Dengue Fever: Clinical, Laboratory Profile and Outcome in Pediatric Patient

Introduction: Infection with any of the 4 dengue virus serotypes results in a diverse range of symptoms, from mild undifferentiated fever to life-threatening hemorrhagic fever and shock. Given that dengue virus infection elicits such a broad range of clinical symptoms, early and accurate laboratory diagnosis is essential for appropriate patient management. So a study was carried out to know its clinical profile, correlation between the laboratory profile and the severity of dengue fever and outcome in dengue patients. Aim: To study the clinical profile, correlation between the laboratory profile and the severity of dengue fever and outcome in dengue patients at tertiary care center. Method: Retrospective Observational study from 1st May 2019 to 31st April 2021. Result: Total 323 patients were studied during 1st May 2019 to 31st April 2021. Most common presentation was fever (100%), most common clinical finding is hepatomegaly (14.2%). All severe dengue infection has platelet count < 50000/cumm. In study of 323 patients 194(60%) of dengue fever,85(26.4%) of DHF GRADE 1,9(2.8%) of DHF GRADE 2 were discharged .13(4%) patients of DSS were expired.22 patients (6.8%) went DAMA. Conclusion: Reliable diagnosis of dengue fever in endemic areas can be done by clinical parameters like presence of nausea, vomiting, pain abdomen and hepatomegaly. Monitoring platelet count, hematocrit and WBC count is very useful for management of dengue cases. Keywords: dengue fever, platelet count, outcome

Prognostic indicators associated with progresses of severe dengue

Background Dengue usually progress abnormally, especially in the critical phase. The main causes of death were shock, severe bleeding and organ failure. The aim of our study was to evaluate prognostic indicators of severe dengue according to the phases of the disease progression. Methods A cross-sectional study was conducted from July to December 2017 at the National Hospital for Tropical Diseases and the Hospital for Tropical Diseases of Ho Chi Minh City. 326 patients, aged 6 years and over, including 99/326 patients with severe dengue and 227/326 patients with non-severe dengue, hospitalized in the first 3 days of illness, confirmed Dengue virus by the RT-PCR assay have been registered for the study. Clinical manifestations were monitored daily. The hematocrit, white blood cells, platelet, serum albumin, ALT, AST, bilirubin, prothrombin time (PT%, PTs), fibrinogen, aPTT, INR and creatinine were evaluated at two times: febrile phase and critical phase. Results Independent factors associated with severe dengue were identified on multivariate logistic regression models. During the first 3 days of the disease, the prognostic indicators were platelet count ≤ 100 G/L (OR = 2.2; 95%CI: 1.2–3.9), or serum albumin < 35 g/L (OR = 3.3; 95%CI: 1.8–6.1). From day 4–6, the indicator were AST > 400 U/L (OR = 3.0; 95%CI: 1.1–7.9), ALT > 400 U/L (OR = 6.6; 95%CI: 1.7–24.6), albumin < 35 g/L (OR = 3.0; 95%CI: 1.5–5.9), and bilirubin total >17 μmol/L (OR = 4.6; 95%CI: 2.0–10.4). Conclusion To predict the risk of patients with severe dengue, prognostic laboratory indicators should be indicated consistent with the progression of the disease. During the first 3 days of illness, prognostic indicators should be platelet count, or serum albumin. From the 4th - 6th day of illness, prognostic indicators should be AST, ALT, albumin, or bilirubin total.

