Severe Dengue Hemorrhagic Fever Research Articles

Causes of Vision Loss Associated with Dengue Fever in Bihar, India - A Case Series.

The incidence and geographic distribution of dengue has increased dramatically in recent years across various parts of the world. Previously, ocular findings in dengue fever were considered rare. We report a spectrum of ocular manifestations presenting with vision loss in the last dengue epidemic in an eastern state of India. This is a retrospective interventional case series of patients with vision loss who were diagnosed with dengue eye disease in the 2022 epidemic. Systemic and ophthalmic examinations were completed on all patients and were analyzed. Fifteen patients had presented with vision loss. The mean age was 41.7 ± 10.8 years, and patients were mostly males. Three patients presented with panophthalmitis and orbital cellulitis. Eight patients were diagnosed with optic neuropathy. Four patients had macular involvement: macular chorioretinitis, macular subhyaloid hemorrhage, and macular hemorrhages in two patients. All patients with optic neuropathy gave a history of mild fever and had remained undiagnosed. The rest had been diagnosed with the more severe dengue hemorrhagic fever. Vision recovered partially or fully in patients with optic neuropathy and macular disease. No eye could be salvaged in any panophthalmitis patients. Thrombocytopenia (platelet count <100 × 109 per liter of blood) was significantly associated with ocular hemorrhage and panophthalmitis, but thrombocytopenia was not significantly seen in optic neuropathy. We conclude that optic neuropathy may be an underreported cause of vision loss in dengue fever. An eye examination is advocated in all patients with dengue eye disease.

Peptide-ligand conjugate based immunotherapeutic approach for targeted dismissal of non-structural protein 1 of dengue virus: A novel therapeutic solution for mild and severe dengue infections

Dengue virus infection has significantly increased, with reported cases soaring from 505,430 in 2000 to 2,809,818 in 2022, emphasizing the need for effective treatments. Among the eleven structural and non-structural proteins of DENV, Non-structural protein 1 (NS1) has emerged as a promising target due to its diverse role in modulating the immune response, inducing vascular leakage, and facilitating viral replication and assembly. Monoclonal antibodies are the sole therapeutics to target NS1, but concerns about their cross-reactivity persist. Given these concerns, our study focuses on designing a novel Peptide Ligand Conjugate (PLC) as a potential alternative immunotherapeutic agent against NS1. This PLC aims to mediate the immune elimination of soluble NS1 and NS1-presenting DENV-infected host cells by pre-existing vaccine-induced immunity. By employing the High Throughput Virtual Screening (HTVS) method, QikProp analysis, and Molecular Dynamics studies, we identified three hits from Asinex Biodesigned Ligands out of 220,177 compounds that show strong binding affinity towards the monoclonal binding site of NS1 protein. After a rigorous analysis of physicochemical characteristics, antigenicity, allergenicity, and toxicity using various servers, we selected two peptides: the minimum epitopic region of the Diphtheria and Tetanus toxins as the peptide components of the PLCs. A non-cleavable, non-reactive oxime linker connected the ligand with the peptide through oxime and amide bonds. DPT vaccine is widely used in dengue-endemic countries, and it has been reported that antibodies titer against MER of Diphtheria toxin and Tetanus toxins persist lifelong in DPT-vaccinated people. Therefore, once the rationally designed PLCs bind to NS1 through the ligands, the peptide will induce an immune response against NS1 by triggering pre-existing DPT antibodies and activating memory cells. This orchestrated immune response will destroy soluble NS1 and NS1-expressing DENV-infected cells, thereby reducing the illness of severe dengue hemorrhagic fever and the DENV infection, respectively. Given the increasing demand for new therapeutics for DENV treatment, further investigation into this novel immune-therapeutic strategy may offer a new avenue for treating mild and severe dengue infections.

