Papaya Leaf Extract Elevates Platelet Levels in Individuals With Dengue Fever.

Dengue, an arboviral illness, is notorious for inducing thrombocytopenia, leading to bleeding and heightened mortality risk. Carica papaya leaf extract has shown efficacy in elevating platelet counts. A 35-year-old male presented with fever, fatigue, and body pain persisting for four days. Additionally, he complained of severe back pain, ocular discomfort, and brief episodes of nosebleeds. Testing revealed a positive NS1 antigen, prompting the initiation of intravenous normal saline, paracetamol, and papaya extract tablets. Despite initial platelet levels of 74,000, a subsequent decline to 30,650 was observed following another nosebleed. Subsequently, the patient's spouse administered freshly prepared papaya leaf extract orally three to four times daily, resulting in a platelet count of 120,320 on day 14. Timely recognition of declining platelet levels and the commencement of C. Papaya leaf extract contributed significantly to averting mortality risks.

Dengue viremia kinetics and effects on platelet count and clinical outcomes: An analysis of 2340 patients from Vietnam.

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.

[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.

Liver involvement in dengue: A systematic review.

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.

Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) as a Novel Score in Early Detection of Complicated Dengue Fever.

Introduction: 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.

Retrospective Analysis of Severe Dengue by Dengue Virus Serotypes in a Population with Social Security, Mexico 2023.

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.

Evaluation of clinical and laboratory characteristics of dengue viral infection and risk factors of dengue hemorrhagic fever: a multi-center retrospective analysis.

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.

Increased frequencies of highly activated regulatory T cells skewed to a T helper 1-like phenotype with reduced suppressive capacity in dengue patients.

The pathogenesis of dengue involves a complex interplay between the viral factor and the host immune response. A mismatch between the infecting serotype and the adaptive memory response is hypothesized to lead to exacerbated immune responses resulting in severe dengue. Here, we aim to define in detail the phenotype and function of different regulatory T cell (Treg) subsets and their association with disease severity in a cohort of acute dengue virus (DENV)-infected Cambodian children. Treg frequencies and proliferation of Tregs are increased in dengue patients compared to age-matched controls. Tregs from dengue patients are skewed to a Th1-type Treg phenotype. Interestingly, Tregs from severe dengue patients produce more interleukin-10 after in vitro stimulation compared to Tregs from classical dengue fever patients. Functionally, Tregs from dengue patients have reduced suppressive capacity, irrespective of disease severity. Taken together, these data suggest that even though Treg frequencies are increased in the blood of acute DENV-infected patients, Tregs fail to resolve inflammation and thereby could contribute to the immunopathology of dengue. IMPORTANCE: According to the World Health Organization, dengue is the fastest-spreading, epidemic-prone infectious disease. The extent of dengue virus infections increased over the years, mainly driven by globalization-including travel and trade-and environmental changes. Dengue is an immunopathology caused by an imbalanced immune response to a secondary heterotypic infection. As regulatory T cells (Tregs) are essential in maintaining immune homeostasis and dampening excessive immune activation, this study addressed the role of Tregs in dengue immunopathology. We show that Tregs from dengue patients are highly activated, skewed to a Th1-like Treg phenotype and less suppressive compared to healthy donor Tregs. Our data suggest that Tregs fail to resolve ongoing inflammation during dengue infection and hence contribute to the immunopathology of severe dengue disease. These data clarify the role of Tregs in dengue immunopathogenesis, emphasizing the need to develop T cell-based vaccines for dengue.

Dengue induced acute liver failure: A meta summary of case reports.

BACKGROUND: Dengue fever is the most common cause of viral hemorrhagic fever, with more than 400 million cases being reported annually, worldwide. Even though hepatic involvement is common, acute liver failure (ALF) is a rare complication of dengue fever. AIM: To analyze the demographic profile, symptomology, hospital course and outcomes of patients presenting with ALF secondary to dengue infection by reviewing the published case reports. METHODS: A systematic search was performed from multiple databases including PubMed, Reference Citation Analysis, Science Direct, and Google Scholar. The search terms used were "dengue" OR "severe dengue" OR "dengue shock syndrome" OR "dengue haemorrhagic syndrome" OR "dengue fever" AND "acute liver failure" OR "hepatic failure" OR "liver injury". The inclusion criteria were: (1) Case reports or case series with individual patient details; (2) Reported acute liver failure secondary to dengue infection; and (3) Published in English language and on adult humans. The data were extracted for patient demographics, clinical symptomatology, clinical interventions, hospital and intensive care unit course, need for organ support and clinical outcomes. RESULTS: Data from 19 case reports fulfilling the predefined inclusion criteria were included. The median age of patients was 38 years (inter quartile range: Q3-Q1 26.5 years) with a female preponderance (52.6%). The median days from diagnosis of dengue to development of ALF was 4.5 d. The increase in aspartate aminotransferase was higher than that in alanine aminotransferase (median 4625 U/L vs 3100 U/L). All the patients had one or more organ failure, with neurological failure present in 73.7% cases. 42.1% patients required vasopressor support and hepatic encephalopathy was the most reported complication in 13 (68.4%) cases. Most of the patients were managed conservatively and 2 patients were taken up for liver transplantation. Only 1 death was reported (5.3%). CONCLUSION: Dengue infection may rarely lead to ALF. These patients may frequently require intensive care and organ support. Even though most of these patients may improve with supportive care, liver transplantation may be a therapeutic option in refractory cases.

