In vitro activity and preliminary toxicity of various diamidine compounds against Trypanosoma evansi (original) (raw)
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.
Mammalian cell invasion by closely related Trypanosoma species T. dionisii and T. cruzi
Acta Tropica
Protozoan parasites of the genus Trypanosoma can infect virtually all mammalian species. Within this genus, Trypanosoma dionisii from bats and Trypanosoma cruzi that causes Chagas' disease, belonging to the subgenus Schizotrypanum, can invade mammalian cells. The mechanisms of cell invasion by T. dionisii are poorly understood. To address that question, metacyclic trypomastigotes (MT) and human epithelial HeLa cells were used. Similarly to genetically divergent T. cruzi strains G (TcI) and CL (TcVI), associated, respectively with marsupial and human infections, T. dionisii infectivity increased under nutritional stress, a condition that induces host cell lysosome exocytosis required for parasite internalization. For efficient internalization, T. dionisii depended on MT protein tyrosine kinase (PTK) and Ca 2+ mobilization from acidocalcisomes, whereas T. cruzi strains also relied on phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC) and Ca 2+ released from thapsigargin-sensitive compartments. T. dionisii-induced signaling in host cells implicated PKC and Ca 2+ mobilized from thapsigargin-sensitive stores, like T. cruzi, but without PI3K involvement. Unlike T. cruzi, T. dionisii metacyclic forms did not use l-proline as source of energy required for internalization. Molecules related to T. cruzi surface glycoproteins involved in MT-host cell interaction were undetectable in T. dionisii. The difference in the surface profile of the two species was also inferred from the susceptibility of T. dionisii metacyclic forms to complement-mediated lysis, as opposed to complete resistance of T. cruzi. In summary, the two Trypanosoma species display distinct surface profiles but invade host cells through a common mechanism involving lysosome mobilization to the site of parasite entry.
A Comprehensive Review on blood protozoan disease of cattle: Trypanosomiasis
Veterinary Sciences and One Health Journal, 2024
Trypanosomiasis is a protozoan disease that is transmitted by biting flies. Trypanosomes species, including Trypanosome evansi (T. evansi) and Trypanosome theileri (T. theileri) have been reported in a wide range of mammalian species worldwide. Owing to the paucity of information, the current study was designed to investigate the prevalence and genomic characterization of T. evansi and T. theileri in the cattle population in Southern Punjab, Pakistan. Therefore, a robust surveillance system is needed to monitor this disease for the accurate diagnosis and understand the prevalence of each species. Here, we explained the detection of trypanosome species through deep amplicon sequencing in co-infection communities and made the concept of haemoprotobiome. The DNA artificial pools from four different Trypanosoma isolates (T. theileri, T. vivax, T. congolense, and T. brucei) were created, and the threshold of the deep amplicon sequencing method and the proportion of each of the species present or absent in the mixer, 3 replicates of 10 "artificial pools mixture" was evaluated. It was revealed that this method could determine the accurate composition of Trypanosoma species in the pooled samples. Second, the technique was applied to validate the detection threshold of Trypanosoma infected samples collected from cattle and were identified as an infection of Trypanosoma using PCR-based assay. Each sample shows the different composition of Trypanosoma species, and the amount of Illumina Mi-Seq reads in the samples where the mixed infection was present. Third, we applied the assay to the field samples to new insight into the species composition of Trypanosoma communities in cattle, camel, buffalo, horse, sheep, and goat in the endemic region of Pakistan. It was confirmed that T. evansi is the primary species in Pakistan, and T. theileri has been observed to reveal the first report of this group of parasites in this country. In this study, we used molecular genetic approaches to provide relevant insight into the emergence of diminazene resistance after intensive positive selection pressure at the AT-1 locus of T. evansi in the endemic regions of Pakistan. We chose this region because animals are treated sporadically often with generic diminazene drugs of unknown quality. Diminazene drugs have been widely used for the therapy of Trypanosomiasis because they are relatively safe and inexpensive. Until recently, it was assumed that diminazene was effective against T. evansi, but the widespread resistance shows the need to investigate the emergence of resistance in this group of parasites. There is a clear need to understand how the resistance mutations against diminazene drugs emerge. The frequency with which diminazene resistance in T. evansi emerges is important for its prevention and control Our findings show that this technology can be used in disease surveillance programs in animals and humans, similar to how our approach revolutionized the research of piroplasms in humans and bovines. These works explore the practical methods which are helpful to determine the epidemiology of different diseases, including Trypanosoma and co-infection. The technology is useful for monitoring the parasite diversity after the emergence and the drug resistance in cattle. The plasticity of this approach is not host-specific and could have future application for the assessment of other animals and human Trypanosoma species.
