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Journal of Infection and Public Health Oct 2023Dengue is caused by the dengue virus (DENVs) infection and clinical manifestations include dengue fever (DF), dengue hemorrhagic fever (DHF), or dengue shock syndrome...
Dengue is caused by the dengue virus (DENVs) infection and clinical manifestations include dengue fever (DF), dengue hemorrhagic fever (DHF), or dengue shock syndrome (DSS). Due to a lack of antiviral drugs and effective vaccines, several therapeutic and control strategies have been proposed. A systemic literature review was conducted according to PRISMA guidelines to select proper references to give an overview of DENV infection. Results indicate that understanding the virus characteristics and epidemiology are essential to gain the basic and clinical knowledge as well as dengue disseminated pattern and status. Different factors and mechanisms are thought to be involved in the presentation of DHF and DSS, including antibody-dependent enhancement, immune dysregulation, viral virulence, host genetic susceptibility, and preexisting dengue antibodies. This study suggests that dissecting pathogenesis and risk factors as well as developing different types of therapeutic and control strategies against DENV infection are urgently needed.
Topics: Humans; Antiviral Agents; Dengue; Genetic Predisposition to Disease; Risk Factors; Virulence
PubMed: 37595484
DOI: 10.1016/j.jiph.2023.08.001 -
Global Heart 2023Dengue is a viral disease transmitted by the bite of a female arthropod, prevalent primarily in tropical and subtropical regions. Its manifestations include asymptomatic... (Review)
Review
Dengue is a viral disease transmitted by the bite of a female arthropod, prevalent primarily in tropical and subtropical regions. Its manifestations include asymptomatic infections, dengue fever, and a severe form called or . Atypical manifestations can also occur, called . We describe the case of a 43-year-old man with an unusual presentation of dengue, demonstrating a workup suggestive of myocardial and pericardial damage. Symptoms and markers indicative of cardiac compromise improved after five days on anti-inflammatory treatment. Dengue myocarditis is considered an uncommon complication of dengue, although its reported incidence is likely an underestimation. In general, most cases of dengue myocarditis are self-limited, with only a minority at risk of progressing to heart failure. In order to improve recognition and prevent progression, healthcare providers should maintain a high degree of suspicion regarding potential cardiac complications in patients with dengue.
Topics: Male; Humans; Female; Adult; Myocarditis; Dengue; Severe Dengue; Heart Diseases; Heart Failure
PubMed: 37547170
DOI: 10.5334/gh.1254 -
Travel Medicine and Infectious Disease 2023Qdenga® has been approved by the European Medicines Agency (EMA) for individuals > 4 years of age and for use according to national recommendations. The vaccine shows...
Qdenga® has been approved by the European Medicines Agency (EMA) for individuals > 4 years of age and for use according to national recommendations. The vaccine shows high efficacy against virologically confirmed dengue and severe dengue in clinical studies on 4-16-year old's living in endemic areas. For individuals 16-60 years old only serological data exists and there is no data for individuals > 60 years. Its use as a travel vaccine is still unclear. We present the studies behind the approval and the recommendations for travelers as issued by the Swedish Society for Infectious Diseases Physicians.
Topics: Humans; Adolescent; Young Adult; Adult; Middle Aged; Child, Preschool; Child; Dengue; Travel; Dengue Vaccines; Sweden
PubMed: 37271201
DOI: 10.1016/j.tmaid.2023.102598 -
Frontiers in Immunology 2023Dengue is the most common viral infection spread by mosquitoes, prevalent in tropical countries. The acute dengue virus (DENV) infection is a benign and primarily... (Review)
Review
Dengue is the most common viral infection spread by mosquitoes, prevalent in tropical countries. The acute dengue virus (DENV) infection is a benign and primarily febrile illness. However, secondary infection with alternative serotypes can worsen the condition, leading to severe and potentially fatal dengue. The antibody raised by the vaccine or the primary infections are frequently cross-reactive; however, weakly neutralizing, and during subsequent infection, they may increase the odds of antibody-dependent enhancement (ADE). Despite that, many neutralizing antibodies have been identified against the DENV, which are thought to be useful in reducing dengue severity. Indeed, an antibody must be free from ADE for therapeutic application, as it is pretty common in dengue infection and escalates disease severity. Therefore, this review has described the critical characteristics of DENV and the potential immune targets in general. The primary emphasis is given to the envelope protein of DENV, where potential epitopes targeted for generating serotype-specific and cross-reactive antibodies have critically been described. In addition, a novel class of highly neutralizing antibodies targeted to the quaternary structure, similar to viral particles, has also been described. Lastly, we have discussed different aspects of the pathogenesis and ADE, which would provide significant insights into developing safe and effective antibody therapeutics and equivalent protein subunit vaccines.
