Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significa...Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significant position in global public health.In recent years,its incidence has continued to rise worldwide[2],making it one of the major diseases threatening human health.The disease course of dengue fever is divided into three typical phases:the acute febrile phase,the critical phase,and the recovery phase.While most patients experience mild symptoms,some may progress to severe dengue and potentially fatal outcomes if not promptly and effectively treated during the critical phase.展开更多
Dengue is an arboviral disease caused by the dengue virus,with 390 million infections reported annually worldwide.It is classified into two categories:dengue without or with warning signs and severe dengue.[1]Given th...Dengue is an arboviral disease caused by the dengue virus,with 390 million infections reported annually worldwide.It is classified into two categories:dengue without or with warning signs and severe dengue.[1]Given the moderate efficacy of the dengue vaccine,[2]there is an urgent necessity to design host-directed therapeutic strategies,such as the repurposing of FDA-approved drugs,to combat dengue virus infection.展开更多
Background:Severe dengue is a life-threatening complication;rapid identifcation of these cases,followed by adequate management is crucial to improve the clinical prognosis.Therefore,this study aimed to identify risk f...Background:Severe dengue is a life-threatening complication;rapid identifcation of these cases,followed by adequate management is crucial to improve the clinical prognosis.Therefore,this study aimed to identify risk factors and predictors of severe dengue.Methods:A literature search for studies reporting risk factors of severe dengue among individuals with dengue virus infection was conducted in PubMed,Scopus and Web of Science database from inception to December 31,2020.Pooled odds ratios(ORs)for patients’demographic characteristics,co-morbidities,and warning signs were estimated using an inverse variance heterogeneity model.Results:We included 143 articles in the meta-analysis from a total of 13090 articles retrieved from the literature search.The risk factors of severe dengue were:being a child[OR=1.96;95%confdence interval(CI):1.22–3.13],secondary infection(OR=3.23;95%CI:2.28–4.57),and patients with pre-existing diabetes(OR=2.88;95%CI:1.72–4.81)and renal disease(OR=4.54;95%CI:1.55–13.31).Warning signs strongly associated with severe disease were increased haematocrit with a concurrent decrease in platelet count(OR=5.13;95%CI:1.61–16.34),abdominal pain(OR=2.00;95%CI:1.49–2.68),lethargy(OR=2.73;95%CI:1.05–7.10),vomiting(OR=1.80;95%CI:1.43–2.26),hepa‑tomegaly(OR=5.92;95%CI:3.29–10.66),ascites(OR=6.30;95%CI:3.75–10.60),pleural efusion(OR=5.72;95%CI:3.24–10.10)and melena(OR=4.05;95%CI:1.64–10.00).Conclusions:Our meta-analysis identifed children,secondary infection,diabetes and renal disease(s)as important predictors of severe dengue.Our fnding also supports the predictive ability of the WHO warning signs to iden‑tify severe dengue.These fndings are useful for clinicians to identify severe dengue for management and timely interventions.展开更多
Dengue fever is considered the most prolific vector-borne disease in the world,with its transmission rate increasing more than eight times in the last two decades.While most cases present mild to moderate symptoms,5%o...Dengue fever is considered the most prolific vector-borne disease in the world,with its transmission rate increasing more than eight times in the last two decades.While most cases present mild to moderate symptoms,5%of patients can develop severe disease.Although the mechanisms are yet not fully comprehended,immune-mediated activation leading to excessive cytokine expression is suggested as a cause of the two main findings in critical patients:increased vascular permeability that may shock and thrombocytopenia,and coagulopathy that can induce hemorrhage.The risk factors of severe disease include previous infection by a different serotype,specific genotypes associated with more efficient replication,certain genetic polymorphisms,and comorbidities such as diabetes,obesity,and cardiovascular disease.The World Health Organization recommends careful monitoring and prompt hospitalization of patients with warning signs or propensity for severe disease to reduce mortality.This review aims to update the diagnosis and management of patients with severe dengue in the intensive care unit.展开更多
Objective:To develop and evaluate predictive models by quantifying warning signs prior to the development of severe dengue.Methods:A retrospective cohort study was conducted in which the total number of warning signs ...Objective:To develop and evaluate predictive models by quantifying warning signs prior to the development of severe dengue.Methods:A retrospective cohort study was conducted in which the total number of warning signs each day was compared between dengue with warning signs and severe dengue.Multivariate logistic regression with forward likelihood ratio method was employed to achieve the best fit models for the prediction of severe dengue.The models were also being explored by adding diarrhoea and removing lethargy.Receiver operating characteristics were then used in these best fit models to identify suitable cut-off probability values derived from the equation of the models.Results:Median age of patients was 26 years old(interquartile range was 15 years)and 65.3%(1110)were males.Age with total number of warning signs at day one of illness(model T1)and age with total number of warning signs at day two of illness(model T2)were identified as the best fit models.The best probability cut-offs for model T1 was 0.0506 with 10.1%positive predictive value,96.4%negative predictive value,99.4%sensitivity,1.8%specificity;for model T2 was 0.0503 with 10.2%positive predictive value,96.4%negative predictive value,99.4%sensitivity,1.8%specificity.Conclusions:The models developed in this study might not reduce the burden effectively.Clinicians may use the models but the models must be re-validated in their clinical settings as the effect size might vary.Furthermore,the risk and benefit in selecting the cut-off values should be evaluated before implementing such models.展开更多
