Epidemiology of dengue and dengue hemorrhagic fever in a cohort of adults living in Bandung, West Java, Indonesia

A prospective study of dengue fever (DF) and dengue hemorrhagic fever (DHF) was conducted in a cohort of adult volunteers from two textile factories located in West Java, Indonesia. Volunteers in the cohort were bled every three months and were actively followed for the occurrence of dengue (DEN) disease. The first two years of the study showed an incidence of symptomatic DEN disease of 18 cases per 1,000 person-years and an estimated asymptomatic/ mild infection rate of 56 cases per 1,000 person-years in areas of high disease transmission. In areas where no symptomatic cases were detected, the incidence of asymptomatic or mild infection was 8 cases per 1,000 person-years. Dengue-2 virus was the predominant serotype identified, but all four serotypes were detected among the cohort. Four cases of DHF and one case of dengue shock syndrome (DSS) were identified. Three of the four DHF cases were due to DEN-3 virus. The one DSS case occurred in the setting of a prior DEN-2 virus infection, followed by a secondary infection with DEN-1 virus. To our knowledge, this is the first report of a longitudinal cohort study of naturally acquired DF and DHF in adults.     

Dengue hemorrhagic fever in Cuba, 1981: a retrospective seroepidemiologic study

In Cuba, 2 epidemics of dengue virus occurred: 1 caused by DEN-1 in 1977 and 1 caused by DEN-2 in 1981. The latter was associated with cases of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). To study viral risk factors for DHF/DSS, a retrospective seroepidemiological survey was conducted in Cerro, a densely populated district in Havana City. The prevalence of plaque reduction neutralizing antibodies to DEN-1 and DEN-2 viruses was measured in 1,295 individuals (children and adults). Of these, 43.7% were immune to DEN-1 virus and 23.6% to DEN-2 virus. Of those individuals who were immune, 26.1% were immune to DEN-1 virus only, 6% to DEN-2 virus only, and 17.6% to both viruses. The DEN-2 virus infection rate in DEN-1 immune individuals was 3.8 times higher than in non-immune individuals. The 5 DHF/DSS cases in the sample had evidence of DEN-1 virus plus DEN-2 virus infections. Three were children and 2 were young adults. No cases were found in individuals infected with DEN-1 virus or DEN-2 virus only. Children infected by DEN-1 virus followed by DEN-2 virus had a high risk of acquiring DHF/DSS. Blacks and whites were equally infected with DEN-1 and DEN-2 viruses.     

Oxidative stress induced changes in plasma protein can be a predictor of imminent severe dengue infection

OBJECTIVES: Oxidative stress in dengue viral infection has been suggested and severity of it was found to be associated with progress of illness. Hence assessing oxidative stress mediated changes in plasma proteins can be an early biomarker for prediction of severe dengue infection. DESIGN AND METHODS: Thirty two dengue hemorrhagic fever (DHF), 21 dengue shock syndrome (DSS), 27 dengue fever (DF) and 63 age and sex matched controls, were included in this study. Blood samples were collected on the 3rd day of fever. Protein carbonylation (PCOs) and protein-bound sulphydryl (PBSH) group levels were determined by spectrophotometric method and analyzed as predictor of dengue hemorrhagic fever and dengue shock syndrome. RESULTS: About 80-84% of cases presented with no signs of DHF/DSS at the time of sampling. Dengue infected individuals had significantly elevated PCOs and low PBSH group levels than the controls. Using one-way ANOVA we found a significant difference with high PCOs and low PBSH group levels between DHF and DSS when compared with DF (P<0.001). However, no difference was observed in PBSH group levels between DHF and DSS. A significant difference in PCOs to PBSH ratio was observed among DF, DHF and DSS (P<0.001). Linear regression analysis revealed that duration of hospitalization is dependent on PCOs and PBSH group levels. Receiver operator curve (ROC) analysis indicated that 5.22nmol/mg protein PCOs; 1.08 PCOs to PBSH group levels ratio were optimal cutoff value for predicting DHF with sensitivity and specificity of 87.5% and 74.1%; 96.9% and 81.5%, respectively. For DSS prediction, 6.13 nmol/mg protein PCOs; 1.16 PCOs to PBSH group levels ratio were found as effective cutoff with sensitivity and specificity of 81% and 71.9%; 95.2% and 56.2%, respectively. CONCLUSION: Oxidative stress has been observed to develop since early days of onset of dengue infection. Plasma PCOs, PCOs to PBSH group ratio were found to very well predict DHF/DSS.     

