Determination of parasitic burden in the brain tissue of infected mice in acute toxoplasmosis after treatment by fluconazole combined with sulfadiazine and pyrimethamine.
14-alpha Demethylase Inhibitors
/ therapeutic use
Acute Disease
Animals
Antiprotozoal Agents
/ therapeutic use
Brain
/ diagnostic imaging
Disease Models, Animal
Drug Therapy, Combination
Female
Fluconazole
/ therapeutic use
Mice
Mice, Inbred BALB C
Pyrimethamine
/ therapeutic use
Sulfadiazine
/ therapeutic use
Toxoplasma
/ isolation & purification
Toxoplasmosis, Cerebral
/ diagnosis
Drug
Parasitic burdens
Real-time PCR
Toxoplasma gondii
Journal
European journal of medical research
ISSN: 2047-783X
Titre abrégé: Eur J Med Res
Pays: England
ID NLM: 9517857
Informations de publication
Date de publication:
30 Jun 2021
30 Jun 2021
Historique:
received:
12
12
2020
accepted:
22
06
2021
entrez:
1
7
2021
pubmed:
2
7
2021
medline:
15
12
2021
Statut:
epublish
Résumé
One of the opportunistic pathogens which cause serious problems in the human immune system is Toxoplasma gondii, with toxoplasma encephalitis (TE) seen in patients affected by it. The treatment of these patients is limited, and if not treated on time, death will be possible. In this study, the effects of the treatment with different doses of fluconazole (FLZ) in combination with the current treatment of acute toxoplasmosis on reducing the mortality rate and the parasitic load in the murine model in vivo were studied. The mice were treated with different doses of fluconazole alone, sulfadiazine, and pyrimethamine plus fluconazole. A day after the end of the treatment and 1 day before death, the mice's brains were collected, and after DNA extraction and molecular tests, the parasite burden was detected. This study showed that a 10-day treatment with 20 mg/kg of fluconazole combined with sulfadiazine and pyrimethamine 1.40 mg/kg per day affected acute toxoplasmosis and reduced the parasitic load significantly in brain tissues and also increased the survival rate of all mice in this group until the last day of the study, in contrast to other treatment groups. These results also indicate the positive effects of combined therapy on Toxoplasma gondii and the prevention of relapse. Reducing the parasitic burden and increasing the survival rate were more effective against acute toxoplasmosis in the combined treatment of different doses of fluconazole with current treatments than current treatments without fluconazole. In other words, combination therapy with fluconazole plus pyrimethamine reduced the parasitic burden in the brain significantly, so it could be a replacement therapy in patients with intolerance sulfadiazine.
Sections du résumé
BACKGROUND/AIMS
OBJECTIVE
One of the opportunistic pathogens which cause serious problems in the human immune system is Toxoplasma gondii, with toxoplasma encephalitis (TE) seen in patients affected by it. The treatment of these patients is limited, and if not treated on time, death will be possible.
METHODS
METHODS
In this study, the effects of the treatment with different doses of fluconazole (FLZ) in combination with the current treatment of acute toxoplasmosis on reducing the mortality rate and the parasitic load in the murine model in vivo were studied. The mice were treated with different doses of fluconazole alone, sulfadiazine, and pyrimethamine plus fluconazole. A day after the end of the treatment and 1 day before death, the mice's brains were collected, and after DNA extraction and molecular tests, the parasite burden was detected.
RESULTS
RESULTS
This study showed that a 10-day treatment with 20 mg/kg of fluconazole combined with sulfadiazine and pyrimethamine 1.40 mg/kg per day affected acute toxoplasmosis and reduced the parasitic load significantly in brain tissues and also increased the survival rate of all mice in this group until the last day of the study, in contrast to other treatment groups. These results also indicate the positive effects of combined therapy on Toxoplasma gondii and the prevention of relapse.
CONCLUSIONS
CONCLUSIONS
Reducing the parasitic burden and increasing the survival rate were more effective against acute toxoplasmosis in the combined treatment of different doses of fluconazole with current treatments than current treatments without fluconazole. In other words, combination therapy with fluconazole plus pyrimethamine reduced the parasitic burden in the brain significantly, so it could be a replacement therapy in patients with intolerance sulfadiazine.
Identifiants
pubmed: 34193287
doi: 10.1186/s40001-021-00537-3
pii: 10.1186/s40001-021-00537-3
pmc: PMC8243906
doi:
Substances chimiques
14-alpha Demethylase Inhibitors
0
Antiprotozoal Agents
0
Sulfadiazine
0N7609K889
Fluconazole
8VZV102JFY
Pyrimethamine
Z3614QOX8W
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
65Subventions
Organisme : Zahedan University of Medical Sciences
ID : 1192
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