Mild Dengue Research Articles

A nationwide longitudinal investigation on the role of prenatal exposure to infectious diseases on the onset of chronic conditions in children and adolescents in Brazil.

In utero exposure to infections might set the stage for a chain of events leading to a wide spectrum of long-term health outcomes observed in children and adolescents. This proposal aims to investigate whether syphilis, zika, dengue and chikungunya during pregnancy can increase the risk of the offspring developing a non-infectious chronic condition during childhood and adolescence. 1) Estimate the risk of non-infectious chronic conditions associated to syphilis, zika, dengue and chikungunya during pregnancy and when appropriate, explore if the risk varies by timing during pregnancy when the infection is acquired (first, second or third trimester) and severity (such as severe or mild dengue); 2) Investigate whether in uterus exposure to maternal infection affects the growth pattern of children and adolescents; 3) Examine the extent to which the relationship between maternal infection and non-infectious chronic outcomes are mediated by intrauterine growth restriction and preterm birth. We will compare health outcomes and growth trajectories of children and adolescents born to mothers with and without specific infections during pregnancy using conventional multivariable regression in the whole study population, in a within sibship design, using the subgroup of offspring with at least one sibling who is not exposed to the infection, and negative control outcome. Then we will decompose the direct and mediated effects (by preterm birth and small for gestational age) of maternal infection on chronic disorders. The results from this study will advance our understanding of the relationship between infections during pregnancy and chronic disorders, with widespread implications enabling targeting of critical points along the path from in utero exposure to outcomes to avoid or mitigate illness and disability over the life course.

C-Reactive Protein (CRP) Value and Platelet Counts in Pediatric Dengue Patients at RSUP Dr. Hasan Sadikin Bandung

Plasma leakage, thrombocytopenia, and cytokines play roles in pathogenesis of dengue infection. Thrombocytopenia correlates with severity of the disease. Dengue virus infection produces cytokines that stimulate C-Reactive Protein (CRP). This study aims to describe the results of CRP and platelet counts with severity of dengue infection in paediatric inpatient at Hasan Sadikin Hospital Bandung. This is a descriptive observational study with retrospective, cross-sectional data collection in January 1-December 31, 2021 at Hasan Sadikin Hospital. From 32 total subjects, there were 24(75%) non-severe dengue infections compared to severe dengue 8(25%). Non-severe dengue 19(79.2%), had the most platelet counts of 50,000-150,000/L, while platelets count 20,000-50,000/µL was mostly in severe dengue 4/8(50%). CRP value was mostly normal (<0.3mg/dl) as many as 18/24(75%) in mild dengue, whereas in severe dengue CRP was mostly high as many as 6/8(75%). CRP examination is mostly done in critical phase, both in severe and non-severe dengue. Severe dengue infection was found mostly in platelet counts of 50,000-150,000/µL and normal CRP level as many as 14(58.3%). In severe dengue infection, platelet counts was found mostly in 20,000-50,000/µL and high CRP (≥0.3mg/dl) as many as 3(37.5%). Most cases of dengue fever infections in children at Hasan Sadikin General Hospital in 2021 were of mild severity, with platelet counts ranging from 50,000 to 150,000/µL and normal CRP levels. Examinations were typically carried out during the critical phase.

A nationwide longitudinal investigation on the role of prenatal exposure to infectious diseases on the onset of chronic conditions in children and adolescents in Brazil

