Adult Dengue Patients Research Articles

Acute liver failure and death predictors in patients with dengue-induced severe hepatitis.

BACKGROUNDLiver injury in patients with dengue infection is common. Most patients have mild and transient hepatitis. Acute liver failure (ALF) in dengue infection is rare but results in an extremely poor prognosis.AIMTo identify prognostic predictors of ALF and death in patients with dengue-induced severe hepatitis (DISH).METHODSWe retrospectively reviewed 2311 serologically confirmed adolescent and adult dengue patients who were hospitalized during a 12-year study period (between 2007 and 2019) at the university hospital of King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Patients with DISH [n = 134 (5.80%)], defined as a baseline transaminase > 10 times the normal reference cut-off level, and DISH with subsequent ALF as defined by the American Association for the Study of the Liver Diseases 2011 criteria [n = 17 (0.74%)], were included. Predictors of ALF and in-hospital death were identified using logistic regression analysis.RESULTSOf the 151 dengue-infected patients with severe liver injury or ALF, 51% were female, with a mean age of 27.9 ± 14.5 years. Capillary leakage syndrome (CLS) occurred in 68.2% (n = 103) of DISH and 100% of ALF patients. The mortality rate was low in DISH patients (0.8%) but was remarkably high if ALF developed (58.8%). In univariate analysis, age, sex, hematocrit, white blood count, atypical lymphocyte count, platelet count, international normalized ratio (INR), bilirubin, serum glutamate-oxaloacetate transaminase, serum glutamate-pyruvate transaminase, alkaline phosphatase, albumin, creatinine, Model for End-Stage Liver Disease (MELD) score, presence of liver comorbidity and presence of CLS were identified as potential prognostic parameters for ALF or death. In multivariate analysis, the MELD score remained the only predictor of ALF with an adjusted odds ratio (aOR) of 1.3 [95% confidence interval (CI): 1.1-1.5; P = < 0.001]. An initial MELD score ≥ 15 was associated with ALF from DISH with an area under the receiver operating characteristic (AUROC) of 0.91, 88.2% sensitivity and 87.3% specificity. Regarding mortality prediction, the deterioration of liver function to ALF was the most significant factor related to death in DISH patients (aOR 108.5, 95%CI: 5.5-2145.4, P = 0.002). Other independent factors associated with death included baseline INR (aOR 10.4, 95%CI: 2.6-40.5, P = 0.001). An INR ≥ 1.5 predicted death from DISH with an AUROC of 0.83 (81.8% sensitivity and 86.8% specificity).CONCLUSIONThe MELD score is the best predictor of ALF in DISH patients, a complication from dengue that is associated with high mortality. The presence of ALF and the baseline INR level are independent markers of death in DISH patients.

Dengue Fever, Expanded Dengue Syndrome and Dengue Shock Syndrome: Clinical Profile, Management and Outcome of Patients at a Tertiary Hospital, Dhaka, Bangladesh

