Prithwiraj De1, Anita G Amin1, Barbara Graham1, Stacey L Martiniano2, Silvia M Caceres3, Katie R Poch3, Marion C Jones3, Milene T Saavedra3, Kenneth C Malcolm3, Jerry A Nick4, Delphi Chatterjee5. 1. Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, 1682 Campus Delivery, Fort Collins, CO 80523, United States. 2. Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States. 3. Department of Medicine, National Jewish Health, Denver, Colorado, United States. 4. Department of Medicine, National Jewish Health, Denver, Colorado, United States. Electronic address: NickJ@NJHealth.org. 5. Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, 1682 Campus Delivery, Fort Collins, CO 80523, United States. Electronic address: Delphi.chatterjee@colostate.edu.
Abstract
BACKGROUND: Individuals with Cystic fibrosis (CF) are the most vulnerable population for pulmonary infection with nontuberculous mycobacteria (NTM). Screening, diagnosis, and assessment of treatment response currently depend on traditional culture techniques, but sputum analysis for NTM in CF is challenging, and associated with a low sensitivity. The cell wall lipoarabinomannan (LAM), a lipoglycan found in all mycobacterial species, and has been validated as a biomarker in urine for active Mycobacterium tuberculosis infection. METHODS: Urine from a CF cohort (n = 44) well-characterized for NTM infection status by airway cultures was analyzed for LAM by gas chromatography/mass spectrometry. All subjects with positive sputum cultures for NTM had varying amounts of LAM in their urine. No LAM was detected in subjects who never had a positive culture (14/45). One individual initially classified as NTM sputum negative subsequently developed NTM disease 657 days after the initial urine LAM testing. Repeat urine LAM testing turned positive, correlating to her positive NTM status. Subjects infected with subspecies of M. abscessus had greater LAM quantities than those infected with M. avium complex (MAC). There was no correlation with disease activity or treatment status and LAM quantity. A TB Capture ELISA using anti-LAM antibodies demonstrated very poor sensitivity in identifying individuals with positive NTM sputum cultures. CONCLUSION: These findings support the conclusion that urine LAM related to NTM infection may be a useful screening test to determine patients at low risk for having a positive NTM sputum culture, as part of a lifetime screening strategy in the CF population.
BACKGROUND: Individuals with Cystic fibrosis (CF) are the most vulnerable population for pulmonary infection with nontuberculous mycobacteria (NTM). Screening, diagnosis, and assessment of treatment response currently depend on traditional culture techniques, but sputum analysis for NTM in CF is challenging, and associated with a low sensitivity. The cell wall lipoarabinomannan (LAM), a lipoglycan found in all mycobacterial species, and has been validated as a biomarker in urine for active Mycobacterium tuberculosisinfection. METHODS: Urine from a CF cohort (n = 44) well-characterized for NTM infection status by airway cultures was analyzed for LAM by gas chromatography/mass spectrometry. All subjects with positive sputum cultures for NTM had varying amounts of LAM in their urine. No LAM was detected in subjects who never had a positive culture (14/45). One individual initially classified as NTM sputum negative subsequently developed NTM disease 657 days after the initial urine LAM testing. Repeat urine LAM testing turned positive, correlating to her positive NTM status. Subjects infected with subspecies of M. abscessus had greater LAM quantities than those infected with M. avium complex (MAC). There was no correlation with disease activity or treatment status and LAM quantity. A TB Capture ELISA using anti-LAM antibodies demonstrated very poor sensitivity in identifying individuals with positive NTM sputum cultures. CONCLUSION: These findings support the conclusion that urine LAM related to NTM infection may be a useful screening test to determine patients at low risk for having a positive NTM sputum culture, as part of a lifetime screening strategy in the CF population.
Authors: Anita G Amin; Prithwiraj De; John S Spencer; Patrick J Brennan; Joshua Daum; Barbara G Andre; Maju Joe; Yu Bai; Lars Laurentius; Marc D Porter; William J Honnen; Alok Choudhary; Todd L Lowary; Abraham Pinter; Delphi Chatterjee Journal: Tuberculosis (Edinb) Date: 2018-06-06 Impact factor: 3.131
Authors: Tobias Broger; Michael Tsionksy; Anu Mathew; Todd L Lowary; Abraham Pinter; Tatiana Plisova; Daniel Bartlett; Simone Barbero; Claudia M Denkinger; Emmanuel Moreau; Kiyonori Katsuragi; Masanori Kawasaki; Payam Nahid; George B Sigal Journal: PLoS One Date: 2019-04-18 Impact factor: 3.240
Authors: Prithwiraj De; Anita G Amin; Eloise Valli; Mark D Perkins; Michael McNeil; Delphi Chatterjee Journal: PLoS One Date: 2015-12-03 Impact factor: 3.240
Authors: George B Sigal; Abraham Pinter; Todd L Lowary; Masanori Kawasaki; Andra Li; Anu Mathew; Michael Tsionsky; Ruixiang Blake Zheng; Tatiana Plisova; Ke Shen; Kiyonori Katsuragi; Alok Choudhary; William J Honnen; Payam Nahid; Claudia M Denkinger; Tobias Broger Journal: J Clin Microbiol Date: 2018-11-27 Impact factor: 5.948
Authors: Anita G Amin; Prithwiraj De; Barbara Graham; Roger I Calderon; Molly F Franke; Delphi Chatterjee Journal: Sci Rep Date: 2021-02-03 Impact factor: 4.379
Authors: Elise Ishida; Devin T Corrigan; Ryan J Malonis; Daniel Hofmann; Tingting Chen; Anita G Amin; Delphi Chatterjee; Maju Joe; Todd L Lowary; Jonathan R Lai; Jacqueline M Achkar Journal: Commun Biol Date: 2021-10-12
Authors: Kenneth C Malcolm; Emily A Wheeler; Kara Calhoun; Patricia M Lenhart-Pendergrass; Noel Rysavy; Katie R Poch; Silvia M Caceres; Milene T Saavedra; Jerry A Nick Journal: Microbiol Spectr Date: 2022-07-06