Adult Dengue Patients Research Articles

Dengue Reinfection and Co-infection: A Study of Incidence and Outcomes in Adults Admitted to a Tertiary Care Hospital, Karachi, Pakistan

Aim: To determine the occurrence of re-infection and co-infection with dengue among the adult population in Karachi, Pakistan. In addition, to determine the frequency of various medical complications among dengue patients with or without co-infection and reinfection. And to identify possible risk factors associated with dengue reinfection. Study Design: Retrospective cross-sectional study. Place and Duration of Study: Department of Internal Medicine, Aga Khan University Hospital, Karachi, Pakistan, between January 2022 and August 2022. Methodology: A total of 500 adult patients aged 18 years or above; admitted with a confirmed diagnosis of dengue were included in the study. Information was collected regarding clinical and demographic data using structured questionnaire. Data was analyzed using SPSS version 25. Results: The current study reported an incidence of 3.8% for dengue re-infection and an incidence of 19% for co-infection among adult dengue patients. The most common clinical symptoms were fever, nausea, vomiting, and abdominal pain while bleeding, acute kidney injury, and nosocomial infection were the most common complications with a proportion of 10.6% (n=53), 7.8% (n=39) and 4.2% (n=21). The study could not find any statistical association between the socio-demographic factors and disease-related characteristics. Conclusion: This study determines a low incidence proportion of dengue re-infection and co-infection among adult patients admitted with a confirmed diagnosis of dengue infection at a private tertiary care hospital in Karachi. Bleeding, nosocomial infection, and acute kidney injury were identified as the most frequent medical complications among hospitalized dengue patients. The study did not show any statistically significant risk factors associated with dengue re-infection. Large scale multi-center studies are warranted with sufficient sample size and objective assessment methods to determine the incidence of dengue re-infection and co-infection as well as for the identification of risk factors associated with dengue re-infection among the adult population of Pakistan.

Intravenous fluid therapy in hospitalized adult dengue patients without shock: Impact on subsequent severe dengue and potential adverse effects.

There is a lack of evidence on the optimal administration of intravenous (IV) fluids in hospitalized adult dengue patients without compensated and hypotensive shock. This study utilized a well-established cohort of dengue patients to compare risks of progressing to severe dengue (SD) over time for patients who were administered IV fluid versus others who were not. We included adult patients (n = 4781) who were hospitalized for dengue infection from 2005 to 2008. Cases were patients who developed SD (n = 689) and controls were patients who did not up until discharge (n = 4092). We estimated the hazardratios (HRs) and risk of SD over time between groups administered different volumes of IV fluids versus the no IV fluid comparison group using Cox models with time-dependent covariates. The doubly-robust estimation approach was used to control for the propensity of fluid administration given clinical characteristics of patients. Subgroup analyses by age, sex, and dengue warning signs before IV fluid administration were conducted. High (>2000 mL/day) IV fluids volume was associated with a higher risk of development of SD for those who had warning signs (HR: 1.77 [1.05-2.97], p: 0.0713) and for those below 55 years old (HR: 1.53 [1.04-2.25], p: 0.0713). Low (<1000 mL/day) IV fluids volume was protective against SD for patients without warning signs (HR: 0.757 [0.578-0.990], p: 0.0883), no lethargy (HR: 0.770 [0.600-0.998], p: 0.0847), and females (HR: 0.711 [0.516-0.980], p: 0.0804). Over the course of hospitalization, there were no significant differences in IV fluid administration and SD risk in most subgroups, except in those who experienced lethargy and were administered IV fluid volume or quantity. Administering high volumes of IV fluids may be associated with an increased risk of SD during hospitalization for adult dengue patients without shock. Judicious use of IV fluids as supportive therapy is warranted.