Background: Dengue fever is endemic in Bangladesh. Its incidence has been increasing and spreadingfrom urban Dhaka to rural areas. In 2019, over 100,000 cases reported with deaths over 250.Clinical profiles varied from classical signs and symptoms to alarming severity and complications,such as, Expanded Dengue Syndrome (EDS), Dengue Shock Syndrome (DSS) along with coinfectionsand comorbidities. No detail study on EDS &amp; DSS carried out yet over 2019 outbreak. This reporthighlights the features, management and the outcome of EDS &amp; DSS cases of 2018-19 admitted in aspecialized tertiary private hospital in Dhaka, Bangladesh.&#x0D; Methods: This cross sectional observational study was performed at Square Hospital, Dhaka,exclusively over 62 adult dengue patients with complications who fulfilled the admission criteria inICU and HDU and managed as per national guidelines and diagnosed by positive NS1 Ag, DengueRT PCR , Anti-dengue IgM, hematological and biochemical tests.&#x0D; Results: Of 343 cases, 62 (18.1%) patients had complications; 17 (27.4%) admitted in ICU and 45(72.6%) patients in HDU. Among 62 patients, 25 patients had EDS (40.3%) and 17 had DSS (27.4%).Of the EDS patients, majority were 40-50 years old with male predominance. Of 62 patients, 42 hadatypical presentations (67.74%), 25 (40.3%) had EDS and 17 (27.4%) had DSS, 16 (25.8%) had coinfection,45 (72.58%) had co-morbidities. Most patients presented with gastrointestinal symptoms(80%). Twenty one cases (84%) of EDS survive; 4 (16%), died after developing rhabdomyolysis, multiorgandysfunction and acute renal failure.&#x0D; Conclusion: Early diagnosis of complicated cases by clinical features, lab predictors and early fluidtherapy are the key to successful management with positive outcome. Death could be averted byrecognizing the stage of plasma leakage indicated by raised CRP, reduced serum Albumin, andultrasonography for detecting ascites, pleural effusion, mucosal thickening and edema of gall bladderand appropriate replacement of fluid loss and maintenance of nutrition.&#x0D; Bangladesh J Medicine July 2020; 31(2) :58-63

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).

Blood pressure trend in hospitalized adult dengue patients.

BackgroundMonitoring of blood pressure is an important part of management of dengue illness. Large scale studies of temporal trend of blood pressure in adult dengue are lacking. In this study, we examined the differences in time trend of systolic (SBP) and diastolic blood pressure (DBP) in patients with and without severe dengue (SD), dengue hemorrhagic fever (DHF) and pre-existing hypertension, and elderly versus non-elderly patients.MethodsWe studied a retrospective cohort from 2005 to 2008 of 6,070 hospitalized adult dengue patients confirmed by polymerase chain reaction or clinical criteria plus positive dengue serology. Dengue severity was defined according to World Health Organization 1997 and 2009 guidelines. We used Bayesian hierarchical Markov models to compare the daily mean SBP and DBP between different subgroups. Analysis was conducted by day of defervescence (denoted as day 0), and day of illness onset (denoted as day 1) respectively.ResultsSBP decreased to a nadir during the critical phase before defervescence and was significantly lower for patients with SD or DHF, compared with patients without SD or DHF. DBP increased marginally more for patients with SD or DHF in the critical phase before defervescence. By day of defervescence, comparison of patients with and without SD showed significant difference in SBP from day -6 to day +6, except days +1, +3 and +5, and similarly in DBP except days 0, and +4 to +6. Comparison of patients with and without DHF showed significant difference in SBP from day -6 to day -1, but for DBP, significant difference was noted from day -6 to day +6, except day -2 to day 0. By day of illness, SBP differed significantly between patients with and without SD from illness days 1 to 10, and DBP from illness days 7 to 12. Between patients with and without DHF, SBP differed significantly on illness days 1, 2, 4 to 7, while DBP from days 7 to 12. On analysis by days of defervescence or by days of illness, elderly patients and those with hypertension showed consistently higher SBP and DBP throughout their hospitalization, as compared with their younger and non-hypertensive counterparts.ConclusionIn SD or DHF, SBP decreased to a nadir around the day of defervescence, and recovered to a level exceeding that in febrile phase by days 2 or 3 post-defervescence. Elderly patients and patients with pre-existing hypertension maintained higher SBP and DBP throughout the duration of dengue infection.

Prevalence and clinical manifestations of dengue in older patients in Bangkok Hospital for Tropical Diseases, Thailand.

