Big Data-Planetary Health approach for evaluating the Brazilian Dengue Control Program.

OBJECTIVE: This study aims to integrate the concepts of planetary health and big data into the Donabedian model to evaluate the Brazilian dengue control program in the state of São Paulo. METHODS: Data science methods were used to integrate and analyze dengue-related data, adding context to the structure and outcome components of the Donabedian model. This data, considering the period from 2010 to 2019, was collected from sources such as Department of Informatics of the Unified Health System (DATASUS), the Brazilian Institute of Geography and Statistics (IBGE), WorldClim, and MapBiomas. These data were integrated into a Data Warehouse. K-means algorithm was used to identify groups with similar contexts. Then, statistical analyses and spatial visualizations of the groups were performed, considering socioeconomic and demographic variables, soil, health structure, and dengue cases. OUTCOMES: Using climate variables, the K-means algorithm identified four groups of municipalities with similar characteristics. The comparison of their indicators revealed certain patterns in the municipalities with the worst performance in terms of dengue case outcomes. Although presenting better economic conditions, these municipalities held a lower average number of community healthcare agents and basic health units per inhabitant. Thus, economic conditions did not reflect better health structure among the three studied indicators. Another characteristic of these municipalities is urbanization. The worst performing municipalities presented a higher rate of urban population and human activity related to urbanization. CONCLUSIONS: This methodology identified important deficiencies in the implementation of the dengue control program in the state of São Paulo. The integration of several databases and the use of Data Science methods allowed the evaluation of the program on a large scale, considering the context in which activities are conducted. These data can be used by the public administration to plan actions and invest according to the deficiencies of each location.

A naturally isolated symbiotic bacterium suppresses flavivirus transmission by Aedes mosquitoes.

The commensal microbiota of the mosquito gut plays a complex role in determining the vector competence for arboviruses. In this study, we identified a bacterium from the gut of field Aedes albopictus mosquitoes named Rosenbergiella sp. YN46 (Rosenbergiella_YN46) that rendered mosquitoes refractory to infection with dengue and Zika viruses. Inoculation of 1.6 × 103 colony forming units (CFUs) of Rosenbergiella_YN46 into A. albopictus mosquitoes effectively prevents viral infection. Mechanistically, this bacterium secretes glucose dehydrogenase (RyGDH), which acidifies the gut lumen of fed mosquitoes, causing irreversible conformational changes in the flavivirus envelope protein that prevent viral entry into cells. In semifield conditions, Rosenbergiella_YN46 exhibits effective transstadial transmission in field mosquitoes, which blocks transmission of dengue virus by newly emerged adult mosquitoes. The prevalence of Rosenbergiella_YN46 is greater in mosquitoes from low-dengue areas (52.9 to ~91.7%) than in those from dengue-endemic regions (0 to ~6.7%). Rosenbergiella_YN46 may offer an effective and safe lead for flavivirus biocontrol.

Seroprevalence of dengue, Japanese encephalitis and Zika among long-term expatriates in Thailand.

BACKGROUND: Travel to Southeast Asia increases the likelihood of acquiring mosquito-borne Flavivirus infections such as dengue (DENV), Japanese encephalitis (JEV) and Zika viruses (ZIKV). Expatriates are long-term travellers who have a higher risk of mosquito-borne illness at their destination country. The purpose of this study was to evaluate the seroprevalence of DENV, JEV and ZIKV infections and the determinants contributing to seropositivity among expatriates living in Thailand. METHODS: A cross-sectional study was performed from December 2017 to February 2020. Expatriates from non-Flavivirus endemic countries were recruited. 5 mL of blood was collected for DENV 1-4, JEV and ZIKV antibody testing by plaque reduction neutralization test (PRNT50). Individuals with vaccination histories or diagnoses for dengue, Japanese encephalitis, yellow fever and tick-borne encephalitis were excluded. RESULTS: Among 254 participants, most participants (83.1%) were male, the mean age was 65 years and the median duration of stay in Thailand was 6 years. Seroprevalence rate of any Flavivirus, non-specific DENV, DENV1-4, JEV and ZIKV were 34.3, 30.7, 20.5, 18.1, 18.9, 10.6, 4.7 and 2.8%, respectively. The presence of neutralizing antibodies against DENV1-4 positively correlates with the duration of stay in Thailand. DENV seropositivity was associated with living in urban areas (aOR 2.75, 95% CI 1.36-5.57). Expatriates were unlikely to have detectable anti-JEV antibodies regardless of time spent in a JEV-endemic area. No risk factors were identified that were significantly associated with JEV or ZIKV seropositivity. Only 48.4% received pre-travel counselling services, while only 18.9% visited a travel medicine specialist. CONCLUSIONS: A high proportion (34.3%) of long-term expatriates living in Thailand were seropositive for flavivirus, mainly from dengue (30.7%). To minimize risk, travel medicine practitioners should provide adequate pre-travel health risk information on mosquito-borne flavivirus infection and offer advice on mosquito bite prevention strategies. Dengue vaccine might be considered in high-risk travellers such as long-term expatriate.

