Detection,management,and prevention of diabetes-related foot disease in the Australian context

Diabetes-related foot disease(DFD)is a widely feared complication among people who live with diabetes.In Australia and globally,rates of disability,cardiovascular disease,lower extremity amputation,and mortality are significantly increased in patients with DFD.In order to understand and prevent these outcomes,we analyse the common pathogenetic processes of neuropathy,arterial disease,and infection.The review then summarises important management considerations through the interdisciplinary lens.Using Australian and international guidelines,we offer a stepwise,evidence-based practical approach to the care of patients with DFD.

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.

Computational Investigation of Hand Foot Mouth Disease Dynamics with Fuzziness

The first major outbreak of the severely complicated hand,foot and mouth disease(HFMD),primarily caused by enterovirus 71,was reported in Taiwan in 1998.HFMD surveillance is needed to assess the spread of HFMD.The parameters we use in mathematical models are usually classical mathematical parameters,called crisp parameters,which are taken for granted.But any biological or physical phenomenon is best explained by uncertainty.To represent a realistic situation in any mathematical model,fuzzy parameters can be very useful.Many articles have been published on how to control and prevent HFMD from the perspective of public health and statistical modeling.However,few works use fuzzy theory in building models to simulateHFMDdynamics.In this context,we examined anHFMD model with fuzzy parameters.A Non Standard Finite Difference(NSFD)scheme is developed to solve the model.The developed technique retains essential properties such as positivity and dynamic consistency.Numerical simulations are presented to support the analytical results.The convergence and consistency of the proposed method are also discussed.The proposed method converges unconditionally while the many classical methods in the literature do not possess this property.In this regard,our proposed method can be considered as a reliable tool for studying the dynamics of HFMD.

Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease(2020 edition)

In recent years,as living standards have continued to improve,the number of diabetes patients in China,along with the incidence of complications associated with the disease,has been increasing.Among these complications,diabetic foot disease is one of the main causes of disability and death in diabetic patients.Due to the differences in economy,culture,religion and level of medical care available across different regions,preventive and treatment methods and curative results for diabetic foot vary greatly.In multidisciplinary models built around diabetic foot,the timely assessment and diagnosis of wounds and appropriate methods of prevention and treatment with internal and external surgery are key to clinical practice for this pathology.In 2019,under the leadership of the Jiangsu Medical Association and Chinese Diabetes Society,the writing group for the Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease(2020 edition)was established with the participation of scholars from the specialist areas of endocrinology,burn injury,vascular surgery,orthopedics,foot and ankle surgery and cardiology.Drawing lessons from diabetic foot guidelines from other countries,this guide analyses clinical practices for diabetic foot,queries the theoretical basis and grades and gives recommendations based on the characteristics of the pathology in China.This paper begins with assessments and diagnoses of diabetic foot,then describes treatments for diabetic foot in detail,and ends with protections for high-risk feet and the prevention of ulcers.This manuscript covers the disciplines of internal medicine,surgical,nursing and rehabilitation and describes a total of 50 recommendations that we hope will provide procedures and protocols for clinicians dealing with diabetic foot.

Characterization of Hand,Foot,and Mouth Disease in China between 2008 and 2009

Objective To investigate the epidemiological and cl （HFMD） since several outbreaks of HFMD caused between 2007 and 2008. inical features of hand, foot and mouth disease by enteroviruses were documented in China Methods HFMD cases reported to the National Infectious Disease Information Management System database between May 2008 and April 2009 were assessed. Clinical features in some of the severe and fatal cases were analyzed the etiology of the outbreaks was investigated. Results 89.1% of reported HFMD cases were found in children〈5 year-old with an age-specific incidence rate of 834.1/100 000 in the first year as the notifiable disease in China from May 2008 to April 2009. The incidence, mortality and percentage of severe cases were studied for three regions of China and found to be highest in the central region. The incidence of severe cases and mortality in rural population were significantly higher than those in urban population. Among the laboratory confirmed EV17 positive cases there were 52.6% mild, 83.5% severe, and 96.1% fatal cases. More myoclonic jerks were found in the severe case group than in group that died. Tachypnea, lip purpling, pink foaming and low limb temperature occurred more frequently in the fatal cases than in the severe cases. Conclusion The epidemic of HFMD in China was characterized predominantly by EV71 infections, had relatively high mortality rates especially in the central region, and was most prevalent in young, rural populations.

