Beyond QuantiFERON-TB Results, the Added Value of a Weak Mitogen Response

Jacquier, Marine; Binquet, Christine; Manoha, Catherine; Audia, Sylvain; Simonet-Lamm, Anne-Laure; Casenaz, Alice; Sow, Amadou-Khalilou; Piroth, Lionel; Blot, Mathieu

doi:10.3389/fmed.2022.876864

Cited by 4 publications

(8 citation statements)

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“…In our study, we found decreased production of IFN-γ in the mitogen tube in 8 out of 10 cases. An altered immune response will lead to an insufficient reaction in the mitogen tube, corresponding to the incapacity of lymphocytes to secrete IFN-γ 46 54–58. Possibly, the T lymphocytes among the participants with indeterminate results were compromised in quality and were thus unable to produce sufficient levels of IFN-γ 46 57.…”

Section: Discussionmentioning

confidence: 99%

Prevalence and predictors of tuberculosis infection among people living with HIV in a high tuberculosis burden context

et al. 2023

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BackgroundTuberculosis (TB) disease is the leading cause of mortality among people living with HIV (PLHIV). Interferon-gamma release assays (IGRAs) are approved for TB infection ascertainment. However, current IGRA data on the prevalence of TB infection in the context of near-universal access to antiretroviral therapy (ART) and TB preventive therapy (TPT) are lacking. We estimated the prevalence and determinants of TB infection among PLHIV within a high TB and HIV burden context.MethodsThis cross-sectional study included data from adult PLHIV age ≥18 years in whom QuantiFERON-TB Gold Plus (QFT-Plus) assay, an IGRA, was performed. TB infection was defined as a positive or indeterminate QFT-Plus test. Participants with TB and those who had previously used TPT were excluded. Regression analysis was performed to identify independent predictors of TB infection.ResultsOf 121 PLHIV with QFT-Plus test results, females were 74.4% (90/121), and the mean age was 38.4 (SD 10.8) years. Overall, 47.9% (58/121) were classified as TB infection (QFT-Plus test positive and indeterminate results were 39.7% (48/121) and 8.3% (10/121), respectively). Being obese/overweight (body mass index ≥25 kg/m2; p=0.013, adjusted OR (aOR) 2.90, 95% CI 1.25 to 6.74) and ART usage for >3 years (p=0.013, aOR 3.99, 95% CI 1.55 to 10.28) were independently associated with TB infection.ConclusionThere was a high TB infection prevalence among PLHIV. A longer period of ART and obesity were independently associated with TB infection. The relationship between obesity/overweight and TB infection may be related to ART use and immune reconstitution and requires further investigation. Given the known benefit of test-directed TPT among PLHIV never exposed to TPT, its clinical and cost implications for low and middle-income countries should be explored further.

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Section: Discussionmentioning

confidence: 99%

Prevalence and predictors of tuberculosis infection among people living with HIV in a high tuberculosis burden context

et al. 2023

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“…In the context of tuberculosis disease (TB), the QFT-TB assay lacks of sensitivity with many indederminate results. These are related to an alteration of the mitogen response ( 62 ) and are encountered in patients where T-cells exhaustion is frequent. Comparative sensitivity and specificity analysis of T-cell assays to SARS-CoV-2 is not available, however, we did not find any such indeterminate result for QFT SARS-CoV-2.…”

Section: Discussionmentioning

confidence: 99%

Humoral and cellular immune response after severe acute respiratory syndrome coronavirus 2 messenger ribonucleic acid vaccination in heart transplant recipients: An observational study in France

Casenaz¹,

Grosjean²,

Aho-Glélé³

et al. 2022

Front. Med.

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IntroductionHeart transplant (HT) recipients have a high risk of developing severe COVID-19. Immunoglobulin G antibodies are considered to provide protective immunity and T-cell activity is thought to confer protection from severe disease. However, data on T-cell response to mRNA vaccination in a context of HT remains limited.MethodsIn 96 HT patients, a IFN-γ release assay and an anti-Spike antibody test were used to evaluate the ability of SARS-CoV-2 mRNA vaccines to generate cellular and humoral immune response. Blood samples were collected few weeks to 7 months after vaccination. Multiple fractional polynomial and LASSO regression models were used to define predictors of T-cell response.ResultsThree to five months after vaccination, three doses of vaccine induced a positive SARS-CoV-2 T-cell response in 47% of recipients and a positive humoral response in 83% of recipients, 11.1% of patients remained negative for both T and B cell responses. Three doses were necessary to reach high IgG response levels (>590 BAU/mL), which were obtained in a third of patients. Immunity was greatly amplified in the group who had three vaccine doses plus COVID-19 infection.ConclusionOur study revealed that T and B immunity decreases over time, leading us to suggest the interest of a booster vaccination at 5 months after the third dose. Moreover, a close follow-up of immune response following vaccination is needed to ensure ongoing immune protection. We also found that significant predictors of higher cellular response were infection and active smoking, regardless of immunosuppressive treatment with mycophenolate mofetil (MMF).

