[Exanthema after dengue vaccine (TAK003): first data of passive surveillance in a private vaccination center in Argentina]. / Exantema luego de la aplicación de la vacuna para dengue (TAK003): primeros datos de vigilancia pasiva en un centro de vacunación privado de Argentina.

INTRODUCTION: The tetravalent live virus vaccine developed by Takeda called Qdenga® is available in Argentina and approved for use from 4 years of age without age limit. The objective was to describe clinical characteristics and evolution of the initial reports of rash after the first dose. MATERIAL AND METHODS: The records of Events Supposedly Attributable to Vaccination or Immunization Reported in a Private Vaccination Center were reviewed between 15/11/2023 and 12/12/2023. Cases with skin rash that occurred outside the application site area were included. The main variables analyzed were age, sex, history of dengue, characteristics of the skin rash, accompanying symptoms, time elapsed from vaccination to the onset of the rash and evolution. The incidence of rash was calculated: cases/10,000 vaccinated. RESULTS: Out of 12 551 doses applied, 15 cases were included. Median age: 35 years, female sex: 8/15. Clinical forms of presentation: generalized micropapular (3/15), maculopapular (3/15), scarlatiniform (1/15), urticarian (1/15), multiform (1/15), erythematous in the face (1/15) and unspecified (5/15). Most common concomitant symptoms: pruritus (5/15), fever or low-grade fever (6/15), headache (3/15), retro-ocular pain (2/15), asthenia (2/15). Three cases reported a history of dengue. The median number of days of rash presentation was 8 days' postvaccination. All patients progressed favorably. The overall incidence was 1.2/1000 vaccinated. CONCLUSIONS: In passive surveillance, after more than 12 000 first doses administered, the presence of rash was observed in less than 0.12% of those vaccinated. Everyone evolved favorably.

Introducción: La vacuna tetravalente a virus vivos del laboratorio Takeda, denominada Qdenga®, está disponible en Argentina y aprobada para su uso a partir de los 4 años sin límite de edad. El objetivo fue describir las características clínicas y evolución de los primeros reportes de exantema post primera dosis. Material y métodos: Se revisaron los registros de los Eventos Supuestamente Atribuidos a la Vacunación e Inmunización reportados en los Centros Vacunar entre el 15/11/2023 al 12/12/2023. Se incluyeron los casos con exantema cutáneo que se presentaron fuera del área del sitio de aplicación. Las principales variables analizadas fueron edad, sexo, antecedente de dengue, características del exantema cutáneo, síntomas acompañantes, tiempo transcurrido desde la vacunación al inicio del exantema y evolución. Se calculó la incidencia del exantema: casos/1000 vacunados. Resultados: Sobre 12551 dosis aplicadas se incluyeron 15 casos. Mediana de edad: 35 años, sexo femenino: 8/15. Formas clínicas de presentación: generalizado micropapular (3/15), maculopapular (3/15), escarlatiniforme (1/15), urticariano (1/15), multiforme (1/15), eritematoso en cara (1/15) y sin especificar (5/15). Síntomas concomitantes más frecuentes: prurito (5/15), fiebre o febrícula (6/15), cefalea (3/15), dolor retro ocular (2/15), astenia (2/15). Tres casos refirieron antecedente de dengue. La mediana de días de presentación del exantema fue de 8 días post vacunación. Todos los pacientes evolucionaron favorablemente. La incidencia fue de 1.2/1000 vacunados. Conclusiones: En la vigilancia pasiva, luego de más de 12 000 primeras dosis administradas, se observó la presencia de exantema en menos del 0.12% de los vacunados. Todos evolucionaron favorablemente.

A single-dose circular RNA vaccine prevents Zika virus infection without enhancing dengue severity in mice.

