Epidemiological characteristics and spatial epidemiology of hand-foot-mouth disease in Hunan Province, China, from 2008 to 2019. / 2008~2019å¹´æ¹–å—çœæ‰‹è¶³å£ç— æµè¡Œç‰¹å¾åŠç©ºé—´æµè¡Œç— å­¦åˆ†æž.

OBJECTIVES: To investigate the epidemic situation of hand-foot-mouth disease (HFMD) in Hunan Province, China, from 2008 to 2019, as well as its spatial autocorrelation characteristics and spatial-temporal clustering, and to provide a reference for the prevention and control of HFMD in Hunan Province. METHODS: Spatial autocorrelation and spatial-temporal clustering analyses were used to analyze the monitoring data of HFMD in Hunan Province from 2008 to 2019. RESULTS: The epidemic situation of HFMD in Hunan Province from 2008 to 2019 showed obvious seasonal distribution, with a low incidence rate in January to March and a high incidence rate in April to July. As for population distribution, children aged 0-5 years had the highest number of HFMD cases and accounted for 95.89% (1 460 391/1 522 910) of all cases, with a mean annual incidence rate of 2 197.784/100 000, and scattered children had the highest number of cases and accounted for 82.59% (1 257 739/1 522 910) of all cases. The global spatial autocorrelation analysis showed that the onset of HFMD in Hunan Province showed a significant clustering distribution, and the local spatial autocorrelation analysis showed that the high clustering areas of HFMD were mainly the districts and counties of Changsha, Zhuzhou, and Yueyang cities. Time-space scanning showed that clustering time was mainly April to July; the cases were clustered in the northeast of Hunan Province from 2008 to 2010 and in the central part of Hunan Province from 2011 to 2019. CONCLUSIONS: The high incidence rate of HFMD is observed in April to July in Hunan Province. Children under 5 years of age are at a high risk of this disease. Spatial-temporal clustering is observed for the epidemic of HFMD, mainly clustered in the northeastern and central areas of Hunan Province. It is suggested that the results may be used as guidance to determine the key areas for HFMD prevention and control in Hunan Province and optimize the allocation of health resources.

Spatio-temporal clustering analysis and its determinants of hand, foot and mouth disease in Hunan, China, 2009-2015.

BACKGROUND: Hand, foot and mouth disease (HFMD) is one of the highest reported infectious diseases with several outbreaks across the world. This study aimed at describing epidemiological characteristics, investigating spatio-temporal clustering changes, and identifying determinant factors in different clustering areas of HFMD. METHODS: Descriptive statistics was used to evaluate the epidemic characteristics of HFMD from 2009 to 2015. Spatial autocorrelation and spatio-temporal cluster analysis were used to explore the spatial temporal patterns. An autologistic regression model was employed to explore determinants of HFMD clustering. RESULTS: The incidence rates of HFMD ranged from 54.31/10 million to 318.06/10 million between 2009 and 2015 in Hunan. Cases were mainly prevalent in children aged 5 years and even younger, with an average male-to-female sex ratio of 1.66, and two epidemic periods in each year. Clustering areas gathered in the northern regions in 2009 and in the central regions from 2010 to 2012. They moved to central-southern regions in 2013 and 2014 and central-western regions in 2015. The significant risk factors of HFMD clusters were rainfall (OR = 2.187), temperature (OR = 4.329) and humidity (OR = 2.070). The protect factor was wind speed (OR = 0.258). CONCLUSIONS: The HFMD incidence from 2009 to 2015 in Hunan showed a new spatiotemporal clustering tendency, with the shifting trend of clustering areas toward south and west. Meteorological factors showed a strong association with HFMD clustering, which may assist in predicting future spatial-temporal clusters.

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.

Molecular characteristics and phylogenetic analysis of N gene of human derived rabies virus.

OBJECTIVE: To investigate the relationship between the molecular characteristics and phylogenetic evolution of rabies N gene. METHODS: Saliva samples were collected from rabies cases, and RT-PCR was used to amplify the N gene of rabies virus with the specific primers. The amplifying product of RT-PCR was cloned to pUCm-T vector and transformed into E.coli XL1-Blue and then the blue-white selection, PCR screening and gene sequencing were carried out to identify the positive clones. Finally, ExPASy and other bioinformatics software were used to analyze and predict the structure and biological characteristics of the N genome. RESULTS: The amplification product of RT-PCR was 1 353 bp, the recombinant plasmid pUCm-T/N was constructed, the whole length of the N gene open reading frame was composed of 1 353 nucleotide residues to code 450 amino acids (20 kinds), the accession number submitted to the Genbank was HM756692, its sequence homology of nucleotides and amino acids compared with the vaccine strain CTN-1-V was 90% and 99% respectively. The evolutionary analysis showed that the isolated strain belonged to genotype I with certain geographic regionality. CONCLUSION: The characteristics investigation and bioinformatics analysis of Hunan0806 N gene will provide fundamental data to reveal the significance of the N gene characteristics for rabies epidemiology and its prevention & control.

