Dengue Shock Syndrome Patients Research Articles

Associations of resuscitation fluid load, colloid-to-crystalloid infusion ratio and clinical outcomes in children with dengue shock syndrome.

Severe respiratory distress and acute kidney injury (AKI) are key factors leading to poor outcomes in patients with dengue shock syndrome (DSS). There is still limited data on how much resuscitated fluid and the specific ratios of intravenous fluid types contribute to the development of severe respiratory distress necessitating mechanical ventilation (MV) and AKI in children with DSS. This retrospective study was conducted at a tertiary pediatric hospital in Vietnam between 2013 and 2022. The primary outcomes were the need for MV and renal function within 48 h post-admission. A predictive model for MV was developed based on covariates from the first 24 h of PICU admission. Changes in renal function within 48 h were analyzed using a linear mixed-effects model. A total of 1,278 DSS children with complete clinical and fluid data were included. The predictive performance of MV based on the total intravenous fluid volume administered yielded an AUC of 0.871 (95% CI, 0.836-0.905), while the colloid-to-crystalloid ratio showed an AUC of 0.781 (95% CI, 0.743-0.819) (both P < 0.001). The optimal cut-off point of the cumulative fluid infusion was 181 mL/kg, whereas that of the colloid-to-crystalloid ratio was 1.6. Multivariable analysis identified female patients, severe bleeding, severe transaminitis, excessive fluid resuscitation, and a higher proportion of colloid solutions in the first 24 h as significant predictors of MV in DSS patients. The predictive model for MV demonstrated high accuracy, with a C-statistic of 89%, strong calibration, and low Brier score (0.04). Importantly, a more pronounced decline in glomerular filtration rate was observed in DSS patients who required MV than in those who did not. This study provides insights into optimizing fluid management protocols, highlighting the importance of monitoring fluid volume and the colloid-to-crystalloid ratio during early resuscitation to improve the clinical outcomes of DSS patients.

The Effect of Dengue Infection Severity on Blood Parameters

Objective: To evaluate the relationship between dengue infection severity, Alanine Aminotransferase levels, and platelet counts. Study Design: Cross-Sectional study. Place and Duration of Study: Akhtar Saeed Medical College-affiliated Farooq Hospital, Tehsil Murree, District Rawalpindi Pakistan, from Oct 2022 to Sep 2023. Methodology: Data from the medical records of individuals admitted to the dengue ward and diagnosed with confirmed dengue fever were evaluated. Demographic data, platelet counts on days 3, 4, and 5, Alanine Aminotransferase levels, and reports of Dengue Shock Syndrome and Dengue Hemorrhagic Fever. Results: Of the 69 participants, 76.8% were men, and most were aged 19–30 years. There was no significant difference in the mean Alanine Aminotransferase levels between the Dengue Hemorrhagic Fever positive and Dengue Hemorrhagic Fever negative patients (p=0.615). Patients with Dengue Shock Syndrome showed significantly different mean Alanine Aminotransferase levels (p=0.031). When comparing Dengue Shock Syndrome-positive individuals with Dengue Shock Syndrome -negative individuals, platelet counts were considerably lower (p=0.023). Conclusion: Thrombocytopenia is an important marker for severe dengue fever outcomes, particularly in Dengue Shock Syndrome patients. Although there was no significant difference in Alanine Aminotransferase levels between Dengue Hemorrhagic Fever cases and Dengue Shock Syndrome-positive cases, there was a discernible increase in Dengue Shock Syndrome-positive cases, suggesting that liver function tests may be helpful in anticipating shock.

Kinetics of cardiovascular and inflammatory biomarkers in paediatric dengue shock syndrome.

