Trypanosoma brucei Modifies the Tsetse Salivary Composition, Altering the Fly Feeding Behavior That Favors Parasite Transmission

Tsetse flies are the notorious transmitters of African trypanosomiasis, a disease caused by the Trypanosoma parasite that affects humans and livestock on the African continent. Metacyclic infection rates in natural tsetse populations with Trypanosoma brucei, including the two human-pathogenic subspecies, are very low, even in epidemic situations. Therefore, the infected fly/host contact frequency is a key determinant of the transmission dynamics. As an obligate blood feeder, tsetse flies rely on their complex salivary potion to inhibit host haemostatic reactions ensuring an efficient feeding. The results of this experimental study suggest that the parasite might promote its transmission through manipulation of the tsetse feeding behavior by modifying the saliva composition. Indeed, salivary gland Trypanosoma brucei-infected flies display a significantly prolonged feeding time, thereby enhancing the likelihood of infecting multiple hosts during the process of a single blood meal cycle. Comparison of the two major anti-haemostatic activities i.e. anti-platelet aggregation and anti-coagulation activity in these flies versus non-infected tsetse flies demonstrates a significant suppression of these activities as a result of the trypanosome-infection status. This effect was mainly related to the parasite-induced reduction in salivary gland gene transcription, resulting in a strong decrease in protein content and related biological activities. Additionally, the anti-thrombin activity and inhibition of thrombin-induced coagulation was even more severely hampered as a result of the trypanosome infection. Indeed, while naive tsetse saliva strongly inhibited human thrombin activity and thrombin-induced blood coagulation, saliva from T. brucei-infected flies showed a significantly enhanced thrombinase activity resulting in a far less potent anti-coagulation activity. These data clearly provide evidence for a trypanosome-mediated modification of the tsetse salivary composition that results in a drastically reduced anti-haemostatic potential and a hampered feeding performance which could lead to an increase of the vector/host contact and parasite transmission in field conditions

A Research Agenda for Helminth Diseases of Humans: Towards Control and Elimination

Human helminthiases are of considerable public health importance in sub-Saharan Africa, Asia, and Latin America. The acknowledgement of the disease burden due to helminth infections, the availability of donated or affordable drugs that are mostly safe and moderately efficacious, and the implementation of viable mass drug administration (MDA) interventions have prompted the establishment of various large-scale control and elimination programmes. These programmes have benefited from improved epidemiological mapping of the infections, better understanding of the scope and limitations of currently available diagnostics and of the relationship between infection and morbidity, feasibility of community-directed or school-based interventions, and advances in the design of monitoring and evaluation (M&E) protocols. Considerable success has been achieved in reducing morbidity or suppressing transmission in a number of settings, whilst challenges remain in many others. Some of the obstacles include the lack of diagnostic tools appropriate to the changing requirements of ongoing interventions and elimination settings; the reliance on a handful of drugs about which not enough is known regarding modes of action, modes of resistance, and optimal dosage singly or in combination; the difficulties in sustaining adequate coverage and compliance in prolonged and/or integrated programmes; an incomplete understanding of the social, behavioural, and environmental determinants of infection; and last, but not least, very little investment in research and development (R&D). The Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to undertake a comprehensive review of recent advances in helminthiases research, identify research gaps, and rank priorities for an R&D agenda for the control and elimination of these infections. This review presents the processes undertaken to identify and rank ten top research priorities; discusses the implications of realising these priorities in terms of their potential for improving global health and achieving the Millennium Development Goals (MDGs); outlines salient research funding needs; and introduces the series of reviews that follow in this PLoS Neglected Tropical Diseases collection, “A Research Agenda for Helminth Diseases of Humans.

Endothelium-Based Biomarkers Are Associated with Cerebral Malaria in Malawian Children: A Retrospective Case-Control Study