Anti-dengue potential and mosquitocidal effect of marine green algae-stabilized Mn-doped superparamagnetic iron oxide nanoparticles (Mn-SPIONs): an eco-friendly approach.

Vector-borne diseases pose a significant public health challenge in economically disadvantaged nations. Malaria, dengue fever, chikungunya, Zika, yellow fever, Japanese encephalitis, and lymphatic filariasis are spread by mosquitoes. Consequently, the most effective method of preventing these diseases is to eliminate the mosquito population. Historically, the majority of control programs have depended on chemical pesticides, including organochlorines, organophosphates, carbamates, and pyrethroids. Synthetic insecticides used to eradicate pests have the potential to contaminate groundwater, surface water, beneficial soil organisms, and non-target species. Nanotechnology is an innovative technology that has the potential to be used in insect control with great precision. The goal of this study was to test the in vitro anti-dengue potential and mosquitocidal activity of Chaetomorpha aerea and C. aerea-synthesized Mn-doped superparamagnetic iron oxide nanoparticles (CA-Mn-SPIONs). The synthesis of CA-Mn-SPIONs using C. aerea extract was verified by the observable alteration in the colour of the reaction mixture, transitioning from a pale green colour to a brown. The study of UV-Vis spectra revealed absorbance peaks at approximately 290 nm, which can be attributed to the surface Plasmon resonance of the CA-Mn-SPIONs. The SEM, TEM, EDX, FTIR, vibrating sample magnetometry, and XRD analyses provided evidence that confirmed the presence of CA-Mn-SPIONs. In the present study, results revealed that C. aerea aqueous extract LC50 values against Ae. aegypti ranged from 222.942 (first instar larvae) to 349.877 ppm in bioassays (pupae). CA-Mn-SPIONs had LC50 ranging from 20.199 (first instar larvae) to 26.918 ppm (pupae). After treatment with 40 ppm CA-Mn-SPIONs and 500 ppm C. aerea extract in ovicidal tests, egg hatchability was lowered by 100%. Oviposition deterrence experiments showed that in Ae. aegypti, oviposition rates were lowered by more than 66% by 100 ppm of green algal extract and by more than 71% by 10 ppm of CA-Mn-SPIONs (oviposition activity index values were 0.50 and 0.55, respectively). Moreover, in vitro anti-dengue activity of CA-Mn-SPIONs has good anti-viral property against dengue viral cell lines. In addition, GC-MS analysis showed that 21 intriguing chemicals were discovered. Two significant phytoconstituents in the methanol extract of C. aerea include butanoic acid and palmitic acid. These two substances were examined using an in silico methodology against the NS5 methyltransferase protein and demonstrated good glide scores and binding affinities. Finally, we looked into the morphological damage and fluorescent emission of third instar Ae. aegypti larvae treated with CA-Mn-SPIONs. Fluorescent emission is consistent with ROS formation of CA-Mn-SPIONs against Ae. aegypti larvae. The present study determines that the key variables for the successful development of new insecticidal agents are rooted in the eco-compatibility and the provision of alternative tool for the pesticide manufacturing sector.

Safety and immunogenicity of a synthetic nanoparticle-based, T cell priming peptide vaccine against dengue in healthy adults in Switzerland: a double-blind, randomized, vehicle-controlled, phase 1 study.

