Study Of Clinical High Risk Factor And Viral Antibody For Hand-foot-and-Mouth Disease Among Children In Guangdong Province

BackgroundHand-foot-and-mouth disease(HFMD) is a common viral illness caused by enteroviruses that predominantly affects the infants and children. The two main pathogens of HFMD are Entero virus type71(EV71) and Coxsakie virus group A type16(CoxA16). In general, HFMD is benign and self-limiting. The clinical manifestation of these benign cases is always asymptomatic or just slightly unwell, such as fever, mouth vesicles/ulcers, rash of palms&/or soles&/or buttocks. However, some patients may develop severe HFMD with complications including encephalitis, meningitis, acute flaccid paralysis, myocarditis, pulmonary edema, or even death. HFMD is worldwide, and, recently, has become more and more dangerous for the children’s health at home and abroad. Therefore, the study of severe HFMD remains to be hot in the world, and the investigation of the clinical risk factor of severe HFMD is very important to the positive treatment, the improvement of prognosis, and the reducation of mortality. Part Ⅰ:Study of Clinical High Risk Factor for Hand-Foot-and-Mouth Disease among Children in Guangdong ProvinceObjective The study aimed to analyze the clinical characteristics of HFMD and find the clinical high risk factor for it among Children in Guangdong ProvinceMethods From April2008to December2011,1204cases of HFMD, identified retrospectively based on Zhujiang Hospital records, are analyzed by descriptive epidemiology method. Of the1204patients,806(66.86%) were males and398(33.14%) were females. The patients’age ranged from3month to14years, and the average age was2.25years. The study was designed as a retrospective frequency study, and aimed to figure out the distribution of HFMD in season, age and sex et,al. Furthermore, according to "Guideline for EV71infection:Diagnosis and Treatment (2010)", the total1204HFMD patients were divided into benign group (1156cases, according for96.01%) and severe group(48cases, for3.99%). According to "Case Questionnaire of HFMD" enacted by Ministry of Health of China, some items were chosen to be observed, which were considered to be closely related to the severity of HFMD patients, including the clinical data (such as sex, age, duration of fever, rash duration, rash location, consciousness, low extremities temperature, running nose, irritation, convulsion, fatigue, vomit, abdominal distension) and laboratory tests(such as complete blood cell, hepatic function and myocardial enzyme). Depending on the severity of illness, Chest X-ray, electrocardiogram, computerized tomography or magnetic resonance imaging of the head were taken. The patient’s condition was observed and reevaluated repeatedly. Taqman one-step real-time fluorescence RT-PCR (Guangzhou Da An Gene Co., Ltd. of Sun Yat-sen University, China) was performed to detect gene fragments of pan-enteroviruses, EV71and CA16on a Light Cycler instrument (Roche Molecular Biochemicals, Germany). All items, including the clinical symptoms, signs and laboratory results, were transformed into ranked data, which was analyzed along with HFMD patients’ condition and pathogens (EV71or CoxA16), using single factor analysis and Logistic regression. Results1. Analysis of epidemiologic dataDuring the study,1204children with HFMD (806males [66.94%] and398females [33.06%]) were recruited from April1st2008to December31st2011. The year incidence of HFMD between these4years showed no significance(P>0.05). From the epidemic survey, outbreaks of HFMD usually occurred with a peak in April to November, and unusually in December to March. The ratio between male and female was2.03:1, the distribution of HFMD between males and females showed no significant difference (P>0.05). The age ranges of patients were from2months to14years, and943(78.32%) were aged≤3years,235(19.51%) were aged>3and≤7years, and26(2.16%) were aged>7years. The RT-PCR for detecting gene fragments of pathogens showed that EV was the main pathogen which caused HFMD, EV71followed and CoxA16ranked the third place. The compare of the year incidence of EV, EV71and CoxA16, respectively, between these4years showed no significant difference (P>0.05). Moreover, the distribution of severity of HFMD in sex showed no significant difference (P>0.05).2. Analysis of clinical dataThe distributional difference of the HFMD cases was studied in sex, age and symptoms in each year. Statistics analysis showed that the following items of HFMD had significant difference(P<0.05):age, duration of fever, ulcers in the oral cavity, cough, seizure, consciousness and fatigue; while the remain items had no(P>0.05).1204HFMD patients were divided into2groups (benign and severe group) depending on the severity of illness. The symptoms and laboratory results between the2groups were taken for single factor analysis, and the result indicated that the duration of fever, rash on buttock, irritation, convulsion, consciousness, fatigue, low extremities temperature, vomit, abdominal distension and Dbil at the early stage of disease(no more than3days) had significant difference(P<0.05). The result of Logistic regression revealed that increased risks of severity were significantly associated with the presence of irritation, fatigue, convulsion, vomit, elevation of WBC andDbil at the early stage of the disease (no more than3days). 