Dengue Hemorrhagic Fever Group Research Articles

Are we contented with achieving universal health coverage in treating dengue patients in Sri Lanka?

Background: The preventive and curative services for dengue illness cause a significant financial burden on the state health sector. Household costs and out-of-pocket expenditure (OOPE) too are important cost components embedded with dengue illness. The objective was to estimate the household costs and out-of-pocket expenses incurred due to dengue infection among adults who received institutional care in Colombo district, Sri Lanka.Methods: A longitudinal study was conducted from July to December 2018. Fifty patients recruited from dengue fever (DF) and dengue hemorrhagic fever (DHF) categories. Adults residing in the Colombo district for more than six months prior to dengue illness were recruited based on systematic sampling. Data was collected via an interviewer-administered questionnaire on the day of discharge from the hospital and followed up for two weeks. Unit cost per patient was calculated. Household costs were calculated for 3 phases: ambulatory, during, and post-hospitalization. These components were described using mean, median, standard deviation and inter-quartile range, and OOPE.Results: The median age in the DF group was 38.5 years and in the DHF group was 28.5 years. The average household cost was US$ 127.69 (SD=93.32) and US$ 134.71 (SD=94.31) for DF and DHF patients respectively. Among DF patients 98.03% were borne using OOPE and among DHF patients it was 95.57%.Conclusions: If an adult member is hospitalized with dengue infection the OOPE is high, which is nearly 25% of a family’s monthly income. Strengthening dengue control programme is the key to universal health coverage (UHC).

Classical and Hemorrhagic Dengue among Bangladeshi Adults: A Single Center Cohort Study

Background: Dengue is a mosquito-borne viral disease worldwide. The number of new cases and mortality in Bangladesh increased in recent years. This study aims to observe the difference between demographic data, warning signs, high-risk co-morbidity, treatment pattern, and laboratory investigations in two different types of dengue fever during the pick tropical season. Method: This retrospective observational study was done in Holy Family Red Crescent Medical College from May to October 2019 from hospital records of a total of 102 dengue NS1 positive patients. The classical dengue fever (CDF) group consists of 72 patients and the dengue hemorrhagic fever (DHF) group consists of 30 patients. Demographic data, high-risk co-morbidity (pregnancy, old age, DM, HTN), ‘warning sign’ (abdominal tenderness, mucosal bleeding, lethargy, restlessness, persistent vomiting, clinical fluid accumulation, liver enlargement > 2cm, increase HCT, decrease Platelet), treatment pattern, and laboratory findings were compiled, analyzed and compared between two varieties. Result: Out of 102 patients, the majority were male 63 (61.76%). The mean age was 34 years in both groups of patients. ‘Warning signs’ were observed in a higher percentage in the dengue hemorrhagic fever group, which were statistically significant (p < 0.01 and p < 0.05). Most of the patients (80.55%, 93.33%) received 1000 ml infusion/day in both groups. Where only 15 patients received fresh frozen plasma. Use of cephalosporin (30%), steroid (43.33%), and tranexamic acid (23.33%) were higher percentages in dengue hemorrhagic fever than classical dengue fever (12.5%, 26.39%, 18.05%). Among hematological tests, changes observed in platelet and total WBC count in between two groups were statistically significant. Radiological and other lab findings also revealed a higher percentage of patients affected in the dengue hemorrhagic fever group. Conclusion: The incidence rate of classical dengue was higher than the hemorrhagic type, but the ‘warning sign’ and significant thrombocytopenia and leucopenia in hemorrhagic dengue fever can be considered for the progression towards dengue shock syndrome. Monitoring hematocrit concentration and plasma therapy are not much of benefit in hemorrhagic type because of fluid accumulation.