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“…An altered immune response will lead to an insufficient reaction in the mitogen tube, corresponding to the incapacity of lymphocytes to secrete IFN-γ. [46,[54][55][56][57][58] Possibly, the T lymphocytes among the participants with indeterminate results were compromised in quality and were thus unable to produce sufficient levels of IFN-γ. [46,57] In support, most of the participants with indeterminate results had been on ART for less than a year, all were ambulatory, and none had a known illness other than HIV.…”

Section: Discussionmentioning

confidence: 99%

“…In cases of immune suppression, repeat testing is advised after recovery. [54, 55] Further, with indeterminate results, TB infection cannot be ruled out with certainty, and the prognosis may be poorer. [54, 55] The increased response in the Nil tube found in three participants may signify residual IFN-γ due to ongoing infection, [58] and TB infection could not be ruled out.…”

Section: Discussionmentioning

confidence: 99%

“…The WHO and local Kenyan guidelines do not require testing for TB infection before initiating TPT, and there’s no guidance for handling indeterminate results where testing is done. [9, 18, 20, 28] Given the clinical implication and potential benefit of TPT in PLHIV [30, 31], the possibility of immune suppression among participants with indeterminate results, the uncertainty around prognostic implications of indeterminate results [54, 55] and the resource limitation that precluded repeat testing during follow-up, the operational definition of TB infection used in the present study was justified. Indeterminate results were included in the definition of TB infection, bringing the proportion of PLHIV classified as having TB infection to 47.9%.…”

Section: Discussionmentioning

confidence: 99%

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Prevalence and predictors of tuberculosis infection among people living with HIV in a high tuberculosis burden context

Njagi

Nduba

Mureithi

et al. 2022

Preprint

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Background: Tuberculosis (TB) is the leading cause of mortality among people living with the Human immunodeficiency virus (PLHIV), and latent TB infection (LTBI) contributes significantly to active TB. Direct diagnostic methods are the most accurate tests for establishing the LTBI burden. However, current interferon-gamma release assay (IGRA) data on LTBI prevalence in the context of near-universal access to antiretroviral therapy (ART) and widespread TB preventive therapy (TPT) implementation are lacking. We estimated the prevalence and determinants of LTBI among PLHIV within a high TB and HIV burden context. Methods: This cross-sectional analysis of a prospectively collected observational study data included adult PLHIV, in whom QuantiFERON-TB Gold Plus assay, an IGRA, was performed. LTBI was defined as a positive or indeterminate IGRA. Participants with TB and those who had used TB preventive therapy in the past were excluded. Regression analysis was performed to identify independent predictors of LTBI. Results Of 121 PLHIV with IGRA results, females were 74.4% (90/121), and the mean age was 38.4 (standard deviation [SD] 10.8) years. Overall, 47.9% (58/121) were classified as LTBI (IGRA positive and indeterminate results were 39.7% [48/121] and 8.3% [10/121], respectively), with mean ages of 38.7 (SD 10.30) vs 38.2 (SD 11.3) years, respectively (p=0.602). Being obese/overweight (body mass index ≥ 25; p=0.046, adjusted odds ratio (aOR) 2.65, 95% confidence interval [CI] 1.02-6.89), alcohol usage (p=0.036, aOR 3.93, 95% CI 1.10-14.13), and ART usage for >3 years (p=0.012, aOR 2.65, 95% CI 1.23-5.69) were independently associated with LTBI. Conclusion: There was a high LTBI prevalence among PLHIV. A longer period of ART and alcohol consumption were independently associated with LTBI. The relationship between obesity/overweight and LTBI may be related to ART and immune reconstitution and requires further investigation. Recommending IGRA to ascertain LTBI status in PLHIV previously unexposed to TPT may be necessary.

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Beyond QuantiFERON-TB Results, the Added Value of a Weak Mitogen Response

Cited by 4 publications

References 27 publications

Prevalence and predictors of tuberculosis infection among people living with HIV in a high tuberculosis burden context

Prevalence and predictors of tuberculosis infection among people living with HIV in a high tuberculosis burden context

Humoral and cellular immune response after severe acute respiratory syndrome coronavirus 2 messenger ribonucleic acid vaccination in heart transplant recipients: An observational study in France

Prevalence and predictors of tuberculosis infection among people living with HIV in a high tuberculosis burden context

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