韦氏智力量表

Original articleClinical characteristics of hand, foot and mouth disease in Harbin and the prediction of severe casesZHOU Hong, GUO Shu-zhen, ZHOU Hao, ZHU Yue-feng, ZHANG Li-juan and ZHANG WeiKeywords: hand, foot and mouth disease; diagnosis; epidemiologyBackground 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 togetherwith pneumonia, carditis, and abnormal electrocardiogram and electroencephalogram in severe cases. Multivariable 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 HFMD attacks.Chin Med J 2012;125(7):1261-1265and, foot and mouth disease (HFMD) is one of themost common contagious diseases caused by an enterovirus, usually enterovirus 71 strain (EV71) or coxsackie virus A Group 16 strain (CA16).1The virus may reach the brainstem and spinal cord,2 causing severe complications in patients, usually infants. The clinical manifestation is mainly maculopapule and erythema on the hands, feet, mouth, and buttocks; severe cases may also present with cephalomeningitis, cephalitis, encephalomyelitis, pneumonedema, and dysaemia.3,4 Cases of HFMD have been reported in most countries and areas of the world. In China, the first confirmed case of HFMD was reported in 1981 in Shanghai.5Today, the disease is one of the most common contagious diseases in China, with a large morbidity area and increasing morbidity. According to national statistics, HFMD is ranked second in morbidity among all contagious diseases and is the sixth leading cause of death.6Despite detailed investigations of the clinical symptoms and etiological diagnosis of HFMD, the epidemiology and clinical features of HFMD in Heilongjiang province are few, and very few reports of severe HFMD have described the key factors. In our study, we examined HFMD cases in Harbin from 2008 to 2011, and used retrospective analysis to determine the clinical features and epidemiology of HFMD. We also looked at the key factors associated with severe cases in this region, to develop effective prevention and control strategies.METHODSPatientsHFMD not only threatens the health of children, but also causes tremendous loss for both families and society. This disease has become a major public health problem for China and Asia at large. We analyzed a random sample of 2379 cases of HFMD who were admitted to the Harbin Center for Disease Control and Prevention from May 2008 to November 2011. Patients were assigned as having either common or severe HRMD, using the diagnostic code (DC) in theHDOI: 10.3760/cma.j.issn.0366-6999.2012.07.013Department of Infectious Diseases, First Affiliated ClinicalHospital of Harbin Medical University, Harbin, Heilongjiang150086, China (Zhou H, Zhu YF, Zhang LJ and Zhang W)Harbin Center for Disease Control and Prevention, Harbin,Heilongjiang 150086, China (Guo SZ and Zhou H)Correspondence to: ZHANG Wei, Department of InfectiousDiseases, First Affiliated Clinical Hospital of Harbin MedicalUniversity, Harbin, Heilongjiang 150086, China (Fax:86-451-53641561. Email: 1245537680@)guidebook published by the Ministry of Health, China.7 Common HFMD was assigned to those with fever accompanying erythema on the hands, foot, mouth, and buttocks.Patients with severe HFMD were those with the following: fever accompanying erythema on the hands, foot, mouth and buttocks, with other manifestations such as neurological impairment, respiratory disorder, dysaemia and other symptoms. The laboratory assay may show an increase in leucocytes in the peripheral blood, abnormal cerebrospinal fluid, increased blood glucose (GLU), and disorders as identified by electrocardiogram (ECG), myelencephalon magnetic resonance, chest X-ray (CX), and ultrasound cardiogram.Statistical analysisRetrospective analysis of the epidemiology, clinical and laboratory results of patients studied included analysis of sex, age, location, course of disease, neurological manifestation, erythema, fever, and laboratory assay and other tests. All data were input into EPIDATE (Epidate, Beijing, China) twice by two persons to ensure data accuracy. χ2Among 2379 HFMD patients, 1385 were male and 994 female, for a male to female ratio of 1.4:1.0; the