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.

Interactions between serotypes of dengue highlight epidemiological impact of cross-immunity

Abstract: Dengue, a mosquito-borne virus of humans, infects over 50 million people annually. Infection with any of the four dengue serotypes induces protective immunity to that serotype, but does not confer long-term protection against infection by other serotypes. The immunological interactions between serotypes are of central importance in understanding epidemiological dynamics and anticipating the impact of dengue vaccines. We analysed a 38-year time series with 12 197 serotyped dengue infections from a hospital in Bangkok, Thailand. Using novel mechanistic models to represent different hypothesized immune interactions between serotypes, we found strong evidence that infection with dengue provides substantial short-term cross-protection against other serotypes (approx. 1–3 years). This is the first quantitative evidence that short-term cross-protection exists since human experimental infection studies performed in the 1950s. These findings will impact strategies for designing dengue vaccine studies, future multi-strain modelling efforts, and our understanding of evolutionary pressures in multi-strain disease systems.

New insights into the immunopathology and control of dengue virus infection

Abstract: Dengue virus poses a major threat to global public health: two-thirds of the world's population is now at risk from infection by this mosquito-borne virus. Dengue virus causes a range of diseases with a small proportion of infected patients developing severe plasma leakage that leads to dengue shock syndrome, organ impairment and bleeding. Infection with one of the four viral serotypes results in the development of homotypic immunity to that serotype. However, subsequent infection with a different serotype is associated with an increased risk of developing severe disease, which has led to the suggestion that severe disease is triggered by immunopathology. This Review outlines recent advances in the understanding of immunopathology, vaccine development and human monoclonal antibodies produced against dengue virus.

Global Situation of Dengue and Dengue Haemorrhagic Fever, and Its Emergence in the Americas

Abstract: About two-thirds of the world's population live in areas infested with dengue vectors, mainly Aedes aegypti. All four dengue viruses are circulating, sometimes simultaneously, in most of these areas. It is estimated that up to 80 million persons become infected annually although marked underreporting results in the notification of much smaller figures. Currently dengue is endemic in all continents except Europe and epidemic dengue haemorrhagic fever (DHF) occurs in Asia, the Americas and some Pacific islands. The incidence of DHF is much greater in the Asian countries than in other regions. In Asian countries the disease continues to affect children predominantly although a marked increase in the number of DHF cases in people over 15 years old has been observed in the Philippines and Malaysia during recent years. In the 1990's DHF has continued to show a higher incidence in South-East Asia, particularly in Viet Nam and Thailand which together account for more than two-thirds of the DHF cases reported in Asia. However, an increase in the number of reported cases has been noted in the Philippines, Lao People's Democratic Republic, Cambodia, Myanmar, Malaysia, India, Singapore and Sri Lanka during the period 1991-1995 as compared to the preceding 5-year period. In the Americas, the emergence of epidemic DHF occurred in 1981 almost 30 years after its appearance in Asia, and its incidence is showing a marked upward trend. In 1981 Cuba reported the first major outbreak of DHF in the Americas, during which a total of 344,203 cases of dengue were notified, including 10,312 severe cases and 158 deaths. The DHF Cuban epidemic was associated with a strain of dengue-2 virus and it occurred four years after dengue-1 had been introduced in the island causing epidemics of dengue fever. Prior to this event suspected cases of DHF or fatal dengue cases had been reported by five countries but only a few of them fulfilled the WHO criteria for diagnosis of DHF. The outbreak in Cuba is the most important event in the history of dengue in the Americas. Subsequently to it, in every year except 1983, confirmed or suspected cases of DHF have been reported in the Region. The second major outbreak in the Americas occurred in Venezuela in 1989 and since then this country has suffered epidemics of DHF every year. Between 1981 and 1996 a total of 42,246 cases of DHF and 582 deaths were reported by 25 countries in the Americas, 53% of which originated from Venezuela and 24% from Cuba. Colombia, Nicaragua and Mexico have each reported over 1,000 cases during the period 1992-1996. About 74% of the Colombian cases and 97% of the Mexican cases were reported during 1995-1996. A main cause of the emergence of DHF in the Americas was the failure of the hemispheric campaign to eradicate Aedes aegypti. Following a successful period that resulted in the elimination of the mosquito from 18 countries by 1962, the programme began to decline and as a result there was a progressive dissemination of the vector so that by 1997 with the exception of Canada, Chile and Bermuda, all countries in the Americas are infested. Other factors contributing to the emergence/re-emergence of dengue/DHF include the rapid growth and urbanization of populations in Latin America and the Caribbean, and increased travel of persons which facilitates dissemination of dengue viruses. Presently, all four dengue serotypes are circulating in the Americas, thus increasing the risk for DHF in this region.

Protection of Mice Against Dengue 2 Virus Encephalitis by Immunization with the Dengue 2 Virus Non-structural Glycoprotein NS1

Abstract: Summary Immunization of mice with the dengue 2 virus (DEN 2)-specified non-structural protein NS1 provided significant protection against intracerebral challenge with the virus in the absence of detectable neutralizing or other anti-virion antibody. NS1, purified from lysates of infected Vero cells by immunoaffinity chromatography, expressed an antigenic site(s) common to each of the four DEN serotypes, and hyperimmunization of rabbits with NS1 stimulated production of complement-fixing (CF) antibody with broad DEN serotype specificity. However, cross-protection was not observed: mice immunized with DEN 2 NS1 developed little or no heterologous CF antibody and were not protected against challenge with neurovirulent DEN 1. Induction of a protective immune response by NS1 suggests that it be considered for incorporation into possible synthetic or recombinant DNA DEN vaccines.

Recognition determinants of broadly neutralizing human antibodies against dengue viruses

Abstract: Dengue disease is caused by four different flavivirus serotypes, which infect 390 million people yearly with 25% symptomatic cases and for which no licensed vaccine is available. Recent phase III vaccine trials showed partial protection, and in particular no protection for dengue virus serotype 2 (refs 3, 4). Structural studies so far have characterized only epitopes recognized by serotype-specific human antibodies. We recently isolated human antibodies potently neutralizing all four dengue virus serotypes. Here we describe the X-ray structures of four of these broadly neutralizing antibodies in complex with the envelope glycoprotein E from dengue virus serotype 2, revealing that the recognition determinants are at a serotype-invariant site at the E-dimer interface, including the exposed main chain of the E fusion loop and the two conserved glycan chains. This 'E-dimer-dependent epitope' is also the binding site for the viral glycoprotein prM during virus maturation in the secretory pathway of the infected cell, explaining its conservation across serotypes and highlighting an Achilles' heel of the virus with respect to antibody neutralization. These findings will be instrumental for devising novel immunogens to protect simultaneously against all four serotypes of dengue virus.