Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure

Stephanus T Malherbe; Shubhada Shenai; Katharina Ronacher; Andre G Loxton; Gregory Dolganov; Magdalena Kriel; Tran Van; Ray Y Chen; James Warwick; Laura E Via; Taeksun Song; Myungsun Lee; Gary Schoolnik; Gerard Tromp; David Alland; Clifton E Barry, 3rd; Jill Winter; Gerhard Walzl; Lance Lucas; Gian van der Spuy; Kim Stanley; Lani Thiart; Bronwyn Smith; Nelita Du Plessis; Caroline G G Beltran; Elizna Maasdorp; Annare Ellmann; Hongjo Choi; Joonsung Joh; Lori E Dodd; Brian Allwood; Coenie Koegelenberg; Morné Vorster; Stephanie Griffith-Richards; Catalysis TB–Biomarker Consortium

doi:10.1038/nm.4177

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Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure

Journal article

Open access

Peer reviewed

Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure

Stephanus T Malherbe, Shubhada Shenai, Katharina Ronacher, Andre G Loxton, Gregory Dolganov, Magdalena Kriel, Tran Van, Ray Y Chen, James Warwick, Laura E Via, …

Nature medicine, Vol.22(10), pp.1094-1100

10/2016

DOI: https://doi.org/10.1038/nm.4177

PMID: 27595324

Abstract

Bronchoalveolar Lavage Fluid

Lung - microbiology

Humans

Middle Aged

Male

Tuberculosis, Pulmonary - drug therapy

Lung - diagnostic imaging

RNA, Messenger - metabolism

Sputum - metabolism

Positron Emission Tomography Computed Tomography

Young Adult

Adolescent

Adult

Female

South Africa

Tuberculosis, Pulmonary - diagnostic imaging

Aged

Lung - metabolism

Antitubercular Agents - therapeutic use

Mycobacterium tuberculosis - genetics

The absence of a gold standard to determine when antibiotics induce a sterilizing cure has confounded the development of new approaches to treat pulmonary tuberculosis (PTB). We detected positron emission tomography and computerized tomography (PET-CT) imaging response patterns consistent with active disease, along with the presence of Mycobacterium tuberculosis (MTB) mRNA in sputum and bronchoalveolar lavage samples, in a substantial proportion of adult, HIV-negative patients with PTB after a standard 6-month treatment plus 1 year follow-up, including patients with a durable cure and others who later developed recurrent disease. The presence of MTB mRNA in the context of nonresolving and intensifying lesions on PET-CT images might indicate ongoing transcription, suggesting that even apparently curative treatment for PTB may not eradicate all of the MTB bacteria in most patients. This suggests an important complementary role for the immune response in maintaining a disease-free state. Sterilizing drugs or host-directed therapies, and better treatment response markers, are probably needed for the successful development of improved and shortened PTB-treatment strategies.

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Title: Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure
Creators: Stephanus T Malherbe - South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Shubhada Shenai - Center for Emerging Pathogens, Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA
Katharina Ronacher - South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Andre G Loxton - South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Gregory Dolganov - Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA
Magdalena Kriel - South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Tran Van - Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA
Ray Y Chen - Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
James Warwick - Division of Nuclear Medicine, Department of Medical Imaging and Clinical Oncology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Laura E Via - Institute of Infectious Disease and Molecular Medicine, Department of Clinical Laboratory Sciences, University of Cape Town, Cape Town, South Africa
Taeksun Song - International Tuberculosis Research Center, Seoul, South Korea
Myungsun Lee - International Tuberculosis Research Center, Seoul, South Korea
Gary Schoolnik - Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA
Gerard Tromp - South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
David Alland - Center for Emerging Pathogens, Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA
Clifton E Barry, 3rd - Institute of Infectious Disease and Molecular Medicine, Department of Clinical Laboratory Sciences, University of Cape Town, Cape Town, South Africa
Jill Winter - Catalysis Foundation for Health, Emeryville, California, USA
Gerhard Walzl - South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Lance Lucas - South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Gian van der Spuy - South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Kim Stanley - South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Lani Thiart - South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Bronwyn Smith - South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Nelita Du Plessis - South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Caroline G G Beltran - South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Elizna Maasdorp - South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Annare Ellmann - Division of Nuclear Medicine, Department of Medical Imaging and Clinical Oncology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Hongjo Choi - International Tuberculosis Research Center, Seoul, South Korea
Joonsung Joh - National Medical Center, Seoul, South Korea
Lori E Dodd - Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
Brian Allwood - Division of Pulmonology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Coenie Koegelenberg - Division of Pulmonology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Morné Vorster - Division of Pulmonology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Stephanie Griffith-Richards - Division of Radiodiagnosis, Department of Medical Imaging and Clinical Oncology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Catalysis TB–Biomarker Consortium
Publication Details: Nature medicine, Vol.22(10), pp.1094-1100
Date published: 10/2016
Grant note: Z01 AI001067-01 / Intramural NIH HHS
Academic Unit: Medicine - Infectious Diseases (NJMS)
Language: English
Resource Type: Journal article
Identifiers: 991031654835104646