Dengue

The purpose of this study is to characterize the effect on dengue viral load, fever clearance time as well as on clinical signs and symptoms with the treatment of EYU688 compared with placebo in patients with dengue fever.

Background: Dengue is a viral disease spread by mosquitoes. Most people bitten by mosquitoes carrying dengue viruses do not get sick, but severe cases can cause shock, internal bleeding, and death. There are no treatments for dengue. To develop treatments, researchers need to understand more about what dengue viruses do in the body. Objective: To infect healthy people with a mild dengue virus to study how their body responds. Eligibility: People ages 18 to 50 years with or without a history of dengue virus infection. Design: Participants will be screened. They will have a physical exam with blood tests. The tests will show whether they have ever been infected with dengue or related viruses in the past. At their first study visit, participants will receive an injection of dengue virus into the arm. The injected virus is weaker than the natural virus, so any symptoms should be milder. Participants will have a total of 11 study visits over 6 months; 8 of those visits will be in the first month. Blood will be drawn at each visit. Some visits will include ultrasound exams of their internal organs. They will discuss any symptoms they are having. Any rashes they develop may be photographed. Two procedures are optional: Participants may have up to 5 lymph node aspirations and 3 bone marrow biopsies during the study. For both procedures, a needle will be inserted into the tissues to draw out immune cells. Two more visits are optional: 1 visit up to 2 months before receiving the virus, for lymph node or bone marrow samples, and 1 about a year after for a blood draw.

Dengue infections are imposing an increasing global burden of disease, particularly in tropical countries such as Bangladesh. The World Health Organization (WHO) has identified Dengue virus as a priority pathogen for the development of medical counter measures because of the high risk of it causing a Public Health Emergency of Intenational Concern (PHEIC). Warning signs for severe dengue, associated with mortality, include gastrointestinal features including abdominal pain, vomiting, and diarrhoea. Multiple alterations may occur in in the gastrointestinal tract that could lead to damaging of the gastrointestinal wall and gut leakage, the translocation of gut metabolites into the bloodstream. Study team hypothesize that gut leakage initiates inflammatory processes underlying the further development of severe dengue, including features associated with plasma leakage. This study aims to investigate intestinal barrier dysfunction (gut leakage) in dengue infection by detecting the translocation of gut-derived bacteria and their products (Lipopolysaccharides, LPS binding protein, sCD14, I-Fatty Acid Binding Protein) into the bloodstream. Study team will recruit hospitalized adult dengue patients (18 years and older) presenting with warning signs or severe disease in a tertiary care public hospital at Chattogram, Bangladesh. Circulating biomarkers indicative of gut permeability and microbial translocation will be measured to assess their presence and association with disease severity. Abdominal ultrasonography will be performed to characterize gastrointestinal alterations and determine their correlation with biochemical markers of gut leakage and clinical severity. In addition, study team will analyze the gut bacteriome from stool/ rectal swab of these patients to explore whether dengue infection induces compositional changes in intestinal microbiota and whether such alterations are linked to gut leakage or disease progression.

The goal of this study is to evaluate the efficacy and safety of emetine administered orally for symptomatic patients aged 18-65 years infected with the dengue virus. The main questions it aims to answer are: 1. Does emetine reduce 28-day mortality or progression to severe dengue (severe plasma leakage, severe bleeding, or severe organ involvement)? 2. What are the safety outcomes of emetine, including serious adverse events and toxicities? Participants will be asked to: 1. Take either 6mg emetine, 12mg emetine, or a placebo pill for 7 consecutive days as part of the treatment regimen. 2. Have blood samples taken for at least 5 days to monitor viral load, inflammatory markers, and safety parameters. 3. Be monitored by healthcare staff for daily vital signs and symptoms for clinical assessments for 28 days.

This randomized, controlled, double blind trial aims at assessing the safety and immunogenicity profiles of the co-administered Live Attenuated Dengue and Chikungunya vaccines comparatively to the isolated administration, in the adult population aged 18 to 59 years without prior exposure to either arbovirus.

This is a randomized, double-blind (60 -79 years) and open-label (40-59 years), three-arm parallel Phase 3b, multicenter study to evaluate the safety and non-inferiority of the humoral immune response of the Butantan Dengue vaccine (Dengue 1,2,3,4 (attenuated)) in participants aged 60 -79 years (elderly) compared to participants aged 40 to 59 years (adults), with or without previous dengue and healthy based on clinical examination.

This is a randomized, double-blind, placebo-controlled Phase 2/3 study to evaluate the efficacy, safety, and antiviral activity of CP-COV03 in adult patients with dengue infection.

