Predictors Of Severe Dengue Research Articles

Pro- and anti-inflammatory cytokines signatures at different severity of dengue infection.

Dengue disease severity and progression are determined by the host immune response, with both pro- and anti-inflammatory cytokines are key mediators. To study pro- and anti-inflammatory cytokines across dengue severity and as a biomarker for predicting severe dengue infection. Hospital-based cross-sectional study was conducted on 125 dengue-positive subjects across the 5-60 years age group of either gender in 2022. Haematological parameters and blood samples were drawn to measure cytokines IL6, IL-10 and TNF alpha using the ELISA technique. One-way ANOVA and the Kruskal - Wallis test were used to compare the dependent variables across categories of the dengue spectrum. Receiver operating characteristic curve was drawn to calculate the predictability of the cytokines as a predictor of severe dengue. A P < 0.05 was considered significant. 34.4% of cases had severe dengue infection with 53.2% of severe cases reported in >40 years of age. Only IL-6 levels significantly increased (P < 0.01) across the spectrum of dengue infection across age groups >20 years with a consistent and significant fall in platelet levels (P < 0.01). The accuracy of IL-6 to predict severe dengue was 74.4% and platelet count was 16.2%. Only IL-6 cytokine levels were significantly increased across the spectrum of dengue infection observed in age >20 years and can significantly predict the probability of severe dengue by 74% (sensitivity 81.4%). A significant decrease in platelet values is consistent with the severity but is not a good predictor for severe dengue infection.

APRI as a predictor of severe dengue fever.

The AST/platelet ratio index (APRI) is a well-researched indicator of liver fibrosis. Some studies have shown that APRI can be used as a predictor of severe dengue, but the data is limited. As dengue epidemics are common in our country with limited healthcare resources, we believe APRI can help emergency physicians/primary physicians in predicting the severity of dengue and plan for the appropriate use of limited healthcare resources. 1) To determine the utility of APRI as a predictor of severe dengue. 2) To determine the association of APRI with length of hospital stay and platelet requirement. A retrospective cross-sectional study was done on patients presented to the Emergency Medicine department at Travancore Medicity Medical College with a positive Dengue NS1 antigen or IgM antibody. We found from the univariate analysis results that ALT > 74.5 IU/L has a sensitivity of 59.6 and a specificity of 76.3 (AUC: 0.696; 95% CI: 0.606-0.786), AST > 160.5 IU/L has a sensitivity of 42.3 and a specificity of 93.7 (AUC: 0.747; 95% CI: 0.665-0.829), and APRI > 3.2 has a sensitivity of 69.2 and a specificity of 84.2 (AUC: 0.806; 95% CI: 0.72-0.884) to predict severe dengue. Patients with an APRI of >3.2 required a mean hospital stay of 5.47 days (P = 0.005); 27 (81.8%) requiring platelet transfusion had an APRI of > 3.2 (P = 0.00). APRI is a straightforward index that can be easily derived from AST and platelet values. APRI values of >3.2 can predict severe dengue with a sensitivity of 69.2 and a specificity of 84.2. APRI values of >3.2 are also associated with the length of hospital stay and requirement of platelet transfusion.

A study on predictors of severe dengue in pediatric patients in a tertiary care hospital in Telangana

