title: Effect of study design and setting on tuberculosis clustering estimates using Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats (MIRU-VNTR): a systematic review.
abstract: OBJECTIVE
  To systematically review the evidence for the impact of study design and setting on the interpretation of tuberculosis (TB) transmission using clustering derived from Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats (MIRU-VNTR) strain typing.
  
  
  METHODS
  MEDLINE, EMBASE, CINHAL, Web of Science and Scopus were searched for articles published before 21st October 2014.
  
  
  METHODS
  Studies in humans that reported the proportion of clustering of TB isolates by MIRU-VNTR were included in the analysis. Univariable meta-regression analyses were conducted to assess the influence of study design and setting on the proportion of clustering.
  
  
  RESULTS
  The search identified 27 eligible articles reporting clustering between 0% and 63%. The number of MIRU-VNTR loci typed, requiring consent to type patient isolates (as a proxy for sampling fraction), the TB incidence and the maximum cluster size explained 14%, 14%, 27% and 48% of between-study variation, respectively, and had a significant association with the proportion of clustering.
  
  
  CONCLUSIONS
  Although MIRU-VNTR typing is being adopted worldwide there is a paucity of data on how study design and setting may influence estimates of clustering. We have highlighted study design variables for consideration in the design and interpretation of future studies.
authors.affiliation: Department of Infection and Population Health, University College London, London, UK.
authors.forename: Jessica
authors.initials: J
authors.lastname: Mears
authors.affiliation: Department of Infection and Population Health, University College London, London, UK Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK Clinical Trials Unit, Medical Research Council, London, UK.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Abubakar
authors.affiliation: Division of Global Health Equity, Brigham and Women's Hospital and Department of Epidemiology, Harvard School of Public Health, Harvard University, Boston, USA.
authors.forename: Theodore
authors.initials: T
authors.lastname: Cohen
authors.affiliation: Department of Infection, Centre for Clinical Microbiology, University College London, London, UK.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: McHugh
authors.affiliation: Department of Infection and Population Health, University College London, London, UK.
authors.forename: Pam
authors.initials: P
authors.lastname: Sonnenberg
mesh_terms: D015373:Bacterial Typing Techniques / Q000379:methods*; D016000:Cluster Analysis; D006801:Humans; D020071:Interspersed Repetitive Sequences; D018598:Minisatellite Repeats; D017720:Molecular Epidemiology / Q000379:methods; D009169:Mycobacterium tuberculosis / Q000145:classification*; D012150:Polymorphism, Restriction Fragment Length; D015203:Reproducibility of Results; D012107:Research Design; D014376:Tuberculosis / Q000453:epidemiology*
keywords: EPIDEMIOLOGY; MOLECULAR BIOLOGY