Browsing by Author "Jacobs, Ruschca"

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    Detection of a combination of serum IgG and IgA antibodies against selected mycobacterial targets provides promising diagnostic signatures for active TB
    (Impact Journals, 2017-03-24) Awoniyi, Dolapo O.; Baumann, Ralf; Chegou, Novel N.; Kriel, Belinda; Jacobs, Ruschca; Kidd, Martin; Loxton, Andre G.; Kaempfer, Susanne; Singh, Mahavir; Walzl, Gerhard
    ENGLISH ABSTRACT: Immunoglobulin G (IgG) based tests for the diagnosis of active tuberculosis (TB) disease often show a lack of specificity in TB endemic regions, which is mainly due to a high background prevalence of LTBI. Here, we investigated the combined performance of the responses of different Ig classes to selected mycobacterial antigens in primary healthcare clinic attendees with signs and symptoms suggestive of TB. The sensitivity and specificity of IgA, IgG and/or IgM to LAM and 7 mycobacterial protein antigens (ESAT-6, Tpx, PstS1, AlaDH, MPT64, 16kDa and 19kDa) and 2 antigen combinations (TUB, TB-LTBI) in the plasma of 63 individuals who underwent diagnostic work-up for TB after presenting with symptoms and signs compatible with possible active TB were evaluated. Active TB was excluded in 42 individuals of whom 21 has LTBI whereas active TB was confirmed in 21 patients of whom 19 had a follow-up blood draw at the end of 6-month anti-TB treatment. The leading single serodiagnostic markers to differentiate between the presence or absence of active TB were anti-16 kDa IgA, anti-MPT64 IgA with sensitivity and specificity of 90%/90% and 95%/90%, respectively. The combined use of 3 or 4 antibodies further improved this performance to accuracies above 95%. After successful completion of anti-TB treatment at month 6, the levels of 16 kDa IgA and 16 kDa IgM dropped significantly whereas LAM IgG and TB-LTBI IgG increased. These results show the potential of extending investigation of anti-tuberculous IgG responses to include IgM and IgA responses against selected protein and non-protein antigens in differentiating active TB from other respiratory diseases in TB endemic settings.
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    Diagnostic potential of novel salivary host biomarkers as candidates for the immunological diagnosis of tuberculosis disease and monitoring of tuberculosis treatment response
    (Public Library of Science, 2016-08-03) Jacobs, Ruschca; Maasdorp, Elizna; Malherbe, Stephanus; Loxton, Andre G.; Stanley, Kim; Van Der Spuy, Gian; Walzl, Gerhard; Chegou, Novel N.
    Background: There is an urgent need for new tools for the early diagnosis of TB disease and monitoring of the response to treatment, especially in resource-constrained settings. We investigated the usefulness of host markers detected in saliva as candidate biomarkers for the immunological diagnosis of TB disease and monitoring of treatment response. Methods: We prospectively collected saliva samples from 51 individuals that presented with signs and symptoms suggestive of TB disease at a health centre in Cape Town, South Africa, prior to the establishment of a clinical diagnosis. Patients were later classified as having TB disease or other respiratory disease (ORD), using a combination of clinical, radiological and laboratory findings. We evaluated the concentrations of 69 host markers in saliva samples using a multiplex cytokine platform, and assessed the diagnostic potentials of these markers by receiver operator characteristics (ROC) curve analysis, and general discriminant analysis. Results: Out of the 51 study participants, 18 (35.4%) were diagnosed with TB disease and 12 (23.5%) were HIV infected. Only two of the 69 host markers that were evaluated (IL-16 and IL-23) diagnosed TB disease individually with area under the ROC curve ≥0.70. A five-marker biosignature comprising of IL-1β, IL-23, ECM-1, HCC1 and fibrinogen diagnosed TB disease with a sensitivity of 88.9% (95% CI,76.7–99.9%) and specificity of 89.7% (95% CI, 60.4–96.6%) after leave-one-out cross validation, regardless of HIV infection status. Eight-marker biosignatures performed with a sensitivity of 100% (95% CI, 83.2–100%) and specificity of 95% (95% CI, 68.1–99.9%) in the absence of HIV infection. Furthermore, the concentrations of 11 of the markers changed during treatment, indicating that they may be useful in monitoring of TB treatment response. Conclusion: We have identified novel salivary biosignatures which may be useful in the diagnosis of TB disease and monitoring of the response to TB treatment. Our findings require further validation in larger studies before these biosignatures could be considered for point-of-care screening test development.
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    Evaluation of novel host markers detected in plasma and saliva as biosignatures for the rapid diagnosis of TB disease and monitoring of the response to TB treatment
    (Stellenbosch : Stellenbosch University, 2016-12) Jacobs, Ruschca; Chegou, Novel N.; Walzl, Gerhard; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences: Molecular Biology and Human Genetics.
