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 弯曲杆菌是全世界细菌性肠炎的主要原因之一，并且其逐渐发展 全球分离株（尤其是低收入和中等收入国家）的抗菌素耐药性已导致 CDC 将耐药弯曲杆菌列为 2019 年严重威胁清单的首位。 欧洲对基因组流行病学的重大投资为成功降低发病率的干预措施提供了信息 人类感染和后遗症，如吉兰-巴利综合征。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，但先进的来源归因方法尚未 用于确定引起人类疾病的主要感染源，或确定 对氟喹诺酮类药物和阿奇霉素（MDR 弯曲杆菌）均具有耐药性的人类感染源， 尽管有记录显示其发病率很高。弯曲杆菌的有限基因组研究在中低水平进行 收入国家表现出人类和人类分离株基因组的重要差异 人畜共患病来源，表明这些环境中的传播动态与高浓度环境中的传播动态不同 收入国家。目前缺乏对人畜共患源种群的准确定量源归因 大多数感染发生的地方是全球控制弯曲杆菌感染的关键知识缺口。这 该项目的目标是告知有针对性的疾病控制措施，以减少疾病的影响 低收入和中等收入国家的弯曲杆菌病和人类耐多药弯曲杆菌。我们的中央 假设工业生产的肉制品是弯曲菌病和多重耐药菌的主要来源 该人群中的人类弯曲杆菌。为了检验我们的中心假设，我们将 1）识别宿主 秘鲁人畜共患来源的弯曲杆菌的分离特征； 2) 表征基因组 引起人类疾病的弯曲杆菌菌株，评估家庭人与人之间的风险 传播并识别与持续无症状人类携带相关的微生物基因组特征 3) 估计家庭和人类造成的弯曲菌病和人类耐多药感染的负担 工业衍生的人畜共患病来源。拟议的项目将联合一个高度互补的群体 在流行病学、弯曲杆菌基因组学、生物信息学和 微生物生态学为控制弯曲菌的战略性和有针对性的疾病控制干预措施提供信息 人类耐多药弯曲杆菌感染率最高的地区之一。该项目是 在高负担中低收入国家中将特征性人类病例和人畜共患病宿主联系起来的方法具有创新性 设置本地、区域和全球参考基因组，以创建强有力的证据来推动政策和实践 改善弯曲菌病的控制并减少耐多药的地理扩张 弯曲杆菌。