Der Erreger der Syphilis (auch Lues genannt) ist ein gramnegatives Bakterium, die Spirochäte Treponema pallidum (subspecies pallidum). Der Mensch stellt das einzige Reservoir des Erregers dar. Die Syphilis ist eine Systemerkrankung und verläuft in verschiedenen Stadien. Sie wird in eine Früh- (primäre, sekundäre, frühlatente) und eine Spätform (spätlatente, gummatöse, kardiovaskuläre, meningovaskuläre und neuroparenchymatöse Syphilis) unterteilt. Die Zahl der gemeldeten Syphilisfälle bei Erwachsenen ist von 2010 bis 2017 stetig angestiegen. Im Jahr 2018 wurde erstmals ein leichter Rückgang der Meldezahlen auf 7332 Fälle beobachtet. Im Gegenzug liegt die Zahl der bei Neugeborenen bzw. Kindern diagnostizierten Fälle von konnataler Syphilis, seit Einführung des Infektionsschutzgesetzes 2001, bei ein bis 6 Fällen/Jahr (RKI, Infektionsepidemiologisches Jahrbuch für 2018). Das klinische Bild einer Syphilis unterscheidet sich bei Schwangeren nicht von dem bei nicht schwangeren Frauen.
Transmissionsrisiko in der Schwangerschaft
Eine diaplazentare Übertragung kann zu jedem Zeitpunkt der Gravidität erfolgen, gehäuft tritt sie nach der 16./18. SSW auf. Die Infektion des Feten kann in jedem Stadium, auch in der späten Latenz der nicht oder ungenügend behandelten Mutter, erfolgen. Bei unbehandelter Syphilis wurden nachfolgende Übertragungsraten beschrieben: Primäre Syphilis 29 %, sekundäre Syphilis 59 %, frühlatente Syphilis 50 % und spätes Latenzstadium 13 %. Ohne Therapie bzw. bei unzureichender Therapie besteht ein erhöhtes Risiko für Spontanaborte, Totgeburten, Frühgeburtlichkeit und Hydrops fetalis sowie erhöhte neonatale Sterblichkeit in Abhängigkeit vom mütterlichen Erkrankungsstadium. Ebenso ist eine Infektion des Kindes bei der Passage der Geburtswege möglich.
Wann sollte die Diagnostik in der Schwangerschaft erfolgen?
Im Rahmen der Mutterschaftsvorsorge (MuVo) sollte jede Schwangere möglichst früh serologisch auf Syphilis gescreent werden. Die sog. Lues-Suchreaktion (LSR) kann z.B. mit dem Treponema-pallidum-Partikelaggluti-nationstest (TPPA) oder alternativ einem Immunoassay erfolgen. Bei Schwangeren mit Risikoanamnese (Risikokontakt, Prostitution, Drogenmissbrauch, Einwanderung aus Gebieten mit hoher Inzidenz etc.) sollte diese LSR zu Beginn des 3. Trimenon zur Vermeidung der kongenitalen Syphilis wiederholt werden.
Diagnostik bei positiver LSR
Bei positiver LSR müssen im Anschluss ein Bestätigungstest und ggf. eine erweiterte Diagnostik durchgeführt werden, um eine behandlungsbedürftige Syphilis auszuschließen bzw. zu bestätigen. Diese sind spezifische IgG-/IgM-Ak-Teste (z.B. Fluoreszenz-Treponema-pallidum-Antikörper-Absorption = FTA-Abs.) und ein nicht treponemenspezifischer Test zum Nachweis von Cardiolipin-Ak (z.B. Veneral-Disease-Research-Laboratory-Test = VDRL-Test). Wobei auch ein negativer IgM-Befund eine Therapiebedürftigkeit nicht ausschließt. Zudem ist die Erhebung der Anamnese ein wichtiger Bestandteil für die Beurteilung der serologischen Befunde im Hinblick auf die Notwendigkeit einer Therapie. Bei Erstdiagnose in der Schwangerschaft, sollte auch ein HIV-Test durchgeführt werden, sofern noch nicht erfolgt. Ebenso werden Ultraschallkontrollen, DEGUM-Stufe II/III, in regelmäßigen Abständen ab SSW 18+0 bis 21+6 empfohlen.
