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However, unusual genetic heterogeneity may indicate more complex transmission dynamics. This case represents an instance of household transmission facilitated by an asymptomatic carrier harbouring genetically diverse\n                    <jats:italic>S.<\/jats:italic>\n                    Typhi strains. A healthy adult developed severe typhoid requiring hospitalization, and two children required treatment. Public health epidemiological connections among the cases supported the findings of the phylogenetic analysis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Hypothesis\/Gap Statement.<\/jats:bold>\n                    We hypothesized that a household cluster of\n                    <jats:italic>S.<\/jats:italic>\n                    Typhi infections, displaying greater-than-expected genetic diversity, may have originated from a chronic carrier with a diverse in-host bacterial population \u2013 an under-recognized transmission route.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Aim.<\/jats:bold>\n                    To investigate the source and genomic diversity of a household cluster of\n                    <jats:italic>S.<\/jats:italic>\n                    Typhi cases with no recent travel history and to assess the role of asymptomatic carriage in transmission.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methodology.<\/jats:bold>\n                    We conducted detailed contact tracing, epidemiological investigations and whole-genome sequencing on isolates from four household cases. An asymptomatic contact, with a history of\n                    <jats:italic>S. Typhi<\/jats:italic>\n                    infection and recent travel to Pakistan, underwent enhanced sampling and genomic analysis of multiple\n                    <jats:italic>S.<\/jats:italic>\n                    Typhi isolates.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results.<\/jats:bold>\n                    The four household cases formed a 25-SNP single linkage cluster, inconsistent with typical isogenic clustering. Genomic analysis of multiple isolates from the asymptomatic carrier revealed a genetically diverse\n                    <jats:italic>S.<\/jats:italic>\n                    Typhi population with evidence of in-host evolution. Two case isolates were nested within the genomic diversity of the carrier\u2019s isolates. Epidemiological investigations identified no alternative sources of infection.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion.<\/jats:bold>\n                    This case series highlights the complexity of defining\n                    <jats:italic>S.<\/jats:italic>\n                    Typhi transmission using discrete SNP thresholds. While epidemiological links suggested a single source, phylogenetic analysis revealed notable genetic diversity among the strains. The findings underscore the public health risks posed by chronic carriers harbouring diverse\n                    <jats:italic>S.<\/jats:italic>\n                    Typhi populations and the complications associated with typhoid transmission and disease severity.\n                  <\/jats:p>","DOI":"10.1099\/jmm.0.002070","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T17:16:10Z","timestamp":1758561370000},"source":"Crossref","is-referenced-by-count":3,"title":["Heterogeneous Salmonella typhi transmission within a household: genomic insights from a chronic carrier"],"prefix":"10.1099","volume":"74","author":[{"given":"Rushana","family":"Hussain","sequence":"first","affiliation":[{"name":"Microbiology Department, Royal Bolton Hospital Foundation Trust, Bolton, 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