Eradication Of Disease Research Articles

DYNAMICS AND CONTROL OF BRUCELLOSIS IN HUMAN AND LIVESTOCK: PUBLIC HEALTH EDUCATION, TREATMENT AND VACCINATION

Brucellosis is a multifaceted zoonotic infection with vital epidemiological, economic, and global health effect, principally for human and Livestock populations within developing nations. In this paper a dynamic model of livestock-to-human transmission of the disease is developed. Model investigation is carried out to obtain and establish the stability of the equilibrium points. The basic reproduction number is calculated and the conditions under which brucellosis can be cleared in the both populations are established. Then, optimal control approach to establish the required conditions for the optimality of the disease eradication or control are applied. Public health education for humans and vaccination for susceptible livestock and treatment for infected humans and livestock. Numerical simulations show the dynamics of disease transmission and the effect of the control strategies.

Epitope Edited Hematopoietic Stem Cells to Enable Synergistic Immunotherapy Combinations for Acute Myeloid Leukemia

Despite treatment advances, acute myeloid leukemia (AML) is still associated with an unfavorable outcome for >50% of patients. Whereas novel immunotherapies, such as CAR-T cells, bispecific and toxin conjugated antibodies (mAb), demonstrated clinical efficacy when targeting dispensable lineage antigens (Ag), such as CD19 in B-ALL, the same approach cannot be exploited for AML, due to lack of actionable leukemia-restricted Ags. Suitable targets are shared with healthy progenitor or mature myeloid cells, leading to on-target/off-tumor toxicity and impairment of hematopoietic reconstitution. Several AML immunotherapies are currently under development, but their use is restricted to a limited time window, likely insufficient for disease eradication. To address these issues, we reasoned that precise modification of the targeted epitopes in donor HSPC used in HSCT results in loss of mAb recognition, without affecting normal protein expression, regulation, and function ( Nature, accepted). Epitope editing allows targeting genes essential for leukemia survival regardless of shared expression or functional role in normal HSPC, thus minimizing the risk of tumor immune escape by Ag loss or downregulation. Cytokine receptors such as FLT3, KIT and CD123 are found in >85% of AML cases and their mutation (e.g., FLT3-ITD) or overexpression is associated with poor prognosis. We identified amino acid substitutions in the FLT3, KIT and CD123 extracellular domains that preserve physiologic surface expression, ligand-binding, kinase phosphorylation, colony-forming capacity, proliferative response, transcriptional and phospho-proteomic profile of CD34+ HSPCs but avoid detection by a therapeutic monoclonal Ab. Cells expressing these variants were resistant to CAR-T killing and did not induce CAR activation and proliferation during in vitro co-culture. We were able to introduce these mutations into CD34+ HSPCs by adenine base editing (ABE) with high efficiencies (90%, 85% and 75% for FLT3, KIT and CD123, respectively) without the need for dsDNA breaks. After xenotransplant into NBSGW mice, FLT3, KIT or CD123 epitope-editedHSPC sustained long-term multilineage hematopoiesis indicating editing and preserved functionality of HSCs. Upon treatment with FLT3 CAR-T in vivo, we observed sparing of human CD34+38- HSPCs, granulo-mono progenitors (GMP), B-cells and B-progenitors in the bone marrow of mice engrafted with FLT3-edited HSPCs compared to AAVS1 controls. Treatment with CD123 CAR-T cells showed protection of epitope-edited myeloid lineages, including granulocytes, DCs and HSPCs. We next generated advanced in vivo models with co-engraftment of human HSPCs and patient-derived AML xenografts (PDX), to demonstrate the selective resistance of epitope edited HSPCs and their progeny, while PDX were eradicated by FLT3 or CD123 CAR-T. To further enhance therapeutic efficacy, we are now exploring the combination of epitope-edited HSPCs and pharmacological agents with potential synergistic effects with CAR-T cells. FLT3 tyrosine kinase inhibitors (e.g., Crenolanib) have the potential to enforce surface expression of FLT3 by impairing its intracellular recycling, thus enhancing CAR-T mediated killing, but their use may be limited by overlapping toxicities on healthy hematopoiesis, in particular in the post-HSCT setting. To assess if epitope-editing could prevent not only CAR- but also TKI-mediated toxicities, we treated mice co-engrafted with FLT3- or AAVS1- edited HSPCs and a FLT3-ITD+ AML PDX with combinations of FLT3-CAR and a 2-week course of Crenolanib. Leukemia burden was reduced by Crenolanib alone and eradicated by FLT3-CAR-T. Critically, we observed preservation of healthy hematopoietic lineages only in mice engrafted with epitope-edited HSPCs, including the CAR+Crenolanib group, while AAVS1 controls showed overlapping off-tumor toxicity when treated with the CAR+Crenolanib combination. In conclusion, we believe that epitope edited HSPCs may not only enable safe and effective CAR-T immunotherapies for AML, but also allow their combination with pharmacological blockade of leukemia survival/proliferative pathways to achieve synthetic lethality mechanisms, while still avoiding dose-limiting toxicities. Further exploration of immunotherapy-synergistic combinations will be fundamental to improve the outcomes of difficult-to-treat high-risk AML patients.

