Nguyen Thi Le Hang1, Ikumi Matsushita2, Takuro Shimbo3, Le Thi Hong4, Do Bang Tam4, Luu Thi Lien5, Pham Huu Thuong6, Vu Cao Cuong6, Minako Hijikata7, Nobuyuki Kobayashi8, Shinsaku Sakurada9, Kazue Higuchi10, Nobuyuki Harada10, Hiroyoshi Endo11, Naoto Keicho12. 1. NCGM-BMH Medical Collaboration Center, 78 Giai Phong, Hanoi, Viet Nam. 2. Department of Pathophysiology and Host Defense, Research Institute of Tuberculosis JATA, 3-1-24 Matsuyama, Kiyose, Tokyo 204-8533, Japan. 3. Clinical Research Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan. 4. Department of Biochemistry, Hematology and Blood Transfusion, Hanoi Lung Hospital, 44 Thanh Nhan, Hanoi, Viet Nam. 5. Hanoi Department of Health, 4 Son Tay, Hanoi, Viet Nam. 6. Hanoi Lung Hospital, 44 Thanh Nhan, Hanoi, Viet Nam. 7. Department of Pathophysiology and Host Defense, Research Institute of Tuberculosis JATA, 3-1-24 Matsuyama, Kiyose, Tokyo 204-8533, Japan; National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan. 8. NHO Tokyo National Hospital, 3-1-1 Takeoka, Kiyose, Tokyo 204-8585, Japan. 9. Bureau of International Medical Cooperation, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan. 10. Research Institute of Immune Diagnosis, 1-34-1 Fujimicho, Tachikawa, Tokyo 190-0013, Japan. 11. Department of International Affairs and Tropical Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. 12. Department of Pathophysiology and Host Defense, Research Institute of Tuberculosis JATA, 3-1-24 Matsuyama, Kiyose, Tokyo 204-8533, Japan; National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan. Electronic address: nkeicho-tky@umin.ac.jp.
Abstract
OBJECTIVES: We investigated the relationship between tuberculosis recurrence and Mycobacterium tuberculosis antigen-stimulated interferon-gamma (IFN-γ) responses during treatment. METHODS: Plasma IFN-γ levels in active pulmonary tuberculosis patients (n = 407) were analyzed using QuantiFERON-TB Gold In-Tube™ (QFT-IT) at 0, 2, and 7 months of the 8-month treatment received from 2007 to 2009 and the patients were followed up for another 16 months after treatment. Risk factors for recurrence were assessed using the log-rank test and Cox proportional hazard models. Random coefficient models were used to compare longitudinal patterns of IFN-γ levels between groups. RESULTS: QFT-IT showed positive results in 95.6%, 86.2%, and 83.5% at 0, 2, and 7 months, respectively. The antigen-stimulated IFN-γ responses varied significantly during the treatment course (P < 0.0001). Unexpectedly, positive-to-negative conversion of QFT-IT results between 0 and 2 months was significantly associated with earlier recurrence (adjusted hazard ratio, 5.57; 95% confidence interval, 2.28-13.57). Time-dependent changes in IFN-γ levels were significantly different between the recurrence and nonrecurrence groups (P < 0.0001). CONCLUSIONS: Although the IGRA response varies individually, early response during the treatment course may provide an insight into host immune responses underlying tuberculosis recurrence.
OBJECTIVES: We investigated the relationship between tuberculosis recurrence and Mycobacterium tuberculosis antigen-stimulated interferon-gamma (IFN-γ) responses during treatment. METHODS: Plasma IFN-γ levels in active pulmonary tuberculosispatients (n = 407) were analyzed using QuantiFERON-TB Gold In-Tube™ (QFT-IT) at 0, 2, and 7 months of the 8-month treatment received from 2007 to 2009 and the patients were followed up for another 16 months after treatment. Risk factors for recurrence were assessed using the log-rank test and Cox proportional hazard models. Random coefficient models were used to compare longitudinal patterns of IFN-γ levels between groups. RESULTS: QFT-IT showed positive results in 95.6%, 86.2%, and 83.5% at 0, 2, and 7 months, respectively. The antigen-stimulated IFN-γ responses varied significantly during the treatment course (P < 0.0001). Unexpectedly, positive-to-negative conversion of QFT-IT results between 0 and 2 months was significantly associated with earlier recurrence (adjusted hazard ratio, 5.57; 95% confidence interval, 2.28-13.57). Time-dependent changes in IFN-γ levels were significantly different between the recurrence and nonrecurrence groups (P < 0.0001). CONCLUSIONS: Although the IGRA response varies individually, early response during the treatment course may provide an insight into host immune responses underlying tuberculosis recurrence.
Authors: S E Medellín-Garibay; N Cortez-Espinosa; R C Milán-Segovia; M Magaña-Aquino; J M Vargas-Morales; R González-Amaro; D P Portales-Pérez; S Romano-Moreno Journal: Antimicrob Agents Chemother Date: 2015-10-05 Impact factor: 5.191