Glycocalyx disruption and hyperinflammatory responses are implicated in the pathogenesis of dengue-associated vascular leak, however little is known about their association with clinical outcomes of patients with dengue shock syndrome (DSS). We investigated the association of vascular and inflammatory biomarkers with clinical outcomes and their correlations with clinical markers of vascular leakage. We performed a prospective cohort study in Viet Nam. Children ≥5 years of age with a clinical diagnosis of DSS were enrolled into this study. Blood samples were taken daily during ICU stay and 7-10 days after hospital discharge for measurements of plasma levels of Syndecan-1, Hyaluronan, Suppression of tumourigenicity 2 (ST-2), Ferritin, N-terminal pro Brain Natriuretic Peptide (NT-proBNP), and Atrial Natriuretic Peptide (ANP). The primary outcome was recurrent shock. Ninety DSS patients were enrolled. Recurrent shock occurred in 16 patients. All biomarkers, except NT-proBNP, were elevated at presentation with shock. There were no differences between compensated and decompensated DSS patients. Glycocalyx markers were positively correlated with inflammatory biomarkers, haematocrit, percentage haemoconcentration, and negatively correlated with stroke volume index. While Syndecan-1, Hyaluronan, Ferritin, and ST-2 improved with time, ANP continued to be raised at follow-up. Enrolment Syndecan-1 levels were observed to be associated with developing recurrent shock although the association did not reach the statistical significance at the P < 0.01 (OR = 1.82, 95% CI 1.07-3.35, P = 0.038). Cardiovascular and inflammatory biomarkers are elevated in DSS, correlate with clinical vascular leakage parameters and follow different kinetics over time. Syndecan-1 may have potential utility in risk stratifying DSS patients in ICU.

Navigating the Haematological Maze: Unraveling the Role of NLR and PLR as Predictors of Dengue Severity- A Cross-sectional Study from Southern India

Introduction: Dengue Fever (DF) poses a critical public health threat in tropical regions, displaying a spectrum of manifestations without distinct diagnostic hallmarks. Neutrophil to Lymphocyte Ratio (NLR) and Platelet to Lymphocyte Ratio (PLR) are useful biomarkers of inflammation and prognostic markers in various diseases. The inflammation that occurs in dengue is due to the exaggerated response of the immune system. Aim: To assess the utility value of NLR and PLR as prognostic markers for dengue severity. Materials and Methods: A cross-sectional study was conducted on 99 admitted Dengue patients. Patients were grouped into three categories: DF, Dengue Haemorrhagic Fever (DHF), and Dengue Shock Syndrome (DSS). Various parameters of Complete Blood Count (CBC), NLR, and PLR were compared among the groups using Analysis of Variance (ANOVA) test (p-value &lt;0.05 considered significant). Sensitivity, specificity, and accuracy were calculated using Receiver Operating Characteristic (ROC) curve. Results: Among the 99 patients, 63.6% exhibited thrombocytopenia (platelet count &lt;1.5 lac/dL), and 7% of patients had a platelet count &lt;20,000/dL. All DHF and DSS patients had thrombocytopenia. Leucopenia was evident in 45.45% of patients, with 6% having a Total Leukocyte Count (TLC) &lt;2000/dL. TLC remained stable across these stages. The mean NLR in DF was 2.47 (range 0.1-15.4), in DHF it was 1.013 (range 0.2-3.2), and in DSS it was 0.41 (range 0.08- 0.65.17) with a p-value of 0.02. The PLR displayed substantial differences, with mean values of 134.4 (range 10.1-273.8) for DF, 50.57 (range 7.1-96.1) for DHF, and 10.39 (range 3.1-38.8) for DSS with a p-value of 0.003. NLR had 63% accuracy, 77.8% sensitivity, and 94.4% specificity. PLR had 81.5% accuracy, 93.3% sensitivity and 33.3% specificity. Conclusion: The specificity of NLR was higher, while PLR exhibited superior accuracy and sensitivity in detecting severe cases.

