Raman spectroscopic analysis of skin as a diagnostic tool for Human African Trypanosomiasis.

Human African Trypanosomiasis (HAT) has been responsible for several deadly epidemics throughout the 20th century, but a renewed commitment to disease control has significantly reduced new cases and motivated a target for the elimination of Trypanosoma brucei gambiense-HAT by 2030. However, the recent identification of latent human infections, and the detection of trypanosomes in extravascular tissues hidden from current diagnostic tools, such as the skin, has added new complexity to identifying infected individuals. New and improved diagnostic tests to detect Trypanosoma brucei infection by interrogating the skin are therefore needed.

Microarray profiling predicts early neurological and immune phenotypic traits in advance of CNS disease during disease progression in Trypanosoma. b. brucei infected CD1 mouse brains.

Human African trypanosomiasis (HAT), also known as sleeping sickness, is a major cause of mortality and morbidity in sub-Saharan Africa. We hypothesised that recent findings of neurological features and parasite brain infiltration occurring at much earlier stages in HAT than previously thought could be explained by early activation of host genetic programmes controlling CNS disease. Accordingly, a transcriptomal analysis was performed on brain tissue at 0, 7, 14, 21 and 28dpi from the HAT CD1/GVR35 mouse model.

Delineating neuroinflammation, parasite CNS invasion, and blood-brain barrier dysfunction in an experimental murine model of human African trypanosomiasis.

Although Trypanosoma brucei spp. was first detected by Aldo Castellani in CSF samples taken from sleeping sickness patients over a century ago there is still a great deal of debate surrounding the timing, route and effects of transmigration of the parasite from the blood to the CNS. In this investigation, we have applied contrast-enhance magnetic resonance imaging (MRI) to study the effects of trypanosome infection on the blood-brain barrier (BBB) in the well-established GVR35 mouse model of sleeping sickness.

Trypanosoma brucei Invasion and T-Cell Infiltration of the Brain Parenchyma in Experimental Sleeping Sickness: Timing and Correlation with Functional Changes.

Background: The timing of Trypanosoma brucei entry into the brain parenchyma to initiate the second, meningoencephalitic stage of human African trypanosomiasis or sleeping sickness is currently debated and even parasite invasion of the neuropil has been recently questioned. Furthermore, the relationship between neurological features and disease stage are unclear, despite the important diagnostic and therapeutic implications.

Methodology: Using a rat model of chronic Trypanosoma brucei brucei infection we determined the timing of parasite and T-cell neuropil infiltration and its correlation with functional changes.

Central Nervous System Parasitosis and Neuroinflammation Ameliorated by Systemic IL-10 Administration in Trypanosoma brucei-Infected Mice.

Invasion of the central nervous system (CNS) by African trypanosomes represents a critical step in the development of human African trypanosomiasis. In both clinical cases and experimental mouse infections it has been demonstrated that predisposition to CNS invasion is associated with a type 1 systemic inflammatory response. Using the Trypanosoma brucei brucei GVR35 experimental infection model, we demonstrate that systemic delivery of the counter-inflammatory cytokine IL-10 lowers plasma IFN-γ and TNF-α concentrations, CNS parasitosis and ameliorates neuro-inflammatory pathology and clinical symptoms of disease.

A sensitive and reproducible in vivo imaging mouse model for evaluation of drugs against late-stage human African trypanosomiasis.

Objectives: To optimize the Trypanosoma brucei brucei GVR35 VSL-2 bioluminescent strain as an innovative drug evaluation model for late-stage human African trypanosomiasis.

Methods: An IVIS® Lumina II imaging system was used to detect bioluminescent T. b.

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 Trypanosoma brucei (T. b.) gambiense or T.

Magnetic resonance imaging to assess blood-brain barrier damage in murine trypanosomiasis.

The ability of trypanosomes to invade the brain and induce an inflammatory reaction is well-recognized. This study uses magnetic resonance imaging (MRI) in conjunction with a murine model of central nervous system (CNS) stage trypanosomiasis to investigate this phenomenon at the level of the blood-brain barrier (BBB). Mice were scanned before and after administration of the contrast agent.

Teachers' Perceptions of Word Callers and Related Literacy Concepts.

The purpose of the study was to investigate teachers' perceptions of word callers as they relate to the concepts of reading fluency and reading comprehension. To this end, second grade students (N = 408) completed a series of reading fluency and reading comprehension assessments, and their teachers (N = 31) completed word caller nominations and a questionnaire regarding their concepts surrounding these issues. Our findings suggested that teachers often over nominated children as word callers.

