Risk factors associated with severe dengue in Latin America: A systematic review and meta-analysis.

OBJECTIVE: Severe dengue is a significant health problem in Latin America, with children being the most affected. Understanding risk factors for severe dengue is crucial for enhancing patient care. Therefore, this study aims to systematically review the literature to identify the risk factors associated with severe dengue in Latin America through systematic review and meta-analysis. METHODS: PubMed, SciELO, LILACS and EMBASE databases were used to search for eligible scientific articles for the review. The outcomes considered were symptoms of severe dengue, hospitalisation and death. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the quality of the studies. Data analysis was performed using STATA v 13.0 software. The degree of heterogeneity between studies was quantified using the I2 measure, and statistically significant results were defined as those with p values <0.05. RESULTS: Of the 1876 articles screened, 47 articles were included in the systematic review and 45 articles were analysed through meta-analysis. Identified risk factors associated with severe dengue included secondary dengue infection, female sex, white or Caucasian ethnicity and specific signs and symptoms such as headache, myalgia and/or arthralgia, vomiting/nausea, abdominal pain or tenderness, diarrhoea, prostration, lethargy, fatigue or similar. For the death outcome, respiratory symptoms and age <18 years were identified as risk factors. On the other hand, in women, the diagnosis of positive tourniquet test, platelet count <100,000 per µL and symptoms of capillary fragility were associated with a lower probability of death. These data highlight the importance of early screening of patients, to identify possible haemorrhagic signs and reduce deaths from dengue. This study has limitations, including possible publication bias, heterogeneity of results and study design biases. CONCLUSION: These findings are significant for shaping strategies, management approaches and identifying high-risk groups, which will help establish future guidelines.

Prediction of mortality in severe dengue cases.

BACKGROUND: Increasing incidence of dengue cases in Malaysia over the last few years has been paralleled by increased deaths. Mortality prediction models will therefore be useful in clinical management. The aim of this study is to identify factors at diagnosis of severe dengue that predicts mortality and assess predictive models based on these identified factors. METHOD: This is a retrospective cohort study of confirmed severe dengue patients that were admitted in 2014 to Hospital Kuala Lumpur. Data on baseline characteristics, clinical parameters, and laboratory findings at diagnosis of severe dengue were collected. The outcome of interest is death among patients diagnosed with severe dengue. RESULTS: There were 199 patients with severe dengue included in the study. Multivariate analysis found lethargy, OR 3.84 (95% CI 1.23-12.03); bleeding, OR 8.88 (95% CI 2.91-27.15); pulse rate, OR 1.04 (95% CI 1.01-1.07); serum bicarbonate, OR 0.79 (95% CI 0.70-0.89) and serum lactate OR 1.27 (95% CI 1.09-1.47), to be statistically significant predictors of death. The regression equation to our model with the highest AUROC, 83.5 (95% CI 72.4-94.6), is: Log odds of death amongst severe dengue cases = - 1.021 - 0.220(Serum bicarbonate) + 0.001(ALT) + 0.067(Age) - 0.190(Gender). CONCLUSION: This study showed that a large proportion of severe dengue occurred early, whilst patients were still febrile. The best prediction model to predict death at recognition of severe dengue is a model that incorporates serum bicarbonate and ALT levels.

Comorbidities increase in-hospital mortality in dengue patients in Brazil.

Dengue remains an unmet public health burden. We determined risk factors for dengue in-hospital mortality in Brazil. Of 326,380 hospitalised dengue cases in 9-45-year-old individuals, there were 971 deaths. Risk of dying was 11-times higher in the presence of underlying common comorbidities (renal, infectious, pulmonary disease and diabetes), similar to the risk of dying from severe dengue and much higher with the combination. Ensuring access to integrated dengue preventative measures in individuals aged ≥ 9 years including those with comorbidities may help achieve the WHO objective of 50% reduction in mortality and 25% reduction in morbidity due to dengue by 2020.

Evaluation of the importance of fever with respect to dengue prognosis according to the 2009 WHO classification: a retrospective study.

