Effectiveness of Enterovirus 71 inactivated vaccines against hand, foot, and mouth disease: A test-negative case-control study.

The Enterovirus A71 (EV-A71) vaccine was introduced in China in December 2015 as a preventive measure against hand, foot, and mouth disease (HFMD) caused by EV-A71. However, the effectiveness of the vaccine (VE) in real-world settings needs to be evaluated. We conducted a test-negative case-control study to assess the effectiveness of EV-A71 vaccines in preventing EV-A71-associated HFMD. Children aged 6-71 months with HFMD were enrolled as participants. The case group comprised those who tested positive for EV-A71, while the control group comprised those who tested negative for EV-A71. To estimate VE, a logistic regression model was employed, adjusting for potential confounders including age, gender, and clinical severity. In total, 3223 children aged 6 to 71 months were included in the study, with 162 in the case group and 3061 in the control group. The proportion of children who received EV-A71 vaccination was significantly lower in the case group compared to the control group (p < .001). The overall VEadj was estimated to be 90.8%. The VEadj estimates for partially and fully vaccinated children were 90.1% and 90.9%, respectively. Stratified by age group, the VEadj estimates were 88.7% for 6 to 35-month-olds and 95.5% for 36 to 71-month-olds. Regarding disease severity, the VEadj estimates were 86.3% for mild cases and 100% for severe cases. Sensitivity analysis showed minimal changes in the VE point estimates, with most changing by no more than 1% point. Our study demonstrates a high level of vaccine effectiveness against EV-A71-HFMD, especially in severe cases. Active promotion of EV-A71 vaccination is an effective strategy in preventing EV-A71 infections.

Circular-target-style bifocal zoom metalens.

Optical zoom plays an important role in realizing high-quality image magnification, especially in photography, telescopes, microscopes, etc. Compared to traditional bulky zoom lenses, the high versatility and flexibility of metalens design provide opportunities for modern electronic and photonic systems with demands for miniature and lightweight optical zoom. Here, we propose an ultra-thin, lightweight and compact bifocal zoom metalens, which consists of a conventional circular sub-aperture and a sparse annular sub-aperture with different focal lengths. The imaging resolutions of such single zoom metalens with 164 lp/mm and 117 lp/mm at magnifications of 1× and 2× have been numerically and experimentally demonstrated, respectively. Furthermore, clear zoom images of a dragonfly wing pattern have been also achieved using this zoom metalens, showing its distinctive aspect in biological imaging. Our results provide an approach for potential applications in integrated optical systems, miniaturized imaging devices, and wearable devices.

Metabolome of flue-cured tobacco is significantly affected by the presence of leaf stem.

BACKGROUND: Leaves of tobacco (Nicotiana tabacum L.) are flue-cured to use as a key industrial supply in various parts of the world. The quality of tobacco leaves is dependent on chemical components and their proportions. Generally, the stem attached to tobacco leaf is detached before curing. However, the leaf stem remains green for an extended period of time (as compared to leaf) during flue-curing. Hence, it is expected to affect the quality of tobacco's final product. RESULTS: To understand the impact of the green stem of leaf on the metabolome of flue-cured tobacco, we employed a broad targeted metabolomics approach. We selected two tobacco cultivars (Yun87 and K326) and cultivated them in five geographic locations in China. For flue-curing, leaves were harvested without a stem (L) or with an attached stem (SPL). After metabolome analysis, a total of 1027 metabolites were annotated in these samples. A variable number of metabolites were differentially accumulated between both types of leaves (depending on geographic location or cultivar) representing an influence of environment or genotype. Interestingly, only 68 metabolites were differentially accumulated between L and SPL samples irrespective of the cultivar or geographic location. These differentially accumulated metabolites belonged to major groups of primary and secondary metabolites. We have discussed the importance of identified metabolites in terms of carbon, nitrogen, and polyphenolic metabolism. CONCLUSION: The present research is the first comprehensive description of several metabolites in tobacco leaves related to the contribution of leaf stem. The current study opens novel prospects for investigating the potential of such metabolites in improving the quality of flue-cured tobacco.

