Non-severe Dengue Research Articles

Association of interleukin-2, -4 and -10 with dengue severity.

Dengue is an arboviral disease caused by four distinct serotypes of dengue virus. The pathogenesis of dengue is not very clearly understood. Various pro- and anti-inflammatory cytokines are involved in the immune pathogenesis of dengue. Interleukin (IL)-2/IL-2 receptor interaction is supposed to play a protective role, while IL-4 acts as pro-inflammatory whereas IL-10 acts as anti-inflammatory cytokines. So far, not much information is available regarding the established role of these cytokines with dengue infection and severity. our study aimed to show the association of IL-2, -4, and -10 with severity of dengue infection. This was a cross-sectional study. The study was conducted in the year 2015; 150 blood samples from suspected dengue cases were confirmed for dengue and then with an equal number of healthy control samples were tested for cytokines levels (IL-2, -4, and -10) by ELISA. Severity of the dengue infection was determined on the basis of clinical manifestations based on the WHO criteria. for statistical analysis, SPSS version 21 (IBM, New York, United States) was used. Out of 150 samples, 56 samples came to be dengue positive. Thirty-eight (67.85%) cases were classified as nonsevere dengue and 18 (32.15%) were severe dengue. The serum levels of IL-4 and -10 were significantly raised in severe dengue cases as compared to nonsevere dengue cases. No significant association was observed between serum IL-2 levels and the severity of dengue. IL-4 and -10 levels can be used as marker of severe dengue and help in early preparedness to start the treatment in the line of severe dengue.

Clinical and laboratory profile of dengue fever in children during an outbreak - one year study at tertiary care hospital, Chennai, Tamilnadu, India

Background: Dengue fever is a mosquito borne arboviral disease which is of global concern. It is endemic in tropical countries with annual incidence of 7.5 to 32.5 million cases. It commonly affects the young adults and paediatric cases of Dengue haemorrhagic fever has high mortality. The objective of this study was to assess the clinical and laboratory profile and outcomes of dengue fever in children of less than 18 years of age. The study was conducted for a period of one year during an outbreak, in a tertiary care hospital of Chennai, Tamilnadu, India.Methods: This was a prospective cross sectional study and 200 cases of dengue fever were enrolled and classified as per WHO guidelines. The clinical profile and demographic profile was recorded in a structured questionnaire form. Haematological parameters were recorded and followed till the day of discharge. The duration of stay was recorded and outcomes were noted.Results: A total of 200 cases with 113 males and 87 females, 177 non severe dengue cases and 23 severe cases of dengue fever were classified. The mean age of admission was 9 years and mean duration of stay in hospital was 4.61 days. Fever was most common presenting symptom (100%) and hepatomegaly (58.5%) was common clinical finding. Bleeding manifestations were seen in severe dengue cases. Statistical significance was seen in rise in SGOT levels, rise in haematocrit and pleural effusion with severe dengue cases and non-severe dengue cases. The case fatality rate was zero.Conclusions: Understanding the knowledge of presentations and associated features would help to predict the severity of the disease. In children, if symptoms like fever, pain, rashes, and vomiting are associated with Hepatomegaly and elevated SGOT in context of low total platelet count, a strong possibility of dengue fever is present, especially in an epidemic setting. Early suspicion and effective management can reduce the severity.

Increased serum levels of macrophage activation marker sCD163 in Dengue patients

BackgroundDengue viruses are known to infect and replicate in macrophages. Thus studying the host responsive molecules that are specifically released by macrophages during the course of dengue infection may provide better understanding on dengue immunopathogenesis. Soluble CD163 (sCD163) is a scavenger receptor, highly expressed on macrophages reported to be involved in some viral disease. The participation of sCD163 in dengue is not known. ObjectiveThe present study aimed to explore the role of sCD163 as a potential biomarker for predicting dengue disease. Study designUsing a case-control design, 82 dengue subjects consisting of 69 non-severe dengue (NSD) and 13 severe dengue (SD) along with 32 non-dengue other febrile illness (OFI) subjects and 30 healthy subjects were involved in the study. The serum concentration of sCD163 was determined in the study subjects at admission and around defervescence using ELISA. Statistical analysis was done using Mann-Whitney U test andWilcoxon signed rank test. ResultsThe study recorded a significant increase in the sCD163 serum level at defervescence phase specifically among dengue group compared to OFI. sCD163 was also found to be significantly higher in secondary cases compared to primary at both admission and defervescence. Furthermore,a higher level of sCD163 was also observed in SD compared to NSD cases, although no statistical significance was observed ConclusionThe study substantiates the role of macrophage activation in dengue pathogenesis and further study is needed to decipher the exact role of sCD163 in the disease pathogenesis and to explore its potential as a marker for the early prediction of dengue severity.