Clinical outcomes of dengue virus infection in pregnant and non-pregnant women of reproductive age: a retrospective cohort study from 2016 to 2019 in Paraná, Brazil

Background The increasing number of dengue cases worldwide implies a greater exposure of at-risk groups, such as pregnant women. DENV infection during pregnancy has been increasingly associated with unfavorable outcomes, but the evolution of the disease and its clinical outcomes remain unclear. The objective of this study was to characterize dengue cases in reproductive aged women by comparing the development of the disease in pregnant and non-pregnant women. Methods A population based retrospective cohort study that used data reported in the Brazilian Mandatory Notifiable Diseases Information System from 2016 to 2019 in Paraná, Brazil. We compared sociodemographic, clinical, and laboratory variables between pregnant and non-pregnant women. Hospitalization and disease severity classification (Dengue, Dengue with warning signs, Severe Dengue) were considered outcome variables. Results The two groups had differences in the year of notification, age distribution, and region of residence. Laboratory investigation was more frequent among pregnant women, and DENV-2 prevailed in both groups. The risks of hospitalization and development of Severe Dengue were higher in pregnant women. There were no deaths observed among pregnant women. Conclusion This study identified pregnancy as a risk factor for an increase in the severity of DENV infection. It reinforces the importance of identifying early signs of complication, close monitoring, and adequate treatment for pregnant women.

Haemophagocytic Lymphohistiocytosis (HLH) in Adult with Dengue Infection

Haemophagocytic lymphohistiocytosis (HLH) or haemophagocytic syndrome is a rare but life-threatening syndrome of excessive immune activation with nonspecific clinical presentation. HLH is one of the complications in dengue infection. A 69-year-old lady was treated for severe dengue with multi-organ dysfunction with superimposed pneumonia, requiring mechanical ventilation. However, persistent cytopenia despite blood transfusion without evidence of haemorrhage raised the suspicion of HLH. Further blood investigations revealed hypertriglyceridaemia, hypofibrinogenaemia and hyperferritinaemia. Bone marrow aspiration showed haemophagocytosis. Patient fulfilled the diagnostic criteria for HLH by HLH-2004 trial. Her HScore is 281, with the probability of having HLH is 99.9%. Patient’s condition improved after administration of intravenous immunoglobulin (IVIG) and intravenous dexamethasone in tapering doses. Early specific treatment of HLH with IVIG and/or corticosteroid is important but diagnosis is usually delayed due to nonspecific clinical findings and laboratory results. High index of suspicion with the aid of diagnostic criteria by HLH-2004 trial and HScore is helpful to recognise this syndrome.

Outcomes among children and adults at risk of severe dengue in Sri Lanka: Opportunity for outpatient case management in countries with high disease burden

Background Healthcare systems in dengue-endemic countries are often overburdened due to the high number of patients hospitalized according to dengue management guidelines. We systematically evaluated clinical outcomes in a large cohort of patients hospitalized with acute dengue to support triaging of patients to ambulatory versus inpatient management in the future. Methods/Principal findings From June 2017- December 2018, we conducted surveillance among children and adults with fever within the prior 7 days who were hospitalized at the largest tertiary-care (1,800 bed) hospital in the Southern Province, Sri Lanka. Patients who developed platelet count ≤100,000/μL (threshold for hospital admission in Sri Lanka) and who met at least two clinical criteria consistent with dengue were eligible for enrollment. We confirmed acute dengue by testing sera collected at enrollment for dengue NS1 antigen or IgM antibodies. We defined primary outcomes as per the 1997 and 2009 World Health Organization (WHO) classification criteria: dengue hemorrhagic fever (DHF; WHO 1997), dengue shock syndrome (DSS; WHO 1997), and severe dengue (WHO 2009). Overall, 1064 patients were confirmed as having acute dengue: 318 (17.4%) by NS1 rapid antigen testing and 746 (40.7%) by IgM antibody testing. Of these 1064 patients, 994 (93.4%) were adults ≥18 years and 704 (66.2%) were male. The majority (56, 80%) of children and more than half of adults (544, 54.7%) developed DHF during hospitalization, while 6 (8.6%) children and 22 (2.2%) adults developed DSS. Overall, 10 (14.3%) children and 113 (11.4%) adults developed severe dengue. A total of 2 (0.2%) patients died during hospitalization. Conclusions One-half of patients hospitalized with acute dengue progressed to develop DHF and a very small number developed DSS or severe dengue. Developing an algorithm for triaging patients to ambulatory versus inpatient management should be the future goal to optimize utilization of healthcare resources in dengue-endemic countries.

