Digital epidemiology and infodemiology of hand-foot-mouth disease (HFMD) in Italy. Disease trend assessment via Google and Wikipedia.

BACKGROUND AND AIM: The study aimed to evaluate the epidemiological trend of hand, foot and mouth disease (HFMD) in Italy using data on Internet search volume. METHODS: A cross-sectional study design was used. Data on Internet searches were obtained from Google Trends (GT) and Wikipedia. We used the following Italian search term: "Malattia mano-piede-bocca" (Hand-foot-mouth disease, in English). A monthly time-frame was extracted, partly overlapping, from July 2015 to December 2022. GT and Wikipedia were overlapped to perform a linear regression and correlation analyses. Statistical analyses were performed using the Spearman's rank correlation coefficient (rho). A linear regression analysis was performed considering Wikipedia and GT. RESULTS: Search peaks for both Wikipedia and GT occurred in the months November-December during the autumn-winter season and in June during the spring-summer season, except for the period from June 2020 to June 2021, probably due to the restrictions of the COVID19 pandemic. A temporal correlation was observed between GT and Wikipedia search trends. CONCLUSIONS: This is the first study in Italy that attempts to clarify the epidemiology of HFMD. Google search and Wikipedia can be valuable for public health surveillance; however, to date, digital epidemiology cannot replace the traditional surveillance system.

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

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.

Daily mean temperature and HFMD: risk assessment and attributable fraction identification in Ningbo China.

BACKGROUND: Hand, foot, and mouth disease (HFMD) remains a significant public health issue, especially in developing countries. Many studies have reported the association between environmental temperature and HFMD. However, the results are highly heterogeneous in different regions. In addition, there are few studies on the attributable risk of HFMD due to temperature. OBJECTIVES: The study aimed to assess the association between temperature and HFMD incidence and to evaluate the attributable burden of HFMD due to temperature in Ningbo China. METHODS: The research used daily incidence of HFMD from 2014 to 2017 and distributed lag non-linear model (DLNM) to investigate the effects of daily mean temperature (Tmean) on HFMD incidence from lag 0 to 30 days, after controlling potential confounders. The lag effects and cumulative relative risk (CRR) were analyzed. Attributable fraction (AF) of HFMD incidence due to temperature was calculated. Stratified analysis by gender and age were also conducted. RESULTS: The significant associations between Tmean and HFMD incidence were observed in Ningbo for lag 0-30. Two peaks were observed at both low (5-11 °C) and high (16-29 °C) temperature scales. For low temperature scale, the highest CRR was 2.22 (95% CI: 1.61-3.07) at 7 °C on lag 0-30. For high temperature scale, the highest CRR was 3.54 (95% CI: 2.58-4.88) at 24 °C on lag 0-30. The AF due to low and high temperature was 5.23% (95% CI: 3.10-7.14%) and 39.55% (95% CI: 30.91-45.51%), respectively. There was no significant difference between gender- and age-specific AFs, even though the school-age and female children had slightly higher AF values. CONCLUSIONS: The result indicates that both high and low temperatures were associated with daily incidence of HFMD, and more burdens were caused by heat in Ningbo.

Regional-level risk factors for severe hand-foot-and-mouth disease: an ecological study from mainland China.

BACKGROUND: Severe hand-foot-and-mouth disease (HFMD) is a life-threatening contagious disease among young children and infants. Although enterovirus A71 has been well acknowledged to be the dominant cause of severe HFMD, there still remain other unidentified risk factors for severe HFMD. Previous studies mainly focused on identifying the individual-level risk factors from a clinical perspective, while rare studies aimed to clarify the association between regional-level risk factors and severe HFMD, which may be more important from a public health perspective. METHODS: We retrieved the clinical HFMD counts between 2008 and 2014 from the Chinese Center for Disease Control and Prevention, which were used to calculated the case-severity rate in 143 prefectural-level cities in mainland China. For each of those 143 cities, we further obtained city-specific characteristics from the China City Statistical Yearbook (social and economic variables) and the national meteorological monitoring system (meteorological variables). A Poisson regression model was then used to estimate the associations between city-specific characteristics (reduced by the principal component analysis to avoid multicollinearity) and the case-severity rate of HFMD. The above analysis was further stratified by age and gender to examine potential modifying effects and vulnerable sub-populations. RESULTS: We found that the case-severity rate of HFMD varied dramatically between cities, ranging from 0 to 8.09%. Cities with high case-severity rates were mainly clustered in Central China. By relating the case-severity rate to city-specific characteristics, we found that both the principal component characterized by a high level of social and economic development (RR = 0.823, 95%CI 0.739, 0.916) and another that characterized by warm and humid climate (RR = 0.771, 95%CI 0.619, 0.960) were negatively associated with the case-severity rate of HFMD. These estimations were consistent across age and gender sub-populations. CONCLUSION: Except for the type of infected pathogen, the case-severity rate of HFMD was closely related to city development and meteorological factor. These findings suggest that social and environmental factors may also play an important role in the progress of severe HFMD.