Background: Dengue is an emerging arthropod borne disease with increasing incidence in recent years in several countries, especially India. Early recognition of progression of disease helps in triage and timely management of fluids to decrease mortality. Objective: The objective of the study was to identify the predictive factors for severe dengue in pediatric patients for hospitalization for close monitoring. Methods: This was a prospective observational study conducted in the department of pediatrics in a tertiary care hospital in Mahbubnagar from June 2019 to May 2020. One hundred and four children between the age group of 0 and 15 years with probable dengue symptoms who were willing to get admitted were included in the study cohort. Thorough history and clinical examination, basic laboratory investigations such as complete blood picture, hematocrit, liver function tests, renal function tests (RFTs), serum electrolytes, serum ferritin, and coagulation profile were done as needed. All the patients were grouped into two groups – non-severe dengue (dengue fever without warning signs and dengue fever with warning signs) and severe dengue as per the World Health Organization guidelines. All the variables were analyzed using SPSS software. Results: Out of 104 confirmed cases, majority of the admissions were in 5–10 years age group (51.9%). Male children were 61.5%. Mean duration of hospitalization was 4.79±2.96 days. Fever (97.1%) was the most common symptom followed by anorexia (86.5%) and lethargy (82.7%). Symptoms such as lethargy, vomiting, abdominal pain/epigastric tenderness, epistaxis, edema, and altered sensorium were more commonly associated with severe dengue. Hepatomegaly (53.9%) was the most common clinical sign followed by epigastric tenderness (58.7%). Hepatomegaly, splenomegaly, ascites, gallbladder edema, pleural effusion, low pulse pressure, hypotension, oliguria, and significant gastrointestinal bleeds were more common in severe dengue group. Platelet count &lt;50,000/mm3, increase in hematocrit more than 20% from baseline, raised transaminases, raised ferritin, decrease in serum sodium, decrease in serum albumin, abnormal coagulation profile, and abnormal RFTs were significantly associated with severe dengue. Mean platelet recovery time was 3–5 days. Conclusion: Dengue is a dynamic disease and progression of dengue with or without warning signs into severe dengue can be appropriately identified by close monitoring of certain clinical signs and symptoms.

The Predictors of the Severity of Dengue Fever: A Cross-Sectional Study in a Tertiary Care Center of Bangladesh

Background: Dengue is an endemic disease for Bangladesh with occasional outbreak. Little is known about the predictors of severe dengue.&#x0D; Methods: This cross sectional study was conducted in the medicine department of Dhaka Medical College from April 2019 to March 2020. Total 199 consecutive patients were enrolled in this study. For the purpose of the analysis, dengue fever was classified as group I and dengue hemorrhagic fever and dengue shock syndrome was classified as group II.&#x0D; Results: The mean (SD) age of the study population was 28.5(12.1) and 87.4% were less than 40 years of age. The male and female ratio was about 3:1. Among the total study population, 149(74.9%) patients had DF, 46 (23.1%) had DHF and only 4 (2%) had DSS on presentation. Baseline demography and clinical presentation did not significantly differ between classical dengue and severe dengue. Previous history of dengue had low association with severity (RR, 95%CI, phi, P value; 1.2, 1.04-1.40, 0.25, 0.001).Most of the laboratory parameters were similar between the groups. The number of platelet count was significantly lower in DHF and DSS [median (IQR) 43500(16500-95250], than DF [median (IQR) 65000(33000-1170000, p-value 0.01]&#x0D; Conclusion: Previous infection with dengue virus and decreasing platelet count are the predictors of the severe dengue.&#x0D; J Dhaka Medical College, Vol. 29, No.1, April, 2020, Page 77-82

Predictors of severe dengue amongst children as per the revised WHO classification.

World Health Organization (WHO) revised its guidelines for classification and management of dengue in 2009. This revised system was found out to have good sensitivity and negative predictive value but poor specificity as well as positive predictive value. This retrospective study was carried out in a tertiary care hospital of Delhi, India to assess factors predicting the occurrence of severe dengue in children as per the revised classification. A total of 647 suspected dengue cases were admitted in the hospital in the year 2015. Detailed clinical and epidemiological data of 170 patients who were confirmed as dengue either by NS1 antigen test or by serology (Ig M positive) were recorded and statistically analyzed. The number of laboratory-confirmed cases was 170 and included thirty (17.65%) dengue fever (DF), 106 (62.35%) dengue with warning signs (DWS) and 34 (20.0%) severe dengue (SD) patients. Regression analysis revealed that presence of vomiting, altered sensorium, shock, peri-orbital edema, hepatomegaly, splenomegaly, severe anemia, thrombocytopenia, elevated urea and creatinine, decreased total protein and globulin were significantly associated with occurrence of severe disease. The addition of clinical features (peri-orbital edema and splenomegaly); and laboratory findings (elevated urea and creatinine, decreased serum protein and globulin) might help improve the sensitivity and specificity of the revised WHO dengue classification in predicting severe dengue.