Difficulty in diagnosis and treatment of dengue hemorrhagic fever in patients with chronic renal failure: report of three cases of mortality

In 2002, an outbreak of dengue fever (DF) in Taiwan caused mortality in some patients with chronic renal failure (CRF). We report three cases of CRF who died of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) despite an intensive care process. The difficulty in diagnosis and the treatment dilemma attributable to ambiguity in symptoms and signs between CRF and DF may delay the diagnosis, contributing to a high risk of mortality. The narrow window of fluid tolerance in patients with CRF further hampers the success of resuscitation in DHF and DSS. Continuous venous to venous hemodialysis (CVVHD) is helpful in managing a condition with unstable hemodynamics. However, to decrease mortality, the physician must pay great attention to ensure an early awareness of DHF/DSS and deliver a prompt and aggressive treatment of patients of dengue viral infections with chronic renal failure.     

Spectrum of hepatic dysfunction in 2012 dengue epidemic in Kolkata, West Bengal

Dengue fever (DF) may present as uncomplicated dengue fever, dengue hemorrhagic fever (DHF), or dengue shock syndrome (DSS). Transient intense viremia is responsible for mild, moderate, or severe hepatic dysfunction. Our aim was to evaluate the spectrum of hepatic dysfunction and evidence of plasma leakage in different stages of dengue fever in this epidemic. Detailed history, physical examination, and laboratory evaluation of 1,226 serologically proved dengue patients. Patients with DF were 170 and DHF was 1,056, among which those with ALT ≥?75 U/L were 43 and 570, respectively. Patients with ALT >?151–300, >?300–450, and >?450 U/L were 186, 77, and 34, respectively. Affected DF (n?=?43) and DHF (n?=?570) patients presented with symptoms and signs similar to viral hepatitis, but ascites, pleural effusion, raised INR, bleeding, and hypoalbuminemia were present only in DHF patients. In dengue fever, there was a wide range of hepatic dysfunction mimicking acute viral hepatitis.     

Use of nucleotide sequencing of the genomic cDNA fragments of the capsid/premembrane junction region for molecular epidemiology of dengue type 2 viruses

The recent emergence of dengue hemorrhagic fever/dengue shock syndrome (DHF/ DSS) in India has been a source of concern. In the present study a quantitative comparison of 406 nucleotide long sequence from the capsid-premembrane junction region (C-PrM) of 9 dengue virus type 2 (DEN-2) isolates from Delhi with 10 DEN-2 isolates from diverse geographic areas provided sufficient information for estimating genetic relationships. The data indicated that the 1996 epidemic of DHF in Delhi was caused by genotype IV strains of DEN-2. This genotype, perhaps, displaced genotype V strains of DEN-2, which was circulating genotype in 1967. The period during which this displacement had occurred is not clear from the present study. Nonetheless, similar experience in four countries in Latin America and in Sri Lanka suggest that the introduction of new genotypes of DEN-2 displacing the circulating genotype may be associated with the appearance of DHF/DSS. More work is required to elucidate this hypothesis. Transitions at nucleotide positions 406 and 431 resulted in amino acid substitutions near (aa position 104, methionine --> valine) and at the hinge region (aa position 112, valine --> alanine) of C-PrM, respectively in all/most genotypes of group III and IV DEN-2 viruses analysed. Most of these virus strains have been isolated from DHF/DSS outbreaks. Significance of this observation is discussed. The data presented in this study suggest the utility of C-PrM sequence analysis for molecular epidemiology of dengue viruses.     

Evaluation of Platelets as Predictive Parameters in Dengue Fever

Dengue is an arboviral disease and occurs in tropical countries where over 2.5 billion people are at risk of infection. Each year an estimated 100 million cases of dengue fever (DF) occur and between 2.5 and 5 lakh cases of dengue hemorrhagic fever (DHF) are reported to WHO. Severe thrombocytopenia and increased vascular permeability are two major characteristics of DHF. A study was conducted to note the relationship between the platelet counts and severity of the disease in pediatric cases of dengue fever. Platelet counts were found to be predictive as well as recovery parameter of DF/DHF/DSS.     

