Molecular epidemiological and genetic characteristics of coxsackievirus A6 circulating in mainland China from 1992 to 2023.

Development of an S protein-based indirect ELISA for detecting IgA antibodies against porcine deltacoronavirus.

Hand, foot, and mouth disease (HFMD) is a common childhood infection caused by enteroviruses, which exhibit distinct regional and seasonal epidemiological patterns. Wastewater-based epidemiology is a crucial tool for monitoring population infection dynamics and viral subtype distribution. However, the lack of effective on-site viral detection methods limits timely early warning and effective surveillance of infectious disease outbreaks. This study developed a one-pot RT-RPA/CRISPR-Cas12a assay-based, string-powered flywheel microfluidic chip for the multiplex detection of HFMD viruses in wastewater. First, by leveraging the regulatory effect of heparin sodium on CRISPR/Cas12a activity, a one-pot RT-RPA/CRISPR-Cas12a system was constructed to detect four major subtypes of HFMD virus (EV-A71, CV-A16, CV-A6, and CV-A10). Subsequently, this method was integrated into a pull-wire, flywheel-type, dual-axis centrifugal microfluidic chip, named the Heparin-Inhibited CRISPR-Associated System Chip (HICAS-Chip), enabling integrated enrichment, purification, elution, and multiplexed detection. The HICAS-Chip allowed visual detection of nucleic acids at 10 aM sensitivity within 1 h, corresponding to the sensitivity of the one-pot RT-RPA/CRISPR-Cas12a assay. During a year-long wastewater monitoring program in Guiyang City, China, the HICAS-Chip identified EV-A71 and CV-A10 as the predominant circulating subtypes, with incidence peaks observed in June, November, and December. The wastewater detection results obtained using HICAS-Chip showed high concordance (95.83%) with RT-qPCR assays. This platform provides an efficient portable device for the early detection and continuous monitoring of HFMD epidemic trends by wastewater-based epidemiology.

Hand, foot, and mouth disease is a common childhood illness increasingly caused by coxsackievirus A6 (CVA6), which can sometimes lead to severe complications. Currently, there are no specific vaccines or treatments available against CVA6. We identified the precise reason for the differing virulence between CVA6 strains. Comparing a lethal strain with a harmless one revealed a single determinant: residue 238 on the VP3 capsid protein. A glutamic acid ("E") at this site confers virulence, while alanine ("A") results in attenuation. By engineering an "E" to "A" mutation, we created a virus that is safe in mice but remains immunogenic. This engineered strain, used as a live vaccine, provided complete protection against lethal CVA6 challenge. Our work pinpoints a key virulence switch and presents a direct strategy for developing a safe CVA6 vaccine.

This paper examines the research output and impact of Veterinary Research Institutes (VRIs) of the Chinese Academy of Agricultural Sciences (CAAS), namely Shanghai Veterinary Research Institute (SHVRI), Harbin Veterinary Research Institute (HVRI), and Lanzhou Veterinary Research Institute (LVRI), to answer research questions. The study explores publication count, citation structure, h-index, most-cited articles, keyword trends, trend topics, co-authorship, thematic maps, and bibliographic coupling. The data is extracted from Scopus, covering publications from 2009 to 2023. Utilizing Excel, R (Biblioshiny), and VOSviewer (version 1.6.20, Leiden University, Netherlands), we found that VRIs of the CAAS demonstrated a steady upward trend in their research output, with SHVRI leading in top-cited articles, HVRI in citations and h-index, and LVRI in publications. Key journals include Veterinary Microbiology and Parasites and Vectors. Leading authors are Chan Ding (SHVRI), Xiaomei Wang (HVRI), and Xing-Quan Zhu (LVRI). Key research focus is on parasitology, virology, immunology, and molecular biology. SHVRI and HVRI's demonstrated focus is on virology, while LVRI's interest is in genetic analyses of the pathogens. Bibliographic coupling highlights core themes: SHVRI on Newcastle disease, Schistosoma japonicum, Toxoplasma gondii, and Porcine reproductive and respiratory syndrome virus; HVRI on African swine fever virus, Influenza viruses, and Porcine epidemic diarrhea virus; and LVRI on Toxoplasma gondii, the parasitic mitochondrial genome, and Foot and Mouth disease virus. Findings reflect CAAS's commitment to addressing critical animal diseases for China's development and food security.