Analysis of Platelet Lymphocyte Ratio on Severe COVID-19 and Dengue Hemorrhagic Fever Grade IV

Thrombocytopenia can occur in severe COVID-19 or grade IV DHF. In COVID-19, lymphopenia occurs gradually due to Angiotensin Converting Enzyme-2 as the primary response to SARS-CoV-2 and cytokines that can damage lymphocytes. Contrastingly, lymphocytosis occurs in dengue virus infection. Platelet-to-lymphocyte ratio (PLR) is a new inflammatory marker in predicting the severity of both diseases. This study aimed to analyze differences in PLR values in severe COVID-19 and grade IV DHF and determine the cut-off values. Retrospective research of a cross-sectional approach was carried out using medical record data of patients diagnosed with severe COVID-19 and grade IV DHF by clinicians at Dr. Wahidin Sudirohusodo Hospital from January 2017 to October 2021. The platelet-to-lymphocyte ratio was obtained from the complete blood count results using the flow cytometry method at the beginning of hospitalization. Mann-Whitney test and Receiver Operating Characteristics (ROC) curve were used for statistical analysis. A total of 74 severe COVID-19 and 33 grade IV DHF patients were involved; PRL of severe COVID-19 in dead patients was higher than in recovered patients (p&gt;0.05). The platelet-to-lymphocyte ratio value was significantly lower in grade IV DHF patients who died compared to those who recovered (p&lt;0.001). Platelet to-lymphocyte ratio cut-off of 48.30 for severe COVID-19 was obtained with an Area Under the Curve (AUC) of 0.631 (sensitivity of 54.3%, specificity of 78.6%) and cut-off of 0.715 for grade IV DHF with an AUC of 0.989 (sensitivity of 94.4%, specificity of 100%). There was a difference in PLR value in severe COVID-19 and grade IV DHF. Severe COVID-19 patients who died had higher PLR, whereas grade IV DHF patients had lower PLR values. Values above the PLR cut-off of 48.30 for severe COVID-19 and 0.715 for grade IV DHF can predict the severity of the disease.

Non-structural protein 1 and hematology parameters as predictors of dengue virus infection severity in Indonesia.

Dengue virus infection (DVI) remains a significant health challenge, and diagnosis must still be considered. Non-structural protein 1 (NS1) is a potential marker of the dengue virus that can help diagnose DVI. The study aimed to assess the role of NS1 as a predictor of the severity of DVI. We utilized Dengue PCR-confirmed samples and employed semi-quantitative NS1Ag ELISA for NS1 examination, adhering to the World Health Organization South-East Asia Region (WHO-SEARO) 2011 criteria for DVI. We included DVI patients from Indonesia aged 1-65 years. Secondary infections had more severe clinical conditions than primary infections. Leukocyte and platelet levels had a more significant effect on NS1 positivity (6.19 (1.9-30.2); p<0.001; 190 (11-417); p=0.015; respectively). Multivariate analysis revealed leukocytes as a more significant predictor of NS1 values than platelets, with an odds ratio of 5.38 contributing to 30.5% of the NS1 value variation. The NS1 value could distinguish undifferentiated fever and dengue fever in the children group with a sensitivity of 76.0% and specificity of 87.5% (p=0.015). The number of NS1(-) in the severe dengue hemorrhagic fever (DHF) group was higher than NS1(+). DENV-4 type and primary infection were dominant in this study, although they did not significantly differ from the NS1 value. NS1 value can be used as a predictor to determine the severity of DVI in children but not in the adult group. The levels of leukocytes and platelets influenced the NS1 value.

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

Characterization of soluble TLR2 and CD14 levels during acute dengue virus infection

Dengue virus infection results in a broad spectrum of diseases ranging from mild dengue fever (DF) to severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Hitherto, there is no consensus biomarker for the prediction of severe dengue disease in patients. Yet, early identification of patients who progress to severe dengue is pivotal for better clinical management. We have recently reported that an increased frequency of classical (CD14 ++CD16−) monocytes with sustained high TLR2 expression in acutely infected dengue patients correlates with severe dengue development. Here, we hypothesized that the relatively lower TLR2 and CD14 expression in mild dengue patients is due to the shedding of their soluble forms (sTLR2 and sCD14) and that these could be used as indicators of disease progression. Therefore, using commercial sandwich ELISAs, we evaluated the release of sTLR2 and sCD14 by peripheral blood mononuclear cells (PBMCs) in response to in vitro dengue virus (DENV) infection and assessed their levels in acute-phase plasma of 109 dengue patients. We show that while both sTLR2 and sCD14 are released by PBMCs in response to DENV infection in vitro, their co-circulation in an acute phase of the disease is not always apparent. In fact, sTLR2 was found only in 20% of patients irrespective of disease status. In contrast, sCD14 levels were detected in all patients and were significantly elevated in DF patients when compared to DHF patients and age-matched healthy donors. Altogether, our results suggest that sCD14 may help in identifying patients at risk of severe dengue at hospital admittance.

