Severe Dengue Infection Research Articles

Severity of Dengue Viral Infection Based on Clinical and Hematological Parameters among Pakistani Patients.

The global burden of dengue infections has increased dramatically. Early diagnosis of dengue infection is critical to proper medical management to avoid further complications in patients. This study was geared to assess the severity of dengue infections based on clinical and hematological examinations. A cross-sectional study was conducted among febrile patients with dengue infection in a teaching hospital in Pakistan. Blood samples were investigated for dengue-specific antibodies (IgM and IgG) and the nonstructural 1 antigen. The clinical findings of each subject were noted to assess the severity of the infection. Tests for hematological parameters were performed. Of 130 patients with confirmed dengue infection, 23 had severe and 107 had nonsevere dengue. Patients with severe dengue experienced mucosal bleeding (71.4%), fluid accumulation (57.1%), shock (35.7%), and gastrointestinal bleeding (28.6%). The most significant hematological findings among severe and nonsevere patients with dengue infection were thrombocytopenia, leukopenia, and a raised hematocrit level (P < 0.001). Patients with severe dengue infection showed marked thrombocytopenia, with a mean platelet count of 49.96 × 109 platelets/L. The clinical presentation of patients with dengue infection along with hematological markers are the most important clues for the diagnosis of, prognosis of, and therapy for dengue infection. Thrombocytopenia, leukopenia, and raised hematocrit levels were the most significant hematological parameters when assessing the severity of dengue infection.

Site-specific imprinting of dengue virus non-structural 1 antigen on a polydopamine-based sensing film for early detection and prognosis of dengue

Serum levels of dengue virus (DENV) non-structural 1 (NS1) antigen can serve as a valuable prognostic indicator of severe dengue infections. A quartz crystal microbalance (QCM)-based biosensor with a biomimetic recognition element was designed to quantitatively detect DENV NS1 as an early disease biomarker. To mitigate the reliance on costly viral antigens during the molecular imprinting process, a synthetic peptide mimicking a DENV NS1 epitope was used as a surrogate template for the synthesis of an epitope-imprinted polydopamine (EMIPDA) sensing film on the biosensor surface. The maximal frequency shift for DENV NS1 was obtained with an EMIPDA film synthesised using 5 mg mL−1 of dopamine monomer and 0.5 mg mL−1 of peptide template. The EMIPDA-QCM biosensor achieved low detection and quantitation limits of 0.091 μg mL−1 and 0.436 μg mL−1, respectively, allowing acute-phase detection of dengue and prognosis of the disease progression. The EMIPDA-QCM biosensor exhibited remarkable selectivity with up to 68-fold larger frequency responses towards DENV NS1 compared to a major serum protein. The site-specific imprinting approach not only enhanced the biosensing performance but also enabled a 26-fold cost reduction for biosensor functionalisation, providing a cost-effective strategy for label-free biosensing of the dengue biomarker via the biopolymer film.

Kinetics of severe dengue virus infection and development of gut pathology in mice.

Dengue virus, an arbovirus, causes an estimated 100 million symptomatic infections annually and is an increasing threat as the mosquito range expands with climate change. Dengue epidemics are a substantial strain on local economies and health infrastructure, and an understanding of what drives severe disease may enable treatments to help reduce hospitalizations. Factors exacerbating dengue disease are debated, but gut-related symptoms are much more frequent in severe than mild cases. Using mouse models of dengue infection, we have shown that inflammation and damage are earlier and more severe in the gut than in other tissues. Additionally, we observed impairment of the gut mucus layer and propose that breakdown of the barrier function exacerbates inflammation and promotes severe dengue disease. This idea is supported by recent data from human patients showing elevated bacteria-derived molecules in dengue patient serum. Therapies aiming to maintain gut integrity may help to abrogate severe dengue disease.

Clinical, Virological, and Immunological Features in Cosmopolitan Genotype DENV-2-Infected Patients during a Large Dengue Outbreak in Sri Lanka in 2017.

