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Κυριότεροι λοιµογόνοι παράγοντες που µπορούν να προκαλέσουν ενδοµήτριες ή περιγεννητικές λοιµώξεις:
- κυτταροµεγαλοϊός (cytomegalovirus, CMV)
- ιός ερυθράς
- ιός απλού έρπητα (HSV)
- ιός ανεµευλογιάς ζωστήρα (varicella zoster virus, VZV)
- ιός Parvo B19
- ιός ηπατίτιδας Β (HBV)
- ιός επίκτητης ανοσολογικής ανεπάρκειας (human immunodeficiency virus, HIV)
- Τοξόπλασµα Gondii
- Πλασµώδιο της ελονοσίας
- Ωχρά σπειροχαίτη
- Μυκοβακτηρίδιο φυµατιώσεως
- Λιστέρια
- Χλαµύδια
- Κοινά µικρόβια
- Ιοί
- Παράσιτα
- Μικρόβια
Μηχανισµοί και οδοί προσβολής του εµβρύου
Το κύηµα µολύνεται (α) ενδοµήτρια (αιµατογενώς διαµέσου του πλακούντα ή µε κατάποση µολυσµένου αµνιακού υγρού), (β) στη διάρκεια του τοκετού από τις µολυσµένες εκκρίσεις του κόλπου ή (γ) µετά τον τοκετό από την άµεση επαφή µε τη µητέρα, µε το θηλασµό ή από το περιβάλλον.
Παράγοντες που καθορίζουν τη συχνότητα, το είδος και τη βαρύτητα των συγγενών λοιµώξεων είναι :
- Το είδος του παθογόνου (λοιµογόνος δύναµη, ιικό φορτίο, τροπισµός).
- Η ηλικία κύησης. Κάθετη µετάδοση των λοιµώξεων από τη µητέρα στο παιδί µπορεί να συµβεί σ΄ όλο το χρονικό διάστηµα από τη σύλληψη, ή και πριν απ’ αυτήν, µέχρι και την περιγεννητική περίοδο. Ωστόσο, λοίµωξη της µητέρας πριν την εµφύτευση, δηλαδή κατά τις πρώτες 15 ηµέρες από τη σύλληψη, συνήθως δεν έχει συνέπειες για το κύηµα, γιατί δύσκολα το προσβάλει, λόγω µη ανάπτυξης της πλακουντιακής κυκλοφορίας. Μετά την εµφύτευση, η συχνότητα κάθετης µετάδοσης είναι µεγαλύτερη αν η έγκυος προσβληθεί στο δεύτερο ήµισυ της κύησης, ενώ η βαρύτητα της νόσου στο κύηµα και νεογνό είναι µεγαλύτερη σε προσβολή της µητέρας στο πρώτο τρίµηνο.
III. Η κατάσταση ανοσίας της µητέρας. Η συχνότητα και η βαρύτητα λοίµωξης του κυήµατος είναι µεγαλύτερη όταν πρόκειται για πρωτοπαθή λοίµωξη της µητέρας στην κύηση. Αντίθετα, σε περιπτώσεις υποτροπιάζουσας λοίµωξης της εγκύου, όπως π.χ. σε λοίµωξη από ιό απλού έρπητα ή CMV, το ανοσιακό σύστηµα της µητέρα βρίσκεται σε ετοιµότητα και παράγει αµέσως ειδικά IgG αντισώµατα, που, περνούν τον πλακούντα και προστατεύουν το κύηµα, µε αποτέλεσµα η λοίµωξή του να είναι λιγότερο συχνή και λιγότερο βαριά.
Η λοίµωξη του κυήµατος µπορεί να οδηγήσει σε:
- Εµβρυονικό θάνατο και απορρόφηση. Όταν προσβληθεί το έµβρυο τις πρώτες εβδοµάδες της κύησης, επέρχεται θάνατος και απορρόφησή του πριν ακόµη γίνει αντιληπτή η κύηση. Η συχνότητα τέτοιας εξέλιξης δεν είναι ακριβώς γνωστή.
- Αυτόµατη αποβολή ή τοκετό θνησιγενούς νεογνού. Αποδίδονται σε βαριά γενικευµένη λοίµωξη ή σε πρόκληση δυσπλασιών ασυµβίβαστων µε την επιβίωση του εµβρύου.
- Προωρότητα ή τοκετό νεογνού µε χαµηλό βάρος γέννησης για την ηλικία κύησης.