Seroepidemiology of enterovirus A71 infection in prospective cohort studies of children in southern China, 2013-2018.

Enterovirus A71 (EV-A71)-related hand, foot, and mouth disease (HFMD) imposes a substantial clinical burden in the Asia Pacific region. To inform policy on the introduction of the EV-A71 vaccine into the National Immunization Programme, we investigated the seroepidemiological characteristics of EV-A71 in two prospective cohorts of children in southern China conducted between 2013 and 2018. Our results show that maternal antibody titres declined rapidly in neonates, with over half becoming susceptible to EV-A71 at 1 month of age. Between 6 months and 2 years of age, over 80% of study participants were susceptible, while one third remained susceptible at 5 years old. The highest incidence of EV-A71 infections was observed in children aged 5-6 months. Our findings support EV-A71 vaccination before 6 months for birth cohorts in southern China, potentially with a one-time catch-up vaccination for children 6 months-5 years old. More regionally representative longitudinal seroepidemiological studies are needed to further validate these findings.

Application of Ultrasound Combined with Magnetic Resonance Imaging in the Diagnosis and Grading of Patients with Prenatal Placenta Accreta.

In order to study the clinical application value of placenta accreta (PIA) diagnosis and grading, the authors propose a method based on ultrasound combined with magnetic resonance imaging in the diagnosis and grading of prenatal placenta accreta patients. This method is adopted in materials and methods: a retrospective analysis of hospital patients with high suspicion of placenta accreta by clinical or ultrasonography between October 2019 and October 2021, the imaging and clinical data of 312 patients who underwent placental MRI examination. The MRI imaging data of all patients were jointly analyzed, and the main observation indicators are as follows: (1) dark zone in the placenta, (2) disruption of the border of the myometrium, (3) disruption of the myometrium, (4) abnormal blood vessels in the placenta, (5) enlargement of the lower part of the uterus, and (6) local bulge of the bladder/or invasion of the adjacent tissues of the uterus. The results show the following: in MRI combined with ultrasonography (P < 0.05), there was no statistical significance in the specificity and accuracy of MRI combined with ultrasound to diagnose PIA (P > 0.05). The comparison of graded diagnostic accuracy showed that in ultrasound alone < MRI alone < MRI combined with ultrasound, the differences were statistically significant (P < 0.05). Ultrasound combined with MRI in the diagnosis of placenta accreta is in good agreement with the clinical and surgical pathological results; MRI examination can be used as an important method for prenatal placenta accreta screening. MRI can classify placenta accreta to some extent.

An Experimental Investigation of the Effect of Platinum on the Corrosion of Cathode Carbon Support in a PEMFC.

The possible role of platinum in the carbon corrosion at cell voltage higher than 1.0 V is controversial yet. To gain more insights into this issue, a square-wave potential cycles between 1.0 to 1.5 V was applied to fuel cells comprising cathodes with and without Pt. Using online non-dispersive infrared spectroscopy, we showed that Pt catalyzed the gasification of carbon in the early stage, while upon prolonged exposure to potential cycling (≥3 h), platinum started to hinder the CO2 production. Based on cyclic voltammetry tests and Raman spectroscopy, the inhibiting effect of platinum on the corrosion was suggested to originate from modifications on carbon surface, where the formation of electroactive sites was limited. Electrode and non-electrode ohmic resistances were distinguished further through electrochemical impedance spectroscopy measurement and the changes in electrode microstructure and surface composition were examined by scanning electron microscope image and energy dispersion X-Ray spectroscopy. The results indicated that Pt reduced the damage of electrode structures after potential cycles.

Impact of the coronavirus disease 2019 interventions on the incidence of hand, foot, and mouth disease in mainland China.

