| BackgroundHand foot mouth disease(HFMD)is an acute children's infectious disease caused by a variety of human enterovirus including as many as more than twenty intestinal virus types,which the coxsackievirus A16 and enterovirus 71 are the main pathogen of HFMD.Because severe cases of HFMD progression,with high mortality and easy to leave sequelae,develop very quickly,and there is no effective indicators for early warning,thus clinical treatment is difficulty in time.It is very important to analysis the influence factors and identify early warning indicators of severe HFMD,which is of great significance to reduce the mortality of HFMD and to develop preventive measures.ObjectThe clinical data of patients with hand foot mouth disease(HFMD)were collected in this study,and the dynamic changes of cytokines in different stages of HFMD progression were detected by ELISA method.By analyzing the influencing factors of HFMD and selecting the early warning indicators of severe HFMD,we aimed to improve the early warning ability of severe HFMD and to reduce the fatality rate of HFMD.Method1.The clinical manifestations,physical signs and laboratory tests which might influence the development of severe HFMD were performed on 428 HFMD cases collected in the first affiliated hospital of Xinxiang Medical University from May to November in2015,and chi-square test and single factor logistic regression analysis were used in the statistic analysis.The multiple factors Logistic regression analysis was conducted to establish the Logistic regression model which was assessed by 525 HFMD cases collectedfrom May to August in 2016.2.A total number of 428 children,among which 196 cases were severe HFMD and 232 cases were non-severe cases,with HFMD collected in the first affiliated hospital of Xinxiang Medical University from May to November in 2015 were investigated.The concentration of interleukin-4(IL-4),interleukin-6(IL-6),interleukin-8(IL-8)and interferon gamma(IFN-?),tumor necrosis factor-?(TNF-?),angiotensin II(Ang II)and norepinephrine(NE)were detected in the serum of samples by ELISA methods.The concentration of various cytokines in the serum of patients with severe HFMD and non-severe HFMD occurred in the same day were compared.The ROC work curve was used to determine the boundary value of severe HFMD cases and to evaluate their early warning efficacy.Result1.Multiple factors logistic regression analysis showed that the degree of fever,mental sluggishness,papules,pharyngeal hyperaemia,neutrophil ratio over 75% accounted for the development of HFMD from mild case to severe case.The patients with neutrophil ratio over 75%(OR=0.556,95%CI:0.320~0.964)and papules(OR=0.246,95%CI:0.064~0.947)were not prone to develop severe HFMD.The degree of fever(38.5~39.5? OR=3.341,95%CI:1.094~10.200;?39.5? OR=32.594,95%CI:3.054 ~ 34.781),mental sluggishness(OR=4.473,95%CI : 2.044 ~ 9.790),pharyngeal hyperaemia(OR=4.515,95%CI : 1.827 ~ 11.158)were risk factors.The sensitivity and specificity of multiple factors Logistic regression model for prediction severe HFMD were 75.6% and 82.0% separately.ROC results showed that the area under the curve was 0.834,and 95% CI was 0.793~0.835.2.ELISA results showed that the contents of IL-4,IL-6,IL-8,TNF-?,IFN-?,AngII and NE in serum of patients with severe HFMD were higher than those in non severe group(P<0.05).All of the cytokines showed the dynamic changes that increase at first and then decrease with the progression of the HFMD.The IL-4,IL-8 and NE in the third and fourthdays,IL-6 in the fourth days,TNF-? in the second days,IFN-? in the fourth and fifth days,Ang II in the third,fourth and fifth days reached to peak in the severe HFMD cases.The serum boundary values of IL-4,IL-6,IL-8,TNF-?,IFN-?,NE and AngII in the serum were308.0ng/L,70.8ng/L,1026.9ng/L,358.6pg/mL,940.6pg/mL,2518.1ng/L,125.9ng/L respectively by ROC curves with the sensitivity of severe cases of HFMD were 74%,80.6%,77%,83%,79.5%,86%,84.1% and the specificity were 75%,81%,74.6%,80.3%,71.5%,73%,80% respectively,and the coincidence rate was greater than 0.74.ConclusionIn conclusion,patients with neutrophil ratio over 75% and papules are not prone to develop severe HFMD.Fever with the temperature equal or more than 38.5 ?,mental sluggishness and pharyngeal hyperaemia are the risk factors of severe HFMD,and the Logistic model constructed by this study could be used to estimate severe cases of HFMD.The dynamic changes with the phase change characteristic of IL-4,IL-6,IL-8,TNF-?,IFN-?,AngII and NE in the serum of patients with severe and non severe HFMD can be used as early warning indicators of severe HFMD. |
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