VALIDATION OF SIGNIFICANT PROTEIN MARKERS FROM THE PLASMA OF SEVERE DENGUE INFECTED ADULT PATIENTS USING SELECTED REACTION MONITORING ASSAY

ABSTRACT Background :Infection with dengue virus (DENV) causes a spectrum of clinical manifestations ranging from mild dengue fever (DF) to the potentially lethal dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Dengue is endemic to the tropical and sub-tropical regions of the world, which are home to over half the population of the world as well as being popular tourist destinations Aim :To study about information of the pathogenesis and clinical profile of dengue virus and Validation of significant protein markers of dengue infected adult patients using selected reaction monitoring assays. Material &amp;Methods :This study was conducted in Department of Medicine, Sardar Patel Medical College, Bikaner from July 2017 to December 2018. Total 26 cases with features of dengue illness along with positive dengue serology in this duration were admitted in hospital. This was a hospital based study. Results : Proteomic analysis in severe dengue patients (DHF/DSS) shows down regulation of three significant proteins CD-44 antigen, complement component C8 beta chain and leucine-rich alpha-2-glycoprotein as compared to healthy controls. According to dengue agglutination test, 100% cases had IgM positive while 69.2% cases had NS1 positive. No case had IgG positive. Mean age in DHF group was 30.4812.58 and in DSS group mean age was 25.0012.39 years and this difference was found statistically insignificant (p&gt;0.05). Most common clinical manifestation was fever, abdominal pain and myalgia (100%) while rash was present in 96.2%, vomiting and headache were present in 92.3% cases each and least common clinical manifestation was retro-orbital pain (88.5%).Gum bleeding, epistaxis and petechiae were found in most cases.According to sensorium 96.2% cases were found normal and 3.8% cases were altered sensorium.According to outcome, 20 cases were cured successfully while 6 cases discharge on request. Patients were on telephonically follow up for one week, there was no mortality. Conclusion : In present study revealed that validating 26 serum samples used for optimization by using selected reaction monitoring. Three significant proteins, CD44 Antigen, Complement component C8 beta chain, Leucine-rich alpha-2-glycoprotein are downregulated in severe dengue (DHF/DSS) patients as compared to healthy controls. These are predictive biomarkers of severe dengue fever (DHF/DSS).

Cross-Reaction, Enhancement, and Neutralization Activity of Dengue Virus Antibodies against Zika Virus: A Study in the Mexican Population.

Zika virus (ZIKV), an emerging mosquito-borne flavivirus, has quickly spread in many regions around the world where dengue virus (DENV) is endemic. This represents a major health concern, given the high homology between these two viruses, which can result in cross-reactivity. The aim of this study was to determine the cross-reacting antibody response of the IgM and IgG classes against the recombinant envelope protein of ZIKV (rE-ZIKV) in sera from patients with acute-phase infection of different clinical forms of dengue, i.e., dengue fever (DF) and dengue hemorrhagic fever (DHF) (before the arrival of ZIKV in Mexico 2010), as well as acute-phase sera of ZIKV patients, together with the implications in neutralization and antibody-dependent enhancement. Differences in IgM responses were observed in a number of DF and DHF patients whose sera cross-reacted with the rE-ZIK antigen, with 42% recognition between acute-phase DHF and ZIKV but 27% recognition between DF and ZIKV. Regarding IgG antibodies, 71.5% from the DF group showed cross-reactivity to rE-ZIKV in contrast with 50% and only 25% of DHF and ZIKV serum samples, respectively, which specifically recognized the homologous antigen. The DHF group showed more enhancement of ZIKV infection of FCRγ-expressing cells compared to the DF group. Furthermore, the DHF group also showed a higher cross-neutralizing ability than that of DF. This is the first report where DF and DHF serum samples were evaluated for cross-reactivity against Zika protein and ZIKV. Furthermore, DENV serum samples cross-protect against ZIKV through neutralizing antibodies but at the same time mediate antibody-dependent enhancement in the sequential ZIKV infection.