BACKGROUND Clinical predictors of dengue fever are crucial for guiding timely management and avoiding life-threatening complications.While prognostic scores are available,a systematic evaluation of these tools is lack...BACKGROUND Clinical predictors of dengue fever are crucial for guiding timely management and avoiding life-threatening complications.While prognostic scores are available,a systematic evaluation of these tools is lacking.AIM To evaluate the performance and accuracy of various proposed dengue clinical prognostic scores.METHODS Three databases,PubMed,EMBASE and Cochrane,were searched for peer-reviewed studies published from inception to 4 September 2023.Studies either developing or validating a prognostic model relevant to dengue fever were included.A total of 29 studies(n=17910)were included.RESULTS Most commonly studied outcomes were severe dengue(15 models)and mortality(8 models).For the paediatric population,Bedside Dengue Severity Score by Gayathri et al(specificity=0.98)and the nomogram model by Nguyen et al(sensitivity=0.87)performed better.For the adult population,the most specific model was reported by Leo et al(specificity=0.98).The most sensitive score is shared between Warning Signs for Severe Dengue as reported by Leo et al and Model 2 by Lee et al(sensitivity=1.00).CONCLUSION While several models demonstrated precision and reliability in predicting severe dengue and mortality,broader application across diverse geographic settings is needed to assess their external validity.展开更多
Objective:To predict the factors associated with progression to severe dengue infection to prevent potentially fatal complications and to identify the determinants of severe complicated dengue.Methods:The study was co...Objective:To predict the factors associated with progression to severe dengue infection to prevent potentially fatal complications and to identify the determinants of severe complicated dengue.Methods:The study was conducted in a tertiary care hospitaldengue ward from September to November 2021 including confirmed dengue infected patients(positive NS1 antigen or antidengue-antibodies IgM).Secondary dengue infection was labelled by positive anti-dengue-antibodies IgG in active dengue infected patients.Detailed history,physical examination,laboratory and radiological parameters,hospital stay(days)and mortality percentages were noted.Patients were classified into three groups according to disease severity:dengue fever(DF),dengue hemorrhagic fever(DHF)and dengue shock syndrome(DSS).The predictors of complicated dengue infection were determined by regression analysis.Results:The most common symptom was fever(96.9%).Among 129 patients,62.8%had DF,31.0%had DHF and only 6.2%developed DSS.History of previous symptomatic dengue and positive anti-dengue-antibodies IgG were present in 100%DSS patients and nearly 75.0%DHF patients(P<0.05).The moratlity rate in patients with DSS,DHF and DF was 50.0%,2.5%and none respectively(P<0.05).Clinical parameters(body aches,bleeding,conjunctival hemorrhage,maculopapular rash,right hypochondrial tenderness,ascites,pleural effusion)and laboratory parameters(thrombocytopenia,raised alanine aminotransferase and secondary dengue infection)were determinants that complicate the dengue infection.Conclusions:Thrombocytopenia,raised alanine aminotransferase and secondary dengue infection are important laboratory parameters to complicate the disease process of dengue infection.展开更多
Objective:To identify the association between serum albumin levels and disease severity among adult patients with dengue in China's Mainland.Methods:This retrospective cohort study analyzed the data of adult patie...Objective:To identify the association between serum albumin levels and disease severity among adult patients with dengue in China's Mainland.Methods:This retrospective cohort study analyzed the data of adult patients(aged≥18 years)hospitalized with laboratory-confirmed dengue in a tertiary center for infectious diseases from 2013 to 2019 in China's Mainland.Serum albumin levels were estimated and compared between patients with severe dengue and non-severe dengue.Additionally,the association between serum albumin levels and severe dengue was evaluated using a generalized linear model[relative risks(RR)].Multivariate logistic regression analysis was performed to identify the potential predictors of severe dengue.Results:Overall,1568 patients were included in this study.Of these patients,34(2.17%)developed severe dengue.The median serum albumin levels were significantly lower in patients with severe dengue than that in those with non-severe dengue(33 g/L vs.37 g/L,P<0.001).After adjustment for age,sex,and comorbidities,hypoalbuminemia(RR 4.877,95%CI 2.193-11.461,P<0.001)was found to be a predictor of severe dengue.Serum albumin levels(OR 1.303,95%CI 1.161-1.462,P<0.001)and age(OR 1.038,95%CI 1.017-1.061,P<0.001)were significant risk factors for severe dengue.The area under the curve for serum albumin levels to distinguish severe dengue was 0.787.Conclusions:Lower serum albumin levels were significantly associated with disease severity in adult patients with dengue.Hypoalbuminemia on admission resulted in at least a four-fold increased risk of severe dengue.展开更多
Dengue hemorrhagic fever(DHF)is one of the most rapidly emerging infections of tropical and subtropical regions worldwide.It affects more rural and urban areas due to many factors,including climate change.Although mos...Dengue hemorrhagic fever(DHF)is one of the most rapidly emerging infections of tropical and subtropical regions worldwide.It affects more rural and urban areas due to many factors,including climate change.Although most people with dengue viral infection are asymptomatic,approximately 25%experience a selflimited febrile illness with mild to moderate biochemical abnormalities.Severe dengue diseases develop in a small proportion of these patients,and the common organ involvement is the liver.The hepatocellular injury was found in 60%-90%of DHF patients manifested as hepatomegaly,jaundice,elevated aminotransferase enzymes,and critical condition as an acute liver failure(ALF).Even the incidence of ALF in DHF is very low(0.31%-1.1%),but it is associated with a relatively high mortality rate(20%-68.3%).The pathophysiology of liver injury in DHF included the direct cytopathic effect of the DENV causing hepatocytes apoptosis,immunemediated hepatocyte injury induced hepatitis,and cytokine storm.Hepatic hypoperfusion is another contributing factor in dengue shock syndrome.The reduction of morbidity and mortality in DHF with liver involvement is dependent on the early detection of warning signs before the development of ALF.展开更多
