Weather effects on hand, foot, and mouth disease at individual level: a case-crossover study

Abstract Background Hand, foot, and mouth disease (HFMD) raises an urgent public health issue in the Asia-Pacific region, especially in China. The associations between weather factors and HFMD have been widely studied but with inconsistent results. Moreover, previous studies utilizing ecological design could not rule out the bias of exposure misclassification and unobserved confounders. Methods We used case-crossover analysis to assess the associations of weather factors on HFMD. Individual HFMD cases from 2009 to 2012 in Guangdong were collected and cases located within 10 km of the meteorological monitoring sites were included. Lag effects were examined through the previous 7 days. In addition, we explored the variability by changing the distance within 20 km and 30 km. Results We observed associations between HFMD and weather factors, including temperature and relative humidity. An approximately U-shaped relationship was observed for the associations of temperature on HFMD across the same day and the previous 7 days, while an approximately exponential-shaped was seen for relative humidity. Statistically significant increases in rates of HFMD were associated with each 10-unit increases in temperature [Excess rate (ER): 7.7%; 95% Confidence Interval (CI): 3.9, 11.7%] and relative humidity (ER: 1.9%; 95% CI: 0.7, 3.0%) on lag days 0–6, when assessing within 10 km of the monitoring sites. Potential thresholds for temperature (30.0 °C) and relative humidity (70.3%) detected showed associations with HFMD. The associations remained robust for 20 km and 30 km. Conclusions Our study found that temperature and relative humidity are significantly associated with the increased rates of HFMD. Thresholds and lag effects were observed between weather factors and HFMD. Our findings are useful for planning on targeted prevention and control of HFMD.

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HAND-FOOT-AND-MOUTH DISEASE EPIDEMIOLOGICAL STATUS AND RELATIONSHIP WITH METEOROLOGICAL VARIABLES IN GUANGZHOU, SOUTHERN CHINA, 2008-2012

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46652014000600014 ◽

2014 ◽

Vol 56 (6) ◽

pp. 533-539 ◽

Cited By ~ 21

Author(s):

Tiegang Li ◽

Zhicong Yang ◽

Xiangyi Liu ◽

Yan Kang ◽

Ming Wang

Keyword(s):

Negative Binomial ◽

Southern China ◽

Foot And Mouth Disease ◽

Negative Binomial Regression ◽

Incidence Rates ◽

Mouth Disease ◽

Meteorological Variables ◽

High Morbidity ◽

Weather Factors ◽

Foot And Mouth

Hand-foot-and-mouth disease (HFMD) is becoming one of the extremely common airborne and contact transmission diseases in Guangzhou, southern China, leading public health authorities to be concerned about its increased incidence. In this study, it was used an ecological study plus the negative binomial regression to identify the epidemic status of HFMD and its relationship with meteorological variables. During 2008-2012, a total of 173,524 HFMD confirmed cases were reported, 12 cases of death, yielding a fatality rate of 0.69 per 10,000. The annual incidence rates from 2008 to 2012 were 60.56, 132.44, 311.40, 402.76, and 468.59 (per 100,000), respectively, showing a rapid increasing trend. Each 1 °C rise in temperature corresponded to an increase of 9.47% (95% CI 9.36% to 9.58%) in the weekly number of HFMD cases, while a one hPa rise in atmospheric pressure corresponded to a decrease in the number of cases by 7.53% (95% CI -7.60% to -7.45%). Similarly, each one percent rise in relative humidity corresponded to an increase of 1.48% or 3.3%, and a one meter per hour rise in wind speed corresponded to an increase of 2.18% or 4.57%, in the weekly number of HFMD cases, depending on the variables considered in the model. These findings revealed that epidemic status of HFMD in Guangzhou is characterized by high morbidity but low fatality. Weather factors had a significant influence on the incidence of HFMD.

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Association between meteorological factors and reported cases of hand, foot, and mouth disease from 2000 to 2015 in Japan

Epidemiology and Infection ◽

10.1017/s0950268817001820 ◽

2017 ◽

Vol 145 (14) ◽

pp. 2896-2911 ◽

Cited By ~ 11

Author(s):

A. SUMI ◽

S. TOYODA ◽

K. KANOU ◽

T. FUJIMOTO ◽

K. MISE ◽

...