BACKGROUND: The 2009 revised World Health Organization (WHO) guidelines for dengue describe fever as the core symptom. Accordingly, the diagnosis of non-febrile patients is complicated. The aim of this study was to evaluate the importance of fever in patients with dengue according to the 2009 revised WHO classification. METHODS: In this study, we assessed 30,670 dengue cases using enzyme-linked immunosorbent assay, detection of the non-structural protein 1, or polymerase chain reaction for diagnostic confirmation. Fisher's exact test was used to evaluate associations between fever and related clinical manifestations. The Mann-Whitney U test was used to assess the association of dengue classification with fever and time to treatment. The effects of fever and time to treatment on the risk of progression were analyzed using an ordinal logistic regression to stereotype the model. RESULTS: Disease classification was found to associate significantly with both fever and time to treatment (both P < 0.001). Non-febrile patients were nearly four-fold more likely to exhibit "dengue without warning signs" than "severe dengue" (odds ratio [OR] = 3.74; 95% confidence interval [CI]: 3.20-4.36). Patients who received treatment within 7 days were twice as likely to have "dengue without warning signs" as opposed to "severe dengue" when compared to those who waited >7 days (OR = 2.23; 95% CI: 1.78-2.80). However, this difference was negligible in the multivariate analysis (OR = 1.02; 95% CI: 0.98-1.07). CONCLUSIONS: Fever is a risk factor for disease progression in patients with dengue. However, non-febrile patients should not be neglected because this may delay treatment and could lead to more severe disease.

Dengue Hemorrhagic Fever: A State-of-the-Art Review Focused in Pulmonary Involvement.

Dengue fever is an arboviral disease transmitted to humans through the bites of infected female Aedes mosquitoes. Dengue virus is a member of the Flaviviridae family, and human infection can be caused by any of the four antigenically distinct serotypes (DENV 1-4). The infection has become recognized as the most important and prevalent arboviral disease in humans, endemic in almost 100 countries worldwide. Nearly 3 billion people live in areas with transmission risk. Autochthonous transmission of the virus in previously disease-free areas, increased incidence in endemic areas, and epidemic resurgence in controlled regions could increase the risk of contracting more severe forms of the disease, such as dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). Symptomatic dengue virus infection can present with a wide range of clinical manifestations, from mild fever to life-threatening DSS. Thoracic complications may manifest as pleural effusion, pneumonitis, non-cardiogenic pulmonary edema, and hemorrhage/hemoptysis. No vaccine is currently available and no specific treatment for dengue fever exists, but prevention and prompt management of complications in patients with DHF can help reduce mortality. This review describes the main clinical, pathological, and imaging findings of thoracic involvement in DHF.

Factors associated with death from dengue in the state of Minas Gerais, Brazil: historical cohort study.

OBJECTIVES: To analyse the clinical and epidemiological profiles of dengue haemorrhagic fever (DHF), dengue shock syndrome (DSS) and complicated dengue cases and deaths from 2008 to 2010 that occurred in the state of Minas Gerais, south-eastern Brazil, and to identify factors associated with death from dengue. METHODS: Historical cohort study using data from the Brazilian Information System for Notifiable Diseases. A descriptive analysis of the DHF, DSS and complicated dengue cases and deaths was performed; the incidence, mortality and case-fatality rates were estimated. Logistic regression analysis was used to identify factors associated with death from dengue. Comorbidities were not included in the analysis because the information system does not contain such data. RESULTS: During the study period, 2214 DHF, DSS and complicated dengue cases were reported, including 156 deaths. The annual case-fatality rates for DHF/DSS and complicated dengue cases in the period of 2008-2010 were 7.3%, 4.8% and 7.9%, respectively. The factors associated with death from dengue included residence in a municipality with a population of fewer than 100,000 inhabitants [odds ratio (OR) 2.46; 95% confidence interval (CI) 1.71-3.55], age over 65 years (OR 3.05; 95% CI 1.99-4.68) and plasma leakage (OR 1.69; 95% CI 1.16-2.46). CONCLUSIONS: The results support the importance of plasma leakage as a warning sign associated with death from dengue as well as the signs and symptoms that allow the diagnosis of DHF. Moreover, our findings suggest that increased attention is necessary for individuals over 65 years of age and in municipalities with populations under 100,000 inhabitants to ensure a better quality of care during the management of severe patients of dengue in these locations. Differences in the interpretation of the DHF definition have hindered the comparison of data from different countries; it can improve from the WHO 2009 dengue classification.

