Hand, Foot, And Mouth Disease Outbreaks Research Articles

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.

Changing Epidemiology of Hand, Foot, and Mouth Disease Causative Agents and Contributing Factors.

Hand, foot, and mouth disease (HFMD) is a common viral infection primarily affecting children. It causes vesicles on the skin and inside the mouth. Although most cases get better on their own, severe cases can lead to complications such as brain stem encephalitis, meningoencephalitis, acute flaccid paralysis, and pulmonary edema. Hand, foot, and mouth disease is caused by various enteroviruses, with enterovirus A71 (EV-A71) and coxsackievirus A16 being the most common. However, recent studies have shown a shift in the molecular epidemiology of HFMD-causing pathogens, with coxsackievirus A6 and coxsackievirus A10 causing more infections. In addition, extensive recombination events have been identified among enterovirus strains, which may have a role in faster evolution and extinction of dominant enterovirus serotypes. Other strains of enterovirus can also cause severe complications, and there has been an increase in mortality associated with brain stem encephalitis in children under 3 years of age and teenagers. Currently, there are no effective antiviral therapies available to treat enterovirus infections. Vaccines against EV-A71 have been approved and are now used in mainland China. Studying the changing epidemiology of HFMD pathogens and the evolution patterns of its causative agents is crucial in developing effective prevention and control strategies. Increased interest in the molecular epidemiology of HFMD causative agents has led to a better understanding of the critical drivers of HFMD outbreaks, which can inform efforts to prevent and control the disease.

Molecular Evolutionary Dynamics of Coxsackievirus A6 Causing Hand, Foot, and Mouth Disease From 2021 to 2023 in China: Genomic Epidemiology Study.

Hand, foot, and mouth disease (HFMD) is a global public health concern, notably within the Asia-Pacific region. Recently, the primary pathogen causing HFMD outbreaks across numerous countries, including China, is coxsackievirus (CV) A6, one of the most prevalent enteroviruses in the world. It is a new variant that has undergone genetic recombination and evolution, which might not only induce modifications in the clinical manifestations of HFMD but also heighten its pathogenicity because of nucleotide mutation accumulation. The study assessed the epidemiological characteristics of HFMD in China and characterized the molecular epidemiology of the major pathogen (CV-A6) causing HFMD. We attempted to establish the association between disease progression and viral genetic evolution through a molecular epidemiological study. Surveillance data from the Chinese Center for Disease Control and Prevention from 2021 to 2023 were used to analyze the epidemiological seasons and peaks of HFMD in Henan, China, and capture the results of HFMD pathogen typing. We analyzed the evolutionary characteristics of all full-length CV-A6 sequences in the NCBI database and the isolated sequences in Henan. To characterize the molecular evolution of CV-A6, time-scaled tree and historical population dynamics regarding CV-A6 sequences were estimated. Additionally, we analyzed the isolated strains for mutated or missing amino acid sites compared to the prototype CV-A6 strain. The 2021-2023 epidemic seasons for HFMD in Henan usually lasted from June to August, with peaks around June and July. The monthly case reporting rate during the peak period ranged from 20.7% (4854/23,440) to 35% (12,135/34,706) of the total annual number of cases. Analysis of the pathogen composition of 2850 laboratory-confirmed cases identified 8 enterovirus serotypes, among which CV-A6 accounted for the highest proportion (652/2850, 22.88%). CV-A6 emerged as the major pathogen for HFMD in 2022 (203/732, 27.73%) and 2023 (262/708, 37.01%). We analyzed all CV-A6 full-length sequences in the NCBI database and the evolutionary features of viruses isolated in Henan. In China, the D3 subtype gradually appeared from 2011, and by 2019, all CV-A6 virus strains belonged to the D3 subtype. The VP1 sequences analyzed in Henan showed that its subtypes were consistent with the national subtypes. Furthermore, we analyzed the molecular evolutionary features of CV-A6 using Bayesian phylogeny and found that the most recent common ancestor of CV-A6 D3 dates back to 2006 in China, earlier than the 2011 HFMD outbreak. Moreover, the strains isolated in 2023 had mutations at several amino acid sites compared to the original strain. The CV-A6 virus may have been introduced and circulating covertly within China prior to the large-scale HFMD outbreak. Our laboratory testing data confirmed the fluctuation and periodic patterns of CV-A6 prevalence. Our study provides valuable insights into understanding the evolutionary dynamics of CV-A6.

