Transmission Dynamics and Optimal Control Strategies of a Hand-Foot-Mouth Disease Model with Treatment and Vaccination Interventions

In this article, the transmission dynamics of a Hand-Foot-Mouth disease model with treatment and vaccination interventions are studied. We calculated the basic reproduction number and proved the global stability of disease-free equilibrium when R0 R0 > 1. Meanwhile, we obtained the optimal control strategies minimizing the cost of intervention and minimizing the infected person. We also give some numerical simulations to verify our theoretical results.

维生素D辅助治疗对EV71型HFMD患儿的疗效和安全性分析

目的:探讨维生素D辅助治疗对EV71型HFMD患儿的疗效和安全性。方法:选取2019年3月—2022年3月我院收治的80例EV71型HFMD患儿作为观察对象,根据数字随机法将患者分为两组,每组40例。对照组接受常规对症治疗,观察组使用维生素D辅助常规对症治疗。比较两组患者临床治疗总有效率、临床症状改善时间和临床体征改善时间、白细胞介素-6(IL-6)水平、白细胞介素-10(IL-10)水平、白细胞介素-13(IL-13)水平以及免疫球蛋白IgA、IgG、IgM水平、不良反应发生情况。结果:观察组临床治疗总有效率明显高于对照组(P<0.05);观察组临床症状消退时间、临床体征改善时间以及住院时间均明显短于对照组(P<0.05);治疗前两组IL-6、IL-10、IL-13水平比较差异无统计学意义(P>0.05),治疗后两组IL-6、IL-10、IL-13水平均明显降低,且观察组低于对照组(P<0.05);治疗前两组免疫球蛋白IgA、IgG、IgM等指标水平比较差异无统计学意义(P>0.05),治疗后两组IgA、IgG、IgM指标水平均有所上升,且观察组高于对照组(P<0.05)。结论:维生素D辅助治疗EV71型HFMD,可改善临床疗效、临床症状以及临床体征,减轻细胞因子水平,提高免疫功能指标水平,值得临床进一步深入研究。

天津市手足口病防控知识科普宣讲活动及效果评价

2023年6—10月,对天津市16个区进行分层抽样,抽取4个宣传地区及其24所托幼机构,对849位幼儿家长、705名校(园)医、129名社区医生开展手足口病防控知识科普宣讲活动,宣传形式包括家长课堂宣讲,校医、社区医生现场活动和答疑解惑,以科普文章制作转发、视频播放等形式传播,并针对现场宣讲活动人群开展问卷调查。科普宣讲活动后,手足口病日常预防知识知晓率及防控行为率明显升高。提出对于需要多次强化或不易记忆的日常防护知识,可采用科普宣讲和短视频循环播放相结合的方式。

深圳市宝安区手足口病经济负担及影响因素

目的:了解深圳市宝安区2021年手足口病经济负担并分析其影响因素。方法:收集某三级甲等医院2021年9月1日—12月1日就诊的1 225例手足口病病人,设计调查问卷,采用电话询问及医院信息系统查询收集资料,评估手足口病造成的经济负担并分析其影响因素。结果:1 225例病人中,门诊病人1 195例(97.55%),住院病人30例(2.45%),无重症病例。1 195例手足口病门诊病人的总体经济负担为422.57(336.70,604.54)元/例,30例手足口病住院病人的总体经济负担为(4 386.88±1 624.61)元/例。年龄、报销类型以及诊疗次数是手足口病门诊病人总体经济负担的影响因素(P<0.05)。结论:手足口病住院病人经济负担高于门诊病人,年龄、报销类型以及诊疗次数是手足口病门诊病人经济负担的影响因素。早发现、早诊断、早治疗能有效降低疾病经济负担。

