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Morrison L.J.,Roslin Institute | Vezza L.,Roslin Institute | Rowan T.,GALVmed | Hope J.C.,Roslin Institute
Trends in Parasitology | Year: 2016

Animal African trypanosomiasis (AAT), caused by Trypanosoma congolense and Trypanosoma vivax, remains one of the most important livestock diseases in sub-Saharan Africa, particularly affecting cattle. Despite this, our detailed knowledge largely stems from the human pathogen Trypanosoma brucei and mouse experimental models. In the postgenomic era, the genotypic and phenotypic differences between the AAT-relevant species of parasite or host and their model organism counterparts are increasingly apparent. Here, we outline the timeliness and advantages of increasing the research focus on both the clinically relevant parasite and host species, given that improved tools and resources for both have been developed in recent years. We propose that this shift of emphasis will improve our ability to efficiently develop tools to combat AAT. The sequencing of the Trypanosoma congolense and Trypanosoma vivax genomes revealed significant differences in key genes and gene families for relevant phenotypes, when compared with Trypanosoma brucei.The variant surface glycoprotein (VSG) repertoires of T. congolense, T. vivax, and T. brucei show significant divergences in structural diversity and the relative role of recombination in generating VSG diversity. Trypanosoma congolense lacks an orthologue of the main diamidine transporter in T. brucei (TbAT1), suggesting that the route of drug uptake and resistance is different in these two species.Unique aspects of the bovine immune system have recently been identified, such as increased frequency of the γδ T cell population and ultralong CDR3 domain antibodies.Natural killer (NK) cells have been implicated in genetic studies of murine and bovine trypanosome susceptibility. NK cells in cattle have been recently identified to have a uniquely expanded NK cell receptor repertoire. © 2016 Elsevier Ltd. Source

Ortiz P.,National University of Cajamarca | Terrones S.,National University of Cajamarca | Cabrera M.,National University of Cajamarca | Hoban C.,National University of Cajamarca | And 6 more authors.
Acta Tropica | Year: 2014

Although oxfendazole (OFZ) is a well know broad-spectrum benzimidazole anthelmintic, the assessment of its potential trematodicidal activity remains unexplored. OFZ administration at single high doses has been recommended to control Taenia solium cysticercus in pigs. The current study investigated the flukicidal activity obtained after a single high (30mg/kg) oral dose of OFZ in pigs harbouring a natural Fasciola hepatica infection. Sixteen (16) local ecotype pigs were randomly allocated into two (2) experimental groups of 8 animals each named as follow: Untreated control and OFZ treated, in which animals received OFZ (Synanthic®, Merial Ltd., 9.06% suspension) orally at 30mg/kg. At seven (7) days post-treatment, all the animals were sacrificed and direct adult liver fluke counts were performed following the WAAVP guidelines. None of the animals involved in this experiment showed any adverse event during the study. OFZ treatment as a single 30mg/kg oral dose showed a 100% efficacy against F. hepatica. In conclusion, the trial described here demonstrated an excellent OFZ activity against F. hepatica in naturally infected pigs, after its administration at a single oral dose of 30mg/kg. © 2014 Elsevier B.V. Source

Munday J.C.,University of Glasgow | Rojas Lopez K.E.,University of Glasgow | Eze A.A.,University of Glasgow | Delespaux V.,Institute of Tropical Medicine | And 6 more authors.
International Journal for Parasitology: Drugs and Drug Resistance | Year: 2013

It has long been established that the Trypanosoma brucei TbAT1/P2 aminopurine transporter is involved in the uptake of diamidine and arsenical drugs including pentamidine, diminazene aceturate and melarsoprol. Accordingly, it was proposed that the closest Trypanosoma congolense paralogue, TcoAT1, might perform the same function in this parasite, and an apparent correlation between a Single Nucleotide Polymorphism (SNP) in that gene and diminazene tolerance was reported for the strains examined. Here, we report the functional cloning and expression of TcoAT1 and show that in fact it is the syntenic homologue of another T. brucei gene of the same Equilibrative Nucleoside Transporter (ENT) family: TbNT10. The T. congolense genome does not seem to contain a syntenic equivalent to TbAT1. Two TcoAT1 alleles, differentiated by three independent SNPs, were expressed in the T. brucei clone B48, a TbAT1-null strain that further lacks the High Affinity Pentamidine Transporter (HAPT1); TbAT1 was also expressed as a control. The TbAT1 and TcoAT1 transporters were functional and increased sensitivity to cytotoxic nucleoside analogues. However, only TbAT1 increased sensitivity to diamidines and to cymelarsan. Uptake of [3H]-diminazene was detectable only in the B48 cells expressing TbAT1 but not TcoAT1, whereas uptake of [3H]-inosine was increased by both TcoAT1 alleles but not by TbAT1. Uptake of [3H]-adenosine was increased by all three ENT genes. We conclude that TcoAT1 is a P1-type purine nucleoside transporter and the syntenic equivalent to the previously characterised TbNT10; it does not mediate diminazene uptake and is therefore unlikely to play a role in diminazene resistance in T. congolense. © 2013 Australian Society for Parasitology. Source

Shittu I.,Exotic and Emerging Avian Viral Diseases Research Unit | Shittu I.,National Veterinary Research Institute | Zhu Z.,Guangxi University | Zhu Z.,University of Georgia | And 13 more authors.
Biologicals | Year: 2016

Traditionally, substrates for production of viral poultry vaccines have been embryonated eggs or adherent primary cell cultures. The difficulties and cost involved in scaling up these substrates in cases of increased demand have been a limitation for vaccine production. Here, we assess the ability of a newly developed chicken-induced pluripotent cell line, BA3, to support replication and growth of Newcastle disease virus (NDV) LaSota vaccine strain. The characteristics and growth profile of the cells were also investigated. BA3 cells could grow in suspension in different media to a high density of up to 7.0 × 106 cells/mL and showed rapid proliferation with doubling time of 21 h. Upon infection, a high virus titer of 1.02 × 108 EID50/mL was obtained at 24 h post infection using a multiplicity of infection (MOI) of 5. In addition, the cell line was shown to be free of endogenous and exogenous Avian Leukosis viruses, Reticuloendotheliosis virus, Fowl Adenovirus, Marek's disease virus, and several Mycoplasma species. In conclusion, BA3 cell line is potentially an excellent candidate for vaccine production due to its highly desirable industrially friendly characteristics of growing to high cell density and capability of growth in serum free medium. © 2015. Source

LIGHTOWLERS M.W.,University of Melbourne | DONADEU M.,University of Melbourne | ELAIYARAJA M.,Indian Immunologicals Ltd | MAITHAL K.,Indian Immunologicals Ltd | And 5 more authors.
Parasitology | Year: 2016

Specific antibody responses were assessed in pigs immunized with the Taenia solium vaccine TSOL18. Anti-TSOL18 responses were compared 2 weeks after secondary immunization, where the interval between primary and secondary immunization was 4, 8, 12, 16 or 20 weeks. All animals responded to the vaccine and there was no diminution in antibody responses in animals receiving their second injection after an interval up to 20 weeks. Pigs receiving vaccinations at an interval of 12 weeks developed significantly increased antibody responses compared with animals receiving immunizations 4 weeks apart (P = 0·046). The ability to deliver TSOL18 vaccination effectively where the revaccination schedule can be delayed for up to 12–16 weeks in pigs increases the options available for designing T. solium control interventions that incorporate TSOL18 vaccination. Copyright © Cambridge University Press 2016 Source

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