ORCID Profile
0000-0002-0004-0526
Current Organisations
Curtin University Sarawak
,
Oxford Brookes University
,
National University of Malaysia
,
BRAC University Business School
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Publications
Use of lateral flow assays to determine IP-10 and CCL4 levels in pleural effusions and whole blood for TB diagnosis
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.TUBE.2015.10.011
Abstract: One of the key problems in combating TB is the lack of fast and accurate diagnostic tests that are affordable and easy to use in resource-limited settings. We have used a field-friendly up-converting phosphor (UCP) reporter technology in a lateral flow (LF) based test for the diagnosis of respiratory infections. In this study we analysed s les obtained from patients presenting with symptoms suggestive of TB but prior to confirmation by microbiology in The Gambia. Following clinical and microbiological evaluation they were classified as either having TB or other respiratory disorder (ORD). Analysis of blood was performed for those with pulmonary TB and pleural fluid for those with pleural TB. UCP-LF test for detection and quantitation of IP-10 and CCL4 were used being the two chemokine markers that have been shown to increase in active TB disease. UCP-LF test accurately determined concentrations of both markers as compared to ELISA and multiplex cytokine array. However, only IP-10 could discriminate between TB and ORD, and this was significantly enhanced by analysing the site of infection (pleural fluid), which showed 92% correct classification. Future work will assess the use of multiple markers to increase diagnostic accuracy.
Measuring consumer understanding and perception of eco‐labelling: Item selection and scale validation
Publisher: Wiley
Date: 29-01-2019
DOI: 10.1111/IJCS.12510
The influence of eco-label knowledge and trust on pro-environmental consumer behaviour in an emerging market
Publisher: Informa UK Limited
Date: 14-10-2016
Validation and Optimization of Host Immunological Bio-Signatures for a Point-of-Care Test for TB Disease
Publisher: Frontiers Media SA
Date: 26-02-2021
DOI: 10.3389/FIMMU.2021.607827
Abstract: The development of a non-sputum-based, point-of-care diagnostic test for tuberculosis (TB) is a priority in the global effort to combat this disease, particularly in resource-constrained settings. Previous studies have identified host biomarker signatures which showed potential, but there is a need to validate and refine these for development as a test. We recruited 1,403 adults presenting with symptoms suggestive of pulmonary TB at primary healthcare clinics in six countries from West, East and Southern Africa. Of the study cohort, 326 were diagnosed with TB and 787 with other respiratory diseases, from whom we randomly selected 1005 participants. Using Luminex ® technology, we measured the levels of 20 host biomarkers in serum s les which we used to evaluate the diagnostic accuracy of previously identified and novel bio-signatures. Our previously identified seven-marker bio-signature did not perform well (sensitivity: 89%, specificity: 60%). We also identified an optimal, two-marker bio-signature with a sensitivity of 94% and specificity of 69% in patients with no history of previous TB. This signature performed slightly better than C-reactive protein (CRP) alone. The cut-off value for a positive diagnosis differed for human immuno-deficiency virus (HIV)-positive and -negative in iduals. Notably, we also found that no signature was able to diagnose TB adequately in patients with a prior history of the disease. We have identified a two-marker, pan-African bio-signature which is more robust than CRP alone and meets the World Health Organization (WHO) target product profile requirements for a triage test in both HIV-negative and HIV-positive in iduals. This signature could be incorporated into a point-of-care device, greatly reducing the necessity for expensive confirmatory diagnostics and potentially reducing the number of cases currently lost to follow-up. It might also potentially be useful with in iduals unable to provide sputum or with paucibacillary disease. We suggest that the performance of TB diagnostic signatures can be improved by incorporating the HIV-status of the patient. We further suggest that only patients who have never had TB be subjected to a triage test and that those with a history of previous TB be evaluated using more direct diagnostic techniques.
