title: Protocol for a population-based molecular epidemiology study of tuberculosis transmission in a high HIV-burden setting: the Botswana Kopanyo study.
abstract: Mycobacterium tuberculosis (Mtb) is transmitted from person to person via airborne droplet nuclei. At the community level, Mtb transmission depends on the exposure venue, infectiousness of the tuberculosis (TB) index case and the susceptibility of the index case's social network. People living with HIV infection are at high risk of TB, yet the factors associated with TB transmission within communities with high rates of TB and HIV are largely undocumented. The primary aim of the Kopanyo study is to better understand the demographic, clinical, social and geospatial factors associated with TB and multidrug-resistant TB transmission in 2 communities in Botswana, a country where 60% of all patients with TB are also infected with HIV. This manuscript describes the methods used in the Kopanyo study.
  
  
  
  The study will be conducted in greater Gaborone, which has high rates of HIV and a mobile population; and in Ghanzi, a rural community with lower prevalence of HIV infection and home to the native San population. Kopanyo aims to enrol all persons diagnosed with TB during a 4-year study period. From each participant, sputum will be cultured, and for all Mtb isolates, molecular genotyping (24-locus mycobacterial interspersed repetitive units-variable number of tandem repeats) will be performed. Patients with matching genotype results will be considered members of a genotype cluster, a proxy for recent transmission. Demographic, behavioural, clinical and social information will be collected by interview. Participant residence, work place, healthcare facilities visited and social gathering venues will be geocoded. We will assess relationships between these factors and cluster involvement to better plan interventions for reducing TB transmission.
  
  
  
  Ethical approval from the Independent Review Boards at the University of Pennsylvania, US Centers for Disease Control and Prevention, Botswana Ministry of Health and University of Botswana has been obtained.
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: N M
authors.initials: NM
authors.lastname: Zetola
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA Botswana-UPenn Partnership, Department of Medicine, University of Pennsylvania Gaborone, Gaborone, Botswana.
authors.forename: C
authors.initials: C
authors.lastname: Modongo
authors.affiliation: Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: P K
authors.initials: PK
authors.lastname: Moonan
authors.affiliation: Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: E
authors.initials: E
authors.lastname: Click
authors.affiliation: Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Oeltmann
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Yale University, New Heaven, Connecticut, USA.
authors.forename: J
authors.initials: J
authors.lastname: Shepherd
authors.affiliation: Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: A
authors.initials: A
authors.lastname: Finlay
mesh_terms: D001902:Botswana / Q000453:epidemiology; D016000:Cluster Analysis; D060085:Coinfection / Q000453:epidemiology*; D005838:Genotype; D062305:Geographic Mapping; D015658:HIV Infections / Q000453:epidemiology*; D006801:Humans; D020071:Interspersed Repetitive Sequences; D017720:Molecular Epidemiology; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D015995:Prevalence; D012107:Research Design; D020080:Tandem Repeat Sequences; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology* / Q000635:transmission*; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology* / Q000635:transmission*
keywords: Molecular Epidemiology; Multi-Drug Resistant Tuberculosis; Transmission