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  1. Low GKK, Gan SC, Zainal N, Naidu KD, Amin-Nordin S, Khoo CS, et al.
    Pathog Glob Health, 2018 09;112(6):334-341.
    PMID: 30246621 DOI: 10.1080/20477724.2018.1516417
    This study aimed to evaluate vascular endothelial growth factor (VEGF) and pentraxin 3 (PTX-3) as predictive and diagnostic markers in differentiating severe dengue from non-severe dengue. The study was conducted in Ampang Health Clinic, Ampang Hospital and Serdang Hospital. The plasma levels of VEGF and PTX-3 were compared between severe dengue and non-severe dengue by ELISA from the day of presentation until discharged. Multiple logistic regression was used to develop predictive and diagnostic models by incorporating other clinical parameters. The receiver operating characteristics (ROC) analysis was used to assess the accuracy of the biomarkers and the developed models. Eighty-two patients were recruited, 29 with severe dengue and four died. The Area Under the Curve (AUC) was statistically significant in VEGF as diagnostic marker at Day 2 and 3 of illness with sensitivity of 80.00%-100.00% and specificity of 76.47%-80.00%. The predictive model with AUC of 0.84 (p 
    Matched MeSH terms: Severe Dengue/diagnosis*
  2. Franco L, Palacios G, Martinez JA, Vázquez A, Savji N, De Ory F, et al.
    PLoS Negl Trop Dis, 2011 Aug;5(8):e1251.
    PMID: 21829739 DOI: 10.1371/journal.pntd.0001251
    Dengue virus (DENV) circulates in human and sylvatic cycles. Sylvatic strains are both ecologically and evolutionarily distinct from endemic viruses. Although sylvatic dengue cycles occur in West African countries and Malaysia, only a few cases of mild human disease caused by sylvatic strains and one single case of dengue hemorrhagic fever in Malaysia have been reported. Here we report a case of dengue hemorrhagic fever (DHF) with thrombocytopenia (13000/µl), a raised hematocrit (32% above baseline) and mucosal bleeding in a 27-year-old male returning to Spain in November 2009 after visiting his home country Guinea Bissau. Sylvatic DENV-2 West African lineage was isolated from blood and sera. This is the first case of DHF associated with sylvatic DENV-2 in Africa and the second case worldwide of DHF caused by a sylvatic strain.
    Matched MeSH terms: Severe Dengue/diagnosis
  3. Thayan R, Huat TL, See LL, Khairullah NS, Yusof R, Devi S
    PMID: 19323035
    We determined the differential expression levels of proteins in peripheral blood mononuclear cells of patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). Proteins were subjected to two-dimensional electrophoresis, mass spectrometry and Western blot analysis. We identified 8 proteins that were 2-fold or more up-regulated in patients compared to healthy control, three of which, aldolase, thioredoxin peroxidase and alpha tubulin, were related to dengue infection. Both thioredoxin peroxidase and alpha tubulin were over-expressed 4.9 and 3.3 times respectively in DHF compared to DF patients while aldolase was up-regulated 2.2 times in DF compared to DHF patients. Alpha tubulin and thioredoxin peroxidase have the potential to be utilized as biomarkers for DHF.
    Matched MeSH terms: Severe Dengue/diagnosis
  4. Thayan R, Huat TL, See LL, Tan CP, Khairullah NS, Yusof R, et al.
    Trans R Soc Trop Med Hyg, 2009 Apr;103(4):413-9.
    PMID: 19203772 DOI: 10.1016/j.trstmh.2008.12.018
    Dengue infection is a major public health problem affecting millions of people living in tropical countries. With no suitable vaccines and specific antiviral drugs, treatment for dengue is usually symptomatic and supportive. Early diagnosis and recognition of severe disease is therefore crucial for better management of the patient. Two-dimension electrophoresis was used to identify disease-associated proteins that can be used for diagnosis and as drug targets for treatment. Two markers, identified by mass spectrometry analysis as alpha1-antitrypsin and NS1 proteins were found to be upregulated in dengue fever (DF; n=10) and dengue haemorrhagic fever (DHF; n=10) patients compared with healthy individuals (n=8). Both alpha1-antitrypsin and NS1 proteins were overexpressed two-fold in DHF patients compared with DF patients. Our study suggests that alpha1-antitrypsin and NS1 protein could be used as biomarkers as early indicators of DHF risk among patients with suspected dengue infection.
    Matched MeSH terms: Severe Dengue/diagnosis*
  5. Mallhi TH, Khan AH, Adnan AS, Sarriff A, Khan YH, Jummaat F
    BMC Infect Dis, 2015 Sep 30;15:399.
    PMID: 26423145 DOI: 10.1186/s12879-015-1141-3
    BACKGROUND: The incidence of dengue is rising steadily in Malaysia since the first major outbreak in 1973. Despite aggressive measures taken by the relevant authorities, Malaysia is still facing worsening dengue crisis over the past few years. There is an urgent need to evaluate dengue cases for better understanding of clinic-laboratory spectrum in order to combat this disease.

