Mortality Rates of Severe Dengue Viral Infection Before and After Implementation of a Revised Guideline for Severe Dengue.

OBJECTIVES: To compare the mortality rate of severe dengue (SD) before and after implementation of a revised SD guideline. METHODS: Medical records of SD patients <15 years of age hospitalized during 1998-2020 were reviewed. The revised SD guidelines were implemented in 2016, including intensive monitoring of vital signs and intra-abdominal pressure, the release of intra-abdominal pressure in cases of abdominal compartment syndrome (ACS) and the use of N-acetyl cysteine in cases of acute liver failure. RESULTS: On initial admission, organ failure including severe bleeding, acute respiratory failure, acute kidney injury and acute liver failure was not significantly different between 78 and 23 patients treated in the pre- and postrevised guideline periods, respectively. After hospitalization, the proportions of patients who developed profound shock (68.8% vs. 41.2%), multiorgan failures (60.4% vs. 73.3%), ACS (37.2% vs. 26.1%) and fatal outcome (33.3% vs. 13.0%) were also not significantly different between the pre- and postrevised guideline periods, respectively. In subgroup analysis, the mortality rates in patients with multiorgan failure (44.1% vs. 15.8%), acute respiratory failure and active bleeding (78.1% vs. 37.5%) and ACS (82.8% vs. 33.3%), respectively, were significantly higher in the pre- than the postrevised guideline periods. The durations of time before the liver function tests returned to normal levels, and the mortality rates in acute liver failure patients treated with and without N-acetyl cysteine were not significantly different. CONCLUSIONS: Although following the revised guidelines could not prevent organ failure, the mortality rates in patients with multiorgan failure and/or ACS decreased significantly when following the revised guidelines.

Dengue y sus manifestaciones atípicas en el departamento de Arauca, Colombia 2010-2015. Revisión de la literatura / Dengue and its atypical manifestations in the department of Arauca, Colombia 2010-2015. Literature review

Objetivo: El propósito de este trabajo ha sido describir las manifestaciones clínicas atípicas del dengue que se han reportado desde una mirada global hasta la situación actual de Colombia, principalmente en el Departamento de Arauca. Método: Se realizó una búsqueda de literatura científica en las bases de datos PubMed y Scielo Public Health, se eligieron los descriptores o palabras relacionadas con la enfermedad y se realizó búsqueda para la descripción de reportes de casos de manifestaciones inusuales producidas por la infección por dengue. Finalmente se buscaron reportes de casos en Colombia por la base de datos SciELO Public Health de manifestaciones atípicas producidas por dengue, así como los reportes del Instituto Nacional de Salud de Colombia. Resultados: De la exploración de 80 revisiones, la búsqueda identificó 26 artículos, se revisaron los resúmenes y se seleccionaron 18 por ajustarse al objetivo de la revisión. Se excluyeron 8 ya que no correspondían directamente a un episodio de complicación directa por dengue. Así mismo de las referencias de los casos reportados en la búsqueda inicial, se tomaron en cuenta para enriquecer el contexto de esta revisión. Conclusiones: Las manifestaciones atípicas resultados de la infección por el virus del dengue, cada vez son más frecuentemente en todo el mundo. Es notorio en esta revisión que la población infantil es blanco de esta infección viral y que la prevención debe estar enfocada a disminuir la transmisión vectorial con el fin de proteger la población en riesgo, además cabe resaltar que las manifestaciones clínicas más prevalentes encontradas fueron las neurológicas y gastrointestinales afectando a la población infantil en su mayoría.(AU)

