P104
Linking long-term and short-term Mycobacterium tuberculosis transmission dynamics inferred form 15 years study in Orizaba, Mexico
P Sinisterra-Sebastián(1) F J Martínez-Martínez(1) L Varón-Pozuelo(1) P Cano-Jiménez(1) V Furió(1) M Torres-Puente(1) G Delgado-Sánchez(2) L Ferreyra-Reyes(2) M Bobadilla Del Valle(3) A Ordaz-Vázquez(3) N Mongua-Rodríguez(2) L García-García(2) I Comas(1,4) M G López(1)
1:Tuberculosis Genomics Unit, Instituto de Biomedicina de Valencia, CSIC, Valencia, 46011 Spain; 2:Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, 62100, México; 3:Laboratorio de Microbiología, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, Mexico City, 14080, México; 4:CIBER de Epidemiología y Salud Pública, CIBERESP, Madrid, Spain
Transmission is the main reason for the persistence of the tuberculosis (TB) pandemic. Although genomic epidemiology of Mycobacterium tuberculosis (Mtb) is increasingly used in public health surveillance, long-term transmission dynamics remain poorly understood, limiting insights into transmission drivers. From 1995 to 2010, passive case-finding was implemented in Orizaba, Veracruz (Mexico), a low TB-burden district. A total of 1,257 TB patients were recruited, with 845 (67.22%) culture-positive samples sequenced using Illumina technology. By combining genomic, evolutionary, and epidemiological data, we aimed to (1) describe the local Mtb population structure; (2) investigate transmission at different levels and time spans, beyond recent genomic clustering, and (3) estimate the origins and long-term transmission dynamics of key genotypes in Orizaba.
In the short term, a high clustering rate was observed, with 48.6% and 61.0% of cases grouped using 5- and 10-SNP threshold, respectively. Furthermore, we unveil the role in transmission of cases not usually prioritized in public health investigations, such as those with negative sputum smear microscopy results. In the long term, a consistent clustering pattern was observed, indicating exponential expansion of the pandemic beginning at the turn of the 20th century. A large-scale global phylodynamic analysis revealed that local genotypes have been expanding for decades, contributing to today's transmission.
In conclusion, Orizaba exhibits high transmission levels driven by locally circulating Mtb genotypes with decades-long persistence. Our findings suggest disease burden poorly predicts transmission. Furthermore, short-term genomic clustering is better interpreted within the long-term transmission dynamics context.