[Risk factors of death cases of hand-foot-and-mouth disease in Hunan province].

OBJECTIVE: To study risk factors of death cases of hand foot and mouth diseases (HFMD) in Hunan province, so as to provide scientific evidence for further prevention and control. METHODS: The 105 death cases of HFMD between January and October, 2010 in Hunan Province were selected as case group; and the 210 survival cases of serious HFMD, which were matched by gender and resident places with a ratio at 2:1 in the same period in Hunan were selected as control group. The basic information, hospitalized experience and previous medical history had been surveyed and the relevant risk factors were analyzed by single factor and multi-factor logistic regression. RESULTS: In case group, 79.05% (83/105) of the cases lived in rural area and 9.52% (10/105) of the cases lived in urban-rural midst area. In control group, 87.62% (184/210) of the cases lived in rural area and 11.43% (24/210) of the cases lived in urban-rural midst area. In case group, 59.05% (62/105) of the patients first visited rural (private) clinics and 20.00% (21/105) first visited community hospitals in villages and towns; while in control group, 43.81% (92/210) and 13.33% (28/210) chose rural (private) clinics and community hospitals in villages and towns as the first choice respectively.22.86% (24/105) of the case group and 39.05% (82/210) of the control group were diagnosed as HFMD in their first visit to hospital.27.62% (29/105) of the case group and 7.14% (15/210) in control group were provided pyrazolone in the treatment. For glucocorticoid, 80.95% (85/105) and 5.71% (6/105) of the case group were given as treatment by rural (private) clinics and community hospitals in villages and towns separately; while the proportions in the control group were 41.43% (87/210) and 0.48% (1/210) respectively. For antibiotics, 35.24% (37/105) and 23.81% (25/105) of the case group were prescribed by rural (private) clinics and community hospitals in villages and towns separately; while the percentages in the control group were 15.71% (33/210) and 7.14% (15/210). 3.81% (4/105) of the case group and 11.90% (25/210) of the control group were vaccinated in one month before the onset. The results of single-factor logistic regression indicated that living in rural areas (OR = 0.075, 95%CI: 0.016 - 0.343) and in rural-urban midst areas (OR = 0.069, 95%CI: 0.013 - 0.368), diagnosis of HFMD in the first visit to hospital (OR = 0.463, 95%CI: 0.271 - 0.788) and vaccination one month before the onset (OR = 0.293, 95%CI: 0.099 - 0.866) were four protective factors; while rural (private) clinics as the first choice (OR = 4.717, 95%CI: 1.891 - 11.767), community hospital in villages and towns as the first choice (OR = 5.250, 95%CI: 1.883 - 14.641), medication of pyrazolone (OR = 4.961, 95%CI: 2.520 - 9.766), medication of glucocorticoid in rural (private) clinics (OR = 6.009, 95%CI: 3.435 - 10.510) and in community hospital in villages and towns (OR = 12.667, 95%CI: 1.505 - 106.638), medication of antibiotics in rural (private) clinics (OR = 2.918, 95%CI: 1.690 - 5.040) and in community hospital in villages and towns (OR = 4.062, 95%CI: 2.036 - 8.108) were seven risk factors. The results of multi-factors logistic regression showed that medication of pyrazolone (OR = 2.311, 95%CI: 1.062 - 5.030), medication of glucocorticoid in rural (private) clinics (OR = 5.480, 95%CI: 3.039 - 9.880), medication of antibiotics in rural (private) clinics (OR = 2.430, 95%CI: 1.301 - 4.538) and medication of antibiotics in community hospitals in villages and towns (OR = 3.344, 95%CI: 1.477 - 7.569) were the risk factors of death of HFMD. CONCLUSION: The risk factors of HFMD deaths include the medication of pyrazolone, glucocorticoid and antibiotics by rural (private) clinics and medical institutions in villages and towns. The department concerned should revise the technical manual to standardize the medication of the above drugs.