Assessment of Temperature-Hand, Foot, and Mouth Disease Association and Its Variability across Urban and Rural Populations in Wuxi, China: A Distributed Lag Nonlinear Analysis.

Hand, foot, and mouth disease (HFMD) has brought millions of attacks and a substantial burden in the Asia-Pacific region. Previous studies assessed disease risks around the world, which demonstrated great heterogeneity, and few determined the modification effect of social factors on temperature-disease relationship. We conducted a time-series study to evaluate the temperature-associated HFMD morbidity risk using daily data (from 2011 to 2017) and to identify potential modifiers relating to urban-rural status and aggregation mode of children. By applying a distributed lag nonlinear model (DLNM) and controlling for time-varying factors and other meteorological factors, we found that the relationship between daily mean temperature and the cumulative risk of HFMD was an approximately M-shaped curve. The effects of higher temperature appeared to be greater and more persistent than those of lower temperature. With the reference of -6°C, the cumulative relative risk (RR) values of high temperature (95 percentile) and low temperature (5 percentile) were 3.74 (95% CI: 2.50-5.61) and 1.72 (95% CI: 1.24-2.37) at lag 4-7, respectively. Temperature-associated HFMD morbidity risks were more pronounced among rural children and those attending kindergartens or schools at specific lags and temperatures. Relative risk values for temperature-disease association was highest among the 3- to 6-year group, whereas no gender difference was observed. Studying effect estimates and their modifications using the DLNM on a daily scale helps to identify susceptible groups and guide policy-making and resource allocation according to specific local conditions.

[Application of moving epidemic method in establishing epidemic intensity threshold of hand, foot, and mouth disease in southern China].

Objective: To evaluate the incidence intensity of hand, foot, and mouth disease (HFMD) in 2018/2019 season in southern China by Moving Epidemic Method (MEM), and compare the intensity among provinces, so as to provide basis for optimizing the allocation of public health resources. Methods: The weekly incidence data of HFMD of children under 5 years old in 15 provinces of southern China from March 1, 2012 to February 28, 2019 were collected from Disease Surveillance Reporting System of Chinese Center for Disease Control and Prevention, and the epidemic intensity threshold of each province in southern China during this period was calculated and evaluated by MEM. Results: In the first incidence peak of 2018/2019 HFMD season, in 15 provinces in the south China, 6 provinces (Jiangsu, Zhejiang, Jiangxi, Chongqing, Sichuan and Yunnan) reported very high incidence rates in children under 5 years old while Guangdong, Guangxi and Hainan provinces had low incidence level. In the second incidence peak, the incidences in 6 provinces (Shanghai, Jiangsu, Zhejiang, Chongqing, Sichuan and Yunnan) reached very high levels. The incidences in remaining provinces also reached medium or high levels. In most provinces, the thresholds in the first incidence peak were higher than those in the second incidence peak, but Chongqing and Sichuan were different. The results of model validation showed that the sensitivity and specificity of MEM were higher than 70% except for Hainan, Chongqing and Yunnan. Conclusions: For southern provinces with two incidence peaks in HFMD season, MEM can be used to determine the epidemic intensity thresholds of different incidence peaks by dividing the disease season to analyze the incidence intensity of HFMD in different stages. The epidemic intensity threshold established by MEM integrates the historical data, and the province (city) with extremely high epidemic level identified represents that the province (city) has an abnormal increase compared with the historical incidence level, which requires more attention from all areas and timely implementation of prevention and control measures.

[Summary of research in economic burden of hand, foot, and mouth disease in China].

