High risk of drug-resistant tuberculosis in IGRA-negative contacts: should preventive treatment be considered?

Purpose: Deciding whether to provide preventive treatment to contacts of individuals with multidrug-resistant (MDR) tuberculosis is complex.

Methods: We present the diagnostic pathways, clinical course and outcome of tuberculosis treatment in eight siblings from a single family. Tuberculosis disease was diagnosed by Mycobacterium tuberculosis culture and molecular detection of M. tuberculosis-specific DNA from bronchopulmonary specimens using GeneXpert^® MTB/RIF. M. tuberculosis infection was diagnosed by an interferon-gamma release assay (IGRA; QuantiFERON^®-TB Gold Plus). Whole exome sequencing for genetic predisposition to mycobacterial infection was performed in one patient.

Results: Six of eight siblings aged 16-20 years from a migrant family of Somali origin were diagnosed with pulmonary MDR tuberculosis over a 12-month period. The remaining male siblings, aged 11 and 14 years, were asymptomatic during contact investigation. Chest radiographs, computed tomography (CT) scans, sputum cultures and nucleic acid amplification tests were negative, and the IGRA did not detect M. tuberculosis infection. A repeat CT scan eight months later was unremarkable, and repeated sputum cultures remained negative. In the absence of sufficient evidence of M. tuberculosis infection, no preventive treatment was offered. At month seven of consistent clinical observation, both children were diagnosed with pulmonary tuberculosis; the older with advanced disease and subsequent post-tuberculosis lung disease. Whole exome sequencing revealed no Mendelian variant associated with susceptibility to mycobacterial infection.

Conclusion: When significant risk of tuberculosis transmission exists, close contacts of MDR tuberculosis patients should be offered preventive treatment with levofloxacin despite a negative IGRA test result.