Hand, Foot And Mouth Disease Infections Research Articles

Detection of hotspots and coldspots of the incidence of hand, foot and mouth diseases: A case study in Ho Chi Minh city, Vietnam

Background: Hand, foot, and mouth disease (HFMD) is a common pediatric illness mostly caused by Coxsackievirus A16 (CV-A16) and Human Enterovirus 71 (EV-A71). HFMD has grown significantly over the last 20 years, and it has drawn a lot of attention. To better understand of the epidemiology of HFMD, this study aims to investigate the use of Getis-Ord’s 𝐺𝑖 ∗ statistic in the identification of hotspots and coldspots of HFMD in Ho Chi Minh city, Vietnam. Methods: Getis-Ord’s 𝐺𝑖 ∗ statistic was first applied to identify hotspots and coldspots of HFMD incidence including highhigh, low-low spatial clusters. HFMD cases and infection rates collected in Ho Chi Minh were then used to explore the spatial clusters of HFMD Finally, the main findings will be discussed and summarised. Results: It was found that the large number of hand, foot and mouth disease cases were mainly concentrated in the western area of Ho Chi Minh City. A total of 04 hotspot clusters and 05 coldspots of HFMD infection rate were detected in the 29th week of 2024 in the west, center and north of Ho Chi Minh City, respectively. Whereas, 06 hotspots and 04 coldspots of HFMD infection rate were detected in the 30th week of 2024 in the west, south and center of Ho Chi Minh City, respectively. Conclusions: The results of this investigation confirm the value of Getis-Ord's 𝐺𝑖 ∗ statistic in the detection of hotspots and coldspots associated with confirmed cases of HFMD.

Modelling the dynamics of hand, foot, and mouth disease transmission through fomites and immigration

Hand, foot, and mouth disease (HFMD) is widely spread in China Mainland, seriously threatening the health of infants and young children. We develop a meta‐population model that includes both local and ecdemic populations to study the impacts of fomites and immigration on the transmission of HFMD in Shanghai. The model includes both direct transmission between susceptible and infected individuals (asymptomatic or symptomatic) and indirect transmission via fomites. The forward bifurcation shows that if the basic reproduction number is less than unity, the epidemic will die out; otherwise, the epidemic will spread. The fitting results show that the basic reproduction numbers of the local population and the ecdemic population are 1.4696 and 1.7288, respectively. Sensitivity analysis of the basic reproduction number showed that there was a high correlation between the basic reproduction number and the transmission rate of asymptomatic infected individuals, as well as the parameters related to the fomites (such as indirect transmission rate and virus shedding rate). Hence, asymptomatic infected individuals and fomites have a significant impact on the new HFMD infection. The numerical simulations on the prevention and control strategy show that reducing the transmission rate between susceptible and asymptomatic infected individuals or reducing the fomites can delay the outbreak of the epidemic and weaken the severity of HFMD. Our findings can provide guidance for the eradication of HFMD epidemic in the presence of indirect transmission and other factors.

Identification Of Local Clusters Of Hand Foot And Mouth Disease Based On Local Geary C Statistic

Background: Hand, foot, and mouth disease (HFMD) is a common childhood illness caused by enteroviruses. Increasingly, the disease has a substantial burden throughout Vietnam. To better understand of the epidemiology of HFMD, this study aims to investigate the use of local Geary’s C statistic in the identification of local clusters of HFMD in Ho Chi Minh city, Vietnam. Methods: Histogram was first used to study the distribution of HFMD cases the incidence of HFMD. Local Geary C statistics was then applied to identify the spatial clusters of HFMD cases and HFMD incidence including high-high, low-low, negative and other positive clusters. Finally, HFMD cases and infection rates collected in Ho Chi Minh were used to explore the spatial clusters of HFMD. Results: It was found that, in the case of using HFMD cases, two high-high clusters in District 12 and Binh Tan in the city center, one low-low cluster in District 5 in the east of the city center and two negative clusters in Binh Thanh and District 7 in the west of the city were successfully detected. On the other hand, in the case of using HFMD infection rates, a total of three high-high clusters, one low-low cluster, one negative and one other positive clusters were successfully detected, in which, the three high-high clusters were found in the districts of Binh Tan (289 cases/100,000 inhabitants), Binh Chanh (283 cases/100,000 inhabitants) and Tan Phu (281 cases/100,000 inhabitants) in the east of the city. Conclusions: findings in this study confirm the usefulness of local Geary’s C statistic in the identification of spatial clusters of HFMD.

