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Competing Interests: None

Objective: Causes of acute febrile illness (AFI) often remain undetermined in developing countries, due to overlap of symptoms and limited available diagnostics. We aimed to assess the aetiology of AFI in adults in a referral hospital in northwest Ethiopia., Methods: While all participants were tested for malaria by rapid diagnostic test (RDT), microscopy was only done on physician's request. Dengue virus (DENV) infections were detected using an RDT and ELISAs and dengue, yellow fever and chikungunya cases were identified by PCR. Bacterial aetiologies were investigated using blood culture and PCR., Results: The aetiology of acute infection was identified for 20.5% of 200 patients enrolled. Eleven percent tested positive for Plasmodium, while microscopy was only requested for half of the identified malaria cases. For 4.0% of the Plasmodium-infected patients, an acute or past DENV (co-)infection was detected. We found 7.5% acute and 13.0% past DENV - all serotype 3 - infections. Bacterial infections were observed in 4.5% of the patients., Conclusion: Malaria is still a considerable aetiology of AFI and dengue is underrecognised. There are areas where both diseases occur concomitantly, and the DENV-3 serotype presumably spreads from Sudan to northern Ethiopia. As only 20.5% of the aetiologies were identified, a broader testing platform is required., (© 2022 John Wiley & Sons Ltd.)

Purpose: To report a retrospective series of three cases of infectious panophthalmitis post-dengue fever with ex vivo confirmation of dengue virusribonucleic acid (RNA) in the tissues of the eye., Methods: Four eyes of three patients, who were diagnosed with panophthalmitis following dengue fever and who underwent evisceration, were included. All demographic and clinical data were recorded. The eviscerated samples were subjected to direct microscopy, culture for bacteria, fungi, and parasites, and molecular virology (dengue virus [DENV] NS1-specific reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay)., Results: The time from the development of dengue fever to the occurrence of ocular symptoms was 4.33 ± 1.15 (median 5) days. DENV NS1 RNA, suggestive of the presence of the dengue virus, was confirmed in all evisceration specimens (uveal tissue, cornea). All the patients recovered completely from dengue fever and on follow-up had healthy eviscerated sockets., Conclusion: Demonstration of the DENV RNA in the eviscerated specimens of panophthalmitis following dengue fever implicates the DENV in the pathophysiology of the ocular infection., Competing Interests: None

Objective: Dengue fever is one of the most important arboviral diseases in the world, and its severe forms are characterised by a broad spectrum of systemic and cardiovascular hallmarks. However, much remains to be elucidated regarding the pathogenesis triggered by Dengue virus (DENV) in the heart. Herein, we evaluated the cardiac outcomes unleashed by DENV infection and the possible mechanisms associated with these effects., Methods: A model of an adapted DENV-3 strain was used to infect male BALB/c mice to assess haemodynamic measurements and the functional, electrophysiological, inflammatory and oxidative parameters in the heart., Results: DENV-3 infection resulted in increased systemic inflammation and vascular permeability with consequent reduction of systolic blood pressure and increase in heart rate. These changes were accompanied by a decrease in the cardiac output and stroke volume, with a reduction trend in the left ventricular end-systolic and end-diastolic diameters and volumes. Also, there was a reduction trend in the calcium current density in the ventricular cardiomyocytes of DENV-3 infected mice. Indeed, DENV-3 infection led to leucocyte infiltration and production of inflammatory mediators in the heart, causing pericarditis and myocarditis. Moreover, increased reactive oxygen species generation and lipoperoxidation were also verified in the cardiac tissue of DENV-3 infected mice., Conclusions: DENV-3 infection induced a marked cardiac dysfunction, which may be associated with inflammation, oxidative stress and electrophysiological changes in the heart. These findings provide new cardiac insights into the mechanisms involved in the pathogenesis triggered by DENV, contributing to the research of new therapeutic targets for clinical practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Acute urticaria (AU) is characterized by the occurrence of spontaneous wheals, angioedema, or both for less than 6 weeks. Viral infection is considered to be one of the common causes of AU, however AU has never been reported in association with dengue infection., Objective: To describe the first case of AU in dengue virus infection., Methods: Case report., Results: A 17-year-old healthy male presented with first episode of AU which associated with confirmed dengue virus infection. He responded well with antihistamine treatment and without recurrence at 2-month follow up., Conclusions: Patients with dengue virus infections can present with AU, possibly from viral-infected mast cell. Future research will have to clarify this association.

Introduction: Neurological manifestation of dengue virus infection is a rare entity. Serotypes commonly associated with neurological manifestation are DENV-2 and DENV-3. We plan to detect the serotypes related to the neurological presentation in dengue infection and its correlation with different neurological complications and outcome., Methods: In this case-control study, consecutive dengue cases with different neurological manifestations were enrolled along with age and sex-matched controls (dengue patients without neurological complication). Serotyping using RT-PCR of samples of cases and controls were done. Level of correlation was analyzed with various parameters and outcomes., Results: In cases out of 33 samples, 6 sample serotypes were detected, which were composed of DENV-1 (n = 2) and DENV-2 (n = 4). In controls, DENV-1 (n = 5), DENV-2 (n = 6), and DENV-3 (n = 3) were detected. When statistically correlated, no significant association was found in cases and controls with dengue virus serotype. The frequency of serotype 2 was higher in hypokalemic paralysis cases than non-hypokalemic paralysis cases and the difference was significant (p < 0.05). The outcome was good (mRS < 3) in all the cases where serotypes were detected, but on statistical correlation, it was not found significant (p > 0.05)., Conclusion: DENV-1 and DENV-2 are associated with neurological manifestation of dengue infection, which is different from the existing literature, where DENV-2 and DENV-3 are reported. The detection of DENV serotype will help in predicting and best management of neurological complication. The serotype 2 of dengue virus is more commonly associated with dengue-associated hypokalemic paralysis than other neurological complication (p < 0.05). There is no significant association of serotypes with outcome or mortality., (© 2021. Fondazione Società Italiana di Neurologia.)

