Background Immunizing infants with various vaccines, including Bacillus Calmette Guerin (BCG), Diphtheria-Pertussis-Tetanus (DPT), and measles, aims to enhance immunity. In instances where vaccine responses have been reported to be compromised, individuals are prone to infection. The BCG vaccine, for example, induces strong type 1 immune responses, particularly interferon-gamma (IFN-g) expression, that are essential for protection against Mycobacterium tuberculosis (Mtb). However, there is scanty evidence on whether this effect is established or sustained when infants are exposed to Mtb either in utero or after birth. We compared TB-specific cytokine responses for IFN-g, interleukin (IL)-2 (IL-2), tumour necrosis factor-alpha (TNF-α), IL-17A, and Granulocyte-macrophage colony-stimulating factor (GM-CSF) using supernatants harvested from QFT-Plus Blood Collection Tubes. Methods This cross-sectional study compared 22 infants born to mothers with bacteriologically confirmed active tuberculosis (TB), defined as TB exposed or cases, to 20 infants born to mothers without active TB, defined as TB non-exposed or controls. Plasma harvested from the QFT-plus tubes (TB1 and TB2) was used to perform a 5-plex Luminex assay using the LX 100/200 Luminex machine and measured in pg/mL. Data was analysed using R (v.4.4.1). The Mann-Whitney U test was used to determine statistical significance at a p-value less than 0.05 and a 95% confidence interval. Data was expressed as median and interquartile ranges (IQR). Results TB-exposed infants showed IFN-g responses were slightly higher among TB-exposed infants compared to non-exposed (Medians (IQR): 15.49 (14.58-16.49) versus 14.96 (14.60-16.60), p=0.68, respectively. There was a strong expression of total IL-17A among TB-exposed compared to non-exposed 11.91 (10.89-13.50) versus 10.69 (10.17-11.64), p=0.035. We observed no differences in IL-2, TNF, and GM-CSF responses. Conclusion TB exposure among infants slightly alters their Mtb-specific cytokine responses, especially IL-17A cytokine responses. This suggests possible ongoing Mtb infection among TB-exposed infants. Follow-up studies of such infants are necessary to assess their risk of future TB infection and disease and the potential need for TB chemoprophylaxis. Keywords Cytokine responses, infants, active TB, pregnancy, Uganda

The authors have declared no competing interest.

This study was funded by the Crick African Network (CAN) through the Francis Crick Institute, United Kingdom, and Health Professions Education and Training for Strengthening the Health System (HEPI-SHSSU) and Services in Uganda.

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This study received ethical approval from the School of Medicine Research and Ethics Committee (SOMREC reference number SOM 2020-11); the School of Biomedical Sciences (SOBSREC reference number SBS-2022-226) at Makerere University; and the Uganda National Council for Science and Technology (UNCST registration number HS1396ES). The mothers provided written informed consent and assent for their babies to participate in the study.

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