Discovery and validation of a personalized risk predictor for incident tuberculosis in low transmission settings


Por: Gupta, RK, Calderwood, CJ, Yavlinsky, A, Krutikov, M, Quartagno, M, Aichelburg, MC, Altet, N, Diel, R, Dobler, CC, Dominguez, J, Doyle, JS, Erkens, C, Geis, S, Haldar, P, Hauri, AM, Hermansen, T, Johnston, JC, Lange, C, Lange, B, van Leth, F, Munoz, L, Roder, C, Romanowski, K, Roth, D, Sester, M, Sloot, R, Sotgiu, G, Woltmann, G, Yoshiyama, T, Zellweger, JP, Zenner, D, Aldridge, RW, Copas, A, Rangaka, MX, Lipman, M, Noursadeghi, M and Abubakar, I

Publicada: 1 dic 2020 Ahead of Print: 1 oct 2020
Resumen:
The risk of tuberculosis (TB) is variable among individuals with latentMycobacterium tuberculosisinfection (LTBI), but validated estimates of personalized risk are lacking. In pooled data from 18 systematically identified cohort studies from 20 countries, including 80,468 individuals tested for LTBI, 5-year cumulative incident TB risk among people with untreated LTBI was 15.6% (95% confidence interval (CI), 8.0-29.2%) among child contacts, 4.8% (95% CI, 3.0-7.7%) among adult contacts, 5.0% (95% CI, 1.6-14.5%) among migrants and 4.8% (95% CI, 1.5-14.3%) among immunocompromised groups. We confirmed highly variable estimates within risk groups, necessitating an individualized approach to risk stratification. Therefore, we developed a personalized risk predictor for incident TB (PERISKOPE-TB) that combines a quantitative measure of T cell sensitization and clinical covariates. Internal-external cross-validation of the model demonstrated a random effects meta-analysis C-statistic of 0.88 (95% CI, 0.82-0.93) for incident TB. In decision curve analysis, the model demonstrated clinical utility for targeting preventative treatment, compared to treating all, or no, people with LTBI. We challenge the current crude approach to TB risk estimation among people with LTBI in favor of our evidence-based and patient-centered method, in settings aiming for pre-elimination worldwide. The risk of developing active tuberculosis (TB) in individuals with latent TB infection is highly variable within and among different risk groups. A personalized risk predictor was developed to better target preventative treatment to individuals at greatest risk, supporting evidence-based clinical decision-making for latent TB.

Filiaciones:
Gupta, RK:
 UCL, Inst Global Hlth, London, England

Calderwood, CJ:
 UCL, Inst Global Hlth, London, England

Yavlinsky, A:
 UCL, Inst Hlth Informat, London, England

Krutikov, M:
 UCL, Inst Global Hlth, London, England

Quartagno, M:
 UCL, Inst Clin Trials & Methodol, MRC Clin Trials Unit, London, England

Aichelburg, MC:
 Donauspital, Dept Dermatol, Sozialmed Zentrum Ost, Vienna, Austria

Altet, N:
 Hosp Univ Vall dHebron Drassanes, Unitat TB, Barcelona, Spain

 Unitat TDO TB Serv Clin, Barcelona, Spain

Diel, R:
 Univ Hosp Schleswig Holstein, Inst Epidemiol, Campus Kiel, Kiel, Germany

 Airway Res Ctr North ARCN, Lung Clin Grosshansdorf, Grosshansdorf, Germany

Dobler, CC:
 Bond Univ, Inst Evidence Based Healthcare, Fac Hlth Sci & Med, Gold Coast, Qld, Australia

 Liverpool Hosp, Dept Resp Med, Sydney, NSW, Australia

:
 Inst Invest Germans Trias & Pujol, Barcelona, Spain

 CIBER Enfermedades Resp, Barcelona, Spain

 Univ Autonoma Barcelona, Barcelona, Spain

Doyle, JS:
 Alfred & Monash Univ, Dept Infect Dis, Melbourne, Vic, Australia

 Burnet Inst, Dis Eliminat Program, Melbourne, Vic, Australia

Erkens, C:
 KNCV TB Fdn, The Hague, Netherlands

Geis, S:
 Philipps Univ Marburg, Inst Med Microbiol & Hosp Hyg, Marburg, Germany

Haldar, P:
 Univ Leicester, Inst Lung Hlth, Dept Resp Sci, Resp Biomed Res Ctr, Leicester, Leics, England

