{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T11:30:13Z","timestamp":1783078213333,"version":"3.54.6"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,3,8]],"date-time":"2019-03-08T00:00:00Z","timestamp":1552003200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,3,8]],"date-time":"2019-03-08T00:00:00Z","timestamp":1552003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The aim of this study was to test the use of IP-10 detection in dried plasma from contact studies individuals (contacts of smear positive patients), by comparing it with IP-10 and IFN-\u03b3 detection in direct plasma, to establish IP-10 detection in DPS as a useful assay for LTBI diagnosis. Whole blood samples were collected from 80 subjects: 12 with active tuberculosis (TB), and 68 from contact studies. The amount of IFN-\u03b3 produced by sensitized T cells was determined in direct plasma by QuantiFERON Gold In-Tube test. IP-10 levels were determined in direct and dried plasma by an <jats:italic>in-house<\/jats:italic> ELISA. For dried plasma IP-10 determination, two 25\u2009\u00b5l plasma drops were dried in Whatman903 filter paper and sent by mail to the laboratory. Regarding TB patients, 100.0%, 91.7% and 75.0% were positive for IFN-\u03b3 detection and IP-10 detection in direct and dried plasma, respectively. In contacts, 69.1%, 60.3% and 48.5% had positive results after IFN-\u03b3 and IP-10 in direct and dried plasma, respectively. The agreement among <jats:italic>in vitro<\/jats:italic> tests was substantial and IP-10 levels in direct and dried plasma were strongly correlated (r\u2009=\u20090.897). In conclusion, IP-10 detection in dried plasma is a simple and safe method that would help improve LTBI management.<\/jats:p>","DOI":"10.1038\/s41598-019-40778-1","type":"journal-article","created":{"date-parts":[[2019,3,8]],"date-time":"2019-03-08T11:03:45Z","timestamp":1552043025000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Use of IP-10 detection in dried plasma spots for latent tuberculosis infection diagnosis in contacts via mail"],"prefix":"10.1038","volume":"9","author":[{"given":"R.","family":"Villar-Hern\u00e1ndez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Latorre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. L.","family":"De Souza-Galv\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. A.","family":"Jim\u00e9nez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Ruiz-Manzano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Pilarte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Garc\u00eda-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Muriel-Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Cantos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Altet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. P.","family":"Millet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Gonz\u00e1lez-D\u00edaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Molina-Pinargote","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Prat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1597-441X","authenticated-orcid":false,"given":"M.","family":"Ruhwald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Dom\u00ednguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,3,8]]},"reference":[{"key":"40778_CR1","first-page":"460","volume":"10","author":"C Dye","year":"2006","unstructured":"Dye, C., Maher, D., Weil, D., Espinal, M. & Raviglione, M. Targets for global tuberculosis control. Int J Tuberc Lung Dis 10, 460\u2013462 (2006).","journal-title":"Int J Tuberc Lung Dis"},{"key":"40778_CR2","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1093\/clinids\/17.6.968","volume":"17","author":"RE Huebner","year":"1993","unstructured":"Huebner, R. E., Schein, M. F. & Bass, J. B. Jr. The tuberculin skin test. Clin Infect Dis 17, 968\u2013975 (1993).","journal-title":"Clin Infect Dis"},{"key":"40778_CR3","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-10-348","volume":"10","author":"I Latorre","year":"2010","unstructured":"Latorre, I. et al. IFN-gamma response on T-cell based assays in HIV-infected patients for detection of tuberculosis infection. BMC Infect Dis 10, 348, https:\/\/doi.org\/10.1186\/1471-2334-10-348 (2010).","journal-title":"BMC Infect Dis"},{"key":"40778_CR4","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1513\/AnnalsATS.201408-394OC","volume":"12","author":"N