Severe Hand-foot-mouth Disease Research Articles

A study of serum proteome expression in patients with severe hand-foot-mouth disease.

Although numerous studies have been conducted on hand-foot-mouth disease (HFMD), the diagnosis of severe HFMD has not been fully clarified. Hence, it is important to further clarify the diagnosis of severe HFMD. In this study, we conducted a clinical biomarker discovery in patients with severe HFMD. In this study, serum samples were isolated from severe HFMD, HFMD, and healthy controls. Each group consisted of 32 cases. Isobaric tagging for relative and absolute quantitation (iTRAQ) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to detect proteome expression in the serum samples. Then, candidate proteins were screened and verified by ELISA. Protein expressions were significantly different between the HFMD group, severe HFMD group, and healthy control group. Comparison of the proteins between the three groups showed that serum amyloid A-1 protein (P0DJ18), C-reactive protein (P02741), fibronectin (P02751), plasminogen (P00747) and apolipoprotein A (P08519) were different, so they were selected as candidate proteins. However, the results of ELISA showed that the expression levels of serum amyloid A-1 protein, C-reactive protein, fibronectin, and apolipoprotein a in the severe HFMD group were significantly different from those in the other two groups (p<0.05). In conclusion, the results showed that serum amyloid A-1, C-reactive protein, fibronectin, and apolipoprotein A may be potential biomarkers for clinical diagnosis of severe HFMD.

Application Effect of Medical Care Integration Combined with Family Intervention under the Evidence-Based Nursing Mode on Child Patients with Severe Hand-Foot-Mouth Disease and Its Influence on Intestinal Function.

Objective To explore the application effect of medical care integration combined with family intervention under the evidence-based nursing mode on child patients with severe hand-foot-mouth disease (HFMD) and its influence on intestinal function. Methods 120 child patients with severe HFMD admitted to Qilu Children's Hospital of Shandong University from January 2019 to January 2020 were selected as the research object and randomly divided into group A and group B, with 60 cases each. Conventional nursing was performed on patients in group B, and medical care integration combined with family intervention under the evidence-based nursing mode was performed on patients in group A. Patients were assessed after the intervention using the hospital-made treatment adherence scale, PedsQLTM 4.0 (Pediatric Quality of Life Inventory Version 4.0) scale, and the faces pain scale-revised (FPS-R). The levels of gastrointestinal function indicators such as serum endotoxin (ET), diamine oxidase (DAO), and d-lactic acid (D-LA) were measured before and after the intervention, and recovery such as time to clear fever and time to relief of oral pain were recorded in both groups. Results Children in group A had significantly higher compliance in diet, behaviour, exercise, and medication than group B (P < 0.05); the time to clear fever, time to relief of oral pain, time to healing of oral ulcers, time to relief of skin herpes, time to hospitalization, and time to eating were shorter in group A than those in group B (P < 0.001); all scores on the PedsQLTM 4.0 scale were higher in group A than those in group B after the intervention (P < 0.001); ET, DAO, and D-LA levels decreased in both groups after the intervention, with group A having lower levels than group B (P < 0.001), in addition, group A had lower eating pain scores after the intervention (P < 0.05). Conclusion Medical care integration combined with family intervention under the evidence-based nursing mode can effectively improve the treatment compliance of child patients with severe HFMD, accelerate their recovery progress, ensure a better prognostic quality of life and gastrointestinal tract function, and reduce the eating pain, indicating that such comprehensive nursing intervention mode should be promoted in practice.

Relationship between polymorphism of receptor SCARB2 gene and clinical severity of enterovirus-71 associated hand-foot-mouth disease

BackgroundTo investigate the relationship between polymorphism of scavenger receptor class B member 2 (SCARB2) gene and clinical severity of enterovirus (EV)-71 associated hand-foot-mouth disease (HFMD).MethodsAmong the 100 recruited cases, 56 were in the severe HFMD group (case group) and 44 were in the general HFMD group (control group). By screening functional single nucleotide polymorphisms (SNPs) and hot SNPs, and performing SNP site optimization, some SNP sites of SCARB2 gene were selected for analysis. Genotyping was performed using a MassArray platform. PLINK software was used for statistical processing and analysis of the correlation differences between the mutant genotypes in the severe and general HFMD groups. The relationship between the SNPs and clinical severity of enterovirus (EV)-71 associated HFMD was assessed.Results28 SNPs in SCARB2 were selected by site optimization. Then three loci were not in agreement with the minor allele frequency (MAF) in the 1000 Han Chinese in Beijing (CHB) dataset. Another three loci could not be detected. Nine loci were not suitable for further analysis (MAF < 0.01 and Hardy–Weinberg [HWE] P < 0.001). A total of 13 sites were subsequently analyzed. Through Fisher analysis, the frequency of the rs6812193 T allele was 0.134 and 0.034 in the severe and general HFMD groups, respectively (P 0.023 < 0.05, odds ratio [OR] 4.381 > 1). Logistic regression analysis of rs6812193 T alleles between the severe and general HFMD groups, respectively (P 0.023 < 0.05, OR 4.412 > 1, L95 1.210 > 1). Genotype logistic regression analysis of the rs6812193 alleles CT + TT versus CC gave an OR of 4.56 (95% confidence interval [95% CI] 1.22–17.04, P = 0.012).ConclusionThe rs6812193 T allele was a susceptibility SNP for SHFMD, and the rs6812193 polymorphism might be significantly associated with the susceptibility to EV-71 infection.

