Search Results (448)

Deer tick virus (DTV) is a Tick-Borne Orthoflavivirus endemic to the United States, transmitted to humans through bites from the deer tick, Ixodes scapularis, which is also the primary vector of Borrelia burgdorferi s.l., the causative agent of Lyme disease. Human infection with DTV can result in acute febrile illness followed by central nervous system complications, such as encephalitis and meningoencephalitis. Currently, there are mouse models established for investigating the pathogenesis and clinical outcomes of DTV that mimic human infections, but the strains of mice utilized are refractory to infection with B. burgdorferi s.l. Here, we describe the pathogenesis and clinical outcomes of DTV infection in C3H/HeJ mice. Neurological clinical signs, mortality, and weight loss were observed in all DTV-infected mice during the investigation. Infected animals demonstrated consistent viral infection in their organs. Additionally, neuropathology of brain sections indicated the presence of meningoencephalitis throughout the brain. This data, along with the clinical outcomes for the mice, indicates successful infection and showcases the neuroinvasive nature of the virus. This is the first study to identify C3H/HeJ mice as an appropriate model for DTV infection. As C3H/HeJ mice are already an established model for B. burgdorferi s.l. infection, this model could serve as an ideal system for investigating disease progression and pathogenesis of co-infections. Full article

In Kenya, Rift Valley fever (RVF) outbreaks pose significant challenges, being one of the most severe climate-sensitive zoonoses. While machine learning (ML) techniques have shown superior performance in time series forecasting, their application in predicting disease outbreaks in Africa remains underexplored. Leveraging data from the International Livestock Research Institute (ILRI) in Kenya, this study pioneers the use of ML techniques to forecast RVF outbreaks by analyzing climate data spanning from 1981 to 2010, including ML models. Through a comprehensive analysis of ML model performance and the influence of environmental factors on RVF outbreaks, this study provides valuable insights into the intricate dynamics of disease transmission. The XGB Classifier emerged as the top-performing model, exhibiting remarkable accuracy in identifying RVF outbreak cases, with an accuracy score of 0.997310. Additionally, positive correlations were observed between various environmental variables, including rainfall, humidity, clay patterns, and RVF cases, underscoring the critical role of climatic conditions in disease spread. These findings have significant implications for public health strategies, particularly in RVF-endemic regions, where targeted surveillance and control measures are imperative. However, this study also acknowledges the limitations in model accuracy, especially in scenarios involving concurrent infections with multiple diseases, highlighting the need for ongoing research and development to address these challenges. Overall, this study contributes valuable insights to the field of disease prediction and management, paving the way for innovative solutions and improved public health outcomes in RVF-endemic areas and beyond. Full article

In this paper, we develop an HIV/AIDS epidemic model that incorporates a saturated incidence rate to reflect the limited transmission capacity and the impact of behavioral saturation in contact patterns. The model is formulated as a system of seven non-linear ordinary differential equations representing key population compartments. In addition to model formulation, we introduce an optimal control problem involving three control measures: educational campaigns, screening of unaware infected individuals, and antiretroviral treatment for aware infected individuals. We begin by establishing the positivity and boundedness of the model solutions under constant control inputs. The existence and local and global stability of both the disease-free and endemic equilibrium points are analyzed, depending on the effective reproduction number (${\mathcal{R}}_e$). Bifurcation analysis reveals that the model undergoes a forward bifurcation at ${\mathcal{R}}_e=1$. A local sensitivity analysis of ${\mathcal{R}}_e$ identifies the disease transmission rate as the most sensitive parameter. The optimal control problem is then formulated by incorporating the dynamics of infected subpopulations, control costs, and time-dependent controls. The existence of optimal control solutions is proven, and the necessary conditions for optimality are derived using Pontryagin’s Maximum Principle. Numerical simulations support the theoretical analysis and confirm the stability of the equilibrium points. The optimal control strategies, evaluated using the Incremental Cost-Effectiveness Ratio (ICER), indicate that implementing both screening and treatment (Strategy D) is the most cost-effective intervention. These results provide important insights for designing effective and economically sustainable HIV/AIDS intervention policies. Full article