3. Analysis of clinical data in HFMD patients with EV71infection240cases of HFMD with EV71infection were further divided into benign group and severe group, and the observed items were analyzed by independent-samples T test. The results showed that several symptoms had significant difference(P<0.05), such as duration of fever, irritation, consciousness, fatigue, low extremities temperature, vomit, abdominal distension and WBC at the early stage of disease(no more than3days). The results of Logistic regression pointed that increased risks of severity were significantly associated with the presence of irritation and fatigue.4. Analysis of clinical data in HFMD patients with CoxA16infection82cases of HFMD with CoxA16infection were divided into benign group and severe group, and the observed items were analyzed by rank sum test. The results showed that severe symptoms had significant difference(.P<0.05), such as rash duration, convulsion and CK_MB at the early stage of disease(no more than3days). Furthermore, using Logistic regression, convulsion was an increased risk of severity.Conclusion HFMD is a common childhood infection particularly in children between2.25-2.5years, and outbreaks of it typically occurred during summer and autumn months. Among all the1204HFMD patients, EV was the dominant pathogen. However, EV71was the major pathogen for severe HFMD, simultaneously, was the main cause of death. Based on the result of single factor, the duration of fever, rash on buttock, irritation, convulsion, consciousness, fatigue, low extremities temperature, vomit, abdominal distension and Dbil at the early stage of disease(no more than3days) had significant difference(P<0.05). The result of Logistic regression revealed that increased risks of severity were significantly associated with the presence of irritation, fatigue, convulsion, vomit, elevation of WBC andDbil at the early stage of the disease (no more than3days).As for cases of HFMD with EV71infection, the results of single factor showed that several symptoms had significant difference(P<0.05), such as duration of fever, irritation, consciousness, fatigue, low extremities temperature, vomit, abdominal distension and WBC at the early stage of disease(no more than3days). The results of Logistic regression pointed that increased risks of severity were significantly associated with the presence of irritation and fatigue.When analyzing cases of HFMD with CoxA16infection, the results of single factor showed that severe symptoms had significant difference(P<0.05), such as rash duration, convulsion and CK_MB at the early stage of disease(no more than3days). Furthermore, using Logistic regression, convulsion was significantly associated with infection. Part Ⅱ:Study of Viral Antibody for Hand-Foot-and-Mouth Disease among Children in Guangdong ProvinceObjective The study aimed to probe the protective effect of EV71-IgG against recurrent HFMD cases.Methods From April2008to December2011,1204cases of HFMD was identified retrospectively based on Zhujiang Hospital records. In the total cases,26relapsed HFMD patients were selected as the study group, and36primary HFMD patients were randomly selected as the control group. In the study group,17(65.38%) were males and9(34,62%) were females. The age ranges were from3months to4.5years, and the average age was2.22years. In the control group,24(66.67%) were males and12(33.33%) were females. The age ranges were from9months to6years, the average age was2.76years. According to "Case Revisit form of HFMD" designed by our hospital, some items were chosen to be observed, which were considered to be closely related to the severity of HFMD patients, including physical data, vital signs, symptoms of respiratory system, cardiovascular system, neurological system and signs. The investigation of the relationship between the anal test paper of EV71in acute stage and the induction of EV71-IgG in the convalescence stage was performed. Statistic analysis was done by chi square test (SPSS software, version13.0; SPSS), and identified P<0.05had significant difference.Results From April2008to December2011,1204cases of HFMD was identified retrospectively based on Zhujiang Hospital records. In the total cases,26relapsed HFMD patients were selected as the study group, and36primary HFMD patients were randomly selected as the control group. The symptoms and signs and laboratory results were analyzed by independent-samples T test or single-factor analysis, and showed that only Cr and Glu had significant difference(P<0.05) and the remain items had no (P>0.05). The analysis between the anal test paper of EV71in acute stage and the induction of EV71-IgG in the convalescence stage showed no significant difference(P>0.05).Conclusion HFMD patients can get the infection again may because the humoral immunity disorder and the following absence of cross protection from the specific immunity of different pathogens infection.