The new gamma interferon (IFN-γ) algorithm for tuberculosis diagnosis in cynomolgus macaques
Issued Date
2024-12-01
Resource Type
eISSN
19326203
Scopus ID
2-s2.0-85212688220
Journal Title
PLoS ONE
Volume
19
Issue
12 December
Rights Holder(s)
SCOPUS
Bibliographic Citation
PLoS ONE Vol.19 No.12 December (2024)
Suggested Citation
Warit S., Meesawat S., Cheawchanlertfa P., Makhao N., Srilohasin P., Kaewparuehaschai M., Noradechanon K., Pomcoke A., Kemthong T., Prammananan T., Kanitpun R., Palaga T., Malaivijitnond S., Chaiprasert A. The new gamma interferon (IFN-γ) algorithm for tuberculosis diagnosis in cynomolgus macaques. PLoS ONE Vol.19 No.12 December (2024). doi:10.1371/journal.pone.0302349 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/102542
Title
The new gamma interferon (IFN-γ) algorithm for tuberculosis diagnosis in cynomolgus macaques
Corresponding Author(s)
Other Contributor(s)
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 in 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. However, a notable incidence of indeterminate results was observed. In this study, we compared two positive mitogen references, phytohemagglutinin (PHA) that is used in the QuantiFERON-TB Gold Plus kit (QFT-PHA) and a combination of Concanavalin A and Pokeweed mitogen (ConA+PWM), in a cohort of 316 MTBC-exposed Mf. Following a 29-month follow-up of 100 selected animals, we established a new mIGRA interpretation algorithm that demonstrated a significant shift in the negative and indeterminate cases regardless of whether the QFT-PHA or ConA+PWM was used as a mitogen. That is, if the ODNIL value was ≤0.18, ODMIT-NIL > ODNIL, and the ODTB1/2-NIL were ≥0.05 and ≥25% of individual ODNIL, the mIGRA result was interpreted as ‘positive’. If the ODNIL value was ≤0.18, ODMIT-NIL > ODNIL, and the ODTB-NIL was <0.05, the mIGRA result was interpreted as ‘negative’. If the ODNIL value was >0.18 or the OD of mitogen references [OD(QFT-PHA) and OD(ConA+PWM)] were ≤0.18, the mIGRA result was interpreted as ‘indeterminate’. As a result, negative cases increased by 10–50%, indeterminate cases decreased by 40–80%, and the number of TB-positive cases remained unchanged. Our findings highlight the critical role of mitogens as positive controls in mIGRA interpretation. This study provides the mIGRA value for the TB screening of cynomolgus macaques that enables the identification of true positive and suspicious TB cases for quarantine programs.