    METHODS: A retrospective analysis of dengue patients admitted to a tertiary care teaching hospital during the period of six years (2008 - 2013) was performed. Patient's demographics, clinical and laboratory findings were recorded via structured data collection form. Patients were categorized into dengue fever (DF) and dengue hemorrhagic fever (DHF). Appropriate statistical methods were used to compare these two groups in order to determine difference in clinico-laboratory characteristics and to identify independent risk factors of DHF.

    RESULTS: A total 667 dengue patients (30.69 ± 16.13 years; Male: 56.7 %) were reviewed. Typical manifestations of dengue like fever, myalgia, arthralgia, headache, vomiting, abdominal pain and skin rash were observed in more than 40 % patients. DHF was observed in 79 (11.8 %) cases. Skin rash, dehydration, shortness of breath, pleural effusion and thick gall bladder were more significantly (P  40 years (OR: 4.1, P 

    Matched MeSH terms: Severe Dengue/diagnosis*
  6. 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
  7. Yong YK, Tan HY, Jen SH, Shankar EM, Natkunam SK, Sathar J, et al.
    J Transl Med, 2017 05 31;15(1):121.
    PMID: 28569153 DOI: 10.1186/s12967-017-1226-4
    BACKGROUND: Currently, several assays can diagnose acute dengue infection. However, none of these assays can predict the severity of the disease. Biomarkers that predicts the likelihood that a dengue patient will develop a severe form of the disease could permit more efficient patient triage and allows better supportive care for the individual in need, especially during dengue outbreaks.

    METHODS: We measured 20 plasma markers i.e. IFN-γ, IL-10, granzyme-B, CX3CL1, IP-10, RANTES, CXCL8, CXCL6, VCAM, ICAM, VEGF, HGF, sCD25, IL-18, LBP, sCD14, sCD163, MIF, MCP-1 and MIP-1β in 141 dengue patients in over 230 specimens and correlate the levels of these plasma markers with the development of dengue without warning signs (DWS-), dengue with warning signs (DWS+) and severe dengue (SD).

    RESULTS: Our results show that the elevation of plasma levels of IL-18 at both febrile and defervescence phase was significantly associated with DWS+ and SD; whilst increase of sCD14 and LBP at febrile phase were associated with severity of dengue disease. By using receiver operating characteristic (ROC) analysis, the IL-18, LBP and sCD14 were significantly predicted the development of more severe form of dengue disease (DWS+/SD) (AUC = 0.768, P 

