Hand, Foot And Mouth Disease Research Articles

Epidemiology of Hand, Foot, and Mouth Disease and Genetic Characterization of Coxsackievirus A16 in Shenyang, Liaoning Province, China, 2013–2023

Hand, foot, and mouth disease (HFMD), a common childhood infection caused by enterovirus, poses a serious public health concern in China. We collected and analyzed epidemiological data on 62,133 HFMD cases in Shenyang City, Liaoning Province, from 2013 to 2023. The average annual incidence was 76.12 per 100,000 person-years; 99.45% of cases were mild, while 0.55% were severe. Only one patient died. HFMD infections peaked annually in July. Children in kindergartens and scattered children accounted for 44.6% and 42.2% of cases, respectively. Real-time RT-PCR detection of enteroviruses in 5534 patient samples revealed 3780 positives, of which 25.1% were CVA16-positive. Positives were randomly sampled, yielding 240 VP1 sequences of CVA16. Phylogenetic tree results showed that all VP1 sequences belonged to the B1 sub-genogroup. However, the sub-genogroup prevalence varied over time: from 2013 to 2014 and 2019 to 2021, the predominant sub-genogroup was B1a, while it was B1b from 2015 to 2018. Further phylogenetic analyses showed substantial divergence between B1a branches in CVA16, suggesting possible turnover of the B1a sub-genogroup in CVA16 due to evolution. This study provides epidemiological data on HFMD in Shenyang, and provides a phylogenetic analysis of CVA16, offering a theoretical basis for preventing and controlling HFMD in Shenyang City.

Onychomadesis and Beau’s Lines- Rare Complications of Handfoot- and-mouth Disease

Hand-foot-and-mouth disease (HFMD) is a common self-limiting viral infection in children caused by Coxsackievirus A16 and human enterovirus 71, presenting with fever, erythematous papulovesicular eruptions/ blisters on the palms, soles, knees, buttocks, and oral mucosa. Although rare, complications may arise in nails e. g. onychomadesis (nail separation) and Beau’s lines (transverse lines on the nails). These typically appear within four to eight weeks of HFMD and persist for around 5-6 weeks. No active treatment is required and these nail changes resolve spontaneously within few weeks as the nail bed remain intact. We present here a boy of 4 years who presented with such nail changes after around 5 weeks of HFM disease and diagnosed as onychomadesis and Beau’s lines after ruling out other possible causes of nail changes. BANGLADESH J CHILD HEALTH 2023; VOL 47 (1) : 47-50

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.

Air pollution’s numerical, spatial, and temporal heterogeneous impacts on childhood hand, foot and mouth disease: a multi-model county-level study from China

BackgroundWhile stationary links between childhood hand, foot and mouth disease (HFMD) and air pollution are known, a comprehensive study on their heterogeneous relationships (nonstationarity), jointly considering numerical, temporal and spatial dimensions, has not been reported.MethodsMonthly HFMD incidence and air pollution data were collected at the county level from Sichuan-Chongqing, China (2009–2011), alongside meteorological and social environmental covariates. Key influential factors were identified using random forest (RF) under the stationary assumption. Factors’ numerically, temporally, and spatially heterogeneous relationships with HFMD were assessed using generalized additive model (GAM) and geographically and temporally weighted regression (GTWR).ResultsOur findings highlighted the relatively higher stationary contributions of fine particulate matter (PM2.5) and ozone (O3) to HFMD incidence across Sichuan-Chongqing counties. We further uncovered heterogeneous impacts of PM2.5 and O3 from three nonstationary perspectives. Numerically, PM2.5 showed an inverse ‘V’-shaped relationship with HFMD incidence, while O3 exhibited a complex pattern, with increased HFMD incidence at low PM2.5 and moderate O3 concentrations. Temporally, PM2.5’s impact peaked in autumn and was weakest in spring, whereas O3’s effect was strongest in summer. Spatially, hotspot mapping revealed high-risk clusters for PM2.5 impact across all seasons, with notable geographical variations, and for O3 in spring, summer, and autumn, concentrated in specific regions of Sichuan-Chongqing.ConclusionsThis study underscores the nuanced and three-perspective heterogeneous influences of air pollution on HFMD in small areas, emphasizing the need for differentiated, localized, and time-sensitive prevention and control strategies to enhance the precision of dynamic early warnings and predictive models for HFMD and other infectious diseases, particularly in the fields of environmental and spatial epidemiology.