The global incidence of dengue has increased with the ageing population. We examined the prevalence, clinical manifestations and risk factors associated with dengue severity among older patients. A retrospective cohort study was conducted at a hospital in Thailand from 2013 to 2018. Data were collected from patient records. Older patients were those aged ≥60 y, whereas adult patients were aged at least 18 y but younger than 60 y. In total, 1822 patients were included in the study. The prevalence of older dengue was 7.96%. Older dengue patients were at a higher risk of developing dengue haemorrhagic fever (DHF) than adult dengue patients (40.69% vs 30.71%). Haematuria was significantly more frequent in older patients (24.82% vs 3.58%), whereas other clinical manifestations had similar frequencies between the groups. Multivariate logistic regression indicated that hypertension (adjusted OR [aOR]=3.549, 95% CI 1.498 to 8.407) and abdominal pain (aOR=10.904, 95% CI 1.037 to 114.710) were significantly associated with DHF among older patients. Dengue is common in older adults, who also have a higher incidence of developing DHF. Older patients with dengue and comorbid hypertension and abdominal pain should be monitored for their increasing risk of DHF.

Efficacy & safety of Carica papaya leaf extract (CPLE) in severe thrombocytopenia (≤30,000/μl) in adult dengue - Results of a pilot study.

Severe thrombocytopenia in dengue often prompts platelet transfusion primarily to reduce bleeding risk. In India, about 11–43% of dengue patients report receiving platelet transfusions which is considered scarce and expensive especially in resource limited settings. Herein, we evaluated the efficacy and safety of Carica papaya leaf extract (CPLE) in the management of severe thrombocytopenia (≤30,000/μL) in dengue infection. 51 laboratory confirmed adult dengue patients with platelet counts ≤30,000/μL were randomly assigned to either treatment (n = 26) or placebo (n = 24) group. By day 3, CPLE treated patients reported significantly (p = 0.007) increased platelet counts (482%± 284) compared to placebo (331%±370) group. In the treatment group, fewer patients received platelet transfusions (1/26 v/s 2/24) and their median time for platelets to recover to ≥ 50,000/μL was 2 days (IQR 2–3) compared to 3 days (IQR 2–4) in placebo. Overall, CPLE was safe and well tolerated with no significant decrease in mean hospitalization days. Plasma cytokine profiling revealed that by day 3, mean percent increase in TNFα and IFNγ levels in treatment group was less compared to that observed in placebos; (TNFα: 58.6% v/s 127.5%; p = 0.25 and IFNγ: 1.93% v/s 62.6% for; p = 0.12). While a mean percent increase in IL-6 levels occurred in placebos (15.92%±29.93%) by day 3, a decrease was noted in CPLE group (12.95%±21.75%; p = 0.0232). Inversely, CPLE treated patients reported a mean percent increase compared to placebo by day 3 (143% ±115.7% v/s 12.03%± 48.4%; p = 0.006). Further, by day 3, a faster clearance kinetics of viral NS1 antigenemia occurred–mean NS1 titers in treatment group decreased to 97.3% compared to 88% in placebos (p = 0.023). This study demonstrates safety and efficacy of CPLE in increasing platelet counts in severe thrombocytopenia in dengue infections. A possible immunomodulatory and antiviral activity may be attributed to CPLE treatment. These findings merit validation in larger prospective studies.Trial registrationName of the registry: Clinical Trials Registry—India (CTRI)Registration No.: CTRI-REF/2017/02/013314

A cohort study of hospitalized adult dengue patients with fatality in Taiwan: The elderly and febrile characteristics matter for prognosis

Objective: To identify the febrile characteristics and clinical presentations associated with fatality in hospitalized adult patients with dengue virus (DENV) infections. Methods: A total of 289 adult hospitalized patients with laboratory-confirmed DENV infections were examined, of which 22 were fatal and 267 were non-fatal. A comparison of the clinical and laboratory characteristics was retrospectively conducted of the deceased and surviving individuals. Multivariate logistic regression and receiver operating characteristic curve analysis were performed to identify predictors of fatality. Results: Fatal patients exhibited significantly more comorbidities, particularly renal and cardiac comorbidities, and they were, in general, older than control individuals (P Conclusions: The aforementioned clinical findings may help clinicians predict fatality among adult inpatients with DENV infection.