Whole-genome sequencing and phylogenetic analysis of coxsackievirus-A16 strains causing hand, foot and mouth disease (HFMD) in 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. The illness is self-limiting, but it can also have serious complications. Since 1997, HFMD infections have become endemic and have increased to epidemic proportions across the Asia Pacific region, including India. Coxsackievirus-A16 (CV-A16) outbreaks occurred in India from 2005 onwards, although the clinical symptoms were noticeably different during this period. Understanding the population dynamics of enteroviruses that cause HFMD is crucial in the post-polio era because one of the circulating strain may replace another as the dominant strain. The aim of this study is to describe the genetic features of the CV-A16 strains isolated from hand, foot and mouth disease (HFMD) patients in India. Reverse transcription PCR (RT-PCR) and cell-culture-based isolation of CV-A16 was done from the 55 clinical samples. The entire genome of the CV-A16 isolate was performed from the seven isolates. After the sequences were analysed, a phylogenetic tree was created using bioinformatics tools. The total genomic length obtained was 7411 base pairs (bp). Nucleotide similarity across various regions, including 5'UTR, P1, P2 and 3'UTR, ranged from 87.0-97.9 %, 77.0-95.4 %, 80.3-96.9 %, and 77.9-96.2 %, respectively. Correspondingly, similarities in the VP1 region's nucleotide and amino acid sequences were 91.4-96.4 % and 99.3-99.7 %, respectively. Phylogenetic analysis highlighted that CV-A16 strains identified in Pune, Maharashtra, were grouped within the same cluster. The analysed CV-A16 isolates in this study aligned with subgenotype B1c. These findings have far-reaching implications for the surveillance, prevention and management of HFMD and CV-A16. Monitoring the dynamics of CV-A16 strains, informed by the genetic characteristics identified here, will significantly impact strategies aimed at tackling HFMD and its associated public health challenges.

Spatial Patterns Of Hand-Foot And Mouth Disease In Ho Chi Minh City, Vietnam

Background: Hand-Foot-and-Mouth Disease (HFMD) is most frequently caused by Enterovirus71 (EV-A71) or Coxsackie virus A16 (CV-A16), infants and young children are at greatest risk. Describing the spatial patterns of HFMD can help develop and better target interventions. The objective of this study is to identify spatial patterns of HFMD in the first 8-months of 2023 in Ho Chi Minh city, Vietnam. Methods: The global Moran’s I statistic, Moran’s I scatterplot and local Moran’s I statistic and Boxplot will be applied to study spatial patterns of HFMD. Spatial patterns including spatial clusters (high-high and low-low) and spatial outliers (low-high and high-low) will be identified for HFMD cases and HFMD infection rates. Results: three high-high spatial clusters were mainly distributed in districts in the western region of the city such as Binh Tan, Binh Chanh, and Tan Phu. These high-high spatial clusters belonged to districts having the highest rates of HFMD infections in the city with their corresponding rates of 289, 283 and 281 cases/100,000 inhabitants, respectively. On the other hand, two low-low spatial clusters were detected in Districts 1 and 5 in the city center with their HFMD infection rates of 190 and 209 cases/100,000 inhabitants, respectively. Conclusions : findings in this study support the usefulness of boxplots, local and global Moran’s I statistics, and Moran’s I scatterplots in the identification of spatial clusters and spatial outliers of HFMD.

