RESUMEN
Molecular epidemiologic studies have shown that the dynamics of tuberculosis transmission varies geographically. We sought to determine which strains of Mycobacterium tuberculosis (MTB) were infecting household contacts (HHC), and which were causing clusters of tuberculosis (TB) disease in Vitoria-ES, Brazil. A total of 741 households contacts (445 TST +) and 139 index cases were characterized according to the proportion of contacts in each household that had a tuberculin skin test positive: low (LT) (≤40% TST+), high (HT) (≥70% TST+) and (40-70% TST+) intermediate (IT) transmission. IS6110-RFLP and spoligotyping analysis were performed only 139 MTB isolates from index cases and 841 community isolates. Clustering occurred in 45% of the entire study population. There was no statistically significant association between MTB household transmission category and clustering. Within the household study population, the proportion of clusters in HT and LT groups was similar (31% and 36%, respectively; p = 0.82). Among index cases isolates associated with households demonstrating TST conversion, the frequency of unique pattern genotypes was higher for index cases of the LT compared to HT households (p = 0.03). We concluded that clusters and lineages associated with MTB infection in HT households had no proclivity for increased transmission of TB in the community.
Asunto(s)
Trazado de Contacto , Composición Familiar , Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/patogenicidad , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/transmisión , Técnicas de Tipificación Bacteriana , Brasil , Análisis por Conglomerados , Dermatoglifia del ADN , Vivienda , Humanos , Epidemiología Molecular , Mycobacterium tuberculosis/genética , Esputo/microbiología , Prueba de Tuberculina , Tuberculosis Pulmonar/diagnósticoRESUMEN
The current study evaluated Mycobacterium tuberculosis isolates from Rio de Janeiro, Brazil, for genomic deletions. One locus in our panel of PCR targets failed to amplify in approximately 30% of strains. A single novel long sequence polymorphism (>26.3 kb) was characterized and designated RD(Rio). Homologous recombination between two similar protein-coding genes is proposed as the mechanism for deleting or modifying 10 genes, including two potentially immunogenic PPE proteins. The flanking regions of the RD(Rio) locus were identical in all strains bearing the deletion. Genetic testing by principal genetic group, spoligotyping, variable-number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR), and IS6110-based restriction fragment length polymorphism analysis cumulatively support the idea that RD(Rio) strains are derived from a common ancestor belonging solely to the Latin American-Mediterranean spoligotype family. The RD(Rio) lineage is therefore the predominant clade causing tuberculosis (TB) in Rio de Janeiro and, as indicated by genotypic clustering in MIRU-VNTR analysis, the most significant source of recent transmission. Limited retrospective reviews of bacteriological and patient records showed a lack of association with multidrug resistance or specific risk factors for TB. However, trends in the data did suggest that RD(Rio) strains may cause a form of TB with a distinct clinical presentation. Overall, the high prevalence of this genotype may be related to enhanced virulence, transmissibility, and/or specific adaptation to a Euro-Latin American host population. The identification of RD(Rio) strains outside of Brazil points to the ongoing intercontinental dissemination of this important genotype. Further studies are needed to determine the differential strain-specific features, pathobiology, and worldwide prevalence of RD(Rio) M. tuberculosis.