APRI as a predictor of severe dengue fever.

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-Associated Hemophagocytic Lymphohistiocytosis: A Narrative Review of Its Identification and Treatment.

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.

Genotype of dengue virus serotype 1 in relation to severe dengue in Guangzhou, China.

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.

Reverse Takotsubo Cardiomyopathy with Severe Dengue: Case Report from Pakistan.

Takotsubo Cardiomyopathy is an established transient cardiomyopathy found predominately in females with intense emotional and physical strain. It has four notable variants: Apical, Mid-Ventricular, Basal and Focal. Mid Ventricular variant is also referred to as Reverse Takotsubo Cardiomyopathy. Dengue is a viral arthopod-borne tropical disease endemic to Pakistan, with multiple reports of cardiovascular involvement. We report an atypical presentation of a 17 year old male, suffering from Dengue Fever, who presented to a tertiary care hospital with Reverse Takotsubo Cardiomyopathy.

Prediction of severity of dengue infection in children based on hepatic involvement.

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.

Mice, myeloid cells, and dengue: a new model for unraveling vascular leakage mysteries.

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/ß 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.

[Clinical Update on Diagnosis, Treatment and Prevention of Dengue]. / Atualização Clínica sobre Diagnóstico, Tratamento e Prevenção da Dengue.

Dengue is a vector-borne disease that has a significant impact on global public health. The vector mosquito belongs to the genus Aedes. Two species play a key role in human transmission: Ae. aegypti, which has adapted to the urban environment of highly populated areas in tropical and subtropical countries, leading to a dramatic increase in dengue cases over the years, and Ae. albopictus, which poses a potential threat to temperate climate countries due to its ability to adapt to colder climates. The disease is widespread across the world, posing a risk to nearly half of the world's population. Although most cases are asymptomatic, dengue causes a burden on healthcare systems and mainly affects the younger population. The disease is also spreading to temperate climate countries, thus becoming a global threat. Vector control measures and vaccine development have been the main prevention strategies, as there is still no effective treatment for the disease.

A dengue é uma doença transmitida por um vetor hematófago (mosquito) que possui um impacto significativo na saúde pública mundial. O mosquito transmissor pertence ao género Aedes. São duas as espécies responsáveis pela transmissão humana: o Ae. aegypti, que se adaptou ao ambiente urbano de áreas altamente populosas de países tropicais e subtropicais, resultando num aumento dramático dos casos de dengue ao longo dos anos; e o Ae. Albopictus, que representa uma potencial ameaça para os países de clima temperado pela sua capacidade de adaptação aos climas mais frios. A doença está presente em grande parte do mundo, colocando cerca de metade da população do planeta em risco. Embora a maioria dos casos seja assintomática, a dengue causa uma sobrecarga nos sistemas de saúde e impacta principalmente os jovens. A doença também tem vindo a alastrar-se a países de clima temperado, tornando-se uma ameaça global. As medidas de controlo vetorial e o desenvolvimento de vacinas têm sido as principais estratégias de prevenção, uma vez que não existe ainda um tratamento eficaz para a doença.

Harness risk stratification of diabetic patients with dengue in a cohort study.

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.

Caso de dengue grave en un niño de 5 años de la ciudad de Lima / A case of severe dengue in a 5-year-old boy in the city of Lima

RESUMEN El dengue es una infección viral transmitida a través del mosquito Aedes aegypti y presenta cuatro serotipos (DENV-1 a DENV-4). La enfermedad desencadena una variedad de manifestaciones clínicas, desde formas leves sin signos de alarma hasta formas graves, potencialmente mortales. Se presenta el caso de un niño de cinco años, procedente de la provincia del Callao, cuyos síntomas iniciales fueron fiebre, cefalea y malestar general. Al tercer día, el niño manifiestó dolor abdominal leve y vómitos escasos; posteriormente, distensión abdominal, ictericia y coluria. Fue hospitalizado en la unidad de cuidados intensivos pediátricos con deshidratación moderada, ictericia, edemas, abdomen distendido y doloroso, matidez desplazable, hígado a 2 cm debajo del reborde costal derecho y lúcido. Por exámenes complementarios, se evidenció falla hepática, hepatoesplenomegalia y derrame pleural en bases. Se diagnosticó dengue grave a través de una prueba de ELISA Ig M reactivo más sobreinfección por probable peritonitis bacteriana espontánea. Se inició el tratamiento con antibióticos, furosemida, plasma fresco congelado, crioprecipitado y metamizol. Al no observarse mejoría, se optimizó el diurético y se administró albúmina humana. Mostró mejoría con disminución de ascitis, edemas, ictericia y efusión pleural; también mejora del perfil hepático y de la coagulación, además de encontrarse afebril. Presentó inesperadamente dificultad respiratoria por insuficiencia cardiaca congestiva debido a miocardiopatía dilatada según ecocardiografía; se manejó con diuréticos. Fue dado de alta en estado afebril, sin edemas y con resolución de falla hepática y trastorno de coagulación.

ABSTRACT 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.

Severe dengue in the intensive care unit.

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.

A comparison of changes in venous lactate and haematocrit during fluid resuscitation of dengue haemorrhagic fever.

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.