In-depth proteomic characterization of Schistosoma haematobium: Towards the development of new tools for elimination
Publisher: Public Library of Science (PLoS)
Date: 15-05-2019
Population Pharmacokinetics and Pharmacodynamics of Praziquantel in Ugandan Children with Intestinal Schistosomiasis: Higher Dosages Are Required for Maximal Efficacy
Publisher: American Society for Microbiology
Date: 07-09-2016
Abstract: Each year, millions of African children receive praziquantel (PZQ) by mass drug administration (MDA) to treat schistosomiasis at a standard single dose of 40 mg/kg of body weight, a direct extrapolation from studies of adults. A higher dose of 60 mg/kg is also acceptable for refractory cases. We conducted the first PZQ pharmacokinetic (PK) and pharmacodynamic (PD) study in young children comparing dosing. Sixty Ugandan children aged 3 to 8 years old with egg patent Schistosoma mansoni received PZQ at either 40 mg/kg or 60 mg/kg. PK parameters of PZQ racemate and enantiomers ( R and S ) were quantified. PD outcomes were assessed by standard fecal egg counts and novel schistosome-specific serum (circulating anodic antigen [CAA]) and urine (circulating cathodic antigen [CCA]) antigen assays. Population PK and PD analyses were performed to estimate drug exposure in in idual children, and the relationship between drug exposure and parasitological cure was estimated using logistic regression. Monte Carlo simulations were performed to identify better, future dosing regimens. There was marked PK variability between children, but the area under the concentration-time curve (AUC) of PZQ was strongly predictive of the parasitological cure rate (CR). Although no child achieved antigenic cure, which is suggestive of an important residual adult worm burden, higher AUC was associated with greater CAA antigenic decline at 24 days. To optimize the performance of PZQ, analysis of our simulations suggest that higher doses ( mg/kg) are needed, particularly in smaller children. IMPORTANCE Schistosomiasis is a neglected tropical disease, typically associated with chronic morbidity, and its control is a global health priority. Praziquantel (PZQ) is the only available antiparasitic drug and is often given out, as a single oral dose (40 mg/kg), to school-aged children by mass drug administration (MDA) schemes operating within preventive chemotherapy c aigns as endorsed by the World Health Organization (WHO). This current strategy has several limitations. (i) It excludes preschool children who can be patently infected. (ii) It delivers PZQ at a dose directly extrapolated from adult pharmacological studies. To address these problems, we conducted the first pharmacokinetic and pharmacodynamic study of young children within an area of Uganda where Schistosoma mansoni is hyperendemic. Our results demonstrate that a higher dose ( mg/kg) is required, especially in smaller children, and draw attention to the need for further optimization of PZQ treatment based on schistosome antigenic assays, which are more sensitive to pharmacodynamic markers.
Multi-center evaluation of a user-friendly lateral flow assay to determine IP-10 and CCL4 levels in blood of TB and non-TB cases in Africa
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.CLINBIOCHEM.2015.08.013
Abstract: Multi-center evaluation of a user-friendly lateral flow test for detection of IP-10 and CCL4 levels in Mycobacterium tuberculosis (Mtb) antigen-stimulated whole blood s les from tuberculosis (TB) suspects. A quantitative lateral flow (LF)-based assay platform was applied to detect chemokines IP-10 and CCL4. Chemokine quantitation was achieved using interference-free, fluorescent up-converting phosphor (UCP) labels. The new assays allowed worldwide shipping and storage without requiring a cold chain and were tested at seven institutes (including Ethiopia, Malawi, The Gambia, South Africa, Uganda and Namibia) employing portable lightweight readers for detection of the UCP label. At each site, clinical s les, confirmed TB and non-TB (i.e. other respiratory diseases (ORD)) cases, were collected and analyzed simultaneously with quality control (QC) human IP-10 or CCL4 standards. Performance of the UCP-LF assay in Africa using QC standards indicated high robustness allowing quantitative detection between 100 and 100,000pg/mL. The optimized assays allowed successful determination of chemokine levels using 1μL whole blood s le from the locally recruited subjects with TB or ORD. This African multi-center trial further demonstrated the applicability of the low-tech and robust UCP-LF platform as a convenient quantitative assay for chemokine detection in whole blood. Ambient shipping and storage of all assay reagents and the availability of lightweight standalone readers were acknowledged as essential requirement for test implementation in particular in remote and resource-limited settings.
