Value of serum pattern recognition receptors Collectin, Dectin and CD14 detection for disease evaluation in children with hand, foot and mouth disease

Objective:To study the value of serum pattern recognition receptors Collectin, Dectin and CD14 detection for disease evaluation in children with hand, foot and mouth disease (HFMD). Methods:76 children diagnosed with hand, foot and mouth disease in our hospital between May 2013 and March 2016 were selected as the HFMD group of the research, 80 healthy children receiving physical examination in our hospital during the same period were selected as the control group of the research, and the serum was collected to determine the levels of pattern recognition receptors, immunoglobulins, complements, inflammatory media and target organ damage indexes. Results:Serum Collectin, Dectin and CD14 levels of HFMD group were significantly higher than those of control group (P<0.05);serum immunoglobulin G (IgG) IgM, IgA, C3 and C4 levels of HFMD group were significantly lower than those of control group (P<0.05) and negatively correlated with Collectin, Dectin and CD14 levels;serum PCT, C-reactive protein (CRP), interleukin-6 (IL-6), IL-10, tumor necrosis factor-α(TNF-α), N-terminal pro-brain natriuretic peptide (NT-proBNP), neuron-specific enolase (NSE), S100βand surfactant protein A (SP-A) levels of HFMD group were significantly higher than those of control group (P<0.05) and positively correlated with Collectin, Dectin and CD14 levels. Conclusions:High expression of serum pattern recognition receptors Collectin, Dectin and CD14 in children with hand, foot and mouth disease is closely related to the immune response, inflammatory response and target organ function damage during the disease progression.

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.

Predictive correlation test of acute respiratory failure in children with hand foot mouth disease

Objective:To investigate the predictive correlation test of acute respiratory failure in children with hand foot mouth disease (HFMD).Methods: Selected from our hospital June 2014 to June 2017 HFMD incidence of acute respiratory failure in 31 cases as a observation group;Selected from our hospital same period HFMD patients without acute respiratory failure in 35 cases as the control group;the other is selected from healthy children 40 cases as normal group. There were collected three groups peripheral venous blood 2 mL, and serum was isolated. Enzyme linked immunosorbent assay was used for the determination of IL-6. The content of CRP was measured by Backman OLYMPUS AU640 automatic biochemical analyzer. The contents of creatine kinase (CK), creatine kinase isozyme (CK-MB) and lactate dehydrogenase (LDH) were determined by Backman OLYMPUS AU640 automatic biochemical analyzer. The content of troponin I (cTnI) was measured by Backman ACCESS2 chemiluminescence immunoanalyzer.Results:The serum levels of IL-6, CRP, CK, CK-MB, LDH and cTnI in the observation group were higher than those in the control group and the normal group. After treatment serum levels of IL-6, CRP, CK, CK-MB, LDH and cTnI were lower than those before treatment, and there were statistically significant differences.Conclusion: serum IL-6, CRP index and serum CK, CK-MB, LDH and cTnI indexes can be used as indicators for the prediction of acute respiratory failure in children with hand foot mouth disease, and have important clinical significance.

Clinical observation of effects of pidotimod combined with ribavirin on inflammatory factors, T lymphocyte subsets, immunoglobulin and blood biochemical markers in children with hand-foot-mouth disease

Objective:To observe the effects of pidotimod combined with ribavirin on inflammatory factors, T lymphocyte subsets, immunoglobulin, lactate, D-dimer and procalcitonin in children with hand-foot-mouth disease.Methods: A total of 108 children with foot-hand-and-mouth epidemic in our hospital from Jan. 2013-Dec. 2016 were divide into the observation group and the control group, each groups has 54 cases. Two groups of children were treated with isolation, the observation group was given pidotimod combined with ribavirin, and the control group was treated with ribavirin. 5 mL venous blood of two group patients were collected at admission and after 6 d treatment, respectively, to compare inflammatory factor, T lymphocyte subsets, immunoglobulin, lactate, D-dimer and procalcitonin in two groups.Results: Before treatment, the levels of inflammatory factor, T lymphocyte subsets, immunoglobulin, lactate, D-dimer and procalcitonin of two groups were not statistically significant. Compared with groups after treatment, the levels of CRP, IL-6, TNF-α were lower than that before treatment, CRP (2.23±0.37) mg/L, IL-6 (21.24±9.81) pg/mL and TNF-α (56.97±50.36) pg/mL levels in observation group after treatment were significantly lower than those in control group, the difference was statistically significant. After treatment, the levels of CD3, CD4, CD4/CD8, IgG, IgA and IgM in control group were significantly higher than that before treatment, the difference was statistically significant;After treatment, the levels of CD3 (51.26±10.27)%, CD4 (36.36±4.09)% and CD4/CD8 (1.60±0.47), IgG (10.24±1.82) mg/L, IgA (1.30±0.31) mg/L and IgM (1.48±0.30) mg/L in observation group were significantly higher than in control group, the difference was statistically significant. After treatment, the levels of lactate, D-dimer and procalcitonin in two groups were significantly lower than that before treatment, the difference was statistically significant;After treatment, the levels of lactate (1.19±0.20) mmol/L, D-dimer (150.23±27.21) ng/mL, and procalcitonin (0.08±0.02) ng/mL in observation group were significantly higher than in control group, the difference was statistically significant. Conclusion: Pidotimod combined with ribavirin has a pronounced effect on children with hand-foot-mouth disease, which can effectively reduce the body's inflammatory response, enhance immune function, improve clinical biochemical indicators, and should be widely recommended for clinical use.

