Analysis of the immunological response elicited by a polyvalent foot and mouth disease vaccine and its compatibility with a diva test in Jimma Town, Ethiopia.

The research was conducted in Jimma town, Oromiya Regional State, from October 2022 to June 2023, with the aim of assessing the immune response of polyvalent FMD (Foot and Mouth Disease) vaccine. The study involved 34 cattle in a longitudinal study, divided into two groups: 29 vaccinated and 5 unvaccinated. The vaccinated cattle received an inactivated polyvalent FMD virus vaccine produced by the National Veterinary Institute. Blood samples were collected on days 0, 14, 21, 35, 80, and 125 after vaccination and tested using Virus Neutralization Test and 3ABC ELISA. The results showed a significant increase in neutralizing antibodies against structural proteins in all vaccinated cattle on day 14 after vaccination for all three serotypes. (A/ETH/21/2000, p = 0.015; O/ETH/38/2005, p = 0.017; SAT2/ETH/64/2009, p = 0.007). On day, fourteen of post-vaccination vaccinated group showed immune response equal or above 1.5 log10 in a proportion of 69%, 73% and 94% for serotype A/ETH/21/2000, O/ETH/38/2005 and SAT2/ETH/64/2009 respectively. The status of raised antibody titer on day 125 post-vaccination showed decreasing by 14%, 18% and 4% for serotype A/ETH/21/2000, O/ETH/38/2005 and SAT2/ETH/64/2009 respectively. The DIVA test, or 3ABC ELISA, used to differentiate infected from vaccinated animals, revealed the absence of immune response to the Non-structural protein in the vaccinated cattle group. Conversely, the unvaccinated group showed no recorded antibody titer to both structural and non-structural proteins. In summary, the commercially available FMD vaccine, comprising serotype A, O, and SAT2, triggers an immune response to the structural protein rather than the non-structural protein after the initial administration. This outcome implies that FMD vaccines from the National Veterinary Institute align with the DIVA test. Nevertheless, additional efforts may be necessary to bolster the strength and duration of the vaccine-induced immune response.

Impact of COVID-19 control measures on respiratory syncytial virus and hand-foot-and-mouth disease transmission in Hong Kong and South Korea.

The public health and social measures (PHSMs) for mitigation/control of COVID-19 pandemic influenced the transmission dynamics of many other infectious diseases, including respiratory syncytial virus (RSV) infection, and hand, foot and mouth disease (HFMD) and their disease-burden. This study aimed to infer the transmission dynamics of these respiratory viruses and assess the impact of COVID-19 PHSMs on their community activity. We developed a compartmental framework to infer the transmission dynamics of RSV and HFMD in Hong Kong and South Korea from January 2014 to May 2024. We assessed the impact of PHSMs by comparing the change in virus transmissibility, reproduction number and population susceptibility before, during, and after the COVID-19 pandemic period. A significant reduction in RSV and HFMD activity was observed starting in January 2020, with a resurgence since late 2021. Transmissibility of both diseases decreased by 46 % - 95 % during the lull, while population susceptibility was estimated to increase by maximum of 19 %. On relaxation of the PHSMs, the transmissibility were recovered up to 70 % in Hong Kong and nearly 100 % in South Korea in 2023 with significant epidemics for these viruses. Strict implementation of COVID-19 PHSMs led to low RSV and HFMD activity, but the absence of community infection resulted in reductions in population immunity, and slightly larger epidemics when these diseases re-emerged following the COVID-19 pandemic.

The Current Epizootiological Situation of Three Major Viral Infections Affecting Cattle in Egypt.

One of the major factors hindering efficient livestock production is the presence of high-impact infectious animal diseases, such as foot and mouth disease (FMD), lumpy skin disease (LSD), and bovine ephemeral fever (BEF), which are notable viral infections affecting cattle in Egypt, leading to significant economic losses. FMD is caused by the foot and mouth disease virus (FMDV) of the genus Aphthovirus in the Picornaviridae family. LSD is caused by lumpy skin disease virus (LSDV) of Capripox genus within the Poxviridae family, subfamily Chordopoxvirinae. BEF is caused by bovine ephemeral fever virus (BEFV) of genus Ephemerovirus in the Rhabdoviridae family. FMD is a highly contagious viral infection of domestic and wild cloven-hooved animals and can spread through the wind. On the other hand, LSD and BEF are arthropod-borne viral diseases that mainly affect domestic cattle and water buffalo. Despite government vaccination efforts, these three viral diseases have become widespread in Egypt, with several reported epidemics. Egypt's importation of large numbers of animals from different countries, combined with unregulated animal movements through trading and borders between African countries and Egypt, facilitates the introduction of new FMDV serotypes and lineages not covered by the current vaccination plans. To establish an effective control program, countries need to assess the real epizootic situation of various infectious animal diseases to develop an efficient early warning system. This review provides information about FMD, LSD, and BEF, including their economic impacts, causative viruses, global burden, the situation in Egypt, and the challenges in controlling these diseases.