- Συγγενείς δυσπλασίες. Προκαλούνται κυρίως στο πρώτο τρίµηνο της κύησης (στάδιο οργανογένεσης), οπότε ο µικροοργανισµός δρα ως τερατογόνο προκαλώντας χρωµοσωµικές βλάβες, νέκρωση κυττάρων και διαταραχές της κυτταρικής αύξησης και του πολλαπλασιασµού. Μετά το πρώτο τρίµηνο, οι συγγενείς δυσπλασίες είναι σπανιότερες και οφείλονται σε καταστροφή ιστών από την ανάπτυξη φλεγµονώδους αντίδρασης και ινώδους ιστού (π.χ. σύφιλη, τοξοπλάσµωση).
- Γενικευµένη νόσος. Η λοίµωξη του κυήµατος στο τελευταίο τρίµηνο µπορεί να εµφανιστεί ως γενικευµένη λοίµωξη µε εκδηλώσεις νεογνικής σηψαιµίας.
Από τις εκδηλώσεις αυτές άλλες είναι παροδικές και ιώνται µόνες τους άλλες είναι πολύ βαριές και προκαλούν το θάνατο του νεογνού ή αφήνουν µόνιµες βλάβες.
- Ασυµπτωµατική λοίµωξη. Μπορεί το κύηµα και νεογνό να µην εµφανίζει κλινικές εκδηλώσεις στη γέννηση, αν και έχει προσβληθεί από τον µικροοργανισµό.
- Καθυστερηµένες εκδηλώσεις και επίµονη µετανεογνική λοίµωξη. Είναι δυνατό µετά από µήνες ή χρόνια να εµφανιστούν καθυστερηµένες εκδηλώσεις, ως συνέπεια ενδοµήτριων βλαβών ή επιµένουσας µετανεογνικής λοίµωξης
Καθυστερηµένες εκδηλώσεις συγγενών λοιµώξεων
- διαταραχές ακοής (νευρογενής βαρηκοΐα)
- διαταραχές όρασης (χοριοαµφιβληστροειδίτιδα, διαθλαστικές ανωµαλίες)
- ΚΝΣ (µικροκεφαλία, νοητική υστέρηση, σπασµοί)
- διαταραχές οδοντοφυΐας (κυρίως CMV, σύφιλη)
- βρεφικός ζωστήρας (VZV)
- επίµονη αποβολή του ιού
∆ιαγνωστική προσέγγιση των συγγενών λοιµώξεων
Την υποψία των συγγενών λοιµώξεων τη θέτουν τα κλινικά ευρήµατα, τα οποία όµως είναι κοινά σε πολλές απ΄ αυτές, ενώ λείπουν τελείως σ’ ένα σηµαντικό ποσοστό νεογνών που έχουν προσβληθεί. Στην διάγνωση µπορούν να βοηθήσουν:
- Το ιστορικό της µητέρας. Το ιστορικό κλινικής λοίµωξης της µητέρας κατά την κύηση είναι πολύ σηµαντικό για τη διάγνωση. Συνήθως, όµως, η λοίµωξη στη µητέρα είναι ασυµπτωµατική ή εκδηλώνεται µε πολύ ήπια και µη ειδικά συµπτώµατα. Έτσι, πρέπει να αναζητείται το ιστορικό επαφής της µητέρας µε πάσχοντες κατά τη διάρκεια της κύησης και τα ευρήµατα ενδεχόµενου προγεννητικού ελέγχου (υπερηχογραφικός, ορολογικός, PCR).
- Τα ακτινολογικά ευρήµατα. Πριν τη γέννηση, µε τον υπερηχογραφικό έλεγχο µπορεί να διαπιστωθούν ενδείξεις προσβολής του κυήµατος (π.χ. υδροκέφαλος). Μετά τη γέννηση, ο ακτινολογικός έλεγχος µπορεί να αποκαλύψει χαρακτηριστικά ευρήµατα, όπως είναι η πνευµονία, οι οστικές βλάβες (διαυγαστικές περιοχές στις µεταφύσεις, οστεοχονδρίτιδα), οι ενδοκρανιακές επασβεστώσεις. Περαιτέρω έλεγχος µε υπερηχογράφηµα εγκεφάλου ή αξονική τοµογραφία µπορεί να αποκαλύψει την ύπαρξη υδροκεφάλου, επασβεστώσεων ή φλοιικής ατροφίας.
- Η αποµόνωση του µικροοργανισµού µε καλλιέργειες ή ανίχνευση του DNA/RNA µε PCR. Η αποµόνωση µπορεί να γίνει µε καλλιέργεια αίµατος, εγκεφαλονωτιαίου υγρού, ούρων, αµνιακού υγρού, υλικού από δερµατικές βλάβες (ιός ανεµευλογιάς-ζωστήρα, απλού έρπητα). Τα τελευταία χρόνια η ανίχνευση του DNA/RNA του ιού στο αµνιακό υγρό ή εµβρυϊκό αίµα την αλυσιδωτή αντίδραση πολυµεράσης (PCR), έχει συµβάλλει σηµαντικά στη διάγνωση των συγγενών λοιµώξεων (CMV, τοξόπλασµα, κ.α.).