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.

Hand Foot and Mouth Disease Due to Enterovirus 71 in Malaysia

Hand foot and mouth disease is a febrile sickness complex characterized by cutaneous eruption (exanthem) on the palms and soles with simultaneous occurrence of muco-cutanous vesiculo-ulcerative lesions (enanthem) affecting the mouth. The illness is caused by a number of enteroviruses with coxsackievirus A16 and enterovirus 71 as the main causative agents. Human enterovirus 71 (EV71) belongs to the species Human enterovirus A under the genus Enterovirus within the family Picornaviridae. EV71 has been associated with an array of clinical diseases including hand foot and mouth disease (HFMD), aseptic meningitis, encephalitis and poliomyelitis-like acute flaccid paralysis. A large outbreak of HFMD due to highly neurovirulent EV71 emerged in Malaysia in 1997, and caused 41 deaths amongst young children. In late 2000, a recurrence of an outbreak of HFMD occurred in Malaysia with 8 fatalities in peninsular Malaysia. Outbreak of HFMD due to EV71 recurred in 2003 with an unknown number of cases and mortalities. A similar outbreak of HFMD with 2 recorded deaths in young children occurred in peninsular Malaysia in late 2005 and this was followed by a larger outbreak in Sarawak (Malaysian Borneo) with 6 reported fatalities in the early part of 2006. The current on-going outbreak of HFMD started in peninsular Malaysia in epidemiological week 12 of 2010. As with other HFMD outbreaks in Malaysia, both EV71 and CA16 were the main aetiological viruses isolated. In similarity with the HFMD outbreak in 2005, the isolation of CA16 preceded the appearance of EV71. Based on the VP1 gene nucleotide sequences, 4 sub-genogroups of EV71 (C1, C2, B3 and B4) co-circulated and caused the outbreak of hand, foot and mouth disease in peninsular Malaysia in 1997. Two sub-genogroups (C1 and B4) were noted to cause the outbreak in 2000 in both peninsular Malaysia and Sarawak. EV71 of sub-genogroup B5 with smaller contribution from sub-genogroup C1 caused the outbreak in 2003. In the 2005 outbreak, besides the EV71 strains of sub-genogroup C1, EV71 strains belonging to sub-genogroup B5 were isolated but formed a cluster which was distinct from the EV71 strains from the sub-genogroup B5 isolated in 2003. The four EV71 strains isolated from clinical specimens of patients with hand, foot and mouth disease in the Sarawak outbreak in early 2006 also belonged to sub-genogroup B5. Phylogenetic analysis of the VP1 gene suggests that the EV71 strains causing the outbreak in Sarawak could have originated from peninsular Malaysia. Epidemiological and molecular data since 1997 show the recurrence of HFMD due to EV71 in Malaysia every 2 to 4 years. In each of the past outbreaks, more than one sub-genogroup of the virus co-circulate.

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.

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.

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.

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.

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.

A randomized controlled clinical study on treatment of hand, foot and mouth disease in children with Reduning injection

