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Background: Dengue infection poses a significant global health challenge, particularly in tropical and subtropical regions. Among its severe complications, Acute kidney injury (AKI) stands out due to its association with increased morbidity, mortality, and healthcare burdens. This Meta-analysis aim to identify and evaluate the predictors of AKI among dengue patients, facilitating early detection and management strategies to mitigate AKI's impact. Methods: We searched PubMed, EMBASE, and Web of Science databases, covering literature up to February 2024. We included human observational studies reporting on AKI predictors in confirmed dengue cases. Nested-Knowledge software was used for screening and data extraction. The Newcastle-Ottawa Scale was used for quality assessment. R software (V 4.3) was utilized to compute pooled odds ratios (ORs) and 95% confidence intervals (CIs) for each predictor. Results: Our search yielded nine studies involving diverse geographic locations and patient demographics. A total of 9,198 patients were included in the studies, with 542 diagnosed with AKI. in which key predictors of AKI identified include severe forms of dengue (OR: 2.22, 95% CI: 1.02–3.42), male gender (OR: 3.13, 95% CI: 1.82–4.44), comorbidities such as diabetes mellitus (OR: 3.298, 95% CI: 0.274–6.322), and chronic kidney disease (OR: 2.2, 95% CI: 0.42–11.24), as well as co-infections and clinical manifestations like rhabdomyolysis and major bleeding. Conclusion: Our study identifies several predictors of AKI in dengue patients. These findings indicate the importance of early identification and intervention for high-risk individuals. Future research should focus on standardizing AKI diagnostic criteria within the dengue context and exploring the mechanisms underlying these associations to improve patient care and outcomes. [ABSTRACT FROM AUTHOR]

Background: While dengue NS1 antigen has been shown to be associated with disease pathogenesis in some studies, it has not been linked in other studies, with the reasons remaining unclear. NS1 antigen levels in acute dengue are often associated with increased disease severity, but there has been a wide variation in results based on past dengue infection and infecting dengue virus (DENV) serotype. As NS1 engages with many host lipids, we hypothesize that the type of NS1-lipid interactions alters its pathogenicity. Methods: Primary human monocyte derived macrophages (MDMs) were co-cultured with NS1 alone or with HDL, LDL, LPS and/or platelet activating factor (PAF) from individuals with a history of past dengue fever (DF = 8) or dengue haemorrhagic fever (DHF = 8). IL-1β levels were measured in culture supernatants, and gene expression analysis carried out in MDMs. Monocyte subpopulations were assessed by flow cytometry. Hierarchical cluster analysis with Euclidean distance calculations were used to differentiate clusters. Differentially expressed variables were extracted and a classifier model was developed to differentiate between past DF and DHF. Results: Significantly higher levels of IL-1β were seen in culture supernatants when NS1 was co-cultured with LDL (p = 0.01, median = 45.69 pg/ml), but lower levels when NS1 was co-cultured with HDL (p = 0.05, median = 4.617 pg/ml). MDMs of those with past DHF produced higher levels of IL-1β when NS1 was co-cultured with PAF (p = 0.02). MDMs of individuals with past DHF, were significantly more likely to down-regulate RPLP2 gene expression when macrophages were co-cultured with either PAF alone, or NS1 combined with PAF, or NS1 combined with LDL. When NS1 was co-cultured with PAF, HDL or LDL two clusters were detected based on IL10 expression, but these did not differentiate those with past DF or DHF. Conclusions: As RPLP2 is important in DENV replication, regulating cellular stress responses and immune responses and IL-10 is associated with severe disease, it would be important to further explore how differential expression of RPLP2 and IL-10 could lead to disease pathogenesis based on NS1 and lipid interactions. [ABSTRACT FROM AUTHOR]

Dengue illness, caused by the dengue viruses, continues to be a major global health concern, with increasing incidence and the emergence of severe manifestations such as neurological complications. An overview of the current understanding of dengue epidemiology, clinical manifestations, and research priorities is presented here. Dengue transmission has escalated in recent years, exacerbated by factors such as vector expansion, climate change, and socioeconomic challenges. The clinical spectrum of dengue ranges from mild febrile illness to severe manifestations, including hemorrhagic fever and neurological complications. Neurological manifestations of dengue, once considered rare, are now increasingly reported, encompassing encephalitis, myelitis, and Guillain–Barré Syndrome, among others. Diagnosis primarily relies on laboratory methods such as RT/PCR, NS1 antigen detection, and serological assays. Despite advancements in understanding the dengue pathogenesis, there remains a critical need for effective vaccines, antiviral drugs, improved surveillance methods, predictive models for disease severity, and long-term studies on post-Dengue sequelae. Integrated programs and holistic approaches to dengue control are essential for mitigating its impact. Addressing these research priorities will be pivotal in combating dengue and reducing its global burden. [ABSTRACT FROM AUTHOR]

Abstract Background Dengue infection poses a significant global health challenge, particularly in tropical and subtropical regions. Among its severe complications, Acute kidney injury (AKI) stands out due to its association with increased morbidity, mortality, and healthcare burdens. This Meta-analysis aim to identify and evaluate the predictors of AKI among dengue patients, facilitating early detection and management strategies to mitigate AKI’s impact. Methods We searched PubMed, EMBASE, and Web of Science databases, covering literature up to February 2024. We included human observational studies reporting on AKI predictors in confirmed dengue cases. Nested-Knowledge software was used for screening and data extraction. The Newcastle-Ottawa Scale was used for quality assessment. R software (V 4.3) was utilized to compute pooled odds ratios (ORs) and 95% confidence intervals (CIs) for each predictor. Results Our search yielded nine studies involving diverse geographic locations and patient demographics. A total of 9,198 patients were included in the studies, with 542 diagnosed with AKI. in which key predictors of AKI identified include severe forms of dengue (OR: 2.22, 95% CI: 1.02–3.42), male gender (OR: 3.13, 95% CI: 1.82–4.44), comorbidities such as diabetes mellitus (OR: 3.298, 95% CI: 0.274–6.322), and chronic kidney disease (OR: 2.2, 95% CI: 0.42–11.24), as well as co-infections and clinical manifestations like rhabdomyolysis and major bleeding. Conclusion Our study identifies several predictors of AKI in dengue patients. These findings indicate the importance of early identification and intervention for high-risk individuals. Future research should focus on standardizing AKI diagnostic criteria within the dengue context and exploring the mechanisms underlying these associations to improve patient care and outcomes.

