Plasma Kynurenine-to-Tryptophan Ratio, a Highly Sensitive Blood-Based Diagnostic Tool for Tuberculosis in Pregnant Women Living With Human Immunodeficiency Virus (HIV).


Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213

Informations de publication

Date de publication:
15 09 2021
Historique:
received: 19 12 2020
pubmed: 16 3 2021
medline: 8 10 2021
entrez: 15 3 2021
Statut: ppublish

Résumé

For pregnant women living with human immunodeficiency virus (HIV), concurrent active tuberculosis (TB) disease increases the risk of maternal mortality and poor pregnancy outcomes. Plasma indoleamine 2,3-dioxygenase (IDO) activity measured by kynurenine-to-tryptophan (K/T) ratio has been proposed as a blood-based TB biomarker. We investigated whether plasma K/T ratio could be used to diagnose active TB among pregnant women with HIV. Using an enzyme-linked immunosorbent assay (ELISA), we measured K/T ratio in 72 pregnant women with and active TB and compared them to 117 pregnant women with HIB but without TB, matched by age and gestational age. Plasma K/T ratio was significantly elevated during pregnancy compared to sampling done after pregnancy (P < .0001). Pregnant women who had received isoniazid preventive therapy (IPT) before enrollment had decreased plasma K/T ratio compared to those who had not received IPT (P = .0174). Plasma K/T ratio was elevated in women with active TB at time of diagnosis compared to those without TB (P < .0001). Using a cutoff of 0.100, plasma K/T ratio gave a diagnostic sensitivity of 94% (95% confidence interval [CI]: 82-95), specificity of 90% (95% CI: 80-91), positive predictive value (PPV) 85% and negative predictive value (NPV) 98%. A receiver operating characteristic curve (ROC) gave an area under the curve of 0.95 (95% CI: .92-.97, P < .0001).In conclusion, plasma K/T ratio is a sensitive blood-based diagnostic test for active TB disease in pregnant women living with HIV. Plasma K/T ratio should be further evaluated as an initial TB diagnostic test to determine its impact on patient care.

Sections du résumé

BACKGROUND
For pregnant women living with human immunodeficiency virus (HIV), concurrent active tuberculosis (TB) disease increases the risk of maternal mortality and poor pregnancy outcomes. Plasma indoleamine 2,3-dioxygenase (IDO) activity measured by kynurenine-to-tryptophan (K/T) ratio has been proposed as a blood-based TB biomarker. We investigated whether plasma K/T ratio could be used to diagnose active TB among pregnant women with HIV.
METHODS
Using an enzyme-linked immunosorbent assay (ELISA), we measured K/T ratio in 72 pregnant women with and active TB and compared them to 117 pregnant women with HIB but without TB, matched by age and gestational age.
RESULTS
Plasma K/T ratio was significantly elevated during pregnancy compared to sampling done after pregnancy (P < .0001). Pregnant women who had received isoniazid preventive therapy (IPT) before enrollment had decreased plasma K/T ratio compared to those who had not received IPT (P = .0174). Plasma K/T ratio was elevated in women with active TB at time of diagnosis compared to those without TB (P < .0001). Using a cutoff of 0.100, plasma K/T ratio gave a diagnostic sensitivity of 94% (95% confidence interval [CI]: 82-95), specificity of 90% (95% CI: 80-91), positive predictive value (PPV) 85% and negative predictive value (NPV) 98%. A receiver operating characteristic curve (ROC) gave an area under the curve of 0.95 (95% CI: .92-.97, P < .0001).In conclusion, plasma K/T ratio is a sensitive blood-based diagnostic test for active TB disease in pregnant women living with HIV. Plasma K/T ratio should be further evaluated as an initial TB diagnostic test to determine its impact on patient care.

Identifiants

pubmed: 33718949
pii: 6170938
doi: 10.1093/cid/ciab232
pmc: PMC8442800
doi:

Substances chimiques

Kynurenine 343-65-7
Tryptophan 8DUH1N11BX

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1027-1036

Subventions

Organisme : NICHD NIH HHS
ID : R01 HD064354
Pays : United States

Informations de copyright

© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.

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Auteurs

Clement Adu-Gyamfi (C)

Center for Vaccines and Immunology, National Institute for 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 and National Health Laboratory Service, Johannesburg, South Africa.

Dana Savulescu (D)

Center for Vaccines and Immunology, National Institute for Communicable Diseases, a division of the National Health Laboratory Service, Johannesburg, South Africa.

Lillian Mikhathani (L)

Center for Vaccines and Immunology, National Institute for Communicable Diseases, a division of the National Health Laboratory Service, Johannesburg, South Africa.

Kennedy Otwombe (K)

Perinatal Health Research Unit (PHRU), Soweto Matlosana Collaborating Centre for HIV/AIDS and TB, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa.
School of Public Health, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa.

Nicole Salazar-Austin (N)

Johns Hopkins University Centre for TB Research, Baltimore, MarylandUSA.
Johns Hopkins School of Medicine, Baltimore, MarylandUSA.

Richard Chaisson (R)

Johns Hopkins University Centre for TB Research, Baltimore, MarylandUSA.

Neil Martinson (N)

Perinatal Health Research Unit (PHRU), Soweto Matlosana Collaborating Centre for HIV/AIDS and TB, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa.
Johns Hopkins University Centre for TB Research, Baltimore, MarylandUSA.

Jaya George (J)

Department of Chemical Pathology, School of Pathology, Faculty of Health Sciences, University of The Witwatersrand and National Health Laboratory Service, Johannesburg, South Africa.

Melinda Suchard (M)

Center for Vaccines and Immunology, National Institute for 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 and National Health Laboratory Service, Johannesburg, South Africa.

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