Unique Immune Blood Markers Between Severe Dengue and Sepsis in Children.

BACKGROUND: Pediatric dengue and sepsis share clinical and pathophysiologic aspects. Multiple inflammatory and regulatory cytokines, decoy receptors and vascular permeability factors have been implicated in the pathogenesis of both diseases. The differential pattern and dynamic of these soluble factors, and the relationship with clinical severity between pediatric dengue and sepsis could offer new diagnosis and therapeutic strategies. METHODS: We evaluated the concentration levels of 11 soluble factors with proinflammatory, regulatory and vascular permeability involvement, in plasma from children with dengue or sepsis, both clinically ranging from mild to severe, in the early, late and convalescence phases of the disease. RESULTS: During early acute infection, children with sepsis exhibited specific higher concentration levels of IL-6, vascular endothelial growth factor (VEGF), and its soluble decoy receptor II (sVEGFR2) and lower concentration levels of IL-10 and the soluble tumor necrosis factor receptor 2 (sTNFR2), in comparison with children with severe dengue. In addition, the circulating amounts of soluble ST2, and VEGF/sVEGFR2 were widely associated with clinical and laboratory indicators of dengue severity, whereas secondary dengue virus infections were characterized by an enhanced cytokine response, relative to primary infections. In severe forms of dengue, or sepsis, the kinetics and the cytokines response during the late and convalescence phases of the disease also differentiate. CONCLUSIONS: Dengue virus infection and septic processes in children are characterized by cytokine responses of a specific magnitude, pattern and kinetics, which are implicated in the pathophysiology and clinical outcome of these diseases.

Hemophagocytic lymphohistiocytosis as a rare complication of dengue haemorrhagic fever: a case report.

BACKGROUND: Haemophagocytic lymphohistiocytosis (HLH) is an uncommon systemic inflammatory syndrome that can happen secondary to numerous conditions. It rarely occurs due to dengue infection causing significant mortality and morbidity even with appropriate treatment. The outcome is further poor if the diagnosis of HLH is delayed or left untreated. Therefore, a high degree of clinical suspicion is paramount in diagnosing HLH. CASE PRESENTATION: A 17-year-old Sinhalese boy was admitted to a tertiary care hospital in Sri Lanka with a 4-day history of fever, headache, nausea, vomiting, and diarrhea. He was hemodynamically stable, and the serological investigation confirmed a dengue infection. On the fifth day of fever, he entered the critical phase of dengue infection, confirmed by ultrasound evidence of plasma leaking. However, he had ongoing high fever spikes during the critical phase, and even after the critical phase was over, the fever spikes continued. Simultaneously, hepatosplenomegaly was noticed, and he showed persistent thrombocytopenia, neutropenia, and anemia despite the resolution of the critical phase. Further, the workup revealed a serum ferritin level of > 3000 ng/mL triglyceride level of 314 mg/dL, and the bone marrow biopsy revealed an increased haemophagocytic activity. Secondary HLH was diagnosed on the basis of criteria used in the HLH-2004 trial and successfully managed with intravenous dexamethasone 10 mg/body surface area/day for the first 2 weeks, followed by a tapering regimen over 8 weeks. CONCLUSION: This case emphasizes the need to consider HLH as a potential complication when persistent fever and cytopenias are present after recovering from dengue fever, particularly in patients with unusual clinical features like hepatosplenomegaly. Early recognition and prompt treatment with appropriate immunosuppressive therapy, such as intravenous dexamethasone, can lead to a successful response and good prognosis.

Perinatal Transmission of Dengue Infection among Dengue Hemorrhagic Fever Outbreaks in Southern Vietnam: The First Case Managed at Tu Du Hospital and Review of Literature.