Antibody-dependent enhancement (ADE) is a potential concern for the development of Zika virus (ZIKV) vaccines. Cross-reactive but poorly neutralizing antibodies, usually targeting viral pre-membrane or envelope (E) proteins, can potentially enhance dengue virus (DENV) infection. Although E domain III (EDIII) contains ZIKV-specific epitopes, its immunogenicity is poor. Here, we show that dimeric EDIII, fused to human IgG1 Fc fragment (EDIII-Fc) and encoded by circular RNA (circRNA), induces better germinal center reactions and higher neutralizing antibodies compared to circRNAs encoding monomeric or trimeric EDIII. Two doses of circRNAs encoding EDIII-Fc and ZIKV nonstructural protein NS1, another protective antigen, prevent lethal ZIKV infection in neonates born to immunized C57BL/6 mice and in interferon-α/ß receptor knockout adult C57BL/6 mice. Importantly, a single-dose optimized circRNA vaccine with improved antigen expression confers potent and durable protection without inducing obvious DENV ADE in mice, laying the groundwork for developing flavivirus vaccines based on circRNAs encoding EDIII-Fc and NS1.

Dengue is a product of the environment: an approach to the impacts of the environment on the Aedes aegypti mosquito and disease cases.

Dengue is an arbovirus infection whose etiologic agent is transmitted by the Aedes aegypti mosquito. Since the early 1980s, when the circulation of the dengue virus (DENV) was confirmed in Brazil, the disease has become a growing multifactorial public health problem. This article presented the main factors that have contributed to the frequent dengue epidemics in recent years, such as the behavior of the vector, climate change, and social, political, and economic aspects. The intersection between these different factors in the dynamics of the disease is highlighted, including the increase in the mosquito population due to higher temperatures and rainy periods, as well as the influence of socioeconomic conditions on the incidence of dengue. Some mosquito control strategies are also addressed, including the use of innovative technologies such as drones and the Wolbachia bacterium, as well as the hope represented by the dengue vaccine. Nevertheless, the need for integrated and effective public policies to reduce social inequalities and the impacts of climate change on the spread of dengue is emphasized.

A mixed method evaluation of knowledge, attitude and practice on dengue fever among Lalitpur Metropolitan City residents: a cross-sectional investigation.

BACKGROUND: Dengue poses a significant global public health challenge, including in Nepal. Understanding community's knowledge, attitudes, and behaviors concerning dengue fever is imperative to developing effective prevention and control strategies. This study aimed to assess the knowledge, attitude, and practices related to dengue fever among residents of Lalitpur Metropolitan City. METHODS: A descriptive cross-sectional household study was conducted using a mixed-method approach, which included quantitatively studying 636 individuals and conducting 20 qualitative interviews. The data was collected between April 2023 and June 2023. The multistage cluster sampling method was applied for household selection during the quantitative study and a purposive judgmental sampling method was used to identify participants for the qualitative interviews. Face-to-face interviews were conducted using a structured questionnaire for the quantitative study and an interview guide for the qualitative study. Quantitative data were analysed using logistic regression in STATA version 13, and thematic analysis was applied to the qualitative data. The findings were validated through triangulation of results from both the qualitative and quantitative study. RESULTS: Regarding knowledge, 64.94% (n = 413/636) reported being informed about dengue fever. In terms of attitude, a substantial majority, 91.51% (n = 582/636), expressed a positive attitudes toward dengue fever, indicating a favorable perception and knowledge of its significance. Concerning practice, 49.84% (n = 317/636) of respondents reported actively engaging in dengue fever prevention measures. The variables gender, previous history of dengue fever and residency were the determinants of dengue fever knowledge. Additionally, gender, residency, and attitude were predictors of preventive practices concerning dengue fever. CONCLUSION: Our study revealed that while the community demonstrated good knowledge of dengue fever and positive attitudes toward prevention, their preventive practices were inconsistent, indicating a gap between knowledge and action. A positive attitude was linked to better adherence to preventive measures. To address this gap, it is crucial to promote a positive attitude toward dengue prevention through initiatives like education efforts and social mobilization programs. Implementing Social and Behavior Change Communication (SBCC) programs focused on dengue prevention and control measures can help bridge this knowledge-action gap.

Vaccination against dengue fever for travellers.