Effect of EV71 Vaccination on Transmission Dynamics of Hand, Foot, and Mouth Disease and Its Epidemic Prevention Threshold.

OBJECTIVE: To investigate the effect of Enterovirus A71 (EV71) vaccination on the transmissibility of different enterovirus serotypes of hand, foot, and mouth disease (HFMD) in Zhejiang, China. METHODS: Daily surveillance data of HFMD and EV71 vaccination from August 2016 to December 2019 were collected. Epidemic periods for each HFMD type were defined, and the time-varying effective reproduction number (Rt) was estimated, which could provide more direct evidence of disease epidemics than case number. General additive models (GAMs) were employed to analyze associations between EV71 vaccination quantity and rate and HFMD transmissibility. The epidemic prevention threshold, represented by required vaccination numbers and rates, was also estimated. RESULTS: Vaccinating every 100,000 children ≤ 5 years could lead to a decrease in the Rt of EV71-associated HFMD by 14.44% (95%CI: 6.76%, 21.42%). Additionally, a positive correlation was observed between vaccinations among children ≤ 5 years old (per 100,000) and the increased transmissibility of other HFMD types (caused by enteroviruses other than EV71 and CA16) at 1.82% (95%CI: 0.80%, 2.84%). It was estimated that an additional 362,381 vaccinations, corresponding to increased vaccine coverage to 54.51% among children ≤ 5 years could effectively prevent EV71 epidemics in Zhejiang. CONCLUSIONS: Our findings highlight the importance of enhancing EV71 vaccine coverage for controlling the epidemic of EV71-HFMD and assisting government officials in developing strategies to prevent HFMD.

The isolation and serotyping of foot-and-mouth disease virus in Iran during 2019-2022.

Foot-and-mouth disease (FMD) is a significant transboundary animal disease that has a considerable economic impact on livestock systems worldwide. In order to determine the presence and type of FMD virus in Iran, a total of 90 samples of vesicular fluid and epithelial tissue were collected from the tongues, tooth pads, and hooves of clinically suspect cattle on 40 vaccinated farms in 9 provinces of Iran. These samples were collected during four years, from January 2019 to December 2022, and the vaccine was a locally produced polyvalent inactivated vaccine. The collected samples were analyzed using ELISA and isolation methods to identify and characterize the FMD virus. The results of the ELISA tests revealed that 66.66% of the samples were positive for FMD, and the serotypes of the virus were determined. Considering ELISA reslut, 62% of the samples were assigned to serotype O, 33% to serotype A, and 5% to serotype Asia-1. Furthermore, 90% of the positive samples were inoculated onto monolayer cultures of pig kidneys (IB-RS2) for isolation and antigen detection by serotype-specific ELISA kit. The great majority of detected serotype O viruses were from Esfahan province, while the most detected serotype A and serotype Asia-1 viruses were from Qom and Tehran provinces, respectively. These findings indicate that the ELISA and isolation methods are suitable for identifying and typing FMD viruses. The vaccination program in Iran, which includes three serotypes (O, A, and Asia-1), appears to be effective in controlling the spread of the disease. However, the continued circulation of these serotypes in most provinces suggests that ongoing surveillance and vaccination efforts are necessary.

Independent and interactive effects of particulate matter and meteorological factors on hand, foot and mouth disease in Fuyang.