    Matched MeSH terms: Severe Dengue/diagnosis
  8. Faisal T, Taib MN, Ibrahim F
    J Med Syst, 2012 Apr;36(2):661-76.
    PMID: 20703665 DOI: 10.1007/s10916-010-9532-x
    With the dramatic increase of the worldwide threat of dengue disease, it has been very crucial to correctly diagnose the dengue patients in order to decrease the disease severity. However, it has been a great challenge for the physicians to identify the level of risk in dengue patients due to overlapping of the medical classification criteria. Therefore, this study aims to construct a noninvasive diagnostic system to assist the physicians for classifying the risk in dengue patients. Systematic producers have been followed to develop the system. Firstly, the assessment of the significant predictors associated with the level of risk in dengue patients was carried out utilizing the statistical analyses technique. Secondly, Multilayer perceptron neural network models trained via Levenberg-Marquardt and Scaled Conjugate Gradient algorithms was employed for constructing the diagnostic system. Finally, precise tuning for the models' parameters was conducted in order to achieve the optimal performance. As a result, 9 noninvasive predictors were found to be significantly associated with the level of risk in dengue patients. By employing those predictors, 75% prediction accuracy has been achieved for classifying the risk in dengue patients using Scaled Conjugate Gradient algorithm while 70.7% prediction accuracy were achieved by using Levenberg-Marquardt algorithm.
    Matched MeSH terms: Severe Dengue/diagnosis
  9. 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: Severe Dengue/diagnosis*
  10. Norlijah O, Khamisah AN, Kamarul A, Mangalam S
    Med J Malaysia, 2006 Mar;61(1):22-7.
    PMID: 16708730 MyJurnal
    Prospective evaluation of repeated standard tourniquet testing as a diagnostic indicator of dengue infection was done. Included were patients admitted to a children's hospital in Kuala Lumpur on a clinical suspicion of dengue infection based on the World Health Organization (WHO) criteria. A standard method of tourniquet was performed on 79 patients on a daily basis following admission. subjects and negative in the remaining 14 subjects. Fifty-eight subjects were serologically confirmed cases, 4 indeterminate and the remaining 17 subjects had negative serology. For diagnostic classification, 13 had dengue fever, 49 with dengue haemmorhagic fever (DHF) while 17 had non-dengue infection. The sensitivity and specificity of the tourniquet test was 82.8% and 23.5% respectively. The positive predictive value (PPV) was 78.7% while the negative predictive value (NPV) was 28.6%. In addition, the tourniquet test aided in the diagnosis of one-fifth of patients with DHF, who presented with a positive tourniquet test as the only bleeding manifestation. It seems that in a hospital setting, the tourniquet test adds little to the diagnosis of dengue infection/DHF. A positive tourniquet test, repeatedly performed, was found clinically useful as a preliminary screening test in dengue infection as recommended by WHO. However, it was not very specific and had a high false positive rate.
    Matched MeSH terms: Severe Dengue/diagnosis*
  11. 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*
  12. 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/diagnosis*
  13. 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/diagnosis*
  14. Tamibmaniam J, Hussin N, Cheah WK, Ng KS, Muninathan P
    PLoS One, 2016;11(8):e0161696.
    PMID: 27551776 DOI: 10.1371/journal.pone.0161696
    BACKGROUND: WHO's new classification in 2009: dengue with or without warning signs and severe dengue, has necessitated large numbers of admissions to hospitals of dengue patients which in turn has been imposing a huge economical and physical burden on many hospitals around the globe, particularly South East Asia and Malaysia where the disease has seen a rapid surge in numbers in recent years. Lack of a simple tool to differentiate mild from life threatening infection has led to unnecessary hospitalization of dengue patients.

    METHODS: We conducted a single-centre, retrospective study involving serologically confirmed dengue fever patients, admitted in a single ward, in Hospital Kuala Lumpur, Malaysia. Data was collected for 4 months from February to May 2014. Socio demography, co-morbidity, days of illness before admission, symptoms, warning signs, vital signs and laboratory result were all recorded. Descriptive statistics was tabulated and simple and multiple logistic regression analysis was done to determine significant risk factors associated with severe dengue.

    RESULTS: 657 patients with confirmed dengue were analysed, of which 59 (9.0%) had severe dengue. Overall, the commonest warning sign were vomiting (36.1%) and abdominal pain (32.1%). Previous co-morbid, vomiting, diarrhoea, pleural effusion, low systolic blood pressure, high haematocrit, low albumin and high urea were found as significant risk factors for severe dengue using simple logistic regression. However the significant risk factors for severe dengue with multiple logistic regressions were only vomiting, pleural effusion, and low systolic blood pressure. Using those 3 risk factors, we plotted an algorithm for predicting severe dengue. When compared to the classification of severe dengue based on the WHO criteria, the decision tree algorithm had a sensitivity of 0.81, specificity of 0.54, positive predictive value of 0.16 and negative predictive of 0.96.

    CONCLUSION: The decision tree algorithm proposed in this study showed high sensitivity and NPV in predicting patients with severe dengue that may warrant admission. This tool upon further validation study can be used to help clinicians decide on further managing a patient upon first encounter. It also will have a substantial impact on health resources as low risk patients can be managed as outpatients hence reserving the scarce hospital beds and medical resources for other patients in need.