- Ανεύρεση ειδικών ιστολογικών αλλοιώσεων. Χαρακτηριστικές ιστολογικές αλλοιώσεις είναι τα πολυπύρηνα γιγαντοκύτταρα και τα ενδοπυρηνικά έγκλειστα σε λοιµώξεις από τους ιούς του απλού έρπητα και της ανεµευλογιάς-ζωστήρα και τα ενδοπυρηνικά έγκλειστα στα επιθηλιακά κύτταρα των ούρων σε συγγενή λοίµωξη από CMV.
- Ορολογική διάγνωση. Αποτελεί το σηµαντικότερο τρόπο διάγνωσης των συγγενών λοιµώξεων στην καθηµερινή πράξη και στηρίζεται στον προσδιορισµό των ειδικών IgG και IgM αντισωµάτων. Ι. Η διαπίστωση τετραπλασιασµού του τίτλου των ειδικών IgG αντισωµάτων σε διαδοχικές µετρήσεις, µια αµέσως µετά τη γέννηση και η επόµενη 6-8 εβδοµάδες µετά είναι ένδειξη συγγενούς λοίµωξης. Αντίθετα, αν παρατηρηθεί ελάττωση των επιπέδων τους, πρόκειται για παθητική δίοδο µητρικών αντισωµάτων. Εναλλακτικά, µπορεί να γίνει ταυτόχρονος προσδιορισµός των ειδικών IgG αντισωµάτων µητέρας και παιδιού 46 ή περισσότερες ηµέρες από τη γέννηση (τουλάχιστον δυο ηµιπεριόδους ζωής της IgG). Αν υπάρχει συγγενής λοίµωξη, τα επίπεδα στο βρέφος είναι υψηλότερα από της µητέρας του. ΙΙ. Η ανεύρεση ειδικών IgM αντισωµάτων θέτει τη διάγνωση της συγγενούς λοίµωξης, αλλά η εξέταση έχει ένα σηµαντικό ποσοστό ψευδώς θετικών και ψευδώς αρνητικών αποτελεσµάτων και πρέπει να επαναλαµβάνεται. III. Avidity test. Όσο πιο πρόσφατη είναι η λοίµωξη τόσο πιο ασθενές είναι το avidity test. ΙV. Στη σύφιλη, αναζητούνται συνήθως τα µη ειδικά αντισώµατα κατά του αντιγόνου καρδιολιπίνη µε τις µη τρεπονηµατικές δοκιµασίες VDRL (Venereal Disease Research Laboratory) και RPR (Rapid Plasma Reagin). Επιπλέον, γίνονται οι ειδικές τρεπονηµατικές δοκιµασίες FTA-ABS (fluorencent treponemal antibody absorption) και MHA-TP (microhemaglutination test for T. Pallidum), οι οποίες δεν αρνητικο- ποιούνται µετά τη θεραπεία.
Στη διάρκεια της κύησης, η έγκυος µπορεί να προσβληθεί από διάφορες λοιµώξεις, οι περισσότερες από τις οποίες είναι τοπικές λοιµώξεις του αναπνευστικού ή πεπτικού συστήµατος, που δεν έχουν συνέπειες για το κύηµα. Οι κύριοι λοιµογόνοι παράγοντες που µπορούν να µεταδοθούν στο κύηµα και να προκαλέσουν συγγενείς λοιµώξεις, ενδοµήτριες ή περιγεννητικές αναφέρονται µε το ακρωνύµιο TORCH, από τα αρχικά Τoxoplasma, Others (ιός ανεµευλογιάς-ζωστήρα, ιός Parvo B19, HIV, κ.α.), Rubella, Cytomegalovirus, Ηerpes simplex
Στη διάρκεια της κύησης η έγκυες είναι δυνατόν να προσβληθούν από διάφορες λοιμώξεις, οι οποίες στην πλειοψηφία των περιπτώσεων δεν προκαλούν συνέπειες στο κύημα.
Οι κύριοι λοιμογόνοι παράγοντες, οι οποίοι δυνητικά μπορούν να μεταδοθούν και να προκαλέσουν βλάβες στο έμβρυο ενδομήτρια ή περιγεννητικά, αναφέρονται με το ακρωνύμιο TORCH (Toxoplasma,Other,Rubella,CMV, Herpes simplex).
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