Search Results (538)

Arboviral diseases are emerging as important public health threats in Saudi Arabia, driven by rapid urbanization, climate variability, the expansion of Aedes aegypti populations, international travel, and large-scale religious mass gatherings. Dengue virus remains the most established arboviral infection in the Kingdom, particularly in the southwestern regions such as Jazan and the western urban centers of Makkah and Jeddah, where ecological and climatic conditions are conducive to sustained vector survival and transmission. This review synthesizes current evidence on the epidemiology, vector ecology, climatic determinants, diagnostics, and prevention strategies of arboviral diseases in Saudi Arabia. Particular attention is paid to the impacts of rising temperatures, changes in rainfall patterns, urban heat island effects, population mobility, and cross-border movement on vector expansion and disease emergence. The review also identifies gaps in surveillance, diagnostics, insecticide resistance monitoring, and integrated vector management programs. Emerging preparedness strategies include climate-informed early warning systems, Geographic Information System-based risk mapping, multiplex molecular diagnostics, genomic surveillance, and community-based vector control. The review emphasizes the importance of implementing a One Health approach that combines data on humans, the environment, entomology, and climate. Currently, sustained endemic transmission of chikungunya and Zika viruses has not been conclusively demonstrated in Saudi Arabia, but increased environmental suitability and connectivity with other areas highlight the need for proactive surveillance and preparedness. Full article

Background/Objectives: Arboviruses including dengue virus (DENV), Zika virus (ZIKV), chikungunya virus (CHIKV), yellow fever virus (YFV), and West Nile virus (WNV) co-circulate across the Americas, generating overlapping febrile syndromes that challenge etiological diagnosis based solely on clinical criteria. Cartridge-based multiplex molecular platforms offer potential for decentralized testing in hyperendemic settings, yet independent real-world evaluations of their clinical and analytical performance remain limited. Methods: A retrospective two-phase analytical study was conducted. Phase 1 assessed clinical diagnostic accuracy for dengue using 163 de-identified serum samples classified using a composite reference standard consisting of Panbio NS1 ELISA reactivity (≥11 Panbio units) combined with compatible clinical and epidemiological data, operationalized in accordance with the PAHO 2023 laboratory confirmation algorithm for dengue; RT-qPCR was not routinely available for all archived samples, and reported sensitivity should therefore be interpreted as a conservative lower-bound estimate; Phase 2 evaluated analytical sensitivity across all eight panel targets using characterized arboviral reference strains in serial dilution experiments, with reference RT-qPCR assays as the comparator; this phase was incorporated to characterize detection thresholds for targets not represented by clinical specimens. Results: In Phase 1, the M10 demonstrated sensitivity of 96.0% (96/100), specificity of 100% (63/63), overall accuracy of 97.5%, and near-perfect agreement with the reference standard (Cohen’s κ = 0.95). DENV-3 was the predominant serotype (74/96; 77.1%), followed by DENV-1 (16.7%) and DENV-4 (6.3%); DENV-2 was not detected. In Phase 2, operational LoDs (defined as the lowest concentration yielding a detectable Ct in all triplicate reactions for the RT-qPCR, and from a single cartridge per dilution point for the STANDARD M10) were equivalent or superior to reference RT-qPCR for six targets (DENV-1, DENV-3, DENV-4, ZIKV, WNV, YFV; range 1–5 PFU/mL), while DENV-2 and CHIKV showed 20-fold higher operational LoDs (20 PFU/mL vs. 1 PFU/mL for the reference RT-qPCR); formal LoD₉₅ estimates were not determined. Conclusions: The STANDARD M10 Arbovirus Panel shows high clinical accuracy for dengue and adequate analytical sensitivity for most targets, supporting its use as a complementary decentralized molecular tool. Reduced sensitivity for DENV-2 and CHIKV and the absence of formal LoD₉₅ estimates remain key limitations to be addressed in future validation studies. Full article