BACKGROUND: Vaccines that minimize the risk of vaccine-induced antibody-dependent enhancement and severe dengue are needed to address the global health threat posed by dengue. This study assessed the safety and immunogenicity of a gold nanoparticle (GNP)-based, multi-valent, synthetic peptide dengue vaccine candidate (PepGNP-Dengue), designed to provide protective CD8+ T cell immunity, without inducing antibodies. METHODS: In this randomized, double-blind, vehicle-controlled, phase 1 trial (NCT04935801), healthy naïve individuals aged 18-45 years recruited at the Centre for primary care and public health, Lausanne, Switzerland, were randomly assigned to receive PepGNP-Dengue or comparator (GNP without peptides [vehicle-GNP]). Randomization was stratified into four groups (low dose [LD] and high dose [HD]), allocation was double-blind from participants and investigators. Two doses were administered by intradermal microneedle injection 21 days apart. Primary outcome was safety, secondary outcome immunogenicity. Analysis was by intention-to-treat for safety, intention-to-treat and per protocol for immunogenicity. FINDINGS: 26 participants were enrolled (August-September 2021) to receive PepGNP-Dengue (LD or HD, n = 10 each) or vehicle-GNP (LD or HD, n = 3 each). No vaccine-related serious adverse events occurred. Most (90%) related adverse events were mild; injection site pain and transient discoloration were most frequently reported. Injection site erythema occurred in 58% of participants. As expected, PepGNP-Dengue did not elicit anti-DENV antibodies of significance. Significant increases were observed in specific CD8+ T cells and dengue dextramer+ memory cell subsets in the LD PepGNP-Dengue but not in the HD PepGNP-Dengue or vehicle-GNP groups, specifically PepGNP-activated CD137+CD69+CD8+ T cells (day 90, +0.0318%, 95% CI: 0.0088-0.1723, p = 0.046), differentiated effector memory (TemRA) and central memory (Tcm) CD8+ T cells (day 35, +0.8/105 CD8+, 95% CI: 0.19-5.13, p = 0.014 and +1.34/105 CD8+, 95% CI: 0.1-7.34, p = 0.024, respectively). INTERPRETATION: Results provide proof of concept that a synthetic nanoparticle-based peptide vaccine can successfully induce virus-specific CD8+ T cells. The favourable safety profile and cellular responses observed support further development of PepGNP-Dengue. FUNDING: Emergex Vaccines Holding Limited.

Linear epitope mapping in the E and NS1 proteins of dengue and Zika viruses: Prospection of peptides for vaccines and diagnostics.

The arrival of the Zika virus (ZIKV) in dengue virus (DENV)-endemic areas has posed challenges for both differential diagnosis and vaccine development. Peptides have shown promise in addressing these issues. The aim of this study was to identify the linear epitope profile recognized by serum samples from dengue and Zika patients in the E and NS1 proteins of DENV and ZIKV. This cross-sectional study included individuals of all ages with laboratory-confirmed DENV and ZIKV infections, who were selected through convenience sampling. The serum samples from dengue and Zika patients detected epitopes evenly distributed across the viral proteins in a peptide microarray platform. However, several epitopes were located within "epitope hotspots", characterized by clusters of peptides recognized in more than 30% of the sub-arrays analyzed using individual or pooled serum samples. The serum samples from dengue and Zika patients showed a high level of cross-reactivity with peptides in the DENV and ZIKV proteins. Analysis using an additional peptide microarray platform, which contained peptides selected based on the results of the initial screening, revealed that two DENV and one ZIKV peptide, highly specific to their related viruses, were located within the epitope hotspots; however, they presented low detection rates (32.5, 35.0, and 28.6%, respectively). In addition, two DENV peptides detected at similarly high rates by both dengue and Zika patients were also found within the epitope hotspots. These hotspots contain several immunodominant epitopes that are recognized by a larger number of individuals when compared to 15-amino acid (aa) sequence peptides. Thus, epitope hotspots may have greater potential to serve as antigens in diagnostic tests and vaccine development than peptides composed of only 15 amino acids.

Computer-aided Affinity Enhancement of a Cross-reactive Antibody against Dengue Virus Envelope Domain III.

The dengue virus (DENV), composed of four distinct but serologically related Flaviviruses, causes the most important emerging viral disease, with nearly 400 million infections yearly. Currently, there are no approved therapies. Although DENV infection induces lifelong immunity against the same serotype, the antibodies raised contribute to severe disease in heterotypic infections. Therefore, understanding the mechanism of DENV neutralization by antibodies is crucial in the design of vaccines against all serotypes. This study reports a comparative structural and energetic analysis of the monoclonal antibody (mAb) 4E11 in complex with its target domain III of the envelope protein for all four DENV serotypes. We use extensive replica molecular dynamics simulations in conjunction with the binding free energy calculations. Further single point and double mutations were designed through computational site-directed mutagenesis and observed that the re-engineered antibody exhibits high affinity to binding and broadly neutralizing activity against serotypes. Our results showed improved binding affinity by the gain of enthalpy, which could be attributed to the stabilization of salt-bridge and hydrogen bond interactions at the antigen-antibody interface. The findings provide valuable results in understanding the structural dynamics and energetic contributions that will be helpful to the design of high-affinity antibodies against dengue infections.

Hydration and clinical warning signs of dengue fever in primary care: An observational prospective study.

