Eine Infektion mit dem Parasiten Toxoplasma gondii führt bei Schwangeren nur selten zu Symptomen. 70-80% der Schwangeren sind nicht vor Erstinfektion geschützt. Die orale Aufnahme von Oozysten aus der Umwelt (z.B. durch ungewaschenes Obst und Gemüse) oder der Verzehr von nicht ausreichend erhitzem Fleisch kann zur Erstinfektion in der Schwangerschaft führen. Ohne Therapie, steigt die Transmissionrate von 25% im 1. Trimester, über 54% im 2. Trimester auf 65% im 3. Trimester, an. Gegenläufig nimmt die Schädigungsrate mit zunehmendem Gestationsalter ab und liegt im 1. Trimester bei >85%, im 2. Trimester bei 80-20% und im 3. Trimester bei <20% (aus Remington & Klein. Toxoplasmosis. In Infectious diseases of the fetus an newborn infant 7th edition, pp 918-1041, Elsevier Sauders, 2011). Reinfektionen in Deutschland stellen bei Immunkompetenten kein Problem dar.
Wann sollte eine Toxoplasma-Diagnostik erfolgen?
Idealerweise sollte bereits vor einer gewünschten Schwangerschaft oder aber möglichst früh nach Feststellung der Schwangerschaft eine Immunstatusbestimmung erfolgen. Hierfür sollten IgG- und am besten auch IgM-Antikörper (Ak) bestimmt werden. Bei fehlender Immunität sind regelmäßige serologische Verlaufskontrollen im Abstand von 8 (-10 ) Wochen als sogenanntes Screeningintervall notwendig. Ggf. kann als Expositionsprophylaxe eine gezielte Hygieneberatung mit Meidung bestimmter Lebensmittel und Einhaltung bestimmter Verhaltensmaßnahmen durchgeführt werden. Allerdings ist der Nutzen dieser Hygienemaßnahmen nicht durch prospektive Studien belegt.
Untersuchungsmaterial: Vollblut 2-3 ml
Hygienemaßnahmen
Fleisch gut durchbraten, keine Rohmilch (-produkte) verzehren
Obst, Gemüse und Salat immer gut waschen
Händehygiene bei Kontakt zu Katzen
Katzentoilette von anderen Personen reinigen lassen
Handschuhe bei der Gartenarbeit
Diagnostik bei positivem Antikörper-Nachweis
a) IgG-Ak positiv und IgM-Aknegativ Schutz vor Erstinfektion vorhanden; keine weiteren serologischen Kontrollen notwendig.
b) IgG-Ak negativ und IgM-Ak positiv: Verdacht auf akute Infektion; weitere zusätzliche IgM-Teste und serologische Verlaufskontrollen erforderlich. Ggf. Therapie entsprechend Gestationsalter durchführen. Ultraschallkontrollen, DEGUM-Stufe II/III, in regelmäßigen Abständen ab SSW 18+0 bis 21+6 empfohlen.
c) IgG-Ak positiv und IgM-Akpositiv Bestimmung der IgG-Avidität. Im Falle hoheAvidität ist nachweisbar (ggf. Bestätigung in Verlaufskontrolle): Frühere Infektion, i.d.R. mehr als 3 Monate zurückliegend, sofern Testung im 1. Trimester. Keine Therapie erforderlich.
d) IgG-Akpositiv und IgM-Akpositiv Bestimmung der IgG-Avidität. Im Falle niedrige Avidität ist nachweisbar: Verdacht auf akute Infektion; Einsatz weiterer Zusatzteste z.B. Line-Blot, IgA-Ak-Bestimmung und serologische Verlaufskontrollen notwendig. Therapie entsprechend Gestationsalter durchführen. Ultraschallkontrollen, DEGUM-Stufe II/III, in regelmäßigen Abständen ab SSW 18+0 bis 21+6 empfohlen.