Neglected infectious diseases in the geriatrics

Infectious diseases in the elderly population pose a significant threat to their lives. Neglected tropical diseases significantly impact the health of the affected patients and populations at risk. Reports show that many of these disorders are among the highest ten most typical causes of disability-adjusted life years. In the present literature review, we have discussed the most common neglected tropical infections in geriatrics based on data from the current studies in the literature. Different infections can affect the geriatric population. However, evidence shows that this population is susceptible to developing severe disease-related conditions. This has been reported with dengue infection, onchocerciasis, and cholera. It has been demonstrated that ocular lesions and other clinical manifestations are highest among the elderly population with onchocerciasis. Severe dengue and dengue hemorrhagic fever are also reported at a high rate in this age group. Concurrent infections and disorders were documented with many of these infections, probably due to reduced immunity. Socioeconomic factors, co-morbidities, access to healthcare settings, environmental factors, sanitation, clustering, and overcrowding contribute to the frequency of neglected tropical diseases in the elderly. Further studies are still needed because the current report is scarce, which might underestimate the current evidence.

Increased Plasma Heparanase Activity and Endothelial Glycocalyx Degradation in Dengue Patients Is Associated With Plasma Leakage

BackgroundEndothelial hyper-permeability with plasma leakage and thrombocytopenia are predominant features of severe dengue virus infection. It is well established that heparanase, the endothelial glycocalyx degrading enzyme, plays a major role in various diseases with vascular leakage. It is yet to be elucidated whether heparanase activity plays a major role in dengue-associated plasma leakage. Moreover, the major source of heparanase secretion and activation in dengue remains elusive. Since a relatively high amount of heparanase is stored in platelets, we postulate that heparanase released by activated platelets contributes to the increased plasma heparanase activity during dengue virus infection.MethodsHeparanase activity (plasma and urine), and heparan sulfate and syndecan-1 (plasma levels) were measured in dengue patients with thrombocytopenia in acute phase (n=30), during course of disease (n=10) and in convalescent phase (n=25). Associations with clinical parameters and plasma leakage markers were explored. Platelets from healthy donors were stimulated with dengue non-structural protein-1, DENV2 virus and thrombin to evaluate heparanase release and activity ex vivo.ResultsHeparanase activity was elevated in acute dengue and normalized during convalescence. Similarly, glycocalyx components, such as heparan sulfate and syndecan-1, were increased in acute dengue and restored during convalescence. Increased heparanase activity correlated with the endothelial dysfunction markers heparan sulfate and syndecan-1, as well as clinical markers of plasma leakage such as ascites, hematocrit concentration and gall-bladder wall thickening. Notably, platelet number inversely correlated with heparanase activity. Ex vivo incubation of platelets with thrombin and live DENV2 virus, but not dengue virus-2-derived non-structural protein 1 induced heparanase release from platelets.ConclusionTaken together, our findings suggest that the increase of heparanase activity in dengue patients is associated with endothelial glycocalyx degradation and plasma leakage. Furthermore, thrombin or DENV2 activated platelets may be considered as a potential source of heparanase.

B-Line Detection and Localization in Lung Ultrasound Videos Using Spatiotemporal Attention

The presence of B-line artefacts, the main artefact reflecting lung abnormalities in dengue patients, is often assessed using lung ultrasound (LUS) imaging. Inspired by human visual attention that enables us to process videos efficiently by paying attention to where and when it is required, we propose a spatiotemporal attention mechanism for B-line detection in LUS videos. The spatial attention allows the model to focus on the most task relevant parts of the image by learning a saliency map. The temporal attention generates an attention score for each attended frame to identify the most relevant frames from an input video. Our model not only identifies videos where B-lines show, but also localizes, within those videos, B-line related features both spatially and temporally, despite being trained in a weakly-supervised manner. We evaluate our approach on a LUS video dataset collected from severe dengue patients in a resource-limited hospital, assessing the B-line detection rate and the model’s ability to localize discriminative B-line regions spatially and B-line frames temporally. Experimental results demonstrate the efficacy of our approach for classifying B-line videos with an F1 score of up to 83.2% and localizing the most salient B-line regions both spatially and temporally with a correlation coefficient of 0.67 and an IoU of 69.7%, respectively.