OBJECTIVES: Dengue fever is an arbovirosis expanding worldwide, for which hydration has been reported to reduce the risk of hospitalization. Our objective was to estimate the volume of hydration in Reunionese patients with dengue. METHODS: A prospective observational study included patients presenting with a 'dengue-like' syndrome in ambulatory care. General practitioners recruited patients during consultation, and beverage consumption over the previous 24 hours was reported at two different times. Warning signs were defined according to the 2009 WHO guidelines. RESULTS: GPs included 174 patients from April to July 2019. Average oral hydration volume was 1863 mL and 1944 mL, at the 1st and 2nd medical consultations, respectively. Water was the most wide consumed liquid. Drinking at least 5 glasses of liquid was significantly associated with fewer clinical warning signs at the 1st medical consultation (p = 0.044). CONCLUSIONS: Sufficient hydration volume could prevent dengue warning signs. Further studies with standardized measurement of hydration would be needed.

Mimotope discovery as a tool to design a vaccine against Zika and dengue viruses.

Vaccine development against dengue virus is challenging because of the antibody-dependent enhancement of infection (ADE), which causes severe disease. Consecutive infections by Zika (ZIKV) and/or dengue viruses (DENV), or vaccination can predispose to ADE. Current vaccines and vaccine candidates contain the complete envelope viral protein, with epitopes that can raise antibodies causing ADE. We used the envelope dimer epitope (EDE), which induces neutralizing antibodies that do not elicit ADE, to design a vaccine against both flaviviruses. However, EDE is a discontinuous quaternary epitope that cannot be isolated from the E protein without other epitopes. Utilizing phage display, we selected three peptides that mimic the EDE. Free mimotopes were disordered and did not elicit an immune response. After their display on adeno-associated virus (AAV) capsids (VLP), they recovered their structure and were recognized by an EDE-specific antibody. Characterization by cryo-EM and enzyme-linked immunosorbent assay confirmed the correct display of a mimotope on the surface of the AAV VLP and its recognition by the specific antibody. Immunization with the AAV VLP displaying one of the mimotopes induced antibodies that recognized ZIKV and DENV. This work provides the basis for developing a Zika and dengue virus vaccine candidate that will not induce ADE.

Dengue en Barbosa (Santander, Colombia): conocimientos, actitudes y prácticas en la comunidad / Dengue in Barbosa (Santander, Colombia): knowledge, attitudes, and practices in the community

Introducción: El dengue es considerado un problema de la salud pública con un comportamiento endémico-epidémico en Colombia, por lo cual los programas de vigilancia epidemiológica se enfocan en la prevención y control. Objetivo: Evaluar la comprensión y el comportamiento de la población del municipio de Barbosa (Santander, Colombia) acerca del virus del dengue y el vector por medio de un instrumento de conocimientos, actitudes y prácticas (CAP). Métodos: Se realizó un estudio transversal analítico en el que participaron 93 habitantes del municipio de Barbosa, seleccionados por un muestreo no probabilístico por conveniencia. Se empleó un instrumento de CAP validado. La información fue sistematizada y analizada en el programa SPSS v. 26.0. Resultados: El 78,5 por cientode los encuestados mostraron conocimientos deficientes con un puntaje obtenido inferior a 70 puntos. El 73,1 por ciento de los habitantes presentó actitudes negativas con un resultado igual o inferior a 24 puntos. El 67,7 por ciento de la población presentó buenas prácticas, con un resultado mayor o igual a 14 puntos. Se evidencia que, a menor edad, son mayores las actitudes desfavorables frente a la infección por dengue (OR 2,67 IC 95 por ciento 1,03-7,1). Conclusiones: Educar a la población de manera más efectiva acerca de los conocimientos básicos sobre el dengue sigue siendo una estrategia necesaria, además de crear conciencia de que las prácticas en el hogar se deben ejecutar con la finalidad de eliminar el vector y no solo como mecanismo de limpieza. Se deben implementar diferentes estrategias comunicativas para educar a los ciudadanos en este sentido(AU)

Introduction: Dengue is considered a public health problem with endemic-epidemic behavior in Colombia; therefore, epidemiological surveillance programs are aimed at its prevention and control. Objective: To evaluate the understanding and behavior of the population from the municipality of Barbosa (Santander, Colombia) on dengue virus and its vector through a knowledge, attitudes, and practices (KAP) survey. Methods: An analytical cross-sectional study was conducted which included 93 residents of the municipality of Barbosa, selected based on non-probabilistic and convenience sampling A validated KAP instrument was used. The information was systematized and analyzed in SPSS v. 26.0. The information was systematized and analyzed in SPSS v. 26.0. Results: Among the respondents, 78.5 percent showed deficient knowledge with a score below 70 points. Negative attitudes were found in 73.1 percent of the residents with a score equal to or lower than 24 points. Best practices were reported by 67.7 percent of the population, with a score greater than or equal to 14 points. It is evident that at younger ages, unfavorable attitudes towards dengue infection are higher (OR 2.67 CI 95% 1.03-7.1). Conclusions: Educating the population more effectively about basic knowledge of dengue remains a necessary strategy, in addition to raising awareness that household practices should be carried out to eliminate the vector and not only as a cleaning mechanism. Different communicative strategies should be implemented to educate citizens in this regard(AU)

