Ocular and adnexal manifestations post dengue hemorrhagic fever.

OBJECTIVE: This study aims to present a case series detailing sight-threatening ocular and adnexal manifestations following dengue fever. METHODS: A retrospective observational study was conducted, analyzing records of patients presenting with ocular manifestations post dengue fever at a tertiary eye care institute in Uttar Pradesh from October 2023 to November 2023. Demographic details, systemic comorbidities, and detailed ophthalmic examinations were recorded. RESULTS: Fifteen eyes of 13 patients with dengue fever were studied. The mean age of presentation was 39.07 years, with a male predominance (84.61%). Systemic comorbidities were noted in 30.76% (diabetes mellitus) and 23.07% (hypertension) of patients. Thrombocytopenia was observed in 53.84% of patients, while 23.07% required blood transfusions, and 15.38% experienced systemic bleeding episodes. The majority of cases were unilateral (84.61%), with the best-corrected visual acuity of perception of light in 84.61% of cases. Diminution of vision was the most common presenting symptom (84.61%), followed by pain (53.84%), redness (38.46%), and watering (23.07%). Major ocular manifestations included panophthalmitis (26.07%), total ophthalmoplegia (26.07%), endogenous endophthalmitis (20%), central retinal artery occlusion (20%), retinal hemorrhage (20%), ischemic optic neuropathy (20%), orbital cellulitis (13.3%), proptosis (13.3%), retrobulbar hemorrhage (13.3%), retinal detachment (13.3%), and foveolitis (6.7%). CONCLUSION: The diverse array of ocular and adnexal manifestations in dengue hemorrhagic fever may result in permanent visual loss, emphasizing the need for adequate treatment and timely intervention. The risk of sight-threatening complications underscores the importance of early screening by ophthalmologists and increased public awareness.

The need for active and integrated involvement of the community and health professionals in the prevention and control of dengue hemorrhagic fever in Indonesia.

Successful control and prevention of dengue fever requires active involvement from all parties. For this reason, three innovative programs are needed, namely: i) increasing knowledge, attitude and practice (KAP) of the community and health professionals as capital in controlling dengue fever in a sustainable manner; ii) application of "3M Plus" to suppress vector breeding in household settings; iii) promotion of the "Jumantik" program as an effective community empowerment approach to prevent and control dengue fever based on community independence. It was concluded that successful control of dengue fever requires integration of the community and health workers through various innovative programs.

A simple nomogram to predict dengue shock syndrome: A study of 4522 south east Asian children.

Dengue shock syndrome (DSS) substantially worsens the prognosis of children with dengue infection. This study aimed to develop a simple clinical tool to predict the risk of DSS. A cohort of 2221 Thai children with a confirmed dengue infection who were admitted to King Chulalongkorn Memorial Hospital between 1987 and 2007 was conducted. Another data set from a previous publication comprising 2,301 Vietnamese children with dengue infection was employed to create a pooled data set, which was randomly split into training (n = 3182), testing (n = 697) and validating (n = 643) datasets. Logistic regression was compared to alternative machine learning algorithms to derive the most predictive model for DSS. 4522 children, including 899 DSS cases (758 Thai and 143 Vietnamese children) with a mean age of 9.8 ± 3.4 years, were analyzed. Among the 12 candidate clinical parameters, the Bayesian Model Averaging algorithm retained the most predictive subset of five covariates, including body weight, history of vomiting, liver size, hematocrit levels, and platelet counts. At an Area Under the Curve (AUC) value of 0.85 (95% CI: 0.81-0.90) in testing data set, logistic regression outperformed random forest, XGBoost and support vector machine algorithms, with AUC values being 0.82 (0.77-0.88), 0.82 (0.76-0.88), and 0.848 (0.81-0.89), respectively. At its optimal threshold, this model had a sensitivity of 0.71 (0.62-0.80), a specificity of 0.84 (0.81-0.88), and an accuracy of 0.82 (0.78-0.85) on validating data set with consistent performance across subgroup analyses by age and gender. A logistic regression-based nomogram was developed to facilitate the application of this model. This work introduces a simple and robust clinical model for DSS prediction that is well-tailored for children in resource-limited settings.