Topics: Animals; Dengue Virus; Antibodies, Viral; Antibody-Dependent Enhancement; Antibodies, Neutralizing; Dengue
PubMed: 37334355
DOI: 10.3389/fimmu.2023.1200195 -
Acta Medica Portuguesa Feb 2024Dengue is a vector-borne disease that has a significant impact on global public health. The vector mosquito belongs to the genus Aedes. Two species play a key role in... (Review)
Review
Dengue is a vector-borne disease that has a significant impact on global public health. The vector mosquito belongs to the genus Aedes. Two species play a key role in human transmission: Ae. aegypti, which has adapted to the urban environment of highly populated areas in tropical and subtropical countries, leading to a dramatic increase in dengue cases over the years, and Ae. albopictus, which poses a potential threat to temperate climate countries due to its ability to adapt to colder climates. The disease is widespread across the world, posing a risk to nearly half of the world's population. Although most cases are asymptomatic, dengue causes a burden on healthcare systems and mainly affects the younger population. The disease is also spreading to temperate climate countries, thus becoming a global threat. Vector control measures and vaccine development have been the main prevention strategies, as there is still no effective treatment for the disease.
Topics: Animals; Humans; Dengue; Dengue Virus; Mosquito Vectors; Aedes
PubMed: 38309298
DOI: 10.20344/amp.20569 -
Medicina 2024
Topics: Humans; Dengue; Dengue Virus
PubMed: 38683527
DOI: No ID Found -
The Lancet. Global Health Feb 2024About half of the world's population lives in dengue-endemic areas. We aimed to evaluate the long-term efficacy and safety of two doses of the tetravalent dengue vaccine... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
About half of the world's population lives in dengue-endemic areas. We aimed to evaluate the long-term efficacy and safety of two doses of the tetravalent dengue vaccine TAK-003 in preventing symptomatic dengue disease of any severity and due to any dengue virus (DENV) serotypes in children and adolescents.
METHODS
In this ongoing double-blind, randomised, placebo-controlled trial, we enrolled healthy participants aged 4-16 years at 26 medical and research centres across eight dengue-endemic countries (Brazil, Colombia, Dominican Republic, Nicaragua, Panama, Philippines, Sri Lanka, and Thailand). The main exclusion criteria were febrile illness (body temperature ≥38°C) at the time of randomisation, hypersensitivity or allergy to any of the vaccine components, pregnancy or breastfeeding, serious chronic or progressive disease, impaired or altered immune function, and previous receipt of a dengue vaccine. Participants were randomly assigned 2:1 (stratified by age and region) using an interactive web response system and dynamic block assignment to receive two subcutaneous doses of TAK-003 or placebo 3 months apart. Investigators, participants, and their parents or legal guardians were blinded to group assignments. Active febrile illness surveillance and RT-PCR testing of febrile illness episodes were performed for identification of virologically confirmed dengue. Efficacy outcomes were assessed in the safety analysis set (all randomly assigned participants who received ≥1 dose) and the per protocol set (all participants who had no major protocol violations), and included cumulative vaccine efficacy from first vaccination to approximately 4·5 years after the second vaccination. Serious adverse events were monitored throughout. This study is registered with ClinicalTrials.gov, NCT02747927.
FINDINGS
Between Sept 7, 2016, and March 31, 2017, 20 099 participants were randomly assigned (TAK-003, n=13 401; placebo, n=6698). 20 071 participants (10 142 [50·5%] males; 9929 [49·5%] females; safety set) received TAK-003 or placebo, with 18 257 (91·0%) completing approximately 4·5 years of follow-up after the second vaccination (TAK-003, 12 177/13 380; placebo, 6080/6687). Overall, 1007 (placebo: 560; TAK-003: 447) of 27 684 febrile illnesses reported were virologically confirmed dengue, with 188 cases (placebo: 142; TAK-003: 46) requiring hospitalisation. Cumulative vaccine efficacy was 61·2% (95% CI 56·0-65·8) against virologically confirmed dengue and 84·1% (77·8-88·6) against hospitalised virologically confirmed dengue; corresponding efficacies were 53·5% (41·6-62·9) and 79·3% (63·5-88·2) in baseline seronegative participants (safety set). In an exploratory analysis, vaccine efficacy was shown against all four serotypes in baseline seropositive participants. In baseline seronegative participants, vaccine efficacy was shown against DENV-1 and DENV-2 but was not observed against DENV-3 and low incidence precluded evaluation against DENV-4. During part 3 of the trial (approximately 22-57 months after the first vaccination), serious adverse events were reported for 664 (5·0%) of 13 380 TAK-003 recipients and 396 (5·9%) of 6687 placebo recipients; 17 deaths (6 in the placebo group and 11 in the TAK-003 group) were reported, none were considered study-vaccine related.
