ABSTRACT
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.
Subject(s)
Liver Failure, Acute , Severe Dengue , Humans , Male , Liver Failure, Acute/etiology , Liver Failure, Acute/virology , Child , Severe Dengue/complications , Severe Dengue/diagnosis , Fatal OutcomeABSTRACT
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.
Subject(s)
Dengue , Interleukin-6 , Interleukin-8 , World Health Organization , Humans , Dengue/immunology , Dengue/diagnosis , Child , Male , Female , Interleukin-6/blood , Child, Preschool , Interleukin-8/blood , Severe Dengue/diagnosis , Severe Dengue/immunology , Severe Dengue/blood , Adolescent , Severity of Illness Index , Biomarkers/blood , Dengue Virus/immunology , Practice Guidelines as Topic , Flow Cytometry , Infant , Cytokines/bloodABSTRACT
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.
Subject(s)
Chemokine CXCL10 , Enzyme-Linked Immunosorbent Assay , Severe Dengue , Viral Nonstructural Proteins , Humans , Chemokine CXCL10/blood , Male , Severe Dengue/blood , Severe Dengue/immunology , Female , Adult , Middle Aged , Leukocytes, Mononuclear/metabolism , Case-Control Studies , Young Adult , Interferon-gamma/blood , Adolescent , Flow CytometryABSTRACT
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.
Subject(s)
Dengue , Humans , Peru/epidemiology , Risk Factors , Male , Adult , Female , Middle Aged , Dengue/epidemiology , Dengue/mortality , Retrospective Studies , Adolescent , Young Adult , Child , Intensive Care Units , Severe Dengue/epidemiology , Severe Dengue/mortality , Prognosis , Cohort StudiesABSTRACT
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.
Subject(s)
Dengue , Severity of Illness Index , Humans , Honduras/epidemiology , Male , Adolescent , Child , Female , Dengue/epidemiology , Adult , Young Adult , Child, Preschool , Infant , Middle Aged , Risk Factors , Severe Dengue/epidemiologyABSTRACT
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.
Subject(s)
Takotsubo Cardiomyopathy , Humans , Takotsubo Cardiomyopathy/etiology , Takotsubo Cardiomyopathy/diagnostic imaging , Takotsubo Cardiomyopathy/diagnosis , Aged , Male , Dengue/complications , Dengue/diagnosis , Electrocardiography , Severe Dengue/complications , Severe Dengue/diagnosis , EchocardiographyABSTRACT
OBJECTIVE: The prevalent symptoms of severe dengue in pediatric patients are divided into three subgroups: severe plasma leakage, severe bleeding, and severe organ damage. In addition, the seasonal patterns of the disease and the outcomes of cure or death from dengue were evaluated. METHODS: An epidemiological, observational, analytical, cross-sectional study was conducted with data from the Notifiable Disease Information System (SINAN - Sistema de Informação de Agravos de Notificação and DATASUS - Departamento de Informática do Sistema Único de Saúde) of the Ministry of Health from 2019 to 2020. RESULTS: During the study period, 1,857 cases of severe dengue were observed in the pediatric age group, with the most common symptoms being respiratory failure, melena, hematemesis, and altered level of consciousness. The total proportion of patients hospitalized for severe dengue was 89.6%, and 51.2% of these patients died, corroborating the importance of early detection of the disease. CONCLUSION: Severe dengue is more prevalent during the seasonal period, with hot and humid characteristics owing to the mechanism involved in the viral cycle. The most prevalent symptoms of severe dengue in pediatric patients were respiratory failure alone, gastrointestinal bleeding, and altered level of consciousness. It is important to identify signs of severity for early intervention and a better prognosis, considering that death is closely related to a delayed diagnosis.
Subject(s)
Seasons , Severe Dengue , Humans , Cross-Sectional Studies , Child, Preschool , Infant , Severe Dengue/epidemiology , Severe Dengue/diagnosis , Severe Dengue/mortality , Male , Female , Child , Brazil/epidemiology , Infant, Newborn , Severity of Illness Index , Hospitalization/statistics & numerical data , PrevalenceABSTRACT
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.