BACKGROUND Dengue fever is the most common cause of viral hemorrhagic fever,with more than 400 million cases being reported annually,worldwide.Even though hepatic involvement is common,acute liver failure(ALF)is a rar...BACKGROUND Dengue fever is the most common cause of viral hemorrhagic fever,with more than 400 million cases being reported annually,worldwide.Even though hepatic involvement is common,acute liver failure(ALF)is a rare complication of dengue fever.AIM To analyze the demographic profile,symptomology,hospital course and outcomes of patients presenting with ALF secondary to dengue infection by reviewing the published case reports.METHODS A systematic search was performed from multiple databases including PubMed,Reference Citation Analysis,Science Direct,and Google Scholar.The search terms used were"dengue"OR"severe dengue"OR"dengue shock syndrome"OR"dengue haemorrhagic syndrome"OR"dengue fever"AND"acute liver failure"OR"hepatic failure"OR"liver injury".The inclusion criteria were:(1)Case reports or case series with individual patient details;(2)Reported acute liver failure secondary to dengue infection;and(3)Published in English language and on adult humans.The data were extracted for patient demographics,clinical sympto-matology,clinical interventions,hospital and intensive care unit course,need for organ support and clinical outcomes.RESULTS Data from 19 case reports fulfilling the predefined inclusion criteria were included.The median age of patients was 38 years(inter quartile range:Q3-Q126.5 years)with a female preponderance(52.6%).The median days from diagnosis of dengue to development of ALF was 4.5 d.The increase in aspartate aminotransferase was higher than that in alanine aminotransferase(median 4625 U/L vs 3100 U/L).All the patients had one or more organ failure,with neurological failure present in 73.7%cases.42.1%patients required vasopressor support and hepatic enceph-alopathy was the most reported complication in 13(68.4%)cases.Most of the patients were managed conser-vatively and 2 patients were taken up for liver transplantation.Only 1 death was reported(5.3%).CONCLUSION Dengue infection may rarely lead to ALF.These patients may frequently require intensive care and organ support.Even though most of these patients may improve with supportive care,liver transplantation may be a therapeutic option in refractory cases.展开更多
Dengue viral infection(DVI)is one of the world’s most significant viral infections spreading.Most of the patients have been asymptomatic,with relatively benign clinical manifestations and outcomes.However,a small num...Dengue viral infection(DVI)is one of the world’s most significant viral infections spreading.Most of the patients have been asymptomatic,with relatively benign clinical manifestations and outcomes.However,a small number of patients have progressed to severe dengue diseases,including hemorrhage,multi-organ impairment,and increased vascular leakage causing hypovolemic shock,which can cause cardiovascular collapse and death.Numerous lines of evidence have demonstrated that DVI could also cause cardiac dysfunction,arrhythmias,and severe myocarditis.The treatment for dengue hemorrhagic fever(DHF)patients remains symptomatic and supportive,with close monitoring of hemodynamic status.The contributory role of cardiac dysfunction in DHF patients has potentially critical implications on the management.This review will address the current knowledge of cardiac involvement in DHF patients and the management strategy to reduce the fatality outcome.展开更多
Multilingual abstracts:Please see Additional file 1 for translations of the abstract into the five official working languages of the United Nations.Background:Currently,in Brazil,there is a co-circulation of the four ...Multilingual abstracts:Please see Additional file 1 for translations of the abstract into the five official working languages of the United Nations.Background:Currently,in Brazil,there is a co-circulation of the four dengue(DENV-1 to DENV-4)serotypes.This study aimed to assess whether different serotypes and antibody response patterns were associated with the severity of the disease during a dengue outbreak,which occurred in 2012/2013 in centre of Brazil.Methods:We conducted a prospective study with 452 patients with laboratory confirmed dengue in central Brazil,from January 2012 to July 2013.The clinical outcome was the severity of cases:dengue,dengue with warning signs,and severe dengue.The patients were evaluated at three different moments.Blood sampling for laboratory testing and confirmatory tests for dengue infection were performed.We performed a multinomial analysis considering the three categories of the dependent variable,as outlined above.The odds ratios(ORs)were calculated.A multinomial logistic regression model was applied for variables with a P-value<0.20.Statistical analysis was performed with STATA 12.0 software.Results:Four hundred fifty-two patients(452/632,71.5%)were diagnosed with dengue.The dengue virus(DENV)serotypes were identified in 243 cases.DENV-4 was detected in 135 patients(55.6%),DENV-1 in 91(37.4%),DENV-3 in 13(5.3%),and DENV-2 in 4(1.6%).Patients with the DENV-1 serotype were more prone to present with several clinical and laboratory features as compared with DENV-4 patients,including spontaneous bleeding(P=0.03),intense abdominal pain(P=0.004),neurological symptoms(P=0.09),and thrombocytopenia(P=0.01).Secondary infection was more predominant among DENV-4 cases(80.0%)compared with DENV-1 cases(62.3%)(P=0.03).The univariate analysis showed that females(OR=2.12;95%CI:1.44-3.13;P<0.01)had a higher risk of having dengue with warning signs.The multinomial analysis showed that severe dengue cases with secondary infection had an adjusted OR of 2.80(95%CI:0.78-10.00;P=0.113)as compared with dengue fever with primary infection when adjusted for age and sex.Conclusion:The current data show that 5.8%of patients recruited for treatment in healthcare centres and hospitals during the study period had severe dengue.DENV-4 was the predominant serotype,followed by DENV-1,in a large outbreak of dengue in central Brazil.Our findings contribute to the understanding of clinical differences and immune status related to the serotypes DENV-1 and DENV-4 in central of Brazil.展开更多