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.

Temporal distribution characteristics of hand, foot and mouth disease in Beijing, 2008-2023

Objective: To analyze the temporal distribution characteristics of hand, foot and mouth disease (HFMD) in Beijing and provide reference evidence in HFMD prevention and control. Methods: The monthly incidence data of HFMD in Beijing from 2008 to 2023 were collected from Notifiable Disease Management Information System of the Chinese Information System of Disease Control and Prevention, and the epidemiological characteristics of HFMD were analyzed by the methods of time series seasonal decomposition graph, concentration degree, and circular distribution.The WPS office software 2019 was used to clean the data, Python software 3.12 was used to analyze and make statistical charts. Results: The monthly incidence fluctuation of HFMD in Beijing from 2008 to 2015 was higher than that from 2016 to 2022. From 2016 to 2022, the fluctuation range of monthly incidence showed a gradually decreasing trend.From 2008 to 2015, the concentration (M) was 0.58, indicating a relatively strong seasonality; the mean angle (α) calculated by the circular distribution method was 174.95°, and the mean angle standard deviation (s) was 60.43°. The annual incidence peak occurred on June 27, and the incidence peak period was from April 27 to August 27. From 2016 to 2019 and 2023, the M was 0.57, indicating a relatively strong seasonality. The α was 228.05°, and s was 61.44°. The annual incidence peak occurred on August 20, and the incidence peak period was from June 18 to October 21. From 2020 to 2022, the M was 0.42, indicating a seasonality, the α was 238.27° and s was 76.35°. The annual incidence peak occurred on July 15, and the incidence peak period was from June 14 to November 14. The α of 2008-2015, 2016-2019 and 2023, and 2020-2022 were tested by the Watson-Williams method and the difference was statistically significant (F=33 443.09, P<0.001). In 2023, the M was 0.77, indicating a strong seasonality. The incidence peak occurred on September 16, and the incidence peak period was from August 5 to October 28. Conclusions: The seasonality of HFMD in Beijing was obvious from 2008 to 2023, and the incidence peak day and peak period overall had rearward shifts. It is necessary to strengthen the comprehensive analysis of the distribution characteristics at different dimensions and the comprehensive prevention and control in key areas, places, and populations during the peak incidence period.

EPIDIDYMO-ORCHITIS CAUSED BY HAND, FOOT, AND MOUTH DISEASE IN ADULTS

Abstract: Hand, Foot, and Mouth disease (HFMD) is predominantly recognized as a childhood disease and is not generally anticipated to manifest in adults. In addition to inducing symptoms such as fever, herpangina, and distal-extremity rashes, HFMD can also lead to rare complications such as encephalitis and onychomadesis. Epididymo-orchitis; however, is not considered an expected complication of HFMD. In our case, a patient diagnosed with HFMD presented with testicular pain four days later, and epididymo-orchitis was subsequently identified in the patient initially suspected of testicular torsion. Cases of Coxsackie virus-related epididymo-orchitis have been reported in the literature, and these cases can be mistaken for torsion, thereby posing the risk of unnecessary surgical interventions. Testicular pain in a young adult with a history of HFMD should be considered as a potential diagnosis of viral epididymo-orchitis.

Optimal control of bi-seasonal hand, foot and mouth disease in mainland China suggests transmission from children and isolating older infected individuals are critical.

Hand, foot and mouth disease (HFMD) is a Class C infectious disease that carries particularly high risk for preschool children and is a leading cause of childhood death in some countries. We mimic the periodic outbreak of HFMD over a 2-year period-with differing amplitudes-and propose a dynamic HFMD model that differentiates transmission between mature and immature individuals and uses two possible optimal-control strategies to minimize case numbers, total costs and deaths. We parameterized the model by fitting it to HFMD data in mainland China from January 2011 to December 2018, and the basic reproduction number was estimated as 0.9599. Sensitivity analysis demonstrates that transmission between immature and mature individuals contributes substantially to new infections. Increasing the isolation rates of infectious individuals-particularly mature infectious individuals-could greatly reduce the outbreak risk and potentially eradicate the disease in a relatively short time period. It follows that we have a reasonable chance of controlling HFMD if we can reduce transmission in children under 7 and isolate older infectious individuals.

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.

Genomic surveillance reveals low-level circulation of two subtypes of genogroup C coxsackievirus A10 in Nanchang, Jiangxi Province, China, 2015-2023.

