Sensitive diagnosis and post-treatment follow-up of Schistosoma mansoni infections in asymptomatic Eritrean refugees by Circulating Anodic Antigen (CAA) detection and PCR

The increasing number of refugees coming from or passing through Schistosoma-endemic areas and arriving in Europe highlights the importance of screening for schistosomiasis on arrival, and focuses attention on the choice of diagnostic test. We evaluate the diagnostic performance of circulating anodic antigen (CAA) detection in 92 asymptomatic refugees from Eritrea. Results were compared with already-available stool microscopy, serology, and urine point-of-care circulating cathodic antigen (POC-CCA) data. For a full diagnostic comparison, real-time polymerase chain reaction (PCR) and the POC-CCA were included. All outcomes were compared against a composite reference standard. Urine and serum samples were subjected to the ultra-sensitive and highly specific up-converting particle lateral flow CAA test, Schistosoma spp. real-time PCR was performed on urine and stool, and the POC-CCA was used on urine using the G-score method. CAA was detected in 43% of urine and in 40% of serum samples. Urine PCR was negative in all 92 individuals, whereas 25% showed Schistosoma DNA in stool. POC-CCA was positive in 30% of individuals. The CAA test confirmed all microscopy positives, except for two cases that were also negative by all other diagnostic procedures. Post-treatment, a significant reduction in the number of positives and infection intensity was observed, in particular regarding CAA levels. Our findings confirm that microscopy, serology, and POC-CCA lack the sensitivity to detect all active Schistosoma infections. Accuracy of stool PCR was similar to microscopy, indicating that this method also lacks sensitivity. The CAA test appeared to be the most accurate method for screening active Schistosoma infections and for monitoring treatment efficacy

Sensitive Diagnosis and Post-Treatment Follow-Up of Schistosoma mansoni Infections in Asymptomatic Eritrean Refugees by Circulating Anodic Antigen Detection and Polymerase Chain Reaction

The increasing number of refugees coming from or passing through Schistosoma-endemic areas and arriving in Europe highlights the importance of screening for schistosomiasis on arrival, and focuses attention on the choice of diagnostic test. We evaluate the diagnostic performance of circulating anodic antigen (CAA) detection in 92 asymptomatic refugees from Eritrea. Results were compared with already-available stool microscopy, serology, and urine point-of-care circulating cathodic antigen (POC-CCA) data. For a full diagnostic comparison, real-time polymerase chain reaction (PCR) and the POC-CCA were included. All outcomes were compared against a composite reference standard. Urine and serum samples were subjected to the ultra-sensitive and highly specific up-converting particle lateral flow CAA test, Schistosoma spp. real-time PCR was performed on urine and stool, and the POC-CCA was used on urine using the G-score method. CAA was detected in 43% of urine and in 40% of serum samples. Urine PCR was negative in all 92 individuals, whereas 25% showed Schistosoma DNA in stool. POC-CCA was positive in 30% of individuals. The CAA test confirmed all microscopy positives, except for two cases that were also negative by all other diagnostic procedures. Post-treatment, a significant reduction in the number of positives and infection intensity was observed, in particular regarding CAA levels. Our findings confirm that microscopy, serology, and POC-CCA lack the sensitivity to detect all active Schistosoma infections. Accuracy of stool PCR was similar to microscopy, indicating that this method also lacks sensitivity. The CAA test appeared to be the most accurate method for screening active Schistosoma infections and for monitoring treatment efficacy

Efficacy of single versus four repeated doses of praziquantel against Schistosoma mansoni infection in school-aged children from Côte d'Ivoire based on Kato-Katz and POC-CCA: An open-label, randomised controlled trial (RePST).

