蛔虫与钩虫感染化疗策略数学模型及再感染模式研究

发布时间：2018-07-06 14:47

本文选题：蛔虫 + 钩虫　；参考：《中国疾病预防控制中心》2012年博士论文

【摘要】：目的研究实施化学药物驱虫后蛔虫和钩虫传播的趋势及定量关系,建立蛔虫和钩虫感染化疗策略数学模型,评价并预测不同化疗策略对控制蛔虫和钩虫感染的效果；研究驱虫后蛔虫、钩虫再感染的模式,探索影响再感染是否发生及发生强度的因素,为优化化疗策略、采取有针对性的干预措施提供理论依据。方法在复习文献、确定建模目的基础上,根据模型假设构建蛔虫和钩虫感染化疗策略数学模型,通过现场纵向观察,采取粪检、驱虫和淘虫获得人群在基线、一个月和一年时的蛔虫及钩虫感染率、感染度等数据,研究模型中参数的计算方法,利用现场数据运行、验证并修正模型,利用模型评价和预测实施不同化疗策略对控制蛔虫和钩虫感染的效果。将现场调查获得的感染率、感染度等疫情数据与问卷调查获得的人口学特征、社会经济条件、户厕类型及粪便使用情况、行为习惯等数据进行匹配,筛选出驱虫后一个月时感染阴性的人群。根据蛔虫和钩虫虫卵计数数据的特点,研究零膨胀的负二项模型(ZINB),与传统的负二项模型(NB)比较,确定最优模型,利用其研究再感染的模式,探索再感染的发生及强度与影响因素的关系。结果 1.本研究在四川宜宾、江西进贤和湖南岳阳的3个现场对2065人进行了药物干预和为期一年的纵向观察。蛔虫和钩虫基线平均感染率分别为23.29%、23.01%,基线平均虫负荷分别为0.82、3.25,一个月平均感染率分别为1.81%和4.03%,一年后的平均感染率分别为12.85%、7.80%、平均虫负荷分别为0.65、2.48。 2.基于Medley等的评价化疗策略的定量框架,构建了适用我国的蛔虫和钩虫感染化疗策略数学模型,包括感染率模型、作用于种群动力学模型、作用于寄生虫分布的模型。研究确定了模型中生物学参数的计算方法,包括负二项分布参数、密度依赖参数和基本繁殖率。对密度依赖参数的计算方法进行了修正,提出了改进的公式,更加适用于我国现场调查数据的拟合。根据现场调查数据获得生物学参数的估计值后代入模型,预测结果较好地拟合了现场数据,理论值均在实际值的95%可信区间范围内。 3.利用模型对干预措施参数进行敏感性分析,结果显示：驱虫后蛔虫和钩虫感染率回升的速率比平均虫负荷快；驱虫覆盖率从60%提高到80%以上时,感染率和平均虫负荷下降明显；驱虫覆盖率达到80%以上时,感染率和平均虫负荷在随后3年基本均维持在较低水平；当药物疗效达85%以上时,采用每年一次、驱虫覆盖率80%对控制蛔虫和钩虫感染水平的效果比每年两次、驱虫覆盖率60%的效果好；不同地区降低感染率和平均虫负荷至同一水平所需的化疗次数不同。 4.用现场数据通过模型预测表明,如仅采用化疗单一措施,按60%驱虫覆盖率、每年一次的策略,江西进贤调查点需8年时间将钩虫感染率控制在1%的水平；如按80%驱虫覆盖率、每年一次的策略,则需5年时间。如按60%驱虫覆盖率、每年一次的策略,四川翠屏调查点需14年时间将蛔虫感染率控制在3%的感染率水平,如按80%驱虫覆盖率、每年一次的策略,则需5年时间达此目标。 5.将问卷调查数据与粪检、淘虫数据按个案号进行匹配后统计分析,蛔虫和钩虫治疗前、后感染程度均呈高度相关性(P0.0001),证实倾向性现象的存在。 6.研究引入了零膨胀的负二项模型(ZINB),通过模型拟合优度的比较,证明了ZINB模型对于拟合蛔虫和钩虫虫卵计数数据,优于传统的负二项模型(NB)。 7.运用零膨胀的负二项模型(ZINB)分析蛔虫、钩虫再感染影响因素显示：不同年龄段对于是否发生蛔虫和钩虫再感染无显著性差异,但对于再感染的强度(用感染度EPG表示)均有意义。5-14岁儿童获得蛔虫再感染时高感染度的风险最高(OR=7.12,95%CI：1.72-29.42),其次是45-64岁组(OR=3.49,95%CI：1.19-10.22),均显著高于65-70岁组,15-44岁组与65-70岁组无显著性差异。5-14岁儿童获得钩虫高感染度的风险最低(OR=0.09,95%CI：0.02-0.51),显著低于65-70岁老年人,虽然其他年龄组与65-70岁组经统计学检验无显著性差异,但从系数可以看出随着年龄增加,高感染度的风险逐渐增加。治疗前感染度高是发生蛔虫和钩虫再感染的危险因素,蛔虫OR=1.96(95%CI：1.32-2.92)、钩虫OR=3.95(95%CI：2.05-7.60)。治疗前感染度高还是蛔虫再感染获得高感染度的危险因素,OR=I.57(95%CI：1.09-2.26)。居住在土坯房者再感染蛔虫和钩虫的风险相对于居住在二层以上砖瓦房者分别是3.96倍(95%CI:1.27-12.35)、4.53倍(95%CI：1.43-14.34)。拥有较高档次家用电器(OR=0.37,95%CI：0.16-0.86)、不喝生水(OR=0.44,95%CI：0.21-0.90)是发生蛔虫再感染的保护因素。结论 1.在修正了密度依赖参数计算方法的基础上,构建的蛔虫和钩虫感染化疗策略数学模型较好地拟合了我国现场调查数据,适用于我国蛔虫和钩虫流行区不同化疗策略效果的评价,并为评价和预测提供了有效的工具,对于制定防治目标、优化化疗策略及科学决策具有理论和实际应用价值。 2.零膨胀的负二项模型(ZINB)适用于拟合蛔虫和钩虫虫卵计数数据,拟合效果优于传统的负二项回归模型(NB)。 3.本研究阐释了再感染的模式,证实再感染过程中倾向性现象的存在。蛔虫和钩虫再感染的发生及强度与治疗前感染度、人口学特征、社会经济条件、环境及行为等因素相关。
[Abstract]:objective
To study the trend and quantitative relationship of the transmission of Ascaris and hookworm after insecticide, establish a mathematical model for the chemotherapy strategy of Ascaris and hookworm infection, evaluate and predict the effect of different chemotherapy strategies on the control of Ascaris and hookworm infection, and study the model of the reinfection of Ascaris Ascaris and hookworm after the insect repellent, and explore the influence of the occurrence and strength of the reinfection. These factors provide theoretical basis for optimizing chemotherapy strategies and adopting targeted interventions.