Differential Proteomic Profiling at Different Phases of Dengue Infection: An Intricate Insight from Proteins to Pathogenesis.

Dengue fever is a rapidly emerging tropical disease and an important cause of morbidity in its severe form worldwide. A wide spectrum of the pathophysiology is associated with the transition of dengue fever to severe dengue, which is driven by the host immune response and might reflect in patients' proteome profile. This study aims to analyze the plasma from different phases of dengue-infected patients at two time points. A mass-spectrometry-based proteomic approach was utilized to understand the involvement of probable candidate proteins toward developing a more severe, hemorrhagic form of dengue fever. Dengue-infected hospital-admitted patients with <5 days of fever were included in this study. Patient samples from the acute phase were screened for the presence of NS1 antigen using ELISA and subjected to molecular serotyping. Dengue molecular serotype-confirmed patient samples, pairwise from acute and critical phases with healthy control were subjected to qualitative and quantitative proteomic analysis, and then pathway analysis was performed. The protein-protein interaction network between the dengue virus and host proteins was depicted in the search for proteins associated with severe dengue pathophysiology. An array of apolipoprotein, cytokines, and endothelial proteins in association with virus replication and endothelial dysfunction were validated as biomolecules involved in severe dengue pathophysiology.

Utility of the WHO dengue guidelines in pediatric immunological studies.

Dengue is a significant health problem due to the high burden of critical infections during outbreaks. In 1997, the World Health Organization (WHO) classified dengue as dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). It was revised in 2009 (updated in 2015), and the new guidelines recommended classifying patients as dengue without warning signs (DNS), dengue with warning signs (DWS), and severe dengue (SD). Although the utility of the revised 2009 classification for clinical studies is accepted, for immunological studies it needs to be clarified. We determined the usefulness of the 2009 classification for pediatric studies that analyze the circulating interleukin (IL)-6 and IL-8, two inflammatory cytokines. Plasma levels of IL-6 and IL-8 were evaluated in the acute and convalescent phases by flow cytometry in children with dengue classified using the 1997 and 2009 WHO guidelines. The plasma levels of IL-6 and IL-8 were elevated during the acute and decreased during convalescence, and both cytokines served as a good marker of acute dengue illness compared to convalescence. There were no differences in the plasma level of the evaluated cytokines among children with different clinical severity with any classification, except for the IL-8, which was higher in DWS than DNS. Based on the levels of IL-8, the 2009 classification identified DWS plus SD (hospital-treated children) compared to the DNS group [area under the curve (AUC): 0.7, p = 0.028]. These results support the utility of the revised 2009 (updated in 2015) classification in studies of immune markers in pediatric dengue.

Mucocutaneous Manifestations in Patients with Dengue Fever: From the EPIDENGUE Cohort on Reunion Island.

Nearly 4 billion people live in a dengue risk area worldwide. The prevalence of dengue-related mucocutaneous manifestations and their association with severe dengue differ across studies. The aim of the study was to describe the characteristics of patients with dengue-related mucocutaneous manifestations and to investigate those were associated with severe dengue. A retrospective study was conducted in 2019 among patients with a positive RT-PCR for dengue at the University Hospital of Reunion, which has been experiencing a re-emergence of dengue since 2018. Of 847 patients with confirmed dengue, 283 (33.4%) developed mucocutaneous manifestations. Only manifestations of dehydration such as glossitis, dysgeusia, or conjunctivitis were associated with severe dengue, unlike pruritus and rash, in bivariate analysis but not in multivariate analysis. The rash and pruritus of dengue appear to be accompanied by a pronounced flu-like syndrome in younger people without comorbidity or severity, although careful examination of mucous membranes would better identify signs of dehydration and thus cases likely to worsen.

