Impact of non-pharmacological interventions on incidence of hand, foot and mouth disease during the COVID-19 pandemic: a large population-based observational study

Abstract

Background

Hand, foot, and mouth disease (HFMD) is a highly prevalent and contagious disease, particularly in children under five years old. Its transmission route resembles that of COVID-19. During the COVID-19 pandemic, non-pharmaceutical interventions (NPIs) were implemented to curb viral spread, which may have concurrently reduced HFMD incidence.

Methods

Utilizing HFMD surveillance data from the Anhui Provincial Center for Disease Control and Prevention (2015–2020) and varying levels of COVID-19 emergency measures, a Bayesian structural time series model predicted the counterfactual HFMD incidence and quantified the causal relationships with NPIs.

Results

During the implementation of NPIs, the 915 cases observed between weeks 4 and 20 of 2020 reflected a 94.9% reduction from the expected cases number (915 vs. 17,790), avoiding approximately 16,875 cases. The relative reduction of male cases (95.2%) was similar to that of female cases (94.3%). Different age groups the number of cases decline roughly similar were 93.1%, 95.3%, 97.8%, 94.9%.

Conclusion

During the COVID-19 pandemic, NPIs implemented in response to COVID-19 effectively reduced HFMD incidence. NPIs should be promoted for future control of enteric infectious diseases such as HFMD.

Introduction

Coronavirus disease 2019 (COVID-19) is an emerging viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]. SARS-CoV-2 is associated with a potentially severe acute respiratory illness [2]. The World Health Organization designated COVID-19 as a pandemic for the first time [3]. In January 2020, the outbreak of COVID-19 led Chinese authorities to implement strict prevention and control measures. The National Health Commission classified COVID-19 as a Class B infectious disease but applied Class A prevention and control measures [4]. In the absence of effective drugs, local governments employed non-pharmaceutical interventions (NPIs) to mitigate the spread of COVID-19 [5].

Faced with the severe COVID-19 situation, Anhui Province initiated a first-level response to major public health emergencies, coordinating emergency measures in line with national directives [6]. Hubei Province, the epicenter of the pandemic in China, experienced a three-month lockdown [7]. The outbreak significantly impacted Anhui Province due to its proximity to Hubei and frequent population movement [8]. A series of non-pharmaceutical interventions have been implemented to mitigate the COVID-19 epidemic, including the imposition of restrictions on group dinners and collective activities involving large gatherings [9]. For the implementation of closed management of residential communities: property management enterprises worked closely with streets and communities to strictly implement access management to reduce the risk of epidemic spread caused by the movement of people. The Ministry of Education has issued a series of notices to comprehensively deploy and coordinate the prevention and control of COVID-19 in the education system and the reform and development of education, and the opening time of primary, middle and secondary schools and kindergartens nationwide has been delayed [10, 11].

The implementation of NPIs in China led to a rapid decline in COVID-19 cases, despite significant economic and social repercussions [12]. Furthermore, studies focusing on children have revealed a direct impact of NPIs employed during the COVID-19 pandemic on the epidemiology of pediatric respiratory infections [13, 14]. The beneficial effects of NPI apply not only to COVID-19 but also extend to other infectious diseases, with studies showing that NPIs can significantly reduce the transmission of common respiratory viruses and the incidence of gastrointestinal infectious diseases in children, including HFMD [15, 16]. Zhao et al. [17] reported a significant decrease in HFMD cases in 2020, with virtually no instances during the primary epidemic period. A study on children in Hangzhou City showed that compared to the pre-COVID-19 period, the peak period of the 2019 coronavirus disease pandemic, and the post-COVID-19 period, NPIs were found to effectively reduce the incidence rate of HFMD [18].

Hand, foot and mouth disease (HFMD), a widely transmitted infectious disease that primarily affects children younger than 5 years of age [19], has been endemic in China since 2007 and was officially included in the national statutory Category B infectious disease surveillance program in May 2008 [20]. HFMD has a large major peak of activity probably in spring and early summer, with a high and increasing incidence, resulting in a huge disease burden [21].

However, to our knowledge, no comprehensive study has described the demographic impact of NPIs on HFMD at both temporal and spatial scales in a large population within Anhui province, where NPIs were rigorously implemented. Anhui province offers an opportunity to study the effects of public health interventions and population behavior changes on HFMD, which could be replicated in other cities in China or other resource-rich countries. This evidence is valuable for future public health policies to prevent and control infectious diseases.

