ハンセン病（らい病）は、現在も年間20万人以上の新規患者が報告される人類史上最古の感染症の一つですが、その起源や大陸間での拡散史には不明な点が多く残されています。従来、アメリカ大陸におけるハンセン病はコロンブス以降に持ち込まれたと考えられてきました。今回、Lopopolo博士らは、米国バトンルージュの国立ハンセン病プログラムに保存されていた患者組織やアルマジロなどの野生動物に加え、アメリカ大陸各地の考古学的人骨試料からDNA解析を行いました。その結果、Mycobacterium lepromatosis による感染がコロンブス以前のカナダ西岸やアルゼンチン・パタゴニアの祖先集団にすでに存在していたことが示されました。分子時計解析により、ヨーロッパ人到来以前にすでに複数の系統が大陸全体に広がっていたことが明らかとなり、さらに英国のリスに見られる感染例との関連を含め、動物との間での人獣共通感染の可能性も示唆されています。本研究は、アメリカ大陸におけるハンセン病の歴史を大きく書き換える成果です。

 

Leprosy (Hansen’s Disease), an overlooked infectious disease, disproportionately impacts developing countries, causing over 200,000 annual cases. While it is commonly believed that leprosy in the Americas emerged relatively recently resulting from post-colonial introduction of M. leprae infections, our research unveils a more complex history on the continent. We conducted an unprecedented screening of patients' histological sections archived at the National Hansen’s Disease Programs in Baton Rouge and wild animals, such as armadillos. By screening for M. leprae and M. lepromatosis, we increased genomes for the latter pathogen from modern human infections tenfold, particularly in today’s territories of Mexico and the United States.

In our exploration of leprosy's history in the Americas, we analysed DNA from archaeological skeletal remains of pre-colonial ancestors in the Southern Cone of the Americas. Additionally, we interrogated public resources to include worldwide samples in our study. Here, we present the first reported cases of M. lepromatosis leprosy in pre-colonial ancestors. Notably, we confirmed M. lepromatosis infections in pre-colonial ancestors from diverse regions, including today’s territory of Prince Rupert, Canada, and Patagonia, Argentina. Molecular clock analyses estimate a comprehensive timeline, showcasing leprosy's presence before the European invasion and its subsequent rapid dissemination across North and South America. Moreover, our research reveals multiple pathogen clades, offering new perspectives on potential zoonotic transmission routes for previously reported infected UK red squirrels. These findings provide valuable insights into leprosy's dynamics and clarify the historical presence and spread of the disease in the Americas.

• M. Lopopolo, C. Avanzi, S. Duchene, P. Luisi, A. de Flamingh, G. Y. Ponce-Soto, et al., Pre-European contact leprosy in the Americas and its current persistence. Science, eadu7144 (2025).

• A. Benjak, C. Avanzi, P. Singh, C. Loiseau, S. Girma, P. Busso, et al., Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae. Nat Commun 9, 352 (2018).

• V. J. Schuenemann, P. Singh, T. A. Mendum, B. Krause-Kyora, G. Jäger, K. I. Bos, et al., Genome-Wide Comparison of Medieval and Modern Mycobacterium leprae. Science 341, 179–183 (2013).

• X. Y. Han, Y.-H. Seo, K. C. Sizer, T. Schoberle, G. S. May, J. S. Spencer, W. Li, R. G. Nair, A New Mycobacterium Species Causing Diffuse Lepromatous Leprosy. Am J Clin Pathol 130, 856–864 (2008).

• X. Y. Han, F. M. Aung, S. E. Choon, B. Werner, Analysis of the Leprosy Agents Mycobacterium leprae and Mycobacterium lepromatosis in Four Countries. American Journal of Clinical Pathology 142, 524–532 (2014).

• P. Singh, A. Benjak, V. J. Schuenemann, A. Herbig, C. Avanzi, P. Busso, K. Nieselt, J. Krause, L. Vera-Cabrera, S. T. Cole, Insight into the evolution and origin of leprosy bacilli from the genome sequence of Mycobacterium lepromatosis. Proc. Natl. Acad.Sci. U.S.A. 112, 4459–4464 (2015).

• C. Avanzi, J. del-Pozo, A. Benjak, K. Stevenson, V. R. Simpson, P. Busso, et al., Red squirrels in the British Isles are infected with leprosy bacilli. Science 354, 744–747 (2016)

• D. A. Ramirez, T. L. Sitter, S. Översti, M. J. Herrera-Soto, N. Pastor, O. E. Fontana-Silva, C. L. Kirkpatrick, J. Castelleti-Dellepiane, R. Nores, K. I. Bos, 4,000-year-old Mycobacterium lepromatosis genomes from Chile reveal long establishment of Hansen’s disease in the Americas. Nat Ecol Evol, doi: 10.1038/s41559-025-02771-y (2025).

• C. A. Roberts, Leprosy in the Americas before Columbus. Nat Ecol Evol, doi: 10.1038/s41559-025-02790-9 (2025).

東京大学大学院理学系研究科・生物科学専攻・ゲノム人類学研究室