Background In utero exposure to infections might set the stage for a chain of events leading to a wide spectrum of long-term health outcomes observed in children and adolescents. This proposal aims to investigate whether syphilis, zika, dengue and chikungunya during pregnancy can increase the risk of the offspring developing a non-infectious chronic condition during childhood and adolescence. Objectives 1) Estimate the risk of non-infectious chronic conditions associated to syphilis, zika, dengue and chikungunya during pregnancy and explore if the risk varies by timing during pregnancy when the infection is acquired (first, second or third trimester) and severity (such as severe or mild dengue); 2) Investigate whether in uterus exposure to maternal infection affects the growth pattern of children and adolescents; 3) Examine the extent to which the relationship between maternal infection and non-infectious chronic outcomes are mediated by intrauterine growth restriction and preterm birth. Methods We will compare health outcomes and growth trajectories of children and adolescents born to mothers with and without specific infections during pregnancy using conventional multivariable regression in the whole study population, in a within sibship design, using the subgroup of offspring with at least one sibling who is not exposed to the infection, and negative control outcome. Then we will decompose the direct and mediated effects (by preterm birth and small for gestational age) of maternal infection on chronic disorders. Results and Conclusions The results from this study will advance our understanding of the relationship between infections during pregnancy and chronic disorders, with widespread implications enabling targeting of critical points along the path from in utero exposure to outcomes to avoid or mitigate illness and disability over the life course.

Misuse of Antibiotics in Dengue Fever—A Contributor to Antimicrobial Resistance?

Abstract Background Dengue, a vector-borne viral infection, is a concern in the tropical and subtropical regions across the world. The rampant use of antibiotics in dengue patients in India reinforces the anticipated threat of emergence of antimicrobial resistance. Aim We aimed to retrospectively investigate the prescribing pattern of antibiotics and compare the clinical status of dengue patients treated with and without antibiotics. Methods Between January 2016 and December 2020 period, data of patients who tested positive for at least 1 of the 3 screening tests (nonstructural protein 1, immunoglobulin M, or immunoglobulin G) were collected from patient medical chart, and we assessed the clinical outcome of dengue patients treated with and without antibiotics. Results Of 370 patients, 196 (52.97%) were managed with antibiotics and 174 (47.02%) were managed without antibiotics along with other supportive measures. A peak in the percentage of prescriptions with antibiotics was seen in 2019, 168 (85.71%) were prescribed with a single antibiotic with a majority of them, and 56.6% received third generation cephalosporins. Only 46 (23.46%) had bacterial co-infection while 150 (76.53%) had no co-infection. Thirty-five patients (70%) with dengue hemorrhagic fever were clinically managed with antibiotics compared with 50% patients in the “dengue fever” category. Only 8% of patients with mild dengue were given 2 antibiotics, whereas 13% with moderate dengue and 16% with severe dengue were prescribed with 2 antibiotics. Conclusions The increased number of prescriptions with antibiotics for a viral infection when not recommended by the guideline may lead to emergence of antibiotic resistance in hospitals as well as community.

Antibody Profiling of Dengue Severities Using Flavivirus Protein Microarrays.

Dengue is a viral disease transmitted by Aedes aegypti mosquitoes. According to the World Health Organization, about half of the world's population is at risk of dengue. There are four serotypes of the dengue virus. After infection with one serotype, it will be immune to such a serotype. However, subsequent infection with other serotypes will increase the risk of severe outcomes, e.g., dengue hemorrhagic fever, dengue shock syndrome, and even death. Since severe dengue is challenging to predict and lacks molecular markers, we aim to build a multiplexed Flavivirus protein microarray (Flaviarray) that includes all of the common Flaviviruses to profile the humoral immunity and cross-reactivity in the dengue patients with different outcomes. The Flaviarrays we fabricated contained 17 Flavivirus antigens with high reproducibility (R-square = 0.96) and low detection limits (172-214 pg). We collected serums from healthy subjects (n = 36) and dengue patients within 7 days after symptom onset (mild dengue (n = 21), hospitalized nonsevere dengue (n = 29), and severe dengue (n = 36)). After profiling the serum antibodies using Flaviarrays, we found that patients with severe dengue showed higher IgG levels against multiple Flavivirus antigens. With logistic regression, we found groups of markers with high performance in distinguishing dengue patients from healthy controls as well as hospitalized from mild cases (AUC > 0.9). We further reported some single markers that were suitable to separate dengue patients from healthy controls (AUC > 0.9) and hospitalized from mild outcomes (AUC > 0.8). Together, Flaviarray is a valuable tool to profile antibody specificities, uncover novel markers for decision-making, and shed some light on early preventions and treatments.