In this study, we used data from the HFMD registry of the Anhui Provincial Notifiable Infectious Disease Surveillance System (NIDSS) to explore the impact of NPIs on HFMD. The objective of this study was to assess the co-benefits of NPIs for COVID-19 and to improve the understanding of prevention and control measures for HFMD. It is crucial to proactively identify and monitor the epidemiological patterns of HFMD in order to prevent, control, and effectively manage its progression.

Method

Study area

Anhui Province is situated in the Yangtze River Delta region of eastern China, with Hefei City as its administrative center. It lies within the transitional zone between warm temperate and subtropical climatic regions. Anhui Province experienced severe COVID-19 outbreaks due to its geographical location and population mobility, leading to the implementation of proactive and stringent non-pharmaceutical interventions (NPIs) throughout 2020 for epidemic containment [22]. Population data were collected from the Anhui Statistics Yearbook (http://tjj.ah.gov.cn/).

Data collection

HFMD. Data

Data on cases of HFMD in Anhui province from weeks 4 to 20 of the years 2015 to 2020 were extracted from the Notifiable Infectious Disease Surveillance System (NIDSS) in China. The NIDSS is an internet-based real-time reporting system developed by the Chinese Center for Disease Control and Prevention. The data collected through NIDSS are widely used by governmental agencies, domestic, and international organizations for the implementation and evaluation of public health initiatives. The NIDSS encompasses all public and private healthcare facilities in Anhui, collecting case data using standardized reporting forms. The current HFMD data are extensively utilized by government departments, as well as domestic and international organizations, for the implementation and evaluation of public health plans [23, 24]. All patients diagnosed with HFMD by a medical professional must be registered in the system. The information for each case includes gender, age, address, ethnicity, diagnosis, date of onset, virus typing, etc. The classification of HFMD in China as a class B infectious disease necessitates its reporting within 24 h, based on the disease’s characteristics and management requirements.

NPIs against COVID-19

The emergency response to public emergencies in accordance with “Anhui Province Emergency Plan for Public Health Emergencies” is categorized into four levels, ranging from level 1 to level 4 (http://www.nhc.gov.cn/). In 2020, three different emergency responses were launched in Anhui Province due to the epidemic trend of COVID-19. The first-level response to the major public health emergency was launched on January 24, 2020; it lasted until February 25 (4–8 weeks); from February 26, the first-level response was adjusted to the second-level response, which lasted until March 14 (9–11 weeks); from March 15, 2020, the second-level response was adjusted to the third-level response, which lasted until the end of May (12–20 weeks) (https://www.gov.cn/). The investigation period of this study was 17 weeks. The level 1 response will initiate the strictest response, including daily reporting of the number of confirmed cases of COVID-19, dividing the epidemic area, enforcing control measures, restricting crowd gathering, suspending work and production and school, and taking on-site isolation, on-site observation and on-site treatment of confirmed or suspected patients, The response level was gradually lowered to level 4 in accordance with the mitigation of the COVID-19 epidemic [13, 25].

Data analysis

This study aimed to investigate the effects of non-pharmacological intervention policies on HFMD in Anhui Province during weeks 4 to 20 of 2020, amidst the COVID-19 pandemic. The HFMD incidence in 2020 was determined by dividing the number of HFMD cases by the population of residents in 2020. The average HFMD incidence from 2015 to 2019 was calculated by dividing the total number of HFMD cases reported between 2015 and 2019 by the corresponding resident population during that period.

To assess the influence of Non-Pharmacological Interventions (NPIs) on HFMD cases, we conducted a comparison between the HFMD incidence during weeks 4–20 of 2020 and the average incidence observed from 2015 to 2019. Subsequently, we compared these findings with the anticipated HFMD incidence during weeks 4–20 of 2020. The predicted number of HFMD cases during weeks 4–20 of 2020 was determined using a Bayesian Structural Time Series (BSTS) model, a methodology commonly utilized in previous research studies [26, 27]. The BSTS model consists of three parts: Kalman filtering, spike-slab method, and Bayesian model averaging, and its counterfactual predictions and observed data are well suited for finding causal relationships [28]. Based on the weekly cases observed from week 4 to week 20 between 2015 and 2019, while considering both seasonal and long-term trends, we employed the BSTS model to estimate the weekly cases for the corresponding period in 2020. The BSTS model provides the following:

$$\:{y}_{t}={Z}_{t}^{T}{\alpha\:}_{t}+{u}_{t}+{\tau\:}_{t}+{\varepsilon\:}_{t\:\:\:\:}{\varepsilon\:}_{t}\sim N(0,{H}_{t})$$