In 2017, Sri Lanka experienced its largest dengue epidemic and reported severe and unusual presentations of dengue with high morbidity. This outbreak was associated with the reemergence of dengue virus-2 (DENV-2), with the responsible strain identified as a variant of the previously circulating DENV-2 cosmopolitan genotype. In this study, we characterized the DENV-2 cosmopolitan genotype from patients during this epidemic. Also, we identified host factors that contributed to the severity of dengue infection in patients infected with this particular virus. Ninety-one acute serum samples from patients at the National Hospital in Kandy were randomly selected. Of these, 40.2% and 48.9% were positive for dengue IgM and IgG, respectively. NS1 antigen levels were significantly higher in primary infections. The severe dengue (SD) and dengue with warning signs (DWWS) groups exhibited significantly higher viral genome and infectivity titers than the dengue without warning signs (DWoWS) group. The highest viremia level was observed in SD patients. As for host cytokine response, interferon α (IFN-α) levels were significantly higher in the DWoWS group than in the DWWS and SD groups, whereas interleukin (IL)-12p40 and tumor necrosis factor α (TNF-α) levels in SD patients were significantly higher than in the other two groups. The TNF-α, IL-4, and monocyte chemoattractant protein-1 concentrations were positively correlated with NS1 antigen levels. From whole-genome analysis, NS4 had the highest frequency of amino acid variants, followed by the E gene. Our study suggests that viremia levels and immune responses contributed to SD outcomes, and these findings may help in identifying an effective therapeutic strategy against SD infection.

Development of a novel lectin-based gold nanoparticle point-of-care immunoassay for rapid diagnosis of patients with severe Dengue infection

ABSTRACT Rapid diagnosis of patients with severe Dengue infection can be useful for the efficient clinical management of cases caused by the Dengue virus. Lateral Flow Immunoassay (LFIA) have been broadly used for rapid Dengue diagnosis, because of their quick readouts with the human eye, simplicity of use, and affordability. Despite the availability of several commercial Dengue point-of-care assays, none has shown to be successful in discriminating between severe and nonsevere forms of Dengue infection. In the current study, for the first time, a novel lectin-based point-of-care assay for the early detection of patients with severe Dengue infection with gold-adorned sheets as detection labels is being reported. In this assay, Dengue severity was diagnosed by detecting the glycosylation profile of vitronectin, a known Dengue severity marker. Two lectins were employed namely DSA (Datura stramonium) and MAA (Maackia amurensis) that can recognize specific glycans like galactose Gal-(1–4) GlcNAc and sialic acid in an (α2–3) linkage, which displayed high sensitivity and high specificity, i.e. 90% and 85% for DSA and 90.91% and 95% for MAA. The new assay has a detection limit of 5 µg µl−1 and enables the quick (30 min) and sensitive detection of severe Dengue cases. The reported point-of-care immunoassay exhibits considerable promise for early identification of patients with Dengue severity.

Clinical Profile, Laboratory Findings and Outcome of Severe Dengue Infection among Children Admitted at a Tertiary Care Hospital in Bangladesh

Background: Dengue infection is endemic in Bangladesh and presents with varying degrees of severity of illness in children. Objective: The purpose of the present study was to assess the common clinical profile, biochemical findings and outcome of severe dengue fever in children. Methodology: This prospective cohot study was conducted on dengue NS1 or IgM or RT-PCR positive admitted children up to 14 years of age from April 2019 to October 2019 for a period of 6 months at the Pediatrics Department of Evercare Hospital, Dhaka. Data were analyzed after collection of demographic variables, presenting complaints and examination findings of 75 enrolled children. Results: A total of 75 cases were classified as severe dengue fever. The most common age of presentation was 4 to 7 years. The most common presenting symptom of severe dengue cases were fever (97.3%), abdominal pain and vomiting (77.3%) and shock (62.7%). Pleural effusion was the most common physical findings seen in 35 cases (46.6%) followed by ascites in 26 cases (34.7%). Elevation in aspartate amino transaminase AST (IU/L) was found in 82.6%, low albumin was found in 78.7% of the cases. Hypernatremia was the most common electrolyte abnormality found in 35 cases (46.7%). Regarding coagulation profile, raised D-dimer &amp; low fibrinogen were found in 53 (70.7%) &amp; 42 cases (56.0%) respectively. Activated partial thromboplastin time (aPTT) was prolonged in 37.3%. Case fatality rate (CFR) was 5.3%. Conclusion: In conclusion, raised AST and D-dimer, low fibrinogen &amp; albumin level as well as hyponatremia are significant laboratory findings indicating severity of the disease. Shock is a common presentation of severe dengue in children. Bangladesh Journal of Infectious Diseases, December 2022;9(2):40-46

