Genomic Epidemiology of Campylobacter to Improve Disease Control in Low and Middle Income Countries

弯曲杆菌的基因组流行病学可改善中低收入国家的疾病控制

• 批准号: 10371146
• 负责人: Margaret N Kosek
• 金额: $ 65.79万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-15 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10371146
• 关键词: Affect; Animals; Antimicrobial Resistance; Area; Azithromycin; Bacteriophages; Bioinformatics; Campylobacter; Campylobacter coli; Campylobacter infection; Campylobacter jejuni; Centers for Disease Control and Prevention (U.S.); Chickens; Childhood; Communicable Diseases; Consequentialism; Country; Data; Databases; Development; Disease; Domestic Animals; Domestic Fowls; Drug-resistant Campylobacter; Ecology; Enteral; Epidemiology; Etiology; Europe; Family suidae; Fluoroquinolones; France; Future; Genetic; Genome; Genomic approach; Genomics; Geography; Goals; Guillain Barré Syndrome; Health; Household; Human; Incidence; Income; Industrialization; Infection; International; Intervention; Investments; Irritable Bowel Syndrome; Knowledge; Link; Livestock; Malnutrition; Measures; Meat; Meat Products; Methodology; Microbiology; Mission; Modernization; Morbidity - disease rate; Multicenter Studies; New Zealand; Oral; Outcome; Persons; Peru; Policies; Population; Production; Public Health; Research; Research Personnel; Resistance; Resolution; Risk; Risk Factors; Ruminants; Source; Syndrome; Testing; Travel; United States; United States National Institutes of Health; Work; Zoonoses; antimicrobial; burden of illness; co-infection; design; disease transmission; disorder control; effective intervention; enteric infection; enteric pathogen; enteritis; evidence base; fluoroquinolone resistance; foodborne illness; genomic data; genomic epidemiology; human disease; improved; innovation; low and middle-income countries; low income country; microbial; microbial genomics; pathogen; prevent; programs; reference genome; resistant strain; successful intervention; transmission process

ABSTRACT Campylobacter is among the principal causes of bacterial enteritis worldwide and the progressive development of antimicrobial resistance among global isolates, particularly in low and middle income countries, has led the CDC to list drug-resistant Campylobacter at the top of its list of serious threats in 2019. In the past decade in Europe major investments in genomic epidemiology have informed successful interventions to decrease rates of human infection and sequelae such as Guillan-Barre syndrome. Despite clear evidence that Campylobacter is a principal cause of enteritis in the developing world, advanced approaches in source attribution have not been employed to identify the principal sources of infection causing disease in humans, or to identify the sources of human infections resistant to both fluoroquinolones and azithromycin (MDR Campylobacter), despite their documented high incidence. The limited genomic study of Campylobacter done in low and middle income countries demonstrates important differences in the genomes of isolates from both humans and zoonotic sources, indicating that transmission dynamics differ in these settings compared to that seen in high income countries. The current deficit in accurate quantitative source attribution to zoonotic source populations where most infections occur is a critical knowledge gap in the global control of Campylobacter infections. The objective of this project is to inform targeted disease control measures to reduce the impact of campylobacteriosis and human MDR Campylobacter in low and middle income countries. Our central hypothesis is that industrially produced meat products are the principal source of campyobacteriosis and MDR Campylobacter in humans in this population. In order to test our central hypothesis we will 1) identify host segregating features of Campylobacter from zoonotic sources in Peru; 2) characterize genomes of Campylobacter strains that cause disease in humans, evaluate the risk of household peron-to-person transmission and identify microbial genomic features associated with persistent asymptomatic human carriage and 3) estimate the burden of campylobacteriosis and human MDR infections attributable to domestic and industrially derived zoonotic sources. The proposed project will unite a highly complementary group of accomplished researchers with expertise in epidemiology, Campylobacter genomics, bioinformatics and microbial ecology to inform strategic and targeted disease control interventions for Campylobacter control in an area with one of the highest documented rates of human MDR Campylobacter infection. The project is innovative in its approach to link characterized human cases and zoonotic reservoirs in a high burden LMIC setting to local, regional, and global reference genomes to create robust evidence to drive policy and practice to improve the control of campylobacteriosis and the diminish the geographic expansion of MDR Campylobacter.

抽象的 弯曲杆菌是全球细菌性肠炎和渐进发展的主要原因之一 全球分离株之间的抗菌素抵抗，尤其是在低收入国家和中等收入国家，已导致 疾病预防控制中心将耐药弯曲杆菌列为2019年严重威胁清单的顶部。在过去的十年中 欧洲基因组流行病学的重大投资已通知成功的干预措施以降低利率 人类感染和后遗症，例如Guillan-Barre综合征。尽管有明确的证据表明弯曲杆菌 是发展中国家肠炎的主要原因，源归因的先进方法尚未 被用来识别引起人类疾病的主要感染的主要来源，或者确定 对氟喹诺酮类和阿奇霉素（MDR弯曲杆菌）抗性的人类感染的来源， 尽管有记录的高发病率。在低和中间进行的弯曲杆菌的有限基因组研究 收入国家表现出在人类和人类分离株的基因组中的重要差异 人畜共动性来源，表明在这些环境中的传输动态与高度相比 收入国家。当前对人畜共患源人群的准确定量源归因的赤字 发生大多数感染的地方是弯曲杆菌感染的全球控制中的关键知识差距。这 该项目的目的是告知有针对性的疾病控制措施，以减少 低收入和中等收入国家的弯曲杆菌和人类MDR弯曲杆菌。我们的中心 假设是，工业生产的肉类产品是弯曲细菌和MDR的主要来源 该人群中人类的弯曲杆菌。为了检验我们的中心假设，我们将1）确定主机 弯曲杆菌与秘鲁的人畜共患病的特征； 2）表征的基因组 引起人类疾病的弯曲杆菌菌株，评估家庭对人的风险 传播并识别与持续无症状人工马车相关的微生物基因组特征 3）估计弯曲杆菌病和人类MDR感染的负担归因于国内和 工业衍生的人畜共患病。拟议的项目将团结一个高度互补的小组 具有流行病学专业知识，弯曲杆菌基因组学，生物信息学和 微生物生态学为弯曲杆菌控制的战略性和有针对性疾病控制干预措施提供信息 人类MDR弯曲杆菌感染率最高的区域之一。该项目是 其链接的方法是人类案例和人畜共患库的特征 设置为本地，区域和全球参考基因组，以创建强大的证据来推动政策和实践 为了改善弯曲杆菌病的控制，并减少了MDR的地理扩张 弯曲杆菌。