Objective:To compare the differences of vomiting and diarrhoea frequency between dengue with warning signs and severe dengue,and to describe the sites of mucosal bleeding among dengue-infected patients.Methods:This wa...Objective:To compare the differences of vomiting and diarrhoea frequency between dengue with warning signs and severe dengue,and to describe the sites of mucosal bleeding among dengue-infected patients.Methods:This was a retrospective cohort study which included patients with laboratory-confirmed dengue infection along with clinical diagnosis of dengue.Exclusion criteria were patients with haematological disorders or any other malignancy.The vomiting and diarrhoea frequency on each day(Day 1 to Day 5)between dengue with warning signs and severe dengue were compared by using Mann-Whitney U test.The different sites of mucosal bleeding were stratified according to the diagnoses and displayed by bar charts.Results:Out of 1700 patients,1003(59.0%)had vomiting and 587(34.5%)had diarrhoea.Both vomiting and diarrhoea frequency were not statistically different between dengue with warning signs and severe dengue from Day 1 to Day 5.Gum bleeding,hematemesis and menorrhagia were the only sites of mucosal bleeding seen in severe dengue for the first three days of illness.Hematemesis was seen only in severe dengue during the first day of illness but not in dengue with warning signs.Conclusions:The frequency of vomiting and diarrhoea could not differentiate severe dengue from dengue with warning signs.Nevertheless,it is important to have high index of suspicion for dengue when patients are presented with diarrhoea.The different sites of mucosal bleeding could possibly predict severe dengue,especially hematemesis on the first three days of illness.展开更多
Objective:To evaluate five biomarkers(neopterin,vascular endothelial growth factor-A,thrombomodulin,soluble vascular cell adhesion molecule 1 and pentraxin 3)in differentiating clinical dengue cases.Methods:A prospect...Objective:To evaluate five biomarkers(neopterin,vascular endothelial growth factor-A,thrombomodulin,soluble vascular cell adhesion molecule 1 and pentraxin 3)in differentiating clinical dengue cases.Methods:A prospective cohort study was conducted whereby the blood samples were obtained at day of presentation and the final diagnosis were obtained at the end of patients’follow-up.All patients included in the study were 15 years old or older,not pregnant,not infected by dengue previously and did not have cancer,autoimmune or haematological disorder.Median test was performed to compare the biomarker levels.A subgroup Mann-Whitney U test was analysed between severe dengue and non-severe dengue cases.Monte Carlo method was used to estimate the 2-tailed probability(P)value for independent variables with unequal number of patients.Results:All biomarkers except thrombomodulin has P value<0.001 in differentiating among the healthy subjects,non-dengue fever,dengue without warning signs and dengue with warning signs/severe dengue.Subgroup analysis for all the biomarkers between severe dengue and non-severe dengue cases was not statistically significant except vascular endothelial growth factor-A(P<0.05).Conclusions:Certain biomarkers were able to differentiate the clinical dengue cases.This could be potentially useful in classifying and determining the severity of dengue infected patients in the hospital.展开更多
Background:Dengue is a major arthropod-borne viral disease spreading rapidly across the globe.The absence of vaccines and inadequate vector control measures leads to further expansion of dengue in many regions globall...Background:Dengue is a major arthropod-borne viral disease spreading rapidly across the globe.The absence of vaccines and inadequate vector control measures leads to further expansion of dengue in many regions globally.Hence,the identification of genes involved in the pathogenesis of dengue will help to understand the molecular basis of the disease and the genes responsible for the disease progression.Methods:In the present study,a meta-analysis was carried out using dengue gene expression data obtained from Gene Expression Omnibus repository.The differentially expressed genes such as CCNB1 and CCNB2(G2/mitotic-specific cyclin-B2 and B1)were upregulated in dengue fever to control(DF-CO)and severe dengue(dengue hemorrhagic fever[DHF])to control(DHF-CO)were identified as key genes for controlling the major pathways(cell cycle,oocyte meiosis,p53 signaling pathway,cellular senescence and progesterone-mediated oocyte mat-uration).Similarly,interferon alpha-inducible(IFI27)genes,type-I and type-III interferon(IFN)signaling genes(STAT1 and STAT2),B cell activation and survival genes(TNFSF13B,TNFRSF17)and toll like receptor(TLR7)genes were differentially up activated during DF-CO and DHF-CO.Followed by,Cytoscape was used to identify the immune system process and topological analysis.Results:The results showed that the top differentially expressed genes under the statistical significance p<0.001,which is majorly involved in Kyoto Encyclopedia of Genes and Genomes orthology K05868 and K21770 with gene names CCNB1 and CCNB2.In addition to this,the immune system profile showed up-regulation of IL12A,CXCR3,TNFSF13B,IFI27,TNFRSF17,STAT,STAT2,and TLR7 genes in DF-CO and DHF-CO act as immunological signatures for inducing the immune response towards dengue infection.Conclusions:The current study could aid in understanding of molecular pathogenesis,genes and correspond-ing pathway upon dengue infection,and could facilitate for identification of novel drug targets and prognostic markers.展开更多
文摘Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significant position in global public health.In recent years,its incidence has continued to rise worldwide[2],making it one of the major diseases threatening human health.The disease course of dengue fever is divided into three typical phases:the acute febrile phase,the critical phase,and the recovery phase.While most patients experience mild symptoms,some may progress to severe dengue and potentially fatal outcomes if not promptly and effectively treated during the critical phase.
