Toxoplasma gondii RH strain infection in a mouse model

Assiut veterinary medical journal, 2010

The present study was designed to clarify the effect of Clindamycin (CLI) combined with Sulfadiazine (SD) on a murine model of acute toxoplasmosis. Albino Swiss mice were intraperitoneally infected with 10 3 tachyzoites of the RH strain of Toxoplasma gondii and were per orally treated with either drug alone (SD) or (CLI) or both combined. Starting with day 1 for 14 days. Survival was monitored during 8 weeks. Residual infection was assessed by a bioassay of representative 4-week survivors and by parasite DNA detection using PCR for representative 8-week survivors. An effect of treatment was shown in all treated groups compared to untreated control mice. Among mice infected with parasite, SD and CLI at any dose combination protected more animals. However, treatment with SD plus CLI at 25 plus 25, 25 plus 50, and 50 plus 50 mg/kg/day protected 25, 37, and 81% of mice, respectively, thus demonstrating a significant synergistic effect of SD and CLI against T. gondii especially in cases of acute infection.

Heliyon, 2020

Successful treatment of Toxoplasma gondii infection is difficult to attain. This study was designed to evaluate the efficacy of sulfamethoxazole-trimethoprim (SMZ-TMP), as the reference drug, nitazoxanide (NTZ), spiramycin (SP) and SP-metronidazole against the virulent RH T. gondii strain in acute experimental toxoplasmosis. One hundred Swiss albino mice were divided into control and experimental groups. Each mouse was infected with 2500 tachyzoites. Twenty infected untreated mice were used as control. The experimental group was subdivided into four subgroups (20 mice each); IIa SMZ-TMP, IIb NTZ, IIc SP and IId SP-metronidazole. All drugs were in tablet form, and were administered orally in suspension, for a period of seven days. Assessment of each drug efficacy was achieved through the study of mice survival time, mortality rate, parasite load, viability and morphological studies of tachyzoites by scanning electron microscope (SEM). The obtained results showed that SMZ-TMP, SP and SP-metronidazole were effective against acute murine toxoplasmosis and caused deformities in the tachyzoites ultrastructure. SP-metronidazole gave the best results on both mice survival rate and parasite load in the brain and liver. SMZ-TMP induced formation of prominent filaments extending from the deformed tachyzoites. NTZ showed little effect. In conclusion, all used drugs succeeded to prolong the survival time of the mice. SP-metronidazole gave the foremost effect on both mice survival rate and parasite load in the liver, spleen and brain. As this combination is nontoxic to human, it is promising for the treatment of human toxoplasmosis.

Jundishapur Journal of Microbiology, 2015

Background: Toxoplasmosis is a public health problem worldwide. This complication principally affects immunodeficient patients and pregnant women. Toxoplasma gondii is an opportunistic parasite, causing severe illness among and death of high-risk individuals and treatment is becoming increasingly difficult owing to side effects and low efficacies of drugs. Objectives: In this study, we investigated the anti-Toxoplasma gondii efficacy of propranolol in vivo. Materials and Methods: This study was performed in two separate pre-treatment and post-treatment groups. In each group, 18 female Balb/c mice in six subgroups (n = 3) were used to assess the anti-Toxoplasma effect of propranolol at 2 and 3 mg/kg/day, pyrimethamine at 50 mg/kg/day, propranolol at 2 and 3 mg/kg/day plus pyrimethamine, and phosphate-buffered saline (PBS; as negative control). Treatment was performed 4, 24, and 48 hours before and after an intraperitoneal challenge of 1 × 10 3 tachyzoites of the virulent RH strain of T. gondii, in pre-treatment and post-treatment groups. Mice peritoneal exudates were collected on the seventh day after the challenge and parasite numbers were recorded as percent of growth inhibition and survival rate. Results: In the pre-treatment group, results showed that propranolol at 2 and 3 mg/kg combined with pyrimethamine was more effective in inhibiting growth of tachyzoites (86% and 98%, respectively) when compared with propranolol at 2 and 3 mg/kg (37% and 39%, respectively) and pyrimethamine (41%) alone. In the post-treatment group, all combined treatments significantly reduced parasite load. The growth inhibition of tachyzoites in mice receiving propranolol (2 and 3 mg/kg) was 75% and 51%, with the mean tachyzoites count being 1526 ± 171.4 and 2948 ± 1452.8, respectively, compared with pyrimethamine treatment outcome, which represents 99.9% growth inhibition. Conclusions: Our results demonstrated the promising prophylactic and therapeutic effects of propranolol against T. gondii infection. Propranolol also increases the efficacy of pyrimethamine in combination therapies.