Monkeypox virus (Mpox) has recently drawn global attention due to outbreaks beyond its traditional endemic regions. Understanding the immune response to Mpox infection is essential for improving disease management and guiding vaccine development. In this study, we used several machine learning algorithms to analyze time series gene expression data from macaques infected with Mpox, aiming to uncover key immune-related genes involved in different stages of infection. The dataset covered early infection, late infection, and rechallenge phases. We applied nine feature ranking methods to analyze the feature importance, obtaining nine feature lists. Then, the incremental feature selection method was applied to each list to extract key genes and build efficient prediction models and classification rules for each list. This procedure employed twelve classification algorithms and the Synthetic Minority Oversampling Technique. Key genes—such as CD19, MS4A1, and TLR10—were repeatedly identified from multiple feature lists, and are known to play vital roles in B-cell activation, antibody production, and innate immunity. Furthermore, we identified several novel key genes (HS3ST1, SPAG16, and MTARC2) that have not been reported previously. These findings offer valuable insights into the host immune response and highlight potential molecular targets for monitoring and intervention in Mpox infections. Full article

Despite initial changes in respiratory illness epidemiology due to SARS-CoV-2, influenza activity has returned to pre-pandemic levels, highlighting its ongoing challenges. This paper investigates an influenza epidemic model using a Susceptible-Exposed-Infected-Recovered (SEIR) framework, extended with fuzzy Atangana–Baleanu–Caputo (ABC) fractional derivatives to incorporate uncertainty (via fuzzy numbers for state variables) and memory effects (via the ABC fractional derivative for non-local dynamics). We establish the theoretical foundation by defining the fuzzy ABC derivatives and integrals based on the generalized Hukuhara difference. The existence and uniqueness of the solutions for the fuzzy fractional SEIR model are rigorously proven using fixed-point theorems. Furthermore, we analyze the system’s disease-free and endemic equilibrium points under the fractional framework. A numerical scheme based on the fractional Adams–Bashforth method is used to approximate the fuzzy solutions, providing interval-valued results for different uncertainty levels. The study demonstrates the utility of fuzzy fractional calculus in providing a more flexible and potentially realistic approach to modeling epidemic dynamics under uncertainty. Full article

Ticks carry a range of pathogens, the best known of which causes Lyme disease, prevalent in the northeastern United States. Emerging diseases do not yet consist of a wide range of Lyme diseases, raising the question of how long it takes for a newly introduced tick-borne disease to establish itself. The aim of this study was to address this question, with the agent of Lyme disease used as the test case. A prior process-based model of the Ixodes scapularis (Say 1821) life cycle and the transmission of Borrelia burgdorferi (Burgdorfer 1982) between this tick and its various hosts was used to predict the dynamics of disease introduction into a new area. The importance of temperature, infection probabilities, and tick host populations, relative to that of other factors, was established by a global sensitivity analysis using Latin hypercube sampling. The results of those samples were analyzed to determine the time to near-equilibrium. Eight locations in New Hampshire were chosen for high/low temperature, high/low mouse, and high/low deer values. Mammal abundance was estimated by relating the known mammal density from previous studies to a MaxEnt analysis output. The time required to reach Borrelia endemicity in the ticks of New Hampshire ranged from 8 to 20 years in regions where the tick population is viable, with a strong dependency on susceptible tick host populations. Full article

As a re-emerging disease, the worldwide burden and trends of yellow fever (YF) remain inadequately quantified. This study aims to assess the incidence of YF both globally and in major endemic regions from 1990 to 2021. Utilizing data from the Global Burden of Disease (GBD) database, we evaluated the burden of YF. We employed an age–period–cohort model to assess the influence of age, period, and cohort on the incidence of YF from 1992 to 2021. A secondary data analysis based on GBD database showed the following: in 2021, there were 86,509 incident cases of YF. Between 1990 and 2021, the number of incident cases decreased by 74.7%, while the age-standardized incidence rate (ASIR) declined at an EAPC of −4.76% (95% confidence interval: −5.10 to −4.42). In 2021, the highest ASIRs of YF were observed in Western Sub-Saharan Africa, Central Sub-Saharan Africa, and Eastern Sub-Saharan Africa. The analysis of age effects indicates that children aged 5–10 years old exhibit the highest incidence rate. Both period and cohort effects demonstrated a decline in morbidity risk. The decomposition analysis identified epidemiological changes as the primary factor contributing to the global reduction in the YF burden. Despite considerable reduction in incidence, YF remains a significant public health threat in Sub-Saharan Africa. Full article