This case illustrates acute myocarditis with complete heart block in a 13-year-old teenager as a rare complication of acute dengue illness. He required urgent temporary pacing with inotropic support and antifailure medications. Complete heart block in dengue myocarditis is an acute but reversible condition. A similar presentation in a dengue-endemic country or with a history of travelling to tropical countries warrants a suspicion of dengue infection.

Rationale: Expanded dengue syndrome (EDS) is the phenomenon coined by the World Health Organization for cases of dengue fever (DF) with rare but dangerous consequences. EDS mainly leads to complications involving the vital organs, thus is also associated with a higher mortality rate. This case report presents the first-ever case where a patient developed EDS with both rhabdomyolysis-induced acute kidney injury and compartment syndrome of the limbs., Patient Concerns: Our patient, an 18-year-old Pakistani male, presented with fever, colicky abdominal pain, vomiting, diarrhea, dark-colored urine, and oliguria., Diagnoses: Dengue rapid NS-1 test came back positive. Along with myoglobinuria both serum creatine phosphokinase and creatine levels were abnormal. Hence, the patient was diagnosed with rhabdomyolysis-induced acute kidney injury. On physical examination, his right arm was painful and tender with restricted movement at the elbow. A Doppler ultrasound of the arm revealed thickening of the skin and underlying muscles, as well as edematous abnormalities affecting the entire right upper limb, both of which are indications of compartment syndrome., Interventions and Outcome: The management included rehydration, administration of dextrose and bicarbonate (bicarbonate infusion) prepared by adding 150 mEq sodium bicarbonate in 850 mL dextrose 5%, pain killers, along with platelet, and packed red cell transfusions. Additionally, right upper limb was kept elevated at 90° for 30 minutes every 2 hours to reduce edema and crept bandages were applied. The patient was discharged after 11 days and the follow-up was uneventful., Lesson: Physicians should be aware that rhabdomyolysis-induced acute kidney damage and limb compartment syndrome are also possible DF consequences, and they should be on the lookout for any indications pointing to these complications in DF. A prompt diagnosis can prevent further complications and fatality., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Dengue virus (DENV) is a flavivirus that is a significant cause of human disease costing billions of dollars per year in medical and mosquito control costs. It is estimated that up to 20% of DENV infections affect the brain. Incidence of DENV infections is increasing, which suggests more people are at risk of developing neurological complications. The most common neurological manifestations of DENV are encephalitis and encephalopathy, and movement disorders such as parkinsonism have been observed. Parkinsonism describes syndromes similar to Parkinson's Disease where tremors, stiffness, and slow movements are observed. Parkinsonism caused by viral infection is characterized by patients exhibiting at least two of the following symptoms: tremor, bradykinesia, rigidity, and postural instability. To investigate DENV-associated parkinsonism, case studies and reports of DENV-associated parkinsonism were obtained from peer-reviewed manuscripts and gray literature. Seven reports of clinically diagnosed DENV-associated parkinsonism and 15 cases of DENV encephalitis, where the patient met the case criteria for a diagnosis of viral parkinsonism were found. Clinically diagnosed DENV-associated parkinsonism patients were more likely to be male and exhibit expressionless face, speech problems, and lymphocytosis. Suspected patients were more likely to exhibit tremor, have thrombocytopenia and low hemoglobin. Viral parkinsonism can cause a permanent reduction in neurons with consequential cognitive and behavior changes, or it can leave a latent imprint in the brain that can cause neurological dysfunction decades after recovery. DENV-associated parkinsonism is underdiagnosed and better adherence to the case definition of viral parkinsonism is needed for proper management of potential sequalae especially if the patient has an ongoing or potential to develop a neurodegenerative disease., Competing Interests: The authors have declared that no competing interests exist.

Background: Dengue virus (DENV) infection may be associated with increased risks of major adverse cardiovascular effect (MACE), but a large-scale study evaluating the association between DENV infection and MACEs is still lacking., Methods and Findings: All laboratory confirmed dengue cases in Taiwan during 2009 and 2015 were included by CDC notifiable database. The self-controlled case-series design was used to evaluate the association between DENV infection and MACE (including acute myocardial infarction [AMI], heart failure and stroke). The "risk interval" was defined as the first 7 days after the diagnosis of DENV infection and the "control interval" as 1 year before and 1 year after the risk interval. The incidence rate ratio (IRR) and 95% confidence interval (CI) for MACE were estimated by conditional Poisson regression. Finally, the primary outcome of the incidence of MACEs within one year of dengue was observed in 1,247 patients. The IRR of MACEs was 17.9 (95% CI 15.80-20.37) during the first week after the onset of DENV infection observed from 1,244 eligible patients. IRR were significantly higher for hemorrhagic stroke (10.9, 95% CI 6.80-17.49), ischemic stroke (15.56, 95% CI 12.44-19.47), AMI (13.53, 95% CI 10.13-18.06), and heart failure (27.24, 95% CI 22.67-32.73). No increased IRR was observed after day 14., Conclusions: The risks for MACEs are significantly higher in the immediate time period after dengue infection. Since dengue infection is potentially preventable by early recognition and vaccination, the dengue-associated MACE should be taken into consideration when making public health management policies., Competing Interests: The authors have declared that no competing interests exist.

We present the case of a 32-year-old male, previously healthy, with a 5-day history of fever, frontal-occipital headache, retro-ocular pain, rash, petechiae, myalgia, arthralgia, and abdominal pain. Blood tests with leukopenia, severe thrombocytopenia, transaminitis, long clotting times. Severe dengue with associated coagulopathy was diagnosed, indicating transfer to ICU. Presents torpid evolution, altered state of consciousness, psychomotor agitation, and aggressiveness. Structural, ischemic-hemorrhagic alterations, bacterial and fungal infections were ruled out. Finally diagnosing dengue encephalitis, confirmed by DENV PCR in CSF. Support measures are provided with favorable evolution. Encephalitis is the most serious neurological complication after dengue virus infection.