Frontiers and hotspots in hand, foot, and mouth disease research during 2006 to 2023: A bibliometric and visual analysis.

Enteroviruses-infected hand, foot, and mouth disease (HFMD) seriously threatens human health. This study aimed to analyze the research status, hotspots, and frontiers of HFMD. Publications on HFMD between January 1, 2006, and January 31, 2023, were retrieved from the Web of Science Core database. Bibliometric tools, including CiteSpace, VOSviewer, R package "Bibiometrix," SCImago Graphica, and Charticulator, were utilized to analyze and visualize the data. A total of 1860 articles from 424 journals, involving 8815 authors from 64 countries and 1797 institutions were analyzed. The number of studies on HFMD has shown an increasing trend over the past 18 years, with an annual increase observed since 2006, which is particularly prominent after 2010. Research in this field has centered on the Asian region. Notably, the research hotspots were mainly focused on vaccines, epidemiology, and pathogenesis of HFMD. Among the researchers in this field, Zhang Yong emerged as the most prolific author, while Xu Wenbo had the most significant influence. The Chinese Academy of Sciences was the most productive institution, and China was the most productive country for HFMD research. By bibliometric analysis, researchers in the HMFD field can efficiently identify and visually represent their research focus and limitations. In the future, it is crucial to maintain ongoing surveillance of HFMD outbreaks and their pathogenic changes. Additionally, future research should extensively explore the molecular mechanisms underlying Enteroviruses-induced HFMD with a focus on developing vaccines and therapies.

Epidemiological and etiological investigations of hand, foot, and mouth disease in Jiashan, northeastern Zhejiang Province, China, during 2016 to 2022.

Hand, foot, and mouth disease (HFMD) is a common infectious disease in children. Enterovirus A71 (EV71) and coxsackievirus A16 (CA16) have been identified as the predominant pathogens for several decades. In recent years, coxsackievirus A6 (CA6) and coxsackievirus A10 (CA10) have played increasingly important roles in a series of HFMD outbreaks. We performed a retrospective analysis of the epidemiology of HFMD and the spectrum of different viral serotypes, to elucidate the genetic and phylogenetic characteristics of the main serotypes in the Jiashan area during 2016 to 2022. Descriptive epidemiological methods were used to analyze the time and population distribution of HFMD in Jiashan during 2016 to 2022 based on surveillance data. Molecular diagnostic methods were performed to identify the viral serotypes and etiological characteristics of HFMD. Phylogenetic analyses was based on VP1 region of CA16 and CA6. The average annual incidence rate of HFMD fluctuated from 2016 to 2022. Children aged 1-5 years accounted for 81.65% of cases and boys were more frequently affected than girls. Except when HFMD was affected by the COVID-19 epidemic in 2020 and 2022, epidemics usually peak in June to July, followed by a small secondary peak from October to December and a decline in February. Urban areas had a high average incidence and rural areas had the lowest. Among 560 sample collected in Jiashan, 472 (84.29%) were positive for enterovirus. The most frequently identified serotypes were CA6 (296, 52.86%), CA16 (102, 18.21%), EV71 (16, 2.86%), CA10 (14, 2.50%) and other enteroviruses (44, 7.86%). There were 71 and 142 VP1 sequences from CA16 and CA6, respectively. Substitution of N218D, A220L and V251I was detected in CA16 and may have been related to viral infectivity. Phylogenetic analysis showed that CA16 could be assigned to two genogroups, B1a and B1b, while all the CA6 sequences belonged to the D3a genogroup. CA6 and CA16 were the two major serotypes of enteroviruses circulating in the Jiashan area during 2016 to 2022. Continuous and comprehensive surveillance for HFMD is needed to better understand and evaluate the prevalence and evolution of the associated pathogens.

Epidemiological and Clinical Profile of Hand, Foot, and Mouth Disease in Children in a Tertiary Care Center in Jammu.

