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

Genetic testing of children for adult-onset conditions: opinions of the British adult population and implications for clinical practice

This study set out to explore the attitudes of a representative sample of the British public towards genetic testing in children to predict disease in the future. We sought opinions about genetic testing for adult-onset conditions for which no prevention/treatment is available during childhood, and about genetic 'carrier' status to assess future reproductive risks. The study also examined participants' level of agreement with the reasons professional organisations give in favour of deferring such testing. Participants (n=2998) completed a specially designed questionnaire, distributed by email. Nearly half of the sample (47%) agreed that parents should be able to test their child for adult-onset conditions, even if there is no treatment or prevention at time of testing. This runs contrary to professional guidance about genetic testing in children. Testing for carrier status was supported by a larger proportion (60%). A child's future ability to decide for her/himself if and when to be tested was the least supported argument in favour of deferring testing.European Journal of Human Genetics advance online publication, 5 November 2014; doi:10.1038/ejhg.2014.221

Epidemiological Interactions between Urogenital and Intestinal Human Schistosomiasis in the Context of Praziquantel Treatment across Three West African Countries

© 2015 Knowles et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

Observed Reductions in Schistosoma mansoni Transmission from Large-Scale Administration of Praziquantel in Uganda: A Mathematical Modelling Study

To date schistosomiasis control programmes based on chemotherapy have largely aimed at controlling morbidity in treated individuals rather than at suppressing transmission. In this study, a mathematical modelling approach was used to estimate reductions in the rate of Schistosoma mansoni reinfection following annual mass drug administration (MDA) with praziquantel in Uganda over four years (2003-2006). In doing this we aim to elucidate the benefits of MDA in reducing community transmission.Age-structured models were fitted to a longitudinal cohort followed up across successive rounds of annual treatment for four years (Baseline: 2003, TREATMENT: 2004-2006; n = 1,764). Instead of modelling contamination, infection and immunity processes separately, these functions were combined in order to estimate a composite force of infection (FOI), i.e., the rate of parasite acquisition by hosts.MDA achieved substantial and statistically significant reductions in the FOI following one round of treatment in areas of low baseline infection intensity, and following two rounds in areas with high and medium intensities. In all areas, the FOI remained suppressed following a third round of treatment.This study represents one of the first attempts to monitor reductions in the FOI within a large-scale MDA schistosomiasis morbidity control programme in sub-Saharan Africa. The results indicate that the Schistosomiasis Control Initiative, as a model for other MDA programmes, is likely exerting a significant ancillary impact on reducing transmission within the community, and may provide health benefits to those who do not receive treatment. The results obtained will have implications for evaluating the cost-effectiveness of schistosomiasis control programmes and the design of monitoring and evaluation approaches in general

A novel isolator-based system promotes viability of human embryos during laboratory processing

In vitro fertilisation (IVF) and related technologies are arguably the most challenging of all cell culture applications. The starting material is a single cell from which one aims to produce an embryo capable of establishing a pregnancy eventually leading to a live birth. Laboratory processing during IVF treatment requires open manipulations of gametes and embryos, which typically involves exposure to ambient conditions. To reduce the risk of cellular stress, we have developed a totally enclosed system of interlinked isolator-based workstations designed to maintain oocytes and embryos in a physiological environment throughout the IVF process. Comparison of clinical and laboratory data before and after the introduction of the new system revealed that significantly more embryos developed to the blastocyst stage in the enclosed isolator-based system compared with conventional open-fronted laminar flow hoods. Moreover, blastocysts produced in the isolator-based system contained significantly more cells and their development was accelerated. Consistent with this, the introduction of the enclosed system was accompanied by a significant increase in the clinical pregnancy rate and in the proportion of embryos implanting following transfer to the uterus. The data indicate that protection from ambient conditions promotes improved development of human embryos. Importantly, we found that it was entirely feasible to conduct all IVF-related procedures in the isolator-based workstations

New approaches to measuring anthelminthic drug efficacy: parasitological responses of childhood schistosome infections to treatment with praziquantel

By 2020, the global health community aims to control and eliminate human helminthiases, including schistosomiasis in selected African countries, principally by preventive chemotherapy (PCT) through mass drug administration (MDA) of anthelminthics. Quantitative monitoring of anthelminthic responses is crucial for promptly detecting changes in efficacy, potentially indicative of emerging drug resistance. Statistical models offer a powerful means to delineate and compare efficacy among individuals, among groups of individuals and among populations.; We illustrate a variety of statistical frameworks that offer different levels of inference by analysing data from nine previous studies on egg counts collected from African children before and after administration of praziquantel.; We quantify responses to praziquantel as egg reduction rates (ERRs), using different frameworks to estimate ERRs among population strata, as average responses, and within strata, as individual responses. We compare our model-based average ERRs to corresponding model-free estimates, using as reference the World Health Organization (WHO) 90 % threshold of optimal efficacy. We estimate distributions of individual responses and summarize the variation among these responses as the fraction of ERRs falling below the WHO threshold.; Generic models for evaluating responses to anthelminthics deepen our understanding of variation among populations, sub-populations and individuals. We discuss the future application of statistical modelling approaches for monitoring and evaluation of PCT programmes targeting human helminthiases in the context of the WHO 2020 control and elimination goals

