Potential value of urine lateral-flow lipoarabinomannan (LAM) test for diagnosing tuberculosis among severely acute malnourished children
Tuberculosis (TB) is a serious co-morbidity among children with severe acute malnutrition (SAM) and TB diagnosis remains particularly challenging in the very young. We explored whether, in a low HIV-prevalence setting, the detection of mycobacterial lipoarabinomannan (LAM) antigen in urine may assis...
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creator | Schramm, Birgit Nganaboy, Rodrigue C Uwiragiye, Piex Mukeba, Didier Abdoubara, Aboubacar Abdou, Illa Nshimiymana, Jean-Claude Sounna, Seyni Hiffler, Laurent Flevaud, Laurence Huerga, Helena |
description | Tuberculosis (TB) is a serious co-morbidity among children with severe acute malnutrition (SAM) and TB diagnosis remains particularly challenging in the very young. We explored whether, in a low HIV-prevalence setting, the detection of mycobacterial lipoarabinomannan (LAM) antigen in urine may assist TB diagnosis in SAM children, a pediatric population currently not included in LAM-testing recommendations. To that end, we assessed LAM test-positivity among SAM children with and without signs or symptoms of TB.
A cross-sectional assessment (February 2016-August 2017) included children |
doi_str_mv | 10.1371/journal.pone.0250933 |
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A cross-sectional assessment (February 2016-August 2017) included children <5 years with SAM from an Intensive-Therapeutic-Feeding-Centre in Madaoua, Niger. Group 1: children with signs or symptoms suggestive of TB. Group 2: children without any sign or symptom of TB. Urine-specimens were subjected to DetermineTM TB-LAM lateral-flow-test (using a 4-grade intensity scale for positives). LAM-results were used for study purposes and not for patient management. Programmatic TB-diagnosis was primarily based on patients' clinical symptoms and TB contact history with no systematic access to X-ray or microbiological reference testing.
102 (Group 1) and 100 children (Group 2) were included (median age 18 months, 59.4% male, 1.0% HIV-positive). In Group 1, 22 (21.6%) children were started on TB-treatment (probable TB) and none of the children in Group 2. LAM-positivity was 52.0% (53/102) and 37.0% (37/100) in Group 1 and 2, respectively. Low-intensity (Grade 1) LAM test-positivity was similarly high in both Groups (37.3% and 36.0%, respectively), while Grade 2 or 3-positives were mainly detected in Group 1 (Group 1: 14.7%, Group 2: 1.0%, p<0.001). When considering only Grades >1 as positive, LAM-testing detected 22.7% (95%CI: 7.8, 45.4) among probable TB cases, while 99% (95%CI: 94.6, 99.9) of unlikely TB cases (Group 2) tested negative.
These findings suggest the potential utility of LAM urine testing in HIV-negative children with SAM. Determine LAM-positivity with Grades >1 may identify HIV-negative SAM children that are eligible for rapid TB-treatment initiation, though low-intensity (Grade 1) LAM-positive results may not be helpful in this way. Further studies in this specific pediatric population are warranted, including evaluations of new generation LAM tests.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0250933</identifier><identifier>PMID: 33951082</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Antigens ; Biology and Life Sciences ; Children ; Children & youth ; Diagnosis ; Diagnostic systems ; Diseases ; Editing ; Fever ; Health aspects ; HIV ; Hospitalization ; Human immunodeficiency virus ; Laboratories ; Malnutrition ; Malnutrition in children ; Medical diagnosis ; Medicine and Health Sciences ; Methodology ; Morbidity ; Pediatrics ; People and Places ; Pneumonia ; Radiography ; Reviews ; Software ; Tuberculosis ; Urine</subject><ispartof>PloS one, 2021-05, Vol.16 (5), p.e0250933-e0250933</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Schramm et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 Schramm et al 2021 Schramm et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c554t-a7a15f82698b85295f5fc920287fed6985dd75ead7c7923f4d747d6f48374ef43</citedby><cites>FETCH-LOGICAL-c554t-a7a15f82698b85295f5fc920287fed6985dd75ead7c7923f4d747d6f48374ef43</cites><orcidid>0000-0001-8316-9896</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099085/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099085/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33951082$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schramm, Birgit</creatorcontrib><creatorcontrib>Nganaboy, Rodrigue C</creatorcontrib><creatorcontrib>Uwiragiye, Piex</creatorcontrib><creatorcontrib>Mukeba, Didier</creatorcontrib><creatorcontrib>Abdoubara, Aboubacar</creatorcontrib><creatorcontrib>Abdou, Illa</creatorcontrib><creatorcontrib>Nshimiymana, Jean-Claude</creatorcontrib><creatorcontrib>Sounna, Seyni</creatorcontrib><creatorcontrib>Hiffler, Laurent</creatorcontrib><creatorcontrib>Flevaud, Laurence</creatorcontrib><creatorcontrib>Huerga, Helena</creatorcontrib><title>Potential value of urine lateral-flow lipoarabinomannan (LAM) test for diagnosing tuberculosis among severely acute malnourished children</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Tuberculosis (TB) is a serious co-morbidity among children with severe acute malnutrition (SAM) and TB diagnosis remains particularly challenging in the very young. We explored whether, in a low HIV-prevalence setting, the detection of mycobacterial lipoarabinomannan (LAM) antigen in urine may assist TB diagnosis in SAM children, a pediatric population currently not included in LAM-testing recommendations. To that end, we assessed LAM test-positivity among SAM children with and without signs or symptoms of TB.