BACKGROUND: In early 2020, non-pharmaceutical interventions (NPIs) were implemented in China to reduce and contain the coronavirus disease 2019 (COVID-19) transmission. These NPIs might have also reduced the incidence of hand, foot, and mouth disease (HFMD). METHODS: The weekly numbers of HFMD cases and meteorological factors in 31 provincial capital cities and municipalities in mainland China were obtained from Chinese Center for Disease Control and Prevention (CCDC) and National Meteorological Information Center of China from 2016 to 2020. The NPI data were collected from local CDCs. The incidence rate ratios (IRRs) were calculated for the entire year of 2020, and for January-July 2020 and August-December 2020. The expected case numbers were estimated using seasonal autoregressive integrated moving average models. The relationships between kindergarten closures and incidence of HFMD were quantified using a generalized additive model. The estimated associations from all cities were pooled using a multivariate meta-regression model. FINDINGS: Stringent NPIs were widely implemented for COVID-19 control from January to July 2020, and the IRRs for HFMD were less than 1 in all 31 cities, and less than 0·1 for 23 cities. Overall, the proportion of HFMD cases reduced by 52·9% (95% CI: 49·3-55·5%) after the implementation of kindergarten closures in 2020, and this effect was generally consistent across subgroups. INTERPRETATION: The decrease in HFMD incidence was strongly associated with the NPIs for COVID-19. HFMD epidemic peaks were either absent or delayed, and the final epidemic size was reduced. Kindergarten closure is an intervention to prevent HFMD outbreaks. FUNDING: This research was supported by the National Natural Science Foundation of China (81973102 & 81773487), Public Health Talents Training Program of Shanghai Municipality (GWV-10.2-XD21), the Shanghai New Three-year Action Plan for Public Health (GWV-10.1-XK16), the Major Project of Scientific and Technical Winter Olympics from National Key Research and Development Program of China (2021YFF0306000), 13th Five-Year National Science and Technology Major Project for Infectious Diseases (2018ZX10725-509) and Key projects of the PLA logistics Scientific research Program (BHJ17J013).

Changing epidemiology of hand, foot, and mouth disease in China, 2013-2019: a population-based study.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is an important public health problem. A monovalent EV-A71 vaccine was launched in China in 2016. Previous studies showed that inactivated monovalent EV-A71 vaccines were highly efficient against HFMD associated with EV-A71 but not against HFMD with other etiologies, leading to a hypothesis that the introduction of EV-A71 vaccines might change the pathogen spectrum and epidemiological trend of HFMD. In this study, we described for the first time the changing epidemiological characteristics of HFMD after the launch of the EV-A71 vaccine. METHODS: We extracted individual-based epidemiological data on HFMD cases reported to the Chinese Center for Disease Control and Prevention between January 2013 and December 2019. We described the changing epidemiological characteristics of HFMD before and after vaccine launch according to the distribution of diseases characteristics (demographic, temporal, and geographical) and evaluated the potential changes in risk factors of severe patients. All analyses were stratified by the phase before and after vaccine launch, and by enterovirus serotype. FINDINGS: During 2013-2019, 15,316,710 probable cases of HFMD were reported. Of these, 787,197 (5·1%) were laboratory confirmed and 76,982 (0·5%) were severe. After the launch of the EV-A71 vaccine, the median age of HFMD patients infected with EV-A71 increased from 2·24 years (IQR:1·43, 3·56) to 2·81 years (IQR:1·58, 4·01). The proportion of patients less than 3 years of age decreased while the proportion of patients 3-5 years of age increased. There was a large decrease (60·7%) in the proportion of severe cases as well as a decline (28·3%) in HFMD patients infected with EV-A71. After the launch of the EV-A71 vaccine, the severe illness rate and mortality rate of HFMD patients in all age groups has decreased sharply, 62·20% and 83·78% respectively. The timing of the HFMD epidemic peak was delayed (1-2 months) . After the launch of EV-A71 vaccine, the risk of becoming a severe case for EV-A71 serotype was decreased, whereas that risk was instead increased for CV-A16 (from 0·17 (95% CI:0·16, 0·18) to 0·23 (95% CI:0·21, 0·25)) and other enterovirus compared to EV-A71 (from 0·38 (95% CI:0·37, 0·39) to 0·58 (95% CI:0·56, 0·61)). The longer the time from onset to diagnosis, the higher was the risk of being a severe case, but the effect size was decreased. INTERPRETATION: The introduction of the EV-A71 vaccine has effectively reduced the proportion of severe HFMD cases and mortality, but changes to the dominant serotypes should be closely monitored. Development of multivalent vaccines to avoid an increased case burden due to other enteroviruses is greatly needed. FUNDING: This research was supported by the National Natural Science Foundation of China (81973102, 81773487), Public Health Talents Training Program of Shanghai Municipality (GWV-10.2-XD21), the 5th Three-year Action Program of Shanghai Municipality for Strengthening the Construction of Public Health System (GWV-10.1-XK05), the Major Project of Scientific and Technical Winter Olympics from National Key Research and Development Program of China (2021YFF0306000), 13th Five-Year National Science and Technology Major Project for Infectious Diseases (2018ZX10725-509) and Key projects of the PLA logistics Scientific research Program (BHJ17J013).

