Abstract
Genomic data on Clostridioides difficile from the African continent are currently lacking, resulting in the region being under-represented in global analyses of C. difficile infection (CDI) epidemiology. For the first time in Nigeria, we utilized whole-genome sequencing and phylogenetic tools to compare C. difficile isolates from diarrhoeic human patients (n=142), livestock (n=38), poultry manure (n=5) and dogs (n=9) in the same geographic area (Makurdi, north-central Nigeria) and relate them to the global C. difficile population. In addition, selected isolates were tested for antimicrobial susceptibility (n=33) and characterized by PCR ribotyping (n=53). Hierarchical clustering of core-genome multilocus sequence typing (cgMLST) allelic profiles revealed large diversity at the level HC150 (i.e. clusters of related genomes with maximally 150 pairwise allelic differences), which was previously shown to correlate with PCR ribotypes (RT). While several globally disseminated strains were detected, including HC150_1 (associated with RT078), HC150_3 (RT001) and HC150_3622 (RT014), 42 HC150 clusters (79%) represented unique genotypes that were new to the public genomic record, and 16 (30%) of these were novel PCR ribotypes. Considerable proportions of the C. difficile isolates displayed resistance to fluoroquinolones, macrolides and linezolid, potentially reflecting human and animal antibiotic consumption patterns in the region. Notably, our comparative phylogenomic analyses revealed human-human, human-livestock and farm-farm sharing of near-identical C. difficile genomes (≤2 core-genome allelic differences), suggesting the continued spread of multiple strains across human and animal (pig, poultry, cattle and dog) host populations. Our findings highlight the interconnectivity between livestock production and the epidemiology of human CDI and inform the need for increased CDI awareness among clinicians in this region. A large proportion of C. difficile strains appeared to be unique to the region, reflecting both the significant geographic patterning present in the C. difficile population and a general need for additional pathogen sequencing data from Africa.