Hand, Foot And Mouth Disease Transmission Research Articles

Antiviral activity of povidone-iodine gargle and mouthwash solution against Enterovirus A71, Coxsackieviruses A16, A10 and A6.

Hand, Foot and Mouth Disease (HFMD), a highly contagious viral disease common among infants and young children, is primarily caused by Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CVA16). Nonetheless, emerging enteroviruses, such as CV-A10 and CV-A6, have also caused widespread outbreaks globally, in part due to the absence of effective antiviral therapies, and the high personto-person transmission rate. Person-to-person transmission is usually through fecal-oral or oral-oral routes, and sometimes via droplets. As the oral cavity is a primary site for early virus infection and replication, controlling oral viral shedding can mitigate the risk of transmission through this route. Povidone-iodine (PVP-I), a widely used antiseptic, has shown broad-spectrum antimicrobial properties but antiviral studies against HFMD-causing enteroviruses are limited, especially for CV-A10 and CVA6. Our study demonstrated that a 1% PVP-I solution (final concentration of 0.5%) exhibited virucidal activity against EV-A71, CV-A16, CV-A10, and CV-A6. All seven EV-A71 isolates and five CV-A16 isolates showed a significant virus titer reduction after a 1-minute incubation, while five CV-A10 isolates and two CV-A6 isolates required a 5-minute incubation to achieve this. The virucidal activity was confirmed through the EN14476:2013+A2:2019 virucidal quantitative suspension test, wherein all four viruses were completely inactivated after a 30-minute incubation with PVP-I at 37°C under both clean and dirty conditions. Western blot analysis suggested that PVP-I could affect the VP1 structural proteins of EV-A71. Our results suggest that PVP-I could serve as a potential virucidal agent to reduce the risk of person-to-person transmission 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.

Fractional Order Mathematical Modelling of HFMD Transmission via Caputo Derivative

This paper studies a nonlinear fractional mathematical model for hand, foot, and mouth Disease (HFMD), incorporating a vaccinated compartment. Our initial focus involves establishing the non-negativity and boundedness of the fractional order dynamical model. The existence and uniqueness of the system are discussed using the Caputo derivative operator formulation. Applying a fixed-point approach, we obtain results that confirm the presence of at least one solution. We analyze the stability behavior at the two equilibrium points (disease-free and endemic states) of the model and derive the basic reproduction number. Numerical simulations are conducted using the fractional Euler approach, and the simulation results confirm our analytical conclusions. This comprehensive approach enhances the understanding of HFMD dynamics and facilitates the policy making of health care centers to control the further spread of this disease.

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.

Dynamics of hand, foot and mouth disease in children under 15 years old: A case study of Malaysia using age-structured modelling approach

Hand, foot, and mouth disease (HFMD) is a viral infection that primarily affects children. The disease is characterized by fever, sores in the mouth, and a rash on the hands, feet, and buttocks. In this case study, we analyze the dynamics of HFMD in children under 15 years old in Malaysia using an age-structured modeling approach. First we prove backward bifurcation for a baseline model which is then extended to an age-structured model. We used data on the incidence of HFMD in Malaysia from 2021 to 2022 to calibrate the model parameters and simulate the disease dynamics. Sensitivity analysis is done by Latin hypercube sampling - partial rank correlation coefficient (LHS/PRCC) method. Simulation is done and the impact of imperfect vaccine and quarantine is explored. Our results show that the dynamics of the disease is mostly driven by children under 5 years old. The model also predicts that vaccination could significantly reduce the incidence of HFMD in Malaysia. Vaccination is most effective when targeted at young children, who are at the highest risk of disease as this will lead to drastic decrease in the incidence of HFMD in all age groups. Our simulations show that quarantining of infected children until they fully recover will reduce the transmission of HFMD, but this strategy needs to be sustained for a sufficient duration to have a significant impact. The result of this paper can inform the development of policies for controlling the spread of HFMD and other infectious diseases in Malaysia and other similar settings.