In recent years, coxsackievirus (CV) A10 has been associated with increasing sporadic hand, foot, and mouth disease (HFMD) cases and outbreaks globally. In addition to mild symptoms such as pharyngitis and herpangina, CVA10-related complications or even fatality can occur. Currently, systematic phylogenetic studies of CVA10 are limited. In this study, we first explored the epidemiological and genetic characteristics of CVA10 in Nanchang, an inland southeastern city of China, based on the HFMD surveillance network from 2015-2023. Among 3429 enterovirus-positive cases, 110 (3.04%) were associated with CVA10, with a male-to-female ratio of 1.62. The median age of the CVA10 patients was 2.3 years (interquartile range, IQR 1.0-4.0), with 94.55% (104/110) of the patients aged less than 5 years. Phylogenetic analyses using the full-length VP1, 5'UTR, P1, P2, P3 sequences and near full-length genomes indicated that CVA10 strains (n = 57) isolated in Nanchang belonged to genogroup C; two strains identified in 2017 belonged to C1 subtypes clustered with strains from Vietnam, Madagascar, France and Spain; and the others belonged to C2 subtypes interdigitating with CVA10 isolates from mainland China, the United States and Australia. Through extensive analysis, we identified a rare F168Y mutation in epitope 4 of VP1 in a Madagascar strain of genogroup F and a Chinese strain of genogroup C. Based on Bayesian evolutionary analyses, the average nucleotide substitution rate for the VP1 gene of CV10 strains was 3.07×10-3 substitutions/site/year. The most recent common ancestor (tMRCA) of genogroup C was dated 1990.84, and the tMRCA of CVA10 strains from Nanchang was dated approximately 2003.16, similar to strains circulating in other regions of China, suggesting that the viruses were likely introduced and cryptically circulated in China before the establishment of the HFMD surveillance network. Recombination analysis indicated intertypic recombination of the Nanchang strain with the genogroup G strain in the 3D region. Given the shifting dominance of viral genotypes and frequent recombination events, the existing surveillance system needs to be regulated to enhance genomic surveillance efforts on a more diverse spectrum of genotypes in the future.

Vascular endothelial growth factor receptor 2 as a potential host target for the inhibition of enterovirus replication.

As the first clinical case was identified in the United States, EV-A71, a significant neurotropic enterovirus, has been a common cause of hand, foot, and mouth disease (HFMD) in infants and young children. Developing an effective antiviral agent for EV-A71 and other human enteroviruses is crucial, as these viral pathogens consistently cause outbreaks in humans. In this study, we demonstrated that multiple inhibitors against VEGFRs effectively reduced EV-A71 replication, with Pazopanib emerging as the top candidate. Furthermore, Pazopanib also attenuated the replication of other enteroviruses, including CVA10, CVB1, EV-D70, and HRV-A, displaying broad-spectrum anti-enterovirus activity. Given that Pazopanib targets various VEGFRs, we narrowed the focus to VEGFR2 using knockdown and overexpression experiments. Transcriptomic analysis suggests that Pazopanib's potential downstream targets involve the TSAd-Src-PI3K-Akt pathway. Our work may contribute to identifying targets for antiviral inhibitors and advancing treatments for human enterovirus infections.

The class III phosphatidylinositol 3-kinase VPS34 supports EV71 replication by promoting viral replication organelle formation.

Enterovirus 71 (EV71) belongs to the family of Picornaviridae; it could cause a variety of illnesses and pose a great threat to public health worldwide. Currently, there is no specific drug treatment for this virus, and a better understanding of virus-host interaction is crucial for novel antiviral development. Here, we find that the class III phosphatidylinositol 3-kinase, VPS34, is an essential host factor for EV71 infection. VPS34 inhibition with either shRNA or specific chemical inhibitor significantly reduces EV71 infection. Meanwhile, EV71 infection upregulates phosphatidylinositol 3-phosphate (PI3P) production in viral replication organelles (ROs), while the depletion of PI3P by phosphatase overexpression inhibits EV71 infection. In addition, the PI3P-binding protein, double FYVE-containing protein 1 (DFCP1), is also required for an efficient replication of EV71. DFCP1 could interact with viral 2C protein and facilitate viral association with lipid droplets (LDs), which are important lipid sources for viral RO biogenesis. Taken together, these results indicate that EV71 virus exploits the VPS34-PI3P-DFCP1-LDs pathway to promote viral RO formation and viral infection, and they also illuminate novel targets for antiviral development.IMPORTANCEEnterovirus 71 (EV71) is a major pathogen that causes hand-foot-and-mouth disease (HFMD) and other serious complications, which are big threats to children under 5 years old. Unravelling the interactions between virus and the host cells will open new avenues in antiviral research. Here, we found the class III phosphatidylinositol 3-kinase, VPS34, and its effector, double FYVE-containing protein 1 (DFCP1), were essential for EV71 infection, both of which could support EV71 viral replication by enhancing the biogenesis of viral replication organelles (ROs). As DFCP1 localizes to lipid droplets, hijacking of these host factors will enable viral utilization of lipids from LDs for the generation of membrane structures during RO biogenesis. In addition, the VPS34 kinase inhibitor was found to be potent against EV71 infection; therefore, this study also brings up a novel target for future anti-EV71 drug development.