Diagnostik bei auffälligem Ultraschallbefund
Zunächst IgG- und IgM-Ak-Bestimmung notwendig. Bei positivem Antikörper-Nachweis sind weitere Zusatzteste erforderlich (siehe oben). Ggf. invasive Pränatale Diagnostik anbieten. Ggf. Therapie erforderlich.
Ab 15+0 SSW: Kombinationstherapie mit Pyrimethamin, Sulfadiazin und Calcium-Folinat
Therapiedauer der Kombinationstherapie mindestens 4 Wochen
Was muss unter Therapie beachtet werden?
Unter Kombinationstherapie: Folinsäure sollte verabreicht werden. Folsäurepräparate für die Dauer der Therapie absetzen! Wöchentliche Kontrollen von großem Blutbild und Leberwerten erforderlich. Bestimmung der Medikamentenspiegel (Pyrimethamin und Sulfadiazin) am 8.-10. Behandlungstag wird empfohlen.
Untersuchungsmaterial: EDTA-Blut 500 µl, Vollblut 2-3 ml
Nutzen der antenatalen Therapie
Aus Beobachtungsstudien geht hervor: Die Therapie senkt das intrauterine Transmissions- und Schädigungsrisiko, insbesondere das Risiko für schwere neurologische Schäden. Dabei ist ein frühzeitiger Therapiebeginn für die Effektivität der Therapie wichtig. Insofern sind möglichst kurze Screeningintervalle <6-8 Wochen bei seronegativen Schwangeren anzustreben.
Welche Untersuchungen sollten beim Neugeborenen/Säugling erfolgen?
Bei Geburt:
Schädelsonographie und Augenhintergrund
Serologische Kontrolle der IgG-/IgM-/IgA-Ak, Immunoblot Mutter/Kind-Profil
Untersuchungsmaterial: Nabelschnur-Vollblut, Nabelschnur-Heparinblut jeweils 2-3 ml; mütterliches Vollblut und Heparinblut jeweils 2-3 ml; ggf. bei DNA-Nachweis mittels PCR – EDTA-Blut und Liquor jeweils 500 µl, Plazenta: 2 walnussgroße Stücke nativ ohne Zusatz
Innerhalb des ersten Lebensjahres:
Regelmäßige serologische Verlaufskontrollen IgG-/IgM-/IgA-Ak, bis passive mütterliche Ak nicht mehr nachweisbar sind
Therapie der kongenitalen Toxoplasma-Infektion
Untersuchungsmaterial: Vollblut 1 ml, Heparinblut 1 ml
Verschiedene Therapieschemata in Abhängigkeit der klinischen Symptome und/oder Nachweis einer eigenen kindlichen Immunantwort (z.B. IgM-/IgA-Ak und/oder Mutter/Kind Profil positiv, zelluläre Immunantwort positiv). Standardtherapie: Pyrimethamin, Sulfadiazin, Ca-Folinat und ggf. Kortikosteroide bei akuten Entzündungszeichen des ZNS bis zum Abklingen der Entzündung (siehe DGPI, aktuelle Auflage).
! Meldepflicht nach IfSG. Nicht namentlich, bei kongenitaler Toxoplasmasmose direkt an das RKI.
@article{Schneider.2023b,
title = {Toxoplasma gondii Infection in Pregnancy - Recommendations of the Working Group on Obstetrics and Prenatal Medicine (AGG - Section on Maternal Disorders)},
author = {MO Schneider and F Faschingbauer and KO Kagan and U Gro\ss and M Enders and S Kehl},
doi = {10.1055/a-2111-7394},
year = {2023},
date = {2023-12-01},
urldate = {2023-12-01},
journal = {Geburtshilfe und Frauenheilkunde},
volume = {83},
number = {12},
pages = {1431\textendash1445},
abstract = {Aim The AGG (Working Group for Obstetrics and Prenatal Diagnostics, Section Maternal Diseases) has issued these recommendations to improve the detection and management of Toxoplasma gondii infection in pregnancy. Methods Members of the Task Force developed the recommendations and statements presented here using recently published literature. The recommendations were adopted after a consensus process by members of the working group. Recommendations This article focuses on the epidemiology and pathophysiology of Toxoplasma gondii infection in pregnancy and includes recommendations for maternal and fetal diagnosis, transmission prophylaxis, therapy, prevention, screening, and peripartum management.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Aim The AGG (Working Group for Obstetrics and Prenatal Diagnostics, Section Maternal Diseases) has issued these recommendations to improve the detection and management of Toxoplasma gondii infection in pregnancy. Methods Members of the Task Force developed the recommendations and statements presented here using recently published literature. The recommendations were adopted after a consensus process by members of the working group. Recommendations This article focuses on the epidemiology and pathophysiology of Toxoplasma gondii infection in pregnancy and includes recommendations for maternal and fetal diagnosis, transmission prophylaxis, therapy, prevention, screening, and peripartum management.