Dengue fever, endemic to most tropical and subtropical countries, is a major cause of illness in travellers, but severe dengue, hospitalisation and death are considered rare in this population. Two vaccines against dengue fever, Dengvaxia® and Qdenga®, are available. While there is no recommendation for the use of Dengvaxia® in travellers, Qdenga® has been licensed for travellers in many European countries since December 2022, most recently (29 July 2024) in Switzerland by Swissmedic. The Swiss Expert Committee for Travel Medicine (ECTM), having assessed available data on the Qdenga® vaccine, issues the following recommendations: (1) Vaccination against dengue fever virus with Qdenga® is not recommended for persons with no previous dengue fever infection. (2) Vaccination with Qdenga® may be recommended for travellers aged 6 years and older who have evidence of previous dengue infection, defined as (a) a laboratory-confirmed dengue infection (PCR, antigen or seroconversion) or (b) a compatible history of dengue infection with a positive IgG serological test AND expected exposure to a region with significant dengue transmission. Travel medicine advisors should provide clear information in accessible language on the complexity of dengue vaccines and the risk/benefit evaluation for their use in travellers.

[The dengue vaccine: a major scientific challenge and a public health issue]. / Le vaccin contre la dengue - Un défi scientifique majeur et un enjeu de santé publique.

Almost half of the world's population is exposed to the risk of transmission of the four dengue virus serotypes (DENV 1-4), by mosquitoes of the genus Aedes. A dengue vaccine is effective if it induces prolonged protective immunity against all circulating viral strains, irrespective of the age and infection history of the vaccinated subject. An effective vaccine strategy against dengue is based on the injection of live attenuated viruses in a tetravalent formulation. In this review, we present the most promising candidate vaccines against dengue, their successes and also the questions raised by the correlates of protection that have been adopted to assess their level of effectiveness against the disease.

Title: Le vaccin contre la dengue - Un défi scientifique majeur et un enjeu de santé publique. Abstract: Près de la moitié de la population mondiale est exposée au risque de transmission des quatre sérotypes du virus de la dengue par les moustiques hématophages du genre Aedes. Pour être efficace, un vaccin contre la dengue doit induire une immunité protectrice prolongée contre l'ensemble des souches virales circulantes, et cela, indépendamment de l'âge et de l'historique d'infection du sujet vacciné. Une stratégie vaccinale performante contre la dengue repose sur l'injection de virus vivants atténués selon une formulation tétravalente. Dans cette revue, nous présentons les principaux candidats vaccins contre la dengue les plus aboutis, leur réussite mais aussi les interrogations suscitées au regard des corrélats de protection qui ont été adoptés nécessaires à l'évaluation de leur efficacité protectrice contre la maladie.

Zika virus T-cell based 704/DNA vaccine promotes protection from Zika virus infection in the absence of neutralizing antibodies.

Zika virus (ZIKV) and dengue virus (DENV) are closely related flaviviruses co-circulating in the same endemic areas. Infection can raise cross-reactive antibodies that can be either protective or increase risk of severe disease, depending on the infection sequence, DENV serotype and elapsed time between infection. On the contrast, T cell-mediated immunity against DENV and ZIKV is considered protective. Therefore, we have developed a T cell vaccine enriched in immunodominant T cell epitopes derived from ZIKV and evaluated its immunogenicity and efficacy against ZIKV and DENV infection. Mice were vaccinated using DNA vaccine platform using the tetrafunctional amphiphilic block copolymer 704. We show that vaccination of 2 different HLA class I transgenic mice with the ZIKV non-structural (NS) poly-epitope elicits T cell response against numerous ZIKV epitopes. Moreover, vaccination induces a significant protection against ZIKV infection, in the absence of neutralizing or enhancing antibodies against ZIKV. However, vaccination does not induce a significant protection against DENV2. In contrast, immunization with a DENV1-NS poly-epitope induces a significant protection against both DENV1 and DENV2, in the absence of humoral immunity. Taken together, we have shown that T-cell based vaccination could protect against multiple flavivirus infections and could overcome the complexity of antibody-mediated enhancement.

DENV Peptides Delivered as Spherical Nucleic Acid Constructs Enhance Antigen Presentation and Immunogenicity in vitro and in vivo.