Using Interrupted Time Series Design to Analyze Changes in Hand, Foot, and Mouth Disease Incidence during the Declining Incidence Periods of 2008-2010 in China

Objective To identify patterns of hand, foot and mouth disease （HFMD） incidence in China during declining incidence periods of 2008, 2009, and 2010. Methods Reported HFMD cases over a period of 25 months were extracted from the National Disease Reporting System （NDRS） and analyzed. An interrupted time series （ITS） technique was used to detect changes in HFMD incidence rates in terms of level and slope between declining incidence periods of the three years. Results Over 3.58 million HFMD cases younger than 5 years were reported to the NDRS between May 1, 2008, and May 31, 2011. Males comprised 63.4% of the cases. ITS analyses demonstrated a significant increase in incidence rate level （P〈0.0001） when comparing the current period with the previous period. There were significant changes in declining slopes when comparing 2010 to 2009, and 2010 to 2008 （all P〈O.O05）, but not 2009 to 2008. Conclusion Incremental changes in incidence rate level during the declining incidence periods of 2009 and 2010 can potentially be attributed to a few factors. The more steeply declining slope in 2010 compared with previous years could be ascribed to the implementation of more effective interventions and preventive strategies in 2010. Further investigation is required to examine this possibility.

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.

Coxsackievirus A6 was the most common enterovirus serotype causing hand,foot,and mouth disease in Shiyan City,central China

BACKGROUND Hand,foot,and mouth disease(HFMD)has become one of the most common infectious diseases in China.Before 2016,the primary causal serotypes were enterovirus A71(EV-A71)and coxsackievirus A16(CV-A16).Following the introduction of EV-A71 vaccines in China since 2016,the situation could change.CV-A6 has recently replaced EV-A71 and CV-A16 in some areas of China.However,the epidemiological characteristics of central China remain unknown.AIM To investigate the clinical symptoms and pathogen spectrum of HFMD in Shiyan City,central China,in recent years.METHODS The epidemiological,clinical,and laboratory data from HFMD cases reported to the Shiyan Center for Disease Control and Prevention between January 2016 and December 2020 were analyzed.196 throat swab specimens were collected from hospitalized HFMD patients between January 2018 and December 2020.To detect and genotype enteroviruses,real-time reverse transcription-polymerase chain reaction and sequencing of the 5'-untranslated region were used.In Shiyan,168 laboratory-confirmed HFMD cases were studied using a logistic regression model to determine the effect of predominant enterovirus serotypes.Based on the logistic regression model,the least absolute shrinkage and selection operator model was used to analyze the correlation between CV-A6 infection and various clinical characteristics in HFMD patients in Shiyan.RESULTS From 2016 to 2020,35840 HFMD cases were reported in Shiyan.The number of cases decreased by 48.4%from 2016 to 2017.Approximately 1.58-fold increases were found in 2018 and 2019 when compared to the previous year,respectively.In 2020,a decrease of about 85.5%was reported when compared to 2019.The most common serotypes shifted from EV-A71 and CV-A16(about 60%-80%in 2016 and 2018)to others(more than 80.0%in 2017,2019,and 2020).EV-A71 lost its dominance in 2017 in Shiyan.Among 196 confirmed HFMD cases,85.7%tested positive for enterovirus,with CV-A6 being the most common serotype(121/168,72.0%).The positive rates for CV-A16 and CVA10 were 4.8%and 3.0%,respectively.There was no EV-A71 discovered.Infection with CV-A6 was linked to fever,myocardial damage,increased creatine kinase MB isoenzyme,and lactate dehydrogenase levels.CONCLUSION CV-A6 was the most common enterovirus serotype in Shiyan City,replacing EV-A71 and CV-A16 as the HFMD pathogen.Developing vaccines against CV-A6 or multiple pathogens,as well as rising CV-A6 surveillance,will help prevent HFMD in central China.

