Interactive effects of meteorological factors and air pollutants on hand, foot, and mouth disease in Chengdu, China: a time-series study.

OBJECTIVES: Hand, foot, and mouth disease (HFMD) is a viral infectious disease that poses a substantial threat in the Asia-Pacific region. It is widely reported that meteorological factors are associated with HFMD. However, the relationships between air pollutants and HFMD are still controversial. In addition, the interactive effects between meteorological factors and air pollutants on HFMD remain unknown. To fill this research gap, we conducted a time-series study. DESIGN: A time-series study. SETTING AND PARTICIPANTS: Daily cases of HFMD as well as meteorological and air pollution data were collected in Chengdu from 2011 to 2017. A total of 184 610 HFMD cases under the age of 15 were included in our study. OUTCOME MEASURES: Distributed lag nonlinear models were used to investigate the relationships between HFMD and environmental factors, including mean temperature, relative humidity, SO2, NO2, and PM10. Then, the relative excess risk due to interaction (RERI) and the proportion attributable to interaction were calculated to quantitatively evaluate the interactions between meteorological factors and air pollutants on HFMD. Bivariate response surface models were used to visually display the interactive effects. RESULTS: The cumulative exposure-response curves of SO2 and NO2 were inverted 'V'-shaped and 'M'-shaped, respectively, and the risk of HFMD gradually decreased with increasing PM10 concentrations. We found that there were synergistic interactions between mean temperature and SO2, relative humidity and SO2, as well as relative humidity and PM10 on HFMD, with individual RERIs of 0.334 (95% CI 0.119 to 0.548), 0.428 (95% CI 0.214 to 0.642) and 0.501 (95% CI 0.262 to 0.741), respectively, indicating that the effects of SO2 and PM10 on HFMD were stronger under high temperature (>17.3°C) or high humidity (>80.0%) conditions. CONCLUSIONS: There were interactive effects between meteorological factors and air pollutants on HFMD. Our findings could provide guidance for targeted and timely preventive and control measures for HFMD.

An epidemiological surveillance of hand foot and mouth disease in paediatric patients and in community: A Singapore retrospective cohort study, 2013-2018.

BACKGROUND: While hand, foot and mouth disease (HFMD) is primarily self-resolving-soaring incidence rate of symptomatic HFMD effectuates economic burden in the Asia-Pacific region. Singapore has seen a conspicuous rise in the number of HFMD cases from 2010s. Here, we aims to identify the serology and genotypes responsible for such outbreaks in hospitals and childcare facilities. METHODS: We studied symptomatic paediatric HFMD cases from 2013 to 2018 in Singapore. Surveillance for subclinical enterovirus infections was also performed in childcares at the same time period. RESULTS: Genotyping 101 symptomatic HFMD samples revealed CV-A6 as the major etiological agent for recent outbreaks. We detected infections with CV-A6 (41.0%), EV-A71 (7%), CV-A16 (3.0%), coxsackievirus A2, CV-A2 (1.0%) and coxsackievirus A10, CV-A10 (1.0%). Phylogenetic analysis of local CV-A6 strains revealed a high level of heterogeneity compared against others worldwide, dissimilar to other HFMD causative enteroviruses for which the dominant strains and genotypes are highly region specific. We detected sub-clinical enterovirus infections in childcare centres; 17.1% (n = 245) tested positive for enterovirus in saliva, without HFMD indicative symptoms at the point of sample collection. CONCLUSIONS: CV-A6 remained as the dominant HFMD causative strain in Singapore. Silent subclinical enteroviral infections were detected and warrant further investigations.

Clinical, etiological and epidemiological investigations of hand, foot and mouth disease in southern Vietnam during 2015 - 2018.