Serum levels of matrix metalloproteinases as prognostic markers for severe dengue with plasma leakage

BackgroundPlasma leakage is a major pathogenic manifestation of severe dengue and is a precursor of life-threatening complications associated with dengue. Accumulating evidence indicates the role of Matrix Metalloproteinases (MMPs) in mediating vascular permeability and plasma leakage following induction by the dengue virus. This study aims to investigate the utility of MMP-2, MMP-3, and MMP-9 in predicting the severity of dengue infection and further explore the relationship of these markers with the pathogenic factors associated with plasma leakage. MethodsThe dengue-positive subjects were classified into mild and severe dengue groups based on the manifestation of warning signs. The samples in each group and healthy controls were quantified for basic laboratory characteristics. The levels of MMP-2, MMP-3, MMP-9, and Macrophage migration inhibitory factor (MIF) were estimated in all serum samples using a multiplex bead-based assay. ResultsMMP-2 and MMP-9 were markedly elevated in severe dengue patients compared to mild dengue patients and healthy controls. No alteration in the circulating levels of MMP-3 was observed between the study groups. ROC curve analysis indicated that MMP-2 and MMP-9 exhibited good potential for predicting severe dengue. Notably, an increase in MMP-9 was associated with increased MIF and Hematocrit levels in severe dengue patients. ConclusionMMP-2 and MMP-9 could serve as prognostic biomarkers for severe dengue. These findings also identify the association of MMP-9 with markers of plasma leakage, thereby encouraging further studies to explore the therapeutic potential of targeting MMP-9 in managing plasma leakage in severe dengue.

Urine Spot Protein Creatinine Ratio as a Predictor of Disease Severity and Adverse Outcome in Children with Dengue: A Cross-sectional Study

Introduction: Dengue is a viral infection with different presentations, hence predicting the disease severity at admission is essential to triage patients needing meticulous monitoring. In severe dengue there is increase of urinary protein clearance due to the increase in systemic vascular permeability. Simple urine protein excretion screening test could guide the triage and monitor the patients with suspected dengue infection. Aim: To evaluate the urine spot Protein Creatinine Ratio (PCR) as a tool in predicting the disease severity and adverse outcome in children with dengue. Materials and Methods: The present cross-sectional study was conducted in Institute of Child Health, Egmore, Tamil Nadu, India, from October 2021 to December 2021. All children aged 1 month to 12 years presenting with symptoms of fever, thrombocytopenia (less than 1, 50, 000 /µL) with or without dengue non structural protein component (NS1)/ Immunoglobulin M Enzyme Linked Immunosorbent Assay (ELISA) positivity were recruited for the study. Study parameters included were demographic factors, severity of dengue classification based on National Vector Borne Disease Control Programme (NVBDCP) guidelines, urine spot PCR. The UPCR (urine protein creatinine ratio) was compared between dengue and non dengue cases and within the different categories of dengue cases. Chi-square was used for comparing proportions. Results: Among 150 children enrolled in present study, 134 (89.3%) were dengue positive, 16 (10.7%) were non dengue. Most predominant age group involved was 6-9 years followed by 3 to 6 years. Among 134 children with dengue, 98 (73.1%) had high UPCR and among 16 non dengue children, 2 (12.5%) had high UPCR which was statistically significant (p<0.0001). Mean spot UPCR was 0.32±0.12 in mild dengue, 0.77±0.40 in moderate dengue and 1.68±1.67 in severe dengue which was statistically significant (p<0.0001). Children with severe dengue had higher PCR values in comparison to mild and moderate dengue. Conclusion: There was a statistically significant association of urine spot PCR with severity of dengue and this simple test can be used for triaging and monitoring children with suspected dengue.

Electrocardiographic and echocardiographic findings in children with dengue infection.