Development of a Synthetic Peptide ELISA Assay for the Detection of Foot-and-Mouth Disease Virus Nonstructural Protein Antibodies

In order to develop an ELISA assay with synthetic peptides for the detection of antibody to the nonstructural proteins of foot-and-mouth disease virus, specific peptides were synthesized by a solid-phase method according to FMDV NSPs B-cell epitopes, and were conjugated to carrier protein BSA. An ELISA system was developed to detect FMDV NSPs antibody with the conjugated proteins as the coating antigen. The optimal coating concentration of the antigen was determined as 2.5 μg mL-1. The comparative study of this assay with UBI NSP ELISA kit and national commercial 3ABC ELISA kit in the detection of 199 serum samples showed that they were very coincident, and the identity rates were 96.48 and 97.48%, respectively. The development of ELISA using the synthetic peptides as coating antigen is specific, reproducible, stable, and easy, and can be used to differentiate FMDV infected pigs from immunized pigs.

Establishment of Indirect ELISA Diagnosis Technique based on the VP1 Protein of Foot and Mouth Disease Virus Serotype A

The VP1 protein of foot-and-mouth disease virus serotype A was prokaryotically expressed and purified to replace the traditional virus antigen for estab- lishing a fast, safe, effective indirect ELISA method, so as to detecting antibody of foot-and-mouth disease virus serotype A. Western-Blot test showed that the VP1 recombinant protein could be used as detective antigen as it can be specifically recognized by bovine positive serum of FMDV serotype A. By employing matrix titra- tion method, the optimal parameters were obtained as follows： 1 mg/L VP1 protein as coating antigen, Vserum：Vblocking solution = 1：50 dilution for serum and Vsecondary enzyme-linked antibedies：Vblocking solution ---1：2 000 for enzyme combined antibodies. The results showod that the sensitivity and specificity of this method were 94.32% and 99.09% respectively, the coefficients of variations in intra-assay and inter-assay reproducibility tests was lower than 8%. Compared with liquid phase blocking ELISA kits, the agreement of 201 serum samples reached 92.54%. The VP1-ELISA method established here is specific, sensitive, stable and simple, which can be used to monitor the antibody level of FMD serotype A.

Evaluation on Common Hand, Foot and Mouth Disease Treated by Integrative Traditional Chinese Medicine and Western Medicine

Objective To evaluate the efifcacy and safety of traditional Chinese medicine (TCM) combined with Western medicine in the treatment of patients with common hand, foot and mouth disease (HFMD) by conducting a prospective, controlled, and randomized trial. Methods A total of 452 patients with common HFMD were randomly assigned to receive Western medicine alone (n=220) or combined with TCM (Reduning or Xiyanping injections) (n=232). The primary outcome was the incidence rate of rash/herpes disappearance within 5 days, while secondary outcomes included the incidence rate for fever, cough, lethargy, agitation, and vomiting clearance within 5 days. Results The rash/herpes disappearance rate was 45.5% (100/220) in Western medicine therapy group, and 67.2% (156/232) in TCM and Western medicine combined therapy group, with significant difference (P<0.001). Moreover, TCM remarkably increased the incidence rate of secondary disappearance, which was 56.4%in Western medicine therapy group and 71.4%in TCM and Western medicine combined therapy group (P=0.001). No drug-related adverse events were observed. Conclusions It’s suggested that the integrative TCM and Western medicine therapy achieved a better therapeutic efficacy. TCM may become an important complementary therapy on relieving the symptoms of HFMD.

Investigation on Factors Associated with Severe Hand, Foot and Mouth Disease

Objective To analyze the clinical and laboratory features of patients with mild and severe HFMD to identify early predictive or diagnostic markers for severe cases. Methods Samples of feces, nasopharyngeal-swab specimens, peripheral blood, serum and cerebral spinal fluid were collected. Postmortem pathological examination was conducted on 2 dead patients with complication due to neurogenic pulmonary edema. Reverse transcription-polymerase chain-reaction(RT-PCR), culture and isolation of enterovirus 71(EV71) were performed to detect EV71 infection. Both univariate and multivariate logistic analysis were used to identify factors associated with severe cases. Results EV71 was mainly responsible for HFMD. In this study, 5 isolated EV71 strains belonged to C4 gene subtype. Compared with mild patients, EV71-RNA detection rate was higher and Cox A16 detection rate was lower among severe patients(P < 0.01). Inflammatory cell infiltration in the lung, cardiac and liver tissues were mild by postmortem pathological examination. It was found that body temperature, vomitting, limb tremor, neutrophil, blood glucose and EV71 infection were significantly related to the severe cases by univariate logistic analysis. However, after multivariate logistic regression analysis, only vomiting(OR 16.1, CI 2.3-110.5, P < 0.01) and limb tremor(OR 117.6, CI 13.8-1004.5, P < 0.01) were significantly and independently correlated with the severe cases.Conclusions EV71 was mainly responsible for HFMD, particularly for severe cases. Vomiting and limb tremor were predictive markers for severe cases.