Previous research has demonstrated the influence of environmental factor on the occurrence of infectious diseases. However, there is insufficient and conflicting evidence regarding the association between Hand, foot and mouth disease (HFMD) and environmental variables, particularly the interaction of environmental variables. This study aims to investigate the individual and interactive effects of particulate matter (PM) and meteorological factors on HFMD incidence in Fuyang. The generalized additive models were combined with distributed lag non-linear models to assess the individual effects between PM and meteorological factor on HFMD incidence in Fuyang. Subsequently, a product term was incorporated into the model to investigate the interaction between PM and meteorological factors. Temperature and PM2.5 were identified as the two primary risk factors for HFMD, with relative risks (RR) of 1.586(1.493,1.685) and 1.349(1.325,1.373), respectively. Furthermore, PM exhibited a synergistic effect with meteorological factors. For instance, the RR values for PM2.5 in relation to HFMD were 1.029 (95% CI: 1.024-1.035) and 1 0.117 (95% CI: 1 0.108 - 11 0.127) under different temperature group categories. Notably, HFMD predominantly affects children under the age of five years old and infants aged between zero to one year old demonstrate heightened susceptibility to environmental variables. The results showed that both PM and meteorological factors were risk factors for HFMD, with evidence of an interaction between these variables. These findings have important implications for local HFMD incidence prediction and the development of effective prevention strategies.

Development and validation of a potential risk area identification model for hand, foot, and mouth disease in metropolitan China.

Maximum Entropy model (MaxEnt), as a machine learning algorithm, is widely used to identify potential risk areas for emerging infectious diseases. However, MaxEnt usually overlooks the influence of the optimal selection of spatial grid scale and the optimal combination of factor information on identification accuracy. Furthermore, the internal level information of factors is closely related to the potential risk of disease occurrence but is rarely applied to enhance MaxEnt's accuracy. In this study, the Optimal Parameters-based Geographical Detectors-Information Value-MaxEnt (OPGD-IV-MaxEnt) was first proposed to identify the potential risk areas of hand, foot, and mouth disease (HFMD) in Shenzhen and compared its identification accuracy with that of OPGD-MaxEnt and MaxEnt. Firstly, the optimal grid scale and optimal combination of factor information were determined by OPGD. Secondly, the contributions of factors' internal level information to the potential risk of HFMD occurrence were quantified and incorporated by IV. Lastly, the spatial patterns of potential risk areas and their main driving factors were elucidated. Results showed that: (i) Area under the curve (AUC) of single MaxEnt were 0.638, 0.688, 0.763, 0.796, and 0.757 at 100 m, 250 m, 500 m, 750 m, and 1000 m scale, respectively, and 750 m were deemed the optimal scale. (ii) At the optimal scale, OPGD-IV-MaxEnt (AUC = 0.868) identified potential risk areas more accurately than MaxEnt (AUC = 0.796) and OPGD-MaxEnt (AUC = 0.827). (iii) Resident (r = 0.61, q = 0.39) and Market (r = 0.61, q = 0.36) were the primary factors affecting the identification of potential risk areas. (iv) Potential high-risk areas of HFMD were mainly distributed in northwestern, southwestern, and central Shenzhen, with dense resident and market distribution. Such insights are instrumental in devising targeted infection prevention and control measures for emerging infectious diseases and provide references for improving the identification accuracy of similar machine learning algorithms.

An evaluation of the efficiency and effectiveness of diagnostic tests for foot and mouth disease: are novel diagnostic tests for FMD more feasible than conventional tests in Southeast Asia?

Foot and mouth disease (FMD) remains endemic in many areas of continental Southeast Asia (SEA). It is responsible for substantial economic losses in the smallholder sector and threatens livelihoods. In recent years, novel diagnostic tests have been developed which reportedly detect FMD virus more effectively and efficiently. This critically appraised topic (CAT) aimed to evaluate the feasibility of these diagnostic tests for FMD in SEA compared to conventional tests. Relevant studies that evaluate diagnostic tests are identified and critically assessed, and recommendations are made on suitable potential diagnostic tests for use in the smallholder sector in SEA. A systematic search of electronic databases (CABI: CAB Abstracts, Web of Science Core Collections) was carried out to identify relevant studies that compared novel and conventional diagnostic tests. The search strategy initially identified 12 papers, of which six fulfilled all the inclusion criteria and were selected for this review. Most of the selected studies had limitations in design and comparability, making it difficult to validly compare the effectiveness and efficiency of the relevant diagnostic tests. These limitations include variation in sample characteristics, methodology, measurable outcomes and the different aspects of the diagnostic tests that each study focused on. Most studies concluded that novel diagnostic tests were more effective and efficient than conventional tests: had greater analytical sensitivity and specificity, were more robust, had a wider range of processable sample types and serotypes, could detect various diseases, had faster testing speeds and provided greater value for money. However, strong recommendations on which specific diagnostic test to rely on could not be made, since there was conflicting evidence and multiple confounding factors. Overall, the evidence found did not entirely apply to the target scenario, being SEA smallholder farms. Recommendations for the target scenario were also made based on the study findings.

