levels, exceeding 30 mg/L, also associated with hospitalization (OR 1.37, 95% CI 1.14-1.64) and longer fever clearance time (HR 0.84, 95% CI 0.76-0.93), especially in adults. CRP levels in patients with dengue were higher than patients with potential viral infection but lower than patients with potential bacterial infection, resulting in a quadratic association between dengue diagnosis and CRP, with levels of approximately 30 mg/L associated with the highest risk of having dengue. CRP had a positive correlation with total white cell count and neutrophils and negative correlation with lymphocytes, but did not correlate with liver transaminases, albumin, or platelet nadir.

    CONCLUSIONS: In summary, CRP measured in the first 3 days of illness could be a useful biomarker for early dengue risk prediction and may assist differentiating dengue from other febrile illnesses.

    Matched MeSH terms: Severe Dengue/blood; Severe Dengue/diagnosis*
  19. Md Sani SS, Han WH, Bujang MA, Ding HJ, Ng KL, Amir Shariffuddin MA
    BMC Infect Dis, 2017 07 21;17(1):505.
    PMID: 28732476 DOI: 10.1186/s12879-017-2601-8
    BACKGROUND: Existing biomarkers such as AST, ALT and hematocrit have been associated with severe dengue but evidence are mixed. Recently, interests in creatine kinase as a dengue biomarker have risen. These biomarkers represent several underlying pathophysiological processes in dengue. Hence, we aimed to assess AST, ALT, CK and hematocrit in identification of severe dengue and to assess the correlational relationship amongst common biomarkers of dengue.

    METHODS: This was a retrospective cohort study of confirmed dengue patients who were warded in Kuala Lumpur Hospital between December 2014 and January 2015. CK, AST, ALT, hematocrit, platelet count, WBC and serum albumin were taken upon ward admission and repeated at timed intervals. Composite indices based on admission AST and ALT were analyzed. Correlation coefficients and coefficients of determination were computed.

    RESULTS: Among the 365 cases reviewed, twenty-two (6%) patients had severe dengue. AST and ALT were found to be good at identification of severe dengue. The AST2/ALT composite index was the most accurate (AUC 0.83; 95% CI 0.73 - 0.93). Optimal cutoff was 402 with a sensitivity of 59.1% (95% CI: 36.4 - 79.3%) and specificity of 92.4% (95% CI: 89.1 - 95.0%). Modified cutoff of 653 had a sensitivity of 40.9% (95% CI: 20.7 - 63.7%) and specificity of 97.4% (95% CI: 95.1 - 98.8%). Our analyses also suggested that several underlying biological processes represented by biomarkers tested were unrelated despite occurring in the same disease entity. Also, markers of plasma leakage were discordant and AST was likely hepatic in origin.

    CONCLUSIONS: The composite index AST2/ALT may be used as a marker for identification of severe dengue based on admission AST and ALT, with two choices of cutoff values, 402 and 653. AST is most likely of liver origin and CK does not provide additional value.

    Matched MeSH terms: Severe Dengue/diagnosis*; Severe Dengue/enzymology*
  20. Ngwe Tun MM, Muthugala R, Rajamanthri L, Nabeshima T, Buerano CC, Morita K
    Jpn J Infect Dis, 2021 Sep 22;74(5):443-449.
    PMID: 33642435 DOI: 10.7883/yoken.JJID.2020.854
    During the 2017 outbreak of severe dengue in Sri Lanka, dengue virus (DENV) serotypes 2, 3, and 4 were found to be co-circulating. Our previous study of 295 patients from the National Hospital Kandy in Sri Lanka between March 2017 and January 2018 determined that the dominant infecting serotype was DENV-2. In this study, we aimed to characterize the DENV-3 strains from non-severe and severe dengue patients from our previous study population. Patients' clinical records and previous laboratory tests, including dengue-specific nonstructural protein 1 antigen rapid test and IgM-capture and IgG enzyme-linked immunosorbent assays, were analyzed together with the present results of real-time reverse transcription polymerase chain reaction and next-generation sequencing of DENV-3. Complete genome analysis determined that DENV-3 isolates belonged to 2 different clades of genotype I and were genetically close to strains from Indonesia, China, Singapore, Malaysia, and Australia. There were 16 amino acid changes among DENV-3 isolates, and a greater number of changes were found in nonstructural proteins than in structural proteins. The emergence of DENV-3 genotype I was noted for the first time in Sri Lanka. Continuous monitoring of this newly emerged genotype and other DENV serotypes and genotypes is needed to determine their effects on future outbreaks and understand the molecular epidemiology of dengue.
    Matched MeSH terms: Severe Dengue/diagnosis; Severe Dengue/epidemiology*
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