Untersuchungsmaterial: Vollblut 2-3 ml
Diagnostik beim Feten
Bei auffälligem Ultraschall wie z.B. Hepatomegalie, Aszites, Hydrops fetalis sollte eine invasive Pränatale Diagnostik (DNA-Nachweis mittels PCR im Fruchtwasser und Fetalblut, IgM-Ak und VDRL-Bestimmung im Fetalblut) durchgeführt werden.
Einsatz von Benzathin Benzylpenicillin gilt weiterhin als Standardtherapie. Die Dosierung ist abhängig vom Infektionsstadium (siehe aktuelle AWMF-S2k-Leitlinie: Diagnostik und Therapie der Syphilis). Bei Penicillinallergie wird eine Desensibilisierung empfohlen.
Welche Untersuchungen sollten beim Neugeborenen/Säugling erfolgen?
Bei Geburt:
Bei positiver Syphilis-Serologie in der Schwangerschaft wird zur Kontrolle des Schwangerschaftsausgangs die Untersuchung von Nabelschnurblut und mütterlicher Blutprobe empfohlen. Ggf. ist zusätzlich noch eine Liquordiagnostik indiziert (siehe aktuelle Auflage DGPI).
TPPA-Titer
IgM-Ak-Bestimmung, beim Neugeborenen mit 2 unterschiedlichen Testarten
Cardiolipin-Ak-Nachweis
Ggf. T. pallidum-DNA-Nachweis (EDTA-Blut, Liquor)
Untersuchungsmaterial: Nabelschnur-Vollblut und mütterliches Vollblut jeweils 2-3 ml ggf. bei DNA-Nachweis mittels PCR – EDTA-Blut und Liquor jeweils 500 µl
Innerhalb des ersten Lebensjahres:
Regelmäßige serologische Verlaufskontrollen (TPPA, IgM-Ak, Cardiolipin-Ak) bis mütterliche Leihantikörper nicht mehr nachweisbar sind.
! Meldepflicht nach IfsG. Nicht namentlich, postnatale und kongenitale Syphilis ans RKI.
Auswahl unserer Publikationen/Beiträge zur Syphilis:
Härtel, C; Bialek, R; Enders, M; Gille, C; Handrick, W
Syphilis Buchkapitel mit eigenem Titel
In: Bialek, Ralf; Berner, Reinhard; Forster, Johannes; Härtel, Christoph; Heininger, Ulrich; Huppertz, Hans-Iko; Liese, Johannes G; Nadal, David; Simon, Arne (Hrsg.): DGPI-Handbuch, S. 764–769, Thieme, Stuttgart, 2018, ISBN: 978-3-13-240790-9.