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.

Patterns and causes of liver involvement in acute dengue infection.

BackgroundLiver involvement in acute dengue infection is frequently observed and sometimes leads to acute liver failure, with fatal outcomes. Many factors are thought to contribute to liver dysfunction, including hypoxic injury due to decreased perfusion, direct damage by the virus and immune mediated injury. In this study, we sought to identify the pattern in the change in liver enzymes throughout the illness and its association with the degree of viraemia, onset and extent of plasma leakage and inflammatory mediators.MethodsSerial daily blood samples were obtained from 55 adult patients with acute dengue from the time of admission to discharge and the liver function tests, viral loads and cytokines were assessed. The onset and extent of fluid leakage was measured by daily ultrasound examinations and all clinical and laboratory features were serially recorded.ResultsAspartate transaminase (AST), alanine transaminase (ALT) and gamma glutamyl transferase (GGT) levels were elevated in patients with dengue infection throughout the illness. The highest AST levels were seen on day 6 of illness and both AST and GGT levels were significantly higher in patients with severe dengue (SD), when compared to those with non-severe dengue (NSD) on day 5 and 6 of illness. Three patients with SD had AST and ALT values of >1000/IU in the absence of any fluid leakage or a rise in the haematocrit (≥20 %). The peak of the AST levels and the lowest serum albumin levels were seen 24 h before the maximum fluid leakage and 24 h after the peak in viraemia. Both serum IL-10 and IL-17 levels were elevated during early illness and were significantly higher in those with SD when compared to NSD.ConclusionDengue associated liver injury appears to peak around day 6 and 7. Therefore, liver function tests done at earlier dates might not reflect the extent of liver involvement in acute infection. Since severe liver involvement can occur in the absence of fluid leakage, after the peak viraemia, and since it is associated with high IL-17 and IL-10 levels, possible immune mechanisms leading to hepatic damage should be investigated.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1656-2) contains supplementary material, which is available to authorized users.

Characterization of the Myocarditis during the worst outbreak of dengue infection in China.

Myocarditis is a common complication of severe dengue infection. However, data about prevalence and characterization of myocarditis in dengue are still lacking. In 2014, the worst outbreak of dengue in the last two decades in China occurred. In this study, we described the clinical and laboratory diagnostic features of dengue with myocarditis. Totally, 1782 diagnosed dengue patients were admitted from August to October, 2014, all of whom were subjected to electrocardiogram, ultrasound cardiogram, and cardiac enzyme test. About 201 cases of dengue patients were diagnosed with myocarditis and the prevalence of myocarditis in hospitalized dengue was 11.28%. The prevalence of myocarditis in nonsevere dengue with warning signs and severe dengue [NSD(WS+)/SD] and nonsevere dengue without warning signs [NSD(WS–)] was 46.66% and 9.72%, respectively. The NSD(WS+)/SD patients with myocarditis presented with higher incidence of cardiac symptoms, supraventricular tachycardia (14.29% vs. 0%, P < 0.001), atrial fibrillation (25.71% vs. 10.24%, P = 0.019) and heart failure compared with NSD (WS–) patients with myocarditis. About 150 cases of dengue patients without myocarditis in the same period of time in department of Cardiology were recruited as control group. The proportion of NSD(WS+)/SD in dengue patients with and without myocarditis was 17.41% and 2.53%, respectively. Dengue patients with myocarditis experienced longer hospital stay than those without myocarditis (7.17 ± 4.64 vs. 5.98 ± 2.69, P = 0.008). There was no difference between patients with and without myocarditis in the proportion of symptoms, auxiliary methods abnormality, arrhythmia, and heart failure on the discharge day. Our study demonstrates the prevalence of myocarditis in worst outbreak of dengue in China was 11.28% and the incidence of myocarditis increased with the severity of dengue. The NSD(WS+)/SD patients with myocarditis presented with higher incidence of cardiac complication compared with NSD (WS–) patients with myocarditis. The prognosis of dengue patients with and without myocarditis had no significant difference even if myocarditis patients experienced longer hospital stay.

