| dc.description.abstract | Background: Intensive usage of antimicrobials in the management of animal diseases may cause selection for resistance among microorganisms. Transmission of resistant bacteria from the wild and domestic food animals to humans may occur via the food chain, environment, or direct interaction with animals and this may lead to the emergence of infections that are challenging to manage. This study aimed to determine the molecular epidemiology of antimicrobial resistance at a human-animal interface in pastoralist communities of Kasese district. Methods: A mixed-methods cross-sectional study was carried out involving participants presenting with fever and/or diarrhea in the health facilities whose samples were taken for culture and sensitivity. Participants from whom multidrug-resistant bacteria were isolated were back-traced to the community and samples were taken from members of the household. Speciation and antibiotic susceptibility of the isolates was done using the Phoenix automated microbiology system (Phoenix 100 ID/DST system) from Becton and Dickson (Franklin Lakes, NJ, USA) and the results interpreted using the CLSI guidelines Whole-genome paired-end sequencing (WGS) was performed at the facilities of Kenya Medical Research Institute-Wellcome trust, Kilifi for the multidrug-resistant isolates from humans and cattle. In the community, questionnaires were administered to the participants and key informant interviews were conducted. Results: A total of 371 participants were recruited and 122 from whom multi-drug resistant bacteria were isolated were followed up to the community. Overall, high resistance patterns were detected among our isolates with many of the isolates being multi-drug resistant. The general trend of antimicrobial resistance among the Cholera isolates showed increased susceptibility to combination therapy as opposed to monotherapy Phenotypic resistance testing revealed similar resistance patterns among the human and the cattle isolates for the 15 antibiotics tested in this study, however, Phylogenetic analysis showed that the genomes of the human E. coli generally clustered together and away from those of cattle origin. The E. coli isolates were assigned to eight different phylogroups: A, B1, B2, Cladel, D, E, F, and G, with a majority being assigned to phylogroup A; while most of the animal isolates were assigned to phylogroup B1. The carriage of multiple AMR genes was higher from the E. coli population from humans than those from cattle. Among these were Beta-lactamase; blaOXA-1: Class D beta-lactamases; blaTEM-1, blaTEM-235: Beta-lactamase; catA1: chloramphenicol acetyltransferase; cmlA1: chloramphenicol efflux transporter; dfrA1, dfrA12, dfrA14, dfrA15, dfrA17, dfrA5, dfrA7, dfrA8: macrolide phosphotransferase; oqxB11: RND efflux pump conferring resistance to fluoroquinolone; qacL, qacEdelta1: quinolone efflux pump; qnrS1: quinolone resistance gene; sul1, sul2, sul3: sulfonamide resistant; tet(A), tet(B): tetracycline efflux pump. A high variation of virulence genes was registered among the E. coli genomes from humans than those of cattle origin. Carriage of multi-drug resistant bacteria among humans was 88 (93%) and 76(80%) among cattle. Consumption of lakeshore water and carriage of multi-drug resistant bacteria in cattle were associated with carriage of multi-drug resistant bacteria in the human population. The key informants reported that antibiotics were used as first aid both in humans and cattle and no surveillance measures for antimicrobial resistance were put in place. The key informants also associated the problem of antimicrobial resistance to poverty, illiteracy, lack of veterinary personnel, ignorance among the community, and the low-cadre of medical staff serving the community. Conclusion: We demonstrated high antimicrobial resistance in bacteria isolated in humans and animals in pastoralist communities of Kasese district. Consumption of lakeshore water and carriage of multi-drug resistant bacteria in cattle were associated with carriage of multi-drug resistant bacteria in the human population. From the analysis of the core genome and phenotypic resistance, this study has demonstrated that the E. coli of human origin and those of cattle origin may have a common ancestry. Limited sharing of virulence genes presents a challenge to the notion that AMR in humans is as a result of antibiotic use in the farm and distorts the picture of the directionality of transmission of AMR at a human-animal interface and presents a task of exploring alternative routes of transmission of AMR. | en_US |