Myth and Reality of the Word Caller: The Relation Between Teacher Nominations and Prevalence Among Elementary School Children.

The purpose of the study was to investigate (a) the prevalence of word callers in elementary school, (b) the accuracy of teachers' word caller nominations, and (c) teachers' conceptualization of reading fluency and reading comprehension. To this end, 2 cross-sectional studies of second- and third- (N = 868) and of third- and fifth-grade (N = 202) children were conducted. Our findings suggest that word callers occur infrequently in the primary grades but that they are more prevalent in late elementary school.

Kynurenine pathway inhibition reduces central nervous system inflammation in a model of human African trypanosomiasis.

Human African trypanosomiasis, or sleeping sickness, is caused by the protozoan parasites Trypanosoma brucei rhodesiense or Trypanosoma brucei gambiense, and is a major cause of systemic and neurological disability throughout sub-Saharan Africa. Following early-stage disease, the trypanosomes cross the blood-brain barrier to invade the central nervous system leading to the encephalitic, or late stage, infection. Treatment of human African trypanosomiasis currently relies on a limited number of highly toxic drugs, but untreated, is invariably fatal.

The blood-brain barrier significantly limits eflornithine entry into Trypanosoma brucei brucei infected mouse brain.

Drugs to treat African trypanosomiasis are toxic, expensive and subject to parasite resistance. New drugs are urgently being sought. Although the existing drug, eflornithine, is assumed to reach the brain in high concentrations, little is known about how it crosses the healthy and infected blood-brain barrier.

Combination chemotherapy with a substance P receptor antagonist (aprepitant) and melarsoprol in a mouse model of human African trypanosomiasis.

Drug therapy for late-stage (encephalitic) human African trypanosomiasis (HAT) is currently very unsatisfactory with the most commonly used drug, melarsoprol, having a 5% overall mortality. There is evidence in a mouse model of HAT that Substance P (SP) receptor antagonism reduces the neuroinflammatory reaction to CNS trypanosome infection. In this study we investigated the effects of combination chemotherapy with melarsoprol and a humanised SP receptor antagonist aprepitant (EMEND) in this mouse model.

Teaching Children to Become Fluent and Automatic Readers.

The purpose of the study was to examine the effects of two instructional approaches designed to improve the reading fluency of 2nd-grade children. The first approach was based on Stahl and Heubach's (2005) fluency-oriented reading instruction (FORI) and involved the scaffolded, repeated reading of grade-level texts over the course of each week. The second was a wide-reading approach that also involved scaffolded instruction.

Meningoencephalitic African trypanosomiasis: Brain IL-10 and IL-6 are associated with protection from neuro-inflammatory pathology.

The relationship of neuropathology to CNS inflammatory and counter-inflammatory cytokine production in African trypanosome-infected mice was studied using an infection model with a defined disease progression. The initial phase of CNS infection by trypanosomes, where only mild neuropathology is evident, was characterised by high levels of IL-10 and IL-6. In the later phase of CNS infection and in a post-drug treatment model, moderate to severe neuropathology was associated with high levels of IFN-gamma and TNF-alpha.

Interaction Quality during Partner Reading.

The influence of social relationships, positive interdependence, and teacher structure on the quality of partner reading interactions was examined. Partner reading, a scripted cooperative learning strategy, is often used in classrooms to promote the development of fluent and automatic reading skills. Forty-three pairs of second grade children were observed during partner reading sessions taking place in 12 classrooms.

Clinical and neuroinflammatory responses to meningoencephalitis in substance P receptor knockout mice.

Human African trypanosomiasis, also known as sleeping sickness, affects the CNS at the late stage of the disease. Untreated the disease is invariably fatal, and melarsoprol, the only available and effective treatment for CNS disease, is associated in up to 10% of cases with a severe post-treatment reactive encephalopathy (PTRE), which can itself cause death. We used a reproducible mouse model of the PTRE to investigate the pathogenesis and treatment of this condition.

Human African trypanosomiasis: potential therapeutic benefits of an alternative suramin and melarsoprol regimen.

Treatment of late-stage human African trypanosomiasis is complicated by the presence of trypanosomes within the central nervous system (CNS). The regimen commonly prescribed to treat CNS-stage disease involves the use of the trypanocidal drugs suramin and melarsoprol. Suramin does not cross the blood-brain barrier efficiently and therefore, at normal dosages, will not cure CNS-stage infections.