Dengue hemorrhagic fever is a high-risk pathology in pregnancy, leading to an increased mortality rate for both the mother and baby. Perinatal transmission of dengue infection may occur during the labor stage of the febrile phase, despite its extreme rarity. In the present case, a young female patient with pregnancy at 39 weeks 3 days of gestational age was hospitalized because of dengue hemorrhagic fever. Upon monitoring, her platelet count gradually decreased to a very low of 13,000 mm3 on the third day of fever. However, her platelet count increased soon afterwards. On the eighth day of admission, she was delivered by emergency cesarean section due to acute fetal distress. The female neonate was promptly assessed by the pediatric team upon cesarean surgery. The neonate was diagnosed with vertical transmission of dengue infection based on positive dengue virus nonstructural protein 1 antigen, and low platelet count was found on the first day postpartum. When there is a high suspicion of perinatal transmission, closely monitoring the newborn helps to avoid the adverse outcomes and mortality for the infant. Herein, we thoroughly report an unusual case of maternal-fetal transmission of dengue during pregnancy at our maternity hospital.

The utility of inflammatory and endothelial factors in the prognosis of severe dengue.

BACKGROUND: Severe dengue is associated with a considerable risk of mortality, and there is currently a lack of appropriate prognostic biomarkers to predict its severity. Pathogenesis of severe dengue is characterized by overt inflammation, endothelial activation, and increased vascular permeability. The current study investigates the utility of endothelial, inflammatory, and vascular permeability factors as biomarkers to identify dengue severity, which could improve disease prognosis and management. METHODS: The dengue-positive subjects were classified based on seropositivity for NS1, IgM, and IgG. The samples in each group were quantified for basic clinical investigations. The levels of Interleukin-6 (IL-6), Tumor necrosis factor receptor 1 (TNFR1), EOTAXIN, Monocyte chemoattractant protein-1 (MCP-1), Monokine induced by interferon-gamma (MIG), Intercellular adhesion molecule-1 (ICAM-1), Vascular cell adhesion molecule-1 (VCAM-1), Thrombomodulin, and Angiopoietin-2 were estimated in all serum samples using the multiplex bead-based assay. RESULTS: IgG seropositive dengue patients showed abnormal laboratory characteristics and severe dengue symptoms. Among the studied markers, only IL-6, TNFR1, ICAM-1, VCAM-1, Thrombomodulin, and Angiopoietin-2 were significantly elevated in IgG seropositive patients compared to healthy controls. Increased IL-6 and TNFR1 levels were associated with decreased platelet count and elevated Hematocrit levels in IgG seropositive patients. Furthermore, ROC curve analysis indicated that IL-6, TNFR1, Thrombomodulin, and Angiopoietin-2 showed good potential for predicting dengue severity. CONCLUSION: Inflammatory markers IL-6 and TNFR1, and endothelial factors Angiopoietin-2 and Thrombomodulin, could serve as prognostic markers for severe dengue. These findings also encourage the future study of these biomarkers in the pathogenesis of severe dengue infection.

Clinical and prognostic relevance of sST2 in adults with dengue-associated cardiac impairment and severe dengue.

BACKGROUND: Dengue can be complicated by severe outcomes including cardiac impairment, and the lack of reliable prognostic biomarkers poses a challenge in managing febrile dengue patients. Here, we investigated the functionality of soluble suppressor of tumorigenicity (sST2) as a predictive marker of severe dengue and its association in dengue-associated cardiac impairment. METHODS: Plasma samples, aged >16 years, collected from 36 dengue fever, 43 dengue with warning signs, 11 severe dengue (collected at febrile, critical and recovery phases) and 30 controls were assayed for plasma levels of sST2, troponin T and N-terminal (NT)-pro hormone brain natriuretic peptide (NT-proBNP) by ELISA. Cardiac parameters: stroke index (SI), cardiac index (CI) and Granov-Goor Index (GGI) were measured with a bioimpedance device during the different phases for dengue subjects and once for the controls. PRINCIPAL FINDINGS: In the febrile, critical and early recovery phases, sST2 levels were significantly elevated in dengue participants and sST2 levels increased with increasing disease severity (P < 0.01 for all). sST2 concentrations were negatively correlated with SI (r = -0.48; P < 0.001, r = -0.55; P < 0.001), CI (r = -0.26; P = 0.02, r = -0.6: P < 0.001) and GGI (r = -0.44; P < 0.001, r = -0.57; P < 0.001) in the critical and early recovery phases. In contrast, sST2 levels in the febrile and critical phases, were positive correlated to troponin T (r = 0.44, P < 0.001; r = 0.22, P = 0.03, respectively) and NT-proBNP (r = 0.21, P = 0.03; r = 0.35, P < 0.001). ROC analysis demonstrated sST2 as a good biomarker of severe dengue in the critical phase, AUROC 0.79, P < 0.001. CONCLUSION/SIGNIFICANCE: sST2 levels were elevated in patients with dengue especially in cases of severe dengue. Furthermore, increased sST2 levels were associated with cardiac indicators suggesting lower cardiac performance. While further research is needed to demonstrate its clinical utility, sST2 may be a useful prognostic biomarker of severe dengue.