@inbook{Enders.2023,
title = {Infektionen in der Schwangerschaft und bei Geburt},
author = {M Enders and KO Kagan},
editor = {C von Kaisenberg and P Klaritsch and I H\"{o}sli-Krais},
doi = {10.1007/978-3-662-44369-9_64-1},
year = {2023},
date = {2023-09-29},
urldate = {2023-09-29},
booktitle = {Die Geburtshilfe},
pages = {1\textendash48},
publisher = {Springer Berlin Heidelberg},
series = {Springer Reference Medizin},
keywords = {},
pubstate = {published},
tppubtype = {inbook}
}
Groß, U; Enders, M; Garweg, J G; Reiter-Owona, I; Schrod, L
Toxoplasmose in der Schwangerschaft und beim Neugeborenen Artikel
In: pädiatrische praxis, Bd. 87, Nr. 2, S. 187–198, 2017.
@article{Gro.2017,
title = {Toxoplasmose in der Schwangerschaft und beim Neugeborenen},
author = {U Gro\ss and M Enders and J G Garweg and I Reiter-Owona and L Schrod},
year = {2017},
date = {2017-01-01},
journal = {p\"{a}diatrische praxis},
volume = {87},
number = {2},
pages = {187--198},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In: Berg, C (Hrsg.): Fetale Therapie, Bd. 1, S. 164–167, Walter de Gruyter, Berlin/Boston, 2017, ISBN: 978-3-11-043841-3.
@incollection{Wagner.2017,
title = {Toxoplasmose in der Schwangerschaft},
author = {P Wagner and K O Kagan and M Enders},
editor = {C Berg},
isbn = {978-3-11-043841-3},
year = {2017},
date = {2017-01-01},
booktitle = {Fetale Therapie},
volume = {1},
pages = {164--167},
publisher = {Walter de Gruyter},
address = {Berlin/Boston},
keywords = {},
pubstate = {published},
tppubtype = {incollection}
}
Enders, M; Reiter-Owona, I; Knotek, F; Rilling, V; Krczal, D; Enders, G
Seroepidemiology of Toxoplasma gondii infection in pregnant women from Southern and North-Western Germany and bone-marrow donors: Abstract Buchabschnitt
In: für Chemotherapie e.V., Paul-Ehrlich-Gesellschaft (Hrsg.): 22. Jahrestagung der Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. Abstracts - Reihenfolge nach Programm, S. 166, 2010.
@incollection{Enders.2010,
title = {Seroepidemiology of Toxoplasma gondii infection in pregnant women from Southern and North-Western Germany and bone-marrow donors: Abstract},
author = {M Enders and I Reiter-Owona and F Knotek and V Rilling and D Krczal and G Enders},
editor = {{Paul-Ehrlich-Gesellschaft f\"{u}r Chemotherapie e.V.},
year = {2010},
date = {2010-01-01},
booktitle = {22. Jahrestagung der Paul-Ehrlich-Gesellschaft f\"{u}r Chemotherapie e.V. Abstracts - Reihenfolge nach Programm},
pages = {166},
keywords = {},
pubstate = {published},
tppubtype = {incollection}
}
Toxoplasmosediagnostik in der Schwangerschaft Artikel
In: Geburtshilfe und Frauenheilkunde, Bd. 68, Nr. 10, S. 1028–1030, 2008, ISSN: 0016-5751.
