Laurent Mandelbrot1, François Kieffer2, Rémi Sitta3, Hélène Laurichesse-Delmas4, Norbert Winer5, Louis Mesnard6, Alain Berrebi7, Gwenaëlle Le Bouar8, Jean-Paul Bory9, Anne-Gaëlle Cordier10, Yves Ville11, Franck Perrotin12, Jean-Marie Jouannic13, Florence Biquard14, Claude d'Ercole15, Véronique Houfflin-Debarge16, Isabelle Villena17, Rodolphe Thiébaut18. 1. Service de Gynécologie-Obstétrique, Assistance Publique-Hôpitaux de Paris, Hôpital Louis Mourier, Colombes, France; Institut national de la santé et de la recherche médicale Iame-U1137, Paris, France; Université Paris-Diderot, Paris, France. Electronic address: laurent.mandelbrot@aphp.fr. 2. Service de Néonatalogie, Assistance Publique-Hôpitaux de Paris, Hôpital Trousseau, Paris, France. 3. Unité de Soutien Méthodologique à la Recherche Clinique et Epidémiologique du Centre Hospitalier Universitaire de Bordeaux, Université Bordeaux, Bordeaux, France. 4. Service de Gynécologie-Obstétrique, Centre Hospitalier Universitaire de Clermond-Ferrand, Clermond-Ferrand, France. 5. Service de Gynécologie-Obstétrique, Centre Hospitalier Universitaire de Nantes, Nantes, France. 6. Centre Hospitalier d'Orléans, Orléans, France. 7. Centre Hospitalier Universitaire de Toulouse, Toulouse, France. 8. Centre Hospitalier Universitaire de Rennes, Rennes, France. 9. Centre Hospitalier Universitaire de Reims, Reims, France. 10. Assistance Publique-Hôpitaux de Paris Hôpital Antoine Béclère, Clamart, France; Université Paris Sud, Kremlin-Bicêtre, Paris, France. 11. Centre Hospitalier Universitaire de Reims, Reims, France; Service de Gynécologie-Obstétrique, Assistance Publique-Hôpitaux de Paris Hôpital Necker, Paris; Université Paris-Descartes, Paris, France. 12. Service de Gynécologie-Obstétrique, Centre Hospitalier Universitaire de Tours, Tours, France. 13. Assistance Publique-Hôpitaux de Paris, Hôpital Trousseau, Paris; Université Pierre et Marie Curie, Paris, France. 14. Service de Gynécologie-Obstétrique, Centre Hospitalier Universitaire d'Angers, Angers, France. 15. Pole Femmes-Parents-Enfants, Assistance Publique-Hôpitaux de Marseille, Marseille, France. 16. Pole Femme-Mère-Nouveau-né, Hôpital Jeanne de Flandre, Centre Hospitalier Universitaire de Lille, Lille, France. 17. Laboratoire Parasitologie-Mycologie, Université Reims Champagne-Ardenne and Hôpital Maison Blanche, Reims, France; Centre National de Référence Toxoplasmose, Reims, France. 18. Unité de Soutien Méthodologique à la Recherche Clinique et Epidémiologique du Centre Hospitalier Universitaire de Bordeaux, Université Bordeaux, Bordeaux, France; Institut national de la santé et de la recherche médicale U1219 Bordeaux Population Health, Bordeaux, France.
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.
RCT Entities:
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.
Authors: Ali Rostami; Seyed Mohammad Riahi; Despina G Contopoulos-Ioannidis; H Ray Gamble; Yadolah Fakhri; Malihe Nourollahpour Shiadeh; Masoud Foroutan; Hamed Behniafar; Ali Taghipour; Yvonne A Maldonado; Ali H Mokdad; Robin B Gasser Journal: PLoS Negl Trop Dis Date: 2019-10-14
Authors: Jose G Montoya; Katherine Laessig; Mir Sohail Fazeli; Gaye Siliman; Sophie S Yoon; Elizabeth Drake-Shanahan; Chengyue Zhu; Akbar Akbary; Rima McLeod Journal: Eur J Med Res Date: 2021-12-11 Impact factor: 2.175