Utility of Serum Transaminases in Predicting Disease Severity in Dengue Fever- A Cross-sectional Study

Introduction: Thrombocytopenia has been known to be a manifestation as well as predictor of severe dengue. However, use of additional biomarkers like Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) alone or in conjunction with platelet count may help in early and better predictability of severe dengue cases. Aim: To determine the correlation between transaminase elevation and severity of dengue fever. Materials and Methods: This was a single centre, cross-sectional study conducted at a tertiary care centre of Western Maharashtra. Total 110 hospitalised patients with a diagnosis of suspected dengue fever, based on clinical signs and symptoms with a positive NS1 antigen test (non structural protein 1)/Immunoglobulin M (IgM) test using rapid test kits were taken as study population. The patients were clinically evaluated on daily basis for development of any warning signs and symptoms along with monitoring of haematological and biochemical parameters. For statistical analysis the technique of percentages, mean and Pearson ‘r’s were employed using IBM Statistical Package for the Social Sciences (SPSS 20.0) version for windows. The p-value of 0.05 was considered as significant value. Results: Out of 110 patients, 83 were males and 27 females. Clinical fluid accumulation was seen in 5 patients (4.5%), bleeding manifestations and fluid accumulation in 4 (3.6%) and bleeding manifestations in 17 (15.5%). Negative correlation was observed between thrombocytopenia with bleeding manifestations (r=-0.17, p=0.04), whereas positive correlation was seen in incidence of bleeding with serositis (r=0.19, p=0.04), AST with serositis (r=0.21, p=0.02) and ALT with Packed Cell Volume (PCV) (r=0.22, p=0.01). Conclusion: Additional biomarkers like AST and ALT alone or in conjunction with platelet count can also help in early prediction of severity of dengue fever.

Serum Ferritin As a Prognostic Indicator in Adult Dengue Patients.

Dengue virus (DENV) infection is increasing with rapid urbanization in India. Treatment of DENV infection is mainly supportive with no specific antiviral therapy. Although most patients show mild illness, some have a severe disease course such as dengue hemorrhagic syndrome, dengue shock, multi-organ failure, and death. The cause for severity is not fully understood. Currently, there are no methods available to predict the course of the illness. Hence, it is crucial to develop an early biomarker to predict the course of dengue illness which can aid in vigorous monitoring and early intervention. Here, we tried to establish a correlation between serum ferritin and severity of dengue illness. We measured ferritin levels in 100 dengue-positive cases on day 1 (D1) (febrile phase) and day 4 (D4) (defervescence or convalescent) of admissions to compare the levels with the severity of the disease. On D1, the serum ferritin level was a "good" predictor of severe dengue, with an area under the curve (AUC) of 0.863 with standard error (SE) = 0.043 and a 95% CI from 0.778 to 0.947 (P < 0.05). On D4, serum ferritin was an "excellent" predictor of severe dengue, with an AUC of 0.947 with SE = 0.021 and a 95% CI from 0.907 to 0.988 (P < 0.05). Serum ferritin is an inexpensive and easily accessible biomarker that can assist in monitoring and prognosticating the dengue-positive patients. This biomarker also directs us to explore the underlying pathogenetic mechanism in severe dengue, which can lay a foundation for future targeted therapeutic options to combat severe illness.

Development of a Prognostic Prediction Model to Determine Severe Dengue in Children.