youngest patient was 2 months, the oldest was 38 years, for an average patient age of 3.2 years. Most patients (82.6%) were children and infants <5 years and most patients who were children were under nursery care (55.2% of all patients). Children too young to go to nursery care comprised of 40.7% of all patients. Only 4.1% of patients were students. Of the 581 severe cases (24.42%), 14 died (2.41%). Statistical analysis showed an average and comparable distribution of age and sex in those with common and severe HFMD (P>0.05), but a statistically significant difference in morbidity location between groups (P <0.05).Time distributionTo determine the seasonality of infection, we analyzed the cases by month in which they presented. Results are shown in Figure 1. The morbidity of HFMD in Harbin starts to increase in April, is concentrated mainly from June to August, and reaches its peak in July. The peak number of HFMD cases reported showed a downward trend since 2008 (Figure 1).Location distributionWe analyzed the location of cases to determine regionality. Results are shown in Figure 2. Among the randomly chosen 2379 cases, 800 (33.63%) were from outside Harbin. About half, or 1200 cases (50.44%), were from four districts of the main city area (Daowai, Daoli, Xiangfang, Nangang, about 300 cases each), as shown in Figure 2.Medical expensestest, t test, and multivariable Logisticregression were performed using SPSS version 13.0software (SPSS, Inc., USA). P <0.05 was consideredstatistically significant.RESULTSEpidemiology featuresGroup distributionIn all, 2295 cases required hospitalization; the averagelength of stay was 7.5 days. The 355 severe casesFigure 1. The timedistribution of patientswith hand, foot and mouthdisease in Harbin fromMay 2008 to November2010.Figure 2.The districtdistribution of patientswith hand, foot and mouthdisease in Harbin fromMay 2008 to November2010.hospitalized incurred an average medical expense of RMB (6697.80±7273.70) Yuan. Statistical analysis showed that the difference in medical expense between common and severe HFMD was statistically significant (P <0.001).Clinical manifestationFever and accompanying symptomsIn the 1917 patients with fever (80.58%), the fever lasted an average of 2–3 days. There were 1462 fever cases in the common group (82.31%) and 455 in the severe group (78.31%). Additionally, 34 cases of common HFMD (1.89%) and 151 cases of severe HFMD (25.99%) had fever lasting longer than three days. Statistical analysis showed a statistically significant difference in the duration of fever between the groups (P <0.001).Mouth manifestationOf the 2356 cases (99.03%) with mouth endermosis, 1786 were in the common group (99.33%) and 570 in the severe group (98.11%). The difference in occurrence between the two groups was statistically significant (P <0.005).ErythemaIn all, 2350 cases had erythema (98.78%), lasting 1–8days; 65% of patients had erythema as a primary symptom. There were 1769 erythema cases (98.38%) in the common group, and 581 in the severe group (100%). The difference in occurrence between the two groups was statistically significant (P <0.001).Laboratory assayIn the laboratory assay of all 2379 cases, 1549 cases (65.11%) exhibited leucocyte >10.0×109Multivariable Logistic regressionThe 12 statistically meaningful factors mentioned above were put into a regression model along with age and location. Results of the multivariable Logistic regression analysis showed that eight factors were independent risk factors for developing severe HFMD. The statistically meaningful results (P <0.05) are shown in Table 2. Treatment and sequelaeCommon cases/L; 640 cases (26.90%) exhibited high levels of the enzyme myocardium; 963 cases (40.50%) had CX indicating bronchitis; 228 cases (9.58%) exhibited pulmonary infection. In addition, 992 cases (63.14%) showed abnormal ECG and 1684 cases (72.15%) had an abnormal electroencephalogram (EEG). Table 1 shows the laboratory results for those with severe and common HFMD, indicating that the two groups differed in a statistically significant way in terms of neutrophils (NEUT), lymphocytes (LYM), hemoglobin (HGB), GLU, bronchitis, pulmonary infection, CX, and EEG (P <0.05). Etiology assayFrom May 2008 to November 2010, 961 specimens were tested, of which 100 tested Cox1A16 positive (10.4%), 326 were EV71 positive (33.9%), and 23 were primer enterovirus (PE) positive (2.4%).Analysis on key factors for severe HFMDOne-factor analysisOne-factor analysis was performed on the epidemiological features and clinical symptoms of severe and common HFMD. The results indicated 12 key factors for severe HFMD: location, duration of fever, mouth endermosis, erythema, NEUT, LYM, HGB, GLU, bronchitis, pulmonary infection, abnormal CX, and abnormal EEG (P <0.05).Treatment should be provided for common HFMDNeutrophil (×109/L) 1791 55.41±2.43 580 57.42±5.12 0.0231 Lymphocyte (×109/L) 1791 37.12±4.03 579 35.27±5.23 0.0168 Hemoglobin (g/L) 1780 119.02±12.45 575 117.05±21.21 0.0017 Glucose (mmol/L) 1622 4.32±2.09 525 5.60±3.12 <0.0010 A lanine aminotransferase (mmol/L) 1715 20.37±15.10 560 19.34±40.21 0.2696 Aspartate aminotransferase (mmol/L) 1711 38.97±11.45 562 38.91±12.54 0.7339 A lkaline phosphatase (mmol/L) 1710 208.17±22.12 560 209.39±24.21 0.5101 Lactate dehydrogenase (U/L) 1709 227.35±10.89 561 229.82±11.00 0.5101 C reatine kinase (U/L) 1711 20.39±2.41 554 20.37±3.01 0.9865 Creatine kinase-MB (U/L) 1720 42.53±3.12 561 41.46±2.09 0.4848 Bronchitis*1118 62.21% 297 51.12% <0.0010679 37.79% 284 48.88%Pulmonary infection*1639 91.16% 512 88.12% 0.0309159 8.84% 69 11.88%Chest X-ray*1091 60.71% 276 47.59% <0.0010706 39.29% 304 52.41%E lectroencephalograph*465 26.36% 185 32.46% 0.00481299 73.64% 385 67.54%Electrocardiograph*405 35.71% 174 39.82% 0.1309729 64.29% 263 60.18%*Up rows denote symptoms did not happen (normal); down rows indicate symptoms occured (abnormal).Table 2. Multivariable Logistic regression analysis on key factors for severe HFMDFactors Estimate SE Wald P values OR 95% CI Age 0.9897 0.1219 65.9317 <0.0010 2.690 2.119–3.416 Location −0.7894 0.1526 26.7589 <0.0010 0.454 0.337–0.612 Area−0.0537 0.0209 6.6194 0.0101 0.948 0.910–0.987 Duration of fever −1.8243 0.1007 328.3428 <0.001 0.161 0.132–0.197 Mouth endermosis 2.2878 0.6701 11.6569 <0.001 9.853 2.650–36.639 Neutrophil −0.2449 0.0952 6.6147 0.0101 0.783 0.650–0.943 Hemoglobin 0.4366 0.1720 6.4458 0.0111 1.547 1.105–2.168 Glucose −0.6350 0.1092 33.7869 <0.0010 0.530 0.428–0.656according to published guidelines.7 For common HFMD, conventional therapy includes patient isolation to prevent cross-infection and treating symptoms, such as fever, using combined traditional Chinese and western medicine.Severe casesTreatment for severe HFMD should be provided according to published guidelines.7 All pediatric patients should be treated with anti-viral therapy and fever reducer. Additional intensive treatment should include: (1) IV large-dose gamma globulin, total dose 2 g/kg, administered over 2–3 days; (2) Sou-Medrol therapy (1–2 mg ⋅kg -1⋅d -1 for common cases; 5–10 mg ⋅kg -1⋅d -1 for severe cases; 15–20 mg ⋅kg -1⋅d -1 for dying cases), the dose to be reduced after three days, and a small dose given on the fourth day; (3) 20% mannitol 1–2 g·kg -1·time -1HFMD is a contagious diseases caused by an enterovirus discovered in New Zealand in 1957.), within 20–30 minutes intravenous drip, albumin and furosemide added if necessary; and (4) respiration support, including timely performance of a trachea cannula and ventilation using a positive pressure respirator. When pediatric patients exhibit symptoms involving the central nervous system, such as a change in consciousness, headache, vomiting, general fatigue, trembling or convulsion, treatment should be given to alleviate symptoms quickly and then treatment for HFMD administered slowly, keeping the child slightly dehydrated. When pediatric patients exhibit symptom involving the circulatory system, such as paleness, cardiac arrhythmia, weak or no pulse, body cooling, cyanosis, or sharp change in blood pressure, treatment should be supplied quickly to alleviate symptoms slowly. To rapidly correct disorders of the circulation system, the best order of treatment is to give gamma globulin, then