Threshold behavior and exponential ergodicity of an sir epidemic model: the impact of random jamming and hospital capacity.

This article uses hospital capacity to determine the treatment rate for an infectious disease. To examine the impact of random jamming and hospital capacity on the spread of the disease, we propose a stochastic SIR model with nonlinear treatment rate and degenerate diffusion. Our findings demonstrate that the disease's persistence or eradication depends on the basic reproduction number [Formula: see text]. If [Formula: see text], the disease is eradicated with a probability of 1, while [Formula: see text] results in the disease being almost surely strongly stochastically permanent. We also demonstrate that if [Formula: see text], the Markov process has a unique stationary distribution and is exponentially ergodic. Additionally, we identify a critical capacity which determines the minimum hospital capacity required.

Using a dynamical model to study the impact of a toxoid vaccine on the evolution of a bacterium: The example of diphtheria

Vaccines are one of humankind's greatest weapons against infectious diseases. However, their usefulness is often questioned and the public tends to distrust vaccines. A mathematical model published in the early 2000s predicts the selection of more virulent strains of pathogens when populations are protected with imperfect vaccines, i.e., vaccines which reduce but do not entirely block pathogen transmission, such as toxoid vaccines. In this study, we built a disease-specific competition model to analyze the evolution of diphtheria's virulence under the pressure of a toxoid vaccine. Our results show that i) high vaccine coverage favors the emergence and increase prevalence of avirulent (or less virulent) strains of Corynebacterium diphtheriae (the etiologic agent of diphtheria) and ii) that competition between strains is crucial in the eradication of toxigenic strains when toxoid vaccines are used. We conclude that the use of toxoid vaccines could lead to disease eradication if the interaction between strains is taken into account. Our results could extend to biologically similar systems such as pertussis.

Harnessing Attenuation-Related Mutations of Viral Genomes: Development of a Serological Assay to Differentiate between Capripoxvirus-Infected and -Vaccinated Animals.

Sheeppox, goatpox, and lumpy skin disease caused by the sheeppox virus (SPPV), goatpox virus (GTPV), and lumpy skin disease virus (LSDV), respectively, are diseases that affect millions of ruminants and many low-income households in endemic countries, leading to great economic losses for the ruminant industry. The three viruses are members of the Capripoxvirus genus of the Poxviridae family. Live attenuated vaccines remain the only efficient means for controlling capripox diseases. However, serological tools have not been available to differentiate infected from vaccinated animals (DIVA), though crucial for proper disease surveillance, control, and eradication efforts. We analysed the sequences of variola virus B22R homologue gene for SPPV, GTPV, and LSDV and observed significant differences between field and vaccine strains in all three capripoxvirus species, resulting in the truncation and absence of the B22R protein in major vaccines within each of the viral species. We selected and expressed a protein fragment present in wildtype viruses but absent in selected vaccine strains of all three species, taking advantage of these alterations in the B22R gene. An indirect ELISA (iELISA) developed using this protein fragment was evaluated on well-characterized sera from vaccinated, naturally and experimentally infected, and negative cattle and sheep. The developed wildtype-specific capripox DIVA iELISA showed >99% sensitivity and specificity for serum collected from animals infected with the wildtype virus. To the best of our knowledge, this is the first wildtype-specific, DIVA-capable iELISA for poxvirus diseases exploiting changes in nucleotide sequence alterations in vaccine strains.

