Latent tuberculosis in HIV positive, diagnosed by the M. tuberculosis specific interferon-gamma test

Abstract

Background: Although tuberculosis (TB) is a minor problem in Denmark, severe and complicated cases occur in HIV positive. Since the new M. tuberculosis specific test for latent TB, the QuantiFERON-TB In-Tube test (QFT-IT) became available the patients in our clinic have been screened for the presence of latent TB using the QFT-IT test. We here report the results from the first patients screened.

Methods: On a routine basis the QFT-IT test was performed and the results from 590 HIV positive individuals consecutively tested are presented here. CD4 cell count and TB risk-factors were recorded from patient files.

Main findings: 27/590(4.6%) of the individuals were QFT-IT test positive, indicating the presence of latent TB infection. Among QFT-IT positive patients, 78% had risk factors such as long-term residency in a TB high endemic area (OR:5.7), known TB exposure (OR:4.9) or previous TB disease (OR:4.9). The prevalence of latent TB in these groups were 13%, 16% and 19% respectively. There was a strong correlation between low CD4 T-cell count and a low mitogen response (P < 0.001;Spearman) and more patients with low CD4 cell count had indeterminate results.

Conclusion: We found an overall prevalence of latent TB infection of 4.6% among the HIV positive individuals and a much higher prevalence of latent infection among those with a history of exposure (16%) and long term residency in a high endemic country (13%). The QFT-IT test may indeed be a useful test for HIV positive individuals, but in severely immunocompromised, the test may be impaired by T-cell anergy.

Figure 1

IFN-γ release after stimulation of whole blood with either TB antigen (left) or Phytohaematglutinin (PHA)(mitogen) (right). All results are stratified into intervals according to the level of IFN-γ released after stimulation and the number of individuals with IFN-γ release within each interval are shown.

Figure 2

Study Flow Diagram for 607 HIV positive patients screened with the QFT- IT test. TB risk factors implies: prior TB diagnosis, history of TB exposure, history of long-term residency in a TB high endemic country (>25 cases per 100.000/year).

Figure 3

IFN-γ release (IU/mL) after stimulation of whole blood with PHA (mitogen). Results are stratified into intervals according to the CD4-cell count for each individual. The median IFN-γ values within each CD4-cell count interval are indicated with horizontal lines. Cut off for PHA response of 0.5 IU/ml is shown by a dotted line.