Detection of Schistosoma eggs in stool or urine is known for its low sensitivity in diagnosing light infections. Alternative diagnostics with better sensitivity while remaining highly specific,... Show moreDetection of Schistosoma eggs in stool or urine is known for its low sensitivity in diagnosing light infections. Alternative diagnostics with better sensitivity while remaining highly specific, such as real-time PCR and circulating antigen detection, are progressively used as complementary diagnostic procedures but have not yet replaced microscopy. This study evaluates these alternative methods for the detection of Schistosoma infections in the absence of microscopy. Schistosomiasis presence was determined retrospectively in 314 banked stool and urine samples, available from a previous survey on the prevalence of taeniasis in a community in the Democratic Republic of the Congo, using real-time PCR, the point-of-care circulating cathodic antigen (POC-CCA) test, as well as the up-converting particle lateral flow circulating anodic antigen (UCP-LF CAA) test. Schistosoma DNA was present in urine (3%) and stool (28%) samples, while CCA (28%) and CAA (69%) were detected in urine. Further analysis of the generated data indicated stool-based PCR and the POC-CCA test to be suitable diagnostics for screening of S. mansoni infections, even in the absence of microscopy. A substantial proportion (60%) of the 215 CAA-positive cases showed low antigen concentrations, suggesting that even PCR and POC-CCA underestimated the "true" number of schistosome positives. Show less
Telgte, A. ter; Scherlek, A.A.; Reijmer, Y.D.; Kouwe, A.J. van der; Harten, T. van; Duering, M.; ... ; Veluw, S.J. van 2020
Small subclinical hyperintense lesions are frequently encountered on brain diffusion-weighted imaging (DWI) scans of patients with cerebral amyloid angiopathy (CAA). Interpretation of these DWI+... Show moreSmall subclinical hyperintense lesions are frequently encountered on brain diffusion-weighted imaging (DWI) scans of patients with cerebral amyloid angiopathy (CAA). Interpretation of these DWI+ lesions, however, has been limited by absence of histopathological examination. We aimed to determine whether DWI+ lesions represent acute microinfarcts on histopathology in brains with advanced CAA, using a combined in vivo MRI-ex vivo MRI-histopathology approach. We first investigated the histopathology of a punctate cortical DWI+ lesion observed on clinical in vivo MRI 7 days prior to death in a CAA case. Subsequently, we assessed the use of ex vivo DWI to identify similar punctate cortical lesions post-mortem. Intact formalin-fixed hemispheres of 12 consecutive cases with CAA and three non-CAA controls were subjected to high-resolution 3 T ex vivo DWI and T2 imaging. Small cortical lesions were classified as either DWI+/T2+ or DWI-/T2+. A representative subset of lesions from three CAA cases was selected for detailed histopathological examination. The DWI+ lesion observed on in vivo MRI could be matched to an area with evidence of recent ischemia on histopathology. Ex vivo MRI of the intact hemispheres revealed a total of 130 DWI+/T2+ lesions in 10/12 CAA cases, but none in controls (p = 0.022). DWI+/T2+ lesions examined histopathologically proved to be acute microinfarcts (classification accuracy 100%), characterized by presence of eosinophilic neurons on hematoxylin and eosin and absence of reactive astrocytes on glial fibrillary acidic protein-stained sections. In conclusion, we suggest that small DWI+ lesions in CAA represent acute microinfarcts. Furthermore, our findings support the use of ex vivo DWI as a method to detect acute microinfarcts post-mortem, which may benefit future histopathological investigations on the etiology of microinfarcts. Show less
We provide an update on diagnostic methods for the detection of urogenital schistosomiasis (UGS) in men and highlight that satisfactory urine-antigen diagnostics for UGS lag much behind that for... Show moreWe provide an update on diagnostic methods for the detection of urogenital schistosomiasis (UGS) in men and highlight that satisfactory urine-antigen diagnostics for UGS lag much behind that for intestinal schistosomiasis, where application of a urine-based point-of-care strip assay, the circulating cathodic antigen (CCA) test, is now advocated. Making specific reference to male genital schistosomiasis (MGS), we place greater emphasis on parasitological detection methods and clinical assessment of internal genitalia with ultrasonography. Unlike the advances made in defining a clinical standard protocol for female genital schistosomiasis, MGS remains inadequately defined. Whilst urine filtration with microscopic examination for ova of Schistosoma haematobium is a convenient but error-prone proxy of MGS, we describe a novel low-cost sampling and direct visualization method for the enumeration of ova in semen. Using exemplar clinical cases of MGS from our longitudinal cohort study among fishermen along the shoreline of Lake Malawi, the portfolio of diagnostic needs is appraised including: the use of symptomatology questionnaires, urine analysis (egg count and CCA measurement), semen analysis (egg count, circulating anodic antigen measurement and real-time polymerase chain reaction analysis) alongside clinical assessment with portable ultrasonography. Show less
Hoekstra, P.T.; Partal, M.C.; Amoah, A.S.; Lieshout, L. van; Corstjens, P.L.A.M.; Tsonaka, S.; ... ; Dam, G.J. van 2018
