Study On Mathematical Model And Re - Infection Pattern Of Infection Strategy Of Ascaris And

ObjectivesTo study the transmission trend and quantitative relationship after implementing chemotherapy measure due to A. lumbricoides and hookworm infections, establish the mathematical models of chemotherapy strategy for A. lumbricoides and hookworm infections, evaluate and predict the effects of different chemotherapy strategies to control the infection of A. lumbricoides and hookworm. To study the pattern of re-infection of A. lumbricoides and hookworm after deworming, explore the risk factors of the occurrence and intensity of re-infection, providing theoretical basis for optimizing the chemotherapy-based control strategies and adopting the targetted intervention measures.MethodsOn the basis of literature review and model establishment purpose, the mathematical models of chemotherapy strategy for A. lumbricoides and hookworm infections were established according to the model hypothesis. Through field longitudinal observations and taking stool examination, deworming, and worm extraction, the infection rates and intensities of A. lumbricoides and hookworm at baseline, one month and one year were acquired, study calculation methods for the parameters in the models, using the field data to operate, validate and modify the models, which were then used to evaluate and predict the effects of A. lumbricoides and hookworm infection control taking different deworming strategies.Questionnaire survey was carried out at one year, including the demography, socio-economic conditions, toilet type and the usage of feces, behaviors related to hygienes, etc. These data were matched with the data of prevalence and intensity through field survey, then those infection negative at one month after deworming were selected out. Study the zero-inflated negative binomial model(ZINB), make comparisons with the traditional negative binomial model, and assure the best model, which was then used to study the pattern of re-infection, and explore the relationship of risk factors with the occurrence and intensity of re-infection.Results1. Chemotherapy intervention and one-year longitudinal observations were carried out in3fields located in Sichuan, Jiangxi and Hunan provinces and involved2065subjects. The baseline average prevalence of A. lumbricoides and hookworm were23.29%and23.01%, respectively, with mean worm burden0.82and3.25. The average prevalence at one month were1.81%and4.03%. The average prevalence at one year were12.85%and7.80%, with mean worm burden0.65and2.48.2. Based on the quantitative framework for evaluating the chemotherapy scheme made by Medley, et al., the mathematical models of chemotherapy strategy for A. lumbricoides and hookworm infection were established, including the prevalence rate model, dynamic models, and parasite distribution models. Study and assure the calculation methods for the biologic parameters in the models, involving the negative binomial distribution parameter, density-dependence parameter, and basic reproductive rate. The calculation method of density-dependence parameter was modified and the new equation was put forward, which is proven to better fit the field survey data in our country. After putting the estimated values of biologic parameters into the models, the predicted prevalence and intensity at one year were within the95%confidence interval of actual values.3. Sensitivity analysis to the chemotherapy parameters showed that the ascending velocity of intensities of A. lumbricoides and hookworm infections after each round of treatment is lower than that of prevalences; If treatment coverage increases from60%to80%, the infection level descends dramatically, once reaches above80%, prevalence and intensity will remain low over the following three years; The effect of taking80%treatment coverage and annual chemotherapy will be better than that of60%treatment coverage and biannual chemotherapy, if the drug efficacy reachs85%and above; The rounds of chemotherapy needed to reduce the prevalence and intensity to the same level in different sites are different.4. Model simulations based on field data show that it would take nine rounds of annual treatment to reach and remain a1%infection rate under60%treatment coverage for the hookworm infection, if only chemotherapy control measure was taken, in the survey spot in Jinxian of Jiangxi province, while only six rounds would be required, if under80%treatment coverage. It would take15rounds of annual treatment to reach a3%infection rate under60%treatment coverage for A. lumbricoides infection, while only six rounds would be required, if under80%treatment coverage.5. Match the questionnaire survey data and the field observation data of stool examination and worm extraction, according to the subject unique ID number, statistical analysis results show that the infection intensities of A. lumbricoides and hookworm before and after deworming were highly correlated(P<0.0001). The phenomenon of predisposition was proved to exist in the study.6. The zero-inflated negative binomial model (ZINB) was invited into the study, through the comparison of goodness of fit, ZINB model was proved to be better than the traditional negative binomial model (NB), for fitting the egg count data of A. lumbricoides and hookworm.7. The analysis of risk factors influencing re-infection using the ZINB model show: All age groups have no significant differences of re-infection occurrence, while significant to the intensity of re-infection(expressed by EPG), both for A. lumbricoides and hookworm infection. Age group of5-14has the highest risk of acquiring high intensity of A. lumbricoides re-infection(OR=7.12,95%CI:1.72-29.42), and followed by age group of45-64(OR=3.49,95%CI:1.19-10.22), which were both significantly higher than that of age group of65-70, while age group of15-44has no significant difference with age group of65-70. Age group of5-14has the lowest risk of acquiring high intensity of hookworm re-infection (OR=0.09,95%CI:0.02-0.51), compared with age group of65-70. Though the other groups have no significant difference with age group of65-70, the model coefficients show that the risk of high intensity of hookworm re-infection increases gradually with the increase of age.High intensity before treatment was the risk factor of A. lumbricoides and hookworm re-infection occurrence, with OR=1.96(95%CI:1.32-2.92) for A.lumbricoides, and OR=3.95(95%CI:2.05-7.60) for hookworm. High intensity before treatment was still the risk factor of acquiring the high intensity of A.lumbricoides re-infection, with OR=1.57(95%CI:1.09-2.26)Residing in adobe house has higher A. lumbricoides and hookworm re-infection risk, compared with residing in brick house, with OR=3.96(95%CI:1.27-12.35) for A.lumbricoides, and OR=4.53(95%CI:1.43-14.34) for hookworm. Owning high grade of household electrical appliances (OR=0.37,95%CI:0.16-0.86), and not drinking unboiled water (OR=0.44,95%CI:0.21-0.90) were protective factors of A.lumbricoides re-infection.Conclusions1. Based on the modification of calculation method for the density-dependence parameter, the established mathematical models of chemotherapy strategy for A.lumbricoides and hookworm infections well fit our country’s field survey data. It could be applied to evaluate the effects of different chemotherapy strategies in the endemic areas of A.lumbricoides and hookworm infections in our country, providing efficient tool for evaluation, and is of theoretical and applicable value for formulating control targets, optimizing chemotherapy strategies and making scientific decisions.2. The zero-inflated negative binomial model (ZINB) applies to fit the egg count data of A.lumbricoides and hookworm, and fits superior than the traditional negative binomial model (NB).3. This study explained the pattern of re-infection, the phenomenon of predisposition was proved to exist. The occurrences and intensities of A.lumbricoides and hookworm re-infection were associated with previous infection intensity, demographic characteristics, socio-economic conditions, environmental and behavior factors.