One-size measures do not fit all areas: Evaluation of area-specific control of foot and mouth disease in Thailand using bioeconomic modelling.

Information on the epidemiological and economic consequences of control measures is fundamental to design effective foot and mouth disease (FMD) control measures. One approach to obtaining this information is through bioeconomic modelling. In this study, a bioeconomic model was used to evaluate FMD control in two different study areas in Thailand: a high farm density area predominantly consisting of dairy farms and a low farm density area with mixed farm types. The bioeconomic model consists of an epidemiological part and an economic part. For the epidemiological part, a stochastic between-farm transmission model was constructed with transmission parameters estimated from FMD outbreaks in Thailand. The outputs from the epidemiological model, i.e. the number of infected farms, the number of affected farms and the outbreak duration, are used as inputs for economic model to calculate the economic consequences. We applied the simulation model with four FMD control measures: culling the animals of infected farms, ring vaccination, animal movement restrictions and isolation of infected farms. Furthermore, we included effect of farmers' compliance to asses its effect on control measures. The simulated FMD outbreaks in the low farm density area were small, thus control measures did not greatly affect the size of outbreaks and, therefore, did not have a positive economic return. In contrast, in the high farm density area, FMD outbreaks were large without control measures. All measures reduced the size of the outbreaks but resulted in different total costs. In terms of outbreak control, culling infectious farms was the best option, but its total cost was higher than ring vaccination or isolation of infected farms. In terms of cost-effectiveness, ring vaccination was the best measure. If farmers' compliance were low, all control measures would be ineffective, resulting in high total cost of the outbreak. The cost distribution between compliant and non-compliant farms showed that non-compliant farms paid more than compliant farms, except for the ring vaccination scenario. The results emphasize the economic significance to customize control measures specific to the area's conditions and highlight the importance of farmers' compliance when designing control measures.

Enhanced production of recombinant coxsackievirus A16 using a serum-free HEK293A suspension culture system for bivalent enterovirus vaccine development.

Coxsackievirus A16 (CVA16) is one of the primary pathogens that causes hand, foot, and mouth disease (HFMD) in young children. In previous studies, CVA16 vaccine development has encountered several challenges, such as inefficient replication of the CVA16 virus in present culture systems, the induction of only mild neutralizing antibody titers, and neutralizing antibodies induced by certain vaccine candidates that are unable to protect against CVA16 viral challenge. In this study, we constructed a DNA-launched CVA16 infectious clone (CVA16ic) based on the genomic sequence of the CVA16 N5079 strain to minimize interference from viral quasispecies. The biochemical properties of this CVA16ic strain were similar to those of its parental strain. Serum-free HEK293A suspension cells, which produced higher virus titers than Vero cells, were demonstrated to improve CVA16 production yields. In addition, our study showed that inactivated EV-A71 antigens could enhance the immunogenicity of inactivated CVA16 mature/full particles (F-particles), suggesting that a bivalent CVA16 and EV-A71 vaccine may be an effective strategy for CVA16 vaccine development. These findings are expected to provide novel strategies and accelerate the development of bivalent HFMD vaccines.

Dual effects of ipecac alkaloids with potent antiviral activity against foot-and-mouth disease virus as replicase inhibitors and direct virucides.

