Tuberculosis transmission by patients with smear-negative pulmonary tuberculosis in a large cohort in the Netherlands

Clin Infect Dis. 2008 Nov 1;47(9):1135-42. doi: 10.1086/591974.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Cluster Analysis
  • Cohort Studies
  • Contact Tracing
  • DNA Fingerprinting
  • DNA, Bacterial / genetics
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / classification
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / isolation & purification
  • Netherlands / epidemiology
  • Polymorphism, Restriction Fragment Length
  • Sputum / microbiology
  • Tuberculosis, Pulmonary / diagnosis
  • Tuberculosis, Pulmonary / epidemiology
  • Tuberculosis, Pulmonary / microbiology
  • Tuberculosis, Pulmonary / transmission*


  • DNA, Bacterial