The relationship of complete blood count on the outcome of childhood patients with Dengue Shock Syndrome (DSS) in the Pediatric Intensive Care Unit (PICU) Dr. Soetomo General Hospital

Dengue Hemorrhagic Fever (DHF) is an acute infectious disease caused by the dengue virus which is spread through the bite of female mosquitoes of the Aedes Aegypti and Aedes Albopictus species. DHF cases often attack children under 15 years of age and if not treated properly it will turn into Dengue Shock Syndrome (DSS). Supporting examinations are needed to diagnose and monitor the condition of DSS patients, one of which is a complete blood test. This study aims to determine the relationship between a complete blood profile and the parameters: platelet count, leukocyte count, hematocrit value, and hemoglobin level on the outcome of pediatric patients with DSS in the Pediatric Intensive Care Unit (PICU) at the Regional General Hospital (RSUD) Dr. Soetomo. This research is a descriptive analytical observational study with a cross sectional approach using medical record data from pediatric patients with DSS in the PICU of Dr. RSUD. Soetomo Surabaya for the 2015-2022 period. The sample consisted of 40 samples in accordance with the inclusion and exclusion criteria taken using total sampling technique. In this study, a significant relationship was found between age, hemoglobin and leukocytes and the mortality outcome of pediatric DSS patients. The values obtained were &lt;0.05 (age), 0.048 (hemoglobin), and 0.048 (leukocytes). Apart from that, there is also a significant relationship between platelets and the outcome of treatment duration for pediatric DSS patients.

Vitamin D Deficiency (VDD) and Susceptibility towards Severe Dengue Fever-A Prospective Cross-Sectional Study of Hospitalized Dengue Fever Patients from Lahore, Pakistan.

Dengue is a mosquito-borne flaviviral serious febrile illness, most common in the tropical and subtropical regions including Pakistan. Vitamin D is a strong immunomodulator affecting both the innate and adaptive immune responses and plays a pivotal role in pathogen-defense mechanisms. There has been considerable interest in the possible role of vitamin D in dengue viral (DENV) infection. In the present prospective cross-sectional study, we assessed a possible association between serum vitamin D deficiency (VDD) and susceptibility towards severe dengue fever (DF) illness. Serum vitamin D levels were measured at the time of hospitalization in 97 patients diagnosed with dengue fever (DF), dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) at Mayo Hospital, King Edward Medical University, Lahore, PK, from 16 November 2021 to 15 January 2022. In terms of disease severity, 37 (38.1%) patients were DF, 52 (53.6%) were DHF grade 1 and 2, and 8 (8.2%) were DSS. The results revealed that most patients (75 (77.3%)) were vitamin-D-deficient (i.e., serum level < 20 ng/mL), including 27 (73.0%) in DF, 41 (78.8%) in DHF grade 1 and 2, and 7 (87.5%) in DSS. The degree of VDD was somewhat higher in DSS patients as compared to DF and DHF grade 1 and 2 patients. Overall, serum vitamin D levels ranged from 4.2 to 109.7 ng/mL, and the median (IQR) was in the VDD range, i.e., 12.2 (9.1, 17.8) ng/mL. Our results suggest that there may be a possible association between VDD and susceptibility towards severe dengue illness. Hence, maintaining sufficient vitamin D levels in the body either through diet or supplementation may help provide adequate immune protection against severe dengue fever illness. Further research is warranted.

Predictors of complicated dengue infections in endemic region of Pakistan

Objective: To predict the factors associated with progression to severe dengue infection to prevent potentially fatal complications and to identify the determinants of severe complicated dengue. Methods: The study was conducted in a tertiary care hospitaldengue ward from September to November 2021 including confirmed dengue infected patients (positive NS1 antigen or anti-dengue-antibodies IgM). Secondary dengue infection was labelled by positive anti-dengue-antibodies IgG in active dengue infected patients. Detailed history, physical examination, laboratory and radiological parameters, hospital stay (days) and mortality percentages were noted. Patients were classified into three groups according to disease severity: dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The predictors of complicated dengue infection were determined by regression analysis. Results: The most common symptom was fever (96.9%). Among 129 patients, 62.8% had DF, 31.0% had DHF and only 6.2% developed DSS. History of previous symptomatic dengue and positive anti-dengue-antibodies IgG were present in 100% DSS patients and nearly 75.0% DHF patients (P&lt;0.05). The moratlity rate in patients with DSS, DHF and DF was 50.0%, 2.5% and none respectively (P&lt;0.05). Clinical parameters (body aches, bleeding, conjunctival hemorrhage, maculopapular rash, right hypochondrial tenderness, ascites, pleural effusion) and laboratory parameters (thrombocytopenia, raised alanine aminotransferase and secondary dengue infection) were determinants that complicate the dengue infection. Conclusions: Thrombocytopenia, raised alanine aminotransferase and secondary dengue infection are important laboratory parameters to complicate the disease process of dengue infection.