Foot-and-Mouth Disease (FMD) is a contagious, blistering disease caused by the Foot-and-Mouth Disease virus (FMDV), which affects livestock globally. Currently, no commercial antiviral agent is available for effective disease control. This study investigated the antiviral potential of natural-derived alkaloids against FMDV in BHK-21 cells. Twelve alkaloids were assessed for their antiviral activities at various stages of FMDV infection, including pre-viral entry, post-viral entry, and prophylactic assays, as well as attachment and penetration assays by evaluating cytopathic effect reduction and directed-virucidal effects. The results showed that ipecac alkaloids, cephaeline (CPL) and emetine (EMT), exhibited dual effects with robust antiviral efficacy by reducing cytopathic effect and inhibiting FMDV replication in a dose-dependent manner. Evaluation through immunoperoxidase monolayer assay and RT-PCR indicated effectiveness at post-viral entry stage, with sub-micromolar EC50 values for CPL and EMT at 0.05 and 0.24 µM, respectively, and high selective indices. Prophylactic effects prevented infection with EC50 values of 0.23 and 0.64 µM, respectively. Directed-virucidal effects demonstrated significant reduction of extracellular FMDV, with CPL exhibiting a dose-dependent effect. Furthermore, the replicase (3Dpol) inhibition activity was identified using the FMDV minigenome assay, which revealed strong inhibition with IC50 values of 0.15 µM for CPL and 4.20 µM for EMT, consistent with the decreased negative-stranded RNA production. Molecular docking confirmed the interaction of CPL and EMT with residues in the active site of FMDV 3Dpol. In conclusion, CPL and EMT exhibited promising efficacy through their dual effects and provide an alternative approach for controlling FMD in livestock.

Evaluation and comparison of performances of six commercial NSP ELISA assays for foot and mouth disease virus in Thailand.

ELISA kits that detect antibodies to the non-structural protein (NSP) of the foot-and-mouth disease virus (FMDV), commonly referred to as NSP-ELISA, can distinguish between vaccinated and naturally infected animals. They can play an essential role in demonstrating 'proof-of-freedom' during the control of FMD. Although various NSP-ELISA kits are available in Thailand, information regarding their performance is lacking. To select the most appropriate NSP-ELISA kit for our specific purpose, we must compare their performance using carefully characterized sera. This will ensure that we maximize the benefits of our testing. In this study, six NSP-ELISA kits sold in Thailand-Biovet, ID Screen, VDPro, IDEXX, PrioCHECK, and KUcheck-F-were evaluated and compared. A total of 800 serum samples were examined, including samples from 357 cattle and 29 buffaloes in outbreak areas, as well as 14 swine serum samples from the Vaccine Quality Control Unit of the Bureau of Veterinary Biologics, Ministry of Agriculture and Cooperation, Thailand. Four hundred samples were confirmed to originate from animals infected with FMDV through ELISA typing (n = 11, tested as representative samples in each farm) and/or RT-PCR (n = 400, all samples), serving as positive control sera. Additionally, 400 negative control sera were obtained from Japan (97 cattle and 300 pigs) and Australia (3 goats), certified by the World Organisation for Animal Health as 'free of FMD'. The sensitivity and specificity of the six tests were determined based on the results obtained from two-by-two tables. Cohen's kappa statistics were calculated for the six tests to assess their concordance, and the diagnostic accuracy of the assays was also determined. For all six NSP-ELISA kits, the sensitivity ranged from 97.75 to 99.50%, and the specificity ranged from 97.25 to 100%. Cohen's kappa statistics ranged from 0.96 to 1.00, and diagnostic accuracy ranged from 98.13 to 99.75%. The study results indicated that the test kits have statistically similar sensitivity, specificity, concordance, and diagnostic accuracy, suggesting they can be used interchangeably. However, ID Screen demonstrated the highest sensitivity and specificity among all kits tested. Therefore, if a single kit were to be selected from the six evaluated, ID Screen would be the most appropriate choice. These findings can aid in selecting the most suitable test kit. Therefore, it is recommended to consider purchasing a diverse range of effective test kits. Furthermore, these findings can provide guidance for expanding the use of test kits, particularly with the growing availability of NSP-ELISA kits in the market.

The Relevance of Bacillary Layer Detachment and Choroidal flow Insufficiency in Unilateral Acute Idiopathic Maculopathy Associated with Hand, Foot, and Mouth Disease: A Case Report.

