Risk Factors For Severe Hand, Foot And Mouth Disease Research Articles

Regional-level risk factors for severe hand-foot-and-mouth disease: an ecological study from mainland China

BackgroundSevere hand-foot-and-mouth disease (HFMD) is a life-threatening contagious disease among young children and infants. Although enterovirus A71 has been well acknowledged to be the dominant cause of severe HFMD, there still remain other unidentified risk factors for severe HFMD. Previous studies mainly focused on identifying the individual-level risk factors from a clinical perspective, while rare studies aimed to clarify the association between regional-level risk factors and severe HFMD, which may be more important from a public health perspective.MethodsWe retrieved the clinical HFMD counts between 2008 and 2014 from the Chinese Center for Disease Control and Prevention, which were used to calculated the case-severity rate in 143 prefectural-level cities in mainland China. For each of those 143 cities, we further obtained city-specific characteristics from the China City Statistical Yearbook (social and economic variables) and the national meteorological monitoring system (meteorological variables). A Poisson regression model was then used to estimate the associations between city-specific characteristics (reduced by the principal component analysis to avoid multicollinearity) and the case-severity rate of HFMD. The above analysis was further stratified by age and gender to examine potential modifying effects and vulnerable sub-populations.ResultsWe found that the case-severity rate of HFMD varied dramatically between cities, ranging from 0 to 8.09%. Cities with high case-severity rates were mainly clustered in Central China. By relating the case-severity rate to city-specific characteristics, we found that both the principal component characterized by a high level of social and economic development (RR = 0.823, 95%CI 0.739, 0.916) and another that characterized by warm and humid climate (RR = 0.771, 95%CI 0.619, 0.960) were negatively associated with the case-severity rate of HFMD. These estimations were consistent across age and gender sub-populations.ConclusionExcept for the type of infected pathogen, the case-severity rate of HFMD was closely related to city development and meteorological factor. These findings suggest that social and environmental factors may also play an important role in the progress of severe HFMD.

Risk factors for severe hand, foot, and mouth disease infected with Coxsackievirus A6: A hospital-based case-control study.

Coxsackievirus 6 (CV-A6) has been emerging as another predominant serotype for severe hand, foot, and mouth disease (HFMD) in China, after the introduction of enterovirus 71 inactivated vaccine (EV71 vaccine) for 3 years. Data on the risk factors for severe HFMD infected with CV-A6 are limited. We interviewed the caregivers to collected data on HFMD patients who sought medical care in the People's Hospital of Baoan district, Shenzhen, from 2015 to 2017. Totally, 131 severe patients were frequency-matched by age and gender with 174 mild patients infected with CV-A6. Univariable and multivariable logistic regression analyses were conducted to analyze the risk factors for severe CV-A6 HFMD. The average age was 20.62 ± 14.18 months and 20.52 ± 12.76 months for severe and mild patients, respectively. Multivariate analyses indicated complications at birth (odds ratio [OR], 4.18; 95% confidence interval [CI]: 1.64-10.63), peak body temperature over 39°C (OR, 4.04; 95% CI: 2.29-7.10) and first-born child (OR, 2.17; 95% CI: 1.27-3.70) increased the risk of severe HFMD infected with CV-A6. Breastfeeding (OR, 0.52; 95% CI: 0.32-0.87), and washing hands after playing frequently (OR, 0.58; 95% CI: 0.34-0.97) were negatively associated with severe illness. Compared with HFMD with infection of EV-A71, complications at birth and first-born child were newly found to be associated with severe illness in HFMD patients infected with CV-A6.

Association of IL-13, S100B, and TLR-7 Gene Polymorphisms with Enterovirus 71 Infection in Hand, Foot, and Mouth Disease in China.

This study was conducted to determine if single nucleotide polymorphisms within the interleukin (IL)-13 (rs20541 locus), the S100B (rs9722 locus), and the toll-like receptor (TLR)-7 (rs179019 and rs3853839 loci) genes are associated with the clinical severity of disease caused by enterovirus 71 (EV71) in children suffering from hand, foot, and mouth disease (HFMD). A total of 355 children, diagnosed with HFMD, were divided into two groups: severe (totaling 162 cases) and mild (totaling 193 cases). Three hundred healthy children were recruited as a control group. The gene polymorphisms of the rs20541 locus in the IL-13 gene; the rs9722 locus in the S100B gene; and the rs179019 and the rs3853839 loci in the TLR-7 gene were analyzed with Sanger sequencing. The expression levels of IL-13, S100B, interferon (IFN)-α, IL-6 and the relative expression level of TLR-7 were calculated for each genotype. This study demonstrated that the T allele at the rs9722 locus of the S100B gene was a significant risk factor for severe HFMD. The rs3853839 C allele of the TLR-7 gene was also a risk factor for severe HFMD in both male and female patients. The G allele at the rs20541 locus of IL-13 gene and the A allele at the rs179019 locus of the TLR-7 gene were not risk factors for severe HFMD in either male or female patients. The T allele at the rs9722 locus of S100B gene is a risk factor for the severe HFMD caused by EV71 infection, of which the mechanism may be due to the promotion of S100B protein secretion. The allele C at TLR-7 rs3853839 locus is a risk factor for the severe HFMD caused by EV71 infection, which may be related to a reduction of the relative expression of TLR-7, IFN-α, and IL-6.