Clinical profile of dengue and predictive severity variables among children at a secondary care hospital of Chilpancingo, Guerrero, Mexico: case series

Abstract Background Dengue continues to increase globally. Currently, the highest incidence of primo-infection occurs in the pediatric population, where severe dengue fever is potentially lethal. This study characterizes the clinical profile of pediatric patients with dengue fever in the South of Mexico. Methods We undertook a case series study of 133 pediatric inpatients with a clinical diagnosis of non-severe dengue and severe dengue fever. We described univariate analysis as means or percentages using a p Results 58% of patients (77/133) 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 of age had a higher proportion of severe dengue (p Conclusions The results of this exploratory study suggest changes in the frequency of clinical signs and symptoms among pediatric inpatients. Pediatric 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.

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.

Is Ultrasound a Useful Tool to Predict Severe Dengue Infection?

To study the role of ultrasound in children with dengue fever and determine its role in predicting the severity of the disease. This was a retrospective hospital based study conducted from 1(st) August 2012 to January 31(st) 2015 at a tertiary care hospital in Puducherry. Two hundred and fifty four children were admitted with dengue fever and among them non-severe dengue and severe dengue were seen in 62.6 % and 37.4% respectively. Mean age of presentation was 7.0 (3.3) years. M: F ratio was 1.2:1 Ultrasound was performed on all children with dengue fever during the critical period of illness as an early sign of plasma leakage and at the time of discharge. The diagnosis was confirmed by NS1 antigen and dengue serology. Ultrasonography showed positive findings in 156 cases (61.4%) during the critical period of illness. Ultrasound findings were analyzed using logistic regression among severe and non-severe dengue and P value of <0.05 was taken as significant. The common ultrasound findings that were significantly associated with severe dengue infection on univariate analysis were gall bladder wall thickening, ascites, pleural effusion, pericardial effusion, pericholecystic fluid, hepatomegaly, splenomegaly and mesenteric adenopathy. On multivariate analysis, gall bladder thickening and hepatomegaly were significantly associated with severe dengue infection. Gall bladder wall thickening (GBWT) with honeycombing pattern was the most specific finding in severe dengue infection in the study and significantly associated with severe thrombocytopenia (Platelet count <50,000/mm(3)). The clinical improvement coincided with resolving of the ultrasound findings at the time of discharge. Ultrasound can be used as an early predictor as well as an important prognostic sign for severe dengue infection especially during an epidemic.

Clinical Profile of Atypical Manifestations of Dengue Fever.