Effects of boosting and waning in highly exposed populations on dengue epidemic dynamics.

Sequential infection with multiple dengue virus (DENV) serotypes is thought to induce enduring protection against dengue disease. However, long-term antibody waning has been observed after repeated DENV infection. Here, we provide evidence that highly immune Nicaraguan children and adults (n = 4478) experience boosting and waning of antibodies during and after major Zika and dengue epidemics. We develop a susceptible-infected-recovered-susceptible (SIRS-type) model that tracks immunity by titer rather than number of infections to show that boosts in highly immune individuals can contribute to herd immunity, delaying their susceptibility to transmissible infection. In contrast, our model of lifelong immunity in highly immune individuals, as previously assumed, results in complete disease eradication after introduction. Periodic epidemics under this scenario can only be sustained with a constant influx of infected individuals into the population or a high basic reproductive number. We also find that Zika virus infection can boost DENV immunity and produce delays and then surges in dengue epidemics, as observed with real epidemiological data. This work provides insight into factors shaping periodicity in dengue incidence and may inform vaccine efforts to maintain population immunity.

Analysis of the impact of treatments on HIV/AIDS and Tuberculosis co-infected population under random perturbations

In this work, we study the impact of treatments at different stages of Human Immunodeficiency Virus (HIV) and Tuberculosis (TB) co-infection in a population under the influence of random perturbations. This is achieved by constructing a stochastic epidemic model describing the transmission and treatment of the diseases. The model is created with the assumption that transmission rates fluctuate rapidly compared to the evolution of the untreated diseases. The basic reproduction numbers corresponding to the population with HIV infection only (with n stages of infections and treatments), the population with tuberculosis infection only, and the overall population with co-infection (with n stages of infection/treatments) are derived in the presence and absence of noise perturbations. These are used to discuss the long term behavior of the population around a disease-free equilibrium and an endemic equilibrium, and to analyze the effect of noise and treatments on the system. We also showed conditions under which TB infected population dynamic undergoes backward bifurcation and give conditions for disease eradication in the entire population. Analysis shows that small perturbations to the disease-free equilibrium can initially grow under certain conditions, and the introduction of TB treatment is effective in eliminating the co-infection. Numerical simulations are presented for validation of our results using published parameters.

Mathematical Modeling and Analysis of COVID-19 Infection: Application to the Kingdom of Saudi Arabia Data

To evaluate the probable effects of the COVID-19 outbreak on Saudi Arabia, a novel dynamical model is developed. Using the most recent instances of COVID-19 infection that have been reported in Saudi Arabia, we examine the roles of quarantine and hospitalization. The model’s mathematical outcomes are displayed. The model’s infection-free equilibrium is displayed, and asymptotically, it is determined to be both locally and globally stable. We demonstrate that the model is locally asymptotically stable (LAS) for the basic reproduction R 0 < 1 . The model is globally asymptotically stable (GAS) when R 0 ≤ 1 . To estimate the model parameters, recent COVID-19 instances in KSA that began between May 1, 2022, and August 4, 2022, are taken into account. We achieve the needed data fitting considering the approach of nonlinear least square, and we demonstrate that the predicted basic reproduction number is R 0 ≈ 1.2988 . Graphical representations of the calculated parameters and their effects on disease eradication are provided. The findings show that the most effective way to reduce the number of new instances of infection is to limit the contact of exposed, asymptomatic, symptomatic, and hospitalized people with vulnerable. The percentage of exposed people who are quarantined also plays a big part in lowering the number of infected cases.

A CAF01-adjuvanted whole asexual blood-stage liposomal malaria vaccine induces a CD4+ T-cell-dependent strain-transcending protective immunity in rodent models.