ABSTRACTBackground:The mechanism of myocardial damage in dengue could be the release of inflammatory mediators or the direct action of the dengue virus on myocytes leading to myocarditis. The release of inflammatory mediators is more in a severe form of the disease that correlates to the higher incidence of cardiac manifestations in patients with severe dengue.Aim:To determine the electrocardiographic and two-dimensional (2D)-echocardiographic findings in children with dengue infection and to find a correlation with disease severity.Materials and Methods:A total of 150 children between 1 month and 12 years of age seropositive for dengue Non-specific antigen 1 (NS1) Enzyme linked immunosorbent assay (ELISA) or dengue Immunoglobulin M (IgM) ELISA were studied in the Department of Pediatric Medicine of a tertiary care government hospital. The patients were undertaken for 12 lead electrocardiograms (ECGs) and echocardiograms.Results:Out of the 150 dengue seropositive cases, 61 cases were of mild dengue, 67 cases were of dengue with warning signs (DWSS), and 22 cases were severe dengue cases. Abnormal ECG was found in 78 cases (52%) in a total of 150 cases in terms of rate, prolonged PR interval (interval between atrial depolarization and ventricular activation), ST (ventricular repolarisation)-segment depression, and low-voltage complexes. Abnormal 2D- echocardiography (ECHO) was found in 70 (46.6%) out of 150 in terms of the ejection fraction (EF) <55%, Early diastole/atrial contraction (E/A) ratio <1, and the presence of pericardial effusion.Conclusion:Nearly 50% of the patients have abnormal ECG and ECHO findings, more so in the severe dengue group. There is a statistically significant association of the EF between mild dengue, DWWS with severe dengue (P =0.001).

Serum IL-18 Is a Potential Biomarker for Predicting Severe Dengue Disease Progression.

Background. Dengue virus (DENV) infection is the most common arboviral disease that affects tropical and subtropical regions. Based on the clinical hallmarks, the different severities of patients range from mild dengue fever (MDF) to severe dengue diseases (SDDs) and include dengue hemorrhagic fever or dengue shock syndrome. These are commonly associated with cytokine release syndrome (CRS). The types and levels of cytokines/chemokines, which are suppressed or enhanced, are varied, indicating CRS's pathogenic and host defensive effects. Principal Finding. In this study, we created an integrated and precise multiplex panel of cytokine/chemokine assays based on our literature analysis to monitor dengue CRS. A 24-plex panel of cytokines/chemokines was evaluated to measure the plasma levels of targeting factors in dengue patients with an MDF and SDD diagnosis without or with comorbidities. As identified in sixteen kinds of cytokines/chemokines, ten were significantly (P < 0.05) (10/16) increased, one was significantly (P < 0.01) (1/16) decreased, and five were potentially (5/16) altered in all dengue patients (n = 30) in the acute phase of disease onset. Compared to MDF, the levels of IL-8 (CXCL-8) and IL-18 in SDD were markedly (P < 0.05) increased, accompanied by positively increased IL-6 and TNF-α and decreased IFN-γ and RANTES. With comorbidities, SDD significantly (P < 0.01) portrayed elevated IL-18 accompanied by increased IL-6 and decreased IFN-α2 and IL-12. In addition, decreased platelets were significantly (P < 0.05) associated with increased IL-18. Significance. These results demonstrate an efficient panel of dengue cytokine/chemokine assays used to explore the possible level of CRS during the acute phase of disease onset; also, we are the first to report the increase of IL-18 in severe dengue with comorbidity compared to severe dengue without comorbidity and mild dengue.

Clinical and Laboratory Profile of Children with Dengue Fever and Predictors of Severe Dengue

