title: Performance of Interferon-Gamma and IP-10 Release Assays for Diagnosing Latent Tuberculosis Infections in Patients with Concurrent Malaria in Tanzania.
abstract: Interferon-gamma (IFN-γ) release assays (IGRAs) are used to detect cellular immune recognition of Mycobacterium tuberculosis The chemokine IFN-γ-inducible protein 10 (IP-10) is an alternative diagnostic biomarker to IFN-γ. Several conditions interfere with IGRA test performance. We aimed to assess the possible influence of Plasmodium falciparum infection on the IGRA test QuantiFERON-TB GOLD® In-Tube (QFT) test and an in-house IP-10 release assay. In total, 241 Tanzanian adults were included; 184 patients with uncomplicated malaria (88 human immunodeficiency virus [HIV] coinfected) and 57 HIV-infected patients without malaria infection. Malaria was treated with artemether-lumefantrine (Coartem®). QFT testing was performed before initiation of malaria treatment and at days 7 and 42. In total, 172 patients completed follow-up. IFN-γ and IP-10 was measured in QFT supernatants. We found that during malaria infection IFN-γ and IP-10 levels in the unstimulated samples were elevated, mitogen responsiveness was impaired, and CD4 cell counts were decreased. These alterations reverted after malaria treatment. Concurrent malaria infection did not affect QFT test results, whereas there were more indeterminate IP-10 results during acute malaria infection. We suggest that IGRA and IP-10 release assay results of malaria patients should be interpreted with caution and that testing preferably should be postponed until after malaria treatment.
authors.affiliation: Department of Pulmonary and Infectious Diseases, Nordsjaelland Hospital, Hillerød, Denmark; Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark; InterACT Project, Muheza District Hospital, Muheza, Tanzania; Centre for Medical Parasitology, Department of Immunology and Microbiology and Department of Public Health, University of Copenhagen; Department of Infectious Diseases and Department of Clinical Microbiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; National Institute for Medical Research, Tanga, Tanzania; Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark camilla.h.drabe@gmail.com.
authors.forename: Camilla H
authors.initials: CH
authors.lastname: Drabe
authors.affiliation: Department of Pulmonary and Infectious Diseases, Nordsjaelland Hospital, Hillerød, Denmark; Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark; InterACT Project, Muheza District Hospital, Muheza, Tanzania; Centre for Medical Parasitology, Department of Immunology and Microbiology and Department of Public Health, University of Copenhagen; Department of Infectious Diseases and Department of Clinical Microbiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; National Institute for Medical Research, Tanga, Tanzania; Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Lasse S
authors.initials: LS
authors.lastname: Vestergaard
authors.affiliation: Department of Pulmonary and Infectious Diseases, Nordsjaelland Hospital, Hillerød, Denmark; Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark; InterACT Project, Muheza District Hospital, Muheza, Tanzania; Centre for Medical Parasitology, Department of Immunology and Microbiology and Department of Public Health, University of Copenhagen; Department of Infectious Diseases and Department of Clinical Microbiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; National Institute for Medical Research, Tanga, Tanzania; Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Marie
authors.initials: M
authors.lastname: Helleberg
authors.affiliation: Department of Pulmonary and Infectious Diseases, Nordsjaelland Hospital, Hillerød, Denmark; Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark; InterACT Project, Muheza District Hospital, Muheza, Tanzania; Centre for Medical Parasitology, Department of Immunology and Microbiology and Department of Public Health, University of Copenhagen; Department of Infectious Diseases and Department of Clinical Microbiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; National Institute for Medical Research, Tanga, Tanzania; Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Nyagonde
authors.initials: N
authors.lastname: Nyagonde
authors.affiliation: Department of Pulmonary and Infectious Diseases, Nordsjaelland Hospital, Hillerød, Denmark; Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark; InterACT Project, Muheza District Hospital, Muheza, Tanzania; Centre for Medical Parasitology, Department of Immunology and Microbiology and Department of Public Health, University of Copenhagen; Department of Infectious Diseases and Department of Clinical Microbiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; National Institute for Medical Research, Tanga, Tanzania; Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Michala V
authors.initials: MV
authors.lastname: Rose
authors.affiliation: Department of Pulmonary and Infectious Diseases, Nordsjaelland Hospital, Hillerød, Denmark; Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark; InterACT Project, Muheza District Hospital, Muheza, Tanzania; Centre for Medical Parasitology, Department of Immunology and Microbiology and Department of Public Health, University of Copenhagen; Department of Infectious Diseases and Department of Clinical Microbiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; National Institute for Medical Research, Tanga, Tanzania; Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Filbert
authors.initials: F
authors.lastname: Francis
authors.affiliation: Department of Pulmonary and Infectious Diseases, Nordsjaelland Hospital, Hillerød, Denmark; Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark; InterACT Project, Muheza District Hospital, Muheza, Tanzania; Centre for Medical Parasitology, Department of Immunology and Microbiology and Department of Public Health, University of Copenhagen; Department of Infectious Diseases and Department of Clinical Microbiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; National Institute for Medical Research, Tanga, Tanzania; Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Ola P
authors.initials: OP
authors.lastname: Theilgaard