Characterisation of tetraspanins from Schistosoma haematobium and evaluation of their potential as novel diagnostic markers
Publisher: Public Library of Science (PLoS)
Date: 24-01-2022
DOI: 10.1371/JOURNAL.PNTD.0010151
Abstract: Schistosoma haematobium is the leading cause of urogenital schistosomiasis and it is recognised as a class 1 carcinogen due to the robust association of infection with bladder cancer. In schistosomes, tetraspanins (TSPs) are abundantly present in different parasite proteomes and could be potential diagnostic candidates due to their accessibility to the host immune system. The large extracellular loops of six TSPs from the secretome (including the soluble excretory/secretory products, tegument and extracellular vesicles) of S . haematobium ( Sh -TSP-2, Sh -TSP-4, Sh -TSP-5, Sh -TSP-6, Sh -TSP-18 and Sh -TSP-23) were expressed in a bacterial expression system and polyclonal antibodies were raised to the recombinant proteins to confirm the anatomical sites of expression within the parasite. Sh -TSP-2, and Sh -TSP-18 were identified on the tegument, whereas Sh -TSP-4, Sh -TSP-5, Sh -TSP-6 and Sh -TSP-23 were identified both on the tegument and internal tissues of adult parasites. The mRNAs encoding these TSPs were differentially expressed throughout all schistosome developmental stages tested. The potential diagnostic value of three of these Sh -TSPs was assessed using the urine of in iduals (stratified by infection intensity) from an endemic area of Zimbabwe. The three Sh -TSPs were the targets of urine IgG responses in all cohorts, including in iduals with very low levels of infection (those positive for circulating anodic antigen but negative for eggs by microscopy). This study provides new antigen candidates to immunologically diagnose S . haematobium infection, and the work presented here provides compelling evidence for the use of a biomarker signature to enhance the diagnostic capability of these tetraspanins.
Evaluation of cytokine responses against novel Mtb antigens as diagnostic markers for TB disease
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.JINF.2016.04.036
Abstract: We investigated the accuracy of host markers detected in Mtb antigen-stimulated whole blood culture supernatant in the diagnosis of TB. Prospectively, blood from 322 in iduals 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. 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 s les. 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. A biosignature of 6 cytokines obtained after stimulation with four Mtb antigens has moderate potential as a diagnostic tool for pulmonary TB disease in iduals and stimulated marker expression had no added value to unstimulated marker performance.
Diagnostic performance of a seven-marker serum protein biosignature for the diagnosis of active TB disease in African primary healthcare clinic attendees with signs and symptoms suggestive of TB
Publisher: BMJ
Date: 04-05-2016
DOI: 10.1136/THORAXJNL-2015-207999
Abstract: User-friendly, rapid, inexpensive yet accurate TB diagnostic tools are urgently needed at points of care in resource-limited settings. We investigated host biomarkers detected in serum s les obtained from adults with signs and symptoms suggestive of TB at primary healthcare clinics in five African countries (Malawi, Namibia, South Africa, The Gambia and Uganda), for the diagnosis of TB disease. We prospectively enrolled in iduals presenting with symptoms warranting investigation for pulmonary TB, prior to assessment for TB disease. We evaluated 22 host protein biomarkers in stored serum s les using a multiplex cytokine platform. Using a pre-established diagnostic algorithm comprising of laboratory, clinical and radiological findings, participants were classified as either definite TB, probable TB, questionable TB status or non-pulmonary TB. Of the 716 participants enrolled, 185 were definite and 29 were probable TB cases, 6 had questionable TB disease status, whereas 487 had no evidence of TB. A seven-marker biosignature of C reactive protein, transthyretin, IFN-γ, complement factor H, apolipoprotein-A1, inducible protein 10 and serum amyloid A identified on a training s le set (n=491), diagnosed TB disease in the test set (n=210) with sensitivity of 93.8% (95% CI 84.0% to 98.0%), specificity of 73.3% (95% CI 65.2% to 80.1%), and positive and negative predictive values of 60.6% (95% CI 50.3% to 70.1%) and 96.4% (95% CI 90.5% to 98.8%), respectively, regardless of HIV infection status or study site. We have identified a seven-marker host serum protein biosignature for the diagnosis of TB disease irrespective of HIV infection status or ethnicity in Africa. These results hold promise for the development of a field-friendly point-of-care screening test for pulmonary TB.