blood plasma and albumin in the blood transfusion. When pediatric patients exhibit respiratory distress with the primary infection, a timely trachea cannula should be performed and then the patient ventilated using a positive pressure respirator. In severe cases in this group, 14 died and all the rest recovered after 7–14 days.DISCUSSION8 After that, the disease spread globally. Each year since the first case was reported in China in 1981, this disease has been reported in more cities. On May 2, 2008, the Ministry of Health classified HFMD as a class C contagious disease,9 and thegovernment of each province and city started programs of strict detection and management.Harbin is in the northeast of China, with unique weather, geography and culture. The epidemiological results of this study showed that HFMD patients are mostly children younger than 5 years, consistent with previous reports of this disease.10 Among patients, children who are under nursery care had the highest morbidity. This is because the nursing institution is a location where children gather and eat and play together. HFMD can be transmitted through bodily contact and respiratory tract droplets.11,12 Therefore, managers of nursing institutions should pay strict attention to disinfection management, making sick children stay home.13 Teachers as well should know about HFMD so they can identify sick children to reduce the spread of infection. The time distribution analysis in this study shows that the morbidity peak is from June to August, late summer in Harbin; the virus is adapted to flourish in a wet and hot environment. In urban areas, the high morbidity results from the large, highly mobile population. In the surrounding cities, the high morbidity is due to poor health habits and living conditions.11HFMD is a self-limited disease, This fact indicates the need for a practical plan to prevent and control contagious disease in schools, and enhance morning check to identify new patients quickly. In the surrounding cities, the government should increase public health efforts, improve living conditions, and encourage the adoption of healthy habits.Because of the imbalance in regional economic development, Harbin remains relatively poor with low per capita income. For the cases in this study, the medical expense, especially for severe cases, was relatively high, representing a significant economic burden to an average family. This fact indicates that we must enhance HFMD detection, identify it earlier and treat it earlier, to decrease the morbidity of HFMD and reduce the number of common cases that convert to severe. In the meantime, we should also increase the level of clinical service to decrease the medical expenses associated with this disease.14 the prognosis is usually good, but some cases develop severe clinical manifestations. Our clinical data indicated that although all cases with clinical symptoms of HFMD present with different symptoms, the primary symptoms are mainlyfever and erythema. Some severe patients have a body temperature >39°C, and may appear lethargic, drowsy, vomit frequently, are nervous, tremble, and even convulse. Some pediatric patients appear irritable, have difficulty breathing or may exhibit tachycardia or bradycardia. These symptoms indicate that doctors should consider accompanying cerebritis, meningitis, carditis or even possible neurogenic pulmonary edema. They should thus perform CX and ECG if necessary, and treat aggressively, to improve prognosis.Non-standard treatment of severe cases will lead to death. In 2008, HFMD was widely prevalent in the Fuyang area of the Anhui province; 90 patients had severe HFMD, of whom 22 died.13 In the cases in our study, 14 children with severe HFMD died. Therefore, to reduce the incidence and mortality from severe HFMD, doctors and health care providers need to understand the risk factors for HFMD, especially for severe cases, and to practice prevention and control measures. Logistic regression analysis of the data in our study found seven key factors for severe HFMD that can provide an early warning for its presence: age, location, area, duration