Exuberant Hand-Foot-Mouth Disease: An Immunocompetent Adult with Atypical Findings.

Non-polio enteroviruses are ubiquitous viruses responsible for a wide spectrum of disease in people of all ages, although infection and illness disproportionately affect infants and young children. Hand-foot-mouth disease (HFMD) is an enteroviral clinical syndrome most frequently caused by coxsackievirus-A16 and enterovirus-A71. Since 2008, a novel coxsackievirus-A6 genotype has been associated with more severe HFMD in both children and adults, presenting with a unique constellation of findings, and whose prevalence has been increasing over the last few years. In this case report, an atypical clinical picture of confirmed enterovirus HFMD is described in an immunocompetent adult, with exuberant clinical findings, clinically consistent with coxsackievirus-A6 infection. This case report highlights the importance of awareness of the clinical presentation of this increasingly common infection in adults.LEARNING POINTSHand-foot-mouth disease (HFMD) caused by coxsackievirus-A6 is associated with more severe illness in adults, and presents with a peculiar constellation of findings that include delayed-onset skin desquamation and nail dystrophy.The prevalence of coxsackievirus-A6 HFMD has been increasing over the last few years.Dactylitis-like inflammatory signs on the distal extremities of the fingers can be a manifestation during the viral illness and may precede nail dystrophy.

Clinical effect of carvedilol in treatment of children with severe hand-foot-mouth disease caused by enterovirus 71 infection

To study the clinical effect of carvedilol in the treatment of children with severe hand-foot-mouth disease (HFMD) caused by enterovirus 71 (EV71) infection. A retrospective analysis was performed for the clinical data of 86 children with severe HFMD caused by EV71 infection who were admitted to the hospital from April 2016 to August 2017. According to whether carvedilol was used, the children were divided into conventional treatment group with 51 children and carvedilol treatment group with 35 children. A total of 56 healthy children who underwent physical examination at the outpatient service during the same period were enrolled as the control group. The two treatment groups were compared in terms of clinical features and levels of catecholamines (norepinephrine, adrenaline and dopamine), and the levels of catecholamines were compared between these two treatment groups and the control group. Before treatment, the conventional treatment group and the carvedilol treatment group had significantly higher levels of norepinephrine and adrenaline than the control group (P<0.05). After treatment, both the conventional treatment group and the carvedilol treatment group had significant reductions in norepinephrine, adrenaline, blood glucose, systolic pressure, diastolic pressure, heart rate, body temperature and leukocyte count (P<0.05). Compared with the conventional treatment group, the carvedilol treatment group had significantly lower dopamine level, blood glucose, heart rate and respiratory rate after treatment (P<0.05). Changes in norepinephrine and adrenaline might be involved in the pathogenesis of severe HFMD caused by EV71 infection. Carvedilol, in addition to the conventional treatment, can improve respiration, heart rate and blood glucose in children with severe HFMD caused by EV71 infection.

Expressions and significance of aquaporin-4 in children with severe hand-foot-mouth disease