A study on length of stay and its predictors among dengue patients in a tertiary care institute in Lucknow

Background: Dengue virus infection is a growing health problem and is prevalent throughout India. Research focusing on length of hospital stay and its predictors is scarce from India. This is important considering the burden of the disease during epidemics and impact on hospital admissions. Hence the study was conducted with the objectives to find out the factors influencing the length of stay in hospital of dengue patients.Methods: A cross sectional retrospective observational study conducted at a tertiary care hospital from August 2016 to October 2016. Data was retrieved from case sheets at Medical Record Department of 350 lab confirmed adult dengue patients admitted in the hospital.Results: The majority of patients admitted were of economically productive age group of 18-45 years and males indicating the occupational exposure to the vector of dengue. The study found that majority had length of stay of less than a week and as age increases the length of stay also increases (statistically significant). The nil case fatality and lesser number of mean days of symptoms before admission possibly indicate that early arrival of patients to hospital can lead to very low fatality rates. Further research required to find out the other predictors of length of stay.Conclusions: The study concludes that the dengue affects the economically productive age group and more males thereby indicating occupational exposure to the vector. The age of the patient can be used as an indicator to the length of stay in the hospital.

Internal migration related factors among dengue patients in Western Province, Sri Lanka

Introduction: In recent years, Sri Lanka has experienced a surge in the incidence of dengue. Among other reasons, internal migration of people into dengue-high risk areas is thought to be an important factor for the rising case load. Objectives: To identify the factors associated with internal migration of low-income adults among dengue patients in Western Province, Sri Lanka Methods: This was a descriptive cross-sectional study conducted in the Western Province in November 2017. The study population consisted of 473 confirmed adult dengue patients. Internal migrant was defined as an adult who has moved from his original place of residence and been living in the district migrated to for less than five years. A pre-tested interviewer-administered questionnaire was used for data collection. Results: There were 53 (11.2%) internal migrants belonging to low-income group among the dengue patients. Of them, 30 (56.6%) stated that the reason for migration was employment while 9 (17%) indicated education. Being of age ≤30 years, coupled with low educational level showed a statistically significant association with internal migration of adults having dengue fever. Although there were more males than females, and more displaced than non-displaced among the internal migrants, these were not statistically significant. Conclusions: Younger age and low educational level were associated with internal migration mainly due to employment.

Risk prediction for severe disease and better diagnostic accuracy in early dengue infection; the Colombo dengue study

BackgroundA major challenge in dengue management in resource limited settings is the confirmation of diagnosis. Clinical features of dengue often overlap with other infections and molecular diagnostic tools are not readily accessible to clinicians at hospitals. In addition, the prediction of plasma leakage in dengue is also difficult. Hematocrit level and ultrasound scans (combined with clinical parameters) are helpful to detect plasma leakage once it has happened, not before.MethodsColombo Dengue Study (CDS) is a prospective cohort study of clinically suspected adult dengue patients recruited from the National hospital of Sri Lanka (within the first 3 days of fever) that aimed to a) identify clinical and basic laboratory test parameters to differentiate dengue from non-dengue fever, b) evaluate the comparative efficacy of loop-mediated isothermal amplification (LAMP) for dengue diagnosis (vs. NS1 antigen test and RT-qPCR) and c) identify early associations that are predictive of plasma leakage or severe dengue. The basic laboratory tests considered here included hematological parameters, serum biochemistry and inflammatory markers.ResultsOnly 70% of clinically suspected patients were confirmed as having dengue by either the NS1 antigen test or RT-qPCR. On a Bayesian latent class model which assumes no “gold standard”, LAMP performed equally or better than RT-qPCR and NS1 antigen test respectively. When confirmed dengue patients were compared with others, the earlier group had significantly lower lymphocyte counts and higher aspartate aminotransferase levels (AST) within the first 3 days of fever. Confirmed dengue patients with plasma leakage had a lower mean age and a higher median baseline AST level compared to those without plasma leakage (p < 0.05).ConclusionClinical suspicion overestimates the true number of dengue patients. RT-LAMP is a potentially useful low-cost diagnostic tool for dengue diagnosis. Confirmed dengue patients had significantly higher AST levels and lower lymphocyte counts in early disease compared to others. In confirmed dengue patients, younger age and a higher AST level in early infection were associated with subsequent plasma leakage.