@incollection{Hartel.2018,
title = {Syphilis},
author = {C H\"{a}rtel and R Bialek and M Enders and C Gille and W Handrick},
editor = {Ralf Bialek and Reinhard Berner and Johannes Forster and Christoph H\"{a}rtel and Ulrich Heininger and Hans-Iko Huppertz and Johannes G Liese and David Nadal and Arne Simon},
isbn = {978-3-13-240790-9},
year = {2018},
date = {2018-01-01},
booktitle = {DGPI-Handbuch},
pages = {764--769},
publisher = {Thieme},
address = {Stuttgart},
keywords = {},
pubstate = {published},
tppubtype = {incollection}
}
@article{Enders.2015,
title = {Reply to "Better method for evaluating a new laboratory test for syphilis"},
author = {M Enders and M Gleich and A M\"{u}hlbacher and T Sakuldamrongpanich and A Turhan and R Sert\"{o}z and S Semprini and V Sambri},
doi = {10.1128/CVI.00109-15},
issn = {1556-6811},
year = {2015},
date = {2015-01-01},
journal = {Clinical and vaccine immunology : CVI},
volume = {22},
number = {5},
pages = {607--608},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
@article{Enders.2015b,
title = {Performance evaluation of the Elecsys syphilis assay for the detection of total antibodies to Treponema pallidum},
author = {M Enders and A Hunjet and M Gleich and R Imdahl and A M\"{u}hlbacher and H Schennach and K Chaiwong and T Sakuldamrongpanich and A Turhan and R Sertoz and E Wolf and W Mayer and C Tao and L L Wang and S Semprini and V Sambri},
doi = {10.1128/CVI.00505-14.},
issn = {1556-6811},
year = {2015},
date = {2015-01-01},
journal = {Clinical and vaccine immunology : CVI},
volume = {22},
number = {1},
pages = {17--26},
abstract = {Syphilis is a health problem of increasing incidence in recent years that may have severe complications if not diagnosed and treated at an early stage. There are many diagnostic tests available for syphilis, but there is no gold standard, and diagnosis therefore usually relies upon a combination of tests. In this multicenter study, we evaluated the treponemal Elecsys syphilis assay for use in the diagnosis of syphilis in routine samples, i.e., when syphilis is suspected or during antenatal or blood donation screening. The sensitivity and specificity of the Elecsys syphilis assay were compared head to head with those of other treponemal assays used in routine clinical practice and were assessed in potentially cross-reactive samples from patients with Epstein-Barr virus, HIV, and Lyme disease. In a total of 8,063 syphilis-negative samples collected from routine diagnostic requests and blood donations, the Elecsys syphilis assay had a specificity of 99.88%. In 928 samples previously identified as syphilis positive, the sensitivity was 99.57 to 100% (the result is presented as a range depending on whether four initially indeterminate samples are included in the assessment). The specificity of the Elecsys syphilis assay in patients with other infections was 100%; no false-positive samples were identified},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Syphilis is a health problem of increasing incidence in recent years that may have severe complications if not diagnosed and treated at an early stage. There are many diagnostic tests available for syphilis, but there is no gold standard, and diagnosis therefore usually relies upon a combination of tests. In this multicenter study, we evaluated the treponemal Elecsys syphilis assay for use in the diagnosis of syphilis in routine samples, i.e., when syphilis is suspected or during antenatal or blood donation screening. The sensitivity and specificity of the Elecsys syphilis assay were compared head to head with those of other treponemal assays used in routine clinical practice and were assessed in potentially cross-reactive samples from patients with Epstein-Barr virus, HIV, and Lyme disease. In a total of 8,063 syphilis-negative samples collected from routine diagnostic requests and blood donations, the Elecsys syphilis assay had a specificity of 99.88%. In 928 samples previously identified as syphilis positive, the sensitivity was 99.57 to 100% (the result is presented as a range depending on whether four initially indeterminate samples are included in the assessment). The specificity of the Elecsys syphilis assay in patients with other infections was 100%; no false-positive samples were identified
In: Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG, 13 (5), S. 472–480, 2015, ISSN: 1610-0379.
@article{Schofer.2015,
title = {S2k guideline "Diagnosis and therapy of syphilis"--short version},
author = {H Sch\"{o}fer and T Weberschock and Wolfgang Br\"{a}uninger and Viviane Bremer and A Dreher and Martin Enders and S Esser and O Hamouda and H J Hagedorn and W Handrick and W Krause and C Mayr and D M\"{u}nstermann and A Nast and F Ochsendorf and U Petry and A Potthoff and H Prange and S Rieg and P Schneede and A Sing and J Weber and T A Wichelhaus and Norbert Brockmeyer},
doi = {10.1111/ddg.12574},
issn = {1610-0379},
year = {2015},
date = {2015-01-01},
journal = {Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG},
volume = {13},
number = {5},
pages = {472--480},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In: Friese, K; Mylonas, Ioannis; Schulze, A (Hrsg.): Infektionserkrankungen der Schwangeren und des Neugeborenen, 3 , S. 371–385, Springer-Verlag, Berlin, Heidelberg, 2013, ISBN: 13 978-3-540-78324-4.