BACKGROUND: Preventive chemotherapy with praziquantel (PZQ) is the cornerstone of schistosomiasis control. However, a single dose of PZQ (40 mg/kg) does not cure all infections. Repeated doses of PZQ at short intervals might increase efficacy in terms of cure rate (CR) and intensity reduction rate (IRR). Here, we determined the efficacy of a single versus four repeated treatments with PZQ on Schistosoma mansoni infection in school-aged children from Côte d'Ivoire, using two different diagnostic tests. METHODS: An open-label, randomized controlled trial was conducted from October 2018 to January 2019. School-aged children with a confirmed S. mansoni infection based on Kato-Katz (KK) and point-of-care circulating cathodic antigen (POC-CCA) urine cassette test were randomly assigned to receive either a single or four repeated doses of PZQ, administered at two-week intervals. The primary outcome was the difference in CR between the two treatment arms, measured by triplicate KK thick smears 10 weeks after the first treatment. Secondary outcomes included CR estimated by POC-CCA, IRR by KK and POC-CCA, and safety of repeated PZQ administration. PRINCIPAL FINDINGS: During baseline screening, 1,022 children were assessed for eligibility of whom 153 (15%) had a detectable S. mansoni infection, and hence, were randomized to the standard treatment group (N = 70) and the intense treatment group (N = 83). Based on KK, the CR was 42% (95% confidence interval (CI) 31-52%) in the standard treatment group and 86% (95% CI 75-92%) in the intense treatment group. Observed IRR was 72% (95% CI 55-83%) in the standard treatment group and 95% (95% CI 85-98%) in the intense treatment group. The CR estimated by POC-CCA was 18% (95% CI 11-27%) and 36% (95% CI 26-46%) in the standard and intense treatment group, respectively. Repeated PZQ treatment did not result in a higher number of adverse events. CONCLUSION/SIGNIFICANCE: The observed CR using KK was significantly higher after four repeated treatments compared to a single treatment, without an increase in adverse events. Using POC-CCA, the observed CR was significantly lower than measured by KK, indicating that PZQ may be considerably less efficacious as concluded by KK. Our findings highlight the need for reliable and more accurate diagnostic tools, which are essential for monitoring treatment efficacy, identifying changes in transmission, and accurately quantifying the intensity of infection in distinct populations. In addition, the higher CR in the intense treatment group suggests that more focused and intense PZQ treatment can help to advance schistosomiasis control. TRIAL REGISTRATION: www.clinicaltrials.gov NCT02868385

Validation of artificial intelligence-based digital microscopy for automated detection of Schistosoma haematobium eggs in urine in Gabon

Introduction Schistosomiasis is a significant public health concern, especially in Sub-Saharan Africa. Conventional microscopy is the standard diagnostic method in resource-limited settings, but with limitations, such as the need for expert microscopists. An automated digital microscope with artificial intelligence (Schistoscope), offers a potential solution. This field study aimed to validate the diagnostic performance of the Schistoscope for detecting and quantifying Schistosoma haematobium eggs in urine compared to conventional microscopy and to a composite reference standard (CRS) consisting of real-time PCR and the up-converting particle (UCP) lateral flow (LF) test for the detection of schistosome circulating anodic antigen (CAA). Methods Based on a non-inferiority concept, the Schistoscope was evaluated in two parts: study A, consisting of 339 freshly collected urine samples and study B, consisting of 798 fresh urine samples that were also banked as slides for analysis with the Schistoscope. In both studies, the Schistoscope, conventional microscopy, real-time PCR and UCP-LF CAA were performed and samples with all the diagnostic test results were included in the analysis. All diagnostic procedures were performed in a laboratory located in a rural area of Gabon, endemic for S. haematobium. Results In study A and B, the Schistoscope demonstrated a sensitivity of 83.1% and 96.3% compared to conventional microscopy, and 62.9% and 78.0% compared to the CRS. The sensitivity of conventional microscopy in study A and B compared to the CRS was 61.9% and 75.2%, respectively, comparable to the Schistoscope. The specificity of the Schistoscope in study A (78.8%) was significantly lower than that of conventional microscopy (96.4%) based on the CRS but comparable in study B (90.9% and 98.0%, respectively). Conclusion Overall, the performance of the Schistoscope was non-inferior to conventional microscopy with a comparable sensitivity, although the specificity varied. The Schistoscope shows promising diagnostic accuracy, particularly for samples with moderate to higher infection intensities as well as for banked sample slides, highlighting the potential for retrospective analysis in resource-limited settings

Sensitive diagnostic tools and targeted drug administration strategies are needed to eliminate schistosomiasis.

