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.

Spontaneous Intracranial Hemorrhage and Acute Respiratory Distress Syndrome Associated with Dengue: A Case Report.

BACKGROUND: Dengue is a major health burden worldwide, notably in tropical and subtropical countries, with symptoms ranging from asymptomatic infection to severe hemorrhagic or shock syndrome. The clinical and biochemical profile of dengue has been shown in the literature to be expanding as more atypical signs have been added over the past few decades. Most dengue-related symptoms are typically mild to moderate and self-limited. However, intracranial hemorrhage and acute respiratory distress syndrome in severe dengue is an event that has been encountered uncommonly. CASE PRESENTATION: A 30-year-old female presented with complaints of fever, headache, cough, and altered sensorium. Later, she was diagnosed with severe dengue fever complicated by dengue hemorrhagic fever, which manifested as subarachnoid and subdural bleeding and acute respiratory distress syndrome. She was managed conservatively with a positive outcome. CONCLUSION: Atypical manifestation, though rare, should be kept in mind while dealing with severe dengue patients, as early detection based on anticipated risk factors and timely treatment have the potential to save lives.

Assessment of the importance of platelet transfusion in patients with severe dengue: a systematic review / Evaluación de la importancia de la transfusión de plaquetas en pacientes con dengue grave: una revisión sistemática

Introduction: Dengue is one of the most important vector-borne viral diseases in subtropical and tropical regions. The World Health Organization (WHO) 2009 classified dengue into three groups: dengue without alarm signs, dengue with alarm signs, and severe dengue. According to the type of dengue, various managements have been proposed. The authors suggest that a predictive factor to avoid a poor prognosis in this disease is to keep platelet levels stable in the patient to prevent a fatal outcome. The aim of this paper is to analyze the efficacy of transfusion of platelet agents in the outcome of patients with severe dengue and thrombocytopenia. Material and methods: A bibliographic search was carried out in the Medline, OVID, and Scielo databases from January 1, 2008, to April 31, 2023, using the MeSH terms. Results: 7 articles were included in the systematic review. A wide range in age was found (18 to 79 years). A minimal number of studies detail the comorbidities of patients in their enrollment. Regarding platelet transfusion, the average number of platelet units used in the transfusion case was 5 (2 - 14). Transfusions of ABO identical and compatible pooled platelets transfusion were found to be more successful in increasing platelets. Almost all of the patients included in the studies had platelets <20,000 at enrollment. One study found a significant increase in platelets after transfusion, while the rest did not find it compelling. No mortality associated with platelet transfusion was recorded. Conclusions: Prophylactic platelet transfusion is not recommended as a routine measure in patients with severe dengue and thrombocytopenia. The uncertainty highlights need to reach a specific consensus establishing the appropriate indications for platelet transfusion and what type of patients with dengue virus would be beneficial. (AU)

Introducción: El dengue es una de las enfermedades virales transmitidas por vectores más importantes en las regiones tropicales y subtropicales. La Organización Mundial de la Salud (OMS) en 2009 clasificó el dengue en tres grupos: dengue sin signos de alarma, dengue con signos de alarma y dengue grave. Según el tipo de dengue se han propuesto diversos manejos. Los autores sugieren que un factor predictivo para evitar un mal pronóstico en esta enfermedad es mantener estables los niveles de plaquetas en el paciente para evitar un desenlace fatal. El objetivo de este trabajo es analizar la eficacia de la transfusión de plaquetas en la evolución de pacientes con dengue grave y trombocitopenia. Material y métodos: Se realizó una búsqueda bibliográfica en las bases de datos Medline, OVID y Scielo desde el 1 de enero de 2008 al 31 de abril de 2023, utilizando los términos MeSH. Resultados: Se incluyeron 7 artículos en la revisión sistemática. Se encontró un amplio rango de edad (18 a 79 años). Un número mínimo de estudios detallan las comorbilidades de los pacientes en su inscripción. En cuanto a la transfusión de plaquetas, el promedio de unidades de plaquetas utilizadas en el caso de transfusión fue de 5 (2 - 14). Se encontró que las transfusiones de plaquetas combinadas ABO idénticas y compatibles tuvieron más éxito en el aumento de plaquetas. Casi todos los pacientes incluidos en los estudios tenían plaquetas <20 000 en el momento del reclutamiento. Un estudio encontró un aumento significativo de plaquetas después de la transfusión, mientras que el resto no lo encontró convincente. No se registró mortalidad asociada con la transfusión de plaquetas. Conclusiones: La transfusión profiláctica de plaquetas no se recomienda como medida de rutina en pacientes con dengue grave y trombocitopenia. ... (AU)