BackgroundLarge scale administration of the anthelminthic drug praziquantel (PZQ) to at-risk populations is the cornerstone of schistosomiasis control, although persisting high prevalence of... Show moreBackgroundLarge scale administration of the anthelminthic drug praziquantel (PZQ) to at-risk populations is the cornerstone of schistosomiasis control, although persisting high prevalence of infections in some areas and growing concerns of PZQ resistance have revealed the limitations of this strategy. Most studies assessing PZQ efficacy have used relatively insensitive parasitological diagnostics, such as the Kato-Katz (KK) and urine-filtration methods, thereby overestimating cure rates (CRs). This study aims to determine the efficacy of repeated PZQ treatments against Schistosoma mansoni infection in school-aged children in Cote d'Ivoire using the traditional KK technique, as well as more sensitive antigen- and DNA-detection methods.MethodsAn open-label, randomised controlled trial will be conducted in school-aged children (5 to 18years) from the region of Taabo, Cote d'Ivoire, an area endemic for S. mansoni. This 8-week trial includes four two-weekly standard doses of PZQ in the intense treatment intervention group and one standard dose of PZQ in the standard treatment control group. The efficacy of PZQ will be evaluated in stool samples using the KK technique and real-time PCR as well as in urine using the point-of-care circulating cathodic antigen test and the up-converting phosphor, lateral flow, circulating anodic antigen assay. The primary outcome of the study will be the difference in CR of intense versus standard treatment with PZQ on individuals with a confirmed S. mansoni infection measured by KK. Secondary outcomes include the difference in CR and intensity reduction rate between the intense and standard treatment groups as measured by the other diagnostic tests, as well as the accuracy of the different diagnostic tests, and the safety of PZQ.DiscussionThis study will provide data on the efficacy of repeated PZQ treatment on the clearance of S. mansoni as measured by several diagnostic techniques. These findings will inform future mass drug administration policy and shed light on position of novel diagnostic tools to evaluate schistosomiasis control strategies.Trial registrationThe study is registered at EudraCT (2016-003017-10, date of registration: 22 July 2016) and (NCT02868385, date of registration: 16 August 2016). Show less
Hoekstra, P.T.; Partal, M.C.; Amoah, A.S.; Lieshout, L. van; Corstjens, P.L.A.M.; Tsonaka, S.; ... ; Dam, G.J. van 2018
The general aim of this thesis was to explore the possibility to detect changes related to amyloid deposition in vivo using ultra-high field MRI. The central finding of the work presented in this... Show moreThe general aim of this thesis was to explore the possibility to detect changes related to amyloid deposition in vivo using ultra-high field MRI. The central finding of the work presented in this thesis is the cortical phase change on T2*-weighted sequences that we observed in AD patients using this novel ultra-high field imaging approach at 7T. It has been demonstrated that such phase measurements are a reliable indicator of iron content in the brain. It is known that amyloid depositions co-localize with iron accumulations. However, in autopsy material of AD patients, in addition to amyloid deposition, neurofibrillary tangles as well as tau deficiency were also found to co-localize with neuronal iron accumulation. In addition to iron, myelin and deoxy-hemoglobin can also contribute to phase changes. Although the exact origin of the observed phase changes in AD is not completely clear, these changes could have value for diagnostic purposes and as a biomarker. Show less
Dam, G.J. van; Dood, C.J. de; Lewis, M.; Deelder, A.M.; Lieshout, L. van; Tanke, H.J.; ... ; Corstjens, P.L.A.M. 2013
Human schistosomiasis (bilharzia) is one of the major parasitic diseases in the world, affecting 200 million people predominantly in third world countries. In areas where the disease is highly... Show moreHuman schistosomiasis (bilharzia) is one of the major parasitic diseases in the world, affecting 200 million people predominantly in third world countries. In areas where the disease is highly prevalent it causes important health problems, and it also has socially-economic effects on the population. Schistosomiasis is caused by the presence of the blood-fluke Schistosoma in the blood-vessels of mammalian hosts. The current method for diagnosis of schistosomiasis in developing countries is the parasitological examination of urine and faeces for the presence of Schistosoma eggs. An alternative method which is now increasingly used is based on the detection of Schistosoma antigens in the circulatory system or the urine of the host. The gut of the parasite is an important source of these antigens since many gut-associated antigens are excreted into the circulation of the host following digestion of food (e.g. blood cells, proteins) by the parasite. Two major gut–associated antigens which have been thoroughly studied with regard to diagnostic detectability, are the circulating anodic antigen (CAA) and the circulating cathodic antigen (CCA). In this thesis, these two unique antigens are further analysed with respect to their biochemical carbohydrate structure, localization, in vitro and in vivo excretion and detection patterns, and their role in a number of host-parasite immune interactions (granulocytes, complement system). Show less