Although preventive chemotherapy has been instrumental in reducing schistosomiasis incidence worldwide, serious challenges remain. These problems include the omission of certain groups from campaigns of mass drug administration, the existence of persistent disease hotspots, and the risk of recrudescent infections. Central to these challenges is the fact that the diagnostic tools currently used to establish the burden of infection are not sensitive enough, especially in low-endemic settings, which results in underestimation of the true prevalence of active Schistosoma spp infections. This central issue necessitates that the current schistosomiasis control strategies recommended by WHO are re-evaluated and, possibly, adapted. More targeted interventions and novel approaches have been used to estimate the prevalence of schistosomiasis, such as establishing infection burden by use of precision mapping, which provides high resolution spatial information that delineates variations in prevalence within a defined geographical area. Such information is instrumental in guiding targeted intervention campaigns. However, the need for highly accurate diagnostic tools in such strategies is a crucial factor that is often neglected. The availability of highly sensitive diagnostic tests also opens up the possibility of applying strategies of sample pooling to reduce the cost of control programmes. To interrupt the transmission of, and eventually eliminate, schistosomiasis, better local targeting of preventive chemotherapy, in combination with highly sensitive diagnostic tools, is crucial

“Role of Adipose-Derived Mesenchymal Stem Cells in Full Thickness Wound Healing .”

Abstract Background: Wound healing problems can arise in donor wounds after harvesting a full-thickness graft. Returning Mesenchymal Stem Cells (MSCs) on the wounds may accelerate wound healing. The aim of this study is to analyse the effect of MSCs in the epithelialization process and collagen density on full-thickness wound healing. Methods: The pilot study included 10 patients undergoing excision of a full-thickness skin graft on the groin. Patients were randomly divided into two groups: Mesenchymal Stem Cells (MSCs) and Non-Mesenchymal Stem Cells (Non-MSCs). The MSCs group had previously undergone fat harvesting which was processed into mesenchymal stem cells. Biopsies were taken from both groups on days 14 (proliferative phase) and 45 (maturation phase), and were compared with normal skin (NS; n=5). Epithelial layers of the epidermis were assessed with hematoxylin eosin staining. Collagen density was evaluated with MT staining, and analysed using a light microscope. Result: In the MSCs group and the Non-MSCs group, the number of epithelial layers were significantly higher compared to the NS-group on day 45 (14.7 ± 0.70 and 8.24 ± 0.76 vs 5.43 ± 0.60 respectively; p<0.001 and p<0.001). The collagen density in the MSCs group on day 14 was 33.3 ± 2.46% in the MSCs group and 45.7 ± 5.84% in the non-MSCs group, compared to 54.3 ± 3.71% in the NS-group (p<0.001 and p=0.012 resp.). These values increased on day 45 to 49.2 ± 3.28% in the MSCs group, and 73.4 ± 1.63% in the non-MSCs group. Conclusion: Mesenchymal stem cells increased the number of epithelial layers in the full-thickness wound healing process compared to normal skin. A higher increase was seen in the MSCs-group. On day 45, an increase in collagen density was observed in the MSCs group and Non-MSCs group. Adipose-derived mesenchymal stem cells can be used in the process of full-thickness wound healing. Future randomized controlled trials are needed to confirm these findings

