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Prenatal therapy with pyrimethamine + sulfadiazine vs spiramycin to reduce placental transmission of toxoplasmosis: a multicenter, randomized trial

      Background

      The efficacy of prophylaxis to prevent prenatal toxoplasmosis transmission is controversial, without any previous randomized clinical trial. In France, spiramycin is usually prescribed for maternal seroconversions. A more potent pyrimethamine + sulfadiazine regimen is used to treat congenital toxoplasmosis and is offered in some countries as prophylaxis.

      Objective

      We sought to compare the efficacy and tolerance of pyrimethamine + sulfadiazine vs spiramycin to reduce placental transmission.

      Study Design

      This was a randomized, open-label trial in 36 French centers, comparing pyrimethamine (50 mg qd) + sulfadiazine (1 g tid) with folinic acid vs spiramycin (1 g tid) following toxoplasmosis seroconversion.

      Results

      In all, 143 women were randomized from November 2010 through January 2014. An amniocentesis was later performed in 131 cases, with a positive Toxoplasma gondii polymerase chain reaction in 7/67 (10.4%) in the pyrimethamine + sulfadiazine group vs 13/64 (20.3%) in the spiramycin group. Cerebral ultrasound anomalies appeared in 0/73 fetuses in the pyrimethamine + sulfadiazine group, vs 6/70 in the spiramycin group (P = .01). Two of these pregnancies were terminated. Transmission rates, excluding 18 children with undefined status, were 12/65 in the pyrimethamine + sulfadiazine group (18.5%), vs 18/60 in the spiramycin group (30%, P = .147), equivalent to an odds ratio of 0.53 (95% confidence interval, 0.23–1.22) and which after adjustment tended to be stronger (P = .03 for interaction) when treatment started within 3 weeks of seroconversion (95% confidence interval, 0.00–1.63). Two women had severe rashes, both with pyrimethamine + sulfadiazine.

      Conclusion

      There was a trend toward lower transmission with pyrimethamine + sulfadiazine, but it did not reach statistical significance, possibly for lack of statistical power because enrollment was discontinued. There were also no fetal cerebral toxoplasmosis lesions in the pyrimethamine + sulfadiazine group. These promising results encourage further research on chemoprophylaxis to prevent congenital toxoplasmosis.

      Key words

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      Linked Article

      • Systematic screening and treatment of toxoplasmosis during pregnancy: is the glass half full or half empty?
        American Journal of Obstetrics & GynecologyVol. 219Issue 4
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          In this issue of the Journal, Mandelbrot et al1 report findings of the first randomized clinical trial (RCT) ever performed on the treatment of acute toxoplasma infection during pregnancy. Treatment of acute toxoplasma infection during gestation is aimed at preventing mother-to-child transmission (MTCT) and to minimize clinical sequelae in already infected offspring (CSIo).1 According to the authors, a placebo-controlled RCT was not possible because most investigators who were surveyed at the time believed that such RCT would be unacceptable, given that spiramycin has been used for this indication in France for >30 years.
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