Abnormalities in Serum Electrolytes in DF, DHF and DSS as Prognostic Indicators for Dengue Severity: A Comparative Model

About 250 positive patients were included in the study for diagnosis, of whom 146 were Male and 104 were Female. The M±SD of severity level in DF and DHF patients was 120.5±53.3, Variance=2841.18, Cl95% 1.960, and P=value was calculated as 0.001. The Comparative Analysis of DF and DHF symptoms between group SS (576), df (1), MS (576), F (0.52978) and p=value was calculated p=.478. Whereas within groups SS (15221.5), df (14), MS (1087.25), F (0.52978) and p=value was calculated as p=.478. The M±SD of severity level in DF and DSS patients was 118.4±59.5, Variance=3551.96, Cl95% 1.960, and P=value was calculated as 0.001. The M±SD of dengue serological markers such as 20±9.26, Variance=85.824, and Cl95% 1.960. The M±SD of Na+ in DF 132.4±3.8, DHF 129.5±2.5, DSS 119.5±2.5. K+ in DF 3.38±0.32, DHF 2.97±1.01, DSS 2.4±0.93. Ca+ in DF 8.81±0.53, DHF 7.82±1.2, DSS 6.36±0.57. Mg+ in DF 1.39±0.71, DHF 1.39±0.41, DSS 1.62±0.31. Po4 in DF 3.47±0.53, DHF 2.21±0.62, and DSS 2.34±0.31. It was concluded that dengue shock syndrome patients were found highly affected by serum electrolytes, so we need to focus on the replacement and treatment of serum electrolytes. Keywords: Dengue virus, Civil Hospital, Serological Markers, Abnormal Serum Electrolytes, Clinical manifestation

Hematological indices as predictors of mortality in dengue shock syndrome

Objective: To explore predictive hematological parameters on admission which are associated with mortality in NS1 positive dengue shock syndrome patients. Methods: Demographic characteristics, hematological parameters, and the outcome of NS1 positive dengue shock syndrome patients without any comorbidity and coexisting infections were collected from the Intensive Care Unit and the results were compared between the survivor and non-survivor groups. Results: The mean age was (30.77±11.48) years and 56 (56.6%) patients were males. Out of the total 99 patients, 72 (72.27%) patients were successfully discharged and 27 (27.27%) patients eventually succumbed to death. The most common hematological finding was thrombocytopenia (95.95%), followed by anemia (52.52%) and decreased mean platelet volume (37.37%). After controlling other variables, logistic regression analysis showed that absolute neutrophil count and mean platelet volume were associated with mortality. Conclusions: Total leucocyte count, absolute neutrophil count, and total platelet count are significantly higher, and mean platelet volume is significantly lower in the non-survivor group as compared to the survivor group. Absolute neutrophil count and mean platelet volume are predictors associated with mortality.

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.

Comparative evaluation of dengue NS1 antigen rapid test and IgM ELISA in a tertiary care hospital in VIMS, Ballari