Infants less than 1 y of age experience high rates of dengue disease in dengue virus (DENV) endemic countries. This burden is commonly attributed to antibody-dependent enhancement (ADE), whereby concentrations of maternally derived DENV antibodies become subneutralizing, and infection-enhancing. Understanding antibody-related mechanisms of enhanced infant dengue disease risk represents a significant challenge due to the dynamic nature of antibodies and their imperfect measurement processes. Further, key uncertainties exist regarding the impact of long-term shifts in birth rates, population-level infection risks, and maternal ages on the DENV immune landscape of newborns and their subsequent risks of severe dengue disease in infancy. Here, we analyze DENV antibody data from two infant cohorts (N = 142 infants with 605 blood draws) and 40 y of infant dengue hospitalization data from Thailand. We use mathematical models to reconstruct maternally derived antibody dynamics, accounting for discretized measurement processes and limits of assay detection. We then explore possible antibody-related mechanisms of enhanced infant dengue disease risk and their ability to reconstruct the observed age distribution of hospitalized infant dengue cases. We find that ADE mechanisms are best able to reconstruct the observed data. Finally, we describe how the shifting epidemiology of dengue in Thailand, combined with declining birth rates, have decreased the absolute risk of infant dengue disease by 88% over a 40-y period while having minimal impact on the mean age of infant hospitalized dengue disease.

Abstract Background Dengue disease is caused by dengue virus, which is transmitted by Aedes mosquitoes in tropical and subtropical regions worldwide. Although most infected individuals have benign febrile illness or no apparent symptoms, a small percentage develop severe dengue, a potentially fatal condition that occurs after a febrile stage. Many studies have identified factors predicting dengue severity among different populations and time courses. To help find practical approaches applicable in remote settings, we focused on the investigation of early factors associated with severe dengue in Thai–Myanmar cross-border region. Methods This retrospective case-control study was performed to determine factors contributing to severe dengue in the pediatric population. We reviewed the hospital records of patients with dengue infection aged 0–19 years who were admitted to Maesot General Hospital, situated near the Thai–Myanmar cross-border region, between 2017 and 2022. Medical data during the first 5 days of illness and outcomes were collected and analyzed. Results This study included 144 patients with a serologically confirmed diagnosis of dengue infection, with 43 severe and 101 non-severe cases. Among biological factors, being an infant and belonging to an ethnic group in Myanmar showed a significant association with severe dengue in the univariable analysis. Multivariable logistic regression revealed that the presence of mucosal bleeding (adjusted OR 5.39, 95% CI 1.06–27.52, P = 0.043), a change in hematocrit ≥ 10% (adjusted OR 3.68, 95% CI 1.15–11.74, P = 0.028), and serum albumin

Abstract Introduction Severe multisystem inflammatory syndrome in children (MIS-C) and severe dengue are challenging to identify during the COVID-19 pandemic in dengue-endemic areas. Fever, multiorgan involvement, and shock characterize both severe MIS-C and severe dengue. Distinguishing between the two diseases is beneficial in initiating proper management. Methods Medical records of children

Background: Dengue fever (DF) is a mosquito‐borne illness with substantial economic and societal impact. Understanding laboratory trends of hospitalized Dominican Republic (DR) pediatric patients could help develop screening procedures in low‐resourced settings. We sought to describe laboratory findings over time in DR children with DF and DF severity from 2018 to 2020. Methods: Clinical information was obtained prospectively from recruited children with DF. Complete blood count (CBC) laboratory measures were assessed across Days 1–10 of fever. Participants were classified as DF‐negative and DF‐positive and grouped by severity. We assessed associations of DF severity with demographics, clinical characteristics, and peripheral blood studies. Using linear mixed‐models, we assessed if hematologic values/trajectories differed by DF status/severity. Results: A total of 597 of 1101 with a DF clinical diagnosis were serologically evaluated, and 574 (471 DF‐positive) met inclusion criteria. In DF, platelet count and hemoglobin were higher on earlier days of fever (p < = 0.0017). Eighty had severe DF. Severe DF risk was associated with thrombocytopenia, intraillness anemia, and leukocytosis, differing by fever day (p < = 0.001). Conclusions: In a pediatric hospitalized DR cohort, we found marked anemia in late stages of severe DF, unlike the typically seen hemoconcentration. These findings, paired with clinical symptom changes over time, may help guide risk‐stratified screenings for resource‐limited settings. [ABSTRACT FROM AUTHOR]

Objective To analyze the changing trends of severe dengue (SD) among adults and children in China and compare the clinical manifestations between the two groups, providing scientific evidence to optimize dengue prevention strategies and reduce severe cases. Methods Literature related to clinical or infection aspects of dengue fever clinical or infection studies published from database inception to December 31, 2023, were retrieved from CNKI, Wanfang, VIP, and Scopus databases using keyword searches. The literature was screened according to predefined inclusion and exclusion criteria, and a meta-analysis was conducted using R (4.2.3) software. Results A total of 7 148 records were retrieved, ultimately including 30 studies on adults and 12 studies on children, involving eight provinces. The severe dengue comorbidity rate in adults decreased from 6.6% during 1978-1995 to 0.9% during 2014-2023, while in children, it significantly dropped from 15.8% during 1980-1995 to 0.5% during 2014-2019. In adult studies, the primary clinical manifestations and their comorbidity rates were: fever (99.2%), myalgia (55.6%), headache (52.0%), rash (45.5%), and fatigue (34.4%). In pediatric studies, the primary clinical manifestations and their comorbidity rates were: fever (97.6%), headache (38.8%), anorexia (31.9%), rash (30.5%), and lymphadenopathy (20.5%). Conclusions In recent years, the severe dengue comorbidity rates have significantly decreased in both adults and children, indicating that China's dengue prevention and control strategies have achieved remarkable results. The prominent clinical manifestations in adults are associated with organ damage, while children predominantly show gastrointestinal symptoms. Moving forward, efforts should be made to strengthen early diagnosis and standardized treatment to further reduce the clinical impact of dengue fever. [ABSTRACT FROM AUTHOR]

Background: Dengue disease is caused by dengue virus, which is transmitted by Aedes mosquitoes in tropical and subtropical regions worldwide. Although most infected individuals have benign febrile illness or no apparent symptoms, a small percentage develop severe dengue, a potentially fatal condition that occurs after a febrile stage. Many studies have identified factors predicting dengue severity among different populations and time courses. To help find practical approaches applicable in remote settings, we focused on the investigation of early factors associated with severe dengue in Thai–Myanmar cross-border region. Methods: This retrospective case-control study was performed to determine factors contributing to severe dengue in the pediatric population. We reviewed the hospital records of patients with dengue infection aged 0–19 years who were admitted to Maesot General Hospital, situated near the Thai–Myanmar cross-border region, between 2017 and 2022. Medical data during the first 5 days of illness and outcomes were collected and analyzed. Results: This study included 144 patients with a serologically confirmed diagnosis of dengue infection, with 43 severe and 101 non-severe cases. Among biological factors, being an infant and belonging to an ethnic group in Myanmar showed a significant association with severe dengue in the univariable analysis. Multivariable logistic regression revealed that the presence of mucosal bleeding (adjusted OR 5.39, 95% CI 1.06–27.52, P = 0.043), a change in hematocrit ≥ 10% (adjusted OR 3.68, 95% CI 1.15–11.74, P = 0.028), and serum albumin < 35 g/L (adjusted OR 8.10, 95% CI 2.55–25.72, P < 0.001) during the first 5 days of illness were significantly associated with developing severe dengue. Conclusions: This study supports the use of certain WHO warning signs and hematocrit change during febrile phase to predict pediatric severe dengue in low-resource settings. Potential factors such as very young age and ethnic groups warrant further exploration to identify risks contributing to severe dengue infection. [ABSTRACT FROM AUTHOR]