Hand, foot and mouth disease （HFMD） has become a major public health problem in China since 2008,which has been widely prevalent in children under 5 years of age. According to the data of the Ministry of Health, the number of cases with HFMD exceeded 1 million during the recent 4 years. The major etiologic agent of HFMD is enterovirus 71 and coxsackievirus A 16. The main clinical manifestations of the disease include fever, maculopapular skin vesicles on the hand, foot and buttock, oral herpes, ulcer; ation severe cases there can be central nervous system infection and/or pulmonary hemorrhage, which are mostly caused by EV71 and may be life-threatening with a fatality rate of 0.3 to 0.5 per thousand cases. There are no specific antiviral drugs, nor vaccine against EV71.~ The difficult problem of the treatment is how to reduce the severe cases and mortality. Reduning injection is a preparation of traditional Chinese herbal medicine composed of Qinghao （Artemisiae annuae）, Jinyinhua （Flos lonicerae） and Zhizi （Gardenia jasminoides）, which was listed among the therapies for HFMD in the 2010 guidelines of the Ministry of Health for diagnosis and treatment of HFMD.2 We now reported the results of our study on the efficacy of Reduning injection in treatment of 81 patients with HFMD. We selected 81 cases who were inpatients treated in 2010 in the Department of Infectious Diseases of Quanzhou Chidren＇s Hospital. The inclusion criteria were as follows： 1. Patients who met either the clinical diagnostic criteria for HFMD ordinary clinical type or the clinical diagnostic criteria for confirmed cases of HFMD （etiologically confirmed cases must account for more than 1/3 of the cases）. 2. The axillary temperature is _〉37.5~C, within 48 hours after onset of the disease; 3. Skin changes such as the rashes and vesicles occurred in no more than 48 hours; 4. Range of age is between 1 and 13 years; 5. Patients or their parents or guardians are willing to participate in the study and sign the informed consent forms. The exclusion criteria were as follows： 1. Patients who are complicated with the following primary diseases： congenital heart disease, chronic hepatitis, acute or chronic nephritis, diseases of hematologic system; 2. Patients who have hypersensitivity with history of allergy to the study drugs or other drugs; 3. Patients who were treated with western or traditional Chinese medicines other than the study medicines for HFMD by the time of the visit to the hospital; 4. Patientswho have been participated in other clinical trial for HFMD. The patients were centrally randomized （the random numbers were obtained from the web version of the Randomization System of Clinical Studies, Clinical Evaluation Center of Chinese Academy of Traditional Chinese Medicine, No. 200907001-3） into the following 3 groups： Reduning group （group 1）, 28 cases with 21 men and 7 women; age 12-72 （mean 29.2＋18.8） months; 24 were positive for EV71, 2 were positive for CoxA16 and 2 were negative for both; treated with intravenous infusion of Reduning （Jiangsu Kangyuan Pharmaceutical Corporation, Ltd., 10 ml in each vial, Batch number 100122） at a dose of 0.5 ml.kg-＇.d＂ added into 10% glucose solution for injection, once a day. Symptomatic treatment group （group 2）, 27 cases with 19 male and 8 female; age 12-96 （mean 28.7＋20.4） months; 19 were positive for EV71, 3 were positive for CoxA16 and 5 were negative for both; these patients were treated with intravenous infusion of vitamin C （0.5-1.0 g/d） and B6 （50-100 mg/d） added into 10% glucose solution for injection and ibuprofen （5-10 mg/kg per day, 6-8 hours repeat p.r.n.） or Aspisol （15-25 mg＇kg＂.d1） was used for antipyretic purpose. Antibiotics were added for patients who had increased peripheral blood leukocyte count. And Reduning plus symptomatic treatment group （group 3）, had 26 cases with 17 male and 9 female; age 12-84 （mean 30.4＋16.6） months; 18 were positive for EV71, 4 were positive for CoxA16 and 5 were negative for both viruses; these cases were treated with both Reduning and symptomatic treatments. No significant difference was found among the 3 groups in age, sex and etiological characteristics compared using chi-square test （P 〉0.05）. The numbers of patients who were positive for EV7I or CoxA 16 accounted for 75.3% and 11.1% for each group.

Xiyanping injection therapy for children with mild hand foot and mouth disease:a randomized controlled trial

OBJECTIVE: To evaluate the clinical effects of Xiyan-ping injection intervention in pediatric patients with mild hand foot and mouth disease(HFMD).METHODS: A total of 329 patients were stratified and block-randomized for symptomatic treatment of HFMD and assigned to one of the following groups: Western Medicine(group A, n = 103), Xiyanping injection(group B, n = 109), or Xiyanping injection and symptomatic treatment using Western Medicine(group C, n = 117). During the trial, fever,rash, ulcers of the mouth were observed among participants in each group before and after treatment, and conversion rates from mild to severe HFMD were measured.RESULTS: After 3-7 days' treatment, no significant differences in the conversion rates from mild to severe HFMD were observed among the three groups(P > 0.05). There was a significantly low number of patients with the onset time of antifebrile effect,vanished time of hand and foot rashes and cumulative time for the ulcers in the mouth vanished,among the three groups(P < 0.05, P < 0.01). The onset time of antifebrile effect of patients in groups B and C were markedly shorter compared with those in group A(P < 0.05, P < 0.01); there was no statically significant difference observed between groups B and C(P > 0.05). No significant differences were observed in the time for body temperature recovery among the three groups(P > 0.05). There were no significant differences in adverse effects among the three groups(P > 0.05).CONCLUSION: Xiyanping injection together with use of Western Medicine is most effective for symptomatic treatment of mild HFMD. No severe adverse reactions were observed.

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.