Exploring the Birthday Week Effect on Hand, Foot, and Mouth Disease in Yunnan Province, China, From 2008 to 2022: Surveillance Data Analysis.

Hand, foot, and mouth disease (HFMD) is a notable infectious disease predominantly affecting infants and children worldwide. Previous studies on HFMD have primarily focused on natural patterns, such as seasonality, but research on the influence of important social time points is lacking. Several studies have indicated correlations between birthdays and certain disease outcomes. This study aimed to explore the association between birthdays and HFMD. Surveillance data on HFMD from 2008 to 2022 in Yunnan Province, China, were collected. We defined the period from 6 days before the birthday to the exact birthday as the "birthday week." The effect of the birthday week was measured by the proportion of cases occurring during this period, termed the "birthday week proportion." We conducted subgroup analyses to present the birthday week proportions across sexes, age groups, months of birth, and reporting years. Additionally, we used a modified Poisson regression model to identify conditional subgroups more likely to contract HFMD during the birthday week. Among the 973,410 cases in total, 116,976 (12.02%) occurred during the birthday week, which is 6.27 times the average weekly proportion (7/365, 1.92%). While the birthday week proportions were similar between male and female individuals (68,849/564,725, 12.19% vs 48,127/408,685, 11.78%; χ21=153.25, P<.001), significant differences were observed among different age groups (χ23=47,145, P<.001) and months of birth (χ211=16,942, P<.001). Compared to other age groups, infants aged 0-1 year had the highest birthday week proportion (30,539/90,709, 33.67%), which is 17.57 times the average weekly proportion. Compared to other months, patients born from April to July and from October to December, the peak months of the HFMD epidemic, had higher birthday week proportions. Additionally, a decreasing trend in birthday week proportions from 2008 to 2022 was observed, dropping from 33.74% (3914/11,600) to 2.77% (2254/81,372; Cochran-Armitage trend test: Z=-102.53, P<.001). The results of the modified Poisson regression model further supported the subgroup analyses findings. Compared with children aged >7 years, infants aged 0-1 year were more likely to contract HFMD during the birthday week (relative risk 1.182, 95% CI 1.177-1.185; P<.001). Those born during peak epidemic months exhibited a higher propensity for contracting HFMD during their birthday week. Compared with January, the highest relative risk was observed in May (1.087, 95% CI 1.084-1.090; P<.001). This study identified a novel "birthday week effect" of HFMD, particularly notable for infants approaching their first birthday and those born during peak epidemic months. Improvements in surveillance quality may explain the declining trend of the birthday week effect over the years. Higher exposure risk during the birthday period and potential biological mechanisms might also account for this phenomenon. Raising public awareness of the heightened risk during the birthday week could benefit HFMD prevention and control.

Biological and ecological determinants of Hand Foot and Mouth Disease (HFMD) in Coastal District of Northeastern Peninsular Malaysia: A 5-Year retrospective study

Hand, foot, and mouth disease (HFMD) is a common viral communicable disease in Malaysia, characterized by its self-limiting nature, yet it leads to numerous outbreaks and fatalities, particularly among young children. The current study aimed to determine the prevalence, geographic distribution, temporal patterns, and associated factors of HFMD cases within the Bachok District of Kelantan, spanning the years 2018 to 2022. A retrospective cohort study analysed extract data on independent factors and notification status from the Communicable Disease Control Information System (CDCIS). Simple and multiple logistic regression analyses were employed on a cohort of 1351 HFMD’s notifications. The retrospective analysis reveals a predominant HFMD’s notification were males (56.7%). Outpatient care was common (98.4%), with primary health care being the main choice. Logistic regression indicates higher odds for HFMD in those attending primary health care or private practitioners, daycare attendees, during the Southwest Monsoon season, and before the Movement Control Order (MCO) implementation, emphasizing key risk factors for HFMD. This study’s integrative approach recognizes that health and disease are often influenced by a combination of factors spanning the ecological, biological, and clinical domains. Thus, emphasizing the need for a comprehensive understanding when formulating public health strategies particularly in primary healthcare settings and daycare facilities during the Southwest Monsoon season.

