Abstract
We evaluated the performance of QuantiFERON-TB Gold Plus (QFT-Plus), which includes two Mycobacterium tuberculosis antigen formulations (TB1 and TB2), for detection of latent tuberculosis infection during pregnancy. Eight-hundred-twenty-nine Ethiopian pregnant women (5.9% HIV-positive) were tested with QFT-Plus, with bacteriological sputum analysis performed for women with clinically suspected tuberculosis and HIV-positive women irrespective of clinical presentation. QFT-Plus read-out was categorized according to the conventional cut-off (0.35 IU/ml) for both antigen formulations. In addition, we analysed the distribution of QFT-Plus results within a borderline zone (0.20–0.70 IU/ml), and interferon-γ response in relation to HIV infection and gestational age. Two-hundred-seventy-seven women (33%) were QFT-Plus-positive (HIV-positive 16/49 [33%]; HIV-negative 261/780 [33%]). There was a strong agreement between the two antigen formulations (κ = 0.92), with discordant results in 29 cases (3.5%). Whereas discordant QFT-Plus results were rare in pregnancy, several results with both TB1 and TB2 within the borderline range were observed (11/49 [22%] vs. 43/780 [5.5%] in HIV-positive and HIV-negative women, respectively; p<0.0001). HIV-positive women had lower absolute interferon-γ levels (TB1: 0.47 vs. 2.16 IU/ml; p<0.001, TB2: 0.49 vs. 2.24 IU/ml, p<0.001, considering results ≥0.20 IU/ml) compared to HIV-negative women. QFT-Plus-positive women who submitted samples at later stages of pregnancy had lower mitogen- (p<0.001) but higher TB-antigen-specific (p = 0.031 for TB1, p = 0.061 for TB2) interferon-γ response. Considering their lower capacity to produce TB-specific interferon-γ, a lower cut-off level for defining QFT-Plus-positivity may be considered in HIV-positive pregnant women.
Highlights
Most persons infected with Mycobacterium tuberculosis (Mtb) have latent tuberculosis infection (LTBI) in which viable bacteria are confined to granulomas regulated by host immunity [1]
We investigated the distribution of QFT-Plus results within a borderline range compared to results below and above the limits of the borderline range selected for this study (0.70 international units per millilitre (IU/ml), respectively)
We found high agreement between QFT-Plus results elicited by TB1 and TB2 antigen formulations
Summary
Most persons infected with Mycobacterium tuberculosis (Mtb) have latent tuberculosis infection (LTBI) in which viable bacteria are confined to granulomas regulated by host immunity [1]. Reactivation of LTBI can lead to active tuberculosis (TB), and is often related to various types of immunosuppression, especially HIV infection [2]. Pregnancy is a physiologic condition during which alterations of the immune system occur, and become more profound with increasing gestational age [3]. Many infections are more likely to have severe manifestations in the third trimester of gestation [4]. It has been suggested that pregnancy may confer an increased risk of LTBI reactivation [5,6]. Since active TB is associated with adverse pregnancy outcomes [7,8,9], TB screening is recommended during antenatal care
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