In utero Treatment of Toxoplasmic Fetopathy with the Combination Pyrimethamine-Sulfadiazine

Couvreur, J; Thulliez, P.; Daffos, F.; aufrant, Ch.; Bompard, Y; Gesquière, A; Desmonts, G

doi:10.1159/000263746

Cited by 73 publications

(48 citation statements)

References 6 publications

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“…In a study of 542 pregnancies in which spiramycin was given to women who seroconverted during pregnancy (388 women given treatment and 154 without treatment) the percentage of children without prenatal infection increased from 39 to 77%, and the percentage of children with severe congenital disease or intrauterine death decreased from 11 to 3% [214]. If transmission to the foetus can be documented in utero (by polymerase chain reaction (PCR) or other techniques [33]) the administration of pyrimethamine and sulfadiazine to the mother can treat the infection in utero and further decrease the severity of symptoms in infected children [216,217].…”

Section: Congenital Toxoplasmosismentioning

confidence: 99%

“…Women who seroconvert during pregnancy should be treated with spiramycin, and if transmission to the foetus is documented, they should be treated with pyrimethamine and sulfadiazine. Once born, all children of mothers who seroconverted during pregnancy should be evaluated for congenital toxoplasmosis and treated if infection is still evident [214,[217][218][219][223][224][225][226][227][228][229][230][231]]. …”

Section: Congenital Toxoplasmosismentioning

confidence: 99%

“…In some cases serial serological testing, serological tests for IgA antibodies to T. gondii, or immunoblots may be needed to clarify if congenital transmission has occurred [33,237]. Treatment of children identified with prenatal T. gondii infections has been demonstrated to decrease adverse sequelae [214,[217][218][219][223][224][225][226][227][228][229][230][231]. Therefore, neonatal screening programmes for T. gondii infection should result in a net health care cost savings.…”

Section: Congenital Toxoplasmosismentioning

confidence: 99%

See 2 more Smart Citations

Toxoplasma gondii: from animals to humans

Tenter

Heckeroth

Weiss

2000

International Journal for Parasitology

3,011

2,476

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Toxoplasmosis is one of the more common parasitic zoonoses world-wide. Its causative agent, Toxoplasma gondii, is a facultatively heteroxenous, polyxenous protozoon that has developed several potential routes of transmission within and between different host species. If first contracted during pregnancy, T. gondii may be transmitted vertically by tachyzoites that are passed to the foetus via the placenta. Horizontal transmission of T. gondii may involve three lifecycle stages, i.e. ingesting infectious oocysts from the environment or ingesting tissue cysts or tachyzoites which are contained in meat or primary offal (viscera) of many different animals. Transmission may also occur via tachyzoites contained in blood products, tissue transplants, or unpasteurised milk. However, it is not known which of these routes is more important epidemiologically. In the past, the consumption of raw or undercooked meat, in particular of pigs and sheep, has been regarded as a major route of transmission to humans. However, recent studies showed that the prevalence of T. gondii in meat-producing animals decreased considerably over the past 20 years in areas with intensive farm management. For example, in several countries of the European Union prevalences of T. gondii in fattening pigs are now <1%. Considering these data it is unlikely that pork is still a major source of infection for humans in these countries. However, it is likely that the major routes of transmission are different in human populations with differences in culture and eating habits. In the Americas, recent outbreaks of acute toxoplasmosis in humans have been associated with oocyst contamination of the environment. Therefore, future epidemiological studies on T. gondii infections should consider the role of oocysts as potential sources of infection for humans, and methods to monitor these are currently being developed. This review presents recent epidemiological data on T. gondii, hypotheses on the major routes of transmission to humans in different populations, and preventive measures that may reduce the risk of contracting a primary infection during pregnancy.

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Section: Congenital Toxoplasmosismentioning

confidence: 99%

Section: Congenital Toxoplasmosismentioning

confidence: 99%

Section: Congenital Toxoplasmosismentioning

confidence: 99%

See 1 more Smart Citation

Toxoplasma gondii: from animals to humans

Tenter

Heckeroth

Weiss

2000

International Journal for Parasitology

3,011

2,476

View full text Add to dashboard Cite

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“…Studies on the effectiveness of pyrimethamine and sulfadiazine for the treatment of congenital T. gondii infections in humans, however, have been scarce. Those studies that have been reported in the literature are from France (10,11,20). Those studies described the effectiveness of treatment with pyrimethamine and sulfadiazine after fetal infection had been proven.…”

mentioning

confidence: 99%

Study of treatment of congenital Toxoplasma gondii infection in rhesus monkeys with pyrimethamine and sulfadiazine

Ven

Galama

Vree

et al. 1995

Antimicrob Agents Chemother

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The efficacy of the combination of pyrimethamine and sulfadiazine for the treatment of congenital Toxoplasma gondii infection in rhesus monkeys was studied. The dosage regimen for pyrimethamine and sulfadiazine was established by pharmacokinetic studies in two monkeys. Those studies showed that the distributions of both drugs followed a one-compartment model. The serum elimination half-lives were found to be 5.2 h for sulfadiazine and 44.4 h for pyrimethamine. Sulfadiazine reached a maximum concentration in serum of 58.7 g/ml, whereas a maximum concentration in serum of 0.22 g/ml was found for pyrimethamine. Ten monkeys were infected intravenously with T. gondii at day 90 of pregnancy, which is comparable to the second trimester of organogenetic development in humans. Treatment was administered to six monkeys, in whose fetuses infection was diagnosed antenatally. From the moment that fetal infection was proven, the monkeys were treated throughout pregnancy with 1 mg of pyrimethamine per kg of body weight per day and 50 mg of sulfadiazine per kg of body weight per day orally. The therapy was supplemented with 3.5 mg of folinic acid once a week. No toxic side effects were found with this drug regimen. The parasite was no longer detectable in the next consecutive amniotic fluid sample, taken 10 to 13 days after treatment was started. Furthermore, T. gondii was also not found in the neonate at birth. The parasite was still present at birth in three of four untreated fetuses that served as controls. Both drugs crossed the placenta very well. Concentrations in fetal serum varied from 0.05 to 0.14 g/ml for pyrimethamine and from 1.0 to 5.4 g/ml for sulfadiazine. In addition, pyrimethamine was found to accumulate in the brain tissue, with concentrations being three to four times higher than the corresponding concentrations in serum. Thirty percent of the sulfadiazine was found to reach the brain tissue when compared with the corresponding serum drug concentration. When administered early after the onset of infection, the combination of pyrimethamine and sulfadiazine was clearly effective in reducing the number of parasites in the fetus to undetectable levels.

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“…The combination of pyrimethamine and sulphadiazine is highly active against T. gondii and is the most widely used treatment for prenatal infection (Hohlfeld et al 1989, Couvreur et al 1993, Villena et al 1998. Moreover, this combination is assumed to have a higher potential than spiramycine in reducing the risk of clinical manifestations in infected children (Foulon et al 1999, SYROCOT Study Group 2007).…”

Section: What Are the Current Practices?mentioning

confidence: 99%