基金funded by grants Pronaii 302979A1-S-9005 CONACyT (México) from RMDA。
文摘Dengue is an arboviral disease caused by the dengue virus,with 390 million infections reported annually worldwide.It is classified into two categories:dengue without or with warning signs and severe dengue.[1]Given the moderate efficacy of the dengue vaccine,[2]there is an urgent necessity to design host-directed therapeutic strategies,such as the repurposing of FDA-approved drugs,to combat dengue virus infection.
文摘Background:Severe dengue is a life-threatening complication;rapid identifcation of these cases,followed by adequate management is crucial to improve the clinical prognosis.Therefore,this study aimed to identify risk factors and predictors of severe dengue.Methods:A literature search for studies reporting risk factors of severe dengue among individuals with dengue virus infection was conducted in PubMed,Scopus and Web of Science database from inception to December 31,2020.Pooled odds ratios(ORs)for patients’demographic characteristics,co-morbidities,and warning signs were estimated using an inverse variance heterogeneity model.Results:We included 143 articles in the meta-analysis from a total of 13090 articles retrieved from the literature search.The risk factors of severe dengue were:being a child[OR=1.96;95%confdence interval(CI):1.22–3.13],secondary infection(OR=3.23;95%CI:2.28–4.57),and patients with pre-existing diabetes(OR=2.88;95%CI:1.72–4.81)and renal disease(OR=4.54;95%CI:1.55–13.31).Warning signs strongly associated with severe disease were increased haematocrit with a concurrent decrease in platelet count(OR=5.13;95%CI:1.61–16.34),abdominal pain(OR=2.00;95%CI:1.49–2.68),lethargy(OR=2.73;95%CI:1.05–7.10),vomiting(OR=1.80;95%CI:1.43–2.26),hepa‑tomegaly(OR=5.92;95%CI:3.29–10.66),ascites(OR=6.30;95%CI:3.75–10.60),pleural efusion(OR=5.72;95%CI:3.24–10.10)and melena(OR=4.05;95%CI:1.64–10.00).Conclusions:Our meta-analysis identifed children,secondary infection,diabetes and renal disease(s)as important predictors of severe dengue.Our fnding also supports the predictive ability of the WHO warning signs to iden‑tify severe dengue.These fndings are useful for clinicians to identify severe dengue for management and timely interventions.
文摘Dengue fever is considered the most prolific vector-borne disease in the world,with its transmission rate increasing more than eight times in the last two decades.While most cases present mild to moderate symptoms,5%of patients can develop severe disease.Although the mechanisms are yet not fully comprehended,immune-mediated activation leading to excessive cytokine expression is suggested as a cause of the two main findings in critical patients:increased vascular permeability that may shock and thrombocytopenia,and coagulopathy that can induce hemorrhage.The risk factors of severe disease include previous infection by a different serotype,specific genotypes associated with more efficient replication,certain genetic polymorphisms,and comorbidities such as diabetes,obesity,and cardiovascular disease.The World Health Organization recommends careful monitoring and prompt hospitalization of patients with warning signs or propensity for severe disease to reduce mortality.This review aims to update the diagnosis and management of patients with severe dengue in the intensive care unit.
文摘Objective:To develop and evaluate predictive models by quantifying warning signs prior to the development of severe dengue.Methods:A retrospective cohort study was conducted in which the total number of warning signs each day was compared between dengue with warning signs and severe dengue.Multivariate logistic regression with forward likelihood ratio method was employed to achieve the best fit models for the prediction of severe dengue.The models were also being explored by adding diarrhoea and removing lethargy.Receiver operating characteristics were then used in these best fit models to identify suitable cut-off probability values derived from the equation of the models.Results:Median age of patients was 26 years old(interquartile range was 15 years)and 65.3%(1110)were males.Age with total number of warning signs at day one of illness(model T1)and age with total number of warning signs at day two of illness(model T2)were identified as the best fit models.The best probability cut-offs for model T1 was 0.0506 with 10.1%positive predictive value,96.4%negative predictive value,99.4%sensitivity,1.8%specificity;for model T2 was 0.0503 with 10.2%positive predictive value,96.4%negative predictive value,99.4%sensitivity,1.8%specificity.Conclusions:The models developed in this study might not reduce the burden effectively.Clinicians may use the models but the models must be re-validated in their clinical settings as the effect size might vary.Furthermore,the risk and benefit in selecting the cut-off values should be evaluated before implementing such models.