Subject(s)
Dengue Virus , Serogroup , Severe Dengue , Humans , Mexico/epidemiology , Female , Male , Dengue Virus/genetics , Dengue Virus/classification , Dengue Virus/isolation & purification , Adolescent , Adult , Child , Middle Aged , Child, Preschool , Young Adult , Retrospective Studies , Infant , Severe Dengue/epidemiology , Severe Dengue/virology , Social Security , Aged , Risk Factors , Severity of Illness Index , Infant, NewbornABSTRACT
OBJECTIVE: Severe dengue is a significant health problem in Latin America, with children being the most affected. Understanding risk factors for severe dengue is crucial for enhancing patient care. Therefore, this study aims to systematically review the literature to identify the risk factors associated with severe dengue in Latin America through systematic review and meta-analysis. METHODS: PubMed, SciELO, LILACS and EMBASE databases were used to search for eligible scientific articles for the review. The outcomes considered were symptoms of severe dengue, hospitalisation and death. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the quality of the studies. Data analysis was performed using STATA v 13.0 software. The degree of heterogeneity between studies was quantified using the I2 measure, and statistically significant results were defined as those with p values <0.05. RESULTS: Of the 1876 articles screened, 47 articles were included in the systematic review and 45 articles were analysed through meta-analysis. Identified risk factors associated with severe dengue included secondary dengue infection, female sex, white or Caucasian ethnicity and specific signs and symptoms such as headache, myalgia and/or arthralgia, vomiting/nausea, abdominal pain or tenderness, diarrhoea, prostration, lethargy, fatigue or similar. For the death outcome, respiratory symptoms and age <18 years were identified as risk factors. On the other hand, in women, the diagnosis of positive tourniquet test, platelet count <100,000 per µL and symptoms of capillary fragility were associated with a lower probability of death. These data highlight the importance of early screening of patients, to identify possible haemorrhagic signs and reduce deaths from dengue. This study has limitations, including possible publication bias, heterogeneity of results and study design biases. CONCLUSION: These findings are significant for shaping strategies, management approaches and identifying high-risk groups, which will help establish future guidelines.
Subject(s)
Severe Dengue , Humans , Risk Factors , Latin America/epidemiology , Severe Dengue/epidemiology , Severe Dengue/mortality , Female , MaleABSTRACT
One of the main challenges in the clinical management of dengue is the early identification of cases that could progress to severe forms of the disease. A biomarker that may enable this identification is the presence of genetic polymorphisms in genes associated with immune responses. The objective of this study was to perform a systematic review of the Latin American literature on these genes. An electronic literature search was carried out in PubMed, Scopus, Lilacs, and the Virtual Health Library, and reference lists of systematic reviews in the area. Case-control studies conducted in Latin American countries examining at least one form of genetic polymorphism related to immune responses against severe dengue were included. In total, 424 articles were identified and 26 were included in this systematic review. Of the 26 selected articles, 16 reported polymorphisms associated with the risk of developing severe dengue (Risk); Similarly, 16 articles reported polymorphisms associated with a decreased risk of severe dengue (Protective). The final analysis revealed that multiple polymorphisms in immune system genes were early markers of the progression of dengue in Latin Americans and found that polymorphisms of the TNF-alpha gene may have a critical role in dengue pathogenesis.