Bleeding associated with endothelial damage is a key feature of severe dengue fever. In the current study, we investigated whether Notch ligands were associated with bleeding in 115 patients with confirmed dengue infection in Vietnam. Soluble Notch ligands were determined by means of enzyme-linked immunosorbent assay. Seventeen of 115 patients (14.8%) experienced bleeding manifestations. High soluble delta-like ligand 1 (sDLL1) plasma levels was associated with bleeding (median, 15 674 vs 7117 pg/mL; P < .001). Receiver operating characteristic (ROC) curve analysis demonstrated that sDLL1 had the best test performance (area under the ROC curve, 0.852), with 88% sensitivity and 84% specificity. The combination with alanine aminotransferase and aspartate aminotransferase slightly increased sDLL1 performance. sDLL1 may be useful to guide clinical management of patients with patients in endemic settings., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Dengue patients have an increased risk of acute gastrointestinal (GI) bleeding. However, whether dengue virus (DENV) infection can cause an increased long-term risk of GI bleeding remains unknown, especially among elderly individuals who commonly take antithrombotic drugs. A retrospective population-based cohort study was conducted by analyzing the National Health Insurance Research Databases. Laboratory-confirmed dengue patients from 2002 to 2012 and four matched nondengue controls were identified. Multivariate Cox proportional hazard regression was used to evaluate the acute (<30 days), medium-term (31-365 days), and long-term (>365 days) risks of nonvariceal upper GI bleeding after DENV infection. Stratified analyses by age group (≤50, 51-64, ≥65 years old) were also performed. In total, 13267 confirmed dengue patients and 53068 nondengue matched controls were included. After adjusting for sex, age, area of residence, comorbidities, and medications, dengue patients had a significantly increased risk of nonvariceal upper GI bleeding within 30 days of disease onset (adjusted HR 55.40; 95% CI: 32.17-95.42). However, DENV infection was not associated with increased medium-term and long-term risks of upper GI bleeding overall or in each age group. Even dengue patients who developed acute GI bleeding did not have increased medium-term (adjusted HR; 0.55, 95% CI 0.05-6.18) and long-term risks of upper GI bleeding (adjusted HR; 1.78, 95% CI 0.89-3.55). DENV infection was associated with a significantly increased risk of nonvariceal upper GI bleeding within 30 days but not thereafter. Recovered dengue patients with acute GI bleeding can resume antithrombotic treatments to minimize the risk of thrombosis., Competing Interests: The authors have declared that no competing interests exist.

Dengue viral (DENV) infections can lead to acute pancreatitis and associated tissue damage. This study examined the pancreas from two fatal cases of DENV for histopathological changes as well as for the detection of cytokines, and other inflammatory mediators. Tissue sections were prepared for examination by ultrastructural and histopathological techniques. Sections from the pancreas of non-infected individuals were prepared in parallel as a control. The presence of viral replication in macrophages was detected by co-staining for the proteins NS3 and CD68 by immunofluorescence. Immunohistochemistry was used to detect cells that expressed cytokines and inflammatory mediators to characterize the inflammatory response. Edema, acinar necrosis and fibrosis areas associated with a mononuclear infiltrate were found in infected tissues. The major site of virus replication appeared to be macrophages based on their exclusive presentation of the viral protein NS3. Pancreatic tissues from the infected individuals also displayed increased levels of high mobility group box-1, caspase-3, gelatinase B and tumor necrosis factor alpha compared to controls. The presence of virus replicating macrophages in the pancreas was associated with multiple changes in tissue structure that included elevated levels of cytokines and inflammatory markers that may differentiate acute pancreatitis due to DENV infections from other causes., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Kidney transplant recipients (KTR) are at increased risk for dengue virus (DENV) infection. The aim of this study was to outline the clinical presentation and laboratory profile of DENV infection in KTR and its impact on renal function., Methods: This was a retrospective study of KTR diagnosed with DENV infection. Adult patients who visited Santa Casa de Belo Horizonte Nephrology Center between April and September 2019 were included. Patients who did not sign the Informed Consent were excluded. Data were collected from the database and medical records. The study was approved by the local Institutional Ethics Committee and the Informed Consent was obtained., Results: Nineteen KTR were evaluated. The main signs and symptoms were myalgia, headache/retro-orbital pain, fever, and gastrointestinal symptoms. Two patients had acute cholecystitis without calculus, three experienced pleural and/or pericardial effusion, and one developed acute myocarditis. All patients were under immunosuppression with prednisone, tacrolimus, and mycophenolate, and most were not receiving induction therapy. Temporary suspension/reduction of immunosuppression was required in 58% of patients and leukopenia was the most common reason. Thrombocytopenia was common and 58% of patients developed acute kidney injury. All patients recovered renal function., Conclusions: DENV infection in KTR patients seems to follow a similar course as in the general population. Although there was no control group, we suspect that immunosuppression, preexisting kidney disease or type of donor was not a determining factor in most patients. Transient renal dysfunction was common but reversible. No patient experienced death or graft loss.

Arthropod-borne viral infections caused by dengue virus (DENV) and chikungunya virus (CHIKV) are prevalent in the same regions and are spread by the same mosquito type (Aedes) and have similar clinical manifestations. This study emphasized the challenges of diagnosing fever in a patient returning from a tropical area. We report a case of a 52-year-old patient who presented with fever, myalgia, and headache after travelling to Laos and Thailand. After ten days of the disease, the diagnosis of chikungunya was made. Recent travel history should be a standard part of assessment when consulting febrile patients and is essential for further diagnosis. Malaria should permanently be excluded from travellers returning from tropical regions with fever. In the differential diagnosis, dengue, chikungunya, and other mosquito-borne infections should be considered. Patients wishing to travel to such areas need to be educated beforehand on the necessary preventative measures., (© National Institute of Public Health NIH – National Research Institute.)