Objective To explore the levels of water channel protein 4 (aquaporin-4, AQP-4) in the serum and the cerebrospinal fluid of patients with severe hand-foot-mouth disease (HFMD) and its clinical significance. Methods Children with the critical HFMD (clinical stage 3) admitted to Xuzhou Children′s Hospital from February 2017 to November 2017 were recruited(critical group). In the same period, another 25 cases of common HFMD (central nervous system infection excluded in cerebrospinal fluid examination, common group), the other 25 cases of severe HFMD (clinical stage 2, severe group) were taken as the controls.The levels of AQP-4 in the serum and and cerebrospinal fluid were measured in all children and the levels of AQP-4 in cerebrospinal fluid were checked again in the critical and severe cases after treatment.The levels of interleukin-6(IL-6), norepinephrine(NE) and neuron-specific enolase(NSE) in the serum were examined simultaneously and the correlation between them was analyzed. Results Before treatment, the levels of AQP-4 in the serum of critical group were(54.42±19.86) μg/L, which were significantly higher than common group[(8.02±1.59) μg/L] and severe group[(22.04±8.14) μg/L] (F=36.684, P<0.01). Compared with before treatment, the levels of AQP-4 in the serum of critical and severe group were significantly lower after treatment (P<0.05). Before treatment, the levels of AQP-4 in the cerebrospinal fluid of critical and severe cases were respectively (9.81±2.27) μg/L and (8.58±1.92) μg/L, which were significantly higher than common group(6.56±1.79) μg/L(F=6.713, P<0.05). After treatment, the levels of AQP-4 in the cerebrospinal fluid of critical and severe cases were (8.41±1.63) μg/L and (7.14±1.69) μg/ L separately, which were significantly lower than before treatment (t=6.340, 5.073, all P<0.01). The levels of IL-6, NE and NSE in serum were significantly different among the three groups(P<0.01). The above indicators were positively correlated with the levels of AQP-4 in the serum(r=0.734, 0.810, 0.729, all P<0.01)and were also positively correlated with AQP-4 in the cerebrospinal fluid(r=0.299, 0.431, 0.363, all P<0.05). Conclusion AQP-4 may participate in pathophysiological processes of HFMD.The levels of AQP-4 in serum can be used as an indicator for judging the severity and monitor prognosis of HFMD. Key words: Aquaporin-4; Hand-foot-mouth disease; Interleukin-6; Norepinephrine; Neuron-specific enolase

Effects of L-carnitine on serum levels of brain natriuretic peptide and N-terminal pro-brain natriuretic peptide and cardiac function in children with severe hand-foot-mouth disease

To observe the effects of L-carnitine treatment on serum levels of brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) and cardiac function in children with heart dysfunction and severe hand-foot-mouth disease (HFMD). A total of 120 children with severe HFMD were enrolled and randomly and equally divided into routine treatment group and L-carnitine treatment group. Thirty healthy children served as the control group. HFMD patients were given anti-fever and antiviral treatment as the basic treatment, while the patients in the L-carnitine treatment group were given L-carnitine as an adjuvant treatment to the basic treatment. Treatment outcomes were observed in the two groups. For all the subjects, serum levels of BNP and NT-proBNP and cardiac function parameters including left ventricular ejection fraction (LVEF), fractional shortening (FS), and cardiac index (CI) were measured at different time points before and after treatment. Before treatment, HFMD patients had significantly higher serum levels of BNP and NT-proBNP and heart rate but significantly lower LVEF, FS, and CI compared with the control group (P<0.05). After treatment, the L-carnitine treatment group had a significantly higher response rate than the routine treatment group (P<0.05). After 3 days of treatment, the serum levels of BNP and NT-proBNP, LVEF, FS, and CI were significantly reduced in the L-carnitine group (P<0.05); the L-carnitine group had significantly lower serum levels of BNP and NT-proBNP, LVEF, FS, and CI than the routine treatment group (P<0.05); there were no significant differences in the serum levels of BNP and NT-proBNP, LVEF, FS, or CI between the L-carnitine treatment and control groups (P>0.05). After 5 days of treatment, there were no significant differences in the serum levels of BNP and NT-proBNP, LVEF, FS, or CI between the L-carnitine treatment and routine treatment groups (P>0.05). Heart rate recovery was significantly slower in the routine treatment group than in the L-carnitine treatment group (P<0.05). As an adjuvant therapy for severe HFMD, L-carnitine treatment has satisfactory short-term efficacy in reducing the serum levels of BNP and NT-proBNP and improving cardiac function, thus improving clinical outcomes.

Analysis on epidemiological characteristics of enterovirus 71 cases of hand-foot-mouth disease based on the active monitoring in Guangdong Province in 2011-2015