Subject(s)
Dengue , Severe Dengue , Humans , Severe Dengue/genetics , Latin America , Dengue/genetics , Systematic Reviews as Topic , Polymorphism, Genetic/geneticsABSTRACT
BACKGROUND: The development of computational methodologies to support clinical decision-making is of vital importance to reduce morbidity and mortality rates. Specifically, prescriptive analytic is a promising area to support decision-making in the monitoring, treatment and prevention of diseases. These aspects remain a challenge for medical professionals and health authorities. MATERIALS AND METHODS: In this study, we propose a methodology for the development of prescriptive models to support decision-making in clinical settings. The prescriptive model requires a predictive model to build the prescriptions. The predictive model is developed using fuzzy cognitive maps and the particle swarm optimization algorithm, while the prescriptive model is developed with an extension of fuzzy cognitive maps that combines them with genetic algorithms. We evaluated the proposed approach in three case studies related to monitoring (warfarin dose estimation), treatment (severe dengue) and prevention (geohelminthiasis) of diseases. RESULTS: The performance of the developed prescriptive models demonstrated the ability to estimate warfarin doses in coagulated patients, prescribe treatment for severe dengue and generate actions aimed at the prevention of geohelminthiasis. Additionally, the predictive models can predict coagulation indices, severe dengue mortality and soil-transmitted helminth infections. CONCLUSIONS: The developed models performed well to prescribe actions aimed to monitor, treat and prevent diseases. This type of strategy allows supporting decision-making in clinical settings. However, validations in health institutions are required for their implementation.
Subject(s)
Severe Dengue , Humans , Warfarin/therapeutic use , Algorithms , Machine Learning , Clinical Decision-MakingABSTRACT
The precise pathogenesis of COVID-19-related multisystem inflammatory syndrome remains largely elusive, despite its rarity. The syndrome symptoms often overlap with those of other infections, posing challenges for prompt diagnosis. A male patient, 34 years old, was admitted with suspicion of severe dengue, rapidly progressing to multiple organ dysfunction. Dengue tests resulted negative, and he passed away after four days. This case occurred approximately four weeks after the initial onset of COVID-19 and met all diagnostic criteria as defined by the Centers for Disease Control and Prevention. This report presents the first documented case of fatal multisystem inflammatory syndrome in adult (MIS-A) in Brazil. Recognizing the significance of suspecting this syndrome and promptly initiating treatment at an early stage are essential for minimizing damage and mortality.
Subject(s)
COVID-19 , Severe Dengue , United States , Humans , Adult , Male , Brazil , HospitalizationABSTRACT
INTRODUCCIÓN. El dengue es una enfermedad infecciosa de origen viral, transmitida principalmente por el mosquito Aedes aegypti. Es un grave problema de salud pública a nivel mundial, en las Américas y en el Ecuador. OBJETIVOS. Analizar el comportamiento epidemiológico del dengue desde 1980 hasta el 2020, los factores de riesgo que mantienen la transmisión y las acciones que el país ha implementado para su prevención y control. METODOLOGÍA. Revisión bibliográfica narrativa, teniendo como fuente las páginas web de la Organización Mundial de la Salud, de la Organización Panamericana de la Salud, Ministerio de Salud Pública del Ecuador, artículos de revistas de bibliotecas virtuales e informes técnicos publicados en Google académico, Scielo, Biblioteca Virtual en Salud y PubMed. RESULTADOS. Los registros encontrados sobre presencia de casos de dengue datan de 1988 cuando se presentó la gran epidemia de dengue en Guayaquil. Posteriormente, mantiene un comportamiento endemo-epidémico. A partir del año 2000 se presentan casos de dengue grave. Su pico más alto de letalidad fue de 2,44% en el 2010. El serotipo DEN 1 es el más frecuente, pero a partir del 2000 circulan los 4 serotipos. Las acciones de prevención y control no han sido sostenidas. CONCLUSIONES. El dengue en Ecuador en los últimos cuarenta años mantiene una importante trasmisión, caracterizada por años epidémicos. No ha podido ser controlado el vector, el cual ha ido infestando más localidades. Las condicionantes climáticas y ecológicas, explican en parte la persistencia, pero la determinación más importante está dada por las inequidades sociales, falta de servicios básicos, y la poca continuidad e impacto de las medidas de prevención y control.