Background: Ultrasound (US) is an investigation available in many acute care settings. Thrombocytopenia is a well-described complication of dengue infection and has been shown to correlate with disease severity. The purpose of this study was to assess the utility of admission ultrasonography in predicting thrombocytopenia and disease severity in patients infected with dengue virus., Methods: Data were collected prospectively on 176 patients (male, n=86; female, n=90) admitted to the Nawaloka Hospital, Sri Lanka with dengue infection between December 2016 and August 2018. All patients had an US scan on admission and disease severity was determined using the World Health Organization 2009 classification., Results: There were 106 (60.2%) cases of dengue with/without warning signs and 70 (39.8%) cases of severe dengue. Patients with an abnormal US on admission were more likely to have severe dengue. Gallbladder wall thickening was the most common US abnormality. Abnormal US findings significantly correlated with more pronounced thrombocytopenia from day 2 of admission., Conclusions: An abnormal US scan on admission can aid in identification of patients at risk of developing severe dengue and can be used as a novel clinical tool to identify patients at risk of severe thrombocytopenia., (© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Competing Interests: Research was supported by a fellowship from the Consejo Nacional de Ciencia y Tecnología (CONACYT) of Paraguay, awarded as part of the Programa de Vinculación de Científicos y Tecnólogos (PVCT 16-66). The authors declare no conflict of interest. The study protocol was reviewed and approved by the Scientific and Ethics Committee of the Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción (IICS-UNA, IRB00011984). Written informed consent was provided by the patient.

Background: The clinical consequences of SARS-CoV-2 and DENGUE virus co-infection are not promising. However, their treatment options are currently unavailable. Current studies have shown that quercetin is both resistant to COVID-19 and DENGUE; this study aimed to evaluate the possible functional roles and underlying mechanisms of action of quercetin as a potential molecular candidate against COVID-19 and DENGUE co-infection., Methods: We used a series of bioinformatics analyses to understand and characterize the biological functions, pharmacological targets and therapeutic mechanisms of quercetin in COVID-19 and DENGUE co-infection., Results: We revealed the clinical characteristics of COVID-19 and DENGUE, including pathological mechanisms, key inflammatory pathways and possible methods of intervention, 60 overlapping targets related to the co-infection and the drug were identified, the protein-protein interaction (PPI) was constructed and TNFα, CCL-2 and CXCL8 could become potential drug targets. Furthermore, we disclosed the signaling pathways, biological functions and upstream pathway activity of quercetin in COVID-19 and DENGUE. The analysis indicated that quercetin could inhibit cytokines release, alleviate excessive immune responses and eliminate inflammation, through NF-κB, IL-17 and Toll-like receptor signaling pathway., Conclusions: This study is the first to reveal quercetin as a pharmacological drug for COVID-19 and DENGUE co-infection. COVID-19 and DENGUE co-infection remain a potential threat to the world's public health system. Therefore, we need innovative thinking to provide admissible evidence for quercetin as a potential molecule drug for the treatment of COVID-19 and DENGUE, but the findings have not been verified in actual patients, so further clinical drug trials are needed., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Dengue fever (DF) is an endemic infectious disease in tropical and subtropical regions. Ocrelizumab is a humanized monoclonal antibody that targets the CD20 antigen on B cells, which is approved for the treatment of both relapsing-remitting multiple sclerosis (RRMS) and primary-progressive multiple sclerosis (PPMS). We describe the favorable clinical outcome of DF in an RRMS patient treated with Ocrelizumab, who neither presented hemorrhagic or systemic shock symptoms nor reported neurological worsening.

Background: Accumulating evidence suggests neurological manifestations after dengue infection. However, the relationship between dengue and long-term neurocognitive sequel remains unclear., Methods: We recruited 816 patients with dengue and 8,160 controls between 1997 and 2012 using data from Taiwan National Health Insurance Research Database and followed them up until the end of 2013. Individuals who exhibited any type of dementia were identified during the follow-up period. Cox regression analyses were performed with adjustments for demographic data and medical and mental comorbidities (cerebrovascular diseases, traumatic brain injury, hypertension, dyslipidemia, diabetes mellitus, depression, alcohol use disorder, and substance use disorder). The E-value for the causality of the evidence was calculated. Sensitivity analysis was conducted to exclude patients with prodromal dementia., Results: Patients with dengue were more likely to develop dementia (hazard ratio [HR]: 2.23, 95% confidence interval [CI]: 1.51-3.28), Alzheimer's disease (HR: 3.03, 95% CI: 1.08-8.45), and unspecified dementia (HR: 2.25, 95% CI: 1.43-3.53), but not vascular dementia compared to controls during the follow-up period. Sensitivity analyses after exclusion of the observation period over the first three years or first five years and after exclusion of patients' enrollment before 2010 or 2008 showed consistent findings. The E-values for the HR (range 3.62-5.51) supported the association between dengue and subsequent dementia among the whole population, men, and women., Conclusion: The risk of dementia was 2.23-fold higher in patients diagnosed with dengue during the follow-up period than in the controls. Further studies are necessary to investigate the underlying pathophysiology of dengue and dementia., Competing Interests: Declaration of Competing Interest No conflict of interest., (Copyright © 2021. Published by Elsevier Ltd.)

The current pandemic of coronavirus disease 2019 (COVID- 19) poses a bigger challenge to the population in tropical countries where dengue fever is also endemic as both diseases share similar clinical and laboratory features. In COVID-19, hyperferritinaemia is associated with severe disease and clinical outcome while in dengue fever, hyperferritinaemia is a key feature of haemophagocytic lymphohistiocytosis (HLH), which is a complication with high mortality. In this case report, we present a case of coinfection of COVID-19 and dengue with hyperferritinaemia in Queen Elizabeth Hospital, Sabah, Malaysia.