Objective: To analyze the hand-foot-mouth disease (HFMD) enterovirus 71 (EV-A71) infection epidemic characteristics of Guangdong Province from 2011 to 2015. Methods: We colleted data on common cases of hand-foot-mouth disease infected with EV-A71 reported from eight sentinel hospitals in Guangdong Province from January 2011 to December 2015, through the "Guangdong Province Acute Infectious Disease Surveillance Information Platform System" , including the age and incidence of cases. Time and etiological data, etc.We also collected data on the number of reported cases of HFMD disease and the number of laboratory-confirmed cases, through the "China Disease Prevention and Control Information System" , including data on common cases of HFMD disease, data on epidemics of severe cases and deaths, and the age, onset time, and pathogens of cases. Learning data, etc.The data from two sources were used to estimate the incidence of HFMD in EV-A71 and describe its distribution characteristics.Chi-square test was used to compare the positive rate of HF-A71 infection in hand-foot-mouth disease and the difference in estimated incidence among different age groups and months. Results: Eight sentinel hospitals from 2011 to 2015 reported a total of 1 855 common cases of EV-A71 infection, of which the highest was in 2014 (31.6%, 605/1 916) and the lowest was in 2015 (6.8%, 134/1 971) (χ(2)=521.85, P<0.001).According to the Disease Surveillance Reporting Information System, 1 772 516 cases of HFMD disease were reported from 2011 to 2015 in Guangdong Province, and 1 902 cases of severe and fatal cases of EV-A71 infection.The composition ratio of EV-A71 infected was 72.6% (1 775/2 444) and 97.0% (127/131) of severe HFMD disease in Guangdong province during 2011-2015.The average annual incidence of HF-A71 infection in all age groups showed a decreasing trend with age (χ(2trend)=990 273.20, P<0.001), and it was the highest in the 1-year-old group, which was 1 697.67/100 000, and the lowest in the 4-year-old group, which was 705.46/100 000. The difference of monthly average incidence of EV-A71 infection in HF-A71 in each month was statistically significant (χ(2)=401.23, P<0.001), the highest in May at 15.51 per 100 000, and the lowest in July at 9.42 per 100 000. Conclusion: EV-A71 infection rate of ordinary HFMD varies in different years. The most severe and death cases of HFMD were EV-A71 infected. 1 year old children were the high-risk group of infected with EV-A71 HFMD. April was the epidemic months of EV-A71 HFMD infection.

Cell injury induced by 3D protein of different enterovirus 71 strains

Objective To compare the degree of cell injury induced by 3D protein (SDLY11 and SDLY107) of enterovirus 71 (EV71) strains. Methods EV71 strains SDLY11 and SDLY107 were respectively isolated from children with mild and severe hand foot mouth disease. The target genes 11-3D-Flag and 107-3D-Flag were amplified by reverse transcription-polymerase chain reation (RT-PCR) and inserted into the eukaryotic expression vector pcDNA3.1. The recombinant plasmids 11-3D-Flag-pcDNA3.1 and 107-3D-Flag-pcDNA3.1 were transformed into Escherichia. coli DH5α, respectively, and were identified by enzyme digestion and sequencing. The recombinant plasmids were transfected into rhabdomyosarcoma (RD) cells, respectively. Expression of 3D protein was detected by indirect immunofluorescence assay and western blot. Cell injury induced by 3D protein was detected with lactate dehydrogenase (LDH) test, cell proliferation was detected by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenylthiazolium bromide (MTT) test, and cell apoptosis was detected with Annexin-V and PI. Multiple comparisons among groups were analyzed using LSD-t test if multiple sets of variables were consistent with homogeneity of variance. If not, Dunnett T3 test was used. Results The 1 400 bp fragments were amplified by reverse tramscription (RT)-polymerase chain reaction (PCR), and the recombinant plasmids were digested by enzyme and the 1 400 bp and 5 400 bp fragments were obtained and identified. Gene sequencing showed that the sequences were consistent with the target genes. The specific fluorescence was observed by indirect immunofluorescence assay, and the western blot showed that the molecular weight of the target protein was 55×103. The LDH test showed that the A490 of SDLY11 3D protein transfection group (0.790±0.048) was higher than that of SDLY107 3D protein transfection group (0.641±0.018). The difference was statistically significant (t=5.14, P<0.05). The cell membrane damage caused by SDLY11 3D protein was more severe than SDLY107 3D protein. The MTT test showed that the A570 of SDLY11 3D protein transfection group (1.028±0.020) was lower than that of SDLY107 3D protein transfection group (1.081±0.002), and the difference was statistically significant (t=3.31, P<0.05). The effect on cell proliferation activity of SDLY11 3D protein was greater than SDLY107 3D protein. The results of Annexin-V/PI showed that the percentage of apoptotic cells of SDLY11 3D protein transfection group and SDLY107 3D protein transfection group were (1.471±0.246)% and (1.465±0.237)%, respectively, and the difference was not statistically significant (t=0.04, P=0.973). Conclusions Compared with the SDLY11 3D protein, SDLY107 3D protein induces slighter cell injury, has weaker effect on cell proliferation activity, and is more favorable for virus replication in cells. Key words: Enterovirus A, human; 3D protein; Cell injury

Phylogenetic analysis of VP1 region of CA16 isolated from children with severe hand-foot-mouth disease.