In a case of unilateral acute idiopathic maculopathy (UAIM) following hand, foot, and mouth disease, we aim to discuss the decreased perfusion of choriocapillaris secondary to systemic inflammation as shown by optical coherence tomography angiography (OCTA) and to assess the prognostic significance of bacillary layer detachment (BALAD). A 33-year-old male presented with a decrease of vision in the right eye (OD) for 5 days preceding viral prodromal symptoms and vesicular lesions on bilateral palms and soles along with vesicles and ulcers on the oral mucosa. The best-corrected visual acuity was finger counting at 1 meter distance in OD and 20/20 in his left eye (OS). Dilated fundus examination revealed a circular white-grey dome-shaped elevated lesion at the macula indicative of serous retinal detachment in OD. Spectral-domain optical coherence tomography demonstrated BALAD associated with adjacent subretinal and intraretinal fluid along with pigment epithelium detachment and disruption of ellipsoid and interdigitation zones. OCTA showed decreased choriocapillaris perfusion. All the investigations were normal in OS. The resolution of BALAD occurred during the first 2 days, which was followed by gradual improvement of choriocapillaris flow that lasted 2 months. UAIM is associated with hand, foot, and mouth disease. OCTA demonstrates both qualitative and quantitative data by detecting alterations in the choriocapillaris flow, which could be monitored during the disease course.

Analysis of miRNAs involved in mouse brain injury upon Coxsackievirus A6 infection.

Introduction: Coxsackievirus A6 (CV-A6) has emerged as the predominant epidemic strain responsible for hand, foot and mouth disease (HFMD). CV-A6 infection can result in severe clinical manifestations, including encephalitis, meningitis, and potentially life-threatening central nervous system disorders. Our previous research findings demonstrated that neonatal mice infected with CV-A6 exhibited limb weakness, paralysis, and ultimately succumbed to death. However, the underlying mechanism of CV-A6-induced nervous system injury remains elusive. Numerous reports have highlighted the pivotal role of miRNAs in various viral infections. Methods: Separately established infection and control groups of mice were used to create miRNA profiles of the brain tissues before and after CV-A6 transfection, followed by experimental verification, prediction, and analysis of the results. Results: At 2 days post-infection (dpi), 4 dpi, and 2dpi vs 4dpi, we identified 175, 198 and 78 significantly differentially expressed miRNAs respectively using qRT-PCR for validation purposes. Subsequently, we predicted target genes of these differentially expressed miRNAs and determined their potential targets through GO (Gene Ontology) enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis. Finally, we verified the miRNA-mRNA pairing via double luciferase experiments while confirming functional enrichment of target genes through Western Blotting analyses. Discussion: The results from this study suggest that transcriptional regulation, neuronal necrosis, pro-inflammatory cytokine release, and antiviral immunity are all implicated in the pathogenesis of central nervous system injury in mice infected with CV-A6. Brain injury resulting from CV-A6 infection may involve multiple pathways, including glial cell activation, neuronal necrosis, synaptic destruction, degenerative diseases of the nervous system. It can even encompass destruction of the blood-brain barrier, leading to central nervous system injury. The dysregulated miRNAs and signaling pathways discovered in this study provide valuable insights for further investigations into the pathogenesis of CV-A6.

Epidemiological characterization of hand, foot, and mouth disease among hospitalized children from 2014 to 2023 in a hospital in Henan Province: Longitudinal surveillance study.

Hand, foot, and mouth disease (HFMD) is an acute infectious illness primarily caused by enteroviruses. The present study aimed to describe the epidemiological characteristics of hospitalized HFMD patients in a hospital in Henan Province (Zhengzhou, China), and to predict the future epidemiological parameters. In this study, we conducted a retrospective analysis of general demographic and clinical data on hospitalized children who were diagnosed with HFMD from 2014 to 2023. We used wavelet analysis to determine the periodicity of the disease. We also conducted an analysis of the impact of the COVID-19 epidemic on the detection ratio of severe illness. Additionally, we employed a Seasonal Difference Autoregressive Moving Average (SARIMA) model to forecast characteristics of future newly hospitalized HFMD children. A total of 19 487 HFMD cases were included in the dataset. Among these cases, 1515 (7.8%) were classified as severe. The peak incidence of HFMD typically fell between May and July, exhibiting pronounced seasonality. The emergence of COVID-19 pandemic changed the ratio of severe illness. In addition, the best-fitted seasonal ARIMA model was identified as (2,0,2)(1,0,1)12. The incidence of severe cases decreased significantly following the introduction of the vaccine to the market (χ2 = 109.9, p < 0.05). The number of hospitalized HFMD cases in Henan Province exhibited a seasonal and declining trend from 2014 to 2023. Non-pharmacological interventions implemented during the COVID-19 pandemic have led to a reduction in the incidence of severe illness.