Method
On the basis of reviewing the literature and establishing the purpose of modeling, the mathematical model of Ascaris and hookworm infection was built on the basis of the model hypothesis. The data of the population at baseline, the infection rate of Ascaris Ascaris and hookworm at one month and a year, and the sensitivity of the hookworm were obtained through the field longitudinal observation. Using field data to verify and modify the model, the effect of different chemotherapy strategies on controlling Ascaris and hookworm infection was evaluated by model evaluation and prediction.
According to the characteristics of the egg count data of Ascaris and hookworm, we studied the demographic characteristics, the socioeconomic conditions, the type of household toilets and the use of feces, behavior habits, and other data obtained by the field survey, and screened out the negative population at one month after the insect repellent. The negative two term expansion model (ZINB) is compared with the traditional negative two term model (NB) to determine the optimal model, and to explore the relationship between the occurrence of reinfection, the intensity of reinfection and the influence factors by using the model of reinfection.
Result
1. in Yibin, Yibin, Jiangxi, Jiangxi, Jinxian, and Yueyang, Jiangxi, 2065 people were treated with drug intervention and longitudinal observation for one year. The average baseline infection rate of Ascaris and hookworm was 23.29%, 23.01%, the average baseline worm load was 0.82,3.25, the average infection rate of one month was 1.81% and 4.03%, and the average infection after one year, respectively. The rates were 12.85%, 7.80% and 0.65,2.48. respectively.
2. based on the quantitative framework of Medley and other evaluation of chemotherapy strategies, a mathematical model of chemotherapeutic strategies for Ascaris and hookworm infection in China is constructed, including the infection rate model, the model of population dynamics and the model of the parasite distribution. The calculation method of biological parameters in the model is determined, including the negative two distribution parameters. Degree dependent parameters and basic reproductive rates. The calculation method of density dependent parameters is amended, and an improved formula is proposed, which is more suitable for fitting the field survey data in China. After obtaining the estimated values of biological parameters according to the field survey data, the model is replaced. The predicted results are better fitted to the field data, and the theoretical values are all in practice. Within the range of 95% confidence intervals of the value.