Clinical profile and prognosis of severe dengue infection in pediatric population admitted to tertiary care hospital

Background: Dengue fever is one of the most important emerging vector-borne viral diseases. Approximately 500,000 out of 100 million cases develop severe dengue infection. Dengue infection is endemic to Bangladesh and presents with varying degrees of severity of illness in Bangladeshi children. Objectives was to assess the common clinical profile, biochemical findings associated with severe dengue fever, and their outcome in children less than 14 years of age. Methods: This was an observational study conducted from April 2022 to October 2022 at the Pediatrics Department of Dhaka Medical College Hospital and Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. Results: A total of 150 cases were classified as severe dengue. The most common age of presentation was 6-8 years. The most common presenting symptom was fever (97.3%) followed by abdominal pain and vomiting (77.3%) followed by shock in 94 cases (62.7%) of severe dengue. Pleural effusion was the most common physical finding seen in 70 cases (46.6%) followed by ascites in 52 cases (34.7%). Elevation in aspartate transaminase AST (IU/L) was found in 60.0%, low albumin was found in 78.7% of the cases. Hyponatremia was the most common electrolyte abnormality found in 70 cases (46.7%). Regarding coagulation profile raised D-dimer and low fibrinogen were found in 106 cases (70.7%) and 84 cases (56.0%) respectively. Activated partial thromboplastin time (aPTT) was prolonged in 37.3% of cases. The case fatality rate (CFR) was (5.3%). Conclusions: Abdominal pain and vomiting, shock, as-cities and pleural effusion were dominant features of severe disease. Raised AST and D-dimer, low fibrinogen and albumin level as well as hyponatremia are very significant findings in severe disease. Early suspicion and effective management can reduce the severity.

In-silico screening and identification of potential drug-like compounds for dengue-associated thrombocytopenia from Carica papaya leaf extracts

Dengue virus is a mosquito-borne pathogen that causes a variety of illnesses ranging from mild fever to severe and fatal dengue haemorrhagic fever or dengue shock syndrome. One of the major clinical manifestations of severe dengue infection is thrombocytopenia. The dengue non-structural protein 1 (NS1) is the primary protein that stimulates immune cells via toll-like receptor 4 (TLR4), induces platelets, and promotes aggregation, which could result in thrombocytopenia. The leaf extracts of Carica papaya seem to have therapeutic benefits in managing thrombocytopenia associated with dengue. The present study focuses on understanding the underlying mechanism of the use of papaya leaf extracts in treating thrombocytopenia. We have identified 124 phytocompounds that are present in the papaya leaf extract. The pharmacokinetics, molecular docking, binding free energy calculations, and molecular dynamic simulations were performed to investigate the drug-like properties, binding affinities, and interaction of phytocompounds with NS1 protein as well as the interactions of NS1 with TLR4. Three phytocompounds were found to bind with the ASN130, a crucial amino acid residue in the active site of the NS1 protein. Thus, we conclude that Rutin, Myricetin 3-rhamnoside, or Kaempferol 3-(2''-rhamnosylrutinoside) may serve as promising molecules by ameliorating thrombocytopenia in dengue-infected patients by interfering the interaction of NS1 with TLR4. These molecules can serve as drugs in the management of dengue-associated thrombocytopenia after verifying their effectiveness and assessing the drug potency, through additional in-vitro assays. Communicated by Ramaswamy H. Sarma

In-Silico CLEC5A mRNA expression analysis to predict Dengue susceptibility in cancer patients

Dengue fever is the fastest-growing infectious disease in the world. It is the leading vector-borne viral neglected tropical disease. The most acute immune response to dengue virus infection is dengue shock syndrome and hemorrhagic fever, which is due to the activation of CLEC5A C-type lectin domain family 5, member A (CLEC5A). It is a cell surface receptor, and its well-known ligand is the dengue virus. It gets activated by the attachment of dengue virion, which, as a result, phosphorylates its adaptor protein DAP12 leading to the induction of various pro-inflammatory cytokines. Clinical data suggested that the kidneys and lungs are among the major hit organs in the case of severe dengue infection. Here we predict kidney and lung cancer patients are vulnerable to dengue virus infection as CLEC5A mRNA expression in tumor samples using publicly available software such as TIMER and GEPIA database. We also identified the immunomodulatory role CLEC5A gene therefore targeting it could be a vital tool to cure dengue.