Altet","year":"2015","unstructured":"Altet, N. et al. Predicting the Development of Tuberculosis with the Tuberculin Skin Test and QuantiFERON Testing. Annals of the American Thoracic. Society 12, 680\u2013688, https:\/\/doi.org\/10.1513\/AnnalsATS.201408-394OC (2015).","journal-title":"Society"},{"key":"40778_CR5","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.diagmicrobio.2009.07.015","volume":"65","author":"I Latorre","year":"2009","unstructured":"Latorre, I. et al. Quantitative evaluation of T-cell response after specific antigen stimulation in active and latent tuberculosis infection in adults and children. Diagnostic microbiology and infectious disease 65, 236\u2013246, https:\/\/doi.org\/10.1016\/j.diagmicrobio.2009.07.015 (2009).","journal-title":"Diagnostic microbiology and infectious disease"},{"key":"40778_CR6","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1164\/rccm.201502-0232OC","volume":"191","author":"JP Zellweger","year":"2015","unstructured":"Zellweger, J. P. et al. Risk Assessment of Tuberculosis in Contacts by IFN-gamma Release Assays. A Tuberculosis Network European Trials Group Study. Am J Respir Crit Care Med 191, 1176\u20131184, https:\/\/doi.org\/10.1164\/rccm.201502-0232OC (2015).","journal-title":"Am J Respir Crit Care Med"},{"key":"40778_CR7","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1016\/S0140-6736(06)68579-6","volume":"367","author":"G Ferrara","year":"2006","unstructured":"Ferrara, G. et al. Use in routine clinical practice of two commercial blood tests for diagnosis of infection with Mycobacterium tuberculosis: a prospective study. Lancet 367, 1328\u20131334, https:\/\/doi.org\/10.1016\/S0140-6736(06)68579-6 (2006).","journal-title":"Lancet"},{"key":"40778_CR8","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1183\/09031936.00151413","volume":"43","author":"NN Chegou","year":"2014","unstructured":"Chegou, N. N., Heyckendorf, J., Walzl, G., Lange, C. & Ruhwald, M. Beyond the IFN-gamma horizon: biomarkers for immunodiagnosis of infection with Mycobacterium tuberculosis. The European respiratory journal 43, 1472\u20131486, https:\/\/doi.org\/10.1183\/09031936.00151413 (2014).","journal-title":"The European respiratory journal"},{"key":"40778_CR9","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1586\/erm.11.97","volume":"12","author":"M Ruhwald","year":"2012","unstructured":"Ruhwald, M., Aabye, M. G. & Ravn, P. IP-10 release assays in the diagnosis of tuberculosis infection: current status and future directions. Expert Rev Mol Diagn 12, 175\u2013187, https:\/\/doi.org\/10.1586\/erm.11.97 (2012).","journal-title":"Expert Rev Mol Diagn"},{"key":"40778_CR10","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-2-19","volume":"2","author":"M Ruhwald","year":"2009","unstructured":"Ruhwald, M., Bjerregaard-Andersen, M., Rabna, P., Eugen-Olsen, J. & Ravn, P. IP-10, MCP-1, MCP-2, MCP-3, and IL-1RA hold promise as biomarkers for infection with M. tuberculosis in a whole blood based T-cell assay. BMC Res Notes 2, 19, https:\/\/doi.org\/10.1186\/1756-0500-2-19 (2009).","journal-title":"BMC Res Notes"},{"key":"40778_CR11","doi-asserted-by":"publisher","first-page":"177","DOI":"10.2217\/BMM.12.13","volume":"6","author":"VO Kasprowicz","year":"2012","unstructured":"Kasprowicz, V. O., Halliday, J. S., Mitchell, J. & Klenerman, P. MIGRAs: are they the new IGRAs? Development of monokine-amplified IFN-gamma release assays. Biomark Med 6, 177\u2013186, https:\/\/doi.org\/10.2217\/BMM.12.13 (2012).","journal-title":"Biomark Med"},{"key":"40778_CR12","first-page":"731","volume":"13","author":"J Lighter","year":"2009","unstructured":"Lighter, J., Rigaud, M., Huie, M., Peng, C. H. & Pollack, H. Chemokine IP-10: an adjunct marker for latent tuberculosis infection in children. Int J Tuberc Lung Dis 13, 731\u2013736 (2009).","journal-title":"Int J Tuberc Lung Dis"},{"key":"40778_CR13","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1183\/09031936.00039010","volume":"36","author":"MG Aabye","year":"2010","unstructured":"Aabye, M. G. et al. Potential of interferon-gamma-inducible protein 10 in improving tuberculosis diagnosis in HIV-infected patients. The European respiratory journal 36, 1488\u20131490, https:\/\/doi.org\/10.1183\/09031936.00039010 (2010).","journal-title":"The European