Tuberculosis Transmission by Patien

Tuberculosis Transmission by Patients with Smear-Negative Pulmonary Tuberculosis in a Large Cohort in The Netherlands
Alma Tostmann1,2, Sandra V. Kik3,4, Nico A. Kalisvaart3, Maruschka M. Sebek3, Suzanne Verver3,4, Martin J. Boeree1,2, and Dick van Soolingen5
+ Author Affiliations

1Department of Pulmonary Diseases, Radboud University Nijmegen Medical Centre, Nijmegen
2University Lung Centre Dekkerswald, Groesbeek
3Royal Netherlands Tuberculosis Association, The Hague
4Center for Infection and Immunity Amsterdam, Academic Medical Centre, Amsterdam
5National Institute for Public Health and the Environment, Bilthoven, The Netherlands
Reprints or correspondence: Dr. Alma Tostmann, Dept. of Pulmonary Diseases (454), Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands (a.tostmann@ulc.umcn.nl).

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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.