Search Results (72)

Background Expanded dengue syndrome represents a severe and atypical spectrum of dengue virus infection characterized by multisystem involvement beyond classic manifestations. While mild gastrointestinal symptoms are common in classic dengue, expanded dengue syndrome may present with clinically significant digestive organ involvement, including hepatitis, fulminant hepatic failure, pancreatitis, and acute acalculous cholecystitis. These manifestations often resemble primary gastrointestinal diseases, leading to diagnostic delays and inappropriate management. Despite increasing recognition, the true frequency of digestive system involvement remains poorly defined due to heterogeneous reporting and limited quantitative evidence. Methodology/Principal Findings A systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251270772). MEDLINE, Scopus, Web of Science, Embase, CENTRAL, Scielo, and BIREME were searched from inception to December 10, 2025. Primary studies reporting laboratory-confirmed dengue infection with atypical digestive system involvement and sufficient quantitative data were included. Seven studies comprising 1774 participants met eligibility criteria. Random-effects meta-analyses were performed to estimate pooled frequencies of gastrointestinal manifestations. The pooled frequency of hepatic involvement was 7% (95% confidence interval: 0–21), including fulminant hepatic failure (3%) and hepatitis (33%), with substantial heterogeneity. Acute pancreatitis occurred in 3% (95% confidence interval: 0–11) of cases. Acute acalculous cholecystitis was the most frequent manifestation, with a pooled frequency of 21% (95% confidence interval: 3–48). All included studies were classified as low risk of bias. Full article

Mosquito-borne diseases, including dengue fever, chikungunya, and Zika, continue to pose a substantial global public health challenge. This is largely attributable to the absence of effective vaccines and the expanding distribution of vectors such as Aedes albopictus (Ae. albopictus). Repellents, therefore, remain a critical component of prevention strategies for disease prevention. However, existing formulations have notable limitations. Synthetic repellents such as DEET provide broad-spectrum efficacy but may raise safety concerns, especially at high concentrations. In contrast, botanical repellents, such as citronella and camphor oils, offer more favorable safety profiles but are restricted by short protection durations due to their high volatility. To overcome these drawbacks, this research developed a composite mosquito repellent through the strategic combination of DEET (5–15%), citronella oil (10–20%), and camphor oil (5–15%). This formulation leverages interactions across multiple olfactory pathways to simultaneously enhance efficacy and reduce the DEET concentration. Orthogonal experimental optimization identified an optimized formulation, Mix-3 (consisting of 15% DEET, 15% citronella oil, and 10% camphor oil in 75% ethanol), which achieved a mean complete protection time of 9.45 h. Mix-3 provided longer protection than 7% DEET (mean difference = 5.50 h, p < 0.001), 4.5% IR3535 (2.83 h, p < 0.001), 10% citronella oil (3.58 h, p < 0.001), and 15% DEET (6.50 h, p < 0.001). Catnip oil did not contribute significantly to repellency (p = 0.895). This study demonstrates that the rational combination of synthetic and botanical repellents effectively overcomes the limitations of single-agent formulations, providing a long-lasting and scalable approach for vector control. Full article

The convergence of artificial intelligence and synthetic biology is innovating and accelerating the design of novel viral genomes, expanding both therapeutic opportunities and dual-use risk. This review articulates a countermeasure strategy for emerging and engineered viruses leveraging the programmable CRISPR modality. Building on mounting in vitro and in vivo evidence that Cas9 degrades DNA viruses (e.g., Orthopoxviruses, HSV-1, ASFV), while Cas13 targets RNA viral genomes (e.g., Influenza A, Dengue, RSV), both leading to reduced viremia, diminished disease burden, and alleviated symptoms. Here, we outline a rapid-response pipeline to position CRISPR-based countermeasures in translational and pandemic-response frameworks, linking real-time sequencing to AI-assisted gRNA selection and multiplexed cassette design to achieve viral targeting efficacy. To minimize resistance and off-target risk, we emphasize multi-gRNA cocktails, continuous genomic surveillance, and adaptive gRNA rotation. We also propose governance mechanisms, such as pre-cleared gRNA repositories, transparent design logs, standardized off-target/safety screening, and alignment with evolving nucleic-acid-synthesis screening frameworks to enable emergency deployment while preserving security. Furthermore, compressing the time from sequence to treatment and complementary to vaccines and small-molecule antivirals, CRISPR represents a technologically agile and strategically essential capability to combat both natural outbreaks and AI-enabled biothreats. Collectively, programmable CRISPR antivirals represent an auditable, rapidly adaptable foundation for next-generation biodefense preparedness. Full article