(1)

$$\:{\alpha\:}_{t+1}={T}_{t}{\alpha\:}_{t}+{R}_{t}{\eta\:}_{t}{\eta\:}_{t}\:\sim\:N\left(0,{Q}_{t}\right)$$

(2)

The Eq. (1) represents the observation equation, while the Eq. (2) defines the transition equation that governs the evolution of the latent state [29]. The number of HFMD cases in week $\:t$, denoted as $\:{y}_{t}$ is linked to a vector of latent state variables. The model matrices $\:{Z}_{t}$, $\:{\alpha\:}_{t}$, $\:{T}_{t}$, and $\:{R}_{t}$comprise combinations of known values (0 and 1). $\:{\epsilon\:}_{t}$and $\:{\eta\:}_{t}$ are the randomly and independently distributed Gaussian error terms with zero mean and variance $\:{H}_{t}$ and $\:{Q}_{t}$. Within this model, the long-term trend is governed by $\:{u}_{t}$, while seasonality is regulated by$\:{\:\tau\:}_{t}$ utilizing the “week” variable (e.g., 53 weeks per year). The model was executed using the Markov Chain Monte Carlo (MCMC) algorithm with 1000 iterations. In the preliminary analysis, the fitted curves exhibited a strong alignment with the model, as evidenced by the presence of high R-squared values. In the initial study, the fitted curves and R-squared values showed a good fit to the model (Fig. S1).

We further used the relative reduction of NID incidence in weeks 4–20 of 2020 as an indicator in order to estimate the co-benefits of NPI on HFMD and COVID-19 according to the three emergency response stages, gender, age group and city (16 prefecture level cities in Anhui Province) [30]. The relative reduction was the difference between the number of expected cases and the number of observed cases divided by the number of expected cases and multiplies the answer by 100. The epidemic curve of COVID-19 in Anhui province in 2020 was drawn, and the NPIs of the same period was included in the curve. NPIs can be classified into three categories: measures based on individual cases (such as conducting epidemiological investigations, implementing health quarantines, and performing nucleic acid screenings), measures implemented within communities (including practicing social distancing, wearing masks, and closing schools), and measures related to travel (such as imposing restrictions on international airlines and managing or isolating residents from overseas countries or high-risk regions) [31, 32]. BSTS model analyses were performed with the use of the “BSTS” and “Causal Impact” packages in R software, version 4.2.1.

Results

Comparing the incidence of HFMD cases in 2020 with the mean annual incidence of HFMD cases from 2015 to 2019

Table 1 showed that Anhui Province reported 915 cases of HFMD in weeks 4–20 of 2020, a 97.1% decrease compared to the average annual number of cases (31482.6) in the same weeks from 2015 to 2019. By gender, the relative reduction was 97.4% in males and 96.6% in females. We found that the reduction rates varied by age group: ≤1 year (96.4%), 2 to 3 years (97.6%), 4 to 5 years (98.3%), and ≥ 6 years (95.5%). The reduction rates varied by year, which were observed 97.7% (2020 vs. 2015), 97.9% (2020 vs. 2016) ,94.9% (2020 vs. 2017),97.4% (2020 vs. 2018), 95.6% (2020 vs. 2019) (Table S1).

Table 1 Comparison between the number of hand, foot, and mouth disease cases during weeks 4–20 in 2020 and the average annual number of hand, foot, and mouth disease cases during weeks 4–20 in 2015–2019 in Anhui Province

Among different population groups in Anhui Province, we found that the HFMD infection rate was highest among scattered children and preschool children. Compared to the same period from 2015 to 2019, the relative reduction in HFMD cases among scattered children during weeks 4–20 in 2020 was 96.8%, while preschool children saw a reduction of 98.7%, and other population groups experienced a reduction of 92.8%.