Hand, foot and mouth disease (HFMD) continues to challenge Asia with pandemic potential. In Vietnam, there have been two major outbreaks occurring during 2011-2012 (>200,000 hospitalizations and >200 deaths) and more recently in 2018 (>130,000 hospitalizations and 17 deaths). Given the high burden and the complex epidemic dynamics of HFMD, synthesizing its clinical and epidemiological data remains essential to inform the development of appropriate interventions and design public health measures. We report the results of a hospital-based study conducted during 2015-2018, covering the severe HFMD outbreak recently documented in Vietnam in 2018. The study was conducted at three major hospitals responsible for receiving HFMD patients from southern Vietnam with a population of over 40 million. A total of 19 enterovirus serotypes were detected in 1196 HFMD patients enrolled in the clinical study during 2015-2018, with enterovirus A71 (EV-A71), coxsackievirus A6 (CV-A6), CV-A10 and CV-A16 being the major causes. Despite the emergence of coxsackieviruses, EV-A71 remains the leading cause of severe HFMD in Vietnam. EV-A71 was consistently detected at a higher frequency during the second half of the years. The emergence of EV-A71 subgenogroup C4 in late 2018 was preceded by its low activity during 2017-early 2018. Compared with EV-A71 subgenogroup B5, C4 was more likely to be associated with severe HFMD, representing the first report demonstrating the difference in clinical severity between subgenogroup C4 and B5, the two predominant EV-A71 subgenogroups causing HFMD worldwide. Our data have provided significant insights into important aspects of HFMD over four years (2015-2018) in Vietnam, and emphasize active surveillance for pathogen circulation remains essential to inform the local public health authorities in the development of appropriate intervention strategies to reduce the burden of this emerging infections. Multivalent vaccines are urgently needed to control HFMD.

Onychomadesis and potential association with HFMD outbreak in a kindergarten in Hubei province, China, 2017.

BACKGROUND: In 2017, an outbreak of onychomadesis occurred in kindergarten H, Hubei province, China. We investigated the field to learn about the magnitude and reason of the outbreak. METHODS: The case definition was that a child with onychomadesis or transverse ridging (Beau's line) in fingernails and toenails without previous traumatic or systemic disease in kindergarten H from Sep. 1st to Nov. 30th, 2017. A retrospective cohort study was carried out to analyze the epidemiological relationship between onychomadesis and the hand-foot-mouth disease (HFMD) in Primary Class #2, kindergarten H. We also performed a serological survey for neutralizing antibodies against coxsackie virus A6 (CVA6), coxsackie virus A10 (CVA10) among 15 cases and six healthy children in the kindergarten. Meanwhile, some children were carried out with routine blood, fungal microscopic and microelement tests. Indoor environment examinations had been done for all classes. RESULTS: A total of 20 cases were identified in Kindergarten H. Seventy-five percent (15/20) cases occurred in Primary Class #2. Fifty-five percent of the cases (11/20) had suffered from HFMD within two months. The median time between onychomadesis and HFMD was 45 days (ranging from 31 to 58 days). A retrospective cohort study in Primary Class #2 showed the attack rate was 90.0% among 10 children who suffered from HFMD in the past two months compared to 30.0% among 20 children who didn't (Rate Ratio [RR] =3.0, 95% Confidence Interval [CI] =1.5-6.0). The positive rates of neutralizing antibodies were 66.7% for CVA6 and 26.7% for CVA10 in tested cases. The result of routine blood, fungal microscopic, microelements tests were normal in cases. The indicators of environment were within the normal range. CONCLUSION: The results of this study suggested that the outbreak of onychomadesis in Hubei province was probably associated with HFMD epidemic within two months.

Development and comparison of forecast models of hand-foot-mouth disease with meteorological factors.

Hand-foot-mouth disease (HFMD) is an acute intestinal virus infectious disease which is one of major public health problems in mainland China. Previous studies indicated that HFMD was significantly influenced by climatic factors, but the associated factors were different in different areas and few study on HFMD forecast models was conducted. Here, we analyzed epidemiological characteristics of HFMD in Yiwu City, Zhejiang Province and constructed three forecast models. Overall, a total of 32554 HFMD cases were reported and 12 cases deceased in Yiwu City, Zhejiang Province. The incidence of HFMD peaked every other year and the curve of HFMD incidence had an approximately W-shape. The majority of HFMD cases were children and 95.76% cases aged ≤5 years old from 2008 to 2016. Furthermore, we constructed and compared three forecast models using autoregressive integrated moving average (ARIMA) model, negative binomial regression model (NBM), and quasi-Poisson generalized additive model (GAM). All the three models had high agreements between predicted values and observed values, while GAM fitted best. The exposure-response curve of monthly mean temperature and HFMD was approximately V-shaped. Our study explored epidemiological characteristics of HFMD in Yiwu City and provided accurate methods for early warning which would be great importance for the control and prevention of HFMD.