Effects of behaviour change on HFMD transmission

ABSTRACT We propose a hand, foot and mouth disease (HFMD) transmission model for children with behaviour change and imperfect quarantine. The symptomatic and quarantined states obey constant behaviour change while others follow variable behaviour change depending on the numbers of new and recent infections. The basic reproduction number R 0 of the model is defined and shown to be a threshold for disease persistence and eradication. Namely, the disease-free equilibrium is globally asymptotically stable if R 0 ≤ 1 whereas the disease persists and there is a unique endemic equilibrium otherwise. By fitting the model to weekly HFMD data of Shanghai in 2019, the reproduction number is estimated at 2.41. Sensitivity analysis for R 0 shows that avoiding contagious contacts and implementing strict quarantine are essential to lower HFMD persistence. Numerical simulations suggest that strong behaviour change not only reduces the peak size and endemic level dramatically but also impairs the role of asymptomatic transmission.

The Effect of COVID-19 on Infectious Disease to Outpatient of Children: A Machine Learning Study

The outbreak of coronavirus disease 2019 (COVID-19) has had a significant impact worldwide. However, the effects of COVID-19 on human enteroviruses such as Herpangina and Hand, Foot, and Mouth Disease (HFMD) in children are still not fully understood. This study aimed to analyze the reported cases of Herpangina and HFMD among child outpatients in Hangzhou, China, from January 2018 to June 2021, before, during, and after the COVID-19 outbreak. Machine learning approaches were employed to analyze the time series data of Herpangina and HFMD from 2018 to 2019 and predict the trends and seasonal patterns from 2020 to 2021. The seasonal patterns at weekly and monthly levels were compared across the three stages of the COVID-19 outbreak. Prior to 2020, the reported incidence of Herpangina and HFMD exhibited a certain degree of seasonal periodicity. However, following the COVID-19 outbreak in 2020, there was a sharp decrease in the cases of Herpangina and HFMD, followed by a rebound in the first half of 2021. The observed cases reached their highest peak in July 2020, showing a decrease of 93.6% for Herpangina and 96.5% for HFMD compared to the predicted values. These findings indicate that the COVID-19 outbreak had a significant impact on the transmission of Herpangina and HFMD. Therefore, integrated strategies should be implemented to control and prevent the resurgence of Herpangina and HFMD, alongside the effective management of COVID-19.

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.

Stability and infectivity of enteroviruses on dry surfaces: Potential for indirect transmission control

Hand, foot, and mouth disease (HFMD) is a contagious disease mainly occurring in young children, and outbreaks commonly occur among young children in the Asia–Pacific region including Thailand. Moreover, the World Health Organization (WHO) monitors HFMD in the Western Pacific region to detect outbreaks and other significant events by the Regional Event Based Surveillance System. HFMD is mainly caused by a group of enteroviruses (EVs) transmitted through direct contact (person to person) and indirect contact with contaminated objects (surface-to-hand). However, few studies have examined the surface stability of EVs. In this study, we investigated the stability of enterovirus A71 (EV-A71) and coxsackievirus A16 (CVA16) on three different dry surfaces (wood, plastic, and stainless steel) using the endpoint titration using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) staining of viable cells and real-time polymerase chain reaction (viral genome detection). The results revealed that virus infectivity dramatically decreased within a few hours on dry surfaces. However, viral RNA could be detected on dry surfaces for up to 28 days. Concerning heat inactivation, both EV-A71 and CVA16 were inactivated after exposure to 60°C for 15 min. Information on virus stability on different dry surfaces will provide useful information for HFMD transmission control.

Epidemiological characteristics and spatiotemporal patterns of hand, foot, and mouth disease in Hubei, China from 2009 to 2019.