文摘BACKGROUND Clinical predictors of dengue fever are crucial for guiding timely management and avoiding life-threatening complications.While prognostic scores are available,a systematic evaluation of these tools is lacking.AIM To evaluate the performance and accuracy of various proposed dengue clinical prognostic scores.METHODS Three databases,PubMed,EMBASE and Cochrane,were searched for peer-reviewed studies published from inception to 4 September 2023.Studies either developing or validating a prognostic model relevant to dengue fever were included.A total of 29 studies(n=17910)were included.RESULTS Most commonly studied outcomes were severe dengue(15 models)and mortality(8 models).For the paediatric population,Bedside Dengue Severity Score by Gayathri et al(specificity=0.98)and the nomogram model by Nguyen et al(sensitivity=0.87)performed better.For the adult population,the most specific model was reported by Leo et al(specificity=0.98).The most sensitive score is shared between Warning Signs for Severe Dengue as reported by Leo et al and Model 2 by Lee et al(sensitivity=1.00).CONCLUSION While several models demonstrated precision and reliability in predicting severe dengue and mortality,broader application across diverse geographic settings is needed to assess their external validity.
文摘Objective:To predict the factors associated with progression to severe dengue infection to prevent potentially fatal complications and to identify the determinants of severe complicated dengue.Methods:The study was conducted in a tertiary care hospitaldengue ward from September to November 2021 including confirmed dengue infected patients(positive NS1 antigen or antidengue-antibodies IgM).Secondary dengue infection was labelled by positive anti-dengue-antibodies IgG in active dengue infected patients.Detailed history,physical examination,laboratory and radiological parameters,hospital stay(days)and mortality percentages were noted.Patients were classified into three groups according to disease severity:dengue fever(DF),dengue hemorrhagic fever(DHF)and dengue shock syndrome(DSS).The predictors of complicated dengue infection were determined by regression analysis.Results:The most common symptom was fever(96.9%).Among 129 patients,62.8%had DF,31.0%had DHF and only 6.2%developed DSS.History of previous symptomatic dengue and positive anti-dengue-antibodies IgG were present in 100%DSS patients and nearly 75.0%DHF patients(P<0.05).The moratlity rate in patients with DSS,DHF and DF was 50.0%,2.5%and none respectively(P<0.05).Clinical parameters(body aches,bleeding,conjunctival hemorrhage,maculopapular rash,right hypochondrial tenderness,ascites,pleural effusion)and laboratory parameters(thrombocytopenia,raised alanine aminotransferase and secondary dengue infection)were determinants that complicate the dengue infection.Conclusions:Thrombocytopenia,raised alanine aminotransferase and secondary dengue infection are important laboratory parameters to complicate the disease process of dengue infection.
基金supported by Special Program of Science and Technology of Guangdong Province(Grant No.:2013A020229001)the Major Program of Guangzhou Healthcare Collaborative Innovation(Grant No.:201803040006)Basic and applied basic research project jointly funded by the University of Guangzhou(Grant No.:2023A03J0810).
文摘Objective:To identify the association between serum albumin levels and disease severity among adult patients with dengue in China's Mainland.Methods:This retrospective cohort study analyzed the data of adult patients(aged≥18 years)hospitalized with laboratory-confirmed dengue in a tertiary center for infectious diseases from 2013 to 2019 in China's Mainland.Serum albumin levels were estimated and compared between patients with severe dengue and non-severe dengue.Additionally,the association between serum albumin levels and severe dengue was evaluated using a generalized linear model[relative risks(RR)].Multivariate logistic regression analysis was performed to identify the potential predictors of severe dengue.Results:Overall,1568 patients were included in this study.Of these patients,34(2.17%)developed severe dengue.The median serum albumin levels were significantly lower in patients with severe dengue than that in those with non-severe dengue(33 g/L vs.37 g/L,P<0.001).After adjustment for age,sex,and comorbidities,hypoalbuminemia(RR 4.877,95%CI 2.193-11.461,P<0.001)was found to be a predictor of severe dengue.Serum albumin levels(OR 1.303,95%CI 1.161-1.462,P<0.001)and age(OR 1.038,95%CI 1.017-1.061,P<0.001)were significant risk factors for severe dengue.The area under the curve for serum albumin levels to distinguish severe dengue was 0.787.Conclusions:Lower serum albumin levels were significantly associated with disease severity in adult patients with dengue.Hypoalbuminemia on admission resulted in at least a four-fold increased risk of severe dengue.