Spatial-temporal heterogeneity of hand, foot and mouth disease and impact of meteorological factors in arid/ semi-arid regions: a case study in Ningxia, China.

BACKGROUND: The incidence of hand, foot and mouth disease (HFMD) varies over space and time and this variability is related to climate and social-economic factors. Majority of studies on HFMD were carried out in humid regions while few have focused on the disease in arid/semi-arid regions, more research in such climates would potentially make the mechanism of HFMD transmission clearer under different climate conditions. METHODS: In this paper, we explore spatial-temporal distribution of HFMD in Ningxia province, which has an arid/semi-arid climate in northwest China. We first employed a Bayesian space-time hierarchy model (BSTHM) to assess the spatial-temporal heterogeneity of the HFMD cases and its relationship with meteorological factors in Ningxia from 2009 to 2013, then used a novel spatial statistical software package GeoDetector to test the spatial-temporal heterogeneity of HFMD risk. RESULTS: The results showed that the spatial relative risks in northern part of Ningxia were higher than those in the south. The highest temporal risk of HFMD incidence was in fall season, with a secondary peak in spring. Meteorological factors, such as average temperature, relative humidity, and wind speed played significant roles in the spatial-temporal distribution of HFMD risk. CONCLUSIONS: The study provide valuable information on HFMD distribution in arid/semi-arid areas in northwest China and facilitate understanding of the concentration of HFMD.

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.

Short-Term Effects of Meteorological Factors and Air Pollutants on Hand, Foot and Mouth Disease among Children in Shenzhen, China, 2009-2017.

BACKGROUND: A few studies have explored the association between meteorological factors and hand, foot, and mouth disease (HFMD) with inconsistent results. Besides, studies about the effects of air pollutants on HFMD are very limited. METHODS: Daily HFMD cases among children aged 0-14 years in Shenzhen were collected from 2009 to 2017. A distributed lag nonlinear model (DLNM) model was fitted to simultaneously assess the nonlinear and lagged effects of meteorological factors and air pollutants on HFMD incidence, and to further examine the differences of the effect across different subgroups stratified by gender, age and childcare patterns. RESULTS: The cumulative relative risk (cRR) (median as reference) of HFMD rose with the increase of daily temperature and leveled off at about 30 °C (cRR: 1.40, 95%CI: 1.29, 1.51). There was a facilitating effect on HFMD when relative humidity was 46.0% to 88.8% (cRR at 95th percentile: 1.18, 95%CI: 1.11, 1.27). Short daily sunshine duration (5th vs. 50th) promoted HFMD (cRR: 1.07, 95%CI: 1.02, 1.11). The positive correlation between rainfall and HFMD reversed when it exceeded 78.3 mm (cRR: 1.41, 95% CI: 1.22, 1.63). Ozone suppressed HFMD when it exceeded 104 µg /m3 (cRR at 99th percentile: 0.85, 95%CI: 0.76, 0.94). NO2 promoted HFMD among infants and the cRR peaked at lag 9 day (cRR: 1.47, 95%CI: 1.02, 2.13) (99th vs. 50th). Besides, children aged below one year, males and scattered children were more vulnerable to high temperature, high relative humidity, and short sunshine duration. CONCLUSIONS: Temperature, relative humidity, sunshine duration, rainfall, ozone and NO2 were significantly associated with HFMD, and such effects varied with gender age and childcare patterns. These findings highlight the need for more prevention effort to the vulnerable populations and may be helpful for developing an early environment-based warning system for HFMD.

[Clinical effect of carvedilol in treatment of children with severe hand-foot-mouth disease caused by enterovirus 71 infection].