ObjectivesTo study the clinical profile and outcome of the atypical manifestations of dengue fever in children.MethodsAll children (0–12 y of age) diagnosed and confirmed as dengue fever at a tertiary care hospital at Puducherry, between the 1st of August 2012 and January 31st 2015 were reviewed retrospectively from hospital case records as per the revised World Health Organization (WHO) guidelines 2011 for dengue fever. The diagnosis was confirmed by NS1 antigen-based ELISA test or dengue serology for IgM and IgG antibodies and the data was analyzed using SPSS 16.0 statistical software.ResultsOut of 254 children admitted with dengue fever, non-severe dengue and severe dengue were seen in 62.6 % and 37.4 % respectively. Atypical manifestations were seen in 106 cases (41.7 %). Mean age of presentation was 6.9(3.3) y. M: F ratio was 1.2:1. The common manifestations of severe dengue infection were shock (37.4 %), bleeding (20.1 %) and multi-organ dysfunction (2.4 %). The most common atypical manifestations of dengue fever were lymphadenopathy (41.7 %), splenomegaly (21.2 %), biphasic fever (18.1 %), hepatitis (11.4 %), febrile diarrhea (6.3 %), refractory shock (2.4 %) and impaired consciousness (1.9 %). The other atypical manifestations present were portal hypertension, acalculous cholecystitis, appendicitis, acute respiratory distress syndrome (ARDS), myocarditis, pericardial effusion, paroxysmal supraventricular tachycardia (PSVT), myositis, acute kidney injury (AKI), hemophagocytic syndrome and disseminated intravascular coagulopathy (DIC). Platelet count did not always correlate well with the severity of bleeding. There were six deaths (2.4 %) and out of them four presented with impaired consciousness (66.6 %). The common causes for poor outcome were multiorgan failure, encephalopathy and refractory shock.ConclusionsThe atypical manifestations of dengue fever are no more a rare entity. Clinicians should have a high index of suspicion and vigilance for atypical manifestations of dengue fever as lack of timely detection and management could be fatal. Impaired consciousness was the most ominous atypical manifestation of severe dengue infection.

Is Reactive Dengue NS1Antigen Test a Warning Call for Hospital Admissions?

Dengue fever is a major public health problem worldwide. The 2011 revised World Health Organization (WHO) guidelines have emphasized on early diagnosis and intervention to reduce the case fatality rate due to dengue fever. Rapid diagnostic tests like NS1 antigen assays have improved the detection of cases in early clinical phase of illness but its role as a predictor of severe dengue infection is not very clear. To evaluate the utility of NS1 Ag assay as an early diagnostic marker and predictor of severe dengue infection. All children (0-12 years of age) diagnosed and confirmed with dengue fever at a tertiary care hospital in Puducherry between 01(st) August 2012 and 31(st) July 2015 were reviewed retrospectively from hospital case records as per the revised WHO guidelines for dengue fever. The diagnosis was confirmed by NS1antigen-based ELISA test or dengue serology for IgM and IgG antibodies and the data were analysed using SPSS 16.0 statistical software. After collecting all the data, all the variables were summarised by descriptive statistics. Categorical variables were expressed as frequencies and percentages, and then analysed by the χ(2) test or fishers exact test, where appropriate. Significance was taken at p-value< 0.05. Among the 261 confirmed cases of dengue fever non-severe dengue and severe dengue infection was seen in 60.9% and 39.1% respectively. The mean age of presentation was 6.9 years and M:F ratio was 1.2:1. NS1 Ag was positive in 217 cases (83.1%) and among them non-severe dengue and severe dengue was seen in 65.9% and 34.1% cases respectively. A total of 44 cases (16.9%) were negative for NS1 Ag assay and positive for IgM MAC ELISA and among them 16 children (36.4%) had non-severe dengue infection where as 28 children (63.6%) had severe dengue infection. Secondary infection with (MAC-ELISA IgG) was seen in 17 cases (6.5%). NS1Ag assay was predominantly positive in acute phase sera, where as IgM/IgG MAC ELISA was predominantly positive in convalescent phase sera. There were six deaths (2.3%) and the common causes of poor outcome were multiorgan failure, encephalopathy and refractory shock. NS1 Ag assay is a useful early diagnostic marker for dengue fever but cannot be used as an early predictor of severe dengue infection. The criteria for admission in hospitals of cases of dengue fever should be based on clinical warning signs rather than positive NS1 Antigen test.

Diagnostic accuracy of peripheral venous lactate and the 2009 WHO warning signs for identifying severe dengue in Thai adults: a prospective observational study.