respiratory journal"},{"key":"40778_CR14","doi-asserted-by":"publisher","first-page":"256","DOI":"10.3109\/00365548.2011.632644","volume":"44","author":"N Alsleben","year":"2012","unstructured":"Alsleben, N. et al. Interferon-gamma inducible protein 10 as a biomarker for active tuberculosis and latent tuberculosis infection in children: a case-control study. Scand J Infect Dis 44, 256\u2013262, https:\/\/doi.org\/10.3109\/00365548.2011.632644 (2012).","journal-title":"Scand J Infect Dis"},{"key":"40778_CR15","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.jinf.2012.03.017","volume":"65","author":"V Vanini","year":"2012","unstructured":"Vanini, V. et al. IP-10 is an additional marker for tuberculosis (TB) detection in HIV-infected persons in a low-TB endemic country. J Infect 65, 49\u201359, https:\/\/doi.org\/10.1016\/j.jinf.2012.03.017 (2012).","journal-title":"J Infect"},{"key":"40778_CR16","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1016\/j.jinf.2014.06.013","volume":"69","author":"I Latorre","year":"2014","unstructured":"Latorre, I. et al. IP-10 is an accurate biomarker for the diagnosis of tuberculosis in children. J Infect 69, 590\u2013599, https:\/\/doi.org\/10.1016\/j.jinf.2014.06.013 (2014).","journal-title":"J Infect"},{"key":"40778_CR17","doi-asserted-by":"publisher","unstructured":"Villar-Hernandez, R. et al. Use of IFN-\u03b3 and IP-10 detection in the diagnosis of latent tuberculosis infection in patients with inflammatory rheumatic diseases. Journal of Infection, https:\/\/doi.org\/10.1016\/j.jinf.2017.07.004 (2017).","DOI":"10.1016\/j.jinf.2017.07.004"},{"key":"40778_CR18","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1183\/09031936.00129412","volume":"42","author":"MG Aabye","year":"2013","unstructured":"Aabye, M. G. et al. Dried plasma spots in the diagnosis of tuberculosis: IP-10 release assay on filter paper. The European respiratory journal 42, 495\u2013503, https:\/\/doi.org\/10.1183\/09031936.00129412 (2013).","journal-title":"The European respiratory journal"},{"key":"40778_CR19","doi-asserted-by":"publisher","first-page":"9223","DOI":"10.1038\/srep09223","volume":"5","author":"K Tonby","year":"2015","unstructured":"Tonby, K., Ruhwald, M., Kvale, D. & Dyrhol-Riise, A. M. IP-10 measured by Dry Plasma Spots as biomarker for therapy responses in Mycobacterium tuberculosis. infection. Scientific reports 5, 9223, https:\/\/doi.org\/10.1038\/srep09223 (2015).","journal-title":"infection. Scientific reports"},{"key":"40778_CR20","doi-asserted-by":"publisher","first-page":"e105628","DOI":"10.1371\/journal.pone.0105628","volume":"9","author":"T Blauenfeldt","year":"2014","unstructured":"Blauenfeldt, T. et al. Development of a one-step probe based molecular assay for rapid immunodiagnosis of infection with M. tuberculosis using dried blood spots. PloS one 9, e105628, https:\/\/doi.org\/10.1371\/journal.pone.0105628 (2014).","journal-title":"PloS one"},{"key":"40778_CR21","doi-asserted-by":"publisher","first-page":"e39228","DOI":"10.1371\/journal.pone.0039228","volume":"7","author":"MG Aabye","year":"2012","unstructured":"Aabye, M. G. et al. A simple method to quantitate IP-10 in dried blood and plasma spots. PloS one 7, e39228, https:\/\/doi.org\/10.1371\/journal.pone.0039228 (2012).","journal-title":"PloS one"},{"key":"40778_CR22","doi-asserted-by":"publisher","unstructured":"Tuuminen, T., Salo, E., Kotilainen, H. & Ruhwald, M. Evaluation of the filter paper IP-10 tests in school children after exposure to tuberculosis: a prospective cohort study with a 4-year follow-up. BMJ open 2, https:\/\/doi.org\/10.1136\/bmjopen-2012-001751 (2012).","DOI":"10.1136\/bmjopen-2012-001751"},{"key":"40778_CR23","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/j.tube.2011.01.001","volume":"91","author":"M Ruhwald","year":"2011","unstructured":"Ruhwald, M. et al. A multicentre evaluation of the accuracy and performance of IP-10 for the diagnosis of infection with M. tuberculosis. Tuberculosis (Edinb) 91, 260\u2013267, https:\/\/doi.org\/10.1016\/j.tube.2011.01.001 (2011).","journal-title":"Tuberculosis (Edinb)"},{"key":"40778_CR24","doi-asserted-by":"publisher","first-page":"e23733","DOI":"10.1371\/journal.pone.0023733","volume":"6","author":"MA Yassin","year":"2011","unstructured":"Yassin, M. A. et al. Can interferon-gamma or interferon-gamma-induced-protein-10 