Associations of obesity and dengue-associated mortality, acute liver failure and mechanical ventilation in children with dengue shock syndrome.

Dengue-associated complications, including dengue shock syndrome, severe respiratory distress, and pediatric acute liver failure (PALF), are associated with high mortality rates in patients with dengue. There is increasing prevalence of overweight and obesity among children worldwide. Obesity may activate inflammatory mediators, leading to increased capillary permeability and plasma leakage in patients with dengue. Several studies have shown a correlation between obesity and DSS, but did not include dengue fatality or PALF. Therefore, we hypothesized possible associations between obesity and critical dengue-associated clinical outcomes among PICU-admitted children with DSS, including dengue-related mortality, mechanical ventilation (MV) requirements, and dengue-associated PALF. The nutritional status of the participants was assessed using World Health Organization growth charts. A total of 858 participants with complete nutritional data were enrolled in this study. Obesity was significantly associated with risk of severe respiratory failure and MV support (odds ratio = 2.3, 95% CI: 1.31-4.06, P < .01); however, it was not associated with dengue-associated mortality or acute liver failure. Obese pediatric patients with DSS should be closely monitored for severe respiratory distress and the need for high-flow oxygenation support, particularly MV, soon after hospitalization.

Dengue hepatitis: Incidence, spectrum and outcome.

BACKGROUND AND AIMS: While dengue infection is common in India, there is scarce information on dengue hepatitis. The aim of this study was to analyze the incidence, spectrum and outcome of dengue hepatitis. METHODS: We retrospectively analyzed consecutive patients, who had hepatitis among those with dengue infection admitted to two tertiary care hospitals in western India from January 2016 to March 2021. Diagnosis of dengue infection was made by serology. Dengue hepatitis was diagnosed and the severity of dengue was categorized by standard criteria. RESULTS: Of 1664 patients admitted with dengue fever during the study period, 199 patients had hepatitis (i.e. incidence of dengue hepatitis was 11.9%). Of the 199 dengue hepatitis patients (age: 29 [13 - 80] years, median [range], 67% males), 100 patients (50%) had severe dengue, 73 (36%) had severe dengue hepatitis, 32 (16%) had dengue shock syndrome and eight (4%) had acute liver failure. Forty-five patients (23%) had acute lung injury and 32 (16%) had acute kidney injury. The dengue hepatitis patients were treated with standard medical care, including vital organ support, as needed-166 (83%) patients survived, while 33 patients (17%) died (cause of death: multi-organ failure: 24 patients, septic shock: nine patients). The presence of shock independently predicted mortality (odds ratio 6.4, 95% confidence interval: 1.2 - 34). Among patients with dengue hepatitis, mortality rate was higher in those with severe dengue (23%), dengue shock syndrome (47%), severe dengue hepatitis (24%) and acute liver failure (38%). CONCLUSION: In this large series of hospitalized patients with dengue infection, the incidence of dengue hepatitis was 11.9%. Among 199 dengue hepatitis, 17% died; multi-organ failure was the commonest cause for death and death rate was higher in patients with more severe disease. The presence of shock at presentation independently predicted mortality.

Dengue hemorrhagic fever with bleeding and fluid overload in a patient with active lupus nephritis: a case report of diagnostic and therapeutic challenges.