文摘Dengue hemorrhagic fever(DHF)is one of the most rapidly emerging infections of tropical and subtropical regions worldwide.It affects more rural and urban areas due to many factors,including climate change.Although most people with dengue viral infection are asymptomatic,approximately 25%experience a selflimited febrile illness with mild to moderate biochemical abnormalities.Severe dengue diseases develop in a small proportion of these patients,and the common organ involvement is the liver.The hepatocellular injury was found in 60%-90%of DHF patients manifested as hepatomegaly,jaundice,elevated aminotransferase enzymes,and critical condition as an acute liver failure(ALF).Even the incidence of ALF in DHF is very low(0.31%-1.1%),but it is associated with a relatively high mortality rate(20%-68.3%).The pathophysiology of liver injury in DHF included the direct cytopathic effect of the DENV causing hepatocytes apoptosis,immunemediated hepatocyte injury induced hepatitis,and cytokine storm.Hepatic hypoperfusion is another contributing factor in dengue shock syndrome.The reduction of morbidity and mortality in DHF with liver involvement is dependent on the early detection of warning signs before the development of ALF.
文摘BACKGROUND Dengue fever is the most common cause of viral hemorrhagic fever,with more than 400 million cases being reported annually,worldwide.Even though hepatic involvement is common,acute liver failure(ALF)is a rare complication of dengue fever.AIM To analyze the demographic profile,symptomology,hospital course and outcomes of patients presenting with ALF secondary to dengue infection by reviewing the published case reports.METHODS A systematic search was performed from multiple databases including PubMed,Reference Citation Analysis,Science Direct,and Google Scholar.The search terms used were"dengue"OR"severe dengue"OR"dengue shock syndrome"OR"dengue haemorrhagic syndrome"OR"dengue fever"AND"acute liver failure"OR"hepatic failure"OR"liver injury".The inclusion criteria were:(1)Case reports or case series with individual patient details;(2)Reported acute liver failure secondary to dengue infection;and(3)Published in English language and on adult humans.The data were extracted for patient demographics,clinical sympto-matology,clinical interventions,hospital and intensive care unit course,need for organ support and clinical outcomes.RESULTS Data from 19 case reports fulfilling the predefined inclusion criteria were included.The median age of patients was 38 years(inter quartile range:Q3-Q126.5 years)with a female preponderance(52.6%).The median days from diagnosis of dengue to development of ALF was 4.5 d.The increase in aspartate aminotransferase was higher than that in alanine aminotransferase(median 4625 U/L vs 3100 U/L).All the patients had one or more organ failure,with neurological failure present in 73.7%cases.42.1%patients required vasopressor support and hepatic enceph-alopathy was the most reported complication in 13(68.4%)cases.Most of the patients were managed conser-vatively and 2 patients were taken up for liver transplantation.Only 1 death was reported(5.3%).CONCLUSION Dengue infection may rarely lead to ALF.These patients may frequently require intensive care and organ support.Even though most of these patients may improve with supportive care,liver transplantation may be a therapeutic option in refractory cases.
文摘Dengue viral infection(DVI)is one of the world’s most significant viral infections spreading.Most of the patients have been asymptomatic,with relatively benign clinical manifestations and outcomes.However,a small number of patients have progressed to severe dengue diseases,including hemorrhage,multi-organ impairment,and increased vascular leakage causing hypovolemic shock,which can cause cardiovascular collapse and death.Numerous lines of evidence have demonstrated that DVI could also cause cardiac dysfunction,arrhythmias,and severe myocarditis.The treatment for dengue hemorrhagic fever(DHF)patients remains symptomatic and supportive,with close monitoring of hemodynamic status.The contributory role of cardiac dysfunction in DHF patients has potentially critical implications on the management.This review will address the current knowledge of cardiac involvement in DHF patients and the management strategy to reduce the fatality outcome.
基金This study was funded by the National Council for Scientific and Technological Development(Conselho Nacional de Desenvolvimento Cientifico e Tecnologico,CNPq)the Foundation for the State of Goiás Research(FAPEG).
文摘Multilingual abstracts:Please see Additional file 1 for translations of the abstract into the five official working languages of the United Nations.Background:Currently,in Brazil,there is a co-circulation of the four dengue(DENV-1 to DENV-4)serotypes.This study aimed to assess whether different serotypes and antibody response patterns were associated with the severity of the disease during a dengue outbreak,which occurred in 2012/2013 in centre of Brazil.Methods:We conducted a prospective study with 452 patients with laboratory confirmed dengue in central Brazil,from January 2012 to July 2013.The clinical outcome was the severity of cases:dengue,dengue with warning signs,and severe dengue.The patients were evaluated at three different moments.Blood sampling for laboratory testing and confirmatory tests for dengue infection were performed.We performed a multinomial analysis considering the three categories of the dependent variable,as outlined above.The odds ratios(ORs)were calculated.A multinomial logistic regression model was applied for variables with a P-value<0.20.Statistical analysis was performed with STATA 12.0 software.Results:Four hundred fifty-two patients(452/632,71.5%)were diagnosed with dengue.The dengue virus(DENV)serotypes were identified in 243 cases.DENV-4 was detected in 135 patients(55.6%),DENV-1 in 91(37.4%),DENV-3 in 13(5.3%),and DENV-2 in 4(1.6%).Patients with the DENV-1 serotype were more prone to present with several clinical and laboratory features as compared with DENV-4 patients,including spontaneous bleeding(P=0.03),intense abdominal pain(P=0.004),neurological symptoms(P=0.09),and thrombocytopenia(P=0.01).Secondary infection was more predominant among DENV-4 cases(80.0%)compared with DENV-1 cases(62.3%)(P=0.03).The univariate analysis showed that females(OR=2.12;95%CI:1.44-3.13;P<0.01)had a higher risk of having dengue with warning signs.The multinomial analysis showed that severe dengue cases with secondary infection had an adjusted OR of 2.80(95%CI:0.78-10.00;P=0.113)as compared with dengue fever with primary infection when adjusted for age and sex.Conclusion:The current data show that 5.8%of patients recruited for treatment in healthcare centres and hospitals during the study period had severe dengue.DENV-4 was the predominant serotype,followed by DENV-1,in a large outbreak of dengue in central Brazil.Our findings contribute to the understanding of clinical differences and immune status related to the serotypes DENV-1 and DENV-4 in central of Brazil.