Early warning of hand, foot, and mouth disease transmission: A modeling study in mainland, China.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a global infectious disease; particularly, it has a high disease burden in China. This study was aimed to explore the temporal and spatial distribution of the disease by analyzing its epidemiological characteristics, and to calculate the early warning signals of HFMD by using a logistic differential equation (LDE) model. METHODS: This study included datasets of HFMD cases reported in seven regions in Mainland China. The early warning time (week) was calculated using the LDE model with the key parameters estimated by fitting with the data. Two key time points, "epidemic acceleration week (EAW)" and "recommended warning week (RWW)", were calculated to show the early warning time. RESULTS: The mean annual incidence of HFMD cases per 100,000 per year was 218, 360, 223, 124, and 359 in Hunan Province, Shenzhen City, Xiamen City, Chuxiong Prefecture, Yunxiao County across the southern regions, respectively and 60 and 34 in Jilin Province and Longde County across the northern regions, respectively. The LDE model fitted well with the reported data (R2 > 0.65, P < 0.001). Distinct temporal patterns were found across geographical regions: two early warning signals emerged in spring and autumn every year across southern regions while one early warning signals in summer every year across northern regions. CONCLUSIONS: The disease burden of HFMD in China is still high, with more cases occurring in the southern regions. The early warning of HFMD across the seven regions is heterogeneous. In the northern regions, it has a high incidence during summer and peaks in June every year; in the southern regions, it has two waves every year with the first wave during spring spreading faster than the second wave during autumn. Our findings can help predict and prepare for active periods of HFMD.

Interaction analysis on transmissibility of main pathogens of hand, foot, and mouth disease: A modeling study (a STROBE-compliant article).

Hand, foot, and mouth disease (HFMD) has spread widely and led to high disease burden in many countries. In this study, we aimed to analyze the interaction of the main pathogens of HFMD using a mathematical model.A dataset on reported HFMD cases was collected from April, 2009 to December, 2017 in Changsha City. A long-term etiological surveillance was conducted focusing on the pathogens of the disease including enterovirus A71 (EV71), coxsachievirus A16 (CA16), and other enteroviruses. A susceptible-infectious-recovered model was adopted to calculate the reproduction number during the ascending period of reported cases (defined as Rasc) and the descending period (defined as Rdes).About 214,178 HFMD cases (including clinically diagnosed cases and confirmed cases) were reported in Changsha City, among which 31 were death cases with a fatality of 0.01%. The number of reported HFMD cases increased yearly with a Linear model of "f(t) = 18542.68 + 1628.91t" where f(t) and t referred to number of reported cases and sequence of year, respectively. The fatality of the disease decreased yearly with a linear model of "f(t) = - 0.012 + 0.083/t". About 5319 stool or anal swab specimens were collected from the reported cases. Among them, 1201 were tested EV71 positive, 836 were CA16 positive, and 1680 were other enteroviruses positive. Rasc and Rdes of HFMD was 1.34 (95% confidence interval [CI]: 1.28-1.40) and 0.73 (95% CI: 0.69-0.76), respectively. EV71 and CA16 interacted with each other, and the interaction between EV71 and other enteroviruses and the interaction between CA16 and other enteroviruses were both directional. However, during the reported cases decreasing period, interactions only occurred between EV71 and other enteroviruses and between CA16 and other enteroviruses. These interactions all decreased Rasc but increased Rdes of affected pathogens.The interactions of the pathogens exist in Changsha City. The effective reproduction number of the affected pathogen is adjusted and verges to 1 by the interaction.

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

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

Hand, Foot, and Mouth Disease in Hunan Province, China, 2009-2014: Epidemiology and Death Risk Factors.

Hand, foot, and mouth disease (HFMD) is an arising public health problem in Asia, including China. Epidemiological data is necessary to enable judicious public health responses and interventions. We analyzed the epidemiological and laboratory data of 759,301 HFMD cases reported to the Hunan Provincial Center for Disease Control and Prevention from 1 January 2009 to 31 December 2014. Univariate and multivariable conditional logistic regression analyses were used to identify risk factors of fatality in HFMD. The incidence of HFMD was highest among children aged 1-3 years, compared with other age groups. Of the total HFMD cases, 7,222 (0.95%) were considered severe and 338 (0.04%) were fatal. Enterovirus-A71 was the major cause of severe and fatal cases (65.75% and 88.78%, respectively). For severe cases, the median time from symptom onset to diagnosis was 0.5 days (interquartile range [IQR] 0-1.5 days); the median time from diagnosis to severe illness was 2 days (IQR 1-3 days). For fatal cases, the median time from symptom onset to diagnosis was 0.5 days (IQR 0-1.5 days); the median time from diagnosis to death was 1.5 days (IQR 0.5-2.5 days). In multivariable analysis, the abuse of antibiotic, glucocorticoid and pyrazolone in village clinics at basic medical institutions were identified as independent risk factors for HFMD fatal cases. In conclusion, our results suggest that the future direction to control and respond to HFMD is intensive surveillance of enterovirus-A71 and improving the ability to diagnose disease and treat patients, especially in basic medical institutions.