Effect of age on outcome of secondary dengue 2 infections.

OBJECTIVE: Dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) is a growing global health problem. It is not known how age affects the outcome of secondary dengue infections. In an island setting, a large DHF/DSS outbreak in Cuba occurred in 1981. Involved were individuals, 3-40 year old, whose only lifetime dengue exposure was to DEN-1 in 1977 and DEN-2 in 1981. In this report we calculate age-specific DHF/DSS hospitalization and death rates based on secondary DEN 2 infections. METHODS: Published and unpublished hospital and seroepidemiologic data from the 1981 DHF/DSS outbreak were used for the analysis. RESULTS: Children, aged 3 and 4 years, with secondary DEN-2 infections were found to have a high death rate (25.4/10 000 secondary DEN-2 infections). The death rate fell with increasing age, being 15.9-fold lower in the 10-14-year age group. The death rate for children aged 3-14 years was 14.5-fold higher than in young adults aged 15-39 years. The death rate rose somewhat in adults aged 50 years and older. DHF/DSS hospitalization rates showed the same trend as death rates. CONCLUSIONS: Age is an important variable in the outcome of secondary DEN-2 infections. DHF/DSS case fatality and hospitalization rates are highest in young infants and the elderly. The risk that a child will die during a secondary DEN-2 infection is nearly 15-fold higher than the risk in adults.     

Correlation of serum levels of macrophage migration inhibitory factor with disease severity and clinical outcome in dengue patients

Dengue virus infection can cause mild dengue fever (DF) or severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Cytokines are believed to be involved in the pathogenesis of dengue infection. However, the role of the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) in dengue infection is unclear. In this study, serum levels of MIF in adult dengue patients with different disease severity and clinical outcome were determined and compared with the levels of other cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-10, and interferon gamma (IFN-gamma), in the same patients. Serum levels of MIF, IL-6, and IL-10, but not IFN-gamma or TNF-alpha, were higher in all DHF patients who died than in DHF survivors and DF patients. We conclude that in addition to IL-6 and IL-10, elevated levels of serum MIF are a potential predictor of disease severity and clinical outcome in dengue patients.     

Desialylation of plasma proteins in severe dengue infection: possible role of oxidative stress

Oxidative stress in dengue infection has been suggested. This study was carried out to explore the plasma protein oxidation and its sialic acid content in dengue infection. Thirty-two dengue hemorrhagic fever (DHF), 25 dengue shock syndrome (DSS), 29 dengue fever (DF), and 63 healthy controls were included in this study. The extent of carbonylation, sulphydryl content, and desialylation of plasma protein was estimated in acute phase sample. Significantly higher levels of protein carbonyls and lower levels of sialic acid and sulphydryl groups were found in DHF and DSS compared with DF using one-way analysis of variance. Regression analysis showed that desialylation is dependent on protein carbonyls in DHF/DSS. This study indicates that, in dengue infection, plasma proteins undergo increased levels of desialylation, which can be attributed to the oxidative stress. Future studies on sialylation status of endothelium and platelets can show light into the pathogenesis of the dengue infection.     

The impact of a program for strengthening dengue hemorrhagic fever case management on the clinical outcome of dengue hemorrhagic fever patients

This study compared the case fatality ratio (CFR) of dengue shock syndrome (DSS) patients admitted to Buri Ram Hospital, an area with CFR of 0.11, 0.43 and 0.23% in 2002, 2003 and 2004, respectively, to obtain a provincial model for dengue case management using the I. development of a special program for strengthening dengue hemorrhagic fever (DHF) case management (No deaths in DSS patients), II. a retrospective review of the medical records of dengue fever (DF), DHF and DSS patients referred to Buri Ram Hospital. We compared the data during the 3 periods of the implementation of this program. Data was statistically analyzed using chi2 or Fisher's exact test for categorical variables, one-way ANOVA for continuous data with normal distribution and Kruskal-Wallis test for nonparametric variables. The numbers of DF, DHF and DSS cases in Buri Ram were 1332, 1700 and 1630 person, respectively, during 2006-2008. The number of DSS patients increased after implementation of the program: 12.2, 51.2 and 47.22 for 2006, 2007 and 2008, respectively, but the complications of the disease decreased. The CFR during 2006, 2007 and 2008 were 0.15, 0 and 0.06% (p > 0.05). The program for strengthening DHF case management did improve clinical outcomes in dengue patients after the implementation. The CFR in 2008 was only 0.06%, lower than the goal of the Ministry of Public Health (<0.13%). This program is still running, sustaining low CFR in dengue patients. It may be used as a model for other provinces in Thailand that have high dengue deaths.     

