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

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.