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A Controlled Study of Tuberculosis Diagnosis in HIV-Infected and Uninfected Children in Peru

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dc.contributor.author Oberhelman, Richard A.
dc.contributor.author Soto-Castellares, Giselle
dc.contributor.author Gilman, Robert H.
dc.contributor.author Castillo, Maria E.
dc.contributor.author Kolevic, Lenka
dc.contributor.author Delpino, Trinidad
dc.contributor.author Saito, Mayuko
dc.contributor.author Salazar-Lindo, Eduardo
dc.contributor.author Negron, Eduardo
dc.contributor.author Montenegro, Sonia
dc.contributor.author Laguna-Torres, V. Alberto
dc.contributor.author Maurtua-Neumann, Paola
dc.contributor.author Datta, Sumona
dc.contributor.author Evans, Carlton A.
dc.date.accessioned 2019-02-06T14:53:11Z
dc.date.available 2019-02-06T14:53:11Z
dc.date.issued 2015
dc.identifier.uri https://hdl.handle.net/20.500.12866/5399
dc.description.abstract BACKGROUND: Diagnosing tuberculosis in children is challenging because specimens are difficult to obtain and contain low tuberculosis concentrations, especially with HIV-coinfection. Few studies included well-controls so test specificities are poorly defined. We studied tuberculosis diagnosis in 525 children with and without HIV-infection. METHODS AND FINDINGS: 'Cases' were children with suspected pulmonary tuberculosis (n = 209 HIV-negative; n = 81 HIV-positive) and asymptomatic 'well-control' children (n = 200 HIV-negative; n = 35 HIV-positive). Specimens (n = 2422) were gastric aspirates, nasopharyngeal aspirates and stools analyzed by a total of 9688 tests. All specimens were tested with an in-house hemi-nested IS6110 PCR that took <24 hours. False-positive PCR in well-controls were more frequent in HIV-infection (P≤0.01): 17% (6/35) HIV-positive well-controls versus 5.5% (11/200) HIV-negative well-controls; caused by 6.7% (7/104) versus 1.8% (11/599) of their specimens, respectively. 6.7% (116/1719) specimens from 25% (72/290) cases were PCR-positive, similar (P>0.2) for HIV-positive versus HIV-negative cases. All specimens were also tested with auramine acid-fast microscopy, microscopic-observation drug-susceptibility (MODS) liquid culture, and Lowenstein-Jensen solid culture that took ≤6 weeks and had 100% specificity (all 2112 tests on 704 specimens from 235 well-controls were negative). Microscopy-positivity was rare (0.21%, 5/2422 specimens) and all microscopy-positive specimens were culture-positive. Culture-positivity was less frequent (P≤0.01) in HIV-infection: 1.2% (1/81) HIV-positive cases versus 11% (22/209) HIV-negative cases; caused by 0.42% (2/481) versus 4.7% (58/1235) of their specimens, respectively. CONCLUSIONS: In HIV-positive children with suspected tuberculosis, diagnostic yield was so low that 1458 microscopy and culture tests were done per case confirmed and even in children with culture-proven tuberculosis most tests and specimens were false-negative; whereas PCR was so prone to false-positives that PCR-positivity was as likely in specimens from well-controls as suspected-tuberculosis cases. This demonstrates the importance of control participants in diagnostic test evaluation and that even extensive laboratory testing only rarely contributed to the care of children with suspected TB. en_US
dc.language.iso eng
dc.publisher Public Library of Science
dc.relation.ispartof urn:issn:1932-6203
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Female en_US
dc.subject Humans en_US
dc.subject Male en_US
dc.subject Child en_US
dc.subject Child, Preschool en_US
dc.subject Infant en_US
dc.subject Peru/epidemiology en_US
dc.subject Polymerase Chain Reaction/methods en_US
dc.subject HIV Infections/complications/diagnosis/epidemiology en_US
dc.subject Tuberculosis/complications/diagnosis/epidemiology en_US
dc.title A Controlled Study of Tuberculosis Diagnosis in HIV-Infected and Uninfected Children in Peru en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1371/journal.pone.0120915
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00 es_PE

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