BACKGROUND: Diagnosis and management of dengue hemorrhagic fever (DHF) can be challenging in the presence of confounding comorbidities. Important confounders are conditions that alter hematological parameters and intra/extra vascular fluid distribution. We report the case of a patient with active lupus nephritis, who developed DHF with subsequent bleeding and fluid overload. This is the first case report to highlight a unique set of diagnostic and therapeutic challenges in DHF in this context. CASE PRESENTATION: A seventeen-year-old girl with lupus nephritis class IV developed a renal flare of lupus and subsequently developed DHF with bleeding per vaginum. Due to acute kidney injury, she was managed with a restrictive fluid approach during the ascending limb with blood transfusion when required, and close monitoring for hemodynamic instability. During the descending limb, hourly input was transiently increased due to a rise in hematocrit. This precipitated nephrogenic pulmonary edema, which was managed with mechanical ventilation and continuous renal replacement therapy. CONCLUSIONS: This patient posed two diagnostic challenges: diagnosis of dengue in a patient with lupus-related bicytopenia, and diagnosis of dengue leakage in a patient with nephrotic syndrome-related ascites. There were three therapeutic difficulties: deciding the fluid quota for DHF in the presence of renal impairment, and balancing the risks and benefits of steroids and anticoagulation in lupus nephritis with dengue. As decisions in such instances are patient-specific, sharing of individual experiences will help guide management decisions.

Spontaneous splenic rupture during dengue fever.

Dengue fever is one of the most frequent arboviral diseases in the world. Dengue is known to cause myocarditis, hepatitis, and neurological illustrations but one of the established presentations is leakage of plasma resulting in circulatory failure. Spontaneous rupture of the spleen is one of the most infrequent but known outcome of dengue fever which has been reported from time to time in literature. We present, here, the case of a 50-year-old patient who developed this condition during dengue fever and was managed in our department successfully. This complication must be kept in mind while treating any case of dengue fever so that it can be avoided or if not then treated timely.

Clinical Profile of Pediatric Cases of Dengue during the 2019 Epidemic in Bangladesh: A Multicenter Cross-Sectional Study.

Bangladesh experienced the largest dengue epidemic during 2019, with more than 100,000 confirmed cases and 164 deaths. Almost one-third of these cases were children. The present study aimed to investigate the clinical and hematological manifestations of pediatric dengue cases during the epidemic. This was a multicenter cross-sectional study conducted in Dhaka Medical College Hospital, Dhaka, Dr. Sirajul Islam Medical College Hospital and Tangail Sadar Hospital, Tangail, Bangladesh between the period of June 2019 and September 2019. The study included 208 pediatric patients (age <18 years) with confirmed dengue fever. Patient's demographics, clinical and laboratory features of dengue were collected through patients' interview, clinical examination and laboratory investigations. Descriptive statistics were used to represent the patients' socio-demographic information, clinical presentations and hematological parameters. The majority of the patients were aged between 6 and 17 years with male predominance. The most commonly presented clinical manifestations were fever (100.0%), headache (59.0%), myalgia (42.0%), rash (36.0%), retro-orbital pain (28.0%) and diarrhea (24.0%). Warning signs abdominal pain (40.0%) and persistent vomiting (29.0%), bleeding manifestations such as melena (17.0%), gum bleeding (7.0%) and epistaxis (6.0%) and evidence of plasma leakage such as oliguria (3.4%), ascites (2.4%), pleural effusion (1.4%), and shock (1.0%) were also present in the patients. Raised HCT levels, leucopenia and thrombocytopenia were present in almost 23.0%, 43.0% and 28.0% of children, respectively. Warning signs and plasma leakage were present in a substantial number of patients indicating potential risk of severe dengue. Prompt diagnosis and management based on best clinical judgment might prevent severe dengue at an early stage.

Blood transfusion in severe dengue infection: a case series.