bioRxiv (Cold Spring Harbor Laboratory), 2023
The objective of this study was to characterize and compare the clinically visible pathological features and drug resistance patterns of two Trypanosoma isolates from two tsetse infested areas of northwest Ethiopia in experimentally infected goats. From the 37 trypanosome free goats, two goats (trypanosome donors) were used to take trypanosome isolates from naturally infected cattle (one from Jawi and the other from Jabitehenen areas). The remaining thirty five goats were randomly assigned into seven experimental groups, each containing five goats. These groups were again randomly selected, and three of them-Group 1 (JWI-1), Group 2 (JWI-DA), and Group 3 (JWI-ISM)-were inoculated with the Trypanosoma of Jawi isolate. Group-4 (JBI-1), Group-5 (JBI-DA), and Group-6 (JBI-ISM) were inoculated with the Trypanosoma of Jabitehenan isolate. The remaining group, Group 7 (NIC), was under negative control. Each experimental goat received 2 ml of trypanosoma positive blood at the 1×10 6 parasites/ml from donor goats through the jugular vein. Group NIC received 2 mL of sterile water as a negative control. For ten weeks following infection, parameters such as parasitaemia, body weight, PCV, and hemoglobin value were measured once per week. When peak parasitaemia was detected on day 14 of post infection, trypanocidal treatment was administered. Diminazine diaceturate (DA) was given at a dose of 28 mg/kg, and isomethamedium chloride (ISM) was given at a dose of 4 mg/kg. Trypanosomosis was detected on days 5 and 6 of post-infection (Pi) in Jabitehenan and Jawi, T. congolense isolates from infected groups, respectively. When peak parasitaemia was detected on day 14 of post infection, trypanocidal treatment was administered. 7 mg/kg for Group 2 and Group 5 and 1 mg/kg for Group 3 and Group 6 were the treatment doses for DA and ISM, respectively. All of the infected groups (groups 1 and 4; positive control) had severe clinical signs and recumbence within 27-59 days of infection. The mean PCV, total RBC, and Hgb concentration values of Jabitehenan isolate infected groups were significantly (P<0.05) lower than Jawi isolate infected groups, and severe clinical signs in group 4 occurred earlier than .
A Biochemical and Immunological Comparative Study on Trypanosoma equiperdum and Trypanosoma evansi
Veterinary Research Communications - VET RES COMMUN, 2003
Trypanosoma equiperdum and Trypanosoma evansi were purified by three or four cycles of low-speed centrifugation and final filtration through DEAE cellulose. The purified trypanosomes were used in comparative biochemical and immunological studies. Comparative polypeptide pattern analysis revealed that T. equiperdum showed 21 polypeptide bands, whose Mr ranged from >200 to 14.8 kDa. T. evansi showed 25 polypeptide bands in the Mr range 97–14.8 kDa. The main differences were associated with the presence of secondary bands, relative intensity and the number of bands. Both species gave seven glycoprotein bands; those of 97 and 68 kDa were present in T. equiperdum but absent in T. evansi. Bands of 61 and 28 kDa were present in T. evansi but not in T. equiperdum. Anti-T. equiperdum sera recognized four homologous antigens and cross-reacted with three antigens of T. evansi. Anti-T. evansi sera recognized three homologous antigens and cross-reacted with four T. equiperdum antigens. Four i...