New gamma interferon (IFN- g) algorithm for tuberculosis diagnosis in cynomolgus macaques

warit, s.; Meesawat, S.; Cheawchanlertfa, P.; Makhoa, N.; Srilohasin, P.; Kaewparuehaschai, M.; Noradechanon, K.; Pomcoke, A.; Kemthong, T.; Prammananan, T.; Kanitpun, R.; Palaga, T.; Malaivijitnond, S.; Chaiprasert, A.

doi:10.1101/2024.04.04.588038

bioRxiv · 10.1101/2024.04.04.588038

New gamma interferon (IFN- g) algorithm for tuberculosis diagnosis in cynomolgus macaques

warit, s.·Meesawat, S.·Cheawchanlertfa, P.·Makhoa, N.·Srilohasin, P.·Kaewparuehaschai, M.·Noradechanon, K.·Pomcoke, A.·Kemthong, T.·Prammananan, T.·Kanitpun, R.·Palaga, T.·Malaivijitnond, S.·Chaiprasert, A.

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Abstract

Tuberculosis (TB) is the first infectious disease to be screened-out from specified pathogen-free cynomolgus macaques (Macaca fascicularis; Mf) using in human pharmaceutical testing. Being either latent or active stage after exposure to the Mycobacterium tuberculosis complex (MTBC), the monkey gamma-interferon release assay (mIGRA) was previously introduced for early TB detection in Mf. However, a high number of indeterminate cases were unexpectedly encountered. The main reasons were a mitogen positive control and an interpretation algorithm. A cohort of 316 Mf exposed to MTBC was tested of two positive mitogen controls [QFT-PHA and a mixture of ConcanavalinA and Pokeweed (ConA+PWM)], and 100 of 316 animals were selected and 26-month followed-up for the establishment of a new mIGRA algorithm for interpretation. As such, the number of indeterminate cases was drastically reduced (80-100%) when the ConA + PWM mixture was used as a positive mitogen control along with a new mIGRA algorithm for interpretation.

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warit, s., Meesawat, S., Cheawchanlertfa, P., Makhoa, N., Srilohasin, P., Kaewparuehaschai, M., Noradechanon, K., Pomcoke, A., Kemthong, T., Prammananan, T., Kanitpun, R., Palaga, T., Malaivijitnond, S., Chaiprasert, A.. 2024-04-04. New gamma interferon (IFN- g) algorithm for tuberculosis diagnosis in cynomolgus macaques. https://doi.org/10.1101/2024.04.04.588038

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