上海市长宁区儿童家长肠道病毒71型灭活疫苗接种意愿及影响因素分析

目的 了解上海市长宁区托幼机构儿童家长为孩子接种肠道病毒71型灭活疫苗(EV71疫苗)的意愿并分析影响因素,为推广EV71疫苗接种提出建议。方法 采用随机抽样的方式抽取长宁区托幼机构就读的儿童,向儿童家长发放问卷进行调查。结果 有75.40%的家长愿意为孩子接种EV71疫苗。Logistic回归分析,不认为EV71会产生强烈副作用、疫苗犹豫量表得分越高、主动获取知识得分越低的家长更愿意为孩子接种EV71疫苗。结论 家长为儿童接种EV71疫苗的意愿受到对EV71疫苗副作用的认知、疫苗犹豫和主动获取知识情况的影响,应对家长开展相关健康教育,以提升接种率。

分析早期观察及综合护理对重症手足口病(HFMD)患儿的影响

目的:对重症手足口病(HFMD)患儿进行分析,探讨早期观察及综合护理对重症手足口病(HFMD)患儿的影响。方法:采取我院收治的40例手足口病(HFMD)患儿,并将其分为两组。研究组20例,对照组20例。研究组采取早期观察及综合护理的方法,而对照组则只进行基本护理,比较其结果。结果:研究组的20例手足口病(HFMD)患儿的并发症低于对照组的20例手足口病(HFMD)患儿,同时恢复时间也较短,并且家长满意程度也高于对照组。结论:早期观察及综合护理有利于重症手足口病(HFMD)患儿的健康恢复,并且有效的减少和缓解了并发症的产生,对重症手足口病(HFMD)患儿有着积极地影响。

2013年长春市儿童医院HFMD患儿病原特点分析

目的分析2013年长春市儿童医院住院手足口病(HFMD)患儿病原学特点,了解住院HFMD患儿病原的变化。方法分析2013年长春市儿童医院住院的1111例HFMD患儿一般情况;应用荧光定量PCR方法检出粪便肠道病毒通用型(EV)、新型肠道病毒71型(EV71)、柯萨奇病毒A16型(CoxA16)和柯萨奇病毒A6型(CoxA6)核酸;在1111份粪便标本中随机抽取10份进行CoxA6型核酸序列检测及分析。结果2013年长春市儿童医院住院HFMD患儿发病高峰年龄段13-24月龄,流行高峰季节6-8月份。引发HFMD的病原有EV、EV71、CoxA16、CoxA6等,以EV和CoxA6为主,阳性检出率分别为50.21%和46.00%;EV和CoxA6流行的高峰季节6月份,CoxA16在10月现流行高峰,EV71未出现流行高峰季节。随机抽取10份进行测序,有7份序列与CoxA6序列的同源性为96%-98%;CoxA6型系统发生学分析显示:其中4份同源性高,位于基因树的同一分支。结论 2013年长春市儿童医院住院HFMD患儿病原流行优势型为CoxA6;HFMD的病原趋于多样性和多种型别共流行的状态。监测HFMD病原的特点对于其预防、临床诊治及预后评估有重要警示作用。

2016至2022年杭州地区14259例儿童肠道病毒流行特征分析

目的了解杭州地区手足口病(hand-foot-mouth disease,HFMD)病原体肠道病毒(entero virus,EV)的阳性检出情况及流行特征,为今后制定杭州地区HFMD防控策略提供科学依据。方法收集整理2016年1月至2022年12月期间杭州市儿童医院检出的EV通用型核酸阳性的14259例的病例信息,对年龄、性别、检出时间等因素进行回顾性分析。结果EV历年平均阳性检出率为45.48%(14259/31354),其中男童阳性检出率为27.20%,女童为18.28%,差异有统计学意义(P<0.01)。不同年龄段患儿EV阳性检出率随年龄增大呈下降趋势,5岁以下儿童的EV阳性检出率占所有阳性检出患儿的90.38%。在季节方面,EV夏季高发,历年夏季5月至7月的总阳性检出数占总检出数的49.16%,自2016年以来EV阳性检出率呈逐年下降趋势。结论杭州地区EV感染具有性别差异,男童易感染,尤其需要重视5岁以下儿童的EV防护。另外HFMD存在一定的季节性,夏季高发,历年检出率自2016年后逐年下降,可能与疫苗推广和健康意识提高存在一定关系。