Keyword(s):

Relative Humidity ◽

Foot And Mouth Disease ◽

Entropy Method ◽

Temperature Data ◽

Mouth Disease ◽

Lower Threshold ◽

Control Measures ◽

Temperature Threshold ◽

Average Temperature ◽

Foot And Mouth

SUMMARYThe purpose of this study was to clarify the association between hand, foot, and mouth disease (HFMD) epidemics and meteorological conditions. We used HFMD surveillance data of all 47 prefectures in Japan from January 2000 to December 2015. Spectral analysis was performed using the maximum entropy method (MEM) for temperature-, relative humidity-, and total rainfall-dependent incidence data. Using MEM-estimated periods, long-term oscillatory trends were calculated using the least squares fitting (LSF) method. The temperature and relative humidity thresholds of HFMD data were estimated from the LSF curves. The average temperature data indicated a lower threshold at 12 °C and a higher threshold at 30 °C for risk of HFMD infection. Maximum and minimum temperature data indicated a lower threshold at 6 °C and a higher threshold at 35 °C, suggesting a need for HFMD control measures at temperatures between 6 and 35 °C. Based on our findings, we recommend the use of maximum and minimum temperatures rather than the average temperature, to estimate the temperature threshold of HFMD infections. The results obtained might aid in the prediction of epidemics and preparation for the effect of climatic changes on HFMD epidemiology.

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Meteorological factors and its association with hand, foot and mouth disease in Southeast and East Asia areas: a meta-analysis

Epidemiology and Infection ◽

10.1017/s0950268818003035 ◽

2018 ◽

Vol 147 ◽

Cited By ~ 6

Author(s):

Chunxiao Duan ◽

Xuefeng Zhang ◽

Hui Jin ◽

Xiaoqing Cheng ◽

Donglei Wang ◽

...

Keyword(s):

East Asia ◽

Meteorological Factors ◽

Global Climate ◽

Meta Analysis ◽

Foot And Mouth Disease ◽

Correlation Coefficients ◽

Mouth Disease ◽

Asia Pacific ◽

China National Knowledge Infrastructure ◽

Foot And Mouth

AbstractSince the late 1990s, hand, foot and mouth disease (HFMD) has become a common health problem that mostly affects children and infants in Southeast and East Asia. Global climate change is considered to be one of the major risk factors for HFMD. This study aimed to assess the correlation between meteorological factors and HFMD in the Asia-Pacific region. PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Data and Weipu Database were searched to identify relevant articles published before May 2018. Data were collected and analysed using R software. We searched 2397 articles and identified 51 eligible papers in this study. The present study included eight meteorological factors; mean temperature, mean highest temperature, mean lowest temperature, rainfall, relative humidity and hours of sunshine were positively correlated with HFMD, with correlation coefficients (CORs) of 0.52 (95% confidence interval (CI) 0.42–0.60), 0.43 (95% CI 0.23–0.59), 0.43 (95% CI 0.23–0.60), 0.27 (95% CI 0.19–0.35), 0.19 (95% CI 0.02–0.35) and 0.19 (95% CI 0.11–0.27), respectively. There were sufficient data to support a negative correlation between mean pressure and HFMD (COR = −0.51, 95% CI −0.63 to −0.36). There was no notable correlation with wind speed (COR = 0.10, 95% CI −0.03 to 0.23). Our findings suggest that meteorological factors affect the incidence of HFMD to a certain extent.

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Virulence of enterovirus-A71 fluctuates depending on the phylogenetic clade formed in the epidemic year and epidemic region

Journal of Virology ◽

10.1128/jvi.01515-21 ◽

2021 ◽

Author(s):

Kyousuke Kobayashi ◽

Hidekazu Nishimura ◽

Katsumi Mizuta ◽

Tomoha Nishizawa ◽

Son T. Chu ◽

...

Keyword(s):

