Browsing by Author "Portugal, I"
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- Emergence of Multidrug-Resistant Mycobacterium Tuberculosis of the Beijing Lineage in Portugal and Guinea-Bissau: a Snapshot of Moving Clones by Whole-Genome SequencingPublication . Perdigão, J; Silva, C; Maltez, F; Machado, D; Miranda, A; Couto, I; Rabna, P; Florez de Sessions, P; Phelan, J; Pain, A; McNerney, R; Hibberd, M; Mokrousov, I; Clark, T; Viveiros, M; Portugal, IThe Beijing genotype comprises a highly disseminated strain type that is frequently associated with multidrug resistant (MDR) tuberculosis (TB) and increased transmissibility but, countries such as Portugal and Guinea-Bissau fall outside the regions phylogeographically associated with this specific genotype. Nevertheless, recent data shows that this genotype might be gradually emerging in these two countries as an underlying cause of primary MDR-TB. Here, we describe the emergence of Mycobacterium tuberculosis Beijing strains associated with MDR-TB in Portugal and Guinea-Bissau demonstrating the presence of the well described superclusters 100-32 and 94-32 in Portugal and Guinea-Bissau, respectively. Genome-wide analysis and comparison with a global genomic dataset of M. tuberculosis Beijing strains, revealed the presence of two genomic clusters encompassing isolates from Portugal and Guinea-Bissau, GC1 (n = 121) and GC2 (n = 39), both of which bore SNP signatures compatible with the 100-32/B0/W148 and 94-32/Central Asia Outbreak clades, respectively. Moreover, GC2 encompasses a cross-border cluster between Portugal, Guinea-Bissau and Brazil thus supporting migration-associated introduction of MDR-TB and subsequent clonal expansion at the community-level. The comparison with global Beijing datasets demonstrates the global reach of the disease and its complex dissemination across multiple countries while in parallel there are clear microevolutionary trajectories towards extensively drug resistant TB.
- Tuberculose Multirresistente por Estirpes da Família Beijing, em Doentes de Lisboa, Portugal: Estudo PreliminarPublication . Maltez, F; Martins, T; Póvoas, D; Cabo, J; Peres, H; Antunes, F; Perdigão, J; Portugal, IIntrodução: As estirpes de Mycobacterium tuberculosis da família Beijing estão associadas à multirresistência. As estirpes da família Lisboa prevalecem entre os doentes com tuberculose multirresistente e extensivamente resistente desta região, mas vários estudos documentam a presença da família Beijing, embora desconhecendo-se as características dos doentes donde foram isoladas. Material e Métodos: Estudo retrospectivo de 104 estirpes multirresistentes e extensivamente resistentes de Mycobacterium tuberculosis, isoladas e genotipadas, de 1993 a 2015, de igual número de doentes de Lisboa. Avaliámos a prevalência de ambas as famílias de estirpes e as características epidemiológicas e clínicas, dos infectados por estirpes Beijing. Resultados: Setenta e quatro estirpes (71,2%) pertenciam à família Lisboa, 25 (24,0%) apresentavam padrão genotípico único e cinco (4,8%) pertenciam à família Beijing, estas identificadas depois de 2009. Os infectados pela estirpe Beijing eram de nacionalidade angolana (n = 1), ucraniana (n = 2) e portuguesa (n = 2), na maioria jovens, quatro em cinco imunocompetentes e sem história de tuberculose anterior. Todos tinham tuberculose multirresistente. Não detectámos apresentações clínicas ou radiológicas diferenciadoras, nem padrão de resistências predominante. A taxa de cura foi alta (quatro doentes). Discussão: Apesar do número de doentes infectados pela estirpe Beijing ser reduzido, sugere proporção importante de tuberculose primária, potencial de transmissão na comunidade, mas, também, melhor evolução clínica do que a descrita para outras estirpes, como a W-Beijing ou a Lisboa. Conclusão: Apesar das estirpes da família Lisboa serem as principais responsáveis pelos casos de tuberculose multirresistente e extensivamente resistente na região de Lisboa, as estirpes Beijing transmitem-se na cidade e poderão modificar as características locais da epidemia.
- Using Genomics to Understand the Origin and Dispersion of Multidrug and Extensively Drug Resistant Tuberculosis in PortugalPublication . Perdigão, J; Gomes, P; Miranda, A; Maltez, F; Machado, D; Silva, C; Phelan, J; Brum, L; Campino, S; Couto, I; Viveiros, M; Clark, T; Portugal, IPortugal is a low incidence country for tuberculosis (TB) disease. Now figuring among TB low incidence countries, it has since the 1990s reported multidrug resistant and extensively drug resistant (XDR) TB cases, driven predominantly by two strain-types: Lisboa3 and Q1. This study describes the largest characterization of the evolutionary trajectory of M/XDR-TB strains in Portugal, spanning a time-period of two decades. By combining whole-genome sequencing and phenotypic susceptibility data for 207 isolates, we report the geospatial patterns of drug resistant TB, particularly the dispersion of Lisboa3 and Q1 clades, which underly 64.2% and 94.0% of all MDR-TB and XDR-TB isolates, respectively. Genomic-based similarity and a phylogenetic analysis revealed multiple clusters (n = 16) reflecting ongoing and uncontrolled recent transmission of M/XDR-TB, predominantly associated with the Lisboa3 and Q1 clades. These clades are now thought to be evolving in a polycentric mode across multiple geographical districts. The inferred evolutionary history is compatible with MDR- and XDR-TB originating in Portugal in the 70's and 80's, respectively, but with subsequent multiple emergence events of MDR and XDR-TB particularly involving the Lisboa3 clade. A SNP barcode was defined for Lisboa3 and Q1 and comparison with a phylogeny of global strain-types (n = 28 385) revealed the presence of Lisboa3 and Q1 strains in Europe, South America and Africa. In summary, Portugal displays an unusual and unique epidemiological setting shaped by >40 years of uncontrolled circulation of two main phylogenetic clades, leading to a sympatric evolutionary trajectory towards XDR-TB with the potential for global reach.