The burden of hand, foot, and mouth disease attributable to climate variability: A nationwide time-series modeling study in Japan.

Hand, foot and mouth disease (HFMD) constitutes a global public health concern. Internet search data offers advantages including vast data volumes, provision of real-time information, and the potential for earlier infectious disease surveillance. The objective of this study is to utilise Baidu Search Index (BSI) to construct a predictive model for HFMD epidemiological surveillance, thereby enhancing HFMD incidence forecasting and early warning capabilities. HFMD cases reported by the National Health Commission of the People's Republic of China from January 2011 to March 2025 were collected. Keywords highly correlated with HFMD were identified using Spearman's rank correlation and cross-correlation analysis, and a comprehensive search index (CSI) for HFMD was constructed. Subsequently, based on the monthly number of HFMD cases and the CSI, autoregressive integrated moving average (ARIMA) and autoregressive integrated moving average with exogenous inputs (ARIMAX) models were established. Finally, the predictive accuracy of the models was evaluated using mean absolute error (MAE), root mean square error (RMSE), mean absolute percentage error (MAPE), and standardised mean absolute percentage Error (SMAPE). From January 2011 to March 2025 (total of 171 months), China reported a total of 24,856,589 HFMD cases, with an average of 145,360.2 cases per month. The highest incidence of HFMD occurred between May and July each year. After correlation analysis, five keywords highly associated with HFMD were ultimately included, with a potential time lag of 0 months. The CSI of HFMD exhibits a high Spearman rank correlation (rs=0.937) with monthly reported HFMD cases. The developed ARIMAX(2,0,1)(1,1,1)(12) + CSI(Lag = 0) performs better in terms of fitting and prediction compared to the ARIMA(2,0,1)(1,1,1)(12). The MAE values for ARIMAX and ARIMA are 42,085.93 and 80,260.93, respectively, the RMSE values are 52,235.39 and 98,444.62, respectively, the MAPE values are 0.96% and 2.10%, respectively, and the SMAPE are 0.86% and 0.82%, respectively. The ARIMAX(2,0,1)(1,1,1)(12) + CSI(Lag = 0) model constructed from extensive internet search data in this study has effectively enhanced the prediction of HFMD incidence. Furthermore, it can serve as an early warning system for HFMD. This research provides valuable support for HFMD surveillance.

BackgroundDue to insufficient routine surveillance, the nationwide disease burden of hand, foot and mouth disease (HFMD) caused by coxsackievirus A6 (CVA6), an emerging serotype, in China remains unclear. This study aimed to estimate the incidence of CVA6-associated HFMD across the Chinese mainland.MethodsCVA6 positive data from 511 locations across the Chinese mainland during 2008–2022 were integrated from the national pathogen surveillance system and literature, and reported HFMD cases during the same period were obtained from the national infectious disease surveillance system. The predicted positivity rate and incidence of CVA6-associated HFMD in children under five years of age across the Chinese mainland were estimated using a Bayesian geostatistical Gaussian model based on positivity data, reported cases, and environmental, socioeconomic, demographic, and vaccination factors.ResultsThe model estimated that the average positivity rate of CVA6 in the Chinese mainland from 2008 to 2022 was 24.1%, with a 95% Bayesian credible interval (BCI) of 11.9–43.3%. The corresponding average annual incidence of CVA6-associated HFMD in children under five years of age was 506 (95% BCI: 272–805) per 100,000. The yearly incidence of CVA6-associated HFMD in children under five years of age peaked in 2018 (873 per 100,000; 95% BCI: 513–1309) before a subsequent decline after 2020. The incidence was highest in South China (1571 per 100,000; 95% BCI: 890–2420) and lowest in Northeast China (208 per 100,000; 95% BCI: 106–340). The estimated CVA6-associated HFMD incidence showed a consistent upward trend across different economic level groups before 2020, and tended to be higher in high-gross domestic product (GDP) per capita regions than in medium- and low-GDP regions.ConclusionsModel-based estimates indicate a potentially high incidence of CVA6-associated HFMD on the Chinese mainland, particularly in South China, highlighting the need for enhanced surveillance of CVA6 and targeted control efforts in high-incidence regions.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1186/s40249-026-01446-5.