Integrated systems immunology approach identifies impaired effector T cell memory responses as a feature of progression to severe dengue fever

BackgroundTypical symptoms of uncomplicated dengue fever (DF) include headache, muscle pains, rash, cough, and vomiting. A proportion of cases progress to severe dengue hemorrhagic fever (DHF), associated with increased vascular permeability, thrombocytopenia, and hemorrhages. Progression to severe dengue is difficult to diagnose at the onset of fever, which complicates patient triage, posing a socio-economic burden on health systems.MethodsTo identify parameters associated with protection and susceptibility to DHF, we pursued a systems immunology approach integrating plasma chemokine profiling, high-dimensional mass cytometry and peripheral blood mononuclear cell (PBMC) transcriptomic analysis at the onset of fever in a prospective study conducted in Indonesia.ResultsAfter a secondary infection, progression to uncomplicated dengue featured transcriptional profiles associated with increased cell proliferation and metabolism, and an expansion of ICOS+CD4+ and CD8+ effector memory T cells. These responses were virtually absent in cases progressing to severe DHF, that instead mounted an innate-like response, characterised by inflammatory transcriptional profiles, high circulating levels of inflammatory chemokines and with high frequencies of CD4low non-classical monocytes predicting increased odds of severe disease.ConclusionsOur results suggests that effector memory T cell activation might play an important role ameliorating severe disease symptoms during a secondary dengue infection, and in the absence of that response, a strong innate inflammatory response is required to control viral replication. Our research also identified discrete cell populations predicting increased odds of severe disease, with potential diagnostic value.

Grape Seed Proanthocyanidins Inhibit Replication of the Dengue Virus by Targeting NF-kB and MAPK-Mediated Cyclooxygenase-2 Expression.

Dengue virus (DENV) infection is a serious global health issue as it causes severe dengue hemorrhagic fever and dengue shock syndrome. Since no approved therapies are available to treat DENV infection, it is necessary to develop new agents or supplements that can do this. In this study, grape seed proanthocyanidins extract (GSPE), which is widely consumed as a dietary supplement, dose-dependently suppressed the replication of four DENV serotypes. The inhibitory mechanism demonstrated that GSPE downregulated DENV-induced aberrant cyclooxygenase-2 (COX-2) expression, revealing that the inhibitory effect of the GSPE on DENV replication involved targeting DENV-induced COX-2 expression. Mechanistic studies on signaling regulation have demonstrated that GSPE significantly reduced COX-2 expression by inactivating NF-κB and ERK/P38 MAPK signaling activities. Administrating GSPE to DENV-infected suckling mice reduced virus replication, mortality, and monocyte infiltration of the brain. In addition, GSPE substantially reduced the expression of DENV-induced inflammatory cytokines associated with severe dengue disease, including tumor necrosis factor-α, nitric oxide synthase, interleukin (IL)-1, IL-6, and IL-8, suggesting that GSPE has potential as a dietary supplement to attenuate DENV infection and severe dengue.

INVESTIGATING THE HEMATOLOGICAL PARAMETERS IN CHILDREN WITH DENGUE HEMORRHAGIC FEVER NEWLY HOSPITALIZED AT TRA VINH OBSTETRICS AND PEDIATRICS HOSPITAL, VIETNAM

The study described several hematological parameters in children with Dengue hemorrhagic fever newly hospitalized at Tra Vinh Obstetrics and Pediatrics Hospital in 2022. The retrospective study investigated 400 selected children. The results showed that children with severe Dengue hemorrhagic fever accounted for 5.5\%. For epidemiological characteristics, within the population of children with the disease, 43.75\% were aged 10 to 16 years old, the male/female ratio was 1.18/1, the majority were Kinh ethnic group (77.5\%) and lived in rural areas (71.8\%). For characteristics of hematological indicators, platelets and white blood cells decreased, PT \% decreased, and APTT prolonged. The factors, including age group, the decrease in platelet counts, the increase in hematocrit, and the increase in APTT time, are associated with the incidence of severe dengue in children. The study results contribute to identifying a group of patients at risk of severe dengue in the first test after being hospitalized, which helps doctors closely monitor and detect early serious complications for timely treatment.