Molecular Epidemiology of Enteroviruses Associated with Hand, Foot, and Mouth Disease in the Mainland of China

Hand, foot, and mouth disease （HFMD） is a common contagious illness which occurs worldwide both sporadically and in epidemics. The disease mainly affects, children and the typical symptoms, which may resolve spontaneously, include mucocutaneous papulovesicular lesions on the hands, feet, mouth, and buttocks. In rare cases, however, the patients may also develop neurological complications such as neurogenic pulmonary edema,

Genetic Variation of Multiple Serotypes of Enteroviruses Associated with Hand, Foot and Mouth Disease in Southern China

Enteroviruses(EVs)species A are a major public health issue in the Asia–Pacific region and cause frequent epidemics of hand,foot and mouth disease(HFMD)in China.Mild infections are common in children;however,HFMD can also cause severe illness that affects the central nervous system.To molecularly characterize EVs,a prospective HFMD virological surveillance program was performed in China between 2013 and 2016.Throat swabs,rectal swabs and stool samples were collected from suspected HFMD patients at participating hospitals.EVs were detected using generic real-time and nested reverse transcription-polymerase chain reactions(RT-PCRs).Then,the complete VP1 regions of enterovirus A71(EV-A71),coxsackievirus A16(CVA16)and CVA6 were sequenced to analyze amino acid changes and construct a viral molecular phylogeny.Of the 2836 enrolled HFMD patients,2,517(89%)were EV positive.The most frequently detected EVs were CVA16(32.5%,819),CVA6(31.2%,785),and EV-A71(20.4%,514).The subgenogroups CVA16B1 b,CVA6D3 a and EV-A71C4 a were predominant in China and recombination was not observed in the VP1 region.Sequence analysis revealed amino acid variations at the 30,29 and 44 positions in the VP1 region of EV-A71,CVA16 and CVA6(compared to the respective prototype strains Br Cr,G10 and Gdula),respectively.Furthermore,in 21 of 24(87.5%)identified EV-A71 samples,a known amino acid substitution(D31 N)that may enhance neurovirulence was detected.Our study provides insights about the genetic characteristics of common HFMD-associated EVs.However,the emergence and virulence of the described mutations require further investigation.

Seroprevalence of Toxoplasma gondii infection among patients with hand, foot and mouth disease in Henan, China: a hospital-based study

Background:The prevalence of infection with Toxoplasma gondii(T.gondii)in humans has been increasing in China due to the growing number of cats in the country.Hand,foot and mouth disease(HFMD)is a serious public health issue in China and still one of the leading causes of child mortality.However,little is known about the epidemiology of T.gondii infection among HFMD patients.Methods:A case–control study of 281 HFMD patients from the First People’s Hospital of Pingdingshan in Pingdingshan city,Henan province,central China,and 222 controls from Pingdingshan city was conducted.Anti-T.gondii antibodies were serologically detected using the enzyme-linked immunosorbent assay.Results:We found that the overall anti-T.gondii immunoglobulin G(IgG)antibody prevalence among HFMD patients was 12.46%,which was significantly higher than that in clinically healthy children(1.80%).The highest T.gondii seroprevalence was detected in critical cases(22.58%),followed by severe cases(11.50%),and the lowest was detected in mild cases(8.33%).Conclusion:The present study is the first survey of T.gondii seroprevalence among HFMD patients in China;12.46%were defined as seropositive.It is imperative that improved integrated measures are taken to prevent and control T.gondii infection among HFMD patients.

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.

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

Association of IFNGR2 and IL-12B gene polymorphisms with susceptibility to hand,foot and mouth disease infected by EV71

Objective:To study the relationship between the single nucleotide polymorphisms(SNPs)of IFNGR2genes(rs9808753,rs11910627 and rs1532) and IL-12 B gene(rs2288831)and the susceptibility to hand,foot and mouth disease(HFMD)caused by enterovirus 71(EV71).Methods:Blood samples were collected from 145 HFMD children infected by EV71,104 children with EV71 covert infection,and 89 normal control children,followed by DNA extraction.IFNGR2 and IL-12 Bpolymorphisms were detected by imLDRTM.Results:Compared with the control group,IFNGR2rs9808753 genotype and allele distributions of EV71-infected group and EV71 covert infection group showed significant differences(P<0.05).A allele frequency in EV71-infected patients and covert EV71-infected patients was higher than that in the control group(P <0.05).While the genotype and allele frequencies of rs2288831 in IL-12 B did not show significant difference between EV71-infected groups and healthy controls.Conclusion:These findings suggested that the single nucleotide polymorphism of IFNGR2 gene site rs9808753(A/G)was associated with the susceptibility to EV71-infection,and A allele of rs9808753 might be one potential genetic susceptibility factor of EV71-infection.While the rs2288831(C/T)polymorphism of IL-12 Bdid not correlate with the susceptibility of EV71-infection.