In vitro activity and preliminary toxicity of various diamidine compounds against Trypanosoma evansi (original) (raw)
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Chemotherapeutic agents against pathogenic animal Trypanosomes
Trypanosomoses are protozoan diseases, affecting both human and animals, and mainly found in tropical Africa, Latin America and Asia. In Africa, trypanosomes produce serious diseases in human beings such as West and East Sleeping Sickness caused by T. brucei gambiense and T. brucei congolense respectively, while in the Americas T. cruzi causes the Chagas disease. Other species of Trypanosoma affect animals and produce enormous economical impact in the endemic areas. Those species could be classified as those transmitted by tsetse flies-(Trypanosoma vivax, T. congolense and T. brucei brucei) producing a disease known as nagana and those non-transmitted by tsetse-(T. evansi -surra-, T. equiperdum -dourine-).
Biology of Trypanosoma (Trypanozoon) evansi in experimental heterologous mammalian hosts
Trypanosoma (Trypanozoon) evansi is a causative agent of the dreadful mammalian disease trypanosomiasis or ‘Surra’ and carried as a latent parasite in domestic cattle but occasionally proves fatal when transmitted to horses and camel. Sporadic outbreak of ‘Surra’ to different animals (beside their natural hosts) reminds that T. evansi may be zoonotic, as their close relative cause sleeping sickness to human being. This haemoflagellate is mechanically transmitted by horse fly and its effect on different host varies depending on certain factors including the effectiveness of transmission by mechanical vector, the suitability and susceptibility of the host as well as most importantly the ability of the disease establishment of parasite to adapt itself to the host’s resistance, etc. The course of the disease caused by T. evansi is similar to that of human sleeping sickness caused by T. (T.) brucei gambiense. The target organs and symptoms show close similarity. T. evansi can successfully be transmitted among unnatural hosts i.e., other classes of vertebrates, like chicken. In transmission experiments, the unnatural hosts may sometimes induce profound changes in the biology of trypanosomes. Hence, in present study the observations are the biology of different morphological changes of T. evansi as well as its ability of disease formation within some heterologous mammal viz., albino rat, guineapig, bandicoot, mongoose, domestic cat and common monkey. Blood smears of infected albino rats, bandicoot, and mongoose revealed only monomorphic form. Interestingly, blood smears of infected cat and monkey, T. evansi shows slender trypomastigote form and short intermediate form whereas organ smears shows other two forms of haemoflagellate viz., sphaeromastigote and amastigote form. The haemoflagellate maintains a common reproductive cycle in all the experimental heterologous hosts whereas disease symptoms differ. T. evansi infected cat and monkey shows nervous symptoms. Infected monkey expresses some symptoms similar to that of human sleeping sickness disease. Thus the paper highlights zoonotic potentialities of T. evansi.
African Trypanosomes: Virulence Factors, Pathogenicity And Host Responses
Journal of Veterinary Advances, 2014
Trypanosomosis is a vector-born protozoan disease of animals and man caused by several Trypanosoma species or subspecies. Many virulence factors of the parasite such as the variant surface glycoproteins, trypanosome enzymes, B-cell mitogens and T lymphocyte triggering factors act in concert to cause the disease. During infection, complex interactions occur between the hosts' immune responses and trypanosomes resulting in anemia, leukopenia, thrombocytopenia, tissue inflammation and damage, meningoencephalitis, splenomegaly and cachexia. The severity of the disease varies among hosts in which some are susceptible and others are resistant. The unlimited capacity of the parasite to change the targeted surface antigens is the major limiting factor in the development of effective vaccines. However, vaccination and treatment strategies targeting the virulence factors are promising approaches. The use of host resistance is one potentially cost effective solution in the control of Trypanosomosis. In addition to the existing methods of control, a deeper understanding of the parasite genomics and proteomics may provide insights to develop means to interfere the associated pathologies and control the disease.