INTRODUCTION. Dengue is an infectious disease of viral origin, transmitted mainly by the Aedes aegypti mosquito. It is a serious public health problem worldwide, in the Americas and in Ecuador. OBJECTIVES: To analyze the epidemiological behavior of dengue fever from 1980 to 2020, the risk factors that maintain transmission and the actions that the country has implemented for its prevention and control. METHODOLOGY. Narrative bibliographic review, taking as sources the web pages of the World Health Organization, Pan American Health Organization, Ministry of Public Health of Ecuador, journal articles from virtual libraries and technical reports published in Google Scholar, Scielo, Virtual Health Library and PubMed. RESULTS. The records found on the presence of dengue cases date back to 1988 when the great dengue epidemic occurred in Guayaquil. Subsequently, it maintained an endemic-epidemic behavior. Beginning in 2000, severe cases of dengue fever occurred. Its highest lethality peak was 2.44% in 2010. DEN 1 serotype is the most frequent, but since 2000 all 4 serotypes have been circulating. Prevention and control actions have not been sustained. CONCLUSIONS. Dengue in Ecuador over the last forty years has maintained an important transmission, characterized by epidemic years. It has not been possible to control the vector, which has been infesting more localities. Climatic and ecological conditions partly explain its persistence, but the most important determinant is given by social inequalities, lack of basic services, and the lack of continuity and impact of prevention and control measures.
Subject(s)
Humans , Male , Female , Risk Factors , Aedes , Dengue , Dengue Virus , Ecuador , Insect Vectors , Epidemiology , Severe DengueABSTRACT
Dengue is a viral disease transmitted by the bite of a female arthropod, prevalent primarily in tropical and subtropical regions. Its manifestations include asymptomatic infections, dengue fever, and a severe form called hemorrhagic dengue or dengue shock syndrome. Atypical manifestations can also occur, called expanded dengue syndrome. We describe the case of a 43-year-old man with an unusual presentation of dengue, demonstrating a workup suggestive of myocardial and pericardial damage. Symptoms and markers indicative of cardiac compromise improved after five days on anti-inflammatory treatment. Dengue myocarditis is considered an uncommon complication of dengue, although its reported incidence is likely an underestimation. In general, most cases of dengue myocarditis are self-limited, with only a minority at risk of progressing to heart failure. In order to improve recognition and prevent progression, healthcare providers should maintain a high degree of suspicion regarding potential cardiac complications in patients with dengue.
Subject(s)
Dengue , Heart Diseases , Heart Failure , Myocarditis , Severe Dengue , Male , Humans , Female , Adult , Myocarditis/diagnosis , Myocarditis/etiology , Dengue/complications , Dengue/diagnosis , Severe Dengue/complications , Severe Dengue/diagnosisABSTRACT
BACKGROUND: Pediatric dengue and sepsis share clinical and pathophysiologic aspects. Multiple inflammatory and regulatory cytokines, decoy receptors and vascular permeability factors have been implicated in the pathogenesis of both diseases. The differential pattern and dynamic of these soluble factors, and the relationship with clinical severity between pediatric dengue and sepsis could offer new diagnosis and therapeutic strategies. METHODS: We evaluated the concentration levels of 11 soluble factors with proinflammatory, regulatory and vascular permeability involvement, in plasma from children with dengue or sepsis, both clinically ranging from mild to severe, in the early, late and convalescence phases of the disease. RESULTS: During early acute infection, children with sepsis exhibited specific higher concentration levels of IL-6, vascular endothelial growth factor (VEGF), and its soluble decoy receptor II (sVEGFR2) and lower concentration levels of IL-10 and the soluble tumor necrosis factor receptor 2 (sTNFR2), in comparison with children with severe dengue. In addition, the circulating amounts of soluble ST2, and VEGF/sVEGFR2 were widely associated with clinical and laboratory indicators of dengue severity, whereas secondary dengue virus infections were characterized by an enhanced cytokine response, relative to primary infections. In severe forms of dengue, or sepsis, the kinetics and the cytokines response during the late and convalescence phases of the disease also differentiate. CONCLUSIONS: Dengue virus infection and septic processes in children are characterized by cytokine responses of a specific magnitude, pattern and kinetics, which are implicated in the pathophysiology and clinical outcome of these diseases.