@article{Enders.2008b,
title = {Toxoplasmosediagnostik in der Schwangerschaft},
author = {M Enders and D Krczal and V Rilling and G Enders},
issn = {0016-5751},
year = {2008},
date = {2008-01-01},
journal = {Geburtshilfe und Frauenheilkunde},
volume = {68},
number = {10},
pages = {1028--1030},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
@article{Pfrepper.2005b,
title = {Seroreactivity to and avidity for recombinant antigens in toxoplasmosis},
author = {K I Pfrepper and G Enders and M Gohl and D Krczal and H Hlobil and D Wassenberg and E Soutschek},
issn = {1071-412X},
year = {2005},
date = {2005-01-01},
volume = {12},
number = {8},
pages = {977--982},
abstract = {To improve serodiagnostic methods for the diagnosis of acute toxoplasmosis during pregnancy, a new test system has been developed and evaluated based on the use of recombinant antigens. Five recombinant Toxoplasma gondii antigens (ROP1, MAG1, SAG1, GRA7, and GRA8) were cloned in Escherichia coli, purified, and applied directly onto nitrocellulose membranes in a line assay (recomLine Toxoplasma). A panel of 102 sera from 25 pregnant women with supposed recent toxoplasmosis and from two symptomatic children was compared to a panel of 71 sera from individuals with past infection. Both panels were analyzed using a recombinant line assay for immunoglobulin G (IgG), IgM, and IgA antibodies and a reference enzyme-linked immunosorbent assay. Within the IgM-positive samples, antibodies against ROP1 were predominant regardless of the infection state. In IgG analysis a characteristic antibody pattern was found for very recent infections. This pattern changed to a different one during the time course of infection: antibodies against GRA7 and GRA8 were characteristic for very early IgG, whereas antibodies against SAG1 and MAG1 appeared significantly later. These results were further confirmed by determination of the IgG antibody avidity for every single recombinant antigen. In the time course of infection, IgG antibodies against the early recognized antigens matured significantly earlier than those directed against the later antigens did. The IgA patterns did not give reliable information about the infection time points. The data revealed that the recombinant line assay provides valuable information on the actual state of infection, especially during the early infection time points},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
To improve serodiagnostic methods for the diagnosis of acute toxoplasmosis during pregnancy, a new test system has been developed and evaluated based on the use of recombinant antigens. Five recombinant Toxoplasma gondii antigens (ROP1, MAG1, SAG1, GRA7, and GRA8) were cloned in Escherichia coli, purified, and applied directly onto nitrocellulose membranes in a line assay (recomLine Toxoplasma). A panel of 102 sera from 25 pregnant women with supposed recent toxoplasmosis and from two symptomatic children was compared to a panel of 71 sera from individuals with past infection. Both panels were analyzed using a recombinant line assay for immunoglobulin G (IgG), IgM, and IgA antibodies and a reference enzyme-linked immunosorbent assay. Within the IgM-positive samples, antibodies against ROP1 were predominant regardless of the infection state. In IgG analysis a characteristic antibody pattern was found for very recent infections. This pattern changed to a different one during the time course of infection: antibodies against GRA7 and GRA8 were characteristic for very early IgG, whereas antibodies against SAG1 and MAG1 appeared significantly later. These results were further confirmed by determination of the IgG antibody avidity for every single recombinant antigen. In the time course of infection, IgG antibodies against the early recognized antigens matured significantly earlier than those directed against the later antigens did. The IgA patterns did not give reliable information about the infection time points. The data revealed that the recombinant line assay provides valuable information on the actual state of infection, especially during the early infection time points
Rilling, V; Dietz, K; Krczal, D; Knotek, F; Enders, G
Evaluation of a commercial IgG/IgM Western Blot assay for early postnatal diagnosis of congenital toxoplasmosis Artikel
In: European journal of clinical microbiology & infectious diseases, Bd. 22, S. 174–180, 2003, ISSN: 0934-9723.