Figure 1 illustrated that the spatial distribution of HFMD in Anhui Province during weeks 4–20 for the years 2020 varied from 0.5 to 3.1 and they figured by 16.3 to 92.7 in 2015 to 2019. Our analysis reveals a significant decrease in HFMD incidence across all 16 cities in Anhui Province compared to the period from 2015 to 2019.

Fig. 1

Spatial distribution of HFMD incidence. The spatial distribution of the incidence of hand, foot and mouth disease during weeks 4 − 20 of 2020 and during the same period of 2015 − 2019 in Anhui Province of China

Comparison between the observed and expected HFMD cases in 2020

Figure 2 depicts the changes in the weekly incidence of infectious diseases and their occurrence in Anhui Province. From weeks 4 to 20 between 2015 and 2019, there was a gradual rise in observed HFMD cases with seasonal variations, followed by a significant decline during the same period in 2020. Throughout most of 2020, we observed considerably lower HFMD figures than anticipated. The outcomes for specific age and gender groups affected by HFMD are shown in Fig. S2 and Fig. S3. In 2020, the number of HFMD cases showed a dropped slightly in the first 7 weeks, a sharp increasing trend after 30 weeks, with the peak of the epidemic shifting from summer to autumn and showing seasonal fluctuations in Fig. S4.

Fig. 2

The weekly observed hand, foot and mouth disease cases during weeks 4 − 20 of 2015–2020 (A) and the comparison of observed diseases with expected diseases (B) during weeks 4 − 20 of 2020 in Anhui Province, China

Table 2 shows the relative reduction in HFMD following the initiation of the first response level on January 24, 2020. Overall, the observed number of 915 cases during weeks 4–20 of 2020 was lower than expected, representing a relative reduction of 94.9% compared to 2020 expectations, i.e. 16,875 cases averted. The relative reduction of male cases (95.2%) was similar to that of female cases (94.3%). Different age groups the number of cases decline roughly similar were 93.1%, 95.3%, 97.8%, 94.9%. Among the different types of patients, the relative reduction of scattered children was similar to other types, and the relative reduction of nursery children was the most obvious, up to 98.8%.

Table 2 The relative reduction (%) of observed number of hand, foot, and mouth diseases during weeks 4–20compared with the expected in Anhui Province of China in 2020

The relative reductions were different during different levels of emergency response to public health events. In general, the relative reduction of level two and level three emergency response was more obvious, and the relative reduction of level three emergency response (98.2%) was greater than that of level two emergency response (86.2%) and level one emergency response (19.2%). The relative reduction of male and female was similar to the overall 4–20 weeks, and the relative reduction of male was slightly higher than that of female. Across age groups, we found a gradual decrease in the duration of the emergency response, with the greatest relative reductions among children in the 4–5 years old age group across the three emergency response periods, and the greatest relative reductions among nursery children across different categories of affected populations. We found that the relative reduction in HFMD cases across the 16 cities in Anhui Province was similar, with larger reductions mainly concentrated in cities with low population density shown in Fig. 3.

Fig. 3

The relative reduction and the observed and expected trends of HFMD in each city of Anhui province. Relative reduction (%) of hand, foot, and mouth disease during weeks 4 − 20 of 2020 in Anhui Province (A) and the observed and expected trends of hand, foot, and mouth disease stratified by city in Anhui Province in 2020. (B) Relative reduction (%) = 100 × ((number of expected cases – number of observed cases)/number of expected cases)

NPIs against COVID-19

The province of Anhui implemented a range of non-pharmaceutical measures to combat the situation, which included regulating the entry of individuals from Wuhan into Anhui, temporary halts in work and production activities, closures of schools and kindergartens, as well as providing on-site isolation, observation, and treatment for confirmed or suspected patients.

Due to the effective control of the epidemic of COVID-19, Anhui Province imposed traffic control on expressways and general highways on January 27, 2020, and extended the Spring Festival holiday to February 2, 2020. Work resumed on February 15, and the emergency response level was downgraded to level 2 on February 26, 2020. Measures to quarantine residents entering the country or having a history of sojourn overseas for 14 days and subject them to health management, international flights were subsequently curtailed, travel was restricted to specific airlines, and the emergency response level was downgraded to level three were promulgated on March 15, 2020.