Background and Objectives: Climate change is modifying the ecological and climatic conditions that influence the distribution and activity of arthropod vectors. Rising temperatures and prolonged warm seasons have favored the establishment of Aedes albopictus in Mediterranean regions, increasing the risk of autochthonous Dengue transmission. Therefore, this study describes the evolution of Dengue surveillance in Sardinia between 2018 and 2024, integrating human and entomological data to assess trends, system performance, and implications for prevention and control. Materials and Methods: Data on human cases were retrieved from national notification systems (namely PREMAL, arbo.iss.it) and the New Health Information System. Entomological surveillance data were obtained from the Experimental Zooprophylactic Institute of Sardinia. Mosquitoes were collected using BG-Sentinel^® traps and ovitraps, covering major cities and points of entry. Descriptive analyses were conducted for both datasets. Results: Sixteen Dengue cases were reported during the study period, all imported and laboratory-confirmed in 81% of cases. Most patients were adults (mean age 38 years), and 77% required hospitalization. The most frequent travel origins were Southeast Asia, Africa, and Latin America. No autochthonous cases were identified. Entomological surveillance showed a progressive increase in Aedes albopictus captures from 2020 onwards, with seasonal peaks between September and October. Despite intensified sampling and expanded geographic coverage, no mosquito pools tested positive for the Dengue virus. Conclusions: Although no locally acquired Dengue infections have been detected, the widespread and increasing presence of Aedes albopictus indicates that Sardinia meets the ecological prerequisites for possible autochthonous transmission. Strengthening the timeliness and completeness of human surveillance, improving clinicians’ awareness of reporting requirements, promoting vaccination for travelers, and maintaining continuous entomological monitoring are essential to prevent and promptly manage future outbreaks. Full article

Dengue fever, a mosquito-borne viral disease, has become a significant global health concern in recent decades, particularly in Iran. This integrative review provides a comprehensive assessment of the epidemiological trends of dengue fever in Iran from its initial emergence to the present, identifying and evaluating factors contributing to both the emergence and re-emergence of the disease at national and international levels. The review highlights critical global determinants influencing dengue transmission, including climate change, environmental modifications, unplanned urbanization, increased international travel and trade, and the pivotal roles of public awareness and healthcare infrastructure. Climatic variables, such as rising temperatures and altered precipitation patterns, create favorable conditions for mosquito breeding, enabling vectors like Aedes aegypti and Aedes albopictus to expand into new regions. We also explore how environmental changes, unplanned urbanization and other factors further exacerbate the situation. Control strategies addressing these factors are presented. In Iran, the incidence of dengue fever is increasing, yet research remains limited. The highest number of local cases has been reported in Chabahar and Bandar Lengeh, Hormozgan and Sistan and Baluchestan Provinces, respectively. Eleven key factors—culminating in socio-cultural practices, climate change, unplanned urbanization, cross-border mobility, and gaps in vector control and healthcare infrastructure—have been identified as contributing to recent outbreaks in Iran. In conclusion, our review underscores that mitigating dengue vulnerability in Iran requires an urgent, multi-faceted strategy targeting improved urban water management, enhanced cross-border surveillance, and strengthened healthcare system capacity. Full article