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.

Parameter estimation of HFMD infection in Malaysia with SIR model

Hand, foot and mouth disease (HFMD) is a mildly infectious disease that happens to children due to low body immunity against viruses. In this paper, a simple SIR model is employed to represent the dynamics of HFMD in Malaysia. A weekly reported data of HFMD infection from week-1 of 2017 to week-36 of 2018 is used in the mathematical analysis. The procedure of parameter estimation is implemented in order to identify the parameter of the SIR model that fits the model with the reported data. The fminsearchbnd routine is used to minimize the objective function, which is the sum of absolute error minimization. By the Chi-squared test, the estimated parameters are reasonable. Based on the average value of the basic reproduction number R0, HFMD infection will remain to exist in the population under the current condition. Overall, this finding may be useful for public health personnel to reduce disease infection risk by planning more effective prevention strategies.

Peripheral Blood Brain Microvascular Endothelial Cells As a Novel Marker in the Detection of Blood-Brain Barrier Injury in EV71 Severe Encephalopathy

Enterovirus 71 (EV71), the main causative agent of hand, foot, and mouth disease (HFMD), is also considered a neuroinvasive virus. EV71 causes sporadic epidemics and outbreaks with more than 13 million people worldwide, predominantly occurring in the Asia-Pacific, and elicited more than 3000 deaths, including 2457 deaths in China from 2008 to 2014. However, there are no available noninvasive biomarkers in peripheral blood for neuro-EV71 infection and optimizing therapeutic options. Brain microvascular endothelial cells (BMECs) are a special type of cells that constitute the blood-brain barrier (BBB), which dynamically shed associated with BBB injury. A mouse model of BBB injury induced by microbial and non-microbial agents was performed, using magnetic bead extraction (MBE) to identify circulating endothelial cells (CECs,CD146+/DAPI+), circulating BMECs (cBMECs, CD146+/S100B+/DAPI+) and endothelial progenitor cells (EPCs, CD146+/CD133+/DAPI+), which are identified based on their S100B (brain marker)+/ CD146 (EC marker) +/CD133+ (PC marker) /DAPI (nuclei)+phenotype with significantly higher levels in the experimental group than in the control group. These results indicate that it is feasible to evaluate BBB injury by quantifying BMECs and EPCs with MBE. The whole cell proteins were prepared by us from EV71 infected BMECs, and among the samples infected with EV71, MALDI TOF / TOF mass spectrometry successfully identified 28 proteins, 4 proteins including vimentin (VIM) were significantly up-regulated, 6 proteins were down regulated, and the other 18 proteins were expressed to various degrees at different incubation times. Furthermore, we performed a glioblastoma model with low vimentin expression and found that EV71 may activate the NLRP3 inflammasome via the VIM-ERK-NFκB pathway during EV71 CNS infection, which promotes caspase-1 activation and the inflammatory factor IL-1β release, causing an inflammatory response that ultimately leads to BBB/CNS disorders and neuronal death. The same results for those experiments with neonatal mice of EV71 infection were also observed. The results showed that cBMECs may be used as potential cell-based biomarkers for indexing of BBB injury. Then peripheral blood samples were obtained from the children with severe HFMD infection from a medical center for women and children, and examination showed that the counts of cBMECs were significantly higher in severe HFMD children than in the control children, indicating that the detection of cBMECs may be used for the early diagnosis of severe HFMD. In addition, Mfsd2 antibody specifically on BMECs were attached to magnetic beads and used directly to isolate BMECs from blood, followed by immunofluorescence staining with CD146 antibody, and the two corresponding fluorophores, CD146 and DPAI, appeared microscopically to preliminarily determine BMECs. The use of mfsd2 antibody to isolate BMECs both simplifies experimental procedures and improves detection precision and efficiency. In conclusion, in this study, cBMECs are demonstrated to serve as cellular biomarkers for BBB injury caused by microbial and non-microbial factors. Proteomics combined with mechanistic studies indicate that cBMECs are important indicators of BBB/CNS disorders in severe HFMD. Ultimately, this study successfully established a method to detect EV71 severe encephalopathy in human peripheral blood, which is safer and noninvasive than conventional cerebrospinal fluid puncture and pathological collection methods, causes minimal physical trauma to patients, and is more intuitive and accurate than conventional imaging examination. Therefore, this assay has good clinical application and may provide a new means for noninvasive and visual detection of EV71 severe encephalopathy. However, further cases were also collected to verify the accuracy of peripheral blood BMEC count for diagnosing severe HFMD, while establishing suitable cut-off values for application in early diagnosis. (Acknowledgements: Corresponding author: Hong Cao, gzhcao@smu.edu.cn; The Basic Research Project of Key Laboratory of Guangzhou, China (No.202102100001) and Grant from School of Public Health of Southern Medical University, China, No.GW202222 to H.C.)

