03011nas a2200541 4500000000100000008004100001260001200042653001200054653001500066653002500081653001300106653001200119653001900131100001300150700001500163700001900178700001300197700001500210700001900225700001500244700002800259700001600287700001700303700001200320700001900332700001600351700001800367700002000385700001600405700001400421700001200435700001600447700001300463700001400476700001400490700001400504700001300518700001200531700002400543700001300567700001100580245010200591856008000693300000800773490000700781520166700788022001402455 2020 d c01/202010aComoros10aMadagascar10aMycobacterium leprae10agenomics10aleprosy10aphylogeography1 aAvanzi C1 aLecorche E1 aRakotomalala F1 aBenjak A1 aRabenja FR1 aRamarozatovo L1 aCauchoix B1 aRakoto-Andrianarivelo M1 aTió-Coma M1 aLeal-Calvo T1 aBusso P1 aBoy-Röttger S1 aChauffour A1 aRasamoelina T1 aAndrianarison A1 aSendrasoa F1 aSpencer J1 aSingh P1 aDashatwar D1 aNarang R1 aBerland J1 aJarlier V1 aSalgado C1 aMoraes M1 aGeluk A1 aRandrianantoandro A1 aCambau E1 aCole S00aPopulation Genomics of Mycobacterium leprae Reveals a New Genotype in Madagascar and the Comoros. uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233131/pdf/fmicb-11-00711.pdf a7110 v113 a

Human settlement of Madagascar traces back to the beginning of the first millennium with the arrival of Austronesians from Southeast Asia, followed by migrations from Africa and the Middle East. Remains of these different cultural, genetic, and linguistic legacies are still present in Madagascar and other islands of the Indian Ocean. The close relationship between human migration and the introduction and spread of infectious diseases, a well-documented phenomenon, is particularly evident for the causative agent of leprosy, . In this study, we used whole-genome sequencing (WGS) and molecular dating to characterize the genetic background and retrace the origin of the strains circulating in Madagascar ( = 30) and the Comoros ( = 3), two islands where leprosy is still considered a public health problem and monitored as part of a drug resistance surveillance program. Most strains (97%) from Madagascar and Comoros belonged to a new genotype as part of branch 1, closely related to single nucleotide polymorphism (SNP) type 1D, named 1D-Malagasy. Other strains belonged to the genotype 1A (3%). We sequenced 39 strains from nine other countries, which, together with previously published genomes, amounted to 242 genomes that were used for molecular dating. Specific SNP markers for the new 1D-Malagasy genotype were used to screen samples from 11 countries and revealed this genotype to be restricted to Madagascar, with the sole exception being a strain from Malawi. The overall analysis thus ruled out a possible introduction of leprosy by the Austronesian settlers and suggests a later origin from East Africa, the Middle East, or South Asia.

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