Parametric characteristics analysis of three cells in 3D and five-directional annular braided composites.

On the basis of analyzing the movement law of 3D circular braided yarn, the three-cell model of 3D five-direction circular braiding composite material is established. By analyzing the node position relationship in various cell models, the calculation formulas of braiding angle, cell volume, fiber volume and fiber volume content in various cell models are obtained. It is found that there are four different braiding angles in four internal cells, and the braiding angles in internal cells gradually increase from inside to outside. The braiding angles of upper and lower surface cells are approximately equal. With the increase of the length of the knuckles, the braiding angles of each cell decrease, and the braiding angles of the four inner cells decrease greatly, while the braiding angles of upper and lower surfaces decrease slightly. The results of parametric analysis showed that with the increase of the length of the knuckles and the inner diameter of cells, the mass of cells increased proportionally, while the total fiber volume content of cells decreased. With the increase of braiding yarn number and axial yarn number, the unit cell mass decreases in direct proportion, and the unit cell total fiber volume content increases. Through the research results of this paper, the geometrical characteristics of the cell model under different braided parameters can be obtained, which greatly improves the analysis efficiency.

CIRP Secretion during Cardiopulmonary Bypass Is Associated with Increased Risk of Postoperative Acute Kidney Injury.

BACKGROUND: Systemic inflammation contributes to cardiac surgery-associated acute kidney injury (AKI). Cardiomyocytes and other organs experience hypothermia and hypoxia during cardiopulmonary bypass (CPB), which induces the secretion of cold-inducible RNA-binding protein (CIRP). Extracellular CIRP may induce a proinflammatory response. MATERIALS AND METHODS: The serum CIRP levels in 76 patients before and after cardiac surgery were determined to analyze the correlation between CIRP levels and CPB time. The risk factors for AKI after cardiac surgery and the in-hospital outcomes were also analyzed. RESULTS: The difference in the levels of CIRP (ΔCIRP) after and before surgery in patients who experienced cardioplegic arrest (CA) was 26-fold higher than those who did not, and 2.7-fold of those who experienced CPB without CA. The ΔCIRP levels were positively correlated with CPB time (r = 0.574, p < 0.001) and cross-clamp time (r = 0.54, p < 0.001). Multivariable analysis indicated that ΔCIRP (odds ratio: 1.003; 95% confidence interval: 1.000-1.006; p = 0.027) was an independent risk factor for postoperative AKI. Patients who underwent aortic dissection surgery had higher levels of CIRP and higher incidence of AKI than other patients. The incidence of AKI and duration of mechanical ventilation in patients whose serum CIRP levels more than 405 pg/mL were significantly higher than those less than 405 pg/mL (65.8 vs. 42.1%, p = 0.038; 23.1 ± 18.2 vs. 13.8 ± 9.2 hours, p = 0.007). CONCLUSION: A large amount of CIRP was released during cardiac surgery. The secreted CIRP was associated with the increased risk of AKI after cardiac surgery.