OBJECTIVE: To study the clinical effect of carvedilol in the treatment of children with severe hand-foot-mouth disease (HFMD) caused by enterovirus 71 (EV71) infection. METHODS: A retrospective analysis was performed for the clinical data of 86 children with severe HFMD caused by EV71 infection who were admitted to the hospital from April 2016 to August 2017. According to whether carvedilol was used, the children were divided into conventional treatment group with 51 children and carvedilol treatment group with 35 children. A total of 56 healthy children who underwent physical examination at the outpatient service during the same period were enrolled as the control group. The two treatment groups were compared in terms of clinical features and levels of catecholamines (norepinephrine, adrenaline and dopamine), and the levels of catecholamines were compared between these two treatment groups and the control group. RESULTS: Before treatment, the conventional treatment group and the carvedilol treatment group had significantly higher levels of norepinephrine and adrenaline than the control group (P<0.05). After treatment, both the conventional treatment group and the carvedilol treatment group had significant reductions in norepinephrine, adrenaline, blood glucose, systolic pressure, diastolic pressure, heart rate, body temperature and leukocyte count (P<0.05). Compared with the conventional treatment group, the carvedilol treatment group had significantly lower dopamine level, blood glucose, heart rate and respiratory rate after treatment (P<0.05). CONCLUSIONS: Changes in norepinephrine and adrenaline might be involved in the pathogenesis of severe HFMD caused by EV71 infection. Carvedilol, in addition to the conventional treatment, can improve respiration, heart rate and blood glucose in children with severe HFMD caused by EV71 infection.

[Review on the etiology and complications of hand, foot and mouth disease, using data from the national sentinel surveillance program, in China, 2015-2016].

Objective: To understand the characteristics relating to the etiology and complications of hand, foot and mouth disease (HFMD) based on data from the pilot National Sentinel Surveillance (NSS) program so as to explore the feasibility, advantages and disadvantages of the NSS. Methods: Data were extracted from the NSS system, conducted in 11 provinces of China from November 2015 to October 2016. Characteristics regarding the etiology, complications of HFMD and factors related to the positive rates of HFMD specimens were analyzed under the logistic regression method by SPSS 20.0 software. Results: A total of 4 783 specimens were collected, including 3 390 from mild, 1 390 from severe and 3 from death cases. The overall positive rate was 81.43% (3 895/4 783). Other enteroviruses (non EV71/Cox A16 enteroviruses) appeared the major serotype (52.68%, 1 482/2 813) for mild infection of the disease while EV71 was for the severe cases (65.31%, 706/1 081). The serotype spectrum revealed by the pilot NSS was almost identical with the existing surveillance system. Other enteroviruses tended to infect younger children (χ(2)=130.17, P<0.001) than EV71 and Cox A16, in China. The multivariate logistic regression results showed that higher positive rate was associated with specimens which were collected from males, at children' hospitals, in peak seasons, timely and in stools. The positive rates presented downwarding trends with the extension of the onset-sampling interval (χ(2)=14.47, P<0.001 in stool specimen; χ(2)=31.99, P<0.001 in throat swab; χ(2)=24.26, P<0.001 in anal swab). Aseptic meningitis, non-brainstem encephalitis and brainstem encephalitis appeared the top three complications of both EV71-associated and other enteroviruses-associated severe HFMD cases. Conclusions: Factors as gender, season/place/timeliness of specimen collection, and types of hospital all appeared independently influenced the positive rates. NSS seemed feasible to be used as an alternative or supplement tool to the existing surveillance program in China.

Enfermedad de mano-pie-boca atípica causada por virus Coxsackie A6 en Argentina, 2015 / Atypical hand, foot, and mouth disease caused by Coxsackievirus A6 in Argentina in 2015

We present two groups of cases of atypical hand, foot, and mouth disease (HFMD) caused by Coxsackievirus A6 (CV-A6) detected in Argentina in 2015. The first group involved 14 patients from Chubut province and the second group affected 12 patients from San Luis province. Molecular analysis of the complete VP1 protein gene revealed the circulation of E2 sublineage, the most predominant worldwide. To our knowledge, this is the first report of CV-A6 infections associated with atypical HFMD in Argentina and South America.

Se describen dos grupos de casos de enfermedad de mano-pie-boca (HFMD) atípica causada por el virus Coxsackie A6 (Coxsackievirus A6, CV-A6) detectados en Argentina en el año 2015. El primero de los grupos involucró a 14 pacientes de Chubut y el segundo a 12 pacientes de San Luis. El análisis molecular del gen de la proteína VP1 completa reveló la circulación del sublinaje E2, el predominante a nivel global. Hasta donde sabemos, este es el primer reporte de infecciones CV-A6 asociadas con HFMD atípica en Argentina y Sudamérica.