A Comparative Study of the Spatial Distribution of Schistosomiasis in Mali in 1984–1989 and 2004–2006

Geostatistical maps are increasingly being used to plan neglected tropical disease control programmes. We investigated the spatial distribution of schistosomiasis in Mali prior to implementation of national donor-funded mass chemotherapy programmes using data from 1984–1989 and 2004–2006. The 2004–2006 dataset was collected after 10 years of schistosomiasis control followed by 12 years of no control. We found that national prevalence of Schistosoma haematobium and S. mansoni was not significantly different in 2004–2006 compared to 1984–1989 and that the spatial distribution of both infections was similar in both time periods, to the extent that models built on data from one time period could accurately predict the spatial distribution of prevalence of infection in the other time period. This has two main implications: that historic data can be used, in the first instance, to plan contemporary control programmes due to the stability of the spatial distribution of schistosomiasis; and that a decade of donor-funded mass distribution of praziquantel has had no discernable impact on the burden of schistosomiasis in subsequent generations of Malians, probably due to rapid reinfection

Surveillance of cirrhosis for hepatocellular carcinoma: a cost-utility analysis.

Using a decision-analytic model, we evaluated the effectiveness and cost-effectiveness of surveillance for hepatocellular carcinoma (HCC) in individuals with cirrhosis. Separate cohorts with cirrhosis due to alcoholic liver disease, hepatitis B and hepatitis C were simulated. Results were also combined to approximate a mixed aetiology population. Comparisons were made between a variety of surveillance algorithms using alpha-foetoprotein (AFP) assay and/or ultrasound at 6- and 12-monthly intervals. Parameter estimates were obtained from comprehensive literature reviews. Uncertainty was explored using one-way and probabilistic sensitivity analyses. In the mixed aetiology cohort, 6-monthly AFP+ultrasound was predicted to be the most effective strategy. The model estimates that, compared with no surveillance, this strategy may triple the number of people with operable tumours at diagnosis and almost halve the number of people who die from HCC. The cheapest strategy employed triage with annual AFP (incremental cost-effectiveness ratio (ICER): 20,700 pounds per quality-adjusted life-year (QALY) gained). At a willingness-to-pay threshold of 30,000 pounds per QALY the most cost-effective strategy used triage with 6-monthly AFP (ICER: 27,600 pounds per QALY gained). The addition of ultrasound to this strategy increased the ICER to 60,100 pounds per QALY gained. Surveillance appears most cost-effective in individuals with hepatitis B-related cirrhosis, potentially due to younger age at diagnosis of cirrhosis. Our results suggest that, in a UK NHS context, surveillance of individuals with cirrhosis for HCC should be considered effective and cost-effective. The economic efficiency of different surveillance strategies is predicted to vary markedly according to cirrhosis aetiology

Acquisition of Ca2+ and HCO3−/CO32− for shell formation in embryos of the common pond snail Lymnaea stagnalis

Embryos of the freshwater common pond snail Lymnaea stagnalis develop to hatch within 10 days under control conditions (22°C, Miami-Dade tap water) and this development is impaired by removal of ambient calcium. In contrast, embryos did not exhibit dependence upon an ambient HCO3−/CO32− source, developing and hatching in HCO3−/CO32−-free water at rates comparable to controls. Post-metamorphic, shell-laying embryos exhibited a significant saturation-type calcium uptake as a function of increasing ambient calcium concentration. However, changes in ambient bicarbonate concentration did not influence calcium or apparent titratable alkalinity uptake. There was a distinct shift from no significant flux in pre-metamorphic embryos to net uptake of calcium in post-metamorphic stages as indicated by an increased uptake from the micro-environment surrounding the egg mass and increased net uptake in 24-h, whole egg mass flux measurements. Furthermore, HCO3−/CO32− acquisition as measured by titratable alkalinity flux is at least partially attributable to an endogenous carbonate source that is associated with acid extrusion. Thus, calcium requirements for embryonic shell formation are met via uptake but HCO3−/CO32−, which is also necessary for shell formation is acquired in part from endogenous sources with no detectable correlation to ambient HCO3−/CO32− availability