DENGUE PATIENTS AT PHOTHARAM HOSPITAL: A CLINICAL TRIAL SITE OF DENGUE VACCINE.

Between 2005 and 2013, 1,868 dengue patients, 916 male and 952 female, were admitted to Photharam Hospital, Ratchaburi, Thailand. Among these patients, there were 1,209 with dengue fever (DF), 598 with dengue hemorrhagic fever (DHF), and 61 with dengue shock syndrome (DSS) with 1 death. The disease was seen all year round with a higher incidence in the rainy season. A trend of shift in age group towards older children and adults was seen during the study period. These data show that dengue patient admissions to Photharam Hospital are common, causing a heavy burden on the health system. Only one death was seen during the period of study, indicating that early recognition and effective management of dengue patients occurred. The trend towards higher age in dengue patients during the study period is a problem of concern and needs further clarification.

The changing incidence of dengue haemorrhagic fever in Indonesia: a 45-year registry-based analysis.

BACKGROUND: Increases in human population size, dengue vector-density and human mobility cause rapid spread of dengue virus in Indonesia. We investigated the changes in dengue haemorrhagic fever (DHF) incidence in Indonesia over a 45-year period and determined age-specific trends in annual DHF incidence. METHODS: Using an on-going nationwide dengue surveillance program starting in 1968, we evaluated all DHF cases and related deaths longitudinally up to 2013. Population demographics were used to calculate annual incidence and case fatality ratios (CFRs). Age-specific data on DHF available from 1993 onwards were used to assess trends in DHF age-distribution. Time-dependency of DHF incidence and CFRs was assessed using the Cochrane-Armitage trend test. RESULTS: The annual DHF incidence increased from 0.05/100,000 in 1968 to ~ 35-40/100,000 in 2013, with superimposed epidemics demonstrating a similar increasing trend with the highest epidemic occurring in 2010 (85.70/100,000; p < 0.01). The CFR declined from 41% in 1968 to 0.73% in 2013 (p < 0.01). Mean age of DHF cases increased during the observation period. Highest incidence of DHF was observed among children aged 5 to 14 years up to 1998, but declined thereafter (p < 0.01). In those aged 15 years or over, DHF incidence increased (p < 0.01) and surpassed that of 5 to 14 year olds from 1999 onwards. CONCLUSIONS: Incidence of DHF over the past 45 years in Indonesia increased rapidly with peak incidence shifting from young children to older age groups. The shifting age pattern should have consequences for targeted surveillance and prevention.

Deaths due to dengue fever at a tertiary care hospital in Lahore, Pakistan.

OBJECTIVE: We conducted this study to review deaths due to dengue fever (DF) during a large outbreak of DF in Lahore, Pakistan. METHODS: We reviewed deaths due to DF at Jinnah Hospital Lahore between August and November 2011. Clinical and laboratory data were abstracted. The 2011 World Health Organization Regional Office for South-East Asia (WHO SEARO) guidelines were used to classify the disease. RESULTS: Out of 128,634 probable DF patients who visited the outpatient department, 2313 patients were hospitalized; 1699 (73.3%) were male. RT-PCR was positive in 92 of 114 hospitalized patients (DENV-2 in 91 patients and DENV-3 in 1 patient). Sixty dengue-related deaths were reported; 41 (68.3%) were male. The mean age (± standard deviation) was 44 (± 20.5) y. The diagnosis at the time of presentation was DF in 5 (8.3%), dengue haemorrhagic fever without shock in 16 (26.6%), dengue shock syndrome in 20 (33%), and expanded dengue syndrome in 19 (31.7%) patients. Expanded dengue syndrome included encephalopathy in 12 (20%) patients, intracerebral bleed in 3 (5%), multiorgan failure in 3 (5%), and Guillain-Barré syndrome in 1 (1.6%). Twenty-nine (48.3%) patients had at least 1 comorbidity. CONCLUSION: Dengue shock syndrome and expanded dengue syndrome were the most common causes of death.