Clinical significance of differential serum-signatures for early prediction of severe dengue among Eastern Indian patients.

Dengue infection can result in simple dengue fever or life-threatening severe dengue. Early identification of severe patients is needed for proper disease management. Dengue infection was screened among 168 symptomatic patients by qRT-PCR, anti-dengue IgM, and IgG ELISA. Dengue patients were categorized according to WHO classification. Viral load and dengue serotypes were determined by qRT-PCR. Levels of acute-phase-proteins (SAP, SAA2; CRP and ApoA1), endothelial (Ang2, VEGF), coagulation (fibrinogen) markers were determined by sandwich ELISA/immunoturbidimetry/western-blotting. Hepatic (ALT, AST, ALP) and other blood biochemical parameters were studied by autoanalyzer and haematology cell counter. Statistical analysis and protein-protein-interaction network were performed by GraphPad-Prism and STRINGS database, respectively. Among 87 dengue patients, significantly higher levels of Ang2, VEGF, CRP, SAA2, ApoA1, AST, ALT, and AST/ALT ratio and low level of fibrinogen were detected in severe-dengue cases compared to dengue without warning-signs, with seven of them severely altered during febrile-phase. Higher fold-change of Ang2 and VEGF as well as decreased fibrinogen were observed among patients with haemorrhagic-manifestation, clinical-fluid accumulation and thrombocytopenia. Functional network analysis predicted Ang2, VEGF, and CRP to be functionally and physically connected and SAA2 and ApoA1 to be functioning together. Correlation analyses also validated this connectivity by a strong positive correlation between Ang2, VEGF, and CRP. PCA analysis followed by hierarchical clustering heatmap analysis segregated severe-dengue patients from the rest, with VEGF, Ang2, ApoA1, AST, and ALT clearly distinguishing the severe-dengue group. Thus, serum levels of VEGF, Ang2, ApoA1, AST, and ALT might act as potential biomarkers for predicting dengue severity during the early stage.

Encefalitis como complicación neurológica por dengue / Encephalitis as neurological complication due dengue

Resumen Se presenta el caso de un varón de 32 años, previamente sano, que consultó por fiebre de cinco días, cefalea, dolor retro-ocular, rash, petequias, mialgias, artralgias y dolor abdominal. Presentaba leucopenia, trombocitopenia intensa, transaminitis y tiempo de coagulación prolongado. Se diagnosticó un dengue grave con coagulopatía que requirió manejo en Unidad de Cuidados Intensivos. Evolucionó con alteración del estado de conciencia, agitación psicomotora y agresividad. Se descartaron alteraciones estructurales, isquémicohemorrágicas, infecciones bacterianas y micóticas. Se confirmó finalmente una encefalitis por dengue por una RPC para virus dengue positiva en LCR. Se brindaron medidas de soporte con una evolución favorable. La encefalitis es la complicación neurológica más grave tras la infección por virus del dengue.

Abstract We present the case of a 32-year-old male, previously healthy, with a 5-day history of fever, frontal-occipital headache, retro-ocular pain, rash, petechiae, myalgia, arthralgia, and abdominal pain. Blood tests with leukopenia, severe thrombocytopenia, transaminitis, long clotting times. Severe dengue with associated coagulopathy was diagnosed, indicating transfer to ICU. Presents torpid evolution, altered state of consciousness, psychomotor agitation, and aggressiveness. Structural, ischemic-hemorrhagic alterations, bacterial and fungal infections were ruled out. Finally diagnosing dengue encephalitis, confirmed by DENV PCR in CSF. Support measures are provided with favorable evolution. Encephalitis is the most serious neurological complication after dengue virus infection.

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.

