Evaluation of the diagnostic accuracy of prototype rapid tests for human African trypanosomiasis

Peer reviewedPublisher PD

Differences between <i>Trypanosoma brucei gambiense</i> groups 1 and 2 in their resistance to killing by Trypanolytic factor 1

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; The three sub-species of &lt;i&gt;Trypanosoma brucei&lt;/i&gt; are important pathogens of sub-Saharan Africa. &lt;i&gt;T. b. brucei&lt;/i&gt; is unable to infect humans due to sensitivity to trypanosome lytic factors (TLF) 1 and 2 found in human serum. &lt;i&gt;T. b. rhodesiense&lt;/i&gt; and &lt;i&gt;T. b. gambiense&lt;/i&gt; are able to resist lysis by TLF. There are two distinct sub-groups of &lt;i&gt;T. b. gambiense&lt;/i&gt; that differ genetically and by human serum resistance phenotypes. Group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; have an invariant phenotype whereas group 2 show variable resistance. Previous data indicated that group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; are resistant to TLF-1 due in-part to reduced uptake of TLF-1 mediated by reduced expression of the TLF-1 receptor (the haptoglobin-hemoglobin receptor (&lt;i&gt;HpHbR&lt;/i&gt;)) gene. Here we investigate if this is also true in group 2 parasites.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methodology:&lt;/b&gt; Isogenic resistant and sensitive group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; were derived and compared to other T. brucei parasites. Both resistant and sensitive lines express the &lt;i&gt;HpHbR&lt;/i&gt; gene at similar levels and internalized fluorescently labeled TLF-1 similar fashion to &lt;i&gt;T. b. brucei&lt;/i&gt;. Both resistant and sensitive group 2, as well as group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt;, internalize recombinant APOL1, but only sensitive group 2 parasites are lysed.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our data indicate that, despite group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; avoiding TLF-1, it is resistant to the main lytic component, APOL1. Similarly group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; is innately resistant to APOL1, which could be based on the same mechanism. However, group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; variably displays this phenotype and expression does not appear to correlate with a change in expression site or expression of &lt;i&gt;HpHbR&lt;/i&gt;. Thus there are differences in the mechanism of human serum resistance between &lt;i&gt;T. b. gambiense&lt;/i&gt; groups 1 and 2.&lt;/p&gt

Melarsoprol cyclodextrin inclusion complexes as promising oral candidates for the treatment of human African trypanosomiasis

Human African trypanosomiasis (HAT), or sleeping sickness, results from infection with the protozoan parasites &lt;i&gt;Trypanosoma brucei&lt;/i&gt; (&lt;i&gt;T.b.&lt;/i&gt;) &lt;i&gt;gambiense&lt;/i&gt; or &lt;i&gt;T.b.rhodesiense&lt;/i&gt; and is invariably fatal if untreated. There are 60 million people at risk from the disease throughout sub-Saharan Africa. The infection progresses from the haemolymphatic stage where parasites invade the blood, lymphatics and peripheral organs, to the late encephalitic stage where they enter the central nervous system (CNS) to cause serious neurological disease. The trivalent arsenical drug melarsoprol (Arsobal) is the only currently available treatment for CNS-stage &lt;i&gt;T.b.rhodesiense&lt;/i&gt; infection. However, it must be administered intravenously due to the presence of propylene glycol solvent and is associated with numerous adverse reactions. A severe post-treatment reactive encephalopathy occurs in about 10% of treated patients, half of whom die. Thus melarsoprol kills 5% of all patients receiving it. Cyclodextrins have been used to improve the solubility and reduce the toxicity of a wide variety of drugs. We therefore investigated two melarsoprol cyclodextrin inclusion complexes; melarsoprol hydroxypropyl-&#846;-cyclodextrin and melarsoprol randomly-methylated-&#946;-cyclodextrin. We found that these compounds retain trypanocidal properties &lt;i&gt;in vitro&lt;/i&gt; and cure CNS-stage murine infections when delivered orally, once per day for 7-days, at a dosage of 0.05 mmol/kg. No overt signs of toxicity were detected. Parasite load within the brain was rapidly reduced following treatment onset and magnetic resonance imaging showed restoration of normal blood-brain barrier integrity on completion of chemotherapy. These findings strongly suggest that complexed melarsoprol could be employed as an oral treatment for CNS-stage HAT, delivering considerable improvements over current parenteral chemotherapy

Csf1r-mApple transgene expression and ligand binding in vivo reveal dynamics of CSF1R expression within the mononuclear phagocyte system

