Search results for: trypanosoma congolense
5 Oral Administration of Azithromycin Ameliorates Trypanosomosis in Trypanosoma congolense and T. Brucei Brucei Infected Mice
Authors: Nthatisi I. Molefe-Nyembe, Keisuke Suganuma, Oriel M. M. Thekisoe, Xuan Xuenan, Noboru Inoue
Abstract:
African trypanosomosis is a devastating disease of animals caused by parasites of the genus Trypanosoma negatively affecting the economic status of more than 36 African countries. Few available drugs for the treatment of trypanosomosis remain inaccessible in remote areas, are associated with severe toxicity and most importantly, resistance has widely developed against their usage. Therefore, safe, effective and easily administrable drugs are urgently in need. The objective of the current study was to determine efficacy of azithromycin (AZM), on T. congolense, T. brucei brucei in vitro and in vivo. A 96 well luciferase assay was conducted to determine the trypanocidal effect of AZM on T. congolense, T. b. brucei and T. evansi as well as the cytotoxicity effect on the MDBK and NIH 3T3 cells. Additionally, TEM analysis was conducted to determine the morphological alteration on the AZM treated samples. Mice were infected with T. congolense and T. b. brucei and orally treated with AZM for 7 and 28 days referred to as the short and the long-term treatment. The in vitro IC50 values of AZM on T. congolense, T. b. brucei and T. evansi was 0.19 ± 0.17; 3.69 ± 2.26 and 1.81 ± 1.82 μg/mL, respectively, while the cytotoxicity effects values were greater than 25 μg/mL. A vacuole-like structure was observed in the TEM imaging of AZM treated T. congolense, while the presence of glycosomes and acidocalcisome-like structured were detected in T. b. brucei samples. In vivo, AZM was more effective against T. congolense infected mice than T. b. brucei. In conclusion, AZM exhibited the trypanocidal effects on T. congolense and T. b. brucei infected mice. However, further studies are necessary to determine the metabolic pathway responsible for the observed efficacy.Keywords: animal trypanosomosis, azithromycin, oral administration, trypanosoma congolense
Procedia PDF Downloads 634 Inhibition of Variant Surface Glycoproteins Translation to Define the Essential Features of the Variant Surface Glycoprotein in Trypanosoma brucei
Authors: Isobel Hambleton, Mark Carrington
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Trypanosoma brucei, the causal agent of a range of diseases in humans and livestock, evades the mammalian immune system through a population survival strategy based on the expression of a series of antigenically distinct variant surface glycoproteins (VSGs). RNAi mediated knockdown of the active VSG gene triggers a precytokinesis cell cycle arrest. To determine whether this phenotype is the result of reduced VSG transcript or depleted VSG protein, we used morpholino antisense oligonucleotides to block translation of VSG mRNA. The same precytokinesis cell cycle arrest was observed, suggesting that VSG protein abundance is monitored closely throughout the cell cycle. An inducible expression system has been developed to test various GPI-anchored proteins for their ability to rescue this cell cycle arrest. This system has been used to demonstrate that wild-type VSG expressed from a T7 promoter rescues this phenotype. This indicates that VSG expression from one of the specialised bloodstream expression sites (BES) is not essential for cell division. The same approach has been used to define the minimum essential features of a VSG necessary for function.Keywords: bloodstream expression site, morpholino, precytokinesis cell cycle arrest, variant surface glycoprotein
Procedia PDF Downloads 1503 Targeting Trypanosoma brucei Using Antibody Drug Conjugates against the Transferrin Receptor
Authors: Camilla Trevor, Matthew K. Higgins, Andrea Gonzalez-Munoz, Mark Carrington
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Trypanosomiasis is a devastating disease affecting both humans and livestock in sub-Saharan Africa. The diseases are caused by infection with African trypanosomes, protozoa transmitted by tsetse flies. Treatment currently relies on the use of chemotherapeutics with ghastly side effects. Here, we describe the development of effective antibody-drug conjugates that target the T. brucei transferrin receptor. The receptor is essential for trypanosome growth in a mammalian host but there are approximately 12 variants of the transferrin receptor in the genome. Two of the most divergent variants were used to generate recombinant monoclonal immunoglobulin G using phage display and we identified cross-reactive antibodies that bind both variants using phage ELISA, fluorescence resonance energy transfer assays and surface plasmon resonance. Fluorescent antibodies were used to demonstrate uptake into trypanosomes in culture. Toxin-conjugated antibodies were effective at killing trypanosomes at sub-nanomolar concentrations. The approach of using antibody-drug conjugates has proven highly effective.Keywords: antibody-drug conjugates, phage display, transferrin receptor, trypanosomes