Neutrophil Activation and Early Features of NET Formation Are Associated With Dengue Virus Infection in Human.

The involvement of the immune system in the protection and pathology of natural dengue virus (DENV) has been extensively studied. However, despite studies that have referred to activation of neutrophils in DENV infections, the exact roles of neutrophils remain elusive. Here, we explored the phenotypic and functional responses of neutrophils in a cohort of adult dengue patients. Results indicated that during an acute DENV infection, neutrophils up-regulate CD66b expression, and produce a more robust respiratory response as compared with that in convalescent or healthy individuals; this confirmed in vivo neutrophil activation during DENV infection. Spontaneous decondensation of nuclei, an early event of neutrophil extracellular trap (NET) formation, was also markedly increased in cells isolated from DENV-infected patients during the acute phase of the infection. In vitro incubation of NETs with DENV-2 virus significantly decreased DENV infectivity. Interestingly, increased levels of NET components were found in the serum of patients with more severe disease form—dengue hemorrhagic fever (DHF), but not uncomplicated dengue fever, during the acute phase of the infection. Levels of pro-inflammatory cytokines IL-8 and TNFα were also increased in DHF patients as compared with those in healthy and DF subjects. This suggested that NETs may play dual roles during DENV infection. The increased ability for NET formation during acute DENV infection appeared to be independent of PAD4-mediated histone H3 hyper-citrullination. Our study suggests that neutrophils are involved in immunological responses to DENV infection.

Hyperlipidemia, statin use and dengue severity

Multiple in vitro and mice model studies suggest statins may attenuate dengue severity. However, little is known about statin use and dengue severity in adult dengue patients with hyperlipidemia. We conducted a retrospective cohort study from 2004–2008 and 2012–2013 in Tan Tock Seng Hospital, Singapore on adult dengue patients with hyperlipidemia, comparing those with and without statin usage at hospitalization in terms of primary outcome of dengue hemorrhagic fever (DHF) or shock syndrome (DSS), and severe dengue (SD). Of 13,975 subjects screened, 257 dengue patients were included; 191 (74.3%) were statin users and 66 (25.7%) were non-users. Compared with non-users, statin use was not associated with decreased risk of DHF/DSS (adjusted risk ratio [aRR] = 0.66, 95%confidence interval [CI]: 0.41–1.08, P = 0.10) and SD (aRR = 1.43, 95%CI: 0.84–2.43, P = 0.19). Therefore, statin usage had minimal effect on dengue severity in our study population in Singapore.

Pattern of dengue virus infections in adult patients from Sri Lanka.

Sri Lanka experienced its largest dengue epidemic in 2017. This study describes the disease pattern of adult dengue patients from two hospitals in Sri Lanka. Demographic, clinical and investigation findings of adult dengue patients admitted to the two hospitals from June to August 2017 were collected and analysed. A total of 1167 patients (777 males [66.2%], mean age 32.9 y) were studied. There were 775 (66.4%) patients with dengue fever (DF), 334 (28.6%) with dengue haemorrhagic fever grade I, 54 (4.6%) with DHF grade II and 4 (0.3%) with DHF grade III. DHF was significantly associated with abdominal symptoms/signs and bleeding manifestations (p<0.001). A considerable variation in time of onset of the critical phase was noted (day 3, 11.9%; day 4-5, 63.1%; day 6, 16.2%; day ≥7, 8.7%). Significantly lower platelet and white blood cell counts and elevated transaminase levels were found in DHF than DF (p<0.001). Other complications included myocarditis (two patients) and mild renal impairment (three patients). None had neurological manifestations. We found abdominal symptoms/signs, low platelet and white blood cell counts and high transaminase to be associated with DHF. The onset of the critical phase was variable and difficult to predict. Compiling data from various regions would help to understand disease patterns, which in turn would help in formulating evidence-based management guidelines and the allocation of limited health care resources.