Objective: To analyze the epidemiological characteristics of hand, foot and mouth disease (HFMD) in Hebei Province from 2008 to 2024, and quantitatively evaluate the impacts of enterovirus A71 (EV-A71) vaccination and non-pharmaceutical interventions (NPIs) during the COVID-19 pandemic period on the incidence trend of HFMD by using the interrupted time series (ITS) method. Methods: The incidence data of HFMD in Hebei from 2008 to 2024 were collected for a descriptive analysis to understand the temporal, population, and regional distributions of HFMD. ITS model was used to quantitatively evaluate the impact of EV-A71 vaccination and the NPIs during the COVID-19 pandemic period on HFMD incidence. Additionally, the children under five years old were divided into two age groups (<2 years and ≥2 years) for subgroup ITS analyses to compare the differential responses of age groups to these interventions. Results: A total of 822 740 HFMD cases were reported in Hebei during the study period, the reported cases increased firstly, then-declined, showing an obvious seasonality, with an uneven geographic distribution. The majority of cases were children aged 0-5 years, especially the scattered children, and the incidence rate was higher in boys than in girls. ITS analysis showed that following the introduction of EV-A71 vaccination in 2016, the annual decline in overall HFMD incidence accelerated from 2.00 per 100 000 (P=0.735) to 10.67 per 100 000 (P=0.186). Age-stratified analysis indicated that in children under 2 years old, HFMD incidence trend reversed from increase to decrease (P=0.014). In children aged ≥2 years, the incidence remained generally stable before and after the vaccination, with no significant immediate or long-term changes observed. In 2020, when COVID-19 control measures were taken, HFMD incidence significantly decreased in both overall population and the two age groups, with a greater decline observed in children aged ≥2 years compared with those aged <2 years. Subsequently, the incidences in both groups showed rebounds. Conclusions: From 2008 to 2024, the HFMD incidence in Hebei exhibited distinct phase-specific changes, resulting from the synergistic effects of pathogen spectrum shifts, vaccine interventions, and public health measures. Following the introduction of the EV-A71 vaccine, the incidence of HFMD showed a decreasing trend, but the intervention effect exhibited age heterogeneity, being more significant in children under 2 years old. The NPIs during the COVID-19 pandemic period significantly suppressed HFMD transmission for a short time. These findings suggest that relying solely on overall incidence is insufficient to fully evaluate type-specific vaccine effects; integrating pathogen type surveillance and age-stratified analyses can provide a more accurate evaluation of HFMD control and inform the optimization of comprehensive prevention strategies.

Objective: To evaluate the impact of the official front-end software for intelligent surveillance and early warning of infectious diseases on the reporting of other infectious diarrheal disease, hand foot and mouth disease (HFMD), and bacillary dysentery in 113 medical institutions at or above grade Ⅱ in Beijing, China. Methods: Based on monthly incidence data from 2012 to 2023, we constructed multiple prediction models, including seasonal autoregressive integrated moving average (SARIMA) model, error-trend-seasonality model, neural network auto regressive (NNAR) model, Prophet model, Bayesian structural time series model and hybrid model. The data in 2024 were used as the test set for the model evaluation, and the optimal prediction models were used to predict the case count from January to August 2025 without the intervention of front-end software use. Changes in reporting case count were analyzed by comparing actual reporting with prediction from January to August 2025 and actual reporting during the same period in 2024 by using paired t-test or Wilcoxon signed-rank test. Results: The optimal prediction models for other infectious diarrheal diseases and HFMD were SARIMA (1,0,1)(1,1,1)12 and SARIMA (3,0,0)(0,1,1)12 respectively, while the optimal prediction model for bacillary dysentery was NNAR (3,1,2)12. After the use of front-end software, the actual reported case count of other infectious diarrheal diseases increased by 1 625.75 cases compared with the prediction from January to August 2025, an increase of 168.71% (P<0.001) and by 1 500.25 cases compared with the actual case count during the same period in 2024, an increase of 152.61% (P<0.001). The actual reported case count of HFMD increase by 103.38 cases compared with prediction from January to August 2025, an increase of 75.80% (P=0.008), but showed no significant difference compared with the same period in 2024 (P=0.461). No significant changes were observed in the reporting bacillary dysentery before and after the front-end software use in the two comparisons (P=0.895 and P=0.239). Conclusion: The application of the official front-end software significantly improved the reporting sensitivity for other infectious diarrheal diseases and HFMD, but no significant effect was observed in the reporting of bacillary dysentery.