CSF1 is the primary growth factor controlling macrophage numbers, but whether expression of the CSF1 receptor differs between discrete populations of mononuclear phagocytes remains unclear. We have generated a Csf1r-mApple transgenic fluorescent reporter mouse that, in combination with lineage tracing, Alexa Fluor 647-labeled CSF1-Fc and CSF1, and a modified Delta Csf1-enhanced cyan fluorescent protein (ECFP) transgene that lacks a 150 bp segment of the distal promoter, we have used to dissect the differentiation and CSF1 responsiveness of mononuclear phagocyte populations in situ. Consistent with previous Csf1r-driven reporter lines, Csf1r-mApple was expressed in blood monocytes and at higher levels in tissue macrophages, and was readily detectable in whole mounts or with multiphoton microscopy. In the liver and peritoneal cavity, uptake of labeled CSF1 largely reflected transgene expression, with greater receptor activity in mature macrophages than monocytes and tissue-specific expression in conventional dendritic cells. However, CSF1 uptake also differed between subsets of monocytes and discrete populations of tissue macrophages, which in macrophages correlated with their level of dependence on CSF1 receptor signaling for survival rather than degree of transgene expression. A double Delta Csf1r-ECFP-Csf1r-mApple transgenic mouse distinguished subpopulations of microglia in the brain, and permitted imaging of interstitial macrophages distinct from alveolar macrophages, and pulmonary monocytes and conventional dendritic cells. The Csf1r-mApple mice and fluorescently labeled CSF1 will be valuable resources for the study of macrophage and CSF1 biology, which are compatible with existing EGFP-based reporter lines

Sheep Updates 2007 - part 4

This session covers eight papers from different authors: GRAZING 1. The impact of high dietary salt and its implications for the management of livestock grazing saline land, Dean Thomas, Dominique Blache, Dean Revell, Hayley Norman, Phil Vercoe, Zoey Durmic, Serina Digby, Di Mayberry, Megan Chadwick, Martin Sillence and David Masters, CRC for Plant-based Management of Dryland Salinity, Faculty of Natural & Agricultural Sciences, The University of Western Australia, WA. 2. Sustainable Grazing on Saline Lands - outcomes from the WA1 research project, H.C. Norman1,2, D.G. Masters1,2, R. Silberstein1,2, F. Byrne2,3, P.G.H. Nichols2,4, J. Young3, L. Atkins1,2, M.G. Wilmot1,2, A.J. Rintoul1,2, T. Lambert1,2, D.R. McClements2,4, P. Raper4, P. Ward1,2, C. Walton5 and T. York6 1CSIRO Centre for Environment and Life Sciences, Wembley, WA 2CRC for Plant-based Management of Dryland Salinity. 3School of Agricultural and Resource Economics, University of Western Australia. 4Department of Agriculture and Food WA. 5Condering Hills, Yealering. 6Anameka Farms, Tammin. MEAT QUALITY 3. Development of intramuscular fat in prime lambs, young sheep and beef cattle, David Pethick1, David Hopkins2 and Malcolm McPhee3,1School of Veterinary and Biomedical Sciences, Murdoch University, Murdoch, WA, 2NSW Department of Primary Industries, Cowra, NSW,3NSW Dept. of Primary Industries, University of New England, Armidale, NSW, 4. Importance of drinking water temperature for managing heat stress in sheep, Savage DB, Nolan JV, Godwin IR, Aoetpah A, Nguyen T, Baillie N and Lawler C University of New England, Armidale, NSW, Australia EWE MANAGEMENT TOOLS 5. E - sheep Management of Pregnant Merino Ewes and their Finishing Lambs, Ken GeentyA, John SmithA, Darryl SmithB, Tim DyallA and Grant UphillA A Sheep CRC and CSIRO Livestock Industries, Chiswick, NSW B Turretfield Research Station, SARDI, Roseworthy, SA 6. Is it important to manage ewes to CS targets? John Young, Farming Systems Analysis Service, Kojonup, WA MULESING 7. Mulesing accreditation - Vital for Wool\u27s Future, Dr Michael Paton, Department of Agriculture and Food WA, 8. Mulesing Alternatives, Jules Dorrian, Affiliation Project Manager Blowfly Control Australian Wool Inovatio

Beyond Core Indicators of Retention in HIV Care: Missed Clinic Visits Are Independently Associated With All-Cause Mortality

Background. The continuum of care is at the forefront of the domestic human immunodeficiency virus (HIV) agenda, with the Institute of Medicine (IOM) and Department of Health and Human Services (DHHS) recently releasing clinical core indicators. Core indicators for retention in care are calculated based on attended HIV care clinic visits. Beyond these retention core indicators, we evaluated the additional prognostic value of missed clinic visits for all-cause mortality

Tracking uncertainties in the causal chain from human activities to climate

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95537/1/grl25489.pd

Structural change in feedlot cattle death loss

When anecdotal evidence suggests that death loss in feedlots is increasing over time, it creates concern among producers because death loss affects pounds of saleable product and cost of gain. Death loss change could be driven by factors such as weather, technology adoption, feed rations, and cattle sourcing. If death loss is changing over time, it is important to understand the nature of the change. The changes can be constant over time or abrupt. Some events may or may not impact death loss. Some may have an immediate or delayed impact. Data from the Kansas Feedlot Performance and Feed Cost Summary, which consist of monthly summary of feedlot performance measures from January 1992 to July 2017, is used to model the death loss percentage over time. Structural change in this model is examined using cumulative sum (CUSUM) test, CUSUM of squares test, and tests by Bai and Perron. These tests can determine whether there are changes in death loss rates or not and identify the coinciding events