Cell strain-derived induced pluripotent stem cell as a genetically controlled approach to investigate age-related host response to flaviviral infection

The expansion of the geographical footprint of dengue viruses (DENVs) and their mosquito vectors have affected more than half of the global population, including older adults who appear to show elevated risk of severe dengue. Despite this epidemiological trend, how ageing contributes to increase dengue pathogenesis is poorly understood. A limitation has been the lack of useful in vitro experimental approaches; cell lines commonly used for infection studies are immortal and hence do not age. Cell strains, such as WI-38 and MRC-5 with diploid genomes, do age with in vitro passaging but these cell strains were isolated decades ago and are now mostly highly passaged. Herein, we show that reprogramming of cell strains with finite lifespan into induced pluripotent stem cells (iPSCs), followed by conversion back into terminally differentiated cells, can be an approach to derive genetically identical cells at different stages of ageing. The iPSC-derived differentiated cells were susceptible to wild-type DENV infection and produced greater levels of type-I interferon expression with increase passaging, despite similar levels of infection. In contrast, infection with the attenuated DENV-2 PDK53 and YF17D-204 strains showed reduced and increased levels of infection with increasing passages; the latter could be clinically pertinent as YF17D-204 vaccination in older adults is associated with increased risk of severe adverse outcome. The differences in infection susceptibility and host response collectively suggest the potential of iPSC-derived cell strains as a genetically controlled approach to understand how ageing impacts viral pathogenesis. Importance Ageing has been a risk factor for poor clinical outcome in several infectious diseases, including dengue. However, age-dependent responses to dengue and other flaviviral infection or vaccination have remained incompletely understood due partly to lack of suitable laboratory tools. We thus developed an in vitro approach to examine age-related changes in host response to flaviviral infection. Notably, this approach uses cell strains with diploid rather than aneuploidic genomes, which are unstable. Conversion of these cells into iPSCs ensure sustainability of this resource and reprogramming back into terminally differentiated cells would, even with limited number of passages, produce cells at different stages of ageing for infection studies. Our findings suggest that this in vitro system has the potential to serve as a genetically-controlled approach to define the age-related response to flavivirus infection.

A 3D Microfluidic ELISA for the Detection of Severe Dengue: Sensitivity Improvement and Vroman Effect Amelioration by EDC–NHS Surface Modification

Serum is commonly used as a specimen in immunoassays but the presence of heterophilic antibodies can potentially interfere with the test results. Previously, we have developed a microfluidic device called: 3D Stack for enzyme-linked immunosorbent assay (ELISA). However, its evaluation was limited to detection from a single protein solution. Here, we investigated the sensitivity of the 3D Stack in detecting a severe dengue biomarker—soluble CD163 (sCD163)—within the serum matrix. To determine potential interactions with serum matrix, a spike-and-recovery assay was performed, using 3D Stacks with and without surface modification by an EDC–NHS (N-ethyl-N′-(3-(dimethylamino)propyl)carbodiimide/N-hydroxysuccinimide) coupling. Without surface modification, a reduced analyte recovery in proportion to serum concentration was observed because of the Vroman effect, which resulted in competitive displacement of coated capture antibodies by serum proteins with stronger binding affinities. However, EDC–NHS coupling prevented antibody desorption and improved the sensitivity. Subsequent comparison of sCD163 detection using a 3D Stack with EDC–NHS coupling and conventional ELISA in dengue patients’ sera revealed a high correlation (R = 0.9298, p < 0.0001) between the two detection platforms. Bland–Altman analysis further revealed insignificant systematic error between the mean differences of the two methods. These data suggest the potentials of the 3D Stack for further development as a detection platform.