Transgenic Mice ◽

Foot And Mouth Disease ◽

Virus Genome ◽

Mouth Disease ◽

Asia Pacific ◽

Enterovirus A71 ◽

Viral Virulence ◽

Foot And Mouth ◽

Potential Risks ◽

A Minor

Although epidemics of hand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) have occurred worldwide, the Asia-Pacific region has seen large sporadic outbreaks with many severe neurological cases. This suggests that the virulence of the circulating viruses fluctuates in each epidemic and that HFMD outbreaks with many severe cases occur when highly virulent viruses are circulating predominantly, which has not been experimentally verified. Here, we analyzed 32 clinically isolated strains obtained in Japan from 2002 to 2013, along with 27 Vietnamese strains obtained from 2015 to 2016 that we characterized previously using human SCARB2 transgenic mice. Phylogenetic analysis of the P1 region classified them into five clades belonging to subgenogroup B5 (B5-I to B5-V) and five clades belonging to subgenogroup C4 (C4-I to C4-V) according to the epidemic year and region. Interestingly, the clade B5-I and B5-II were very virulent, while clades B5-III, B5-IV, and B5-V were less virulent. Clades C4-II, C4-III, C4-IV, and C4-V were virulent, while clade C4-I was not. The result experimentally showed for the first time that several clades with different virulence levels emerged one after another. The experimental virulence evaluation of circulating viruses using SCARB2 transgenic mice is helpful to assess potential risks of circulating viruses. These results also suggest that a minor nucleotide or amino acid substitution in the EV-A71 genome during circulation may cause fluctuations in virulence. The data presented herein may increase our understanding of the dynamics of viral virulence during epidemics. IMPORTANCE Outbreaks of hand, foot, and mouth disease (HFMD) with severe enterovirus A71 (EV-A71) cases have occurred repeatedly, mainly in Asia. In severe cases, central nervous system complications can lead to death, making it an infectious disease of importance to public health. An unanswered question about this disease is why outbreaks of HFMD with many severe cases sometimes occur. Here, we collected EV-A71 strains that were prevalent in Japan and Vietnam over the past 20 years and evaluated their virulence in a mouse model of EV-A71 infection. This method clearly revealed that viruses belonging to different clades have different virulence, indicating that the method is powerful to assess the potential risks of the circulating viruses. The results also suggested that factors in the virus genome may potentially cause an outbreak with many severe cases and that further studies may facilitate the prediction of large epidemics of EV-A71 in the future.

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Early Evidence of Inactivated Enterovirus 71 Vaccine Impact Against Hand, Foot, and Mouth Disease in a Major Center of Ongoing Transmission in China, 2011–2018: A Longitudinal Surveillance Study

Clinical Infectious Diseases ◽

10.1093/cid/ciz1188 ◽

2019 ◽

Cited By ~ 4

Author(s):

Jennifer R Head ◽

Philip A Collender ◽

Joseph A Lewnard ◽

Nicholas K Skaff ◽

Ling Li ◽

...

Keyword(s):

Time Series ◽

Incidence Rate ◽

Enterovirus 71 ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Asia Pacific ◽

Full Time ◽

Study Region ◽

Foot And Mouth ◽

Vaccine Impact

Abstract Background Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD), associated with severe manifestations of the disease. Pediatric immunization with inactivated EV71 vaccine was initiated in 2016 in the Asia-Pacific region, including China. We analyzed a time series of HFMD cases attributable to EV71, coxsackievirus A16 (CA16), and other enteroviruses in Chengdu, a major transmission center in China, to assess early impacts of immunization. Methods Reported HFMD cases were obtained from China’s notifiable disease surveillance system. We compared observed postvaccination incidence rates during 2017–2018 with counterfactual predictions made from a negative binomial regression and a random forest model fitted to prevaccine years (2011–2015). We fit a change point model to the full time series to evaluate whether the trend of EV71 HFMD changed following vaccination. Results Between 2011 and 2018, 279 352 HFMD cases were reported in the study region. The average incidence rate of EV71 HFMD in 2017–2018 was 60% (95% prediction interval [PI], 41%–72%) lower than predicted in the absence of immunization, corresponding to an estimated 6911 (95% PI, 3246–11 542) EV71 cases averted over 2 years. There were 52% (95% PI, 42%–60%) fewer severe HFMD cases than predicted. However, the incidence rate of non-CA16 and non-EV71 HFMD was elevated in 2018. We identified a significant decline in the trend of EV71 HFMD 4 months into the postvaccine period. Conclusions We provide the first real-world evidence that programmatic vaccination against EV71 is effective against childhood HFMD and present an approach to detect early vaccine impact or intended consequences from surveillance data.

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Hand-foot-and-mouth disease and weather factors in Guangzhou, southern China

Epidemiology and Infection ◽

10.1017/s0950268813002938 ◽

2013 ◽

Vol 142 (8) ◽

pp. 1741-1750 ◽

Cited By ~ 27

Author(s):

T. LI ◽

Z. YANG ◽

B. DI ◽

M. WANG

Keyword(s):