The Comparative Study on Two Models of Syndrome Differentiation of the Hand, Foot and Mouth Disease: An Investigation Analysis of the Signs and Symptoms on 2325 Cases

Objective To realize the characteristics of "zheng" differentiation-treatment for hand, foot and mouth disease(HFMD), a new methodology of syndrome differentiation for different stages of HFMD has been explored. Methods Total of 2 325 cases with HFMD were recorded by distributing them into exterior syndrome stage, interior syndrome stage, severe syndrome stage and recovered syndrome stage, respectively, and the main symptoms and subsidiary symptoms of different stages of HFMD have been observed. The major and minor pathogenesis of HFMD in different stages were obtained, and compared with the "2010 Guideline for the Diagnosis and Treatment of HFMD". Results It was found that the major pathogenesis of exterior stage was defined as "the invation of the wenevil to the defender of the body with the collaterals got involved ", and the minor as "qi deficiency"; in interior stage, "the fury of Gan-Yang" was the main pathogenesis, and "qi in chaos and qi deficiency" was the minor; in severe syndrome stage, "the damage of heart, liver and lung" was the main pathogenesis, and "qi in chaos" was the minor; and the pathogenesis of recovered stage was "qi-yin deficiency". Compared with the "2010 Guideline for the Diagnosis and Treatment of HFMD", it showed that "the obstruction of the fei-pi qi by the mixture of shi-re evil" and "the mixture of shi-re" in vivo was quite difficult to be explained in completely different context in the general situation; in the severe stage, the TCM clinical characteristics of syndrome differentiation might lose; in the early acute severe cases, the phenomenon that xin-yang and fei-qi almost ran out was difficult to be observed, then, the line between the severe and the acute severe became vague.Conclusions The theory of syndrome differentiation by stages of HFMD was reasonable in the actual situation of clinical description on HFMD which was expected to be further tested and widely applied in the "zheng" differentiation-treatment of HFMD in the future.

Results on Pathogen Detection of Foot and Mouth Disease in Guangxi China and Analysis on Its Popular Spectrum

Objective: The study aims to understand the characteristics and epidemic trend of the pathogen of hand, foot and mouth disease (HFMD) in Guangxi regions, China. Besides, it aims to analyze the differences of intestinal virus detection rate between anal swab and pharyngeal swab samples. Methods: Anal swab and pharyngeal swabs of suspected HFMD children were collected in our hospital from 2012 to 2015. Real-time fluorescent PCR (Polymerase Chain Reaction) was used to detect enterovirus 71 (EV71), coxsackie virus type 16 (CA16), and universal intestinal virus nucleic acid (EV). Composition and conversion of predominant pathogens were analyzed, and paired samples’ test results of swabs anal and pharyngeal swab were statistically analyzed. Results: There are 681 cases with enterovirus in 2351 cases of patients. Among those who got enterovirus, there are 501 cases of EV71, 102 cases of CA16 and 79 cases of EV. From 2012 to 2015, the total proportion of the virus detection is 46.47%, 16.23%, 41.02% and 15.33% respectively in each year, while the proportion of predominant epidemic virus is 93.93% of EV71, 66.12% of CA16, 89.30% of EV71 and 98.73% of EV, non-EV71, non-CA16 EV (from October to December in 2015). It’s obvious that the total virus detection rate in 2012 and 2014 is significantly higher than that in 2013 and 2015. There is statistical significance. Conclusion: The main HFMD pathogens are EV71 from 2012 to 2015 in Guangxi regions. In 2012 and 2014, the predominant epidemic pathogens were EV71, while in 2013 and 2015, the predominant epidemic pathogens turn to be CA16 and non-EV71, non-CA16 EV respectively. What’s more, collecting anal swab and pharyngeal swab virus at the same time for nucleic acid detection is of great significance to improve the HFMD laboratory diagnostic.