Background Hand, foot, and mouth disease (HFMD) is a viral illness commonly seen in children under five years of age, characterized by typical manifestations such as oral lesions and rashes on the hands and feet. Coxsackievirus A-16 (CV-A16) and Enterovirus A-71 (EV-A71) are the major etiological agents of this disease. Over the past two decades, there have been several outbreaks of HFMD all across India. As there is no chemoprophylaxis available for the disease, it becomes even more significant to conduct regular research and surveillance for HFMD. Aim and objective To observe the clinico-epidemiologicalprofile along with constitutional symptoms in HFMD patients attending pediatric OPD. Methods This hospital-based prospective observational study was conducted in the Post Graduate Department of Pediatrics, Acharya Shri Chander College of Medical Sciences and Hospital (ASCOMS & H), Sidra, Jammu and Kashmir, India, oversix months from April to September 2023. A total of 132 children with symptoms of HFMD visited the pediatric OPD. After using inclusive and exclusive criteria, we selected a sample size of 112 children with HFMD. The descriptive data were expressed in terms of percentages and proportions, and their graphical representation was done using MS Excel (Microsoft Corporation, Redmond, Washington, United States). Results Among the 112 HFMD patients examined, the highest peak was seen in August, followed by another one in September. Most of the cases were seen in the age group of zero to three years, and it was observed that there wasa linear fall in the number of cases with the increase in age. Nearly 61% of cases were male, showing a slight male preponderance. Vesiculopapular rash on the hand and foot was the most common clinical characteristic, whereas painful deglutitionwas noted to be the most common constitutional symptom in HFMD patients. About 27% had a positive family history, and nail changes post-recovery were present in 1.79% of cases during their regular follow-ups. Conclusions This study reveals that HFMD cases surged in August and September, with a history of contact in one-fourth of cases. Disease is seen more commonly in children under three years of age, and the incidence of cases decreases with the increase in age. The illness is usually contagious and can spread quickly; therefore, more awareness programs should be done toeducate parents and promote hygiene to prevent contact cases.

Modeling and analysis of the effect of optimal virus control on the spread of HFMD

A within-host and between-host hand, foot and mouth disease (HFMD) mathematical model is established and the affect of optimal control in its within-host part on HFMD transmission is studied. Through define two basic reproduction numbers, by using the fast-slow system analysis method of time scale, the global stabilities of the between-host (slow) system and within-host (fast) system are researched, respectively. An optimal control problem with drug-treatment control on coupled within-host and between-host HFMD model is formulated and analysed theoretically. Finally, the purposed optimal control measures are applied to the actual HFMD epidemic analysis in Zhejiang Province, China from April 1, 2021 to June 30, 2021. The numerical results show that the drug control strategies can reduce the virus load per capita and can effectively prevent large-scale outbreaks of HFMD.

Assessing the impact of COVID-19 interventions on the hand, foot and mouth disease in Guangdong Province, China: a Bayesian modeling study.

The non-pharmaceutical interventions (NPIs) against COVID-19 may have affected the transmission of hand, foot and mouth disease (HFMD). We aimed to assess the impact of the NPIs on HFMD in the high epidemic area of HFMD, Guangdong Province. The data of HFMD cases, etiological information, and meteorological factors in Guangdong from January 1, 2012, to December 31, 2021, were collected. Using a Bayesian structural time series (BSTS) model integrated counterfactual framework, we assessed the effect of NPIs on HFMD by different intervention periods, populations (gender, age, occupation), and cities. We further explored the correlation between the reduction of HFMD and socioeconomic factors in 21 cities. A total of 351,217 HFMD cases were reported and 455,327 cases were averted in Guangdong Province during 2020-2021 with a reduction of 84.94% (95%CI: 81.63-87.22%) in 2020 and 29.49% (95%CI: 15.26-39.54%) in 2021. The impact of NPIs on HFMD differed by age and gender. The effects of NPIs were more remarkable for children aged 0-2 years and scattered children. We found that the relative reductions in 21 cities were related to the composition ratio of children and COVID-19 incidence. The reduction of HFMD incidence was significantly associated with COVID-19 NPIs, and school closure was an effective intervention to prevent HFMD outbreaks. Our findings will contribute to the development of HFMD prevention and control measures.

A Hand-Foot-and-Mouth Disease Outbreak in an Atypical Population of College Students.

Hand-foot-and-mouth disease (HFMD), which is typically seen in the younger pediatric population, is uncommon in older adolescent and young adult populations. We report on an atypical outbreak of HFMD among college students at a mid-size university in the mid-Atlantic U.S. The outbreak included 138 qualifying cases of HFMD among students at the institution between August and November 2018. All tested samples were positive for CVA6, a less common cause of HFMD. Signs and symptoms and campus mitigation strategies are described. This case report aims to highlight an atypical outbreak of HFMD for clinicians who care for older adolescent and college-aged patients in primary care and community settings, and may see cases and/or outbreaks of HFMD in these populations.