Subject(s)
Dengue , Sepsis , Severe Dengue , Humans , Child , Severe Dengue/diagnosis , Severe Dengue/complications , Vascular Endothelial Growth Factor A , Dengue/diagnosis , Dengue/complications , Convalescence , Cytokines , Sepsis/diagnosis , Sepsis/complications , BiomarkersABSTRACT
Dengue is a global and growing health threat, especially in Southeast Asia, West Pacific and South America. Infection by the dengue virus (DENV) results in dengue fever, which can evolve to severe forms. Cytokines, especially interferons, are involved in the immunopathogenesis of dengue fever, and so may influence the disease outcomes. The aim of this study was to investigate the association between severe forms of dengue and two single nucleotide polymorphisms (SNPs) in the interferon-gamma gene (IFNG): A256G (rs2069716) and A325G (rs2069727). We included 274 patients infected with DENV serotype 3: 119 cases of dengue without warning signs (DWoWS), and 155 with warning signs (DWWS) or severe dengue (SD). DNA was extracted, and genotyped with Illumina Genotyping Kit or real time PCR (TaqMan probes). We estimated the adjusted Odds Ratios (OR) by multivariate logistic regression models. When comparing with the ancestral AA/AA diplotype (A256G/A325G), we found a protective association of the AA/AG against DWWS/SD among patients with secondary dengue (OR 0.51; 95% IC 0.24-1.10, p = 0.085), adjusting for age and sex. The variant genotype at locus A325G of the IFNG, in combination with the ancestral genotype at locus A256G, can protect against severe clinical forms of secondary dengue in Brazilian DENV3-infected patients.
Subject(s)
Interferon-gamma , Severe Dengue , Humans , Brazil , Dengue Virus , Genotype , Interferon-gamma/genetics , Severe Dengue/genetics , Polymorphism, Single NucleotideABSTRACT
Motivation for the study. To describe the characteristics of patients who died from severe dengue fever during the 2017 El Niño in Piura. Main findings. Mortality from severe dengue was higher in adult women. First contact with healthcare took place mostly in higher level hospitals. Admission to a specialized unit was late for severe dengue cases. Implications. Control of dengue fever involves several aspects, such as, access to health, prevention, water availability, vector control and education; therefore, it is important to strengthen public health policies in this regard. In order to achieve this goal, local and central government sectors must be involved.
Motivación para realizar el estudio. Describir las características de los pacientes fallecidos por dengue grave durante el fenómeno de El Niño del 2017 en Piura. Principales hallazgos. La mortalidad del dengue grave fue mayoritaria en las mujeres adultas, la primera atención se realizó en hospitales de mayor nivel y la atención para casos graves de dengue en una unidad especializada fue tardía. Implicancias. La mortalidad del dengue grave fue mayoritaria en las mujeres adultas, la primera atención se realizó en hospitales de mayor nivel y la atención para casos graves de dengue en una unidad especializada fue tardía.
Subject(s)
Dengue , Severe Dengue , Adult , Humans , Female , Dengue/epidemiology , Dengue/prevention & control , Severe Dengue/epidemiology , Peru/epidemiology , Disease Outbreaks , El Nino-Southern OscillationABSTRACT
BACKGROUND: Dengue is a disease caused by dengue virus (DENV-1 through -4). Among the four serotypes, DENV-4 remains the least studied. Acute kidney injury is a potential complication of dengue generally associated with severe dengue infection. OBJECTIVES: The goal of this study was to investigate the alterations caused by experimental dengue infection in the kidney of adult BALB/c mice. METHODS: In this study, BALB/c mice were infected through the intravenous route with a DENV-4 strain, isolated from a human patient. The kidneys of the mice were procured and subject to histopathological and ultrastructural analysis. FINDINGS: The presence of the viral antigen was confirmed through immunohistochemistry. Analysis of tissue sections revealed the presence of inflammatory cell infiltrate throughout the parenchyma. Glomerular enlargement was a common find. Necrosis of tubular cells and haemorrhage were also observed. Analysis of the kidney on a transmission electron microscope allowed a closer look into the necrotic tubular cells, which presented nuclei with condensed chromatin, and loss of cytoplasm. MAIN CONCLUSIONS: Even though the kidney is probably not a primary target of dengue infection in mice, the inoculation of the virus in the blood appears to damage the renal tissue through local inflammation.