Sero-prevalence, Risk Factor and Community Perception of Foot and Mouse Disease in Cattle under Extensive Management in Southern Tigray, Ethiopia

To determine the sero-prevalence of foot and mouth disease in southern zone of Tigray,North Ethiopia,a cross-sectional examination of 340 sera samples were conducted from November 2015 up to May 2016.In addition,a structured questionnaire survey was done to know the perception and knowledge of the local community about the disease and 120 informants were interviewed.The overall sero-prevalence was 20.9%and there was no statistical significant difference(P>0.05)in prevalence of foot and mouth disease between sexes,agro-ecology,breed and vaccination history.However,a statistical significant difference(P<0.05)was noticed between the age groups,different body conditions,farming systems,and history of contact with wild life.The logistic regression analysis indicated that all the factors which had an association with sero-positivity were found significant risk factors for the disease.The questionnaire survey indicated that 65%of the contacted informants described the disease consistent with the major clinical signs mentioned in literature.The study revealed that the virus is circulating in the area and requires further identification of the serotypes.Moreover,implementing control of foot and mouth disease with integrated approaches has paramount importance.

Construction of Plant Expression Vector for Hand,Foot and Mouth Virus EV71-VP1 Gene and Its Expression in Tomato

EV71-type virus is one of the main pathogens causing the occurrence of hand,foot and mouth disease(HFMD),and VP1 protein,a factor that directly determines the antigenicity of the virus,has been isolated.The tomato was selected as a bioreactor for the production of an edible EV71 vaccine designed for the VP1 capsid protein.Using molecular biology techniques,the fusion gene EV71-VP1 was cut from vector PGEX-4T-2,a vector containing the p2300-EV71 gene with CaMV35S promoter and TL regulatory elements was constructed,and the hypocotyl and cotyledons of tomato were transformed using Agrobacterium(EHA105)-mediated method,screened,elongated and rooted,and finally 20 resistant tomato plants were obtained.Five transgenic positive seedlings were obtained by digestion and PCR assay,among which three plants were detected by RT-PCR to be capable of transcriptional translation at the RNA level.The experimental results aimed to explore new material support for the preparation of transgenic plant oral vaccines against EV71 infection and provide a theoretical basis for accelerating the development of transgenic plant vaccines in the future.

Use of orthotics with orthotic sandals versus the sole use of orthotics for plantar fasciitis:Randomised controlled trial

BACKGROUND Plantar fasciitis(PF)affects around 10%of the population.Prefabricated orthotics with arch support has been shown to provide symptom relief in PF by decreasing the repetitive stress sustained by the plantar fascia.However,prefabricated orthotics are only effective when shoes are worn,meaning the foot may be left unsupported when it is impractical to wear shoes.Using orthotic sandals in conjunction with prefabricated orthotics may increase PF symptom relief,as they can be worn inside the home,extending the period in which the foot is supported.AIM To compare the combined use of prefabricated orthotics and orthotic sandals vs the sole use of prefabricated orthotics in the treatment of PF.METHODS 98 participants with PF were randomised into two groups.The intervention group received the Aetrex L420 Compete orthotics and the Aetrex L3000 Maui Flips(orthotic sandals),whilst the control group received the Aetrex L420 Compete orthotics only.Foot pain was assessed both by the numerical rating scale(NRS)and the pain sub-scale of the foot health status questionnaire(FHSQ).Foot functionality was measured using the function sub-scale of the FHSQ.Symptom change was measured using the global rating of change scale(GROC).RESULTS Foot pain scores measured both by NRS and FHSQ pain sub-scale showed statistically significant reductions in foot pain in both groups(P<0.05)at six months.Both groups also reported statistically significant improvements(P<0.05)in function as measured by the FHSQ function subscale and improvement of symptoms as measured by the GROC scale.Between-group analysis showed that the intervention group with the combined use of orthotics and orthotic sandals scored better on all four outcome measures as compared to the control group with the sole use of orthotics.However,the between-group analysis only reached statistical significance on the NRS pain score(P<0.05).CONCLUSION Combined use of prefabricated orthotics and orthotic sandals provides a greater decrease in foot pain and improvement in foot function in PF compared to using prefabricated orthotics alone.