Background: Understanding the immune mechanisms that differentiate protective from pathogenic responses during dengue virus (DENV) infection is critical for effective vaccine development. Objective: To investigate how CD4⁺ T cell depletion alters viral control and the humoral immune response during primary DENV2 infection in a non-human primate (NHP) model. Methods: Rhesus macaques were depleted of CD4⁺ T cells prior to DENV2 infection. Viral kinetics, B cell activation, antibody specificity, and functional outcomes were evaluated longitudinally, including cross-reactivity and antibody-dependent enhancement (ADE) potential. Results: CD4⁺ T cells were essential for early viral clearance and the generation of robust, type-specific neutralizing antibodies. In their absence, animals exhibited early non-specific polyclonal B cell activation, delayed isotype switching, and an expanded repertoire of cross-reactive antibodies to DENV and Zika virus (ZIKV), with diminished neutralizing capacity. CD4-depleted macaques also showed increased ADE potential, particularly against ZIKV, and elevated anti-NS1 IgG titers that persisted one-year post-infection. Conclusion: CD4⁺ T cells play a critical role in orchestrating effective, durable, and type-specific antibody responses during primary DENV infection. Their absence leads to delayed antibody maturation, greater cross-reactivity, and higher ADE potential. These findings emphasize the need for DENV and ZIKV vaccines to include CD4⁺ T cell epitopes that promote high-quality, type-specific antibody responses and minimize ADE risk. Full article

Dengue, caused by the dengue virus (DENV), is rapidly expanding its geographical footprint, with increasing incidence not only in over 100 endemic countries in the southern hemisphere but also with more autochthonous transmissions now reported in the northern hemisphere, including regions of Europe and the United States. The clinical presentation of DENV infection ranges from mild febrile illness to severe and potentially fatal conditions, such as dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS), and diverse neurological complications. While vaccine development efforts are underway, significant challenges remain, underscoring the urgent need for a deeper understanding of the virus. This urgency is particularly palpable in Brazil, which has faced an unprecedented surge in dengue cases during the 2024–2025 period. The country has recorded an alarmingly high number of infections and related deaths, stretching its public health infrastructure and highlighting the complex interplay of climate change, urbanization, and viral dynamics in disease propagation. This review provides a global perspective on dengue, systematically exploring its history, morphology, viral cycle, pathogenesis, and epidemiology. By integrating these critical aspects, this article aims to identify pivotal knowledge gaps and guide future research directions essential for developing improved public health interventions against this complex and evolving disease. Full article

Climate change is increasingly recognized as a major driver of emerging infectious diseases, particularly vector-borne diseases (VBDs), which are expanding in range and intensity worldwide. Europe, traditionally considered low-risk for many arboviral infections, is now experiencing autochthonous transmission of pathogens such as dengue, chikungunya, Zika virus, West Nile virus, malaria, and leishmaniasis. Rising temperatures, altered precipitation patterns, and milder winters have facilitated the establishment and spread of competent vectors, including Aedes, Anopheles, Phlebotomus, and Culex species, in previously non-endemic areas. These climatic shifts not only impact vector survival and distribution but also influence vector competence and pathogen development, ultimately increasing transmission potential. This narrative review explores the complex relationship between climate change and VBDs, with a particular focus on pediatric populations. It highlights how children may experience distinct clinical manifestations and complications, and how current data on pediatric burden remain limited for several emerging infections. Through an analysis of existing literature and reported outbreaks in Europe, this review underscores the urgent need for enhanced surveillance, integrated vector control strategies, and climate-adapted public health policies. Finally, it outlines research priorities to better anticipate and mitigate future disease emergence in the context of global warming. Understanding and addressing this evolving risk is essential to safeguard public health and to protect vulnerable populations, particularly children, in a rapidly changing climate. Full article

In 2024, the Americas experienced the largest dengue outbreak on record and Brazil was among the worst affected countries, reporting 6.6 million cases and 6200 deaths. We report the long-term entomological and epidemiological effectiveness of city-wide deployment of wMel-strain Wolbachia-infected Aedes aegypti in Niterói, a city of half a million people in Rio de Janeiro state, where Wolbachia releases across three-quarters of the urban population in 2017–2019 were expanded to remaining populated areas in 2023. wMel was durably established at ≥95% prevalence in Ae. aegypti populations throughout Niterói four years post-release, and up to seven years in the earliest release sites. Notified dengue case incidence in Niterói was 89% lower following Wolbachia releases, compared to the 10-year pre-intervention period of 2007–2016. Dengue incidence in Niterói in 2024, during a period of record high incidence in Brazil and the region, was 374 per 100,000 population, substantially lower than overall in Rio de Janeiro state (1884 per 100,000) and nationwide in Brazil (3157 per 100,000). Our findings show that city-wide Wolbachia coverage in Niterói provided sustained population-level reduction in dengue incidence throughout the five years post-intervention, including during the 2024 epidemic surge, averting an estimated three-quarters of the dengue case burden that may otherwise have been expected in Niterói in 2024. Full article

