Prenatal diagnosis and treatment of congenital Toxoplasma gondii infections: an experimental study in rhesus monkeys.
The efficacy of treatment in fetuses in whom congenital Toxoplasma gondii infection has ben established has been investigated using rhesus monkeys as a model for humans. A polymerase chain reaction has been developed for the detection of Toxoplasma gondii. Using this polymerase chain reaction congenital infection can be established within 2 days of receiving an amniotic fluid sample. The polymerase chain reaction has subsequently been used to monitor the effect of treatment on fetal infection. The results show that early treatment with the combination of pyrimethamine and sulfadiazine was clearly effective in reducing the number of parasites in the infected fetus. The parasite was no longer detectable in the amniotic fluid 10 to 13 days after treatment was started. Spiramycin, on the other hand, has to be administered for at least 3 weeks to achieve the same effect. Moreover, pharmacokinetic studies revealed that spiramycin does not reach the brain. Pyrimethamine and sulfadiazine are able to pass the blood-brain barrier. Pyrimethamine appears to accumulate in the brain tissue and reaches concentrations which are also effective in vitro.
Schoondermark-van de Ven
E M
EM
Department of Medical Microbiology, Academic Hospital St. Radboud Nijmegen, The Netherlands.
Melchers
W J
WJ
Galama
J M
JM
Meuwissen
J H
JH
Eskes
T K
TK
D000653:Amniotic Fluid / Q000469:parasitology*; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D016054:DNA, Protozoan / Q000032:analysis / Q000235:genetics; D004275:DNA, Ribosomal / Q000032:analysis / Q000235:genetics; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000188:drug therapy / Q000469:parasitology; D008253:Macaca mulatta; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000175:diagnosis* / Q000188:drug therapy; D011296:Prenatal Diagnosis; D011446:Prospective Studies; D011739:Pyrimethamine / Q000008:administration & dosage / Q000627:therapeutic use; D013411:Sulfadiazine / Q000008:administration & dosage / Q000627:therapeutic use; D014122:Toxoplasma / Q000235:genetics / Q000302:isolation & purification; D014124:Toxoplasmosis, Animal / Q000151:congenital / Q000175:diagnosis* / Q000188:drug therapy / Q000196:embryology
D000890:Anti-Infective Agents; D016054:DNA, Protozoan; D004275:DNA, Ribosomal; D013411:Sulfadiazine; D011739:Pyrimethamine