Comparación clínica y laboratorial de la fiebre amarilla severa versus dengue grave en Perú / Clinical and laboratory differences between severe yellow fever and severe dengue in emergency patients

En los centros de Emergencia con poco apoyo de laboratorio, es difícil diferenciar a los pacientes con dengue grave y fiebre amarilla severa. El objetivo fue comparar el perfil clínico y de laboratorio de los pacientes con dengue grave y fiebre amarilla severa en Urgencias. Se realizó un estudio observacional retrospectivo de pacientes con diagnóstico confirmado de dengue y fiebre amarilla en el período 2018 a 2020 atendidos en la Unidad de Emergencia del Hospital Carrión, Huancayo-Perú. Se evaluaron un total de 35 pacientes, 11 pacientes (31,4%) fueron diagnosticados con fiebre amarilla severa y 24 pacientes (68,5%) con dengue grave. La media de los resultados de laboratorio con fiebre amarilla severa fueron bilirrubina indirecta 4,7 ml/dL, aspartato transaminasa 4463 UI/L, transaminasa aminotransferasa 4329 UI/L, creatinina 4,9 mg/dl. En pacientes con dengue grave el hematocrito promedio fue 51,8, hemoglobina 17,6 g/dl, plaquetas 24 × 103/mm. En pacientes con síndrome ictérico-febril la presencia de bradicardia, bilirrubina indirecta elevada y transaminasas muy elevadas debe hacer sospechar de fiebre amarilla; mientras que los pacientes que acuden por ascitis, derrame pleural, aumento de hematocrito y deficiencia de plaquetas, se debe tratar como dengue grave sobre todo en Unidades de Emergencia con poco apoyo de laboratorio(AU)

In Emergency centers with little laboratory support, differentiating patients with dengue and yellow fever is difficult. The Aim was to compare the clinical and laboratory profile of patients with severe dengue and severe yellow fever in the Emergency unit. We conducted a retrospective observational study of patients with a confirmed diagnosis of dengue and yellow fever in the period 2018 to 2020 treated in the Emergency Unit of the Carrión hospital, Huancayo-Peru. A total of 35 patients were evaluated, 11 patients (31.4%) were diagnosed with severe yellow fever and 24 patients (68.5%) with severe dengue. The mean laboratory results in patients with severe yellow fever were indirect bilirubin 4.7 ml/dL, aspartate transaminase 4463 IU/L, transaminase aminotransferase 4329 IU/L, creatinine 4.9 mg / dl. In patients with severe dengue were hematocrit 51.8, hemoglobin 17.6 g / dl, platelets 24 × 103 / mm. In patients with syndrome jaundice and fever the presence of bradycardia, elevated indirect bilirubin, and very elevated transaminases should be suspicious for yellow fever; while in patients who come for ascites, pleural effusion, increased hematocrit and platelet deficiency, it should be treated as severe dengue especially in Emergency Units with little laboratory support(AU)

Total serum cortisol level is low in children with severe dengue shock syndrome.

Dengue shock syndrome (DSS) is a potentially critical and life-threatening concern, especially in children of tropical countries. The serum cortisol levels in severe DSS or later stages of DSS are limited references. We prospectively studied an association between of serum cortisol as well as interleukin levels and the severity of DSS in pediatric patients. A prospective cross-sectional study of 35 consecutive DSS cases (3 months to 16 years old) admitted to our institution from July 1, 2019, to June 30, 2020 was conducted. Serum cortisol, IL-6, and IL-10 were measured at T0 (shock recognition) and T12 (12 hours after T0); their values were presented as median and interquartile ranges (25%-75%). Severe DSS included patients with impalpable pulses or systolic blood pressure < 70 mmHg, recurrent shock, and prolonged shock. In contrast, non-severe DSS presented circulatory failure without any features of severe DSS. A total of 8 (22.8%) severe DSS patients expressed the cortisol (T0) significantly lower compared to the non-severe DSS group (7.3 µg/dl versus 14.3 µg/dl, p=0.008). In severe DSS, there was a minimal change in cortisol levels between T0 and T12 (7.3 µg/dl and 4.7 µg/dl p>0.05), whereas the decrease is significant in their counterparts (14.3 µg/dl to 5.6 µg/dl, p<0.005). Additionally, there were moderate correlations between IL-6 (T0), IL-10 (T0), IL-10 (T12) and total fluid requirement (Spearman's rho = 0.47, 0.4, and 0.36, respectively; p<0.05). Our study demonstrated that adrenal dysfunction was present in patients with severe and non-severe DSS, as noted by cortisol level at T12. In addition, IL-6 and IL-10 levels are correlated with the total fluid requirement, which is a marker of DSS severity. Further studies could reveal how adrenal dysfunction in pediatric patients with DSS can affect outcomes and the potential roles of interleukin levels in fluid management strategy.