of fever and mouth mucosal symptoms, elevated NEUT, HGB and GLU. The duration of fever was proportional to the risk of severe disease, which is consistent with other studies.15,16 The results indicate that those younger than 5 years infected by EV7117 are the most likely of common cases to develop into severe ones. When receiving pediatric patients from a nursery care institution or from surrounding cities with high HFMD morbidity, one should consider the possibility of EV71 infection in the presence of persistent fever and indicative laboratory results. It is important to try to identify severe patients early and provide appropriate treatment, to reduce the morbidity and number of severe cases.18Acknowledgement: We are grateful for the information on the hand, foot and mouth disease provided by Harbin Center for Disease Control and Prevention.REFERENCESIn our study, among laboratory criteria, abnormal levels of NEUT, HGB and GLU were key factors for identifying severe cases. These factors can be used to identify cases requiring aggressive treatment.1.Wong KT, Munisamy B, Ong KC, Kojima H, Noriyo N, Chua KB, et al. The distribution of inflammation and virus in human enterovirus 71 encephalomyelitis suggests possible viral spread by neural pathways. J Neuropathol Exp Neurol 2008; 2: 162-169.2.Lin HS, Yang SD, Ning SR, Zheng KL, Zhang YN. Clinical analysis on 19 cases of hand-foot-mouth disease accompanying brainstem cerebritis. Chin J EvideBased Pediatr (Chin) 2009; 14: 520-523.3.Ang LW, Kon BK, Chan KP, Chua LT, James L, Goh KT. Epidemiology and control of hand, foot and mouth disease in Singapore, 2001–2007. Ann Acad Med 2009; 38: 106-112.4.Sun GL, Zhang J. The progress of researches on epidemiology of hand-foot-mouth disease. Chin J Epidemiol (Chin) 2009; 30: 973-976.5.Wei NG , Xu CF. Analysis of epidemiology and clinical features on 967 cases of children hand-foot-mouth disease. Chin J Child Health Care (Chin) 2010; 18: 888-890.6.The Ministry of Health of the People’s Republic of China. The official national cases report of contagious diseases of 2009 and January of 2010. (Accessed February 10, 2010 at /publicfiles/business/htmlfiles/mohbgt/ s3582/201002/46043.htm.)7.The Ministry of Health of the People’s Republic of China. A guidebook of HFMD diagnosis and treatment (2010 edition). (Accessed February 11, 2011 at / publicfiles/business/htmlfiles/mohyzs/s3586/201004/46884.htm ) 8.Wang XH, Zhao ZT, Yang BS, Liu JM, Wang YH. Analysis on epidemiology features and steps of prevention and control in 2008 in Yuanping. Shanxi Med J (Chin) 2009; 38: 722-723.9.Yao XJ, Hao C, Xu H, Chen C, Zhang HX, Deng ZM. Epidemiology investigation on the dangerous factors of hand-foot-mouth disease in Changzhou. Acta Universit Med Nanjing (Chin) 2010; 30: 1275-1278.10.Li YT. Epidemiology features, prevention and control of hand-foot-mouth disease. Shanghai J Prev Med (Chin) 2008; 20: 316-317.11.Pan YJ. Cases analysis of hand-foot-mouth disease in qingpu district of shanghai from 2006-2007. Shanghai J Prev Med (Chin) 2010; 22: 354-355.12.Nong GM, Liu YM. Clinical distribution and diagnosis of hand-foot-mouth disease of children. Pract Pediatr Clin Magazine 2009; 22: 1706-1708.13.The Ministry of Health. Cases of hand-foot-mouth disease in Fuyang, Anhui Province reported by the Ministry of Health. (Accessed February 11, 2011 at /gzdt/2008- 05/03/content-960290.htm )14. Li LJ, General M, Li LJ. Hand, foot and mouth disease. Hangzhou: Zhejiang Science and Technology Press; 2009: 1. 15.Lü HK, Wang XX, Liao ZP. Analysis on dangerous factors of hand-foot-mouth disease in Zhejiang Province. Dis Surveillance (Chin) 2009; 24: 658-660.16. Liu ML. Care of foot and mouth disease with viral encephalitis. Zhejiang Pract Med (Chin) 2011; 4: 308-309. 17.Lu JY , Lü JL. Clinical diagnosis analysis of 60 cases of hand, foot and mouth disease among children. Chin Pract Med (Chin) 2009; 4: 4-85.18.Wu HY , Zheng YX, Mao SH, Gu BK, Pan J. Research on dangerous factors of severe cases of hand-foot-mouth disease in Shanghai. J Environ Occup Med 2011; 28: 257-261.(Received November 12, 2011)Edited by SUN Jing。