Veterinary Parasitology, 2015
Salivarian trypanosomes sequentially express only one variant surface glycoprotein (VSG) on their cell surface from a large repertoire of VSG genes. Seven cryopreserved animal trypanosome isolates known as TeAp-ElFrio01, TEVA1 (or TeAp-N/D1), TeGu-N/D1, TeAp-Mantecal01, TeGu-TerecayTrino, TeGu-Terecay03 and TeGu-Terecay323, which had been isolated from different hosts identified in several geographical areas of Venezuela were expanded using adult albino rats. Soluble forms of predominant VSGs expressed during the early infection stages were purified and corresponded to concanavalin A-binding proteins with molecular masses of 48-67 kDa by sodium dodecyl sulfate-polyacrylamide gel electropohoresis, and pI values between 6.1 and 7.5. The biochemical characterization of all purified soluble VSGs revealed that they were dimers in their native form and represented different gene products. Sequencing of some of these proteins yielded peptides homologous to VSGs from Trypanosoma (Trypanozoon) brucei and Trypanosoma (Trypanozoon) evansi and established that they most likely are mosaics generated by homologous recombination. Western blot analysis showed that all purified VSGs were cross-reacting antigens that were recognized by sera from animals infected with either T. evansi or Trypanosoma (Dutonella) vivax. The VSG glycosyl-phosphatidylinositol cross-reacting determinant epitope was only partially responsible for the cross-reactivity of the purified proteins, and antibodies appeared to recognize cross-reacting conformational epitopes from the various soluble VSGs. ELISA experiments were performed using infected bovine sera collected from cattle in a Venezuelan trypanosome-endemic area. In particular, soluble VSGs from Abbreviations: ABTS, 2,2 -azino-bis(3-ethylbenzothiazoline-6-sulphonic acid); BCIP, 5-bromo-4-chloro-3 indolyl phosphate; Con A, concanavalin A; CRD, cross-reacting determinant; DAB, diaminobenzidine; IEF, isoelectric focusing; LC/ESI-MS/MS, liquid chromatography/electrospray ionization-tandem mass spectrometry; NBT, nitro blue tetrazolium; o-PDM, N-N -1,2 phenylenedimaleimide; p-PDM, N-N -1,4 phenyllenedimaleimide; PMSF, phenyl methyl sulfonyl fluoride; RAPD, random amplification polymorphic DNA; Rf, relative mobility; RoTat, Rode Trypanozoon antigen type; SDS-PAGE, sodium dodecyl G Model VETPAR-7444; No. of Pages 17 2 R. Camargo et al. / Veterinary Parasitology xxx (2014) xxx-xxx
Clinicopathological Studies and New Markers for Trypanosoma evansi in Experimentally Infected Rats
Advances in Animal and Veterinary Sciences, 2019
T rypanosomiasis is a serious parasitic infection that affects both human and animals, as it has several species. Among their most dangerous species T. evansi, which is a constraint in the expansion of camel breeding in the producing countries (Ahmadi-hamedani, et al., 2014; Zewdu, et al., 2018). Whereas, it affects widely different dromedaries resulting in severe economic losses related to the disease symptoms such as decreased milk production and body gain, abortion, severe damages in vital organs such as kidney, heart, brain and finally death. The cost of the treatment and prophylaxis must be taken in consideration as another losses for camel trypanosomiasis. (Abd El-Baky and Salem 2011; Ahmadi-hamedani et al., 2014). The nature of camel trypanosomiasis as a silent disease as well as its late detection, maximize its effect and decrease its recovery rates. So, there is a need to improve our information about hematological, biochemical and pathological changes related to the disease and find new diagnostic and prognostic tools for trypanosomasis (Abd El-Baky and
Experimental Parasitology, 2016
Beside typical human trypanosomes responsible of sleeping sickness in Africa and Chagas disease in Latin America, there is a growing number of reported atypical human infections due to Trypanosoma evansi, a livestock parasite, or Trypanosoma lewisi, a rat parasite, especially in Asia. Drugs available for the treatment of T. brucei ssp. in humans are obviously of choice for the control of T. evansi because it is derived from T. brucei. However, concerning T. lewisi, there is an urgent need to determine the efficacy of trypanocidal drugs for the treatment in humans. In a recent study, pentamidine and fexinidazole were shown to have the best efficacy against one stock of T. lewisi in rats. In the present study suramin, pentamidine, eflornitine, nifurtimox, benznidazole and fexinidazole, were evaluated at low and