@article{Rilling.2003,
title = {Evaluation of a commercial IgG/IgM Western Blot assay for early postnatal diagnosis of congenital toxoplasmosis},
author = {V Rilling and K Dietz and D Krczal and F Knotek and G Enders},
issn = {0934-9723},
year = {2003},
date = {2003-01-01},
journal = {European journal of clinical microbiology \& infectious diseases},
volume = {22},
pages = {174--180},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Pinon, J M; Dumon, H; Chemla, C; Franck, J; Petersen, E; Lebech, M; Zufferey, J; Bessieres, M H; Marty, P; Holliman, R; Johnson, J; Luyasu, V; Lecolier, B; Guy, E; Joynson, D H M; Decoster, A; Enders, G; Pelloux, H; Candolfi, E
Strategy for diagnosis of congenital toxoplasmosis: Evaluation of methods comparing mothers and newborns and standard methods for postnatal detection of immunoglobulin G, M, and A antibodies Artikel
In: Journal of clinical microbiology, Bd. 39, Nr. 6, S. 2267–2271, 2001, ISSN: 0095-1137.
@article{Pinon.2001,
title = {Strategy for diagnosis of congenital toxoplasmosis: Evaluation of methods comparing mothers and newborns and standard methods for postnatal detection of immunoglobulin G, M, and A antibodies},
author = {J M Pinon and H Dumon and C Chemla and J Franck and E Petersen and M Lebech and J Zufferey and M H Bessieres and P Marty and R Holliman and J Johnson and V Luyasu and B Lecolier and E Guy and D H M Joynson and A Decoster and G Enders and H Pelloux and E Candolfi},
issn = {0095-1137},
year = {2001},
date = {2001-01-01},
journal = {Journal of clinical microbiology},
volume = {39},
number = {6},
pages = {2267--2271},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Roberts, A; Hedman, K; Luyasu, V; Zufferey, J; Bessi`ere, M -H; Blatz, R -M; Candolfi, E; Decoster, A; Enders, G; Gross, U; Guy, E; Hayde, M; Ho-Yen, D; Johnson, J; L´colier, B; Naessens, A; Pelloux, H; Thulliez, P; Petersen, E
Multicenter Evaluation of Strategies for Serodiagnosis of Primary Infection with Toxoplasma gondii Artikel
In: European journal of clinical microbiology & infectious diseases, Bd. 20, S. 467–474, 2001, ISSN: 0934-9723.
@article{Roberts.2001,
title = {Multicenter Evaluation of Strategies for Serodiagnosis of Primary Infection with Toxoplasma gondii},
author = {A Roberts and K Hedman and V Luyasu and J Zufferey and M -H Bessi`ere and R -M Blatz and E Candolfi and A Decoster and G Enders and U Gross and E Guy and M Hayde and D Ho-Yen and J Johnson and B L´colier and A Naessens and H Pelloux and P Thulliez and E Petersen},
issn = {0934-9723},
year = {2001},
date = {2001-01-01},
journal = {European journal of clinical microbiology \& infectious diseases},
volume = {20},
pages = {467--474},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Gross, U; Lüder, C G K; Hendgen, V; Heeg, C; Sauer, I; Weidner, A; Krczal, D; Enders, G
Comparative Immunoglobulin G Antibody Profiles Between Mother and Child (CGMC Test) for Early Diagnosis of Congenital Toxoplasmosis Artikel
In: Journal of clinical microbiology, Bd. 38, Nr. 10, S. 3619–3622, 2000, ISSN: 0095-1137.
@article{Gross.2000,
title = {Comparative Immunoglobulin G Antibody Profiles Between Mother and Child (CGMC Test) for Early Diagnosis of Congenital Toxoplasmosis},
author = {U Gross and C G K L\"{u}der and V Hendgen and C Heeg and I Sauer and A Weidner and D Krczal and G Enders},
issn = {0095-1137},
year = {2000},
date = {2000-01-01},
journal = {Journal of clinical microbiology},
volume = {38},
number = {10},
pages = {3619--3622},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
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