Japanese Journal of Infectious Diseases, 2015

The aim of this study is to evaluate the effects of pyrimethamine (PYR) and sulfadiazine (SDZ) combined with levamisole and echinacea on the survival of mice infected with Toxoplasma gondii. For this, we used 99 specific pathogen-free BALB/c mice. All the mice were infected intraperitoneally with 10 5 T. gondii tachyzoites and were divided into 11 groups, each including 9 mice. Except for the control group, oral treatment was initiated in all groups 24 h post infection and was continued for 10 days. The treatment regimen included dual combinations of PYR (dose, 6.25 and 12.5 mg/kg/day) and SDZ (dose, 100 and 200 mg/kg/day), triple combinations of PYR ＋ SDZ, and levamisole (dose, 2.5 mg/kg/day) or echinacea (dose, 130 and 260 mg/kg/day) and echinacea alone (dose, 130 and 260 mg/kg/day). We observed that an effective dose of the combination of PYR ＋ SDZ and levamisole resulted in a statistically significant increase in the survival rate from 33.3z to 88.9z. Similarly, half the dose of this combination resulted an increase in the survival rate from 0z to 44.4z ( p ＜ 0.05). Survival rate also increased in the groups treated with the combinations including echinacea; however, the difference did not reach statistical significance. The triple combination of PYR-SDZ-levamisole could be an alternative treatment option in case of infections caused by T. gondii.

Frontiers in Cellular and Infection Microbiology, 2020

Treatment for toxoplasmosis is not completely successful because of their unwanted side effects, and new treatments are needed. Imiquimod has ability to moderate immune response and used to treat a wide variety of infections and tumors. The aim of the present study was to evaluate the effect of imiquimod on the tachyzoites of T. gondii and infected macrophages in vitro and in BALB/c mice. The viability of T. gondii was assessed in the presence of various concentrations of imiquimod by direct counting after 6 and 24 h. The MTT assay was used to identify the viability of uninfected macrophages. The apoptotic effects were determined with flow cytometry on the tachyzoites and infected macrophages. For evaluation of parasite load in pre-treatment or post-treatment of macrophages Quantitative real time PCR (qPCR) was performed. For in vivo experiments, BALB/c mice received imiquimod before and after challenge with parasites. The mortality rate of mice, parasite numbers in spleen, and the INF-γ and IL-4 cytokine levels in spleen lymphocytes were evaluated. Imiquimod demonstrated anti-Toxoplasma effects by reducing the number of tachyzoites. The results of flow cytometry for drug-treated tachyzoites showed that apoptosis did not rise significantly relative to the control group (p < 0.05). Moreover, apoptosis was enhanced in infected macrophages as the concentration of imiquimod was reduced. The parasitic burden in imiquimod pretreated macrophages was significantly lower than those treated after infection (p < 0.01). A marked reduction was observed in survival rate, parasite load and INF-γ level in BALB/c mice that received imiquimod before parasitic challenge relative to those received drug after parasitic challenge (p < 0.01). Overall, imiquimod in the pretreated group had greater anti-Toxoplasma effects than imiquimod in posttreated group in vitro and in vivo. imiquimod may be considered as a candidate for use against Toxoplasmosis both therapeutically and prophylactically.

Parasite, 2005

The efficacy of atovaquone and sulfadiazine was examined alone or in combination for the treatment of mice infected with six Brazilian Toxoplasma gondii strains previously genotyped using the PCR-RFLP assays of the SAG2 gene, in addition to RH strain. Swiss mice were infected intraperitoneally with 10 2 tachyzoites from each strain of T. gondii and treated with 6.25, 12.5, 25 and 50 mg/Kg/day of atovaquone or 40, 80, 160 and 320 mg/Kg/day of sulfadiazine. In a second experiment, mice were treated with the association of previously determined doses of each drug. Treatment started 48 hours post-infection, and lasted 10 days. The susceptibility of T. gondii to atovaquone and to sulfadiazine was different according to the parasite strain. It was observed strains that are susceptible to atovaquone, and strains that are resistant to it. Type I strains were more susceptible to the activity of sulfadiazine and more resistant to atovaquone. Yet type III strains were susceptible to atovaquone and to sulfadiazine. Association of atovaquone and sulfadiazine presented a synergic effect in the treatment of mice infected with RH type I strain and an additive effect in the treatment of mice infected with one type I strain and with two type III strains. Résumé : EFFICACITÉ DE L'ATOVAQUONE ET DE LA SULFADIAZINE DANS LE TRAITEMENT DE SOURIS INFECTÉES PAR DES SOUCHES TOXOPLASMA GONDII ISOLÉES AU BRÉSIL L'atovaquone et la sulfadiazine on été évaluées, seules ou en association, quant à leur efficacité dans le traitement de souris infectées par six souches brésiliennes de Toxoplasma gondii, dont le type génétique a été préalablement déterminé par l'intermédiaire d'une PCR-RFLP du gène SAG2 ; la souche RH a été évaluée conjointement. Des souris Swiss ont été infectées par voie intra-péritonéale avec 102 tachyzoïtes de chaque souche de T. gondii, puis traitées avec 6,25, 12,5, 25 et 50 mg/kg/jour d'atovaquone ou 40, 80, 160 et 320 mg/kg/jour de sulfadiazine, pendant dix jours. Dans un second essai, les souris ont été traitées par l'association de ces médicaments à des doses préalablement évaluées. Le traitement des souris a commencé 48 heures après l'infection. La susceptibilité de T. gondii à l'atovaquone et à la sulfadiazine a été différente selon la souche du parasite. On a observé des souches sensibles et résistantes à l'atovaquone. Les souches du type I se sont montrées plus susceptibles à la sulfadiazine et plus résistantes à l'atovaquone. Les souches du type III se sont montrées sensibles à l'atovaquone et à la sulfadiazine. L'association de l'atovaquone et de la sulfadiazine a montré un effet synergique dans le traitement des souris infectées par la souche RH du type I et un effet additif dans le traitement des souris infectées avec une souche du type I et deux souches du type III.

