title: Validation of genotype cluster investigations for Mycobacterium tuberculosis: application results for 44 clusters from four heterogeneous United States jurisdictions.
abstract: BACKGROUND
  Tracking the dissemination of specific Mycobacterium tuberculosis (Mtb) strains using genotyped Mtb isolates from tuberculosis patients is a routine public health practice in the United States. The present study proposes a standardized cluster investigation method to identify epidemiologic-linked patients in Mtb genotype clusters. The study also attempts to determine the proportion of epidemiologic-linked patients the proposed method would identify beyond the outcome of the conventional contact investigation.
  
  
  METHODS
  The study population included Mtb culture positive patients from Georgia, Maryland, Massachusetts and Houston, Texas. Mtb isolates were genotyped by CDC's National TB Genotyping Service (NTGS) from January 2006 to October 2010. Mtb cluster investigations (CLIs) were conducted for patients whose isolates matched exactly by spoligotyping and 12-locus MIRU-VNTR. CLIs were carried out in four sequential steps: (1) Public Health Worker (PHW) Interview, (2) Contact Investigation (CI) Evaluation, (3) Public Health Records Review, and (4) CLI TB Patient Interviews. Comparison between patients whose links were identified through the study's CLI interviews (Step 4) and patients whose links were identified earlier in CLI (Steps 1-3) was conducted using logistic regression.
  
  
  RESULTS
  Forty-four clusters were randomly selected from the four study sites (401 patients in total). Epidemiologic links were identified for 189/401 (47 %) study patients in a total of 201 linked patient-pairs. The numbers of linked patients identified in each CLI steps were: Step 1 - 105/401 (26.2 %), Step 2 - 15/388 (3.9 %), Step 3 - 41/281 (14.6 %), and Step 4 - 28/119 (30 %). Among the 189 linked patients, 28 (14.8 %) were not identified in previous CI. No epidemiologic links were identified in 13/44 (30 %) clusters.
  
  
  CONCLUSIONS
  We validated a standardized and practical method to systematically identify epidemiologic links among patients in Mtb genotype clusters, which can be integrated into the TB control and prevention programs in public health settings. The CLI interview identified additional epidemiologic links that were not identified in previous CI. One-third of the clusters showed no epidemiologic links despite being extensively investigated, suggesting that some improvement in the interviewing methods is still needed.
authors: Houston Methodist Research Institute, Houston, TX, USA.|Present Address: Texas Department of State Health Services, HSR 6/5, South Houston, TX, USA.
authors: Larry D
authors: LD
authors: Teeter
authors: Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors: Padmaja
authors: P
authors: Vempaty
authors: Houston Methodist Research Institute, Houston, TX, USA.
authors: Duc T M
authors: DT
authors: Nguyen
authors: Emory School of Medicine, Atlanta, GA, USA.
authors: Jane
authors: J
authors: Tapia
authors: Massachusetts Department of Public Health, Jamaica Plain, MA, USA.
authors: Sharon
authors: S
authors: Sharnprapai
authors: Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors: Smita
authors: S
authors: Ghosh
authors: Centers for Disease Control and Prevention, Atlanta, GA, USA.|Northrop Grumman Corporation, Centers for Disease Control and Prevention Programs, Atlanta, GA, USA.
authors: J Steven
authors: JS
authors: Kammerer
authors: Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors: Roque
authors: R
authors: Miramontes
authors: Maryland Department of Health and Mental Hygiene, Baltimore, MD, USA.
authors: Wendy A
authors: WA
authors: Cronin
authors: Houston Methodist Research Institute, Houston, TX, USA. eagraviss@houstonmethodist.org.|Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Mail Station: R6-414, 6670 Bertner, Houston, TX, 77030, USA. eagraviss@houstonmethodist.org.
authors: Edward A
authors: EA
authors: Graviss
mesh_terms: D002487:Centers for Disease Control and Prevention, U.S.; D005838:Genotype; D005845:Georgia / Q000453:epidemiology; D006801:Humans; D016015:Logistic Models; D008396:Maryland / Q000453:epidemiology; D008404:Massachusetts / Q000453:epidemiology; D018598:Minisatellite Repeats; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000302:isolation & purification; D013781:Texas / Q000453:epidemiology; D014376:Tuberculosis / Q000453:epidemiology* / Q000382:microbiology*; D014481:United States / Q000453:epidemiology
keywords: Cluster investigation; Contact investigation; Epidemiology; Genotype; MIRU-VNTR; Spoligotype; Surveillance; Tuberculosis