Genomics of Salmonella Typhi in Samoa: Population structure and genomic epidemiology

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Project Summary / Abstract Samoa is an island nation in the South Pacific (population ~200,000). For decades and despite improved water quality and sanitation, Samoans have faced endemic typhoid fever, a potentially fatal human host-restricted bacterial infection of the blood, hepatobiliary tree, and intestine caused by Salmonella enterica serovar Typhi (S. Typhi). We recently described the epidemiology of endemic typhoid fever in Samoa by person, place, and time (Sikorski et al., accepted, Clinical Infectious Diseases, 2020), but the mechanisms sustaining transmission – either direct spread or indirect environmental amplification – remain unknown. Bacterial whole genome sequencing (WGS) is a modern molecular tool that can establish phylogenetic relationships, test for antibiotic resistance and virulence factors, as well as detect outbreaks. Paired with high resolution epidemiologic and geospatial data (i.e., data generated by the Samoa Typhoid Fever Surveillance Initiative) WGS can help to explain origins, evolution, clustering, and transmission patterns. Our long-term goals are to examine the genomic population structure and evolution of S. Typhi circulating in Samoa using WGS and to combine comparative genomics with geospatial epidemiology to help explain its endemicity. Large-scale genomic studies describe the emergence and global spread of aggressive extensively-drug resistant S. Typhi strains, but none have focused on Samoa. The genomics S. Typhi in Samoa not known nor is the date or geographical source of introduction. Our preliminary WGS analyses of 176 S. Typhi isolates from Samoa from 1992-2018 show (i) an exclusive Samoan genotype that appears nowhere else in the world, (ii) geospatial clustering of genomically related isolates, and (iii) the presence of unique genes found only in the Samoan isolates. We hypothesize that a unique strain of S. Typhi entered Samoa decades ago and expanded into the dominant circulating strain, and asymptomatic chronic gallbladder carriers of the strain serve as an effective long-term reservoir and source of infection. We propose two Specific Aims: (1) characterize the genomics of S. Typhi causing clinical disease in Samoa, and (2) define the role of asymptomatic S. Typhi carriers (N=24 to date) using combined WGS and geospatial analyses. Isolates from Samoa will be sequenced and assembled and then compared with the global collection of S. Typhi (~3,400 isolates) using single nucleotide polymorphism and Bayesian evolutionary phylogenetic analyses. We will apply our lab's large-scale blast score ratio pipeline to identify any new and/or deleted genes. After funded training from the Institute for Disease Modeling we will combine the data on genomic relatedness among S. Typhi isolates with clinical, epidemiologic, and geospatial data to demonstrate local patterns of transmission. These detailed analyses have never been completed on Samoan S. Typhi, and the results will be integrated into public health decisions and policies.