Objectives: To study the Clinical and Laboratory profile of children upto 12 years of age with Dengue fever and to study the predictors of Severe Dengue among these children. Methods: Design: Descriptive study over 1 year 9 months. Setting: SAT hospital, Thiruvananthapuram, a tertiary care center. Study Population: 204 children aged 1month to 12 years admitted with serologically confirmed dengue fever without any co-infections; consecutive sampling. Procedure: Relevant history, detailed physical examination and investigations were noted. Patients were classified for their severity based on DENGUE guidelines-WHO 2009. Children were followed up till discharge during hospital stay. Categorical values were expressed as proportions and quantitative variables in mean and standard deviation. Association between various study variables and severe dengue were statistically analysed. Results: Mild dengue was seen in 96 children(47.1%), moderate dengue in 78 children(38.2%) and severe dengue in 30 children(14.7%). Mean age of presentation was 6.4 years. Age distribution- infants were 4.4%, 38.7% were between 1 year and 5 years; 56.9% were between 6 and 12 years.51% of children were males. Common clinical presentation was fever (100%), vomiting(46.6%), abdominal pain(32.4%), lethargy(24.5%), myalgia(22%), headache(16.7%) and reduced appetite(15.7%). Mean fever duration was 5 days. Hypotension was noted in 13.2%, Tender hepatomegaly in 44%, signs of plasma leakage in 6%, hypoalbuminemia in 7.8%. Total number of death was 2(1%). Variables with significant association with severe dengue on univariate analysis were Lethargy (p-&lt;0.001, OR- 11.6), reduced appetite (p- &lt;0.001,OR- 17.14), mucosal bleed (p&lt;0.001, OR- 15.45), Fever spike &gt;39◦C (p- 0.001, OR- 4.3), tender hepatomegaly (p- 0.001, OR- 4.2), decreased urine output (p &lt;0.001, OR- 23.04), hypoalbuminemia (p &lt;0.001, OR-43.5), platelet count below 80,000 (p &lt;0.001, OR-4.43), SGOT above 85 (p &lt;0.001, OR-4.9). According to the maximum area under ROC curve, a cutoff of platelet count 80,000 had 75% sensitivity and 60% specificity for predicting severe dengue. Conclusion: Proportion of children developed severe dengue was 14.7%. Independent predictors of severe dengue after multiple logistic regression were Lethargy, Reduced appetite, Reduced urine output and Hypoalbuminemia. Keywords: severe dengue; urine output; shock; hypoalbuminemia.

Innate Immune Cytokine Profiling and Biomarker Identification for Outcome in Dengue Patients.

BackgroundEarly biomarkers of progression to severe dengue are urgently required to enable effective patient management and control treatment costs. Innate immune cells, which comprise the earliest responders to infection and along with the cytokines and chemokines they secrete, play a vital role in orchestrating the subsequent adaptive immune response and have been implicated in the enhancement of infection and “cytokine storm” associated with dengue severity. We investigated the early innate immune cytokine profile of dengue patients during acute phase of disease in a prospective blinded study that included subjects with acute dengue and febrile controls from four major hospitals in Bengaluru, India along with healthy controls. We used intracellular cytokine staining and flow cytometry to identify innate immune biomarkers that can predict progression to severe dengue.ResultsDengue infection resulted in enhanced secretion of multiple cytokines by all queried innate immune cell subsets, dominated by TNF-α from CD56+CD3+ NKT cells, monocyte subsets, and granulocytes along with IFN-γ from CD56+CD3+ NKT cells. Of note, significantly higher proportions of TNF-α secreting granulocytes and monocyte subsets at admission were associated with mild dengue and minimal symptoms. Dengue NS1 antigenemia used as a surrogate of viral load directly correlated with proportion of cytokine-secreting innate immune cells and was significantly higher in those who went on to recover with minimal symptoms. In patients with secondary dengue or those with bleeding or elevated liver enzymes who revealed predisposition to severe outcomes, early activation as well as efficient downregulation of innate responses were compromised.ConclusionOur findings suggested that faulty/delayed kinetics of innate immune activation and downregulation was a driver of disease severity. We identified IFN-γ +CD56+CD3+ NKT cells and IL-6+ granulocytes at admission as novel early biomarkers that can predict the risk of progression to severity (composite AUC = 0.85–0.9). Strong correlations among multiple cytokine-secreting innate cell subsets revealed that coordinated early activation of the entire innate immune system in response to dengue virus infection contributed to resolution of infection and speedy recovery.