Acta Parasitologica, 2019

Purpose Toxoplasma gondii is a protozoan from phylum Apicomplexa, which causes the toxoplasmosis infection; this one exhibits an apicoplast organelle which assists in the metabolism of isoprenoids and other pivotal mediators for the parasite survival. Statins are drugs that inhibit cholesterol synthesis, blocking the conversion of the substrate HMG-CoA to mevalonate, thus preventing the initial processes of the biosynthesis of these precursors, both in humans and parasite. Our goal was to verify whether the Toxoplasma gondii (RH strain) tachyzoites form pretreated with pravastatin and simvastatin in association with pyrimethamine and sulfadiazine at low concentrations could affect the infection processes, suggesting direct action on protozoa intracellular proliferation through the inhibition of isoprenoids in the parasite's apicoplast. Methods To have the adhesion, infection, and parasite proliferation during experimental infection investigated, HeLa cells (10 5) were subjected to a 24-hour infection by T. gondii tachyzoites forms of RH strain (5 × 10 5) pretreated for 30 min with pravastatin and/or simvastatin combined or not with pyrimethamine and sulfadiazine. Results Combined with conventional drugs at low concentrations pravastatin and simvastatin inhibit the adhesion, invasion, and intracellular proliferation of T. gondii in HeLa cells which are similar to the positive control. Conclusion Pravastatin and simvastatin in association with pyrimethamine and sulfadiazine at low concentrations can be regarded as a promising, effective alternative to toxoplasmosis treatment with reduced side effects.

Revista de Patologia Tropical, 2014

Toxoplasma gondii is the most common protozoan found in animals and humans and has been found in several of the host's organs, including the liver. This study aimed to evaluate hepatic injury in experimental toxoplasmosis caused by two strains of T. gondii (RH and Me-49 strains). Biochemical and histopathological analyses were performed. It was possible to detect significant increases in serum levels of AST, ALT and LDH in both infections. The histopathological analysis showed inflammatory infiltration in the Me-49 strain infection and hyperemia and vasodilation in the RH strain infection. The acute infection (RH strain) induced hepatic failure and the death of the host. The chronic infection (ME-49 strain) caused liver damage but not enough to kill the host. Therefore this study validates the importance of biochemical concentrations for the evaluation of the infection, showing the importance of rigorous clinical assessment of T. gondii infected individuals.

Japanese Journal of Tropical Medicine and Hygiene, 2003

The Toxoplasma gondii number was evaluated by quantitative competitive polymerase chain reaction (QC-PCR) assay with or without sulfamethoxazole treatment in the heart, blood, brain, and small intestine of IFN-γ knockout (GKO) BALB/c (B/c) mice after peroral infection with the cyst-forming Fukaya strain. T. gondii infection was observed in the heart, blood, and brain, but not in the small intestine, of mice treated with sulfamethoxazole for 4 weeks. No correlation between T. gondii loads and sulfamethoxazole concentrations in tissues and blood was observed. T. gondii was not detected in the heart and blood after continuous sulfamethoxazole treatment for two months, but a small number of parasites was demonstrated in the brain. Thus, we successfully established an animal model for evaluating chemotherapy regimens in immunocompromised hosts by using GKO B/c mice infected with T. gondii.

2020

Toxoplasma gondii parasite is one of the world&#39;s most common parasites which is an intracellular parasite. The aim of this work is to investigate the effect of nitrofurantoin given at a dose of 100mg/kg(2mg for each mouse) , spiramycin given at a dose of 200mg/k.g (4mg for each mouse) and a combination of both(4 days post infection for 2 weeks) on the brain cyst count of infected mice (54 laboratory-bred Swiss albino mice). Mice were contaminated for 10 cysts for Toxoplasma gondii (ME 49 strain). Five aggregations for mice were utilized within those study,three bunches for them accepted medicines and the different two were ordinary Furthermore contaminated non treated aggregations. One bunch approached with spiramycin,other approached for nitrofurantoin, and the final one approached for the blending for both. The mice were sacrified then afterward 8 weeks. The blending for both pills made 4 days post spoiling for two weeks brought about critical diminishment in the mind growth c...