Dengue research opportunities in the americas

Dengue is a systemic arthropod-borne viral disease of major global public health importance. At least 2.5 billion people who live in areas of the world where dengue occurs are at risk of developing dengue fever (DF) and its severe complications, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Repeated reemergences of dengue in sudden explosive epidemics often cause public alarm and seriously stress healthcare systems. The control of dengue is further challenged by the lack of effective therapies, vaccines, and point-of-care diagnostics. Despite years of study, even its pathogenic mechanisms are poorly understood. This article discusses recent advances in dengue research and identifies challenging gaps in research on dengue clinical evaluation, diagnostics, epidemiology, immunology, therapeutics, vaccinology/clinical trials research, vector biology, and vector ecology. Although dengue is a major global tropical pathogen, epidemiologic and disease control considerations in this article emphasize dengue in the Americas.     

Dengue and dengue hemorrhagic fever among adults: clinical outcomes related to viremia, serotypes, and antibody response

BACKGROUND: Clinical manifestations of dengue vary in different areas of endemicity and between specific age groups, whereas predictors of outcome have remained controversial. In Brazil, the disease burden predominantly affects adults, with an increasing trend toward progression to dengue hemorrhagic fever (DHF) noted. METHODS: A cohort of adults with confirmed cases of dengue was recruited in central Brazil in 2005. Patients were classified according to the severity of their disease. Associations of antibody responses, viremia levels (as determined by real-time polymerase chain reaction [PCR]), and serotypes (as determined by multiplex PCR) with disease severity were evaluated. RESULTS: Of the 185 symptomatic patients >14 years of age who had a confirmed case of dengue, 26.5% and 23.2% were classified as having intermediate dengue fever (DF)/DHF (defined as internal hemorrhage, plasma leakage, manifested signs of shock, and/or thrombocytopenia [platelet count, < or =50,000 platelets/mm3]) and DHF, respectively. The onset of intermediate DF/DHF and DHF occurred at a late stage of disease, around the period of defervescence. Patients with DHF had abnormal liver enzyme levels, with a >3-fold increase in aspartate aminotransferase level, compared with the range of values considered to be normal. Overall, 65% of patients presented with secondary infections with dengue virus, with such infection occurring in similar proportions of patients in each of the 3 disease category groups. Dengue virus serotype 3 (DV3) was the predominant serotype, and viremia was detected during and after defervescence among patients with DHF or intermediate DF/DHF. CONCLUSIONS: Viremia was detected after defervescence in adult patients classified as having DHF or intermediate DF/DHF. Secondary infection was not a predictor of severe clinical manifestation in adults with infected with the DV3 serotype.     

Age- and region-specific hepatitis B prevalence in Turkey estimated using generalized linear mixed models: a systematic review

Background

In view of the long term discussion on the appropriateness of the dengue classification into dengue fever (DF), dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), the World Health Organization (WHO) has outlined in its new global dengue guidelines a revised classification into levels of severity: dengue fever with an intermediary group of "dengue fever with warning sings", and severe dengue. The objective of this paper was to compare the two classification systems regarding applicability in clinical practice and surveillance, as well as user-friendliness and acceptance by health staff.

Methods

A mix of quantitative (prospective and retrospective review of medical charts by expert reviewers, formal staff interviews), semi-quantitative (open questions in staff interviews) and qualitative methods (focus group discussions) were used in 18 countries. Quality control of data collected was undertaken by external monitors.

Results

The applicability of the DF/DHF/DSS classification was limited, even when strict DHF criteria were not applied (13.7% of dengue cases could not be classified using the DF/DHF/DSS classification by experienced reviewers, compared to only 1.6% with the revised classification). The fact that some severe dengue cases could not be classified in the DF/DHF/DSS system was of particular concern. Both acceptance and perceived user-friendliness of the revised system were high, particularly in relation to triage and case management. The applicability of the revised classification to retrospective data sets (of importance for dengue surveillance) was also favourable. However, the need for training, dissemination and further research on the warning signs was highlighted.

