A case of laboratory-acquired Salmonella Typhi infection due to phage typing in Japan: whole-genome sequencing confirms the source of infection

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This paper reports a single laboratory-acquired case of typhoid fever in Japan: a 48-year-old researcher undergoing phage typing of Salmonella enterica serovar Typhi developed high fever, diarrhea, malaise, and loss of appetite, and initial clinical impressions included autoimmune disease before blood cultures confirmed S. Typhi. Whole-genome comparative genomic analysis showed that the patient’s isolates were clonal with the strain handled in the laboratory, linking the infection source. The authors explicitly frame this as the first reported Japanese case linked to phage typing and highlight whole-genome sequencing as a method for tracking such events, with the main limitation being that it is a single case report without broader epidemiologic validation. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Introduction: Typhoid fever, caused by Salmonella enterica serovar Typhi, is a systemic infection. Approximately 40 cases occur annually in Japan, most of which are imported. In August 2023, a researcher engaged in phage typing of S. Typhi was diagnosed with typhoid fever.   Case Presentation A 48-year-old man presented with high fever, diarrhea, malaise, and loss of appetite. Initial findings, including liver dysfunction and severe inflammation, led to a suspected diagnosis of autoimmune disease. However, blood cultures identified S. Typhi, confirming typhoid fever. Comparative genomic analysis demonstrated clonality between the strain handled in the laboratory and the patient isolates, indicating a laboratory-acquired infection.   Conclusion This case underscores the need for ongoing vigilance regarding the risk of laboratory-acquired infections and highlights the value of whole-genome sequencing for tracking. It would be also emphasizes that this is the first reported case in Japan linked to phage typing, a conventional typing method for S. Typhi. This raises the urgency of transitioning from phage typing to genotyping and recommends mandatory typhoid vaccination for laboratory personnel working with S. Typhi to minimize infection risk.
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Abstract

Introduction Typhoid fever, caused by Salmonella enterica serovar Typhi, is a systemic infection. Approximately 40 cases occur annually in Japan, most of which are imported. In August 2023, a researcher engaged in phage typing of S. Typhi was diagnosed with typhoid fever. Case Presentation A 48-year-old man presented with high fever, diarrhea, malaise, and loss of appetite. Initial findings, including liver dysfunction and severe inflammation, led to a suspected diagnosis of autoimmune disease. However, blood cultures identified S. Typhi, confirming typhoid fever. Comparative genomic analysis demonstrated clonality between the strain handled in the laboratory and the patient isolates, indicating a laboratory-acquired infection.

Conclusion

This case underscores the need for ongoing vigilance regarding the risk of laboratory-acquired infections and highlights the value of whole-genome sequencing for tracking. It would be also emphasizes that this is the first reported case in Japan linked to phage typing, a conventional typing method for S. Typhi. This raises the urgency of transitioning from phage typing to genotyping and recommends mandatory typhoid vaccination for laboratory personnel working with S. Typhi to minimize infection risk. - Received: - Version Posted: Funding - Japan Agency for Medical Research and Development (Award JP24wm0225023) - Principal Award Recipient: Masatomo Morita - Japan Agency for Medical Research and Development (Award JP24fk0108663) - Principal Award Recipient: Hidemasa Izumiya - Japan Agency for Medical Research and Development (Award JP24fk0108683) - Principal Award Recipient: Yukihiro Akeda

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