Intervención educativa sobre dengue en adultos / Educational Intervention on Dengue in Adults

Introducción: El dengue es una infección transmitida por mosquitos que en los últimos decenios se ha convertido en un importante problema de salud pública internacional. Objetivo: Evaluar la efectividad de una intervención educativa sobre dengue en adultos. Métodos: Se realizó un estudio cuasi-experimental de intervención educativa, antes y después, sobre dengue en adultos del consultorio 2 del policlínico Alex Urquiola, en el municipio Holguín, en el período comprendido de febrero a marzo de 2021. Tuvo 3 etapas: diagnóstico, intervención y evaluación. Resultados: Antes de la aplicación de la estrategia solo 80 pacientes poseían conocimientos sobre el dengue, después 130 pacientes adquirieron estos conocimientos. Solo 23 pacientes conocían la conducta a seguir ante la sospecha de dengue; después 126 pacientes se incluían. Solo 19 pacientes conocían las medidas de prevención del dengue (13,57 por ciento). Después de aplicada la estrategia educativa 135 pacientes (96,42 por ciento) tenían una adecuada percepción del riesgo. Conclusiones: Se evaluó la efectividad educativa, el nivel de conocimientos sobre el dengue, sus síntomas y signos, forma de transmisión, medidas de prevención y conducta a seguir, así como la percepción del riesgo por estos pacientes(AU)

Introduction: Dengue is a mosquito-borne infection that in recent decades has become a major international public health problem. Objective: To evaluate the effectiveness of an educational intervention on dengue in adults. Methods: A quasi-experimental study of educational intervention was carried out, before and after, on dengue in adults from doctor´s office 2 of Alex Urquiola community clinic, in Holguín municipality, from February to March 2021. It had 3 stages : diagnosis, intervention and evaluation. Results: Before the implementation of the strategy, only 80 patients had knowledge about dengue; after, 130 patients acquired this knowledge. Only 23 patients knew the behavior to follow in case of suspicion of dengue; then 126 patients were included. Only 19 patients knew about dengue prevention measures (13.57percent). After implementing the educational strategy, 135 patients (96.42percent) had an adequate perception of risk. Conclusions: The educational effectiveness, the level of knowledge about dengue, its symptoms and signs, mode of transmission, prevention measures and behavior to follow, as well as the perception of risk by these patients were evaluated(AU)

Experiências em divulgação científica e sensibilização da população: importância do controle mecânico do vetor Aedes aegypti / Experiences in scientific outreach and public awareness: the importance of mechanical control of the Aedes aegypti vector / Experiencias en divulgación científica y sensibilización de la población: importancia del control mecánico del vector Aedes aegypti

Aedes aegypti é o principal vetor dos agentes etiológicos de dengue, zika e chikungunya, doenças para as quais não existem vacinas totalmente eficazes. Alternativas de controle visando mitigar essas arboviroses são primordiais. Entre essas, o controle mecânico aborda práticas de eliminação e/ou limpeza de criadouros do vetor. Neste relato, apresentamos e avaliamos criticamente ações realizadas pelo grupo, ocorridas entre 2016 e 2019, nas quais divulgamos informação científica clara através do diálogo com a população. Os métodos utilizados foram: 1) palestras em escolas (público infantojuvenil) utilizando slides, fotos e vídeos; 2) oficinas (público misto), estande com material in vivo do ciclo de vida do Aedes, jogos e desenhos. Analisamos dez palestras em escolas do ensino fundamental e médio e vinte oficinas realizadas em diferentes regiões do Brasil. Concluímos que tais ações e suas análises críticas devem ser realizadas continuamente para que sejam bem-sucedidas

