Oxidative Phosphorylation Is Required for Powering Motility and Development of the Sleeping Sickness Parasite Trypanosoma brucei in the Tsetse Fly Vector

African trypanosomes cause disease in humans and their livestock and are transmitted by tsetse flies. The insect ingests these parasites with its blood meal, but to be transmitted to another mammal, the trypanosome must undergo complex development within the tsetse fly and migrate from the insect's gut to its salivary glands.

The cost of tsetse control using ‘Tiny Targets’ in the sleeping sickness endemic forest area of Bonon in Côte d’Ivoire: Implications for comparing costs across different settings

Background Work to control the gambiense form of human African trypanosomiasis (gHAT), or sleeping sickness, is now directed towards ending transmission of the parasite by 2030. In order to supplement gHAT case-finding and treatment, since 2011 tsetse control has been implemented using Tiny Targets in a number of gHAT foci. As this intervention is extended to new foci, it is vital to understand the costs involved. Costs have already been analysed for the foci of Arua in Uganda and Mandoul in Chad. This paper examines the costs of controlling Glossina palpalis palpalis in the focus of Bonon in Côte d’Ivoire from 2016 to 2017. Methodology/Principal findings Some 2000 targets were placed throughout the main gHAT transmission area of 130 km2 at a density of 14.9 per km2. The average annual cost was USD 0.5 per person protected, USD 31.6 per target deployed of which 12% was the cost of the target itself, or USD 471.2 per km2 protected. Broken down by activity, 54% was for deployment and maintenance of targets, 34% for tsetse surveys/monitoring and 12% for sensitising populations. Conclusions/Significance The cost of tsetse control per km2 of the gHAT focus protected in Bonon was more expensive than in Chad or Uganda, while the cost per km2 treated, that is the area where the targets were actually deployed, was cheaper. Per person protected, the Bonon cost fell between the two, with Uganda cheaper and Chad more expensive. In Bonon, targets were deployed throughout the protected area, because G. p. palpalis was present everywhere, whereas in Chad and Uganda G. fuscipes fuscipes was found only the riverine fringing vegetation. Thus, differences between gHAT foci, in terms of tsetse ecology and human geography, impact on the cost-effectiveness of tsetse control. It also demonstrates the need to take into account both the area treated and protected alongside other impact indicators, such as the cost per person protected.

Imperial Aetiologies: Violence, Sleeping Sickness, and the Colonial Encounter

In this chapter Taylor-Pirie examines how one particular tropical disease—sleeping sickness—was conceptualised as a form of tropical violence across a range of medical and nonmedical genres. Using the repetition of an African curse ‘owa na ntolo’ as an access point, she reveals how sensational literary depictions of sleeping sickness circulated between newspaper reports and clinical case studies, augmenting debates about racial susceptibility. Depictions of African sleeping sickness, she argues, were filtered through an emotional register that produced new aetiologies of race and illness visible in Henry Seton Merriman’s hugely popular imperial romance novel With Edged Tools (1894), as well as in medical essays and tropical travel guides. The melodramatic mode and a flexible approach to representations of disease transmission produced Africa as a place productive of illness and immorality in equal measure. Ultimately, she demonstrates how Britain’s encounters with tropical disease—fictional and nonfictional—were used to map not only the epidemiological but also the sociocultural topographies of empire.

Second stage African Trypanosomiasis presented as Non Convulsive Status Epilepticus

Human African Trypanosomiasis also known as sleeping sickness is a common disease in South Sudan. There are two recognized sstage, The early hemolymphatic stage and The late encephalitic stage when the CNS is involved specially with Gambians infection, broad neurologic spectrum has been reported such as psychiatric, motor, sensory.

Second stage African Trypanosomiasis presented as Non Convulsive Status Epilepticus

Human African Trypanosomiasis also known as sleeping sickness is a common disease in South Sudan. There are two recognized sstage, The early hemolymphatic stage and The late encephalitic stage when the CNS is involved specially with Gambians infection, broad neurologic spectrum has been reported such as psychiatric, motor, sensory.

Novel Cytoskeleton-Associated Proteins in Trypanosoma brucei Are Essential for Cell Morphogenesis and Cytokinesis

Trypanosome brucei, the causative agent of African sleeping sickness, harbours a highly ordered, subpellicular microtubule cytoskeleton that defines many aspects of morphology, motility and virulence. This array of microtubules is associated with a large number of proteins involved in its regulation. Employing proximity-dependent biotinylation assay (BioID) using the well characterised cytoskeleton-associated protein CAP5.5 as a probe, we identified CAP50 (Tb927.11.2610). This protein colocalises with the subpellicular cytoskeleton microtubules but not with the flagellum. Depletion by RNAi results in defects in cytokinesis, morphology and partial disorganisation of microtubule arrays. Published proteomics data indicate a possible association of CAP50 with two other, yet uncharacterised, cytoskeletal proteins, CAP52 (Tb927.6.5070) and CAP42 (Tb927.4.1300), which were therefore included in our analysis. We show that their depletion causes phenotypes similar to those described for CAP50 and that they are essential for cellular integrity.

T3P-Promoted Synthesis of a Series of 2-Aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones and Their Activity against the Kinetoplastid Parasite Trypanosoma brucei

A series of fourteen 2-aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones was prepared at room temperature by T3P-mediated cyclization of N-phenyl-C-aryl imines with thionicotinic acid, two difficult substrates. The reactions were operationally simple, did not require specialized equipment or anhydrous solvents, could be performed as either two or three component reactions, and gave moderate–good yields as high as 63%. This provides ready access to N-phenyl compounds in this family, which have been generally difficult to prepare. As part of the study, the first crystal structure of neutral thionicotinic acid is also reported, and showed the molecule to be in the form of the thione tautomer. Additionally, the synthesized compounds were tested against T. brucei, the causative agent of Human African Sleeping Sickness. Screening at 50 µM concentration showed that five of the compounds strongly inhibited growth and killed parasites.