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Optimizing the detection of recent tuberculosis infection in children in a high tuberculosis-HIV burden setting
Children who are young, malnourished, and infected with HIV have significant risk of tuberculosis (TB) morbidity and mortality following TB infection. Treatment of TB infection is hindered by poor detection and limited pediatric data. Identify improved testing to detect pediatric TB infection. This...
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Published in: | American journal of respiratory and critical care medicine 2015-04, Vol.191 (7), p.820-830 |
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container_title | American journal of respiratory and critical care medicine |
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creator | Mandalakas, Anna M Kirchner, H Lester Walzl, Gerhard Gie, Robert P Schaaf, H Simon Cotton, Mark F Grewal, Harleen M S Hesseling, Anneke C |
description | Children who are young, malnourished, and infected with HIV have significant risk of tuberculosis (TB) morbidity and mortality following TB infection. Treatment of TB infection is hindered by poor detection and limited pediatric data.
Identify improved testing to detect pediatric TB infection.
This was a prospective community-based study assessing use of the tuberculin skin test and IFN-γ release assays among children (n = 1,343; 6 mo to |
doi_str_mv | 10.1164/rccm.201406-1165OC |
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Identify improved testing to detect pediatric TB infection.
This was a prospective community-based study assessing use of the tuberculin skin test and IFN-γ release assays among children (n = 1,343; 6 mo to <15 yr) in TB-HIV high-burden settings; associations with child characteristics were measured.
Contact tracing detects TB in 8% of child contacts within 3 months of exposure. Among children with no documented contact, tuberculin skin test and QuantiFERON-TB Gold In-Tube positivity was greater than T-SPOT.TB. Nearly 8% of children had IFN-γ release assay positive and skin test negative discordance. In a model accounting for confounders, all tests correlate with TB contact, but IFN-γ release assays correlate better than the tuberculin skin test (P = 0.0011). Indeterminate IFN-γ release assay results were not associated with age. Indeterminate QuantiFERON-TB Gold In-Tube results were more frequent in children infected with HIV (4.7%) than uninfected with HIV (1.9%), whereas T-SPOT.TB indeterminates were rare (0.2%) and not affected by HIV status. Conversion and reversion were not associated with HIV status. Among children infected with HIV, tests correlated less with contact as malnutrition worsened.
Where resources allow, use of IFN-γ release assays should be considered in children who are young, recently exposed, and infected with HIV because they may offer advantages compared with the tuberculin skin test for identifying TB infection, and improve targeted, cost-effective delivery of preventive therapy. Affordable tests of infection could dramatically impact global TB control.</description><identifier>ISSN: 1073-449X</identifier><identifier>ISSN: 1535-4970</identifier><identifier>EISSN: 1535-4970</identifier><identifier>DOI: 10.1164/rccm.201406-1165OC</identifier><identifier>PMID: 25622087</identifier><language>eng</language><publisher>United States: American Thoracic Society</publisher><subject>Adolescent ; Child ; Child, Preschool ; Early Diagnosis ; Female ; HIV Infections - complications ; Humans ; Infant ; Interferon-gamma Release Tests ; Latent Tuberculosis - diagnosis ; Latent Tuberculosis - etiology ; Male ; Mass Screening - methods ; Mycobacterium tuberculosis ; Original ; Prospective Studies ; South Africa ; Tuberculin Test ; Tuberculosis, Pulmonary - diagnosis ; Tuberculosis, Pulmonary - etiology</subject><ispartof>American journal of respiratory and critical care medicine, 2015-04, Vol.191 (7), p.820-830</ispartof><rights>Copyright American Thoracic Society Apr 1, 2015</rights><rights>Copyright © 2015 by the American Thoracic Society 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c430t-60af4843755b4762c3430f75c19cfa3fbccef653946ec1c9555e74cd08ae83e43</citedby><cites>FETCH-LOGICAL-c430t-60af4843755b4762c3430f75c19cfa3fbccef653946ec1c9555e74cd08ae83e43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25622087$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mandalakas, Anna M</creatorcontrib><creatorcontrib>Kirchner, H Lester</creatorcontrib><creatorcontrib>Walzl, Gerhard</creatorcontrib><creatorcontrib>Gie, Robert P</creatorcontrib><creatorcontrib>Schaaf, H Simon</creatorcontrib><creatorcontrib>Cotton, Mark F</creatorcontrib><creatorcontrib>Grewal, Harleen M S</creatorcontrib><creatorcontrib>Hesseling, Anneke C</creatorcontrib><title>Optimizing the detection of recent tuberculosis infection in children in a high tuberculosis-HIV burden setting</title><title>American journal of respiratory and critical care medicine</title><addtitle>Am J Respir Crit Care Med</addtitle><description>Children who are young, malnourished, and infected with HIV have significant risk of tuberculosis (TB) morbidity and mortality following TB infection. Treatment of TB infection is hindered by poor detection and limited pediatric data.