BackgroundDengue is the most common mosquito-borne viral disease in humans. However, the sensitivities of warning signs (WSs) for identifying severe dengue in adults are low, and the utility of lactate levels for identifying severe dengue in adults has not been verified. Therefore, we aimed to evaluate the diagnostic accuracy of using peripheral venous lactate levels (PVL), as well as WSs established by the World Health Organization, for identifying severe dengue.MethodsWe prospectively evaluated individuals hospitalized for dengue who were admitted to the Hospital for Tropical Diseases in Thailand between May 2013 and January 2015. Blood samples to evaluate PVL levels were collected at admission and every 24 h until the patient exhibited a body temperature of <37.8 °C for at least 24 h. Data were recorded on a pre-defined case report form, including baseline characteristics, clinical parameters, and laboratory findings.ResultsAmong 125 patients with confirmed dengue, 105 (84.0 %) patients had non-severe dengue, and 20 (16.0 %) patients had severe dengue. The presence of clinical fluid accumulation as a WS provided high sensitivity (75.0 %, 95 % confidence interval [CI]: 50.9–91.3 %) and specificity (90.5 %, 95 % CI: 83.2–95.3 %). The PVL level at admission was used to evaluate its diagnostic value, and receiver operating characteristic curve analysis revealed an area under the curve of 0.84 for identifying severe dengue. At the optimal cutoff value (PVL: 2.5 mmol/L), the sensitivity and specificity were 65.0 % (95 % CI: 40.8–84.6 %) and 96.2 % (95 % CI: 90.5–99.0 %), respectively. A combined biomarker comprising clinical fluid accumulation and/or PVL of ≥2.5 mmol/L provided the maximum diagnostic accuracy for identifying severe dengue, with a sensitivity of 90.0 % (95 % CI: 68.3–98.8 %) and a specificity of 87.6 % (95 % CI: 79.8–93.2 %).ConclusionsClinical fluid accumulation and/or PVL may be used as a diagnostic biomarker of severe dengue among adults. This biomarker may facilitate early recognition and timely treatment of patients with severe dengue, which may reduce dengue-related mortality and hospital burden.

Biomarkers in differentiating clinical dengue cases: A prospective cohort study

Objective: To evaluate five biomarkers (neopterin, vascular endothelial growth factor-A, thrombomodulin, soluble vascular cell adhesion molecule 1 and pentraxin 3) in differentiating clinical dengue cases. Methods: A prospective cohort study was conducted whereby the blood samples were obtained at day of presentation and the final diagnosis were obtained at the end of patients’ follow-up. All patients included in the study were 15 years old or older, not pregnant, not infected by dengue previously and did not have cancer, autoimmune or haematological disorder. Median test was performed to compare the biomarker levels. A subgroup Mann-Whitney U test was analysed between severe dengue and non-severe dengue cases. Monte Carlo method was used to estimate the 2-tailed probability (P) value for independent variables with unequal number of patients. Results: All biomarkers except thrombomodulin has P value < 0.001 in differentiating among the healthy subjects, non-dengue fever, dengue without warning signs and dengue with warning signs/severe dengue. Subgroup analysis for all the biomarkers between severe dengue and non-severe dengue cases was not statistically significant except vascular endothelial growth factor-A (P < 0.05). Conclusions: Certain biomarkers were able to differentiate the clinical dengue cases. This could be potentially useful in classifying and determining the severity of dengue infected patients in the hospital.

Identification of clinical factors associated with severe dengue among Thai adults: a prospective study.

BackgroundDengue is the most common mosquito-borne viral disease in humans. Recently, there has been an epidemic shift of dengue from mainly affecting children to affecting more adults with increased severity. However, clinical factors associated with severe dengue in adults have varied widely between studies. We aimed to identify the clinical factors associated with the development of severe dengue according to the World Health Organization (WHO)’s 2009 definition.MethodsWe conducted a prospective study of adults with dengue admitted to the Hospital for Tropical Diseases in Bangkok, Thailand, from October 2012 to December 2014. Univariate and stepwise multivariate logistic regression analyses were performed.ResultsOf the 153 hospitalized patients with confirmed dengue viral infections, 132 (86.3 %) patients had non-severe dengue including dengue without warning signs (7 patients, 5.3 %) and dengue with warning signs (125, 94.7 %). The rest (21, 13.7 %) had severe dengue including severe plasma leakage (16, 76.2 %), severe organ involvement (16, 76.2 %), and severe clinical bleeding (8, 38.1 %). Using stepwise multivariate logistic regression, clinical factors identified as independently associated with the development of severe dengue were: (1) being >40 years old (odds ratio [OR]: 5.215, 95 % confidence interval [CI]: 1.538–17.689), (2) having persistent vomiting (OR: 4.817, CI: 1.375–16.873), (3) having >300 cells per μL of absolute atypical lymphocytes (OR: 3.163, CI: 1.017–9.834), and (4) having lactate levels ≥2.0 mmol/L (OR: 7.340, CI: 2.334–23.087). In addition, increases in lactate and absolute atypical lymphocyte levels corresponded with severe dengue (p < 0.05).ConclusionsOur study identified several clinical factors independently associated with the development of severe dengue among hospitalized adults with dengue. This can aid in the early recognition and prompt management of at-risk patients to reduce morbidity and mortality.