BACKGROUND: Dengue is still a recurrent challenge to the global population, without specific antiviral therapy. Clinical management strategies are aimed to mitigate the deaths. The use of blood products in dengue is recommended mainly in cases of bleeding. CASE PRESENTATION: We prospectively collected data on Sri Lankan dengue cases in the Teaching Hospital, Peradeniya, Sri Lanka from 2017, and selected ten severe cases where blood transfusions were involved in the management. The series comprises seven females and three males, with a median age of 36 years (range 12-53 years). All patients were critically ill at the time of blood transfusion, with dramatic stabilization of vital parameters after the transfusions. Only one patient had detectable bleeding, while five patients had occult blood loss as indicated by dropping hematocrit. Even though four patients had stable hematocrit, they had metabolic acidosis. Two patients had a very high increase of hepatic transaminases along with acidosis. Two patients had myocarditis with dropping hematocrit, suggestive of occult bleeding. CONCLUSIONS: Clinical deterioration despite fluid management commonly occurs due to occult bleeding in dengue infection. Blood transfusion is lifesaving in such cases of blood loss, acidosis, and severe hepatic damage. The mechanism of this effect needs an explanation, such as enhanced oxygen delivery to the tissues and hemostasis to hypothesize a few possibilities.

Management of Dengue: An Updated Review.

Dengue is an important public health problem with a wide clinical spectrum. The World Health Organization classifies dengue into probable dengue, dengue with warning signs, and severe dengue. Severe dengue, characterized by plasma leakage, severe bleeding, or organ impairment, entails significant morbidity and mortality if not treated timely. There are no definitive curative medications for dengue; management is supportive. Judicious fluid resuscitation during the critical phase of dengue is the cornerstone of management. Crystalloids are the initial fluid of choice. Prophylactic platelet transfusion is not recommended. Organ involvement in severe dengue should be carefully looked for and managed. Secondary hemophagocytic lymphohistiocytosis is a potentially fatal complication of dengue that needs to be recognized, as specific management with steroids or intravenous immunoglobulin may improve outcomes. Several compounds with anti-dengue potential are being studied; no anti-dengue drug is available so far.

Fluid management in children with severe dengue: a narrative review.

Dengue is a mosquito-borne arboviral infection of increasing public health importance. Globally, children account for a significant proportion of infections. No pathogen-specific treatment currently exists, and the current approach to reducing disease burden is focused on preventative strategies such as vector control, epidemiological interventions, and vaccination in selected populations. Once infected, the mainstay of treatment is supportive, of which appropriate fluid management is a cornerstone. The timely provision of fluid boluses has historically been central to the management of septic shock. However, in patients with dengue shock, particular emphasis is placed on judicious fluid administration. Certain colloids such as hydroxyethyl starches and dextran, despite no longer being used routinely in intensive care units due to concerns of acute kidney injury and impairment of coagulation, are still commonly used in dengue shock syndrome. Current guidelines recommend initial crystalloid therapy, with consideration of colloids for severe or recalcitrant shock in patients with dengue. In this review, we discuss the pathophysiology of septic shock, and consider whether any differences in dengue exist that may warrant a separate approach to fluid therapy. We critically review the available evidence for fluid management in dengue, including the role of colloids. In dengue, there is increasing recognition of the importance of tailoring fluid therapy to phases of disease, with attention to the need for fluid "deresuscitation" once the critical phase of vascular leak passes.

A rare case of acute liver failure with intrahepatic cholestasis due to dengue hemorrhagic fever: CytoSorb® and plasma exchange aided in the recovery: case report.

BACKGROUND: Dengue haemorrhagic fever is a severe form of acute dengue infection characterized by leakage of plasma through capillaries into body spaces resulting in circulatory insufficiency leading to shock. Despite varying degrees of liver involvement occurring in acute dengue infection, intrahepatic cholestasis is very rare in the literature with only two cases reported so far. We report a challenging case of a middle-aged woman with DHF complicated by acute liver failure, coagulopathy, acute renal failure and prolonged intrahepatic cholestasis. She was successfully managed in the intensive care unit with supportive therapy, Cytosorb® and therapeutic plasma exchange. CASE PRESENTATION: A 54-year-old Sri Lankan obese woman with multiple comorbidities presented with fever, headache, vomiting and generalized malaise for 3 days and was diagnosed with dengue haemorrhagic fever. Despite the standard dengue management, she clinically deteriorated due to development of complications such as, acute liver injury, intrahepatic cholestasis and acute renal injury. Acute liver failure was evidenced by transaminitis, lactic acidosis, coagulopathy with pervaginal bleeding and severe encephalopathy necessitating elective intubation and mechanical ventilation. She was immediately transferred to intensive care facilities where she underwent supportive management for liver failure, continuous renal replacement therapy coupled with cytosorb and therapeutic plasma exchange with which she made a remarkable recovery. CONCLUSION: Acute liver failure with a prolonged phase of intrahepatic cholestasis is a very rare complication of acute dengue illness which is sparsely documented in medical literature so far. This patient was managed successfully with supportive therapy, aided by cytoSorb hemo-adsorption and therapeutic plasma exchange.