HMGB1 Release Induced by EV71 Infection Exacerbates Blood-Brain Barrier Disruption via VE-cadherin Phosphorylation

PurposeEV71 (Enterovirus 71) is a major causative agent of the outbreaks of HFMD (hand, foot, and mouth disease), which is associated with neurological damage caused by permeability disruption of BBB (blood-brain barrier). HMGB1 (high-mobility group box 1) is a widely expressed nuclear protein that triggers host inflammatory responses. Our work aimed to explore the function of HMGB1 in EV71 infection and its contributions to EV71-related BBB damage. MethodsHeLa cells, HT-29 cells and AG6 mice were used to explore the translocation of HMGB1 in EV71 infection in vitro and in vivo. The roles of released HMGB1 on EV71 replication and associated inflammatory cytokines were investigated using recombinant HMGB1 in HeLa cells. The mechanisms of released HMGB1 in EV71-induced BBB injury were explored using recombinant HMGB1 and anti-HMGB1 neutralizing antibodies in monolayer HCMECs (immortalized human brain microvascular endothelial cells) and AG6 mice brain. ResultsEV71 induced HMGB1 nucleocytoplasmic translocation and extracellular release in vitro and in vivo. Released HMGB1 acted as an inflammatory mediator in EV71 infection rather than affecting viral replication in vitro. Released HMGB1 disrupted BBB integrity by enhancing VE-cadherin phosphorylation at tyrosine 685 in HCMECs, and reducing total VE-cadherin levels in HCMECs and AG6 mice in EV71 infection. And released HMGB1 induced an increase in activated astrocytes. Neutralization of HMGB1 reversed the increased endothelial hyperpermeability and phosphorylation of VE-cadherin in HCMECs. ConclusionThe inflammatory mediator HMGB1 released by EV71 exacerbated BBB disruption by enhancing VE-cadherin phosphorylation, which in turn aggravated EV71-induced neuroinflammation.

Molecular evolutionary dynamics of enterovirus A71, coxsackievirus A16 and coxsackievirus A6 causing hand, foot and mouth disease in Thailand, 2000–2022

Hand, foot and mouth disease (HFMD) is a public health threat worldwide, particularly in the Asia–Pacific region. Enterovirus A71 (EV-A71), coxsackievirus A16 (CVA16), and CVA6 are the major pathogens causing HFMD outbreaks in several countries, including Thailand. We retrieved 385 VP1 nucleotide sequences, comprising 228 EV-A71, 33 CVA16, and 124 CVA6, deposited in the databases between 2000 and 2022 for molecular evolutionary characterization using Bayesian phylogeny. All EV-A71 identified belonged to genotype B, subgenotypes B4, and B5, and to genotype C, subgenotypes C1, C2, C4a, C4b, and C5. The analyzes demonstrated these viruses’ co-circulation and subgenotypic changes throughout the past two decades. The CVA16 was grouped in genotype B1, predominantly subgenotype B1a, and the CVA6 was grouped in subgenotype D3, clades 1–4. The tMRCA of EV-A71 genotypes B and C, CVA16 B1, and CVA6 D3 dated 1993.79, 1982.62, 1995.86, and 2007.31, respectively, suggesting that the viruses were likely introduced and cryptically circulated in Thailand before the HFMD cases were recognized. We demonstrated these viruses’ fluctuation and cyclical pattern throughout the two decades of observation. This study provided insight into evolutionary dynamics concerning molecular epidemiology and supported the selection of current genotype-matched vaccines, vaccine development, and implementation.

'Hand Foot Mouth and Disease' - is it time for an update?

Hand, foot and mouth disease (HFMD) is a viral illness caused most commonly in the past by coxsackievirus A16 and enterovirus 71. The disease mainly affects paediatric populations younger than 5 years of age and is characterized by lesions of the oral mucosa, palms and soles, lasting for 7–10 days. In recent years, coxsackievirus 6 has become a major cause of HFMD outbreaks in Ireland and worldwide. This strain causes more severe disease with unique findings compared with typical viral strains. We review the increasing presentation of patients with atypical cases in our institution and the implications.