肠道病毒A组71型手足口病的流行病学研究进展

手足口病(hand,foot,and mouth disease,HFMD)是一种急性传染病,由多种肠道病毒引起,5岁以下儿童普遍易感^([1])。大多数肠道病毒引起的手足口病症状轻微,但肠道病毒A组71型(enterovirus A group 71,EV-A71)具有致病性强、传染性高、嗜神经等特点,可致严重甚至致命的神经系统及心肺并发症^([2]),曾在世界各地尤其是亚太地区引起各种规模的反复流行和暴发^([3]),给社会及儿童健康带来极大危害。

Molecular Epidemiology and Clinical Characteristics of Hand, Foot and Mouth Disease in North Sichuan Region, China, 2018-2023: A Descriptive Study

Background: Hand, foot and mouth disease (HFMD) remains an important public health problem in China. Many studies on the epidemiological characteristics of HFMD have been reported, but studies in North Sichuan region have been neglected. Methods: HFMD-related enterovirus infected cases were clinically confirmed and underwent real-time RT-PCR (rRT-PCR) from May 2018 to October 2023 in Guangyuan Central Hospital. Results: During 2018-2023, other EV (437 cases, 81.08%) was the most predominant serotype followed by CV-A16 (94 cases, 17.44%), EV-A71 (8 cases, 1.48%) was the least predominant serotype. Peak infections occurred in July and October. There were no significant differences in gender, age and serotypes. HFMD was concentrated in children under 47 months of age, with the highest incidence in children aged 12 - 23 months and the highest proportion of other EV infections in the whole age group. COVID-19 did not cause significant changes in gender, age and serotype. Overall, there was a significant increase in the proportion of children aged 12 - 23 months infected with CV-A16, and an increase in the proportion of children aged over 36 months infected with other EVs. Conclusions: The incidence of HFMD caused by EV-A71 has decreased significantly, and other EVs have become the main pathogens of HFMD in North Sichuan region in recent years. In the prevention and control of CV-A16, more attention should be paid to children aged 12 - 23 months and the dominant serotype should be closely monitored. Our study highlights the importance of developing of new diagnostic reagents and vaccines for the prevention and control of enterovirus infection. This study for the first time provides insights into district interventions to local conditions.

Expression and clinical significance of pattern recognition receptor-associated genes in hand, foot and mouth disease

Objective:To explore which pattern recognition receptors(PRRs)play a key role in the development of hand,foot,and mouth disease(HFMD)by analyzing PRR-associated genes.Methods:We conducted a comparative analysis of PRR-associated gene expression in human peripheral blood mononuclear cells(PBMCs)infected with enterovirus 71(EV-A71)which were derived from patients with HFMD of different severities and at different stages.A total of 30 PRR-associated genes were identified as significantly upregulated both over time and across different EV-A71 isolates.Subsequently,ELISA was employed to quantify the expression of the six most prominent genes among these 30 identified genes,specifically,BST2,IRF7,IFI16,TRIM21,MX1,and DDX58.Results:Compared with those at the recovery stage,the expression levels of BST2(P=0.027),IFI16(P=0.016),MX1(P=0.046)and DDX58(P=0.008)in the acute stage of infection were significantly upregulated,while no significant difference in the expression levels of IRF7(P=0.495)and TRIM21(P=0.071)was found between different stages of the disease.The expression levels of BST2,IRF7,IFI16 and MX1 were significantly higher in children infected with single pathogen than those infected with mixed pathogens,and BST2,IRF7,IFI16 and MX1 expression levels were significantly lower in coxsackie B virus(COXB)positive patients than the negative patients.Expression levels of one or more of BST2,IRF7,IFI16,TRIM21,MX1 and DDX58 genes were correlated with PCT levels,various white blood cell counts,and serum antibody levels that reflect disease course of HFMD.Aspartate aminotransferase was correlated with BST2,MX1 and DDX58 expression levels.Conclusions:PRR-associated genes likely initiate the immune response in patients at the acute stage of HFMD.