[Fulminant acute liver failure secondary to severe dengue in a child: case report]. / Falla hepática aguda fulminante secundaria a dengue severo en un niño: reporte de un caso.

Dengue is a common infectious disease in tropical areas such as Peru. This virus can cause underreported and potentially fatal complications such as acute liver failure. We report the case of a 7-year-old boy who presented with fever, headache, and abdominal pain. On ultrasound, we found hepatomegaly and labs severe thrombocytopenia and elevated transaminases. During hospitalization he was diagnosed with severe dengue and developed acute liver failure, kidney injury, and encephalopathy. Although intensive care management and assisted ventilation, he developed multiple organ dysfunctions with fluid refractoriness and capillary leak. Acute liver failure secondary to severe dengue is a rare complication with an unfavorable outcome.

Risk of severe dengue during secondary infection: A population-based cohort study in Taiwan.

BACKGROUND: Dengue poses a significant public health concern. Secondary dengue infections with different dengue virus (DENV) serotypes have been linked to an increased risk of severe dengue. This study aimed to assess the risk of severe dengue during secondary infection in Taiwan. METHODS: A retrospective cohort study was conducted using Taiwan's National Health Insurance Research Database to identify dengue cases with secondary dengue infection born after 1944 from 2014 to 2015. Ten matched patients with primary infection were selected as controls using propensity score matching for each secondary dengue infection case. The odds ratio (OR) for severe dengue in secondary versus primary infections was calculated using conditional logistic regression. RESULTS: This study included 357 cases with secondary dengue infection and 3570 matched controls. The risk of severe dengue was found to be 7.8% in individuals with secondary infection, compared to 3.8% in those with primary dengue infection. Secondary infection significantly increased the risk of severe dengue (OR 2.13, 95% CI: 1.40-3.25, P = 0.0004). Notably, a significant association between secondary infection and severe dengue was observed only when the interval between the first and secondary infection was greater than two years (OR 3.19, 95% CI 2.04-5.00, P < 0.0001). CONCLUSION: Secondary dengue infection significantly increases the risk of severe disease in Taiwan, particularly when the interval between infections is over two years. Healthcare professionals should maintain heightened vigilance for individuals with a history of previous dengue infection, particularly if their initial diagnosis was more than two years prior.

Incidence of acute liver failure and its associated mortality in patients with dengue infection: A systematic review and meta-analysis.

Acute liver failure (ALF) is a devastating consequence of dengue infection. This systematic review and meta-analysis assessed the incidence of ALF in dengue infection and its associated mortality. We systematically searched the EMBASE and MEDLINE databases from inception to December 2023 for observational studies reporting ALF incidence and mortality in dengue patients. Twenty-one studies encompassing 26,839 dengue-infected patients were included. Meta-analysis revealed a pooled incidence of ALF in cases of general dengue infection of 2.0 % (95 % CI, 1.2-3.0 %), with 1.2 % (95 % CI, 0.6-2.1 %) in adults and 5.0 % (95 % CI, 1.5-10.2 %) in children. ALF incidence was 17.3 % (95 % CI, 6.5 %-31.5 %) in severe dengue and 7.4 % (95 % CI, 0.8-18.5 %) in dengue shock syndrome. The pooled mortality rate of dengue-associated ALF was 47.0 % (95 % CI, 32.9-61.2 %). These findings underscore the detrimental impact of dengue infection on the development of the relatively uncommon, albeit life-threatening, condition of ALF.

Elevated NS1 serum levels reduce CD119 expression and CXCL-10 synthesis in patients with dengue hemorrhagic fever.