Predictive markers for the early prognosis of dengue severity: A systematic review and meta-analysis.

BACKGROUND: Predictive markers represent a solution for the proactive management of severe dengue. Despite the low mortality rate resulting from severe cases, dengue requires constant examination and round-the-clock nursing care due to the unpredictable progression of complications, posing a burden on clinical triage and material resources. Accordingly, identifying markers that allow for predicting disease prognosis from the initial diagnosis is needed. Given the improved pathogenesis understanding, myriad candidates have been proposed to be associated with severe dengue progression. Thus, we aim to review the relationship between the available biomarkers and severe dengue. METHODOLOGY: We performed a systematic review and meta-analysis to compare the differences in host data collected within 72 hours of fever onset amongst the different disease severity levels. We searched nine bibliographic databases without restrictive criteria of language and publication date. We assessed risk of bias and graded robustness of evidence using NHLBI quality assessments and GRADE, respectively. This study protocol is registered in PROSPERO (CRD42018104495). PRINCIPAL FINDINGS: Of 4000 records found, 40 studies for qualitative synthesis, 19 for meta-analysis. We identified 108 host and viral markers collected within 72 hours of fever onset from 6160 laboratory-confirmed dengue cases, including hematopoietic parameters, biochemical substances, clinical symptoms, immune mediators, viral particles, and host genes. Overall, inconsistent case classifications explained substantial heterogeneity, and meta-analyses lacked statistical power. Still, moderate-certainty evidence indicated significantly lower platelet counts (SMD -0.65, 95% CI -0.97 to -0.32) and higher AST levels (SMD 0.87, 95% CI 0.36 to 1.38) in severe cases when compared to non-severe dengue during this time window. CONCLUSION: The findings suggest that alterations of platelet count and AST level-in the first 72 hours of fever onset-are independent markers predicting the development of severe dengue.

Comportamiento clínico y de laboratorio del choque por dengue en pacientes pediátricos / Clinical and laboratory behavior of dengue shock among pediatric patients

Introducción: El dengue es la enfermedad viral transmitida por artrópodos que más morbilidad y mortalidad ocasiona mundialmente. En el mundo actual, esta arbovirosis se considera la décima causa de muerte sobre todo en edades pediátricas. Objetivo: Caracterizar el comportamiento clínico y de laboratorio del choque por dengue en niños a partir de un año de edad. Métodos: Se realizó un estudio de corte transversal. Se estudiaron 19 pacientes con diagnóstico de choque por dengue. Para el análisis estadístico se utilizaron medidas de resumen como frecuencias, porcentaje, rango, mediana y moda. Resultados: Los signos de choque por dengue predominaron en los pacientes mayores de 5 años, femeninos y blancos, normopesos con antecedentes de salud. La mayoría ingresó al cuarto día; la fiebre fue el principal motivo de ingreso. El aumento progresivo del hematocrito fue el principal signo de alarma, y la hipotensión sin otra manifestación de choque constituyó la manifestación clínica más frecuente. Las soluciones cristaloides fueron las más utilizadas con muy buena respuesta clínica. Conclusiones: Todos los pacientes evolucionaron satisfactoriamente; no hubo ningún fallecimiento por dengue a pesar de que la mayoría fueron hospitalizados durante la fase crítica de la enfermedad, existiendo una identificación adecuada de los signos de alarma, y un adecuado control y tratamiento de las formas clínicas de choque por dengue(AU)