Background: CA16 and enterovirus 71 are two key etiological agents for children's hand-foot-mouth disease (HFMD). Large-scale HFMD outbreaks have taken place every year in Liaocheng City, Shandong Province of China since 2008. Objective: We investigated the genetic background and phyletic evolution of coxsackie virus A16 (CA16)-related severe HFMD in children from Liaocheng City. Method: CA16 was screened from throat swab and anus specimens obtained from children with severe HFMD between 2008 and 2010. Specific primers were used to amplify the VP1 region of CA 16 for sequence analysis. Result: A total of 461 specimens were detected to be enterovirus positive from 2008 to 2010 and 401 specimens were CA16 positive. The nucleotide and amino acid sequences of 16 isolates from children with severe HFMD were compared with the reference sequences, and the nucleotide homology was 91.43%-98.65%, and the amino acid homology was 97.98%-100%. Of the16 isolates, 9 isolates and BJ03-ZDP (AY821798), Shzh00-1 (AY790926), Shzh05-1 (EU262658), and GZ08 (FJ198212) strains isolated from Chinese mainland were located on the same branch; the remaining 7 isolates, the strains isolated from Malaysia, Thailand, Vietnam, Australia and other neighboring countries. AF177911 from Taiwan andshzh01-69 strain (AY895111) from Shenzhen were located on another branch. Conclusion: CA16 is one of the major pathogens of HFMD and the homology of strains is high. Keywords: Coxsackie virus A16, enterovirus, hand-foot-mouth disease

Spatial Clustering of Severe Hand-Foot-Mouth Disease Cases on Hainan Island, China.

The incidence of severe hand-foot-mouth disease (HFMD) in Southeast and East Asia has increased in recent years. This study explored spatial clusters of the incidence and proportion of severe HFMD cases on Hainan Island, where the prevalence and mortality of HFMD were the highest in China during 2011. A spatial autocorrelation statistic (Anselin's Local Moran I) was calculated for the Empirical Bayesian (EB)-smoothed dataset of severe HFMD cases. Significant spatial clusters were detected for both the incidence and proportion of severe HFMD cases. Population density was higher in spatial clusters with a high proportion of severe HFMD cases among total HFMD cases. We speculate that a higher proportion of severe HFMD cases were diagnosed in densely populated townships. This should be considered when analyzing the HFMD database of Hainan Island.

Expression of Treg cells, TH17 cells and related cytokines in peripheral blood of patients with severe hand-foot-mouth disease caused by Enterovirus 71 virus

Objective To investigate the changes of Treg cells, Th17 cells and related cytokines in peripheral blood of patients with severe hand-foot-mouth disease(HFMD) in the initial stage of infection caused by Enterovirus 71 virus. Methods Thirty-five cases of severe HFMD children in the Fifth Hospital of Shijiazhuang from May 2013 to December 2013 were selected as the research subjects, including 27 cases of severe formed group and 8 cases of danger severe formed group.The frequencies of Th17 cells(CD3+ CD8-IL-17+ ) and Treg cells(CD4+ CD25+ Foxp3+ ) in peripheral blood were detected by flow cytometry in patients with severe HFMD and 31 healthy children(control group). Moreover the serum levels of interleukin 6(IL-6), interleukin 17(IL-17), interleukin 10(IL-10), interleukin 23(IL-23), and human transforming growth factor β 1 (TGF-β 1) were measured by ELISA. Results As compared with those in control group, the frequencies of Treg cells, ratio of Treg/Th17, serum levels of TGF-β1, IL-10 in severe HFMD groups were significantly decreased(F=23.23, 30.88, 10.766, 11.680 respectively; P<0.05). However the frequency of Th17 cells, serum levels of IL-6, IL-17, IL-23 in severe HFMD groups were significantly increased(F=646.81, 5.904, 10.557, 3.490 respectively; P<0.05). Conclusion The changes of Treg and Thl7 cells and related cytokines appear in peripheral blood of patients with HFMD in the initial stage of infection caused by Enterovirus 71 virus.The frequency of Treg cell is decreased, however, the frequency of Thl7 cells frequency is increased, as a result, which may spread inflammatory reaction and cause complication. Key words: Hand-foot-mouth disease; Treg cells; Thl7 cells; Cytokines

Etiology study on severe cases caused by hand-foot-mouth disease in children from Henan province, 2014