Posthepatectomy Bile Leakage: How to Manage

Background: Biliary leakage after liver resection continues to be reported. Management of bile leakage has changed in recent years, with nowadays non-surgical procedures as the preferred treatment. Methods: Biliary leakage and management were assessed in 381 patients who underwent liver resection between January 2005 and April 2011. Results: The overall rate of biliary leakage after liver resection was 5.0%, with a higher incidence in patients who had undergone concomitant hepaticojejunostomy (Hi; 13.6 vs. 3.2%). Hospital stay (p = 0.047), major resections (p = 0.018), operation time (p = 0.011), and relaparotomy (p = 0.002) were risk factors for postoperative bile leakage. Multivariate analysis identified relaparotomy as an independent factor (OR 4.216, p = 0.034). Bile leakage in patients without HJ (n = 10) was managed in 6 patients by percutaneous transhepatic biliary drainage (PTD), and in 3 patients by endoscopic drainage. One patient was treated surgically. All patients with an Hi and postoperative bile leakage (n = 9) underwent PTD. Conclusion:The incidence of posthepatectomy biliary leakage has decreased over time, while PTD and endoscopic stenting are effective treatment modalities. PTD is the treatment of choice in bile leakage after resection combined with HJ. Copyright (C) 2012 S. Karger AG, Base

A review of animal models for portal vein embolization

Portal vein embolization (PVE) is a preoperative intervention to increase the future remnant liver (FRL) through regeneration of the non-embolized liver lobes. This review assesses all the relevant animal models of PVE available, to guide researchers who intend to study PVE. We performed a systematic literature search in Medline and Pubmed, from 1993-June 2013, using search headings "PVE" and "portal vein ligation". Articles were included when meeting the selection criteria: experimental animal study on PVE or portal vein ligation and experiments described in 5 animals or more. Sixty-one articles were selected, describing six different animal models. Most articles reported experiments with rats, rabbits, and pigs. In rats, the increase in wet-weight ratio of the non-occluded liver or total liver weight is greatest in the first 7 d with values ranging from 75%-80.5% on day 7. The volume increase of FRL in the rabbit model is greatest in the first 7 d with values ranging from 33.6%-80% on day 7. In pigs, the largest gain in volume of the FRL was seen in the first 2 wk. The choice of the model depends on the specific aim of the study. Evaluating the increase in liver volume and liver function after PVE, larger animals as the pig, rabbit, or the dog is useful because of the possibility to apply computed tomography volumetry. To evaluate mechanisms of regeneration after PVE, the rat model is useful, because of the variety of antibodies commercially availabl

Staging laparoscopy in patients with hepatocellular carcinoma: is it useful?

Staging laparoscopy (SL) is not regularly performed for patients with hepatocellular carcinoma (HCC). It may change treatment strategy, preventing unnecessary open exploration. An additional advantage of SL is possible biopsy of the nontumorous liver to assess fibrosis/cirrhosis. This study aimed to determine whether SL for patients with HCC still is useful. Patients with HCC who underwent SL between January 1999 and December 2011 were analyzed. Their demographics, preoperative imaging studies, surgical findings, and histology were assessed. The 56 patients (34 men and 22 women; mean age, 60 ± 14 years) in this study underwent SL for assessment of extensive disease or metastases. For two patients, SL was unsuccessful because of intraabdominal adhesions. For four patients (7.1 %), SL showed unresectability because of metastases (n = 1), tumor progression (n = 1), or severe cirrhosis in the contralateral lobe (n = 2). An additional five patients did not undergo laparotomy due to disease progression detected on imaging after SL. Exploratory laparotomy for the remaining 47 patients showed 6 (13 %) additional unresectable tumors due to advanced tumor (n = 5) or nodal metastases (n = 1). Consequently, the yield of SL was 7 % (95 % confidence interval (CI), 3-17 %), and the accuracy was 27 % (95 % CI, 11-52 %). A biopsy of the contralateral liver was performed for 45 patients who underwent SL, leading to changes in management for 4 patients (17 %) with cirrhosis. The overall yield of SL for HCC was 7 %, and the accuracy was 27 %. When accurate imaging methods are available and additional percutaneous liver biopsy is implemented as a standard procedure in the preoperative workup of patients with HCC, the benefit of SL will become even les