authors.affiliation: Department of Pulmonary and Infectious Diseases, Nordsjaelland Hospital, Hillerød, Denmark; Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark; InterACT Project, Muheza District Hospital, Muheza, Tanzania; Centre for Medical Parasitology, Department of Immunology and Microbiology and Department of Public Health, University of Copenhagen; Department of Infectious Diseases and Department of Clinical Microbiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; National Institute for Medical Research, Tanga, Tanzania; Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Asbjørn
authors.affiliation: Department of Pulmonary and Infectious Diseases, Nordsjaelland Hospital, Hillerød, Denmark; Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark; InterACT Project, Muheza District Hospital, Muheza, Tanzania; Centre for Medical Parasitology, Department of Immunology and Microbiology and Department of Public Health, University of Copenhagen; Department of Infectious Diseases and Department of Clinical Microbiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; National Institute for Medical Research, Tanga, Tanzania; Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Ben
authors.initials: B
authors.lastname: Amos
authors.affiliation: Department of Pulmonary and Infectious Diseases, Nordsjaelland Hospital, Hillerød, Denmark; Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark; InterACT Project, Muheza District Hospital, Muheza, Tanzania; Centre for Medical Parasitology, Department of Immunology and Microbiology and Department of Public Health, University of Copenhagen; Department of Infectious Diseases and Department of Clinical Microbiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; National Institute for Medical Research, Tanga, Tanzania; Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Ib Christian
authors.initials: IC
authors.lastname: Bygbjerg
authors.affiliation: Department of Pulmonary and Infectious Diseases, Nordsjaelland Hospital, Hillerød, Denmark; Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark; InterACT Project, Muheza District Hospital, Muheza, Tanzania; Centre for Medical Parasitology, Department of Immunology and Microbiology and Department of Public Health, University of Copenhagen; Department of Infectious Diseases and Department of Clinical Microbiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; National Institute for Medical Research, Tanga, Tanzania; Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Ruhwald
authors.affiliation: Department of Pulmonary and Infectious Diseases, Nordsjaelland Hospital, Hillerød, Denmark; Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark; InterACT Project, Muheza District Hospital, Muheza, Tanzania; Centre for Medical Parasitology, Department of Immunology and Microbiology and Department of Public Health, University of Copenhagen; Department of Infectious Diseases and Department of Clinical Microbiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; National Institute for Medical Research, Tanga, Tanzania; Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Pernille
authors.initials: P
authors.lastname: Ravn
mesh_terms: D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D054357:Chemokine CXCL10 / Q000097:blood; D060085:Coinfection; D005188:False Negative Reactions; D005260:Female; D015658:HIV Infections / Q000150:complications; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D059425:Interferon-gamma Release Tests / Q000592:standards; D055985:Latent Tuberculosis / Q000150:complications / Q000175:diagnosis*; D016778:Malaria, Falciparum / Q000150:complications*; D008297:Male; D008875:Middle Aged; D013636:Tanzania / Q000453:epidemiology; D055815:Young Adult
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D007371:Interferon-gamma
references.citation: PLoS One. 2010;5(9):e12577
references.pmid: 20830287
references.citation: Ann Trop Med Parasitol. 1999 Oct;93(7):669-78
references.pmid: 10715693
references.citation: J Leukoc Biol. 2010 Dec;88(6):1131-43
references.pmid: 20610802
references.citation: Dis Markers. 2011;30(1):39-49
references.pmid: 21508508
references.citation: Inflamm Bowel Dis. 2011 Nov;17(11):2340-9
references.pmid: 21319275
references.citation: Dis Markers. 2011;31(6):327-35
references.pmid: 22182805
references.citation: Expert Rev Mol Diagn. 2012 Mar;12(2):175-87
references.pmid: 22369377
references.citation: PLoS One. 2012;7(3):e32482
references.pmid: 22403663
references.citation: J Infect. 2012 Jul;65(1):49-59
references.pmid: 22465752
references.citation: PLoS One. 2012;7(6):e38556
references.pmid: 22701664
references.citation: PLoS One. 2012;7(6):e39228
references.pmid: 22761744
references.citation: Clin Microbiol Rev. 2014 Jan;27(1):3-20
references.pmid: 24396134
references.citation: FEMS Microbiol Immunol. 1991 Aug;3(4):219-27
references.pmid: 1931134
references.citation: Clin Exp Immunol. 1992 Dec;90(3):405-8
references.pmid: 1458676
references.citation: Am J Trop Med Hyg. 1994 Sep;51(3):372-9
references.pmid: 7524374
references.citation: Infect Immun. 1997 Oct;65(10):4090-3
references.pmid: 9317012
references.citation: Nat Rev Immunol. 2005 Sep;5(9):722-35
references.pmid: 16138104
references.citation: J Acquir Immune Defic Syndr. 2006 Nov 1;43(3):363-7
references.pmid: 17079994
references.citation: Malar J. 2007;6:147
references.pmid: 17997848
references.citation: AIDS. 2010 Jan 16;24(2):323-5
references.pmid: 20010069
references.citation: Thorax. 2010 May;65(5):442-8
references.pmid: 20435869
references.citation: Pathog Glob Health. 2013 Mar;107(2):69-77
references.pmid: 23683333
references.citation: PLoS One. 2012;7(7):e37851
references.pmid: 22808002
references.citation: BMC Infect Dis. 2014;14:109
references.pmid: 24568311
references.citation: Eur Respir J. 2014 May;43(5):1472-86
references.pmid: 24311770
references.citation: Ann Am Thorac Soc. 2014 Oct;11(8):1267-76
references.pmid: 25188809
references.citation: Am J Respir Crit Care Med. 2014 Nov 15;190(10):1168-76
references.pmid: 25303140
references.citation: BMC Infect Dis. 2012;12:379
references.pmid: 23270417
references.citation: Biomed Res Int. 2015;2015:589471
references.pmid: 26346028
references.citation: Eur Respir J. 2010 Dec;36(6):1488-90
references.pmid: 21119209