INTERPRETATION
TAK-003 demonstrated long-term efficacy and safety against all four DENV serotypes in previously exposed individuals and against DENV-1 and DENV-2 in dengue-naive individuals.
FUNDING
Takeda Vaccines.
TRANSLATIONS
For the Portuguese, Spanish translations and plain language summary of the abstract see Supplementary Materials section.
Topics: Adolescent; Child; Female; Humans; Male; Dengue; Dengue Vaccines; Dengue Virus; Double-Blind Method; Hypersensitivity; Vaccination; Child, Preschool
PubMed: 38245116
DOI: 10.1016/S2214-109X(23)00522-3 -
Proceedings of the National Academy of... Jun 2023Dengue virus (DENV) is the most important human virus transmitted by mosquitos. Dengue pathogenesis is characterized by a large induction of proinflammatory cytokines....
Dengue virus (DENV) is the most important human virus transmitted by mosquitos. Dengue pathogenesis is characterized by a large induction of proinflammatory cytokines. This cytokine induction varies among the four DENV serotypes (DENV1 to 4) and poses a challenge for live DENV vaccine design. Here, we identify a viral mechanism to limit NF-κB activation and cytokine secretion by the DENV protein NS5. Using proteomics, we found that NS5 binds and degrades the host protein ERC1 to antagonize NF-κB activation, limit proinflammatory cytokine secretion, and reduce cell migration. We found that ERC1 degradation involves unique properties of the methyltransferase domain of NS5 that are not conserved among the four DENV serotypes. By obtaining chimeric DENV2 and DENV4 viruses, we map the residues in NS5 for ERC1 degradation, and generate recombinant DENVs exchanging serotype properties by single amino acid substitutions. This work uncovers a function of the viral protein NS5 to limit cytokine production, critical to dengue pathogenesis. Importantly, the information provided about the serotype-specific mechanism for counteracting the antiviral response can be applied to improve live attenuated vaccines.
Topics: Humans; Cytokines; Dengue; Dengue Virus; NF-kappa B; Serogroup; Viral Nonstructural Proteins
PubMed: 37252973
DOI: 10.1073/pnas.2220005120 -
ELife Feb 2024Understanding the kinetics of dengue viruses in the bloodstream can provide insights into the clinical outcomes of the disease.
Understanding the kinetics of dengue viruses in the bloodstream can provide insights into the clinical outcomes of the disease.
Topics: Humans; Dengue; Dengue Virus; Viremia; Kinetics; Antibodies, Viral
PubMed: 38357933
DOI: 10.7554/eLife.96018 -
Human Vaccines & Immunotherapeutics Aug 2023Dengue is caused by a mosquito-transmitted flavivirus. The disease is now endemic to many tropical and subtropical regions, manifesting as approximately 96 million...
An open-label, Phase 3 trial of TAK-003, a live attenuated dengue tetravalent vaccine, in healthy US adults: immunogenicity and safety when administered during the second half of a 24-month shelf-life.
Dengue is caused by a mosquito-transmitted flavivirus. The disease is now endemic to many tropical and subtropical regions, manifesting as approximately 96 million symptomatic cases of dengue each year. Clinical trials have shown TAK-003 (Qdenga®), a live attenuated dengue tetravalent vaccine, to be well-tolerated, immunogenic, and efficacious in adults with no prior exposure to dengue virus infection living in non-endemic regions, as well as in adults and children living in dengue-endemic areas. This open-label, single-arm phase 3 trial (NCT03771963) was conducted in two dengue non-endemic areas of the USA, and it evaluated the immunogenicity and safety of naturally-aged TAK-003 administered to adult participants. Overall, the immunogenicity data from this trial are consistent with those reported from other TAK-003 phase 2 and 3 trials, and the safety data are consistent with the broader integrated safety data analysis. The data show that naturally-aged TAK-003 had a well-tolerated reactogenicity and adverse events profile when administered in the second half of its clinical 24-month shelf-life and that it still elicited an immune response that persisted up to 6 months after the second dose against all four dengue serotypes, with no important safety risks identified during the trial.
Topics: Child; Adult; Humans; Aged; Dengue; Dengue Vaccines; Dengue Virus; Vaccines, Attenuated; Vaccines, Combined; Antibodies, Viral; Immunogenicity, Vaccine
PubMed: 37846724
DOI: 10.1080/21645515.2023.2254964