Analysis of the effect of PM10 on hand, foot and mouth disease in a basin terrain city.

Hand, foot, and mouth disease (HFMD) is a common childhood infection that causes a substantial disease burden in the Asia-Pacific region. Various climate variables, such as humidity and temperature, have been associated with HFMD. However, few studies have assessed the impact of PM10 on childhood HFMD. This study investigated the association between PM10 and HFMD. We fitted a standard distributed lag non-linear model to investigate the temporal lagged relationship between PM10 and HFMD, and then further assessed whether this relationship varied by gender and pathogen. Between 2011 and 2015, a total of 122,564 HFMD cases under 15 years of age were reported in Chengdu. The PM10-HFMD associations were shown to be non-linear in all subgroups, with the peak at 101-218 µg/m3. Male children were more sensitive to PM10 effects. For pathogen-specific relative risks, we found that the risk estimates were generally higher in cases of CVA16 infection. Our study provides evidence that PM10 increases the risk of HFMD. Authorities and parents should be fully aware of the impact of PM10 on childhood HFMD. Furthermore, appropriate protective measures should be taken to reduce risks.

Profiles of Human Enteroviruses Associated with Hand, Foot, and Mouth Disease in Nanjing, China.

OBJECTIVE: Hand, foot, and mouth disease (HFMD) is a common infectious disease caused by a group of viruses. The causative viruses have changed over time, and there is a need for a more effective protective vaccine. In this study, we investigated the profiles of human enteroviruses that caused HFMD outbreaks in Nanjing in 2015, with the goal of guiding the future prevention and treatment of HFMD. METHODS: Specimens were collected from 1097 patients admitted to our hospital and diagnosed with HFMD. Enteroviruses in the specimens were identified by real-time polymerase chain reaction and epidemiological patterns were analyzed with the clinical data. RESULTS: Among the 1097 clinically diagnosed HFMD cases, 916 cases were confirmed by laboratory tests. The results showed that the main infectious virus was coxsackievirus A6 (CVA6) (41.75%), followed by enterovirus 71 (EV71) (27.48%), coxsackievirus A16 (7.43%), coxsackievirus A10 (6.84%), and others (16.51%). Further investigation indicated that CVA6 caused mild cases of HFMD, while EV71 caused severe cases. More enterovirus positive cases were reported from rural areas than from urban areas. CONCLUSIONS: CA6 and EV71 were the chief pathogenic viruses of HFMD cases in the present study. Schools, childcare centers, and families from rural areas should be the major targets for prevention and awareness of HFMD. This study will provide information useful in the prevention and management of HFMD and the development of relevant vaccines for HFMD in the future. (Disaster Med Public Health Preparedness. 2019;13:740-744).

Developing a Nomogram for Risk Prediction of Severe Hand-Foot-and-Mouth Disease in Children.

OBJECTIVE: Early recognition of children with severe Hand-Foot-and-Mouth disease (HFMD) is especially important, as severe cases are associated with poor prognosis. To accomplish this, authors designed a quantitative assessment tool to build a nomogram to assist in clinical diagnosis. METHODS: A total of 2332 HFMD patients were enrolled in this study; 1750 cases in the mild group and 582 cases in the severe group. Analysis of all of the data was performed using R software version 3.4.3. Multivariate logistic regression was utilized to screen predictors to construct a nomogram model. Finally, predictive performance of the model was evaluated using a receiver operating characteristic (ROC) curve and classifier calibration plot. RESULTS: A nomogram was constructed with five variables: age, peak temperature, fever duration, pathogen, and vomiting. For the nomogram, the area under the curve was 0.87, and the model prediction accuracy rate was 85.2%. Depending upon the comparison of the area under the ROC curve, the nomogram model was superior to the traditional pediatric clinical illness score (PCIS). With the help of the Hosmer-Lemeshow test and resampling model calibration curve, the fitting performance of the nomogram was stable. CONCLUSIONS: With advantages such as simplicity, intuitiveness, and practicality, the nomogram (including age, peak temperature, fever duration, pathogen, and vomiting) is capable of predicting severe HFMD and has certain auxiliary value in clinical applications.