The correlation of clinical and subclinical presentations with dengue serotypes and plasma viral load: the case of children with dengue hemorrhagic fever in Vietnam

Numerous studies have been carried out on patients afflicted with dengue hemorrhagic fever (DHF), but various issues related to the disease, including the characteristics of the dengue virus (DENV), remain unclear. To address this deficiency, the current research was conducted to determine the correlation of clinical and subclinical presentations with dengue serotypes and plasma viral load. This prospective cohort study, which was performed at Tien Giang General Hospital from 2009 to 2014, involved 481 children who were under 15 years of age and had DHF for less than 72 hours. Results showed that among the patients, the highest proportion were composed of those suffering from DENV-1 infection (44.7%). The progression of the disease to dengue shock syndrome (DSS) owing to infection with DENV-2 and DENV-1 was significantly higher than that caused by infection with DENV-3 and DENV-4. No statistically significant differences in DENV viremia were found between the non-shock DHF and DSS groups. Finally, no correlation was found between dengue plasma viral load and clinical and subclinical presentations. The findings led to the conclusion that dengue serotypes can be used as a basis in ascertaining the prognosis of DSS and DHF.

A study of hepatobiliary manifestations in dengue viral infection

Background: Dengue viral infection is a major and important public health problem in many South East Asian (SEA) countries and also in more than 100 countries of tropical and subtropical region. The aim of study was to assess the frequency and degree of hepatobiliary dysfunction in adults with dengue infection presenting to our tertiary hospital, Karimnagar.Methods: The study was a prospective observational study conducted on 120 adult patients of serological proven dengue infection with hepatic and biliary manifestations, admitted during the period of from June 2016 to June 2017. Investigations included complete blood count, liver function test, viral serology, sepsis screen, ultrasound abdomen.Results: Majority of cases in age group of 20-56 years with male: female ration of 1.7:1. Of all the cases, 53% patients were categorized into dengue fever group, 25% into dengue hemorrhagic fever group, and 27.7% into dengue shock syndrome group in accordance to WHO guidelines.Conclusions: This study was showed that a significant hepatobiliary derangement is seen in severe cases of dengue. Early recognition of such perturbations helps guide further management to prevent mortality.

TROMBOSIT TERENDAH, KENAIKAN HEMATOKRIT DAN KADAR TNF-α SEBAGAI INDIKASI KEPARAHAN INFEKSI VIRUS DENGUE PADA PASIEN DD DAN DBD

Clinical manifestations of dengue virus infection vary from unspecified fever, dengue fever (DF) and dengue hemorrhagic fever (DHF). The fundamental difference in the diagnosis between DF and DHF is plasma leakage, hypotension, thrombocytopenia and hemorrhagic diathesis in DHF. The objectives of the study were to determine the lowest platelet, haematocrit increase, and TNF-α levels in DF and DHF patients as an indication of severity of dengue virus infection. The cross-sectional study was conducted by taking 54 blood samples of patients aged 26-45 years who were infected by dengue virus and grouped into two groups: DF patient group (27 blood samples) and DHF group (27 blood samples). The lowest platelets and hematocrit rise were determined by Hematology Analyzer and the TNF-α levels were determined by ELISA. The data obtained were statistically analyzed by independent Mann-Whitney test. The results showed that the lowest mean platelet counts of DF patients were significantly (p &lt;0.01) higher than those of DHF patients. The mean hematocrit increase in DF patients was significantly (p &lt;0.01) lower than that of the DHF patients and the mean TNF-α levels of DF patients were significantly (p &lt;0.01) lower than the DHF patients. Based on the results of this study it can be concluded that the lowest platelets, hematocrit increase and TNF-α levels are an indication of the severity of dengue virus infection.