Platelets in dengue infection: more than a numbers game

Dengue virus (DENV) infection is responsible for the development of dengue illness, which can be either asymptomatic, present mild manifestations or evolve to severe dengue. Thrombocytopenia is an important characteristic during DENV infection, being observed both in mild and severe dengue, although the lowest platelet counts are encountered during severe cases. This review gathers information regarding several mechanisms that have been related to alterations in platelet number and function, leading to thrombocytopenia but also platelet-mediated immune and inflammatory response. On this regard, we highlight that the decrease in platelet counts may be due to bone marrow suppression or consumption of platelets at the periphery. We discuss the infection of hematopoietic progenitors and stromal cells as mechanisms involved in bone marrow suppression. Concerning peripheral consumption of platelets, we addressed the direct infection of platelets by DENV, adhesion of platelets to leukocytes and vascular endothelium and platelet clearance mediated by anti-platelet antibodies. We also focused on platelet involvement on the dengue immunity and pathogenesis through translation and secretion of viral and host factors and through platelet-leukocyte aggregates formation. Hence, the present review highlights important findings related to platelet activation and thrombocytopenia during dengue infection, and also exhibits different mechanisms associated with decreased platelet counts. Graphical abstract: Schematic mechanistic representation of platelet-mediated immune responses and thrombocytopenia during dengue infection. (A) DENV-infected platelets secrete cytokines and chemokines and also adhere to activated vascular endothelium. Platelets aggregate with leukocytes, inducing the secretion of NETs and inflammatory mediators by neutrophils and monocytes, respectively. (B) DENV directly infects stromal cells and hematopoietic precursors, including megakaryocytes, which compromises megakaryopoiesis. Both central and peripheric mechanisms contribute to DENV-associated thrombocytopenia.

Analysis of dengue cases and severity classifications in Cavite Province, Philippines

Dengue is considered endemic in many countries in the world including the Philippines, and factors associated with dengue infections have not been adequately explored in the Philippines. The aim of this study was to assess demographic and location-related factors associated with different classifications of dengue: mild dengue, dengue fever, and hemorrhage dengue fever. This study used consolidated dengue reports of 18482 individual cases from the Provincial Hospital (PH) of Cavite province from 2009-2014 and clinical classifications of dengue used by the Philippine Integrated Disease Surveillance and Response (PIDSR). Multinomial logistic regression and marginal effects were used to analyze factors associated with different dengue classifications. Living in densely populated cities and municipalities, individuals aged 19 years and below, and being female were closely associated with severe dengue (DHF) type, while being male and older (above 19 years old) decreased the risk of contracting severe dengue. Our study provides a preliminary assessment of association between demographic factors (gender and age-group), locations (municipalities and cities); and three classifications of dengue (mild, moderate, and severe) in Cavite province in the Philippines. To establish whether dengue is linked to populated areas, age and gender will require further assessments.

ERG-Associated lncRNA (ERGAL) Promotes the Stability and Integrity of Vascular Endothelial Barrier During Dengue Viral Infection via Interaction With miR-183-5p.

Dengue virus (DENV) continues to be a major public health problem. DENV infection will cause mild dengue and severe dengue. Severe dengue is clinically manifested as serious complications, including dengue hemorrhagic fever and/or dengue shock syndrome (DHF/DSS), which is mainly characterized by vascular leakage. Currently, the pathogenesis of severe dengue is not elucidated thoroughly, and there are no known therapeutic targets for controlling the disease effectively. This study aimed to further reveal the potential molecular mechanism of severe dengue. In this study, the long non-coding RNA, ERG-associated lncRNA (lncRNA-ERGAL), was activated and significantly up-regulated in DENV-infected vascular endothelial cells. After knockdown of lncRNA-ERGAL, the expression of ERG, VE-cadherin, and claudin-5 was repressed; besides, cell apoptosis was enhanced, and cytoskeletal remodeling was disordered, leading to instability and increased permeability of vascular endothelial barrier during DENV infection. Fluorescence in situ hybridization (FISH) assay showed lncRNA-ERGAL to be mainly expressed in the cytoplasm. Moreover, the expression of miR-183-5p was found to increase during DENV infection and revealed to regulate ERG, junction-associated proteins, and the cytoskeletal structure after overexpression and knockdown. Then, ERGAL was confirmed to interact with miR-183-5p by luciferase reporter assay. Collectively, ERGAL acted as a miRNA sponge that can promote stability and integrity of vascular endothelial barrier during DENV infection via binding to miR-183-5p, thus revealing the potential molecular mechanism of severe dengue and providing a foundation for a promising clinical target in the future.