Introduction: Severe multisystem inflammatory syndrome in children (MIS-C) and severe dengue are challenging to identify during the COVID-19 pandemic in dengue-endemic areas. Fever, multiorgan involvement, and shock characterize both severe MIS-C and severe dengue. Distinguishing between the two diseases is beneficial in initiating proper management. Methods: Medical records of children < 18 years old who were hospitalized at Hasan Sadikin General Hospital's PICU between December 2020 and July 2022 with severe MIS-C or severe dengue were recorded. Differences were assessed using comparative and descriptive analyses. Results: Seventeen severe dengue patients and 4 severe MIS-C were included. The average age of severe MIS-C was 11.5 years (SD ± 2.9, 95% CI), and that of severe dengue patients was 6.2 years (SD ± 4.4, 95% CI) (p value = 0.034, 95%). Fever and abdominal pain were the most common symptoms in both groups (p = 0.471, 95% CI). Rash (p = 0.049) and nonpurulent conjunctivitis (p = 0.035) were two symptoms with significant differences. The highest platelet count (p-value = 0.006, 95% CI), AST (p-value = 0.026, 95% CI), and D-dimer level (p-value = 0.025, 95% CI) were significantly different between the two cohorts. Cardiac abnormalities were found in all (100%) severe MIS-C patients, but only one (5.9%) in severe dengue patients. Conclusion: Age, rash, nonpurulent conjunctivitis, platelet count, AST and D-dimer level may distinguish severe MIS-C from severe dengue fever. [ABSTRACT FROM AUTHOR]

Liver involvement is an unusual yet frequently overlooked dengue complication. Pivotal for an efficient clinical management, the early diagnosis of dengue‐associated liver involvement relies on an accurate description of its clinical and biological characteristics, its prognosis factors, its association with severe dengue and its clinical management. We conducted a systematic review by searching PubMed and Web of Science databases for original case reports, cohort and cross‐sectional studies reporting the clinical and/or biological features of dengue‐associated liver involvement. The study was registered in PROSPERO (CRD42021262657). Of the 2552 articles identified, 167 were included. Dengue‐associated liver involvement was characterised by clinical features including abdominal pain, hepatomegaly, jaundice, nausea/vomiting, and an echogenic liver exhibiting hepatocellular necrosis and minimal inflammation. Elevated Aspartate Aminotransferase and Alanine Aminotransferase but also elevated bilirubin, Alkaline Phosphatase, gamma‐glutamyl transferase, increased International Normalised Ratio, creatinine and creatine kinase, lower albumin and prolonged prothrombin and activated partial thromboplastin time were prevalent in dengue‐associated liver involvement. Cardiovascular and haematological systems were frequently affected, translating in a strong association with severe dengue. Liver involvement was more common in males and older adults. It was associated with dengue virus serotype‐2 and secondary infections. Early paracetamol intake increased the risk of liver involvement, which clinical management was mostly conservative. In conclusion, this systematic review demonstrates that early monitoring of transaminases, clinical assessment, and ultrasound examination allow an efficient diagnosis of dengue‐associated liver involvement, enabling the early identification and management of severe dengue. [ABSTRACT FROM AUTHOR]

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Few studies have investigated whether SARS-CoV-2 infections increase the incidence of dengue haemorrhagic fever/shock syndrome (DHF/DSS) and/or severe dengue (SD) in dengue virus (DENV)-infected patients. This study was performed on a site with high incidences of classical dengue, but relatively few DHF/DSS or SD cases as defined by the WHO 1997 or 2009 criteria, respectively. Clinical, haematological/biochemical, and viral diagnostic data were collected from febrile patients before, during, and after the COVID-19 epidemic to assess whether (a) DENV-infected patients with prior SARS-CoV-2 infections or (b) DENV-SARS-CoV-2-co-infected patients had increased incidences of SD/DHF/DSS using logistic regression and machine learning models. Higher numbers of DHF/DSS/SD occurred during the COVID-19 epidemic, particularly in males and 18–40-year-olds. Significantly increased symptoms in the DENV-SARS-CoV-2-co-infected cases were (a) haemoconcentration (p < 0.0009) and hypotension (p < 0.0005) (DHF/DSS and SD criteria), (b) thrombocytopenia and mucosal bleeding (DHF/DSS-criteria), (c) abdominal pain, persistent vomiting, mucosal bleeding, and thrombocytopenia (SD warning signs) and (d) dyspnoea, but without fluid accumulation. DENV-infected patients with prior SARS-CoV-2 infections had significantly increased incidences of thrombocytopenia (DHF/DSS-criteria) and/or abdominal pain and persistent vomiting and also thrombocytopenia (SD warning signs), but without significant haemoconcentration or hypotension. DENV-SARS-CoV-2 co-infections significantly increased the incidence of DHF/DSS/SD, while DENV-infected patients with prior SARS-CoV-2 infections displayed significantly increased incidences of thrombocytopenia (DHF/DSS-criteria) and three important SD warning signs, which are therefore very important for health workers/clinicians in assessing patients' DHF/DSS/SD risk factors and planning their optimal therapies. [ABSTRACT FROM AUTHOR]

Introduction: Host immune responses may impact dengue severity in adults. Vitamin D has multiple immunomodulatory effects on innate and adaptive immunity. Methods: We evaluated the association between systemic 25-hydroxyvitamin D [25-(OH) D] and dengue disease severity in adults. We measured plasma for total 25-(OH) D levels with an electrochemiluminescence immunoassay using stored samples from participants with laboratory-confirmed dengue, who were prospectively enrolled in 2012-2016 at our institution. Results: A total of 80 participants (median age 43 years) were enrolled in the study. Six participants had severe dengue based on the World Health Organization (WHO) 1997 criteria (i.e. dengue haemorrhagic fever/dengue shock syndrome) and another six had severe dengue based on the WHO 2009 criteria. Median 25-(OH) D at the acute phase of dengue was 6.175 (interquartile range 3.82-8.21, range 3.00-15.29) mcg/L in all participants. The 25-(OH) D showed an inverse linear trend with severe dengue manifestations based on the WHO 2009 criteria (adjusted risk ratio 0.72, 95% confidence interval 0.57-0.91, P < 0.01) after adjustment for age, gender and ethnicity. Conclusion: Limited studies have evaluated the role of systemic 25-(OH) D on dengue severity. Our study found low systemic 25-(OH) D was associated with increased dengue disease severity, particularly for severe bleeding that was not explained by thrombocytopenia. Further studies investigating the underlying immune mechanisms and effects on the vascular endothelium are needed. [ABSTRACT FROM AUTHOR]