Correlation of enhancement Platelet Distribution Width (PDW) with severity of dengue infection

Dengue infections are currently one of the most rapidly emerging arboviral infections in the world. During this time the emphasis of platelets only limited about number of platelets and very rarely discuss about the quality of platelets (activation and dysfunction). Changes in PDW reflects the activation of platelets. Aim of this study is to analyze the prevalence ratio of PDW enhancement in dengue hemorrhagic fever (DHF) compared to dengue fever (DF). This was a cross-sectional study to analyze the prevalence ratio of enhancement PDW in DHF compared to DF. The subjects were dengue suspected patients who meet the inclusion and exclusion criteria. Venous blood were collected for automatical hematology analysis (include PDW). Different proportions of PDW enhancement between DHF and DF groups was analyzed by Chi-square. One hundred subjects were participated in this study and classified into DF and DHF. Prevalence ratio of PDW enhancement (>64.8%) was 3.1 (95% CI 1.5 – 20.7), p 0.006. The result indicates that PDW enhancement was a risk factor of worsening dengue infection.

Correlation of enhancement Mean Platelet Volume (MPV) with severity of dengue infection

Dengue infection is one of the infectious diseases which become a health problem in the world. Platelets play an important role in the pathogenesis of dengue. The quantity of platelet related to dengue were often discussed but the quality of platelet related to dengue infection were rarely discussed. The activation of platelets can be observe indirectly through changes in MPV. Aim of this study is to analyze the prevalence ratio of MPV enhancement in dengue hemorrhagic fever (DHF) compared to dengue fever (DF). This study is an observational analytical study with a cross-sectional design to analyze the prevalence ratio of enhancement MPV in DHF compared to DF. The subjects were dengue suspected patients that hospitalized in Dr. Sardjito General Hospital and PKU Muhammadiyah Hospital Yogyakarta who meet the inclusion and exclusion criteria. Venous blood were collected into 2 mL EDTA tube for automatical hematology analysis. Chi-square was used to analyze different proportions of MPV enhancement between DHF and DF groups. One hundred subjects were participated in this study and classified into DF and DHF based on WHO 2011 criteria. Prevalence ratio of MPV enhancement ≥ 9.7 fL was 4.8 (95% CI 2.8-37.0), p < 0.0001. The result indicates that MPV enhancement was a risk factor of worsening dengue infection.

Plasma Neutrophil Elastase, α1-Antitrypsin, α2-Macroglobulin and Neutrophil Elastase-α1-Antitrypsin Complex Levels in patients with Dengue Fever.

Dengue fever (DF) is characterized by systemic inflammatory response including neutrophil activation leading to uncontrolled elastase activity. This study was aimed to measure the activity of plasma neutrophil elastase (NE), its endogenous inhibitors α1-antitrypsin (α1-AT) and α2-macroglobulin (α2-MG) and elastase in complex with α1-AT (NE-α1-AT complex) in DF. 50 dengue patients [39 DF and 11 dengue hemorrhagic fever (DHF)] and 52 healthy subjects were included in the study. NE was measured using N-succinyl-tri-alanine-p-nitroanilide as substrate. α1-AT, α2-MG and NE-α1-AT complex were estimated by ELISA. The result analysis indicated that the dengue patients had significantly higher elastase activity with significantly reduced inhibitor levels compared to controls. Between DF and DHF patients, DHF group had significantly higher elastase activity. In conclusion, significantly elevated NE and reduced inhibitors level in dengue fever indicate these parameters could be of significance in DF particularly for the assessment of progression of inflammatory processes.

Association of BAK1 single nucleotide polymorphism with a risk for dengue hemorrhagic fever