Explanation of hand, foot, and mouth disease cases in Japan using Google Trends before and during the COVID-19: infodemiology study

BackgroundCoronavirus Disease 2019 (COVID-19) pandemic affects common diseases, but its impact on hand, foot, and mouth disease (HFMD) is unclear. Google Trends data is beneficial for approximate real-time statistics and because of ease in access, is expected to be used for infection explanation from an information-seeking behavior perspective. We aimed to explain HFMD cases before and during COVID-19 using Google Trends.MethodsHFMD cases were obtained from the National Institute of Infectious Diseases, and Google search data from 2009 to 2021 in Japan were downloaded from Google Trends. Pearson correlation coefficients were calculated between HFMD cases and the search topic “HFMD” from 2009 to 2021. Japanese tweets containing “HFMD” were retrieved to select search terms for further analysis. Search terms with counts larger than 1000 and belonging to ranges of infection sources, susceptible sites, susceptible populations, symptoms, treatment, preventive measures, and identified diseases were retained. Cross-correlation analyses were conducted to detect lag changes between HFMD cases and search terms before and during the COVID-19 pandemic. Multiple linear regressions with backward elimination processing were used to identify the most significant terms for HFMD explanation.ResultsHFMD cases and Google search volume peaked around July in most years, excluding 2020 and 2021. The search topic “HFMD” presented strong correlations with HFMD cases, except in 2020 when the COVID-19 outbreak occurred. In addition, the differences in lags for 73 (72.3%) search terms were negative, which might indicate increasing public awareness of HFMD infections during the COVID-19 pandemic. The results of multiple linear regression demonstrated that significant search terms contained the same meanings but expanded informative search content during the COVID-19 pandemic.ConclusionsThe significant terms for the explanation of HFMD cases before and during COVID-19 were different. Awareness of HFMD infections in Japan may have improved during the COVID-19 pandemic. Continuous monitoring is important to promote public health and prevent resurgence. The public interest reflected in information-seeking behavior can be helpful for public health surveillance.

Disease burden in patients with severe hand, foot, and mouth disease in Jiangsu Province: a cross-sectional study

ABSTRACT This study aimed to estimate the disease burden and health-related quality of life (HRQOL) among patients with severe hand, foot, and mouth disease (HFMD) in Jiangsu Province, China. We analyzed the surveillance data of HFMD cases in Jiangsu Province from 2009 to 2020. Moreover, a cross-sectional study was conducted in Nanjing and Suzhou, China, between January 2017 and May 2018. Patients with severe HFMD and their parents were recruited from selected hospitals. Questionnaires and hospital management systems were used to collect data on direct economic burden. The HRQOL of children was assessed using the TNO-AZL Preschool Quality of Life (TAPQOL) scale. A total of 1,348,737 confirmed cases of HFMD were reported to the NNDRS in Jiangsu province during 2009–2020. Of these, 9,622 were severe cases, with 62 (.64%) of these being fatal. From January 2017 to May 2018, data was collected from 362 severe HFMD cases using a structured questionnaire. The median per capita direct economic burden was RMB 16142.88, and was associated with the region and length of hospital stay (P < .05). The direct economic burden for all cases of severe HFMD in Jiangsu province between 2017 and 2018 was approximately RMB 16.64 million. Finally, the median (IQR) of the TAPQOL scale for children with severe HFMD was 69.23 (56.20, 82.27). Severe HFMD infection is a relatively large burden for individuals, and the burden of EV-A71 infection was seen to be even greater for the population. Prevention of severe HFMD should strengthen hygiene habits and targeted measures for EV-A71 vaccination.