Background: Aedes albopictus, the tiger mosquito, is an invasive exotic species native to Southeast Asia, currently established in Europe, including Spain and the region of Navarre. This vector poses an emerging public health threat due to its ability to transmit dengue, Zika, and chikungunya viruses, which cause diseases in humans. This study presents novel findings by documenting the progression of the invasion of Aedes albopictus in the Navarre region in northern Spain, tracing its status from initial absence to its definitive establishment in certain areas. Methods: Surveillance in Navarre within the LIFE-IP NAdapta-CC project was conducted through a network of strategically placed ovitraps and adult traps to collect eggs and adult mosquitoes. Awareness campaigns and outreach events were organized to inform local authorities and the public about monitoring results and preventive measures. Results: Monitoring confirms Aedes albopictus’ expansion across Navarre despite training, information dissemination, and control efforts, including entomological containment in targeted areas. Conclusions: Eliminating breeding sites remains the most effective strategy to limit its spread. Complete eradication is unlikely given its invasive nature, and the species is expected to expand and colonize at least part of the region in the coming years. Full article

The expanding distribution and geographic range of mosquitoes have potentially contributed to increased flaviviral dissemination and transmission. Despite the growing burden of flaviviral infections, there are no effective antiviral treatments or vaccines, highlighting the need for novel therapeutic targets. Tetraspanins, a superfamily of transmembrane domain glycoproteins involved in cellular organization, signaling, and protein–protein interactions have been recognized as potential mediators of flaviviral infection and transmission. While their roles in vertebrate hosts have been explored, their involvement in flaviviral replication and dissemination within medically important vectors remains poorly understood. In this study, we investigated the role of arthropod tetraspanins in mosquito cells and extracellular vesicles (EVs) derived from cells infected with Zika virus (ZIKV) and dengue virus (serotype 2; DENV2). Among several of the tetraspanins analyzed, only CD151 was significantly upregulated in both mosquito cells and in EVs derived from ZIKV/DENV2-infected cells. RNAi-mediated silencing of CD151 led to a marked reduction in viral burden, suggesting its crucial role in flavivirus replication. Inhibition of EV biogenesis using GW4869 further demonstrated that EV-mediated viral transmission contributes to flavivirus propagation. Additionally, co-immunoprecipitation and immunofluorescence analyses revealed direct interactions between CD151 and ZIKV NS2B and DENV2 capsid proteins. Overall, our findings highlight the functional importance of mosquito CD151 in the replication and transmission of ZIKV and DENV2. This study provides new insights into the molecular mechanisms of flaviviral infection in mosquitoes and suggests that targeting vector tetraspanins may offer a potential approach to controlling mosquito-borne flaviviruses. Full article

Dengue virus serotypes 1-4 (DENV1-4) have spread through tropical and subtropical countries, causing endemic and epidemic diseases. Recently, a novel field approach using the Wolbachia symbiont was proposed to suppress DENV transmission via the mosquito vectors Aedes aegypti and Aedes albopictus. Previously, we showed that a Wolbachia strain, wMelPop, suppresses DENV2 replication in the C6/36 albopictus cell line, with the mutant DENV2 appearing and replacing the wild type DENV2. In this study, we expanded the analysis to include replications of all DENV serotypes 1-4, effects of wAu Wolbachia in C6/36 cells, and wMelPop-influences on the Aag2 aegypti cell line. It was revealed that both wAu and wMelPop reduce all DENV infectious titers without dominant appearances of the mutant viruses, despite varied effects on the viral copy numbers. The host transcriptomic profiles by RNA-seq were also variously altered by wAu and wMelPop (ranging from 10 to 30%, Log₂FC > 2 or <−2, p < 0.05). Those transcripts were not further altered by DENV infection. In contrast, abundant transcriptomic alterations by DENV infection in naïve C6/36 and Aag2 cells were blocked by either wAu or wMelPop. These results indicate that Wolbachia prevents host cellular transcriptomic alterations which are induced by DENV infection, affecting the cellular homeostasis necessary for DENV replication. Full article