BackgroundDengue hemorrhagic fever (DHF) is a severe life-threatening form of dengue infection. Low platelet count is one of the characteristic clinical manifestations in patients with severe dengue. However, little is known about genetic factors in the host that cause low platelet count in patients with dengue.MethodsA previous genome-wide association study of hematological and biochemical traits identified single nucleotide polymorphisms (SNPs) associated with low platelet count in healthy subjects. To examine the possible association of these SNPs with DHF, 918 Thai patients with dengue [509 patients with DHF and 409 with dengue fever (DF)] were genotyped for five SNPs: rs5745568 in BAK1, rs6141 in THPO, rs6065 in GP1BA, rs739496 in SH2B3, and rs385893 in RCL1. In addition, rs4804803 in CD209, that has been reported to be associated with dengue infection, was also genotyped to examine if rs4804803 affects the association detected in this study.ResultsThe allele frequencies of each SNP were compared between the DHF and DF groups. Among the five SNPs, the G allele of rs5745568 in BAK1 was significantly associated with a risk for DHF [P = 0.006 and crude odd ratio (95 % confidence interval) = 1.32 (1.09–1.60)]. The association of this allele with DHF was also significant in a logistic regression analysis adjusted for age, sex, hospital (i.e., geographic region), immune status (i.e., primary or secondary infection), and virus serotype [P = 0.016 and adjusted odd ratio (95 % confidence interval) = 1.29 (1.05–1.58)]. The result was not influenced by rs4804803 [P = 0.0167 and adjusted OR (95 % CI) = 1.29 (1.05–1.58)]. No other SNPs including rs4804803 showed significant association.ConclusionsThe low-level constitutive production of platelets caused by the G allele of rs5745568 seems to increase the risk of bleeding in dengue infection. Our results suggest that BCL-2 homologous antagonist/killer (BAK) protein, encoded by BAK1, plays a crucial role in the pathogenesis of DHF.

Association between nutritional status and dengue infection: a systematic review and meta-analysis.

BackgroundDengue infection has various clinical manifestations, often with unpredictable clinical evolutions and outcomes. Several factors including nutritional status have been studied to find the relationship with dengue severity. However, the nutritional status had conflicting effects on the complication of dengue in some previous studies. Therefore, we conducted a systematic review and performed a meta-analysis to analyze the association between nutritional status and the outcome of dengue infection.MethodsEleven electronic databases and manual searching of reference lists were used to identify the relevant studies published before August 2013. At least two authors worked independently in every step to select eligible studies and extract data. Dengue severity in the included studies must be classified into three categories: dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS).ResultsThirteen articles that met the inclusion criteria came to final analysis. A meta-analysis using fixed- or random-effects models was conducted to calculate pooled odds ratios (OR) with corresponding 95 % confidence intervals. It has shown that there was no statistically significant association between DHF group and DSS group in malnutritional and overweight/obesity patients with OR: 1.17 (95 % CI: 0.99–1.39), 1.31 (0.91–1.88), respectively. A significantly inverse relation between DF and DHF groups of malnutritional patients was revealed (OR = 0.71, 95 % CI: 0.56–0.90). Our meta-analysis also indicated a statistically significant negative correlation between malnourished children with dengue virus infection and healthy children (OR = 0.46, 95 % CI: 0.3–0.70). When analyzing patients with normal nutrition status, we found out that there was a significantly negative relationship between DHF and DSS groups (0.87; 95 % CI: 0.77–0.99). Other comparisons of DSS with DF/DHF groups, DSS/DHF with DF groups, and DHF with DF groups in normal nutritional patients showed no significant correlation. However, the findings should be interpreted cautiously because all significant associations were lost after removing of the largest study.ConclusionsResults from previous studies failed to show any solid consistency regarding the association between the nutritional status and dengue infection. Consequently, the effects of nutritional status on dengue disease outcome has been controversial. Further studies are recommended to clarify the impact of nutritional status on dengue infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1498-y) contains supplementary material, which is available to authorized users.