Conclusions

The revised dengue classification has a high potential for facilitating dengue case management and surveillance.     

Fatal dengue hemorrhagic fever in Cuba, 1997.

OBJECTIVES: After more than 15 years without dengue activity, a dengue II epidemic was reported in Cuba in 1997. Three thousand and twelve serologically confirmed cases were reported, with 205 dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) cases and 12 fatalities. This report presents the clinical, serologic, and virologic findings in the 12 fatal DHF/DSS cases. METHODS: Serum and necropsy samples were studied by viral isolation in C636 cell line and polymerase chain reaction. Serum samples were tested by IgM capture enzyme-linked immunoassay (ELISA) and ELISA inhibition method (EIM). RESULTS: All 12 cases were classified as DHF/DSS according to the Pan American Health Organization Guidelines for Control and Prevention of Dengue and Dengue Hemorrhagic Fever in the Americas. All patients were older than 15 years. Women were more frequently affected. The symptoms and signs presented by these patients were similar to those previously described in DHF/DSS cases. Clinical deterioration occurred on average at day 3.75. Abdominal pain and persistent vomiting were the earliest and most frequent warning signs. Dengue infection was confirmed in all cases. IgM antibodies were detected in 11 of 12 cases, all of them with a secondary infection. Dengue II virus was detected by viral isolation in 12 samples and by polymerase chain reaction in 17. Virus or RNA was detected in various tissues, including kidney, heart, lung, and brain. CONCLUSION: The clinical, pathologic, and laboratory features of 12 cases of fatal dengue hemorrhagic fever were reviewed. The results obtained demonstrate that adults with a primary dengue infection are at risk of developing the severe disease (DHF) if they are infected with a different serotype.     

Molecular epidemiology of dengue 2 viruses in the Philippines: genotype shift and local evolution

The pre-membrane (prM) and envelope (E) genes of 41 viruses isolated from dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) patients from 1995 to 2002 were sequenced to determine the genetic variability of dengue 2 (DENV 2) viruses in the Philippines. The envelope sequence data were compared with a global sample of DENV 2 obtained from GenBank. Phylogenetic analysis revealed that two distinct genotypes, Asian 2 and Cosmopolitan, are currently circulating locally, each with the potential to cause severe hemorrhagic disease. After the initial isolation in 1998, the Cosmopolitan genotype has gradually and effectively replaced Asian genotype 2 in the Philippines. Members of this genotype were closely related to viruses from Australia, Singapore, and Thailand.     

福建省1株登革Ⅱ型病毒的鉴定

目的对2005年福建省分离的1株登革病毒(DV)进行鉴定,并从分子水平追踪其可能的传染源。方法采用酶联免疫吸附试验(ELISA)检测疑似登革热患者血清中DV(IgM、IgG抗体;同时应用C6/36细胞、单克隆抗体间接免疫荧光(McAb-IFA)、逆转录(套式PCR法分别进行病毒的分离和鉴定,并对分离株的部分基因进行核苷酸序列分析。结果患者血清登革病毒特异性IgM抗体阳性、IgG抗体可疑,表明该患者在近期感染过登革病毒。患者血清接种C6/36细胞,观察到登革病毒特有的CPE。受感染的C6/36细胞能与登革病毒Ⅱ型单克隆抗体反应,表明分离的病毒株为登革Ⅱ型病毒。分离株的核酸提取物经RT(PCR扩增,登革病毒通用引物可扩增出511bp的特异性条带,型特异性引物扩增出119bp的特异性条带,进一步证实分离的病毒株为登革Ⅱ型病毒。分离株RT(PCR扩增产物的核苷酸序列与30株不同地域来源的登革Ⅱ型病毒相应序列构建的系统发生树表明,此毒株与东南亚地区的毒株比较接近。此次分离株的序列与1999年登革Ⅱ型病毒福建株的对应序列在亲缘关系上有一定程度距离。结合流行病学调查资料,进一步确定此病例为输入性感染病例。结论福建省首次从输入性登革热患者血清中分离出登革Ⅱ型病毒,该病毒来源于东南亚地区。     