Dynamic modeling and data fitting of climatic and environmental factors and people's behavior factors on hand, foot, and mouth disease (HFMD) in Shanghai, China

BackgroundHand, foot, and mouth disease (HFMD) appear to be a multi-wave outbreak with unknown mechanisms. We investigate the effects of climatic and environmental factors and changes in people's behavior factors that may be caused by external factors: temperature, relative humidity, and school opening and closing. MethodsDistributed lag nonlinear model (DLNM) and dynamic model are used to research multi-wave outbreaks of HFMD. Climatic and environmental factors impact on transmission rate β(t) is modeled through DLNM and then substituted into this relationship to establish the dynamic model with reported case data to test for validity. ResultsRelative risk (RR) of HFMD infection increases with increasing temperature. The RR of infection first increases and then decreases with the increase of relative humidity. For the model fitting HFMD dynamic, time average basic reproduction number [R0] of Stage I (without vaccine) and Stage II (with EV71 vaccine) are 1.9362 and 1.5478, respectively. Temperature has the highest explanatory power, followed by school opening and closing, and relative humidity. ConclusionWe obtain three conclusions about the prevention and control of HFMD. 1) According to the temperature, relative humidity and school start time, the outbreak peak of HFMD should be warned and targeted prevention and control measures should be taken. 2) Reduce high indoor temperature when more than 31.5 oC, and increase low relative humidity when less than 77.5% by opening the window for ventilation, adding houseplants, using air conditioners and humidifiers, reducing the incidence of HFMD and the number of infections. 3) The risk of HFMD transmission during winter vacations is higher than during summer vacations. It is necessary to strengthen the publicity of HFMD prevention knowledge before winter vacations and strengthen the disinfection control measures during winter vacations in children's hospitals, school classrooms, and other places where children gather to reduce the frequency of staff turnover during winter vacations.

Widespread Hand, Foot, and Mouth Disease Outbreaks: Interventions and Control Measures, Surin Province, 2020

In 2020, Surin Province had the highest incidence proportion of hand, foot, and mouth disease (HFMD) in Thailand, primarily concentrated in Mueang District. Numerous outbreaks occurred in kindergarten schools and child development centers despite the implementation of prevention and control measures. This study aimed to evaluate these interventions using observation and interviews and assess associated factors for the prolonged outbreaks. A cross-sectional study was conducted among 37 facilities that reported HFMD outbreaks. Linear regression analysis was performed to assess the association between factors and the duration of the outbreak. There were 369 confirmed HFMD cases. The attack rate in child development centers was 11.6%; in kindergarten schools was 5.1%. Most facilities with outbreak followed the recommendations and control measures issued by the Department of Disease Control; however, improper sanitation was observed in some facilities. A high student-toilet ratio (coefficient 0.64 days, [95% CI 0.11–1.17]) and a high student-janitor ratio (coefficient 0.12 days, [95% CI 0.07-0.17]) were associated with a longer outbreak duration. Prevention and control measures should include promoting personal hygiene, using an appropriate concentration of disinfectant solution, training teachers about common communicable diseases, early screening for detection and isolation of sick children, and communication with parents about HFMD.

Combined impacts of environmental and socioeconomic covariates on HFMD risk in China: A spatiotemporal heterogeneous perspective.

Understanding geospatial impacts of multi-sourced influencing factors on the epidemic of hand-foot-and-mouth disease (HFMD) is of great significance for formulating disease control policies tailored to regional-specific needs, yet the knowledge is very limited. We aim to identify and further quantify the spatiotemporal heterogeneous effects of environmental and socioeconomic factors on HFMD dynamics. We collected monthly province-level HFMD incidence and related environmental and socioeconomic data in China during 2009-2018. Hierarchical Bayesian models were constructed to investigate the spatiotemporal relationships between regional HFMD and various covariates: linear and nonlinear effects for environmental covariates, and linear effects for socioeconomic covariates. The spatiotemporal distribution of HFMD cases was highly heterogeneous, indicated by the Lorenz curves and the corresponding Gini indices. The peak time (R2 = 0.65, P = 0.009), annual amplitude (R2 = 0.94, P<0.001), and semi-annual periodicity contribution (R2 = 0.88, P<0.001) displayed marked latitudinal gradients in Central China region. The most likely cluster areas for HFMD were located in south China (Guangdong, Guangxi, Hunan, Hainan) from April 2013 to October 2017. The Bayesian models achieved the best predictive performance (R2 = 0.87, P<0.001). We found significant nonlinear associations between monthly average temperature, relative humidity, normalized difference vegetation index and HFMD transmission. Besides, population density (RR = 1.261; 95%CI, 1.169-1.353), birth rate (RR = 1.058; 95%CI, 1.025-1.090), real GDP per capita (RR = 1.163; 95%CI, 1.033-1.310) and school vacation (RR = 0.507; 95%CI, 0.459-0.559) were identified to have positive or negative effects on HFMD respectively. Our model could successfully predict months with HFMD outbreaks versus non-outbreaks in provinces of China from Jan 2009 to Dec 2018. Our study highlights the importance of refined spatial and temporal data, as well as environmental and socioeconomic information, on HFMD transmission dynamics. The spatiotemporal analysis framework may provide insights into adjusting regional interventions to local conditions and temporal variations in broader natural and social sciences.

