Author:
Magni Ruben,Rruga Fatlum,Alsaab Fahad M.,Sharif Sara,Howard Marissa,Espina Virginia,Kim Brianna,Lepene Benjamin,Lee Gwenyth,Alayouni Mohamad A.,Steinberg Hannah,Araujo Robyn,Kashanchi Fatah,Riccardi Fabio,Morreira Sargento,Araujo Antonia,Poli Fernando,Jaganath Devan,Semitala Fred C.,Worodria William,Andama Alfred,Choudhary Alok,Honnen William J.,Petricoin Emanuel F.,Cattamanchi Adithya,Colombatti Raffaella,de Waard Jacobus H.,Oberhelman Richard,Pinter Abraham,Gilman Robert H.,Liotta Lance A.,Luchini Alessandra
Abstract
AbstractAn accurate urine test for diverse populations with active tuberculosis could be transformative for preventing TB deaths. Urinary liporabinomannan (LAM) testing has been previously restricted to HIV co-infected TB patients. In this study we evaluate urinary LAM in HIV negative, pediatric and adult, pulmonary and extrapulmonary tuberculosis patients. We measured 430 microbiologically confirmed pretreatment tuberculosis patients and controls from Peru, Guinea Bissau, Venezuela, Uganda and the United States using three monoclonal antibodies, MoAb1, CS35, and A194, which recognize distinct LAM epitopes, a one-sided immunoassay, and blinded cohorts. We evaluated sources of assay variability and comorbidities (HIV and diabetes). All antibodies successfully discriminated TB positive from TB negative patients. ROAUC from the average of three antibodies’ responses was 0.90; 95% CI 0.87–0.93, 90% sensitivity, 73.5% specificity (80 pg/mL). MoAb1, recognizing the 5-methylthio-d-xylofuranose(MTX)-mannose(Man) cap epitope, performed the best, was less influenced by glycosuria and identified culture positive pediatric (N = 19) and extrapulmonary (N = 24) patients with high accuracy (ROAUC 0.87, 95% CI 0.77–0.98, 0.90 sensitivity 0.80 specificity at 80 pg/mL; ROAUC = 0.96, 95% CI 0.92–0.99, 96% sensitivity, 80% specificity at 82 pg/mL, respectively). The MoAb1 antibody, recognizing the MTX-Man cap epitope, is a novel analyte for active TB detection in pediatric and extrapulmonary disease.
Funder
National Institute of Allergy and Infectious Diseases
Bill and Melinda Gates Foundation Global Health Program
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Publisher
Springer Science and Business Media LLC