Corticosteroids for dengue infection.

BACKGROUND: Dengue is a common and important mosquito-borne viral infection. In many low- and middle-income countries it is endemic and is an important public health problem. Severe dengue is an important cause of death in children. There is no specific treatment for dengue, but observational studies suggest corticosteroids may have a benefit in dengue-related shock, and some people believe corticosteroids may prevent the progression to severe illness if given early in the course of the illness. OBJECTIVES: To compare treatment of dengue with and without use of corticosteroids or placebo in relation to preventing shock-related death and disease progression in children and adults. SEARCH METHODS: We searched the Cochrane Infectious Disease Group Centralized Register; CENTRAL; MEDLINE; EMBASE; and LILACS, up to 6 January 2014. We screened reference lists and contacted the relevant study authors for additional information where required. SELECTION CRITERIA: Randomized controlled trials or quasi-randomized controlled trials comparing corticosteroids with placebo or no corticosteroids in patients diagnosed with dengue-related shock, or patients in an early symptomatic state of dengue with positive serology. DATA COLLECTION AND ANALYSIS: Two researchers independently screened eligibility of records, extracted data and assessed quality of the studies. We presented findings in meta-analysis and summary of findings tables and evaluated the quality of evidence using GRADE. MAIN RESULTS: We included eight studies enrolling 948 participants in this review. Paitents with dengue-related shock Four studies enrolled children younger than 15 years with dengue-related shock at hospitals in Southeast Asia and evaluated intravenous corticosteroids. The trials did not detect an effect on death (four trials, 284 participants, very low quality evidence), the need for blood transfusion (two trials, 89 participants, very low quality evidence), pulmonary haemorrhage (one trial, 63 participants, very low quality evidence), convulsions (one trial, 63 participants, very low quality evidence), or duration of hospitalization (one trial, 63 participants, very low quality evidence). The body of evidence is too small to confidently prove or exclude clinically important effects. Furthermore, the trials are more than 20 years old with several methodological limitations. Patients with dengue at an early stage Four studies enrolled 664 children and adults with dengue at an early stage of infection (without shock) in Columbia, India, Sri Lanka and Vietnam. In these participants there were no evidence of effects of oral or intravenous corticosteroids on mortality (four trials, 664 participants, low quality evidence), or on the development of complications of severe dengue such as shock (two trials, 286 participants, very low quality evidence), severe bleeding (two trials, 425 participants, very low quality evidence), severe thrombocytopaenia (one trial, 225 participants, very low quality evidence), ascites (one trial, 178 participants, very low quality evidence) and intensive care unit (ICU) admissions (two trials, 286 participants, very low quality evidence). AUTHORS' CONCLUSIONS: The evidence from trials using corticosteroids in dengue is inconclusive and the quality of evidence is low to very low. This applies to both the use of corticosteroids in dengue-related shock and for dengue at an early stage. There is insufficient evidence to evaluate the effects of corticosteroids in the treatment of early stage dengue fever and dengue-related shock outside of the context of a randomized controlled trial.

Analysis of signs and symptoms in confirmed cases of severe dengue among children aged 0 to 10 years old.