Factors influencing the adhesive behavior of carboxymethyl cellulose-based hydrogel for food applications.

Carboxymethyl cellulose (CMC) hydrogels have been used as adhesive materials for food and other newly emerged innovative applications. To increase the knowledge of CMC hydrogel-based adhesives and optimize the preparation and storage conditions in practical, we prepared CMC hydrogels for cigar wrapper application and investigated their adhesive performance as affected by different CMC type, concentration, pH, temperature, and storage time, etc. Two parameters, initial adhesiveness and peel strength were used to evaluate the adhesive behavior of CMC with paper and tobacco leaf. Sample C2 with relatively medium molecular weight and medium degree of substitution values showed the best adhesive performance. Hydrogels prepared using boiled water at neutral pH presented better adhesive behavior, which was not significantly affected by storage temperature (up to 13 days). The wettability, steady shear flow behavior, dynamic rheological properties, and stress recovery performance of CMC hydrogel were measured, and their correlations to the adhesive behavior were discussed.

Assessing Asymptomatic, Presymptomatic, and Symptomatic Transmission Risk of Severe Acute Respiratory Syndrome Coronavirus 2.

BACKGROUND: The relative contributions of asymptomatic, presymptomatic, and symptomatic transmission of severe acute respiratory syndrome coronavirus 2 have not been clearly measured, although control measures may differ in response to the risk of spread posed by different types of cases. METHODS: We collected detailed information on transmission events and symptom status based on laboratory-confirmed patient data and contact tracing data from 4 provinces and 1 municipality in China. We estimated the variation in risk of transmission over time and the severity of secondary infections by symptomatic status of the infector. RESULTS: There were 393 symptomatic index cases with 3136 close contacts and 185 asymptomatic index cases with 1078 close contacts included in the study. The secondary attack rates among close contacts of symptomatic and asymptomatic index cases were 4.1% (128 of 3136) and 1.1% (12 of 1078), respectively, corresponding to a higher transmission risk from symptomatic cases than from asymptomatic cases (odds ratio, 3.79; 95% confidence interval, 2.06-6.95). Approximately 25% (32 of 128) and 50% (6 of 12) of the infected close contacts were asymptomatic from symptomatic and asymptomatic index cases, respectively, while more than one third (38%) of the infections in the close contacts of symptomatic cases were attributable to exposure to the index cases before symptom onset. CONCLUSIONS: Asymptomatic and presymptomatic transmissions play an important role in spreading infection, although asymptomatic cases pose a lower risk of transmission than symptomatic cases. Early case detection and effective test-and-trace measures are important to reduce transmission.

Coronary computed tomography angiography before on-pump cardiac surgery does not reduce the risk of postoperative acute kidney injury compared to coronary angiography.