Background: The global prevalence of Dengue virus (DENV) infection poses a significant health risk, urging the need for effective vaccinations. Peptide vaccines, known for their capacity to induce comprehensive immunity against multiple virus serotypes, offer promise due to their stability, safety, and design flexibility. Spherical nucleic acid (SNA), particularly those with gold nanoparticle cores, present an attractive avenue for enhancing peptide vaccine efficacy due to their modularity and immunomodulatory properties. Methods: The spherical nucleic acid-TBB (SNA-TBB), a novel nanovaccine construct, was fabricated through the co-functionalization process of SNA with epitope peptide, targeting all four serotypes of the DENV. This innovative approach aims to enhance immunogenicity and provide broad-spectrum protection against DENV infections. The physicochemical properties of SNA-TBB were characterized using dynamic light scattering, zeta potential measurement, and transmission electron microscopy. In vitro assessments included endocytosis studies, cytotoxicity evaluation, bone marrow-dendritic cells (BMDCs) maturation and activation analysis, cytokine detection, RNA sequencing, and transcript level analysis in BMDCs. In vivo immunization studies in mice involved evaluating IgG antibody titers, serum protection against DENV infection and safety assessment of nanovaccines. Results: SNA-TBB demonstrated successful synthesis, enhanced endocytosis, and favorable physicochemical properties. In vitro assessments revealed no cytotoxicity and promoted BMDCs maturation. Cytokine analyses exhibited heightened IL-12p70, TNF-α, and IL-1ß levels. Transcriptomic analysis highlighted genes linked to BMDCs maturation and immune responses. In vivo studies immunization with SNA-TBB resulted in elevated antigen-specific IgG antibody levels and conferred protection against DENV infection in neonatal mice. Evaluation of in vivo safety showed no signs of adverse effects in vital organs. Conclusion: The study demonstrates the successful development of SNA-TBB as a promising nanovaccine platform against DENV infection and highlights the potential of SNA-based peptide vaccines as a strategy for developing safe and effective antiviral immunotherapy.

Impact of storm drains on the maintenance of dengue endemicity in Presidente Prudente, São Paulo, Brazil: a geospatial and epidemiologic approach.

Introduction: Dengue is a public health challenge worldwide. Brazil registered about 70% of cases in Latin America in 2023; in 2024, the country is experiencing an unprecedented increase in the number of infected individuals. By May 2024, more than 4 million people were infected. Our goal was to: (1) determine the epidemiology of dengue cases and their spatiotemporal distribution and (2) carry out a survey of the storm drains and through a geospatial analysis to determine their possible correlation with cases of dengue in Presidente Prudente, São Paulo, Brazil. Methods: Cases and information on the habitat of mosquito in the storm drain underground drainage system from 2020 to 2021 were obtained from public agencies. Larvae, pupae, and Ae. aegypti were identified according to species and described in taxonomic keys. Kernel density maps were constructed. Results: From 1996 to 2023, the prevalence of cases peaked in 2016 and 2019, and in 2023 reached alarming levels, and the city was considered hyperendemic. In 2021, 2,609 cases were registered with 2 clusters of high density. Of 5,492 storm drains analyzed, 18.0% were found to have water, 9.0% had larvae or pupae of Aedes aegypti and 91.0% were classified as dirty or damaged. A direct correlation between the kernel layer of cases in 2021 with the kernel layer of storm drains containing water (r = 0.651) and larvae and pupae (r = 0.576) was found, suggesting that storm drains are risk factors and have an impact on the maintenance of dengue endemicity. The high number of damaged units found demonstrated the lack of storm drain management, compromising the urban drainage system and possibly contributing to dengue outbreaks. Conclusion: Policymakers may use these findings to improve existing dengue control strategies focusing on the control of storm drains and increase local and global perspectives on reducing dengue outbreaks.

Progress and challenges in development of animal models for dengue virus infection.