Enterovirus 71-Associated Infection in South Vietnam: Vaccination Is a Real Solution.

Hand-foot-and-mouth disease (HFMD) is the most common enteroviral infection in South-East Asia. When evaluating the role of enterovirus 71 (EVA71) as an etiological agent of infectious disease in South Vietnam, we revealed a high proportion of EVA71 among identified species A enteroviruses found in 3542 samples from HFMD cases; 125 samples from cases of enteroviral meningitis; and 130 samples from acute flaccid paralysis (AFP) cases. These represent 50%, 54.8%, and 51.5%, respectively. According to molecular analysis, 90% of EVA71 were attributed to genotype C4 and 10% were attributed to genotype B5. The predominance of EVA71 circulation among the population proves the need to strengthen surveillance (with monitoring of enterovirus circulation for facilitation of HFMD outbreak prediction) and to increase the effectiveness of preventative measures by the implementation of vaccination against EVA71-associated infections. A phase III trial of a Taiwanese vaccine (EV71vac) in Taiwan and South Vietnam showed its safety, tolerability, and efficacy in children aged 2-71 months. This B4 genotype-based vaccine, which features cross-protection against B5 and C4 genotypes, and other existing EV71 vaccines can serve as a good approach to solving the HFMD problem, which is so important for Vietnam.

Largest outbreak of hand, foot and mouth disease (HFMD) in India at an altitude of 3524 meters (11,562 ft.) in Leh, Union Territory (UT) of Ladakh, India 2016

Introduction: There is an increasing occurrence of Hand, Foot and Mouth Disease (HFMD) in India, Asia, and Australia. The largest ever outbreak in India is discussed in this paper. The geographic location of the case control study was in Leh province which has an average altitude over 3,000 meters (11,000 feet). Objective: This case control study, and review was done to determine if there is evidence of an increase in HFMD. There is concern that the increase of HFMD will lead to an increase in the number of attributed deaths. Methods: District Surveillance Unit (DSU) collected the data on a daily basis upon presentation of symptoms. The unit was comprised of: an epidemiologist, a pediatrician, and a District Health Officer (DHO). Results: There were four hundred and sixty-five confirmed cases of HFMD recorded in the study. Two hundred and sixty-one, 56%, of the cases were male. Two hundred and four, 44%, of the cases were female. The majority of cases affect children ages less than 5. Discussion: HFMD is usually a childhood disease. Adults who contract the disease are most often caregivers. HFMD is caused by a virus, most often one of the picornaviruses belonging to serotypes EV-A or less frequently the enterovirus EV-A71. EV-A71 infections may more often result in severe complications or death. Conclusion: Healthcare professionals and government oversight agencies must be vigilant in the detection and control of HFMD outbreaks. Appropriate protocol and incident reporting needs to be standardized.

Clinico Virological Characterization of Hand, Foot and Mouth Disease in a Tertiary Care Hospital, South India.