BACKGROUND: The intensity of dengue virus (DV) replication and circulating non-structural protein 1 (NS1) levels may promote changes in the human immune response and favor severe forms of infection. We investigated the correlations between NS1 with CXCL-8, CXCL-10, IFN-γ, and IL-12p40 serum levels, and IFN-γ receptor α chain (CD119) expression, and CXCL10 production by peripheral blood mononuclear cells (PBMCs) stimulated with recombinant IFN-γ in DV-infected patients with different clinical forms. METHODS: Dengue virus NS1, CXCL-8, CXCL-10, IFN-γ, and IL-12p40 serum levels were measured in 152 DV-infected patients with different clinical forms and 20 non-infected individuals (NI) using enzyme-linked immunosorbent assay (ELISA). In addition, we investigated the CXCL-10 production after in vitro IFN-γ stimulation of PBMCs from 48 DV-infected individuals (with different clinical forms of dengue fever) and 20 NI individuals using ELISA, and CD119 expression on CD14+ cells with flow cytometry. RESULTS: Patients with dengue hemorrhagic fever (DHF) had significantly higher NS1, CXCL-8, and CXCL-10 serum levels than those with classic dengue fever (DF). The response of PBMCs to IFN-γ stimulation was lower in patients with DHF than in those with DF or dengue with complications (DWC), with lower CD119 expression and reduced CXCL-10 synthesis. In addition, these alterations are associated with high NS1 serum levels. CONCLUSIONS: Patients with DHF reported high NS1 levels, low CD119 expression, and low CXCL-10 synthesis in PBMCs, which may be associated with infection progression and severity.

Early-phase factors associated with pediatric severe dengue in the Thai-Myanmar cross-border region.

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.

Severe Organ Impairment Was Common in Elderly Individuals with Dengue in Guangdong, China.

Guangdong, China, has experienced several dengue epidemics involving thousands of confirmed cases in recent decades, and elderly individuals suffered severe dengue (SD) most seriously. However, the clinical characteristics and risk factors for SD among elderly patients in Guangdong have not been investigated. Patients older than 65 years were recruited and divided into a dengue fever (DF) group and an SD group according to the 2009 Dengue Guidelines of the WHO. We analyzed the clinical manifestations of the elderly patients with dengue and then assessed the risk factors for SD. Of a total of 1,027 patients, 868 patients were diagnosed as having DF and 159 as having SD. Of the 159 elderly patients with SD, 129 (81%) had comorbidities, with hypertension being the most common. Severe organ impairment (SOI) (115, 54%) was the most common presentation in SD patients, followed by severe plasma leakage (52, 24.4%) and severe hemorrhage (46, 21.6%). The most common symptom of SOI was kidney injury, followed by heart injury and central nervous system injury. Furthermore, multivariate regression revealed that the presence of chronic obstructive pulmonary disease (COPD), a lower red blood cell (RBC) count (≤3.5 × 1012/L; odds ratio [OR], 0.35; 95% CI, 0.17-0.55; P <0.001), lower serum albumin (ALB) (≤35 U/L; OR, 0.18; 95% CI, 0.09-0.32; P <0.001), and hyperpyrexia (body temperature ≥39°C; OR, 1.8; 95% CI, 1.2-2.6, P <0.001) were risk factors for SD. Severe organ impairment was the predominant manifestation in elderly individuals with SD characterized by kidney injury. The potential risk factors of SD such as presence of COPD and hyperpyrexia and lower RBC and ALB levels might help clinicians identify patients with SD early.

Mechanisms of programmed cell death associated to severe dengue in human renal lesions.