Objective: The purpose of this work has been to describe the atypical clinical manifestations of dengue that have been reported from a global perspective to the current situation in Colombia, mainly in the Department of Arauca. Method: A scientific literature search was carried out in the PubMed and Scielo Public Health databases, the descriptors or words related to the disease were chosen and a search was carried out for the description of case reports of unusual manifestations produced by dengue infection. Finally, reports of cases in Colombia were searched through the Scielo Public Health database of atypical manifestations produced by dengue, as well as reports from the National Institute of Health of Colombia. Results: From the exploration of 80 reviews, the search identified 26 articles, the abstracts were reviewed, and 18 were selected to fit the purpose of the review. 8 of them were excluded because, they did not correspond directly to an episode of complication from dengue. Likewise, the references of the cases reported in the initial search were taken into account to enrich the context of this review. Conclusions: Atypical manifestations resulting from dengue virus infection are becoming more and more frequent throughout the world. It is well known in this review that the child population is the target of this viral infection and that prevention should be focused on reducing vector transmission in order to protect the population at risk, it should also be noted that the most prevalent clinical manifestations found were neurological and gastrointestinal, affecting the majority of the child population.(AU)

Antibody fucosylation predicts disease severity in secondary dengue infection.

Although antiviral antibodies generally confer protective functions, antibodies against dengue virus (DENV) are associated with enhanced disease susceptibility. Antibodies can mediate DENV infection of leukocytes via Fcγ receptors, likely contributing to dengue disease pathogenesis. To determine if this mechanism accounts for variable disease severity, we examined Fab and Fc structures of anti-DENV antibodies from patients before and after infection and with variable disease outcomes. Neither antibody titers nor neutralizing activity correlated with disease severity in DENV-infected populations. Rather, DENV infection induced a specific increase in immunoglobulin G1 (IgG1) afucosylation, and the levels of afucosylated IgG1 were predictive of dengue disease severity. Thus, the IgG1 fucosylation status represents a robust prognostic tool for dengue disease, highlighting the key role of the Fc glycan structure in dengue pathogenesis.

Ultrasound in Dengue: A Scoping Review.

To improve dengue triage and treatment decisions, the WHO recommends classifying the disease as dengue with or without warning signs or severe dengue. Vascular leakage is a key component of the pathophysiology of severe dengue and is detectable by ultrasound. The objective of this scoping review is to describe the primary literature on the use of ultrasound in dengue, summarize the findings, and identify knowledge gaps. Our database search retrieved 1,489 records which were reduced to 177 studies following eligibility screening. Descriptive analyses were conducted. Results showed most studies are from South Asia (n = 92, 52%) and assessed hospitalized dengue patients (130, 82%). Radiologists were the most reported ultrasonographers (14, 8%), and conventional ultrasound (39, 68%) was preferred over portable (9, 16%). The most common ultrasound findings in dengue were ascites (107, 60%), pleural effusion (102, 58%), and gallbladder wall thickening (97, 55%). However, the lack of a standard protocol to perform the ultrasound examination in dengue patients hinders conclusions about the frequency of ultrasound findings in dengue. Given the progress of current ultrasound technology, a focused point-of-care ultrasound protocol for early detection of vascular leakage in dengue is needed to generate the evidence required for its implementation in routine care.

Dengue fever after coronary artery bypass grafting with ventricular dysfunction.

A 67-year-old man who had undergone a percutaneous coronary intervention, presented with cardiac symptoms. He was managed for acute coronary syndrome and left ventricular dysfunction. After stabilization, he underwent coronary artery bypass grafting but developed dengue hemorrhagic fever postoperatively. He was monitored for hematocrit, platelet count, liver enzymes, and daily fluid balance. His platelet count fell below 40,000/µL, and due to the increased risk of bleeding, warfarin was discontinued and single antiplatelet therapy (aspirin) was continued. After 2 weeks, parameters had normalized. Regular monitoring of hematocrit, platelet count, liver enzymes, and fluid balance played a vital role in the patient's successful recovery.

Understanding immunopathology of severe dengue: lessons learnt from sepsis.

