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Endemic transmission of Mycobacterium tuberculosis sublineage Beijing L2.2.M3 within Colon, Panama: A prospective study

F Acosta(1) D Candanedo(1,2) P Patel(1) A Llanes(1) J E Ku(1) K Salazar(2) M Morán(1) D Sambrano(1) J Jurado(3) M Delgado(3) L Solís(4) O Luque(4) K Da Silva(5) J Andrews(5) A Goodridge(1)

1:Centro de Biología Celular y Molecular de Enfermedades, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología de Panamá, Ciudad del Saber, Panamá.; 2:Universidad Latina de Panamá, Ciudad de Panamá.; 3:Caja de Seguro Social, Colón, Panamá.; 4:Programa de Control de Tuberculosis, Ministerio de Salud, Colón, Panamá.; 5:Division of Infectious Diseases & Geographic Medicine, Stanford University, California, United States

Tuberculosis remains a major public health threat worldwide. We aim to perform a prospective analysis of Mycobacterium tuberculosis Beijing sublineage isolates from Colon, Panama. Between 2021 to mid-October 2023 we collected Mycobacterium tuberculosis isolates.  Drug resistance was determined using GeneXpert and MTBDRplus-Genotype.  Genotyping and lineage identification were conducted using allele-specific oligonucleotide PCRs and MIRU-VNTR typing, and whole-genome sequencing.  Sequence data were analyzed using the mtb-call2 pipeline and TB-gen tools to predict drug resistance and sublineage, respectively. Genome-wide SNPs were also used for phylogenetic and evolutionary analyses including other Latin American isolates. 

Our results show ASO-PCR identified all 66 as Modern Beijing L2.2 isolates. The MIRU-VNTR genotyping revealed eight transmission clusters representing 27/66 (40.9%).  WGS analysis with pipeline mtb-call2 confirmed all isolates belong to the L2.2.1 Beijing sublineage, including 96.9% (62/64) pansusceptible and 3.1% (2/64) rifampicin mono-resistant.  The strains were genotyped by SNP at position 2078246C>G (gene gcvB, locus Rv1832).  In contrast, TB-gen genotyped all 64 strains as L.2.2.M3 Beijing sublineage by SNP at position 1219683G>A (gene coaA, locus Rv1092c).  The phylogenetic analysis revealed a correlation with geographical distribution when compared with other Latin American Beijing isolates. This analysis also confirmed a relatively low evolutionary rate within Panama Beijing isolates and a highly conserved common ancestor shared with Beijing isolates from Peru, Colombia, and Guatemala.

Our findings revealed an endemic transmission of the Mycobacterium tuberculosis Beijing sublineage in Colon, Panama. This study highlights the need for combining molecular/genomic with epidemiological data, to design new and reinforce tuberculosis control strategies. 

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