T-cells producing multiple combinations of IFNγ, TNF and IL10 are associated with mild forms of dengue infection.

Multifunctional interleukin 10 (IL10)+ Th1 cells have been implicated in favorable evolution of many infectious diseases, promoting an efficacious immune response while limiting immunopathology. Here, we investigated the presence of multifunctional CD4+ and CD8+ T-cells that expressed interferon gamma (IFNγ), IL10 and tumor necrosis factor (TNF), or its combinations during dengue infection. Peripheral blood mononuclear cells (PBMCs) from outpatients with dengue (mild dengue forms) and hospitalized patients (or patients with dengue with warning signs and severe dengue) were cultured in the presence of envelope (ENV) or NS3 peptide libraries of DENV during critical (hospitalization period) and convalescence phases. The production of IFNγ, IL10 and TNF by CD4+ and CD8+ T-cells was assessed by flow cytometry. Our data show that patients with mild dengue, when compared with patients with dengue with warning signs and severe dengue, presented higher frequencies of multifunctional T-cells like NS3-specific IFNγ/IL10-producing CD4+ T-cells in critical phase and NS3- and ENV-specific CD8+ T-cells producing IFNγ/IL10. In addition, NS3-specific CD8+ T-cells producing high levels of IFNγ/TNF and IFNγ/TNF/IL10 were also observed in the mild dengue group. We observed that multifunctional T-cells produced higher levels of cytokines as measured by intracellular content when compared with single producer T-cells. Importantly, multifunctional CD4+ and CD8+ T-cells producing IFNγ, TNF and IL10 simultaneously displayed positive correlation with platelet levels, suggesting a protective role of this population. The presence of IL10+ Th1 and IL10+ Tc1 multifunctional cells was associated with mild dengue presentation, suggesting that these cells play a role in clinical evolution of dengue infection.

Study of liver enzyme variation in children with dengue fever

Background: Dengue fever continues to be one of the major public health problems in large parts of the world, with an estimated 50 million dengue infections occurring annually. Liver enzyme variation is commonly seen in patients with dengue fever. This study was undertaken to assess the pattern of liver enzyme variation in children with dengue fever and to correlate it with the severity of this disease.Methods: Observational, descriptive hospital-based study involving 100 children who were serologically positive for dengue fever. The cases were classified as Mild, Moderate and Severe Dengue based on National Guidelines of clinical management of Dengue fever, 2015 and severity was assessed in each category. The study assessed the variability of liver enzymes in these children.Results: Aspartate Aminotransferase (AST) was elevated in 56 cases whereas Alanine Aminotransferase (ALT) was elevated in 44 cases. The elevation in liver enzymes in mild cases was 52%, moderate cases was 75% and severe cases was 100%. In cases presenting on day 1 of fever, enzymes were elevated in 0%, on day 2 in 20%, on day 3 in 38%, on day 4 in 51%, on day 5 in 90% and on day 6 in 88%.Conclusions: Liver Enzyme (AST and ALT) elevation in Dengue is a common feature. AST elevation was more common than ALT. Highest elevation in liver enzymes were observed on 5th and 6th day of fever. Liver enzyme elevation was more commonly seen in moderate and severe cases.

Significance of RANTES-CCR5 axis and linked downstream immunomodulation in Dengue pathogenesis: A study from Guwahati, India.

