Prediction of Susceptibility to First-Line Tuberculosis Drugs by DNA Sequencing
Por:
Allix-Beguec, C, Arandjelovic, I, Bi, L, Beckert, P, Bonnet, M, Bradley, P, Cabibbe, A, Cancino-Munoz, I, Caulfield, M, Chaiprasert, A, Cirillo, D, Clifton, D, Comas, I, Crook, D, De Filippo, M, de Neeling, H, Diel, R, Drobniewski, F, Faksri, K, Farhat, M, Fleming, J, Fowler, P, Fowler, T, Gao, Q, Gardy, J, Gascoyne-Binzi, D, Gibertoni-Cruz, A, Gil-Brusola, A, Golubchik, T, Gonzalo, X, Grandjean, L, He, G, Guthrie, J, Hoosdally, S, Hunt, M, Iqbal, Z, Ismail, N, Johnston, J, Khanzada, F, Khor, C, Kohl, T, Kong, C, Lipworth, S, Liu, Q, Maphalala, G, Martinez, E, Mathys, V, Merker, M, Miotto, P, Mistry, N, Moore, D, Murray, M, Niemann, S, Ong, R, Peto, T, Posey, J, Prammananan, T, Pym, A, Rodrigues, C, Rodrigues, M, Rodwell, T, Rossolini, G, Padilla, E, Schito, M, Shen, X, Shendure, J, Sintchenko, V, Sloutsky, A, Smith, E, Snyder, M, Soetaert, K, Starks, A, Supply, P, Suriyapol, P, Tahseen, S, Tang, P, Teo, Y, Thuong, T, Thwaites, G, Tortoli, E, Omar, V, van Soolingen, D, Walker, A, Walker, T, Wilcox, M, Wilson, D, Wyllie, D, Yang, Y, Zhang, H, Zhao, Y, Zhu, B, CRyPTIC Consortium and 100000 Genomes Project
Publicada:
11 oct 2018
Categoría:
Medicine (miscellaneous)
Resumen:
BACKGROUND
The World Health Organization recommends drug-susceptibility testing of Mycobacterium tuberculosis complex for all patients with tuberculosis to guide treatment decisions and improve outcomes. Whether DNA sequencing can be used to accurately predict profiles of susceptibility to first-line antituberculosis drugs has not been clear.
METHODS
We obtained whole-genome sequences and associated phenotypes of resistance or susceptibility to the first-line antituberculosis drugs isoniazid, rifampin, ethambutol, and pyrazinamide for isolates from 16 countries across six continents. For each isolate, mutations associated with drug resistance and drug susceptibility were identified across nine genes, and individual phenotypes were predicted unless mutations of unknown association were also present. To identify how whole-genome sequencing might direct first-line drug therapy, complete susceptibility profiles were predicted. These profiles were predicted to be susceptible to all four drugs (i.e., pansusceptible) if they were predicted to be susceptible to isoniazid and to the other drugs or if they contained mutations of unknown association in genes that affect susceptibility to the other drugs. We simulated the way in which the negative predictive value changed with the prevalence of drug resistance.
RESULTS
A total of 10,209 isolates were analyzed. The largest proportion of phenotypes was predicted for rifampin (9660 [95.4%] of 10,130) and the smallest was predicted for ethambutol (8794 [89.8%] of 9794). Resistance to isoniazid, rifampin, ethambutol, and pyrazinamide was correctly predicted with 97.1%, 97.5%, 94.6%, and 91.3% sensitivity, respectively, and susceptibility to these drugs was correctly predicted with 99.0%, 98.8%, 93.6%, and 96.8% specificity. Of the 7516 isolates with complete phenotypic drug-susceptibility profiles, 5865 (78.0%) had complete genotypic predictions, among which 5250 profiles (89.5%) were correctly predicted. Among the 4037 phenotypic profiles that were predicted to be pansusceptible, 3952 (97.9%) were correctly predicted.
CONCLUSIONS
Genotypic predictions of the susceptibility of M. tuberculosis to first-line drugs were found to be correlated with phenotypic susceptibility to these drugs. (Funded by the Bill and Melinda Gates Foundation and others.)
