Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure.
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.
Department of Science and Technology-National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.|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.
Stephanus T
ST
Malherbe
Center for Emerging Pathogens, Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA.
Shubhada
S
Shenai
Department of Science and Technology-National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.|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.
Katharina
K
Ronacher
Department of Science and Technology-National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.|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
AG
Loxton
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.
Gregory
G
Dolganov
Department of Science and Technology-National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.|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.
Magdalena
M
Kriel
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.
Tran
T
Van
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.
Ray Y
RY
Chen
Western Cape Academic Positron Emission Tomography-Computed Tomography Centre, Tygerberg Academic Hospital, Cape Town, South Africa.|Division of Nuclear Medicine, Department of Medical Imaging and Clinical Oncology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
James
J
Warwick
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.|Institute of Infectious Disease and Molecular Medicine, Department of Clinical Laboratory Sciences, University of Cape Town, Cape Town, South Africa.
Laura E
LE
Via
International Tuberculosis Research Center, Seoul, South Korea.
Taeksun
T
Song
International Tuberculosis Research Center, Seoul, South Korea.
Myungsun
M
Lee
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.
Gary
G
Schoolnik
Department of Science and Technology-National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.|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.
Gerard
G
Tromp
Center for Emerging Pathogens, Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA.
David
D
Alland
Department of Science and Technology-National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.|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.|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.|Institute of Infectious Disease and Molecular Medicine, Department of Clinical Laboratory Sciences, University of Cape Town, Cape Town, South Africa.
Clifton E
CE
Barry
Catalysis Foundation for Health, Emeryville, California, USA.
Jill
J
Winter
Department of Science and Technology-National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.|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.
Gerhard
0000-0003-2487-125X
G
Walzl
Department of Science and Technology-National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.|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
L
Lucas
Department of Science and Technology-National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.|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
GV
Spuy
Department of Science and Technology-National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.|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
K
Stanley
Department of Science and Technology-National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.|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
L
Thiart
Department of Science and Technology-National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.|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
B
Smith
Department of Science and Technology-National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.|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
N
Du Plessis
Department of Science and Technology-National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.|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
CG
Beltran
Department of Science and Technology-National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.|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
E
Maasdorp
Western Cape Academic Positron Emission Tomography-Computed Tomography Centre, Tygerberg Academic Hospital, Cape Town, South Africa.|Division of Nuclear Medicine, Department of Medical Imaging and Clinical Oncology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Annare
A
Ellmann
International Tuberculosis Research Center, Seoul, South Korea.
Hongjo
H
Choi
National Medical Center, Seoul, South Korea.
Joonsung
J
Joh
Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Lori E
LE
Dodd
Division of Pulmonology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Brian
B
Allwood
Division of Pulmonology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Coenie
C
Koegelenberg
Division of Pulmonology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Morné
M
Vorster
Division of Radiodiagnosis, Department of Medical Imaging and Clinical Oncology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Stephanie
S
Griffith-Richards
D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid; D005260:Female; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D000072078:Positron Emission Tomography Computed Tomography; D012333:RNA, Messenger / Q000378:metabolism*; D013019:South Africa; D013183:Sputum / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000000981:diagnostic imaging* / Q000188:drug therapy; D055815:Young Adult
D000995:Antitubercular Agents; D012333:RNA, Messenger