Risk factors for death in children with severe hand, foot, and mouth disease in Hunan, China.

BACKGROUND: In recent years, outbreaks of hand, foot, and mouth disease (HFMD) have increased throughout East and Southeast Asia, especially in mainland China. The disease now presents as an increasingly serious public health threat in China. METHODS: A case-control study was designed to examine risk factors associated with death from severe HFMD. A total of 553 severe HFMD cases were collected from the National Surveillance System. RESULTS: Multifactorial logistic regression was used to analyse independent associations between potential influence factors and death from severe HFMD. We found that the migrants were more likely to die from severe HFMD than the resident population (OR = 3.07, 95%CI: 1.39-8.32). Additionally, the children whose first visit was to a village-level clinic had a high risk of death from severe HFMD. Patients with EV71 infection or symptoms of convulsion, dyspnoea, cyanosis, coolness of extremities, and vomiting had an increased risk of death from severe HFMD. While breastfeeding children, having a confirmed diagnosis at the first visit to the hospital and with symptom of hyperarousal were identified as protective factors for death from severe HFMD. CONCLUSIONS: To reduce the mortality from severe HFMD, doctors and health care providers need to pay attention to the patients with EV71 infection or with symptoms of convulsion, dyspnoea, cyanosis, coolness of extremities, and vomiting. Health administration departments should pay more attention to the rational allocation of health resources. Furthermore, they should increase financial support and manpower in village-level health institutions.

Neurological complications and risk factors of cardiopulmonary failure of EV-A71-related hand, foot and mouth disease.

From 2010 to 2012, large outbreaks of EV-A71-related- hand foot and mouth disease (HFMD) occurred annually in China. Some cases had neurological complications and were closely associated with fatal cardiopulmonary collapse, but not all children with central nervous system (CNS) involvement demonstrated a poor prognosis. To identify which patients and which neurological complications are more likely to progress to cardiopulmonary failure, we retrospectively studied 1,125 paediatric inpatients diagnosed with EV-A71-related HFMD in Hunan province, including 1,017 cases with CNS involvement. These patients were divided into cardiopulmonary failure (976 people) group and group without cardiopulmonary failure (149 people). A logistic regression analysis was used to compare the clinical symptoms, laboratory test results, and neurological complications between these two groups. The most significant risk factors included young age, fever duration ≥3 days, coma, limb weakness, drowsiness and ANS involvement. Patients with brainstem encephalitis and more CNS-involved regions were more likely to progress to cardiopulmonary failure. These findings can help front-line clinicians rapidly and accurately determine patient prognosis, thus rationally distributing the limited medical resources and implementing interventions as early as possible.

Correlation analysis of EV71 detection and case severity in hand, foot, and mouth disease in the Hunan Province of China.

An increase in the incidence of hand, foot and mouth disease (HFMD) cases has been observed in the Hunan province of mainland China since 2009 with a particularly higher level of severe cases in 2010-2012. Intestinal viruses of the picornaviridae family are responsible for the human syndrome associated with HFMD with enterovirus 71 (EV71) and Coxsackievirus A16 (Cox A16) being the most common causative strains. HFMD cases associated with EV71 are generally more severe with an increased association of morbidity and mortality. In this study, the etiology surveillance data of HFMD cases in Hunan province from March 2010 to October 2012 were analyzed to determine if there is a statistically relevant linear correlation exists between the detection rate of EV71 in mild cases and the proportion of severe cases among all HFMD patients. As the cases progressed from mild to severe to fatal, the likelihood of EV71 detection increased (25.78%, 52.20% and 84.18%, respectively). For all cases in the timeframe evaluated in this study, the presence of virus was detected in 63.21% of cases; among cases showing positivity for virus, EV71 infection accounted for 50.14%. These results provide evidence to support the observed higher morbidity and mortality associated with this outbreak and emphasizes the importance of early detection in order to implement necessary prevention measures to mitigate disease progression.