The Efficiency of Metronidazole ‘Flagyl’* Against Trypanosoma Evansi in vivo

Abstract Surra's disease is caused by Trypanosoma evansi parasite has been established as one of the strategic infectious animal diseases. Drug resistance in this case is one of the major challenges in handle and control them. The aim of this study is to evaluate the provision drug resistance diminazene aceturate (Tryponil®) on Trypanosoma evansi isolate from Pemalang and Brebes Central Java province with in vivo test in mice. Total 50 mice, BALB / c strain, male, 2 months, body weight ± 30 gram are obtained from LPPT-UGM, adapted for one week. Mice were divided into 10 groups consist of 5 each. Each mouse was infected with Trypanosoma evansi by intraperitonial route. Treatment was given when mice had reached the level of parasitemia 108 – 109 trypanosoma / mL of blood this was predicted 24 hours post-infection (Eisler et al., 2001). The administration of the drug tryapanosidal was done intraperitonial with doses 1mg/kg, 3mg / kg, 5 mg / kg and 7mg / kg. Observation of parasitemia did every 2 times in one week till 60 days of observation. Parasitemia observation was performed using 3 techniques. The first method was native examination used a microscope, if the negative results would be followed by MHCT (Microhaematocrit centrifugation Technique) and BCT (Buffy Coat Technique) according to OIE (2012). Data obtained from the treatment group were the level of parasitemia, the number of deaths and the number of live mice from each test dose. The results are analysed by standard logit or probit. The results of this study showed the effects of the drug Dimianzene aceturate on both isolates varied. On Brebes Isolate was effective at doses of 7 mg / kg BW (100%) and 5mg / kg BW (80%), whereas in the effective dose Pemalang isolate at 3 mg dose / kg BW (80%), 5 and 7 mg / kg BW (100%). While at the lowest dose of 1 mg / kg obtained a level of effectiveness of 0% in both isolates. It could be concluded that both isolates have different pathogens and indicate resistance subpopulation to diminazene aceturate.Keywords : diminazene aceturate, in vivo, resistance, Trypanosoma evansi.

Download Full-text

In vitro and in vivo trypanocidal action of aescin and aescin liposomes against Trypanosoma evansi in experimental mice

Asian Pacific Journal of Tropical Biomedicine ◽

10.12980/apjtb.4.2014apjtb-2014-0435 ◽

2014 ◽

Vol 4 (12) ◽

pp. 947-951 ◽

Cited By ~ 2

Author(s):

Matheus Dellaméa Baldissera ◽

Nathieli Bianchin Bottari ◽

Thirssa Helena Grando ◽

Roberto Christ Vianna Santos ◽

Ana Júlia Figueiró Dalcin ◽

...

Keyword(s):

Trypanosoma Evansi

Download Full-text

Liposomes produced by reverse phase evaporation: in vitro and in vivo efficacy of diminazene aceturate against Trypanosoma evansi

Parasitology ◽

10.1017/s0031182013002114 ◽

2014 ◽

Vol 141 (6) ◽

pp. 761-769 ◽

Cited By ~ 11

Author(s):

CAMILA BELMONTE OLIVEIRA ◽

LUCAS ALMEIDA RIGO ◽

LUCIANA DALLA ROSA ◽

LUCAS TREVISAN GRESSLER ◽

CARINE ELOISE PRESTES ZIMMERMANN ◽

...

Keyword(s):

Culture Medium ◽

Similar Efficacy ◽

Trypanosoma Evansi ◽

Diminazene Aceturate ◽

Reverse Phase ◽

Dependent Effect ◽

Dose Dependent ◽

Dose Dependent Effect

SUMMARYThis study aimed to develop and test the in vitro and in vivo effectiveness of diminazene aceturate encapsulated into liposomes (L-DMZ) on Trypanosoma evansi. To validate the in vitro tests with L-DMZ, the efficacy of a commercial formulation of diminazene aceturate (C-DMZ) was also assessed. The tests were carried out in culture medium for T. evansi, at concentrations of 0·25, 0·5, 1, 2 and 3 μg mL−1 of L-DMZ and C-DMZ. A dose-dependent effect was observed for both formulations (L-DMZ and C-DMZ), with the highest dose-dependent mortality of trypomastigotes being observed at 1 and 3 h after the onset of tests with L-DMZ. The results of in vivo tests showed the same effects in the animals treated with L-DMZ and C-DMZ in single doses of 3·5 mg kg−1 and for 5 consecutive days (3·5 mg kg−1 day−1). It was possible to conclude that T. evansi showed greater in vitro susceptibility to L-DMZ when compared with C-DMZ. In vivo tests suggest that treatment with the L-DMZ and C-DMZ showed similar efficacy in vivo. The potential of the formulation developed in this study was clearly demonstrated, as it increased the efficacy of the treatment against trypanosomosis, but more studies are needed to increase the effectiveness in vivo.