To investigate the etiology of severe hand-foot-mouth disease (HFMD) in children in Henan province. A total of 244 HFMD cases admitted to a hospital in Zhengzhou from April to June of 2014 were recruited for research sampling, Real-time RT-PCR, virus isolation, VP1 sequencing and alignment methods were used to test the enterovirus-related etiology. SPSS 17.0 was used in performing statistical analysis. There were 109 severe and 135 mild cases among all the 244 HFMD cases. The number of enterovirus positive stool samples was 229, with positive rate as 93.85%. EV71, Cox A16 and Cox A10 made up 83.84%, 5.68% and 8.30% of the enterovirus etiologicy, strains, respectively. EV71 infection caused 8 HFMD cases with heart-lung failure and 2 death, Cox A10 infection led to 1 HFMD case with heart-lung failure and death. There were statistically differences seen regarding the enterovirus infection rates between severe and the mild HFMD cases (χ(2)=5.312,P=0.021). Statistically significant difference was seen in the constituent ratio of EV71, Cox A16 and the others by Fisher' s exact test (P=0.048). There was statistically significant difference seen between the cardiorespiratory failure rate and the fatality rate by EV71 and Cox A10 infection (χ(2)=0.051,P=0.821; χ(2)=2.198,P=0.138). Cox A10 strains idenfied in Henan in 2014 belonged to genotype 6. The rates on homology of nucleotide and amino acid among the Cox A10 strains in Henan in 2014 were 94.3%-99.7% and 96.3%-100.0% respectively. EV71 still remained the most common pathogen that causing severe HFMD in children, with the increasing Cox A10 percentage in the pathogens spectrum of HFMD infection. Cox A10 strains in Henan in 2014 belonged to genotype 6. Genotype 6 Cox A10 had appeared and widely distributed in Henan for long time, but not yet variated or reconstructed. Cox A10 infection could lead to cardio-respiratory failure thus called for the monitoring program on non-EV71 and non-Cox A16 enterovirus, especially Cox A10 to be strenthened.

Clinical significance of combined liver function and high-sensitivity C-reactive protein measurement in children with hand-foot-mouth disease.

Hand-foot-mouth disease (HFMD) is a common pediatric disease responsible for the development of rashes or herpes on the hand, foot, and mouth. Severe complications of HFMD include myocarditis, pulmonary edema, aseptic meningoencephalitis, and even death. Therefore, early diagnosis of HFMD is of particular importance. In this study, we determined the clinical value of the combined detection of liver function and high-sensitivity C-reactive protein (hs-CRP) expression in children with HFMD. Three hundred children with HFMD were recruited to this study between July 2013 and July 2015 and divided into the mild and severe HFMD groups (N = 150 per group). The liver function [aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) levels] and hs-CRP expression were evaluated using standardized tests, and the clinical value of combined detection of these indices (in parallel and serially) was determined. Patients in the severe HFMD group showed significantly higher levels of ALT, AST, ALP, and hs-CRP compared to those in the mild HFMD group (P < 0.05). The hs-CRP and liver function tests had low specificity and sensitivity, respectively. However, parallel combined detection improved the sensitivity and negative predicted value of these indices, whereas serial combined detection improved the specificity and positive predicted value. In conclusion, hs-CRP and liver function play a major role in the diagnosis of HFMD (and identifying its severity), and serial combined detection of these indices enhances the positive predicted value, and could be employed to diagnose severe HFMD at an earlier stage.

Risk factors for severe hand foot mouth disease in Singapore: a case control study.

BackgroundHand foot mouth disease (HFMD) is a common childhood infection that can potentially lead to serious complications. The aim of this study is to identify risk factors of acquiring severe HFMD in our population.MethodsWe performed a case control study using patients admitted to our hospital from August 2004 to July 2014. Cases were patients with severe HFMD disease while controls were age-matched patients obtained from the same year, in a 2:1 ratio. Data comprising demographic characteristics, clinical symptoms and signs, and lab findings were collected. Conditional univariable logistic regression was performed to determine risk factors for severe disease.ResultsA total of 24 cases of severe HFMD were identified and matched with 48 controls. Seventeen (70.8 %) cases had central nervous system complications. Seven (29.2 %) had cardiovascular complications without evidence of myocarditis. One patient died of encephalitis. The overall mortality of severe disease is 4 %. Evidence of hypoperfusion, seizure, altered mentation, meningeal irritation, tachycardia, tachypnea, raised absolute neutrophil count and EV-A71 (Enterovirus A71) positivity were significantly associated with a severe course of HFMD.ConclusionIn managing children with HFMD, physicians should consider these factors to help identify patients at risk for severe disease.