Enterovirus 71 (EV-A71), a neurotropic member of the Picornaviridae family, is a positive-strand RNA virus comprising of seven recognized genogroups (A-G) and has caused significant outbreaks of hand, foot, and mouth disease worldwide. Despite prior identification of D and G genogroups in India, comprehensive full-genome characterization of these indigenous lineages remains unreported. We performed next-generation sequencing (NGS) and molecular phylogenetic analyses on two Indian isolates from acute flaccid paralysis cases: R13223-IND-02 (genogroup D) and V11-2209-01 (genogroup G). The complete genomes generated through NGS were aligned with publicly available full-length and partial EV-A71 sequences using MAFFT, and phylogenetic trees were constructed employing the maximum-likelihood method. Amino acid variations were then compared across the genogroups, as well as with prototype and neurovirulent reference strains. Phylogenetic reconstruction revealed robust clustering of these strains within distinct clades (bootstrap support ≥ 99%)", divergent from globally prevalent genogroups B and C. Both D and G genogroups appear geographically restricted to India, while genogroup D persists as an endemic lineage. Comparative genomic analyses demonstrated extensive nucleotide divergence, including numerous non-synonymous substitutions across both structural (VP1-VP4) and non-structural (2A-3D) coding regions. An E-Q substitution at amino acid position 145 in the VP1 structural protein was detected in both D and G genogroups, a site functionally linked to receptor binding and mouse virulence. The findings highlight the evolutionary independence and sustained circulation of D and G genogroups in India, suggesting a unique regional evolutionary trajectory. The implications hold significant global relevance, offering valuable insights for molecular surveillance, advancing pathogenesis research, and supporting the development of genogroup-specific vaccine strategies tailored to diverse epidemiological landscapes. This study is the first to report the complete genome of EV-A71 D and G genotypes in India, and its unique mutation characteristics provide a direct target for the development of region-specific vaccines.

Coxsackievirus A16 (CVA16) is one of the primary viral etiological agents of hand, foot, and mouth disease (HFMD) in infants and children under five years of age. Prompt and reliable detection of CVA16 is crucial for guiding immediate therapeutic interventions and for implementing effective epidemic prevention and control strategies, particularly in settings with limited resources. Herein, a diagnostic platform for CVA16 (CVA16-RT-MCDA-CRISPR) was developed by combining reverse transcription multiple cross displacement amplification (RT-MCDA) with CRISPR-Cas12a-based detection. In this system, the CVA16 VP1 gene was preamplified using RT-MCDA technology. The resulting amplicons were then specifically recognized and cleaved by the CRISPR-Cas12a-based detection system. MCDA primers, an engineered CP1 primer, and a specific guide RNA (gRNA) were designed to target the VP1 gene of CVA16. The assay achieved a limit of detection of 2.8 × 10-1 copies per microliter for CVA16 RNA standard templates and showed no cross-reactivity against non-CVA16 pathogens. Furthermore, the CVA16-RT-MCDA-CRISPR assay's feasibility was validated using 96 clinical samples. Taken together, these results demonstrate that the CVA16-RT-MCDA-CRISPR assay is a reliable diagnostic tool for rapidly and sensitively detecting CVA16.