Hand, foot, and mouth disease (HFMD) is a common childhood infectious disease, caused by enteroviruses (EVs) which can present with typical or atypical lesions. Although the disease is self-limiting, it can also lead to serious complications. In the era of polio eradication, it is important to understand the population dynamics of enteroviruses causing HFMD as one of the circulating strains may become dominant. It was a collaborative study carried out in the Department of Dermatology and Microbiology of a tertiary care teaching hospital. The throat swabs were collected from 132 suspected HFMD cases. Real-time polymerase chain reaction (PCR) was performed to detect the presence of pan enteroviruses, followed by genotype-specific PCR targeting Human Enterovirus 71 (HEV-71) and Coxsackie virus A16 (CVA-16) and CVA-6 for pan Enterovirus-positive samples. Follow-up samples were collected from 14 children in the 2nd week and subjected to molecular testing to detect enteroviruses. Among 132 children suspected to have HFMD, 44 were girls and 88 were boys, and the majority of them 76.5% (101/132) were under 2 years of age. A history of exposure to a similar clinical presentation was present in 15 children. Of 132 suspected cases, 60 samples (45.5%) were positive for pan Enterovirus. The predominantly circulating genotype was found to be CVA-6 (31.6% [19/60]). There were about 10 cases (16.6%) which had co-infection with both HEV71 and CVA-6. Rash with fever was the most common presentation (57%). In most of the cases with HEV 71, 92.3% (12/13) presented within 3 days of illness to the health-care facility. Of 60 positive cases, 25% (15/60) of children had the atypical distribution of rashes in the face, trunk, genitalia, thigh, neck, and axilla and 16.7% of children (10/60) had the atypical type of lesion either only papular lesions or erythema multiforme. Out of 14 follow-up samples, 13 were negative for EVs; one was positive for pan EV in the 2nd week, however, the patient lost to follow-up after that. HFMD outbreaks in our region were caused by various genotypes of enteroviruses. No severe complications were seen in the affected children. Nearly 30% had atypical presentation either in the form of lesion or site. Robust molecular epidemiological surveillance of HFMD is required to know the strain variations and other emerging genotypes in our setup.

Drug Repositioning for Hand, Foot, and Mouth Disease.

Hand, foot, and mouth disease (HFMD) is a highly contagious disease in children caused by a group of enteroviruses. HFMD currently presents a major threat to infants and young children because of a lack of antiviral drugs in clinical practice. Drug repositioning is an attractive drug discovery strategy aimed at identifying and developing new drugs for diseases. Notably, repositioning of well-characterized therapeutics, including either approved or investigational drugs, is becoming a potential strategy to identify new treatments for virus infections. Various types of drugs, including antibacterial, cardiovascular, and anticancer agents, have been studied in relation to their therapeutic potential to treat HFMD. In this review, we summarize the major outbreaks of HFMD and the progress in drug repositioning to treat this disease. We also discuss the structural features and mode of action of these repositioned drugs and highlight the opportunities and challenges of drug repositioning for HFMD.

Effects of different levels of non-pharmaceutical interventions on hand, foot and mouth disease in Guangzhou, China

BackgroundNon-pharmaceutical interventions (NPIs) against coronavirus disease 2019 (COVID-19) may have suppressed the transmission of other infectious diseases. This study aimed to evaluate the impact of different degrees of NPIs during the COVID-19 pandemic on hand, foot and mouth disease (HFMD) in Guangzhou, China.MethodsWeekly reported HFMD cases and pathogens information during 2015–2021 in Guangzhou were collected from the China National Notifiable Disease Reporting System. The observed number of HFMD cases in 2020 and 2021 was compared to the average level in the same period during 2015–2019. Then, an interrupted time-series segmented regression analysis was applied to estimate the impact of NPIs on HFMD, such as social distancing, suspension of schools, community management and mask wearing. The effects across different subgroups stratified by gender, children groups and enterovirus subtype of HFMD were also examined.ResultsA total of 13,224 and 36,353 HFMD cases were reported in 2020 and 2021, which decreased by 80.80% and 15.06% respectively compared with the average number of cases in the same period during 2015–2019. A significant drop in the number of HFMD cases during time when strict NPIs were applied (relative change: 69.07% [95% confidence interval (CI): 68.84%–69.30%]). The HFMD incidence rebounded to historical levels in 2021 as the lockdown eased. The slightest reduction of HFMD cases was found among children at kindergartens or childcare centres among the three children groups (children at kindergartens or childcare centres: 55.50% [95% CI: 54.96%–56.03%]; children living at home: 72.64% [95% CI: 72.38%–72.89%]; others: 74.06% [95% CI: 73.19%–74.91%]).ConclusionsThe strong NPIs during the COVID-19 epidemic may have a significant beneficial effect on mitigating HFMD. However, the incidence of HFMD rebounded as the NPIs became less stringent. Authorities should consider applying these NPIs during HFMD outbreaks and strengthening personal hygiene in routine prevention.