Introduction: Dengue and Chikungunya arboviral diseases are considered major public health challenges in tropical regions due to high infection rates and the occurrence of musculoskeletal sequelae that impair strength, balance, and functionality. After the acute phase, symptoms such as fatigue, joint pain, muscle weakness, and postural instability are common, reducing quality of life and hindering social and occupational reintegration.Objective: To analyze the effects of a rehabilitation protocol on muscle fatigue, muscle strength, and postural control in post-Dengue and Chikungunya patients.Methods: This is a non-randomized clinical trial conducted at the Integrated Laboratory for Research and Care in Infectious and Sequelae Diseases (LabDIS/UEPA). Individuals of both sexes, aged over 18 years, with a confirmed diagnosis of Dengue and/or Chikungunya within the last five years will be included. Data collection will include a clinical interview, surface electromyography of the flexor carpi radialis, tibialis anterior, lateral and medial gastrocnemius muscles, hydraulic and electronic dynamometry, manovacuometry, and baropodometry. The rehabilitation protocol will consist of twenty supervised sessions of aerobic, anaerobic, and respiratory exercises.Expected Results: Improvements in muscle strength, muscle fatigue, and postural control are expected following the intervention.Conclusion: The findings may support physiotherapeutic strategies aimed at improving strength, fatigue, and balance, expanding knowledge on the neuromuscular and respiratory consequences of arboviral diseases, and contributing to the development of evidence-based rehabilitation protocols, with potential positive impacts on healthcare delivery and public health policies.

This is a randomized, open-label adaptive platform trial aiming to screen the antiviral effectiveness of the experimental drug(s) in early dengue infection * Primary objectives: * To determine the antiviral effectiveness of the experimental drug(s) in early dengue infection * To assess the safety and tolerability of the experimental drug(s) in dengue patients * Secondary objective: * To assess the effect of the experimental drug(s) in dengue patients on physiological, clinical and virological parameters

The purpose of this multi-site, factorial randomised, platform trial is to evaluate host-directed therapeutic agents in patients hospitalised with moderate and severe dengue virus infection. Our primary aim is to find safe and affordable therapeutics which prevent disease progression among those at high risk for severe dengue, and improve outcomes for those with established severe disease, thereby also reducing the substantial burden placed on health systems in dengue endemic regions.

This study aims to conduct a safe human infection challenge using an attenuated serotype DEN3 dengue virus in adult volunteers. The clinical, viral and immune response characteristics of the model will be analysed to understand the pathophysiology of dengue fever. This data will be used to inform future studies, including a planned follow up study (DEN-CHIM-02) which will investigate the efficacy of an investigational dengue vaccine at protecting against DEN3 infection. Study conditions that result in a safe, reproducible infection in ≥80% of research participants (attack rate) with the DEN3 challenge agent have been identified during studies conducted by our collaborators in the US. This includes the inoculum dose, safety monitoring, and necessary participant pre-screening to exclude prior Orthoflavivrus infection or vaccinations. Study objectives are to: 1. Establish in seronegative volunteers in Singapore a safe DENV controlled human infection (CHI) model, with an infection rate of ≥80%, suitable for future studies of interventions. 2. Characterise the clinical, haematological and virological response following controlled inoculation of the attenuated DEN3 challenge agent. 3. Conduct deep immunophenotyping to understand the cellular, humoral and innate immune response to dengue infection. 4. Explore the longitudinal immune response in the 3 years after challenge, including following subsequent dengue vaccination.

RACSMEI addresses the high burden of infectious diseases in low- and middle-income countries, including Cambodia, where limited surveillance and laboratory capacity often obscure etiologies and transmission dynamics. This knowledge gap hinders the design of effective prevention and control strategies. RACSMEI will improve understanding across multiple pathogens using a multidisciplinary One Health approach. We will answer key questions on burden, ecology, transmission and population immune status to inform targeted and culturally appropriate interventions. The project combines a nationally representative One Health survey, social-science methods, and multiplex, diverse diagnostics to efficiently test for 57 priority pathogens, including zoonotic and vector-borne agents, vaccine-preventable and elimination-targeted diseases, enteric, respiratory, and environmentally transmitted pathogens and selected neglected tropical diseases and parasites relevant to Cambodia. Mathematical modelling will reconstruct and forecast transmission dynamics and assess the potential impact of future public-health strategies. By integrating intersectoral data and innovative methods, RACSMEI will generate actionable evidence for public-health authorities, support precision One Health interventions, and help reduce disease burden in affected communities. The project also aims to ensure the transferability of methods and insights to other countries facing similar challenges.