OBJECTIVES: Cardiac surgery and contrast media are both related to acute kidney injury. We investigated whether undergoing coronary computed tomography angiography, which uses less contrast medium, before on-pump cardiac surgery could reduce the risk of postoperative acute kidney injury compared to coronary angiography. METHODS: In this retrospective study, 745 and 171 patients underwent coronary angiography and coronary computed tomography angiography, respectively, within 30 days before on-pump cardiac surgery. Postoperative acute kidney injury was defined according to Kidney Disease Improving Global Outcomes Definition and Staging criteria. RESULTS: Age, hypertension, cardiopulmonary bypass time, and performing cardiac surgery within 24 h of preoperative angiography (odds ratio: 1.507, 95% confidence interval: 1.111‒2.045, P = 0.008) independently predicted postoperative acute kidney injury on multivariable analysis. After propensity score matching, the acute kidney injury incidence in coronary angiography and computed tomography angiography groups was 43% and 46%, respectively (P = 0.65), and the groups had similar intensive care unit stay (2 days vs. 2 days, P = 0.209), postoperative hospital stay (11 days vs. 12 days, P = 0.084), postoperative continuous renal replacement therapy use (0.6% vs 1.9%, P = 0.314), and in-hospital mortality (0 vs. 1.3%, P = 0.156). In-hospital outcomes were similar among patients who underwent preoperative coronary angiography or computed tomography angiography within 24 h before cardiac surgery. CONCLUSION: Although coronary computed tomography angiography uses less contrast medium, it does not reduce the risk of postoperative acute kidney injury or improve in-hospital outcomes compared to coronary angiography.

[Development of Liver Normothermic Machine Perfusion Repair and Assessment System].

This paper introduced a liver normothermic machine perfusion repair and assessment system. This system consists of a liver normothermic machine perfusion device, a fluorescence imaging system and a tissue oxygen detector. The normothermic machine perfusion device can continuously perfuse the donor liver and monitor and control the perfusion parameters in real time. The fluorescence imaging system can detect the indocyanine green metabolized by the liver to evaluate the microcirculation and the metabolism function of hepatocytes. The tissue oxygen detector can monitor the change of oxygen partial pressure of liver tissue in real time to evaluate the state of cell oxygen consumption.

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.

The transfer and decay of maternal antibodies against enterovirus A71, and dynamics of antibodies due to later natural infections in Chinese infants: a longitudinal, paired mother-neonate cohort study.

BACKGROUND: Since 1997, epidemics of hand, foot, and mouth disease associated with enterovirus A71 (EV-A71) have affected children younger than 5 years in the Asia-Pacific region, including mainland China. EV-A71 vaccines have been licensed for use in children aged 6-71 months in China, but not for infants younger than 6 months. We aimed to assess the dynamics of maternal EV-A71 antibodies to inform choice of potential vaccination strategies to protect infants younger than 6 months, because they have a substantial burden of disease. METHODS: We did a longitudinal cohort study with mother-neonate pairs in local hospitals in southern China during 2013-18. We collected cord blood from neonates and venous blood from mothers at delivery. We followed up and collected blood samples from the children at ages 2, 4, 6, 12, 24, and 36 months and tested for the presence of neutralising antibodies against EV-A71 with virus neutralisation assays. Seropositivity, or protective titre, was defined as a neutralisation antibody titre of 16 or higher. We estimated the seroprevalence, geometric mean titre (GMT), and transfer ratio of maternal antibodies. We used a binomial distribution to derive the 95% CIs of seroprevalence. Seropositivity between mothers and neonates was compared by use of an agreement (κ), while GMTs were compared by use of paired Student's t tests. FINDINGS: Between Sept 20, 2013, and Oct 14, 2015, 1054 mothers with 1066 neonates were enrolled. The EV-A71 GMT was similar among pairs of neonates (22·7, 95% CI 20·8-24·9) and mothers (22·1, 95% CI 20·2-24·1; p=0·20). The mean transfer ratio of maternal antibodies was 1·03 (95% CI 0·98-1·08). Although 705 (66%) of 1066 neonates acquired protective concentrations of EV-A71 antibodies from mothers, these declined rapidly, with a half-life of 42 days (95% CI 40-44). The time to loss of protective immunity was extended to 5 months in neonates with mothers who had titres of 128 or higher. By age 30 months, 28% of children had become seropositive because of natural infection. INTERPRETATION: EV-A71 maternal antibodies were efficiently transferred to neonates, but declined quickly to below the protective threshold, particularly among those whose mothers had low antibody titres. Our findings suggest that maternal vaccination could be explored to provide neonatal protection against EV-A71 through maternal antibodies. Catch-up vaccination between ages 6 months to 5 years could provide protection to the approximately 30-90% of children that have not had natural EV-A71 infection by that age. FUNDING: National Science Fund for Distinguished Young Scholars, National Natural Science Foundation of China.

