Spatial-temporal and phylogenetic analyses of epidemiologic data to help understand the modes of transmission of endemic typhoid fever in Samoa


Michael J. Sikorski, Jianguo Ma, Tracy H. Hazen, Sachin N. Desai, Siaosi Tupua, Susana Nimarota-Brown, Michelle Sialeipata, Savitra Rambocus, Susan A. Ballard, Mary Valcanis, Robert E. Thomsen, Roy M. Robins-Browne, Benjamin P. Howden, Take K. Naseri, Myron M. Levine, View ORCID ProfileDavid A. Rasko


Salmonella enterica serovar Typhi (S. Typhi) is either widely distributed or proximally transmitted via fecally-contaminated food or water to cause typhoid fever. In Samoa, where endemic typhoid fever has persisted over decades despite water quality and sanitation improvements, the local patterns of S. Typhi circulation remain undistinguished. From April 2018-June 2020, epidemiologic data and GPS coordinates were collected during household investigations of 260 acute cases of typhoid fever, and 27 asymptomatic shedders of S. Typhi were detected among household contacts. Spatial and temporal distributions of cases were examined using Average Nearest Neighbor and space-time hotspot analyses. In rural regions, infections occurred in sporadic, focal clusters contrasting with persistent, less clustered cases in the Apia Urban Area. Restrictions to population movement during nationwide lockdowns in 2019-2020 were associated with marked reductions of cases. Phylogenetic analyses of isolates with whole genome sequences (n=186) revealed one dominant genotype 3.5.4 (n=181/186) that contains three Samoa-exclusive sub-lineages:,, and Variables of patient sex, age, and geographic region were examined by phylogenetic groupings, and significant differences (p<0.05) associated genetically-similar isolates in urban areas with working ages (20-49 year olds), and in rural areas with age groups typically at home (<5, 50+). Isolates from asymptomatic shedders were among all three sub-lineages. Whole genome sequencing also corroborated bacterial genetic similarity in 10/12 putative epidemiologic linkages among cases and asymptomatic shedders as well as 3/3 repeat positives (presumed relapses), with a median of one single nucleotide polymorphism difference. These findings highlight various patterns of typhoid transmission in Samoa that differ between urban and rural regions as well as genomic subtypes. Asymptomatic shedders, detectable only through household investigations, are likely an important reservoir and mobile agent of infection. This study advances a “Samoan S. Typhi framework” that supports current and future typhoid surveillance and control efforts in Samoa.

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