Association between sex, nutritional status, severity of dengue hemorrhagic fever, and immune status in infants with dengue hemorrhagic fever

The association between sex, nutritional status, and the severity of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), and immune status was investigated in 245 Vietnamese infants with predominantly primary infections with dengue virus. Male and female infants were at equal risk of developing DHF/DSS. However, infants of low height and weight for age were under-represented among DHF/DSS cases compared with 533 healthy baby clinic infant controls. Acute illness phase blood levels of selected cytokines (interferon-gamma and tumor necrosis factor-alpha) and serum levels of antibodies to dengue virus were elevated in the same range in male and female infants with DHF/DSS, as well as in infants with and without malnutrition.     

Oxidative stress in severe dengue viral infection: association of thrombocytopenia with lipid peroxidation

Oxidative stress in viral infections has been suggested. The study was carried out to assess the oxidative stress in the different clinical spectrums of dengue infection and to evaluate if thrombocytopenia is associated with lipid and protein oxidative injury. Twenty-seven dengue fever (DF), 32 dengue hemorrhagic fever (DHF) and 21 dengue shock syndrome (DSS) cases were studied at 3, 5 and 7 days of illness. Sixty-three healthy subjects were selected as controls. Serum protein carbonyls (PCOs), malendialdehyde (MDA) and total antioxidant status (TAS) were estimated in blood. Dengue infected individuals had significantly high levels of PCOs and MDA on the three days tested in comparison to controls. In DF cases, no significant changes in the levels of MDA and PCOs were found in course of time. However, among DHF and DSS, significant increase in MDA levels was found in the fifth and seventh day samples in comparison to their respective third day sample (P < 0.05). Using one way ANOVA, high PCOs levels were found in DSS in comparison to DF and DHF cases on all the three days tested (P < 0.001). TAS levels were found to be low among DSS on days 5 and 7 and day 7 in DHF when compared with DF cases. Correlation analysis between MDA and hematocrit revealed a significant positive association between them in DHF and DSS on day 5 (DHF r = 0.372; p = 0.024 and DSS r = 0.535; p = 0.0-01) and day 7 (DHF r = 0.412; p = 0.003 and DSS r = 0.765; p < 0.0001). There was an important negative correlation between platelet count and plasma lipid peroxidation levels among DHF and DSS on all three days tested [day 3 (DHF r = -0.392; p = 0.012 and DSS r = -0.453; p = 0.004), day 5 (DHF r = -0.592; p < 0.001 and DSS r = -0.581; p < 0.001) and day 7 (DHF r = -0.418; p = 0.001 and DSS r = -0.515; p = 0.002)]. This study concludes that an increase in oxidative stress was found in dengue viral infection. The level of oxidative stress was maximal in DSS followed by DHF and its severity was minimal in DF. The thrombocytopenia of dengue infection was associated with the extent of lipid peroxidation. Future studies might be carried out to find the role of oxidative damage in the ethiopathogenesis of thrombocytopenia and vascular leakage in dengue infection.     

Fatal dengue hemorrhagic fever in adults during a dengue epidemic in Singapore.

BACKGROUND: Dengue fever has seen a significant re-emergence in Southeast Asia. Associated with the rise of dengue has been the increase in dengue-associated mortality. To better understand the predictors of mortality, we conducted a review of hospitalized adult dengue infections within our institution. METHODS: This was a retrospective case-control study of dengue-associated deaths at a large tertiary care hospital. RESULTS: In 2004, of 3186 cases of dengue fever (DF)/hemorrhagic dengue fever (DHF) admitted to our institution, there were 130 cases of DHF and seven dengue-associated deaths (case-fatality rate 5.4%). At least three of the seven fatal cases had serological evidence of primary dengue infection. All dengue-mortality cases had rapidly progressive clinical deterioration at an average of day 4 of fever with intensive care admission occurring on a mean of 5.6 days of fever. Adult respiratory distress syndrome, disseminated intravascular coagulopathy, and multi-organ failure were the most common causes of death despite early hospitalization, intravenous fluid, and blood-product support. CONCLUSION: Dengue is associated with severe disease, and deaths do occur despite current supportive management. Fatal DHF/dengue shock syndrome (DSS) does occur in adults and in primary dengue infection. Better early predictors of disease severity and clinical interventions are needed.