Endothelial dysfunction leading to vascular permeability and plasma leakage are characteristic features of severe dengue and sepsis. However, the mechanisms underlying these immune-pathologies remain unclear. The risk of severe dengue and sepsis development depend on patient-related and pathogen-related factors. Additionally, comorbidities increase the risk of severe disease and their incidence hampers correct diagnosis and treatments. To date, there is no efficient therapy to combat severe dengue and sepsis. Here, we discuss the differences and similarities between the pathogenesis of severe dengue and that of bacterial sepsis. We identify gaps in knowledge that need to be better understood in order to move towards the rational development and/or usage of therapeutic strategies to ameliorate severe dengue disease.

A favorable outcome of dengue hemorrhagic fever despite poor prognostic indices: a case report with a mix of classic and unusual clinical and laboratory features.

The report describes a 32-year-old man with dengue hemorrhagic fever presenting with acute onset high-grade intermittent fever with chills and rigors, headache, myalgia, abdominal pain, and vomiting. His laboratory results revealed neutrophilia, thrombocytopenia, microscopic hematuria, and a markedly elevated D-dimer. While on admission, he developed diarrhea, hypertension, and respiratory symptoms which evolved into respiratory distress with low oxygen saturation, eventually warranting his admission to the Intensive Care Unit (ICU). Despite his adverse prognostic indices, the patient made an uneventful recovery with conservative management after 16 days of admission. Thus illustrating how aggressive management could influence the outcome of dengue illness.

Clinical Course and Management of Dengue in Children Admitted to Hospital: A 5 Years Prospective Cohort Study in Jakarta, Indonesia.

BACKGROUND: Dengue incidence is rising globally which was estimated 100 million per year, whereas in Indonesia was estimated 7.5 million per year. Dengue clinical course varies from mild dengue fever (DF) to dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Patients, clinicians and care facilities would benefit if reliable predictors can determine at admission which cases with clinically suspected dengue will progress to DHF or DSS. METHODS: From 2009 through 2013, a cohort of 494 children admitted with clinically suspected dengue at a tertiary care hospital in Jakarta, Indonesia, was followed until discharge. We evaluated the clinical course and disease outcome of admitted patients and estimated the burden of dengue cases hospitalized over time. RESULTS: Of all 494 children, 185 (37%) were classified at admission as DF, 158 (32%) as DHF and 151 (31%) as DSS. Of DF patients, 52 (28%) progressed to DHF or DSS, 10 (5%) had other viral diseases. Of DHF patients, 9(6%) progressed to DSS. Of 33 routinely collected parameters at admission, duration of fever ≤4 days was the only significant predictor of disease progression (P = 0.01). Five cases (3%) admitted with DSS died. Between 2009 and 2013, annual dengue admissions declined, while distribution of disease severity remained stable. CONCLUSIONS: Almost a third of children admitted to tertiary care with clinically suspected DF progress to DHF or DSS. Among routinely collected parameters at admission, only fever duration was significantly associated with clinical progression, emphasizing unpredictability of dengue disease course from parameters currently routinely collected.

Upregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in renal tissue in severe dengue in humans: Effects on endothelial activation/dysfunction.

INTRODUCTION: Dengue is an important mosquito-borne disease in tropical and subtropical regions. Adhesion molecules have not been systematically characterized in the renal tissue of patients with severe dengue (SD). The objective of this study was to detect viral antigens in samples from patients that evolved with SD, correlating with the expression of ICAM-1, VCAM-1, VE-cadherin, and E-selectin to contribute to a better understanding of the pathophysiology of SD. METHODS: Kidney specimens from patients with SD were selected according to clinical and laboratorial data and submitted to histological and immunohistochemistry analysis. A semiquantitative evaluation was performed considering positive immunostaining in 20 glomeruli. RESULTS: Viral antigens were mainly detected in distal tubules. The intense immunostaining of VCAM-1 and ICAM-1 was observed. The expression of E-selectin was discrete, and VE-cadherin expression varied from mild to moderate. VCAM-1 was slightly intense in the glomerular capsule; the expression of ICAM-1 was diffuse. E-selectin was diffuse, and VE-cadherin varied from mild to moderate. The most frequent histological findings were glomerular congestion, mild glomerulitis, acute renal injury, and glomerular atrophy. CONCLUSIONS: The results appear to demonstrate an imbalance between vascular endothelial permeability regulating events in renal lesions in SD. The increase in the expression of ICAM-1 and VCAM-1 is an in-situ indicator of higher permeability with a consequent influx of cells favoring the inflammation of the endothelium. These molecules are important in the pathophysiology of the disease and provide the possibility of developing new markers for the evaluation, clinical follow-up, and therapeutic response of patients with SD.