Background: The clinical presentation of dengue fever had been observed to change with time since its first outbreak in 2000 in Bangladesh. This report showed the clinical presentation of the 2019 outbreak in Bangladesh along with its comparison to previous outbreaks witnessed in this region., Methods: This hospital-based cross-sectional study was conducted in one of the largest tertiary care hospitals in Dhaka city. A total of 553 laboratory-confirmed and 194 probable dengue cases were interviewed. The clinical manifestation of the confirmed cases of the current outbreak was compared with three of the outbreak reports retrieved from the databases. R version 3.6.3 was used for data analysis., Results: Among the confirmed cases, two-thirds were male (63.2%) and the average age was 27(± 11) years. Positive tests for NS1 and IgM were present in 99.6% (n = 525/527) and 82.6% (n = 38/46) of the cases, respectively. Thrombocytopenia was present in 66.1% of cases. Fever (100%) was common for all. Gastrointestinal (GIT) features, including abdominal pain (86.5%), anorexia and/or vomiting (69.6%), and Diarrhea (> 3 motions/day) (26.2%) were more frequent than typical rash and other pain symptoms. Hypotension was present in approximately a quarter of patients (25%). GIT features (anorexia, nausea, and/or vomiting) and hypotension were more common among adult participants while bleeding manifestation (melena and vaginal bleeding, p = 0.009 & 0.032) was more frequent in pediatric patients. Compared to outbreaks of 2008, 2016, and 2018, increasing trends in GIT symptoms e.g. anorexia, abdominal pain, and diarrhea were observed. While a negative trend in hemorrhagic manifestations (skin rash, melena, and conjunctival hemorrhage/hemorrhagic sclera) and arthralgia/joint pain were found., Conclusion: The present outbreak was noticeably characterized by GIT symptoms and hypotension in addition to the typical clinical features like rash and pain symptoms. An increasing trend in GIT features and decreasing trend in hemorrhagic manifestations was noted over the last decade of dengue outbreaks., (© 2021. The Author(s).)

The novel coronavirus disease 2019 (COVID-19) presents with non-specific clinical features. This may result in misdiagnosis or delayed diagnosis, and lead to further transmission in the community. We aimed to derive early predictors to differentiate COVID-19 from influenza and dengue. The study comprised 126 patients with COVID-19, 171 with influenza and 180 with dengue, who presented within 5 days of symptom onset. All cases were confirmed by reverse transcriptase polymerase chain reaction tests. We used logistic regression models to identify demographics, clinical characteristics and laboratory markers in classifying COVID-19 versus influenza, and COVID-19 versus dengue. The performance of each model was evaluated using receiver operating characteristic (ROC) curves. Shortness of breath was the strongest predictor in the models for differentiating between COVID-19 and influenza, followed by diarrhoea. Higher lymphocyte count was predictive of COVID-19 versus influenza and versus dengue. In the model for differentiating between COVID-19 and dengue, patients with cough and higher platelet count were at increased odds of COVID-19, while headache, joint pain, skin rash and vomiting/nausea were indicative of dengue. The cross-validated area under the ROC curve for all four models was above 0.85. Clinical features and simple laboratory markers for differentiating COVID-19 from influenza and dengue are identified in this study which can be used by primary care physicians in resource limited settings to determine if further investigations or referrals would be required., (© 2021. The Author(s).)

Background: Neuromyelitis Optica Spectrum Disorder can be associated with parainfectious and post-infectious triggers. Dengue virus infection is one of the most common arbovirus infections in the world, and may present with neurological manifestations., Objectives: We present a case of DENV-associated with LETM and positive aquaporin-4 IgG, and a systematic review of published cases., Methods: Medline (Ovid) and PubMed were search through June 2021, for case reports, series and observational studies that described patients with DENV-associated LETM and/or NMOSD., Results: An adolescent girl who had recently immigrated from a Dengue-endemic region presented with a LETM with high positive AQP4-IgG titer and seropositive DENV IgM/IgG antibodies. She responded well to steroids and subsequently started maintenance rituximab for her NMOSD diagnosis., Literature Review: 22 publications describing 27 patients met inclusion criteria. In addition to this case, three published cases met current criteria for NMOSD with serological evidence of acute DENV infection., Conclusions: It is unknown whether there is a pathophysiological association between DENV infection and NMOSD. Regardless, if an immune-mediated event is suspected, particularly NMOSD, appropriate immunotherapy should be considered early. Decision regarding long term immunotherapy may depend on index of suspicion of true NMOSD, and this is where AQP4-IgG status and follow-up is helpful., (Copyright © 2021. Published by Elsevier B.V.)

The aim was to assess neurological complications in children with an invasive neurological disease by dengue virus (DENV) and the time to resolve symptoms after hospital discharge. A prospective study was conducted at a referral hospital for infectious diseases in Brazil between March 2014 and July 2019. All children hospitalized with neurologic manifestations and DENV RNA detected by real-time reverse transcription-polymerase chain reaction (RT-qPCR) in cerebrospinal fluid (CSF) were followed up until complete resolution of neurological complications. On average, they were followed up for 16 months. Among 56 DENV-positive children, 39% had some neurologic complications after hospital discharge and found that 19.6% were discharged with anticonvulsants due to seizures, 10.7% developed motor complications (e.g. muscle weakness, paresis, ataxia, and walking disability), 5.4% had headaches, and 14.3% had sleep disorders. Among the 56 children, only three had a clinical diagnosis of dengue because the symptoms are nonspecific and 35% showed no change in cerebrospinal fluid (CSF). The average time to resolve complications was 5.9 months (ranging from 1 m to 32 m). These results should alert physicians to the difficulties of a clinical diagnosis of an infection that causes neurological complications after discharge in a significant number of children. RT-qPCR's etiological diagnosis of DENV infection enabled better clinical follow-up for early intervention in children with neurological complications.

Background & Objectives: World Health Organization (WHO) revised its guidelines for classification and management of dengue in 2009. This revised system was found out to have good sensitivity and negative predictive value but poor specificity as well as positive predictive value., Methods: This retrospective study was carried out in a tertiary care hospital of Delhi, India to assess factors predicting the occurrence of severe dengue in children as per the revised classification. A total of 647 suspected dengue cases were admitted in the hospital in the year 2015. Detailed clinical and epidemiological data of 170 patients who were confirmed as dengue either by NS1 antigen test or by serology (Ig M positive) were recorded and statistically analyzed., Results: The number of laboratory-confirmed cases was 170 and included thirty (17.65%) dengue fever (DF), 106 (62.35%) dengue with warning signs (DWS) and 34 (20.0%) severe dengue (SD) patients. Regression analysis revealed that presence of vomiting, altered sensorium, shock, peri-orbital edema, hepatomegaly, splenomegaly, severe anemia, thrombocytopenia, elevated urea and creatinine, decreased total protein and globulin were significantly associated with occurrence of severe disease., Interpretation & Conclusion: The addition of clinical features (peri-orbital edema and splenomegaly); and laboratory findings (elevated urea and creatinine, decreased serum protein and globulin) might help improve the sensitivity and specificity of the revised WHO dengue classification in predicting severe dengue., Competing Interests: None

Dengue fever is the most prevalent flavivirus infection in tropical and subtropical areas of the world. It is transmitted by the haematophagous mosquito Aedes aegypti, and it manifests clinically as classical dengue fever, dengue haemorrhagic fever and dengue shock syndrome. Rarely, dengue can be associated with neurophthalmic manifestations. We present the case of a 21-year-old woman, suffering from dengue with an isolated abducens nerve palsy.