Ongoing change of severe hand, foot, and mouth disease pathogens in Yunnan, China, 2012 to 2016.

Hand, foot, and mouth disease (HFMD) is a common infectious disease caused by enteroviruses (EVs). In this study, a total of 341 children with serious HFMD were admitted to a pediatric hospital in Yunnan, China in 2012 to 2016. EVs were detected in 283 specimens (83.0%) and were assigned to 17 EV types. Enterovirus A71 (EV-A71) was predominant, accounting for 41.6%, and was followed by coxsackievirus A16 (CV-A16; 18.8%), CV-A6 (9.1%), CV-A10 and E-9 (2.9%), CV-B5 (1.8%), CV-A9 (1.2%), E-30 (0.9%), E-18, CV-A4, C-B3, and CV-A2 (0.6%) and other EV types such as CV-A8, CV-A14, E-14, E-11, and CV-B4 (0.3%). All of the EV-A71 isolates belonged to C4a; the CV-A16 belonged to B1b or B1a, although the B1b strains were predominant; and CV-A6 belonged to D3. In 2012 to 2014, E-9 was the third most frequent serotype (8.2%, 5.0%, and 6.5%, respectively). E-9 was not detected in 2015 and 2016. CV-A6 was not detected in 2012 but was the second most frequent serotype (25.3%) in 2015. Active etiological surveillance of HFMD makes it necessary to be aware of these emerging pathogens.

Surveillance for severe hand, foot, and mouth disease from 2009 to 2015 in Jiangsu province: epidemiology, etiology, and disease burden.

BACKGROUND: Severe hand, foot, and mouth disease (HFMD) is a common childhood illness caused by various enteroviruses. The disease has imposed increased burden on children younger than 5 years old. We aimed to determine the epidemiology, CNS complication, and etiology among severe HFMD patients, in Jiangsu, China. METHODS: Epidemiological, clinical, and laboratory data of severe HFMD cases were extracted from 2009 to 2015. The CNS complication, annually severe illness rates, mortality rates, severity-PICU admission rates, severity-hospitalization rates, and so on were analyzed to assess the disease burden of severe HFMD. All analyses were stratified by time, region, population, CNS involvement and serotypes. The VP1 gene from EV-A71, CV-A16, CV-A6, CV-A10 and other enteroviruses isolates was amplified. Phylogenetic analysis was performed using MEGA5.0. RESULTS: Seven thousand nine hundred ninety-four severe HFMD cases were reported, of them, 7224 cases were inpatients, 611 were PICU inpatients, and 68 were fatal. The average severe illness rate, mortality rate, severity-fatality rate, severity-PICU admission rate, and severity-hospitalization rate were 14.54, 0.12,8506, 76,430, and 903,700 per 1 million, respectively. The severe illness rate was the highest in the 12-23 months age group, and the greatest mortality rate was in the 6-11 months age group. Geographical difference in severe illness rate and mortality were found. Patients infected with EV-A71 were at a higher proportion in different CNS involvement even death. EV-A71, CV-A16 and other enteroviruses accounted for 79.14, 6.49, and 14.47%, respectively. A total of 14 non-EV-A71/ CV-A16 genotypes including CV-A2, CV-A4, CV-A 6, CV-A9, CV-A10, CV-B1, CV-B2, CV-B3, CV-B4, CV-B5, E-6, E-7, E-18, and EV-C96 were identified. Phylogentic analyses demonstrated that EV-A71 strains belonged to subgenotype C4a, while CV-A16 strains belonged to sub-genotype B1a and sub-genotype B1b of genotype B1. CV-A6 strains were assigned to genogroup F, and CV-A10 strains belonged to genogroup D. CONCLUSIONS: Future mitigation policies should take into account the age, region heterogeneities, CNS conditions and serotype of disease. Additional a more rigorous study between the mild and severe HFMD should be warranted to elucidate the difference epidemiology, pathogen spectrum and immunity patterns and to optimize interventions in the following study.

Genetic characteristics of the P1 coding region of Coxsackievirus A16 associated with hand, foot, and mouth disease in China.

