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Current Opinion in Virology Aug 2020Endothelial dysfunction leading to vascular permeability and plasma leakage are characteristic features of severe dengue and sepsis. However, the mechanisms underlying... (Review)
Review
Endothelial dysfunction leading to vascular permeability and plasma leakage are characteristic features of severe dengue and sepsis. However, the mechanisms underlying these immune-pathologies remain unclear. The risk of severe dengue and sepsis development depend on patient-related and pathogen-related factors. Additionally, comorbidities increase the risk of severe disease and their incidence hampers correct diagnosis and treatments. To date, there is no efficient therapy to combat severe dengue and sepsis. Here, we discuss the differences and similarities between the pathogenesis of severe dengue and that of bacterial sepsis. We identify gaps in knowledge that need to be better understood in order to move towards the rational development and/or usage of therapeutic strategies to ameliorate severe dengue disease.
Topics: Animals; Capillary Permeability; Dengue Virus; Humans; Sepsis; Severe Dengue
PubMed: 32896675
DOI: 10.1016/j.coviro.2020.07.010 -
The Cochrane Database of Systematic... Jul 2014Dengue is a common and important mosquito-borne viral infection. In many low- and middle-income countries it is endemic and is an important public health problem. Severe... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dengue is a common and important mosquito-borne viral infection. In many low- and middle-income countries it is endemic and is an important public health problem. Severe dengue is an important cause of death in children. There is no specific treatment for dengue, but observational studies suggest corticosteroids may have a benefit in dengue-related shock, and some people believe corticosteroids may prevent the progression to severe illness if given early in the course of the illness.
OBJECTIVES
To compare treatment of dengue with and without use of corticosteroids or placebo in relation to preventing shock-related death and disease progression in children and adults.
SEARCH METHODS
We searched the Cochrane Infectious Disease Group Centralized Register; CENTRAL; MEDLINE; EMBASE; and LILACS, up to 6 January 2014. We screened reference lists and contacted the relevant study authors for additional information where required.
SELECTION CRITERIA
Randomized controlled trials or quasi-randomized controlled trials comparing corticosteroids with placebo or no corticosteroids in patients diagnosed with dengue-related shock, or patients in an early symptomatic state of dengue with positive serology.
DATA COLLECTION AND ANALYSIS
Two researchers independently screened eligibility of records, extracted data and assessed quality of the studies. We presented findings in meta-analysis and summary of findings tables and evaluated the quality of evidence using GRADE.
MAIN RESULTS
We included eight studies enrolling 948 participants in this review. Paitents with dengue-related shock Four studies enrolled children younger than 15 years with dengue-related shock at hospitals in Southeast Asia and evaluated intravenous corticosteroids. The trials did not detect an effect on death (four trials, 284 participants, very low quality evidence), the need for blood transfusion (two trials, 89 participants, very low quality evidence), pulmonary haemorrhage (one trial, 63 participants, very low quality evidence), convulsions (one trial, 63 participants, very low quality evidence), or duration of hospitalization (one trial, 63 participants, very low quality evidence). The body of evidence is too small to confidently prove or exclude clinically important effects. Furthermore, the trials are more than 20 years old with several methodological limitations. Patients with dengue at an early stage Four studies enrolled 664 children and adults with dengue at an early stage of infection (without shock) in Columbia, India, Sri Lanka and Vietnam. In these participants there were no evidence of effects of oral or intravenous corticosteroids on mortality (four trials, 664 participants, low quality evidence), or on the development of complications of severe dengue such as shock (two trials, 286 participants, very low quality evidence), severe bleeding (two trials, 425 participants, very low quality evidence), severe thrombocytopaenia (one trial, 225 participants, very low quality evidence), ascites (one trial, 178 participants, very low quality evidence) and intensive care unit (ICU) admissions (two trials, 286 participants, very low quality evidence).
AUTHORS' CONCLUSIONS
The evidence from trials using corticosteroids in dengue is inconclusive and the quality of evidence is low to very low. This applies to both the use of corticosteroids in dengue-related shock and for dengue at an early stage. There is insufficient evidence to evaluate the effects of corticosteroids in the treatment of early stage dengue fever and dengue-related shock outside of the context of a randomized controlled trial.