Anemia in children has become a serious global public health problem, which may lead to delayed growth and possibly have long term effects on neurodevelopmental and behavioral outcomes. Therefore, this study aimed to determine the prevalence and determinants of anemia among children in urban and rural areas of West Java, Indonesia. An observational analysis and cross-sectional study was conducted, with data was taken from secondary data of serosurvey of hand, foot, and mouth disease (HFMD) study of 560 healthy children aged 6-59 months in November 2022-January 2023 at the Garuda Primary Health Care in Bandung City as urban area and Padalarang Primary Health Care in West Bandung Region as rural area. The Chi-square test and logistic regression model were used to identify risk factors of anemia in urban and rural areas. The results showed anemia was not significantly higher in urban areas (25.6%) than in rural areas (21.3%) with a p-value 0.220. In urban areas, anemia was significantly associated with children aged 6-23 months (AOR = 2.17 4; 95% CI: 1.44-3.26), stunting children (AOR = 1.71; 95% CI: 1.07-2.72) and children with parents income below regional minimum wage (AOR = 1.73 1.74; 95% CI: 1.14-2.63). In rural areas, no variables had a significant relationship with anemia. The current study showed that children in rural and urban areas can have anemia. Further research and evaluation are needed in the detection and monitoring of risk factors through a multisectoral approach.

Enterovirus A71 (EV-A71), the primary causative agent of hand, foot, and mouth disease (HFMD), can cause severe neurological complications and even death, particularly in young children. Despite the availability of inactivated vaccines, their protective efficacy has been compromised due to frequent intra- and intertypic recombination events and ongoing mutations among circulating EV-A71 strains. To address this, we employed immunoinformatic approaches and identified conserved epitopes and constructed a multi-epitope vaccine (MEV) candidate against EV-A71. A total of 1,627 structural protein sequences from EV-A71 strains encompassing all major circulating subtypes were retrieved and aligned to generate a consensus sequence. With this consensus sequence, 11 conserved, antigenic, and non-allergenic epitopes capable of eliciting B-cell, T-cell, and interferon-gamma (IFN-γ) responses were identified. The constructed MEV demonstrated superior immunological potential with a high antigenicity score of 0.94 and was predicted to be non-allergenic and non-toxic. Structural characterization via AlphaFold 3 and 300ns molecular dynamics (MD) simulations confirmed the formation of a stable β-strand framework. Molecular docking followed by trajectory-stabilized interaction analysis revealed that the MEV maintains a high-affinity and stable binding profile with Toll-like receptor 3 (TLR-3). To ensure optimal translational efficiency, the vaccine gene was codon-optimized with a GC content of 52.8%, and the protein was successfully expressed in a bacterial system. Collectively, this study provides a high-performance MEV candidate with robust structural stability and potent immunogenicity, offering a promising and cost-effective strategy for broad-spectrum protection against EV-A71.

Neutral sphingomyelinase 2 knockdown attenuates disease severity and modulates immune responses in enterovirus A71-infected mice.