Association between Meteorological Parameters and Hand, Foot and Mouth Disease in Mainland China: A Systematic Review and Meta-Analysis.

Background:This study reports a systematic review of association between meteorological parameters and hand, foot and mouth disease (HFMD) in mainland China.Methods:Using predefined study eligibility criteria, three electronic databases (PubMed, Web of Science, and Embase) were searched for relevant articles. Using a combination of search terms, including “Hand foot and mouth disease,” “HFMD,” “Meteorological,” “Climate,” and “China,” After removal of duplicates, our initial search generated 2435 studies published from 1990 to December 31, 2019. From this cohort 51 full-text articles were reviewed for eligibility assessment. The meta-analysis was devised in accordance with the published guidelines of the Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Effect sizes, heterogeneity estimates and publication bias were computed using R software and Review Manager Software.Results:The meta-analysis of 18 eligible studies showed that the meteorological parameters played an important role in the prevalence of HFMD. Lower air pressure may be the main risk factor for the incidence of HFMD in Chinese mainland, and three meteorological parameters (mean temperature, rainfall and relative humidity) have a significant association with the incidence of HFMD in subtropical regions.Conclusion:Lower air pressure might be the main risk factor for the incidence of HFMD in Chinese mainland. The influence of meteorological parameters on the prevalence of HFMD is mainly through changing virus viability in aerosols, which may be different in different climate regions. In an environment with low air pressure, wearing a mask that filters the aerosol outdoors may help prevent HFMD infection.

Neonatal Murine Model of Coxsackievirus A2 Infection for the Evaluation of Antiviral Therapeutics and Vaccination.

Coxsackievirus (CV) A2 has emerged as an important etiological agent in the pathogen spectrum of hand, foot, and mouth disease (HFMD). The symptoms of CVA2 infections are generally mild, but worsen rapidly in some people, posing a serious threat to children’s health. However, compared with enterovirus 71 detected frequently in fatal cases, limited attention has been paid to CVA2 infections because of its benign clinical course. In the present study, we identified three CVA2 strains from HFMD infections and used the cell-adapted CVA2 strain HN202009 to inoculate 5-day-old BALB/c mice intramuscularly. These mice developed remarkably neurological symptoms such as ataxia, hind-limb paralysis, and death. Histopathological determination showed neuronophagia, pulmonary hemorrhage, myofiberlysis and viral myocarditis. Viral replication was detected in multiple organs and tissues, and CVA2 exhibited strong tropism to muscle tissue. The severity of illness was associated with abnormally high levels of inflammatory cytokines, including interleukin (IL)-6, IL-10, tumor necrosis factor α, and monocyte chemotactic protein 1, although the blockade of these proinflammatory cytokines had no obvious protection. We also tested whether an experimental formaldehyde-inactivated CVA2 vaccine could induce protective immune response in adult mice. The CVA2 antisera from the vaccinated mice were effective against CVA2 infection. Moreover, the inactivated CVA2 vaccine could successfully generate immune protection in neonatal mice. Our results indicated that the neonatal mouse model could be a useful tool to study CVA2 infection and to develop CVA2 vaccines.