OBJECTIVE: The prevalent symptoms of severe dengue in pediatric patients are divided into three subgroups: severe plasma leakage, severe bleeding, and severe organ damage. In addition, the seasonal patterns of the disease and the outcomes of cure or death from dengue were evaluated. METHODS: An epidemiological, observational, analytical, cross-sectional study was conducted with data from the Notifiable Disease Information System (SINAN - Sistema de Informação de Agravos de Notificação and DATASUS - Departamento de Informática do Sistema Único de Saúde) of the Ministry of Health from 2019 to 2020. RESULTS: During the study period, 1,857 cases of severe dengue were observed in the pediatric age group, with the most common symptoms being respiratory failure, melena, hematemesis, and altered level of consciousness. The total proportion of patients hospitalized for severe dengue was 89.6%, and 51.2% of these patients died, corroborating the importance of early detection of the disease. CONCLUSION: Severe dengue is more prevalent during the seasonal period, with hot and humid characteristics owing to the mechanism involved in the viral cycle. The most prevalent symptoms of severe dengue in pediatric patients were respiratory failure alone, gastrointestinal bleeding, and altered level of consciousness. It is important to identify signs of severity for early intervention and a better prognosis, considering that death is closely related to a delayed diagnosis.

Risk factors associated with dengue complications and death: A cohort study in Peru.

BACKGROUND: Dengue has emerged as an unprecedented epidemic in Peru, and it is anticipated that this issue will escalate further owing to climate change. This study aimed to determine the risk factors associated with death from dengue in patients treated at Hospital II in Pucallpa, Peru. METHODOLOGY: This retrospective cohort study collected information from the medical records of patients with a diagnosis of dengue treated at Hospital II Pucallpa-Peru between January 2019 and March 2023. The primary outcome was death, and the secondary outcome was death, development of severe dengue, or Intensive Care Unit (ICU) admission. Cox regression models were used to determine risk factors. FINDINGS: The clinical records of 152 patients were evaluated, with a median age of 27.5 years (interquartile range, 11-45). Among all patients, 29 (19.1%) developed severe dengue, 31 (20.4%) were admitted to the ICU, and 13 (8.6%) died during follow-up. In the survival analysis, bilirubin >1.2 mg/dL was associated with a higher risk of death aHR: 11.38 (95% CI: 1.2 106.8). Additionally, factors associated with poor prognosis included having 1 to 3 comorbidities aRR: 1.92 (1.2 to 3.2), AST ≥251 U/L aRR: 6.79 (2.2 to 21.4), history of previous dengue aRR: 1.84 (1.0 to 3.3), and fibrinogen ≥400 mg/dL aRR: 2.23 (1.2 to 4.1). SIGNIFICANCE: Elevated bilirubin was associated with death from dengue, whereas an increase in comorbidities and a history of previous dengue were related to a poor prognosis of the disease. Early identification of severe dengue would be more feasible with improved access to laboratory testing, particularly in tropical areas with a high dengue incidence.

Incidence of acute liver failure and its associated mortality in patients with dengue infection: A systematic review and meta-analysis.

Acute liver failure (ALF) is a devastating consequence of dengue infection. This systematic review and meta-analysis assessed the incidence of ALF in dengue infection and its associated mortality. We systematically searched the EMBASE and MEDLINE databases from inception to December 2023 for observational studies reporting ALF incidence and mortality in dengue patients. Twenty-one studies encompassing 26,839 dengue-infected patients were included. Meta-analysis revealed a pooled incidence of ALF in cases of general dengue infection of 2.0 % (95 % CI, 1.2-3.0 %), with 1.2 % (95 % CI, 0.6-2.1 %) in adults and 5.0 % (95 % CI, 1.5-10.2 %) in children. ALF incidence was 17.3 % (95 % CI, 6.5 %-31.5 %) in severe dengue and 7.4 % (95 % CI, 0.8-18.5 %) in dengue shock syndrome. The pooled mortality rate of dengue-associated ALF was 47.0 % (95 % CI, 32.9-61.2 %). These findings underscore the detrimental impact of dengue infection on the development of the relatively uncommon, albeit life-threatening, condition of ALF.

Prognostic values of serum lactate-to-bicarbonate ratio and lactate for predicting 28-day in-hospital mortality in children with dengue shock syndrome.