Background: Vascular endothelial growth factor (VEGF) is one of the proteins involved in dengue immunopathogenesis. It is overexpressed in severe dengue and contributes to vascular permeability and plasma leakage. In this study, we investigated the effects of VEGF and anti-VEGF treatments on endothelial cells in vitro, to assess the potential use of anti-VEGF antibodies in managing severe dengue. Methods: Human pulmonary microvascular endothelial cells were treated with VEGF and a VEGF/anti-VEGF combination. The effects of the treatments were studied using an endothelial permeability assay and microarray gene expression profiling. In the permeability assay, the fluorescein isothiocyanate (FITC)-dextran fluorescence signal across the endothelial monolayer was recorded, and the cells were stained with PECAM-1 to detect gap formation. RNA was extracted from treated cells for microarray gene profiling and analysis. The results were analyzed for differentially expressed genes (DEGs) and gene enrichment analysis. The DEGs were subjected to STRING to construct the protein-protein interaction network and then Cytoscape to identify the hub genes. Results: VEGF-treated endothelial cells showed greater movement of FITC-dextran across the monolayer than VEGF/anti-VEGF-treated cells. There were 111 DEGs for VEGF-treated cells and 118 DEGs for VEGF/anti-VEGF-treated cells. The genes upregulated in VEGF-treated cells were enriched in inflammatory responses and regulation of the endothelial barrier, nitric oxide synthesis, angiogenesis, and the nucleotide-binding oligomerization domain-like receptor signaling pathway. Top 10 hub genes were identified from the DEGs. Conclusions: VEGF treatment increased permeability across endothelial cells, while anti-VEGF reduced this leakage. Analysis of VEGF-treated endothelial cells identified hub genes implicated in severe dengue. The top 10 hub genes were TNF, IL1B, IL6, CCL2, PTGS2, ICAM1, CXCL2, CXCL1, CSF2, and TLR2. The results of this study show that using anti-VEGF antibodies to neutralize VEGF may be a promising therapy to prevent the progression of dengue to severe dengue.

Abstract Background Dengue Viral Infection (DVI) has become endemic in Pakistan since the first major outbreak in Karachi in 1996. Despite aggressive measures taken by relevant authorities, Pakistan has been dealing with a worsening dengue crisis for the past two decades. DHF is severe form of dengue infection which is linked with significant morbidity and mortality. Early identification of severe dengue infections can reduce the morbidity and mortality. In this context we planned current study in which we find out the different factors related with DHF as well as clinical laboratory features of DHF and compare them to DF so that patients can be best evaluated for DHF and managed accordingly at admission. Methods Retrospective study conducted over a period of 6 years (2013–2018) in two tertiary care hospitals in Pakistan. Data were collected by using a pre-structured data collection form. Data were statistically analyzed to determine the clinical and laboratory characteristics of DVI and risk factors of dengue hemorrhagic fever (DHF). Results A total 512 dengue cases (34.05 ± 15.08 years; Male 69.53%) were reviewed. Most common clinical manifestations of DVI were fever (99.60%), headache (89.1%), chills (86.5%), rigors (86.5%), myalgia (72.3%). Less common clinical manifestations were vomiting (52.5%), arthralgia (50.2%) and skin rashes (47.5%). Furthermore, nasal bleeding (44.1%), gum bleeding (32.6%), pleural effusion (13.9%) and hematuria (13.1%) were more profound clinical presentations among DHF patients. Mortality rate was 1.5% in this study. Logistic regression analysis indicated that delayed hospitalization (OR: 2.30) and diabetes mellitus (OR:2.71), shortness of breath (OR:2.21), association with risk groups i.e., living near stagnant water, travelling to endemic areas, living in endemic regions (OR:1.95), and presence of warning signs (OR:2.18) were identified as risk factors of DHF. Statistically we found that there is strong association of diabetes mellitus (DM) with DHF while the patient suffering from DM individually had higher odds (2.71) of developing DHF than patients without disease. Conclusions The current study demonstrated that the clinical and laboratory profiles of DF and DHF are significantly distinct. Significant predictors of DHF were advanced age, diabetes mellitus, ascites, pleural effusion, thick gallbladder and delayed hospitalization. The identification of these factors at early stage provides opportunities for the clinicians to identify high risk patients and to reduce dengue-related morbidity and mortality.

Zubia Jamil,1 Samreen Khalid,1 Hafiz Muhammad Manan Haider Khan,2 Ikram Waheed,1,3 Amna Ehsan,1,3 Mohammed Alissa,4 Khalid Muhammad,5 Nayla Munawar,6 Yasir Waheed7,8 1Department of Medicine, Foundation University School of Health Sciences, Foundation University, Islamabad, 44000, Pakistan; 2Department of Rehabilitation Sciences, Shifa Tameer-E-Millat University, Islamabad, 44000, Pakistan; 3Department of Medicine, Fauji Foundation Hospital, Rawalpindi, 43600, Pakistan; 4Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia; 5Department of Biology, College of Science, UAE University, Al Ain, 15551, United Arab Emirates; 6Department of Chemistry, College of Science, UAE University, Al Ain, 15551, United Arab Emirates; 7Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos, 1401, Lebanon; 8MEU Research Unit, Middle East University, Amman, 11831, JordanCorrespondence: Yasir Waheed, Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos, 1401, Lebanon, Email yasir_waheed_199@hotmail.com Nayla Munawar, Department of Chemistry, College of Science, UAE University, Al Ain, 15551, United Arab Emirates, Email nmunawar@uaeu.ac.aeIntroduction: The occurrence of dengue fever presents a considerable burden for public health care in developing countries. This study aims to validate APRI as predictor score for severity of dengue fever so that catastrophic events could be prevented, and early triage can save lives.Methods: The retrospective cross-sectional study was done on dengue positive patients from August to November 2023. APRI score was calculated for every patient at the time of admission. The primary end-point was non-complicated disease (Simple dengue fever) vs complicated disease (dengue hemorrhagic fever and dengue shock syndrome). ROC curve was used to identify the role of APRI in prediction of dengue complication. Youden index was used to find the cut-off value of APRI along with sensitivity, specificity, positive and negative likelihood ratios. To further evaluate the role of APRI score, patients were divided into two groups, patients with APRI score greater and lesser than cut-off value. The qualitative variables among two groups were compared by chi-square testing. The predictors of complicated dengue were first determined by univariate regression analysis and then confirmed by multivariate regression analysis.Results: The mean APRI score of 135 patients was 20.06 ± 6.31. AUC for APRI score was 0.93 (p < 0.0001) indicating that APRI score calculated at the time of admission is an excellent marker in determining the complicated dengue. The cut-off value for APRI score was 9.04 (sensitivity 84.91%, specificity 89.02%, p < 0.0001). The patients with APRI < 9.04 mostly developed simple dengue fever (54.1%) vs DHF (4.4%) and DSS (1.5%), while patients with APRI > 9.04 had more DHF (20.7%) and DSS (12.6%) vs simple dengue fever (6.7%). None of the patient died with APRI < 9.04 while the mortality rate was 3.7% in patients with APRI > 9.04.Conclusion: The APRI score, calculated at the time of admission, is an excellent marker in determining the severe dengue.Keywords: dengue, severe dengue, dengue hemorrhagic fever, aspartate aminotransferase, ROC curve, area under curve