Aedes aegypti is the main vector of dengue, zika, and chikungunya etiological agents, diseases for which no effective vaccines are available. Control alternatives aimed at mitigating these arboviruses are essential. Among such, mechanical control addresses practices of elimination and/or cleaning of vector breeding sites. Here, we presented and critically evaluated actions carried out by ourselves. These actions took place between 2016 and 2019, where we disseminated clear scientific information through dialogue with the population. The following methods were employed: 1) lectures in schools (children and youth audiences) using slides, photos, and videos; 2) workshops (mixed audience), stand with in vivo material from the Aedeslife cycle, games, and drawings. Ten lectures in elementary and high schools and twenty workshops held in different regions of Brazil were analyzed. It was concluded that such actions and their critical analyzes must be carried out continuously to be successful

Aedes aegypti es el principal vector de los agentes etiológicos del dengue, zika y chikungunya, enfermedades para las que no existen vacunas totalmente eficaces. Las alternativas de control para mitigar estas arbovirosis son fundamentales. El control mecánico, representa una de estas alternativas, aborda prácticas de eliminación y/o limpieza de criaderos del vector. En este informe presentamos y evaluamos de manera crítica las acciones realizadas por el grupo entre los años 2016 y 2019. Presentamos información científica clara a través del diálogo con la población mediante los siguientes métodos: 1) conferencias en escuelas (público infantil) utilizando diapositivas, fotos y videos; 2) Talleres (público mixto), stand con material in vivo del ciclo de vida del Aedes, juegos y dibujos. Analizamos diez conferencias en escuelas (primarias y secundarias) y veinte talleres realizados en diferentes regiones de Brasil. Concluimos que tales acciones y el análisis crítico de las mismas deben llevarse a cabo de manera continua para que resulten exitosas.

The Immunogenicity of DENV1-4 ED3s Strongly Differ despite Their Almost Identical Three-Dimensional Structures and High Sequence Similarities.

The development of a dengue (DENV) vaccine remains challenging due to the heteroserotypic infection, which can result in a potentially deadly hemorrhagic fever or dengue shock syndrome, and only a tetravalent vaccine can overcome this issue. Here, we report the immunogenicity of DENV envelope protein domain 3 (ED3) from all four DENV serotypes (DENV1-4) in Swiss albino and BALB/c mice models. Firstly, we observed that despite having very similar sequences and structures, both the humoral and cellular immunogenicity of ED3s varied significantly, with strength ranging from DENV2 ED3 (2ED3)~3ED3 > 1ED3 > 4ED3, which was assessed through anti-ED3 IgG titers, and DENV1 ED3 (1ED3) > 2ED3~3ED3 > 4ED3 as determined by monitoring T-cell memory (CD44+CD62L+ T cells with IL-4 and IFN-γ expression). Secondly, anti-1ED3 sera cross-reacted with 2ED3 and 3ED3; anti-2ED3 and anti-3ED3 sera cross-reacted with each other, but anti-4ED3 was completely serotype-specific. The lack of reciprocity of anti-1ED3's cross-reaction was unanticipated. Such disparity in the ED3 responses and cross-reaction might underlie the appearance of hemorrhagic fever and dengue shock syndrome. Hence, the development of an ED3-based tetravalent subunit vaccine would require understanding the aforementioned disparities.

Recombinant Protein Mimicking the Antigenic Structure of the Viral Surface Envelope Protein Reinforces Induction of an Antigen-Specific and Virus-Neutralizing Immune Response Against Dengue Virus.

Dengue virus (DENV), belonging to the family Flaviviridae, is the causative agent of dengue and comprises four serotypes. A second heterologous DENV infection is a critical risk factor for severe dengue, and no effective vaccine is available to prevent infection by all four DENV serotypes. Recombinant DENV vaccines are primarily based on the envelope proteins, prM and E. The E protein and its envelope domain III (EDIII) have been investigated as candidate antigens (Ags) for recombinant subunit vaccines. However, most EDIII-based Ags are monomers that do not display the cognate antigenic structure of E protein, which is essential for induction of virus-neutralizing immunity. Here, we developed recombinant DENV-2 envelope domain (r2ED) protein as an Ag that mimics the quaternary structure of E protein on the DENV surface. We confirmed that r2ED retained the conformational epitope displayed at the E-dimer interface, which reportedly exhibits broad virus-neutralizing capacity, without displaying the fusion loop epitope that causes antibody (Ab)-dependent enhancement. Furthermore, compared with EDIII alone, r2ED elicited stronger Ag-specific and cross-reactive neutralizing Ab and T cell-mediated immune responses in mice. This Ag-specific immunity was maintained at an elevated level 6 months after the last immunization, suggesting sustained Ag-specific immune memory. Taken together, these observations suggest that r2ED could be used to develop an improved subunit vaccine capable of inducing a broadly cross-reactive and long-lasting immune response against DENV infection.

A bivalent form of nanoparticle-based dengue vaccine stimulated responses that potently eliminate both DENV-2 particles and DENV-2-infected cells.