high doses, in single day administration to normal rats experimentally infected with a stock of T. lewisi recently isolated in Thailand. Because none of these treatments was efficient, a trial was made with the most promising trypanocide identified in a previous study, fexinidazole 100mg/kg, in 5 daily administrations. Results observed were unclear. To confirm the efficacy of fexinidazole, a mixed infection protocol was set up in cyclophosphamide immunosuppressed rats. Animals were infected successively by T. lewisi and T. evansi, and received 10 daily PO administrations of 200mg/kg fexinidazole. Drastic effects were observed against T. evansi which was cleared from the rat's blood within 24 to 48 hours; however, the treatment did not affect T. lewisi which remained in high number in the blood until the end of the experiment. This mixed infection / treatment protocol clearly demonstrated the efficacy of fexinidazole against T. evansi and its inefficacy against T. lewisi. Since animal trypanocides were also recently shown to be inefficient, other protocols as well as other T. lewisi stocks should be investigated in further studies. respectively applied to Group 7, 8 and 9 (see below). Groups 1-8 received single day administration treatments, and Group 9 received 5 daily serial administrations. Group 1: Control group; 0.2ml of physiological water was administered by IM injection, once. Group 2: suramin, 20mg/Kg (low dose) and/or 40mg/Kg (high dose); Group 3: pentamidine diisetionate 8mg/Kg and/or 16mg/Kg; Group 4: eflornitine hydrochloride: 800mg/Kg and/or 1600mg/Kg; Group 5: nifurtimox: 30mg/kg and 60mg/Kg; Group 6: benznidazole 20mg/kg and 40 mg/Kg; Group 7: fexinidazole 100mg/kg; Group 8: fexinidazole 200mg/Kg; Group 9: fexinidazole 100mg/kg per day for five days. After treatments, animals were followed-up daily by parasite counting in peripheral blood, for 6-9 days between low and high dose, or more than 14 days after high dose treatments. Highlights There is an increasing number of clinical reports of T. lewisi infections in humans. The 6 human trypanocidal drugs used were unable to cure T. lewisi infected rats In rats infected by T. lewisi and T. evansi, fexinidazole treatment cured T. evansi only. So far no human trypanocidal drug proved to be efficient against T. lewisi in rats. Further investigations are needed to identify efficient drugs for the control of T. lewisi in humans.
Pathogenicity of Ethiopian Trypanosoma evansi Type A and B in Swiss Albino Mice Model
East African Journal of Veterinary and Animal Sciences, 2019
Surra caused by Trypanosoma evansi is one of the important pathogenic parasitic diseases of camels, equines, other domestic and wild animals. T. evansi type A is endemic to Africa, Latin America, and Asia while T. evansi type B is so far identified only in Ethiopian and Kenyan camels. Little is known about the pathogenicity of T. evansi. This study was conducted to determine the pathogenicity of T. evansi type A and B in Swiss albino mice colony. We genetically characterized two T. evansi type A and two T. evansi type B isolated from camels in Tigray and Afar. Six mice were infected by each of the isolates and compared with 6 uninfected mice (control). Parasitemia was followed on Matching Method. Weight and PCV of each mouse were measured pre-infection and after 6 days post-infection. Each mouse was examined for visible clinical signs. Highly parasitaemic mice were euthanized on diethyl ether to collect vital organs for gross and histopathologic examination. Major clinical signs in infected mice were rough hair coats, pale mucous membranes of the eye, and incoordination. Compared to the control, there were no significant reductions in the body weight of mice (T. evansi type A, p= 0.493, T. evansi type B, p=0.299), but there was significant reduction in the mean PCV values in both T. evansi type A (p= 0.0001) and T. evansi type B (p= 0.0008) stocks. Splenomegaly, hepatomegaly, edema and pneumonia were the prominent lesions observed at necropsy. Microscopic lesions seen in vital organs were congestion, capillaries distended with red blood cells, cellular infiltration, accumulation of hemosiderin, necrosis and degenerative changes. The clinical signs and gross and histopathologic lesions were comparable between mice infected by T. evansi type A and B. In conclusion, T. evansi type A and B showed similar in vivo pathogenicity. As a result, a special model for comparative pathological study on host-trypanosome interaction is essential.