Differentiating cerebral malaria (CM) from other causes of serious illness in African children is problematic, owing to the non-specific nature of the clinical presentation and the high prevalence of incidental parasitaemia. CM is associated with endothelial activation. In this study we tested the hypothesis that endothelium-derived biomarkers are associated with the pathophysiology of severe malaria and may help identify children with CM.Plasma samples were tested from children recruited with uncomplicated malaria (UM; n = 32), cerebral malaria with retinopathy (CM-R; n = 38), clinically defined CM without retinopathy (CM-N; n = 29), or non-malaria febrile illness with decreased consciousness (CNS; n = 24). Admission levels of angiopoietin-2 (Ang-2), Ang-1, soluble Tie-2 (sTie-2), von Willebrand factor (VWF), its propeptide (VWFpp), vascular endothelial growth factor (VEGF), soluble ICAM-1 (sICAM-1) and interferon-inducible protein 10 (IP-10) were measured by ELISA. Children with CM-R had significantly higher median levels of Ang-2, Ang-2:Ang-1, sTie-2, VWFpp and sICAM-1 compared to children with CM-N. Children with CM-R had significantly lower median levels of Ang-1 and higher median concentrations of Ang-2:Ang-1, sTie-2, VWF, VWFpp, VEGF and sICAM-1 compared to UM, and significantly lower median levels of Ang-1 and higher median levels of Ang-2, Ang-2:Ang-1, VWF and VWFpp compared to children with fever and altered consciousness due to other causes. Ang-1 was the best discriminator between UM and CM-R and between CNS and CM-R (areas under the ROC curve of 0.96 and 0.93, respectively). A comparison of biomarker levels in CM-R between admission and recovery showed uniform increases in Ang-1 levels, suggesting this biomarker may have utility in monitoring clinical response.These results suggest that endothelial proteins are informative biomarkers of malarial disease severity. These results require validation in prospective studies to confirm that this group of biomarkers improves the diagnostic accuracy of CM from similar conditions causing fever and altered consciousness

Adenomyoepithelioma of the breast: A proposal for classification

Breast lesions with a prominent myoepithelial cell component constitute a heterogeneous group of benign and malignant neoplastic proliferations. These lesions are often dual epithelial‐myoepithelial but may be purely myoepithelial cell in nature. Benign epithelial‐myoepithelial lesions typically maintain the morphology and immunophenotype of the normal bilayer epithelial myoepithelial structures. However, the distinction between the two cell components is not always clear‐cut in malignant lesions in which the histogenesis of myoepithelial cells remains uncertain. Neoplastic biphasic epithelial‐myoepithelial lesions of the breast include adenomyoepithelioma (AME), pleomorphic adenoma and adenoid cystic carcinoma. Four histological patterns of classical AME have been described: tubular, lobulated, spindle cell and adenosis variants. Overlapping patterns occur and some AMEs display an intraductal papillary pattern that may represent a fifth variant. AME can be benign or malignant. Classical AME may show atypical features, which are not sufficient for the diagnosis of malignancy (atypical AME). Atypical AME is recognised as a lesion of uncertain malignant potential with limited metastatic capability. Based on the histological features, we propose a classification of malignant AME (M‐AME) into three variants: M‐AME in situ, M‐AME invasive and AME with invasive carcinoma. In this review, we provide an overview of myoepithelial lesions of the breast focusing on the classification of AME to improve not only the consistency of reporting but also help guide further management decision making

Економічна ефективність, еластичність масштабу та ефект масштабу в банківському секторі арабських країн

This study investigates Cost Efficiency, Scale Elasticity and Scale Economies of the Jordanian, Egyptian, Saudi Arabian and Bahraini banking systems. Our sample comprises information on 82 banks operating in the countries under study over 1992-2000. The stochastic frontier and Fourierflexible form are used to estimate cost efficiency, scale elasticity and scale efficiency levels. The cost efficiency averaged around 95% over the 1992-2000 period. Islamic banks are found to be the most cost efficient while investment banks are the least. The cost scale elasticity estimates reveal diseconomies of around five percent and the cost scale inefficiency estimates suggest that banks are 65% scale efficient. У даній роботі вивчаються питання економічної ефективності, еластичності масштабу та ефекту масштабу в банківських секторах Йорданії, Єгипту, Саудівської Аравії та Бахрейну. Під час проведення дослідження використано дані про діяльність 82 банків протягом 1992-2000 рр. З метою оцінки рівнів вищезгаданих змінних у роботі використано метод стохастичної межі та гнучкий ряд Фур’є. Як виявилось, протягом 1992-2000 рр. середній показник економічної ефективності становив понад 95%. Також результати дослідження говорять, що ісламські банки є найбільш ефективними, тоді як продуктивність інвестиційних банків є найнижчою. Результати оцінювання еластичності масштабу вказали на те, що рівень негативних наслідків господарювання становить 5%