Abstract
BackgroundDosing recommendations for the treatment of pregnancy-acquired toxoplasmosis are empirical and widely based on experimental data. There are no pharmacological data on pregnant women with acute Toxoplasma gondii infection under treatment with pyrimethamine (PY) and sulfadiazine (SA) and our study intends to tighten this gap.MethodsIn this retrospective case–control study, we included 89 pregnant women with primary Toxoplasma infection (PT) treated with PY (50 mg first dose, then 25 mg/day), SA (50 mg/kg of body weight/day), and folinic acid (10–15 mg per week). These were compared to a group of 17 women with acute ocular toxoplasmosis (OT) treated with an initial PY dose of 75 mg, thereafter 25 mg twice a day but on the same SA and folinic acid regimen. The exact interval between drug intake and blood sampling and co-medication had not been recorded. Plasma levels of PY and SA were determined 14 ± 4 days after treatment initiation using liquid chromatography–mass spectrometry and compared using the Mann–Whitney U test at a p < 0.05 level.ResultsIn 23 PT patients (26%), SA levels were below 20 mg/l. Fifteen of these 23 patients (17% of all patients) in parallel presented with PY levels below 700 µg/l. Both drug concentrations differed remarkably between individuals and groups (PY: PT median 810 µg/l, 95% CI for the median [745; 917] vs. OT 1230 µg/l [780; 1890], p = 0.006; SA: PT 46.2 mg/l [39.9; 54.4] vs. OT 70.4 mg/l [52.4; 89], p = 0.015) despite an identical SA dosing scheme.ConclusionsSA plasma concentrations were found in the median 34% lower in pregnant women with PT compared to OT patients and fell below a lower reference value of 50 mg/l in a substantial portion of PT patients. The interindividual variability of plasma concentrations in combination with systematically lower drug levels and possibly a lower compliance in pregnant women may thus account for a still not yet supportable transmission risk. Systematic drug-level testing in PT under PY/SA treatment deserves to be considered.
Highlights
Dosing recommendations for the treatment of pregnancy-acquired toxoplasmosis are empirical and widely based on experimental data
By grouping ocular toxoplasmosis (OT) samples according to the time of sampling (Group 1: 10–12 days, Group 2: 13–15 days, and Group 3: 16–18 days after treatment initiation), we observed no difference in plasma concentrations, indicating that both PY and SA concentrations had already reached a steady-state by the time of blood sampling (Fig. 1a, b)
By comparing the median values of both drugs for both groups, we found that the PY levels (Fig. 2a) were 34% higher in women with OT (1230 [780; 1890] μg/l) compared to those in pregnant women with primary Toxoplasma infection (PT) (810 [745; 917] μg/l; p = 0.006), which is in line with the difference in dosing (50 mg/day vs. 25 mg/day)
Summary
Dosing recommendations for the treatment of pregnancy-acquired toxoplasmosis are empirical and widely based on experimental data. There are no pharmacological data on pregnant women with acute Toxoplasma gondii infection under treatment with pyrimethamine (PY) and sulfadiazine (SA) and our study intends to tighten this gap. Maternal infection with Toxoplasma gondii during pregnancy may lead to transmission of the infection to the foetus. Reiter‐Owona et al Eur J Med Res (2020) 25:59 may be completely asymptomatic (with subclinical infection) or develop severe clinical symptoms, such as hydrocephalus, retinochoroiditis, or intracranial calcifications. In children with subclinical infection, the parasite can reactivate later in life and induce retinochoroiditis (ocular toxoplasmosis [OT]). To reduce the risk of transmission and congenital toxoplasmosis, early treatment of newly infected pregnant women is justified [1,2,3,4,5]. Observational studies have demonstrated an association of prenatal treatment with the prevention of symptomatic disease in infants [6]
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