分析早期观察及综合护理对重症手足口病(HFMD)患儿的影响

目的:对重症手足口病(HFMD)患儿进行分析,探讨早期观察及综合护理对重症手足口病(HFMD)患儿的影响。结论:早期观察及综合护理有利于重症手足口病(HFMD)患儿的健康恢复,并且有效的减少和缓解了并发症的产生,对重症手足口病(HFMD)患儿有着积极地影响。

重组人干扰素α-2b联合喜炎平治疗重症EV71 HFMD的疗效观察

目的:观察重组人干扰素α-2b联合喜炎平治疗重症EV71 HFMD的疗效及对PCT、IL-6、CRP的影响。方法:选取60例重症EV71HFMD患者作为观察对象,分为治疗组(n=30)和对照组(n=30)。对照组给予利巴韦林静滴加对症处理的基础治疗;治疗组在基础治疗上采用重组人干扰素α-2b雾化吸入联合喜炎平静滴。比较两组患者退热时间、疱疹消退时间、治疗效率与不良反应发生情况及PCT、IL-6、CRP变化情况。结果:治疗组患者退热时间、疱疹消退时间、显效率均优于对照组,差异有统计学意义(P<0.05);两组不良反应发生情况比较,差异无统计学意义(P>0.05)。两组PCT比较,差异无统计学意义(P>0.05)。治疗后,治疗组IL-6、CRP均低于对照组,差异有统计学意义(P<0.05)。结论:重症EV71HFMD患者在利巴韦林静滴加对症处理的基础治疗上,应用重组人干扰素α-2b雾化吸入联合喜炎平静滴治疗,在缩短退热时间、疱疹消退时间及提高显效率上效果显著,使IL-6、CRP指标得到有效改善,值得临床推广。

Molecular Epidemiological Analysis of Echovirus 19 Isolated From an Outbreak Associated With Hand, Foot, and Mouth Disease (HFMD) in Shandong Province of China

To elucidate the genetic characterization and molecular epidemiological features of Echovirus 19 （El9） isolates collected from an outbreak associated with hand, foot and mouth disease （HFMD） in Tai＇an city of Shandong Province of China from July to September, 2003. Methods Thirty seven Echovirus 19 isolates were isolated from stool specimens and throat swabs collected during the outbreak, then major capsid （VP1） genomic sequence was determined, and phylogenetic tree was done based on the VP1 sequences among these 37 and other El9 viruses deposited in the Genbank. Also a representative strain named CHN-SD03-TN12 was selected for sequencing of 5′-untranslated regions （5′-UTR）. Results The identity rate was about 98.9%-100% among all these 37 El9 viruses. The genetic relationships between these 37 El9 isolates and other strains reported were also depicted. The identity rate was about 78.4%-78.9% compared with El9 reference strain Burke. The substitutions in the sequence of 5′-UTR resulted in changes in the conjectural properties of 5′-UTR of El9 viruses. Condusion The genetic features of El9 viruses isolated during the outbreak in Shandong Province in 2003 may be associated with a genetic and antigenic drift that changes the virulence of the Shandong isolates, but the molecular changes in Shandong El9 viruses contributing to their phenotype remain to be further illuminated. However, the sequences described in this paper substantiate the changes taken place in capsid VPI and 5′UTR regions. These substitutions may contribute to their tropism and virulence, and play a significant role in pathogenesis and clinical manifestations of the disease.