Severe Dengue and Associated Hemophagocytic Lymphohistiocytosis in PICU.

OBJECTIVES: To study the clinico-laboratory profile and outcome of children with severe dengue and dengue-associated hemophagocytic lymphohistiocytosis (HLH). METHODS: In this retrospective study, 22 children with laboratory confirmed severe dengue admitted to pediatric intensive care unit (PICU) were enrolled. Clinical features, laboratory parameters, and outcome were noted and compared between cases fulfilling HLH-2004 criteria and those without HLH. RESULTS: Median (IQR) age was 8 (5-10.3) y. Fever was present for mean (SD) duration of 5.3 (2.1) d. Vomiting, respiratory distress, pain abdomen and hepatomegaly were other clinical features. Thrombocytopenia, anemia and elevated serum transaminases were noted in 91%, 41% and 30% respectively; coagulopathy and hypoalbuminemia were seen in 36% each. Half (n = 11, 50%) had dengue shock syndrome. Acute respiratory distress syndrome (ARDS) (n = 7, 32%) and acute kidney injury (AKI) (n = 6, 28%) were other major organ dysfunctions. Mean (SD) duration of PICU stay was 3.6 (1.5) d with 13.6% mortality. HLH was noted in 7 (32%) cases at a median (IQR) hospital stay of 5 (2-8) d. Children with HLH had significantly higher Pediatric Index of Mortality 2 (PIM 2) score at admission and higher frequency of pain abdomen, anemia, hypoalbuminemia, elevated alanine aminotransferase (ALT) and ARDS. Length of PICU stay (5.1 vs. 2.9 d) and mortality (28.6% vs. 6.7%) were higher in HLH group, however the difference was not statistically significant. Steroids were used in 4 cases with HLH and all survived, whereas among 3 who did not receive steroids, 2 died (p = 0.23). CONCLUSIONS: Severe dengue presents with life-threatening organ dysfunctions. HLH is increasingly recognized in dengue infection and maybe considered as a differential diagnosis in children with lower hemoglobin, hypoalbuminemia, elevated ALT and severe organ dysfunction.

Plasma cell-free DNA: a potential biomarker for early prediction of severe dengue.

BACKGROUND: Considerable progress has been made in dengue management, however the lack of appropriate predictors of severity has led to huge number of unwanted admissions mostly decided on the grounds of warning signs. Apoptosis related mediators, among others, are known to correlate with severe dengue (SD) although no predictive validity is established. The objective of this study was to investigate the association of plasma cell-free DNA (cfDNA) with SD, and evaluate its prognostic value in SD prediction at acute phase. METHODS: This was a hospital-based prospective cohort study conducted in Vietnam. All the recruited patients were required to be admitted to the hospital and were strictly monitored for various laboratory and clinical parameters (including progression to SD) until discharged. Plasma samples collected during acute phase (6-48 h before defervescence) were used to estimate the level of cfDNA. RESULTS: Of the 61 dengue patients, SD patients (n = 8) developed shock syndrome in 4.8 days (95% CI 3.7-5.4) after the fever onset. Plasma cfDNA levels before the defervescence of SD patients were significantly higher than the non-SD group (p = 0.0493). From the receiver operating characteristic (ROC) curve analysis, a cut-off of > 36.9 ng/mL was able to predict SD with a good sensitivity (87.5%), specificity (54.7%), and area under the curve (AUC) (0.72, 95% CI 0.55-0.88; p = 0.0493). CONCLUSIONS: Taken together, these findings suggest that cfDNA could serve as a potential prognostic biomarker of SD. Studies with cfDNA kinetics and its combination with other biomarkers and clinical parameters would further improve the diagnostic ability for SD.

