發(fā)布時(shí)間：2018-07-06 14:47

  本文選題：蛔蟲 + 鉤蟲��； 參考：《中國疾病預(yù)防控制中心》2012年博士論文

【摘要】：目的 研究實(shí)施化學(xué)藥物驅(qū)蟲后蛔蟲和鉤蟲傳播的趨勢及定量關(guān)系,建立蛔蟲和鉤蟲感染化療策略數(shù)學(xué)模型,評(píng)價(jià)并預(yù)測不同化療策略對(duì)控制蛔蟲和鉤蟲感染的效果；研究驅(qū)蟲后蛔蟲、鉤蟲再感染的模式,探索影響再感染是否發(fā)生及發(fā)生強(qiáng)度的因素,為優(yōu)化化療策略、采取有針對(duì)性的干預(yù)措施提供理論依據(jù)。 方法 在復(fù)習(xí)文獻(xiàn)、確定建模目的基礎(chǔ)上,根據(jù)模型假設(shè)構(gòu)建蛔蟲和鉤蟲感染化療策略數(shù)學(xué)模型,通過現(xiàn)場縱向觀察,采取糞檢、驅(qū)蟲和淘蟲獲得人群在基線、一個(gè)月和一年時(shí)的蛔蟲及鉤蟲感染率、感染度等數(shù)據(jù),研究模型中參數(shù)的計(jì)算方法,利用現(xiàn)場數(shù)據(jù)運(yùn)行、驗(yàn)證并修正模型,利用模型評(píng)價(jià)和預(yù)測實(shí)施不同化療策略對(duì)控制蛔蟲和鉤蟲感染的效果。 將現(xiàn)場調(diào)查獲得的感染率、感染度等疫情數(shù)據(jù)與問卷調(diào)查獲得的人口學(xué)特征、社會(huì)經(jīng)濟(jì)條件、戶廁類型及糞便使用情況、行為習(xí)慣等數(shù)據(jù)進(jìn)行匹配,篩選出驅(qū)蟲后一個(gè)月時(shí)感染陰性的人群。根據(jù)蛔蟲和鉤蟲蟲卵計(jì)數(shù)數(shù)據(jù)的特點(diǎn),研究零膨脹的負(fù)二項(xiàng)模型(ZINB),與傳統(tǒng)的負(fù)二項(xiàng)模型(NB)比較,確定最優(yōu)模型,利用其研究再感染的模式,探索再感染的發(fā)生及強(qiáng)度與影響因素的關(guān)系。 結(jié)果 1.本研究在四川宜賓、江西進(jìn)賢和湖南岳陽的3個(gè)現(xiàn)場對(duì)2065人進(jìn)行了藥物干預(yù)和為期一年的縱向觀察�；紫x和鉤蟲基線平均感染率分別為23.29%、23.01%,基線平均蟲負(fù)荷分別為0.82、3.25,一個(gè)月平均感染率分別為1.81%和4.03%,一年后的平均感染率分別為12.85%、7.80%、平均蟲負(fù)荷分別為0.65、2.48。 2.基于Medley等的評(píng)價(jià)化療策略的定量框架,構(gòu)建了適用我國的蛔蟲和鉤蟲感染化療策略數(shù)學(xué)模型,包括感染率模型、作用于種群動(dòng)力學(xué)模型、作用于寄生蟲分布的模型。研究確定了模型中生物學(xué)參數(shù)的計(jì)算方法,包括負(fù)二項(xiàng)分布參數(shù)、密度依賴參數(shù)和基本繁殖率。對(duì)密度依賴參數(shù)的計(jì)算方法進(jìn)行了修正,提出了改進(jìn)的公式,更加適用于我國現(xiàn)場調(diào)查數(shù)據(jù)的擬合。根據(jù)現(xiàn)場調(diào)查數(shù)據(jù)獲得生物學(xué)參數(shù)的估計(jì)值后代入模型,預(yù)測結(jié)果較好地?cái)M合了現(xiàn)場數(shù)據(jù),理論值均在實(shí)際值的95%可信區(qū)間范圍內(nèi)。 3.利用模型對(duì)干預(yù)措施參數(shù)進(jìn)行敏感性分析,結(jié)果顯示：驅(qū)蟲后蛔蟲和鉤蟲感染率回升的速率比平均蟲負(fù)荷快；驅(qū)蟲覆蓋率從60%提高到80%以上時(shí),感染率和平均蟲負(fù)荷下降明顯；驅(qū)蟲覆蓋率達(dá)到80%以上時(shí),感染率和平均蟲負(fù)荷在隨后3年基本均維持在較低水平；當(dāng)藥物療效達(dá)85%以上時(shí),采用每年一次、驅(qū)蟲覆蓋率80%對(duì)控制蛔蟲和鉤蟲感染水平的效果比每年兩次、驅(qū)蟲覆蓋率60%的效果好；不同地區(qū)降低感染率和平均蟲負(fù)荷至同一水平所需的化療次數(shù)不同。 4.