直肠滴入中药对CoxA16、EV71肠道病毒感染手足口病的疗效

目的观察直肠滴入中药对CoxA16、EV71肠道病毒感染手足口病的疗效。方法选取2019年8月—2022年8月贵州水矿控股集团有限公司总医院CoxA16、EV71肠道病毒感染手足口病患儿85例,按照随机数表法分为观察组(42例)和对照组(43例),其中对照组患儿给予利巴韦林治疗,观察组患儿给予直肠滴入中药治疗。对比两组患儿治疗前后口腔疱疹、发热、皮疹等症状的评分,治疗前后患儿炎症因子、免疫指标水平及两组患儿治疗后不良反应发生率。结果治疗前,两组患儿的口腔疱疹、发热、皮疹评分差异无统计学意义(P>0.05),治疗后,两组患儿的口腔疱疹、发热、皮疹评分均降低,并且治疗后观察组患儿的以上症状评分低于对照组(P<0.05);治疗后,两组患儿白细胞介素(IL)-6、IL-8、肿瘤坏死因子(TNF)-α均降低,并且治疗后观察组患儿的以上降低幅度大于对照组(P<0.05);治疗后,两组患儿CD4^(+)、CD3^(+)、CD4^(+)/CD8^(+)水平均升高,CD8^(+)水平降低,并且治疗后观察组患儿的变化幅度大于对照组(P<0.05);观察组患儿不良反应发生率为4.76%,对照组患儿不良反应发生率为18.60%,观察组不良反应发生率低于对照组(P<0.05)。结论给予CoxA16、EV71肠道病毒感染手足口病患儿直肠滴入中药治疗,能减轻患儿临床症状及炎性反应,改善免疫功能,且不良反应少,值得借鉴。

HPLC-UV法检测EV71-CA16二价手足口病灭活疫苗原液相关抗原纯度的方法建立与评价

为建立一种准确可靠的高效液相色谱-紫外(HPLC-UV)方法,检测EV71-CA16二价手足口病(HFMD)灭活疫苗原液中的相关抗原,肠道病毒71型(EV71)和柯萨奇病毒A组16型(CA16)的纯度。本文采用Waters体积排阻色谱柱(SEC,UltrahydrogelTM 2507.8×300 mm,6μm),流动相为0.01 mol/L的PBS中再加入0.1 mol/L氯化钠溶液,等度洗脱,流速0.3 mL/min,检测波长280 nm,进样量50μL,柱温21℃,进行EV71与CA16病毒原液的纯度检测,并对该方法的检测限、拖尾因子、专属性、重复性及检测范围进行验证。结果显示,2种抗原的灵敏度溶液的信噪比(S/N)分别为37.053和47.710,均远大于3,各试样的拖尾因子均小于3;CA16原液和EV71原液经HPLC分离纯化后的目标抗原峰馏分经SDS-PAGE和Western-Blot特异性鉴定,结果显示,色谱峰样品组成分别为CA16和EV71的2种病毒衣壳的结构蛋白,表明本检测方法专属性高。不同浓度的EV71与CA16病毒抗原经多次检测后,各浓度条件下的峰面积百分比与保留时间的RSD均小于1%,重复性良好。不同抗原浓度批样品检测结果显示,CA16原液抗原浓度在89 U/mL~26398 U/mL之间,EV71原液抗原浓度在170 U/mL~9074 U/mL之间时,2种抗原溶液经多次检测统计显示峰面积百分比与保留时间的RSD均小于1%,本方法在该抗原浓度范围内准确可靠,适用于EV71-CA16二价手足口病灭活疫苗原液中病毒抗原纯度的检测。

Clinical and neuroimaging features of enterovirus71 related acute flaccid paralysis in patients with hand-foot-mouth disease