Dengue virus infection is becoming a major public health problem in recent decades because of the mortality and morbidity associated with it. Dengue is endemic in many parts of India and epidemics are frequently reported from various parts of India and abroad. The mortality rate in patients with dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) is as high as 44%. Hence early and rapid laboratory diagnosis of dengue is crucial. Appropriate clinical management can save the lives of DHF and DSS patients and mortality can be reduced to less than 1%. It is also worthwhile for planning appropriate control strategies. The present communication reports the seroprevalence of dengue infections occurred in Central India.To detect Dengue infection by NS1 Antigen Rapid detection and by IgM ELISA and compare Rapid NS1 Antigen detection test and IgM ELISA test.Blood samples from 5273 suspected cases were collected from January 2016 to December 2016. Sera were separated and subjected for NS1 antigen detection testing by the solid phase immunochromatographic assay, a commercial dengue virus rapid test kit. and antidengue IgM antibody ELISA in the Department of Microbiology, VIMS, Ballari. All samples were put for ELISA.3036 samples were tested for NS1 Antigen detection rapid method.2272 samples were tested for both rapid test and ELISA. Out of 5273 cases, 446 (8.46%) were found to be positive by IgM ELISA. 3036 samples WHICH were tested for NS1 Antigen detection by rapid method 208 (6.85%)samples were positive. The most affected age group was 5-10yrs with 284 cases, out of which 29 were positive, followed by the age group 0f 15yrs and above with 8.74%. Males were affected more than females with a percentage of 9.2 and 7.4 respectively. The highest number of suspected dengue patients admitted was in the month of November, i.e., 459 with 68 positive (14.81%) followed by August (12.16%) and September (11.03%), i.e., 28 with 7 (25%) positive. For the 2272 samples for which both tests were done, 153 cases were positive for rapid test and 137 cases were positive by ELISA. Dengue cases were more during September to November in the post monsoon season which is useful to plan special preventive strategies. The study draws attention toward the male, young and adult age group. To conclude, in countries lacking infrastructure for the diagnostic labs especially in the rural and remote areas, the rapid dengue ICT tests can play a major role in diagnosis and in patient management of acute dengue infection. The rapid ICTs are very simple, easy to perform, and can be used as point of care tests. We suggest that the rapid ICT for NS1 Ag detection may be used in patients presenting with fever less than 5 days

Implementation of Dengue Recurrent Shock Prediction Score in pediatric dengue shock syndrome

Background Global morbidities due to dengue viral infection increase yearly. The pediatric mortality rate from dengue shock syndrome (DSS) remains high. Early identification of the risk of recurrent shock may serve to increase awareness and reduce mortality. The Dengue Recurrent Shock Prediction Score (DRSPS) is a tool to predict recurrent shock in children with DSS, but the optimal cut-off point in our population is still unknown.&#x0D; Objective To assess the validity of the DRSPS by determining the optimal cut-off point that can be used in Indonesia&#x0D; Methods This cross-sectional prospective study was done at Sanglah Hospital, Denpasar, Bali, from January 2019. Risk of reccurent shock were classify based on DRSPS in all DSS patient, and they were observed whether they will experienced recurrent shock or not.&#x0D; Results Of 56 children with DSS, 27 subjects had recurrent shock and 29 subjects did not. The optimal DRSPS cut-off point was -189.9 for predicting recurrent shock, with 87.4% area under the curve (AUC), 81.5% sensitivity and 82.8% specificity.&#x0D; Conclusion The optimal cut-off point of DRSPS was -189.9 and it has good validity. The results of this study are expected not only to be used as the basis for further study, but to increase physician awareness in treating DSS patients.

The role of macrophage Migration Inhibitory Factor (MIF) in pediatric dengue infection at Sanglah Hospital, Bali, Indonesia

Background: Macrophage migration inhibitory factor (MIF) is known had pleiotropic properties particularly participating in inflammatory and immune responses. MIF has initially involved phagocytosis, spreading, and tumoricidal activity in macrophage. Recently, MIF was determined as a proinflammatory cytokine that has a pivotal role in viral infection such as dengue. This study aims to evaluate the role of MIF levels in patients with dengue infection at Sanglah General Hospital, Bali, IndonesiaMethods: A cross-sectional study was conducted among 48 children aged 1 to 12 years who hospitalized in the Children's Ward of Sanglah General Hospital, Bali, Indonesia, from August 2016 to July 2017. The respondents were divided into two groups: 24 children with a diagnosis of Dengue Shock Syndrome (DSS) (Group 1) and 24 non-DSS children. Data regarding age group, gender, obesity status, history of secondary infection, grading for dengue infection, and levels of MIF were assessed in this study. The MIF levels between both groups were evaluated and analyzed using SPSS version 23 for Mac. Results: Most of the patients were age &gt; 5 years old in Non-DSS (87.5%) and DSS (54.2%) groups. However, females were predominant in the Non-DSS group (66.7%), but males in the DSS group (58.3%). The non-obesity history was more frequent in both Non-DSS (87.5%) and DSS (87.5%) groups. But, the history of secondary infection was more common in the DSS (70.8%) compared with a non-DSS group (37.5%). A significant difference in mean MIF levels was found between patients with DSS (102 (42.91-141.12) ng/ml) and non-DSS (24.85 (12.61-50.80) ng/ml) (p &lt;0.001). MIF levels were significantly different between several degrees of dengue infection (P&lt;0.05).Conclusions: Serum MIF levels in non-DSS patients significantly differ from MIF levels in DSS patients. MIF serum levels increase in accordance with the increasing degree of severity of dengue infection. This data shows that MIF has a role in the occurrence of severe dengue infection.