Since 2010, the incidence of hand, foot, and mouth disease (HFMD) has ranked top in notifiable infectious disease in China, causing economic losses to many families and the society of China. This paper summarizes the related methods, results and problems systematically in the research of economic burden of HFMD in China to provide reference for the better estimation of the economic burden caused by HFMD. Many studies showed that HFMD, especially severe and fatal cases, had posed heavy economic burden on the society. To mitigate the burden caused by HFMD, it is necessary to decrease the risk of severe and fatal cases, as well as to reduce the incidence of mild cases.

Spatial-temporal variation and risk factor analysis of hand, foot, and mouth disease in children under 5 years old in Guangxi, China.

BACKGROUND: Hand, foot and mouth disease (HFMD) incidence is a critical challenge to disease control and prevention in parts of China, particularly Guangxi. However, the association between socioeconomic factors and meteorological factors on HFMD is still unclear. METHODS: This study applied global and local Moran's I to examine the spatial pattern of HFMD and series analysis to explore the temporal pattern. The effects of meteorological factors and socioeconomic factors on HFMD incidence in Guangxi, China were analyzed using GeoDetector Model. RESULTS: This study collected 45,522 cases from 87 counties in Guangxi during 2015, among which 43,711 cases were children aged 0-4 years. Temporally, there were two HFMD risk peaks in 2015. One peak was in September with 7890 cases. The other appeared in May with 4687 cases of HFMD. A high-risk cluster was located in the valley areas. The tertiary industry, precipitation and second industry had more influence than other risk factors on HFMD incidence with explanatory powers of 0.24, 0.23 and 0.21, respectively. The interactive effect of any two risk factors would enhance the risk of HFMD. CONCLUSIONS: This study suggests that precipitation and tertiary industry factors might have stronger effects on the HFMD incidence in Guangxi, China, compared with other factors. High-risk of HFMD was identified in the valley areas characterized by high temperature and humidity. Local government should pay more attention and strengthen public health services level in this area.

Epidemics and underlying factors of multiple-peak pattern on hand, foot and mouth disease inWenzhou, China.

Background: Several outbreaks of severe hand-foot-mouth disease (HFMD) in East Asia and Southwest Asia in recent years have had a serious impact on the countries. However, the factors that contribute to annual multiple-peak pattern of HFMD outbreaks, and how and when do these factors play the decisive role in the HFMD transmission is still unclear. METHODS: Based on the surveillance data of HFMD between 1 January 2010 to 31 December 2015 in Wenzhou, China, the daily modelfree basic reproduction number and its annual average were first estimated by incorporating incubation and infection information, then the annual model-based basic reproduction number was computed by the proposed kinetic model, and finally the potential impact factors of multiple-peak pattern are assessed through the global and time-varying sensitivity analyses. RESULTS: All annual model-based and model-free basic reproduction numbers were significantly higher than one. The school opening both in the spring and fall semester, meteorological e ect in the spring semester, and the interactions among them were strongly correlated with the annual model-based basic reproduction number, which were the main underlying factors on the annual multiple-peak pattern of HFMD outbreaks. CONCLUSIONS: School opening was primarily responsible for peaks of HFMD outbreaks and meteorological factors in the spring semester should also be highly concerned. The optimum timing for social distance implementation is at the beginning of every school semester and health education focusing on personal hygiene and good sanitation should be highlighted in the spring semester.

Exploring spatiotemporal nonstationary effects of climate factors on hand, foot, and mouth disease using Bayesian Spatiotemporally Varying Coefficients (STVC) model in Sichuan, China.