Dengue virus (DENV) is a global health problem. Severe dengue can manifest with hemorrhage and signs of organ dysfunction, including the kidneys. The innate immune system is an important barrier against arbovirus infection and, specifically in dengue, the cytokines IL1ß and IL18 and caspase-1 activation make up a set of host immune strategies. Cell death mechanisms include pyroptosis, necroptosis and autophagy, each with peculiar markers: gasdermin, RIPK3/MLKL, LC3, respectively. In DENV infection, necrosis and apoptosis are involved and, when infecting monocytes and macrophages in vitro, DENV is capable of inducing pyroptosis. Our objective was to explore the presence of markers of necroptosis, pyroptosis and autophagy in renal lesions caused by DENV. MATERIAL AND METHODS: twenty specimens of lesions from patients who died due to DENV infection, from the pathology department of Hospital Guilherme Álvaro, Santos, SP, were subjected to histological and immunohistochemical studies. Histological sections were stained with hematoxylin-eosin to evaluate tissue changes or collected for research with antibodies: anti-DENV (Instituto Evandro Chagas-PA), RIPK3 (NBP2-45592), MLKL (ab184718), gasdermin D (#36425), LC3 (14600-AP), caspase 1 (#98033), IL1ß (AF201-NA) and IL18 (SC6178). Semi-quantitative analysis was performed on 20 glomeruli and evaluation on tubules and mononuclear cells. This study was approved by the ethics committee of the USP Faculty of Medicine. RESULTS: histological analysis demonstrated glomerular congestion, glomerulitis (medium to severe), acute kidney injury and hyalinization of the glomeruli. Viral antigens were visualized on mononuclear cells. LC3 (autophagy) expression ranged from moderate to intense (++/+++) in glomeruli, tubules and mononuclear cells. The expression of gasdermin (pyroptosis) was mild (+) in most cases in the glomeruli and moderate (++) in the tubules. RIPK3 and MLKL (necroptosis) mild in tubules and mononuclear cells (+). The expression of the cytokines IL1ß and IL18 and caspase 1 was moderate (++). Statistical analysis showed greater expression of LC3 over the others. CONCLUSIONS: Our results contribute to the understanding of the pathogenesis of renal involvement in severe dengue, considering the likely anti-viral mechanism of autophagy. To a lesser extent, pyroptosis is also present, corroborating previous data.

Immune responses and severe dengue: what have we learned?

PURPOSE OF REVIEW: With the marked rise in dengue globally, developing well tolerated and effective vaccines and therapeutics is becoming more important. Here we discuss the recent developments in the understanding of immune mechanisms that lead to severe dengue and the learnings from the past, that can help us to find therapeutic targets, prognostic markers, and vaccines to prevent development of severe disease. RECENT FINDINGS: The extent and duration of viraemia often appears to be associated with clinical disease severity but with some variability. However, there also appear to be significant differences in the kinetics of viraemia and nonstructural protein 1 (NS1) antigenemia and pathogenicity between different serotypes and genotypes of the DENV. These differences may have significant implications for development of treatments and in inducing robust immunity through dengue vaccines. Although generally higher levels of neutralizing antibodies are thought to protect against infection and severe disease, there have been exceptions and the specificity, breadth and functionality of the antibody responses are likely to be important. SUMMARY: Although there have been many advances in our understanding of dengue pathogenesis, viral and host factors associated with occurrence of severe dengue, vascular leak and the immune correlates of protection remain poorly understood.

Intravenous fluid therapy in hospitalized adult dengue patients without shock: Impact on subsequent severe dengue and potential adverse effects.

There is a lack of evidence on the optimal administration of intravenous (IV) fluids in hospitalized adult dengue patients without compensated and hypotensive shock. This study utilized a well-established cohort of dengue patients to compare risks of progressing to severe dengue (SD) over time for patients who were administered IV fluid versus others who were not. We included adult patients (n = 4781) who were hospitalized for dengue infection from 2005 to 2008. Cases were patients who developed SD (n = 689) and controls were patients who did not up until discharge (n = 4092). We estimated the hazard ratios (HRs) and risk of SD over time between groups administered different volumes of IV fluids versus the no IV fluid comparison group using Cox models with time-dependent covariates. The doubly-robust estimation approach was used to control for the propensity of fluid administration given clinical characteristics of patients. Subgroup analyses by age, sex, and dengue warning signs before IV fluid administration were conducted. High (>2000 mL/day) IV fluids volume was associated with a higher risk of development of SD for those who had warning signs (HR: 1.77 [1.05-2.97], p: 0.0713) and for those below 55 years old (HR: 1.53 [1.04-2.25], p: 0.0713). Low (<1000 mL/day) IV fluids volume was protective against SD for patients without warning signs (HR: 0.757 [0.578-0.990], p: 0.0883), no lethargy (HR: 0.770 [0.600-0.998], p: 0.0847), and females (HR: 0.711 [0.516-0.980], p: 0.0804). Over the course of hospitalization, there were no significant differences in IV fluid administration and SD risk in most subgroups, except in those who experienced lethargy and were administered IV fluid volume or quantity. Administering high volumes of IV fluids may be associated with an increased risk of SD during hospitalization for adult dengue patients without shock. Judicious use of IV fluids as supportive therapy is warranted.