Restrictive versus Liberal Fluid Resuscitation in Children with Dengue Shock Syndrome: the differences in Clinical Outcomes and Hemodynamic Parameters

Background: Fluid resuscitation is the mainstay of treatment to counteract massive plasma leakage in dengue shock syndrome. We aimed to determine the differences in clinical outcomes and hemodynamic parameters of children with dengue shock syndrome post restrictive and liberal fluid resuscitation. Materials and Methods: A retrospective observational study of pediatric patients who were between one month to 18 years old, presented with clinical criteria for dengue hemorrhagic fever (DHF) grade III and IV based on WHO classification of dengue fever in 2011, and admitted to the Saiful Anwar General Hospital, Malang- Indonesia, from January 2016 to December 2016. Patients were divided in two groups: resuscitated with either 40ml/kg BW (liberal group) solutions; then we analyzed the clinical outcomes and hemodynamic parameters between two groups. Results Among 100 patients, 92 patients were classified as DHF grade III and 8 patients were DHF grade IV. 74 patients were in the restrictive group and 24 patients were in the liberal group. Median age at diagnosis was 6 years old, and 56% of patients were female. No significant differences were observed between length of stay in pediatric intensive care unit (P=0.09), and duration of ventilator use (P=0.68). The restrictive group had 53% lower mortality compared to the liberal group (P=0.18). This study also showed that there were no significant differences in hemodynamic parameters between two groups based on measurement with USCOM which were preload component (SVV) (P=0.89), inotropy components (SMII) (P=0.07), SVRI (P=0.85) as well as the cardiac index (P=0.66). Conclusion This study showed that there is no difference in clinical outcomes (length of mechanical ventilation and length of PICU stay), and hemodynamic parameters (preload, inotropy, afterload, and cardiac index) in Dengue Shock Syndrome patients who receive restrictive or liberal fluid resuscitation.

Initial Hemodynamic Profiles of Children with Dengue Shock Syndrome in Referral Settings

Background: Fluid therapy for dengue shock syndrome (DSS) requires a dynamic approach that involves monitoring of the pathophysiological processes as well as the preload, contractility, and afterload assessment during the course dengue infection. Hemodynamically unstable DSS patients received in referral setting often complicated by fluid overload and secondary infection. Objective: This study aims to provide hemodynamic profiles and fluid responsiveness of pediatric patients admitted to the PICU with DSS. Methods: Hemodynamic profiles, laboratories, and demographic data were collected from patients aged 1 month to 18 years old with DSS who were admitted to the Pediatric Intensive Care Unit (PICU) at Dr. Sardjito General Hospital, Yogyakarta, Indonesia from January to December 2016. Hemodynamic profiles were assessed in clinically shock and not clinically shock group at PICU admission using the non-invasive Ultrasonic Cardiac Output Monitor (USCOM). Fluid responsiveness in clinically shock group was evaluated after fluid challenge with 10 ml/kgBW crystalloid or colloid. Results: Eighty six subjects were included in this study. Sixty six subjects were admitted to PICU with clinically shock condition. This group received less intravenous fluid than hemodynamically stable group (6.9 vs 7.52 ml/kgBW/hour respectively), had higher mean hematocrit level (42.09% vs 40.32% respectively), had higher hematocrit level during PICU stay (43.37% vs 42.06% respectively), significantly higher percentage to receive inotropes agent (62,1% vs 5%, p 0,000) and longer duration of inotropes usage (23,5 vs 0 hours, p 0.72). From the clinically shock patients admitted to PICU, only 19,69% were fluid responsive. Other subjects in this group with fluid non responsive state, 90,38% had low inotropic index and high systemic vascular resistance index. Among 8 patients in clinically shock group who died during PICU stay, 6 of them had low cardiac Index, fluid non responsive condition, low inotropic index and high systemic vascular resistance index. Conclusion: Only a small percentage of DSS patients with clinically shock admitted to the PICU were fluid responsive. Majority of DSS cases in children had low inotropy index and high systemic vascular resistance index.