Malaria is a devastating disease that has claimed many lives, especially children <5 years of age in Sub-Saharan Africa, as documented in World Malaria Reports by WHO. Even though vector control and chemoprevention tools have helped with elimination efforts in some, if not all, endemic areas, these efforts have been hampered by serious issues (including drug and insecticide resistance and disruption to social cohesion caused by the COVID-19 pandemic). Development of an effective malaria vaccine is the alternative preventative tool in the fight against malaria. Vaccines save millions of lives each year and have helped in elimination and/or eradication of global diseases. Development of a highly efficacious malaria vaccine that will ensure long-lasting protective immunity will be a "game-changing" prevention strategy to finally eradicate the disease. Such a vaccine will need to counteract the significant obstacles that have been hampering subunit vaccine development to date, including antigenic polymorphism, sub-optimal immunogenicity, and waning vaccine efficacy.

Mathematical and Stability Analysis of Dengue–Malaria Co-Infection with Disease Control Strategies

Historically, humans have been infected by mosquito-borne diseases, including dengue fever and malaria fever. There is an urgent need for comprehensive methods in the prevention, control, and awareness of the hazards posed by dengue and malaria fever to public health. We propose a new mathematical model for dengue and malaria co-infection with the aim of comprehending disease dynamics better and developing more efficient control strategies in light of the threat posed to public health by co-infection. The proposed mathematical model comprises four time-dependent vector population classes (SEIdIm) and seven host population classes (SEIdImIdmTR). First, we show that the proposed model is well defined by proving that it is bounded and positive in a feasible region. We further identify the equilibrium states of the model, including disease-free and endemic equilibrium points, where we perform stability analysis at equilibrium points. Then, we determine the reproduction number R0 to measure the level of disease containment. We perform a sensitivity analysis of the model’s parameters to identify the most critical ones for potential control strategies. We also prove that the proposed model is well posed. Finally, the article examines three distinct co-infection control measures, including spraying or killing vectors, taking precautions for one’s own safety, and reducing the infectious contact between the host and vector populations. The control analysis of the proposed model reveals that all control parameters are effective in disease control. However, self-precaution is the most effective and accessible method, and the reduction of the vector population through spraying is the second most effective strategy to implement. Disease eradication is attainable as the vector population decreases. The effectiveness of the implemented strategies is also illustrated with the help of graphs.

Dog screening as a novel complementary guinea worm disease control tool to mitigate persistence in Chad: A modeling study

A free-roaming dog population remains one of the major public health problems in many developing countries. In this study, we investigated the potential impact of owned roaming and stray dogs on the persistence and possible eradication of Guinea worm disease (GWD) in Chad. We developed and analysed a multi-host of Guinea worm; and considered dogs as the definitive hosts, and fish as the intermediate hosts. Currently, GWD cases in the human population are low; hence, we ignored the human population in this study. We derived the reproduction number and explored how it depends on different model parameters that define it. We calibrated the proposed model with data from literature and validated it with recently reported GWD monthly data for dog infection in Chad from 2019 to 2022. Results show that detection and tethering of infectious owned free-roaming dogs combined with culling of stray dogs are effective disease management strategies. Hence, attainment of certain threshold levels for these interventions could lead to disease eradication. Overall, the study revealed how different factors could be applied to effectively manage GWD transmission in the dog population. Findings from this study could be used to support decision-making in GWD control strategies.Mathematics Subject Classification (2010): 92B05, 93A30, 93C15.

A non-integer order model for Zika and Dengue co-dynamics with cross-enhancement

A novel fractional derivative model with nine compartments is formulated to investigate the transmission dynamics of zika and dengue co-infection. The Atangana–Baleanu fractional derivative in the Caputo sense was employed. The conditions for a unique solution are identified, and the solutions’ positivity and boundedness are demonstrated. The disease-free equilibrium point (DFE) and basic reproduction number, R0, were obtained. The DFE was shown to be locally asymptotically stable when the basic reproduction number is less than one. Zika-associated reproduction number, R0z, and dengue-associated reproduction number, R0d, were estimated to be 1.0144 and 1.1724, respectively. The system was shown to be generalized Ulam Hyers–Rassias stable, and the Adam–Bashforth method was used to provide its’ numerical solution. Sensitivity analysis using the Latin Hyper-cube Sampling (LHS) and Partial Rank Correlation Coefficient (PRCC) (|PRCC|> 0.45) with 200 runs was carried out using various variables as response functions per time. The most significant parameters were found to be zika human-to-human transmission rate, βhz1, vector death rate, μv, zika recovery rate, γhz1 and dengue vector-to-human transmission rate, βhd. Real data from Espirito Santo in Brazil is used to validate the model and fit needed parameter values. Numerical simulations illustrated the impact of varying the fractional order derivative, recovery rates, transmission rates, and cross-enhancement parameters on the infected human compartments. The zika Human-to-human transmission rate, βhz1, was found to be a very significant parameter in the control of zika disease transmission. Increasing the vector death rate, μv, was more important in curbing dengue prevalence and incidence than the attainment of recovery from the dengue disease, and the absence of the zika Vector-to-human transmission rate, βhz3, was almost insignificant in the presence of the zika Human-to-human transmission rate, βhz1, for disease eradication. This study suggested control measures and strategies to decrease the dengue and zika human-to-human transmission rates.