The acute effects of nonstructural-1 protein dengue virus type 2 on wet liver weight, zonulin expression and serum zonulin.

Intestinal leakage commonly occurs in severe dengue infection with zonulin as a biomarker. The aim of this study was to determine the effects of NS1 on liver weight, zonulin expression and serum zonulin levels. This laboratory experiment used 18 ddY mice, which were randomly divided into control (C), PBS (T1), and PBS + NS1 (T2) groups. Mice in the T1 and T2 groups were intravenously injected with 500 μl PBS only and 50 μg NS1 respectively. Mice blood samples were collected before and after three-day treatment for measurement of zonulin level. The fresh liver was weighted directly and were then used for immunostaining. The C group had lower wet liver weight compared to the T groups (p=0.001). Increased expression of liver zonulin was found in the T2 group, significant different from the C (p=0.014) and T1 groups (p=0.020). After treatment, serum zonulin levels in the T1 group was higher than that of the T1 group before treatment (p=0.035) but not in control (p=0.753) and T2 groups (p=0.869). Administration of 50 μg NS 1 increases wet liver weight and zonulin expression in hepatocytes, but did not increase serum zonulin levels in ddY mice.

Magnitude and kinetics of the human immune cell response associated with severe dengue progression by single-cell proteomics.

Approximately 5 million dengue virus-infected patients progress to a potentially life-threatening severe dengue (SD) infection annually. To identify the immune features and temporal dynamics underlying SD progression, we performed deep immune profiling by mass cytometry of PBMCs collected longitudinally from SD progressors (SDp) and uncomplicated dengue (D) patients. While D is characterized by early activation of innate immune responses, in SDp there is rapid expansion and activation of IgG-secreting plasma cells and memory and regulatory T cells. Concurrently, SDp, particularly children, demonstrate increased proinflammatory NK cells, inadequate expansion of CD16+ monocytes, and high expression of the FcγR CD64 on myeloid cells, yet a signature of diminished antigen presentation. Syndrome-specific determinants include suppressed dendritic cell abundance in shock/hemorrhage versus enriched plasma cell expansion in organ impairment. This study reveals uncoordinated immune responses in SDp and provides insights into SD pathogenesis in humans with potential implications for prediction and treatment.

Serum Cortisol as a Biomarker of Severe Dengue

Dengue infection presents a wide range of clinical symptoms. Serum cortisol is known as a severity predictor of serious infection but is not yet clearly understood in dengue infection. We aimed to investigate the pattern of cortisol response after dengue infection and evaluate the possibility of using serum cortisol as the biomarker to predict the severity of dengue infection. This prospective study was conducted in Thailand during 2018. Serum cortisol and other laboratory tests were collected at four time points: day 1 at hospital admission, day 3, day of defervescence (DFV) (4-7 days post-fever onset), and day of discharge (DC). The study recruited 265 patients (median age (IQR) 17 (13, 27.5)). Approximately 10% presented severe dengue infection. Serum cortisol levels were highest on the day of admission and day 3. The best cut-off value of serum cortisol level for predicting severe dengue was 18.2 mcg/dL with an AUC of 0.62 (95% CI, 0.51, 0.74). The sensitivity, specificity, PPV and NPV were 65.4, 62.3, 16 and 94%, respectively. When we combined serum cortisol with persistent vomiting and day of fever, the AUC increased to 0.76. In summary, serum cortisol at day of admission was likely to be associated with dengue severity. Further studies may focus on the possibility of using serum cortisol as one of the biomarkers for dengue severity.

Blood transfusion in severe dengue infection: a case series

BackgroundDengue is still a recurrent challenge to the global population, without specific antiviral therapy. Clinical management strategies are aimed to mitigate the deaths. The use of blood products in dengue is recommended mainly in cases of bleeding.Case presentationWe prospectively collected data on Sri Lankan dengue cases in the Teaching Hospital, Peradeniya, Sri Lanka from 2017, and selected ten severe cases where blood transfusions were involved in the management. The series comprises seven females and three males, with a median age of 36 years (range 12–53 years). All patients were critically ill at the time of blood transfusion, with dramatic stabilization of vital parameters after the transfusions. Only one patient had detectable bleeding, while five patients had occult blood loss as indicated by dropping hematocrit. Even though four patients had stable hematocrit, they had metabolic acidosis. Two patients had a very high increase of hepatic transaminases along with acidosis. Two patients had myocarditis with dropping hematocrit, suggestive of occult bleeding.ConclusionsClinical deterioration despite fluid management commonly occurs due to occult bleeding in dengue infection. Blood transfusion is lifesaving in such cases of blood loss, acidosis, and severe hepatic damage. The mechanism of this effect needs an explanation, such as enhanced oxygen delivery to the tissues and hemostasis to hypothesize a few possibilities.

