Browsing by Author "Walzl, Gerhard"

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    Delaying BCG Vaccination from Birth to 10 Weeks of Age May Result in an enhanced Memory CD4 T Cell Response
    (Vaccine, 2009) Kagina, Benjamin M.N.; Bowmaker, Mark; Erasmus, Mzwandile; Walzl, Gerhard
    In most tuberculosis (TB) endemic countries, bacillus Calmette–Guérin (BCG) is usually given around birth to prevent severe TB in infants. The neonatal immune system is immature. Our hypothesis was that delaying BCG vaccination from birth to 10 weeks of age would enhance the vaccine-induced immune response. In a randomized clinical trial, BCG was administered intradermally either at birth (n=25) or at 10 weeks of age (n=21). Ten weeks after vaccination, and at 1 year of age, vaccine-specific CD4 and CD8 T cell responses were measured with a whole blood intracellular cytokine assay. Infants who received delayed BCG vaccination demonstrated higher frequencies of BCG-specific CD4 T cells, particularly polyfunctional T cells co-expressing IFN-γ, TNF-α and IL-2, and most strikingly at 1 year of age. Delaying BCG vaccination from birth to 10 weeks of age enhances the quantitative and qualitative BCG-specific T cell response, when measured at 1 year of age.
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    Diagnostic accuracy of the Cepheid 3-gene host response fingerstick blood test in a prospective, multi-site study: interim results
    (Clinical Infectious Diseases, 2021) Sutherland, Jayne S.; Spuy, Gian van der; Gindeh, Awa; Thuong, Nguyen Thuy; Namuganga, AnnRitah; Owolabi, Olumuyiwa; Mayanja-Kizza, Harriet; Nsereko, Mary; Thwaites, Guy; Winter, Jill; Dockrell, Hazel M.; Scriba, Thomas J.; Geluk, Annemieke; Corstjens, Paul; Stanley, Kim; Richardson, Tracy; Shaw, Jane A.; Smith, Bronwyn; Walzl, Gerhard
    The development of a fast and accurate, non-sputum-based point-of-care triage test for tuberculosis (TB) would have a major impact on combating the TB burden worldwide. A new fingerstick blood test has been developed by Cepheid (the Xpert-MTB-Host Response (HR)-Prototype), which generates a ‘TB score’ based on mRNA expression of 3 genes. Here we describe the first prospective findings of the MTB-HR prototype.
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    Evaluation of cytokine responses against novel Mtb antigens as diagnostic markers for TB disease
    (Journal of Infection, 2016) Awoniyi, Dolapo O.; Teuchert, Andrea; Sutherland, Jayne S.; Mayanja-Kizza, Harriet; Howe, Rawleigh; Mihret, Adane; Loxton, Andre G.; Sheehama, Jacob; Kassa, Desta; Crampin, Amelia C.; Dockrell, Hazel M.; Kidd, Martin; Rosenkrands, Ida; Geluk, Annemieke; Ottenhoff, Tom H.M.; Chegou, Novel N.; Walzl, Gerhard
    We investigated the accuracy of host markers detected in Mtb antigenstimulated whole blood culture supernatant in the diagnosis of TB. Methods: Prospectively, blood from 322 individuals with presumed TB disease from six African sites was stimulated with four different Mtb antigens (Rv0081, Rv1284, ESAT-6/CFP-10, and Rv2034) in a 24 h whole blood stimulation assay (WBA). The concentrations of 42 host markers in the supernatants were measured using the Luminex multiplex platform. Diagnostic biosignatures were investigated through the use of multivariate analysis techniques. Results: 17% of the participants were HIV infected, 106 had active TB disease and in 216 TB was excluded. Unstimulated concentrations of CRP, SAA, ferritin and IP-10 had better discriminating ability than markers from stimulated samples. Accuracy of marker combinations by general discriminant analysis (GDA) identified a six analyte model with 77% accuracy for TB cases and 84% for non TB cases, with a better performance in HIV uninfected patients. Conclusions: A biosignature of 6 cytokines obtained after stimulation with four Mtb antigens has moderate potential as a diagnostic tool for pulmonary TB disease individuals and stimulated marker expression had no added value to unstimulated marker performance.