Comparison of 2009 and 2011 WHO Guidelines, and Scoring Models for Adult Hospitalized Dengue Infection: A Single Observation in Tangerang, Indonesia

&lt;p&gt;&lt;strong&gt;Background:&lt;/strong&gt; World Health Organization (WHO) published a dengue guideline in 2009 and in 2011 by WHO-SEARO. However, many of dengue cases in early phase do not meet all the criteria by WHO classification. Because of this condition there is a scoring model that was published in 2015, that might help in primary health care. Therefore, a study to compare those diagnostic tools especially in adult dengue patients in Banten is needed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aims:&lt;/strong&gt; This study is to know the comparison between 2009 version and 2011 version of dengue diagnostic guidelines by WHO and scoring model version.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and Material:&lt;/strong&gt; This study used a descriptive method with a cross-sectional design at 60 adult dengue patients. Each patient is grouped according to diagnostic tools’ classification and will be analyzed using Chi-square.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results:&lt;/strong&gt; Results are grouped according to the WHO diagnosis from 2009 and 2011, presumptive model and probable models where there are 46 (77%), 48 (78%), 31(52%), and 15 (25%) of patients diagnosed with dengue infection. Overall, the diagnosis made by the 2009 WHO and the probable models has the most superior sensitivity and specificity values of 84,6% and 25%, and 82,4% and 97,7% respectively compared to other diagnostic tools. However, from the results of positive predictive values, probable models have a higher percentage than the 2009 WHO diagnosis.&lt;/p&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; The probable model is more sensitive and specific than other diagnostic results. These conclude that probable model is best tool for dengue infection screening in early phase of infection.

Association Between Leucopenia, Transaminitis, Nonstructural Protein One Antigen (Ns1Ag) Level, and Thrombocytopenia in Adult Dengue Patients in a Tertiary Care Hospital: A Cross-Sectional Study.

The dengue virus is present throughout the tropics. Thrombocytopenia is one of the severe manifestations of the dengue virus. We studied the association of thrombocytopenia with serum transaminase level, leucopenia, and nonstructural protein one antigen (Ns1Ag) level. Data were taken retrospectively from hospital records after obtaining ethical committee approval. In the study, we included 102 patients with acute febrile illness with clinical features suggestive of dengue fever (dengue Ns1Ag positive, dengue IgM positive, or both). We excluded patients with thrombocytopenia due to other causes. Patients' demographic, clinical, and laboratory parameters were collected. We also noted episodes of bleeding or the need for a platelet transfusion. We did a statistical analysis to find out the correlation between age, sex, leucopenia, transaminitis, Ns1Ag level, and thrombocytopenia and its severity. Multiple regression analysis was used to find thrombocytopenia predictors among aspartate transaminase (AST), alanine transaminase (ALT), Ns1Aglevel, and leucopenia. AST and ALT correlated inversely with thrombocytopenia, with p-values of 0.012 and 0.027, respectively. Ns1Ag and leucopenia were not associated with thrombocytopenia, with p-values of 0.802 and 0.532, respectively (p-values significant at 0.01<= p<=0.05). Serum AST and ALT levels correlate with thrombocytopenia in dengue fever.