Hauri, AM:
 Hesse State Hlth Off, Dillenburg, Germany

Hermansen, T:
 Statens Serum Inst, Int Reference Lab Mycobacteriol, Copenhagen, Denmark

Johnston, JC:
 British Columbia Ctr Dis Control, Vancouver, BC, Canada

Lange, C:
 Res Ctr Borstel, Div Clin Infect Dis, Borstel, Germany

 German Ctr Infect Res DZIF, Clin TB Ctr, Borstel, Germany

 TB Network European Trials Grp TBnet, Borstel, Germany

 Karolinska Inst, Dept Med, Stockholm, Sweden

Lange, B:
 Helmholtz Ctr Infect Res, Dept Epidemiol, Braunschweig, Germany

van Leth, F:
 TB Network European Trials Grp TBnet, Borstel, Germany

 Amsterdam Inst Global Hlth & Dev, Amsterdam, Netherlands

 Univ Amsterdam, Dept Global Hlth, Med Ctr, Amsterdam, Netherlands

Munoz, L:
 Univ Barcelona, Dept Clin Sci, Barcelona, Spain

Roder, C:
 Alfred & Monash Univ, Dept Infect Dis, Melbourne, Vic, Australia

 Burnet Inst, Dis Eliminat Program, Melbourne, Vic, Australia

Romanowski, K:
 British Columbia Ctr Dis Control, Vancouver, BC, Canada

Roth, D:
 British Columbia Ctr Dis Control, Vancouver, BC, Canada

Sester, M:
 TB Network European Trials Grp TBnet, Borstel, Germany

 Saarland Univ, Dept Transplant & Infect Immunol, Homburg, Germany

Sloot, R:
 Stellenbosch Univ, Desmond Tutu TB Ctr, Dept Paediat & Child Hlth, Fac Med & Hlth Sci, Cape Town, South Africa

Sotgiu, G:
 TB Network European Trials Grp TBnet, Borstel, Germany

 Uniivers Sassari, Dept Med Surg & Expt Sci, Clin Epidemiol & Med Stat Unit, Sassari, Italy

Woltmann, G:
 Univ Leicester, Inst Lung Hlth, Dept Resp Sci, Resp Biomed Res Ctr, Leicester, Leics, England

Yoshiyama, T:
 Res Inst TB, Tokyo, Japan

Zellweger, JP:
 TB Network European Trials Grp TBnet, Borstel, Germany

 Swiss Lung Assoc, Bern, Switzerland

Zenner, D:
 UCL, Inst Global Hlth, London, England

Aldridge, RW:
 UCL, Inst Hlth Informat, London, England

Copas, A:
 Univ Autonoma Barcelona, Barcelona, Spain

Rangaka, MX:
 UCL, Inst Global Hlth, London, England

 UCL, Inst Clin Trials & Methodol, MRC Clin Trials Unit, London, England

 Univ Cape Town, Inst Infect Dis & Mol Med, Wellcome Ctr Infect Dis Res Africa, Cape Town, South Africa

 Univ Cape Town, Sch Publ Hlth, Div Epidemiol & Biostat, Cape Town, South Africa

Lipman, M:
 UCL, UCL TB & UCL Resp, London, England

 Royal Free London NHS Fdn Trust, London, England

Noursadeghi, M:
 UCL, Div Infect & Immun, London, England

Abubakar, I:
 UCL, Inst Global Hlth, London, England
ISSN: 10788956





Nature Medicine
Editorial
Nature Publishing Group, 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA, Reino Unido
Tipo de documento: Article
Volumen: 26 Número: 12
Páginas: 1941-1949
WOS Id: 000579706700005
ID de PubMed: 33077958
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