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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 unclear. 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: 3.5.4.1, 3.5.4.2, and 3.5.4.3. 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 provided evidence of bacterial genetic similarity, which corroborated 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. Author summary: Many typhoid endemic countries have evident transmission contributions from widely distributed contaminated water supplies and/or asymptomatic S. Typhi carriers who intermittently cause sporadic outbreaks. However, these patterns have not yet been examined in the island nation of Samoa, where typhoid has remained endemic for decades. In this study, we incorporated the discerning powers of spatial-temporal cluster analyses as well as phylogenetics of whole genome sequences (WGS) of S. Typhi isolates to examine detailed epidemiologic data collected through household investigations of culture-confirmed cases of typhoid fever occurring in Samoa from April 2018 through June 2020. We detected patterns consistent with both modes of transmission, varying between urban and rural regions, and we provided evidence of intra-household transmission of genetically similar isolates, thereby supporting a majority of putative epidemiologic linkages made during household investigations, and identifying important roles for asymptomatic shedders of S. Typhi. These findings advance our understanding of persistently endemic typhoid fever in Samoa and directly support the efforts of the Samoa Typhoid Fever Control Program of the Ministry of Health of Samoa. [ABSTRACT FROM AUTHOR]

Background Typhoid fever has been endemic on the island nation of Samoa (2016 population, 195 979) since the 1960s and has persisted through 2019, despite economic development and improvements in water supply and sanitation. Methods Salmonella enterica serovar Typhi isolates from the 2 hospitals with blood culture capability and matched patient demographic and clinical data from January 2008 through December 2019 were analyzed. Denominators to calculate incidence by island, region, and district came from 2011 and 2016 censuses and from 2017–2019 projections from Samoa's Bureau of Statistics. Data were analyzed to describe typhoid case burden and incidence from 2008 to 2019 by time, place, and person. Results In sum, 53–193 blood culture-confirmed typhoid cases occurred annually from 2008 to 2019, without apparent seasonality. Typhoid incidence was low among children age < 48 months (17.6–27.8/105), rose progressively in ages 5–9 years (54.0/105), 10–19 years (60.7–63.4/105), and 20–34 years (61.0–79.3/105), and then tapered off; 93.6% of cases occurred among Samoans < 50 years of age. Most typhoid cases and the highest incidence occurred in Northwest Upolu, but Apia Urban Area (served by treated water supplies) also exhibited moderate incidence. The proportion of cases from short-cycle versus long-cycle transmission is unknown. Samoan S. Typhi are pansusceptible to traditional first-line antibiotics. Nevertheless, enhanced surveillance in 2019 detected 4 (2.9%) deaths among 140 cases. Conclusions Typhoid has been endemic in Samoa in the period 2008–2019. Interventions, including mass vaccination with a Vi-conjugate vaccine coadministered with measles vaccine are planned. [ABSTRACT FROM AUTHOR]