To develop a prognostic prediction model using the seven warning signs highlighted by WHO revised Dengue fever classification 2009 to determine severe dengue in children. In this prospective analytical study conducted in a tertiary care centre, consecutive sampling of all children aged 1mo to 12y admitted with serologically confirmed Dengue was done from May 2015 through August 2016. After excluding 27 patients with co-infections and co-morbidities, 359 patients were followed up daily to assess clinical and laboratory progression till discharge/ death. Independent predictors were abdominal pain or tenderness, persistent vomiting, lethargy, mucosal bleed, clinical fluid accumulation, hepatomegaly >2cm and rising hematocrit concurrent with platelet count <100 × 109/L. Outcome measure was severe dengue defined as per WHO guidelines 2009. Among 359 children, 93 progressed to severe dengue. In univariate analysis, significant predictors were clinical fluid accumulation (OR 4.773, p = 0.000, 95%CI 2.511-9.075), persistent vomiting (OR 1.944, p = 0.010, 95%CI 1.170-3.225), mucosal bleed (OR 2.045, p = 0.019, 95%CI 1.127-3.711) and hematocrit ≥0.40 concurrent with platelet count <100 × 109/L (OR 2.985, p = 0.000, 95%CI 1.783-4.997). The final multivariable model included clinical fluid accumulation (aOR 3.717, p = 0.000, 95%CI 1.901-7.269), hematocrit ≥0.40 concurrent with platelet count <100 × 109/L (aOR 2.252, p = 0.004, 95%CI 1.302-3.894) and persistent vomiting (p = 0.056) as predictors of severe dengue. Among seven WHO warning signs, predictors of severe dengue as suggested by the present multivariable prediction model include clinical fluid accumulation, persistent vomiting and hematocrit ≥0.40 concurrent with platelet count <100 × 109/L.

A Multicenter Study of Clinical Presentations and Predictive Factors for Severe Manifestation of Dengue in Adults.

Severe dengue is more prevalent in adults than in children. Our objectives were to determine the clinical presentations of dengue in adults and to identify predictive factors for severe dengue. A retrospective cohort study was performed in adults with dengue, as confirmed by a positive NS1 antigen test result. Patients were classified as with non-severe or severe dengue. A total of 357 patients were enrolled; 45.4% were men, with a median (interquartile range [IQR]) age of 27.9 (21.8-43.5) years. Of all patients, 28.3% had warning signs and 10.6% had severe dengue. Patients with severe dengue were significantly older (35.1 [26.2-50.6] vs. 26.7 [21.7-43.3] years, P = 0.010), immunocompromised (7.9% vs. 0.9%, P = 0.018), and had cough (29% vs. 16%, P = 0.046), hepatomegaly (10.5% vs. 3.1%, P = 0.050), impaired consciousness (5.3% vs. 0%, P = 0.011) or higher (IQR) alanine aminotransferase (ALT) level (151 [57-295] vs. 66 [37-114] U/L, P = 0.008). By multivariate analysis, having cough (odds ratio [OR], 8.07; 95% confidence interval [CI], 2.51-30.16, P = 0.001) and ALT>120 U/L (OR, 3.51; 95% CI, 1.11-11.14, P = 0.033) were predictors of severe dengue. Early recognition of risk variables may be important for healthcare providers to appropriately manage dengue patients.

Combination of three laboratory data as predictor of severe dengue in adults : a retrospective cohort study

&lt;p&gt;Introduction&lt;br /&gt;Skin hydration decreases with aging. Aquaporin-3 (AQP3) is a major protein that plays a role in skin hydration, therefore it is a novel target for skin moisturizing treatment. Retinoic acid (RA) as a well-known active agent in antiaging treatment increases AQP3 expression, but frequently causes harmful side effects. Asiaticoside, a saponin compound isolated from Centella asiatica (CA) is also known as an antiaging cosmetic and plays a role in wound healing. The aim of this study was to evaluate and compare the effect of asiaticoside isolated from CA and the effect of RA on the AQP3 expression in normal human epidermal keratinocytes (NHEKs).&lt;/p&gt;&lt;p&gt;Methods &lt;br /&gt;An experimental laboratory study was performed using primary NHEKs that were derived from the foreskin of a boy. AQP3 expression in NHEKs was examined in vitro after the cells were incubated for 24 hours with asiaticoside or with RA at several concentrations. The AQP3 expression was evaluated by immunocytochemistry and quantitatively analyzed by Image-J software. Independent t-test and one-way ANOVA were used to analyze the data, followed by post-hoc Tukey test.&lt;/p&gt;&lt;p&gt;Results&lt;br /&gt;There was an increasing trend of AQP3 expression upon exposure to asiaticoside at all concentrations compared to the control group. However, RA exposure seemed to induce a higher level of AQP3 expression. Asiaticoside effected a lower increase in AQP3 expression in NHEKs than did RA (p=0.042). Optimal results were achieved at 1 mg/ml concentration of asiaticoside.&lt;/p&gt;&lt;p&gt;Conclusions&lt;br /&gt;Asiaticoside isolated from CA can enhance the AQP3 expression in NHEKs. Therefore it can be used as an active ingredient in cosmetic moisturizer formulation for dry skin treatment.&lt;/p&gt;

