Use of Whole-genome Sequencing in a Tuberculosis Outbreak among Young Immigrants in a Japanese Language School, 2024

In early April 2024, three Nepalese students (Pt1-Pt3) in the morning classes of a Japanese language school in Western Japan were diagnosed with sputum smear-positive pulmonary tuberculosis (TB). The smear status of Pt1 and Pt3 was 3+, whereas Pt2 was scanty positive. This study aims at describing cases with active TB as well as latent TB infection (LTBI) in this outbreak.

The outbreak cases are epidemiologically described in terms of time, place, and person.

An intensive contact investigation using chest X-rays found 13 cases with active TB as of January 2025. Ten cases, including Pt1 and Pt2, were found in Classroom A, whereas one case each was found in the morning classes of Classrooms B (Pt3) and C and in Classroom D (afternoon class). In addition, 10 other cases of LTBI were found in Classroom A. Whole-genome sequencing (WGS) revealed that Pt3 and another case in Classroom A had genetically distinct Mycobacterium tuberculosis strains, with 1072 and 466 single nucleotide variants, respectively, indicating they were unrelated to the outbreak. On the other hand, the case of Classroom C shared the outbreak strain, and the person had frequently visited the apartment of Pt1 and Pt2. The case of Classroom D did not have close contact with those of Classroom A and was eventually excluded from the outbreak cases.

WGS is useful in distinguishing outbreak-related cases from coincidentally found ones in TB outbreak investigations.