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

• Published in: American journal of obstetrics and gynecology Vol. 219; no. 4; pp. 386.e1 - 386.e9
• Main Authors: Mandelbrot, Laurent, Kieffer, François, Sitta, Rémi, Laurichesse-Delmas, Hélène, Winer, Norbert, Mesnard, Louis, Berrebi, Alain, Le Bouar, Gwenaëlle, Bory, Jean-Paul, Cordier, Anne-Gaëlle, Ville, Yves, Perrotin, Franck, Jouannic, Jean-Marie, Biquard, Florence, d’Ercole, Claude, Houfflin-Debarge, Véronique, Villena, Isabelle, Thiébaut, Rodolphe, Pons, Denis, Nourrisson, C., Lavergne, Rose-Anne, Fillaux, Judith, Assouline, Corinne, Robert-Gangneux, Florence, L’Ollivier, Coralie, Bretelle, Florence, Guidicelli, Béatrice, Garcia, Patricia, Cordier, Anne-Gaelle, Benachi, Alexandra, Vauloup-Fellous, Christelle, Letamendia, Emmanuelle, Bougnoux, Marie-Elisabeth, Van Langendonck, Nathalie, Potin, Jérôme, Marty, Pierre, Pomarès, Christelle, Trastour, Cynthia, Deleplancque, Anne Sophie, Costa, Jean-Marc, Chève, Marie-Thérèse, Col, Jean-Yves, Cimon, Bernard, Sterkers, Y., Lachaud, Laurence, Burlet, Gilles, Maréchaud, Martine, Perraud, Estelle, Grébille, Anne-Gaelle, Valentin, Morgane, Houzé, Sandrine, Omnès, Sophie, Chitrit, Yvon, Boissinot, Christine, Yéra, Hélène, Anselem, Olivia, Tsatsaris, Vassilis, Sénat, Marie-Victoire, Fuchs, Florent, Angoulvant, Adela, Muszynski, Charles, Totet, Anne, Noël, Catherine, Bidat, Laurent, Barjat, Tiphaine, Flori, Pierre, Pelloux, Hervé, Brenier-Pinchart, Marie-Pierre, Thong-Vanh, Catherine, Floch, Corinne, Carbillon, Lionel, Lachassine, Eric, Ricbourg, Aude, Paris, Luc, Dommergues, Marc, Rousseau, Thierry, Dalle, Frederic, Dardé, Marie Laure, Aubard, Véronique, Olivier, Camille, Verspyk, Eric, Favennec, Loic
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2018
• Subjects: pregnancy; prenatal diagnosis; pyrimethamine-sulfadiazine; spiramycin; tolerance; toxoplasmosis; prenatal diagnosis; pyrimethamine-sulfadiazine; toxoplasmosis; tolerance; pregnancy; spiramycin
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2018.05.031

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