Background: Identifying predictors of severe dengue (SD) is key for triage and management of patients as well as for advising travellers to countries where dengue is endemic. In this, meta-analyses have raised diabetes mellitus as a risk factor for SD and a prognostic factor for dengue-related mortality. The purpose of this study was to assess whether diabetic patients (DPs) are at increased risk for SD in comparison to non-diabetic patients (NDPs) in a setting of high prevalence of type 2 diabetes mellitus and increasing endemicity for dengue. Methods: In a cohort study conducted during the 2019 dengue epidemic on Reunion Island, we estimated the risk ratios (RR) of DPs for SD (WHO 2009 definition), hospitalisation, intensive care unit (ICU) admission, critical care need or death in the ICU, and scales rating severity or multiple organ dysfunction syndrome (MODS), among confirmed cases of dengue (positive RT-PCR or NS1 antigen). Results: In a Poisson regression model adjusted for age, gender and comorbidity, DPs were more likely to develop SD (adjusted RR: 1.46, 95%CI 1.10–1.95), to be hospitalised, admitted to the ICU, and need critical care or die in the ICU. Subgroup analyses identified female DPs, non-elderly DPs (< 65 years) and DPs with low Charlson score (< 3) to be at higher risk for SD, the two first subgroups trough more severe presentation (higher Simplified Acute Physiology Score-2 values; higher MODS scores, respectively). Male gender, age less than 65 years and mixed comorbidity were identified as prognostic factors for critical care need or death in the ICU, male and non-elderly DPs being more likely to develop MODS than their non-diabetic counterparts. Conclusions: Together, these data highlight the role of diabetes mellitus in the progression from dengue to SD through higher severity per se or the event of MODS.

Dengue fever is the most common arboviral disease transmitted globally. It was estimated about 400,000 cases of severe dengue occur in Asian countries. Patients with severe dengue are at risk of developing secondary Haemophagocytic Lymphohistiocytosis (HLH) which contribute to high morbidity and mortality. Thus, a high index of suspicion should be considered in critical dengue patient. We presented a case of young girl, who initially had classical symptoms and sign of dengue fever and was in compensated shock at presentation. The condition further deteriorated as she developed Acute respiratory distress syndrome (ARDS) and secondary HLH due to severe infection. She developed unremitting fever despite already out of defervenscence window period. With some positive laboratory findings; highly elevated serum ferritin of more than 10,000 mcg/L, low natural killer (NK) cells, bicytopenias and hypertriglyceridemia in which directed towards diagnosis of secondary HLH. However, due to ill condition, the bone marrow aspiration was not able to be performed to confirm the presence of haemophagocytosis. HLH is a hyper inflammatory condition which is characterized by macrophage activation with phagocytosis of blood cells in the bone marrow and cytokine storm, leading to organ dysfunction and death. [ABSTRACT FROM AUTHOR]

Background: Risk factors for severe dengue manifestations have been attributed to various factors, including specific serotypes, sex, and age. Mexico has seen the re-emergence of DENV-3, which has not circulated in a decade. Objective: To describe dengue serotypes by age, sex, and their association with disease severity in dengue-positive serum samples from epidemiological surveillance system units. Materials and Methods: A descriptive analysis was conducted to evaluate the frequency of dengue severity by sex, age, disease quarter, geographical location, and dengue virus serotypes. The study was conducted using laboratory samples from confirmed dengue cases through RT-qPCR from the epidemiological surveillance laboratory network of the Mexican Social Security Institute, Mexico. Simple frequencies and proportions were calculated using the z-test for proportional differences between groups. Bivariate analysis with adjusted Chi2 was performed, and binary logistic regression models were constructed using the forward Wald method considering the model's predictive capacity. The measure of association was the odds ratio, with 95% confidence intervals. Statistical significance was set to an alpha level of <0.05. Results: In 2023, 10,441 samples were processed for dengue RT-qPCR at the IMSS, with a predominance of serotype DENV-3 (64.4%). The samples were mostly from women (52.0%) and outpatient cases (63.3%). The distribution of dengue severity showed significant variations by age, with a lower proportion of severe cases in young children and a higher proportion in the 5- to 14-year-old group. Hospitalizations increased significantly with severity. Warm regions had more cases overall and severity. Cases were most frequent from July to September. While DENV-2 was associated with severity, DENV-4 was not. Binary regression identified higher risk in women, age extremes, and DENV-2, with an overall predictive model of 58.5%. Conclusions: Women, age groups at the extremes of life, and the DENV-2 serotype presented severe risk of dengue in a population with social security in Mexico during 2023. [ABSTRACT FROM AUTHOR]

Guangzhou has been the city most affected by the dengue virus (DENV) in China, with a predominance of DENV serotype 1 (DENV‐1). Viral factors such as dengue serotype and genotype are associated with severe dengue (SD). However, none of the studies have investigated the relationship between DENV‐1 genotypes and SD. To understand the association between DENV‐1 genotypes and SD, the clinical manifestations of patients infected with different genotypes were investigated. A total of 122 patients with confirmed DENV‐1 genotype infection were recruited for this study. The clinical manifestations, laboratory tests, and levels of inflammatory mediator factors were statistically analyzed to investigate the characteristics of clinical manifestations and immune response on the DENV‐1 genotype. In the case of DENV‐1 infection, the incidence of SD with genotype V infection was significantly higher than that with genotype I infection. Meanwhile, patients infected with genotype V were more common in ostealgia and bleeding significantly. In addition, levels of inflammatory mediator factors including IFN‐γ, TNF‐α, IL‐10, and soluble vascular cell adhesion molecule 1 were higher in patients with SD infected with genotype V. Meanwhile, the concentrations of regulated upon activation normal T‐cell expressed and secreted and growth‐related gene alpha were lower in patients with SD infected with genotype V. The higher incidence of SD in patients infected with DENV‐1 genotype V may be attributed to elevated cytokines and adhesion molecules, along with decreased chemokines. [ABSTRACT FROM AUTHOR]

Dengue's lack of specific treatments beyond supportive care prompts a focus on uncovering additional pathophysiological factors. Dengue-associated hemophagocytic lymphohistiocytosis (HLH), characterized by dysregulated macrophage activation and cytokine storm, remains underexplored despite its potential to worsen disease severity and mortality. While rare, dengue-associated HLH disproportionately affects severe cases, significantly impacting mortality rates. To mitigate high mortality, early identification and familiarity with dengue-associated HLH are imperative for prompt treatment by clinicians. This narrative review therefore aims to examine the current clinical and therapeutic knowledge on dengue-associated HLH, and act as a resource for clinicians to improve their management of HLH associated with severe dengue. Dengue-associated HLH should be considered for all cases of severe dengue and may be suspected based on the presence of prolonged or recurrent fever for >7 days, or anemia without intravascular hemolysis or massive bleeding. Diagnosis relies on fulfilling at least five of the eight HLH-2004 criteria. Treatment predominantly involves short courses (3–4 days) of high-dose steroids (e.g., dexamethasone 10 mg/m2), with additional therapies considered in more severe presentations. Notably, outcomes can be favorable with steroid therapy alone. [ABSTRACT FROM AUTHOR]