Introduction: Dengue is the arthropod-borne disease causing the highest morbidity and mortality worldwide. This condition is currently considered the tenth leading cause of death in the world, mainly in pediatric ages. Objective: Characterize the clinical and laboratory behavior of dengue shock in children aged one year and over. Methods: A cross-sectional study was conducted of 19 patients diagnosed with dengue shock. Statistical analysis was based on the summary measurements frequency, percentage, range, median and mode. Results: Dengue shock signs prevailed in white female patients aged over five years, of normal weight and with a history of good health. Most were admitted on the fourth day; fever was the main reason for admission. Gradual hematocrit increase was the main warning sign, whereas hypotension without any other shock symptom was the most common clinical manifestation. Crystalloid solutions were the most frequently used, with a very good clinical response. Conclusions: All the patients evolved satisfactorily; no death occurred due to dengue, despite the fact that many patients were admitted during the critical stage of the disease; warning signs were appropriately identified and clinical manifestations of dengue shock were controlled and treated(AU)

A Review of Piezoelectric and Magnetostrictive Biosensor Materials for Detection of COVID-19 and Other Viruses.

The spread of the severe acute respiratory syndrome coronavirus has changed the lives of people around the world with a huge impact on economies and societies. The development of wearable sensors that can continuously monitor the environment for viruses may become an important research area. Here, the state of the art of research on biosensor materials for virus detection is reviewed. A general description of the principles for virus detection is included, along with a critique of the experimental work dedicated to various virus sensors, and a summary of their detection limitations. The piezoelectric sensors used for the detection of human papilloma, vaccinia, dengue, Ebola, influenza A, human immunodeficiency, and hepatitis B viruses are examined in the first section; then the second part deals with magnetostrictive sensors for the detection of bacterial spores, proteins, and classical swine fever. In addition, progress related to early detection of COVID-19 (coronavirus disease 2019) is discussed in the final section, where remaining challenges in the field are also identified. It is believed that this review will guide material researchers in their future work of developing smart biosensors, which can further improve detection sensitivity in monitoring currently known and future virus threats.

Dengue fever after coronary artery bypass grafting with ventricular dysfunction.

A 67-year-old man who had undergone a percutaneous coronary intervention, presented with cardiac symptoms. He was managed for acute coronary syndrome and left ventricular dysfunction. After stabilization, he underwent coronary artery bypass grafting but developed dengue hemorrhagic fever postoperatively. He was monitored for hematocrit, platelet count, liver enzymes, and daily fluid balance. His platelet count fell below 40,000/µL, and due to the increased risk of bleeding, warfarin was discontinued and single antiplatelet therapy (aspirin) was continued. After 2 weeks, parameters had normalized. Regular monitoring of hematocrit, platelet count, liver enzymes, and fluid balance played a vital role in the patient's successful recovery.

Early hematological parameters as predictors for outcomes in children with dengue in northern India: A retrospective analysis

Abstract INTRODUCTION: Dengue presents with a variable clinical course, ranging from mild illness to potentially fatal hemorrhage and shock. We aimed to evaluate the capabilities of various hematological parameters observed early in the course of illness for predicting the clinical outcomes of illness. METHODS: We retrospectively analyzed the records of children admitted in the pediatric inpatient services of the institute with dengue between 2017 and 2019. We determined the relationships between the hematological parameters observed during the first evaluation and the various clinical outcomes. RESULTS: We evaluated data from 613 patients (age range, 26 days to 17 years). Of these, 29.85% exhibited fever with warning signs, and 8.97% had severe dengue. Lower values of hemoglobin, platelet count, mean corpuscular volume, mean corpuscular hemoglobin concentration, and mean platelet volume, and higher values of total leukocyte count (TLC), hematocrit, and red cell distribution width variably correlated with numerous clinical outcomes-duration of hospital stay, development of complications, requirement of blood component transfusion, inotropic support, and mortality. Among the parameters, TLC ≥20,000/mL and initial platelet count ≤20,000/mL significantly associated with mortality, with odds ratios (95% confidence interval) of 11.81 (4.21-33.80) and 5.53 (1.90-16.09), respectively. CONCLUSIONS: Hematological parameters observed early during dengue infection may predict its clinical outcomes in infected children. Initial high TLC and low platelet count are potential predictors of fatal outcomes in the course of disease.