A Multicenter Study of Clinical Presentations and Predictive Factors for Severe Manifestation of Dengue in Adults

Severe dengue is more prevalent in adults than in children. Our objectives were to determine the clinical presentations of dengue in adults and to identify predictive factors for severe dengue. A retrospective cohort study was performed in adults with dengue, as confirmed by a positive NS1 antigen test result. Patients were classified as with non-severe or severe dengue. A total of 357 patients were enrolled; 45.4% were men, with a median (interquartile range [IQR]) age of 27.9 (21.8-43.5) years. Of all patients, 28.3% had warning signs and 10.6% had severe dengue. Patients with severe dengue were significantly older (35.1 [26.2-50.6] vs. 26.7 [21.7-43.3] years, P = 0.010), immunocompromised (7.9% vs. 0.9%, P = 0.018), and had cough (29% vs. 16%, P = 0.046), hepatomegaly (10.5% vs. 3.1%, P = 0.050), impaired consciousness (5.3% vs. 0%, P = 0.011) or higher (IQR) alanine aminotransferase (ALT) level (151 [57-295] vs. 66 [37-114] U/L, P = 0.008). By multivariate analysis, having cough (odds ratio [OR], 8.07; 95% confidence interval [CI], 2.51-30.16, P = 0.001) and ALT>120 U/L (OR, 3.51; 95% CI, 1.11-11.14, P = 0.033) were predictors of severe dengue. Early recognition of risk variables may be important for healthcare providers to appropriately manage dengue patients.

Caracterización clínica del dengue y variables predictoras de gravedad en pacientes pediátricos en un hospital de segundo nivel en Chilpancingo, Guerrero, México: serie de casos

BackgroundDengue continues to increase globally. Currently, the highest incidence of first infection occurs in paediatric population, where severe dengue fever is potentially lethal. This study characterizes the clinical profile of paediatric patients with dengue fever in the South of Mexico. MethodsWe undertook a series case study of 133 paediatric inpatients who presented clinical diagnosis of non-severe dengue and severe dengue fever. We described univariate analysis as means or percentages, using 0.05 as significance level. We estimated the prediction of severe dengue considering clinical signs and symptoms only using GLMM (Generalised Linear Mixed Models). Results58% (77/133) patients had severe dengue. There were significant differences among the dengue groups, in the following signs and symptoms: Fever, abdominal pain, epistaxis and platelet count. Children older than four years old had a higher proportion of severe dengue (p<0.05). GLMM identified a group of four clinical signs and symptoms (fever ≥39°C, myalgia, arthralgia and abdominal pain) as predictors of severe dengue. ConclusionsThe results of this exploratory study suggest changes in the frequency of clinical signs and symptoms among paediatric inpatients. Paediatric patients with a presumptive diagnosis of dengue, showing fever of ≥39° C, myalgia, arthralgia and abdominal pain should be considered as potential cases of severe dengue.

