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

Am J Obstet Gynecol. 2018 Oct;219(4):386.e1-386.e9. doi: 10.1016/j.ajog.2018.05.031. Epub 2018 Jun 2.

Abstract

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.

Keywords: pregnancy; prenatal diagnosis; pyrimethamine-sulfadiazine; spiramycin; tolerance; toxoplasmosis.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiprotozoal Agents / administration & dosage
  • Antiprotozoal Agents / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • France
  • Humans
  • Infectious Disease Transmission, Vertical / prevention & control
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy*
  • Prenatal Care
  • Pyrimethamine / administration & dosage
  • Pyrimethamine / therapeutic use
  • Sulfadiazine / administration & dosage
  • Sulfadiazine / therapeutic use
  • Toxoplasmosis / drug therapy*
  • Toxoplasmosis / transmission
  • Toxoplasmosis, Congenital / prevention & control
  • Treatment Outcome

Substances

  • Antiprotozoal Agents
  • Sulfadiazine
  • Pyrimethamine