@incollection{Enders.2013,
title = {Syphilis},
author = {M Enders and W Handrick},
editor = {K Friese and Ioannis Mylonas and A Schulze},
isbn = {13 978-3-540-78324-4},
year = {2013},
date = {2013-01-01},
booktitle = {Infektionserkrankungen der Schwangeren und des Neugeborenen},
volume = {3},
pages = {371--385},
publisher = {Springer-Verlag},
address = {Berlin, Heidelberg},
keywords = {},
pubstate = {published},
tppubtype = {incollection}
}
In: Berner, R; Bialek, R; Borte, M; Forster, J; Heininger, U; Liese, J G; Nadal, D; Roos, R; Scholz, H (Hrsg.): DGPI Handbuch, 6 , S. 521–526, Georg Thieme Verlag, Stuttgart, New York, 2013, ISBN: 978-3-13-144716-6.
@incollection{Enders.2013c,
title = {Syphilis},
author = {M Enders and W Handrick and H Schroten},
editor = {R Berner and R Bialek and M Borte and J Forster and U Heininger and J G Liese and D Nadal and R Roos and H Scholz},
isbn = {978-3-13-144716-6},
year = {2013},
date = {2013-01-01},
booktitle = {DGPI Handbuch},
volume = {6},
pages = {521--526},
publisher = {Georg Thieme Verlag},
address = {Stuttgart, New York},
keywords = {},
pubstate = {published},
tppubtype = {incollection}
}
In: pädiatrische praxis, 76 (3), S. 445–450, 2011.
@article{Handrick.2011,
title = {Konnatale Syphilis - es gibt sie noch!},
author = {W Handrick and Martin Enders and M Borte},
year = {2011},
date = {2011-01-01},
journal = {p\"{a}diatrische praxis},
volume = {76},
number = {3},
pages = {445--450},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
@article{Enders.2006b,
title = {[Congenital syphilis despite prenatal screening? An evaluation of 14 cases]},
author = {Martin Enders and I Knaub and M Gohl and I Pieper and C Bialek and H J Hagedorn},
issn = {0948-2393},
year = {2006},
date = {2006-01-01},
journal = {Zeitschrift fur Geburtshilfe und Neonatologie},
volume = {210},
number = {4},
pages = {141--146},
abstract = {BACKGROUND: Congenital syphilis (CS) can be effectively avoided by adequate treatment of the mother during pregnancy. Nevertheless, in recent years, the Robert Koch Institute has reported 6-8 of CS cases per year. The aim of this study was to investigate cases of CS with regard to obstetrical history and results of maternal syphilis serology during pregnancy and postpartum. PATIENTS AND METHODS: Between 1997 and 2001, a total of 14 cases of CS were diagnosed after birth in the Stuttgart laboratory. Information on clinical and serological data obtained during prenatal care and at birth had been provided by the treating gynaecologists and paediatricians. Furthermore, serum samples from 11 of the 14 mothers were investigated at the Stuttgart laboratory after birth and also retrospectively at the Herford laboratory. RESULTS: All mothers presented without clinical signs of syphilis. Delayed prenatal care was observed in 6 out of 14 cases. Eleven of the 14 mothers had a positive treponemal screening test. Treatment was initiated only in two of them. During pregnancy treponemal IgM and cardiolipin antibodies were detected in none of 9 and in 5 of 8 sera of untreated mothers, respectively. In contrast, maternal serum samples investigated after birth were all positive for cardiolipin antibodies and 7 of 10 serum samples were positive for TP IgM antibodies. CONCLUSIONS: Delayed or absent prenatal care and misinterpretation of syphilis serology (or laboratory failures) in the presence of latent syphilis are mostly responsible for the inadequate management of syphilis during pregnancy and thus the occurrence of CS},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Congenital syphilis (CS) can be effectively avoided by adequate treatment of the mother during pregnancy. Nevertheless, in recent years, the Robert Koch Institute has reported 6-8 of CS cases per year. The aim of this study was to investigate cases of CS with regard to obstetrical history and results of maternal syphilis serology during pregnancy and postpartum. PATIENTS AND METHODS: Between 1997 and 2001, a total of 14 cases of CS were diagnosed after birth in the Stuttgart laboratory. Information on clinical and serological data obtained during prenatal care and at birth had