This study explored the contribution of viral respiratory infections (VRIs) in dengue-like illness (DLI) patients and their distinguishing clinicolaboratory parameters. Two hundred DLI patients were prospectively recruited (July 1- October 1, 2019) from a community clinic in Southern Malaysia. Patients ≥ 18 years with acute fever and fulfilling the WHO criteria of probable dengue were recruited. They underwent blood testing: blood counts, rapid dengue tests (nonstructural antigen-1/IgM) and polymerase chain reaction (PCR) for dengue, Zika, chikungunya, and Leptospira. Nasopharyngeal swabs (NPSs) were collected for FilmArray®RP2plus testing. From the 200 NPSs, 58 respiratory viruses (RVs) were detected in 54 patients. Of the 96 dengue-confirmed cases, 86 had dengue mono-infection, and 10 were coinfected with RVs. Of the 104 nondengue, 44 were RV positive and 4 Leptospira positive. Zika and chikungunya virus were not detected. Overall, the etiological diagnosis was confirmed for 72% of patients. Clinicolaboratory parameters were compared between dengue mono-infection and VRI mono-infection. Patients with coinfections were excluded. Multiple logistic regression showed that recent household/neighborhood history of dengue (adjusted odds ratio [aOR]: 5.9, 95% CI = 1.7-20.7), leukopenia (aOR: 12.5, 95% CI = 2.6-61.4) and thrombocytopenia (aOR: 5.5, 95% CI = 1.3-23.0) predicted dengue. Inversely, rhinorrhoea (aOR: 0.1, 95% CI = 0.01-0.3) and cough (aOR: 0.3, 95% CI = 0.1-0.9) favored VRI. Thus, VRIs comprise many infections diagnosed initially as DLIs. Early clinicolaboratory parameters can guide physicians screen patients for further testing.

The global burden of dengue is increasing against a background of rising global prevalence of chronic noncommunicable diseases (NCDs) and an epidemiological shift of dengue toward older age groups. The contribution of NCDs toward risk for adverse clinical and healthcare utilization outcomes was assessed in a national linked-database study. About 51,433 adult dengue cases between 2014 and 2015 were assessed for outpatient and inpatient claims data in Taiwan's National Health Insurance Research Database for the 30 days after their dengue diagnosis. A multivariable logistic regression with generalized estimating equations was used to estimate the probability of adverse dengue outcomes in patients with NCDs compared with dengue patients without underlying diseases. Rheumatoid arthritis and related disease were associated with the highest risk of hospitalization after dengue diagnosis (odds ratio: 1.78; 95% CI: 1.37-2.30), followed by stroke, chronic kidney disease (CKD), liver cirrhosis, asthma, coronary artery disease, chronic obstructive pulmonary disease, diabetes, congestive heart failure, hypertension, and malignancy. Chronic kidney disease and diabetes were associated with higher risks of hospitalization, intensive care unit (ICU) use, and all-cause mortality. After adjusting for socioeconomic status and other variables, the number of coexisting chronic diseases was associated with increasing risk of adverse dengue outcomes. Specific NCDs were associated with longer hospitalizations, ICU admission, and higher healthcare costs. Quantifying the risks of adverse dengue outcomes and health expenditures among dengue patients with preexisting NCDs provides insights for improved clinical management and essential inputs for health economic analyses on the cost-benefit of risk-based routine or catch-up immunization programs.

Dengue is a neglected viral arthropod-borne tropical disease transmitted by the bite of infected Aedes spp. mosquitoes. It is responsible for a significant global burden of disease and corresponding socio-economic implications. There are four different virus serotypes, all of which are found predominantly in countries with tropical climates. Patients with dengue may present with cardiovascular (CV) manifestations, contributing to associated death and disability. A systematic review was conducted to identify CV manifestations of dengue, wherein 30 relevant studies were identified in the MEDLINE and PubMed databases. CV complications of dengue include rhythm abnormalities, hypotension, myocarditis, pericarditis and deterioration in myocardial function. Prompt recognition and treatment of CV complications of dengue are essential to reduce morbidity and mortality in these patients, who are at risk of progressing to cardiogenic shock and heart failure.

Neurological complications are increasingly being reported in dengue fever, and the dengue virus is now recognized as a neurotrophic virus. The damage caused by inflammatory cytokines in the febrile phase and molecular mimicry in the recovery phase is responsible for these neurological manifestations. We report such an unusual neurological complication occurring in a 27-year-old female in the recovery phase of dengue fever, who developed an acute onset of ascending symmetric weakness of all four limbs without any sensory, autonomic, cerebellar, or cranial nerve involvement. She was diagnosed as having an acute motor axonal neuropathy (AMAN) variant of Guillain-Barre syndrome (GBS) based on a nerve conduction study (NCS) showing axonal neuropathy and contrast-enhanced magnetic resonance imaging (CE-MRI) showing root enhancement at the region of the cauda equina. She was treated with intravenous immunoglobulin (IVIG) and showed full recovery from symptoms with treatment. Our case highlights the importance of being aware of such rare neurological complications in dengue fever. Early detection and rapid initiation of treatment can lead to the complete reversal of neurological deficits.