Public Health ◽

Negative Binomial ◽

Southern China ◽

Foot And Mouth Disease ◽

Incidence Rates ◽

Mouth Disease ◽

Control Measures ◽

High Morbidity ◽

Weather Factors ◽

Foot And Mouth

SUMMARYHand-foot-and-mouth disease (HFMD) is becoming one of the common airborne and contact transmission diseases in Guangzhou, southern China, leading public health authorities to be concerned about its increased incidence. In this study, we aimed to examine the effect of weather patterns on the incidence of HFMD in the subtropical city of Guangzhou for the period 2009–2012, and assist public health prevention and control measures. A negative binomial multivariable regression was used to identify the relationship between meteorological variables and HFMD. During the study period, a total of 166 770 HFMD-confirmed cases were reported, of which 11 died, yielding a fatality rate of 0·66/10 000. Annual incidence rates from 2009 to 2012 were 132·44, 311·40, 402·76, and 468·59/1 000 00 respectively. Each 1°C rise in temperature corresponded to an increase of 9·38% (95% CI 8·17–10·51) in the weekly number of HFMD cases, while a 1 hPa rise in atmospheric pressure corresponded to a decrease in the number of cases by 6·80% (95% CI −6·99 to −6·65), having an opposite effect. Similarly, a 1% rise in relative humidity corresponded to an increase of 0·67% or 0·51%, a 1 m/h rise in wind velocity corresponded to an increase of 4·01% or 2·65%, and a 1 day addition in the number of windy days corresponded to an increase of 24·73% or 25·87%, in the weekly number of HFMD cases, depending on the variables considered in the model. Our findings revealed that the epidemic status of HFMD in Guangzhou is characterized by high morbidity but low fatality. Weather factors had a significant influence on occurrence and transmission of HFMD.

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The Effects of Weather Factors on Hand, Foot and Mouth Disease in Beijing

Scientific Reports ◽

10.1038/srep19247 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 23

Author(s):

Weihua Dong ◽

Xian’en Li ◽

Peng Yang ◽

Hua Liao ◽

Xiaoli Wang ◽

...

Keyword(s):

Foot And Mouth Disease ◽

Mouth Disease ◽

Weather Factors ◽

Foot And Mouth

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Structure, Immunogenicity, and Protective Mechanism of an Engineered Enterovirus 71-Like Particle Vaccine Mimicking 80S Empty Capsid

Journal of Virology ◽

10.1128/jvi.01330-17 ◽

2017 ◽

Vol 92 (1) ◽

Cited By ~ 3

Author(s):

Xiaoli Wang ◽

Zhiqiang Ku ◽

Xiang Zhang ◽

Xiaohua Ye ◽

Jinhuan Chen ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Enterovirus 71 ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Asia Pacific ◽

Protective Mechanism ◽

Particle Assembly ◽

Virus Like Particle ◽

Empty Capsid ◽

Foot And Mouth

ABSTRACTEnterovirus 71 (EV71) is the major causative agent of severe hand, foot, and mouth disease, which affects millions of young children in the Asia-Pacific region annually. In this study, we engineered a novel EV71 virus-like particle (VLP) that lacks VP4 (therefore designated VLPΔVP4) and investigated its structure, antigenicity, and vaccine potential. The cryo-electron microscopy (cryo-EM) structure of VLPΔVP4was reconstructed to 3.71-Å resolution. Results from structural and biochemical analyses revealed that VLPΔVP4resembles the end product of the viral uncoating process, the 80S empty capsid. VLPΔVP4is able to elicit high-titer neutralizing antibodies and to fully protect mice against lethal viral challenge. Mechanistic studies showed that, at the cellular level, the anti-VLPΔVP4sera exert neutralization effects at both pre- and postattachment stages by inhibiting both virus attachment and internalization, and at the molecular level, the antisera can block multiple interactions between EV71 and its key receptors. Our study gives a better understanding of EV71 capsid assembly and provides important information for the design and development of new-generation vaccines for EV71, and perhaps for other enteroviruses, as well.IMPORTANCEEnterovirus 71 (EV71) infection may lead to severe hand, foot, and mouth disease, with significant morbidity and mortality. Knowledge regarding EV71 particle assembly remains limited. Here, we report the generation and characterization of a novel EV71 virus-like particle that lacks the VP4 capsid subunit protein. This particle, termed VLPΔVP4, structurally mimics the 80S empty capsid, which is the end stage of EV71 uncoating. We further show that VLPΔVP4exhibits desirable immunogenicity and protective efficacy in proof-of-concept studies. In addition, the inhibitory mechanisms of the VLPΔVP4-induced antibodies are unraveled at both the cellular and molecular levels. Our work provides the first evidence of picornaviral particle assembly in the complete absence of VP4 and identifies VLPΔVP4as an improved EV71 vaccine candidate with desirable traits. These findings not only enhance our understanding of particle assembly and uncoating of picornaviruses, but also provide important information for structure-guided vaccine design for EV71 and other enteroviruses.