3. using the model to analyze the sensitivity of the intervention parameters, the results showed that the rate of infection rate of Ascaris Ascaris and hookworm after insect repellent was faster than that of the average worm, and the infection rate and average insect load decreased obviously when the rate of the insect repellent coverage increased from 60% to more than 80%, and the infection rate and the average insect load were later than 80%. 3 years were basically maintained at a lower level; when the drug effect was more than 85%, each year, the effect of an anthelmintic coverage rate of 80% on controlling the infection level of Ascaris and hookworm was two times a year, and the effect of anthelmintic coverage rate was 60%, and the number of chemotherapy times needed to reduce the infection rate and the average insect load to the same level in different regions was different.
4. using field data through model prediction shows that, for example, only a single measure of chemotherapy, 60% insect repellent coverage and one annual strategy, Jiangxi Jinxian survey point will take 1% of the hookworm infection rate in 8 years. For example, the annual strategy is 5 years, such as 60% insect repellent coverage, once each year. Briefly, the Sichuan Cuiping survey point will take 14 years to control the infection rate of Ascaris to 3% of the infection rate, such as the coverage rate of 80% insect repellents, and the annual strategy will take 5 years to reach this goal.
5. the statistical analysis of the questionnaire survey data was matched with the dung test and the data of the naughty insects according to the case number. The infection degree of Ascaris and hookworm was highly correlated (P0.0001) before the treatment of Ascaris and hookworm, which confirmed the existence of the tendency.
6. the negative two term model of zero expansion (ZINB) was introduced. By comparing the goodness of fit of the model, it was proved that the ZINB model was better than the traditional negative two model (NB) to fit the egg count data of Ascaris and hookworm.
7. the negative two term model (ZINB) of zero expansion (ZINB) was used to analyze the influence factors of ascariasis and reinfection of hookworm, which showed that there was no significant difference between different ages of Ascaris Ascaris and hookworm reinfection, but the intensity of reinfection (EPG) had the highest risk of high infection of Ascaris reinfection in.5-14 years old children (OR=7. 12,95%CI:1.72-29.42), followed by a 45-64 year old group (OR=3.49,95%CI:1.19-10.22), which was significantly higher than the 65-70 year old group, and there was no significant difference between the 15-44 year old group and the 65-70 year old group. The risk of getting high infection of the hookworm was the lowest (OR=0.09,95%CI:0.02-0.51), significantly lower than that of the 65-70 years old, although the other age group and the 65-70 year old group were statistically analyzed. There was no significant difference in learning test, but from the coefficient we could see that the risk of high infectivity increased with age.
High infection rate before treatment is a risk factor for reinfection of Ascaris and hookworm, Ascaris OR=1.96 (95%CI:1.32-2.92), and hookworm OR=3.95 (95%CI:2.05-7.60). High infection before treatment or a risk factor for high infection of Ascaris reinfection, OR=I.57 (95%CI:1.09-2.26).
The risk of reinfection of Ascaris and hookworm in the adobe house was 3.96 times (95%CI:1.27-12.35), 4.53 times (95%CI:1.43-14.34), 4.53 times (95%CI:1.43-14.34), compared with those living in the brick tile house of more than two layers. It was a high grade household appliance (OR=0.37,95%CI:0.16-0.86) and no OR=0.44,95% CI:0.21-0.90 was a protective factor for the reinfection of Ascaris.
conclusion
1. on the basis of the modified density dependent parameter calculation method, the mathematical model of Ascaris Ascaris and hookworm infection is well fitted to the field survey data in China, which is suitable for the evaluation of different chemotherapeutic strategies in China's Ascaris and hookworm epidemic areas, and provides an effective tool for the evaluation and prediction. It is of theoretical and practical value to optimize chemotherapy strategy and scientific decision.
2. the zero inflated negative two model (ZINB) is suitable for fitting the count data of Ascaris and hookworm eggs, and the fitting effect is better than the traditional negative two regression model (NB).
3. the study explained the pattern of reinfection and confirmed the presence of tendentious phenomena in the process of reinfection. The occurrence and intensity of Ascaris and hookworm reinfection were related to pre treatment infection, demographic characteristics, socioeconomic conditions, environment and behavior.
【学位授予单位】：中国疾病预防控制中心
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R311

【参考文献】