Dengue virus

About: Dengue virus is a research topic. Over the lifetime, 12671 publications have been published within this topic receiving 461406 citations. The topic is also known as: DENV.

A prospective study of dengue infections in Bangkok.

Abstract: Dengue infections were prospectively studied among 4- to 16-year-old students at a Bangkok school. Blood samples were obtained from 1,757 students in June 1980, before the dengue season, and in January 1981, after the season, and tested for dengue antibodies by the hemagglutination inhibition method. Classrooms were monitored daily for school absences. Fifty percent of the children had antibodies to, and were presumably immune to, at least 1 dengue serotype by the age of 7 years. Most (90/103, 87%) students who became infected by dengue viruses during the study period were either asymptomatic or minimally symptomatic (absent only 1 day). Most (7/13, 53%) of the symptomatic dengue infections (absent with fever for greater than or equal to 2 days) were clinically recognized as cases of dengue hemorrhagic fever which required hospitalization. None of 47 primary dengue infections required hospitalization, whereas 7 of 56 secondary infections did (P = 0.012). Preexistent dengue immunity, as detected by conventional serologic techniques, was a significant (odds ratio greater than or equal to 6.5) risk factor for development of dengue hemorrhagic fever.

Efficacy of a Tetravalent Dengue Vaccine in Children in Latin America

Abstract: Background In light of the increasing rate of dengue infections throughout the world despite vector-control measures, several dengue vaccine candidates are in development. Methods In a phase 3 efficacy trial of a tetravalent dengue vaccine in five Latin American countries where dengue is endemic, we randomly assigned healthy children between the ages of 9 and 16 years in a 2:1 ratio to receive three injections of recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV) or placebo at months 0, 6, and 12 under blinded conditions. The children were then followed for 25 months. The primary outcome was vaccine efficacy against symptomatic, virologically confirmed dengue (VCD), regardless of disease severity or serotype, occurring more than 28 days after the third injection. Results A total of 20,869 healthy children received either vaccine or placebo. At baseline, 79.4% of an immunogenicity subgroup of 1944 children had seropositive status for one or more dengue serotypes. In the per-protocol population, there were 176 VCD cases (with 11,793 person-years at risk) in the vaccine group and 221 VCD cases (with 5809 person-years at risk) in the control group, for a vaccine efficacy of 60.8% (95% confidence interval [CI], 52.0 to 68.0). In the intention-to-treat population (those who received at least one injection), vaccine efficacy was 64.7% (95% CI, 58.7 to 69.8). Serotype-specific vaccine efficacy was 50.3% for serotype 1, 42.3% for serotype 2, 74.0% for serotype 3, and 77.7% for serotype 4. Among the severe VCD cases, 1 of 12 was in the vaccine group, for an intention-to-treat vaccine efficacy of 95.5%. Vaccine efficacy against hospitalization for dengue was 80.3%. The safety profile for the CYD-TDV vaccine was similar to that for placebo, with no marked difference in rates of adverse events. Conclusions The CYD-TDV dengue vaccine was efficacious against VCD and severe VCD and led to fewer hospitalizations for VCD in five Latin American countries where dengue is endemic. (Funded by Sanofi Pasteur; ClinicalTrials.gov number, NCT01374516.)

Cross-Reacting Antibodies Enhance Dengue Virus Infection in Humans

Abstract: Dengue virus co-circulates as four serotypes, and sequential infections with more than one serotype are common. One hypothesis for the increased severity seen in secondary infections is antibody-dependent enhancement (ADE) leading to increased replication in Fc receptor-bearing cells. In this study, we have generated a panel of human monoclonal antibodies to dengue virus. Antibodies to the structural precursor-membrane protein (prM) form a major component of the response. These antibodies are highly cross-reactive among the dengue virus serotypes and, even at high concentrations, do not neutralize infection but potently promote ADE. We propose that the partial cleavage of prM from the viral surface reduces the density of antigen available for viral neutralization, leaving dengue viruses susceptible to ADE by antibody to prM, a finding that has implications for future vaccine design.

Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with zika virus

Abstract: Zika virus (ZIKV) was discovered in 1947 and was thought to lead to relatively mild disease. The recent explosive outbreak of ZIKV in South America has led to widespread concern, with reports of neurological sequelae ranging from Guillain Barre syndrome to microcephaly. ZIKV infection has occurred in areas previously exposed to dengue virus (DENV), a flavivirus closely related to ZIKV. Here we investigated the serological cross-reaction between the two viruses. Plasma immune to DENV showed substantial cross-reaction to ZIKV and was able to drive antibody-dependent enhancement (ADE) of ZIKV infection. Using a panel of human monoclonal antibodies (mAbs) to DENV, we showed that most antibodies that reacted to DENV envelope protein also reacted to ZIKV. Antibodies to linear epitopes, including the immunodominant fusion-loop epitope, were able to bind ZIKV but were unable to neutralize the virus and instead promoted ADE. Our data indicate that immunity to DENV might drive greater ZIKV replication and have clear implications for disease pathogenesis and future vaccine programs for ZIKV and DENV.

Dengue: the risk to developed and developing countries

Abstract: Dengue viruses are members of the Flaviviridae, transmitted principally in a cycle involving humans and mosquito vectors. In the last 20 years the incidence of dengue fever epidemics has increased and hyperendemic transmission has been established over a geographically expanding area. A severe form, dengue hemorrhagic fever (DHF), is an immunopathologic disease occurring in persons who experience sequential dengue infections. The risk of sequential infections, and consequently the incidence of DHF, has risen dramatically, first in Asia and now in the Americas. At the root of the emergence of dengue as a major health problem are changes in human demography and behavior, leading to unchecked populations of and increased exposure to the principal domestic mosquito vector, Aedes aegypti. Virus-specified factors also influence the epidemiology of dengue. Speculations on future events in the epidemiology, evolution, and biological expression of dengue are presented.