The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was funded in 2008 to conduct research that would support country schistosomiasis control programs. As schistosomiasis prevalence decreases in many places and elimination is increasingly within reach, a sensitive and specific test to detect infection with Schistosoma mansoni and Schistosoma haematobium has become a pressing need. After obtaining broad input, SCORE supported Leiden University Medical Center (LUMC) to modify the serum-based antigen assay for use with urine, simplify the assay, and improve its sensitivity. The urine assay eventually contributed to several of the larger SCORE studies. For example, in Zanzibar, we demonstrated that urine filtration, the standard parasite egg detection diagnostic test for S. haematobium, greatly underestimated prevalence in low-prevalence settings. In Burundi and Rwanda, the circulating anodic antigen (CAA) assay provided critical information about the limitations of the stool-based Kato-Katz parasite eggdetection assay for S. mansoni in low-prevalence settings. Other SCORE-supported CAA work demonstrated that frozen, banked urine specimens yielded similar results to fresh ones; pooling of specimens may be a useful, cost-effective approach for surveillance in some settings; and the assay can be performed in local laboratories equipped with adequate centrifuge capacity. These improvements in the assay continue to be of use to researchers around the world. However, additional work will be needed if widespread dissemination of the CAA assay is to occur, for example, by building capacity in places besides LUMC and commercialization of the assay. Here, we review the evolution of the CAA assay format during the SCORE period with emphasis on urine-based applications.

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Radiosynthesis of ML03 (N-{4 Key words: carbon-11; cancer; biodistribution; PET; EGFrGrowth factors mediate their pleiotropic actions by binding to and activating receptor tyrosine kinases. Epidermal growth factor receptor (EGFr, erb-B1) belongs to a family of proteins involved in the proliferation of normal and malignant cells. 1,2 The binding of activating ligands such as EGF, TGF ␣, AR, BTC or HB-EGF to the EGFr results in activation of the cytosolic kinase domain. Overexpression of EGFr is the hallmark of many human tumors such as breast cancer, glioma, laryngeal cancer, squamous cell carcinoma of the head and neck and prostate cancer. 3 Since the late 1980s continuous effort has been invested in the development of EGFr tyrosine kinase inhibitors as anti-neoplastic drugs. 4,5-11 Radioactively labeled small molecules with high affinity and selectivity for the tyrosine kinase domain of EGFr might offer a specific and sensitive tool to be used in positron emission tomography (PET) for diagnosis of tumors overexpressing EGFr. PET provides 3D and quantitative maps of the distribution of radioactive tracers within the human body and hence permits the measurement of physiological, biochemical and pharmacological function at the molecular level, both in healthy and pathological states. PET is based on the use of short half-life positron-emitting isotopes, such as 11 C (t 1/2 20.39 min.), 18 F (t 1/2 109.8 min.), 15 O (t 1/2 2.037 min.) and 13 N (t 1/2 9.965 min.). After injection of a suitable biomarker, the PET scan provides a mapping of the biomarker distribution and hence of a specific receptor, transporter or enzyme in the human body. Biomarkers with high selectivity for a specific receptor or enzyme might accumulate in those organs and tissues where the targeted protein is overexpressed. In the case of EGFr, its overexpression in human tumors could be non-invasively detected by labeling tyrosine kinase inhibitors with positron-emitting isotopes. The PET application of these potential biomarkers represents a new strategy for the diagnosis of EGFr-expressing tumors. [12][13][14] Moreover, the increasing demand to incorporate diagnostics into clinical studies of EGFr-targeted therapies suggests a potential future use of EGFrTK labeled inhibitors. These labeled inhibitors could help select patients for clinical trials. Cancer patients could undergo a non-invasive diagnostic PET study with labeled EGFrTK inhibitor, and if their tumor is found to overexpress EGFrTK, they could then be selected for a clinical trial that utilizes anti-EGFr therapy.In our previous work, 15 we synthesized, labeled and evaluated 4-(fluoroanilino)quinazoline derivatives as EGFrTK PET biomarkers. These molecules bind reversibly to the ATP binding site of the receptor and inhibit the autophosphorylation of the EGFrTK. Competition with intracellular ATP results in their fast dissociation from the EGFr kinase site, however, making these compounds ineffective as PET reporter probes. We therefore concluded that irreversible EGFr tyrosine kinase ...

