title: Tuberculosis transmission by patients with smear-negative pulmonary tuberculosis in a large cohort in the Netherlands.
abstract: BACKGROUND
  Sputum smear microscopy is commonly used for diagnosing tuberculosis (TB). Although patients with sputum smear-negative TB are less infectious than patients with smear-positive TB, they also contribute to TB transmission. The objective of this study was to determine the proportion of TB transmission events caused by patients with smear-negative pulmonary TB in The Netherlands.
  
  
  METHODS
  All patients in The Netherlands with culture-confirmed TB during the period 1996-2004 were included in this study. Patients with identical DNA fingerprints in Mycobacterium tuberculosis isolates from sputum samples were clustered. The first patients in a cluster were considered to be the index patients; all other patients were considered to have secondary cases. In addition, we examined transmission from sources by conventional contact tracing.
  
  
  RESULTS
  We analyzed 394 clusters with a total of 1285 patients. On the basis of molecular linkage only, 12.6% of the secondary cases were attributable to transmission from a patient with smear-negative TB. The relative transmission rate among patients with smear-negative TB, compared with patients with smear-positive TB, was 0.24 (95% confidence interval, 0.20-0.30). Secondary cases in clusters with an index patient with smear-negative TB more frequently had smear-negative status (odds ratio, 1.86; 95% confidence interval, 1.18-2.93), compared with secondary cases in clusters with an index patient with smear-positive TB. Conventional contact tracing revealed that 26 (6.2%) of the 417 sources, as identified by the Municipal Health Services, had smear-negative TB.
  
  
  CONCLUSIONS
  In The Netherlands, patients with smear-negative, culture-positive TB are responsible for 13% of TB transmission. Countries that have ample resources should expand their TB-control efforts to include prevention of transmission from patients with smear-negative, culture-positive pulmonary TB.
authors.affiliation: Department of Pulmonary Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. a.tostmann@ulc.umcn.nl
authors.forename: Alma
authors.initials: A
authors.lastname: Tostmann
authors.forename: Sandra V
authors.initials: SV
authors.lastname: Kik
authors.forename: Nico A
authors.initials: NA
authors.lastname: Kalisvaart
authors.forename: Maruschka M
authors.initials: MM
authors.lastname: Sebek
authors.forename: Suzanne
authors.initials: S
authors.lastname: Verver
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Boeree
authors.forename: Dick
authors.initials: D
authors.lastname: van Soolingen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D015331:Cohort Studies; D016358:Contact Tracing; D016172:DNA Fingerprinting; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D009426:Netherlands / Q000453:epidemiology; D012150:Polymorphism, Restriction Fragment Length; D013183:Sputum / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000453:epidemiology / Q000382:microbiology / Q000635:transmission*
chemical_list: D004269:DNA, Bacterial