Introduction: Severe dengue is thought to be caused by an excessive host immune response. Methods: To study the pathogenesis of severe dengue, we developed a novel model using LysM Cre+Ifnarflox/flox mice carrying depleted Ifnar expression only in subsets of murine myeloid cells. Results: Although dengue virus (DENV) clinical isolates were not virulent in LysM Cre+Ifnarflox/flox mice, mouse-adapted DV1-5P7Sp and DV3P12/08P4Bm, which were obtained by passaging the spleen or bone marrow of mice, demonstrated 100% lethality with severe vascular leakage in the liver and small intestine. DV1-5P7Sp and DV3P12/08P4Bm harbored five and seven amino acid substitutions, respectively. Infection also induced neutrophil infiltration in the small intestine, and increased expression of IL-6 and MMP-8 and blockade of TNF-α signaling protected the mice, as demonstrated in a previous severe dengue mouse model using C57/BL6 mice lacking both IFN-α/β and IFN-γ receptors. Notably, the new models with DV1-5P7Sp and DV3P12/08P4Bm showed an increased proliferative capacity of the adapted viruses in the thymus and bone marrow. Discussion: These observations suggest that myeloid cell infection is sufficient to trigger cytokine storm-induced vascular leakage. This model can refine the factors involved in the pathology of severe dengue leading to vascular leakage. [ABSTRACT FROM AUTHOR]

Background Dengue cases continue to rise and can overwhelm healthcare systems during outbreaks. In dengue, neutrophil mediators, soluble urokinase plasminogen activator receptor (suPAR) and olfactomedin 4, and mast cell mediators, chymase and tryptase, have not been measured longitudinally across the dengue phases. The utility of these proteins as prognostic biomarkers for severe dengue has also not been assessed in an older adult population. Methods We prospectively enrolled 99 adults with dengue—40 dengue fever, 46 dengue with warning signs and 13 severe dengue, along with 30 controls. Plasma levels of suPAR, olfactomedin 4, chymase and tryptase were measured at the febrile, critical and recovery phases in dengue patients. Results The suPAR levels were significantly elevated in severe dengue compared to the other dengue severities and controls in the febrile (P <.001), critical (P <.001), and recovery (P =.005) phases. In the febrile phase, suPAR was a prognostic biomarker of severe dengue, with an AUROC of 0.82. Using a cutoff derived from Youden's index (5.4 ng/mL) and an estimated prevalence of severe dengue (16.5%) in our healthcare institution, the sensitivity was 71.4% with a specificity of 87.9% in the febrile phase, and the positive and negative predictive values were 54.7% and 95.8%, respectively. Olfactomedin 4 was elevated in dengue patients but not in proportion to disease severity in the febrile phase (P =.04) There were no significant differences in chymase and tryptase levels between dengue patients and controls. Conclusions In adult dengue, suPAR may be a reliable prognostic biomarker for severe dengue in the febrile phase. [ABSTRACT FROM AUTHOR]

Identifying predictors of severe dengue (SD) is key for triage and management of patients as well as for advising travellers to countries where dengue is endemic. In this, meta-analyses have raised diabetes mellitus as a risk factor for SD and a prognostic factor for dengue-related mortality. The purpose of this study was to assess whether diabetic patients (DPs) are at increased risk for SD in comparison to non-diabetic patients (NDPs) in a setting of high prevalence of type 2 diabetes mellitus and increasing endemicity for dengue. In a cohort study conducted during the 2019 dengue epidemic on Reunion Island, we estimated the risk ratios (RR) of DPs for SD (WHO 2009 definition), hospitalisation, intensive care unit (ICU) admission, critical care need or death in the ICU, and scales rating severity or multiple organ dysfunction syndrome (MODS), among confirmed cases of dengue (positive RT-PCR or NS1 antigen). In a Poisson regression model adjusted for age, gender and comorbidity, DPs were more likely to develop SD (adjusted RR: 1.46, 95%CI 1.10–1.95), to be hospitalised, admitted to the ICU, and need critical care or die in the ICU. Subgroup analyses identified female DPs, non-elderly DPs (< 65 years) and DPs with low Charlson score (< 3) to be at higher risk for SD, the two first subgroups trough more severe presentation (higher Simplified Acute Physiology Score-2 values; higher MODS scores, respectively). Male gender, age less than 65 years and mixed comorbidity were identified as prognostic factors for critical care need or death in the ICU, male and non-elderly DPs being more likely to develop MODS than their non-diabetic counterparts. Together, these data highlight the role of diabetes mellitus in the progression from dengue to SD through higher severity per se or the event of MODS. • Diabetics are at higher risk for severe dengue than non-diabetics. • Young age and lack of comorbidity are risk factors for severe dengue in diabetics. • Male gender, young age and comorbidities prognosticate diabetics with dengue. • Male diabetics with dengue are more likely to develop multiple organ dysfunctions. [ABSTRACT FROM AUTHOR]

Background and Aim: To assess the spectrum of hepatic involvement in children with dengue fever (DF) and prediction of severity of dengue infection by early detection of elevated liver enzymes. Methods: This prospective observational study was conducted at a tertiary care hospital from June 2019 to September 2019. Children admitted with DF were included. Severity of DF was graded as dengue without warning sign (DNWS), with warning sign (DWS), and severe dengue fever (SDF) according to WHO criteria. Liver injury (LI) was defined as alanine aminotransferase (ALT) more than upper limit of normal irrespective of sex. Results: Of 190 children (male, 109) with DF, 60 had DNWS, 49 had DWS, and 81 had SDF. A total of 100 children (52.6%) had LI. The distribution of hepatic involvement spectrum involves hepatomegaly (26.3%), hepatic tenderness (25.2%), features of acute liver failure (1.5%), raised level of ALT (52.6%), raised level of aspartateaminotransferase (AST) (65.8%), prolonged prothrombin time (7.3%), and reduced level of serum albumin (44.7%) in children. Of them, 5.8% and 6.8% of children had >tenfold increase in ALT and AST values. The degree of liver function derangement significantly (P < 0.05) increased with DF severity. In our study, ALT at 422 IU/L (10 times upper limit of normal [ULN]) and AST 689 IU/L (17 times ULN) had similar sensitivity and specificity as WHO recommended cutoff of 1000 IU/L (25 times of ULN) to detect SDF. Conclusion: ALT ≥10 times and AST ≥17 times of ULN are as sensitive as ≥25 times (as recommended by WHO) to detect SDF. [ABSTRACT FROM AUTHOR]

Background: Viremia is a critical factor in understanding the pathogenesis of dengue infection, but limited data exist on viremia kinetics. This study aimed to investigate the kinetics of viremia and its effects on subsequent platelet count, severe dengue, and plasma leakage. Methods: We pooled data from three studies conducted in Vietnam between 2000 and 2016, involving 2340 dengue patients with daily viremia measurements and platelet counts after symptom onset. Viremia kinetics were assessed using a random effects model that accounted for left-censored data. The effects of viremia on subsequent platelet count and clinical outcomes were examined using a landmark approach with a random effects model and logistic regression model with generalized estimating equations, respectively. The rate of viremia decline was derived from the model of viremia kinetics. Its effect on the clinical outcomes was assessed by logistic regression models. Results: Viremia levels rapidly decreased following symptom onset, with variations observed depending on the infecting serotype. DENV-1 exhibited the highest mean viremia levels during the first 5–6 days, while DENV-4 demonstrated the shortest clearance time. Higher viremia levels were associated with decreased subsequent platelet counts from day 6 onwards. Elevated viremia levels on each illness day increased the risk of developing severe dengue and plasma leakage. However, the effect size decreased with later illness days. A more rapid decline in viremia is associated with a reduced risk of the clinical outcomes. Conclusions: This study provides comprehensive insights into viremia kinetics and its effect on subsequent platelet count and clinical outcomes in dengue patients. Our findings underscore the importance of measuring viremia levels during the early febrile phase for dengue studies and support the use of viremia kinetics as outcome for phase-2 dengue therapeutic trials. Funding: Wellcome Trust and European Union Seventh Framework Programme.