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

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

Fluid requirement in adult dengue haemorrhagic fever patients during the critical phase of the illness: an observational study.

BACKGROUND: Dengue fever prevalence is rising globally and it causes significant morbidity and mortality. Fluid extravasation during the critical phase of dengue haemorrhagic fever (DHF) leads to shock, multi-organ failure and death if not resuscitated appropriately with fluids. The mainstay of management is judicious fluid replacement using a guideline based, calculated fluid quota of maintenance (M) fluid plus 5% deficit (M +  5% deficit) to prevent organ hypoperfusion. METHODS: We conducted an observational follow-up study in Sri Lanka from January-July 2017 to identify the fluid requirements of DHF patients and to identify whether features of fluid overload are present in patients who exceeded the fluid quota. Patients who developed DHF following admission to the place of study, were recruited and the amount of fluid received during the critical phase was documented. RESULTS: A total of 115 DHF patients with a mean age of 30.3 (SD 12.2) years were recruited to the study. There were 65 (56.5%) males and the mean fluid requirement was 5279.7 ml (SD 735) over the 48 h. Majority of the study participants (n = 80, 69.6%) received fluid in excess of the recommended maintenance + 5% deficit and this group had higher body mass index (22.75 vs 20.76, p0.03) and a lower white cell count at the onset of the critical phase (3.22 × 103 vs 4.78 × 103, p < 0.001). The highest fluid requirement was seen within the first 12 and 24 h of the critical phase in patients requiring fluid M +  5%-7.5% deficit and ≥ M +  7.5% deficit respectively. Patients exceeding M + 5% deficit had narrow pulse pressure and hypotension compared to the rest. DHF grades III and IV were seen exclusively in patients exceeding the fluid quota indicating higher amount of fluid was given for resuscitation. Fluid overload was detected in 14 (12.1%) patients and diuretic therapy was required in 6 (5.2%) patients. CONCLUSIONS: The majority of patients received fluid in excess of the recommended quota and this group represents patients with narrow pulse pressure and hypotension. Although, fluid overload was infrequent in the study population, clinicians should be cautious when administering fluid in excess of M +  7.5% deficit.

Risk predictors of progression to severe disease during the febrile phase of dengue: a systematic review and meta-analysis.