This study aimed to assess the clinical utility of blood lactate-to-bicarbonate (L/B) ratio, as a prognostic factor for 28-day in-hospital mortality in children with dengue shock syndrome (DSS), admitted to the pediatric intensive care unit (PICU). This single-center retrospective study was conducted at a tertiary children hospital in southern Vietnam from 2013 to mid-2022. Prognostic models for DSS mortality were developed, using a predefined set of covariates in the first 24 hours of PICU admission. Area under the curves (AUCs), multivariable logistic and Least Absolute Shrinkage and Selection Operator (LASSO) regressions, bootstrapping and calibration slope were performed. A total of 492 children with DSS and complete clinical and biomarker data were included in the analysis, and 26 (5.3%) patients died. The predictive values for DSS mortality, regarding lactate showing AUC 0.876 (95% CI, 0.807-0.944), and that of L/B ratio 0.867 (95% CI, 0.80-0.934) (P values of both biomarkers < .001). The optimal cutoff point of the L/B ratio was 0.25, while that of lactate was 4.2 mmol/L. The multivariable model showed significant clinical predictors of DSS fatality including severe bleeding, cumulative amount of fluid infused and vasoactive-inotropic score (>30) in the first 24 hours of PICU admission. Combined with the identified clinical predictors, the L/B ratio yielded higher prognostic values (odds ratio [OR] = 8.66, 95% confidence interval [CI], 1.96-38.3; P < .01) than the lactate-based model (OR = 1.35, 95% CI, 1.15-1.58; P < .001). Both the L/B and lactate models showed similarly good performances. Considering that the L/B ratio has a better prognostic value than the lactate model, it may be considered a potential prognostic biomarker in clinical use for predicting 28-day mortality in PICU-admitted children with DSS.

Fatal dengue hemorrhagic fever imported into Germany.

Dengue virus (DENV) is an arthropod-borne virus (family Flaviviridae) causing dengue fever or dengue hemorrhagic fever. Here, we report the first fatal DENV infection imported into Germany. A female traveler was hospitalized with fever and abdominal pain after returning from Ecuador. Due to a suspected acute acalculous cholecystitis, cholecystectomy was performed. After cholecystectomy, severe spontaneous bleeding from the abdominal wound occurred and the patient died. Postmortem analysis of transudate and tissue demonstrated a DENV secondary infection of the patient and a gallbladder wall thickening (GBWT) due to an extensive edema.

Prognostic indicators associated with progresses of severe dengue.

BACKGROUND: Dengue usually progress abnormally, especially in the critical phase. The main causes of death were shock, severe bleeding and organ failure. The aim of our study was to evaluate prognostic indicators of severe dengue according to the phases of the disease progression. METHODS: A cross-sectional study was conducted from July to December 2017 at the National Hospital for Tropical Diseases and the Hospital for Tropical Diseases of Ho Chi Minh City. 326 patients, aged 6 years and over, including 99/326 patients with severe dengue and 227/326 patients with non-severe dengue, hospitalized in the first 3 days of illness, confirmed Dengue virus by the RT-PCR assay have been registered for the study. Clinical manifestations were monitored daily. The hematocrit, white blood cells, platelet, serum albumin, ALT, AST, bilirubin, prothrombin time (PT%, PTs), fibrinogen, aPTT, INR and creatinine were evaluated at two times: febrile phase and critical phase. RESULTS: Independent factors associated with severe dengue were identified on multivariate logistic regression models. During the first 3 days of the disease, the prognostic indicators were platelet count ≤ 100 G/L (OR = 2.2; 95%CI: 1.2-3.9), or serum albumin < 35 g/L (OR = 3.3; 95%CI: 1.8-6.1). From day 4-6, the indicator were AST > 400 U/L (OR = 3.0; 95%CI: 1.1-7.9), ALT > 400 U/L (OR = 6.6; 95%CI: 1.7-24.6), albumin < 35 g/L (OR = 3.0; 95%CI: 1.5-5.9), and bilirubin total >17 µmol/L (OR = 4.6; 95%CI: 2.0-10.4). CONCLUSION: To predict the risk of patients with severe dengue, prognostic laboratory indicators should be indicated consistent with the progression of the disease. During the first 3 days of illness, prognostic indicators should be platelet count, or serum albumin. From the 4th - 6th day of illness, prognostic indicators should be AST, ALT, albumin, or bilirubin total.