Characteristics and predictors for gastrointestinal hemorrhage among adult patients with dengue virus infection: Emphasizing the impact of existing comorbid disease(s).

BackgroundGastrointestinal (GI) bleeding is a leading cause of death in dengue. This study aims to identify predictors for GI bleeding in adult dengue patients, emphasizing the impact of existing comorbid disease(s).MethodsOf 1300 adults with dengue virus infection, 175 (mean age, 56.5±13.7 years) patients with GI bleeding and 1,125 (mean age, 49.2±15.6 years) without GI bleeding (controls) were retrospectively analyzed.ResultsAmong 175 patients with GI bleeding, dengue hemorrhagic fever was found in 119 (68%) patients; the median duration from onset dengue illness to GI bleeding was 5 days. Gastric ulcer, erythematous gastritis, duodenal ulcer, erosive gastritis, and hemorrhagic gastritis were found in 52.3%, 33.3%, 28.6%, 28.6%, and 14.3% of 42 patients with GI bleeding who had undergone endoscopic examination, respectively. Overall, nine of the 175 patients with GI bleeding died, giving an in-hospital mortality rate of 5.1%. Multivariate analysis showed age ≥60 years (cases vs. controls: 48% vs. 28.3%) (odds ratio [OR]: 1.663, 95% confidence interval [CI]: 1.128–2.453), end stage renal disease with additional comorbidities (cases vs. controls: 1.7% vs. 0.2%) (OR: 9.405, 95% CI: 1.4–63.198), previous stroke with additional comorbidities (cases vs. controls: 7.4% vs. 0.6%) (OR: 9.772, 95% CI: 3.302–28.918), gum bleeding (cases vs. controls: 27.4% vs. 11.5%) (OR: 1.732, 95% CI: 1.1–2.727), petechiae (cases vs. controls: 56.6% vs. 29.1%) (OR: 2.109, 95% CI: 1.411–3.153), and platelet count <50×109 cells/L (cases vs. controls: 53.1% vs. 25.8%) (OR: 3.419, 95% CI: 2.103–5.558) were independent predictors of GI bleeding in patients with dengue virus infection.ConclusionsOur study is the first to disclose that end stage renal disease and previous stroke, with additional comorbidities, were strongly significant associated with the risk of GI bleeding in patients with dengue virus infection. Identification of these risk factors can be incorporated into the patient assessment and management protocol of dengue virus infection to reduce its mortality.

Metformin Use and Severe Dengue in Diabetic Adults

Diabetes mellitus is a risk factor for severe dengue in adults, but few studies have examined the association between metformin use and disease severity in dengue. In addition to its effect on glucose control, metformin has been associated with pleiotropic properties in preclinical studies. Using a cohort of laboratory-confirmed adult (≥21 years) dengue patients with diabetes mellitus admitted to Tan Tock Seng Hospital, we conducted a retrospective cohort study involving 131 (58.7%) metformin users and 92 (41.3%) non-users. Dengue severity was categorized as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) in World Health Organization (WHO) 1997 criteria and severe dengue (SD) in WHO 2009 criteria. Multivariable Poisson regression with robust error variance was used to estimate risk ratio (RR). Compared with non-use, metformin use was associated with a decreased risk of developing severe dengue (adjusted risk ratio [aRR] = 0.60, 95% confidence interval [CI]: 0.37–0.98, P = 0.04). Additionally, there was an inverse dose-response relationship (aRR = 0.69, 95% CI: 0.49–0.98, P = 0.04) with dengue severity as classified by WHO 2009 criteria. Use of metformin, however, was not associated with dengue severity based on WHO 1997 criteria; and no dose-response relationship was noted. Our results suggest metformin use could attenuate disease severity in dengue-infected diabetes mellitus individuals.

Household costs of hospitalized dengue illness in semi-rural Thailand.