Topics: Adrenal Cortex Hormones; Adult; Blood Transfusion; Child; Humans; Randomized Controlled Trials as Topic; Severe Dengue; Shock, Hemorrhagic
PubMed: 24984082
DOI: 10.1002/14651858.CD003488.pub3 -
Acta Medica Indonesiana Apr 2011Dengue virus (DENV) infection is a mosquito born disease that is endemic in all WHO regions, except European region, and may present a broad range of severity. It may... (Review)
Review
Dengue virus (DENV) infection is a mosquito born disease that is endemic in all WHO regions, except European region, and may present a broad range of severity. It may appear as an asymptomatic condition, dengue fever (DF), or life threatening forms, such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), or the currently defined severe dengue. Currently there are means to diagnose DENV infection, but there is no accurate means to early predict the progress into severe manifestations. Therefore, this article addresses the factors that might be used to predict the progress into severe dengue. Predictors for severe dengue are the previously established warning signs, and coexisting conditions, as is recommended by the WHO, in addition to Caucasian race, and people with AB blood group. In the future, viral load assessment, viral serotype testing, NS1, cytokine, elastase, hyaluronan, soluble thrombomodulin, and NO level, and circulating endothelial cell detection test are promising to be studied and developed as early predictors of severe dengue.
Topics: Cytokines; Dengue Virus; Elastin; Humans; Hyaluronic Acid; Nutritional Status; Risk Factors; Severe Dengue; Severity of Illness Index; Viral Load
PubMed: 21785176
DOI: No ID Found -
Viruses Jan 2022Dengue is a re-emerging neglected disease of major public health importance. This review highlights important considerations for dengue disease in Africa, including... (Review)
Review
Dengue is a re-emerging neglected disease of major public health importance. This review highlights important considerations for dengue disease in Africa, including epidemiology and underestimation of disease burden in African countries, issues with malaria misdiagnosis and co-infections, and potential evidence of genetic protection from severe dengue disease in populations of African descent. The findings indicate that dengue virus prevalence in African countries and populations may be more widespread than reported data suggests, and that the mosquito vectors appear to be increasing in dissemination and number. Changes in climate, population, and plastic pollution are expected to worsen the dengue situation in Africa. Dengue misdiagnosis is also a problem in Africa, especially due to the typical non-specific clinical presentation of dengue leading to misdiagnosis as malaria. Finally, research suggests that a protective genetic component against severe dengue exists in African descent populations, but further studies should be conducted to strengthen this association in various populations, taking into consideration socioeconomic factors that may contribute to these findings. The main takeaway is that Africa should not be overlooked when it comes to dengue, and more attention and resources should be devoted to this disease in Africa.
Topics: Africa; Black People; Coinfection; Dengue; Diagnostic Errors; Disease Outbreaks; Endemic Diseases; Humans; Malaria; Risk Factors; Severe Dengue
PubMed: 35215827
DOI: 10.3390/v14020233 -
Journal of Infection and Public Health 2018Determining the disease and economic burden of dengue is critical for the allocation of public health resources. Several studies have used disability-adjusted life-years... (Review)
Review
BACKGROUND
Determining the disease and economic burden of dengue is critical for the allocation of public health resources. Several studies have used disability-adjusted life-years (DALYs) to estimate the disease burden of dengue in different regions. However, there are no published studies discussing the estimates of dengue-related economic and disease burden specifically in Taiwan.
OBJECTIVES
We assessed the economic cost and disease burden of dengue infections in Taiwan for the period 1998-2014, and compared these during epidemic and non-epidemic years.
METHODS
We estimated the annual DALYs per million population using the disability weights for dengue fever (DF), dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS), and death cases. Economic costs were estimated and divided into direct (medical costs) and indirect costs (lost work days and caregiver fees).
RESULTS
For the period 1998-2014, a mean of 115.3 (range: 6.3-934.3) DALYs per million population annually were lost to dengue. In epidemic years, direct costs associated with dengue resulted mostly from hospitalization (86.09%), emergency (7.77%), outpatient (6.10%), and drug costs (0.03%). For indirect costs, lost productivity due to death (70.76%) was the dominant contributor. Overall, the costs were 12.3 times higher in epidemic years than in non-epidemic years (Wilcoxon rank sum test, p<0.05).