We aimed to evaluate the significance of the RANTES-CCR5 axis and resulting immunomodulatory status in Dengue pathogenesis involving a Guwahati, India based population where Dengue cases have increased alarmingly. An increased CC-chemokine receptor type 5 (CCR5) messenger RNA expression and CCR5 positive cell count profile was observed in Dengue cases, the highest being in severe cases. CCR5 ligand RANTES expression was significantly decreased in Dengue cases and inversely correlated with Dengue viremia fold change in severe cases. Monocytes are involved in Dengue virus homing and replication. Its levels and activation profile were higher in Dengue cases. A hyper Th1-biased immunomodulatory profile with upregulated tumor necrosis factor-α levels, and downregulated expression of antiviral cytokine interferon-γ and key regulatory Th2 anti-inflammatory cytokine interleukin 10 was observed in severe Dengue cases compared with mild Dengue cases and controls. The results, therefore, suggest the significance of RANTES-CCR5 axis deregulation and resulting altered immunomodulation in Dengue pathogenesis, and holds prognostic and therapeutic significance.

Multiple Lineages of Dengue Virus Serotype 2 Cosmopolitan Genotype Caused a Local Dengue Outbreak in Hangzhou, Zhejiang Province, China, in 2017

During July to November 2017, a large dengue outbreak involving 1,138 indigenous cases occurred in Hangzhou, Zhejiang Province, China. All patients were clinically diagnosed as mild dengue. Epidemiology investigation and phylogenetic analysis of circulating viruses revealed that at least three lineages of dengue virus serotype 2 (DENV-2) Cosmopolitan genotype initiated the outbreak during a short time. The analysis of the time to most recent common ancestor estimated that the putative ancestor of these DENV-2 lineages might rise no later than March, 2017, suggesting independent introductions of these lineages into Hangzhou. We presumed that group travelers visiting dengue-endemic areas gave rise to multiple introductions of these lineages during so short a time. Co-circulating of multiple DENV-2 lineages, emerging of disease in urban areas, hot and humid weather in Hangzhou adequate for mosquito breeding, and limited dengue diagnosis abilities of local hospitals, were the reasons causing the large local outbreak in Hangzhou.

Zika virus: raising awareness to prevent a pandemic

Zika virus is a flavivirus which is transmitted through Aedes female mosquito species or sexually. “Mild dengue” like symptoms are noticed which usually subside shortly and uneventfully. In 1969 ZIKV was isolated in West Malaysia for the first time. Since then no case has been reported in Malaysia. WHO has declared a global threat of an epidemic spread after the outbreak in Brazil. Rain forest climate regions are at a constant state of emergency as pools of water are abundantly formed as a result of rain showers throughout the year which provides a habitat for mosquitos. We try to raise awareness and alert health governing bodies and institutions to take necessary steps to prevent and eradicate the potential pandemic threat. Counselling of females who are planning to conceive is required to minimize the threat to newborn babies. Travellers visiting the equatorial regions should be screened and counselled to detect and prevent viral infection transfer and to avoid complications on a larger scale.Bangladesh Journal of Medical Science Vol.17(3) 2018 p.327-328

Increased Levels of Txa₂ Induced by Dengue Virus Infection in IgM Positive Individuals Is Related to the Mild Symptoms of Dengue.

The inflammatory process plays a major role in the prognosis of dengue. In this context, the eicosanoids may have considerable influence on the regulation of the Dengue virus-induced inflammatory process. To quantify the molecules involved in the cyclooxygenase and lipoxygenase pathways during Dengue virus infection, plasma levels of thromboxane A2, prostaglandin E2 and leukotriene B4; mRNA levels of thromboxane A2 synthase, prostaglandin E2 synthase, leukotriene A4 hydrolase, cyclooxygenase-2 and 5-lipoxygenase; and the levels of lipid bodies in peripheral blood leukocytes collected from IgM-positive and IgM-negative volunteers with mild dengue, and non-infected volunteers, were evaluated. Dengue virus infection increases the levels of thromboxane A2 in IgM-positive individuals as well as the amount of lipid bodies in monocytes in IgM-negative individuals. We suggest that increased levels of thromboxane A2 in IgM-positive individuals plays a protective role against the development of severe symptoms of dengue, such as vascular leakage.