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Associations between ambient air pollution and daily incidence of pediatric hand, foot and mouth disease in Ningbo, 2014–2016: a distributed lag nonlinear model

Epidemiology and Infection ◽

10.1017/s0950268820000321 ◽

2020 ◽

Vol 148 ◽

Author(s):

Shaohua Gu ◽

Decheng Li ◽

Beibei Lu ◽

Ruixue Huang ◽

Guozhang Xu

Keyword(s):

Air Pollution ◽

Nonlinear Models ◽

Critical Role ◽

Foot And Mouth Disease ◽

Ambient Air ◽

Mouth Disease ◽

Ambient Air Pollution ◽

Targeted Prevention ◽

Distributed Lag ◽

Foot And Mouth

Abstract Hand, foot and mouth disease (HFMD) has high prevalence around the world, with serious consequences for children. Due to the long survival period of HFMD virus in ambient air, air pollutants may play a critical role in HFMD epidemics. We collected data on daily cases of HFMD among children aged 0–14 years in Ningbo City between 2014 and 2016. Distributed lag nonlinear models were used to assess the effects of particulate matter (PM2.5), sulphur dioxide (SO2), nitrogen dioxide (NO2) and ozone (O3) on the daily incidence of HFMD among children, with analyses stratified by gender and age. Compared with moderate levels of air pollution, high SO2 levels had a relative risk (RR) of 2.32 (95% CI 1.42–3.79) and high NO2 levels had a RR of 2.01 (95% CI 1.22–3.31). The RR of O3 was 2.12 (95% CI 1.47–3.05) and that of PM2.5 was 0.77 (95% CI 0.64–0.92) at moderate levels of air pollution. Specifically, high levels of SO2 and NO2 had RRs of 2.39 (95% CI 1.44–3.96) and 2.02 (95% CI 1.21–3.39), respectively, among 0–4-year-old children, while high O3 had an RR of 2.31 (95% CI 1.09–4.89) among 5–14-year-old children. Our findings suggest significant associations of high SO2 and NO2 levels and moderate O3 levels in HFMD epidemics, and also indicate that air pollution causes lagged effects on HFMD epidemics. Our study provides practical and useful data for targeted prevention and control of HMFD based on environmental evidence.

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Hand, Foot and Mouth Disease (HFMD): An Update

Bangladesh Journal of Child Health ◽

10.3329/bjch.v40i2.31567 ◽

2017 ◽

Vol 40 (2) ◽

pp. 115-119 ◽

Cited By ~ 4

Author(s):

Probir Kumar Sarkar ◽

Nital Kumar Sarker ◽

Md Abu Tayab

Keyword(s):

Enterovirus 71 ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Coxsackie Virus ◽

Asia Pacific ◽

Human Enterovirus ◽

Small Scale ◽

Human Enterovirus 71 ◽

Mild Disease ◽

Foot And Mouth

Hand, foot, and mouth disease (HFMD) also known as vesicular stomatitis with exanthema, first reported in New Zealand in 1957 is caused by Coxsackie virus A16 (CVA16), human enterovirus 71 (HEV71) and occasionally by other HEV-A serotypes, such as Coxsackie virus A6 and Coxsackie virus A10, are also associated with HFMD and herpangina. While all these viruses can cause mild disease in children, EV71 has been associated with neurological disease and mortality in large outbreaks in the Asia Pacific region over the last decade. It is highly contagious and is spread through direct contact with the mucus, saliva, or feces of an infected person. This is characterized by erythrematous papulo vesicular eruptions over hand, feet, perioral area, knee, buttocks and also intra-orally mostly in children, typically occurs in small epidemics usually during the summer and autumn months. HFMD symptoms are usually mild and resolve on their own in 7 to 10 days. Treatment is symptomatic but good hygiene during and after infection is very important in preventing the spread of the disease. Though only small scale outbreaks have been reported from United States, Europe, Australia Japan and Brazil for the first few decade, since 1997 the disease has conspicuously changed its behavior as noted in different Southeast Asian countries. There was sharp rise in incidence, severity, complications and even fatal outcomes that were almost unseen before that period. There are reports of disease activity in different corners of India since 2004, and the largest outbreak of HFMD occurred in eastern part of India in and around Kolkata in 2007and Bhubaneswar, Odisha in 2009. In recent years there are cases of HFMD have been seen in Bangladesh also. Although of milder degree, continuous progress to affect larger parts of the neighboring may indicate vulnerability of Bangladesh from possible future outbreaks.Bangladesh J Child Health 2016; VOL 40 (2) :115-119

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