Molecular Epidemiological Study of Hand, Foot, and Mouth Disease in a Kindergarten-Based Setting in Bangkok, Thailand.

Hand, foot, and mouth disease (HFMD) is a contagious childhood illness and annually affects millions of children aged less than 5 years across the Asia–Pacific region. HFMD transmission mainly occurs through direct contact (person-to-person) and indirect contact with contaminated surfaces and objects. Therefore, public health measures to reduce the spread of HFMD in kindergartens and daycare centers are essential. Based on the guidelines by the Department of Disease Control, a school closure policy for HFMD outbreaks wherein every school in Thailand must close when several HFMD classrooms (more than two cases in each classroom) are encountered within a week, was implemented, although without strong supporting evidence. We therefore conducted a prospective cohort study of children attending five kindergartens during 2019 and 2020. We used molecular genetic techniques to investigate the characteristics of the spreading patterns of HFMD in a school-based setting in Bangkok, Thailand. These analyses identified 22 index cases of HFMD (symptomatic infections) and 25 cases of enterovirus-positive asymptomatic contacts (24 students and one teacher). Enterovirus (EV) A71 was the most common enterovirus detected, and most of the infected persons (8/12) developed symptoms. Other enteroviruses included coxsackieviruses (CVs) A4, CV-A6, CV-A9, and CV-A10 as well as echovirus. The pattern of the spread of HFMD showed that 45% of the subsequent enteroviruses detected in each outbreak possessed the same serotype as the first index case. Moreover, we found a phylogenetic relationship among enteroviruses detected among contact and index cases in the same kindergarten. These findings confirm the benefit of molecular genetic assays to acquire accurate data to support school closure policies designed to control HFMD infections.

Characterization of oral virome and microbiome revealed distinctive microbiome disruptions in paediatric patients with hand, foot and mouth disease

While the underlying determinants are unclear, hand, foot and mouth disease (HFMD) presents a wide spectrum of clinical manifestations with varying severity in different individuals. Recently, many studies identified the human microbiome as a critical factor in the pathogenesis of various diseases. Therefore, we here investigated the ecological dynamics of the oral microbiome changes during the HFMD infection. After targeted enrichment of all known vertebrate viruses, the virome profiles of symptomatic and asymptomatic HFMD patients were examined and revealed to be significantly altered from those of healthy individuals, with nine discriminative viruses detected. Further characterization of the prokaryotic microbiome revealed an elevated level of Streptococcus sp. as the most important signature of the symptomatic HFMD cohort, positively correlating to the level of enterovirus A RNA. In addition, we found that while coxsackievirus A5 is detected in saliva RNA of all asymptomatic cases, coxsackievirus A6 dominates the majority of the symptomatic cohort.

Identifying pre-outbreak signals of hand, foot and mouth disease based on landscape dynamic network marker

BackgroundThe high incidence, seasonal pattern and frequent outbreaks of hand, foot and mouth disease (HFMD) represent a threat for billions of children around the world. Detecting pre-outbreak signals of HFMD facilitates the timely implementation of appropriate control measures. However, real-time prediction of HFMD outbreaks is usually challenging because of its complexity intertwining both biological systems and social systems.ResultsBy mining the dynamical information from city networks and horizontal high-dimensional data, we developed the landscape dynamic network marker (L-DNM) method to detect pre-outbreak signals prior to the catastrophic transition into HFMD outbreaks. In addition, we set up multi-level early warnings to achieve the purpose of distinguishing the outbreak scale. Specifically, we collected the historical information of clinic visits caused by HFMD infection between years 2009 and 2018 respectively from public records of Tokyo, Hokkaido, and Osaka, Japan. When applied to the city networks we modelled, our method successfully identified pre-outbreak signals in an average 5 weeks ahead of the HFMD outbreak. Moreover, from the performance comparisons with other methods, it is seen that the L-DNM based system performs better when given only the records of clinic visits.ConclusionsThe study on the dynamical changes of clinic visits in local district networks reveals the dynamic or landscapes of HFMD spread at the network level. Moreover, the results of this study can be used as quantitative references for disease control during the HFMD outbreak seasons.