Changing clinical profile of Dengue infection: A newer perspective in the pediatric population

Background: Traditionally complications of Dengue infection is limited to vascular and haematological system. The present study describes the changing clinico-epidemiological and laboratory profile of children hospitalized with dengue infec- tion. Methods: Prospective observational study of children hospitalized with a diagnosis of dengue illness from October to December, 2010 at a tertiary care centre in Kolkata. Results: Of 50 children admitted with dengue infection, 24 had dengue fever (DF), 18 dengue hemorrhagic fever (DHF) and 8 had dengue shock syndrome (DSS). The mean age of affected children was 6.25 ± 3.34 years, mostly being males from rural areas. The common clinical manifestations were fever, rash, body ache, hemorrhagic manifestations and oedema. While headache and body ache was commoner among DF cases, rash and hemorrhagic manifesta- tions were significantly more among DHF group. Incidence of altered sensorium, neck rigidity, fulminant hepatitis, and sple- nomegaly were significantly higher among the DHF/DSS group. 12% case fatality rate was found. Conclusion: Clinical mani- festations of dengue seem to be changing. Fever, rash and bodyache are not the only clinical presentations. Encephalopathy, encephalitis, 6 th cranial nerve palsy, fulminant hepatic failure, acute acalculous cholecystitis, myocarditis, myelitis, spleno- megaly are some unusual but novel presentations of dengue in pediatric population that clinician in endemic area should be aware of though they are not mentioned in conventional guidelines Dengue is no longer restricted to urban areas but has propensity to spread to rural areas also.

Serum Angiopoietin-2 as Marker of Plasma Leakage in Dengue Viral Infection

Background. The immunopathology of DHF/DSS is yet completely understood. Angiopoietin-2 (Ang-2) produced by endothelial cell could promote vascular leakage by disrupting endothelial junction. Few studies reported the role of Ang-2 in dengue viral infection. Objective. To study the role of Ang-2 in promoting vascular leakage in dengue viral infection. Methods. Prospective cohort study conducted at Prof. Dr. R.D. Kandou, Pancaran Kasih and R.W. Mongonsidi General Hospitals in Manado, from March 2013 to October 2014. Children, aged 1-15 years old, with the diagnosis of dengue viral infection according to 1997 World Health Organization (WHO) criteria [Dengue Fever (DF), Dengue Hemorrhagic Fever (DHF), Dengue Shock Syndrome (DSS)],were recruited consecutively. Written informed consent was obtained from parents or legal guardian. Blood samples were obtained at the time of diagnosis and 48 hours after, evaluated for complete blood counts, albumin, NS-1, Ig M, Ig G anti-dengue, and Ang-2. Results. During the study period, there were 119 children with dengue viral infections (39 DF, 39 DHF, 41 DSS). Patient’s characteristics: female predominance, age between 1.5-8.5 years old, well nourished, and mean albumin level were less than ≤3.5 gr% in the DHF and DSS group. Ang-2 level at admission were 2,486.21 pg/dl, 3,194.95 pg/dl and 4,005.32 pg/dl in DF, DHF and DSS group, respectively. Anova test analyses shows significant differences in serum Ang-2 level at admission between DF, DHF and DSS group (p<0.0001). Between those groups, DSS group had the highest level of Ang-2, followed with DHF and DF. Discussion. Mean albumin level were 3.88 gr%, 3.39 gr% and 2.63gr% in DF, DHF and DSS group, respectively. This results shows increasing plasma leakage with increasing severity of dengue viral infection. Increasing level of Ang-2 can promote blood vessels instability therefore causing increased vascular permeability and subsequent plasma leakage. In this study, we found significant elevation of serum Ang-2 in patiens with DSS compared to DHF and DF but the difference was not significant between DF and DHF group. Conclusions. Angiopoietin-2 contributes in transient systemic vascular leak in dengue viral infection.