The Risk Factors of Acquiring Severe Hand, Foot, and Mouth Disease: A Meta-Analysis.

Objectives The incidence of severe hand, foot, and mouth disease (HFMD) is not low, especially in mainland China in almost every year recently. In this study, we conducted a meta-analysis to generate large-scale evidence on the risk factors of severe HFMD to provide suggestions on prevention and controlling. Methods PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang (Chinese) were searched to identify relevant articles. All analyses were performed using Stata 14.0. Results We conducted a meta-analysis of 11 separate studies. Fever (odds ratio (OR) 7.396, 95% confidence interval (CI) 3.565–15.342), fever for more than 3 days (OR 5.773, 95% CI 4.199–7.939), vomiting (OR 6.023, 95% CI 2.598–13.963), limb trembling (OR 42.348, 95% CI 11.765–152.437), dyspnea (OR 12.869, 95% CI 1.948–85.017), contact with HFMD children (OR 5.326, 95% CI 1.263–22.466), rashes on the hips (OR 1.650, 95% CI 1.303–2.090), pathologic reflexes (OR 3057.064, 95% CI 494.409–19000), Lethargy (OR 31.791, 95% CI 3.369–300.020), convulsions (OR 23.652, 95% CI 1.973–283.592), and EV71 infection (OR 9.056, 95% CI 4.102–19.996) were significantly related to the risk of severe HFMD. We did not find an association between female sex (OR 0.918, 95% CI 0.738–1.142), scatter-lived children (OR 1.347, 95% CI 0.245–7.397), floating population (OR 0.847, 95% CI 0.202–3.549), rash on the hands (OR 0.740, 95% CI 0.292–1.874), rash on the foot (OR 0.905, 95% CI 0.645–1.272), the level of the clinic visited first (below the country level) (OR 5.276, 95% CI 0.781–35.630), breast feeding (OR 0.523, 95% CI 0.167–1.643), and the risk of severe HFMD. Conclusions Fever, fever for more than 3 days, vomiting, limb trembling, dyspnea, contact with HFMD children, rashes on the hips, pathologic reflexes, lethargy, convulsions, and EV71 infection are risk factors for severe HFMD.

Abstract P-134: RISK FACTORS OF SEVERE HAND FOOT AND MOUTH DISEASE IN AN EPIDEMIOLOGICAL SURVEY: A PROSPECTIVE MULTICENTER STUDY.

Aims & Objectives: carry out a multicenter epidemiological study of the severe hand foot and mouth disease (HFMD), to find out the clinical features, laboratory results, risk factors of severe HFMD. Methods A collaborative study group was established.Prospective epidemiologic approaches were adopted. Results We collected 128 HFMD cases in stage 2, 61 HFMD cases in stage 3, 37 HFMD cases in stage 4 from April 2014 to October 2016. The age ranged from 2 months to 13 years old, the mean age was 2.4 ± 1.3 years old, younger than 3 years accounted for 86.3%. Fever was obsevered in all the severe HFMD, mean temperature was 39.2 ± 0.7 (37.5~42) –, fever lasted for 4.54 ± 2.89 (1–16) days. 78.3% had typical rashes, 14.6% had atypic rashes, 7.1% had no rashes. The mean heart rate was 162.7 ± 28.6 (68–243) /min. The mean respiratory rate was 39.0 ± 8.4 (25–68) /min. Respiratory rhythm abnormality in stage 2, 3, 4 was 9.4%, 16.4%, 56.8% respectively. The mean blood glucose in stage 2, 3, 4 was 8.73 ± 3.18, 9.17 ± 3.99, 12.4 ± 4.74 respectively. The incidence of coma in stage 2, 3, 4 was 5.6%, 15.3%, and 47.2% respectively. Tachycardia, hypertension, drowsiness, dystonia, coma, respiratory rate increase, respiratoy rhythm abnormality, CRT more than 3 seconds, hyperglycemia, fever lasted more than 3 days were risk factors for severe HFMD. Conclusions The severe patients had obvious changes in the nervous, respiratory and circulatory system. Tachycardia, hypertension, drowsiness, dystonia, coma, respiratory rate increase, respiratoy rhythm abnormality, CRT more than 3 seconds, hyperglycemia, fever lasted more than 3 days were risk factors for severe HFMD.