Challenges on the development of a dengue vaccine: a comprehensive review of the state of the art.

Dengue virus (DENV) is the mosquito-borne virus of greatest human health concern. There are four serotypes of DENV (1-4) that co-circulate in endemic areas. Each serotype of DENV is individually capable of causing the full spectrum of disease, ranging from self-resolving dengue fever to the more severe dengue haemorrhagic fever (DHF) or dengue shock syndrome (DSS). Based on data published by the CDC, one in four people who become infected with dengue will become ill. Of those that do develop symptomology, the symptoms can range from mild to severe. Symptoms can vary from rash, ocular aches and pains to more intense symptoms in the manifestation of severe dengue. Roughly, 1 in 20 people who become ill will develop severe dengue, which can result in shock, internal bleeding and death. There is currently no specific treatment for dengue and only one licensed vaccine (Dengvaxia) for children 9 through 16 years of age in just a few countries. Despite its licensure for clinical use, Dengvaxia has performed with low efficacy in children and dengue naïve individuals and critically has resulted in increased risk of developing severe dengue in young, vaccinated recipients. Currently, there are various novel strategies for the development of a dengue vaccine. In this review we have conducted a detailed overview of the DENV vaccine landscape, focusing on nine vaccines in the pipeline to provide a comprehensive overview of the most state-of-the-art developments in strategies for vaccines against DENV.

Differentiating Secondary Dengue Using IgG/IgM Antibody Ratio: A Cross-sectional Study

Introduction: Dengue is a viral infection with diverse clinical manifestations. Infection in most of the patients is subclinical. It may also present as undifferentiated fever, severe dengue like Dengue Haemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS). Secondary dengue infection predisposes to severe dengue, a serious threat to the community as they increase morbidities and mortality. The diagnosis of secondary infection is either by Polymerase Chain Reaction (PCR) to detect the serotype or dengue IgG/IgM antibody ratio. A ratio of more than 1.1 is evidence of secondary dengue. Aim: To find out the prevalence of secondary dengue by measuring the dengue anti-IgG/IgM ratio by Enzyme Linked Immunosorbent Assay (ELISA) test. Materials and Methods: This cross-sectional observational study was conducted at Government Kilpauk Medical College, Chennai for a period of six months from July 2021 to December 2021. Sample size was 450 calculated at 95% confidence level, (CI 28.3-38.3) with 33.3% as prevalence. Blood samples were collected and Nonstructural Protein 1 (NS1) antigen assay was done. The IgG and IgM antibodies assays were done for NS1 antigen positive individuals. The IgG/IgM ratio was calculated in patients who were positive for both IgG and IgM. Statistical analysis was done with Statistical Package for Social Sciences (SPSS) version 20.0. Percentage, mean and standard deviation were calculated. Results: Total of 450 patients were included, out of which 194 were NS1 antigen positive, 106 were males and 88 females with the mean age 25±14.85 years. NS1 antigen was positive in 89.17%. Two-tailed Fisher’s-exact test showed a significant proportion of patients among NS1 positive were positive for both IgG and IgM. An IgG/IgM ratio of &gt;1.1 was found in 62.04%. The association between IgG/IgM ratio of &gt;1.1 and thrombocytopenia was significant [p-value=0.00504, Odd’s ratio (OD) =3.316]. Conclusion: Dengue IgG/IgM antibody ratio of more than 1.1 on the third day of symptom onset and the platelet count assist in the early diagnosis of secondary dengue thereby helps clinicians to initiate the appropriate treatment at the right time, reduce mortality rate and decrease the economic burden of the country.