RISK6, a 6-gene transcriptomic signature of TB disease risk, diagnosis and treatment response
Publisher: Springer Science and Business Media LLC
Date: 25-05-2020
DOI: 10.1038/S41598-020-65043-8
Abstract: Improved tuberculosis diagnostics and tools for monitoring treatment response are urgently needed. We developed a robust and simple, PCR-based host-blood transcriptomic signature, RISK6, for multiple applications: identifying in iduals at risk of incident disease, as a screening test for subclinical or clinical tuberculosis, and for monitoring tuberculosis treatment. RISK6 utility was validated by blind prediction using quantitative real-time (qRT) PCR in seven independent cohorts. Prognostic performance significantly exceeded that of previous signatures discovered in the same cohort. Performance for diagnosing subclinical and clinical disease in HIV-uninfected and HIV-infected persons, assessed by area under the receiver-operating characteristic curve, exceeded 85%. As a screening test for tuberculosis, the sensitivity at 90% specificity met or approached the benchmarks set out in World Health Organization target product profiles for non-sputum-based tests. RISK6 scores correlated with lung immunopathology activity, measured by positron emission tomography, and tracked treatment response, demonstrating utility as treatment response biomarker, while predicting treatment failure prior to treatment initiation. Performance of the test in capillary blood s les collected by finger-prick was noninferior to venous blood collected in PAXgene tubes. These results support incorporation of RISK6 into rapid, capillary blood-based point-of-care PCR devices for prospective assessment in field studies.
In-depth proteomic characterization of Schistosoma haematobium: towards the development of new tools for elimination
Publisher: Cold Spring Harbor Laboratory
Date: 10-12-2018
DOI: 10.1101/486662
Abstract: Schistosomiasis is a neglected disease affecting hundreds of millions worldwide. Of the three main species affecting humans, Schistosoma haematobium is the most common, and is the leading cause of urogenital schistosomiasis. S . haematobium infection can cause different urogential clinical complications, particularly in the bladder, and furthermore, this parasite has been strongly linked with squamous cell carcinoma. A comprehensive analysis of the molecular composition of its different proteomes will contribute to developing new tools against this devastating disease. By combining a comprehensive protein fractionation approach consisting of OFFGEL electrophoresis with high-throughput mass spectrometry, we have performed the first in-depth characterisation of the different discrete proteomes of S . haematobium that are predicted to interact with human host tissues, including the secreted and tegumental proteomes of adult flukes and secreted and soluble egg proteomes. A total of 662, 239, 210 and 138 proteins were found in the adult tegument, adult secreted, soluble egg and secreted egg proteomes, respectively. In addition, we probed these distinct proteomes with urine to assess urinary antibody responses from naturally infected human subjects with different infection intensities, and identified adult fluke secreted and tegument extracts as being the best predictors of infection. We provide a comprehensive dataset of proteins from the adult and egg stages of S . haematobium and highlight their utility as diagnostic markers of infection intensity for the development of novel tools to control this important neglected tropical disease. Schistosomiasis is a neglected tropical disease affecting millions of people worldwide. Of the main three species affecting humans, Schistosoma haematobium is the most common, and is the leading cause of urogenital schistosomiasis. This parasite can cause a range of clinical complications associated with bladder pathogenesis, including squamous cell carcinoma as well as genital malignancy in women. Herein, we have performed the first comprehensive characterisation of the proteins implicated in host-parasite interactions (secreted and surface proteins from the adult flukes and secreted and soluble egg proteins) in order to advance our understanding of the parasite’s biology. Furthermore, we have characterised the different antibody responses in urine from infected human subjects from an endemic area presenting different infection intensities. The data obtained in this study can be used as a first step towards the development of novel tools for the control of urogenital schistosomiasis.
Related Organisations
National Applied Research Laboratories National Nano Device Laboratories
Location: Taiwan, Province of China
Oxford Brookes University
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
No related grants have been discovered for Paul Corstjens.