A cross-sectional assessment (February 2016-August 2017) included children <5 years with SAM from an Intensive-Therapeutic-Feeding-Centre in Madaoua, Niger. Group 1: children with signs or symptoms suggestive of TB. Group 2: children without any sign or symptom of TB. Urine-specimens were subjected to DetermineTM TB-LAM lateral-flow-test (using a 4-grade intensity scale for positives). LAM-results were used for study purposes and not for patient management. Programmatic TB-diagnosis was primarily based on patients' clinical symptoms and TB contact history with no systematic access to X-ray or microbiological reference testing.
102 (Group 1) and 100 children (Group 2) were included (median age 18 months, 59.4% male, 1.0% HIV-positive). In Group 1, 22 (21.6%) children were started on TB-treatment (probable TB) and none of the children in Group 2. LAM-positivity was 52.0% (53/102) and 37.0% (37/100) in Group 1 and 2, respectively. Low-intensity (Grade 1) LAM test-positivity was similarly high in both Groups (37.3% and 36.0%, respectively), while Grade 2 or 3-positives were mainly detected in Group 1 (Group 1: 14.7%, Group 2: 1.0%, p<0.001). When considering only Grades >1 as positive, LAM-testing detected 22.7% (95%CI: 7.8, 45.4) among probable TB cases, while 99% (95%CI: 94.6, 99.9) of unlikely TB cases (Group 2) tested negative.
These findings suggest the potential utility of LAM urine testing in HIV-negative children with SAM. Determine LAM-positivity with Grades >1 may identify HIV-negative SAM children that are eligible for rapid TB-treatment initiation, though low-intensity (Grade 1) LAM-positive results may not be helpful in this way. Further studies in this specific pediatric population are warranted, including evaluations of new generation LAM tests.</description><subject>Antigens</subject><subject>Biology and Life Sciences</subject><subject>Children</subject><subject>Children & youth</subject><subject>Diagnosis</subject><subject>Diagnostic systems</subject><subject>Diseases</subject><subject>Editing</subject><subject>Fever</subject><subject>Health aspects</subject><subject>HIV</subject><subject>Hospitalization</subject><subject>Human immunodeficiency virus</subject><subject>Laboratories</subject><subject>Malnutrition</subject><subject>Malnutrition in children</subject><subject>Medical diagnosis</subject><subject>Medicine and Health Sciences</subject><subject>Methodology</subject><subject>Morbidity</subject><subject>Pediatrics</subject><subject>People and Places</subject><subject>Pneumonia</subject><subject>Radiography</subject><subject>Reviews</subject><subject>Software</subject><subject>Tuberculosis</subject><subject>Urine</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptUstuEzEUHSEQLYU_QGCJTVkkePwY2xukqOJRKQgWsLY84-vEkccOnpmgfgJ_jUOmVYtY2b4-99xzj05VvazxsqaifrdLU44mLPcpwhITjhWlj6rzWlGyaAimj-_dz6pnw7DDmFPZNE-rM0oVr7Ek59Xvb2mEOHoT0MGECVByaMo-AgpmhGzCwoX0CwW_Tyab1sfUmxhNRJfr1Ze3aIRhRC5lZL3ZxDT4uEHj1ELuplBeAzJ9KqUBDpAh3CDTTSOg3oRY1PthCxZ1Wx9shvi8euJMGODFfF5UPz5--H71ebH--un6arVedJyzcWGEqbmTpFGylZwo7rjrFMFECge2VLm1goOxohOKUMesYMI2jkkqGDhGL6rXJ959UahnFwdNOCFUsho3BXF9QthkdnqffW_yjU7G67-FlDfa5NF3ATRRzEkJtJYKGCa0Jcy0VrGGC9UAbgvX-3na1PZgu-J1MfUB6cOf6Ld6kw5aYqWw5IXgcibI6edU7Na9HzoIwURI00l3U0tGjrrf_AP9_3YzamPKAj66VOZ2R1K9ahospGgkKSh2QnU5DUMGdye5xvqYv1tufcyfnvNX2l7dX_eu6TZw9A-rR9o9</recordid><startdate>20210505</startdate><enddate>20210505</enddate><creator>Schramm, 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value of urine lateral-flow lipoarabinomannan (LAM) test for diagnosing tuberculosis among severely acute malnourished children</title><author>Schramm, Birgit ; Nganaboy, Rodrigue C ; Uwiragiye, Piex ; Mukeba, Didier ; Abdoubara, Aboubacar ; Abdou, Illa ; Nshimiymana, Jean-Claude ; Sounna, Seyni ; Hiffler, Laurent ; Flevaud, Laurence ; Huerga, Helena</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c554t-a7a15f82698b85295f5fc920287fed6985dd75ead7c7923f4d747d6f48374ef43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antigens</topic><topic>Biology and Life Sciences</topic><topic>Children</topic><topic>Children & youth</topic><topic>Diagnosis</topic><topic>Diagnostic systems</topic><topic>Diseases</topic><topic>Editing</topic><topic>Fever</topic><topic>Health aspects</topic><topic>HIV</topic><topic>Hospitalization</topic><topic>Human immunodeficiency virus</topic><topic>Laboratories</topic><topic>Malnutrition</topic><topic>Malnutrition in children</topic><topic>Medical diagnosis</topic><topic>Medicine and Health