PMID- 32800860
OWN - NLM
STAT- MEDLINE
DCOM- 20201204
LR  - 20201214
IS  - 1878-3511 (Electronic)
IS  - 1201-9712 (Linking)
VI  - 99
DP  - 2020 Oct
TI  - Diagnostic accuracy of plasma kynurenine/tryptophan ratio, measured by 
      enzyme-linked immunosorbent assay, for pulmonary tuberculosis.
PG  - 441-448
LID - S1201-9712(20)30657-3 [pii]
LID - 10.1016/j.ijid.2020.08.028 [doi]
AB  - INTRODUCTION: The World Health Organization has identified the need for a 
      non-sputum-based test capable of detecting active tuberculosis (TB) as a 
      priority. The plasma kynurenine-to-tryptophan (K/T) ratio, largely mediated by 
      activity of the enzyme indoleamine 2,3-dioxygenase, may have potential as a 
      suitable biomarker for active TB. METHOD: We evaluated a commercial enzyme-linked 
      immunosorbent assay (ELISA) in comparison to mass spectrometry for measuring the 
      K/T ratio. We also used ELISA to determine the K/T ratio in plasma from patients 
      with active TB compared to latently infected controls, with and without HIV. 
      RESULTS: The two methods showed good agreement, with a mean bias of 0.01 (limit 
      of agreement from -0.06 to 0.10). Using ELISA, it was found that HIV-infected 
      patients with active TB disease had higher K/T ratios than those without TB 
      (median, 0.101 [interquartile range (IQR), 0.091-0.140] versus 0.061 [IQR, 
      0.034-0.077], P<0.0001). At a cutoff of 0.080, the K/T ratio produced a 
      sensitivity of 90%, a specificity of 80%, a positive predictive value (PPV) of 
      82%, and a negative predictive value (NPV) of 90%. In a receiver operating 
      characteristics analysis, the K/T ratio had an area under the curve of 0.93. 
      HIV-uninfected patients with active TB also had higher K/T ratios than those with 
      latent TB infections (median, 0.064 [IQR, 0.040-0.088] versus 0.022 [IQR, 
      0.016-0.027], P<0.0001). A cutoff of 0.040 gave a sensitivity of 85%, a 
      specificity of 92%, a PPV of 91%, and an NPV of 84%. CONCLUSION: The plasma K/T 
      ratio is a sensitive biomarker for active TB. The K/T ratio can be measured from 
      blood using ELISA. The K/T ratio should be evaluated as an initial test for TB.
CI  - Copyright (c) 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Adu-Gyamfi, Clement Gascua
AU  - Adu-Gyamfi CG
AD  - Centre for Vaccines & Immunology, National Institute of Communicable Diseases, A 
      Division of the National Health Laboratory Service, Johannesburg, South Africa; 
      Department of Chemical Pathology, School of Pathology, Faculty of Health 
      Sciences, University of the Witwatersrand, Johannesburg, South Africa. Electronic 
      address: clementgascua@yahoo.com.
FAU - Snyman, Tracy
AU  - Snyman T
AD  - Department of Chemical Pathology, School of Pathology, Faculty of Health 
      Sciences, University of the Witwatersrand, Johannesburg, South Africa.
FAU - Makhathini, Lillian
AU  - Makhathini L
AD  - Centre for Vaccines & Immunology, National Institute of Communicable Diseases, A 
      Division of the National Health Laboratory Service, Johannesburg, South Africa.
FAU - Otwombe, Kennedy
AU  - Otwombe K
AD  - Perinatal Health Research Unit (PHRU), DST/NRF Centre of Excellence for 
      Biomedical TB Research, and SA MRC Soweto Matlosana Collaborating Centre for 
      HIV/AIDS and TB, University of The Witwatersrand, Johannesburg, South Africa; 
      School of Public Health, Faculty of Health Sciences, University of the 
      Witwatersrand, Johannesburg, South Africa.
FAU - Darboe, Fatoumatta
AU  - Darboe F
AD  - South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease 
      and Molecular Medicine, and Division of Immunology, Department of Pathology, 
      University of Cape Town, Cape Town, South Africa.
FAU - Penn-Nicholson, Adam
AU  - Penn-Nicholson A
AD  - South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease 
      and Molecular Medicine, and Division of Immunology, Department of Pathology, 
      University of Cape Town, Cape Town, South Africa.