Clinical Indicators of Fatal Dengue in Two Endemic Areas of Colombia: A Hospital-Based Case-Control Study.

According to the World Health Organization, 98% of fatal dengue cases can be prevented; however, endemic countries such as Colombia have recorded higher case fatality rates during recent epidemics. We aimed to identify the predictors of mortality that allow risk stratification and timely intervention in patients with dengue. We conducted a hospital-based, case-control (1:2) study in two endemic areas of Colombia (2009-2015). Fatal cases were defined as having either 1) positive serological test (IgM or NS1), 2) positive virological test (RT-PCR or viral isolation), or 3) autopsy findings compatible with death from dengue. Controls (matched by state and year) were hospitalized nonfatal patients and had a positive serological or virological dengue test. Exposure data were extracted from medical records by trained staff. We used conditional logistic regression (adjusting for age, gender, disease's duration, and health-care provider) in the context of multiple imputation to estimate exposure to case-control associations. We evaluated 110 cases and 217 controls (mean age: 35.0 versus 18.9; disease's duration pre-admission: 4.9 versus 5.0 days). In multivariable analysis, retro-ocular pain (odds ratios [OR] = 0.23), nausea (OR = 0.29), and diarrhea (OR = 0.19) were less prevalent among fatal than nonfatal cases, whereas increased age (OR = 2.46 per 10 years), respiratory distress (OR = 16.3), impaired consciousness (OR = 15.9), jaundice (OR = 32.2), and increased heart rate (OR = 2.01 per 10 beats per minute) increased the likelihood of death (AUC: 0.97, 95% confidence interval: 0.96, 0.99). These results provide evidence that features of severe dengue are associated with higher mortality, which strengthens the recommendations related to triaging patients in dengue-endemic areas.

Upregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in renal tissue in severe dengue in humans: Effects on endothelial activation/dysfunction

Abstract INTRODUCTION: Dengue is an important mosquito-borne disease in tropical and subtropical regions. Adhesion molecules have not been systematically characterized in the renal tissue of patients with severe dengue (SD). The objective of this study was to detect viral antigens in samples from patients that evolved with SD, correlating with the expression of ICAM-1, VCAM-1, VE-cadherin, and E-selectin to contribute to a better understanding of the pathophysiology of SD. METHODS: Kidney specimens from patients with SD were selected according to clinical and laboratorial data and submitted to histological and immunohistochemistry analysis. A semiquantitative evaluation was performed considering positive immunostaining in 20 glomeruli. RESULTS: Viral antigens were mainly detected in distal tubules. The intense immunostaining of VCAM-1 and ICAM-1 was observed. The expression of E-selectin was discrete, and VE-cadherin expression varied from mild to moderate. VCAM-1 was slightly intense in the glomerular capsule; the expression of ICAM-1 was diffuse. E-selectin was diffuse, and VE-cadherin varied from mild to moderate. The most frequent histological findings were glomerular congestion, mild glomerulitis, acute renal injury, and glomerular atrophy. CONCLUSIONS: The results appear to demonstrate an imbalance between vascular endothelial permeability regulating events in renal lesions in SD. The increase in the expression of ICAM-1 and VCAM-1 is an in-situ indicator of higher permeability with a consequent influx of cells favoring the inflammation of the endothelium. These molecules are important in the pathophysiology of the disease and provide the possibility of developing new markers for the evaluation, clinical follow-up, and therapeutic response of patients with SD.

The reintroduction of DENV-2 in 2011 in Panama and subsequent outbreak characteristic.