    Study site: single ward, in Hospital Kuala Lumpur, Malaysia
    Matched MeSH terms: Severe Dengue/diagnosis*
  15. 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*
  16. 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
  17. Zulkipli MS, Dahlui M, Jamil N, Peramalah D, Wai HVC, Bulgiba A, et al.
    PLoS Negl Trop Dis, 2018 02;12(2):e0006263.
    PMID: 29415036 DOI: 10.1371/journal.pntd.0006263
    BACKGROUND: Severe dengue infection often has unpredictable clinical progressions and outcomes. Obesity may play a role in the deterioration of dengue infection due to stronger body immune responses. Several studies found that obese dengue patients have a more severe presentation with a poorer prognosis. However, the association was inconclusive due to the variation in the results of earlier studies. Therefore, we conducted a systematic review and meta-analysis to explore the relationship between obesity and dengue severity.

    METHODS: We performed a systematic search of relevant studies on Ovid (MEDLINE), EMBASE, the Cochrane Library, Web of Science, Scopus and grey literature databases. At least two authors independently conducted the literature search, selecting eligible studies, and extracting data. Meta-analysis using random-effects model was conducted to compute the pooled odds ratio with 95% confidence intervals (CI).

    FINDINGS: We obtained a total of 13,333 articles from the searches. For the final analysis, we included a total of fifteen studies among pediatric patients. Three cohort studies, two case-control studies, and one cross-sectional study found an association between obesity and dengue severity. In contrast, six cohort studies and three case-control studies found no significant relationship between obesity and dengue severity. Our meta-analysis revealed that there was 38 percent higher odds (Odds Ratio = 1.38; 95% CI:1.10, 1.73) of developing severe dengue infection among obese children compared to non-obese children. We found no heterogeneity found between studies. The differences in obesity classification, study quality, and study design do not modify the association between obesity and dengue severity.

    CONCLUSION: This review found that obesity is a risk factor for dengue severity among children. The result highlights and improves our understanding that obesity might influence the severity of dengue infection.

    Matched MeSH terms: Severe Dengue/diagnosis
  18. 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: Severe Dengue/diagnosis
  19. Zakaria Z, Zainordin NA, Sim BL, Zaid M, Haridan US, Aziz AT, et al.
    J Infect Dev Ctries, 2014 Jul;8(7):869-75.
    PMID: 25022297 DOI: 10.3855/jidc.4283
    INTRODUCTION: The latest revised version of the World Health Organization's dengue classification was released in 2009. A handful of studies have taken initiatives to evaluate the old and revised guidelines to determine early signs and symptoms of severe dengue. This retrospective study aimed to compare the classification of dengue using both the 1997 and 2009 guidelines in a selected cohort of dengue patients from Peninsular Malaysia between 2008 and 2012.
    METHODOLOGY: Adult dengue patients were recruited from tertiary hospitals in two different states, Selangor and Kelantan, in Peninsular Malaysia. Their clinical manifestations were assessed.
    RESULTS: A total of 281 confirmed dengue patients were enrolled; the mean duration of illness at admission was five days. Of these, 88.6%, 10.7%, and 0.7% were classified according to the 1997 guidelines as having dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS), respectively. When the WHO 2009 guidelines were applied, 17.1%, 78.3%, and 4.6% were classified as dengue without warning signs, dengue with warning signs, and severe dengue, respectively.
    CONCLUSIONS: Our data suggests that the revised WHO 2009 guidelines stratify a much larger proportion of patients into a category that requires a higher level of medical and nursing care.
    Matched MeSH terms: Severe Dengue/diagnosis
  20. Faisal T, Taib MN, Ibrahim F
    Med Biol Eng Comput, 2010 Mar;48(3):293-301.
    PMID: 20016950 DOI: 10.1007/s11517-009-0561-x
    Even though the World Health Organization criteria's for classifying the dengue infection have been used for long time, recent studies declare that several difficulties have been faced by the clinicians to apply these criteria. Accordingly, many studies have proposed modified criteria to identify the risk in dengue patients based on statistical analysis techniques. None of these studies utilized the powerfulness of the self-organized map (SOM) in visualizing, understanding, and exploring the complexity in multivariable data. Therefore, this study utilized the clustering of the SOM technique to identify the risk criteria in 195 dengue patients. The new risk criteria were defined as: platelet count less than or equal 40,000 cells per mm(3), hematocrit concentration great than or equal 25% and aspartate aminotransferase (AST) rose by fivefold the normal upper limit for AST/alanine aminotransfansferase (ALT) rose by fivefold the normal upper limit for ALT. The clusters analysis indicated that any dengue patient fulfills any two of the risk criteria is consider as high risk dengue patient.
    Matched MeSH terms: Severe Dengue/diagnosis*
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