Dengue is the most prevalent mosquito-borne viral disease and continues to be a global public health concern. Although a licensed dengue vaccine is available, its efficacy and safety profile are not satisfactory. Hence, there remains a need for a safe and effective dengue vaccine. We are currently developing a bivalent dengue vaccine candidate. This vaccine candidate is composed of a C-terminus truncated non-structural protein 1 (NS11-279) and envelope domain III (EDIII) of DENV-2 encapsidated in the nanocarriers, N, N, N-trimethyl chitosan nanoparticles (TMC NPs). The immunogenicity of this bivalent vaccine candidate was investigated in the present study using BALB/c mice. In this work, we demonstrate that NS1 + EDIII TMC NP-immunized mice strongly elicited antigen-specific antibody responses (anti-NS1 and anti-EDIII IgG) and T-cell responses (NS1- and EDIII-specific-CD4+ and CD8+ T cells). Importantly, the antibody response induced by NS1 + EDIII TMC NPs provided antiviral activities against DENV-2, including serotype-specific neutralization and antibody-mediated complement-dependent cytotoxicity. Moreover, the significant upregulation of Th1- and Th2-associated cytokines, as well as the increased levels of antigen-specific IgG2a and IgG1, indicated a balanced Th1/Th2 response. Collectively, our findings suggest that NS1 + EDIII TMC NPs induced protective responses that can not only neutralize infectious DENV-2 but also eliminate DENV-2-infected cells.

Análise da prevalência de internações por dengue no estado do Tocantins entre 2017 e 2022 / The prevalence of hospitalizations and deaths for dengue in the state of Tocantins between 2017 and 2022 / Prevalencia de hospitalizaciones y muertes por dengue en el estado de Tocantins entre 2017 y 2022

O Tocantins é um Estado endêmico para dengue devido aos elevados índices pluviométricos e do saneamento básico escasso. Esta pesquisa objetivou investigar o número de internações por dengue no Estado do Tocantins entre 2017 e 2022. O estudo consiste em um delineamento transversal retrospectivo quantitativo, realizado a partir de dados coletados no Tabnet/DataSUS. Os resultados encontrados foram compilados no programa Microsoft Excel®, e por meio de gráficos e tabelas, foram evidenciados 28.355 casos de dengue confirmados, dos quais apenas 1.798 (6%) necessitaram de hospitalizações, com maior incidência em 2019, tendo Palmas como município mais acometido. Conclui-se, portanto, que a dengue segue sendo uma doença prevalente no Estado, de modo a demandar atenção de gestores de saúde com vistas a reduzir os números altos de casos por meio de vigilância epidemiológica ativa como, também, fornecer o melhor cuidado para os pacientes diagnosticados com dengue, quer seja no âmbito ambulatorial quer no hospitalar.

Tocantins is an endemic state for dengue due to high rainfall rates and poor sanitation. This research aimed to investigate the number of dengue hospitalizations in the State of Tocantins between 2017 and 2022. The study consists of a retrospective quantitative cross-sectional design, performed from data collected in Tabnet/DataSUS. The results found were compiled in Microsoft Excel® program, and by means of graphs and tables, 28,355 confirmed dengue cases were evidenced, of which only 1,798 (6%) required hospitalizations, with a higher incidence in 2019, with Palmas as the most affected municipality. It is concluded, therefore, that dengue remains a prevalent disease in the state, so as to demand attention from health managers with a view to reducing the high numbers of cases through active epidemiological surveillance as well as providing the best care for patients diagnosed with dengue, whether in the outpatient or hospital setting.

Tocantins es un estado endémico para el dengue debido a las altas tasas de precipitación y al saneamiento deficiente. Esta investigación tuvo como objetivo investigar el número de hospitalizaciones por dengue en el Estado de Tocantins entre 2017 y 2022. El estudio consiste en un diseño cuantitativo transversal retrospectivo, realizado a partir de datos recogidos en Tabnet/DataSUS. Los resultados encontrados fueron compilados en el programa Microsoft Excel®, y por medio de gráficos y tablas, se evidenciaron 28.355 casos confirmados de dengue, de los cuales sólo 1.798 (6%) requirieron hospitalizaciones, con mayor incidencia en 2019, siendo Palmas el municipio más afectado. Se concluye, por lo tanto, que el dengue continúa siendo una enfermedad prevalente en el estado, por lo que demanda la atención de los gestores de salud con miras a reducir las altas cifras de casos a través de la vigilancia epidemiológica activa, así como brindar la mejor atención a los pacientes diagnosticados con dengue, ya sea en el ámbito ambulatorio u hospitalario.