A new highly pathogenic strain of influenza virus, H5N1, has emerged causing severe outbreaks in poultry and high mortality rates when humans are infected. The threat of a new influenza pandemic has prompted countries to draft national strategic preparedness plans to prevent, contain and mitigate the next human influenza pandemic. To evaluate preparedness for an influenza pandemic in the African region we analysed African national preparedness plans available in the public domain. A data extraction tool, based on a World Health Organization checklist for influenza epidemic preparedness, was designed in consultation with pandemic influenza planning experts and experts on the region's public health challenges. Thirty-five plans were identified and available from 53 African countries. Most plans are relatively robust in addressing detection and containment of influenza in animals but strategic preparedness to respond to pandemic human influenza is weak. In most plans communication strategies have been developed with the aim to raise awareness of transmission factors and promote hygiene measures. By contrast, the human health care sector is ill-prepared. Case management, triage procedures, identification of health care facilities for patient treatment (including home care and provisions for the distribution and administration of pharmaceuticals) are poorly addressed by most plans. The maintenance of essential services in the event of a pandemic is absent from most plans. Whilst many African countries have strategic pandemic influenza preparedness plans, most are developmental in nature and lack operational clarity, or focus principally on the containment of avian influenza rather than pandemic human influenza. Clear strategies, that are operational, need to be developed that reflect the realities of national context and resource constraints and that meet national objectives. These objectives need also to be coherent with international imperatives such that the global threat of pandemic influenza can be met effectively and efficiently.

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BackgroundKato-Katz examination of stool smears is the field-standard method for detecting Schistosoma mansoni infection. However, Kato-Katz misses many active infections, especially of light intensity. Point-of-care circulating cathodic antigen (CCA) is an alternative field diagnostic that is more sensitive than Kato-Katz when intensity is low, but interpretation of CCA-trace results is unclear. To evaluate trace results, we tested urine and stool specimens from 398 pupils from eight schools in Burundi using four approaches: two in Burundi and two in a laboratory in Leiden, the Netherlands. In Burundi, we used Kato-Katz and point-of-care CCA (CCAB). In Leiden, we repeated the CCA (CCAL) and also used Up-Converting Phosphor Circulating Anodic Antigen (CAA).MethodsWe applied Bayesian latent class analyses (LCA), first considering CCA traces as negative and then as positive. We used the LCA output to estimate validity of the prevalence estimates of each test in comparison to the population-level infection prevalence and estimated the proportion of trace results that were likely true positives.ResultsKato-Katz yielded the lowest prevalence (6.8%), and CCAB with trace considered positive yielded the highest (53.5%). There were many more trace results recorded by CCA in Burundi (32.4%) than in Leiden (2.3%). Estimated prevalence with CAA was 46.5%. LCA indicated that Kato-Katz had the lowest sensitivity: 15.9% [Bayesian Credible Interval (BCI): 9.2–23.5%] with CCA-trace considered negative and 15.0% with trace as positive (BCI: 9.6–21.4%), implying that Kato-Katz missed approximately 85% of infections. CCAB underestimated disease prevalence when trace was considered negative and overestimated disease prevalence when trace was considered positive, by approximately 12 percentage points each way, and CAA overestimated prevalence in both models. Our results suggest that approximately 52.2% (BCI: 37.8–5.8%) of the CCAB trace readings were true infections.ConclusionsWhether measured in the laboratory or the field, CCA outperformed Kato-Katz at the low infection intensities in Burundi. CCA with trace as negative likely missed many infections, whereas CCA with trace as positive overestimated prevalence. In the absence of a field-friendly gold standard diagnostic, the use of a variety of diagnostics with differing properties will become increasingly important as programs move towards elimination of schistosomiasis. It is clear that CCA is a valuable tool for the detection and mapping of S. mansoni infection in the field and CAA may be a valuable field tool in the future.Electronic supplementary materialThe online version of this article (10.1186/s13071-018-2700-4) contains supplementary material, which is available to authorized users.

Following implementation of the national control program, a reassessment of Schistosoma mansoni prevalence was conducted in Burundi to determine the feasibility of moving toward elimination. A countrywide cluster-randomized cross-sectional study was performed in May 2014. At least 25 schools were sampled from each of five eco-epidemiological risk zones for schistosomiasis. Fifty randomly selected children 13–14 years of age per school were included for a single urine-circulating cathodic antigen (CCA) rapid test and, in a subset of schools, for duplicate Kato-Katz slide preparation from a single stool sample. A total of 17,331 children from 347 schools were tested using CCA. The overall prevalence of S. mansoni infection, when CCA trace results were considered negative, was 13.5% (zone range [zr] = 4.6–17.8%), and when CCA trace results were considered positive, it was 42.8% (zr = 34.3–49.9%). In 170 schools, prevalence of this infection determined using Kato-Katz method was 1.5% (zr ==0–2.7%). The overall mean intensity of S. mansoni infection determined using Kato-Katz was 0.85 eggs per gram (standard deviation = 10.86). A majority of schools (84%) were classified as non-endemic (prevalence = 0) using Kato-Katz; however, a similar proportion of schools were classified as endemic when CCA trace results were considered negative (85%) and nearly all (98%) were endemic when CCA trace results were considered positive. The findings of this nationwide reassessment using a CCA rapid test indicate that Schistosoma infection is still widespread in Burundi, although its average intensity is probably low. Further evidence is now needed to determine the association between CCA rapid test positivity and low-intensity disease transmission.

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