Comparison of TST and IGRA in Diagnosis of Latent Tuberculosis Infection in a High TB-Burden Setting

Sharma, Surendra Kumar; Vashishtha, Richa; Chauhan, L. S.; Sreenivas, V.; Seth, Divya

doi:10.1371/journal.pone.0169539

Cited by 107 publications

(83 citation statements)

References 22 publications

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“…However, these assays failed to discriminate between different phases of infection nor to predict the occurrence of disease . Indeed, it was recently shown that neither TST nor IGRAs predicted subsequent development of active TB among household contacts of pulmonary TB patients during follow‐up …”

Section: Discussionmentioning

confidence: 99%

Granzyme B induced by Rv0140 antigen discriminates latently infected from active tuberculosis individuals

Ouni

Gharsalli

Dirix

et al. 2018

Journal of Leukocyte Biology

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Nearly two billion people are latently infected with Mtb (LTBI). Detection of LTBI with high risk to develop active tuberculosis (aTB) is considered the cornerstone to control the disease. The current challenge is to identify markers that better classify LTBI versus aTB. It has been previously shown that Rv0140, a reactivation-associated antigen of Mtb, induces significantly higher IFN-γ production in LTBI individuals as compared to aTB patients. Herein, we show that Rv0140 induces high granzyme B level by PBMCs derived from LTBI (n = 34) as compared to aTB (n = 18). Receiving operator characteristic (ROC) curves were used to evaluate the capacity of Rv0140 to discriminate between LTBI and aTB by measuring IFN-γ and granzyme B secretion. Our results show that, in response to Rv0140, granzyme B seems to allow better discrimination of LTBI from aTB with areas under the curve (AUC) of 0.88 (95% CI 0.79-0.98) as compared to IFN-γ with AUC of 0.85 (95% CI 0.74-0.96) even though CI overlap. Intracellular staining (ICS) experiments and the use of anti-MHC I antibody showed that granzyme B is mainly produced by CD8+ T cells in response to Rv0140. Thus, we propose granzyme B as a host marker to help identify LTBI individuals.

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Section: Discussionmentioning

confidence: 99%

Granzyme B induced by Rv0140 antigen discriminates latently infected from active tuberculosis individuals

Ouni

Gharsalli

Dirix

et al. 2018

Journal of Leukocyte Biology

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“…Further, due to their comparable performances in different settings, replacing the TST by IGRAs as a public health intervention is not recommended [3]. The fact that neither test has the desired sensitivity to detect LTBI is also evident from a recent study from north India in which, during the followup period, incidence of TB in test-positive (TST or IGRA) and test-negative contacts was comparable [4]. Another recent report has suggested that certain differences in adaptive immunity in a subset of persons who are exposed to Mtb could be responsible for their test-negativity for TST and IGRA [5].…”

Section: Introductionmentioning

confidence: 99%

Immune responses to Mycobacterium tuberculosis membrane-associated antigens including alpha crystallin can potentially discriminate between latent infection and active tuberculosis disease

et al. 2020

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Changes in expression of membrane antigens may accompany the transition of Mycobacterium tuberculosis (Mtb) from 'dormant' to 'active' states. We have determined whether antibody and T cell responses to Mtb membrane (MtM)-associated antigens, especially the latency-induced protein alpha crystallin (Acr), can discriminate between latent tuberculosis infection (LTBI) and active TB (ATB) disease. Study subjects comprised a previously described cohort of healthcare workers (HCWs, n = 43) and smear-positive ATB patients (n = 10). HCWs were further categorized as occupational contacts (OC, n = 30), household contacts of TB (HC, n = 8) and cured TB (CTB, n = 5). Levels (ΔOD) of serum antibody isotypes (IgG, IgA and IgM) were determined by ELISA and blood T cell proliferative responses were determined by flow cytometry using Ki67 protein as marker for DNA synthesis. Antibodies to MtM and Acr were predominantly IgG and their levels in HCWs and ATB did not differ significantly. However, HCWs showed a significantly higher level of anti-MtM IgM and a significantly lower level of anti-Acr IgA antibodies than the ATB patients. Also, a larger proportion of HCWs showed a high (>1) ΔOD Acr /ΔOD MtM ratio for IgG. HCWs also showed a higher, though not significantly different from ATB, avidity of anti-MtM (IgG) antibodies. A higher proportion of HCWs (35% of OC, 62.5% of HC and 20% of CTB), compared with ATB (10%) showed a positive T cell response to Acr along with significant difference (P <0.05) between HC and ATB. A significant correlation (r = 0.60, P <0.0001) was noted between T cell responses of HCWs towards Acr and MtM (reported earlier by us) and both responses tended to decline with rising exposure to the infection. Even so, positive responses to Acr (38.5%) were significantly lower than to MtM (92%). Neither antibody nor T cell responses to either antigen appeared affected by BCG vaccination or reactivity to tuberculin. Results of the study suggest that the levels of IgM antibodies to MtM, IgA antibodies to Acr and

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“…Variability in immune responses can contribute to the difficulty of TB diagnosis. Currently, the tuberculin skin test and blood IFNγ release assay are used to assess TB infection (Sharma et al, 2017). Due to the different mechanisms by which these tests operate, results do not always agree (Gallant et al, 2010).…”

Section: Immune Diversity and The Challenge Of Global Tb Diagnostics mentioning

confidence: 99%

Challenges of Immune Response Diversity in the Human Population Concerning New Tuberculosis Diagnostics, Therapies, and Vaccines

Azad

Lloyd

Sadée

et al. 2020

Front. Cell. Infect. Microbiol.

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Universal approaches to the prevention and treatment of human diseases fail to take into account profound immune diversity resulting from genetic variations across populations. Personalized or precision medicine takes into account individual lifestyle, environment, and biology (genetics and immune status) and is being adopted in several disease intervention strategies such as cancer and heart disease. However, its application in infectious diseases, particularly global diseases such as tuberculosis (TB), is far more complex and in a state of infancy. Here, we discuss the impact of human genetic variations on immune responses and how they relate to failures seen in current TB diagnostic, therapy, and vaccine approaches across populations. We offer our perspective on the challenges and potential for more refined approaches going forward.

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Comparison of TST and IGRA in Diagnosis of Latent Tuberculosis Infection in a High TB-Burden Setting

Cited by 107 publications

References 22 publications

Granzyme B induced by Rv0140 antigen discriminates latently infected from active tuberculosis individuals

Granzyme B induced by Rv0140 antigen discriminates latently infected from active tuberculosis individuals

Immune responses to Mycobacterium tuberculosis membrane-associated antigens including alpha crystallin can potentially discriminate between latent infection and active tuberculosis disease

Challenges of Immune Response Diversity in the Human Population Concerning New Tuberculosis Diagnostics, Therapies, and Vaccines

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