Since March 15, 2020, with the local epidemic under control, the emergency response level has dropped to level 3, indicating a shift to regular prevention and control. Schools have resumed normal activities, starting with the return of graduating classes on April 26, 2020. Off-campus training for college entrance exams has also resumed. The second stage, beginning May 6, 2020, involves the resumption of classes for specific grades, while the timing for lower grades and kindergarten return will be determined later, no earlier than May 11, 2020.

Additionally, travel-related and case-based NPIs maintain quarantine and health management for residents returning from abroad for 14 days, with reduced international flights and restricted travel on specific airlines. However, certain NPIs have been relaxed. The implementation of the main NPIs were shown in Fig. 4.

Fig. 4

The epidemic process of COVID-19 and synchronous nonpharmaceutical interventions in 2020 in Anhui Province, China

Discussion

Our research identified a significant decline in reported HFMD cases in Anhui Province during the COVID-19 pandemic, particularly from weeks 4 to 20 in 2020. This reduction suggests that COVID-19 NPIs effectively mitigate the transmission of infectious diseases such as HFMD. We also found a strong correlation between the decrease in HFMD cases and the timely enforcement of NPIs across all 16 cities. These findings provide compelling evidence for the efficacy of NPIs in reducing HFMD transmission.

The annual average number of HFMD cases during 4–20 weeks from 2015 to 2019 compared with the number of HFMD cases in 2020, a significant decrease in HFMD cases was observed in 2020. The results of a study conducted in mainland China regarding HFMD align with existing research, indicating that the implementation of non-pharmaceutical measures for COVID-19 containment has effectively reduced the spread of HFMD [17]. One possible reason is that Anhui Province has adopted aggressive NPIs against COVID-19 since early 2020. If necessary, the closure of kindergarten is a feasible measure to prevent outbreaks of HFMD. This finding was also reported by Chen et al. [33]. Most NPIs, implementation of social distancing [34], closure of workplaces and schools, obligatory mask wearing [35], and imposition of travel restrictions [36], has not only interrupted the spread of COVID-19 but also reduced the likelihood of acquiring other illnesses.

We further found that the largest decrease between weeks 4–20 of 2020 and the same period of 2015–2019 was in the children 4 to 5 years age group. It is well known that children under 5 years of age are the most susceptible to notifiable infectious diseases such as HFMD [37], influenza, mumps, and other infectious diseases primarily transmitted through personal contact or airborne routes [38]. During the emergency response period, the reopening time of schools and kindergartens in Anhui Province shall not be lower than May 11, 2020 at the earliest. Therefore, children in this age group have more time to stay at home, pay more attention to personal hygiene, and reduce the number of outdoor gatherings, which may be related to the reduction of HFMD cases. This result is consistent with previous studies [39], highlighting the importance of school closure and childcare closure in the prevention and control of HFMD.

Generally, we find that the incidence of HFMD will show a peak in spring and summer, and rebound in autumn with a small peak [40]. We can clearly observe according to the counterfactual data predicted by BSTS that the expected number of cases in 2020 is much higher than the actual observed cases. We found that the number of HFMD cases increased from week 9 to week 20, which was the same as the epidemic trend of HFMD before [41]. Because the survey time in this study was up to the time when schools, kindergartens, and kindergartens resumed school, the peak in the 20th week was not the highest peak of the epidemic trend of HFMD.

In 2020, due to the impact of COVID-19, the public’s adherence to strict NPIs changed greatly. Comparing with the expected number of HFMD cases in 2020, we found that the study results were also similar to those in the same 4-week periods from 2015 to 2020. Boys, children aged 4–5 years and children in nursery care were more sensitive to the relative reduction of HFMD cases, reaching 98.6%, 99.1% and 99.4% respectively in weeks 12–20. The decline in the incidence of HFMD was the main reason for the decline in intestinal infectious diseases [42]. With the gradual implementation of the response level, HFMD and other diseases were transmitted through close contact in schools and other population gathering places. Due to the delay of school reopening in Anhui Province during the level 2 response period, children’s time in public places was reduced, and their personal contact with other children was also greatly reduced [43]. Furthermore, children who prioritized personal hygiene practices, such as regular hand washing, exhibited a more notable reduction in cases of HFMD.