Mortality Rates of Severe Dengue Viral Infection Before and After Implementation of a Revised Guideline for Severe Dengue.

OBJECTIVES: To compare the mortality rate of severe dengue (SD) before and after implementation of a revised SD guideline. METHODS: Medical records of SD patients <15 years of age hospitalized during 1998-2020 were reviewed. The revised SD guidelines were implemented in 2016, including intensive monitoring of vital signs and intra-abdominal pressure, the release of intra-abdominal pressure in cases of abdominal compartment syndrome (ACS) and the use of N-acetyl cysteine in cases of acute liver failure. RESULTS: On initial admission, organ failure including severe bleeding, acute respiratory failure, acute kidney injury and acute liver failure was not significantly different between 78 and 23 patients treated in the pre- and postrevised guideline periods, respectively. After hospitalization, the proportions of patients who developed profound shock (68.8% vs. 41.2%), multiorgan failures (60.4% vs. 73.3%), ACS (37.2% vs. 26.1%) and fatal outcome (33.3% vs. 13.0%) were also not significantly different between the pre- and postrevised guideline periods, respectively. In subgroup analysis, the mortality rates in patients with multiorgan failure (44.1% vs. 15.8%), acute respiratory failure and active bleeding (78.1% vs. 37.5%) and ACS (82.8% vs. 33.3%), respectively, were significantly higher in the pre- than the postrevised guideline periods. The durations of time before the liver function tests returned to normal levels, and the mortality rates in acute liver failure patients treated with and without N-acetyl cysteine were not significantly different. CONCLUSIONS: Although following the revised guidelines could not prevent organ failure, the mortality rates in patients with multiorgan failure and/or ACS decreased significantly when following the revised guidelines.

Emergence of the severe syndrome and mortality associated with dengue and dengue-like illness: historical records (1890 to 1950) and their compatibility with current hypotheses on the shift of disease manifestation.

Outbreaks of the severe dengue syndrome, dengue hemorrhagic fever (DHF), emerged beginning in the 1950s, marking a dramatic change in the dengue syndrome. While intense investigations in multiple directions have been conducted for many years to elucidate the intrinsic mechanisms conducive to the development of DHF, no consensus has yet emerged. Meanwhile, relatively little attention has been paid to the occurrence of severe dengue and death prior to the 1950s. This comprehensive review was designed to evaluate outbreak records in the early dengue history to better understand the epidemiologic background and other factors that existed before the emergence of DHF outbreaks. By applying a set of stringent criteria to remove unreliable data as much as possible and by interpreting the results conservatively, a short list of etiologically more reliable outbreaks with high mortality was obtained. The results show that severe dengue syndrome, clinically very much compatible with DHF, occurred far more frequently in multiple locations than it had been assumed before; that the magnitudes of mortality in several outbreaks were not negligible; and that the epidemiologic background features shared among these outbreaks in the early period were, with the exceptions of more limited demographic changes, generally similar to the post-1950 conditions.

Dengue shock syndrome at the emergency room of Queen Sirikit National Institute of Child Health, Bangkok, Thailand.