BACKGROUND: The ability to accurately predict early progression of dengue to severe disease is crucial for patient triage and clinical management. Previous systematic reviews and meta-analyses have found significant heterogeneity in predictors of severe disease due to large variation in these factors during the time course of the illness. We aimed to identify factors associated with progression to severe dengue disease that are detectable specifically in the febrile phase. METHODS: We did a systematic review and meta-analysis to identify predictors identifiable during the febrile phase associated with progression to severe disease defined according to WHO criteria. Eight medical databases were searched for studies published from Jan 1, 1997, to Jan 31, 2020. Original clinical studies in English assessing the association of factors detected during the febrile phase with progression to severe dengue were selected and assessed by three reviewers, with discrepancies resolved by consensus. Meta-analyses were done using random-effects models to estimate pooled effect sizes. Only predictors reported in at least four studies were included in the meta-analyses. Heterogeneity was assessed using the Cochrane Q and I2 statistics, and publication bias was assessed by Egger's test. We did subgroup analyses of studies with children and adults. The study is registered with PROSPERO, CRD42018093363. FINDINGS: Of 6643 studies identified, 150 articles were included in the systematic review, and 122 articles comprising 25 potential predictors were included in the meta-analyses. Female patients had a higher risk of severe dengue than male patients in the main analysis (2674 [16·2%] of 16 481 vs 3052 [10·5%] of 29 142; odds ratio [OR] 1·13 [95% CI 1·01-1·26) but not in the subgroup analysis of studies with children. Pre-existing comorbidities associated with severe disease were diabetes (135 [31·3%] of 431 with vs 868 [16·0%] of 5421 without; crude OR 4·38 [2·58-7·43]), hypertension (240 [35·0%] of 685 vs 763 [20·6%] of 3695; 2·19 [1·36-3·53]), renal disease (44 [45·8%] of 96 vs 271 [16·0%] of 1690; 4·67 [2·21-9·88]), and cardiovascular disease (nine [23·1%] of 39 vs 155 [8·6%] of 1793; 2·79 [1·04-7·50]). Clinical features during the febrile phase associated with progression to severe disease were vomiting (329 [13·5%] of 2432 with vs 258 [6·8%] of 3797 without; 2·25 [1·87-2·71]), abdominal pain and tenderness (321 [17·7%] of 1814 vs 435 [8·1%] of 5357; 1·92 [1·35-2·74]), spontaneous or mucosal bleeding (147 [17·9%] of 822 vs 676 [10·8%] of 6235; 1·57 [1·13-2·19]), and the presence of clinical fluid accumulation (40 [42·1%] of 95 vs 212 [14·9%] of 1425; 4·61 [2·29-9·26]). During the first 4 days of illness, platelet count was lower (standardised mean difference -0·34 [95% CI -0·54 to -0·15]), serum albumin was lower (-0·5 [-0·86 to -0·15]), and aminotransferase concentrations were higher (aspartate aminotransferase [AST] 1·06 [0·54 to 1·57] and alanine aminotransferase [ALT] 0·73 [0·36 to 1·09]) among individuals who progressed to severe disease. Dengue virus serotype 2 was associated with severe disease in children. Secondary infections (vs primary infections) were also associated with severe disease (1682 [11·8%] of 14 252 with vs 507 [5·2%] of 9660 without; OR 2·26 [95% CI 1·65-3·09]). Although the included studies had a moderate to high risk of bias in terms of study confounding, the risk of bias was low to moderate in other domains. Heterogeneity of the pooled results varied from low to high on different factors. INTERPRETATION: This analysis supports monitoring of the warning signs described in the 2009 WHO guidelines on dengue. In addition, testing for infecting serotype and monitoring platelet count and serum albumin, AST, and ALT concentrations during the febrile phase of illness could improve the early prediction of severe dengue. FUNDING: Wellcome Trust, National Institute for Health Research, Collaborative Project to Increase Production of Rural Doctors, and Royal Thai Government.

Case Report: Severe COVID-19 and Dengue in an Indonesian Infant.

We report a case of a 10-month infant with dual severe infection of COVID-19 and dengue fever who was admitted to the hospital with an influenza-like illness. The patient experienced severe conditions of COVID-19 and dengue fever with shock followed by disseminated intravascular coagulation. The standard of COVID-19 care was given coupled with fluid resuscitation and blood transfusion. The pitfalls of this case are how to differentiate the clinical manifestation of dengue fever in a patient with confirmed COVID-19; the difficulty to monitor the dengue course of illness of the patient in the COVID-19 isolation room; and to differentiate the severe dengue from the multisystem inflammatory syndrome-C when the patient was in critical condition. The infant recovered without sequale, but the management of new probable cases must be improved more thoroughly, especially during dengue peak period in tropical and developing countries such as Indonesia.

Severe ocular and adnexal complications in dengue hemorrhagic fever: A report of 29 eyes.