BACKGROUND: Pediatric hand, foot, and mouth disease (HFMD) has generally been found to be associated with climate. However, knowledge about how this association varies spatiotemporally is very limited, especially when considering the influence of local socioeconomic conditions. This study aims to identify multi-sourced HFMD environmental factors and further quantify the spatiotemporal nonstationary effects of various climate factors on HFMD occurrence. METHODS: We propose an innovative method, named spatiotemporally varying coefficients (STVC) model, under the Bayesian hierarchical modeling framework, for exploring both spatial and temporal nonstationary effects in climate covariates, after controlling for socioeconomic effects. We use data of monthly county-level HFMD occurrence and data of related climate and socioeconomic variables in Sichuan, China from 2009 to 2011 for our experiments. RESULTS: Cross-validation experiments showed that the STVC model achieved the best average prediction accuracy (81.98%), compared with ordinary (68.27%), temporal (72.34%), spatial (75.99%) and spatiotemporal (77.60%) ecological models. The STVC model also outperformed these models in the Bayesian model evaluation. In this study, the STVC model was able to spatialize the risk indicator odds ratio (OR) into local ORs to represent spatial and temporal varying disease-climate relationships. We detected local temporal nonlinear seasonal trends and spatial hot spots for both disease occurrence and disease-climate associations over 36 months in Sichuan, China. Among the six representative climate variables, temperature (OR = 2.59), relative humidity (OR = 1.35), and wind speed (OR = 0.65) were not only overall related to the increase of HFMD occurrence, but also demonstrated spatiotemporal variations in their local associations with HFMD. CONCLUSION: Our findings show that county-level HFMD interventions may need to consider varying local-scale spatial and temporal disease-climate relationships. Our proposed Bayesian STVC model can capture spatiotemporal nonstationary exposure-response relationships for detailed exposure assessments and advanced risk mapping, and offers new insights to broader environmental science and spatial statistics.

Population based hospitalization burden of laboratory-confirmed hand, foot and mouth disease caused by multiple enterovirus serotypes in Southern China.

BACKGROUND: Hand, foot and mouth disease (HFMD) is spread widely across Asia, and the hospitalization burden is currently not well understood. Here, we estimated serotype-specific and age-specific hospitalization rates of HFMD in Southern China. METHODS: We enrolled pediatric HFMD patients admitted to 3/3 county-level hospitals, and 3/23 township-level hospitals in Anhua county, Hunan (CN). Samples were collected to identify enterovirus serotypes by RT-PCRs between October 2013 and September 2016. Information on other eligible, but un-enrolled, patients were retrospectively collected from the same six hospitals. Monthly numbers of all-cause hospitalizations were collected from each of the 23 township-level hospitals to extrapolate hospitalizations associated with HFMD among these. RESULTS: During the three years, an estimated 3,236 pediatric patients were hospitalized with lab-confirmed HFMD, and among these only one case was severe. The mean hospitalization rate was 660 (95% CI: 638-684) per 100,000 person-years for lab-confirmed HFMD, with higher rates among CV-A16 and CV-A6 associated HFMD (213 vs 209 per 100,000 person-years), and lower among EV-A71, CV-A10 and other enterovirus associated HFMD (134, 39 and 66 per 100,000 person-years respectively, p<0.001). Children aged 12-23 months had the highest hospitalization rates (3,594/100,000 person-years), followed by those aged 24-35 months (1,828/100,000 person-years) and 6-11 months (1,572/100,000 person-years). Compared with other serotypes, CV-A6-associated hospitalizations were evident at younger ages. CONCLUSIONS: Our study indicates a substantial hospitalization burden associated with non-severe HFMD in a rural county in southern China. Future mitigation policies should take into account the disease burden identified, and optimize interventions for HFMD.

Risk Assessment and Mapping of Hand, Foot, and Mouth Disease at the County Level in Mainland China Using Spatiotemporal Zero-Inflated Bayesian Hierarchical Models.

Hand, foot, and mouth disease (HFMD) is a worldwide infectious disease, prominent in China. China's HFMD data are sparse with a large number of observed zeros across locations and over time. However, no previous studies have considered such a zero-inflated problem on HFMD's spatiotemporal risk analysis and mapping, not to mention for the entire Mainland China at county level. Monthly county-level HFMD cases data combined with related climate and socioeconomic variables were collected. We developed four models, including spatiotemporal Poisson, negative binomial, zero-inflated Poisson (ZIP), and zero-inflated negative binomial (ZINB) models under the Bayesian hierarchical modeling framework to explore disease spatiotemporal patterns. The results showed that the spatiotemporal ZINB model performed best. Both climate and socioeconomic variables were identified as significant risk factors for increasing HFMD incidence. The relative risk (RR) of HFMD at the local scale showed nonlinear temporal trends and was considerably spatially clustered in Mainland China. The first complete county-level spatiotemporal relative risk maps of HFMD were generated by this study. The new findings provide great potential for national county-level HFMD prevention and control, and the improved spatiotemporal zero-inflated model offers new insights for epidemic data with the zero-inflated problem in environmental epidemiology and public health.

A spatiotemporal mixed model to assess the influence of environmental and socioeconomic factors on the incidence of hand, foot and mouth disease.