been provided by the treating gynaecologists and paediatricians. Furthermore, serum samples from 11 of the 14 mothers were investigated at the Stuttgart laboratory after birth and also retrospectively at the Herford laboratory. RESULTS: All mothers presented without clinical signs of syphilis. Delayed prenatal care was observed in 6 out of 14 cases. Eleven of the 14 mothers had a positive treponemal screening test. Treatment was initiated only in two of them. During pregnancy treponemal IgM and cardiolipin antibodies were detected in none of 9 and in 5 of 8 sera of untreated mothers, respectively. In contrast, maternal serum samples investigated after birth were all positive for cardiolipin antibodies and 7 of 10 serum samples were positive for TP IgM antibodies. CONCLUSIONS: Delayed or absent prenatal care and misinterpretation of syphilis serology (or laboratory failures) in the presence of latent syphilis are mostly responsible for the inadequate management of syphilis during pregnancy and thus the occurrence of CS
@article{Enders.2002,
title = {[Syphilis in pregnancy]},
author = {Martin Enders and H J Hagedorn},
issn = {0948-2393},
year = {2002},
date = {2002-01-01},
journal = {Zeitschrift fur Geburtshilfe und Neonatologie},
volume = {206},
number = {4},
pages = {131--137},
abstract = {Syphilis, a sexually transmitted infection, has a major impact on the disease burden worldwide. Globally, an estimated 12 million new cases of sexually acquired syphilis occurred in 1997. Developing countries in Africa, Southeast Asia and regions of the former Soviet Union are mainly affected. With rising numbers of human immunodeficiency virus-infected pregnant women and an increase in gonorrhoea in some areas, the incidence of syphilis is expected to increase again. As a consequence of migration from Eastern bloc countries to Europe after the breakdown of the former Soviet Union, the resurgence of syphilis will also affect Germany. Therefore, we present the clinical picture of syphilis as well as review the current recommendations of the German STD Society, the Centers of Disease Control (CDC), USA, and the Clinical Effectiveness Group (CEG), England, for diagnosis and treatment of syphilis with special emphasis on pregnancy. Considering the current epidemiological situation, physicians should include syphilis in their differential diagnosis. Although recommended therapy regimens differ, penicillin is the treatment of choice. Pregnant patients who are allergic to penicillin should be desensitized and treated with penicillin. Early recognition and timely treatment of syphilis are essential to prevent or treat potentially fatal fetal infection},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Syphilis, a sexually transmitted infection, has a major impact on the disease burden worldwide. Globally, an estimated 12 million new cases of sexually acquired syphilis occurred in 1997. Developing countries in Africa, Southeast Asia and regions of the former Soviet Union are mainly affected. With rising numbers of human immunodeficiency virus-infected pregnant women and an increase in gonorrhoea in some areas, the incidence of syphilis is expected to increase again. As a consequence of migration from Eastern bloc countries to Europe after the breakdown of the former Soviet Union, the resurgence of syphilis will also affect Germany. Therefore, we present the clinical picture of syphilis as well as review the current recommendations of the German STD Society, the Centers of Disease Control (CDC), USA, and the Clinical Effectiveness Group (CEG), England, for diagnosis and treatment of syphilis with special emphasis on pregnancy. Considering the current epidemiological situation, physicians should include syphilis in their differential diagnosis. Although recommended therapy regimens differ, penicillin is the treatment of choice. Pregnant patients who are allergic to penicillin should be desensitized and treated with penicillin. Early recognition and timely treatment of syphilis are essential to prevent or treat potentially fatal fetal infection
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