title: Genetic diversity, transmission dynamics, and drug resistance of Mycobacterium tuberculosis in Luanda, Angola.
abstract: OBJECTIVE
  Despite the important role that the African region plays in a global tuberculosis (TB) epidemiological context, many countries in the region still lack data on the prevalence of specific Mycobacterium tuberculosis strains and drug resistance. This is the case for Angola, which presently lacks any data concerning drug-resistance rates and prevalence of specific M. tuberculosis genotypes and respective population structure. In this study, we made the first characterization of the genetic diversity and drug resistance of M. tuberculosis complex strains circulating in Luanda, Angola's most important setting concerning TB epidemiology.
  
  
  METHODS
  We have analyzed 89 M. tuberculosis isolates recovered from the same number of patients. All clinical isolates were genotyped by spoligotyping and 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTRs). First-line drug-susceptibility testing was performed by the standard BACTEC 960 Mycobacteria Growth Indicator Tube (MGIT) procedure.
  
  
  RESULTS
  We have detected 33 different spoligotype profiles corresponding to 24 different shared international types (SITs) and nine orphan profiles. SIT 20 (LAM1) was the most prevalent (n=16, 18.2%) followed by SIT 42 (LAM9; n=15, 17.1%). Overall, the M. tuberculosis population structure in this sample was dominated by LAM (64.8%) and T (33.0%) strains. Twenty-four-loci MIRU-VNTR analysis revealed that a total of 13 isolates were grouped into five distinct clusters. Drug-susceptibility testing revealed a worrying situation concerning resistance rates. Drug-susceptibility data showed that 22 (24.7%) of the 89 clinical isolates were resistant to one or more antibacillary drugs of which four (4.5%) were multidrug resistant (MDR). Drug-resistant isolates were found across distinct clades and MIRU-VNTR clusters.
  
  
  CONCLUSIONS
  This first cross-sectional study conducted in Luanda, Angola, provides a framework for future studies and programmatic management of TB in Angola. We provide sufficient evidence for cluster-based transmission with a high predominance of LAM strains, with differential geographic dispersion. The moderate rate of MDR-TB found in this sample has major public health implications and highlights the need for further studies specifically focused on MDR-TB transmission.
authors.affiliation: iMed.ULisboa - Instituto de Investigação do Medicamento, Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Perdigão
authors.affiliation: Hospital da Divina Providência, Serviço de Doenças Infecciosas, Luanda, Angola.
authors.forename: Sofia
authors.initials: S
authors.lastname: Clemente
authors.affiliation: Unidade de Microbiologia Médica, Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL), Lisboa, Portugal.
authors.forename: Jorge
authors.initials: J
authors.lastname: Ramos
authors.affiliation: Hospital da Divina Providência, Serviço de Doenças Infecciosas, Luanda, Angola.
authors.forename: Pedro
authors.initials: P
authors.lastname: Masakidi
authors.affiliation: Unidade de Microbiologia Médica, Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL), Lisboa, Portugal.
authors.forename: Diana
authors.initials: D
authors.lastname: Machado
authors.affiliation: iMed.ULisboa - Instituto de Investigação do Medicamento, Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Carla
authors.initials: C
authors.lastname: Silva
authors.affiliation: Unidade de Microbiologia Médica, Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL), Lisboa, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Couto
authors.affiliation: Unidade de Microbiologia Médica, Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL), Lisboa, Portugal.
authors.forename: Miguel
authors.initials: M
authors.lastname: Viveiros
authors.affiliation: iMed.ULisboa - Instituto de Investigação do Medicamento, Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal; Centro de Investigação Interdisciplinar Egas Moniz, Instituto Superior de Ciências da Saúde Egas Moniz, Monte de Caparica, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Taveira
authors.affiliation: iMed.ULisboa - Instituto de Investigação do Medicamento, Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal. Electronic address: isabel.portugal@ff.ul.pt.
authors.forename: Isabel
authors.initials: I
authors.lastname: Portugal
keywords: Angola; Multidrug-resistant tuberculosis; Mycobacterial interspersed repetitive unit–variable number of tandem repeats; Mycobacterium tuberculosis; Spoligotyping; Tuberculosis