1376. A Retrospective Analysis of Intravenous Fluid Therapy Practice at Hospital Admission for Adults with Dengue

Abstract Background Dengue epidemics in Asia was almost exclusively a childhood disease but recently dengue in adults have become increasingly prevalent. Yet intravenous fluid replacement (IVFR), the main supportive therapy for dengue, was developed for pediatric dengue. Evidence-based guidance for fluid replacement, especially for older adults with concomitant chronic diseases that both increases risk of severe dengue and complicate fluid replacement, is lacking. We retrospectively analyzed the use of IVFR in adult dengue patients at admission to a tertiary hospital. Methods Medical records of patients diagnosed with dengue (confirmed by rapid NS1 kit or laboratory confirmation of RT-PCR, NS1 or IgM) from January 2020 to December 2022 were analyzed. Recovery phase was defined as fever defervescence for &amp;gt;12 hours with rising platelet count. Appropriateness of IVFR was based on disease severity according to the 2009 WHO dengue classification scheme. Results Preliminary analysis of the first 30 patients found an almost equal number of males (47%) and females. The median age was 52.5 years (range 15.0-83.0). 20 patients had at least one comorbidity with hyperlipidemia (33%), hypertension (23%) and ischemic heart disease (10%) being the most common. Average time from onset to presentation was 4.3 days (95% CI: 3.8-4.9). 16 (53%) met the WHO classification scheme as requiring IVFR at admission; 4 hypotension, 5 acute kidney injury (AKI), 2 hypotension with AKI, 4 hemoconcentration, 1 AKI with hemoconcentration. Of these 16, one also had altered mental status and another had hemophagocytic lymphohistiocytosis-like presentation. Despite 47% having uncomplicated dengue, all patients had IVFR at admission. Total fluid volume administered during hospitalization varied across the population and fluctuated daily for each patient, with 8 patients receiving IVFR beyond the recovery phase. One developed fluid overload while another had IV cannula-related thrombophlebitis. There was no mortality. Conclusion Preliminary findings of our on-going study suggest excessive use of IVFR and the lack of standardization possibly contributed to two iatrogenic complications. We call for development of evidence-based protocol on fluid management in older dengue patients. Disclosures All Authors: No reported disclosures

A predictive score for severity in patients with confirmed dengue fever in a tertiary care hospital in Kerala, India.

The study aimed to identify predictors of severe dengue during the 2017 epidemic and to develop and validate a simple predictive score for severity. A retrospective analytical study was conducted using clinical and laboratory data from adult dengue patients with a confirmed microbiological diagnosis. The study included patients who presented to a tertiary care centre in Kerala, India, during the febrile phase (≤4d) between June 2017 and February 2019. Using appropriate statistical tests, we derived predictors of severe disease and computed a risk score model. Of the 153 patients (mean age 50±17y; 64% males), 31 (20%) had severe dengue and 4 (3%) died. Petechial lesions, hypoalbuminemia (<3.5 g/dl), elevated alanine aminotransferase (>40IU/l) and urea >40IU/l were significant predictors. Our scoring system (cut-off: 2) showed excellent performance, with an area under the receiver operating characteristics curve of 0.9741, sensitivity of 100%, specificity of 96% and accuracy of 98%. The risk score was secondarily validated on 48 patients hospitalized from March 2019 to June 2019. Our scoring system is easy to implement and will help primary healthcare practitioners in promptly identifying severe dengue cases upon hospital presentation.

Epidemiological Investigation of the 2019 Dengue Outbreak in Dhaka, Bangladesh.

Bangladesh experienced its largest dengue epidemic in 2019. Our objective was to investigate the epidemiological, clinical, and laboratory characteristics of the hospital-admitted dengue patients during this epidemic. This cross-sectional study was conducted among 369 adult dengue patients admitted to two tertiary care hospitals in Dhaka, Bangladesh, from June to September 2019. The disease severity was determined according to the WHO's 2009 classification. The average age of the patients was 33.3 (SD 14) years with a predominance of men. Almost 10% developed severe dengue (plasma leakage 67%, clinical bleeding 25%, and organ involvement 25%). Fever, headache, retro-orbital pain, diarrhea, and warning signs such as abdominal pain, clinical fluid accumulation, and persistent vomiting were the most common clinical presentations. Thrombocytopenia, leukopenia, elevated HCT levels, and ALT/AST were common laboratory findings. Severe dengue was mostly attributable to plasma leakage with warning signs, especially abdominal pain, clinical fluid accumulation, persistent vomiting, and altered hematological parameters which might assist in the early prediction of severe dengue.

