title: A Mycobacterial Perspective on Tuberculosis in West Africa: Significant Geographical Variation of M. africanum and Other M. tuberculosis Complex Lineages.
abstract: BACKGROUND
  Phylogenetically distinct Mycobacterium tuberculosis lineages differ in their phenotypes and pathogenicity. Consequently, understanding mycobacterial population structures phylogeographically is essential for design, interpretation and generalizability of clinical trials. Comprehensive efforts are lacking to date to establish the West African mycobacterial population structure on a sub-continental scale, which has diagnostic implications and can inform the design of clinical TB trials.
  
  
  RESULTS
  We collated novel and published genotyping (spoligotyping) data and classified spoligotypes into mycobacterial lineages/families using TBLineage and Spotclust, followed by phylogeographic analyses using statistics (logistic regression) and lineage axis plot analysis in GenGIS, in which a phylogenetic tree constructed in MIRU-VNTRplus was analysed. Combining spoligotyping data from 16 previously published studies with novel data from The Gambia, we obtained a total of 3580 isolates from 12 countries and identified 6 lineages comprising 32 families. By using stringent analytical tools we demonstrate for the first time a significant phylogeographic separation between western and eastern West Africa not only of the two M. africanum (West Africa 1 and 2) but also of several major M. tuberculosis sensu stricto families, such as LAM10 and Haarlem 3. Moreover, in a longitudinal logistic regression analysis for grouped data we showed that M. africanum West Africa 2 remains a persistent health concern.
  
  
  CONCLUSIONS
  Because of the geographical divide of the mycobacterial populations in West Africa, individual research findings from one country cannot be generalized across the whole region. The unequal geographical family distribution should be considered in placement and design of future clinical trials in West Africa.
authors.affiliation: Mycobacterial Unit, Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.|Vaccines and Immunity Theme, Medical Research Council (MRC) Unit, Fajara, The Gambia.
authors.forename: Florian
authors.initials: F
authors.lastname: Gehre
authors.affiliation: Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Samrat
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Statistics and Bioinformatics Department, Medical Research Council (MRC) Unit, Fajara, The Gambia.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Kendall
authors.affiliation: Mycobacterial Unit, Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.|University of Gondar, Gondar, Ethiopia.
authors.forename: Mebrat
authors.initials: M
authors.lastname: Ejo
authors.affiliation: Vaccines and Immunity Theme, Medical Research Council (MRC) Unit, Fajara, The Gambia.
authors.forename: Oumie
authors.initials: O
authors.lastname: Secka
authors.affiliation: Mycobacterial Unit, Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.|Vaccines and Immunity Theme, Medical Research Council (MRC) Unit, Fajara, The Gambia.
authors.forename: Boatema
authors.initials: B
authors.lastname: Ofori-Anyinam
authors.affiliation: Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Abatih
authors.affiliation: Vaccines and Immunity Theme, Medical Research Council (MRC) Unit, Fajara, The Gambia.
authors.forename: Martin
authors.initials: M
authors.lastname: Antonio
authors.affiliation: Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Dirk
authors.initials: D
authors.lastname: Berkvens
authors.affiliation: Mycobacterial Unit, Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.|Vaccines and Immunity Theme, Medical Research Council (MRC) Unit, Fajara, The Gambia.|Division of Infectious Diseases, Department of Medicine, New York University (NYU), New York, New York, United States of America.
authors.forename: Bouke C
authors.initials: BC
authors.lastname: de Jong
mesh_terms: D000354:Africa, Western / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D058889:Molecular Typing; D009161:Mycobacterium / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D058974:Phylogeography; D014376:Tuberculosis / Q000453:epidemiology* / Q000382:microbiology*