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Infections with Salmonella enterica serovars Typhi and Paratyphi A cause an estimated 14 million cases of enteric fever annually. Here, the controlled nature of challenge studies is exploited to identify genetic variants associated with enteric fever susceptibility. Human challenge participants were genotyped by Illumina OmniExpress-24 BeadChip array (n = 176) and/or transcriptionally profiled by RNA sequencing (n = 174). While the study was underpowered to detect any single nucleotide polymorphisms (SNPs) significant at the whole-genome level, two SNPs within CAPN14 and MIATNB were identified with P < 10⁻⁵ for association with development of symptoms or bacteremia following oral S. Typhi or S. Paratyphi A challenge. Imputation of classical human leukocyte antigen (HLA) types from genomic and transcriptomic data identified HLA-B*27:05, previously associated with nontyphoidal Salmonella …