The burden of childhood hand-foot-mouth disease morbidity attributable to relative humidity: a multicity study in the Sichuan Basin, China

Hand, foot and mouth disease (HFMD) is a growing threat to children's health, causing a serious public health burden in China. The relationships between associated meteorological factors and HFMD have been widely studied. However, the HFMD burden due to relative humidity from the perspective of attributable risk has been neglected. This study investigated the humidity-HFMD relationship in three comprehensive perspectives, humidity-HFMD relationship curves, effect modification and attributable risks in the Sichuan Basin between 2011 and 2017. We used multistage analyses composed of distributed lag nonlinear models (DLNMs), a multivariate meta-regression model and the calculations of attributable risk to quantify the humidity-HFMD association. We observed a J-shaped pattern for the pooled cumulative humidity-HFMD relationship, which presented significant heterogeneity relating to the geographical region and number of primary school students. Overall, 27.77% (95% CI 25.24–30.02%) of HFMD infections were attributed to humidity. High relative humidity resulted in the greatest burden of HFMD infections. The proportion of high humidity-related HFMD in the southern basin was higher than that in the northern basin. The findings provide evidence from multiple perspectives for public health policy formulation and health resource allocation to develop priorities and targeted policies to ease the HFMD burden associated with humidity.

Isolation and molecular characterization of coxsackievirus A6 and coxsackievirus A16 from a case of recurrent Hand, Foot and Mouth Disease in Mumbai,Maharashtra, India, 2018.

Hand, Foot and Mouth Disease (HFMD) is caused by multiple Enterovirus (EV) serotypes mainly coxsackievirus A6 (CV-A6), coxsackievirus A16 (CV-A16) and Enterovirus 71 (EV-A71). Recurrent HFMD infections are rarely reported. An unusual rise in HFMD cases was reported in Mumbai during May-June 2018. Stool and throat swab specimens were referred from seven children from two hospitals for laboratory diagnosis. The age group of cases ranged from 9months to 5years with median age 13months. Out of seven cases, three were males and four females. One 13-month-old female case was reported twice within 21days. Stool, throat swab specimens were tested by pan enterovirus RT-PCR and also by virus isolation using human rhabdomyosarcoma cell line for detection of Enteroviruses. Out of seven HFMD cases, CV-A6 and CV-A16 viruses were isolated from five and two cases respectively. The phylogenetic analysis of CV-A6 viruses showed their similarity with CV-A6 viruses from Finland and China, whereas the two CV-A16 isolates showed similarity with those from Japan, France, China, Sarawak and Thailand. For the recurrent HFMD case, CV-A6 and CV-A16 were isolated from the stool specimens collected during the first and second episodes, respectively. There are no reports of isolation and molecular characterization of CV-A6 and CV-A16 viruses from recurrent HFMD cases. The present study reports molecular characterization of two Enterovirus serotypes CV-A6 and CV-A16 from a recurrent HFMD case, highlighting need of virological and molecular surveillance of HFMD.

Enterovirus-Associated Hand-Foot and Mouth Disease and Neurological Complications in Japan and the Rest of the World.