Nodal pCR and overall survival following neoadjuvant chemotherapy for node positive ER+/Her2- breast cancer.

The role of neoadjuvant chemotherapy (NAC) in node-positive (N+) ER+/HER2- breast cancer (BC) is debated, given low total pathologic complete response (pCR) rates. However, the rate and impact of nodal pCR is unknown. We sought to evaluate nodal pCR rates and the impact on overall survival (OS). Further, we sought to validate the association between nodal pCR with age and Ki67. We queried the National Cancer Database for cN + ER+/HER2- BC patients treated with NAC and surgery. Data from 2010 to 2018 were used to evaluate nodal pCR and OS, with multivariable Cox proportional hazards modeling for OS, as well as Ki67 for the years 2018-2019. From 2010 to 2018, we identified 19,611 cN + ER+/HER2- BC patients treated with NAC. While total pCR occurred in only 7.4%, nodal pCR rates were nearly double (14.3%). Nodal pCR (+/- breast pCR) was seen in 21.7% and associated with 5-year OS rate of 86.1% (95% CI: 84.9-87.4%) versus 77.1% (95% CI: 76.3-77.9%) in patients without nodal pCR (p < 0.001). On multivariable analysis, nodal pCR had better OS (adjusted HR 0.57, 95%CI 0.52-0.63, p < 0.001) across all age groups. Of 2,444 patients with available Ki67, those with age < 50 and Ki67 ≥ 20% had the highest nodal pCR at 31.6%. In cN + ER+/HER2- BC treated with NAC, nodal pCR is common, associated with age and Ki67, and prognostic for OS. These data strongly suggest that for cN + patients, eradication of nodal disease is critical for OS, and total pCR may not be the optimal measure of NAC benefit.

Preferential differential gene expression within the WC1.1+ γδ T cell compartment in cattle naturally infected with Mycobacterium bovis.

Bovine tuberculosis (bTB), caused by infection with Mycobacterium bovis, continues to cause significant issues for the global agriculture industry as well as for human health. An incomplete understanding of the host immune response contributes to the challenges of control and eradication of this zoonotic disease. In this study, high-throughput bulk RNA sequencing (RNA-seq) was used to characterise differential gene expression in γδ T cells - a subgroup of T cells that bridge innate and adaptive immunity and have known anti-mycobacterial response mechanisms. γδ T cell subsets are classified based on expression of a pathogen-recognition receptor known as Workshop Cluster 1 (WC1) and we hypothesised that bTB disease may alter the phenotype and function of specific γδ T cell subsets. Peripheral blood was collected from naturally M. bovis-infected (positive for single intradermal comparative tuberculin test (SICTT) and IFN-γ ELISA) and age- and sex-matched, non-infected control Holstein-Friesian cattle. γδ T subsets were isolated using fluorescence activated cell sorting (n = 10-12 per group) and high-quality RNA extracted from each purified lymphocyte subset (WC1.1+, WC1.2+, WC1- and γδ-) was used to generate transcriptomes using bulk RNA-seq (n = 6 per group, representing a total of 48 RNA-seq libraries). Relatively low numbers of differentially expressed genes (DEGs) were observed between most cell subsets; however, 189 genes were significantly differentially expressed in the M. bovis-infected compared to the control groups for the WC1.1+ γδ T cell compartment (absolute log2 FC ≥ 1.5 and FDR P adj. ≤ 0.1). The majority of these DEGs (168) were significantly increased in expression in cells from the bTB+ cattle and included genes encoding transcription factors (TBX21 and EOMES), chemokine receptors (CCR5 and CCR7), granzymes (GZMA, GZMM, and GZMH) and multiple killer cell immunoglobulin-like receptor (KIR) proteins indicating cytotoxic functions. Biological pathway overrepresentation analysis revealed enrichment of genes with multiple immune functions including cell activation, proliferation, chemotaxis, and cytotoxicity of lymphocytes. In conclusion, γδ T cells have important inflammatory and regulatory functions in cattle, and we provide evidence for preferential differential activation of the WC1.1+ specific subset in cattle naturally infected with M. bovis.

