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Corstjens, P. L. A. M.

Publications and source records attributed to Corstjens, P. L. A. M..

3 recordsLinked to original sources

Proteomic And Transcriptomic Host Biomarkers For Detection Of Pleural Tuberculosis

Current diagnosis of pleural tuberculosis (PLTB) is based on highly invasive procedures. Therefore, blood-based host biomarkers could represent a low-invasive diagnostic alternative. Plasma and pleural effusion, as well as blood-and pleural fluid mononuclear cells (PBMCs and PFMCs), were sampled from patients with PLTB and other pleural diseases (OPLDs). In pleural effusion, ApoA1, C1q, CRP, IL-6, IFN-{gamma}, IP-10, MIG, S100A12, SAA1/A2, and serpin-A3 were significantly higher in PLTB compared to OPLD, whereas only SAA1/A2 showed discriminatory potential in plasma. Increased mRNA levels were observed in PFMCs of PLTB for CD8A, GBP5, SLAMF7, CXCL10, IL2, GNLY, IL23A, PDCD1 and BCMA, whereas HMOX1, CD163, DUSP3, IGF1, GUSB and MARCO were decreased. In PBMCs of PLTB, only CCL22 expression was decreased. GBP5 was significantly higher expressed in PLTB for both cell types. This study shows the potential of transcriptomic and proteomic host biomarkers to differentiate PLTB from OPLDs also when applying low-invasive methods.

microbiology↗

Sensitivity and specificity of human point-of-care circulating cathodic antigen (POC-CCA) test in African livestock for rapid diagnosis of schistosomiasis: a Bayesian latent class analysis

Schistosomiasis is a major neglected tropical disease (NTD) affecting both humans and animals. The morbidity and mortality inflicted upon livestock in sub-Saharan Africa has been largely overlooked, in part due to a lack of validated sensitive and specific tests, which do not require specialist training or equipment to deliver and interpret. Inexpensive, non-invasive, and sensitive diagnostic tests for livestock-use would also facilitate both prevalence mapping and appropriate intervention programmes. The aim of this study was to assess the sensitivity and specificity of the currently available point-of-care circulating cathodic antigen test (POC-CCA), designed for Schistosoma mansoni detection in humans, for the detection of intestinal livestock schistosomiasis caused by Schistosoma bovis and Schistosoma curassoni. POC-CCA, together with the circulating anodic antigen (CAA) test, miracidial hatching technique (MHT) and organ and mesentery inspection (for animals from abattoirs only), were applied to samples collected from 195 animals (56 cattle and 139 small ruminants (goats and sheep) from abattoirs and living populations) from Senegal. POC-CCA sensitivity varied by ruminant group and by location/parasite species: sensitivity was greater in Barkedji (cattle: mean 81% (95% credible interval (CrI): 55%-98%); small ruminants: 49% (29%-87%), where livestock were primarily infected by S. curassoni, than in Richard Toll (cattle: 62% (41%-84%); small ruminants: 12% (1%-37%), where S. bovis was the main parasite species. Mean POC-CCA specificity across sites in small ruminants was 91% (77%-99%) with little variation between locations/parasites (Barkedji: 91% (73%-99%); Richard Toll: 88% (65% - 99%). Specificity could not be assessed in cattle owing to the low number of uninfected cattle surveyed. Overall, our results indicate that, whilst the current POC-CCA does represent a potential diagnostic tool for animal schistosomiasis, future work is needed to develop a livestock-specific affordable and field-applicable diagnostic tests to enable determination of the true extent of livestock schistosomiasis. Author summarySchistosomiasis is a debilitating neglected tropical and zoonotic disease, infecting over 230 million people and multiple millions of animals worldwide, most notably amongst the poorest regions and populations. The potential contribution of livestock schistosomiasis to disease transmission in human populations has implications for the design of effective disease management and elimination programmes. However, our understanding of the true prevalence, transmission and impact of animal schistosomiasis is severely limited, in part due to a lack of inexpensive, accessible, sensitive and specific diagnostic tools. As a point-of-care circulating cathodic antigen (POC-CCA) diagnostic test is now in widespread use to assess intestinal schistosomiasis caused by Schistosoma mansoni in humans, we hypothesised that the same test could be used to detect livestock intestinal schistosomiasis caused by Schistosoma bovis and Schistosoma curassoni. The aim of this study was thus to evaluate the sensitivity and specificity of the POC-CCA for the detection of intestinal livestock schistosomiasis in Senegal. POC-CCA sensitivity varied by ruminant group and by location/parasite species, while POC-CCA specificity in small ruminants, at least, did not vary across sites. We conclude that the currently-available POC-CCA does represent a potential diagnostic tool for animal schistosomiasis, but that the factors determining test performance warrant further investigation.

pathology↗

In-depth proteomic characterization of Schistosoma haematobium: towards the development of new tools for elimination

BackgroundSchistosomiasis 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.\n\nMethods and FindingsBy 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.\n\nConclusionWe 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.\n\nAuthor SummarySchistosomiasis 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 parasites 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.

microbiology↗