Introduction: Coinfection with dengue and hepatitis A is rare and challenging for physicians since their clinical features can be overlapping. These infections are self-limiting but can become complicated by subsequent infective endocarditis. We report a case of infective endocarditis following a coinfection with dengue and hepatitis A., Case Presentation: A 17-year-old Yemeni male patient was admitted to the hospital complaining of yellowish discoloration of the skin and sclera associated with dark urine and a diffuse skin rash on the trunk and upper limbs followed by intermittent high-grade fever. Coinfection was confirmed by hepatitis A immunoglobulin M and dengue immunoglobulin M. At the time of diagnosis, white blood cells were normal, with mild neutrophilia and thrombocytopenia along with elevated C-reactive protein. Five days later, the patient was readmitted to the emergency department, complaining of high-grade fever, fatigue, myalgia, nausea, and vomiting. A systolic heart murmur was heard, and infective endocarditis was confirmed by the visualization of two vegetations on the mitral valve and coagulase-negative staphylococci after blood culture. Supportive therapies were initiated for hepatitis A and dengue fever, whereas infective endocarditis was treated with antibiotics for 4 weeks. The patient recovered completely from dengue, hepatitis A, and infective endocarditis., Conclusion: In endemic areas, it is reasonable to screen for coinfection with dengue and hepatitis A since they are superimposed on each other. Subacute infective endocarditis may occur following initial dengue and hepatitis A coinfection, especially among patients with rheumatic heart disease. An echocardiogram is a pivotal workup for evaluating a patient with persistent fever of unknown origin., (© 2021. The Author(s).)

Dengue fever (DF) is an important public health problem, and it is now endemic in more than 100 countries worldwide. Dengue associated neurological complication is estimated to be affecting 0.5 to 6.2% of patients. Even though this is rare, neurological manifestation of DF is an increasingly recognized entity in recent years due to significant mortality and morbidity reported/seen. Reported central nervous system manifestations due to dengue include encephalitis, encephalopathy, myelitis, myositis, acute disseminated encephalomyelitis, Guillain-Barré syndrome, stroke and etc. We report here a case of acute necrotizing encephalopathy secondary to DF in a previously healthy 12-year-old girl.

Guillain-Barré syndrome (GBS) is the commonest post-infectious inflammatory peripheral neuropathy with undiscerned aetiology. The commonly reported antecedent infections implicated in India include Campylobacter jejuni, chikungunya, dengue, and Japanese encephalitis (JE). In this study from south India, we investigated the role of these four agents in triggering GBS. This case-control study was performed on 150 treatment-naive patients with GBS and 150 age and sex-matched controls from the same community. IgM immunoreactivity for C. jejuni, chikungunya, and dengue was detected by enzyme-linked immunosorbent assay (ELISA) in serum of patients with GBS and control subjects. Immunoreactivity against JE was detected in serum as well as cerebrospinal fluid (CSF) from patients (n = 150) and orthopaedic control (n = 45) subjects. The immunoreactivity against infections was compared between demyelinating and axonal subtypes of GBS. Overall, 119/150 patients with GBS had serological evidence of antecedent infection. Amongst those with evidence of antecedent infection, 24 (16%), 8 (5%), and 9 (6%) patients were exclusively immunoreactive to chikungunya, JE, and C. jejuni, respectively. In the remaining patients (78/119), immunoreactivity to multiple pathogens was noted. Immunoreactivity to C. jejuni infection was found in 32% of GBS patients compared to 2.7% controls (P < .001), whereas to chikungunya virus was reported in 66.7% of patients with GBS compared to 44.7% controls (P = .006). Anti-dengue immunoreactivity was significantly associated with the demyelinating subtype of GBS. Patients positive for JE IgM (CSF) manifested demyelinating electrophysiology. In this large case-control study, immunoreactivity against multiple infectious agents was observed in a subset of patients. Chikungunya was the commonest antecedent infection, followed by C. jejuni., (© 2021 Peripheral Nerve Society.)

Objectives: Progression of dengue is often associated with thrombocytopenia resulting from viral-induced bone marrow suppression and immune-mediated peripheral platelet consumption. Immature platelet fraction (IPF), which can be measured using a haematology analyser, is a precursor indicating platelet formation in the bone marrow. This study evaluated the trend of IPF as an early recovery indicator of platelets in dengue patients with thrombocytopenia, and its relationship with severe dengue in conjunction with reticulocyte count., Methods: Hospitalized patients with dengue were enrolled and followed-up daily until discharge. Blood investigations included daily full blood counts and IPF measured using a haematology analyser., Results: In total, 287 patients with confirmed dengue were enrolled in this study, 25 of whom had severe dengue. All patients had a decreasing trend in platelet count in the first week of illness, concomitant with an increasing trend in the percentage of immature platelets to total platelets (IPF%) for more than 3 days prior to platelet recovery. IPF% was significantly increased in patients with severe dengue compared with patients with non-severe dengue on days 3-5 after the onset of fever. Reticulocyte count increased significantly in patients with severe dengue on day 5., Conclusions: IPF can be utilized as an early recovery indicator of platelets in patients with dengue and thrombocytopenia., Competing Interests: Conflict of interest statement YM, MK and NK are employees of Sysmex Corporation., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Abstract: We report a rare case of isolated partial left III cranial nerve palsy due to inflammatory oculomotor neuritis after dengue fever with unique neuro-imaging findings of enhancement seen along the entire course of the oculomotor nerve., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by North American Neuro-Ophthalmology Society.)