BACKGROUND: As a common infectious disease, hand, foot and mouth disease (HFMD) is affected by multiple environmental and socioeconomic factors, and its pathogenesis is complex. Furthermore, the transmission of HFMD is characterized by strong spatial clustering and autocorrelation, and the classical statistical approach may be biased without consideration of spatial autocorrelation. In this paper, we propose to embed spatial characteristics into a spatiotemporal additive model to improve HFMD incidence assessment. METHODS: Using incidence data (6439 samples from 137 monitoring district) for Shandong Province, China, along with meteorological, environmental and socioeconomic spatial and spatiotemporal covariate data, we proposed a spatiotemporal mixed model to estimate HFMD incidence. Geo-additive regression was used to model the non-linear effects of the covariates on the incidence risk of HFMD in univariate and multivariate models. Furthermore, the spatial effect was constructed to capture spatial autocorrelation at the sub-regional scale, and clusters (hotspots of high risk) were generated using spatiotemporal scanning statistics as a predictor. Linear and non-linear effects were compared to illustrate the usefulness of non-linear associations. Patterns of spatial effects and clusters were explored to illustrate the variation of the HFMD incidence across geographical sub-regions. To validate our approach, 10-fold cross-validation was conducted. RESULTS: The results showed that there were significant non-linear associations of the temporal index, spatiotemporal meteorological factors and spatial environmental and socioeconomic factors with HFMD incidence. Furthermore, there were strong spatial autocorrelation and clusters for the HFMD incidence. Spatiotemporal meteorological parameters, the normalized difference vegetation index (NDVI), the temporal index, spatiotemporal clustering and spatial effects played important roles as predictors in the multivariate models. Efron's cross-validation R2 of 0.83 was acquired using our approach. The spatial effect accounted for 23% of the R2, and notable patterns of the posterior spatial effect were captured. CONCLUSIONS: We developed a geo-additive mixed spatiotemporal model to assess the influence of meteorological, environmental and socioeconomic factors on HFMD incidence and explored spatiotemporal patterns of such incidence. Our approach achieved a competitive performance in cross-validation and revealed strong spatial patterns for the HFMD incidence rate, illustrating important implications for the epidemiology of HFMD.

Cost-effectiveness of a national enterovirus 71 vaccination program in China.

BACKGROUND AND AIMS: Enterovirus 71 (EV71) has caused great morbidity, mortality, and use of health service in children younger than five years in China. Vaccines against EV71 have been proved effective and safe by recent phase 3 trials and are now available in China. The purpose of this study was to evaluate the health impact and cost-effectiveness of a national EV71 vaccination program in China. METHODS: Using Microsoft Excel, a decision model was built to calculate the net clinical and economic outcomes of EV71 vaccination compared with no EV71 vaccination in a birth cohort of 1,000,000 Chinese children followed for five years. Model parameters came from published epidemiology, clinical and cost data. RESULTS: In the base-case, vaccination would annually avert 37,872 cases of hand, foot and mouth disease (HFMD), 2,629 herpangina cases, 72,900 outpatient visits, 6,363 admissions to hospital, 29 deaths, and 945 disability adjusted life years. The break-even price of the vaccine was $5.2/dose. When the price was less than $8.3 or $14.6/dose, the vaccination program would be highly cost-effective or cost-effective, respectively (incremental cost-effectiveness ratio less than or between one to three times China GDP per capita, respectively). In one-way sensitivity analyses, the HFMD incidence was the only influential parameter at the price of $5/dose. CONCLUSIONS: Within the price range of current routine vaccines paid by the government, a national EV71 vaccination program would be cost-saving or highly cost-effective to prevent EV71 related morbidity, mortality, and use of health service among children younger than five years in China. Policy makers should consider including EV71 vaccination as part of China's routine childhood immunization schedule.

Hand, foot and mouth disease (HFMD): emerging epidemiology and the need for a vaccine strategy.