The clinical effect of ibuprofen in treatment of severe hand foot mouth disease and its effect on relative cytokines

Objective To investigate the clinical effect of ibuprofen in treating severe hand foot mouth disease and its effect on serum IL-6,TNF-αand IL-8. Methods 154 cases of severe hand foot and mouth disease were randomly divided into conventional treatment group and ibuprofen treatment group(each group 77 cases).And 77 cases of hand foot and mouth disease in the same period were admitted as normal control group.,.Two treatment group were given conventional antiviral and symptomatic treatment, ibuprofen treatment group was conducted with application of ibuprofen suspension liquid or drops of oral or nasal feeding. The clinical symptoms and signs, blood biochemical indexes, cerebrospinal fluid index and related cytokines were observed in the ibuprofen treated group and the routine treatment group. Results 72 hours after treatment, the treated with ibuprofen group of body temperature(t= 10.330,P=0.000),respiration(t=2.460,P=0.016),pulse(t=3.200,P=0.002)and blood pressure(Systolic pressure:t=2.000,P=0.049,Diastolic blood pressure:t=4.890,P=5.42)better than the conventional treatment group, cerebrospinal fluid pressure(t=3.330,P=0.001),protein(t=3.370,P=0.001),cell number(t=3.780,P=0.0003) and sugar level(t=3.410,P=0.001)were lower than the conventional treatment group;serum IL-6(t=6.961,P= 1.038),IL-8(t=4.229,P=6.463),and TNF-α(t=2.020,P=0.047)were significantly lower than those of the conventional treatment group,the differences had statistical significance(P<0.05). In addition,the treatment group of ibuprofen was superior to the conventional treatment group in the hot withdrawal time(t=5.210,P=1.59)and average hospitalization days(t=3.090,P=0.003). Conclusion Severe hand foot and mouth disease on the basis of routine treatment plus cloth ibuprofen treatment,is ideal effect, and can regulate the serum IL-6,IL-8,and TNF-α.It is worthy of popularization and application. Key words: Buprofen; Cytokine; Hand-foot-mouth disease

The value of N-terminal pro-Brain Natriuretic Peptide in children with severe hand-foot-mouth disease

Objective To explore the value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in assessing severity and predicting prognosis in children with severe hand-foot-mouth disease (HFMD). Methods A total of 119 eligible children with severe HFMD admitted in the pediatric intensive care unit were enrolled in this retrospective study from March 2012 to March 2014. According to NT-proBNP level, children were divided into ≤ 500 pg/mL group (n =70) and >500 pg/mL group (n =49) ; whereas according to severity, children were divided into severe-type (n =74) and critical-type (n =45) ; and based on 28 days outcome in children with critical-type HFMD, children were divided into fatal group (n =27) and survival group (n =18). The chi-square test, two-samplet test, rank sum test Pearson or Spearman' s correlation , area under the receiver operating characteristic curve (AUC) were used to analyze119 children with severe hand-foot-mouth disease (HFMD). Results Within 24 hours after admission, NT-proBNP>500 pg /mL group had higher rates of fever, abnormal breathing, abnormal heart rate, abnormal systolic blood pressure, capillary refill time >2 seconds and higher levels of laboratory biomarkers than NT-proBNP ≤ 500 pg/mL group (P <0.05) ; and during hospitalization, the rates of pulmonary edema, pulmonary hemorrhage and death also higher than NT-proBNP ≤ 500 pg/mL group (P <0.05 ). NT-proBNP, BS, WBC were higher in critical-type group than severe-type group (P =0.00) , while the PCIS (pediatric critical illness score) was lower in critical-type group (χ2 =14.70 , P =0.00). NT-proBNP was higher in fatal group than that in survival group (t =-2.60 , P =0.01) , PCIS was lower in fatal group (Z =2.70 , P =0.01) ; and there were no statistically significant differences in BS and WBC between fatal and survival groups (BS : t =-0.60 , P =0.55 ; WBC : t =-0.72 , P =0.48). NT-proBNP, BS and WBC were negatively correlated with PCIS (r values were -0.58 , -0.46, -0.56 , P values were 0.00). The AUCs of NT-proBNP, BS, WBC and PCIS to determine the severity of severe HFMD children were 0.94, 0.80, 0.74, and 0.97, respectively; and to predict 28 days survival in critical-type HFMD were 0.73 , 0.56 , 0.53 , and 0.73 , respectively. Conclusions Higher level of NT-proBNP could prompt cardiopulmonary involvement. NT-proBNP could reflect the severity of illness and served as a sensitive marker in predicting 28-day survival, being better than BS and WBC. Key words: N-terminal pro-brain natriuretic peptide; Severe; Hand-foot-mouth disease; Cardiopulmonary function; Pediatric critical illness score; Blood sugar; White blood cell; Prognosis

Therapeutic effect of nebulized human recombinant interferon α1b on severe hand-foot-mouth disease children with early study of nervous system complications