Background/Objectives: Vector-borne diseases (VBDs) remain a major global public health challenge, particularly in tropical and subtropical regions. In eastern Colombia, the department of Meta reports a high incidence of arboviral infections such as dengue, as well as parasitic diseases including malaria and leishmaniasis. This study aimed to conduct baseline entomological surveillance and molecular screening of Diptera vectors to detect the circulation of arboviruses and parasitic pathogens in two municipalities of Meta, Fuente de Oro and Vista Hermosa. Methods: Adult mosquitoes and sand flies were collected in both municipalities and identified primarily at the genus level, with Anopheles specimens identified to species level. A total of 790 insects were collected, of which 780 were processed in 148 pools and 10 were analyzed individually. Molecular detection of pathogens was performed using PCR and RT-PCR to screen for dengue virus (DENV) serotypes, Zika virus (ZIKV), Chikungunya virus (CHIKV), Oropouche virus (OROV), Plasmodium spp., and Leishmania spp. Results: DENV was detected in 34.8% (55/158) of the processed pools, with DENV-1 identified as the most prevalent serotype. Culex was the most abundant genus overall, particularly in Fuente de Oro, while Aedes predominated in Vista Hermosa. MIR estimates indicated higher molecular detection likelihood in Aedes compared with Culex. Plasmodium vivax and P. falciparum were detected in pools of Anopheles darlingi and Anopheles rangeli, respectively. No molecular evidence of Leishmania DNA was detected in Lutzomyia specimens, and no positive detections were observed for ZIKV, CHIKV, or OROV. Conclusions: The molecular detection of DENV and Plasmodium spp. in field-collected vectors provides valuable baseline evidence of pathogen circulation in Meta, Colombia. While the findings do not imply vector competence, they highlight the importance of sustained entomological surveillance to inform integrated vector control strategies and guide future studies incorporating species-level identification and longitudinal sampling in endemic regions. Full article

In this study, a fractional-order epidemic compartmental model is formulated using the Caputo derivative to account for the memory effects of the chikungunya virus. Based on Banach contractions, fixed-point theorems are used to prove existence and uniqueness, and fundamental properties such as positivity and boundedness are established. Normalized forward sensitivity indices are employed to evaluate the relative impact of model parameters on the transmission dynamics and control of the disease. To reduce the spreading of infection, an optimal control problem is formulated by introducing time-dependent control measures with four control strategies that include public health prevention, treatment enhancement, and vector-control measures. Necessary conditions for optimality are derived using Pontryagin’s Maximum Principle. The predictor–corrector Adams–Bashforth–Moulton scheme is applied across different fractional orders and effectively reduces infection levels. The influence of the fractional order $\xi$ on the epidemic dynamics is investigated, showing that lower values of $\xi$ slow disease progression through a memory effect inherent in the Caputo operator. Moreover, an artificial neural network (ANN) trained via the Levenberg–Marquardt algorithm independently validates the numerical solutions. Full article

Protein–protein interactions (PPIs) are fundamental to viral replication, regulating processes such as assembly, genome packaging, and virion maturation. Despite their biological importance, these interactions remain challenging to study and are relatively underexploited as therapeutic targets. Split reporter systems, based on protein-fragment complementation, provide quantitative platforms to measure PPIs by reconstituting reporter activity when interacting protein partners are brought into proximity. These systems can be applied in vitro and in live cells which enables detection of dynamic and multimeric interactions in physiologically relevant contexts. Major classes of split reporter systems include β-lactamase, alkaline phosphatase, luciferase-based platforms, green fluorescent protein, and horseradish peroxidase. Assay performance depends on factors such as fusion protein stability, expression levels, and reporter kinetics, which influence sensitivity, dynamic range, and reliability. These approaches have been applied to study viral protein interactions across diverse systems, including HIV-1 matrix and nucleocapsid proteins, flaviviral capsid proteins, hepatitis B virus core protein, and chikungunya virus capsid. Split reporter assays also enable high-throughput screening for small-molecule inhibitors that disrupt viral PPIs and multimerization. This provides a functional readout linked to viral replication. Despite the challenges that exist in assay optimization and protein stability, the sensitivity and versatility of these systems provide a framework to interrogate viral protein interactions and support the development of antiviral therapeutics.: Full article

This study applied a syndemic framework to chikungunya virus (CHIKV) infection during the 2014–2015 Colombian epidemic, integrating biological and social determinants. Methods: A community-based cohort of 279 serologically confirmed adults from six cities was analyzed. Clinical, sociodemographic, and cytokine data were evaluated using multilevel and multivariate statistical approaches. Results: Among 279 patients, 141 (50.5%) met World Health Organization (WHO) criteria for acute CHIKV infection. The cohort was predominantly female and of lower socioeconomic status (SES). The most frequent manifestations were arthralgia (91%), fatigue (58%), fever (50.5%), myalgia (45.9%), and rash (45.2%). Multivariate models identified IL-15, IL-17A, IL-12p40, MCP-1, and MIP-1α as significant correlates of fever, rash, and myalgia. Socioeconomic and ethnic factors influenced cytokine expression; Caucasian patients showed higher proinflammatory cytokine levels than Afro-American patients. Lower SES was associated with greater symptom burden. Network analyses revealed distinct immune signatures linking biological responses with clinical and demographic variables. Conclusion: Immune responses, clinical manifestations, and social disadvantages interact significantly in CHIKV infection. These findings support a syndemic model in which socioeconomic vulnerability amplifies disease impact, highlighting the need for integrated biosociological public health strategies, particularly targeting populations with low socioeconomic status. Full article