West Nile virus (WNV) causes thousands of arboviral infections in the United States each year. Patients with immune-compromising conditions and elderly people are at higher risk of severe WNV neuroinvasive disease (WNND). Despite its broad endemicity nationwide, no U.S. Food and Drug Administration-approved vaccine or therapeutic treatments exist. We summarized existing peer-reviewed literature on the preclinical development of monoclonal antibody (MAb) prophylaxis and therapeutics for the prevention and treatment of WNND. Five bibliographical databases (CINAHL, Cochrane Library, Embase, MEDLINE, and Scopus) were searched for applicable research studies performed from 1 January 1998 to 1 May 2025. In total, 2347 titles and abstracts were screened, 263 full-text publications reviewed, and 25 studies included. Studies included detailed preclinical development and evaluations of MAbs targeting the envelope (E) protein (n = 13), other viral proteins (n = 3), flaviviral cross-protective monoclonal antibodies (n = 4), and novel antibody configurations or delivery methods (n = 5). The most well-studied MAb, E16, targeting E- Domain III (E-DIII), was effective at inhibiting and treating WNND in experimental animal models. No work investigated ways to traffic therapeutic antibodies across the blood–brain barrier. This review summarizes the current research in the development of monoclonal antibody therapeutics for WNV and addresses gaps in the knowledge for future consideration. Full article

Visceral leishmaniasis (VL), a chronic disease caused by Leishmania infantum, is more prevalent in males than females. Control strategies that do not take this disparity into account can be suboptimal. We extended a sex-structured VL model by introducing four control variables: insecticide-treated bed nets, vector control, medical treatment, and animal culling. The study evaluates six intervention strategies and calculates the incremental cost-effectiveness ratio to assess their impact on disease transmission and cost-effectiveness. The analysis shows that, without interventions, the disease remains endemic with significant health and socioeconomic consequences. The proposed strategy, which applies all four controls, emerges as the most effective and cost-efficient strategy, leading to an exponential reduction in disease prevalence across human, vector, and animal populations. Strategies without animal culling and vector control followed in effectiveness. Moreover, it was found that applying up to 50% of the controls to females, compared to males, can still eliminate VL within the planning period. Full article

Background/Objectives: Lip and oral cavity cancer (LOC) remains a critical public health challenge in Asia. This study evaluated spatiotemporal trends and risk factor contributions to LOC-related disability-adjusted life years (DALYs) from 1990 to 2021 to inform evidence-based healthcare policies. Methods: Using Global Burden of Disease (GBD) 2021 data, we analyzed LOC DALYs stratified by age, gender, risk factors (smoking, alcohol use, tobacco chewing), and subregions in Asia. Temporal trends were quantified via estimated annual percentage change (EAPC) across five geographic regions and sociodemographic index (SDI) categories. Age–period–cohort (APC) modeling was used to assess age-specific risk distributions. Results: From 1990 to 2021, Asia’s age-standardized DALY rate (ASDR) for LOC marginally increased (EAPC: 0.0883, 95% CI: 0.0802–0.0963). The alcohol-related ASDR increased sharply (EAPC: 1.033, 95% CI: 1.00–1.06), whereas decreases were detected in the smoking- and tobacco chewing-attributable ASDRs. Pronounced upward trends were observed in South Asia and low/low-middle-SDI regions. Tobacco chewing was the primary risk factor for women and for the populations in South Asia and lower-SDI regions, whereas smoking dominated among men and those in other geographic regions and in higher-SDI areas. APC analysis revealed age-driven increases in ASDR, with alcohol use and tobacco chewing risk increased with age. Notably, the steepest ASDR increase occurred in individuals aged 20–25 years. Conclusions: The LOC burden in Asia reflects divergent risk factor dynamics. Policy strategies must prioritize geographic and demographic targeting: alcohol control in rapidly developing areas and intensified tobacco cessation programs in endemic zones. Early prevention efforts focusing on adolescents and tailored to subregional risk profiles are essential to mitigate future disease burden. Full article

Background/Objectives: Syphilis, a chronic sexually transmitted disease caused by the spirochete Treponema pallidum subspecies pallidum (T. pallidum), is still endemic in low- and middle-income countries and has been resurgent for decades in many high-income nations despite being treatable. Improving our understanding of syphilis pathogenesis, immunology, and T. pallidum biology could result in novel measures to curtail syphilis spread, including new therapeutics, a preventive vaccine, and, most importantly, improved diagnostics. Methods: Using overlapping synthetic peptides spanning the length of the T. pallidum Tp0435 mature lipoprotein, an abundant antigen known to induce an immunodominant humoral response during both natural and experimental infection, we evaluated which Tp0435 linear epitopes are most significantly recognized by antibodies from an infected host. Specifically, we used sera from 63 patients with syphilis at different stages, sera from non-syphilis patients (n = 40), and sera longitudinally collected from 10 rabbits infected with either the Nichols or SS14 isolates of T. pallidum, which represent the model strains for the two known circulating clades of this pathogen, to further evaluate the use of this animal model for syphilis studies. Recognized amino acid sequences were then mapped to the experimentally determined Tp0435 structure. Results: Reactive epitopes in both serum groups mapped predominantly to the α-helix preceding Tp0435 soluble β-barrel and the loops of the barrel. Conclusions: In the current effort to improve current syphilis diagnostics, the peptides corresponding to these immunodominant epitopes could help develop epitope-based assays such as peptide-based ELISAs and lateral flow point-of-care tests to improve the performance of treponemal tests and expedite diagnosis in low-income settings, where the infection is still a significant concern for public health and access to facilities with laboratories equipped to perform complex procedures might be challenging. Full article

