Detection of TB Infection among Indian Infants Using Non-Interferon Gamma Cytokines Restricted; Files Only

Grossman, Alison (Spring 2023)

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Background: Infants who are infected with Mycobacterium tuberculosis (Mtb) have a high risk of progression to tuberculosis (TB) disease compared to older children and adults1 . Detection of Mtb infection among infants has been hampered by low sensitivity of Interferon-gamma (IFNγ) release assays (IGRAs) such as QuantiFERON® (QFT). Recent studies have explored the use of non-IFNγ cytokines to detect Mtb immune responses. Our objective was to assess the prevalence and consistency of Mtb-specific cytokine responses over the first year of life using QFT and Luminex among Indian infants, evaluate clinical and sociodemographic cofactors of TBI, and assess agreement with traditional IGRA results to detect TBI in infants. Methods: HIV exposed uninfected (HEU) and HIV unexposed uninfected (HUU) were enrolled at birth and followed for one year. We performed QFT at 6 months and 12 months of life and measured non-IFNγ cytokine secretion in cryopreserved QFT supernatants using a Luminex assay after the study’s completion. Prevalence of TBI was evaluated by Luminex and QFT. Agreement between Luminex and QFT was calculated using the kappa statistic and clinical cofactors of infant TBI were assessed by univariable linear regression. Results: Thirteen (5.9%) of the 222 live-born infants were QFT positive, 6 (3.4%) at 6 months and 7 (4.2%) at 12 months. The Luminex panel detected an additional 74 possible infections (74/216, 34%) that were QFT negative, 49 (21%) at 6 months and 25 (11%) at 12 months. At 6 months there was no agreement (κ = -0.009) and slight agreement (κ = 0.110) at 12 months. Eight (3.5%) of the infants had sustained Luminex positive results. There was no association of TBI with maternal HIV exposure in contrast to prior studies. Weight-for-age z-score < -2 was associated with TBI using by Luminex at 6 months (RR = 0.29, CI95%: 0.12, 0.69). Conclusion: Luminex detected additional Mtb specific immune responses that QFT could not. A combined QFT and Luminex test may be effective in the detection of TBI in infants whose mothers with TBI during pregnancy. Future studies are needed to evaluate the prognostic value of Mtb-specific non-IFNγ cytokines for progression to TB disease. 

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