Reactivation of Toxoplasma Retinochoroiditis Under Atovaquone Therapy in an Immunocompetent Patient

Baatz, H.; Mirshahi, Alireza; Puchta, Joachim; Gümbel, H.; Hattenbach, Lars‐Olof

doi:10.1080/09273940600659740

Cited by 47 publications

(33 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Clearly, all existing antitoxoplasmosis therapies, including the antimalarial compound pyrimethamine and the antibiotics clindamycin and sulfadiazine, are ineffective against bradyzoites. In addition, resistance to some of these drugs was recently reported (10)(11)(12), highlighting the urgent need for new and improved antitoxoplasmosis agents. An ideal anti-Toxoplasma drug would be potent and nontoxic and would eliminate latent infection (bradyzoites).…”

mentioning

confidence: 99%

Repurposing the Open Access Malaria Box To Discover Potent Inhibitors of Toxoplasma gondii and Entamoeba histolytica

Boyom

Fokou

Tchokouaha

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

mentioning

confidence: 99%

Repurposing the Open Access Malaria Box To Discover Potent Inhibitors of Toxoplasma gondii and Entamoeba histolytica

Boyom

Fokou

Tchokouaha

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

“…Treatment failures have been reported for most drug regimens used for the treatment of toxoplasmic encephalitis, chorioretinitis, and congenital toxoplasmosis (7,12,21,36,46). Whether these failures are related to host factors (drug intolerance and malabsorption) and/or to the development of drug resistance parasites or a lower susceptibility of the parasite strain is debated.…”

mentioning

confidence: 99%

In Vitro Susceptibility of Various Genotypic Strains of Toxoplasma gondii to Pyrimethamine, Sulfadiazine, and Atovaquone

Méneceur

Bouldouyre

Aubert

et al. 2008

Antimicrob Agents Chemother

128

115

View full text Add to dashboard Cite

Sulfadiazine, pyrimethamine, and atovaquone are widely used for the treatment of severe toxoplasmosis. Their in vitro activities have been almost exclusively demonstrated on laboratory strains belonging to genotype I. We determined the in vitro activities of these drugs against 17 strains of Toxoplasma gondii belonging to various genotypes and examined the correlations among 50% inhibitory concentrations (IC 50 s), growth kinetics, strain genotypes, and mutations on drug target genes. Growth kinetics were determined in THP-1 cell cultures using real-time PCR. IC 50 s were determined in MRC-5 cell cultures using a T. gondii-specific enzyme-linked immunosorbent assay performed on cultures. Mutations in dihydrofolate reductase (DHFR), dihydropteroate synthase (DHPS), and cytochrome b genes were determined by sequencing. Pyrimethamine IC 50 s ranged between 0.07 and 0.39 mg/liter, with no correlation with the strain genotype but a significant correlation with growth kinetics. Several mutations found on the DHFR gene were not linked to lower susceptibility. Atovaquone IC 50 s were in a narrow range of concentrations (mean, 0.06 ؎ 0.02 mg/liter); no mutation was found on the cytochrome b gene. IC 50 s for sulfadiazine ranged between 3 and 18.9 mg/liter for 13 strains and were >50 mg/liter for three strains. High IC 50 s were not correlated to strain genotypes or growth kinetics. A new mutation of the DHPS gene was demonstrated in one of these strains. In conclusion, we found variability in the susceptibilities of T. gondii strains to pyrimethamine and atovaquone, with no evidence of drug resistance. A higher variability was found for sulfadiazine, with a possible resistance of three strains. No relationship was found between drug susceptibility and strain genotype.

show abstract

“…Atovaquone in combination with pyrimethamine or sulfadiazine was reported to prevent relapse of toxoplasmosis in AIDS patients (7). However, it has also been associated with breakthrough failures in other cases (4,24). Hence, there is a need for the development of new therapeutics for treatment of toxoplasmosis.…”

mentioning

confidence: 99%

Artemisone and Artemiside Control Acute and Reactivated Toxoplasmosis in a Murine Model

Dunay

Chan

Haynes

et al. 2009

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Immunocompromised patients are at risk of developing toxoplasmosis, and although chemotherapy is available, standard treatments are often complicated by severe side effects. Artemisinin is a new highly potent antimalarial drug that has activity against Toxoplasma gondii in vitro. However, artemisinin derivatives have previously been ineffective in vivo using a rat model of toxoplasmosis. In the present study, the efficacy of several new artemisinin derivates was investigated for treatment of mice infected with the parasite Toxoplasma gondii. Artemiside and artemisone displayed better inhibition than either artemisinin or artesunate against the parasite in vitro. Artemiside and artemisone treatment controlled parasite replication in vivo, and mice survived the acute infection. In a murine model of reactivated toxoplasmosis, both drugs increased survival, although artemiside was more effective. These results indicate that these newer derivatives of artemisinin may have potential for treatment of toxoplasmosis.

show abstract

Reactivation of Toxoplasma Retinochoroiditis Under Atovaquone Therapy in an Immunocompetent Patient

Abstract: To our knowledge, this is the first report of a reactivation of toxoplasma retinochoroiditis in an immunocompetent patient under atovaquone therapy, possibly indicating tachyzoite resistance to atovaquone.

Cited by 47 publications

References 10 publications

Repurposing the Open Access Malaria Box To Discover Potent Inhibitors of Toxoplasma gondii and Entamoeba histolytica

Repurposing the Open Access Malaria Box To Discover Potent Inhibitors of Toxoplasma gondii and Entamoeba histolytica

In Vitro Susceptibility of Various Genotypic Strains of Toxoplasma gondii to Pyrimethamine, Sulfadiazine, and Atovaquone

Artemisone and Artemiside Control Acute and Reactivated Toxoplasmosis in a Murine Model

Contact Info

Product

Resources

About