Hand, foot, and mouth disease (HFMD) is a contagious viral disease and mainly affects infants and young children. The main manifestations are fever, vesicular rashes on hand, feet and buttocks and ulcers in the oral mucosa. Usually, HFMD is self-limiting, but a small proportion of children may experience severe complications such as meningitis, encephalitis, acute flaccid paralysis and neurorespiratory syndrome. Historically, outbreaks of HFMD were mainly caused by two enteroviruses: the coxsackievirus A16 (CV-A16) and the enterovirus 71 (EV-A71). In the recent years, coxsackievirus A6 and coxsackievirus A10 have been widely associated with both sporadic cases and outbreaks of HFMD worldwide, particularly in India, South East Asia and Europe with an increased frequency of neurological complications as well as mortality. Currently, there is no pharmacological intervention or vaccine available for HFMD. A formalin-inactivated EV-A71 vaccine has completed clinical trial in several Asian countries. However, this vaccine cannot protect against other major emerging etiologies of HFMD such as CV-A16, CV-A6 and CV-A10. Therefore, the development of a globally representative multivalent HFMD vaccine could be the best strategy.

Spatial-temporal mapping of hand foot and mouth disease and the long-term effects associated with climate and socio-economic variables in Sichuan Province, China from 2009 to 2013.

BACKGROUND: Hand, foot and mouth disease (HFMD) is a common infectious disease caused by enteroviruses. The annual HFMD incidence increased from 37.6/100,000 in 2008 to 139.6/100,000 in 2014 in mainland China. In this study, we try to model spatial-temporal association between HFMD incidence and climate and socio-economic variables. METHODS: The annual numbers of reported cases of HFMD and populations from 2009 to 2013 were obtained from the Chinese infectious disease surveillance system. The climate data were obtained from a data sharing website hosted by the China Meteorological Administration. The socio-economic data were obtained from the statistic Yearbook of Sichuan province. Moran's I statistics were used to detect the counties' global spatial clusters. The hierarchical Bayesian spatial temporal interactive models were used to analyze the association between the annual HFMD incidence rate and climate variables. RESULTS: An increasing trend in the annual HFMD incidence was detected in south-western counties. Spatial temporal clusters existed in Sichuan Province. A highly county level spatial structured RR (relative risk, RR) of HFMD incidence was detected in the northern and central of Sichuan Province. Annual HFMD incidence of counties were positively associated with the average annual temperature (RR:1.171, 95%CI:1.0435-1.3134), the second quartile of the per capital of GDP (reference: the first quartile of GDP, RR: 1.258, 95%CI: 1.0418-1.5200), the third quartile of per capital of GDP (RR:1.7726, 95%CI:1.3709-2.2907) and the fourth quartile of the per capital GDP (RR:1.9026, 95%CI1.3318-2.7086). CONCLUSION: The HFMD incidence exhibited a heterogeneous spatial-temporal distribution in Sichuan Province. In the counties with greater wealth, the temperature was the primary risk factor, whereas in the counties with less wealth, GDP was the primary risk factor attributed to the spatial structured of HFMD incidence. Different preventive measures should be implemented in counties with different economic conditions.

Boosted regression tree model-based assessment of the impacts of meteorological drivers of hand, foot and mouth disease in Guangdong, China.

BACKGROUND: Hand, foot and mouth disease (HFMD) is a common childhood infection and has become a major public health issue in China. Considerable research has focused on the role of meteorological factors in HFMD development. Nonlinear relationship, delayed effects and collinearity problems are key issues for achieving robust and accurate estimations in this kind of weather-health relationship explorations. The current study was designed to address these issues and assess the impact of meteorological factors on HFMD in Guangdong, China. METHODS: Case-based HFMD surveillance data and daily meteorological data collected between 2010 and 2012 was obtained from China CDC and the National Meteorological Information Center, respectively. After a preliminary variable selection, for each dataset boosted regression tree (BRT) models were applied to determine the optimal lag for meteorological factors at which the variance of HFMD cases was most explained, and to assess the impacts of these meteorological factors at the optimal lag. RESULTS: Variance of HFMD cases was explained most by meteorological factors about 1 week ago. Younger children and those from the Pearl-River Delta Region were more sensitive to weather changes. Temperature had the largest contribution to HFMD epidemics (28.99-71.93%), followed by precipitation (6.52-16.11%), humidity (3.92-17.66%), wind speed (3.84-11.37%) and sunshine (6.21-10.36%). Temperature between 10°C and 25°C, as well as humidity between 70% and 90%, had a facilitating effect on the epidemic of HFMD. Sunshine duration above 9h and wind speed below 2.5m/s also contributed to an elevated risk of HFMD. The positive relationship between HFMD and precipitation reversed when the daily amount of rainfall exceeded 25 mm. CONCLUSIONS: This study indicated significantly facilitating effects of five meteorological factors within some range on the epidemic of HFMD. Results from the current study were particularly important for developing early warning and response system on HFMD in the context of global climate change.

