Fecal occult blood and fecal calprotectin as point-of-care markers of intestinal morbidity in Ugandan children with Schistosoma mansoni infection.

BACKGROUND: Calprotectin is a calcium-binding cytoplasmic protein found in neutrophils and increasingly used as a marker of bowel inflammation. Fecal occult blood (FOB) is also a dependable indicator of bowel morbidity. The objective of our study was to determine the applicability of these tests as surrogate markers of Schistosoma mansoni intestinal morbidity before and after treatment with praziquantel (PZQ). METHODS: 216 children (ages 3-9 years old) from Buliisa District in Lake Albert, Uganda were examined and treated with PZQ at baseline in October 2012 with 211 of them re-examined 24 days later for S. mansoni and other soil transmitted helminths (STH). POC calprotectin and FOB assays were performed at both time points on a subset of children. Associations between the test results and infection were analysed by logistic regression. RESULTS: Fecal calprotectin concentrations of 150-300 µg/g were associated with S. mansoni egg patent infection both at baseline and follow up (OR: 12.5 P = 0.05; OR: 6.8 P = 0.02). FOB had a very strong association with baseline anemia (OR: 9.2 P = 0.03) and medium and high egg intensity schistosomiasis at follow up (OR: 6.6 P = 0.03; OR: 51.3 P = 0.003). Both tests were strongly associated with heavy intensity S. mansoni infections. There was a significant decrease in FOB and calprotectin test positivity after PZQ treatment in those children who had egg patent schistosomiasis at baseline. CONCLUSIONS: Both FOB and calprotectin rapid assays were found to correlate positively and strongly with egg patent S. mansoni infection with a positive ameloriation response after PZQ treatment indicative of short term reversion of morbidity. Both tests were appropriate for use in the field with excellent operational performance and reliability. Due to its lower-cost which makes its scale-up of use affordable, FOB could be immediately adopted as a monitoring tool for PC campaigns for efficacy evaluation before and after treatment

Matrix Metalloproteinases in Cytotoxic Lymphocytes Impact on Tumour Infiltration and Immunomodulation

To efficiently combat solid tumours, endogenously or adoptively transferred cytotoxic T cells and natural killer (NK) cells, need to leave the vasculature, traverse the interstitium and ultimately infiltrate the tumour mass. During this locomotion and migration in the three dimensional environment many obstacles need to be overcome, one of which is the possible impediment of the extracellular matrix. The first and obvious one is the sub-endothelial basement membrane but the infiltrating cells will also meet other, both loose and tight, matrix structures that need to be overridden. Matrix metalloproteinases (MMPs) are believed to be one of the most important endoprotease families, with more than 25 members, which together have function on all known matrix components. This review summarizes what is known on synthesis, expression patterns and regulation of MMPs in cytotoxic lymphocytes and their possible role in the process of tumour infiltration. We also discuss different functions of MMPs as well as the possible use of other lymphocyte proteases for matrix degradation

Treatment and Monitoring of Children with Chronic Hepatitis C in the Pre‐DAA Era: a European Survey of 38 Paediatric Specialists

The burden of paediatric Hepatitis C virus (HCV) infection across Europe is unknown, as are current policies regarding monitoring and treatment. This collaborative study aimed to collect aggregate data to characterise the population of ≤18-year-olds with HCV infection in specialist follow up in a 12-month period (2016) across the PENTAHep European consortium, and investigate current policies around monitoring and treatment. A cross-sectional, web-based survey was distributed in April 2017 to 50 paediatricians in 19 European countries, covering patients' profile, and monitoring and treatment practices. Responses were received from 38/50 clinicians collectively caring for 663 children with chronic HCV infection of whom three-quarters were aged ≥6 years and 90% vertically infected. HCV genotype 1 was the most common (n 380; 57.3%), followed by genotype 3, 4 and 2. Seventeen children (3%) with chronic HCV infection were diagnosed with cirrhosis, and six were reported to have received liver transplantation for HCV-related liver disease. The majority (n 425; 64.1%) of the European children with HCV infection remained treatment-naive in 2016. Age affected clinicians' attitudes towards treatment; 94% reported being willing to use direct-acting antivirals, if available, in adolescents (aged ≥11 years), 78% in children aged 6-10 and 42% in those 3-5 years of age (Pearson correlation coefficient -0.98; P 0.0001). This survey provides the largest characterisation of the population of children in clinical follow-up for chronic HCV infection in Europe, alongside important contextual information on their management and treatment. Discussion is needed around strategies and criteria for use of direct-acting antivirals in these children