SERUM LEVELS OF COPPER AND IRON IN DENGUE FEVER.

SUMMARYThe role of trace elements in dengue virulence is not yet known. The present study assessed the serum levels of two micronutrients, copper and iron, in cases of dengue fever. The study involved 96 patients of whom 48 had either severe or non-severe forms of dengue (with and without warning signs), and the remaining 48 were patients with other febrile illnesses (OFI), used as controls. Serum levels of copper and iron were evaluated at admission and by the time of defervescence using commercially available kits. At admission, no difference in the level of serum copper was observed between cases and controls. In the group of dengue cases, the copper level was found to be significantly decreased in severe and non-severe cases with warning signs, compared to non-severe cases without warning signs. In contrast, by the time of defervescence the copper level was found to be increased in all dengue cases compared to OFI controls, but no difference was observed among dengue cases. Unlike OFI controls, dengue cases showed an increasing pattern of copper levels from admission until defervescence. On the other hand, no such significant differences were observed in the serum level of iron in the clinical groups, except for a decreased iron level found in severe cases, compared to non-severe dengue without warning signs. The results show that copper is associated with dengue severity and this finding emphasizes the need to investigate the involvement of trace elements in disease severity so as to improve the prognosis of dengue.

Dengue in adults admitted to a referral hospital in Hanoi, Vietnam.

Knowledge of adult dengue virus (DENV) infection from Hanoi, Vietnam, is limited. In 2008, we prospectively studied 143 (77 male) confirmed (nonstructural 1 antigen enzyme-linked immunosorbent assay [ELISA], DENV polymerase chain reaction, paired serology) adult dengue patients of median age 23.5 (range 16–72) years. They were admitted to the National Hospital for Tropical Diseases, Hanoi, on median illness day (D) 5 (range 1–8). By D8, 141 (98.6%) were afebrile. Platelet counts and hematocrit (median, interquartile range [IQR]) nadired and peaked on D5 and D4, respectively: 40,000/μL (10,000–109,000/μL), 43.4% (34.9–49.7%). Four (2.8%) patients had severe dengue: 1) D10 shock (N = 1) and 2) aspartate aminotransferase (AST) ≥ 1,000 IU/L (N = 3, D5 and D7). Of 143 patients, 118 (82.5%) had ≥ 1 warning sign (World Health Organization [WHO] 2009 criteria): mucosal bleeding 66/143 (46.1%), soft tissue edema 54/143 (37.7%), and ultrasound detected plasma leakage (pleural effusions/ascites) 30/129 (23.25%). 138 (96.5%) patients received intravenous (IV) fluids: 3 L (IQR: 0.5–8.5 L). Most patients had non-severe dengue with warning signs. High rates of edema and plasma leakage may be explained partly by liberal use of IV fluids. Studies are needed on optimizing fluid management in non-severe adult dengue.

Normal free interleukin-18 (IL-18) plasma levels in dengue virus infection and the need to measure both total IL-18 and IL-18 binding protein levels.