Atypical Human Infections by Animal Trypanosomes
PLoS Neglected Tropical Diseases, 2013
The two classical forms of human trypanosomoses are sleeping sickness due to Trypanosoma brucei gambiense or T. brucei rhodesiense, and Chagas disease due to T. cruzi. However, a number of atypical human infections caused by other T. species (or sub-species) have been reported, namely due to T. brucei brucei, T. vivax, T. congolense, T. evansi, T. lewisi, and T. lewisi-like. These cases are reviewed here. Some infections were transient in nature, while others required treatments that were successful in most cases, although two cases were fatal. A recent case of infection due to T. evansi was related to a lack of apolipoprotein L-I, but T. lewisi infections were not related to immunosuppression or specific human genetic profiles. Out of 19 patients, eight were confirmed between 1974 and 2010, thanks to improved molecular techniques. However, the number of cases of atypical human trypanosomoses might be underestimated. Thus, improvement, evaluation of new diagnostic tests, and field investigations are required for detection and confirmation of these atypical cases.
A review on the diagnosis of animal trypanosomoses
Parasites & Vectors, 2022
This review focuses on the most reliable and up-to-date methods for diagnosing trypanosomoses, a group of diseases of wild and domestic mammals, caused by trypanosomes, parasitic zooflagellate protozoans mainly transmitted by insects. In Africa, the Americas and Asia, these diseases, which in some cases affect humans, result in significant illness in animals and cause major economic losses in livestock. A number of pathogens are described in this review, including several Salivarian trypanosomes, such as Trypanosoma brucei sspp. (among which are the agents of sleeping sickness, the human African trypanosomiasis [HAT]), Trypanosoma congolense and Trypanosoma vivax (causing “Nagana” or animal African trypanosomosis [AAT]), Trypanosoma evansi (“Surra”) and Trypanosoma equiperdum (“Dourine”), and Trypanosoma cruzi, a Stercorarian trypanosome, etiological agent of the American trypanosomiasis (Chagas disease). Diagnostic methods for detecting zoonotic trypanosomes causing Chagas disease ...
2010
The present research investigated the presence of T. evansi antibodies in animals from the subregion of Nhecolandia, in the Pantanal Sul-mato-grossense, by means of an enzyme linked immunosorbent assay (ELISA) and indirect immunofluorescence antibody test (IFAT), and the pattern of polypeptide recognition by sera from experimentally and naturally infected hosts using Western blotting. Serum samples were obtained from bovines (n = 102), horses (n = 98), and dogs (n = 55), and from 32 free-ranging coatis (Nasua nasua). None of the bovines were found positive, while sera from 16 dogs (29%) and 23 horses (23.4%) were positive by ELISA. Sera from 8 coatis (25%) were found positive using IFAT. Western blotting revealed major polypeptides of T. evansi with molecular weight ranging from 74 to 38 kDa. The polypeptides of 66, 48-46, and 38 kDa were identified by sera from experimentally infected bovines, donkeys, dogs, and coatis. The 48-46 and 38 kDa bands were mainly recognized in chronic phase of infection. The antigen with apparent molecular weight of 66 kDa, revealed by antibodies from all experimental animals, was also recognized in sera of horses and dogs from the Pantanal. The 48-46 kDa polypeptide was identified by antibodies from all naturally infected animals and must be further evaluated for use in specific diagnosis of T. evansi infection.