The Levels of Troponin T in Patients with Dengue Hemorrhagic Fever

Introduction: The incidence of myocarditis on Dengue Hemorrhagic Fever (DHF) is still controversial because the disease was asymptomatic and definitive diagnosis only with endocardial biopsy. More specific and sensitive examination to detect the cardiac disorder is cardiac enzyme likes the level of troponin T. Objective: This study aims to evaluate the level of troponin T in patients with dengue shock syndrome (DSS) and dengue hemorrhagic fever without shock. Methods: The research conducted a cross-sectional study at Child Health Department of Dr. Wahidin Sudirohusodo Hospital, Makassar, from July to October 2012. The population included children with DHF admitted to the hospital of Dr. Wahidin Sudirohusodo, Ibnu Sina and Faisal Islamic. Diagnosis of DHF was established based on history taking, physical and laboratory examination. Results: There were 70 samples who met the criteria, including 35 patients of DSS and 35 patients of dengue hemorrhagic fever without shock. The level of troponin T was higher on DSS group than DHF group with the cut off point of ≥0.007 ng/ml is the best level to distinguish between dengue shock syndrome and dengue hemorrhagic fever without shock (p=0.000, sensitivity 97.1%, specificity 88.6%, positive predictive value 89.5%, negative predictive value 96.9%,OR 18.7; 95% CI 15.3–1417.5). Conclusion: The level of troponin T was higher on DSS group than dengue hemorrhagic fever without shock group because on DSS occurs to stress caused by hypoperfusion. But the level of troponin T between two groups within normal limits, not found cardiac disorder such as myocarditis on DHF.

Study of Hepatic Dysfunction in Patientsinfected with Dengue Virus

Dengue fever is a fatal infection affecting the lives of the patients and this study was designed to further explore its pathological effects. A total of 200 consecutives of dengue viral infection were included in this prospective descriptive study conducted at the Department of Pathology, University of Veterinary and Animal Sciences, Lahore from October, 2009 to September, 2010. A special proforma was designed to collect all the relevant clinical information from each patient. All the strip positive cases of dengue virus were further confirmed by performing IgM capture ELISA and then analyzed for hepatic impairment through liver function tests including serum bilirubin, serum alkaline phosphatase, serum ALT and AST. The results were then gathered and analyzed. The already existing liver diseases like hepatitis A, B, C, E and inherited liver disorders were not included in the study. Total number of patients included in study with Dengue IgM +ve were 200. Out of 200 cases 130 were male and 70 were females. The patients were categorized into two classes according to severity of sign symptoms like puerperal rash on the body. The classes are dengue fever (DF) and dengue hemorrhagic fever (DHF). The total number of DF cases was 28.50% (57/200) and number of DHF cases was 71.50% (143/200). The patients of DHF group were found to have more liver derangement that is 90.20% (128/200) while the patients belonging to DF group were at a less risk for impairment of liver function that is 9.80% (15/200). The patients with dengue hemorrhagic fever are more prone to have liver enzyme derangement and it has a direct relation with the titer IgM in the body of patients infected with dengue virus. The liver enzyme which are found to be more raised are serum ALT and AST while serum alkaline phosphatase and serum bilirubin are not markedly raised.

Elevated levels of full-length and thrombin-cleaved osteopontin during acute dengue virus infection are associated with coagulation abnormalities

IntroductionDengue virus (DENV) is transmitted by the mosquito vector, and causes a wide range of symptoms that lead to dengue fever (DF) or life-threatening dengue hemorrhagic fever (DHF). The host and viral correlates that contribute to DF and DHF are complex and poorly understood, but appear to be linked to inflammation and impaired coagulation. Full-length osteopontin (FL-OPN), a glycoprotein, and its activated thrombin-cleaved product, trOPN, integrate multiple immunological signals through the induction of pro-inflammatory cytokines. Materials and MethodTo understand the role of OPN in DENV-infection, we assessed circulating levels of FL-OPN, trOPN, and several coagulation markers (D-dimer, thrombin-antithrombin complex [TAT], thrombomodulin [TM], and ferritin in blood obtained from 65 DENV infected patients in the critical and recovery phases of DF and DHF during a dengue virus epidemic in the Philippines in 2010. ResultsLevels of FL-OPN, trOPN, D-dimer, TAT, and TM were significantly elevated in the critical phase in both the DF and DHF groups, as compared with healthy controls. During the recovery phase, FL-OPN levels declined while trOPN levels increased dramatically in both the DF and DHF groups. FL-OPN levels were directly correlated with D-dimer and ferritin levels, while the generation of trOPN was associated with TAT levels, platelet counts, and viral RNA load. ConclusionOur study demonstrated the marked elevation of plasma levels of FL-OPN and thrombin-cleaved OPN product, trOPN, in DENV-infection for the first time. Further studies on the biological functions of these matricellular proteins in DENV-infection would clarify its pathogenesis.

