Plasma kynurenine-to-tryptophan ratio, a highly sensitive blood-based diagnostic tool for Tuberculosis in HIV-infected pregnant women
Clement Adu-Gyamfi1, 2, Dana Savulescu2, Lillian Mikhathani1, Kennedy Otwombe3,5, Nicole Salazar-Austin,4,6, Neil Martinson3, 4, Jaya George2 & Melinda Suchard1, 2
1Centre for Vaccines & Immunology, National Institute for Communicable Diseases, a division of the National Health Laboratory Service, Johannesburg, South Africa. 2Department of Chemical Pathology, School of Pathology, Faculty of Health Sciences, University of The Witwatersrand & National Health Laboratory Service, Johannesburg, South Africa.
3Perinatal Health Research Unit (PHRU), Soweto Matlosana Collaborating Centre for HIV/AIDS and TB, University of The Witwatersrand, Johannesburg, South Africa. 4Johns Hopkins University Centre for TB Research, Baltimore, USA. 5School of Public Health, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg. 6Johns Hopkins School of Medicine, Baltimore, USA.
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 disease among HIV-infected pregnant women.
Methods: Using an enzyme-linked immunosorbent assay (ELISA), we measured K/T ratio in 72 HIV-infected pregnant women with active TB and 117 HIV-infected pregnant women 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 < 0.0001). Pregnant women who had received isoniazid preventive therapy (IPT) before enrolment had decreased plasma K/T ratio compared to those who had not received IPT (p = 0.0174). Plasma K/T ratio was elevated at the time TB diagnosis compared to those without TB (p < 0·0001). Using a cut-off of 0.100, plasma K/T ratio gave a diagnostic sensitivity of 94% (CI 82-95), specificity of 90% (CI 80-91), PPV 85% and NPV 98%. A receiver operating characteristic curve (ROC) gave an area under the curve of 0.95 (CI 0.92-0.97, p < 0.0001).
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.