BackgroundDengue-related illness is a leading cause of hospitalization and death in Thailand and other Southeast Asian countries, imposing a major economic burden on households, health systems, and governments. This study aims to assess the economic impact of hospitalized dengue cases on households in Chachoengsao province in eastern Thailand.MethodsWe conducted a prospective cost-of-illness study of hospitalized pediatric and adult dengue patients at three public hospitals. We examined all hospitalized dengue cases regardless of disease severity. Patients or their legal guardians were interviewed using a standard questionnaire to determine household-level medical and non-medical expenditures and income losses during the illness episode.ResultsBetween March and September 2015, we recruited a total of 224 hospitalized patients (<5 years, 4%; 5–14 years, 20%, 15–24 years, 36%, 25–34 years, 15%; 35–44 years, 10%; 45+ years, 12%), who were clinically diagnosed with dengue. The total cost of a hospitalized dengue case was higher for adult patients than pediatric patients, and was US$153.6 and US$166.3 for pediatric DF and DHF patients, respectively, and US$171.2 and US$226.1 for adult DF and DHF patients, respectively. The financial burden on households increased with the severity of dengue illness.ConclusionsAlthough 74% of the households reported that the patient received free medical care, hospitalized dengue illness cost approximately 19–23% of the monthly household income. These results indicated that dengue imposed a substantial financial burden on households in Thailand where a great majority of the population was covered by the Universal Coverage Scheme for health care.

Serum Metabolomics Investigation of Humanized Mouse Model of Dengue Virus Infection.

ABSTRACTDengue is an acute febrile illness caused by dengue virus (DENV) and a major cause of morbidity and mortality in tropical and subtropical regions of the world. The lack of an appropriate small-animal model of dengue infection has greatly hindered the study of dengue pathogenesis and the development of therapeutics. In this study, we conducted mass spectrometry-based serum metabolic profiling from a model using humanized mice (humice) with DENV serotype 2 infection at 0, 3, 7, 14, and 28 days postinfection (dpi). Forty-eight differential metabolites were identified, including fatty acids, purines and pyrimidines, acylcarnitines, acylglycines, phospholipids, sphingolipids, amino acids and derivatives, free fatty acids, and bile acid. These metabolites showed a reversible-change trend—most were significantly perturbed at 3 or 7 dpi and returned to control levels at 14 or 28 dpi, indicating that the metabolites might serve as prognostic markers of the disease in humice. The major perturbed metabolic pathways included purine and pyrimidine metabolism, fatty acid β-oxidation, phospholipid catabolism, arachidonic acid and linoleic acid metabolism, sphingolipid metabolism, tryptophan metabolism, phenylalanine metabolism, lysine biosynthesis and degradation, and bile acid biosynthesis. Most of these disturbed pathways are similar to our previous metabolomics findings in a longitudinal cohort of adult human dengue patients across different infection stages. Our analyses revealed the commonalities of host responses to DENV infection between humice and humans and suggested that humice could be a useful small-animal model for the study of dengue pathogenesis and the development of dengue therapeutics.IMPORTANCE Dengue virus is the most widespread arbovirus, causing an estimated 390 million dengue infections worldwide every year. There is currently no effective treatment for the disease, and the lack of an appropriate small-animal model of dengue infection has greatly increased the challenges in the study of dengue pathogenesis and the development of therapeutics. Metabolomics provides global views of small-molecule metabolites and is a useful tool for finding metabolic pathways related to disease processes. Here, we conducted a serum metabolomics study on a model using humanized mice with dengue infection that had significant levels of human platelets, monocytes/macrophages, and hepatocytes. Forty-eight differential metabolites were identified, and the underlying perturbed metabolic pathways are quite similar to the pathways found to be altered in dengue patients in previous metabolomics studies, indicating that humanized mice could be a highly relevant small-animal model for the study of dengue pathogenesis and the development of dengue therapeutics.

Predictors of Dengue-Related Mortality and Disease Severity in a Tertiary Care Center in North India.