Monitoring the Influence of Hand, Foot, and Mouth Disease: New Guidelines on Patient Care during the 2011-2012 Multiwaves and Multivariant Outbreak in Hai Phong City, Vietnam.

From 2011 to 2012, Northern Vietnam suffered its first large-scale hand, foot, and mouth disease (HFMD) epidemic. Two sets of official guidelines were issued during the outbreak to handle the HFMD crisis. The city of Hai Phong was used as a model to analyze the impact of the released guidelines. A total of 9621 HFMD cases were reported in Hai Phong city from April 2011 to December 2012. Three distinct waves of HFMD occurred. Enterovirus A71 and Coxsackievirus A16 were successively associated with the epidemics. Two periods, before and after the guidelines' release, could be distinguished and characterized by different patient patterns. The time to admission and severity changed notably. Guideline publications help the health system refocus on the 0.5-3 years age group with the highest incidence of the disease. The three waves showed different special distribution, but the main routes of infection were rivers and local secondary roads, most likely through local trade and occupational movements of people.

Effectiveness of EV-A71 Vaccine and Its Impact on the Incidence of Hand, Foot and Mouth Disease: A Systematic Review.

Vaccination is a highly effective strategy for the prevention of enterovirus A71 (EV-A71)-hand, foot, and mouth disease (HFMD). Three inactivated EV-A71 vaccines in China have demonstrated remarkable efficacy against EV-A71-HFMD during clinical trials, exhibiting vaccine effectiveness (VE) exceeding 90% and few adverse events (AEs). However, the effectiveness of vaccines in the real world and its impact on the epidemiological characteristics of HFMD after the use of EV-A71 inactivated vaccine are uncertain. The odd ratio (OR) and 95% confidence (CI) were used as the effect estimates of the meta-analysis in the test-negative design (TND), and the OR was used to calculate VE: VE = (1 - OR) × 100%. According to the literature search strategy, a comprehensive search was conducted in PubMed, Web of Science (including Chinese Science Citation Database and MEDLINE), and Embase, and 18 records were ultimately included in this study. Subsequently, the overall VE and 95% CI of different vaccine doses were analyzed, with the one-dose vaccine at 66.9% (95% CI: 45.2-80.0%) and the two-dose vaccine at 84.2% (95% CI: 79.4-87.9%). Additionally, the most reported AEs were mild general reactions without any rare occurrences. Simultaneously, the widespread use of the EV-A71 vaccine would lead to a reduction in both the incidence of EV-A71-associated HFMD and severe cases caused by EV-A71. The administration of the two-dose EV-A71 vaccine is highly effective in preventing HFMD in the real world, and the widespread use of the EV-A71 vaccine leads to a reduction in the incidence of EV-A71-associated HFMD and that of severe cases caused by EV-A71. The findings suggest that administering the two-dose EV-A71 inactivated vaccine to children aged 6 months to 71 months can be effective in preventing EV-A71-associated HFMD, highlighting the need for developing a multivalent HFMD vaccine for preventing cases not caused by EV-A71.

A review of enterovirus-associated hand-foot and mouth disease: preventive strategies and the need for a global enterovirus surveillance network.

Enterovirus (EV)-associated hand, foot, and mouth disease (HFMD) is a significant public health issue worldwide, commonly occurring in children five years of age or younger. The leading causes of most HFMD cases are EVs, which are members of the Picornaviridae family. The typical clinical manifestations of EV-associated HFMD are febrile presentations with mucosal herpangina, oral ulcerations, and skin rashes on the hands and feet. The majority of HFMD cases resolve without consequence; however, a subset progresses to severe neurological and cardiopulmonary complications, which can be fatal. In the past two decades, EV-associated HFMD has received significant attention. In this review, we organize published papers and provide updates on epidemiology, pathogenesis, surveillance, and vaccine developments for EV-associated HFMD. The impact of EV-associated HFMD is increasing globally. Developing efficacious vaccines has become a priority for preventing EV infections without adequate treatment. Simultaneously, emerging EV infections (including EV-D68, EV-A71, Coxsackieviruses, and echoviruses) are increasing, highlighting the need to create a vigilant surveillance system for EV infections worldwide.