Filiaciones:
Allix-Beguec, C:
Genoscreen, Lille, France
Arandjelovic, I:
Univ Belgrade, Fac Med, Inst Microbiol & Immunol, Belgrade, Serbia
Bi, L:
Chinese Acad Sci, Inst Biophys, Key Lab RNA Biol, Beijing 100101 2, Peoples R China
Beckert, P:
Forschungszentrum Borstel, Leibniz Lungenzentrum, Borstel, Germany
Bonnet, M:
Epictr, Paris, France
Univ Montpellier, INSERM U1175, IRD UMI233, Montpellier, France
Bradley, P:
European Bioinformat Inst Hinxton, Cambridge, England
Cabibbe, A:
IRCCS, Emerging Bacterial Pathogens Unit, San Raffaele Sci Inst, WHO Collaborating Ctr & TB Supranational Referenc, Milan, Italy
Cancino-Munoz, I:
CSIC, IBV, Calle Jaime Roig, Valencia, Spain
FISABIO Publ Hlth, Valencia, Spain
Caulfield, M:
Genom England, London, England
NIHR Biomed Res Ctr Barts, London, England
Queen Mary Univ London, William Harvey Res Inst, London, England
Chaiprasert, A:
Mahidol Univ, Fac Med, Siriraj Hosp, Salaya, Nakhon Pathom, Thailand
Cirillo, D:
IRCCS, Emerging Bacterial Pathogens Unit, San Raffaele Sci Inst, WHO Collaborating Ctr & TB Supranational Referenc, Milan, Italy
Clifton, D:
Univ Oxford, Inst Biomed Engn, Dept Engn Sci, Oxford, England
:
CSIC, IBV, Calle Jaime Roig, Valencia, Spain
FISABIO Publ Hlth, Valencia, Spain
CIBER Epidemiol & Publ Hlth, Madrid, Spain
Crook, D:
Univ Oxford, John Radcliffe Hosp, Nuffield Dept Med, Oxford, England
Natl Infect Serv, Publ Hlth England, London, England
De Filippo, M:
IRCCS, Emerging Bacterial Pathogens Unit, San Raffaele Sci Inst, WHO Collaborating Ctr & TB Supranational Referenc, Milan, Italy
de Neeling, H:
Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands
Diel, R:
Univ Med Hosp Schleswig Holstein, ARCN, Inst Epidemiol, Kiel, Germany
Drobniewski, F:
Imperial Coll, London, England
Faksri, K:
Khon Kaen Univ, Fac Med, Dept Microbiol, Khon Kaen, Thailand
Farhat, M:
Harvard Med Sch, Boston, MA USA
Fleming, J:
Chinese Acad Sci, Inst Biophys, Key Lab RNA Biol, Beijing 100101 2, Peoples R China
Fowler, P:
Univ Oxford, John Radcliffe Hosp, Nuffield Dept Med, Oxford, England
Fowler, T:
Genom England, London, England
Gao, Q:
Fudan Univ, Shanghai Med Coll, Shanghai, Peoples R China
Gardy, J:
British Columbia Ctr Dis Control, Vancouver, BC, Canada
Univ British Columbia, Vancouver, BC, Canada
Gascoyne-Binzi, D:
Leeds Teaching Hosp NHS Trust, Leeds, W Yorkshire, England
Gibertoni-Cruz, A:
Univ Oxford, John Radcliffe Hosp, Nuffield Dept Med, Oxford, England
Gil-Brusola, A:
Hosp Univ & Politecn La Fe, Avinguda Fernando Abril Martorell, Valencia, Spain
Golubchik, T:
Univ Oxford, Big Data Inst, Old Rd Campus, Oxford, England
Gonzalo, X:
Imperial Coll, London, England
Publ Hlth England, Natl Mycobacterial Reference Lab, London, England
Grandjean, L:
Imperial Coll London, Dept Med, Sect Paediat, London, England
He, G:
Chinese Ctr Dis Control & Prevent, Beijing 2, Peoples R China
Guthrie, J:
British Columbia Ctr Dis Control, Vancouver, BC, Canada
Hoosdally, S:
Univ Oxford, John Radcliffe Hosp, Nuffield Dept Med, Oxford, England
Hunt, M:
European Bioinformat Inst Hinxton, Cambridge, England
Univ Oxford, John Radcliffe Hosp, Nuffield Dept Med, Oxford, England
Iqbal, Z:
European Bioinformat Inst Hinxton, Cambridge, England
Ismail, N:
Omar, Shaheed, V, NICD, Johannesburg, South Africa
Johnston, J:
British Columbia Ctr Dis Control, Vancouver, BC, Canada
Khanzada, F:
Natl TB Reference Lab, Natl TB Control Program, Islamabad, Pakistan
Khor, C:
Genome Inst Singapore, Agcy Sci Technol & Res, Singapore, Singapore
Kohl, T:
Forschungszentrum Borstel, Leibniz Lungenzentrum, Borstel, Germany
Kong, C:
British Columbia Ctr Dis Control, Vancouver, BC, Canada
Lipworth, S:
Univ Oxford, John Radcliffe Hosp, Nuffield Dept Med, Oxford, England
Liu, Q:
Fudan Univ, Key Lab Med Mol Virol, Sch Basic Med, Shanghai, Peoples R China
Maphalala, G:
Minist Hlth, NRL, Mbabane, Switzerland
Martinez, E:
Westmead Hosp, Ctr Infect Dis & Microbiol, Wentworthville New South Wales, Wentworthville, NSW, Australia
Mathys, V:
Sci Inst Publ Hlth WIV ISP, Bacterial Dis Serv, Operat Direct Communicable & Infect Dis, Brussels, Belgium
Merker, M:
Forschungszentrum Borstel, Leibniz Lungenzentrum, Borstel, Germany
Miotto, P:
IRCCS, Emerging Bacterial Pathogens Unit, San Raffaele Sci Inst, WHO Collaborating Ctr & TB Supranational Referenc, Milan, Italy
Mistry, N:
Fdn Med Res, Bombay, Maharashtra, India
Moore, D:
London Sch Hyg & Trop Med, TB Ctr, London, England
Murray, M:
Harvard Med Sch, Boston, MA USA
Niemann, S:
Forschungszentrum Borstel, Leibniz Lungenzentrum, Borstel, Germany
German Ctr Infect Res, Borstel Site, Borstel, Germany
Ong, R:
Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore
Peto, T:
Univ Oxford, John Radcliffe Hosp, Nuffield Dept Med, Oxford, England
Posey, J:
Ctr Dis Control & Prevent, Atlanta, GA USA
Prammananan, T:
Natl Sci & Technol Dev Agcy, Biotec, Biotec, Thailand
Pym, A:
UKZN, AHRI, Nelson Mandela Sch Med, Durban, South Africa
Rodrigues, C:
Hinduja Hosp, Dept Microbiol, Bombay, Maharashtra, India
Rodrigues, M:
British Columbia Ctr Dis Control, Vancouver, BC, Canada
Rodwell, T:
Univ Calif San Diego, La Jolla, CA 92093 USA
FIND, Geneva, Switzerland
Rossolini, G:
Florence Careggi Univ Hosp, Clin Microbiol & Virol Unit, Florence, Italy
Padilla, E:
Epictr, Paris, France
Schito, M:
Crit Path Inst, Tucson, AZ 85718 USA
Shen, X:
Shenzhen Ctr Chron Dis Control, Shenzhen, Peoples R China
Shendure, J:
Univ Washington, Seattle, WA 98195 USA
Sintchenko, V:
Univ Sydney, Ctr Infect Dis & Microbiol Publ Hlth, Sydney, NSW, Australia
Sloutsky, A:
Univ Massachusetts, Sch Med, Worcester, MA 01655 USA
Massachusetts State TB Lab Jamaica Plain, Boston, MA 02130 USA
Smith, E:
Natl Mycobacterial Reference Serv, Publ Hlth England, Publ Hlth Lab Birmingham, Birmingham, W Midlands, England
Snyder, M:
Univ Washington, Seattle, WA 98195 USA
Soetaert, K:
Sci Inst Publ Hlth WIV ISP, Bacterial Dis Serv, Operat Direct Communicable & Infect Dis, Brussels, Belgium
Starks, A:
Ctr Dis Control & Prevent, Atlanta, GA USA
Supply, P:
Univ Lille, CNRS, INSERM, CHU Lille,Inst Pasteur Lille,U1019,UMR 8204,CIIL, F-59000 Lille, France
Suriyapol, P:
Mahidol Univ, Fac Med, Siriraj Hosp, Salaya, Nakhon Pathom, Thailand
Tahseen, S:
Natl TB Reference Lab, Natl TB Control Program, Islamabad, Pakistan
Tang, P:
British Columbia Ctr Dis Control, Vancouver, BC, Canada
Sidra Med & Res Ctr, Dept Pathol, Doha, Qatar
Teo, Y:
Genome Inst Singapore, Agcy Sci Technol & Res, Singapore, Singapore
Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore
Natl Univ Singapore, Life Sci Inst, Singapore, Singapore
Thuong, T:
Univ Oxford, Clin Res Unit, Hosp Trop Dis, Ho Chi Minh City, Vietnam
Thwaites, G:
Univ Oxford, Clin Res Unit, Hosp Trop Dis, Ho Chi Minh City, Vietnam
Tortoli, E:
IRCCS, Emerging Bacterial Pathogens Unit, San Raffaele Sci Inst, WHO Collaborating Ctr & TB Supranational Referenc, Milan, Italy
van Soolingen, D:
Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands
Walker, A:
Univ Oxford, John Radcliffe Hosp, Nuffield Dept Med, Oxford, England
Walker, T:
Univ Oxford, John Radcliffe Hosp, Nuffield Dept Med, Oxford, England
Wilcox, M:
Leeds Teaching Hosp NHS Trust, Leeds, W Yorkshire, England
Univ Leeds, Leeds, W Yorkshire, England
Wilson, D:
Univ Oxford, John Radcliffe Hosp, Nuffield Dept Med, Oxford, England
Wyllie, D:
Univ Oxford, John Radcliffe Hosp, Nuffield Dept Med, Oxford, England
Yang, Y:
Univ Oxford, Inst Biomed Engn, Dept Engn Sci, Oxford, England
Oxford Suzhou China Adv Res Ctr, Shanghai, Peoples R China
Zhang, H:
Chinese Acad Sci, Inst Biophys, Key Lab RNA Biol, Beijing 100101 2, Peoples R China
Zhao, Y:
Chinese Ctr Dis Control & Prevent, Natl TB Reference Lab, Beijing 2, Peoples R China
Zhu, B:
Chinese Acad Sci, Microbial Genome Res Ctr, Beijing 2, Peoples R China
|