Encephalitis, a severe neurological condition caused by human-to-human (H2H) transmitted viruses, such as herpes simplex virus (HSV), requires a rigorous mathematical framework to understand its transmission dynamics. This study develops a nonlinear compartmental model, SEITR (Susceptible–Exposed–Infected–Treated–Recovered), to characterize the progression of viral encephalitis. The basic reproduction number (R₀) is derived using the next-generation matrix method, serving as a threshold parameter determining disease persistence. The local and global stability of the disease-free and endemic equilibria are established through a rigorous mathematical analysis. Additionally, a sensitivity analysis quantifies the impact of key parameters on R₀, offering more profound insights into their mathematical significance. Numerical simulations validate the theoretical results, demonstrating the system’s dynamical behavior under varying epidemiological conditions. This study provides a mathematically rigorous approach to modeling viral encephalitis transmission, filling a gap in the literature and offering a foundation for future research in infectious disease dynamics. Full article

In this paper, we establish an age-structured SEIAR epidemic model that incorporates media effects and employ the exponential function approach to demonstrate the crucial role of media influence in disease prevention and control. Notably, our model accounts for the possibility of recessive infected individuals becoming dominant through contact with infectious individuals. Theoretical analysis yields the explicit expression for the basic reproduction number $R_0$, which serves as a critical threshold for disease dynamics. Through comprehensive threshold analysis, we investigate the existence and stability of both disease-free and endemic equilibrium states. By applying characteristic equation analysis and the method of characteristics, we establish the following: (1) when $R_0<1$, the disease-free equilibrium is globally asymptotically stable; (2) when $R_0>1$, a unique endemic equilibrium exists and maintains local asymptotic stability under specific conditions. This study shows that strengthening media promotion, raising awareness, and reducing the density of recessive infected individuals can effectively control the further spread of a disease. To validate our theoretical results, we present numerical simulations that quantitatively assess the impact of varying media reporting intensities on epidemic containment measures. These simulations provide practical insights for public health intervention strategies. Full article

Background/Objectives: COVID-19 pandemic had a significant impact on endemic respiratory illnesses. Through behavioral changes in populations and government policy, mainly through non-pharmaceutical interventions (NPIs), Canada saw historic lows in the number of influenza A cases from 2020 through 2022. In this study, we use historical influenza A data for Canada and three provincial jurisdictions within Canada—Ontario, Quebec, and Alberta—to quantify the effects of these NPIs on influenza A. Methods: We aim to see which base parameters and derived parameters of an SIR model are most affected by NPIs. We fit a simple SIR model to historical influenza data to get average paramters for seasonal influenza. We then compare these parameters to those predicted by fitting influenza cases during the COVID-19 pandemic. Results: We find substantial differences in the effective population size and basic reproduction number during the COVID-19 pandemic. We also see the effects of fatigue and relaxation of NPIs when comparing the years 2020, 2021, and 2022. Conclusions: We find that the effective population size is the main driver of change to disease spread and discuss how these retrospective estimates can be used for future forecasting. Full article

Bovine pestiviruses, namely bovine viral diarrhea virus (BVDV) and HoBi-like pestiviruses (HoBiPevs), are endemic viruses in Latin America, and the disease causes significant losses in the agricultural sector. The present review aims to perform a systematic assessment and meta-analysis of the prevalence of bovine pestiviruses in Latin America and their risk factors. Notable heterogeneity was observed in the analyzed groups, with significant prevalence variations based on age and country. However, no differences were found between temporal trends, production systems, or models. Identified risk factors included age, breed, location, reproductive practices, animal purchase, farm management, and biosecurity measures. This systematic review and meta-analysis of BVDV in Latin America provides critical insights to inform decision-making and strategic actions for disease control in the region. The high serological prevalence of bovine pestivirus across Latin America underscores the urgent need for standardized surveillance programs, biosecurity reinforcement, and targeted vaccination strategies. The presence of HoBiPev further complicates current diagnostic and control measures. Future research should focus on disease transmission dynamics, economic impact assessments, and the effectiveness of intervention programs tailored to the region’s diverse livestock production systems. Full article