Cepharanthine inhibits dengue virus production and cytokine secretion

Dengue virus (DENV) infection is a public health problem in tropical and subtropical regions. It can cause a spectrum of clinical manifestations ranging from mild dengue fever (DF) to severe dengue haemorrhagic fever (DHF) and potentially life-threatening disease including dengue shock syndrome (DSS). Severe DENV infection is caused by high viral load and cytokine storm in dengue-infected patients. Currently, there is no specific antiviral drug for DENV infection. An anti-DENV agent that demonstrates inhibitory effects on both DENV replication and cytokine secretion is urgently needed. In this study, cepharanthine (CEP), which is an anti-inflammatory, anti-HIV, and anti-tumor compound isolated from Stephania cepharantha Hayata, was tested for inhibition of DENV infection. We investigated the efficacy of CEP to inhibit DENV infection, replication, and cytokine production. The inhibitory effect of CEP treatment was studied in DENV-infected human chronic myeloid leukemia (K562) cells. The levels of DENV E protein and DENV production were determined by flow cytometry and FFU assay, respectively. CEP treatment significantly reduced viral E protein and viral production in all DENV-1, 2, 3, 4 serotypes. In addition, CEP treatment reduced the IL-6 proinflammatory cytokine production in DENV-infected A549 cells. Taken together, CEP has inhibitory effects on DENV infection specifically at the initial viral replication states and proinflammatory cytokine secretion, and is a promising candidate for further development as an anti-DENV treatment.

Elevated serum PAR-1 levels as an emerging biomarker of inflammation to predict the dengue infection severity.

The present study was designed to check the serum levels of protease-activated receptor (PAR-1) in patients during different phases of dengue severity. Moreover, a correlation between serum PAR-1 levels and hematological parameters, inflammatory cytokine levels, and liver functional changes was also determined. Based on the World Health Organization criteria, the study population was divided into: nonsevere dengue fever (DF; n = 30), severe dengue hemorrhagic fever (DHF; n = 19), and severe dengue shock syndrome (DSS; n = 11). The platelet count (PLT) and hematocrit (HCT) were analyzed using an automated hematology analyzer and liver function enzymes aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphate (ALP), bilirubin were checked by auto-analyzer using diagnostic kits. Moreover, the levels of inflammatory mediators C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-17 (IL-17), and PAR-1 were determined using respective ELISA kits. The HCT levels were elevated and platelet count decreased significantly during dengue complications (DHF andDSS) compared to the DF patients, while the levels of liver functional biomarkers AST, ALT, ALP, and bilirubin remained elevated in DHF and DSS groups than in the corresponding DF group. Similarly, the inflammatory cytokine levels of CRP, TNF-α, IL-6, and IL-17 in DHF and DSS subjects were markedly increased when observed against DF subjects. Notably, the PAR-1 levels were significantly elevated in DHF and DSS groups than in the DF group and positively correlated with changes in HCT levels, inflammatory biomarkers, and liver enzymes. Our findings conclude that PAR-1 levels persistently increased with the severity of the dengue infection and are strongly associated with various clinical manifestations. Thus, PAR-1 levels can be used as a diagnostic marker for assessing dengue severity.

Development and Characterization of a Genetically Stable Infectious Clone for a Genotype I Isolate of Dengue Virus Serotype 1.

Dengue virus (DENV) is primarily transmitted by the bite of an infected mosquito of Aedes aegypti and Aedes albopictus, and symptoms caused may range from mild dengue fever to severe dengue hemorrhagic fever and dengue shock syndrome. Reverse genetic system represents a valuable tool for the study of DENV virology, infection, pathogenesis, etc. Here, we generated and characterized an eukaryotic-activated full-length infectious cDNA clone for a DENV serotype 1 (DENV-1) isolate, D19044, collected in 2019. Initially, nearly the full genome was determined by sequencing overlapping RT-PCR products, and was classified to be genotype I DENV-1. D19044 wild-type cDNA clone (D19044_WT) was assembled by four subgenomic fragments, in a specific order, into a low-copy vector downstream the CMV promoter. D19044_WT released the infectious virus at a low level (1.26 × 103 focus forming units per milliliter [FFU/mL]) following plasmid transfection of BHK-21 cells. Further adaptation by consecutive virus passages up to passage 37, and seven amino acid substitutions (7M) were identified from passage-recovered viruses. The addition of 7M (D19044_7M) greatly improved viral titer (7.5 × 104 FFU/mL) in transfected BHK-21 culture, and virus infections in 293T, Huh7.5.1, and C6/36 cells were also efficient. D19044_7M plasmid was genetically stable in transformant bacteria after five transformation-purification cycles, which did not change the capacity of producing infectious virus. Moreover, the D19044_7M virus was inhibited by mycophenolic acid in a dose-dependent manner. In conclusion, we have developed a DNA-launched full-length infectious clone for a genotype I isolate of DENV-1, with genetic stability in transformant bacteria, thus providing a useful tool for the study of DENV-1.