Evaluation of commercial quadrivalent foot-and-mouth disease vaccines against east African virus strains reveals limited immunogenicity and duration of protection.

Foot-and-mouth disease virus (FMDV) causes a contagious disease (FMD) in cloven-hoofed animals. For FMD-endemic countries, vaccination is critical for controlling disease but is rarely monitored, despite substantial funds spent on vaccine purchases. We evaluated antibody responses in cattle to two commercial vaccines each containing antigens of four FMDV serotypes. Sampling was done over 360 days, with serology for each serotype performed using commercially available solid phase competition ELISAs (SPCE) and with virus neutralization tests (VNT) employing regionally relevant test viruses. A primary course of each vaccine was administered to 37 calves, some of which received a second dose after 28 days. Using new production batches of vaccines, all calves received a booster vaccination 180 days post vaccination, while 10 additional naïve calves were also vaccinated using the new batches and followed up for ∼180 days. Simple and general linear models were used to compare antibody responses which varied substantially according to vaccine, dose regime, serotype, and test, but were mostly insufficient to ensure a high likelihood of adequate or sustained probable protection. One of the vaccines administered as a two-dose primary course of vaccination was superior to other options, but even then, data trajectories from VNT responses suggested probable protection of 75 % of calves for 6 months for only one virus serotype. Calves administered with the other vaccine and those given a single primary dose developed low levels of antibodies, offering predicted likely protection lasting less than two months. Individual SPCE results were weakly correlated (r2 = 0.48) to neutralization and associated likelihoods of protection but SPCE and VNT agreed on which vaccine and dose regime performed best. Our findings highlight gaps in immunogenicity of FMD vaccines used in East Africa and reinforce the importance of independent quality control studies to evaluate and improve commercial FMD vaccines and vaccination regimes.

The key mechanisms of multi-system responses triggered by central nervous system damage in hand, foot, and mouth disease severity.

Hand, foot, and mouth disease (HFMD) is a prevalent infectious affliction primarily affecting children, with a small portion of cases progressing to neurological complications. Notably, in a subset of severe HFMD cases, neurological manifestations may result in significant sequelae and pose a risk of mortality. We systematically conducted literature retrieval from the databases PubMed (1957-2023), Embase (1957-2023), and Web of Science (1957-2023), in addition to consulting authoritative guidelines. Subsequently, we rigorously selected the most relevant articles within the scope of this review for comprehensive analysis. It is widely recognized that the severity of HFMD is attributed to a multifaceted array of pathophysiological mechanisms. The implication of multi-system dysfunction appears to be perturbances of the human defense system; therefore, it contributes to the severity of HFMD. In this review, we provide an overview and analysis of recent insights into the molecular mechanisms contributing to the severity of HFMD, with a particular focus on cytokine release syndrome, the involvement of the renin-angiotensin system, regional immunity, endothelial dysfunction, catecholamine storm, viral invasion, and the molecular mechanisms of neurological damage. We speculate that the domino effect of diverse physiological systems, initiated by damage to the central nervous system, serve as the primary mechanisms governing the severity of HFMD. Simultaneously, we emphasize the knowledge gaps and research urgently required to delineate a quick roadmap for ongoing and essential studies on HFMD.

Dendritic cell-based biomimetic nanoparticles for foot-and-mouth disease induce robust cellular immunity.

Foot-and-mouth disease (FMD) is a highly contagious and economically devastating viral disease of ruminants and swine, badly affecting the livestock industry worldwide. In clinical practice, vaccination is a frequently employed strategy to prevent foot-and-mouth disease (FMDV). However, commercial inactivated vaccines for FMD mainly rely on humoral immunity, exhibiting poor cellular immune responses and causing adverse reactions. Here, we use the double emulsion method to prepare poly (lactic-co-glycolic acid) nanoparticles (PLGA-NP) encapsulated with IL-2 cytokines, wrap the dendritic cell (DC) membrane carrying FMDV antigen information on the surface of the nanoparticles, obtaining a biomimetic nanoparticle vaccine Biom@DC with uniform size. This vaccine can effortlessly move through lymph nodes due to its nanoscale size advantage. It also possesses DC ability to present antigens, and antigen presentation can be made more effective with high biocompatibility. The sustained release of IL-2 encapsulated in the core of PLGA-NP in vivo can effectively promote the body's cellular immune response. Immune tests on mice have shown that Biom@DC may greatly increase T cell activation and proliferation both in vivo and in vitro, while also significantly reducing the fraction of inhibitory Treg cells. Furthermore, in the micro serum neutralization assay for FMDV, it has been demonstrated that the group vaccinated with Biom@DC exhibits a clear neutralizing effect. Given its strong immunogenicity, Biom@DC has the potential to develop into a novel, potent anti-FMDV vaccination.

