Use of resuscitation promoting factors to screen for tuberculosis infection in household-exposed children in The Gambia

W. van Loon, M. P. Gomez, D. Jobe, K. L. M. C. Franken, T. H. M. Ottenhoff, M. Coninx, L. Kestens, J. S. Sutherland, B. Kampmann, L. D. Tientcheu

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    BackgroundInterferon-gamma release assays (IGRA) with Resuscitation promoting factor (Rpf) proteins enhanced tuberculosis (TB) screening and diagnosis in adults but have not been evaluated in children. Children often develop paucibacillary TB and their immune response differs from that of adults, which together affect TB disease diagnostics and immunodiagnostics. We assessed the ability of Rpf to identify infection among household TB-exposed children in The Gambia and investigated their ability to discriminate Mycobacterium tuberculosis complex (MTBC) infection from active TB disease in children.MethodsDetailed clinical investigations were done on 93 household TB-exposed Gambian children and a tuberculin skin test (TST) was administered to asymptomatic children. Venous blood was collected for overnight stimulation with ESAT-6/CFP-10-fusion protein (EC), purified protein derivative and RpfA, B, C, D and E. Interferon gamma (IFN-gamma) production was measured by ELISA in supernatants and corrected for the background level. Infection status was defined by IGRA with EC and TB disease by mycobacterial confirmation and/or clinical diagnosis. We compared IFN-gamma levels between infected and uninfected children and between infected and TB diseased children using a binomial logistic regression model while correcting for age and sex. A Receiver Operating Characteristics analysis was done to find the best cut-off for IFN-gamma level and calculate sensitivity and specificity.ResultsInterferon gamma production was significantly higher in infected (IGRA+, n=45) than in uninfected (IGRA-, n=20) children after stimulation with RpfA, B, C, and D (P=0.03; 0.007; 0.03 and 0.003, respectively). Using RpfB and D-specific IFN-gamma cut-offs (33.9pg/mL and 67.0pg/mL), infection was classified with a sensitivity-specificity combination of 73-92% and 77-72% respectively, which was similar to and better than 65-75% for TST. Moreover, IFN-gamma production was higher in infected than in TB diseased children (n=28, 5 bacteriologically confirmed, 23 clinically diagnosed), following RpfB and D stimulation (P=0.02 and 0.03, respectively).ConclusionRpfB and RpfD show promising results for childhood MTBC infection screening, and both performed similar to and better than the TST in our study population. Additionally, both antigens appear to discriminate between infection and disease in children and thus warrant further investigation as screening and diagnostic antigens for childhood TB.

    Original languageEnglish
    Article number469
    JournalBMC Infectious Diseases
    Issue number1
    Number of pages9
    Publication statusPublished - 2020


    • Pediatric tuberculosis
    • IGRA
    • RpfB
    • RpfD
    • Immunology
    • Diagnostics
    • ASSAYS
    • DOSR


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