基于血清学贝叶斯模型的血吸虫病疫情评估研究

发布时间：2018-04-03 17:30

本文选题：酶联免疫吸附测定(ELISA)　切入点：Meta分析　出处：《江苏省血吸虫病防治研究所》2017年硕士论文

【摘要】：目前,日本血吸虫病主要流行于我国湖区5省(安徽、湖北、湖南、江苏、江西)和山区2省(四川、云南),血清学诊断在防治工作中发挥了重要的作用。关于血清学诊断方法检测效能方面的研究开展的比较多,研究显示血清学诊断方法在不同流行类型、流行程度、年龄及性别之间的检测效能存在较大差异。随着血吸虫病防治工作的开展,人群感染率显著下降,粪便检查方法的低灵敏度问题日益突出。因此,探索一种能准确估算人群血吸虫感染率的统计学方法,对于评估当前血吸虫病疫情变化,协助制定防治策略十分重要。本研究首先根据Meta分析获得的检验效能筛选出较优的检测方法,然后采用贝叶斯分级模型,纳入不同性别组和年龄组灵敏度与特异度等先验信息,构建优化后的血吸虫病血清学贝叶斯模型,随后利用构建的模型对镇江市丹徒区连续5年的血清库数据进行统计分析,分析人群估算血吸虫感染率变化趋势,评估其防治效果。首先,通过对诊断实验结果进行Meta分析,综合评价不同流行程度下间接血凝实验(indirect hemagglutination test,IHA)、酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)和胶体染料试纸条法(dipstick dye method,DDIA)的日本血吸虫病诊断效果。IHA、ELISA与DDIA的加权合并灵敏度分别为0.83、0.87和0.90;加权合并特异度为0.69、0.60和0.62。IHA、ELISA和DDIA的总体SROC曲线下面积分别为0.89、0.96和0.92。ELISA曲线下面积大于IHA和DDIA,提示ELISA的诊断效能较高。然后对江西、安徽及湖北3省7个调查点的8248个样本人群,同时开展Kato-Katz法(一粪三检)病原学检测与ELISA法血清学检测。其中ELISA法在男性6~、10~、20~、30~、40~、50~和60~年龄组的灵敏度分别为0.7500、0.9500、1.0000、1.0000、0.9667、0.9512、1.0000和特异度分别为0.8898、0.6958、0.5105、0.4118、0.3549、0.3059、0.3180;ELISA法在女性6~、10~、20~、30~、40~、50~和60~年龄组的灵敏度分别为0.5000、0.8889、0.0000、0.9048、1.0000、0.9615、1.0000和特异度分别为0.8960、0.8193、0.6995、0.4930、0.4631、0.5086、0.5505。不同年龄组的灵敏度(t=16.231,P0.01)与特异度(t=7.727,P0.01)均有统计学差异。随着年龄增加,男性与女性的灵敏度在6~30岁间呈上升趋势后,趋于稳定;其特异度均呈下降趋势,男性的特异度低于同年龄段的女性。第二,基于第一部分研究获得的先验信息,利用威尔逊区间算法,得到不同年龄组、性别组的灵敏度与特异度95%可信区间。采用分层抽样方法进行样本数据调查,年龄嵌套于性别、性别嵌套于村的巢式(nested)结构,同时纳入了年龄组、性别灵敏度与特异度的先验分布信息,利用贝叶斯分级模型,从而构建血吸虫病血清学贝叶斯模型,并根据调查结果,验证模型;改变灵敏度、特异度等参数的先验分布范围,开展模型敏感性分析。结果显示不同样本村庄(P=0.068,P0.05)、性别(男性:P=0.096,P0.05;女性:P=0.09,P0.05)和年龄组(P=0.266,P0.05)的模型估算感染率和真实感染率差异均无统计学意义,提示本研究构建模型可以估算人群血吸虫病感染率,不但解决了样本数据相互嵌套的问题,而且可以提供样本总体、性别及年龄组的估算血吸虫病感染率。随后,用ELISA法检测江苏省镇江市丹徒区血吸虫病国家监测点连续5年的血清库样本(2011-2015年),开展血清ELISA法检测,并利用已经构建日本血吸虫病血清学贝叶斯模型,推算人群血吸虫病感染率变化趋势。对血清库的2180份血清样本进行检测,2012年血清学阳性率最高为37.38%,2015年的最低为7.36%,2012年以后血清阳性率通过趋势分析呈逐年下降趋势,血清学检测阳性率存在统计学差异(P=0.0001,P0.05)。5年的估算人群感染率分别为1.288%、1.456%、1.032%、1.485%和1.358%,不同年份估算人群感染率差异无统计学差异(P=0.998,P0.05),提示2011-2015年此地区血吸虫病传播风险因素可能依然存在,需要继续加强血吸虫病风险监测,防治工作需要进一步加强。总之,ELISA检测方法具有较高的诊断效能;不同年龄组及性别组之间的灵敏度与特异度存在显著差异;血吸虫病血清学贝叶斯模型可以有效估算人群血吸虫病感染率,用于血吸虫病疫情评估。
[Abstract]:At present, schistosomiasis mainly popular in China's 5 provinces (Anhui, Hubei, Hunan, Jiangsu, Jiangxi) and 2 (Sichuan, Yunnan Province mountain), serological diagnosis plays an important role in the prevention and control work. Research on the serological diagnosis methods of the detection performance to carry out more research shows serological diagnostic method in different types of popular, popularity, there is a big difference between the detection performance of age and gender. With schistosomiasis prevention and control work, the infection rate decreased significantly, low stool examination method sensitivity problem has become increasingly prominent. Therefore, to explore a statistical method to estimate the schistosome infection rate, to evaluate the changes of schistosomiasis assist, the prevention and control strategy is very important. In this study, according to the analysis of Meta test efficiency can be obtained by selecting the optimum detection method, and then the Bias classification model, different gender and age groups included in the sensitivity and specificity of the prior information, the construction of the model after optimization of schistosomiasis serological Bias, then the Dantu District of Zhenjiang City, 5 consecutive years of data for statistical analysis using serum bank model, analysis of population estimate schistosome infection rate trends, evaluate the control effect. First of all, through the Meta analysis of diagnostic test results, comprehensive evaluation of different epidemic under the indirect hemagglutination test (indirect hemagglutination, test, IHA), enzyme-linked immunosorbent assay (enzyme-linked immunosorbent, assay, ELISA) and dipstick dye immunoassay (dipstick dye method, DDIA) in the diagnosis of schistosomiasis japonica.IHA, weighted sensitivity ELISA and DDIA were 0.83,0.87 and 0.90 respectively; the weighted specificity