ABSTRACT Background: Dengue is a disease that accounts for a major morbidity and mortality in Honduras. Methods: This descriptive study used an analytical component based on the data from the National Virology Laboratory between 2016-2022. Ordinal logistic regression was used to identify the factors associated with the classification of dengue without warning signs (DWOS), dengue with warning signs (DWS), and severe dengue (SD). Results: Overall, 14,687 dengue cases were included; 50.1% had DWOS, 36.5% had DWS, and 13.4% had SD. Patients that were more associated with a higher probability of DWS and SD were patients in the age groups 1-4 years (DWS OR 1.61; 95%CI:1.33-1.94), (SD OR 1.52; 95% CI:1.26-1.84), 5-9 years (DWS OR 2.01; 95% CI:1.68-2.40), (SD OR 2.00; 95% CI:1.67-2.40), and 10-19 years (DWS OR 1.55; 95% CI:1.30-1.85) (SD OR 1.57; 95% CI:1.31-1.88). The departments that were associated with a higher probability of DWS and SD were La Paz (OR 6.35; 95% CI:3.53-11.42), (OR 10.94; 95% CI:5.96-20.08), Copán (OR 6.94; 95% CI:5.05-9.53) (OR 7.33; 95% CI: 5.35-10.03), Valle (OR 5.22; 95% CI:1.25-21.82) (OR 10.71; 95% CI:2.21-51.88). Conclusions: During the study period, dengue presented endemic behavior, with peaks consistent with the last two epidemics in Honduras in 2015 and 2019. The main factors associated with dengue severity were age< 19 years, male sex, and being from La Paz, Copán, or Valle.

Introduction: Dengue is one of the most important vector-borne viral diseases in subtropical and tropical regions. The World Health Organization (WHO) 2009 classified dengue into three groups: dengue without alarm signs, dengue with alarm signs, and severe dengue. According to the type of dengue, various managements have been proposed. The authors suggest that a predictive factor to avoid a poor prognosis in this disease is to keep platelet levels stable in the patient to prevent a fatal outcome. The aim of this paper is to analyze the efficacy of transfusion of platelet agents in the outcome of patients with severe dengue and thrombocytopenia. Material and methods: A bibliographic search was carried out in the Medline, OVID, and Scielo databases from January 1, 2008, to April 31, 2023, using the MeSH terms. Results: 7 articles were included in the systematic review. A wide range in age was found (18 to 79 years). A minimal number of studies detail the comorbidities of patients in their enrollment. Regarding platelet transfusion, the average number of platelet units used in the transfusion case was 5 (2 - 14). Transfusions of ABO identical and compatible pooled platelets transfusion were found to be more successful in increasing platelets. Almost all of the patients included in the studies had platelets

Introduction: The AST/platelet ratio index (APRI) is a well-researched indicator of liver fibrosis. Some studies have shown that APRI can be used as a predictor of severe dengue, but the data is limited. As dengue epidemics are common in our country with limited healthcare resources, we believe APRI can help emergency physicians/primary physicians in predicting the severity of dengue and plan for the appropriate use of limited healthcare resources. Objective: 1) To determine the utility of APRI as a predictor of severe dengue. 2) To determine the association of APRI with length of hospital stay and platelet requirement. Materials and Methods: A retrospective cross-sectional study was done on patients presented to the Emergency Medicine department at Travancore Medicity Medical College with a positive Dengue NS1 antigen or IgM antibody. Results: We found from the univariate analysis results that ALT > 74.5 IU/L has a sensitivity of 59.6 and a specificity of 76.3 (AUC: 0.696; 95% CI: 0.606–0.786), AST > 160.5 IU/L has a sensitivity of 42.3 and a specificity of 93.7 (AUC: 0.747; 95% CI: 0.665–0.829), and APRI > 3.2 has a sensitivity of 69.2 and a specificity of 84.2 (AUC: 0.806; 95% CI: 0.72–0.884) to predict severe dengue. Patients with an APRI of >3.2 required a mean hospital stay of 5.47 days (P = 0.005); 27 (81.8%) requiring platelet transfusion had an APRI of > 3.2 (P = 0.00). Conclusion: APRI is a straightforward index that can be easily derived from AST and platelet values. APRI values of >3.2 can predict severe dengue with a sensitivity of 69.2 and a specificity of 84.2. APRI values of >3.2 are also associated with the length of hospital stay and requirement of platelet transfusion.

Dengue fever is considered the most prolific vector-borne disease in the world, with its transmission rate increasing more than eight times in the last two decades. While most cases present mild to moderate symptoms, 5% of patients can develop severe disease. Although the mechanisms are yet not fully comprehended, immune-mediated activation leading to excessive cytokine expression is suggested as a cause of the two main findings in critical patients: increased vascular permeability that may shock and thrombocytopenia, and coagulopathy that can induce hemorrhage. The risk factors of severe disease include previous infection by a different serotype, specific genotypes associated with more efficient replication, certain genetic polymorphisms, and comorbidities such as diabetes, obesity, and cardiovascular disease. The World Health Organization recommends careful monitoring and prompt hospitalization of patients with warning signs or propensity for severe disease to reduce mortality. This review aims to update the diagnosis and management of patients with severe dengue in the intensive care unit.

Background: Recently, a wide range variety of manifestations, including a self‑limiting to severe illness, has been increasingly reported in dengue. Few studies attract attention to severe dengue, mainly observed in secondary infection. With this background, this study aims to provide a comprehensive overview to differentiate primary from secondary dengue using serology (IgG) and the possible association of severity of illness in secondary dengue. Methods: Present retrospective cross-sectional study was conducted at a North Indian tertiary care center from September 2021 to January 2022. Clinical data of confirmed dengue patients from the medicine department were collected and assigned as primary and secondary dengue. Results: Of the 220 dengue patients, 22 (10 %) had secondary dengue infection. Hemorrhagic manifestations were reported in 58/220 (26.4 %) cases while 7/22 (31.8 %) in secondary dengue. Prevalent hemorrhagic manifestations in secondary dengue include purpura (27.3 %), vaginal bleeding (4.5 %), melaena (9.1 %), and epistaxis (4.5 %). In addition, 42 (19.1 %) patients had pancytopenia, and 8 (36.6 %) cases were of secondary dengue. Hepatic dysfunction was noted in 164 (74.5 %) cases. Notably, all secondary dengue cases (22;100 %) had hepatic dysfunction and severe in 9 (40.9 %) cases. In addition, in secondary dengue patients, evidence of plasma leakages such as hypoproteinemia 7 (31.8 %) and ascites (35 %) were statistically more frequent. Overall, two deaths (0.9 %) were reported, and were one in each group. Conclusions: Many parameters, including hemorrhagic manifestation (melaena), hematological characteristic (pancytopenia), evidence of plasma leakage (hypoproteinemia and ascites), gastrointestinal (GB wall thickening and hepatic dysfunction) and reduction in mean hemoglobin and platelet count were found to be statistically significant in secondary dengue infection. Additionally, early classification of secondary dengue may help to anticipate its severity and allow for early strategic intervention/management to lower morbidity and mortality.