Procedia PDF Downloads 1542 Studies on Anaemia in Camels (Camelus dromedarius) Brought for Slaughter at Sokoto Metropolitan Abattoir: A Preliminary Report
Authors: Y. S. Baraya, B. Umar, A. Aliyu, A. A. Raji, K. A. N. Esievo
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This study was performed to determine the presence of anaemia in randomly selected apparently healthy camels (Camelus dromedarius) brought for slaughter at the Sokoto metropolitan abattoir, Sokoto State, Nigeria. The camels were derived from both sexes, different age groups, functional usages and kept at various localities within and outside Sokoto town. In the study area, studies involving camels were limited in particular the emphasis on the anaemic status of camels brought daily for human consumption. A total of eighty (80) blood samples were collected once a week from these camels within the period of eight (8) weeks to investigate the haematological variations especially packed cell volume (PCV). The PCV analysis revealed anaemia in more than fifty (50) % of the camels studied. However, the actual cause of the anaemia was not investigated but could be caused by infectious agent like protozoan parasite Trypanosoma specie and non-infectious cause such as nutritional deficiency. The PCV examination as a simple, inexpensive and reliable procedure could be part of the routine ante-mortem assessment to evaluate camels for the existence of anaemia since many of the causes of anaemia besides being affecting the meat quality could also be of zoonotic significance.Keywords: anaemia, camels, packed cell volume, Sokoto abattoir
Procedia PDF Downloads 3721 Investigation of Leishmaniasis, Babesiosis, Ehrlichiosis, Dirofilariasis, and Hepatozoonosis in Referred Dogs to Veterinary Hospitals in Tehran, 2022
Authors: Mohamad Bolandmartabe, Nafiseh Hassani, Saeed Abdi Darake, Maryam Asghari
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Dogs are highly susceptible to diseases, nutritional problems, toxins, and parasites, with parasitic infections being common and causing hardship in their lives. Some important internal parasites include worms (such as roundworms and tapeworms) and protozoa, which can lead to anemia in dogs. Important bloodborne parasites in dogs include microfilariae and adult forms of Dirofilaria immitis, Dipetalonema reconditum, Babesia, Trypanosoma, Hepatozoon, Leishmania, Ehrlichia, and Hemobartonella. Babesia and Hemobartonella are parasites that reside inside red blood cells and cause regenerative anemia by directly destroying the red blood cells. Hepatozoon, Leishmania, and Ehrlichia are also parasites that reside within white blood cells and can infiltrate other tissues, such as the liver and lymph nodes. Since intermediate hosts are more commonly found in the open environment, the prevalence of parasites in stray and free-roaming dogs is higher compared to pet dogs. Furthermore, pet dogs are less exposed to internal and external parasites due to better care, hygiene, and being predominantly indoors. Therefore, they are less likely to be affected by them. Among the parasites, Leishmania carries significant importance as it is shared between dogs and humans, causing a dangerous disease known as visceral Leishmaniasis or kala-azar and cutaneous Leishmaniasis. Furthermore, dogs can act as reservoirs and spread the disease agent within human communities. Therefore, timely and accurate diagnosis of these diseases in dogs can be highly beneficial in preventing their occurrence in humans. In this article, we employed the Giemsa staining technique under a light microscope for the identification of bloodborne parasites in dogs. However, considering the negative impact of these parasites on the natural life of dogs, the development of chronic diseases, and the gradual loss of the animal's well-being, rapid and timely diagnosis is essential. Serological methods and PCR are available for the diagnosis of certain parasites, which have high sensitivity and desirable characteristics. Therefore, this research aims to investigate the molecular aspects of bloodborne parasites in dogs referred to veterinary hospitals in Tehran city.Keywords: leishmaniasis, babesiosis, ehrlichiosis, dirofilariasis, hepatozoonosis
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