Identify improved testing to detect pediatric TB infection.
This was a prospective community-based study assessing use of the tuberculin skin test and IFN-γ release assays among children (n = 1,343; 6 mo to <15 yr) in TB-HIV high-burden settings; associations with child characteristics were measured.
Contact tracing detects TB in 8% of child contacts within 3 months of exposure. Among children with no documented contact, tuberculin skin test and QuantiFERON-TB Gold In-Tube positivity was greater than T-SPOT.TB. Nearly 8% of children had IFN-γ release assay positive and skin test negative discordance. In a model accounting for confounders, all tests correlate with TB contact, but IFN-γ release assays correlate better than the tuberculin skin test (P = 0.0011). Indeterminate IFN-γ release assay results were not associated with age. Indeterminate QuantiFERON-TB Gold In-Tube results were more frequent in children infected with HIV (4.7%) than uninfected with HIV (1.9%), whereas T-SPOT.TB indeterminates were rare (0.2%) and not affected by HIV status. Conversion and reversion were not associated with HIV status. Among children infected with HIV, tests correlated less with contact as malnutrition worsened.
Where resources allow, use of IFN-γ release assays should be considered in children who are young, recently exposed, and infected with HIV because they may offer advantages compared with the tuberculin skin test for identifying TB infection, and improve targeted, cost-effective delivery of preventive therapy. Affordable tests of infection could dramatically impact global TB control.</description><subject>Adolescent</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Early Diagnosis</subject><subject>Female</subject><subject>HIV Infections - complications</subject><subject>Humans</subject><subject>Infant</subject><subject>Interferon-gamma Release Tests</subject><subject>Latent Tuberculosis - diagnosis</subject><subject>Latent Tuberculosis - etiology</subject><subject>Male</subject><subject>Mass Screening - methods</subject><subject>Mycobacterium tuberculosis</subject><subject>Original</subject><subject>Prospective Studies</subject><subject>South Africa</subject><subject>Tuberculin Test</subject><subject>Tuberculosis, Pulmonary - diagnosis</subject><subject>Tuberculosis, Pulmonary - etiology</subject><issn>1073-449X</issn><issn>1535-4970</issn><issn>1535-4970</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNpdkU2LFDEQhoMo7of-AQ8S8OKl16Tz2RdBBt1dWJiLireQTlems3R3xiQt6K8344yL66mKqqfe5OVF6BUlV5RK_i45N1-1hHIimzoQ280TdE4FEw3vFHlae6JYw3n37Qxd5HxPCG01Jc_RWStk2xKtzlHc7kuYw6-w7HAZAQ9QwJUQFxw9TuBgKbisPSS3TjGHjMPiT0BYsBvDNCT401s8ht34CG5ubr_ifk1DJTKUUh95gZ55O2V4eaqX6Munj583N83d9vp28-GucZyR0khiPdecKSF6rmTrWB17JRztnLfM986Bl4J1XIKjrhNCgOJuINqCZsDZJXp_1N2v_QzDwUeyk9mnMNv000QbzOPNEkaziz8M50RxzarA25NAit9XyMXMITuYJrtAXLOhUnaaKSV0Rd_8h97HNS3VXqUU6XQrO1Wp9ki5FHNO4B8-Q4k55GkOeZpjnuaYZz16_a-Nh5O_AbLfo2qfMg</recordid><startdate>20150401</startdate><enddate>20150401</enddate><creator>Mandalakas, Anna M</creator><creator>Kirchner, H Lester</creator><creator>Walzl, Gerhard</creator><creator>Gie, Robert P</creator><creator>Schaaf, H Simon</creator><creator>Cotton, Mark F</creator><creator>Grewal, Harleen M S</creator><creator>Hesseling, Anneke C</creator><general>American Thoracic Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150401</creationdate><title>Optimizing the detection of recent tuberculosis infection in children in a high tuberculosis-HIV burden setting</title><author>Mandalakas, Anna M ; Kirchner, H Lester ; Walzl, Gerhard ; Gie, Robert P ; Schaaf, H Simon ; Cotton, Mark F ; Grewal, Harleen M S ; Hesseling, Anneke C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c430t-60af4843755b4762c3430f75c19cfa3fbccef653946ec1c9555e74cd08ae83e43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adolescent</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Early Diagnosis</topic><topic>Female</topic><topic>HIV Infections - complications</topic><topic>Humans</topic><topic>Infant</topic><topic>Interferon-gamma Release Tests</topic><topic>Latent Tuberculosis - diagnosis</topic><topic>Latent Tuberculosis - etiology</topic><topic>Male</topic><topic>Mass Screening - methods</topic><topic>Mycobacterium tuberculosis</topic><topic>Original</topic><topic>Prospective