Activated monocytes/macrophages and T lymphocytes that produce a cytokine storm are assumed to play a pivotal role in the pathogenesis of dengue. Interleukin-18 (IL-18) is a proinflammatory cytokine that is increased during dengue and known to induce gamma interferon (IFN-γ), which is crucial for dengue immune response. No data are available regarding the balance between IL-18 and its natural inhibitor IL-18 binding protein (IL-18BP) and how they interact within the inflammatory reaction of patients with dengue virus infections. Circulating levels of IL-18; IL-18BP; free, biologically active IL-18; the IL-18-dependent proinflammatory cytokine IFN-γ; monocyte-derived cytokines; and ferritin were assessed in adult Indonesian dengue patients (n = 95). Healthy individuals (n = 22) and leptospirosis (n = 19) and enteric fever (n = 6) patients served as controls. Total IL-18 levels were increased during dengue, leptospirosis, and enteric fever compared to healthy controls. However, due to a concurrent increase in IL-18BP levels, biologically active IL-18 levels remained similar in the different phases of dengue and in patients with leptospirosis. Biologically active IL-18 levels were also similar in patients with severe and nonsevere dengue. In conclusion, high total IL-18 and IL-18BP levels concur in dengue virus infections, leptospirosis, and enteric fever. This resulted in unchanged levels of free, biologically active IL-18 in dengue and leptospirosis, which underlines the importance of measuring both IL-18 and IL-18BP when studying the role of IL-18 in diseases.

Time since onset of disease and individual clinical markers associate with transcriptional changes in uncomplicated dengue.

BackgroundDengue virus (DENV) infection causes viral haemorrhagic fever that is characterized by extensive activation of the immune system. The aim of this study is to investigate the kinetics of the transcriptome signature changes during the course of disease and the association of genes in these signatures with clinical parameters.Methodology/Principle FindingsSequential whole blood samples from DENV infected patients in Jakarta were profiled using affymetrix microarrays, which were analysed using principal component analysis, limma, gene set analysis, and weighted gene co-expression network analysis. We show that time since onset of disease, but not diagnosis, has a large impact on the blood transcriptome of patients with non-severe dengue. Clinical diagnosis (according to the WHO classification) does not associate with differential gene expression. Network analysis however, indicated that the clinical markers platelet count, fibrinogen, albumin, IV fluid distributed per day and liver enzymes SGOT and SGPT strongly correlate with gene modules that are enriched for genes involved in the immune response. Overall, we see a shift in the transcriptome from immunity and inflammation to repair and recovery during the course of a DENV infection.Conclusions/SignificanceTime since onset of disease associates with the shift in transcriptome signatures from immunity and inflammation to cell cycle and repair mechanisms in patients with non-severe dengue. The strong association of time with blood transcriptome changes hampers both the discovery as well as the potential application of biomarkers in dengue. However, we identified gene expression modules that associate with key clinical parameters of dengue that reflect the systemic activity of disease during the course of infection. The expression level of these gene modules may support earlier detection of disease progression as well as clinical management of dengue.

Naturally activated B-lymphocytes for dengue infection secrete CD27 and their plasma level is associated with severe forms of pediatric dengue

Naturally activated B-lymphocytes for dengue infection secrete CD27 and their plasma level is associated with severe forms of pediatric dengue

Utility of C-Reactive Protein Levels for Early Prediction of Dengue Severity in Adults.

Dengue has broad clinical presentation with unpredictable clinical evolution and outcome. We aimed to evaluate the utility of C-reactive protein (CRP) levels for distinguishing between mild and severe cases in the early phase of the dengue illness. We retrospectively evaluated adults with dengue from 2006 to 2014, according to 1997 and 2009 World Health Organization (WHO) criteria for severity. Of 191 included patients, 32.9% had nonshock dengue hemorrhagic fever (DHF), 3.1% dengue shock syndrome (DSS), and 7.9% severe dengue. The risk of DHF/DSS and severe dengue is significantly related to the increasing levels of CRP. Of 191 patients, 97 had CRP levels measured during the febrile (days 1–3); 85 during the critical (days 4–6); and 9 during the convalescent (days 7–10) illness phases. During the febrile phase, there was significant higher CRP level for DSS versus DF/nonshock DHF and severe dengue versus nonsevere dengue, with CRP cutoff level 30.1 mg/L (area under the receiver operating characteristic curve (AUC), 0.938; 100% sensitivity, 76.3% specificity) and 24.2 mg/L (AUC, 0.717; 70% sensitivity, 71.3% specificity), respectively. Our study highlights the utility of the CRP levels in early prediction of DSS and severe dengue in adult patients.