CRS3123 is a potent inhibitor of protein synthesis in bacteria that express type 1 methionyl-tRNA ligase, resulting in selective antibacterial activity that holds promise as a novel treatment for Clostridioides difficile infection (CDI). The purpose of this study was to evaluate the safety and efficacy of CRS3123 in adults with a primary episode or first recurrence of CDI. This multicentre, randomised, double-blind, vancomycin-controlled, phase 2 study was conducted across 14 enrolling sites in the USA and Canada. Enrolled patients were 18 years or older, with a clinical diagnosis of CDI, including diarrhoea (at least three unformed bowel movements in the 24 h before randomisation) and C difficile toxin A or B, or both, detected in stools. Patients were excluded if they had more than one episode of CDI within the past 3 months or more than two within the past 12 months. Patients were randomly assigned (1:1:1) to receive 10 days of treatment with one of two dose regimens of CRS3123 (200 mg and 400 mg orally twice daily) or oral vancomycin (125 mg orally four times daily). Randomisation used an interactive response technology system and was stratified by history of CDI (first episode vs first recurrence within the past 3-12 months). Masking was maintained by use of matching dummy capsules. Safety was a primary endpoint and was assessed in patients who received at least one dose of study drug. The primary efficacy endpoint was clinical cure (survival and resolution of diarrhoea) at the test-of-cure (TOC) visit (day 12 up to day 15) in the intention-to-treat (ITT) population. The rate of CDI recurrence was a crucial secondary outcome measure assessed at study days 40 and 70 in the microbiological ITT population, which included all patients in the ITT population who tested positively for C difficile toxin at screening or day 1 and who had C difficile isolated in culture. This trial was registered with ClinicalTrials.gov (NCT04781387) and is complete. Between May 12, 2021, and April 26, 2024, 58 individuals were assessed for eligibility, 43 of whom were recruited and randomly assigned: 14 (33%) to the CRS3123 200 mg group, 15 (35%) to the CRS3123 400 mg group, and 14 (33%) to the vancomycin group. The mean age of patients was 58·4 years (SD 18·0), 33 (77%) patients were female, and ten (23%) patients were male. 31 (72%) patients had a primary episode of CDI and 12 (28%) patients had a first recurrence of CDI. All patients received at least one dose of the assigned drug. Treatment-emergent adverse events (TEAEs) were mild to moderate in severity and similar across treatment groups. TEAEs considered possibly related to study drug (all grade 1 or 2) were reported in one patient in the CRS3123 200 mg group (dry mouth, asthenia and gastro-oesophageal reflux disease, nausea, vomiting, increased alanine aminotransferase, and increased aspartate aminotransferase), three patients in the CRS3123 400 mg group (one with increases in alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase; one with malaise, nausea, and feeling abnormal; and one with headache); and in no patients in the vancomycin group. The only serious adverse event reported, pneumonia, was in the vancomycin group and was considered unrelated to the study drug. 13 (93%) of 14 patients in the CRS3123 200 mg group, all 15 (100%) patients in the CRS3123 400 mg group, and 13 (93%) of 14 patients in the vancomycin group had clinical cure at the TOC visit. No patient had clinical failure at the TOC visit; two patients (one each in the CRS3123 200 mg and vancomycin groups) had indeterminate responses due to missing data. Recurrence through day 40 occurred in one (7%) of 14 patients in the CRS3123 400 mg group, none of the 13 patients in the CRS3123 200 mg group, and three (23%) of 13 patients in the vancomycin group, and there was an additional recurrence on day 70 in the CRS3123 400 mg group. Both doses of CRS3123 were deemed safe and well tolerated and showed efficacy similar to vancomycin at the TOC visit, with lower rates of recurrence. Together, these data support further development of CRS3123. US National Institute of Allergy and Infectious Diseases at the National Institutes of Health, Department of Health and Human Services.

Hand, Foot, and Mouth Disease (HFMD) is an acute and contagious viral infection that commonly affects children, especially those under 5 years of age. A 1-year-old male patient presented to the Dermatology Clinic at Cut Meutia General Hospital with the primary complaint of watery blisters on his hands, feet, and mouth, accompanied by fever and loss of appetite. These watery blisters first appeared one week before admission and have worsened over the past three days, spreading rapidly and rupturing easily. The patient has also experienced fluctuating fever over the past three days, loss of appetite, and red spots on the back. The patient lives in an environment where he frequently interacts with neighborhood children and has poultry kept near the house. Dermatological findings: The oral region showed multiple vesicles on the tongue mucosa with an erythematous base; some lesions had ruptured, forming shallow erosions. The upper extremities showed vesicles and erythematous papules with well-defined borders, ranging in size from lenticular to nummular, distributed in multiple clusters; some had a whitish center and were scattered across the extensor surfaces of the arms. The lower extremities show multiple erythematous vesicles of lenticular size; some exhibit hyperpigmented macules from old lesions with indistinct borders. The thoracic and dorsal regions show erythematous macules and multiple small papules; some exhibit post-inflammatory hyperpigmentation. The patient was prescribed steroid medication, specifically Fusycom cream, cefixime syrup, and cetirizine syrup