ABSTRACTThe severity of the dengue epidemic is on the rise, with its geographic range had expanded to southern Europe by 2024. In this August, the WHO updated the pathogens that could spark the next pandemic, dengue virus was on the list. Vaccines and drugs serve as powerful tools for both preventing dengue infections and treating patients. Animal models play a pivotal role in vaccine development and drug screening. Available potential susceptible animals, including non-human primates, rodents, pigs, and tree shrews, have been extensively explored to establish animal models of dengue disease. Despite significant advancements, there are still notable limitations. Different animal models exhibit distinct constraining factors such as viraemia, host susceptibility, immune function of the host, clinical symptoms, ADE (antibody-dependent enhancement) phenomena, cytokine storm response to various serotypes and strain variations. Furthermore, despite extensive research on the dengue virus receptor in recent years, genetically modified animal models immunocompetent harbouring dengue virus susceptibility receptors have not yet been available. This work reviewed the research progress of dengue virus receptors and dengue animal models, suggesting that the development of genetically modified murine models expressing dengue virus functional receptors may hold a promise for future dengue disease research, especially for its vaccine development.

The greatest Dengue epidemic in Brazil: Surveillance, Prevention, and Control.

In this review, we discuss dengue surveillance, prevention, and control measures in Brazil. Data on dengue epidemics between 2000 and 2024 indicates an increase in the number of dengue cases and deaths. Global climate change is a key driver of this growth. Over the past 25 years, nearly 18 million Brazilians have been infected with the dengue virus, and the highest number of dengue cases in Brazil's history is projected to reach 2024. Dengue mortality in Brazil increased geographically over time. As of June, there were approximately 6 million probable cases and 4,000 confirmed deaths in Brazil, which represents the greatest dengue epidemic to date. Several technologies have been developed to control Aedes aegypti, including the deployment of Wolbachia-infected mosquitoes, indoor residual spraying, sterile insect techniques, and mosquito-disseminated insecticides. The Ministry of Health recommends integrating these technologies into health services. Brazil is the first country to incorporate the Takeda vaccine into its public health system, and the Butantan vaccine is currently undergoing Phase 3 clinical trials. Increasing the vaccination coverage and implementing novel Ae. aegypti control technologies could reduce the number of dengue cases in Brazil in the coming years. Community activities such as home cleaning and elimination of potential mosquito breeding sites, facilitated by social media and health education initiatives, must continue to achieve this reduction. Ultimately, a multisectoral approach encompassing sanitary improvements, mosquito control, vaccination, and community mobilization is crucial in the fight against dengue epidemics.

Current status of the sterile insect technique for the suppression of mosquito populations on a global scale.

BACKGROUND: The World Health Organization (WHO) has emphasized the urgent need for alternative strategies to chemical insecticides for controlling mosquito populations, particularly the invasive Aedes species, which are known vectors of arboviruses. Among these alternative approaches, the sterile insect technique (SIT) is experiencing rapid development, with numerous pilot trials being conducted worldwide. MAIN TEXT: This review aims to elucidate the principles of SIT and highlight the significant recent advancements that have facilitated its scalability. I also employ a phased conditional approach to categorize the progression of 39 projects, drawing on peer reviewed studies, press releases and direct communication with project managers. This review indicates that a substantial number of projects illustrate the efficacy of SIT in suppressing Aedes populations, with one project even demonstrating a reduction in dengue incidence. I offer several recommendations to mitigate potential failures and address the challenges of compensation and overcompensation when implementing SIT field trials. Furthermore, I examine the potential implications of male mating harassment on the effectiveness of SIT in reducing disease transmission. CONCLUSIONS: This comprehensive assessment underscores the promise of SIT as a viable strategy for mosquito control. The insights gained from these trials not only contribute to the understanding of SIT's effectiveness but also highlight the importance of careful project management and ecological considerations in the pursuit of public health objectives.

Pre-vax metabolic clues: Cracking the code to a better dengue vaccine.

Multi-omic analysis deciphers the impact of cell-intrinsic and systemic metabolomes on dengue vaccination immunogenicity.

Estimating dengue disease and economic burden to inform municipal-level policymakers: Method for a pragmatic city-level observational cohort study.