The circulation of the South-east Asian/American (AS/AM) dengue 2 virus (DENV-2) genotype in the Americas has been associated with a high rate of severe disease. From 1993, the year DENV was reintroduced in Panama, until 2011 there were 29 dengue-associated deaths, 17 of which occurred in 2011, the most severe outbreak with a case fatality rate (CFR) of 44% (17 deaths out of 38 severe dengue cases). During this outbreak DENV-2 was reintroduced into the country, whereas over the prior five years DENV-1 and -3 were predominant. Herein, we describe the 2011 Panama outbreak and genetically characterize the Panamanian DENV-2 strains, which were associated with severe dengue disease in Panama. Our results suggest that the DENV-2 isolates from this outbreak belonged to the AS/AM genotype sub-clade 2BI and were genetically close to viruses described in the outbreaks in Nicaragua, Honduras, Guatemala and Mexico from 2006-2011. Sub-clade 2BI has previously been associated with severe disease in Nicaragua during outbreaks from 2005-2007.

Analyses of clinical and laboratory characteristics of dengue adults at their hospital presentations based on the World Health Organization clinical-phase framework: Emphasizing risk of severe dengue in the elderly.

BACKGROUND/PURPOSE: Dengue clinically dynamically changes over time; the World Health Organization (WHO) dengue classification framework proposed 3 dengue clinical phases-febrile (days 1-3), critical (days 4-6) and recovery (days ≥7) phases. This study aimed to better understand clinical and laboratory characteristics in adults (≥18 years) suffering dengue in different clinical phases at their hospital presentations. METHODS: A retrospective analysis of adults suffering dengue between 2008 and 2014. RESULTS: Of the 669 included dengue adults, 146 (21.8%) were elderly (≥65 years), and 27 (4%) suffered severe dengue. When compared with those in febrile phase, significantly higher incidence of ascites, mucosal bleeding, and/or gastrointestinal bleeding; lower white blood cell (WBC) and platelet counts; higher hematocrit, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values were found in critical phase. When compared with their younger counterparts, elderly at febrile phase had significantly lower frequencies of bone pain, myalgia, headache and rash; higher frequencies of vomiting, pleural effusion and mucosal bleeding; higher WBC count, AST and ALT levels, and lower platelet count; in critical phase, elderly had significantly higher frequencies of pleural effusion, mucosal bleeding and gum bleeding. Four (0.6%) patients experienced severe dengue in recovery phase. Significantly higher proportions of elderly developed severe dengue in both febrile and critical phases as compared with younger adults. CONCLUSIONS: Elderly had lower frequency of classical dengue symptoms, yet were at higher risk of development of severe dengue during their early dengue course. A small number of patients developed severe dengue at the WHO-proposed recovery phase.

Clinical, laboratory, and demographic determinants of hospitalization due to dengue in 7613 patients: A retrospective study based on hierarchical models.

In Brazil, the incidence of hospitalization due to dengue, as an indicator of severity, has drastically increased since 1998. The objective of our study was to identify risk factors associated with subsequent hospitalization related to dengue. We analyzed 7613 dengue confirmed via serology (ELISA), non-structural protein 1, or polymerase chain reaction amplification. We used a hierarchical framework to generate a multivariate logistic regression based on a variety of risk variables. This was followed by multiple statistical analyses to assess hierarchical model accuracy, variance, goodness of fit, and whether or not this model reliably represented the population. The final model, which included age, sex, ethnicity, previous dengue infection, hemorrhagic manifestations, plasma leakage, and organ failure, showed that all measured parameters, with the exception of previous dengue, were statistically significant. The presence of organ failure was associated with the highest risk of subsequent dengue hospitalization (OR=5·75; CI=3·53-9·37). Therefore, plasma leakage and organ failure were the main indicators of hospitalization due to dengue, although other variables of minor importance should also be considered to refer dengue patients to hospital treatment, which may lead to a reduction in avoidable deaths as well as costs related to dengue.

Chymase Level Is a Predictive Biomarker of Dengue Hemorrhagic Fever in Pediatric and Adult Patients.