Proteomic Profile of Circulating Immune Complexes in Dengue Infected Patients

Dengue virus is a flavivirus that causes Dengue Fever (DF), Dengue Hemorrhagic Fever (DHF), and Dengue Shock Syndrome (DSS), a serious public health problem in many countries. An auto-immune response is thought to play an important role in the pathogenesis of severe dengue and the increased level of Circulating Immune Complexes (CIC) in dengue infected patients. Therefore, a proteomic analysis of proteins in the CIC can provide a better knowledge of the pathogenesis and a potential biomarker for severe dengue. A proteomic strategy based immune complexome analysis was performed to analyze the composition of CIC from plasma of fifteen dengue infected patients and five healthy control children. A total of 111 proteins were identified in the CIC from all individuals, with 17 proteins shared by healthy, DF, DHF, and DSS groups. All detected proteins were of similar relative proportion in the CIC of healthy, DF, DHF, and DSS groups. The results also revealed a high similarity of CIC profiles between four groups of subjects when classifying identified proteins according to cellular components or functional protein categories. These results showed no evidence to support the roles of CIC mediated by auto-immune response in the pathogenesis of severe dengue.

Risk Factors of Dengue Shock Syndrome in Children

This retrospective hospital-based study was conducted to evaluate the various risk factors associated with dengue shock syndrome (DSS) in patients (≤18 years of age) of dengue hemorrhagic fever (DHF). Medical records of these 483 patients with DHF (IgM serology positive) were analyzed with reference to shock for various clinical and biochemical parameters. Of the 483 children, 405 were categorized in DHF group (grade I, 282 children; grade II, 123 children) and 78 in DSS group (grade III, 59 children; grade IV, 19 children). Using univariate and multivariate logistic regression and p-value of <0.05 as significant, the presence of spontaneous bleeding, hepatomegaly, signs of capillary leakage like ascitis and pleural effusion, leucopenia <4000 mm(3) and age >5 years were found out to be significant risk factors of shock in pediatrics patients of DHF.

Endothelial Dysfunction in Dengue Hemorhagic Fever

Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 Dengue hemorrhagic fever (DHF) is characterized by fever, bleeding, and pleural effusion which may be caused by increased vascular permeability. Based on these findings it is assumed that endothelial dysfunction plays a role in the pathogenesis of DHF. The aims of this study was to know whether endothelial dysfunction occurs in DHF by measuring sVCAM-1, vWF, and D dimer. The relationship between endothelial dysfunction and severity of the disease would also be analyzed. This was a cross sectional study which involved 31 DHF patients and 30 non DHF fever patients as control group. The level of sVCAM-1 was determined by ELISA method, vWF by enzyme linked fluorescent assay , and D dimer by sandwich enzyme immunoassay. The results indicated that mean of sVCAM-1 level in DHF group and control group were 1323 ng/mL and 1003 ng/mL, while standard deviation (SD) were 545 ng/mL and 576 ng/mL respectively. The mean of vWF level in DHF group and control group were 284% and 327%, with SD 130% and 141% respectively. The level of sVCAM-1 did not correlate with platelet count, albumin level, D dimer level and severity of disease. There was a weak correlation between vWF level with D dimer and severity of disease ( r = 0,472 and r = -0,450 ). Conclusion: The results of this study indicate that endothelial dysfunction occurs in DHF, but there is no correlation between sVCAM-1 with severity of disease, only a weak correlation between vWF with D dimer and severity of disease is found.