Background: Malaria remains hyperendemic in the Democratic Republic of the Congo, while arboviral infections are increasingly reported but remain under-surveilled, particularly in remote regions. Overlapping ecological niches and non-specific clinical presentations complicate case management and surveillance. Methods: A cross-sectional door-to-door survey was conducted in December 2023 in Inkanamongo village (Lokolia Health Area, Boende Health Zone, Tshuapa Province). Blood samples were collected from 379 adults; malaria infection was assessed by using HRP2-based rapid diagnostic tests, and arboviral IgG antibodies were measured on dried blood spots using Luminex^® multiplex immunoassay. Sociodemographic data were collected via standardized questionnaires. Results: Malaria prevalence was 51.7% (95%CI: 46.7–56.7). Overall arboviral seroprevalence reached 78.4% (95%CI: 73.1–81.5), dominated by O’nyong-nyong virus, 42.8% (95%CI: 37.6–47.5), Rift Valley fever virus, 32.0% (95%CI: 26.9–36.2), and chikungunya virus, 23.4% (95%CI: 19.0–27.4). Concurrent malaria infection and arboviral exposure were observed in 40.4% (95%CI: 35.6–45.4) of participants. No sociodemographic factors were significantly associated with co-exposure in the multivariable analysis. Conclusions: Substantial co-exposure of malaria and multiple arboviruses occurs in this remote Congo Basin setting. Integrated surveillance and improved diagnostics are urgently needed to guide febrile illness management and preparedness in under-resourced regions. Full article

Chikungunya virus (CHIKV) is an alphavirus that infects dermal fibroblasts as a primary target cell during natural mosquito-borne transmission. While primary human dermal fibroblasts (hDFs) have been implicated as a key source of type I interferon (IFN-I) during CHIKV infection, the dynamics of this response and its sufficiency for antiviral protection remain incompletely understood. Here, we systematically characterize in vitro CHIKV infection of primary hDFs, evaluating the effects of single-passage viral stock origin (mammalian- vs. mosquito-propagated), donor variability, and multiplicity of infection (MOI) on infection kinetics and innate immune induction. We demonstrate that hDFs support high-titered CHIKV replication at both MOI 1 and 0.01, resulting in universal cell death by 72 hpi despite robust IFNβ transcript induction—reaching up to ~2800-fold over mock—and secretion of pro-inflammatory cytokines, including IFNα2, TNFα, IL-1β, and IL-8. Notably, IFNβ protein levels remained below 10 pg/mL under all infection conditions, revealing a disconnect between transcriptional and translational responses, suggesting CHIKV-mediated translational suppression. Pharmacological inhibition of TBK1/IKKε via amlexanox did not suppress IFNβ transcript induction at any tested concentration, suggesting that canonical PRR signaling through this node—including both RIG-I/MAVS and TLR3/TRIF pathways—is not the major driver of the observed transcriptional response. In contrast, co-inoculation with exogenous IFNβ as low as 20 pg/mL activated IFNAR signaling, robustly upregulated interferon-stimulated genes (ISGs), and fully rescued hDFs from otherwise lethal infection. Together, these findings demonstrate that CHIKV-infected hDFs mount a transcriptionally robust but translationally insufficient innate immune response and that the transcriptional response appears to operate independently of TBK1/IKKε. These results have direct implications for understanding how the skin microenvironment may modulate early CHIKV pathogenesis and suggest that paracrine IFNβ signaling from neighboring cell types may be critical for fibroblast survival during natural infection. Full article