Subject(s)
Dengue Virus , Severe Dengue , Adult , Humans , Animals , Mice , Kidney , Antigens, Viral , Mice, Inbred BALB CABSTRACT
BACKGROUND: Identification of pleural effusion (PE) in dengue infection is an objective measure of plasma leakage and may predict disease progression. However, no studies have systematically assessed the frequency of PE in patients with dengue, and whether this differs across age and imaging modality. METHODS: We searched Pubmed, Embase Web of Science and Lilacs (period 1900-2021) for studies reporting on PE in dengue patients (hospitalized and outpatient). We defined PE as fluid in the thoracic cavity detected by any imaging test. The study was registered in PROSPERO (CRD42021228862). Complicated dengue was defined as hemorrhagic fever, dengue shock syndrome or severe dengue. RESULTS: The search identified 2,157 studies of which 85 studies were eligible for inclusion. The studies (n = 31 children, n = 10 adults, n = 44 mixed age) involved 12,800 patients (30% complicated dengue). The overall frequency of PE was 33% [95%CI: 29 to 37%] and the rate of PE increased significantly with disease severity (P = 0.001) such that in complicated vs. uncomplicated dengue the frequencies were 48% and 17% (P < 0.001). When assessing all studies, PE occurred significantly more often in children compared to adults (43% vs. 13%, P = 0.002) and lung ultrasound more frequently detected PE than conventional chest X-ray (P = 0.023). CONCLUSIONS: We found that 1/3 of dengue patients presented with PE and the frequency increased with severity and younger age. Importantly, lung ultrasound demonstrated the highest rate of detection. Our findings suggest that PE is a relatively common finding in dengue and that bedside imaging tools, such as lung ultrasound, potentially may enhance detection.
Subject(s)
Dengue , Pleural Effusion , Severe Dengue , Adult , Child , Humans , Severe Dengue/complications , Severe Dengue/diagnostic imaging , Severe Dengue/epidemiology , Exudates and Transudates , Pleural Effusion/diagnostic imaging , Pleural Effusion/epidemiology , Pleural Effusion/complications , Plasma , Ultrasonography , Dengue/complications , Dengue/diagnostic imaging , Dengue/epidemiologyABSTRACT
BACKGROUND: Pregnancy increases a woman's risk of severe dengue. To the best of our knowledge, the moderation effect of the dengue serotype among pregnant women has not been studied in Mexico. This study explores how pregnancy interacted with the dengue serotype from 2012 to 2020 in Mexico. METHOD: Information from 2469 notifying health units in Mexican municipalities was used for this cross-sectional analysis. Multiple logistic regression with interaction effects was chosen as the final model and sensitivity analysis was done to assess potential exposure misclassification of pregnancy status. RESULTS: Pregnant women were found to have higher odds of severe dengue [1.50 (95% CI 1.41, 1.59)]. The odds of dengue severity varied for pregnant women with DENV-1 [1.45, (95% CI 1.21, 1.74)], DENV-2 [1.33, (95% CI 1.18, 1.53)] and DENV-4 [3.78, (95% CI 1.14, 12.59)]. While the odds of severe dengue were generally higher for pregnant women compared with non-pregnant women with DENV-1 and DENV-2, the odds of disease severity were much higher for those infected with the DENV-4 serotype. CONCLUSION: The effect of pregnancy on severe dengue is moderated by the dengue serotype. Future studies on genetic diversification may potentially elucidate this serotype-specific effect among pregnant women in Mexico.