BackgroundThere is lack of reliable predictors of disease severity and mortality in dengue. The present study was carried out to identify these predictors during the 2015 outbreak in India.MethodsThis prospective observational study included confirmed adult dengue patients hospitalized between August and November 2015 in a tertiary care centre in New Delhi, India. Appropriate statistical tests were used to compare clinicolaboratory characteristics, derive predictors of severe disease and mortality, and compute a predictive score for mortality. Serotyping was done.ResultsData of 369 patients were analyzed (mean age, 30.9 years; 67% males). Of these, 198 (54%) patients had dengue fever, 125 (34%) had dengue hemorrhagic fever (grade 1 or 2), and 46 (12%) developed dengue shock syndrome (DSS). Twenty-two (6%) patients died. Late presentation to the hospital (≥5 days after onset) and dyspnea at rest were identified as independent predictors of severe disease. Age ≥24 years, dyspnea at rest and altered sensorium were identified as independent predictors of mortality. A clinical risk score was developed (12*age + 14*sensorium + 10*dyspnea), which, if ≥22, predicted mortality with a high sensitivity (81.8%) and specificity (79.2%). The predominant serotypes in Delhi (2015) were dengue virus DENV2 and DENV4.ConclusionAge ≥24 years, dyspnea at rest, and altered sensorium were identified as independent predictors of mortality. Platelet counts did not determine outcome in dengue patients. Timely referral/access to healthcare is important. The clinical risk score for mortality prediction that was developed in this study can be used in all healthcare settings, after validation in larger cohorts.

Association of Endothelial Glycocalyx and Tight and Adherens Junctions With Severity of Plasma Leakage in Dengue Infection.

Background.The role of vascular endothelial (VE) components in dengue infection with plasma leakage is unknown. Therefore, we conducted a study to determine the adjusted association of the endothelial glycocalyx layer (EGL) and tight and adherens junction markers with plasma leakage. Methods.A prospective observational study was conducted at Cipto Mangunkusumo Hospital and Persahabatan Hospital, Jakarta, Indonesia. Adult dengue patients admitted to the hospital on the third day of fever from November 2013 through August 2015 were included in the study. Multiple regression analysis was used to determine the adjusted association of the VE biomarkers with the severity of the plasma leakage. Results.A total of 103 dengue-infected patients participated in the study. In the critical phase, levels of syndecan-1 (odds ratio [OR] = 1.004; 95% confidence interval [CI] = 1.001–1.007) and chondroitin sulfate (OR = 1.157; 95% CI = 1.025–1.307) had an adjusted association with plasma leakage, whereas levels of syndecan-1 (OR = 1.004; 95% CI = 1.000–1.008) and claudin-5 (OR = 1.038; 95% CI = 1.004–1.074) had an adjusted association with severe plasma leakage.Conclusions.In dengue-infected patients, elevated levels of syndecan-1 and chondroitin sulfate are strongly associated with plasma leakage, and elevated levels of syndecan-1 and claudin-5 are strongly associated with severe plasma leakage.

Diabetes, cardiac disorders and asthma as risk factors for severe organ involvement among adult dengue patients: A matched case-control study

Progression to severe organ involvement due to dengue infection has been associated with severe dengue disease, intensive care treatment, and mortality. However, there is a lack of understanding of the impact of pre-existing comorbidities and other risk factors of severe organ involvement among dengue adults. The aim of this retrospective case-control study is to characterize and identify risk factors that predispose dengue adults at risk of progression with severe organ involvement. This study involved 174 dengue patients who had progressed with severe organ involvement and 865 dengue patients without severe organ involvement, matched by the year of presentation of the cases, who were admitted to Tan Tock Seng Hospital between year 2005 and 2008. Age group of 60 years or older, diabetes, cardiac disorders, asthma, and having two or more pre-existing comorbidities were independent risk factors of severe organ involvement. Abdominal pain, clinical fluid accumulation, and hematocrit rise and rapid platelet count drop at presentation were significantly associated with severe organ involvement. These risk factors, when validated in a larger study, will be useful for triage by clinicians for prompt monitoring and clinical management at first presentation, to minimize the risk of severe organ involvement and hence, disease severity.