    ENGLISH SUMMARY: BACKGROUND: There is an urgent need for new tools for the rapid diagnosis of tuberculosis (TB) disease and monitoring of the response to treatment. OBJECTIVES: To investigate the usefulness of host markers detected in plasma and saliva, as well as antibodies against M. tuberculosis (M.tb) antigens, as biomarkers for the diagnosis of TB disease and monitoring of the response to treatment. To investigate the usefulness of a diagnostic approach involving the combination of antibodies and cytokines as a tool for diagnosing TB disease. METHODS: We prospectively collected plasma and saliva samples from individuals that presented with symptoms requiring investigation for TB disease at a health centre in Cape Town, South Africa, prior to the establishment of a clinical diagnosis. Patients were later classified as having TB disease or other respiratory diseases (ORD), using a combination of clinical, radiological and laboratory findings. The concentrations of host inflammatory biomarkers were investigated in plasma and saliva samples from all study participants using a multiplex platform, whereas antibody responses against seven M.tb antigens, were investigated by ELISA. The diagnostic accuracies of individual biomarkers were assessed by receiver operator characteristics (ROC) curve analysis, whereas the accuracies of combinations between different biomarkers were assessed by General Discriminant Analysis (GDA). RESULTS: Of the 74 host markers evaluated in plasma, 18 showed diagnostic potential as determined by area under the ROC curve (AUC), with the most promising being NCAM, CRP, SAP, IP-10, ferritin, TPA, I-309, and MIG, which diagnosed TB disease individually with AUC ≥0.80. A six-marker plasma protein biosignature comprising of NCAM, SAP, IL-1β, sCD40L, IL-13 and Apo A-1 diagnosed TB disease with a sensitivity of 100% (95% CI, 86.3-100%) and specificity of 89.3% (95% CI, 67.6-97.3%), irrespective of HIV status, whereas six-marker plasma protein biosignatures diagnosed TB disease with 100% accuracy in the absence of HIV. Of the 69 host markers that were investigated in saliva, only two (IL-16 and IL-23) showed diagnostic potential with AUC ≥0.70. A five-marker salivary biosignature comprising of IL-1β, IL-23, ECM-1, HCC1 and fibrinogen diagnosed TB disease with a sensitivity of 88.9% (95% CI,76.7-99.9%) and specificity of 89.7% (95% CI, 60.4-96.6%), regardless of HIV infection status, whereas eight-marker salivary biosignatures performed with a sensitivity of 100% (95% CI, 83.2-100%) and specificity of 95% (95% CI, 68.1-99.9%) in the absence of HIV infection. IgA responses against four M.tb antigens (NarL, Rv3019c, “Kit1” and “Kit2”) were significantly different between TB patients and individuals with ORD, with combinations between different antibodies diagnosing TB disease with an AUC of 0.80. The diagnostic accuracy of the antibodies increased when used in combination with patient’s symptoms or cytokines. Finally, the concentrations of biomarkers detected in plasma and saliva changed during TB treatment, thereby indicating that they may be useful in monitoring of the response to TB treatment. CONCLUSIONS: We have identified novel plasma and salivary biosignatures which may be useful in the diagnosis of TB disease and monitoring of the response to TB treatment. Our findings require further validation in larger studies.
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    Identification of novel host biomarkers in plasma as candidates for the immunodiagnosis of tuberculosis disease and monitoring of tuberculosis treatment response
    (Impact Journals, 2016-08-19) Jacobs, Ruschca; Malherbe, Stephanus; Loxton, Andre G.; Stanley, Kim; Van Der Spuy, Gian; Walzl, Gerhard; Chegou, Novel N.
    ENGLISH ABSTRACT: There is an urgent need for new tools for the rapid diagnosis of tuberculosis disease. We evaluated the potentials of 74 host markers as biomarkers for the immunological diagnosis of tuberculosis and monitoring of treatment response. Fifty-five individuals that presented with signs and symptoms requiring investigation for tuberculosis disease were prospectively recruited prior to clinical diagnosis, at a health centre in Cape Town, South Africa. Patients were later classified as having tuberculosis disease or other respiratory diseases (ORD) using a combination of clinical, radiological and laboratory findings. Out of 74 host markers that were evaluated in plasma samples from study participants using a multiplex platform, 18 showed potential as tuberculosis diagnostic candidates with the most promising being NCAM, CRP, SAP, IP-10, ferritin, TPA, I-309, and MIG, which diagnosed tuberculosis disease individually, with area under the ROC curve ≥0.80. Six-marker biosignatures containing NCAM diagnosed tuberculosis disease with a sensitivity of 100% (95%CI, 86.3-100%) and specificity of 89.3% (95%CI, 67.6-97.3%) irrespective of HIV status, and 100% accuracy in the absence of HIV infection. Furthermore, the concentrations of 11 of these proteins changed with treatment, thereby indicating that they may be useful in monitoring of the response to tuberculosis treatment. Our findings have potential to be translated into a point-of-care screening test for tuberculosis, after future validation studies.