Coagulation abnormalities and their relationship with bleeding manifestations in patients with dengue-A single center observational study

Objective: To evaluate coagulation abnormalities and their relationship with bleeding manifestations among patients with dengue. Methods: This observational study was conducted on 292 adult dengue patients who were admitted to a tertiary care hospital of Western India from July 2021 to June 2022. Coagulation tests including prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, and D-dimer were performed. Patients were monitored for bleeding manifestations. Results: Coagulation abnormalities were reported in 42.8% of the patients. Overall, prolonged aPTT was the most common coagulation abnormality (40.8%), followed by low fibrinogen (38.7%), raised D-dimer (31.2%), raised INR (26.0%) and prolonged PT (19.2%). Bleeding manifestations were present in 19.9% patients. PT, INR, aPTT and D-dimer levels were significantly higher (P&lt;0.01) and fibrinogen level was significantly lower (P&lt;0.001) in patients with bleeding compared to patients without bleeding. Patients with bleeding had a significantly higher rate of all coagulation abnormalities than patients without bleeding (P&lt;0.01). Conclusions: Patients with bleeding showed a significantly higher frequency of coagulation abnormalities compared to patients without bleeding. Patients with dengue should be assessed for coagulation abnormalities.

Effect of prior Zika and dengue virus exposure on the severity of a subsequent dengue infection in adults

Given the structural similarity between Zika and dengue viruses, prior infection from one virus is hypothesized to modulate the severity of a subsequent infection from the other virus. A previous paediatric cohort study observed that a prior Zika infection may increase the risk of a subsequent symptomatic or severe dengue infection. The Colombo Dengue study is a prospective hospital-based cohort study in Sri Lanka that recruits symptomatic adult dengue patients within the first three days of fever. Anti-Dengue Envelope and anti-Zika NS1 IgG antibodies were tested by ELISA (Euroimmun, Lubeck, Germany) in all recruited patients. Associations between pre-morbid seroprevalence for either or both infections and adverse clinical outcomes of the current dengue infection were explored. A total of 507 dengue infected patients were assessed of whom 342 (68%) and 132 (26%) patients had anti-dengue IgG and anti-Zika IgG respectively. People with combined prior dengue and zika exposure as well as prior dengue exposure alone, were at increased risk of plasma leakage, compensated and uncompensated shock, and severe dengue (p < 0·05), compared to people without prior exposure to either infection. The effect of prior Zika exposure alone could not be established due to the small the number of primary dengue infections with prior Zika exposure.

Patient Characteristics and Outcome of Multi-organ Involvement in Dengue with Reference to SOFA Score

Background: Mortality in severe Dengue infection is attributed to development of MODS. Clinical profile, outcome and utility of SOFA score in Dengue MODS is not well studied in Indian context. Hence, this study was conducted to describe the “patient`s” characteristics and outcome in Dengue MODS with reference to SOFA score.&#x0D; Methods: We conducted an observational cross –sectional study in medicine department, Sassoon General Hospital Pune between January 2016 to January 2020. Adult dengue patients with multiorgan dysfunction based on SOFA score were included. Demographic, clinical and laboratory data were collected and analyzed. SOFA score was calculated at admission and monitor throughout admission course.&#x0D; Results: Total 69 patients were included. Male were 53.6% and mean age was 38.7±18.7 years. Most common symptoms were fever (98.6%), body ache &amp; joint pain (69.6%), generalized weakness (62.3%), breathlessness (59.4%), headache (58%), anorexia (58%), abdominal pain &amp; vomiting (55.1%) and bleeding manifestations (47.8%). Total 28% patients had two, 33% had three, 24.6% had four and 14.4% had ≥ 5 organs involvement. Maximum number of patients had hematological involvement (95.7%) followed by respiratory system involvement (63.8%). Mean duration of hospital stay was 9.8 days. Mortality was 43.5%. There was significant correlation of number of organs involved, pulse rate, respiratory rate, serum albumin, nervous system, respiratory system, SOFA score at admission and delta SOFA score with outcome.&#x0D; Conclusion: Dengue MODS has high mortality. Tachypnoea, tachycardia, hypoalbuminemia, respiratory failure and nervous system involvement are predictors of poor outcome. SOFA score at admission and its monitoring can serve as a useful marker to predict prognosis in dengue with multiple organ involvement.

Prevalence, clinical, and demographic characteristics of concomitant dengue fever and leptospirosis among acute dengue fever patients in The Western Province of Sri Lanka.