Risk factors associated with dengue complications and death: A cohort study in Peru.

BACKGROUND: Dengue has emerged as an unprecedented epidemic in Peru, and it is anticipated that this issue will escalate further owing to climate change. This study aimed to determine the risk factors associated with death from dengue in patients treated at Hospital II in Pucallpa, Peru. METHODOLOGY: This retrospective cohort study collected information from the medical records of patients with a diagnosis of dengue treated at Hospital II Pucallpa-Peru between January 2019 and March 2023. The primary outcome was death, and the secondary outcome was death, development of severe dengue, or Intensive Care Unit (ICU) admission. Cox regression models were used to determine risk factors. FINDINGS: The clinical records of 152 patients were evaluated, with a median age of 27.5 years (interquartile range, 11-45). Among all patients, 29 (19.1%) developed severe dengue, 31 (20.4%) were admitted to the ICU, and 13 (8.6%) died during follow-up. In the survival analysis, bilirubin >1.2 mg/dL was associated with a higher risk of death aHR: 11.38 (95% CI: 1.2 106.8). Additionally, factors associated with poor prognosis included having 1 to 3 comorbidities aRR: 1.92 (1.2 to 3.2), AST ≥251 U/L aRR: 6.79 (2.2 to 21.4), history of previous dengue aRR: 1.84 (1.0 to 3.3), and fibrinogen ≥400 mg/dL aRR: 2.23 (1.2 to 4.1). SIGNIFICANCE: Elevated bilirubin was associated with death from dengue, whereas an increase in comorbidities and a history of previous dengue were related to a poor prognosis of the disease. Early identification of severe dengue would be more feasible with improved access to laboratory testing, particularly in tropical areas with a high dengue incidence.

[Takotsubo syndrome in dengue patient]. / Síndrome de Takotsubo en paciente con dengue.

Takotsubo syndrome, was described in Japan in 1990, it is a stress cardiomyopathy, predominantly in women, usually postmenopausal. Cardiac hypokinesia occurs, with involvement of multiple coronary territories. In intensive care unit (ICU), it is considered underdiagnosed. Manifestations of severe dengue fever include cardiovascular involvement, mainly arrhythmias and systolic dysfunction. A case of a 72-year-old man is presented, who was hospitalized in ICU for dengue fever, with plateletopenia (15000 cells/mm3) and dehydration. After fluid management the patient reported respiratory discomfort, auscultating crackling rales. A pulmonary ultrasound was made where bilateral B lines were found with B7 pattern compatible with interstitial syndrome and pulmonary edema. Basal hyperkinesia, medial and apical hypokinesia with an image consistent with apical ballooning were observed in the transthoracic echocardiogram. The electrocardiogram showed complete right bundle branch block. Chagas serology was negative and quantitative troponin I was increased. In the context of severe dengue, a Takotsubo syndrome was diagnosed. The patient evolved favorably. After discharge, a normalization of the cardiac function was stated in ultrasound images. The case is of clinical importance due to the low association of these two diseases and the need to screen for cardiac involvement in severe dengue.