Dengue infection in Agra region, Uttar Pradesh: An observational study of seroprevalence, clinicoepidemiological profile, and serotype of dengue virus from tertiary care center

Background: Dengue is the most widespread mosquito-borne viral infection, found in tropical and subtropical climates worldwide. The World Health Organization has included dengue as one of the 10 threats to global health in 2019 with rapidly evolving epidemiology. Aims and Objectives: Given the limitation of data in regard to dengue burden, we have planned the present study with the objectives to provide a comprehensive overview of the seroprevalence, clinicoepidemiological profile, and serotype of dengue virus in Agra region of Uttar Pradesh. Materials and Methods: We conducted an observational study at viral diagnostic and research laboratory, Sarojini Naidu Medical College, Agra, Uttar Pradesh, from August to December 2021. Our study included all blood specimens received at virology laboratory from clinically suspected cases of dengue infection. For the identification of serotype, NS1-positive samples were sent to King Georges Medical University, Lucknow. For clinical-epidemiological profile of dengue positive patients, data were obtained from records of 203 patients from our hospital. Results: We received total of 5457 serum samples from suspected patients for dengue serology during the study period. In total, positivity rate was 27.29% (1489/5457) and peak of cases was reported in month of October. Median age of dengue positive cases was 17 years. Dengue hemorrhagic fever (DHS) was diagnosed in almost 41% of patients of 203 patients admitted in our hospital. DEN-2 was reported to be most common serotype (97.1%). In our analsyis, we found that in most patients fall in platelets levels below 50,000 happened during the 5th and 6th day in Dengue fever. Conclusion: We conclude that our study showed higher seroprevalence of dengue in Agra region with the age group of 0–20 years being infected most. DEN-2 was most prevalent circulating strain, which leads to more severe dengue infection.

Dengue beyond the tropics: a time-series study comprising 2015-2016 versus 2019-2020 at a children's hospital in the City of Buenos Aires.

Dengue is a public health problem worldwide. It was originally confined to tropical and subtropical areas, but it is now present in other regions, such as Argentina. Epidemic outbreaks have been observed in the City of Buenos Aires since 2008, with few reports in children. To analyze and compare the clinical, epidemiological, laboratory, and evolutionary characteristics of the latest 2 dengue outbreaks outside the endemic area. Time-series study. Patients under 18 years of age with probable or confirmed dengue and evaluated in a children's hospital of the City of Buenos Aires during the periods 2015-2016 and 2019-2020 were included. A total of 239 patients were included; 29 (12%) had a history of travel. Their median age was 132 months (interquartile range: 102- 156). All had a fever. Other symptoms included headache in 170 (71%), myalgia in 129 (54%), and rash in 122 (51%). Forty patients (17%) had comorbidities. Warning signs were observed in 79 patients (33%); 14 (6%) developed severe dengue; 115 (45%) were hospitalized; none died. DENV-1 was the most common serotype. A history of travel and hospitalization prevailed in the first period; severe dengue and prior infection, in the second period. No patient died due to dengue in either study period. Statistically significant differences were observed in the frequency of hospitalization; a history of travel was more common in the 2015-2016 period and severe dengue, in the 2019-2020 period.

Demographic, Clinical and Hematological Parameters of Patients with Severe and Non Severe Dengue Infection

