Kentaro Sakashita1, Rikiya Takeuchi2, Keita Takeda3, Mikio Takamori4, Kensuke Ito2, Yuriko Igarashi5, Eiji Hayashi6, Mari Iguchi6, Masahiro Ono6, Tetsuya Kashiyama6, Masatoshi Tachibana4, Jun Miyakoshi4, Koichi Yano4, Yu Sato4, Miyake Yamamoto4, Kengo Murata4, Akihiko Wada4, Kinuyo Chikamatsu7, Akio Aono7, Akiko Takaki7, Hideaki Nagai8, Akira Yamane8, Masahiro Kawashima8, Mariko Komatsu2, Kazunari Nakaishi2, Satoshi Watabe2, Satoshi Mitarai9. 1. Department of Respiratory Medicine, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan; Department of Basic Mycobacteriology, Graduate School of Biomedical Science, Nagasaki University, Nagasaki, Japan; Department of Internal Medicine, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan; Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan. 2. Department of Research and Development, TAUNS Laboratories Inc., Shizuoka, Japan. 3. Department of Basic Mycobacteriology, Graduate School of Biomedical Science, Nagasaki University, Nagasaki, Japan; Department of Respiratory Medicine, National Hospital Organization Tokyo National Hospital, Tokyo, Japan; Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan. 4. Department of Respiratory Medicine, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan. 5. Department of Basic Mycobacteriology, Graduate School of Biomedical Science, Nagasaki University, Nagasaki, Japan; Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan. 6. Department of Internal Medicine, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan. 7. Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan. 8. Department of Respiratory Medicine, National Hospital Organization Tokyo National Hospital, Tokyo, Japan. 9. Department of Basic Mycobacteriology, Graduate School of Biomedical Science, Nagasaki University, Nagasaki, Japan; Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan. Electronic address: mitarai@jata.or.jp.
Abstract
OBJECTIVES: This study examined Mycobacterium tuberculosis (MTB)-secreted MPT64 as a surrogate of bacterial viability for the diagnosis of active pulmonary TB (PTB) and for follow-up treatment. METHODS: In this proof-of-concept prospective study, 50 PTB patients in the Tokyo metropolitan region, between 2017 and 2018, were consecutively included and 30 healthy individuals were also included. Each PTB patient submitted sputum on days 0, 14 and 28 for diagnosis and follow-up, and each healthy individual submitted one sputum sample. The following were performed: smear microscopy, Xpert MTB/RIF, MGIT and solid culture, and MPT64 detection on the sputum samples. Ultrasensitive ELISA (usELISA) was used to detect MPT64. The receiver operating characteristic analyses for diagnosis and follow-up revealed the optimal cut-off value of MPT64 absorbance for detecting culture positivity at multiple intervals. RESULTS: The sensitivity of MPT64 for diagnosing PTB was 88.0% (95% CI 75.7-95.5) and the specificity was 96.7% (95% CI 82.8-99.9). The specificity of MPT64 for predicting negative culture results on day 14 was 89.5% (95% CI 66.9-98.7). The sensitivity of MPT64 for predicting positive culture results on day 28 was 81.0% (95% CI 58.1-94.6). CONCLUSIONS: This study revealed that MPT64 is useful for diagnosing active PTB in patients and predicting treatment efficacy at follow-up.
OBJECTIVES: This study examined Mycobacterium tuberculosis (MTB)-secreted MPT64 as a surrogate of bacterial viability for the diagnosis of active pulmonary TB (PTB) and for follow-up treatment. METHODS: In this proof-of-concept prospective study, 50 PTB patients in the Tokyo metropolitan region, between 2017 and 2018, were consecutively included and 30 healthy individuals were also included. Each PTB patient submitted sputum on days 0, 14 and 28 for diagnosis and follow-up, and each healthy individual submitted one sputum sample. The following were performed: smear microscopy, Xpert MTB/RIF, MGIT and solid culture, and MPT64 detection on the sputum samples. Ultrasensitive ELISA (usELISA) was used to detect MPT64. The receiver operating characteristic analyses for diagnosis and follow-up revealed the optimal cut-off value of MPT64 absorbance for detecting culture positivity at multiple intervals. RESULTS: The sensitivity of MPT64 for diagnosing PTB was 88.0% (95% CI 75.7-95.5) and the specificity was 96.7% (95% CI 82.8-99.9). The specificity of MPT64 for predicting negative culture results on day 14 was 89.5% (95% CI 66.9-98.7). The sensitivity of MPT64 for predicting positive culture results on day 28 was 81.0% (95% CI 58.1-94.6). CONCLUSIONS: This study revealed that MPT64 is useful for diagnosing active PTB in patients and predicting treatment efficacy at follow-up.
Authors: Jan Heyckendorf; Sophia B Georghiou; Nicole Frahm; Norbert Heinrich; Irina Kontsevaya; Maja Reimann; David Holtzman; Marjorie Imperial; Daniela M Cirillo; Stephen H Gillespie; Morten Ruhwald Journal: Clin Microbiol Rev Date: 2022-03-21 Impact factor: 50.129