The decrease in Anhui Province in the 4–20 weeks of 2020 was higher than in pediatric outpatient visits for HFMD in a university hospital in Beijing during the COVID-19 outbreak [44]. This may be due to the fact that Hubei province is the center of this COVID-19 outbreak, and Anhui Province, which is adjacent to Hubei province and faces higher risk in the early stage of the epidemic, has adopted a stricter and more efficiently NPIs. In addition, the reason why the relative reduction is more obvious than other studies may be related to the study period of this study, which is the period from 4 to 20 weeks in 2020 when the emergency response level in Anhui Province is the strictest.

In 2020, usual seasonal activities were almost completely suppressed in 16 cities in Anhui province, with people trying to avoid crowded places, staying at home, using masks more frequently, and paying more attention to hand washing during primary and secondary emergency response [45]. For example, during emergency response, the demand for medical protective equipment increases, and the supply of masks and medical alcohol is insufficient. This indicates that the people in Anhui Province have a strong protective awareness and action ability against COVID-19, and the risk of being infected with other infectious diseases, including HFMD, is low [22]. In our study, we observed that the relative degree of reduction in HFMD was greater in the second response period than in the first response period, possibly because of the delayed effect of non-pharmacological interventions in controlling infectious diseases [46]. In the early stage of the three-level emergency response (12–20 weeks), the people in Anhui Province still maintained good public health habits, such as no aggregation and no transmission. Since the epidemic was effectively controlled in late May 2020, social and economic activities in Anhui Province gradually began to recover, and mass tourism and social activities increased.

Our study period ends 20 weeks into 2020. 21 weeks in Anhui province grade three emergency response, school resumption to return to work and production schooling, population flows, NPIs measures to reduce, fading, HFMD in most parts of index rebounded sharply, many areas in the seasonal rebound, increase the risk of human interaction and other infectious diseases spread, many parts of the incidence of HFMD index rose sharply, The number of HFMD cases in the second half of the year was significantly higher than that in previous years, which was consistent with the characteristics of the national HFMD report in 2023 [47]. This may be the reason why the incidence of some infectious diseases increased in the second half of 2020 relative to the primary or secondary response, and even showed non-seasonal peaks.

This study covered the population of 16 cities in Anhui province and comprehensively investigated the spatial and temporal impact of NPI implemented to fight COVID-19 on other HFMD. In the face of the COVID-19 pandemic, China responded quickly and made a great contribution to the fight against the epidemic in the world. The progression of the COVID-19 pandemic in 2020, along with the simultaneous implementation of non-pharmaceutical interventions, offers compelling evidence for informing future strategies for preventing and controlling infectious diseases [48].

This is the first study on non-pharmaceutical interventions for HFMD against COVID-19 in Anhui province. Through this study, we can explore the versatility and effectiveness of non-pharmaceutical interventions in the prevention and control of infectious diseases, so as to provide experience for the prevention and control of other infectious diseases. The extrapolation of the results will help to form a comprehensive model for the prevention and control of infectious diseases in Anhui Province, and provide scientific basis and guidance for the prevention and control of infectious diseases in this region. Through this study, we can establish a comprehensive and flexible model for the prevention and control of infectious diseases, provide useful reference for the prevention and control of infectious diseases in Anhui Province and even other regions.

However, there should be several limitations to this study. First of all, the survey time of this study was limited to the latest opening time of schools in Anhui Province, and extending the study time can provide more observation and data collection opportunities. This allows for a better understanding of the evolution and long-term effects of the phenomenon, and thus more accurate corroboration of existing evidence. Second, during the COVID-19 epidemic, some HFMD patients may delay seeking medical care for fear of being infected with COVID-19, or some medical institutions are not operating normally. These changes may lead to underreporting of HFMD patients. Third, it is possible to overestimate the impact of NPIs on the incidence of HFMD due to significant improvements in personal hygiene practices such as wearing masks and frequent hand washing since the outbreak. Finally, the seasonal nature of HFMD is more pronounced, which may lead to challenges in modeling expected incidence.

Conclusion

In conclusion, the prevention and control measures against COVID-19, including border control, quarantine and isolation, community management, social distancing, wearing masks and personal hygiene, had great synergistic effects on the prevention and control of communicable diseases such as COVID-19 and HFMD in Anhui Province. The relative reduction was upper than 90% for all various population subgroup (, age gender, time and space). This finding highlights the importance of NPIs to control and prevent communicable diseases and should be promoted for future control of enteric infectious diseases such as HFMD.