Hand, foot, and mouth disease (HFMD) is a public health issue in Hubei and studies of- spatiotemporal clustering at a fine scale are limited. The purpose of this research was to analyze the epidemiological characteristics, temporal variation characteristics, and spatiotemporal clustering of HFMD cases at the town level from 2009 to 2019 to improve public health outcomes. Mathematical statistics, a seasonal index, wavelet analysis, and spatiotemporal scans were used to analyze epidemiological characteristics, time series trends, and spatiotemporal clusters of HFMD in Hubei. EV-A71 (Enterovirus A71) and CVA16 (Coxsackievirus A16) constitute the two primary pathogens of the HFMD epidemic in Hubei, among which EV-A71 is the dominant pathogen, especially in 2016. In terms of age distribution, a major peak occurred at 0-5 years and a very small increase appeared at 25-35 years, with the former having a higher incidence among males than females and the latter having the opposite difference between males and females. The number/rate of HFMD cases exhibited a considerable increase followed by a moderate decline from 2009 to 2019, with the first large peak in April-July and a smaller peak in November-December. HFMD in Hubei exhibited the characteristics of a 270-day cycle with multiscale nesting, which was similar to the periodicity of HFMD cases caused by EV-A71 (9 months). Cities with a higher incidence of HFMD formed a part of an "A-shaped urban skeleton". Subdistricts had the highest incidence of HFMD, followed by towns and villages. The spatiotemporal scan results showed one most likely cluster and 22 secondary clusters, which was consistent with the geographic location of railways and rivers in Hubei. These findings may be helpful in the prevention and control of HFMD transmission and in implementing effective measures in Hubei Province.

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.

Exploring Bipartite Network Approach in Hand, Foot and Mouth Disease Hotspot Identification

Mathematical modeling of hand, foot, and mouth disease (HFMD) mainly focuses on compartmental modeling approaches. It classifies human population into compartments and assumes homogeneity that regards every human has equal chance of contacting other individuals in the population. However, the transmission of HFMD is complicated and dynamic with the interactions of the intertwined biomedical and social factors. Describing the disease transmission dynamic that involves high-dimensional space is mathematically challenging. The graph theoretic bipartite network modeling (BNM) approach has the potential to handle this challenge by abstracting the real-world disease transmission system and incorporating the individual features of the bipartite nodes. This study aims to seize the advantages portrayed by the BNM approach in capturing the heterogeneous features of the entities within a disease transmission system. It intends to explore adopting the BNM approach in modeling the transmission of HFMD at Kuching, Malaysia and identify the hotspot by employing the BNM approach comprising a four-stage methodology adapted from the BNM methodology framework. The bipartite HFMD contact (BHC) network is formulated with the basic building block consisting of the location and human nodes. The individual parameters of the location and human node are incorporated. The resulting BHC network formulated comprises 10 human nodes, 20 location nodes, and 23 edges. Then, six top-ranked location nodes were identified and agreed with the chosen benchmark system. The potential HFMD hotspots are thus identified by determining the location nodes ranking. The result from this study has enabled timely and effective measures and policies to be customized accordingly by the public health authorities and related policymakers.

Global dynamics of a fractional-order HFMD model incorporating optimal treatment and stochastic stability

Hand, foot and mouth disease (HFMD) is highly contagious and occurs primarily among children under the age of five. Analysis of transmission dynamics of infectious diseases is essential to prevent the adverse effects caused by the diseases. The current study presents a fractional-order SEIR-type epidemic model to investigate the dynamics of HFMD transmission. The biological feasibility of the proposed model system is demonstrated from an epidemiological perspective. The basic reproduction number, R0, is obtained through the next-generation matrix approach. Around the feasible equilibrium points, the asymptotic dynamics of the proposed model system are examined, both at local and global levels. It is found that, the model undergoes transcritical bifurcation at R0 = 1. As a result, R0 plays the role of threshold in determining the future course of the disease. The optimal treatment control of fractional epidemic models are less explored. Here, an optimal control problem is formulated considering a time-dependent treatment measure u(t) both in exposed and infected classes. The findings are also visualized and verified by simulating the model using some feasible parameter values, from which it can be concluded that fractional-order gives better results. A gradual decrease in the total cases as well as in the peak is observed in the presence of treatment control. Further, we extend the study in a stochastic environment with the help of white noise and investigate the stochastic stability of the endemic equilibrium point. Finally, parameters defining the threshold quantity R0 are scaled with the normalized forward sensitivity index.