Objective:To investigate clinical and neuroimaging features of enterovirus71(EV71) related acute flaccid paralysis in patients with hand-fool-mouth disease.Methods:Nine patients with acute flaccid paralysis met the criterion of EV71 induced hand-foot-mouth disease underwent spinal and brain MR imaging from May 2008 to Sep 2012.Results:One extremity flaccid was found in four cases(3 with lower limb,1 with upper limb),two limbs flaccid in three cases(2 with lower limbs,1 with upper limbs),and four limbs flaccid in two cases.Spinal MRI studies showed lesion with high signal in T2-weighted images(T2WI) and low signal T1-weighted images(T1WI) in the spinal cord of all nine cases,and the lesions were mainly in bilateral and unilateral anterior hom of cervical spinal cord and spinal cord below thoracic 9(T9) level.In addition,the midbrain,pons, and medulla,which were involved in 3 cases with brainstem encephalitis,demonstrated abnormal signal.Moreover,spinal cord contrast MRI studies showed mild enhancement in corresponding anterior hom of the involved side,and strong enhancement in its ventral root.Conclusions: EV71 related acute flaccid paralysis in patients with hand-foot-mouth disease mainly affected the anterior hom regions and ventral root of cervical spinal cord and spinal cord below T9 level. MR imaging could efficiendy show the characteristic pattern and extent of the lesions which correlated well with the clinical features.

The Application Research of WBC Morphology Combined with NAP in the HFMD Co-Infection of Children

In this manuscript the authors have studied the application value of White blood cell morphology combined with neutrophils alkaline phosphatase staining integral value in treatment of pediatric HFMD combined with infection. They showed that comparing the NAP positive rate of HFMD co-infection with the NAP positive rate of other three groups respectively—reference group, HFMD group and anti-infection HFMD group—the t value is 25.7964, 28.2326, 28.3696 and the values of P are 0.0000;Comparing the NAP integral value of HFMD co-infection with the NAP integral value of other three groups respectively, which are reference group, HFMD group and anti-infection HFMD, the t value is 35.8687, 36.2664, 36.1374 and the values of P are 0.0000. They concluded that it is useful to apply WBC morphological examination combined with the positive rate and integral value of NAP staining to diagnose and treatment HFMD.

Molecular Epidemiology of Coxsackievirus B1-5 Associated with HFMD in Fujian Province, China, 2011-2016

Hand,foot and mouth disease(HFMD)is a common infectious disease that usually affects children less than 5 years of age.HFMD is caused by human enteroviruses(HEVs).HEVs,members of the Enterovirus genus of the Picornaviridae(small RNA virus)family.

Application of Seasonal Auto-regressive Integrated Moving Average Model in Forecasting the Incidence of Hand-foot-mouth Disease in Wuhan,China

Outbreaks of hand-foot-mouth disease（HFMD） have occurred many times and caused serious health burden in China since 2008. Application of modern information technology to prediction and early response can be helpful for efficient HFMD prevention and control. A seasonal auto-regressive integrated moving average（ARIMA） model for time series analysis was designed in this study. Eighty-four-month（from January 2009 to December 2015） retrospective data obtained from the Chinese Information System for Disease Prevention and Control were subjected to ARIMA modeling. The coefficient of determination（R^2）, normalized Bayesian Information Criterion（BIC） and Q-test P value were used to evaluate the goodness-of-fit of constructed models. Subsequently, the best-fitted ARIMA model was applied to predict the expected incidence of HFMD from January 2016 to December 2016. The best-fitted seasonal ARIMA model was identified as（1,0,1）（0,1,1）12, with the largest coefficient of determination（R^2=0.743） and lowest normalized BIC（BIC=3.645） value. The residuals of the model also showed non-significant autocorrelations（P_（Box-Ljung（Q））=0.299）. The predictions by the optimum ARIMA model adequately captured the pattern in the data and exhibited two peaks of activity over the forecast interval, including a major peak during April to June, and again a light peak for September to November. The ARIMA model proposed in this study can forecast HFMD incidence trend effectively, which could provide useful support for future HFMD prevention and control in the study area. Besides, further observations should be added continually into the modeling data set, and parameters of the models should be adjusted accordingly.