Evolving pathogen trends and spatial–temporal dynamics of hand, foot, and mouth disease in Fengxian District, Shanghai (2009–2022)

Hand, foot, and mouth disease (HFMD) is a prevalent acute infectious disease caused by enteroviruses, presenting substantial public health challenges in Shanghai, especially among children. The dynamic nature of HFMD’s etiology necessitates an ongoing evaluation of its epidemiological and virological trends to inform effective control strategies. This study aims to investigate the epidemiological patterns and viral evolution of HFMD in Fengxian District, Shanghai, China, with a focus on shifts in predominant viral strains over a 14-year period. We conducted a retrospective analysis of HFMD cases reported to the National Notifiable Disease Reporting System in Fengxian District from January 1, 2009 to December 31, 2022. Epidemiological trends, strain prevalence, and demographic impacts were assessed. A total of 27,272 HFMD cases were documented during the study period, with incidence showing pronounced seasonal fluctuations—peaking in spring and summer and a lesser peak in autumn. The disease incidence demonstrated significant positive correlations with several meteorological variables: daily average temperature (r = 0.30, P < 0.05), relative humidity (r = 0.20, P < 0.05), wind speed (r = 0.17, P < 0.05), and precipitation (r = 0.17, P < 0.05). Geographically, Nanqiao Town, Fengcheng Town, and Xidu Subdistrict reported the highest incidence rates. The demographic analysis revealed a male-to-female ratio of 1.60:1, predominantly affecting children aged 1–3 years. Prior to 2017, Enterovirus 71 (EV71) and Coxsackievirus A16 (CoxA16) were the primary detected strains; post-2017, Coxsackievirus A6 (CoxA6) emerged as the dominant strain. Statistical analysis confirmed significant year-to-year variations in virus detection rates, with decreasing trends for EV71 and other enteroviruses and an increasing trend for CoxA6. The findings indicate a distinct seasonal incidence of HFMD in Fengxian District. This study underscores the need for targeted public health education, enhanced surveillance, and proactive measures in childcare facilities to mitigate disease spread during peak seasons. Moreover, the evolving viral landscape warrants accelerated efforts in vaccine development against new strains to reduce HFMD incidence.

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.

Effectiveness of the enterovirus A71 vaccine on hand, foot, and mouth disease: a real-world study in China

ObjectivesFor the prevention of hand, foot, and mouth disease (HFMD), enterovirus A71 (EV-A71) vaccines have been used in China since 2016. To better inform vaccination strategies, we assess the real-world effectiveness of EV-A71 vaccination in China. MethodsThe analysis was based on surveillance data of HFMD caused by EV-A71 in children under the age of 5 in China, along with meteorological and demographic data. The seasonal autoregressive integrated moving average model and the interrupted time series analysis were used to estimate the effectiveness of the EV-A71 vaccination on the EV-A71 HFMD incidence and to predict the counterfactual cases with no EV-A71 vaccine. ResultsBetween 2010 and 2018, 6 712 613 cases of HFMD caused by EV-A71 were reported in children under 5 years old in 260 Chinese cities. During 2017–2018, the EV-A71 vaccination was associated with a reduction in EV-A71 HFMD incidence, with a relative risk of 0.83 (95% CI, 0.81–0.86), and an estimated reduction of 297 946 (95% CI, 250 534–346 658) cases. However, this association varied across cities (I2 = 85.6%, p < 0.001) and the effectiveness of the EV-A71 vaccination decreased as population density increased. Higher vaccination coverage was associated with greater effectiveness of the EV-A71 vaccination and an earlier point in EV-A71 case reduction. Specifically, when the vaccination coverage exceeded ∼20%, the relative risk was rapidly reduced to below 0.71 (95% CI, 0.69–0.72). DiscussionOur study demonstrated that the EV-A71 vaccination was associated with a reduction in the incidence of EV-A71 HFMD, but the association varied with regions and was influenced by vaccination coverage and population density. To optimize EV-A71 HFMD prevention, increasing vaccination coverage (>20%) is recommended for children under 5 years old.