Risk factors of severe hand, foot and mouth disease in Shantou, China: a case-control study.

In clinical perspectives, how to distinguish a small proportion of children at risk of developing neurological complications from a large number of children with mild symptoms still remains a challenge for primary care doctors. From January 2012 to December 2015, 225 cases with severe hand, foot and mouth disease (HFMD) matched with 492 controls were enrolled in the age-matched, case-control study. Continuous variables were examined by univariate analysis using a chi-squared or Fisher's exact test, and categorical variables were reported by relative risks (odd's ratio). Multivariate logistic regression was used to analyze the independent risk factors for severe HFMD. Peak body temperature over 37.5℃，total duration of fever over 3 days, lethargy, enterovirus 71 (EV71) infection were independent risk factors for severe HFMD. Peak body temperature over 37.5℃，total duration of fever over 3 days, lethargy, EV71 infection were independent risk factors for severe HFMD.

A multicenter study on clinical characteristics of severe hand, foot and mouth disease in East China

Objective To investigate the clinical features of severe hand, foot and mouth disease(HFMD) in recent three years, and to analyse the risk factors of severe HFMD. Methods A multicenter collaborative research group was set up, including five children′s hospitals(pediatric department)with high incidence of HFMD.Prospective epidemiologic approaches were adopted.After training, staffs from the collaborative center executed the study by filling up the record forms. Results We collected 114 HFMD cases in stage 2, 75 cases of HFMD in stage 3, 37 cases of HFMD in stage 4 from April 2014 to October 2016.The age ranged from 2 months to 13 years old, the median age was 2 years old, younger than 3 years accounted for 86.3%.Fever was observed in all the severe HFMD, mean temperature was (39.2±0.7) ℃, fever lasted for (4.54±2.89)d.The mean heart rates in stage 2, 3, 4 were (128.2±13.3, 176.1±22.2, 184.2±27.5)times/min, respectively.The mean arterial pressure was (84.4±14.6) mmHg(1 mmHg=0.133 kPa), the mean respiratory rate was (39.0±8.4)times/min, the mean respiratory rates in stage 2, 3, 4 were (37.8±7.36, 38.7±8.13, 43.4±10.7) times/min, respectively.Respiratory rhythm abnormality in stage 2, 3, 4 were 9.6%, 14.9% and 56.8%, respectively.The blood glucose increased gradually in 2, 3 and 4 stages, the mean blood glucose in stage 4 was (12.4±4.74)mmol/L.The incidence of coma in stage 4 was higher than those in stage 2 and 3.Multivariate Logistic regression analysis found that tachycardia, drowsiness, coma, respiratory rate increase, respiratory rhythm abnormality, capillary refilling time more than 3 seconds were risk factors for severe HFMD. Conclusion The incidence of severe HFMD is still high in children under 3 years of age in last three years.The severe patients have obvious changes in the nervous, respiratory and circulatory system.Tachycardia, drowsiness, coma, respiratory rate increase, respiratoy rhythm abnormality, capillary refilling time more than 3 seconds are risk factors for severe HFMD. Key words: Severe hand, foot and mouth disease; Risk factors; Epidemiology,

A Case-control Study on Risk Factors for Severe Hand, Foot and Mouth Disease

The objective of this study was to identify potential risk factors for severe hand, foot and mouth disease (HFMD). In this case-control study, 459 severe HFMD patients and 246 mild HFMD patients from Guangdong province and Henan province, China were included. Data comprising demographic characteristics, clinical symptoms and signs, laboratory findings and other factors were collected. Univariate analysis revealed 30 factors associated with severe cases. Further multivariate analysis indicated four independent risk factors: fatigue (p < 0.01, odd ratio [OR] = 204.7), the use of glucocorticoids (p = 0.03, OR = 10.44), the use of dehydrant drugs (p < 0.01, OR = 73.7) and maculopapular rash (p < 0.01, OR = 84.4); and one independent protective factor: herpes or ulcers in mouth (p = 0.01, OR = 0.02). However, more systematic research and validation are needed to understand the underlying risk factors for severe HFMD.