Sulforaphane suppresses dengue virus replication by inhibition of dengue protease and enhancement of antiviral interferon response through Nrf2-mediated heme oxygenase-1 induction

Dengue virus (DENV) infection is a life-threatening disease that causes severe dengue hemorrhagic fever and dengue shock syndrome. There is currently no effective therapeutic agent or widely used vaccine for treating DENV infections. In this study, sulforaphane (SFN), an antioxidant phytocompound, exhibited significant antiviral activity, with a half-inhibitory concentration value of 5.8 ± 0.7 μM to suppress viral RNA replication. Mechanistic studies demonstrated that SFN-induced heme oxygenase-1 (HO-1) expression, which inhibited viral protease activity, leading to the restoration of antiviral interferon (IFN) responses against DENV replication. Its antiviral activity can be attenuated by the knockdown of HO-1 expression by short hairpin RNA and blockage of activity with a specific inhibitor, supporting the contention that HO-1 induction contributes to the anti-DENV activity of SFN. SFN also stimulated HO-1 induction through an Nrf2-dependent pathway. SFN effectively prolonged the survival rate and reduced the virus titer in DENV-infected ICR suckling mice with activated expression of interferon-stimulated genes. The anti-DENV activity of SFN was also observed in the IFN-deficient AG129 mouse model. Collectively, SFN represents significant anti-DENV activity in vitro and in vivo and is a promising drug candidate or dietary supplement against DENV.

Liver transcriptomics reveals features of the host response in a mouse model of dengue virus infection.

BackgroundDengue virus (DENV) infection induces various clinical manifestations and even causes organ injuries, leading to severe dengue haemorrhagic fever and dengue shock syndrome. Hepatic dysfunction was identified as a risk predictor of progression to severe disease during the febrile phase of dengue. However, the underlying mechanisms of hepatic injury remain unclear.MethodsA model of dengue disease was established in IFNAR −/− C57BL/6 mice by challenge with DENV-2. Body weight, symptoms, haematological parameters and liver pathological observations in mice were used to determine the effects of DENV infection. Liver transcriptome sequencing was performed to evaluate the features of the host response in IFNAR −/− mice challenged with DENV. Functional enrichment analysis and analysis of significantly differentially expressed genes (DEGs) were used to determine the critical molecular mechanism of hepatic injury.ResultsWe observed haemoconcentration, leukopenia and liver pathologies in mice, consistent with findings in clinical dengue patients. Some differences in gene expression and biological processes were identified in this study. Transcriptional patterns in the liver indicated that antiviral responses to DENV and tissue damage via abnormal expression of proinflammatory cytokines were induced. Further analysis showed that the upregulated DEGs were significantly enriched in the leukocyte transendothelial migration, complement and coagulation cascades, and cytokine-cytokine receptor interactions signalling pathways, which are considered to be closely associated with the pathogenic mechanism of dengue. IL6, IL 10, ICAM-1, VCAM-1, MMP9 and NLRP3 were identified as biomarkers of progression to severe disease.ConclusionsThe interactions of these cytokines, which activate inflammatory signalling, may lead to organ injury and haemoconcentration and even to vascular leakage in tissues, including the mouse liver. Our study identifies candidate host targets that could be used for further functional verification.