Choque por dengue interpretado inicialmente como sepsis grave / Shock by dengue initially interpreted as severe sepsis

Introducción: La forma más frecuente de dengue grave es el choque por dengue. Sin embargo, los lactantes con dengue no presentan las manifestaciones clinicas que lo caracterizan ni tienen tan a menudo esta complicación como lo hacen los pacientes con edades mayores. Objetivo: Dar a conocer las características clinicas y laboratoriales de una paciente menor de un año de edad cuyo síndrome de choque por dengue fue interpretado inicialmente como un caso de sepsis grave. Presentación del caso: Paciente femenina de 8 meses de edad con fiebre y diarreas que concurre a más de un centro hospitalario y la madre se niega a ingresarla. Al quinto dia de enfermedad apareció exantema y ya estando afebril presenta cianosis y otros signos de hipoperfusión tissular, haciéndole diagnóstico inicial de choque por sepsis. Responde satisfactoriamente a la reposición de líquidos cristaloides por via intravenosa administrados inicialmente y es enviada despues a una unidad de terapia intensiva pediátrica donde continua recibiendo tratamiento de rehidratacion y se inicia antibioticoterapia. Posteriormente, la sepsis fue descartada por la evolución del caso y los resultados de laboratorio clinico y microbiológicos, asi como una serología positiva a dengue. Conclusiones. El choque por dengue en el lactante puede expresarse sin su cuadro clinico típico y para su diagnostico es imprescindible considerar el antecedente epidemiológico(AU).

Introduction: The most common form of severe dengue is the dengue shock syndrome. However, infants with dengue don´t present the clinical manifestations that characterize it neither have this complication as often as older patients do. Objective: To know the clinical and laboratory characteristics of a patient of less than one-year-old whose dengue shock syndrome was initially interpreted as a case of severe sepsis. Case presentation: 8-months-old female patient with fever and diarrhea that was checked in more than one hospital and the mother refuses to hospitalize her. In the fifth day of being ill appeared exanthem, and having fever she presented cyanosis and other signs of tisular hypoperfusion, being initially diagnosed a sepsis shock. She responded satisfactorily to the replacement of crystalloid fluids intravenously administered initially and she was sent to a pediatric intensive care unit where she continued receiving rehydration treatment and antibiotic therapy was started. Subsequently, sepsis was ruled out due to the case´s evolutions and the clinical and microbiological laboratory´s results, as well as a serology positive to dengue fever. Conclusions: Dengue shock syndrome in an infant can present without its typical clinical manifestations and for its diagnosis is essential to consider the epidemiological history(AU)

Dengue Infection Complicated by Hemophagocytic Lymphohistiocytosis: Experiences From 180 Patients With Severe Dengue.

BACKGROUND: Globally, ~500 000 people with severe dengue (SD) require hospitalization yearly; ~12 500 (2.5%) die. Secondary hemophagocytic lymphohistiocytosis (sHLH) is a potentially fatal hyperinflammatory condition for which HLH-directed therapy (as etoposide and dexamethasone) can be life-saving. Prompted by the high mortality in SD and the increasing awareness that patients with SD may develop sHLH, our objectives were to (1) determine the frequency of dengue-HLH in SD, (2) describe clinical features of dengue-HLH, (3) assess mortality rate in SD and dengue-HLH, and (4) identify mortality-associated risk factors in SD. METHODS: A 5-year retrospective single-center study in all adult patients with SD admitted to a tertiary intensive care unit in Malaysia. RESULTS: Thirty-nine of 180 (22%) patients with SD died. Twenty-one of 180 (12%) had HLH defined as an HLH probability ≥70% according to histo score (HScore); 9 (43%) died. Similarly, 12 of 31 (39%) fulfilling ≥4 and 7 of 9 (78%) fulfilling ≥5 HLH-2004 diagnostic criteria died. Peak values of aspartate aminotransferase (AST), alanine aminotransferase, lactate dehydrogenase, and creatinine correlated to fatality (odds ratios [ORs], 2.9, 3.4, 5.8, and 31.9; all P < .0001), as did peak ferritin (OR, 2.5; P = .0028), nadir platelets (OR, 1.9; P = .00068), hepatomegaly (OR, 2.9; P = .012), and increasing age (OR, 1.2; P = .0043). Multivariable logistic regression revealed peak AST (OR, 2.8; P = .0019), peak creatinine (OR, 7.3; P = .0065), and SOFA (Sequential Organ Failure Assessment) score (OR, 1.4; P = .0051) as independent risk factors of death. CONCLUSIONS: Be observant of dengue-HLH due to its high mortality. A prospective study is suggested on prompt HLH-directed therapy in SD patients with hyperinflammation and evolving multiorgan failure at risk of developing dengue-HLH.