Assessment of temperature effect on childhood hand, foot and mouth disease incidence (0-5years) and associated effect modifiers: A 17 cities study in Shandong Province, China, 2007-2012.

BACKGROUND: Previous studies examining temperature-disease associations of hand, foot and mouth disease (HFMD) mainly focused on a single city. The results demonstrated great heterogeneity. A multi-city study is necessary to better understand temperature risk on the childhood incidence of HFMD and the associated modified factors. OBJECTIVE: To assess the effect of ambient temperature on childhood HFMD incidence and explore the potential associated effect modifiers in the study area. METHODS: Daily morbidity data and meteorological variables of the 17 cities were collected for the period from 2007 to 2012. Distributed lag non-linear model (DLNM) was used to estimate city-specific effects of temperature on HFMD incidence. A multivariate meta-analysis was then applied to pool the estimated city-specific effect. Potential effect modifiers were included in the multivariate meta-regression as meta-predictors. RESULTS: A total of 504,017 childhood HFMD cases were included in the study. The high-incidence period of HFMD was detected in late spring and early summer (April to June). The temperature-disease associations of the 17 cities demonstrated great heterogeneity and the pooled exposure-response curve was an approximately inverted V-shape. Regional indicator, numbers of healthcare institution and annual household income were considered as associated modifiers. CONCLUSION: Our findings can provide a practical reference for the early warning and intervention strategies of HFMD. Different temperature-disease associations among different regions should be considered when formulating and optimizing public health policy.

Assessing the impact of humidex on HFMD in Guangdong Province and its variability across social-economic status and age groups.

Humidex is a meteorological index that combines the impacts of temperature and humidity, and is directly comparable with dry temperature in degrees Celsius. However, to date, no research has focused on the effect of humidex on hand, foot and mouth disease (HFMD). The current study was designed to address this research need. Case-based HFMD surveillance data and daily meteorological data collected between 2010 and 2012 was obtained from the China CDC and the National Meteorological Information Center, respectively. Distributed lag nonlinear models were applied to assess the impact of humidex on HFMD among children under 15 years oldin Guangdong, and its variability across social-economic status and age groups. We found that relative risk (RR) largely increased with humidex. Lag-specific and cumulative humidex-RR curves for children from the Pearl-River Delta Region as well as older children were more likely to show two-peak distribution patterns. One RR peak occurred at a humidex of between 15 and 20, and the other occurred between 30 and 35. This study provides a comprehensive picture of the impact of humidex on HFMD incidence in Guangdong Province. Results from the present study should be important in the development of area-and-age-targeted control programs.

Disease burden of enterovirus infection in Taiwan: Implications for vaccination policy.

OBJECTIVES: This study aimed to assess the disease burden and economic impacts of human nonpolio enteroviruses (NPEV) and enterovirus A71 (EV-A71) infection in Taiwan. MATERIALS AND METHODS: We included children under five years old (n=983,127-1,118,649) with ICD-9-CM codes 0740 (herpangina) or 0743 (hand-foot-and-mouth disease) from the 2006 to 2010 National Health Insurance Database. Severity of enterovirus infection was assessed from outpatient/emergency visits, hospitalization (with/without intensive care unit [ICU] admission), infection with severe complications, and death. We estimated medical costs and indirect costs from the societal perspective. RESULTS: The annual rates of NPEV events for children under five years old ranged from 13.9% to 38.4%, of which 5.1-8.8% were hospitalized. EV-A71 accounted for 7.8% of all NPEV medical costs, but 79.1% of NPEV ICU costs. Travel costs and productivity loss of caregivers were $37.1 (range: $24.5-$64.7) million per year. These costs were not higher in the EV-A71 dominant year ($34.4 million) compared with those in the other years. Productivity losses resulting from premature mortality by NPEV infection were $0.8 (range: $0.0-$2.9) million per year, of which 96.3% were caused by EV-A71. CONCLUSIONS: Diseases associated with NPEV other than EV-A71 were responsible for most of the medical expenses. In addition, caregiver productivity loss by high rates of NPEV infection impacted the society much more than medical costs. A multi-valent vaccine that includes EV-A71 and other serotypes, for example coxsackievirus A16, may be beneficial to the health of children in Taiwan.