Dengue and leptospirosis are hyperendemic diseases in Sri Lanka. We aimed to determine the prevalence and clinical manifestations of concomitant infections of leptospirosis and acute dengue infection (ADI) in clinically suspected dengue patients. A descriptive cross-sectional study was carried out in five hospitals in the Western Province, from December 2018 to April 2019. Venous blood and sociodemographic and clinical details were collected from clinically suspected adult dengue patients. Acute dengue was confirmed by DENV NS1 antigen ELISA, IgM ELISA, IgG ELISA, and IgG quantification assay. Leptospirosis was confirmed by the microscopic agglutination test and real-time polymerase chain reaction. There were 386 adult patients. The median age was 29 years, with male predominance. Among them, 297 (76.9%) were laboratory confirmed as ADI. Concomitant leptospirosis was present in 23 (7.74%) patients. In the concomitant group, the majority (65.2%) were female, in contrast to ADI (46.7%). Myalgia was significantly more common in patients with acute dengue fever. All other symptoms were similar in both groups. In conclusion, the 7.74% of patients of ADI had concomitant leptospirosis, and it was more common in females.

The association of ultrasound assessment of gallbladder wall thickness with dengue fever severity

ObjectivesTo evaluate the association between ultrasound assessment of gallbladder wall thickness (GBWT) among severe dengue patients and dengue patients with warning signs to their clinical outcomes.MethodsA prospective, cross-sectional study involving adult dengue patients presented to our emergency department between March until September 2018. The patients were classified based on WHO classification. A gallbladder wall scan was performed on all patients.ResultsA total of 44 patients were enrolled into the study; majority of the patients with GBWT had severe dengue, significantly more than the dengue patients with warning signs (90.5% sensitivity; 69.6% specificity). The sensitivity of GBWT in determining admission to critical care areas or general ward was 100% with a specificity of 62.1%. Our analysis showed that the two variables significant in determining the severity of dengue were age (p = 0.045) and GBWT (p < 0.001). Both factors together gave 81.0% sensitivity and 78.3% specificity in predicting patients for severe dengue. The receiver operator characteristic curve revealed that using variable GBWT status can discriminate 87.1% (95%CI 66.3, 93.7%) of having severe dengue or dengue with warning signs.ConclusionThe finding of GBWT when consolidated with other clinical parameters may assist clinicians to perform risk stratification in the emergency department and become another adjunct to the assessment of severe dengue.

Direct costs of managing in-ward dengue patients in Sri Lanka: A prospective study.

IntroductionThe cost in managing hospitalised dengue patients varies across countries depending on access to healthcare, management guidelines, and state sponsored subsidies. For health budget planning, locally relevant, accurate costing data from prospective studies, is essential.ObjectiveTo characterise the direct costs of managing hospitalised patients with suspected dengue infection in Sri Lanka.MethodsColombo Dengue Study is a prospective single centre cohort study in Sri Lanka recruiting suspected hospitalised dengue fever patients in the first three days of fever and following them up until discharge. The diagnosis of dengue is retrospectively confirmed and the cohort therefore has a group of non-dengue fever patients with a phenotypically similar illness, managed as dengue while in hospital. The direct costs of hospital admission (base and investigation costs, excluding medication) were calculated for all recruited patients and compared between dengue and non-dengue categories as well as across subgroups (demographic, clinical or temporal) within each of these categories. We also explored if excluding dengue upfront, would lead to an overall cost saving in several hypothetical scenarios.ResultsFrom October 2017 to February 2020, 431 adult dengue patients and 256 non-dengue fever patients were recruited. The hospitalisation costs were USD 18.02 (SD: 4.42) and USD 17.55 (SD: 4.09) per patient per day for dengue and non-dengue patients respectively (p>0.05). Laboratory investigations (haematological, biochemical and imaging) accounted for more than 50% of the total cost. The costs were largely homogenous in all subgroups within or across dengue and non-dengue categories. Excluding dengue upfront by subsidised viral genomic testing may yield overall cost savings for non-dengue patients.ConclusionAs non-dengue patients incur a similar cost per day as the dengue patients, confirming dengue diagnosis using subsidised tests for patients presenting in the first three days of fever may be cost-efficient.