文摘Objective:To compare the differences of vomiting and diarrhoea frequency between dengue with warning signs and severe dengue,and to describe the sites of mucosal bleeding among dengue-infected patients.Methods:This was a retrospective cohort study which included patients with laboratory-confirmed dengue infection along with clinical diagnosis of dengue.Exclusion criteria were patients with haematological disorders or any other malignancy.The vomiting and diarrhoea frequency on each day(Day 1 to Day 5)between dengue with warning signs and severe dengue were compared by using Mann-Whitney U test.The different sites of mucosal bleeding were stratified according to the diagnoses and displayed by bar charts.Results:Out of 1700 patients,1003(59.0%)had vomiting and 587(34.5%)had diarrhoea.Both vomiting and diarrhoea frequency were not statistically different between dengue with warning signs and severe dengue from Day 1 to Day 5.Gum bleeding,hematemesis and menorrhagia were the only sites of mucosal bleeding seen in severe dengue for the first three days of illness.Hematemesis was seen only in severe dengue during the first day of illness but not in dengue with warning signs.Conclusions:The frequency of vomiting and diarrhoea could not differentiate severe dengue from dengue with warning signs.Nevertheless,it is important to have high index of suspicion for dengue when patients are presented with diarrhoea.The different sites of mucosal bleeding could possibly predict severe dengue,especially hematemesis on the first three days of illness.
基金Supported by Universiti Tunku Abdul Rahman Research Fund[IPSR/RMC/UTARRF/2013-C2/G03].
文摘Objective:To evaluate five biomarkers(neopterin,vascular endothelial growth factor-A,thrombomodulin,soluble vascular cell adhesion molecule 1 and pentraxin 3)in differentiating clinical dengue cases.Methods:A prospective cohort study was conducted whereby the blood samples were obtained at day of presentation and the final diagnosis were obtained at the end of patients’follow-up.All patients included in the study were 15 years old or older,not pregnant,not infected by dengue previously and did not have cancer,autoimmune or haematological disorder.Median test was performed to compare the biomarker levels.A subgroup Mann-Whitney U test was analysed between severe dengue and non-severe dengue cases.Monte Carlo method was used to estimate the 2-tailed probability(P)value for independent variables with unequal number of patients.Results:All biomarkers except thrombomodulin has P value<0.001 in differentiating among the healthy subjects,non-dengue fever,dengue without warning signs and dengue with warning signs/severe dengue.Subgroup analysis for all the biomarkers between severe dengue and non-severe dengue cases was not statistically significant except vascular endothelial growth factor-A(P<0.05).Conclusions:Certain biomarkers were able to differentiate the clinical dengue cases.This could be potentially useful in classifying and determining the severity of dengue infected patients in the hospital.
文摘Background:Dengue is a major arthropod-borne viral disease spreading rapidly across the globe.The absence of vaccines and inadequate vector control measures leads to further expansion of dengue in many regions globally.Hence,the identification of genes involved in the pathogenesis of dengue will help to understand the molecular basis of the disease and the genes responsible for the disease progression.Methods:In the present study,a meta-analysis was carried out using dengue gene expression data obtained from Gene Expression Omnibus repository.The differentially expressed genes such as CCNB1 and CCNB2(G2/mitotic-specific cyclin-B2 and B1)were upregulated in dengue fever to control(DF-CO)and severe dengue(dengue hemorrhagic fever[DHF])to control(DHF-CO)were identified as key genes for controlling the major pathways(cell cycle,oocyte meiosis,p53 signaling pathway,cellular senescence and progesterone-mediated oocyte mat-uration).Similarly,interferon alpha-inducible(IFI27)genes,type-I and type-III interferon(IFN)signaling genes(STAT1 and STAT2),B cell activation and survival genes(TNFSF13B,TNFRSF17)and toll like receptor(TLR7)genes were differentially up activated during DF-CO and DHF-CO.Followed by,Cytoscape was used to identify the immune system process and topological analysis.Results:The results showed that the top differentially expressed genes under the statistical significance p<0.001,which is majorly involved in Kyoto Encyclopedia of Genes and Genomes orthology K05868 and K21770 with gene names CCNB1 and CCNB2.In addition to this,the immune system profile showed up-regulation of IL12A,CXCR3,TNFSF13B,IFI27,TNFRSF17,STAT,STAT2,and TLR7 genes in DF-CO and DHF-CO act as immunological signatures for inducing the immune response towards dengue infection.Conclusions:The current study could aid in understanding of molecular pathogenesis,genes and correspond-ing pathway upon dengue infection,and could facilitate for identification of novel drug targets and prognostic markers.