Download Full-text

DSETHVASAN: A NOVEL NANODRUG AGAINST SLEEPING SICKNESS

International Journal of Nanoscience ◽

10.1142/s0219581x1100779x ◽

2011 ◽

Vol 10 (01n02) ◽

pp. 187-192

Author(s):

D. SETH ◽

R. L. BRAHMACHARY ◽

C. ULRICHS ◽

M. MONDAL ◽

S. MUKHOPADHAYAY ◽

...

Keyword(s):

Density Lipoprotein ◽

Volume Ratio ◽

Trypanosoma Evansi ◽

Sleeping Sickness ◽

Supramolecular Interactions ◽

Mitochondrial Enzymes ◽

Approved Drugs ◽

Surface Modified

Sleeping sickness (causal agent, Trypanosoma sp. parasite) causes huge morbidity and mortality in Africa (both human and livestock) in particular and zoo animals worldwide. Three of the four currently approved drugs (Pentamidine, Melarsoprol, Eflornithine, and Nifurtimox) were developed over 50 years ago. Current therapies are unsatisfactory due to unacceptable level of side effects. Pentamidine, an aromatic diamidine, safest so far, inhibits mitochondrial enzymes. Furthermore, it is effective only in early stages of infections and not on the later stage. Melarsoprol, practically insoluble in water, is very toxic and it is given intravenously (i.v.) for later stage infections only. Other drugs like eflornithine and nitfurtimox are also unsatisfactory for various reasons. Human serum derived high-density lipoprotein (HDL; not mouse or any other mammalian HDL) shows trypanolytic effect in vitro and in vivo on T. brucei. But the mechanism of action of human HDL is far from clear. In the absence of novel drug leads, nanodrugs might be valid options as nanoparticles show better accessibility to cells, supramolecular interactions due to enormous increase in surface area to volume ratio, altered partition coefficient, etc. Surface-modified hydrophobic microsilica (FS), mixture of micro- and nanosilica (Dsethvasan) and nanosilica (AL) were characterized by UV–Vis, DLS, SEM, EDAX, AFM, and XRD. Trypanosoma evansi collected from infected horses were injected in mice. Control infected mouse (n = 30) showed 100% mortality within 72±24 h of injection. Dsethvasan-treated mice (n = 30) survived for 192±24 h. FS-treated mice (n = 30) survived for 120±24 h but the AL-treated mice (n = 30) died within 72±24 h of inoculation like infected control. Hydrophobic Dsethvasan which consists of pure amorphous forms of micro- and nanosilica works better than FS (AL is not at all effective). Therefore, micro- and nanomixture of amorphous silica is best suited for treating Trypanosoma infection in mice. The possible role of ratio of higher to lower size class has been discussed.

Download Full-text

Suscetibilidade de Trypanosoma evansi à anfotericina B

Ciência Rural ◽

10.1590/s0103-84782009000900026 ◽

2009 ◽

Vol 39 (9) ◽

pp. 2550-2555 ◽

Cited By ~ 5

Author(s):

Aleksandro Schafer da Silva ◽

Juliano Botton ◽

Patrícia Wolkmer ◽

Régis Adriel Zanette ◽

Sonia Terezinha dos Anjos Lopes ◽

...

Keyword(s):

Trypanosoma Evansi

O objetivo deste estudo foi avaliar a suscetibilidade do Trypanosoma evansi in vitro e in vivo à anfotericina B. Nos testes in vitro, foram utilizadas quatro concentrações (0,06; 0,25; 1,0; 4,0µg mL-1) de anfotecicina B frente a uma suspensão de T. evansi em solução tampão fosfato rico em glicose (PBS - glicose). Para avaliar a eficácia in vivo, foram utilizados 15 ratos parasitados com T. evansi. Em dois grupos de cinco ratos infectados, doses únicas diárias de 1 (grupo A) e de 3mg kg-1 (grupo B) foram administradas via intraperitonial durante 10 dias, e a parasitemia foi avaliada por meio de esfregaço sanguíneo. Grupo C (n=5) foi utilizado como grupo controle positivo, infectados com T. evansi e não tratados, e o grupo D (n=5), como controle negativo. Os ensaios in vitro evidenciaram suscetibilidade de 100% do T. evansi à anfotericina B após 7h, em todas as concentrações avaliadas. Nos ratos, nem a maior dose testada curou os roedores, apesar de ter prolongado a vida destes em comparação à vida dos animais infectados, mas não tratados. Foi também investigada a função hepática e renal dos ratos após a terapia, e os parâmetros bioquímicos analisados mantiveram-se dentro da normalidade. Conclui-se que o T. evansi in vitro é suscetível à anfotericina B. A dose 3mg kg-1 testada aumentou a expectativa de vida de ratos infectados, porém não teve efeito curativo.