Sciences</topic><topic>Methodology</topic><topic>Morbidity</topic><topic>Pediatrics</topic><topic>People and Places</topic><topic>Pneumonia</topic><topic>Radiography</topic><topic>Reviews</topic><topic>Software</topic><topic>Tuberculosis</topic><topic>Urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schramm, Birgit</creatorcontrib><creatorcontrib>Nganaboy, Rodrigue C</creatorcontrib><creatorcontrib>Uwiragiye, Piex</creatorcontrib><creatorcontrib>Mukeba, Didier</creatorcontrib><creatorcontrib>Abdoubara, Aboubacar</creatorcontrib><creatorcontrib>Abdou, Illa</creatorcontrib><creatorcontrib>Nshimiymana, Jean-Claude</creatorcontrib><creatorcontrib>Sounna, Seyni</creatorcontrib><creatorcontrib>Hiffler, Laurent</creatorcontrib><creatorcontrib>Flevaud, 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Didier</au><au>Abdoubara, Aboubacar</au><au>Abdou, Illa</au><au>Nshimiymana, Jean-Claude</au><au>Sounna, Seyni</au><au>Hiffler, Laurent</au><au>Flevaud, Laurence</au><au>Huerga, Helena</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Potential value of urine lateral-flow lipoarabinomannan (LAM) test for diagnosing tuberculosis among severely acute malnourished children</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2021-05-05</date><risdate>2021</risdate><volume>16</volume><issue>5</issue><spage>e0250933</spage><epage>e0250933</epage><pages>e0250933-e0250933</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Tuberculosis (TB) is a serious co-morbidity among children with severe acute malnutrition (SAM) and TB diagnosis remains particularly challenging in the very young. We explored whether, in a low HIV-prevalence setting, the detection of mycobacterial lipoarabinomannan (LAM) antigen in urine may assist TB diagnosis in SAM children, a pediatric population currently not included in LAM-testing recommendations. To that end, we assessed LAM test-positivity among SAM children with and without signs or symptoms of TB.
A cross-sectional assessment (February 2016-August 2017) included children <5 years with SAM from an Intensive-Therapeutic-Feeding-Centre in Madaoua, Niger. Group 1: children with signs or symptoms suggestive of TB. Group 2: children without any sign or symptom of TB. Urine-specimens were subjected to DetermineTM TB-LAM lateral-flow-test (using a 4-grade intensity scale for positives). LAM-results were used for study purposes and not for patient management. Programmatic TB-diagnosis was primarily based on patients' clinical symptoms and TB contact history with no systematic access to X-ray or microbiological reference testing.
102 (Group 1) and 100 children (Group 2) were included (median age 18 months, 59.4% male, 1.0% HIV-positive). In Group 1, 22 (21.6%) children were started on TB-treatment (probable TB) and none of the children in Group 2. LAM-positivity was 52.0% (53/102) and 37.0% (37/100) in Group 1 and 2, respectively. Low-intensity (Grade 1) LAM test-positivity was similarly high in both Groups (37.3% and 36.0%, respectively), while Grade 2 or 3-positives were mainly detected in Group 1 (Group 1: 14.7%, Group 2: 1.0%, p<0.001). When considering only Grades >1 as positive, LAM-testing detected 22.7% (95%CI: 7.8, 45.4) among probable TB cases, while 99% (95%CI: 94.6, 99.9) of unlikely TB cases (Group 2) tested negative.
These findings suggest the potential utility of LAM urine testing in HIV-negative children with SAM. Determine LAM-positivity with Grades >1 may identify HIV-negative SAM children that are eligible for rapid TB-treatment initiation, though low-intensity (Grade 1) LAM-positive results may not be helpful in this way. Further studies in this specific pediatric population are warranted, including evaluations of new generation LAM tests.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33951082</pmid><doi>10.1371/journal.pone.0250933</doi><orcidid>https://orcid.org/0000-0001-8316-9896</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Antigens Biology and Life Sciences Children Children & youth Diagnosis Diagnostic systems Diseases Editing Fever Health aspects HIV Hospitalization Human immunodeficiency virus Laboratories Malnutrition Malnutrition in children Medical diagnosis Medicine and Health Sciences Methodology Morbidity Pediatrics People and Places Pneumonia Radiography Reviews Software Tuberculosis Urine |
title | Potential value of urine lateral-flow lipoarabinomannan (LAM) test for diagnosing tuberculosis among severely acute malnourished children |
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