Leader‐following consensus and qualitative analysis of a new multi‐agent‐based epidemic model

AbstractThis paper addresses an investigation into a leader‐following consensus problem in a novel multi‐agent‐based SIS (Susceptible‐Infected‐Susceptible) epidemic model. As infectious diseases are easily spread through travel, the model considers each agent to represent a city in an infected country, interacting with neighbouring cities towards achieving disease eradication through consensus. To make the model more realistic, the Effect Terms (ETs) arising from the effects of agent states on each other are also considered. The differential equations' positivity and existence of solutions are examined, and the proposed model's equilibrium points are obtained, with stability analysed using new local and global basic reproduction numbers defined in this study. Additionally, a leader‐following consensus control for the multi‐agent‐based system is proposed to drive each agent to follow a virtual leader agent. Finally, numerical simulations are included to validate the theoretical findings corresponding to the proposed scheme.

Investigating Awareness Regarding Travel-Related Infectious Disease Prevention in a Metropolitan Area.

The rise in international travel has led to an increase in travel-related infectious diseases. It is predicted that by 2030, the number of international travelers will reach 1.8 billion, with over 250 million people affected globally. This issue also has an economic impact, as the eradication of travel-related infectious diseases leads to a loss of USD 12 billion in tourism. To understand the association between demographic variables and knowledge, attitude, and behaviors related to travel-related infectious diseases, a cross-sectional survey-based study was conducted among 1191 individuals in the metropolitan city of Naples, Italy. Multiple linear regression was performed over three models. The results revealed that knowledge about travel-related infectious diseases was positively associated with age, female gender, non-smoking habits, being single, and higher education attainment. The attitude towards travel-related infectious diseases was positively associated with being female, non-smoking habits, being single, higher education attainment, and a higher level of knowledge. A statistically significant association was observed between behaviors and non-smoking habits and between higher levels of knowledge and attitudes. To address this issue, public health programs could be implemented to improve behaviors in the general population. Overall, this study provides valuable information about the determinants of knowledge, attitude, and behaviors related to travel-related infectious diseases in the general population.

Extensive Sequestration Chronic Maxillary Osteomyelitis in an Uncontrolled Diabetic Patient: Comprehensive Case Management of a Rare Entity.

The hallmark of osteomyelitis was progressive bone destruction and sequestrum formation. In the underlying disease, like diabetes mellitus, osteomyelitis becomes severe and exacerbates the condition. It was essential for the oral and maxillofacial surgeon to comprehend its complex medical and surgical management to achieve complete disease eradication. The aim of this article was to report a rare case and comprehensive management of extensive sequestrating maxillary osteomyelitis with uncontrolled diabetes mellitus patients. A 58-year-old male patient with pain and swelling accompanied by discharge of pus in the sinistra maxilla region. The systemic disease was identified as uncontrolled diabetes mellitus, and had a history of unhealing wounds 1 year ago after upper left molar extraction. Computed tomography scan result showed extensive sequester formation and bony destruction in the right extending to the left maxilla. Microbial culture results were Klebsiella pneumoniae and Morganella morganii. Subsequently, extensive sequestrectomy and multiple extractions of the involved jaw and teeth were performed after diabetes mellitus was regulated. A suspension suture against oral and nasal mucosa was performed to avoid dead space formation. Comprehensive perioperative management in maxillary osteomyelitis in uncontrolled diabetes mellitus includes sequestrectomy, definitive antibiotic therapy based on culture results, and diabetes regulation to improve the successful management of this case.