Background: Recent trials have confirmed the effectiveness of promising dengue control technologies - two vaccines and Wolbachia. These would generally be applied at the municipal level. To help local officials decide which, if any, control strategy to implement, they need affordable, timely, and accurate data on dengue burden. Building on our previous work in Mexico, Indonesia, and Thailand, we developed a streamlined prospective method to estimate dengue burden at the municipal level quickly, accurately, and efficiently. Methods: The method entails enrolling and repeatedly interviewing 100 patients with laboratory-confirmed dengue. They will be selected after screening and testing about 1,000 patients with clinical dengue. The method will capture both acute and chronic effects relating to disease, economic burden, and psychological impacts (presenteeism). The total time requirements are 1.5 years, comprised of 0.25 years for planning and approvals, 1 year for data collection (a full dengue cycle), and 0 .25 years for data cleaning and analysis. A collaboration with municipal and academic colleagues in the city of Semarang, Central Java, Indonesia shows how the method could be readily applied in Indonesia's eighth largest city (population 1.8 million). Conclusions: Many surveillance studies gather only information on numbers of cases. This proposed method will provide a comprehensive picture of the dengue burden to the health system, payers, and households at the local level.

Gut symbiont-derived sphingosine modulates vector competence in Aedes mosquitoes.

The main vectors of Zika virus (ZIKV) and dengue virus (DENV) are Aedes aegypti and Ae. albopictus, with Ae. aegypti being more competent. However, the underlying mechanisms remain unclear. Here, we find Ae. albopictus shows comparable vector competence to ZIKV/DENV with Ae. aegypti by blood-feeding after antibiotic treatment or intrathoracic injection. This suggests that midgut microbiota can influence vector competence. Enterobacter hormaechei_B17 (Eh_B17) is isolated from field-collected Ae. albopictus and conferred resistance to ZIKV/DENV infection in Ae. aegypti after gut-transplantation. Sphingosine, a metabolite secreted by Eh_B17, effectively suppresses ZIKV infection in both Ae. aegypti and cell cultures by blocking viral entry during the fusion step, with an IC50 of approximately 10 µM. A field survey reveals that Eh_B17 preferentially colonizes Ae. albopictus compared to Ae. aegypti. And field Ae. albopictus positive for Eh_B17 are more resistant to ZIKV infection. These findings underscore the potential of gut symbiotic bacteria, such as Eh_B17, to modulate the arbovirus vector competence of Aedes mosquitoes. As a natural antiviral agent, Eh_B17 holds promise as a potential candidate for blocking ZIKV/DENV transmission.

The Citizen as a Public Health Actor: Complaints as Public Engagement with Aedes Mosquito Control in Singapore, 1965-1985.

In 1986, the World Health Organization heralded Singapore as a model for the control of dengue fever, a viral disease spread by the Aedes aegypti mosquito. Between 1965 and 1985, public health officials successfully employed educational campaigns and mandatory home inspections to convince citizens to guard against mosquito breeding at home. Although this story appears to recapitulate standard narratives of top-down progress in Singapore, this paper argues that the significant role of the public in public health has been overlooked. Citizens complained frequently, sometimes publicly, to public health authorities and often compelled direct responses from them. Through these complaints, citizens modified official anti-mosquito measures and expanded the reach of public health. Public health in Singapore thus appears not simply as the imposition of an autonomous state's vision onto a docile or even resistant citizenry but as a coevolution of the state and the public.

Dengue virus and the 2024 Paris Olympics.

The 2024 Paris Olympics and Paralympics face concerns over dengue virus transmission, despite Paris's lower mosquito activity. Preventive measures include eliminating breeding sites, insecticide spraying, and public awareness. Health systems will monitor and respond to cases. Large gatherings like the Olympics can amplify disease spread, as seen with Zika in Rio 2016. Recent reports confirm dengue presence in Europe, highlighting global risks. While Paris's overall dengue risk is low, even a few cases could impact global health. Collaboration among health authorities, researchers, and event organizers is crucial to ensure participant and public safety during the games.