Changing trends in clinicopathological parameters in dengue with evaluation of predictors of poor outcome in children

Background: A study was planned to evaluate the changing trends in dengue according to the revised WHO guidelines in children and at identifying and evaluating the association between clinical features the child and the outcome. Methods: This was a retrospective observational study conducted in Safdarjung Hospital. Children with signs and symptoms of dengue fever along with serological or antigen NS1 positivity were included. Continuous variables were analysed using percentage, mean, standard deviation. Categorical variables were analysed using chi-square test. P value 5 days) (p < 0.000) and progression to shock. Conclusions: Lethargy, presence of more than 3 warning signs at the time of presentation can be used as predictors of severe dengue.

The early clinical features and predictors of severe dengue and dengue shock syndrome in adult patients

The early clinical features and predictors of severe dengue and dengue shock syndrome in adult patients

Utilities and Limitations of the World Health Organization 2009 Warning Signs for Adult Dengue Severity

BackgroundIn 2009, the World Health Organization (WHO) proposed seven warning signs (WS) as criteria for hospitalization and predictors of severe dengue (SD). We assessed their performance for predicting dengue hemorrhagic fever (DHF) and SD in adult dengue.MethodDHF, WS and SD were defined according to the WHO 1997 and 2009 dengue guidelines. We analyzed the prevalence, sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of WS before DHF and SD onset.ResultsOf 1507 cases, median age was 35 years (5th–95th percentile, 17–60), illness duration on admission 4 days (5th–95th percentile, 2–6) and length of hospitalization 5 days (5th–95th percentile, 3–7). DHF occurred in 298 (19.5%) and SD in 248 (16.5%). Of these, WS occurred before DHF in 124 and SD in 65 at median of two days before DHF or SD. Three commonest warning signs were lethargy, abdominal pain/tenderness and mucosal bleeding. No single WS alone or combined had Sn >64% in predicting severe disease. Specificity was >90% for both DHF and SD with persistent vomiting, hepatomegaly, hematocrit rise and rapid platelet drop, clinical fluid accumulation, and any 3 or 4 WS. Any one of seven WS had 96% Sn but only 18% Sp for SD.ConclusionsNo WS was highly sensitive in predicting subsequent DHF or SD in our confirmed adult dengue cohort. Persistent vomiting, hepatomegaly, hematocrit rise and rapid platelet drop, and clinical fluid accumulation, as well as any 3 or 4 WS were highly specific for DHF or SD.

Evaluation of the WHO revised criteria for classification of clinical disease severity in acute adult dengue infection

BackgroundThe WHO guidelines were revised recently to identify patients with severe dengue (SD) early. We proceeded to determine the usefulness of the warning signs in the new WHO guidelines in predicting SD and we have also attempted to define other simple laboratory parameters that could be useful in predicting SD.MethodsClinical and laboratory parameters were recorded in 184 patients in 2011, with confirmed dengue viral infections, admitted to a medical ward in two tertiary care hospitals in Colombo, Sri Lanka.ResultsWe found that the presence of 5 or more dengue warning signs were significantly (p = 0.02) associated with the development of SD (odds ratio 5.14, 95% CI = 1.312 to 20.16). The AST levels were significantly higher (p = 0.0001) in patients with abdominal pain (mean 243.5, SD ± 200.7), when compared to those who did not have abdominal pain (mean 148.5, SD ± 218.6). Lymphocyte counts <1,500 cells/mm3 were significantly (p = 0.005) associated with SD (odds ratio 3.367, 95% CI 1.396 to 8.123). High AST levels were also significantly associated (p < 0.0001) with SD (odds ratio 27.26, 95% CI 1.632 to 455.2). Platelet counts <20,000cells/mm3, were again significantly associated (p < 0.001) with severe disease (odds ratio 1.632 to 455.2, 95% CI 3.089 to 14.71). The PCR was positive in 26/84 of the patients and we found that the infecting serotype was DEN-1 in all 26 patients.ConclusionsThe presence of 5 or more warning signs appears to be a predictor of SD. Lymphocyte counts <1,500 cells/mm3, platelet counts <20,000/mm3 and raised AST levels were associated with SD and could be used to help identify patients who are likely to develop SD.