The objective of this study is to collect well-characterized serum and plasma specimens from confirmed dengue positive and dengue negative subjects to support dengue diagnostic products development.

This 3-year prospective observational study aims to identify clinical and laboratory risk factors associated with hospitalization in patients with confirmed dengue virus infection. It also seeks to analyze real-world transfusion practices and their outcomes. The study will be conducted in a second-level hospital in northern Mexico and will follow patients from emergency department entry to clinical resolution or hospital discharge.

The goal of this research study is to help the investigators better understand serious dengue disease. The investigators will collect clinical information and up to four blood samples from participants with dengue, sepsis, or healthy people. The investigators will perform multiple analyses on the blood samples and compare results between dengue patients and those with sepsis and healthy people.

The goal of this clinical trial is to learn if drug montelukast works to treat dengue in adults. It will also learn about the safety of drug montelukast . The main questions it aims to answer are: Does drug montelukast lower the incidence of liver enzyme elevations in participants ? What medical problems do participants have when taking drug montelukast ?

The goal of this cluster randomized controlled trial is to evaluate the effect of health education interventions on the score of the knowledge, attitudes, and practices (KAP) of dengue in in primary and middle school students in the city of Guangzhou and Foshan in China. Individuals aged 6 to 15 years who are in grades 1-9 in primary schools in Guangzhou and Foshan will be enrolled. 20 primary schools will be randomly selected, with half designated as intervention group schools and the remaining half as control group schools. The intervention group will receive a health education intervention focused on dengue prevention every semester for 6 months, while the control group will continue with their routine school health education for 6 months. Researchers will compare the differences in the score of the KAP of dengue between the intervention and control groups after 6 months to see if health education can improve knowledge, attitudes and practices of dengue among primary and middle school students.

rDEN2Δ30-7169 is a dengue challenge strain that previously reports its viremia induction effect in participants with minimal symptoms in US flavivirus naïve participants. Moreover, preliminary result of five Thai dengue naïve participants from previous project (registered number NCT05476757) demonstrated 100% viremia status without severe adverse event after 60 days post-virus challenge. However, result from previous project may not fully represent the clinical manifestation and immunological responses of major population of endemic areas, where most people in endemic area have dengue immune status. Therefore, this controlled human infection model protocol proposes to challenge the attenuated virus in 12 dengue-immune participants recruited from Bangkok metropolitan area, Thailand. We aim to assess the safety, viremia, NS1 antigenemia profile, and immunogenicity of the challenge virus in the dengue immune participants. After finish safety assessment, all participants will be vaccinated with a full course of dengue vaccines to prevent recurrent dengue infection. Immunological responses after vaccination will be also evaluated the vaccine efficacy. Our expected outcomes are all participants present viremia profiles after virus challenge without serious adverse events (SAE). The exploratory profiles include assesment of immune profiles and parameters comparison with the other dengue challenge study.

This randomized controlled trial aims to evaluate the efficacy of Wolbachia-infected male mosquitoes combined with sterile insect technique (IIT-SIT) to mitigate active dengue transmission in Singapore.

Dengue fever, an arbovirus transmitted by the Aedes mosquito, is a public health problem in all tropical and subtropical regions of the world. There is currently no antiviral treatment and vector control has shown its limits. The 2018 European marketing authorization of the tetravalent chimeric yellow fever / dengue vaccine (Dengvaxia®) is a major step forward in the fight against the disease. Dengvaxia® is indicated for the prevention of dengue due to serotypes DENV 1-4 in subjects aged 9 to 45 years with a history of infection with the dengue virus and living in endemic areas (seroprevalence of at least 70% in the target population). Dengue seroprevalence data in the French Caribbean territories of Martinique and Guadeloupe dates back to 2011 and concerns only adult blood donors aged 18 to 70 years. To date, no data exists for individuals aged 9 to 17 years in the region. In order to implement an optimal vaccine introduction strategy for these territories, the main aim of the DengueSEA study is to estimate the seroprevalence of the Dengue viruses (DENV 1-4) in 9-17 year olds giving a blood sample as part of care in hospital departments of the French Caribbean islands of Martinique and Guadeloupe.

It is not known whether there is a different clinical profile of dengue in patients with immune system dysfunction. Preliminary data and previous literature suggest that autoimmune diseases, and in particular their treatment, may favour the evolution to severe forms of dengue. Our research hypothesis is that the clinico-biological presentation of dengue might be different in case of autoimmune disease, either on the side of overactivation (autoimmune and auto inflammatory diseases without treatment) or immunodepression (autoimmune and auto inflammatory diseases under immunosuppressive treatment).