Objective To evaluate the efficacy and safety of nebulized recombinant human interferon α1b (IFN-α1b) for severe hand-foot-mouth disease(HFMD)children with central nervous system complications (CNSC). Methods This was a multi-center, prospective, cohort study.Severe HFMD children with CNSC from 3 hospitals were assigned to the control group with conventional therapy, and therapeutic group based on convetional therapy with nebulization of recombinant human IFN-α1b, 30 μg twice each day, for 5-7 days.The curative effect between 2 groups was compared by using SPSS 17.0 software. Results Sixty-six cases were enrolled from May to November 2013.Compared with conventional therapy, the treatment of nebulized IFN-α1b could significantly reduce the duration of fever[treatment group (1.9±1.1) d vs control group (2.7±1.2) d, P<0.05 ], the recovery time of food intake[treatment group (3.9±1.4) d vs control group (4.9±1.6) d, P<0.05] and the duration of the central nervous system syndrome[(2.6±1.1) d vs (3.2±1.0) d, P<0.05], especially shorten the duration of convulsion[treatment group (2.4±1.0) d vs control group (3.2±0.9) d, P<0.05]and myoclonic jerk[(2.0±1.1) vs (2.9±1.2) d, P<0.05]. Vital signs, routine hematological and biochemical parameters were monitored and no adverse effect was observed during the treatment. Conclusion Nebulization of human recombinant IFN-α1b can significantly and safely alleviate early clinical syndrome of severe HFMD children. Key words: Nebulization; Hand- foot-mouth disease; Human recombinant interferon α1b; Nervous system complications

Risk Factors for Severe Hand-Foot-Mouth Disease in Children in Hainan, China, 2011-2012.

The incidence of severe/fatal cases of hand-foot-mouth disease (HFMD) has increased in South Asia. In China, Hainan Province had the highest incidence of mortality associated with HFMD in 2011. This study investigated the risk factors for severe HFMD in Hainan. The HFMD survey database for Hainan Province for 2011 and 2012 was analyzed, and the biological and behavioral characteristics of severe (n = 980) and nonsevere (n = 1679) HFMD were compared. The association between each explanatory variable and the severity of HFMD was investigated using a logistic regression model after adjusting for confounders. Human enterovirus 71 infection, a peak body temperature >39°C, living outside urban areas, visiting a village clinic, low birth weight, never breastfed, cared for by grandparents, and caregiver with <6 years of education were associated with severe HFMD. Individual characteristics that are generally shared by children in households of low socioeconomic status tended to increase the risk of severe HFMD.

Dynamic changes in serum inflammatory cytokines and their association with neurogenic pulmonary edema in patients with severe hand-foot-mouth disease

Objective To investigate the dynamic changes in the serum inflammatory cytokines and their association with neurogenic pulmonary edema (NPE)in the patients with severe hand-foot-mouth disease (HFMD). Methods Eighty-nine patients with severe HFMD from March 2010 to December 2012 were recruited in the study.The patients were divided into NPE group and central nervous system diseases(CNSD) group according whether they had NPE.The cytokines, including interleukin (IL)-4, IL-6, IL-10, IL-17, tumor necrosis factor-α(TNF-α) and interferon-γ(IFN-γ)were evaluated by using enzyme-linked immunosorbent assay on day 1, 3 and 5 after admission to hospital.Risk factors for NPE involvement during hospital stay were analyzed with multivariate Logistic regression analysis. Results (1)Compared with the CNSD group, the serum levels of IL-6(Ftime=1.876, P=0.177, Ftime*group=2.192, P=0.145, Fgroup=7.855, P=0.007), TNF-α(Ftime=13.133, P=0.001, Ftime*group=0.291, P=0.592, Fgroup=3.644, P=0.042), IL-10(Ftime=14.580, P=0.001, Ftime*group=2.612, P=0.078, Fgroup=16.823, P=0.000), INF-γ(Ftime=3.093, P=0.045, Ftime*group= 0.513, P=0.600, Fgroup=20.141, P=0.000)were significantly higher than those in NPE group.(2)The serum levels of TNF-α, IL-10, INF-γ rose to the peak on the third day.(3) By using multivariate Logistic regression analysis, age (OR=3.383, 95% CI: 1.173-4.759), days of fever (OR=4.925, 95%CI: 1.758-3.794), hyperglycaemia (OR=3.465, 95%CI: 1.303-5.220), leucocytosis (OR=7.579, 95%CI: 2.530-12.704)and elevation of IL-10 (OR=1.228, 95%CI: 1.007-1.523) were entered into equation.In the risk evaluation model, these variables remained independent predictors for NPE. Conclusions Abnormal cytokine productions appear to be responsible for the pathogenesis of NPE, and might be an effective tool for predicting NPE in infants with severe HFMD. Key words: Hand-foot-mouth disease; Cytokine; Dynamic change; Neurogenic pulmonary edema