Background: Most patients with dengue experience mild disease, dengue fever (DF), while few develop the life-threatening diseases dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). No laboratory tests predict DHF or DSS. We evaluated whether the serum chymase level can predict DHF or DSS in adult and pediatric patients and the influence of preexisting conditions (PECs) on chymase levels. Methods: Serum chymase levels were measured in patients presenting with undifferentiated fever to hospitals in Colombo District, Sri Lanka. The value of serum the chymase concentration and clinical signs and symptoms as predictors of DHF and/or DSS was evaluated by multivariate analysis. We assessed the influence of age, PECs, and day after fever onset on the robustness of the chymase level as a biomarker for DHF and/or DSS. Results: An elevated chymase level in acute phase blood samples was highly indicative of later diagnosis of DHF or DSS for pediatric and adult patients with dengue. No recorded PECs prevented an increase in the chymase level during DHF. However, certain PECs (obesity and cardiac or lung-associated diseases) resulted in a concomitant increase in chymase levels among adult patients with DHF. Conclusions: These results show that patients with acute dengue who present with high levels of serum chymase consistently are at greater risk of DHF. The chymase level is a robust prognostic biomarker of severe dengue for adult and pediatric patients.

Dengue Virus Serotypes 1 and 2 Responsible for Major Dengue Outbreaks in Nepal: Clinical, Laboratory, and Epidemiological Features.

Dengue virus (DENV) is expanding toward previously nonendemic areas. DENV has recently been introduced in Nepal with limited information. We report the clinical features and serotype distribution of DENV in Nepal during the 2010 outbreaks. A total of 1,215 clinical dengue cases at two major hospitals of central and western Nepal were investigated. Demographic, clinical, and laboratory parameters were recorded. Serum specimens were tested for DENV by IgM/IgG enzyme-linked immunosorbent assays (ELISAs) and reverse transcription polymerase chain reaction (RT-PCR). We confirmed DENV infection in 403 (33%) patients from 12 districts with an estimated case fatality rate of 1.5%. DENV infection was more common in adults (87%) and urban settings (74%). We detected all four serotypes but DENV-1 and -2 were mainly responsible for major outbreaks (92%). Overall, 60% of all DENV infections were secondary and 17% were severe dengue; both being more frequent among the DENV-2 infections. Rash, bleeding, abdominal pain, hepatomegaly, elevated liver enzymes, and thrombocytopenia were significantly more common in severe dengue compared with nonsevere infections. We also confirmed the expansion of dengue to hill urban areas (DENV-1 and -2), including the capital Kathmandu (altitude, 1,300 m) though > 90% cases were from southern plains. Differential clinical and laboratory features probably help in clinical decisions. Multiple serotypes circulation and elevated secondary infections pose potential risk of severe outbreaks and deaths in the future. Therefore, a country with recent dengue introduction, like Nepal, urgently requires a systematic surveillance and appropriate control measures in place to respond to any disastrous outbreaks.

[Dengue with unusual clinical features in an infant: Case report]. / Dengue, presentación inusual en un lactante: Reporte de un caso.

The state of Yucatan, in Mexico, is an endemic area for dengue. During 2015, there was an unpredicted increase in the number of expected cases of dengue fever. OBJECTIVE: To describe and analyse the clinical presentation, progress, and management of a case of dengue infection with non-specific clinical manifestations in an infant which resulted in a dengue shock syndrome. CASE REPORT: One month old infant admitted to hospital with a generalised rash and a history of being bitten by an insect. He was diagnosed with anaphylaxis based on clinical manifestations and anamnesis. While in hospital, he developed hypotension, tachycardia, anaemia, and respiratory distress. He was transferred to the intensive care unit, but died on the fifth day. He tested positive to dengue virus in the PCR test and for IgG antibodies using Elisa. The basic cause of death was dengue shock syndrome. CONCLUSIONS: Dengue fever in young infant infections may be afebrile, so it is important to suspect them appropriately in the presence of a generalised rash, tachycardia, and hypotension, in order to avoid the deadly consequences of dengue shock.