The Effect of Overnutrition Toward the Risk of Dengue Shock Syndrome in Pediatric Patient: In-Depth Investigation of sVCAM-1 and Adiponectin Level

Introduction: Overnutrition has become an emergent health problem worldwide and could signifcantly alter the normal human physiology. It still unknown how overnutrition could affect theoutcome of pediatric patient with dengue infection. This study aimed to unveil how overnutrition affects the risk of dengue shock syndrome (DSS) in dengue pediatric patient by evaluating the adiponectin which has immune-modulatory property and the inflammationmarker sVCAM-1.Methods: An analytic observational nested case-control study was conducted in Paediatric Division Sanglah General Hospital, Bali, Indonesia from January 2015 to October 2016. Initially, patient’s anthropometric parameters were measured and the diagnosis of thedengue infection was established according to the medical record and blood plasma was isolated to determine the level of adiponectin and sVCAM-1.Result: The study showed that overnutrition increased the risk of DSS as much as 2.67 times greater than normal but it was not statistically signifcant (95%CI: 0.72 - 9.95). The mean level of sVCAM-1 was observed to be higher in overnutrition patients in almost all categoriesof dengue infection, but none is statistically signifcant. However, its level appears to be lower in over nutritious DSS patients compared to their non-DSS counterparts (4638.64 (±934.99) vs. 5680.80 (±601.77); P = 0.013). The adiponectin level was found to be consistently lowerin patients with overnutrition regardless the category of dengue infection, but signifcant differences only observed in over nutritious DHF and overnutritious non-DSS comparisons.Conclusion: It can be concluded that overnutrition increase the risk of DSS in pediatric patient with dengue infection whether it was not statistically signifcant. The lower level of adiponectin and elevated expression of sVCAM-1 could be the explanation of this phenomenon.

Skin dendritic cell and T cell activation associated with dengue shock syndrome

The pathogenesis of severe dengue remains unclear, particularly the mechanisms underlying the plasma leakage that results in hypovolaemic shock in a small proportion of individuals. Maximal leakage occurs several days after peak viraemia implicating immunological pathways. Skin is a highly vascular organ and also an important site of immune reactions with a high density of dendritic cells (DCs), macrophages and T cells. We obtained skin biopsies and contemporaneous blood samples from patients within 24 hours of onset of dengue shock syndrome (DSS), and from healthy controls. We analyzed cell subsets by flow cytometry, and soluble mediators and antibodies by ELISA; the percentage of migratory CD1a+ dermal DCs was significantly decreased in the DSS patients, and skin CD8+ T cells were activated, but there was no accumulation of dengue-specific antibodies. Inflammatory monocytic cells were not observed infiltrating the skin of DSS cases on whole-mount histology, although CD14dim cells disappeared from blood.

Cardio-haemodynamic assessment and venous lactate in severe dengue: Relationship with recurrent shock and respiratory distress.