Purpose: To describe a series of sight-threatening ocular and adnexal involvement associated with dengue hemorrhagic fever and their treatment options. Methods: Retrospective, interventional, non-comparative case series. Medical records of patients who presented with ocular symptoms attributed to dengue hemorrhagic fever were reviewed. Demography, presenting features, and treatment outcomes were recorded. Outcome measures assessed included globe salvage, vision salvage, and visual improvement. The outcome was deemed as favorable if vision salvage was possible and unfavorable if the vision was lost. Results: Twenty-nine eyes of 23 patients were included. Bilateral ocular involvement was seen in 6 (26%) patients. The mean age was 37.62 ± 18.68 years (range: 14 to 81 years). Coexistent diabetes mellitus and enteric fever were present in three patients. History of blood transfusion was present in nine (40%) and thrombocytopenia in eight (35%) patients at the time of presentation with ocular complaints. Presenting features included endophthalmitis in 11 (38%), panophthalmitis in 10 (35%), orbital cellulitis with panophthalmitis in four (14%), isolated corneal or scleral melt in three (10%), and orbital hemorrhage with panophthalmitis in one (3%) patient. Globe salvage was achieved in 21/29 eyes (72.4%), vision salvage in 6/29 eyes (20.68%), and improvement in visual acuity was noted in 5/29 eyes (17.24%). Logistic regression analysis revealed no significant effect of any clinical-microbiological factors on globe salvage, vision salvage, and visual improvement. However, visual improvement and globe salvage were possible in eyes that underwent early endoscopic vitrectomy. Conclusion: Dengue fever can present with sight-threatening ocular and adnexal inflammation resulting in endophthalmitis and panophthalmitis, orbital cellulitis, corneal and scleral melt, and orbital hemorrhage. Early vitrectomy may improve vision and globe salvage in cases with significant vitritis.

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.

A case report of dengue hemorrhagic fever complicated with diabetic ketoacidosis in a child: challenges in clinical management.

BACKGROUND: Diabetic ketoacidosis (DKA) is a common presentation of type 1 diabetes mellitus (T1DM) precipitated by various bacterial and viral infections. Dengue infection is no exception for this and can be a precipitating factor for DKA. The presentation of DKA with dengue haemorrhagic fever (DHF) has been reported in adults. However, it is very rarely observed in children. CASE PRESENTATION: We present the case of a paediatric patient who was previously healthy and subsequently, developed polyuria (above 3 ml/kg/hour), irritability and high blood glucose (724 mg/dl) during the critical phase of DHF. DKA was diagnosed with DHF and managed successfully with insulin and intravenous fluids. He recovered without complications and discharged home with follow up being arranged at the endocrinology clinic. CONCLUSIONS: When both DHF and DKA present together in a patient, meticulous monitoring of glycaemic control as well as fluid management is required to reduce the potential risk for severe complications of both conditions. Since there are no similar paediatric case reported in the literature, this case report might inspire paediatricians to anticipate the possibility of DKA in children with DHF.

Clinical and Laboratory Profile of Fatal Dengue Cases at a Tertiary Care Private Hospital in Mumbai, India.

Dengue-related mortality has significantly reduced with early and appropriate fluid resuscitation. However, we continue to see dengue-related fatalities in patients despite early intervention and advanced critical care support. This was a retrospective study conducted at a tertiary care private hospital in Mumbai, India. All patients dying of dengue in the calendar year 2017 were studied. Details related to age, gender, condition at presentation, laboratory parameters, treatment administered, and time to death were abstracted from case records. A total of 575 patients with a diagnosis of dengue were admitted to the hospital in 2017, of which 15 died (mortality rate 2.6%). Four patients died in the emergency medical unit; 11 patients who died after admission to the inpatient unit had multi-organ dysfunction at the time of presentation, with shock, severe liver dysfunction, and severe metabolic acidosis. Only 4/11 patients had hemoconcentration, and 10/11 patients had high white cell counts. In five patients where serum ferritin was performed, it was more than 40,000 ng/mL. Death occurred at a median time of 2 days after hospitalization despite good supportive care. Although there is scope for improvement of supportive care in these patients, it appears that other interventions are urgently needed to improve outcomes in severe dengue. This calls for more research into the immunopathology of dengue, evaluation of anti-inflammatory drugs, intravenous immunoglobulins, antivirals, and improved vaccines.