Download Full-text

In vivo and in vitro sensitivity of Trypanosoma evansi and T. equiperdum to diminazene, suramin, MelCy, quinapyramine and isometamidium

Acta Tropica ◽

10.1016/0001-706x(91)90002-2 ◽

1991 ◽

Vol 50 (2) ◽

pp. 101-110 ◽

Cited By ~ 44

Author(s):

Z.Q. Zhang ◽

C. Giroud ◽

T. Baltz

Keyword(s):

Trypanosoma Evansi ◽

In Vitro Sensitivity

Download Full-text

Trypanocidal action of tea tree oil (Melaleuca alternifolia) against Trypanosoma evansi in vitro and in vivo used mice as experimental model

Experimental Parasitology ◽

10.1016/j.exppara.2014.03.007 ◽

2014 ◽

Vol 141 ◽

pp. 21-27 ◽

Cited By ~ 28

Author(s):

Matheus D. Baldissera ◽

Aleksandro S. Da Silva ◽

Camila B. Oliveira ◽

Roberto C.V. Santos ◽

Rodrigo A. Vaucher ◽

...

Keyword(s):

Experimental Model ◽

Trypanosoma Evansi ◽

Tea Tree Oil ◽

Melaleuca Alternifolia ◽

Tea Tree

Download Full-text

Cordycepin (3′-deoxyadenosine) pentostatin (deoxycoformycin) combination treatment of mice experimentally infected withTrypanosoma evansi

Parasitology ◽

10.1017/s0031182012001990 ◽

2013 ◽

Vol 140 (5) ◽

pp. 663-671 ◽

Cited By ~ 11

Author(s):

LUCIANA DALLA ROSA ◽

ALEKSANDRO S. DA SILVA ◽

LUCAS T. GRESSLER ◽

CAMILA B. OLIVEIRA ◽

MARIA G. C. DAMBRÓS ◽

...

Keyword(s):

Liver Enzymes ◽

Trypanosoma Evansi ◽

Curative Effect ◽

Therapeutic Protocol ◽

Liver And Kidney ◽

Effect Of Treatment ◽

Dose Dependent ◽

Different Doses

SUMMARYThe aim of this study was to evaluate the anti-trypanosomal effect of treatment with 3′-deoxyadenosine (cordycepin) combined with deoxycoformycin (pentostatin: inhibitor of the enzyme adenosine deaminase)in vitroby using mice experimentally infected withTrypanosoma evansi. In vitro, a dose-dependent trypanocidal effect of cordycepin was observed against the parasite. In thein vivotrials, the two drugs were used individually and in combination of different doses. The drugs when used individually had no curative effect on infected mice. However, the combination of cordycepin (2 mg kg−1) and pentostatin (2 mg kg−1) was 100% effective in theT. evansi-infected groups. There was an increase in levels of some biochemical parameters, especially on liver enzymes, which were accompanied by histological lesions in the liver and kidneys. Based on these results we conclude that treatment using the combination of 3′-deoxyadenosine with deoxycoformycin has a curative effect on mice infected withT. evansi. However, the therapeutic protocol tested led to liver and kidney damage, manifested by hepatotoxicity and nephrotoxicity.

Download Full-text

In Vivo Investigations of Selected Diamidine Compounds against Trypanosoma evansi Using a Mouse Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00422-09 ◽

2009 ◽

Vol 53 (12) ◽

pp. 5074-5079 ◽

Cited By ~ 7

Author(s):

Kirsten Gillingwater ◽

Arvind Kumar ◽

Mariappan Anbazhagan ◽

David W. Boykin ◽

Richard R. Tidwell ◽

...

Keyword(s):

Mouse Model ◽

Trypanosoma Evansi ◽

Chemotherapeutic Agents ◽

Control Measures ◽

Lead Compounds ◽

Protozoan Infection ◽

Drug Doses ◽

Mouse Model Of Infection

ABSTRACT Surra is an animal pathogenic protozoan infection, caused by Trypanosoma evansi, that develops into a fatal wasting disease. Control measures rely on diagnosis and treatment. However, with the continuous emergence of drug resistance, this tactic is failing, and the pressing need for new chemotherapeutic agents is becoming critical. With the introduction of novel aromatic diamidines, a new category of antitrypanosomal drugs was discovered. Nevertheless, their efficacy within a T. evansi-infected mouse model was not known. In total, 30 compounds previously selected based on their in vitro activity were tested in a T. evansi mouse model of infection. Six of the compounds were capable of curing T. evansi-infected mice at drug doses as low as 0.5 and 0.25 mg/kg of body weight administered for 4 consecutive days, and they were more effective than the standard drugs suramin, diminazene, and quinapyramine. After all selection criteria were applied, three diamidine compounds (DB 75, DB 867, and DB 1192) qualified as lead compounds and were considered to have the potential to act as preclinical candidates against T. evansi infection.

Download Full-text