El síndrome de Takotsubo, fue descripto en Japón en 1990, se trata de una miocardiopatía por estrés, predominante en mujeres, generalmente postmenopáusicas. Se produce una hipoquinesia cardiaca, con compromiso de múltiples territorios coronarios. En las unidades de terapia intensiva (UTI), se considera subdiagnosticada. En las manifestaciones del dengue grave, se encuentra el compromiso cardiovascular, principalmente arritmias y disfunción sistólica. Se presenta el caso de un hombre de 72 años, internado en UTI por dengue, con plaquetopenia (15000 células/mm3) y deshidratación. Luego de la administración de fluidos refirió disconfort respiratorio, auscultándose estertores pulmonares. Se realizó ecografía pulmonar donde se apreció líneas B bilaterales con patrón B7 compatible con síndrome intersticial y edema pulmonar. En el ecocardiograma transtorácico se objetivó hiperquinesia basal, hipoquinesia medial y apical con imagen compatible con balonamiento apical. En el electrocardiograma se evidenció bloqueo completo de rama derecha. La serología para Chagas fue negativa y la troponina I cuantitativa se detectó aumentada. Se diagnosticó síndrome de Takotsubo en el contexto de dengue grave. El paciente evolucionó favorablemente. Posterior al alta, se constató normalización de la motilidad cardíaca, en las imágenes ecográficas. El caso es de importancia clínica por la baja asociación de las dos enfermedades y la necesidad de pesquisar el compromiso cardíaco en el dengue grave.

Dengue Burden and Factors Influencing Severity in Honduras: A Descriptive and Analytical Study.

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.

Reduced protein-coding transcript diversity in severe dengue emphasises the role of alternative splicing.

Dengue fever, a neglected tropical arboviral disease, has emerged as a global health concern in the past decade. Necessitating a nuanced comprehension of the intricate dynamics of host-virus interactions influencing disease severity, we analysed transcriptomic patterns using bulk RNA-seq from 112 age- and gender-matched NS1 antigen-confirmed hospital-admitted dengue patients with varying severity. Severe cases exhibited reduced platelet count, increased lymphocytosis, and neutropenia, indicating a dysregulated immune response. Using bulk RNA-seq, our analysis revealed a minimal overlap between the differentially expressed gene and transcript isoform, with a distinct expression pattern across the disease severity. Severe patients showed enrichment in retained intron and nonsense-mediated decay transcript biotypes, suggesting altered splicing efficiency. Furthermore, an up-regulated programmed cell death, a haemolytic response, and an impaired interferon and antiviral response at the transcript level were observed. We also identified the potential involvement of the RBM39 gene among others in the innate immune response during dengue viral pathogenesis, warranting further investigation. These findings provide valuable insights into potential therapeutic targets, underscoring the importance of exploring transcriptomic landscapes between different disease sub-phenotypes in infectious diseases.

The alteration of NK cells phenotypes related to the functions and dengue disease outcomes.

Natural killer cells (NK cells) are the front line of immune cells to combat pathogens and able to influence the subsequent adaptive immune responses. One of the factors contributing to pathogenesis in dengue hemorrhagic fever (DHF) disease is aberrant immune activation during early phase of infection. This study explored the profile of NK cells in dengue infected pediatric patients with different degrees of disease severity. DHF patients contained higher frequency of activated NK cells but lower ratio of CD56dim:CD56bright NK subsets. Activated NK cells exhibited alterations in several NK receptors. Interestingly, the frequencies of NKp30 expressing activated NK cells were more pronounced in dengue fever (DF) than in DHF pediatric patients. In vitro functional analysis indicated that degranulation of NK cells in responding to dengue infected dendritic cells (DCs) required cell-cell contact and type I IFNs. Meanwhile, Interferon gamma (IFN-γ) production initially required cell-cell contact and type I IFNs followed by Interleukin-12 (IL-12), Interleukin-15 (IL-15) and Interleukin-18 (IL-18) resulting in the amplification of IFN-γ producing NK cells over time. This study highlighted the complexity and the factors influencing NK cells responses to dengue virus. Degree of activation, phenotypes of activated cells and the crosstalk between NK cells and other immune cells, could modulate the outcome of NK cells function in the dengue disease.