Dengue virus (DENV) remains a critical global health challenge, with no approved antiviral treatments currently available. The growing prevalence of DENV infections highlights the urgent need for effective therapeutics. Antiviral peptides (AVPs) have gained significant attention due to their potential to inhibit viral replication. However, traditional drug discovery methods are often time-consuming and resource-intensive. Advances in artificial intelligence, particularly deep generative models (DGMs), offer a promising approach to accelerating AVP discovery. This report provides a comprehensive assessment of the role of DGMs in identifying novel AVPs for DENV. It presents an extensive survey of existing antimicrobial and AVP datasets, peptide sequence feature representations, and the integration of DGMs into computational peptide design. Additionally, in vitro and in silico screening data from previous studies highlight the therapeutic potential of AVPs against DENV. Variational autoencoders and generative adversarial networks have been extensively documented in the literature for their applications in AVP generation. These models have demonstrated a remarkable capacity to generate diverse and structurally viable compounds, significantly expanding the repertoire of potential antiviral candidates. Additionally, this report assesses both the strengths and limitations of DGMs, providing valuable insights for guiding future research directions. As a data-driven and scalable framework, DGMs offer a promising avenue for the rational design of potent AVPs targeting DENV and other emerging viral pathogens, contributing to the advancement of next-generation therapeutic strategies. Full article

Background/objectives: In Brazil, the co-circulation of arboviruses—such as dengue, Zika, yellow fever, and Chikungunya viruses—creates a complex epidemiological landscape, drawing attention from health authorities due to high morbidity and mortality rates. Also present in this context is the Mayaro virus (MAYV), a neglected arbovirus, which can also cause severe syndromes and has been expanding beyond its usual endemic areas in northern and central-western Brazil. Epidemiological surveillance measures remain limited, and there are no effective prophylactic strategies or antiviral treatments for this neglected arbovirus. In this study, we evaluated the antiviral activity of commercial and synthetic compounds against MAYV using an image high-throughput screening (iHTS) system. Methods: A total of 52 compounds from an FDA-approved commercial library (Tocriscreen) and 50 other compounds were tested. Results: Seven compounds showed anti-MAYV activity and were non-toxic for the following cell lines: Naringenin, LLA9A, chrysin, and its ester C6. Post-infection treatments with these selected compounds significantly decreased the percentage of infected cells and the release of infectious viral particles in the supernatant. Additionally, anti-MAYV activity of these four selected hits was confirmed using several human cell lines and two different MAYV genotypes. Conclusions: Our results indicate that the iHTS platform is effective for screening anti-MAYV drugs and that four promising compounds can efficiently inhibit MAYV replication in human cell lines. Although in vivo studies are still required to confirm the efficacy of the selected hits, our findings provide a starting point for developing a potential treatment for MAYV infections. Full article

Dengue, a febrile disease that has caused epidemics and deaths in South America, especially Peru, is vectored by the Aedes aegypti mosquito. Despite the seriousness of dengue fever, and the expanding range of Ae. aegypti, future distributions of the vector and disease in the context of climate change have not yet been clearly determined. Expanding on previous findings, our study employed bioclimatic and topographic variables to model both the present and future distribution of the Ae. aegypti mosquito using the Maximum Entropy algorithm (MaxEnt). The results indicate that 10.23% (132,053.96 km²) and 23.65% (305,253.82 km²) of Peru’s surface area possess regions with high and moderate distribution probabilities, respectively, predominantly located in the departments of San Martín, Piura, Loreto, Lambayeque, Cajamarca, Amazonas, and Cusco. Moreover, based on projected future climate scenarios, it is anticipated that areas with a high probability of Ae. aegypti distribution will undergo expansion; specifically, the extent of these areas is estimated to increase by 4.47% and 2.99% by the years 2070 and 2100, respectively, under SSP2-4.5 in the HadGEM-GC31-LL model. Given the increasing dengue epidemic in Peru in recent years, our study seeks to identify tools for effectively addressing this pressing public health concern. Consequently, this research serves as a foundational framework for assessing areas with the highest likelihood of Ae. aegypti distribution in response to projected climate change in the second half of the 21st century. Full article