Clinical characteristics and risk factors for intracranial hemorrhage or infarction in patients with dengue.

Intracranial hemorrhage (ICH) or infarction in dengue cases is rare but very challenging for clinicians. We report these uncommon complications of dengue patients and focused on the significant factors associated with ICH or infarction in dengue patients. This investigation was a retrospective study of 182 adult dengue patients who received brain computed tomography at three Taiwan hospitals during the 2014 and 2015 dengue outbreaks. This included 13 hemorrhage cases, 26 infarction cases and 143 cases without brain infarction or hemorrhage. Among them, 13 (7.14%) suffered from ICH (6 had subdural hemorrhage, 3 had subarachnoid hemorrhage, 1 had subdural and subarachnoid hemorrhage, and 3 had intracerebral hemorrhage) and 26 (14.3%) had brain infarction. The overall mortality rate was 4/13 (30.8%) in the ICH group and 3/26 (11.5%) in the infarction group. The significant variables from the univariate analysis, including difference between 2014 and 2015, age, history of cerebrovascular accident, bone pain, arthralgia, dizziness, altered consciousness, and a higher Charlson comorbidity score. Multivariate analysis revealed that significant risk factors for ICH/infarction in dengue cases were the year of occurrence, 2014 vs. 2015 (p<0.0001, OR=25.027, 95% CI=8.205-76.336), Charlson score >4 (p=0.01, OR=3.764, 95% CI=1.364-10.386) and altered consciousness (p<0.0001, OR=6.3, 95% CI=2.242-17.7). The factors physicians should notice in dengue endemic regions for brain infarction or ICH include altered consciousness and a Charlson score >4, especially in the year that a higher frequency of infarction/ICH was observed.

Metformin as adjunctive therapy for dengue in overweight and obese patients: a protocol for an open-label clinical trial (MeDO).

Background: Dengue is a disease of major global importance. While most symptomatic infections are mild, a small proportion of patients progress to severe disease with risk of hypovolaemic shock, organ dysfunction and death. In the absence of effective antiviral or disease modifying drugs, clinical management is solely reliant on supportive measures. Obesity is a growing problem among young people in Vietnam and is increasingly recognised as an important risk factor for severe dengue, likely due to alterations in host immune and inflammatory pathways. Metformin, a widely used anti-hyperglycaemic agent with excellent safety profile, has demonstrated potential as a dengue therapeutic in vitro and in a retrospective observational study of adult dengue patients with type 2 diabetes. This study aims to assess the safety and tolerability of metformin treatment in overweight and obese dengue patients, and investigate its effects on several clinical, immunological and virological markers of disease severity. Methods: This open label trial of 120 obese/overweight dengue patients will be performed in two phases, with a metformin dose escalation if no safety concerns arise in phase one. The primary endpoint is identification of clinical and laboratory adverse events. Sixty overweight and obese dengue patients aged 10-30 years will be enrolled at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam. Participants will complete a 5-day course of metformin therapy and be compared to a non-treated group of 60 age-matched overweight and obese dengue patients. Discussion: Previously observed antiviral and immunomodulatory effects of metformin make it a promising dengue therapeutic candidate in appropriately selected patients. This study will assess the safety and tolerability of adjunctive metformin in the management of overweight and obese young dengue patients, as well as its effects on markers of viral replication, endothelial dysfunction and host immune responses. Trial registration: ClinicalTrials.gov: NCT04377451 (May 6 th 2020).