Enteroviruses (EVs) are responsible for extremely large-scale, periodic epidemics in pediatric cohorts, particularly in East and Southeast Asia. Clinical presentation includes a diverse disease spectrum, including hand-foot and mouth disease (HFMD), aseptic meningitis, encephalitis, acute flaccid paralysis, and acute flaccid myelitis. HFMD is predominantly attributable to EV-A types, including the major pathogen EV-A71, and coxsackieviruses, particularly CV-A6, CV-A16, and CV-A10. There have been multiple EV-A71 outbreaks associated with a profound burden of neurological disease and fatal outcomes in Asia since the early 1980s. Efficacious vaccines against EV-A71 have been developed in China but widespread pediatric vaccination programs have not been introduced in other countries. Encephalitis, as a consequence of complications arising from HFMD infection, leads to damage to the thalamus and medulla oblongata. Studies in Vietnam suggest that myoclonus is a significant indicator of central nervous system (CNS) complications in EV-A71-associated HFMD cases. Rapid response in HFMD cases in children is imperative to prevent the progression to a CNS infection; however, prophylactic and therapeutic agents have not been well established internationally, therefore surveillance and functional studies including development of antivirals and multivalent vaccines is critically important to reduce disease burden in pediatric populations.

Estimation of the reproduction number and identification of periodicity for HFMD infections in northwest China

Repeated outbreaks of Hand, foot and mouth disease (HFMD) infections have been observed in recent decades and dominated by various enteroviral serotypes. In particular, enterovirus 71 (EV-A71), coxsackievirus A16 (CV-A16) and coxsackievirus A6 (CV-A6) dominated the prevalence of HFMD infections alternatively in recent years with various outbreak sizes in Baoji, a city of Shaanxi Province in Northwest China. Estimating the reproduction number for various enteroviruses serotypes in northwest China (north temperate zone) and identification of cyclicity of HFMD infections are therefore an issue of great importance for future epidemics prediction and control. The basic/effective reproduction numbers for EV-A71, CV-A16 and CV-A6 were estimated based on daily new cases in 2010, 2011 and 2018, respectively, in which the corresponding pathogen dominated the epidemic. Two different methods based on serial interval were adopted and the basic reproduction number were estimated to be in the range of (1.33, 1.46) for CV-A16, (1.20, 1.29) for EV-A71, and (1.38, 1.59) for CV-A6, respectively. The estimated daily effective reproduction numbers significantly fluctuated before June or after July but varied mildly in (0.5,2) in around June to July for three serotypes. The weekly effective reproduction number for HFMD was estimated based on weekly new cases from year 2010 to 2018, and in most years it peaked in the range of (1.6,2.0) in February to March as well as in the range of (1.0,1.2) in September to October. The wavelet analysis based on the time series of HFMD cases from 2008 to 2018 showed obvious annual and semi-annual cyclicity, while the inter-annual cycles are infeasible. In this study we found that CV-A6 shows the greatest transmission ability among these three pathogens while EV-A71 exhibits the weakest ability of transmission, and moreover, the estimated values of basic reproduction number in northwest China are lower than those in Singapore, Hongkong and Guangdong, which may be due to different climatic circumstances.

Epidemiological study on hand, foot and mouth disease in Tongzhou District, Beijing, 2013-2017.

ObjectiveTo study the epidemiological characteristics of hand, foot and mouth disease (HFMD) in Tongzhou District, Beijing between 2013 and 2017.MethodsData on HFMD infections from 1 January 2013 to 31 December 2017 were collected from the Notifiable Infectious Diseases Reporting Information System and analysed. Serotyping of enteroviruses from samples from patients with HFMD was undertaken using reverse transcription–polymerase chain reaction.ResultsA total of 15 341 patients with HFMD were reported and 32 patients (0.2%) were classified as having severe HFMD. The annual mean incidence rate of HFMD was 219.3/100 000 of the general population. The incidence and case-severity rates of HFMD generally decreased between 2013 and 2017. In the floating migrant population, the incidence and cases-severity rates of HFMD were significantly higher than in the local population. The peak incidence and severity-case rates were at 2 years of age and > 90% of patients were ≤5 years. Enterovirus A71 and Coxsackievirus A16 were the predominant pathogens in 2013–2017.ConclusionsDuring the 5-year period 2013–2017, the incidence rate and case-severity rate of HFMD generally decreased in Tongzhou District, Beijing. The floating migrant population and children ≤5 years of age were at the highest risk of HFMD.