BackgroundDengue can cause plasma leakage that may lead to dengue shock syndrome (DSS). In approximately 30% of DSS cases, recurrent episodes of shock occur. These patients have a higher risk of fluid overload, respiratory distress and poor outcomes. We investigated the association of echocardiographically-derived cardiac function and intravascular volume parameters plus lactate levels, with the outcomes of recurrent shock and respiratory distress in severe dengue.Methods/Principle findingsWe performed a prospective observational study in Paediatric and adult ICU, at the Hospital for Tropical Diseases (HTD), Ho Chi Minh City, Vietnam. Patients with dengue were enrolled within 12 hours of admission to paediatric or adult ICU. A haemodynamic assessment and portable echocardiograms were carried out daily for 5 days from enrolment and all interventions recorded.102 patients were enrolled; 22 patients did not develop DSS, 48 had a single episode of shock and 32 had recurrent shock. Patients with recurrent shock had a higher enrolment pulse than those with 1 episode or no shock (median: 114 vs. 100 vs. 100 b/min, P = 0.002), significantly lower Stroke Volume Index (SVI), (median: 21.6 vs. 22.8 vs. 26.8mls/m2, P<0.001) and higher lactate levels (4.2 vs. 2.9 vs. 2.2 mmol/l, P = 0.001). Higher SVI and worse left ventricular function (higher Left Myocardial Performance Index) on study days 3–5 was associated with the secondary endpoint of respiratory distress. There was an association between the total IV fluid administered during the ICU admission and respiratory distress (OR: 1.03, 95% CI 1.01–1.06, P = 0.001). Admission lactate levels predicted patients who subsequently developed recurrent shock (P = 0.004), and correlated positively with the total IV fluid volume received (rho: 0.323, P = 0.001) and also with admission ALT (rho: 0.764, P<0.001) and AST (rho: 0.773, P<0.001).Conclusions/SignificanceEcho-derived intravascular volume assessment and venous lactate levels can help identify dengue patients at high risk of recurrent shock and respiratory distress in ICU. These findings may serve to, not only assist in the management of DSS patients, but also these haemodynamic endpoints could be used in future dengue fluid intervention trials.

Alpha tryptase allele of Tryptase 1 (TPSAB1) gene associated with Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) in Vietnam and Philippines

We previously reported, significantly higher levels of Chymase and Tryptase in early stage plasma of DSS patients prior to the occurrence of shock suggesting a possible role of mast cells in dengue pathogenesis. To further investigate, we analyzed CMA1 promoter SNP (rs1800875) and TPSAB1 gene alleles, which encode the Human Chymase and α- and β- tryptase 1 enzymes respectively, for susceptibility to Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) in patients from hospitals in Vietnam (Ho Chi Minh City and Vinh Long) and the Philippines. While the CMA1 promoter SNP (rs1800875) was not associated with DHF/DSS, the homozygous form of α-tryptase allele was associated with DSS patients in Vinh Long and the Philippines (OR=3.52, p<0.0001; OR=3.37, p<0.0001, respectively) and with DHF in Ho Chi Minh City (OR=2.54, p=0.0084). Also, a statistically significant association was observed when DHF and DSS were combined in Vinh Long (OR=1.5, p=0.034) and the Philippines (OR=2.36, p=0.0004); in Ho Chi Minh City when DHF and DSS were combine an association was observed, but it was not statistically significant (OR=1.5, p=0.0505). Therefore, the α-tryptase might have a possible effect on the susceptibility to severe form of Dengue infection.

Vascular leakage in dengue hemorrhagic Fever is associated with dengue infected monocytes, monocyte activation/exhaustion, and cytokines production.

The vascular leakage was shown by the increment of hematocrit (Hct), dengue viral infected monocyte, monocyte status, and cytokines production in patients infected with dengue virus. Dengue viral antigens were demonstrated in monocytes (CD14+) from peripheral blood mononuclear cells. The increased levels of Hct, interleukin- (IL-) 10, and tumor necrosis factor-alpha (TNF-α) were detected in dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) patients as compared with other febrile illnesses (OFIs). The highest levels of Hct and IL-10 were detected in DSS patients as compared with other groups (P < 0.05) especially on one day before and after defervescence. The unstimulated and lipopolysaccharide- (LPS-) stimulated monocytes from DSS patients showed the significantly decreased of intracellular IL-1β and TNF-α. In addition, the lowest level of mean fluorescence intensity (MFI) of CD11b expression on monocytes surface in DSS patients was also demonstrated. Furthermore, the negative correlations between IL-10 levels and intracellular IL-1β and MFI of CD11b expression in unstimulated and LPS-stimulated monocytes were also detected. Nevertheless, not only were the relationships between the prominent IL-10 and the suppression of intracellular monocyte secretion, namely, IL-1β, TNF-α, demonstrated but also the effect of vascular leakage was observed.