In vitro antiviral activity of medicinal mushroom Ganoderma neo-japonicum Imazeki against enteroviruses that caused hand, foot and mouth disease

Hand, foot and mouth disease (HFMD) is a highly contagious viral disease that predominantly affects children younger than 5 years old. HFMD is primarily caused by enterovirus A71 (EVA71) and coxsackievirus A16 (CV-A16). However, coxsackievirus A10 (CV-A10) and coxsackievirus A6 (CV-A6) are being increasingly reported as the predominant causative of HFMD outbreaks worldwide since the past decade. To date, there are still no licensed multivalent vaccines or antiviral drugs targeting enteroviruses that cause HFMD, despite HFMD outbreaks are still being frequently reported, especially in Asia-Pacific countries. The high rate of transmission, morbidity and potential neurological complications of HFMD is indeed making the development of broad-spectrum antiviral drugs/agents against these enteroviruses a compelling need. In this study, we have investigated the in vitro antiviral effect of 4 Ganoderma neo-japonicum Imazeki (GNJI) crude extracts (S1-S4) against EV-A71, CV-A16, CV-A10 and CV-A6. GNJI is a medicinal mushroom that can be found growing saprophytically on decaying bamboo clumps in Malaysian forests. The antiviral effects of this medicinal mushroom were determined using cytopathic inhibition and virus titration assays. The S2 (1.25 mg/ml) hot aqueous extract demonstrated the highest broad-spectrum antiviral activity against all tested enteroviruses in human primary oral fibroblast cells. Replication of EV-A71, CV-A16 and CVA10 were effectively inhibited at 2 hours post-infection (hpi) to 72 hpi, except for CV-A6 which was only at 2 hpi. S2 also has virucidal activity against EV-A71. Polysaccharides isolated and purified from crude hot aqueous extract demonstrated similar antiviral activity as S2, suggesting that polysaccharides could be one of the active compounds responsible for the antiviral activity shown by S2. To our knowledge, this study demonstrates for the first time the ability of GNJI to inhibit enterovirus infection and replication. Thus, GNJI is potential to be further developed as an antiviral agent against enteroviruses that caused HFMD.

Control measures during the COVID-19 outbreak reduced the transmission of hand, foot, and mouth disease

Control measures during the coronavirus disease 2019 (COVID-19) outbreak may have limited the spread of infectious diseases. This study aimed to analyze the impact of COVID-19 on the spread of hand, foot, and mouth disease (HFMD) in China. A mathematical model was established to fit the reported data of HFMD in six selected cities in mainland China from 2015 to 2020. The absolute difference (AD) and relative difference (RD) between the reported incidence in 2020, and simulated maximum, minimum, or median incidence of HFMD in 2015–2019 were calculated. The incidence and Reff of HFMD have decreased in six selected cities since the outbreak of COVID-19, and in the second half of 2020, the incidence and Reff of HFMD have rebounded. The results show that the total attack rate (TAR) in 2020 was lower than the maximum, minimum, and median TAR fitted in previous years in six selected cities (except Changsha City). For the maximum, median, minimum fitted TAR, the range of RD (%) is 42·20–99·20%, 36·35–98·41% 48·35–96·23% (except Changsha City) respectively. The preventive and control measures of COVID-19 have significantly contributed to the containment of HFMD transmission.

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.

Control Measures During the COVID-19 Outbreak Reduced the Transmission of Hand, Foot, and Mouth Disease

Background: Control measures during the coronavirus disease 2019 (COVID-19) outbreak may have limited the spread of infectious diseases. This study aimed to analyse the impact of COVID-19 on the spread of hand, foot, and mouth disease (HFMD) in China. Methods: A mathematical model was established to fit the reported data of HFMD in six selected cities in mainland China from 2015 to 2020. The absolute difference (AD) and relative difference (RD) between the reported incidence in 2020, and simulated maximum, minimum, or median incidence of HFMD in 2015-2019 were calculated. Findings: The incidence and Reff of HFMD have decreased in six selected cities since the outbreak of COVID-19, and in the second half of 2020, the incidence and R eff of HFMD have rebounded. The results show that the total attack rate (TAR) in 2020 was lower than the maximum, minimum, and median TAR fitted in previous years in six selected cities (except Changsha city). For the maximum, median, minimum fitted TAR, the range of RD (%) is 42·20-99·20%, 36·35-98·41% 48·35-96·23% (except Changsha city) respectively. Interpretation: Based on the incidence data of six cities from 2015 to 2019, the SEIAR model demonstrated a significant effect on the incidence of HFMD. During the period of COVID-19, the incidence and R eff of HFMD decreased, the prevention and control measures taken during the period of COVID-19, such as school suspension, home quarantine, closing all kinds of leisure places, wearing masks, advocating frequent hand washing, etc., have not only effectively suppressed the spread of COVID-19 epidemic, but also have significantly contributed to the containment of HFMD transmission.Funding Statement: This study was partly supported by the Bill & Melinda Gates Foundation (INV-005834).Declaration of Interests: The authors declare no conflicts of interests.