Diagnostic performance of different specimens in detecting enterovirus A71 in children with hand,foot and mouth disease

Hand,foot and mouth disease(HFMD)is a major public health problem among children in the Asia-Pacific region.The optimal specimen for HFMD virological diagnosis remains unclear.Enterovirus A71(EV-A71)neutralizing antibody titres detected in paired sera were considered the reference standard for calculating the sensitivity,specificity,positive and negative predictive value of throat swabs,rectal swabs,stool,blood samples and cerebrospinal fluid(CSF)by RT-PCR or ELISA assay.In this study,clinical samples from 276 HFMD patients were collected for analysing the sensitivity of different kind of specimens.Our results showed that stool had the highest sensitivity(88%,95%CI:74%–96%)and agreement with the reference standard(91%).The order of diagnostic yield for EV-A71 infection was stool samplerectal swab>throat swab>blood sample>CSF sample,and using a combination of clinical samples improved sensitivity for enterovirus detection.The sensitivity of ELISA for IgM antibody detection in sterile-site specimens was significantly higher than that of RT-PCR(serum/plasma:62%vs.2%,CSF:47%vs.0%)(P<0.002).In conclusion,our results suggest that stool has the highest diagnostic yield for EV-A71-infected HFMD.If stool is unavailable,rectal swabs can be collected to achieve a similar diagnostic yield.Otherwise,throat swabs may be useful in detecting positive samples.Although IgM in blood or CSF is diagnostically accurate,it lacks sensitivity,missing 40%–50%of cases.The higher proportion of severe cases and shorter interval between onset and sampling contributed to the increase in congruency between clinical testing and the serological reference standard.

The impact of EV71 vaccination program on hand,foot and mouth disease in Zhejiang Province,China:A negative control study

Objective:To estimate the potential causal impact of Enterovirus A71(EV71)vaccination program on the reduction of EV71-infected hand,foot,and mouth disease(HFMD)in Zhejiang Province.Methods:We utilized the longitudinal surveillance dataset of HFMD and EV71 vaccination in Zhejiang Province during 2010-2019.We estimated vaccine efficacy using a Bayesian structured time series(BSTS)model,and employed a negative control outcome(NCO)model to detect unmeasured confounding and reveal potential causal association.Results:We estimated that 20,132 EV71 cases(95%CI:16,733,23,532)were prevented by vaccination program during 2017-2019,corresponding to a reduction of 29%(95%CI:24%,34%).The effectiveness of vaccination increased annually,with reductions of 11%(95%CI:6%,16%)in 2017 and 66%(95%CI:61%,71%)in 2019.Children under 5 years old obtained greater benefits compared to those over 5 years.Cities with higher vaccination coverage experienced a sharper EV71 reduction compared to those with lower coverage.The NCO model detected no confounding factors in the association between vaccination and EV71 cases reduction.

Clinical characteristics of hand, foot and mouth disease in Harbin and the prediction of severe cases

Background Hand, foot and mouth disease （HFMD） is an emerging public health problem in China, not only threatening the health of children, but also causing tremendous loss and burden to both families and society. The aim of this study was to characterize the epidemiology and clinical features of HFMD, and to understand the key factors affecting HFMD in the Harbin region to provide scientific evidence for effective prevention and control strategies. Methods Epidemiological and clinical information from 2379 randomly chosen cases of HFMD treated at the Harbin Center for Disease Control and Prevention from May 2008 to November 2011 were analyzed. All cases were separated into common and severe HFMD, with key factors for severe HFMD analyzed using multivariable Logistic regression. Results Among the 2379 patients, 1798 were common cases and 581 severe cases, 14 of which resulted in death. Most cases were in children younger than 5 years. Morbidity peaked in July and was higher in the surrounding country and cities than in Harbin proper. Medical expenses were significantly higher for severe than for common cases （P 〈0.001）. The primary clinical symptoms were fever and erythema; laboratory examination showed leucocytosis together with pneumonia, carditis, and abnormal electrocardiogram and electroencephalogram in severe cases. Multivariabie Logistic regression analysis showed that the key factors for severe HFMD were age, morbidity location, morbidity area, fever duration, mouth mucosal symptoms, and abnormal serum levels of neutrophils （NEUT）, hemoglobin and glucose （P 〈0.05）. Conclusions To improve prognosis, reduce medical expense and prevent the development of severe cases, we should improve the epidemiological detection of HFMD to treat patients quickly. We should also closely monitor children with the EV71 virus, who present with continuous fever as well as abnormal laboratory results, from areas highly susceptible to