N-terminal pro-brain natriuretic peptide levels associated with severe hand, foot and mouth disease.

BackgroundSevere hand, foot, and mouth disease (HFMD) is sometimes associated with serious complications such as acute heart failure that can cause substantial child mortality. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a sensitive and specific biomarker of congestive heart failure. The aim of this study was to use plasma NT-proBNP levels to establish the severity of childhood HFMD.MethodsA retrospective study was performed in 128 Chinese patients with severe HFMD and 88 patients with mild HFMD treated between January 2014 and October 2015. Univariate and multiple logistic regression analyses were used to analyze the risk factors for severe HFMD. NT-proBNP levels were analyzed in 128 severe HFMD patients, and the predictive value of NT-proBNP was assessed by receiver operating characteristic analyses.ResultsMultivariate analysis controlling for several potential confounders showed that enterovirus 71 infection [odds ratio (OR) 19.944, 95 % confidence interval (CI) 6.492–61.271], peripheral WBC count (OR 3.428, 95 % CI 1.186–9.914), fasting glucose (OR 19.428, 95 % CI 2.236–168.784), procalcitonin (OR 9.084, 95 % CI 3.462–23.837, and NT-proBNP (>125 pg/mL) (OR 16.649, 95 % CI 4.731–58.585) were each associated with the severity of HFMD. The 45 dead severe patients had higher pre-procedural levels of NT-proBNP than the 83 cured severe patients (12776 ± 13115 versus 1435 ± 4201 pg/mL, P < 0.001). An NT-proBNP cutoff value of 982 pg/mL predicted mortality with 87 % sensitivity and 86 % specificity.ConclusionPlasma NT-pro-BNP level appears to be a useful biological marker for predicting the severity and mortality of HFMD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1929-9) contains supplementary material, which is available to authorized users.

The risk factors of critical hand, foot and mouth disease

Objective To explore the risk factors of severe hand, foot and mouth disease(HFMD)that progressed to critical illness among children. Methods The clinical data of 100 cases with severe and critical HFMD(82 cases were severe HFMD and 18 cases were critical)treated in the First Affiliated Hospital of Guangxi Medical University from January 2009 to September 2010 were analyzed retrospectively.We used univariate and multiple non-conditional Logistic regression analysis to compare the differences of the clinical features and laboratory examination between two groups, survey the risk factors of severe HFMD progressing. Results Most of the patients in both groups were under 5 years old, mainly under 3 years old which accounted for 85.4% of severe HFMD cases and 88.9% of critical HFMD cases.The dominant sex was male in both groups, the sex ratio were 2.28∶1 and 8.00∶1.The main pathogen was enteral virus 71.Fever and rash were found in most of the severe and critical patients.The main neurological symptoms were myoclonus, tremors, limb asthenia, somnolence, vomiting and convulsion.Nervous system symptoms in critical cases were even worse to develop to coma and accompany with serious respiratory and circulatory manifestations.Univariate analysis showed that age<2 years, tachycardia, tachypnea, elevated leukocyte count, platelet count and blood glucose level, persistent high fever, limb asthenia, pulmonary moist rales and changes on chest radiograph were the risk factors that progressed to critical illness.The multiple non-conditional Logistic regression analysis showed that age<2 years, tachycardia, limb asthenia and pulmonary moist rales were independent risk factors for severe HFMD cases progressing to critical illness. Conclusion The patients aged<2-year-old, tachycardia, limb asthenia and pulmonary moist rales are closely related to severe HFMD cases progressing to fatal condition. Key words: Hand, foot and mouth disease; Severe and critical; Risk factor,

Risk factors of severe hand, foot and mouth disease complicated with cardiopulmonary collapse

Background: The aim of this study was to investigate the risk factors for severe hand, foot and mouth disease (HFMD) complicated with cardiopulmonary collapse in children. Methods: In total, 176 children aged 6–45 months with severe HFMD from March 2013 to May 2014 were enrolled in the study and divided into two groups, one with cardiopulmonary collapse and the other without. Univariate analysis and multiple logistic regression analysis were used to analyze the risk factors for severe HFMD complicated with cardiopulmonary collapse. Results: The univariate analysis showed that there was no significant correlation between age, body temperature, consciousness disorders, blood glucose level and severe HFMD complicated with cardiopulmonary collapse. The multiple logistic regression analysis demonstrated that vomiting, circulatory disturbance, enterovirus 71 infection, dysfunction of respiratory rhythm and high level of brain natriuretic peptide were five independent risk factors for severe HFMD complicated with cardiopulmonary collapse. Conclusion: Children with HFMD and the above five risk factors may be at risk for cardiopulmonary collapse and poor prognosis.

