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

Area of Science:

• Veterinary Immunology
• Primate Models in Pharmaceutical Research
• Infectious Disease Diagnostics

Background:

• Tuberculosis screening in cynomolgus macaques (Macaca fascicularis) is crucial for pharmaceutical testing.
• The monkey gamma-interferon release assay (mIGRA) aids early detection of Mycobacterium tuberculosis complex (MTBC) exposure.
• Previous mIGRA protocols yielded a high incidence of indeterminate results, limiting their utility.

Purpose of the Study:

• To compare phytohemagglutinin (QFT-PHA) and a combination of Concanavalin A and Pokeweed mitogen (ConA+PWM) as positive controls in mIGRA.
• To develop and validate a new mIGRA interpretation algorithm for improved tuberculosis detection in macaques.
• To enhance the accuracy and reliability of mIGRA for screening MTBC-exposed cynomolgus macaques.

Main Methods:

• Comparison of two mitogen references (QFT-PHA vs. ConA+PWM) in 316 MTBC-exposed macaques.
• Development of a novel mIGRA interpretation algorithm based on optical density (OD) values.
• Longitudinal follow-up of 100 selected animals over 29 months to assess algorithm performance.

Main Results:

• The new algorithm demonstrated a significant shift in negative and indeterminate mIGRA results.
• Negative cases increased by 10-50%, while indeterminate cases decreased by 40-80%.
• The number of confirmed TB-positive cases remained unchanged, indicating improved classification accuracy.

Conclusions:

• Mitogens play a critical role in the interpretation of mIGRA results for tuberculosis screening.
• The developed mIGRA algorithm enhances the identification of true positive and suspicious TB cases in cynomolgus macaques.
• This refined mIGRA approach is valuable for quarantine programs and pharmaceutical testing involving macaques.