Recurrent treatment: Effect on rural and urban S. mansoni population structure

反复治疗：对农村和城市曼氏沙门氏菌种群结构的影响

• 批准号: 7208362
• 负责人: Ronald E Blanton
• 金额: $ 37.66万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7208362
• 关键词: Affect; Alleles; Area; Biology; Characteristics; Cities; Communities; Contracts; Count; Cross-Sectional Studies; DNA; Databases; Developed Countries; Developing Countries; Dimensions; Disease; Drug Design; Epidemiology; Feces; Gene Frequency; Genes; Genetic Structures; Genome; Genotype; Heterogeneity; Human; Immigration; Individual; Infection; Laboratories; Measures; Methodology; Methods; Microsatellite Repeats; Morbidity - disease rate; Nature; Numbers; Parasites; Pattern; Persons; Polymorphic Microsatellite Marker; Population; Population Analysis; Population Dynamics; Population Sizes; Population Study; Praziquantel; Prevalence; Public Health; Publishing; Rate; Recovery; Recurrence; Relative (related person); Research; Research Personnel; Risk Factors; Rural; Rural Population; Sampling; Schistosoma; Schistosoma mansoni; Schistosomiasis; Site; Source; Statistical Methods; Structure; Sum; Time; Visit; World Health Organization; base; chemotherapy; egg; improved; indexing; migration; pathogen; programs; response; rural area; sample fixation; tool; transmission process; treatment effect

DESCRIPTION (provided by applicant): The biologic heterogeneity that exists within local Schistosoma mansoni populations is difficult to study, yet this diversity and local parasite population dynamics are important risk factors for disease; they may assist drug design and may affect control strategies. Control programs for S. mansoni center on repeated rounds of chemotherapy every 2-3 years to reduce infection intensities and thereby reduce morbidity. Prevalence is much less affected and transmission is not interrupted, since these populations rapidly recover. The resultant effect of periodic contracting and re-expanding populations on schistosome biology is not known in large part due to the lack of tools and methodologies for differentiating subpopulations of worms. We have identified 7 polymorphic microsatellite markers that behave like single-copy loci, are species-specific, and produce interpretable patterns for DNA isolated from parasite eggs. Further, to optimize sampling, we have developed methods to isolate parasite egg DNA from stool and statistical methods that utilize allele frequencies from pooled samples rather than discrete genotypes. In order to understand how repeated chemotherapy changes S. mansoni population structure, this proposal will directly determine the allele frequency distribution of S. mansoni by isolating and genotyping egg DNA from the stool of infected individuals. These allele frequencies will then be related to the regional and microgeographic distribution of the parasite before and after yearly chemotherapy. With the tools we have developed, this project will: 1) Determine how microgeography relates to subpopulation distribution and gene flow, 2) Determine how widespread chemotherapy changes population structure, 3) Determine how populations that persist after chemotherapy are related to pre-treatment populations, 4) Measure the contribution of migration or increase in the resident population to recovery of schistosome populations, 5) Assess the contribution of local parasite transmission versus immigration to urban foci, 6) Compare urban foci to rural populations before and after therapy. Population structure will be compared using the between populations fixation index (Fsr) and by estimation of both effective population size (Ne) and the immigration rate (m). Mixed stock analysis will also be used to analyze migration.

描述(申请人提供)：存在于当地曼氏血吸虫种群内的生物异质性很难研究，但这种多样性和当地寄生虫种群动态是疾病的重要风险因素；它们可能有助于药物设计并可能影响控制策略。曼氏沙门氏菌的控制计划集中在每2-3年重复进行一轮化疗，以降低感染强度，从而减少发病率。流行率受到的影响要小得多，传播也不会中断，因为这些人口迅速恢复。在很大程度上，由于缺乏区分虫子亚群的工具和方法，周期性收缩和重新扩大种群对血吸虫生物学的综合影响尚不清楚。我们已经确定了7个多态微卫星标记，它们的行为类似于单拷贝基因座，具有物种特异性，并对从寄生虫卵中分离的DNA产生可解释的模式。此外，为了优化采样，我们开发了从粪便中分离寄生虫卵DNA的方法，以及从混合样本中利用等位基因频率而不是离散基因类型的统计方法。为了了解重复化疗是如何改变曼氏血吸虫种群结构的，这一建议将通过从感染者粪便中分离虫卵DNA并进行基因分型，直接确定曼氏血吸虫的等位基因频率分布。这些等位基因频率将与每年化疗前后寄生虫的地区和微地理分布有关。利用我们开发的工具，该项目将：1)确定微观地理与亚群分布和基因流动的关系；2)确定广泛的化疗如何改变人口结构；3)确定化疗后持续存在的人口与治疗前人口的关系；4)衡量迁徙或增加的常住人口对血吸虫种群恢复的贡献；5)评估当地寄生虫传播相对于城市疫源地移民的贡献；6)比较治疗前后城市和农村人口的病源。种群结构将使用种群固定指数(FSR)进行比较，并通过估计有效种群数量(Ne)和迁移率(M)进行比较。混合种群分析也将用于分析迁徙。