Dengue control in the State of Goiás-Brazil using "wMel Wolbachia": a cost-effectiveness study

Dengue and other arboviruses have a considerable economic impact in Brazil. There are vector control strategies for dengue: traditional control with pesticides, Incompatible Insect Technique (IIT) with "wMel Wolbachia", and Sterile Insect Technique (SIT). Objective: To analyze the cost-effectiveness ratio of the IIT/SIT strategy, compared to traditional vector control with pesticides, for dengue prevention from the perspective of the Brazilian Public Health System (BPHS) as the payer and from the societal perspective in the state of Goiás, Brazil. Methods: The two strategies were compared using a decision tree model developed in Amua® software. All estimated parameters were derived from published articles or SUS information systems. The willingness-to-pay threshold (WTP), quality-adjusted life years (QALYs), years of life gained, costs, incremental cost-effectiveness ratios (ICERs), and incremental cost-utility ratios (ICURs) were adopted as study outcomes and parameters. We conducted deterministic and probabilistic sensitivity analyses. Results: Form the BPHS perspective, the IIT-SIT strategy is cost-effective, with an ICUR of R$ 72,200 per QALY gained, which is lower than the WTP of R$ 122,064.30/QALY gained. From the societal perspective, the IIT-SIT strategy is dominant (cheaper and more effective than traditional vector control). Sensitivity analyses showed that these results are reliable. Conclusion: In the state of Goiás, Brazil, the IIT/SIT strategy is cost-effective from the perspective of BPHS and dominant from the societal perspective, when compared to traditional vector control

A dengue e demais arboviroses têm impacto econômico considerável no Brasil. Há estratégias para controle vetorial da dengue: controle vetorial tradicional com pesticidas; Técnica do Inseto Incompatível (TII) com "wMel Wolbachia" e Técnica do Inseto Estéril (TIE). Objetivo: Analisar a razão de custo-efetividade da estratégia de TII/TIE, comparada ao controle vetorial tradicional com pesticidas, para prevenção da dengue, na perspectiva do Sistema Único de Saúde (SUS) como pagador e na perspectiva societal no Estado de Goiás, Brasil. Métodos: As duas estratégias foram comparadas usando um modelo de árvore de decisão desenvolvido no software Amua®. Todos os parâmetros estimados foram derivados de artigos publicados ou dos sistemas de informação do SUS. Limite de disposição para pagar (LDAP), Anos de vida ajustados pela qualidade (QALYs), anos de vida ganho, custos e razões de custo-efetividade incremental (RCEI) e custo-utilidade incremental (RCUI) foram adotados como desfechos e parâmetros do estudo. Análises de sensibilidade determinísticas e probabilísticas foram conduzidas. Resultados: Na perspectiva do SUS como pagador, a estratégia de TII-TIE é custo-efetiva, com RCUI de R$ 72,2 mil reais por QALY ganho, que é inferior ao LDAP de R$ 122.064,30/QALY ganho. Na perspectiva societal, a estratégia de TII-TIE é dominante (mais barata e mais efetiva que o controle vetorial tradicional). As análises de sensibilidade mostraram que esses resultados são confiáveis. Conclusão: No Estado de Goiás, Brasil, a estratégia de TII/TIE parece ser custo-efetiva na perspectiva do SUS e dominante na perspectiva societal, quando comparada ao controle vetorial tradicional

A standalone incompatible insect technique enables mosquito suppression in the urban subtropics.

The strong suppression of Aedes albopictus on two Guangzhou islands in China has been successfully achieved by releasing males with an artificial triple-Wolbachia infection. However, it requires the use of radiation to sterilize residual females to prevent population replacement. To develop a highly effective tool for dengue control, we tested a standalone incompatible insect technique (IIT) to control A. albopictus in the urban area of Changsha, an inland city where dengue recently emerged. Male mosquitoes were produced in a mass rearing facility in Guangzhou and transported over 670 km under low temperature to the release site. After a once-per-week release with high numbers of males (phase I) and a subsequent twice-per-week release with low numbers of males (phase II), the average numbers of hatched eggs and female adults collected weekly per trap were reduced by 97% and 85%, respectively. The population suppression caused a 94% decrease in mosquito biting at the release site compared to the control site. Remarkably, this strong suppression was achieved using only 28% of the number of males released in a previous trial. Despite the lack of irradiation to sterilize residual females, no triple-infected mosquitoes were detected in the field post release based on the monitoring of adult and larval A. albopictus populations for two years, indicating that population replacement was prevented. Our results support the feasibility of implementing a standalone IIT for dengue control in urban areas.