Coxsackievirus A16 (CVA16) is one of the major etiological agents of hand, foot, and mouth disease (HFMD) in young children. To investigate the genetic characteristics of the P1 coding region gene of CVA16 associated with HFMD in China, we included the sequences of CVA16 specimens obtained from outbreak investigations and sporadic HFMD cases between 1998 and 2014 in China from GenBank, we genotyped the CVA16 sequences and analyzed P1 coding region sequences that encode structural proteins with bioinformatics software. CVA16 was classified into genotypes A and B1 based on the VP1 gene; the B1b and B1a subgenotypes were the major CVA16 strains and predominated in the coastal areas of China. Four strains were found to show inter- and intra-typic recombination in the P1 region. The amino acid identities of VP1, VP2, VP3, and VP4 proteins in all Chinese CVA16 strains were 88.2-100%, 83.0-100%, 87.6-100%, and 72.4-100%, respectively. A total of 251 amino acid substitution sites were detected in the structural proteins encoded by the P1 coding region gene. The amino acid sequences of the P1 coding region in Chinese CVA16 strains were highly conserved, although some amino acid mutations occurred with high frequency: VP1-T11A (10%), N14S (14%), L23M/V (11%), T98M (16%), V107A (14%), N102D (6.1%), E145V (8.8%), N218D (10%), E241K (22%), T248A/I (6.8%); VP2-I217V (22%), T226A (38%); VP3-N141S/G (5.4%), and N240D (15%). The genetic characteristics of CVA16 in the P1 coding region gene may provide a basis for developing a CVA16 vaccine and preventing and controlling HFMD in China.

Características clínico epidemiológicas de pacientes pediátricos con enfermedad boca, mano, pie / Clinical epidemiological characteristics of pediatric patients with mouth, hand and foot disease

Introducción: la enfermedad boca, mano, pie es una enfermedad febril eruptiva provocada por la infección por los virus Coxsackie, consistente en fiebre, exantema pápulo-vesicular en las manos, los pies y un enantema ulceroso en la boca. Objetivos: indagar la etiología viral y describir las características clínico epidemiológicas de la entidad. Métodos: estudio descriptivo prospectivo en 54 pacientes menores de 18 años, diagnosticados con la enfermedad boca, mano, pie, atendidos en el Hospital Pediátrico Docente del Cerro, de septiembre a noviembre de 2017. Se incluyeron aquellos con lesiones vesiculares o pápulas vesiculares, distribuidas en la piel y úlceras en la mucosa oral; y se excluyeron los pacientes con otras entidades exantemáticas o vesiculares. Las variables investigadas resultaron: la edad, el sexo, los signos, los síntomas clínicos de infección, el leucograma y el estudio virológico. La selección de la muestra fue de manera no probabilística consecutiva. Los datos se procesaron por el paquete estadístico XLSTAT con análisis univariado. Resultados: el grupo entre 1-3 años obtuvo 53,7 por ciento, y el sexo masculino el 68,5 por ciento. Las lesiones cutáneas fueron más frecuentes en la cara, las extremidades, los glúteos y el tronco (68,6 por ciento), seguido de la zonas de la cara, las extremidades y el tronco (29,6 por ciento). El enantema fue apreciado en el 48,1 por ciento, la fiebre en el 61,1 por ciento, la fiebre más secreción nasal en el 44,4 por ciento y el prurito en el 70,3 por ciento. El conteo leucocitario alcanzó 11,1 x 109 células. Los polimorfonucleares obtuvieron promedio de 37,9 y los linfocitos 70,3. En 49 de los 54 pacientes se aisló el virus Coxsackie A6. Conclusiones: se describe la enfermedad boca, mano, pie en forma atípica, cuyo cuadro clínico coincide con lo aparecido en la literatura(AU)