BACKGROUND: Dengue virus infection is an important mosquito-borne disease with the reported 40,000-100,000 cases per year in Thailand. Shock is one of the common presentations at the emergency room (ER) and dengue shock syndrome (DSS) is among the common causes of shock. Proper and timely management of DSS determines the outcomes and prognosis of DSS patients. OBJECTIVE: To find the prevalence of DSS at the ER and evaluate the medical management and risk factors associated with the outcome of DSS patients. MATERIAL AND METHOD: A retrospective study on patients who presented with shock, including DSS patients at the ER of Queen Sirikit National Institute of Child Health (QSNICH), Bangkok, Thailand, from 1st January 2008 to 31st December 2009 was done. The prevalence of patients who presented with shock at the ER was retrieved from the Statistical and Information Technology Departments. Out-patient cards and In-patient charts of DSS patients were reviewed. Clinical and laboratory data were compared between recovered and death cases. Statistical analysis was done by using SPSS version 14.0. RESULTS: There were 109 shock patients seen at the ER during the present study period with 59 DSS (54.1%), 30 septic shock (27.5%), 13 hypovolemic shock (11.9%), 1 cardiogenic shock (0.9%) and 6 other non-specific shock (5.5%). DSS cases were found all year round with the peak prevalence from June to August which is the rainy season. Twenty-six of DSS (44.1%) were referred cases and 5 of them died, case fatality rate was 8.8%. All death cases had prolonged shock, massive bleeding and liver failure at presentation while these findings were found in 2 (4.4%), 16 (35.6%) and 10 (22.2%) cases of recovered cases. Encephalopathy, renal failure and respiratory failure were found in 80, 60 and 60% of the death cases while in recovered cases they were found in 11.1, 4.4 and 2.2%. Acidosis was found higher in the death group (60%) than in recovered group (8.9%). Other common presenting findings in death and recovered groups were bleeding (35.6 vs 100.0%), fluid over load (31.1 vs. 80%), hyponatremia (40% for both groups) and hypocalcemia (83.3 vs. 80%). Among the 45 recovered cases; 3 cases were misdiagnosed and another 8 cases (17.8%) received no i.v. fluid at the ER. Cross matching was done in 32 cases (64%) and blood was transfused in 16 cases (50% of the cross matching). CONCLUSION: DSS is the most common shock found at the ER especially during June to August. ER physicians should be alert for making the correct diagnosis of DSS with proper intravenous fluid resuscitation and correction of the common complications/laboratory abnormalities, i.e. acidosis, hyponatremia, hypocalcemia and cross matching for massive bleeding. A referred case with liver failure together with renal and respiratory failure was likely associated with mortality while fluid overload and significant bleeding do not if they are managed properly. Early signs of shock should be detected in walk in cases to prevent later shock after admission.

Early Predictors of Mortality in Children with Severe Dengue Fever: A Prospective Study.

OBJECTIVE: The aim of the study was to identify early predictors of mortality in children with severe dengue fever admitted to pediatric intensive care unit (PICU). MATERIALS AND METHODS: All consecutive children with laboratory-confirmed severe dengue fever were enrolled in this prospective observational study. Besides demographic data, disease severity and organ dysfunction scores, laboratory investigations and interventions are done in PICU were recorded and analyzed. RESULTS: During the study period of 42 months, 172 patients with dengue fever were admitted to PICU. A total of 78 (45.3%) patients with severe dengue fever were included and analyzed. There were 20 (25.6%) deaths. There were significant differences in disease severity and organ dysfunction scores, transaminases, blood lactate level and serum creatinine between survivors and nonsurvivors. A significantly higher number of nonsurvivors required interventions in first 24 hours of admission. Platelet counts (P value 0.22) and hematocrit (P value 0.47) were not statistically different in 2 groups. There was a significantly high vasopressor-inotrope score (VIS) (<0.001) and positive fluid balance >10% (0.002) in nonsurvivors. Multivariate stepwise logistic regression analysis identified serum glutamic pyruvic transaminases (≥ 284 IU/L; odds ratio [OR] 1.002, 95% confidence interval [CI]: 1.001-1.003), blood lactate level (≥2.73 mmol/L; OR 2.08, 95% CI: 1.354-3.202), Pediatric Risk of Mortality score at 12 hours (≥14.5; OR 1.35, 95% CI: 1.077-1.693), VIS (≥22.5, OR 1.129, 95% CI: 1.059-1.204) and positive fluid balance >10% (OR 22.937, 95% CI: 2.393-219.84) at 24 hours of admission as independent predictors of mortality. CONCLUSION: Disease severity, hyperlactatemia at admission, need for multiple vasoactive drugs and positive fluid balance are predictors of mortality in severe dengue infection in children admitted to PICU.