Browsing by Author "Van der Spuy, Gian D."

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    Differential expression of host biomarkers in saliva and serum samples from individuals with suspected pulmonary tuberculosis
    (Hindawi Publishing Corporation, 2013-09) Phalane, Khutso G.; Kriel, Magdalena; Loxton, Andre G.; Menezes, Angela; Stanley, Kim; Van der Spuy, Gian D.; Walzl, Gerhard; Chegou, Novel N.
    The diagnosis of tuberculosis remains challenging in individuals with difficulty in providing good quality sputum samples such as children. Host biosignatures of inflammatory markers may be valuable in such cases, especially if they are based on more easily obtainable samples such as saliva. To explore the potential of saliva as an alternative sample in tuberculosis diagnostic/biomarker investigations, we evaluated the levels of 33 hostmarkers in saliva samples fromindividuals presenting with pulmonary tuberculosis symptoms and compared them to those obtained in serum. Of the 38 individuals included in the study, tuberculosis disease was confirmed in 11 (28.9%) by sputum culture. In both the tuberculosis cases and noncases, the levels of most markers were above the minimum detectable limit in both sample types, but there was no consistent pattern regarding the ratio ofmarkers in serum/saliva. Fractalkine, IL-17, IL-6, IL-9, MIP-1𝛽�, CRP, VEGF, and IL-5 levels in saliva and IL-6, IL-2, SAP, and SAA levels in serum were significantly higher in tuberculosis patients (𝑃� < 0.05). These preliminary data indicate that there are significant differences in the levels of host markers expressed in saliva in comparison to those expressed in serumand that inflammatory markers in both sample types are potential diagnostic candidates for tuberculosis disease.
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    Multi-phenotype genome-wide association study of clades causing tuberculosis in a Ghanaian- and South African cohort
    (Elsevier Inc., 2021-04) Müller, Stephanie J.; Haiko, Schurz; Tromp, Gerard; Van der Spuy, Gian D.; Hoal, Eileen G.; Van Helden, Paul D.; Owusu-Dabo, Ellis; Meyer, Christian G.; Muntau, Birgit; Thye, Thorsten; Niemann, Stefan; Warren, Robin M.; Streicher, Elizabeth; Muller, Marlo; Kinnear, Craig
    Despite decades of research and advancements in diagnostics and treatment, tuberculosis remains a major public health concern. New computational methods are needed to interrogate the intersection of host- and bacterial genomes. Paired host genotype datum and infecting bacterial isolate information were analysed for associations using a multinomial logistic regression framework implemented in SNPTest. A cohort of 853 admixed South African participants and a Ghanaian cohort of 1359 participants were included. Two directly genotyped variants, namely rs529920 and rs41472447, were identified in the Ghanaian cohort as being statistically significantly associated with risk for infection with strains of different members of the MTBC. Thus, a multinomial logistic regression using paired host-pathogen data may prove valuable for investigating the complex relationships driving infectious disease.
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    Potential of host markers produced by infection phase-dependent antigen-stimulated cells for the diagnosis of tuberculosis in a highly endemic area
    (Public Library of Science, 2012-06-05) Chegou, Novel N.; Essone, Paulin N.; Loxton, Andre G.; Stanley, Kim; Black, Gillian F.; Van der Spuy, Gian D.; Van Helden, Paul D.; Franken, Kees L.; Parida, Shreemanta K.; Klein, Michel R.; Kaufmann, Stefan H. E.; Ottenhoff, Tom H. M.; Walzl, Gerhard
    Background: Recent interferon gamma (IFN-γ)-based studies have identified novel Mycobacterium tuberculosis (M.tb) infection phase-dependent antigens as diagnostic candidates. In this study, the levels of 11 host markers other than IFN-γ, were evaluated in whole blood culture supernatants after stimulation with M.tb infection phase-dependent antigens, for the diagnosis of TB disease. Methodology and Principal Findings: Five M.tb infection phase-dependent antigens, comprising of three DosR-regulon-encoded proteins (Rv2032, Rv0081, Rv1737c), and two resucitation promoting factors (Rv0867c and Rv2389c), were evaluated in a case-control study with 15 pulmonary TB patients and 15 household contacts that were recruited from a high TB incidence setting in Cape Town, South Africa. After a 7-day whole blood culture, supernatants were harvested and the levels of the host markers evaluated using the Luminex platform. Multiple antigen-specific host markers were identified with promising diagnostic potential. Rv0081-specific levels of IL-12(p40), IP-10, IL-10 and TNF-α were the most promising diagnostic candidates, each ascertaining TB disease with an accuracy of 100%, 95% confidence interval for the area under the receiver operating characteristics plots, (1.0 to 1.0). Conclusions: Multiple cytokines other than IFN-γ in whole blood culture supernatants after stimulation with M.tb infection phase-dependent antigens show promise as diagnostic markers for active TB. These preliminary findings should be verified in well-designed diagnostic studies employing short-term culture assays. © 2012 Chegou et al.