用現(xiàn)場數(shù)據(jù)通過模型預(yù)測表明,如僅采用化療單一措施,按60%驅(qū)蟲覆蓋率、每年一次的策略,江西進(jìn)賢調(diào)查點(diǎn)需8年時(shí)間將鉤蟲感染率控制在1%的水平；如按80%驅(qū)蟲覆蓋率、每年一次的策略,則需5年時(shí)間。如按60%驅(qū)蟲覆蓋率、每年一次的策略,四川翠屏調(diào)查點(diǎn)需14年時(shí)間將蛔蟲感染率控制在3%的感染率水平,如按80%驅(qū)蟲覆蓋率、每年一次的策略,則需5年時(shí)間達(dá)此目標(biāo)。 5.將問卷調(diào)查數(shù)據(jù)與糞檢、淘蟲數(shù)據(jù)按個(gè)案號(hào)進(jìn)行匹配后統(tǒng)計(jì)分析,蛔蟲和鉤蟲治療前、后感染程度均呈高度相關(guān)性(P0.0001),證實(shí)傾向性現(xiàn)象的存在。 6.研究引入了零膨脹的負(fù)二項(xiàng)模型(ZINB),通過模型擬合優(yōu)度的比較,證明了ZINB模型對(duì)于擬合蛔蟲和鉤蟲蟲卵計(jì)數(shù)數(shù)據(jù),優(yōu)于傳統(tǒng)的負(fù)二項(xiàng)模型(NB)。 7.運(yùn)用零膨脹的負(fù)二項(xiàng)模型(ZINB)分析蛔蟲、鉤蟲再感染影響因素顯示：不同年齡段對(duì)于是否發(fā)生蛔蟲和鉤蟲再感染無顯著性差異,但對(duì)于再感染的強(qiáng)度(用感染度EPG表示)均有意義。5-14歲兒童獲得蛔蟲再感染時(shí)高感染度的風(fēng)險(xiǎn)最高(OR=7.12,95%CI：1.72-29.42),其次是45-64歲組(OR=3.49,95%CI：1.19-10.22),均顯著高于65-70歲組,15-44歲組與65-70歲組無顯著性差異。5-14歲兒童獲得鉤蟲高感染度的風(fēng)險(xiǎn)最低(OR=0.09,95%CI：0.02-0.51),顯著低于65-70歲老年人,雖然其他年齡組與65-70歲組經(jīng)統(tǒng)計(jì)學(xué)檢驗(yàn)無顯著性差異,但從系數(shù)可以看出隨著年齡增加,高感染度的風(fēng)險(xiǎn)逐漸增加。 治療前感染度高是發(fā)生蛔蟲和鉤蟲再感染的危險(xiǎn)因素,蛔蟲OR=1.96(95%CI：1.32-2.92)、鉤蟲OR=3.95(95%CI：2.05-7.60)。治療前感染度高還是蛔蟲再感染獲得高感染度的危險(xiǎn)因素,OR=I.57(95%CI：1.09-2.26)。 居住在土坯房者再感染蛔蟲和鉤蟲的風(fēng)險(xiǎn)相對(duì)于居住在二層以上磚瓦房者分別是3.96倍(95%CI:1.27-12.35)、4.53倍(95%CI：1.43-14.34)。擁有較高檔次家用電器(OR=0.37,95%CI：0.16-0.86)、不喝生水(OR=0.44,95%CI：0.21-0.90)是發(fā)生蛔蟲再感染的保護(hù)因素。 結(jié)論 1.在修正了密度依賴參數(shù)計(jì)算方法的基礎(chǔ)上,構(gòu)建的蛔蟲和鉤蟲感染化療策略數(shù)學(xué)模型較好地?cái)M合了我國現(xiàn)場調(diào)查數(shù)據(jù),適用于我國蛔蟲和鉤蟲流行區(qū)不同化療策略效果的評(píng)價(jià),并為評(píng)價(jià)和預(yù)測提供了有效的工具,對(duì)于制定防治目標(biāo)、優(yōu)化化療策略及科學(xué)決策具有理論和實(shí)際應(yīng)用價(jià)值。 2.零膨脹的負(fù)二項(xiàng)模型(ZINB)適用于擬合蛔蟲和鉤蟲蟲卵計(jì)數(shù)數(shù)據(jù),擬合效果優(yōu)于傳統(tǒng)的負(fù)二項(xiàng)回歸模型(NB)。 3.本研究闡釋了再感染的模式,證實(shí)再感染過程中傾向性現(xiàn)象的存在�；紫x和鉤蟲再感染的發(fā)生及強(qiáng)度與治療前感染度、人口學(xué)特征、社會(huì)經(jīng)濟(jì)條件、環(huán)境及行為等因素相關(guān)。
[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.
【學(xué)位授予單位】：中國疾病預(yù)防控制中心
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2012
【分類號(hào)】：R311

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