Dengue fever

About: Dengue fever is a research topic. Over the lifetime, 17463 publications have been published within this topic receiving 485745 citations. The topic is also known as: Dengue & dengue disease.

Multicentre prospective study on dengue classification in four South-east Asian and three Latin American countries

Abstract: OBJECTIVE To evaluate the existing WHO dengue classification across all age groups and a wide geographical range and to develop a revised evidence-based classification that would better reflect clinical severity. METHODS We followed suspected dengue cases daily in seven countries across South-east Asia and Latin America and then categorised them into one of three intervention groups describing disease severity according to the overall level of medical and nursing support required. Using a pre-defined analysis plan, we explored the clinical and laboratory profiles characteristic of these intervention categories and presented the most promising options for a revised classification scheme to an independent group of WHO dengue experts for consideration. Potential warning signs were also evaluated by comparing contemporaneous data of patients who progressed to severe disease with the data of those who did not. RESULTS A total of 2259 patients were recruited during 2006-2007 and 230 (13%) of the 1734 laboratory-confirmed patients required major intervention. Applying the existing WHO system, 47/210 (22%) of patients with shock did not fulfil all the criteria for dengue haemorrhagic fever. However, no three-tier revision adequately described the different severity groups either. Inclusion of readily discernible complications (shock/severe vascular leakage and/or severe bleeding and/or severe organ dysfunction) was necessary to devise a system that identified patients requiring major intervention with sufficient sensitivity and specificity to be practically useful. Only a small number of subjects (5%) progressed to severe disease while under observation; several warning signs were identified, but much larger studies are necessary to fully characterize features associated with disease progression. CONCLUSIONS Based on these results, a revised classification system comprised of two entities, 'Dengue' and 'Severe Dengue', was proposed and has now been incorporated into the new WHO guidelines.

Antibodies from dengue patient sera cross-react with endothelial cells and induce damage

Abstract: Dengue virus infection causes a wide range of diseases from the mild febrile illness dengue fever to the life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Vascular leakage and hemorrhagic syndrome are the clinical features associated with dengue infection, yet the mechanisms remain unclear. In this study, the cross-reactivity of dengue patient sera with endothelial cells was demonstrated. There were higher percentages of endothelial cells reactive with dengue hemorrhagic fever/dengue shock syndrome patient sera than those with dengue fever patient sera. The percentages of endothelial cells reactive with patient serum IgM were higher than those with IgG. Further studies showed that the endothelial cell binding activity was inhibited by pretreatment with dengue virus nonstructural protein 1 (NS1). The antibodies against NS1 produced after dengue virus infection may, at least in part, account for the cross-reactivity of patient sera with endothelial cells. Furthermore, dengue patient sera induced endothelial cell apoptosis via a caspase-dependent pathway that was also inhibited by NS1 pretreatment. In addition to apoptosis, patient sera caused cell lysis in the presence of complement, and DHF/DSS patient sera showed higher percentages of cytotoxicity than dengue fever patient sera. Thus, the generation of cross-reactive autoantibodies against endothelial cells would lead to their dysfunction, which may play a role in the pathogenesis of dengue virus infection.

Benefits and risks of the Sanofi-Pasteur dengue vaccine: Modeling optimal deployment.

Abstract: The first approved dengue vaccine has now been licensed in six countries. We propose that this live attenuated vaccine acts like a silent natural infection in priming or boosting host immunity. A transmission dynamic model incorporating this hypothesis fits recent clinical trial data well and predicts that vaccine effectiveness depends strongly on the age group vaccinated and local transmission intensity. Vaccination in low-transmission settings may increase the incidence of more severe “secondary-like” infection and, thus, the numbers hospitalized for dengue. In moderate transmission settings, we predict positive impacts overall but increased risks of hospitalization with dengue disease for individuals who are vaccinated when seronegative. However, in high-transmission settings, vaccination benefits both the whole population and seronegative recipients. Our analysis can help inform policy-makers evaluating this and other candidate dengue vaccines.

Dengue in Southeast Asia: epidemiological characteristics and strategic challenges in disease prevention

Abstract: Dengue emerged as a public health burden in Southeast Asia during and following the Second World War and has become increasingly important, with progressively longer and more frequent cyclical epidemics of dengue fever/dengue hemorrhagic fever. Despite this trend, surveillance for this vector-borne viral disease remains largely passive in most Southeast Asian countries, without adequate laboratory support. We review here the factors that may have contributed to the changing epidemiology of dengue in Southeast Asia as well as challenges of disease prevention. We also discuss a regional approach to active dengue virus surveillance, focusing on urban areas where the viruses are maintained, which may be a solution to limited financial resources since most of the countries in the region have developing economies. A regional approach would also result in a greater likelihood of success in disease prevention since the large volume of human travel is a major factor contributing to the geographical spread of dengue viruses.

Animal Models of Dengue Virus Infection

Abstract: The development of animal models of dengue virus (DENV) infection and disease has been challenging, as epidemic DENV does not naturally infect non-human species. Non-human primates (NHPs) can sustain viral replication in relevant cell types and develop a robust immune response, but they do not develop overt disease. In contrast, certain immunodeficient mouse models infected with mouse-adapted DENV strains show signs of severe disease similar to the ‘vascular-leak’ syndrome seen in severe dengue in humans. Humanized mouse models can sustain DENV replication and show some signs of disease, but further development is needed to validate the immune response. Classically, immunocompetent mice infected with DENV do not manifest disease or else develop paralysis when inoculated intracranially; however, a new model using high doses of DENV has recently been shown to develop hemorrhagic signs after infection. Overall, each model has its advantages and disadvantages and is differentially suited for studies of dengue pathogenesis and immunopathogenesis and/or pre-clinical testing of antiviral drugs and vaccines.