Introduction: The AST/platelet ratio index (APRI) is a well-researched indicator of liver fibrosis. Some studies have shown that APRI can be used as a predictor of severe dengue, but the data is limited. As dengue epidemics are common in our country with limited healthcare resources, we believe APRI can help emergency physicians/primary physicians in predicting the severity of dengue and plan for the appropriate use of limited healthcare resources. Objective: 1) To determine the utility of APRI as a predictor of severe dengue. 2) To determine the association of APRI with length of hospital stay and platelet requirement. Materials and Methods: A retrospective cross-sectional study was done on patients presented to the Emergency Medicine department at Travancore Medicity Medical College with a positive Dengue NS1 antigen or IgM antibody. Results: We found from the univariate analysis results that ALT > 74.5 IU/L has a sensitivity of 59.6 and a specificity of 76.3 (AUC: 0.696; 95% CI: 0.606–0.786), AST > 160.5 IU/L has a sensitivity of 42.3 and a specificity of 93.7 (AUC: 0.747; 95% CI: 0.665–0.829), and APRI > 3.2 has a sensitivity of 69.2 and a specificity of 84.2 (AUC: 0.806; 95% CI: 0.72–0.884) to predict severe dengue. Patients with an APRI of >3.2 required a mean hospital stay of 5.47 days (P = 0.005); 27 (81.8%) requiring platelet transfusion had an APRI of > 3.2 (P = 0.00). Conclusion: APRI is a straightforward index that can be easily derived from AST and platelet values. APRI values of >3.2 can predict severe dengue with a sensitivity of 69.2 and a specificity of 84.2. APRI values of >3.2 are also associated with the length of hospital stay and requirement of platelet transfusion. [ABSTRACT FROM AUTHOR]

Dengue is a viral infection which is transmitted by the Aedes aegypti mosquito and has four serotypes (DENV-1 to DENV-4). The disease triggers a variety of clinical manifestations, ranging from mild forms without warning signs to severe lifethreatening forms. We present the case of a 5-year-old boy, from the province of Callao, whose first symptoms were fever, headache and general malaise. On the third day, the child had mild abdominal pain and little vomiting; subsequently, abdominal distension, jaundice and choluria. He was admitted to the pediatric intensive care unit being alert and with moderate dehydration, jaundice, edema, distended and tender abdomen, shifting dullness and liver 2 cm below the right costal margin. Complementary tests revealed liver failure, hepatosplenomegaly and pleural effusion in the bases. Using a reactive IgM ELISA, severe dengue was diagnosed, as well as a superinfection due to probable spontaneous bacterial peritonitis. He started treatment with antibiotics, furosemide, fresh frozen plasma, cryoprecipitate and metamizole. As the child did not get better, the diuretic was optimized, and human albumin was administered. Thereafter, he got better showing decreased ascites, edema, jaundice and pleural effusion; improvement of the liver and coagulation profile; and being afebrile. He unexpectedly presented respiratory distress due to congestive heart failure caused by dilated cardiomyopathy diagnosed by echocardiography; thus, he was treated with diuretics. The patient was discharged afebrile, without edema and with resolution of liver failure and coagulation disorder. [ABSTRACT FROM AUTHOR]

Background Judicious fluid resuscitation and stringent monitoring of clinical parameters improve the outcome of dengue haemorrhagic fever (DHF). The usefulness of serum lactate to monitor adequate fluid therapy has not been adequately explored. Methods An observational study was conducted in Sri Lanka, recruiting 162 DHF patients within 12 h of diagnosis of the critical phase. Venous lactate level was measured at each time of performing haematocrit (HCT), using a prevalidated handheld lactate analyser. Results The median venous lactate level was 1.3 (range 0.3–6) mmol/L in the study population and 154 (95.2%) patients had median lactate levels of <2 mmol/L. The HCT values in the study participants ranged from 28 to 62, with a median value of 43. There was no statistically significant correlation between the lactate and HCT values obtained at the same time. A significant reduction in venous lactate was not observed following the administration of fluid boluses. The expected reduction in HCT was seen following the administration of dextran and crystalloid/dextran combination. The maximum recorded lactate level positively correlated with the duration of hospital stay. Conclusions This study concludes that venous lactate is not an appropriate parameter with which to monitor the response to fluid therapy in uncomplicated DHF. [ABSTRACT FROM AUTHOR]

Recently, a wide range variety of manifestations, including a self‑limiting to severe illness, has been increasingly reported in dengue. Few studies attract attention to severe dengue, mainly observed in secondary infection. With this background, this study aims to provide a comprehensive overview to differentiate primary from secondary dengue using serology (IgG) and the possible association of severity of illness in secondary dengue. Present retrospective cross-sectional study was conducted at a North Indian tertiary care center from September 2021 to January 2022. Clinical data of confirmed dengue patients from the medicine department were collected and assigned as primary and secondary dengue. Of the 220 dengue patients, 22 (10 %) had secondary dengue infection. Hemorrhagic manifestations were reported in 58/220 (26.4 %) cases while 7/22 (31.8 %) in secondary dengue. Prevalent hemorrhagic manifestations in secondary dengue include purpura (27.3 %), vaginal bleeding (4.5 %), melaena (9.1 %), and epistaxis (4.5 %). In addition, 42 (19.1 %) patients had pancytopenia, and 8 (36.6 %) cases were of secondary dengue. Hepatic dysfunction was noted in 164 (74.5 %) cases. Notably, all secondary dengue cases (22;100 %) had hepatic dysfunction and severe in 9 (40.9 %) cases. In addition, in secondary dengue patients, evidence of plasma leakages such as hypoproteinemia 7 (31.8 %) and ascites (35 %) were statistically more frequent. Overall, two deaths (0.9 %) were reported, and were one in each group. Many parameters, including hemorrhagic manifestation (melaena), hematological characteristic (pancytopenia), evidence of plasma leakage (hypoproteinemia and ascites), gastrointestinal (GB wall thickening and hepatic dysfunction) and reduction in mean hemoglobin and platelet count were found to be statistically significant in secondary dengue infection. Additionally, early classification of secondary dengue may help to anticipate its severity and allow for early strategic intervention/management to lower morbidity and mortality. [ABSTRACT FROM AUTHOR]