Spatiotemporal effects of climate factors on childhood hand, foot, and mouth disease: a case study using mixed geographically and temporally weighted regression models

ABSTRACT Hand, foot, and mouth disease (HFMD) is a global infectious disease severely threatening children’s health. It has been recognized that climate factors play an important role in the transmission of HFMD. In this paper, the bootstrap test in the geographically weighted regression (GWR) literature is extended to geographically and temporally weighted regression (GTWR) models for identifying homogeneous explanatory variables and spatiotemporally heterogeneous ones. The resulting mixed GTWR model is then used to investigate spatiotemporal effect of climate factors on the HFMD incidence in Inner Mongolia, China, a provincial autonomous region with extensive area and different climatic conditions. The results demonstrate that the effect of relative humidity is global over space and time, while that of air temperature, air pressure and wind speed varies spatiotemporally. The extended bootstrap test provides a solid statistical basis for model selection. The findings from the study may provide not only a deep understanding of spatiotemporal variation characteristics of the climatic effect on the HFMD incidence, but also some useful evidences for taking measures of the disease prevention and control at the county level in different seasons.

Intra-area factors dominate the spatio-temporal transmission heterogeneity of hand, foot, and mouth disease in China: A modelling study

Hand, foot, and mouth disease (HFMD) has been a serious threat to children's health in China since 2008, and quantifying the transmission heterogeneity of HFMD is crucial for understanding its spatio-temporal dynamic mechanisms and developing precise disease containment strategies. In this study, surveillance data of HFMD cases for patients 15 years of age or younger in east Mainland China between 2009 and 2015 was retrieved from the national surveillance system, and then an age and gender–stratified spatiotemporal Bayesian hierarchical model was built with three types of transmission hazards (intra-area transmission, inter-area transmission, and environmental risk factors). Spatial and temporal heterogeneities of HFMD transmission were quantified by the contribution of the hazard components over time and regions. In addition, the transmission heterogeneity by age–gender subgroups was determined by the transmission probabilities derived from the transmission rate matrix. We found that the intra-area transmission hazard dominated HFMD transmission (56.4% to 96.3%), followed by environmental risk factors (1.1% to 42.1%), whereas the contribution of the inter-area transmission hazard component was relatively small (1.5% to 3.6%). During school holidays, the contribution of the inter-area transmission component caused an instantaneous increase in the overall transmission hazard. In addition, the cumulative hazard contribution across time varied with the geographic region, and three distinct clusters were identified and related with the size of the local population. Moreover, the transmission probability was the highest among the same age–gender group within the intra-area transmission hazard, whereas inter-area and environmental transmission hazards had stronger effects among older children. HFMD transmission varied significantly over time, geographical regions, and age–gender subgroups. Development of targeted and individualized precise policies of HFMD control can benefit from illuminating its spatiotemporal transmission heterogeneity and consideration of the characteristics of population at risk.

A stage structure HFMD model with temperature-dependent latent period

A stage structures (scattered and school children) model with temperature-dependent latent period to investigate hand, foot and mouth disease (HFMD) transmission is proposed. The periodic delay induced by latent period in modelling brings new challenges to dynamics analysis. With the help of defined basic reproduction number R0, we prove: when R0<1, the disease-free equilibrium is globally attractive; when R0>1, this model is uniformly persistent. Next, the model is applied to simulate the HFMD reported data in Guangxi province, China from January 2018 to December 2019. The simulation results are consistent with our theories, and it also shows that scattered children are the main affected population. Finally, by comparing with time-averaged latent period, numerical experiments analyze the effect of time-varying latent period on HFMD transmission. Based on the HFMD transmission case in Guangxi Province, we find that the use of time-averaged latent period underestimates the real value of R0 and the number of new infections containing scattered and school children is also underestimated.