Universidad Peruana Cayetano Heredia

Urine lipoarabinomannan glycan in HIV-negative patients with pulmonary tuberculosis correlates with disease severity

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dc.contributor.author Paris, Luisa
dc.contributor.author Magni, Ruben
dc.contributor.author Zaidi, Fatima
dc.contributor.author Araujo, Robyn
dc.contributor.author Saini, Neal
dc.contributor.author Harpole, Michael
dc.contributor.author Coronel, Jorge
dc.contributor.author Kirwan, Daniela E.
dc.contributor.author Steinberg, Hannah
dc.contributor.author Gilman, Robert Hugh
dc.contributor.author Petricoin, Emanuel F.
dc.contributor.author Nisini, Roberto
dc.contributor.author Luchini, Alessandra
dc.contributor.author Liotta, Lance
dc.date.accessioned 2019-01-25T16:20:55Z
dc.date.available 2019-01-25T16:20:55Z
dc.date.issued 2017
dc.identifier.uri https://hdl.handle.net/20.500.12866/4790
dc.description.abstract An accurate urine test for pulmonary tuberculosis (TB), affecting 9.6 million patients worldwide, is critically needed for surveillance and treatment management. Past attempts failed to reliably detect the mycobacterial glycan antigen lipoarabinomannan (LAM), a marker of active TB, in HIV-negative, pulmonary TB-infected patients' urine (85% of 9.6 million patients). We apply a copper complex dye within a hydrogel nanocage that captures LAM with very high affinity, displacing interfering urine proteins. The technology was applied to study pretreatment urine from 48 Peruvian patients, all negative for HIV, with microbiologically confirmed active pulmonary TB. LAM was quantitatively measured in the urine with a sensitivity of >95% and a specificity of >80% (n = 101) in a concentration range of 14 to 2000 picograms per milliliter, as compared to non-TB, healthy and diseased, age-matched controls (evaluated by receiver operating characteristic analysis; area under the curve, 0.95; 95% confidence interval, 0.9005 to 0.9957). Urinary LAM was elevated in patients with a higher mycobacterial burden (n = 42), a higher proportion of weight loss (n = 37), or cough (n = 50). The technology can be configured in a variety of formats to detect a panel of previously undetectable very-low-abundance TB urinary analytes. Eight of nine patients who were smear-negative and culture-positive for TB tested positive for urinary LAM. This technology has broad implications for pulmonary TB screening, transmission control, and treatment management for HIV-negative patients. en_US
dc.language.iso eng
dc.publisher American Association for the Advancement of Science
dc.relation.ispartofseries Science Translational Medicine
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Adult en_US
dc.subject Female en_US
dc.subject Humans en_US
dc.subject Male en_US
dc.subject Young Adult en_US
dc.subject Middle Aged en_US
dc.subject Case-Control Studies en_US
dc.subject Cost of Illness en_US
dc.subject Coloring Agents en_US
dc.subject Copper en_US
dc.subject Immunoassay en_US
dc.subject Linear Models en_US
dc.subject Reproducibility of Results en_US
dc.subject Biomarkers/metabolism en_US
dc.subject Severity of Illness Index en_US
dc.subject Cytokines/metabolism en_US
dc.subject Antibodies, Bacterial/metabolism en_US
dc.subject Antigens, Bacterial/metabolism en_US
dc.subject HIV Infections/complications/pathology/urine en_US
dc.subject Lipopolysaccharides/urine en_US
dc.subject Tuberculosis, Pulmonary/complications/microbiology/pathology/urine en_US
dc.title Urine lipoarabinomannan glycan in HIV-negative patients with pulmonary tuberculosis correlates with disease severity en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1126/scitranslmed.aal2807
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00
dc.relation.issn 1946-6242


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