FAU - Fisher, Michelle
AU  - Fisher M
AD  - South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease 
      and Molecular Medicine, and Division of Immunology, Department of Pathology, 
      University of Cape Town, Cape Town, South Africa.
FAU - Savulescu, Dana
AU  - Savulescu D
AD  - Department of Chemical Pathology, School of Pathology, Faculty of Health 
      Sciences, University of the Witwatersrand, Johannesburg, South Africa.
FAU - Hoffmann, Christopher
AU  - Hoffmann C
AD  - Johns Hopkins University Centre for TB Research, Baltimore, USA.
FAU - Chaisson, Richard
AU  - Chaisson R
AD  - Johns Hopkins University Centre for TB Research, Baltimore, USA; Perinatal Health 
      Research Unit (PHRU), DST/NRF Centre of Excellence for Biomedical TB Research, 
      and SA MRC Soweto Matlosana Collaborating Centre for HIV/AIDS and TB, University 
      of The Witwatersrand, Johannesburg, South Africa.
FAU - Martinson, Neil
AU  - Martinson N
AD  - Johns Hopkins University Centre for TB Research, Baltimore, USA; Perinatal Health 
      Research Unit (PHRU), DST/NRF Centre of Excellence for Biomedical TB Research, 
      and SA MRC Soweto Matlosana Collaborating Centre for HIV/AIDS and TB, University 
      of The Witwatersrand, Johannesburg, South Africa.
FAU - Scriba, Thomas Jens
AU  - Scriba TJ
AD  - South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease 
      and Molecular Medicine, and Division of Immunology, Department of Pathology, 
      University of Cape Town, Cape Town, South Africa.
FAU - George, Jaya Anna
AU  - George JA
AD  - Department of Chemical Pathology, School of Pathology, Faculty of Health 
      Sciences, University of the Witwatersrand, Johannesburg, South Africa.
FAU - Suchard, Melinda Shelley
AU  - Suchard MS
AD  - Centre for Vaccines & Immunology, National Institute of Communicable Diseases, A 
      Division of the National Health Laboratory Service, Johannesburg, South Africa; 
      Department of Chemical Pathology, School of Pathology, Faculty of Health 
      Sciences, University of the Witwatersrand, Johannesburg, South Africa.
LA  - eng
PT  - Comparative Study
PT  - Evaluation Study
PT  - Journal Article
DEP - 20200812
PL  - Canada
TA  - Int J Infect Dis
JT  - International journal of infectious diseases : IJID : official publication of the 
      International Society for Infectious Diseases
JID - 9610933
RN  - 0 (Biomarkers)
RN  - 343-65-7 (Kynurenine)
RN  - 8DUH1N11BX (Tryptophan)
SB  - IM
MH  - Adult
MH  - Biomarkers/blood
MH  - *Enzyme-Linked Immunosorbent Assay/methods
MH  - Female
MH  - HIV Infections/blood/complications
MH  - Humans
MH  - Kynurenine/*blood
MH  - Latent Tuberculosis/blood/diagnosis
MH  - Male
MH  - Middle Aged
MH  - Reproducibility of Results
MH  - Sensitivity and Specificity
MH  - Tryptophan/*blood
MH  - Tuberculosis, Pulmonary/blood/complications/*diagnosis
OTO - NOTNLM
OT  - HIV
OT  - IDO
OT  - Kynurenine/tryptophan ratio
OT  - Sensitivity
OT  - Specificity
OT  - TB
OT  - Target product profile
EDAT- 2020/08/18 06:00
MHDA- 2020/12/15 06:00
CRDT- 2020/08/18 06:00
PHST- 2020/06/26 00:00 [received]
PHST- 2020/08/05 00:00 [revised]
PHST- 2020/08/08 00:00 [accepted]
PHST- 2020/08/18 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/08/18 06:00 [entrez]
AID - S1201-9712(20)30657-3 [pii]
AID - 10.1016/j.ijid.2020.08.028 [doi]
PST - ppublish
SO  - Int J Infect Dis. 2020 Oct;99:441-448. doi: 10.1016/j.ijid.2020.08.028. Epub 2020 
      Aug 12.