Chikungunya virus (CHIKV) infection presents a wide spectrum of clinical outcomes, ranging from mild self-limiting disease to severe and fatal manifestations, which are influenced by both host and viral factors. Animal models are essential for elucidating CHIKV pathogenesis and for preclinical evaluation of antiviral strategies; however, a well-characterized model evaluating the effect of different viral doses in AG129 mice remains limited. In this study, we investigated the clinical, virological, and pathological outcomes of CHIKV infection in male AG129 mice inoculated intraperitoneally with different viral doses (10, 100, and 1000 PFU/mL) of a Brazilian strain belonging to the East/Central/South African (ECSA) lineage. Lower-dose inoculation (10 PFU/mL) resulted in a milder disease course, characterized by transient viremia, limited tissue viral dissemination, minimal histopathological alterations, partial survival, and viral clearance. In contrast, higher doses (≥100 PFU/mL) led to rapid systemic viral dissemination, severe histopathological damage in the spleen, liver, and kidneys, and uniform lethality. Viral RNA was detected in serum and multiple organs in a time-dependent manner, with limited differences among inoculum doses in most tissues. Notably, dose-related differences were observed in specific compartments and time points, particularly in hind-limb muscles at early time points and in serum at later stages. Full article

Background/Objectives: Febrile illness in returning travelers presents a diagnostic and operational challenge for emergency medicine clinicians as early symptoms of high-consequence tropical infections often overlap with common viral syndromes. This review synthesizes current evidence to guide frontline clinicians in the systematic evaluation, diagnosis, and management of internally acquired febrile illnesses with a focus on pathogen of greatest relevance to United States (US) emergency departments (ED). Methods: We conducted a narrative review of the literature addressing epidemiology, clinical presentation, diagnostic testing, and management strategies for key travel-associated infections. Special consideration was given to rapid diagnostic modalities, pediatric risk factors, and infections most frequently implicated in returning travelers, including chikungunya (CHIK), dengue virus (DENV) disease, Ebola virus (EBV) disease, malaria, Mpox, typhoid fever (TF), yellow fever (YF), and Zika virus (ZIKV) disease. Results: Effective evaluation begins with a detailed travel and exposure history, recognition of epidemiologic and clinical red flags, and targeted use of rapid diagnostic tests. Malaria remains the most common life-threatening cause of post-travel fever and the only pathogen with reliable Food and Drug Administration (FDA)-cleared rapid testing available in the ED. Arboviral infections such as DENV, CHIK, ZIKV, and YFrequire region-specific consideration and phase-appropriate molecular or serologic evaluation. Emerging and high-consequence pathogens, including Mpox and EBV, necessitate strict infection control measures and coordination with public health authorities. Pediatric travelers, particularly those visiting friends and relatives, face disproportionate risk for severe systemic infections and often require broader diagnostic testing. Conclusions: A structured approach integrating travel history, focused examination, rapid diagnostics, and early recognition of high-risk features is essential to improving outcomes for febrile returning travelers. Strengthened vector control, enhanced vaccination uptake, and global surveillance are critical to reducing future disease burden. Full article

Chikungunya virus (CHIKV) pathogenesis research has long been constrained by the lack of suitable immunocompetent rodent models. Through serial passaging in A129 and C57BL/6 mice, we obtained an adapted strain (CHIKV-Adapt) harboring an E2-K200R substitution along with non-structural protein mutations. Phenotypic analysis in C57BL/6 mice, BALB/c mice, and hamster models demonstrated that compared to the wild-type virus CHIKV-Adapt induced significantly higher and more prolonged viremia, broader tissue tropism, and more severe internal joint inflammation, without exacerbating external swelling. Notably, the K200R mutation did not alter the viral replication kinetics in vitro and was predicted not to affect its binding pattern to the MXRA8 receptor. Furthermore, mice challenged 160 days after primary infection exhibited nearly complete protective immunity. These findings indicate that E2-K200R is a critical adaptive mutation that, together with accompanying non-structural mutations, significantly enhances CHIKV replication capacity and pathogenicity in immunocompetent rodents without changing its in vitro replication ability or predicted receptor-binding mode. The acquisition of this adapted strain provides a new tool for CHIKV pathogenesis research and vaccine evaluation. Full article

