Abstract

BackgroundToxoplasma gondii is a protozoan parasite that causes congenital toxoplasmosis by transplacental transmission. Parasite strains are genetically diverse and disease severity is related to the genotype. In Uberlândia city, Brazil, two virulent strains were isolated: TgChBrUD1 and TgChBrUD2. Congenital toxoplasmosis is more prevalent in South America compared to Europe, and more often associated with severe symptoms, usually as a result of infection with atypical strains.MethodsConsidering that T. gondii has shown high genetic diversity in Brazil, the effectiveness of traditional treatment may not be the same, as more virulent strains of atypical genotypes may predominate. Thus, the aim of this study were to evaluate the Brazilian strain infection rate in human villous explants and the azithromycin efficacy with regard to the control of these strains compared to traditional therapy. Villi were infected with RH, ME49, TgChBrUD1 or TgChBrUD2 strains and treated with azithromycin, spiramycin or a combination of pyrimethamine plus sulfadiazine. The villous viability was analyzed by LDH assay and morphological analysis. Parasite proliferation, as well as production of cytokines was analyzed by qPCR and ELISA, respectively. Statistical analysis was performed using the GraphPad Prism 5.0.ResultsThe treatments were not toxic and TgChBrUD1 infected villi showed a higher parasite burden compared with others strains. Treatments significantly reduced the intracellular proliferation of T. gondii, regardless of the strain. TgChBrUD1-infected villi produced a larger amount of MIF, IL-6 and TGF-β1 compared with other infected villi. Azithromycin treatment increased MIF production by RH- or TgChBrUD2-infected villi, but in ME49- or TgChBrUD1-infected villi, the MIF production was not altered by treatment. On the other hand, azithromycin treatment induced lower IL-6 production by ME49- or TgChBrUD1-infected villi.ConclusionsAzithromycin treatment was effective against T. gondii Brazilian strains compared with conventional treatment. Also, the TgChBrUD1 strain replicated more in villi and modulated important cytokines involved in parasite control, showing that different strains use different strategies to evade the host immune response and ensure their survival.

Highlights

  • Toxoplasma gondii is a protozoan parasite that causes congenital toxoplasmosis by transplacental transmission

  • No significant difference in lactate dehydrogenase (LDH) secretions was observed between uninfected/ treated villous explants and uninfected/untreated villous explants (Fig. 1a)

  • Villous explants infected with TgChBrUD1 strain present higher parasite burden and azithromycin reduces the tissue parasitism in all strain types The parasite intracellular proliferation in villous explants was determined using quantitative real-time PCR (Fig. 2)

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Summary

Introduction

Toxoplasma gondii is a protozoan parasite that causes congenital toxoplasmosis by transplacental transmission. Congenital toxoplasmosis is more prevalent in South America compared to Europe, and more often associated with severe symptoms, usually as a result of infection with atypical strains. Toxoplasmosis is a disease caused by Toxoplasma gondii, an obligate intracellular protozoan parasite that infects a wide range of hosts, including humans [1]. As an opportunistic human pathogen, T. gondii causes a devastating disease in immunocompromised individuals and congenitally infected neonates or children [2]. The infection can result in the vertical transmission of T. gondii tachyzoites and the parasitic infestation can negatively affect the developing fetus [1]. The frequency of congenital transmission increases according to the stage of the pregnancy, the severity of the fetal infection decreases with this gestational progression [4, 5]. Most infected newborns have no symptoms at birth, but serious clinical manifestations can develop during childhood and early adulthood [6]

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