CONCLUSIONS
This study is the first to evaluate the economic costs and disease burden of dengue infections for this period in Taiwan, and reveals significant differences in economic impact between epidemic and non-epidemic years.
Topics: Asia, Southeastern; Cost of Illness; Dengue; Disabled Persons; Epidemics; Female; Humans; Male; Quality-Adjusted Life Years; Severe Dengue; Taiwan
PubMed: 28757293
DOI: 10.1016/j.jiph.2017.07.021 -
The American Journal of Tropical... Jan 2021To improve dengue triage and treatment decisions, the WHO recommends classifying the disease as dengue with or without warning signs or severe dengue. Vascular leakage...
To improve dengue triage and treatment decisions, the WHO recommends classifying the disease as dengue with or without warning signs or severe dengue. Vascular leakage is a key component of the pathophysiology of severe dengue and is detectable by ultrasound. The objective of this scoping review is to describe the primary literature on the use of ultrasound in dengue, summarize the findings, and identify knowledge gaps. Our database search retrieved 1,489 records which were reduced to 177 studies following eligibility screening. Descriptive analyses were conducted. Results showed most studies are from South Asia (n = 92, 52%) and assessed hospitalized dengue patients (130, 82%). Radiologists were the most reported ultrasonographers (14, 8%), and conventional ultrasound (39, 68%) was preferred over portable (9, 16%). The most common ultrasound findings in dengue were ascites (107, 60%), pleural effusion (102, 58%), and gallbladder wall thickening (97, 55%). However, the lack of a standard protocol to perform the ultrasound examination in dengue patients hinders conclusions about the frequency of ultrasound findings in dengue. Given the progress of current ultrasound technology, a focused point-of-care ultrasound protocol for early detection of vascular leakage in dengue is needed to generate the evidence required for its implementation in routine care.
Topics: Diagnostic Techniques and Procedures; Humans; Severe Dengue; Symptom Assessment; Ultrasonography
PubMed: 33534759
DOI: 10.4269/ajtmh.20-0103 -
Journal of Microbiology, Immunology,... Dec 2020The 2009 WHO guideline established warning signs (WS) to predict severe dengue (SD). However, their positive predictive value has been found to be low in the general...
BACKGROUND/PURPOSE
The 2009 WHO guideline established warning signs (WS) to predict severe dengue (SD). However, their positive predictive value has been found to be low in the general adult population, but they might be higher in a different population. This study investigated the association between WS and SD in end stage renal disease (ESRD) patients on maintenance dialysis in Taiwan where both diseases are prevalent.
METHODS
This study enrolled ESRD dialysis patients with dengue in 2015. Demographic, laboratory data, symptoms/signs and complication of dengue were retrospectively collected from medical records at our hospital.
RESULTS
Of 49 ESRD patients with dengue, 44 patients were receiving hemodialysis and 5 peritoneal dialysis. Older patients (>65 years old) tended to have the WS(56% vs 16.7%, P = 0.007). The rate of hospitalization, intensive care unit admission and in-hospital mortality was 79.6%, 22.5%, and 8.2%, respectively. Eighteen patients (36.7%) presented WS and eighteen patients (36.7%) developed to SD, including ten with plasma leakage, twelve with hemorrhage, and six with organ failure. Patients with WS were seven times more likely to develop SD than those without (OR: 7.06; 95%CI: 1.34-37.21). WS was associated with plasma leakage (OR: 12.36; 95% CI: 1.56-97.74) and severe hemorrhage (OR: 5.1; 95% CI: 1.03-25.18), but not organ failure.
CONCLUSIONS
Prevalence of SD is high in ESRD dialysis patients. The presence of WSs in this group was highly correlated with SD. Thus, more attention should be paid to treating ESRD patients with dengue fever if they present WSs.
Topics: Aged; Aged, 80 and over; Biomarkers; Comorbidity; Female; Hospitalization; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prevalence; Renal Dialysis; Retrospective Studies; Severe Dengue; Taiwan
PubMed: 31628090
DOI: 10.1016/j.jmii.2019.08.005 -
PLoS Neglected Tropical Diseases Oct 2021Predictive markers represent a solution for the proactive management of severe dengue. Despite the low mortality rate resulting from severe cases, dengue requires... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Predictive markers represent a solution for the proactive management of severe dengue. Despite the low mortality rate resulting from severe cases, dengue requires constant examination and round-the-clock nursing care due to the unpredictable progression of complications, posing a burden on clinical triage and material resources. Accordingly, identifying markers that allow for predicting disease prognosis from the initial diagnosis is needed. Given the improved pathogenesis understanding, myriad candidates have been proposed to be associated with severe dengue progression. Thus, we aim to review the relationship between the available biomarkers and severe dengue.