Background: The study is motivated by the persistent low productivity of dairy cattle farming in Bogor Regency, specifically within the Kawasan Usaha Peternakan (KUNAK), which has been further aggravated by the Foot and Mouth Disease (FMD) outbreak and inefficient input management in the area. The sector faces significant challenges, including the dominance of smallholder farms with poor feed management, shrinking land for forage, and heavy reliance on imports, all of which weaken local farmers’ bargaining power.Purpose: This study aimed to analyze the factors influencing milk production, technical efficiency, and farm profitability in KUNAK. It seeks to evaluate how effectively farmers manage inputs, such as cattle and feed, to maximize output and determine the financial feasibility of these operations post-FMD.Design/methodology/approach: Data were collected from 67 purposively sampled farmers in Cibungbulang and Pamijahan (January–April 2025) who owned cows in their second or third lactation. This study utilized a stochastic frontier translog production function estimated via Maximum Likelihood Estimation (MLE) to measure technical efficiency, alongside a revenue-cost (R/C) ratio analysis for profitability.Findings/Result: MLE results indicated that lactating cows (0.656), concentrate (0.193), and tofu dregs (0.159) significantly affected milk yield. Conversely, labor's negative elasticity (-0.083) reflects severe overutilization. The farms operate under increasing returns to scale, with a high mean technical efficiency of 0.868. Efficiency improves with farmer age but declines as the number of family dependents increases. While economically feasible (R/C ratio=1.10), operations face tight profit margins of Rp207,951 per head per month.Conclusion: Although smallholder dairy farming in the KUNAK cluster demonstrates high technical efficiency (0.868), this operational mastery does not translate into proportional economic welfare due to low market pricing and high input costs. Policy interventions must target labor reallocation and cooperative pricing reforms to bridge the gap between technical proficiency and economic sustainability.Originality/value (State of the art): This study contributes a post-FMD analysis of smallholder dairy clusters, revealing a critical disconnect where high technical efficiency does not guarantee economic welfare due to external market and institutional failures. Keywords: dairy cattle, production function, profitability, stochastic frontier, technical efficiency

Enterovirus A71 (EV-A71), a causative virus of hand, foot, and mouth disease, primarily infects and replicates in the intestine and, in severe cases, spreads to the central nervous system, leading to neurological complications. Therefore, suppressing viral replication in the intestine is important to prevent severe complications. However, the intestinal pathophysiological changes in EV-A71-infected patients remain poorly understood. In this study, we aimed to examine the intestinal response to EV-A71 infection using the intestinal microphysiological system (MPS) we previously developed using human pluripotent stem cells and microfluidic devices. The viral titers were detectable in the cell culture supernatant of the intestinal MPS for 14 days after the viral infection. Despite this, EV-A71 infection did not induce significant morphological changes in the intestinal MPS or alter the expression of epithelial cell markers, suggesting that the virus can infect the intestinal MPS without causing intestinal epithelial damage. In addition, we found that the secretion of interferons (IFNs) in the cell culture supernatant was not increased by viral infection. Interestingly, treatment with recombinant IFNs increased the expression of innate immune response-related genes and reduced viral mRNA levels. A strong association was observed between EV-A71 infection and IFN signaling in the intestinal MPS. We believe that the intestinal MPS would be a valuable platform for studying EV-A71 infection and evaluating antiviral strategies.IMPORTANCEEnterovirus A71 (EV-A71), a major cause of hand, foot, and mouth disease, primarily replicates in the intestine and can spread to the central nervous system, causing severe neurological complications. Suppressing intestinal replication is therefore critical, yet the intestinal pathophysiology of EV-A71 remains poorly understood. Here, we examined EV-A71 infection using a human pluripotent stem cell-derived intestinal microphysiological system (MPS). Viral titers were detectable in the culture supernatant for 14 days. However, EV-A71 did not induce significant morphological changes or alter epithelial marker expression, indicating persistent infection without intestinal damage. Additionally, EV-A71 infection did not enhance interferon (IFN) secretion. Treatment with recombinant IFNs increased innate immune gene expression and reduced viral mRNA, demonstrating the key role of IFN signaling in restricting infection. These findings suggest that the intestinal MPS would be a useful platform for studying EV-A71 infection and antiviral strategies.

Tomato flu is an emerging viral illness reported mainly in children under five years of age in India, characterized by fever and distinctive red, tomato-like vesicular lesions. It is likely associated with enteroviral infections, particularly Hand, Foot, and Mouth Disease. Transmission occurs through close contact, respiratory droplets, and contaminated surfaces. The disease presents with nonspecific symptoms, making differential diagnosis important to distinguish it from infections such as dengue, chikungunya, and varicella. Diagnosis is primarily clinical, and management is supportive, including hydration, antipyretics, and isolation. Although generally self-limiting with a favorable prognosis, preventive measures such as hygiene practices and infection control are essential to limit spread. Further research is needed to better understand its etiology, improve diagnostic approaches, and develop targeted therapies.