Background/Objectives: Since 2023, a significant increase in measles cases has been reported worldwide, and Italy has been among the most affected European countries. In this context, the integration of laboratory and epidemiological data enables timely case classification and helps distinguish between imported and indigenous cases, supporting disease control. However, most studies address only selected aspects of surveillance. Therefore, this study aimed to provide an integrated analysis of virological and epidemiological surveillance activities conducted between November 2023 and December 2025 by the Regional Reference Laboratory in the Emilia-Romagna Region (ERR). Methods: A total of 806 clinical samples (269 urine, 267 oral fluids—saliva or oropharyngeal swabs—and 270 sera) from 291 suspected measles cases were tested by molecular and/or serological methods, and MV genotyping was performed. Samples from discarded cases were also analysed for parvovirus B19 (B19V), human herpesvirus 6 (HHV-6), enterovirus (EV), and varicella zoster virus (VZV), chikungunya virus (CHIKV) and dengue virus (DENV). Results: Of 291 suspected cases, 176 (60.5%) were confirmed. Median age was 33 years, with 46% in the 15–39 year group. Vaccination status was available for 165: 90.3% were unvaccinated, 5.4% had one dose, and 4.2% had two doses. Notably, over half of confirmed cases occurred in areas with vaccine-hesitant communities. MV strain characterisation was performed in 99.4% of MV-RNA positive cases, with 84.3% genotype D8 and 15.6% genotype B3; 83% of strains were of indigenous origin, suggesting an ongoing endemic circulation. Clinical data showed complications in 19.3%, mainly pneumonia and diarrhoea. Additionally, differential diagnosis enabled the identification of the etiological agent in 37.5% of measles/rubella discarded cases, and 37.6% (29/77) tested positive for B19V. Conclusions: The study results highlight that effective measles surveillance must be supported by integrating timely virological diagnosis, molecular and epidemiological investigations, and differential diagnosis, to achieve the WHO goals of eliminating measles transmission. Full article

Chikungunya virus (CHIKungunya Virus, CHIKV) is a mosquito-borne plus-stranded RNA virus. Adaptive mutations such as A226V in the E1 envelope protein of CHIKV significantly enhance the transmission efficiency of the virus in Aedes albostriae, leading to multiple rounds of epidemics around the world including the large-scale outbreak in Guangdong Province in 2025. After a viral infection, a significant proportion of patients will progress from acute arthralgia to chronic arthritis that persists. The pathogenesis of the disease involves the persistence of the virus in joint tissues, the persistent inflammatory response with IL-1β, IL-6 and IL-17 as the core mediated by macrophages, possible autoimmune cross-reactions, and individual genetic susceptibility. At present, there is no specific antiviral drug, but important progress has been made in vaccine development against the virus. Vaccines based on live attenuated virus (VLA1553) and virus-like particle (VLP) platforms have been approved for the market and provide a tool to prevent and control this important public health threat. This review synthesizes current knowledge on CHIKV-induced chronic arthritis pathogenesis and recent vaccine advances, providing a framework for understanding disease mechanisms and guiding future prevention strategies. Full article

The re-emergence of alphaviruses (family Togaviridae), such as chikungunya virus, poses significant public health risks, with direct impact on quality of life and work productivity. There are no approved antiviral drugs for the treatment of infections with alphaviruses. Several alphaviruses are classified as risk group 3 agents which require handling in high-containment laboratories. To facilitate antiviral screening efforts against alphaviruses, we established a high-throughput antiviral screening assay using reporter Sindbis virus [SINV-GFP; expresses the green fluorescent protein] as a surrogate model for more pathogenic alphaviruses. The assay has strong reproducibility and was validated by reference small-molecule antivirals with various mechanisms of action. The use of high-content imaging as a readout, as demonstrated here, allows for high-throughput antiviral screening and provides a tool for early-stage antiviral discovery against emerging alphavirus threats at a lower biosafety level. Full article

Mosquito-borne diseases are an emerging public health challenge in Europe, driven by the spread of invasive mosquito species capable of sustaining outbreaks of tropical arboviral diseases. Rising temperatures, shifting precipitation patterns, human-driven habitat changes, and prolonged transmission seasons have increased the risk of dengue, chikungunya, and West Nile virus outbreaks, among other vector-borne diseases. Effective control requires a multifaceted approach, combining traditional and novel methods with advanced surveillance technologies and community involvement. However, growing insecticide resistance and concerns about insecticide use highlight the need for more prudent management of current tools and the development of innovative alternatives. Genetic control strategies, including the Sterile Insect Technique (SIT), Wolbachia-based approaches, and genetically modified (GM) mosquitoes, offer promising solutions but still face scientific, regulatory, and societal challenges. This review explores the current landscape of mosquito-borne disease control in Mediterranean Europe, emphasizing key challenges and emerging solutions. An integrated approach that strengthens surveillance, promotes sustainable control methods, and incorporates novel biotechnological tools supported by smart technologies will be essential to reduce the future burden of mosquito-borne diseases in the region. Full article