Risk factors of severe hand, foot and mouth disease: a meta-analysis.

In recent years, outbreaks of hand, foot and mouth disease (HFMD) have increased, and more and more severe cases have appeared. We conducted a meta-analysis to generate large-scale evidence on the risk factors of severe HFMD. PubMed, Elsevier Science Direct, China National Knowledge Infrastructure (CNKI), and Wanfang (Chinese) were searched to identify relevant articles. All analyses were performed using Stata 11.0. We conducted a meta-analysis of 19 separate studies. Duration of fever ≥ 3 days (odds ratio (OR) 10.09, 95% confidence interval (CI) 6.22-16.35), body temperature ≥ 37.5°C (OR 4.91, 95% CI 1.26-19.18), lethargy (OR 7.75, 95% CI 3.78-15.89), hyperglycemia (OR 2.77, 95% CI 2.06-3.71), vomiting (OR 8.83, 95% CI 1.05-74.57), increased neutrophil count (weighted mean difference (WMD) 0.61, 95% CI 0.52-0.70), enterovirus 71 (EV71) infection (OR 5.13, 95% CI 3.11- 8.46), young age (WMD - 0.44, 95% CI - 0.69 to -0.19), and home care (OR 1.65, 95% CI 1.26-2.17) were significantly related to the risk of severe HFMD. We also found that a confirmed diagnosis at first visit to hospital significantly decreased the risk of severe HFMD (OR 0.30, 95% CI 0.09-0.99). We did not find an association between oral rash (OR 1.07, 95% CI 0.82-1.39), increased leukocyte count (WMD 0.51, 95% CI - 0.05-1.06), male sex (OR 1.06, 95% CI 0.91-1.24), or living in a rural area (OR 1.39, 95% CI 0.95-2.02) and the risk of severe HFMD. Duration of fever ≥ 3 days, body temperature ≥ 37.5°C, lethargy, hyperglycemia, vomiting, increased neutrophil count, EV71 infection, and young age are risk factors for severe HFMD. A confirmed diagnosis at first visit to hospital can significantly decrease the risk of severe HFMD.

Breastfeeding, previous Epstein-Barr virus infection, Enterovirus 71 infection, and rural residence are associated with the severity of hand, foot, and mouth disease

Severe hand, foot, and mouth disease (HFMD) is likely to develop critical complications such as brainstem encephalitis, acute pulmonary edema, and circulatory failure, which cause child mortality during outbreaks. This study aims to investigate factors that predict the severity of HFMD. One hundred sixteen in-patient children with severe HFMD and 202 with mild HFMD were retrospectively enrolled. Potential factors were collected for each child including sex, age, residence, modes of delivery, birth weight, virus types causing HFMD, and virus exposure history. Univariate and multivariable logistic regression were used to determine which factors were associated with HFMD severity. In the univariate analysis, breastfeeding (OR 0.514, 95 % CI 0.309-0.856), rural residence (OR 1.971, 95 % CI 1.239-3.137), current Enterovirus 71 (EV71) infection (OR 2.539, 95 % CI 1.504-4.287), and previous Epstein-Barr virus (EBV) exposure (OR 3.136, 95 % CI 1.863-5.278) were each associated with the severity of HFMD. In the multivariate model, breastfeeding (OR 0.570, 95 % CI 0.332-0.980), rural residence (OR 1.973, 95 % CI 1.202-3.237), current EV71 infection (OR 2.290, 95 % CI 1.315-3.987), and previous EBV exposure (OR 2.550, 95 % CI 1.470-4.422) remained independently associated with the severity of HFMD. In conclusion, previous EBV exposure, EV71 infection, and rural residence are risk factors for severe HFMD; breastfeeding is a protective factor.

Progress of severe hand, food and mouth disease

The virus of hand, foot and mouth disease(HFMD) damages nerve system. Brainstem is the main site and has some specific receptors. Severe HFMD has a high mortality. The main causes of death are cardiopulmonary and brain failure, so it is very important that risk factors of severe HFMD are timely judged and treated. Pulmonary edema of severe HFMD is mainly caused by neurological damage. At present, although it has still no standardized treatment scheme, the diagnosis and treatment for different stages have a significant effect. Key words: Severe hand, foot and mouth disease; Neurogenic pulmonary edema; Circulatory failure; Brainstem encephalitis