Background: There has been a remarkable rise in the worldwide frequency of dengue in recent decades owing to the ineffectiveness of existing management methods including vaccinations and pesticides. Objective: To assess the demographic, clinical and hematological parameters of patients infected with severe and non severe dengue Methodology: This cross sectional study was carried out at the Medicine department, Khalifa Gul Nawaz Teaching Hospital, Bannu Medical College Bannu from May 2022 to October 2022. All the data like demographic, clinical and data related to hematological parameters was recorded on pre-designed Performa. The data was analyzed using SPSS 23. Results: In the current study, totally 180 patients were enrolled. The patients were categorized into NSDI and SD1 group. There were 96 (67.8%) males and 46 (32.4%) females’ patients in NSDI group while there were 28 (73.7%) males and 10 (26.3%) females in SD1 group. Fever was observed in 138 (97.2%) patients in NSDI group and 38 (100%) patients in SDI group. Platelet transfusion was needed in 55 (38.7%) patients in NSDI group while it was needed in 26 (68.4%) patients in SDI group. The mean ±SD Platelet Count x 103mm3 was 39 ±52.5 in NSDI group and 31.5±67.6 in SDI group. The mean ±SD Lowest Platelet Count x 103 mm3 was 28±42 and 21.5± 17 in NSDI group and SDI group respectively. The mean ±SD HCT % was 40.8± 6.7 in NSDI group and 36.0± 12.1 in SDI group. The mean ±SD Leukocytes Count x 103 mm3 was 4400±5425 and 8050±9350 in NSDI group and SDI group respectively. Conclusion: The key to treating and predicting dengue as severe and non-severe cases is to be aware of clinical aspects as well as test results such hematological parameters. Keywords: Demographic, clinical and hematological parameters, severe and non severe dengue infection

Predictors of complicated dengue infections in endemic region of Pakistan

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

Effect of prior Zika and dengue virus exposure on the severity of a subsequent dengue infection in adults

Given the structural similarity between Zika and dengue viruses, prior infection from one virus is hypothesized to modulate the severity of a subsequent infection from the other virus. A previous paediatric cohort study observed that a prior Zika infection may increase the risk of a subsequent symptomatic or severe dengue infection. The Colombo Dengue study is a prospective hospital-based cohort study in Sri Lanka that recruits symptomatic adult dengue patients within the first three days of fever. Anti-Dengue Envelope and anti-Zika NS1 IgG antibodies were tested by ELISA (Euroimmun, Lubeck, Germany) in all recruited patients. Associations between pre-morbid seroprevalence for either or both infections and adverse clinical outcomes of the current dengue infection were explored. A total of 507 dengue infected patients were assessed of whom 342 (68%) and 132 (26%) patients had anti-dengue IgG and anti-Zika IgG respectively. People with combined prior dengue and zika exposure as well as prior dengue exposure alone, were at increased risk of plasma leakage, compensated and uncompensated shock, and severe dengue (p < 0·05), compared to people without prior exposure to either infection. The effect of prior Zika exposure alone could not be established due to the small the number of primary dengue infections with prior Zika exposure.

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

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

Patient Characteristics and Outcome of Multi-organ Involvement in Dengue with Reference to SOFA Score

Background: Mortality in severe Dengue infection is attributed to development of MODS. Clinical profile, outcome and utility of SOFA score in Dengue MODS is not well studied in Indian context. Hence, this study was conducted to describe the “patient`s” characteristics and outcome in Dengue MODS with reference to SOFA score.&#x0D; Methods: We conducted an observational cross –sectional study in medicine department, Sassoon General Hospital Pune between January 2016 to January 2020. Adult dengue patients with multiorgan dysfunction based on SOFA score were included. Demographic, clinical and laboratory data were collected and analyzed. SOFA score was calculated at admission and monitor throughout admission course.&#x0D; Results: Total 69 patients were included. Male were 53.6% and mean age was 38.7±18.7 years. Most common symptoms were fever (98.6%), body ache &amp; joint pain (69.6%), generalized weakness (62.3%), breathlessness (59.4%), headache (58%), anorexia (58%), abdominal pain &amp; vomiting (55.1%) and bleeding manifestations (47.8%). Total 28% patients had two, 33% had three, 24.6% had four and 14.4% had ≥ 5 organs involvement. Maximum number of patients had hematological involvement (95.7%) followed by respiratory system involvement (63.8%). Mean duration of hospital stay was 9.8 days. Mortality was 43.5%. There was significant correlation of number of organs involved, pulse rate, respiratory rate, serum albumin, nervous system, respiratory system, SOFA score at admission and delta SOFA score with outcome.&#x0D; Conclusion: Dengue MODS has high mortality. Tachypnoea, tachycardia, hypoalbuminemia, respiratory failure and nervous system involvement are predictors of poor outcome. SOFA score at admission and its monitoring can serve as a useful marker to predict prognosis in dengue with multiple organ involvement.