differentiate tuberculosis infection and disease in children of high endemic areas? PloS one 6, e23733, https:\/\/doi.org\/10.1371\/journal.pone.0023733 (2011).","journal-title":"PloS one"},{"key":"40778_CR25","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.diagmicrobio.2011.07.012","volume":"71","author":"BS Kabeer","year":"2011","unstructured":"Kabeer, B. S., Sikhamani, R. & Raja, A. Comparison of interferon gamma-inducible protein-10 and interferon gamma-based QuantiFERON TB Gold assays with tuberculin skin test in HIV-infected subjects. Diagnostic microbiology and infectious disease 71, 236\u2013243, https:\/\/doi.org\/10.1016\/j.diagmicrobio.2011.07.012 (2011).","journal-title":"Diagnostic microbiology and infectious disease"},{"key":"40778_CR26","doi-asserted-by":"publisher","first-page":"e51338","DOI":"10.1371\/journal.pone.0051338","volume":"7","author":"S Wang","year":"2012","unstructured":"Wang, S. et al. Evaluation of the diagnostic potential of IP-10 and IL-2 as biomarkers for the diagnosis of active and latent tuberculosis in a BCG-vaccinated population. PloS one 7, e51338, https:\/\/doi.org\/10.1371\/journal.pone.0051338 (2012).","journal-title":"PloS one"},{"key":"40778_CR27","doi-asserted-by":"publisher","first-page":"e0146098","DOI":"10.1371\/journal.pone.0146098","volume":"11","author":"IA Biraro","year":"2016","unstructured":"Biraro, I. A. et al. The Use of Interferon Gamma Inducible Protein 10 as a Potential Biomarker in the Diagnosis of Latent Tuberculosis Infection in Uganda. PloS one 11, e0146098, https:\/\/doi.org\/10.1371\/journal.pone.0146098 (2016).","journal-title":"PloS one"},{"key":"40778_CR28","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1183\/09031936.00196608","volume":"35","author":"I Latorre","year":"2010","unstructured":"Latorre, I. et al. Evaluating the non-tuberculous mycobacteria effect in the tuberculosis infection diagnosis. The European respiratory journal 35, 338\u2013342, https:\/\/doi.org\/10.1183\/09031936.00196608 (2010).","journal-title":"The European respiratory journal"},{"key":"40778_CR29","first-page":"1015","volume":"7","author":"CB Beggs","year":"2003","unstructured":"Beggs, C. B., Noakes, C. J., Sleigh, P. A., Fletcher, L. A. & Siddiqi, K. The transmission of tuberculosis in confined spaces: an analytical review of alternative epidemiological models. Int J Tuberc Lung Dis 7, 1015\u20131026 (2003).","journal-title":"Int J Tuberc Lung Dis"},{"issue":"Suppl 4","key":"40778_CR30","first-page":"221","volume":"36","author":"S Tornee","year":"2005","unstructured":"Tornee, S. et al. The association between environmental factors and tuberculosis infection among household contacts. The Southeast Asian journal of tropical medicine and public health 36(Suppl 4), 221\u2013224 (2005).","journal-title":"The Southeast Asian journal of tropical medicine and public health"},{"key":"40778_CR31","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.arbres.2010.02.010","volume":"46","author":"J Gonzalez-Martin","year":"2010","unstructured":"Gonzalez-Martin, J. et al. Consensus document on the diagnosis, treatment and prevention of tuberculosis. Arch Bronconeumol 46, 255\u2013274, https:\/\/doi.org\/10.1016\/j.arbres.2010.02.010 (2010).","journal-title":"Arch Bronconeumol"},{"key":"40778_CR32","doi-asserted-by":"publisher","first-page":"276","DOI":"10.11613\/BM.2012.031","volume":"22","author":"ML McHugh","year":"2012","unstructured":"McHugh, M. L. Interrater reliability: the kappa statistic. Biochemia medica 22, 276\u2013282 (2012).","journal-title":"Biochemia medica"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40778-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40778-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40778-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T07:15:58Z","timestamp":1671261358000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40778-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,8]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["40778"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-40778-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,8]]},"assertion":[{"value":"12 June 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 February 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 March 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"3943"}}