METHODOLOGY
We performed a systematic review and meta-analysis to compare the differences in host data collected within 72 hours of fever onset amongst the different disease severity levels. We searched nine bibliographic databases without restrictive criteria of language and publication date. We assessed risk of bias and graded robustness of evidence using NHLBI quality assessments and GRADE, respectively. This study protocol is registered in PROSPERO (CRD42018104495).
PRINCIPAL FINDINGS
Of 4000 records found, 40 studies for qualitative synthesis, 19 for meta-analysis. We identified 108 host and viral markers collected within 72 hours of fever onset from 6160 laboratory-confirmed dengue cases, including hematopoietic parameters, biochemical substances, clinical symptoms, immune mediators, viral particles, and host genes. Overall, inconsistent case classifications explained substantial heterogeneity, and meta-analyses lacked statistical power. Still, moderate-certainty evidence indicated significantly lower platelet counts (SMD -0.65, 95% CI -0.97 to -0.32) and higher AST levels (SMD 0.87, 95% CI 0.36 to 1.38) in severe cases when compared to non-severe dengue during this time window.
CONCLUSION
The findings suggest that alterations of platelet count and AST level-in the first 72 hours of fever onset-are independent markers predicting the development of severe dengue.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aspartate Aminotransferases; Biomarkers; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Platelet Count; Prognosis; Severe Dengue; Young Adult
PubMed: 34610027
DOI: 10.1371/journal.pntd.0009808 -
Emerging Infectious Diseases Apr 2020In 2017, a dengue epidemic of unexpected magnitude occurred in Sri Lanka. A total of 186,101 suspected cases and 440 dengue-related deaths occurred. We conducted a...
In 2017, a dengue epidemic of unexpected magnitude occurred in Sri Lanka. A total of 186,101 suspected cases and 440 dengue-related deaths occurred. We conducted a comprehensive analysis of this epidemic by comparing national surveillance data for 2017 with data from the preceding 5 years. In all Sri Lanka districts, dengue incidence in 2017 increased significantly over incidence during the previous 5 years. Older schoolchildren and young adults were more clinically symptomatic than those at extremes of age. Limited virologic surveillance showed the dominant circulating variant was dengue virus type 2 cosmopolitan genotype in the most affected district. One quarter of total annual cases were reported 5 weeks after the southwest monsoon started. Changes in vector abundance were not predictive of the increased incidence. Direct government expenditures on dengue control activities in 2017 were US $12.7 million. The lessons learned from this outbreak are useful for other tropical nations facing increasing dengue incidence.
Topics: Child; Dengue; Dengue Virus; Epidemics; Humans; Severe Dengue; Sri Lanka; Young Adult
PubMed: 32186490
DOI: 10.3201/eid2604.190435 -
Journal of Virology Nov 2023Dengue virus, an arbovirus, causes an estimated 100 million symptomatic infections annually and is an increasing threat as the mosquito range expands with climate...
Dengue virus, an arbovirus, causes an estimated 100 million symptomatic infections annually and is an increasing threat as the mosquito range expands with climate change. Dengue epidemics are a substantial strain on local economies and health infrastructure, and an understanding of what drives severe disease may enable treatments to help reduce hospitalizations. Factors exacerbating dengue disease are debated, but gut-related symptoms are much more frequent in severe than mild cases. Using mouse models of dengue infection, we have shown that inflammation and damage are earlier and more severe in the gut than in other tissues. Additionally, we observed impairment of the gut mucus layer and propose that breakdown of the barrier function exacerbates inflammation and promotes severe dengue disease. This idea is supported by recent data from human patients showing elevated bacteria-derived molecules in dengue patient serum. Therapies aiming to maintain gut integrity may help to abrogate severe dengue disease.
Topics: Animals; Humans; Mice; Culicidae; Dengue Virus; Inflammation; Severe Dengue; Kinetics
PubMed: 37850747
DOI: 10.1128/jvi.01251-23