Modeling Dengue Fever by using Conditional Autoregressive Bessag-York-Mollie

Dengue fever is a tropical disease caused by the dengue virus. The small proportional of this dengue fever disease can develops into a more severe dengue hemorrhagic fever (DHF). This research discussed about the model for disease mapping in Ciamis District. The purpose of this research is to characterize relative risk and factors correlated with case DHF. Independent variables used in this research are population density, attitude of region, and the number of health worker. To analysis this data, we used conditional autoregressive Bessag-York-Mollie (CAR-BYM) model. Based on descriptive statistic, the maximum and minimum DHF cases are Ciamis and Sukamantri, respectively. Furthermore, basedon model results, we found that the maximum and minimum relative risk are Cijeungjing and Sukamantri, respectively. Furthermore, there were 7 sub districts which relative risk are greater than one and 20 sub districts which relative risk are less than one. The sub districts which relative risk are greater than one show that DHF cases in these sub districts are greater than expectation. Based on the CAR-BYM model result showed that Each increase the population density by one unit contributes to the addition of DHF cases by 0.0012 units. Each additional health worker one unit, it will reduce the number of DHF cases by 0.0675 units. Each additional altitude of one unit will reduce the number of dengue cases by 0.0011 units. Based on relative risk (RR) value of the CAR-BYM model we found that the Cijengjing and Ciamis Districts have darkest color. The RR values in the two sub-districts are 3,449 and 3,240, respectively. The RR values of the two sub-districts are more than expected values.

168 Asymptomatic dengue illness complicated by Guillain Barre syndrome

Arboviral infection Dengue can cause a spectrum of disease varying from asymptomatic illness to dengue fever to the severe dengue hemorrhagic fever. Neurological complications are rarely reported in the lit- erature (0.5–6%), mostly from dengue-endemic areas in tropics and subtropical regions. We report a case of a 59-year-old man who returned from a recent work-related travel from India. Three weeks following a mild viral prodrome, he developed bilateral lower motor neuron facial palsy with absent deep tendon reflexes. CSF showed albuminocytologic dissociation and electrophysiological studies showed demyeli- nating neuropathy. Routine GBS screen for common etiological viruses was negative and subsequently additional testing based on recent travel was performed which showed positive Dengue IgM and RNA in serum. The patient was treated with plasma exchange for 5 days and his facial weakness improved to a great extent.This case demonstrates the importance of considering arboviral infections such as Dengue in patients with GBS particularly in people living in or travelling from endemic areas. Additionally, like many other viral illnesses, there may not be clear clinical evidence of Dengue fever and the prodrome may go unnoticed and undiagnosed, hence a high index of suspicion is required.s_hasan_s@yahoo.com

Seroprevalence and changing trend of dengue in a tertiary care hospital, Bhubaneswar, Odisha: Four-year retrospective study

Dengue virus is a single stranded positive sense RNA virus belonging to the genus flavivirus family flaviviridae. Dengue fever is a seasonal and emerging acute mosquito borne arbo-viral illness affecting tropical and sub-tropical countries. This illness ranges from a mild asymptomatic form to severe dengue hemorrhagic fever (DHF) with or without dengue shock syndrome (DSS). This study was conducted to know the seroprevalence and changing trend of Dengue virus in a tertiary care hospital, Bhubaneswar, Odisha, India. Over a period of four years from August 2016 to December 2019, a total of 5147 blood samples from clinically suspected dengue patients were received in department of Microbiology laboratory. Serum was separated and subjected to enzyme immunoassay for detection of both Non Structural (NS1) antigen and IgM antibody.During this study period, a total of 5147 blood samples were processed from suspected dengue cases, out of which 1314(25%) samples were found to be positive by different serological markers like NS1 Antigen (Ag), IgM antibody(Ab), or both NS1 Ag &amp; IgM Ab. The overall seroprevalence rate was found to be 25%. In this study period of four years, the year-wise seroprevalence rate was found to be 12% (153) in the year 2016 and was 26% (350) in the year 2017 and was 40% (522) in the year 2018, and was 22% (289) in the year 2019. It clearly shows that there is an increase in the dengue cases.

Dengue fever with encephalitis: An uncommon presentation of common illness

The dengue virus is a type of Flavivirus that causes dengue fever. It is mostly found in tropical and subtropical countries, with Southeast Asia bearing the brunt of the disease burden. The virus can affect a wide range of organ systems, and the disease can range from a mild flu-like illness to severe dengue hemorrhagic fever or dengue shock syndrome. We present a case of a 21-year-old female who presented with dengue fever with neurological manifestations. Findings from a brain MRI, electroencephalogram, CT scan, and some routine investigations were supported our diagnosis of dengue encephalitis. Conservative and supportive care was provided, including intravenous fluid therapy, antibiotics, antivirals, antiseizure medications, and corticosteroids. The patient's GCS gradually improved with treatment, and physical therapy was also provided. Treatment that is both effective and timely can reduce associated morbidity and result in complete recovery.