Effect of GnRH treatment as a potential solution for ovarian disorders in dairy cows infected with foot and mouth disease in Indonesian smallholder farms.

Background: The outbreak of foot and mouth disease (FMD) in Indonesia induces reproductive disorders in dairy cows that lead to economic losses to smallholder dairy farms. Aim: The study was to assess the influence of FMD on reproductive traits and evaluate the effect of gonadotropin hormone-releasing hormone (GnRH) administrations on the reproductive performance in FMD-infected dairy cows. Methods: The study was conducted in Jemowo village, Taman Sari sub-district, Boyolali district, Central Java, Indonesia. A total of 155 cows were used to identify the reproductive disorders on FMD-infected dairy cows aged 2-10 years old. Cows were raised in similar conditions and fed diets. A single dose of 2 ml GnRH was injected intramuscularly into 96 ovarian disorder cows. Reproductive performance was measured by service per conception (S/C), conception rate (CR), and pregnancy rate (PR). A descriptive study was conducted to demonstrate the results. Results: The study showed that 61.9% of FMD-infected cows had reproductive disorders, whereby 53.5% ovarian hypofunction, 4.52% silent heat, 1.94% repeat breeder, 1.29% ovarian atrophy, and 0.65% endometritis. FMD-infected cows injected with GnRH had a 98% reproductive recovery rate. Moreover, the S/C, CR, and PR of cows injected with GnRH were 2.02%, 51%, and 85%. Conclusion: GnRH administrations enhanced the reproductive traits of FMD-infected dairy cows indicated by the improvement of CR and PR.

Protein characterization of an Indonesian isolate of foot and mouth disease virus inactivated with formaldehyde and binary ethylenimine.

Background and Aim: Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-footed animals. It is a major threat to livestock production worldwide, causing significant economic losses. Inactivation of FMD virus (FMDV) is crucial for vaccine development and control of outbreaks. However, traditional inactivation methods can sometimes damage the viral protein, affecting vaccine efficacy. Therefore, finding new inactivating agents that effectively inactivate the virus while preserving the integrity of its proteins is an important research area. This study investigated the optimal materials (0.04% formaldehyde, 0.001 M binary ethylenimine [BEI], or a combination) for inactivating and preserving the specific molecular weight of Serotype O FMDV protein. Materials and Methods: This study used serotype O FMDV isolated from several areas of East Java. The virus was inoculated into baby hamster kidney-21 cells, and the titer was calculated using the TCID50 Assay. The virus was inactivated using 0.04% formaldehyde, 0.001 M BEI, or a combination of 0.04% formaldehyde and 0.001 M BEI. Inactive viral proteins were characterized using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blotting. Results: Serotype O FMDV can be inactivated using 0.04% formaldehyde while preserving specific FMDV proteins, specifically VP0 and VP3 with a molecular weight (MW) of 36 kDa and VP3 with a MW of 24 kDa. Serotype O FMDV can be inactivated by 0.001 M BEI while preserving specific FMDV proteins, specifically VP0 with a MW of 35 kDa, VP3 with a MW of 28 kDa, and VP1 with a MW of 23 kDa. FMDV serotype O can be inactivated using a combination of 0.04% formaldehyde and 0.001 M BEI while preserving specific FMDV proteins, specifically VP0 and VP3 with a MW of 36 kDa and VP3 with a MW of 24 kDa. Conclusion: This study found that 0.04% formaldehyde, alone or in combination with 0.001 M BEI, was effective for inactivating and preserving the specific molecular weight of Serotype O FMDV protein. The limitation of this study was the inactivations of the virus have not yet been tested for their potency on experimental animals. Further research is warranted to investigate the inactivation kinetics of these materials, including their potency on experimental animals. Additionally, a comparison of the inactivation rates between 0.04% formaldehyde alone and the combination with BEI would help to determine the optimal inactivation agent for future applications.