Introduction: mouth, hand and foot disease is an eruptive febrile illness caused by the infection of Coxsackie viruses, and it consists in fever, papulo-vesicular exanthema in the hands, feet and an ulcer enanthema in the mouth. Objectives: to investigate the viral etiology and describe the clinical epidemiological characteristics of the entity. Methods: prospective descriptive study in 54 patients under 18 years old diagnosed with mouth, hand and foot disease, and whom were attended at the Pediatric Teaching Hospital of Cerro from September to November 2017. Those with vesicular lesions or vesicular papules distributed in the skin, and ulcers in the oral mucosa were included in the research; and patients with other exanthematic or vesicular entities were excluded. The variables investigated were: age, sex, signs, clinical symptoms of infection, leukogram and virological study. The selection of the sample was consecutive non-probabilistic. The data was processed by the XLSTAT statistical package with univariate analysis. Results: the group from 1 to 3 years old represented the 53.7 percent, and the male sex the 68.5 percent y. Skin lesions were more frequent on the face, extremities, buttocks and trunk (68.6 percent), followed by facial, limbs and trunk areas (29.6 percent). Enanthem was visible in 48.1 percent, and fever appeared in 61.1 percent, fever plus nasal discharge in 44.4 percent and itching in 70.3 percent y The leukocyte count reached 11.1 x 109 cells. Polymorphonuclear cells obtained an average of 37.9 and lymphocytes of 70.3. In 49 of the 54 patients the Coxsackie A6 virus was isolated. Conclusions: mouth, hand, and foot disease is described in an atypical form, whose clinical manifestations coincide with what appeared in the literature(AU)

Spatio-temporal analysis of the relationship between meteorological factors and hand-foot-mouth disease in Beijing, China.

BACKGROUND: Hand-foot-mouth disease (HFMD) is a common infectious disease in China and occurs mostly in infants and children. Beijing is a densely populated megacity, in which HFMD has been increasing in the last decade. The aim of this study was to quantify spatio-temporal characteristics of HFMD and the relationship between meteorological factors and HFMD incidence in Beijing, China. METHODS: Daily counts of HFMD cases from January 2010 to December 2012 were obtained from the Beijing Center for Disease Prevention and Control (CDC). Seasonal trend decomposition with Loess smoothing was used to explore seasonal patterns and temporal trends of HFMD. Bayesian spatiotemporal Poisson regression models were used to quantify spatiotemporal patterns of HFMD incidence and associations with meteorological factors. RESULTS: There were 114,777 HFMD cases reported to Beijing CDC from 1 January 2010 to 31 December 2012 and the raw incidence was 568.6 per 100,000 people. May to July was the peak period of HFMD incidence each year. Low-incidence townships were clustered in central, northeast and southwest regions of Beijing. Mean temperature, relative humidity, wind velocity and sunshine hours were all positively associated with HFMD. The effect of wind velocity was significant with a RR of 3.30 (95%CI: 2.37, 4.60) per meter per second increase, as was sunshine hours with a RR of 1.20 (95%CI: 1.02, 1.40) per 1 hour increase. CONCLUSIONS: The distribution of HFMD in Beijing was spatiotemporally heterogeneous, and was associated with meteorological factors. Meteorological monitoring could be incorporated into prediction and surveillance of HFMD in Beijing.

Impact of meteorological factors on the incidence of childhood hand, foot, and mouth disease (HFMD) analyzed by DLNMs-based time series approach.

BACKGROUND: Hand, foot, and mouth disease (HFMD) has become an emerging infectious disease in China in the last decade. There has been evidence that meteorological factors can influence the HFMD incidence, and understanding the mechanisms can help prevent and control HFMD. METHODS: HFMD incidence data and meteorological data in Minhang District, Shanghai were obtained for the period between 2009 and 2015. Distributed lag non-linear models (DLNMs) were utilized to investigate the impact of meteorological factors on HFMD incidence after adjusting for potential confounders of long time trend, weekdays and holidays. RESULTS: There was a non-linear relationship between temperature and HFMD incidence, the RR of 5th percentile compared to the median is 0.836 (95% CI: 0.671-1.042) and the RR of 95th percentile is 2.225 (95% CI: 1.774-2.792), and the effect of temperature varied across age groups. HFMD incidence increased with increasing average relative humidity (%) (RR = 1.009, 95% CI: 1.005-1.015) and wind speed (m/s) (RR = 1.197, 95% CI: 1.118-1.282), and with decreasing daily rainfall (mm) (RR = 0.992, 95% CI: 0.987-0.997) and sunshine hours (h) (RR = 0.966, 95% CI: 0.951-0.980). CONCLUSIONS: There were significant relationships between meteorological factors and childhood HFMD incidence in Minhang District, Shanghai. This information can help local health agencies develop strategies for the control and prevention of HFMD under specific climatic conditions.