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

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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.