Mast cell mediators in relation to dengue severity: A systematic review and meta-analysis.

BACKGROUND: Degranulation of mast cells (MCs) releases several mediators such as vascular endothelial growth factor (VEGF), chymase, tryptase, histamine, and cytokines, which all have important roles in the severity of dengue infection. We aimed to investigate the role of MCs in severity of dengue. METHODS: We searched for relevant studies in 10 databases on 15 August 2016. Meta-analysis (MA) was conducted by R version 3.5.0. RESULTS: We included 24 studies. in vivo and in vitro studies showed higher MC products released from infected mice/cells with dengue virus. In addition, when administering MC stabilizers or antihistaminic drugs, there was a decrease in vascular/capillary permeability. In human and at early stages, studies revealed an insignificant difference in VEGF levels in dengue fever (DF) versus dengue hemorrhagic fever (DHF) (standardized mean difference [SMD] 0.145; 95% confidence interval [CI], -0.348-0.638). Meanwhile, at acute stages and compared with healthy controls, high heterogeneity with an inconclusive difference in VEGF levels were noted in DF and DHF. However, pooled serum and plasma levels of VEGF were increased significantly in dengue shock syndrome (DSS) versus healthy controls (SMD 0.65; 95% CI, 0.3-0.95). There were also significantly higher chymase levels in DHF patients compared with DF during the acute phase (MD -6.531; 95% CI, -12.2 to -0.9). CONCLUSION: VEGF and chymase levels are mediators in dengue pathogenesis. However, limited data were available to support their role in severe dengue cases. Further studies are needed to evaluate the function of other mediators in dengue severity.

Severe Dengue and Associated Hemophagocytic Lymphohistiocytosis in PICU.

OBJECTIVES: To study the clinico-laboratory profile and outcome of children with severe dengue and dengue-associated hemophagocytic lymphohistiocytosis (HLH). METHODS: In this retrospective study, 22 children with laboratory confirmed severe dengue admitted to pediatric intensive care unit (PICU) were enrolled. Clinical features, laboratory parameters, and outcome were noted and compared between cases fulfilling HLH-2004 criteria and those without HLH. RESULTS: Median (IQR) age was 8 (5-10.3) y. Fever was present for mean (SD) duration of 5.3 (2.1) d. Vomiting, respiratory distress, pain abdomen and hepatomegaly were other clinical features. Thrombocytopenia, anemia and elevated serum transaminases were noted in 91%, 41% and 30% respectively; coagulopathy and hypoalbuminemia were seen in 36% each. Half (n = 11, 50%) had dengue shock syndrome. Acute respiratory distress syndrome (ARDS) (n = 7, 32%) and acute kidney injury (AKI) (n = 6, 28%) were other major organ dysfunctions. Mean (SD) duration of PICU stay was 3.6 (1.5) d with 13.6% mortality. HLH was noted in 7 (32%) cases at a median (IQR) hospital stay of 5 (2-8) d. Children with HLH had significantly higher Pediatric Index of Mortality 2 (PIM 2) score at admission and higher frequency of pain abdomen, anemia, hypoalbuminemia, elevated alanine aminotransferase (ALT) and ARDS. Length of PICU stay (5.1 vs. 2.9 d) and mortality (28.6% vs. 6.7%) were higher in HLH group, however the difference was not statistically significant. Steroids were used in 4 cases with HLH and all survived, whereas among 3 who did not receive steroids, 2 died (p = 0.23). CONCLUSIONS: Severe dengue presents with life-threatening organ dysfunctions. HLH is increasingly recognized in dengue infection and maybe considered as a differential diagnosis in children with lower hemoglobin, hypoalbuminemia, elevated ALT and severe organ dysfunction.