Evolutionary-Game-Theory-Based Epidemiological Model for Prediction of Infections with Application to Demand Forecasting in Pharmaceutical Inventory Management Problems

Pharmaceuticals play a critical role in the eradication of infectious diseases. Effective pharmaceutical inventory management is important for controlling epidemics since medical resources such as pharmaceuticals, medical staff, and hospitals are limited. In this study, a novel epidemiological model is proposed to evaluate the resource requirements for pharmaceuticals and is applied to analyze different pharmaceutical inventory management strategies. We formulate the relationship between the number of infected individuals and the risk of infection to account for virus mutation. Evolutionary game theory is integrated into an epidemiological model to represent human behavioral choices. The proposed model can be developed to forecast the demand for pharmaceuticals and analyze how human behavior affects the demand of pharmaceuticals. This study found that making people aware of the risk of disease has a positive impact on both reducing the number of infections and managing the pharmaceutical inventory. The main contribution of this study is to enhance areas of research in pharmaceutical inventory management. This study revealed that the correct recognition of the risk of disease leads to appropriate pharmaceutical management. There are a few studies on the application of infectious disease models to inventory control problems. This study provides clues toward proper pharmaceutical management.

Assessing the Impact of Time-Varying Optimal Vaccination and Non-Pharmaceutical Interventions on the Dynamics and Control of COVID-19: A Computational Epidemic Modeling Approach

Vaccination strategies remain one of the most effective and feasible preventive measures in combating infectious diseases, particularly during the COVID-19 pandemic. With the passage of time, continuous long-term lockdowns became impractical, and the effectiveness of contact-tracing procedures significantly declined as the number of cases increased. This paper presents a mathematical assessment of the dynamics and prevention of COVID-19, taking into account the constant and time-varying optimal COVID-19 vaccine with multiple doses. We attempt to develop a mathematical model by incorporating compartments with individuals receiving primary, secondary, and booster shots of the COVID-19 vaccine in a basic epidemic model. Initially, the model is rigorously studied in terms of qualitative analysis. The stability analysis and mathematical results are presented to demonstrate that the model is asymptotically stable both locally and globally at the COVID-19-free equilibrium state. We also investigate the impact of multiple vaccinations on the COVID-19 model’s results, revealing that the infection risk can be reduced by administrating the booster vaccine dose to those individuals who already received their first vaccine doses. The existence of backward bifurcation phenomena is studied. A sensitivity analysis is carried out to determine the most sensitive parameter on the disease incidence. Furthermore, we developed a control model by introducing time-varying controls to suggest the optimal strategy for disease minimization. These controls are isolation, multiple vaccine efficacy, and reduction in the probability that different vaccine doses do not develop antibodies against the original virus. The existence and numerical solution to the COVID-19 control problem are presented. A detailed simulation is illustrated demonstrating the population-level impact of the constant and time-varying optimal controls on disease eradication. Using the novel concept of human awareness and several vaccination doses, the elimination of COVID-19 infections could be significantly enhanced.

The combination of vaccines and adjuvants to prevent the occurrence of high incidence of infectious diseases in bovine.

As the global population grows, the demand for beef and dairy products is also increasing. The cattle industry is facing tremendous pressures and challenges. The expanding cattle industry has led to an increased risk of disease in cattle. These diseases not only cause economic losses but also pose threats to public health and safety. Hence, ensuring the health of cattle is crucial. Vaccination is one of the most economical and effective methods of preventing bovine infectious diseases. However, there are fewer comprehensive reviews of bovine vaccines available. In addition, the variable nature of bovine infectious diseases will result in weakened or even ineffective immune protection from existing vaccines. This shows that it is crucial to improve overall awareness of bovine vaccines. Adjuvants, which are crucial constituents of vaccines, have a significant role in enhancing vaccine response. This review aims to present the latest advances in bovine vaccines mainly including types of bovine vaccines, current status of development of commonly used vaccines, and vaccine adjuvants. In addition, this review highlights the main challenges and outstanding problems of bovine vaccines and adjuvants in the field of research and applications. This review provides a theoretical and practical basis for the eradication of global bovine infectious diseases.