Ivermectin Accelerates Circulating Nonstructural Protein 1 (NS1) Clearance in Adult Dengue Patients: A Combined Phase 2/3 Randomized Double-blinded Placebo Controlled Trial

Dengue is the most significant mosquito-borne viral disease; there are no specific therapeutics. The antiparasitic drug ivermectin efficiently inhibits the replication of all 4 dengue virus serotypes in vitro. We conducted 2 consecutive randomized, double-blind, placebo-controlled trials in adult dengue patients to evaluate safety and virological and clinical efficacies of ivermectin. After a phase 2 trial with 2 or 3 days of 1 daily dose of 400 µg/kg ivermectin, we continued with a phase 3, placebo-controlled trial with 3 days of 400 µg/kg ivermectin. The phase 2 trial showed a trend in reduction of plasma nonstructural protein 1 (NS1) clearance time in the 3-day ivermectin group compared with placebo. Combining phase 2 and 3 trials, 203 patients were included in the intention to treat analysis (100 and 103 patients receiving ivermectin and placebo, respectively). Dengue hemorrhagic fever occurred in 24 (24.0%) of ivermectin-treated patients and 32 (31.1%) patients receiving placebo (P = .260). The median (95% confidence interval [CI]) clearance time of NS1 antigenemia was shorter in the ivermectin group (71.5 [95% CI 59.9-84.0] hours vs 95.8 [95% CI 83.9-120.0] hours, P = .014). At discharge, 72.0% and 47.6% of patients in the ivermectin and placebo groups, respectively had undetectable plasma NS1 (P = .001). There were no differences in the viremia clearance time and incidence of adverse events between the 2 groups. A 3-day 1 daily dose of 400 µg/kg oral ivermectin was safe and accelerated NS1 antigenemia clearance in dengue patients. However, clinical efficacy of ivermectin was not observed at this dosage regimen.

Prevalence, Characteristics, and Factors Associated with Acute Kidney Injury among Adult Dengue Patients in Vietnam.

Acute kidney injury (AKI) is a serious and potentially lethal complication of dengue disease; however, the actual incidence in dengue patients in Vietnam is unknown. This study aimed to determine the prevalence, clinical and laboratory characteristics, and risk factors for AKI in adults with dengue. This is a multicenter, cross-sectional study conducted between January and December 2017 in 2,417 adult patients with dengue. Indicators of demographic, clinical, and laboratory findings were evaluated. The prevalence of dengue disease-associated AKI was 2.7% (64/2,417), and dengue patients with AKI had a higher mortality rate than patients without AKI (12.5% versus 0.6%; P < 0.01). Characteristics of AKI were more common in male gender (male: female was 6.1:1), a history of hypertension (7.8% versus 2.3%; P < 0.02), the situations of hemoconcentration (hematocrit > 44%; P < 0.008), hypovolemic shock (21.9% versus 6.8%; P < 0.01), organ failure (42.3% versus 2.3%; P < 0.01), or manifestations of myocarditis (20.3% versus 6.6%; P < 0.01), hyperbilirubinemia (28.7 ± 7.6 versus 12.0 ± 0.9; P < 0.01), elevated enzymes such as alanine aminotransferase (ALT) (407 ± 151 versus 113 ± 6; P < 0.01) and aspartate aminotransferase (AST) (891 ± 475 versus 172 ± 11; P < 0.01), and prolonged PT Prothrombin Time (s) (13.9 ± 4.6 versus 12.3 ± 1.5; P < 0.01). Independent risk factors for AKI by multivariate analysis were male gender (odds ratio [OR]: 43.6; 95% CI: 2.4-810), severe dengue classification (OR: 25.7; 95% CI: 2-333), and creatine kinase > 190 U/L (OR: 11.7; 95% CI: 1.1-122.4). The study results indicate a need to continue studying the association between AKI and mortality in dengue disease and the need for improved management of AKI with dengue.