Basic Reproduction Number of Enterovirus 71 and Coxsackievirus A16 and A6: Evidence From Outbreaks of Hand, Foot, and Mouth Disease in China Between 2011 and 2018.

BACKGROUND: Enterovirus 71 (EV-A71), coxsackievirus A16 (CV-A16), and coxsackievirus A6 (CV-A6) are common serotypes causing hand, foot, and mouth disease (HFMD). Analyses on the basic reproduction number (R0) of common pathogens causing HFMD are limited and there are no related studies using field data from outbreaks in mainland China. METHODS: We estimated the pathogen-specific basic reproduction number based on laboratory-confirmed HFMD outbreaks (clusters of ≥10 HFMD cases) reported to the national surveillance system between 2011 and 2018. The reproduction numbers were calculated using a mathematical model and the cumulative cases during the initial growth periods. RESULTS: This study included 539 outbreaks, of which 198 were caused by EV-A71, 316 by CV-A16, and 25 by CV-A6. All 10 417 cases involved were children. Assuming the outbreaks occurred in closed systems and the incubation period is 5 days, the median (interquartile range [IQR]) R0 estimates of EV-A71, CV-A16, and CV-A6 were 5.06 (2.81, 10.20), 4.84 (3.00, 9.00), and 5.94 (3.27, 10.00). After adjusting for seroprevalences, the R0 (IQR) estimates for EV-A71, CV-A16 (optimistic and conservative scenarios), and CV-A6 were 12.60 (7.35, 25.40), 9.29 (6.01, 19.20), 15.50 (9.77, 30.40), and 25.80 (14.20, 43.50), respectively. We did not observe changes in the R0 of EV-A71 after vaccine licensure (P = .67). CONCLUSIONS: HFMD is highly transmissible when caused by the 3 most common serotypes. In mainland China, it primarily affects young children. Although a vaccine became available in 2016, we have not yet observed any related changes in the disease dynamics.

Short-term effects of rainfall on childhood hand, foot and mouth disease and related spatial heterogeneity: evidence from 143 cities in mainland China.

BACKGROUND: Numerous studies have demonstrated the potential association between rainfall and hand, foot and mouth disease (HFMD), but the results are inconsistent. This study aimed to quantify the relationship between rainfall and HFMD based on a multicity study and explore the potential sources of spatial heterogeneity. METHODS: We retrieved the daily counts of childhood HFMD and the meteorological variables of the 143 cities in mainland China between 2009 and 2014. A common time series regression model was applied to quantify the association between rainfall and HFMD for each of the 143 cities. Then, we adopted the meta-regression model to pool the city-specific estimates and explore the sources of heterogeneity by incorporating city-specific characteristics. RESULTS: The overall pooled estimation suggested a nonlinear exposure-response relationship between rainfall and HFMD. Once rainfall exceeded 15 mm, the HFMD risk stopped increasing linearly and began to plateau with the excessive risk ratio (ERR) peaking at 21 mm of rainfall (ERR = 3.46, 95% CI: 2.05, 4.88). We also found significant heterogeneity in the rainfall-HFMD relationships (I2 = 52.75%, P < 0.001). By incorporating the city-specific characteristics into the meta-regression model, temperature and student density can explain a substantial proportion of spatial heterogeneity with I2 statistics that decreased by 5.29 and 6.80% at most, respectively. CONCLUSIONS: Our findings verified the nonlinear association between rainfall and HFMD. The rainfall-HFMD relationship also varies depending on locations. Therefore, the estimation of the rain-HFMD relationship of one location should not be generalized to another location.