title: Alternative Quantiferon cytokines for diagnosis of children with active tuberculosis and HIV co-infection in Ghana.
abstract: IFN-γ release assays (IGRAs) often present false-negative or indeterminate results in children with tuberculosis. HIV co-infection may contribute to decreased sensitivity of IGRAs by impairing T-cell IFN-γ expression. Measurement of alternative cytokines in QuantiFERON®(QFT) supernatants can circumvent the IFN-γ-dependency and may improve QFT sensitivity. We aimed to identify additional cytokines from QFT supernatants for detection of Mycobacterium tuberculosis infection in children with tuberculosis and HIV co-infection from Ghana. Concentrations of 18 cytokines in QFT supernatants from children (0-16 years) with tuberculosis concomitantly infected with HIV (n = 25) or without HIV (n = 24) from Ghana were measured using cytometric bead array (CBA). 29% of the children showed positive IFN-γ test results, and five cytokines, i.e., IL-6, IL-21, TNF-α, IL-1α and IP-10, detected M. tuberculosis infection with comparable or, for IL-6, with significantly higher sensitivity (59%). Increased age and HIV co-infection were associated with decreased cytokine induction, and especially IL-21 and IP-10 were less prevalent in HIV co-infected children with tuberculosis. Combined cytokine analyses increased proportions of positive tests, and a four-cytokine subset (i.e., IL-6, IL-21, IFN-γ, IL-1α) predicted 78% of the children with tuberculosis correctly. Combined evaluation of IFN-γ and alternative cytokines improved IGRA-sensitivity in children with tuberculosis.
authors.affiliation: Pediatric Infectious Diseases Group, Department of General Pediatrics, Neonatology, and Pediatric Cardiology, University Children's Hospital, Moorenstr. 5, 40225, Duesseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Lundtoft
authors.affiliation: Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana.|School of Public Health, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana.
authors.forename: Anthony Afum-Adjei
authors.initials: AA
authors.lastname: Awuah
authors.affiliation: Pediatric Infectious Diseases Group, Department of General Pediatrics, Neonatology, and Pediatric Cardiology, University Children's Hospital, Moorenstr. 5, 40225, Duesseldorf, Germany.
authors.forename: Norman
authors.initials: N
authors.lastname: Nausch
authors.affiliation: Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana.
authors.forename: Anthony
authors.initials: A
authors.lastname: Enimil
authors.affiliation: Pediatric Infectious Diseases Group, Department of General Pediatrics, Neonatology, and Pediatric Cardiology, University Children's Hospital, Moorenstr. 5, 40225, Duesseldorf, Germany.
authors.forename: Ertan
authors.initials: E
authors.lastname: Mayatepek
authors.affiliation: Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana.|School of Public Health, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana.
authors.forename: Ellis
authors.initials: E
authors.lastname: Owusu-Dabo
authors.affiliation: Pediatric Infectious Diseases Group, Department of General Pediatrics, Neonatology, and Pediatric Cardiology, University Children's Hospital, Moorenstr. 5, 40225, Duesseldorf, Germany. marc.jacobsen@med.uni-duesseldorf.de.
authors.forename: Marc
authors.initials: M
authors.lastname: Jacobsen
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D060085:Coinfection / Q000175:diagnosis*; D016207:Cytokines / Q000032:analysis*; D005260:Female; D005869:Ghana; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007223:Infant; D059425:Interferon-gamma Release Tests / Q000379:methods*; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D012680:Sensitivity and Specificity; D014376:Tuberculosis / Q000175:diagnosis*
chemical_list: D016207:Cytokines
keywords: Cytometric bead assay; HIV co-infection; IL-21; IL-6; QuantiFERON (QFT); Tuberculosis