Studies</topic><topic>South Africa</topic><topic>Tuberculin Test</topic><topic>Tuberculosis, Pulmonary - diagnosis</topic><topic>Tuberculosis, Pulmonary - etiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mandalakas, Anna M</creatorcontrib><creatorcontrib>Kirchner, H Lester</creatorcontrib><creatorcontrib>Walzl, Gerhard</creatorcontrib><creatorcontrib>Gie, Robert P</creatorcontrib><creatorcontrib>Schaaf, H Simon</creatorcontrib><creatorcontrib>Cotton, Mark F</creatorcontrib><creatorcontrib>Grewal, Harleen M S</creatorcontrib><creatorcontrib>Hesseling, Anneke C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>ProQuest - Health & Medical Complete保健、医学与药学数据库</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database (Proquest)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>British Nursing Database</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>American journal of respiratory and critical care medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mandalakas, Anna M</au><au>Kirchner, H Lester</au><au>Walzl, Gerhard</au><au>Gie, Robert P</au><au>Schaaf, H Simon</au><au>Cotton, Mark F</au><au>Grewal, Harleen M S</au><au>Hesseling, Anneke C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Optimizing the detection of recent tuberculosis infection in children in a high tuberculosis-HIV burden setting</atitle><jtitle>American journal of respiratory and critical care medicine</jtitle><addtitle>Am J Respir Crit Care Med</addtitle><date>2015-04-01</date><risdate>2015</risdate><volume>191</volume><issue>7</issue><spage>820</spage><epage>830</epage><pages>820-830</pages><issn>1073-449X</issn><issn>1535-4970</issn><eissn>1535-4970</eissn><abstract>Children who are young, malnourished, and infected with HIV have significant risk of tuberculosis (TB) morbidity and mortality following TB infection. Treatment of TB infection is hindered by poor detection and limited pediatric data.
Identify improved testing to detect pediatric TB infection.
This was a prospective community-based study assessing use of the tuberculin skin test and IFN-γ release assays among children (n = 1,343; 6 mo to <15 yr) in TB-HIV high-burden settings; associations with child characteristics were measured.
Contact tracing detects TB in 8% of child contacts within 3 months of exposure. Among children with no documented contact, tuberculin skin test and QuantiFERON-TB Gold In-Tube positivity was greater than T-SPOT.TB. Nearly 8% of children had IFN-γ release assay positive and skin test negative discordance. In a model accounting for confounders, all tests correlate with TB contact, but IFN-γ release assays correlate better than the tuberculin skin test (P = 0.0011). Indeterminate IFN-γ release assay results were not associated with age. Indeterminate QuantiFERON-TB Gold In-Tube results were more frequent in children infected with HIV (4.7%) than uninfected with HIV (1.9%), whereas T-SPOT.TB indeterminates were rare (0.2%) and not affected by HIV status. Conversion and reversion were not associated with HIV status. Among children infected with HIV, tests correlated less with contact as malnutrition worsened.
Where resources allow, use of IFN-γ release assays should be considered in children who are young, recently exposed, and infected with HIV because they may offer advantages compared with the tuberculin skin test for identifying TB infection, and improve targeted, cost-effective delivery of preventive therapy. Affordable tests of infection could dramatically impact global TB control.</abstract><cop>United States</cop><pub>American Thoracic Society</pub><pmid>25622087</pmid><doi>10.1164/rccm.201406-1165OC</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adolescent Child Child, Preschool Early Diagnosis Female HIV Infections - complications Humans Infant Interferon-gamma Release Tests Latent Tuberculosis - diagnosis Latent Tuberculosis - etiology Male Mass Screening - methods Mycobacterium tuberculosis Original Prospective Studies South Africa Tuberculin Test Tuberculosis, Pulmonary - diagnosis Tuberculosis, Pulmonary - etiology |
title | Optimizing the detection of recent tuberculosis infection in children in a high tuberculosis-HIV burden setting |
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