of 0.69,0.60 and 0.62.IHA, the overall SROC curve and DDIA under ELISA The area was 0.89,0.96 and the area under the 0.92.ELISA curve is greater than IHA and DDIA, suggesting that high diagnostic efficiency of ELISA. And then to Jiangxi, a sample of 8248 people in Anhui and Hubei 3 provinces in 7 survey, carried out at the same time Kato-Katz method (a fecal seized three) pathogen detection and serological detection method ELISA ELISA method in which. Male 6~, 10~, 20~, 30~, 40~, 50~ and 60~ groups were 0.7500,0.9500,1.0000,1.0000,0.9667,0.9512,1.0000 sensitivity and specificity for 0.8898,0.6958,0.5105,0.4118,0.3549,0.3059,0.3180; ELISA in 10~, 20~, female 6~, 30~, 40~, 50~ and 60~ age groups respectively. The sensitivity of 0.5000,0.8889,0.0000,0.9048,1.0000,0.9615,1.0000 sensitivity and specificity were of different age groups (0.8960,0.8193,0.6995,0.4930,0.4631,0.5086,0.5505. t=16.231, P0.01) and specificity (t=7.727, P0.01) were statistically significant with age. Increase the sensitivity of male and female increased among 6~30 years, tends to be stable; the specificity decreased, male specificity was lower than women the same age. Second, the first part of the study was based on a priori information, the use of Wilson interval algorithm, to different age groups, gender sensitivity group with a specificity of 95% confidence intervals. Using stratified sampling method to sample survey data, age nested in gender, gender in the village of nested nested (nested) structure, included in the same age group, gender sensitivity and specificity of the prior distribution of information, using the Bias classification model, so as to construct the schistosomiasis serological Bias model, and according to the survey the results validate the model; change the sensitivity, specificity and other parameters of the prior distribution range, carry out model sensitivity analysis. The results showed that different sample villages (P=0.068, P0.05), gender (male : P=0.096, P0.05; P=0.09, P0.05): women and age groups (P=0.266, P0.05) model to estimate the infection rate and the infection rate of real differences were not statistically significant, suggesting that this research model can estimate the schistosomiasis infection rate, not only solves the problem of mutual nested sample data, and can provide the overall sample. The estimation of schistosomiasis infection rate of sex and age groups. Then, ELISA was used to detect the Zhenjiang province Jiangsu city Dantu district national schistosomiasis monitoring points for 5 consecutive years, the serum sample library (2011-2015 years), to carry out the method of serum ELISA detection, and using the constructed schistosomiasis serological Bayesian model, population projections schistosomiasis infection rate trends. 2180 serum samples of serum pool were detected, the positive rate in 2012 was the highest in 2015 37.38% serum, the lowest was 7.36%, in 2012 after the serum positive rate through trend analysis Decreased year by year, there was a statistically significant difference between the positive rate of serological detection (P=0.0001, P0.05) to estimate the population during.5 infection rates were 1.288%, 1.456%, 1.032%, 1.485% and 1.358%, in different years estimated infection rate difference was statistically difference (P=0.998, P0.05), suggesting that the risk factors of schistosomiasis transmission in 2011-2015 years may still exist schistosomiasis, need to continue to strengthen risk monitoring, to further strengthen the prevention and control work required. In short, ELISA detection method has high diagnostic efficiency; between different age groups and gender groups the sensitivity and specificity of significant differences; schistosomiasis serological Bayesian model can effectively estimate the infection rate of schistosomiasis, for schistosomiasis epidemic situation assessment.

【学位授予单位】：江苏省血吸虫病防治研究所
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R532.21

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