Safety of temporary interruption of antiplatelet therapy in dengue fever with thrombocytopenia

Thrombocytopenia commonly occurs in dengue and may be complicated by bleeding. Dengue can occur in adults who may be on long term antiplatelet therapy for ischemic heart disease or stroke. In these cases, clinicians may temporarily discontinue antiplatelet therapy to minimize the risk of bleeding in the absence of clear guidelines. We conducted a retrospective cohort study of laboratory-confirmed adult dengue patients on antiplatelet therapy and evaluated participants whose antiplatelet therapy was continued versus discontinued. Primary outcome was a composite outcome of major adverse cardiac and cerebrovascular events (MACCE), and all-cause mortality in-hospital and for 1-year post discharge. Secondary outcomes were platelet and blood transfusion, and occurrence of dengue haemorrhagic fever (DHF), dengue shock syndrome, dengue with warning signs and severe dengue according to World Health Organization criteria. Discontinuation of antiplatelet therapy did not result in higher composite outcome (p=0.192). Continuation of antiplatelet therapy did not result in more platelet or blood transfusion (p=0.489 and p=0.567 respectively), DHF (p=0.923). Our results suggest that discontinuation or continuation of antiplatelet therapy based on clinical judgement in dengue with thrombocytopenia, is largely safe but further studies are needed.

Metformin as adjunctive therapy for dengue in overweight and obese patients: a protocol for an open-label clinical trial (MeDO)

Background: Dengue is a disease of major global importance. While most symptomatic infections are mild, a small proportion of patients progress to severe disease with risk of hypovolaemic shock, organ dysfunction and death. In the absence of effective antiviral or disease modifying drugs, clinical management is solely reliant on supportive measures. Obesity is a growing problem among young people in Vietnam and is increasingly recognised as an important risk factor for severe dengue, likely due to alterations in host immune and inflammatory pathways. Metformin, a widely used anti-hyperglycaemic agent with excellent safety profile, has demonstrated potential as a dengue therapeutic in vitro and in a retrospective observational study of adult dengue patients with type 2 diabetes. This study aims to assess the safety and tolerability of metformin treatment in overweight and obese dengue patients, and investigate its effects on several clinical, immunological and virological markers of disease severity. Methods: This open label trial of 120 obese/overweight dengue patients will be performed in two phases, with a metformin dose escalation if no safety concerns arise in phase one. The primary endpoint is identification of clinical and laboratory adverse events. Sixty overweight and obese dengue patients aged 10-30 years will be enrolled at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam. Participants will complete a 5-day course of metformin therapy and be compared to a non-treated group of 60 age-matched overweight and obese dengue patients. Discussion: Previously observed antiviral and immunomodulatory effects of metformin make it a promising dengue therapeutic candidate in appropriately selected patients. This study will assess the safety and tolerability of adjunctive metformin in the management of overweight and obese young dengue patients, as well as its effects on markers of viral replication, endothelial dysfunction and host immune responses. Trial registration: ClinicalTrials.gov: NCT04377451 (May 6 th 2020).

Dengue and post-infection fatigue: findings from a prospective cohort-the Colombo Dengue Study.

Previous studies on post-infection fatigue in dengue are few but suggest that up to 25% of dengue patients may suffer from fatigue. This study aimed to evaluate the prevalence and associations of post-infection fatigue in dengue patients compared with non-dengue fever patients. Post-infection fatigue and its demographic and clinical associations were assessed in adult dengue and non-dengue fever patients 2months after the acute infection in a prospective cohort study in Sri Lanka. Fatigue at 2months (primary endpoint) was assessed with the fatigue questionnaire as a dichotomous outcome based on a pre-recommended cut-off (score ≥4) and as the total score from the questionnaire (higher score indicates more fatigue). Of 260 patients, 158 had dengue and, of these, 51 (32%) had fatigue at 2months. Risk was higher in dengue patients (vs non-dengue; relative risk [RR] 4.93 [95% confidence interval {CI} 2.3 to 10.4]) and more so in female dengue patients (vs male dengue patients; RR 2.45 [95% CI 1.24 to 4.86]). Severe dengue patients had a higher mean fatigue score (p=0.024). Post-infection fatigue is an underappreciated burden of this widely prevalent infection. Our findings are useful to triage patients at risk of fatigue for follow-up.