Introduction: Before the Coronavirus Disease 2019 (COVID-19) arrival and its pandemic, dengue was already a significant cause of epidemics in South East Asia and Latin America. In 2020 with their cocirculation, coinfections began to be observed and reported in different countries. As expected, this syndemic is evident in different areas and deserves proper characterisation and studies in Peru., Methods: We retrospectively assessed the clinical, epidemiological, diagnostic characteristics and outcomes in a Social Security Hospital of Chiclayo, Lambayeque, Peru, of patients that were diagnosed simultaneously with COVID-19 and dengue during May-August 2020., Results: A total of 50 patients with COVID-19/dengue coinfection were identified. Of them, 60% presented thrombocytopenia, and 52% fever, among other findings. The case fatality rate in this group was 28%, being higher in those patients initially classified as severe dengue (100%), as well as in females (55%) than males (21%) (OR = 4.65; 95%CI 1.18-18.45)., Discussion: Co-occurrence of COVID-19/Dengue is growing as a consequence of the syndemic of these viral diseases in endemic areas, such as Latin America, and as both conditions may evolve to severe disease, their epidemiological but clinical interaction in terms of outcomes need further assessment in future studies in the region., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Dengue fever and coronavirus disease 2019 have now begun to overlap within tropical and subtropical regions. This is due to the high prevalence of dengue fever in these regions and the current severe acute respiratory syndrome coronavirus 2 pandemic situation. The similarity of symptoms between the two diseases can confuse diagnoses, but coinfection can also occur., Case Presentation: We present two cases of patients with dengue and severe acute respiratory syndrome coronavirus 2 coinfection. The first case is that of a 24-year-old Hispanic woman with acute fever, odynophagia, and diarrhea, without respiratory symptoms and with positive molecular tests for both dengue and severe acute respiratory syndrome coronavirus 2. The second case is that of a 59-year-old Hispanic male patient with fever and respiratory symptoms of 2 weeks duration, negative molecular tests, and positive serological tests for both viruses. The clinical and epidemiological characteristics of both viral infections can help elucidate diagnoses and prognoses., Conclusions: Severe dengue infection is common in young adults, while coronavirus disease 2019 is generally asymptomatic. In older people, the severity of dengue fever will depend on their comorbidities or the infectious serotype, but coronavirus disease 2019 is consistently more severe in this group. The accurate diagnosis of both infections can better guide clinical management, as well as public health actions in transmission control, now especially important during the coronavirus disease 2019 pandemic., (© 2021. The Author(s).)

Background: Coagulation mechanisms are reported to be affected in dengue illness and evidenced by prolonged activated partial thromboplastin time (APTT) and prothrombin time (PT). The main aim of this systematic review and meta-analysis is to determine the magnitude of coagulation abnormalities among patients with dengue fever infection., Method: This systematic review and meta-analysis were conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The Joana Brigg's Institute (JBI) critical appraisal checklist was used for quality appraisal. STATA version 11 software was used for meta-analysis. The magnitude of coagulation abnormalities among dengue fever patients was determined by using a random-effects model. Subgroup and sensitivity analysis were performed to investigate the possible source of heterogeneity. Egger weighted regression tests were used to check the presence of publication bias among the included articles., Result: Forty-two studies with a total of 12,221 dengue fever patients were eligible for meta-analysis in this study. Of which 22, 15, and 26 studies were used to determine the magnitude of prolonged APTT, PT, and thrombocytopenia, respectively. The magnitude of prolonged APTT and PT among patients with dengue fever infection were 42.91% (95% CI: 30.95, 54.87) I2 = 99.1% and 16.48% (95% CI: 10.95, 22.01) I2 = 97.0%, respectively. Besides, the magnitude of thrombocytopenia among dengue fever patients was 70.29% (95% CI: 62.69, 77.89) I2 = 99.3%. The magnitude of prolonged APTT in children and adults was 51.21% (95% CI: 24.54, 77.89) and 44.89% (95% CI: 28.32, 61.45), respectively. Similarly, the overall magnitude of prolonged PT in children and adults were 13.40% (95% CI: 6.09, 20.71) and 18.73% (95% CI: 7.49, 29.96), respectively., Conclusion: The result of this study showed that there is a high magnitude of prolonged APTT and PT in dengue fever patients. Therefore, screening and early correction of coagulation abnormalities may be helpful to reduce further complications in those patients., Competing Interests: The authors have declared that no competing interests exist.

Dengue is a mosquito-borne virus that causes an influenza-like illness ranging in severity from asymptomatic to fatal. Dengue in pregnancy has been associated with adverse outcomes including miscarriage, preterm birth and fetal and neonatal death. We present the case of a multiparous woman who presented at 9 weeks' gestation with vaginal bleeding and abdominal cramping after a 1 month stay in Mexico. She was initially diagnosed with miscarriage with plan for outpatient follow-up. She was readmitted 3 days later with fever, retro-orbital pain, arthralgia, rash, pancytopenia and transaminitis and managed with intravenous fluids and acetaminophen. Of note, dengue serology was initially negative but retesting 2 days later was positive. It is imperative that clinicians have heightened suspicion for dengue in pregnant women with history of travel to or residence in a dengue-endemic area and consistent clinical evidence., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

In 2020, a considerable overlap occurred between the COVID-19 pandemic and seasonal dengue transmission in India. This study aimed to evaluate the effects of acute or recent infection with SARS-CoV-2 on the course and outcomes of dengue fever in children. We prospectively enrolled 44 children with a clinical and laboratory diagnosis of dengue fever. Assessment of acute and recent SARS-CoV-2 infection was done using reverse transcription-polymerase chain reaction and IgG antibody through ELISA. Children were grouped based on evidence of SARS-CoV-2 exposure and clinical severity, and outcomes were compared. The median age of the study cohort was 96 months (interquartile range [IQR]: 69-129 months). Fever (98%), vomiting (78%), abdominal pain (68%), hepatomegaly (68%), and edema (32%) were the common features. About two-thirds (N = 30) had severe dengue; 20 (45%) had dengue shock. Liver dysfunction (58%) and acute kidney injury (25%) were other major organ dysfunctions. Nineteen (43%) children stayed in the pediatric intensive care unit for a median duration of 5 days (IQR: 2-11 days). None had acute SARS-CoV2 infection; however, IgG against SARS-CoV-2 was detected in 15 (34%) cases. Children with recent exposure to SARS-CoV-2 showed a trend toward a lower incidence of acute kidney injury, fewer organ dysfunctions, and a lower frequency of invasive ventilation. Four children (9%) died; none of the deaths were in the SARS-CoV-2-exposed group. The present study exposes preliminary evidence that dengue fever might follow a less severe course in children with recent exposure to SARS-CoV-2 infection. However, it is pertinent to understand the antigenic similarity and cross-protective antibody response between the two viruses and their clinical relevance.