{"id":1042,"date":"2017-01-30T21:00:34","date_gmt":"2017-01-30T20:00:34","guid":{"rendered":"http:\/\/www.newslab.sk\/2017\/01\/30\/infekcie-vyvolane-cytomegalovirusom-diagnostika-a-terapia\/"},"modified":"2017-10-03T09:58:44","modified_gmt":"2017-10-03T07:58:44","slug":"infections-caused-by-cytomegalovirus-diagnosis-and-therapy","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/infections-caused-by-cytomegalovirus-diagnosis-and-therapy\/","title":{"rendered":"Infections caused by cytomegalovirus &#8211; diagnosis and therapy"},"content":{"rendered":"<pre><span style=\"color: #ff0000;\"><strong>*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf\u00a0\r\nattachment at the end of the paper.<\/strong><\/span><\/pre>\n<p>&nbsp;<\/p>\n<p><strong>C<\/strong><strong>y<\/strong><strong>to<\/strong><strong>m<\/strong><strong>e<\/strong><strong>gal<\/strong><strong>ov\u00edrus<\/strong><\/p>\n<p>Cytomegalov\u00edrus \u013eud\u00ed (CMV, HCMV, \u013eudsk\u00fd herpesv\u00edrus 5, HHV-5) patr\u00ed medzi \u013eudsk\u00e9 herpetick\u00e9 v\u00edrusy; konkr\u00e9tne do pod\u010de\u013eade \u00a0<em>B<\/em><em>et<\/em><em>ah<\/em><em>e<\/em><em>r<\/em><em>p<\/em><em>e<\/em><em>s<\/em><em>v<\/em><em>i<\/em><em>r<\/em><em>i<\/em><em>na<\/em><em>e<\/em><em>, <\/em>do ktorej sa zara\u010fuje spolu s ostatn\u00fdmi cytomegalov\u00edrusmi\u00a0 in\u00fdch cicavcov a herpesv\u00edrusmi \u013eud\u00ed 6 a 7 (1).<\/p>\n<p>Gen\u00f3m CMV \u013eud\u00ed je najv\u00e4\u010d\u0161\u00ed \u00a0zo skupiny hum\u00e1nnych v\u00edrusov (~ 230 k bp). \u00a0Tvor\u00ed ho line\u00e1rna dvojvl\u00e1knov\u00e1 DNA , \u00a0ktor\u00e1 k\u00f3duje pribli\u017ene 180 prote\u00ednov, z toho asi 60 glykoprote\u00ednov, tak \u017ee antig\u00e9nov\u00e1 komplexnos\u0165 obalu je ve\u013ek\u00e1. Niektor\u00e9 \u0161trukt\u00farne a ne\u0161trukt\u00farne prote\u00edny (napr\u00edklad pp150, pp65, gB, gH, UL97, UL54, IE) sa vyu\u017e\u00edvaj\u00fa v diagnostike CMV infekci\u00ed, respekt\u00edve pri \u0161t\u00fadiu niektor\u00fdch typov vakc\u00edn (1).<\/p>\n<p>\u013dudsk\u00fd CMV sa vyskytuje v popul\u00e1cii ubikvit\u00e1rne ako heterog\u00e9nna zmes kme\u0148ov. \u00a0Taxonomicky ide o jedin\u00fd druh bez rozli\u0161ovania s\u00e9rotypov, \u00a0av\u0161ak pri porovnan\u00ed \u00a0sekvenci\u00ed gen\u00f3mov \u00a0jednotliv\u00fdch izol\u00e1tov a laborat\u00f3rne pas\u00e1\u017eovan\u00fdch kme\u0148ov bola zisten\u00e1 zna\u010dn\u00e1 variabilita (1). P\u00f4vodne \u00a0sa predpokladalo, \u017ee variabilita kme\u0148ov CMV m\u00e1 len mal\u00fd vplyv na hostite\u013ea, av\u0161ak v posledn\u00fdch\u00a0 rokov viacer\u00e9 \u0161t\u00fadie nazna\u010duj\u00fa, \u017ee rozdiely v kme\u0148och m\u00f4\u017eu v\u00fdrazne ovplyv\u0148ova\u0165 klinick\u00fd priebeh infekcie u pacientov s \u0165a\u017ek\u00fdm imunodeficitom a pri kongenit\u00e1lnych infekci\u00e1ch \u00a0(2). Navy\u0161e, kme\u0148ovo-\u0161pecifick\u00e9 imunitn\u00e9 odpovede m\u00f4\u017eu br\u00e1ni\u0165 v\u00fdvoju efekt\u00edvnej vakc\u00edny.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>E<\/strong><strong>pi<\/strong><strong>d<\/strong><strong>e<\/strong><strong>m<\/strong><strong>i<\/strong><strong>ol\u00f3gia<\/strong><\/p>\n<p>Infekcie CMV s\u00fa be\u017en\u00e9, prevalencia \u0161pecifick\u00fdch protil\u00e1tok sved\u010diacich o prekonan\u00ed infekcie postupne st\u00fapa s vekom a u dospelej popul\u00e1cie dosahuje v r\u00f4znych geografick\u00fdch oblastiach v z\u00e1vislosti od sp\u00f4sobu \u017eivota od cca 40 \u2013 60 % v rozvinut\u00fdch krajin\u00e1ch a\u017e po skoro 100 % v krajin\u00e1ch s n\u00edzkym hygienick\u00fdm \u0161tandardom (3).<\/p>\n<p>Cytomegalov\u00edrus sa \u0161\u00edri podobne ako ostatn\u00e9 herpetick\u00e9 v\u00edrusy, najm\u00e4 bl\u00edzkym kontaktom (horizont\u00e1lne), v\u00fdznamn\u00fd je v\u0161ak i vertik\u00e1lny prenos. Zdrojom n\u00e1kazy s\u00fa chor\u00ed, \u010dastej\u0161ie v\u0161ak nosi\u010di (v\u00edrus sa aktivuje hlavne pri oslaben\u00ed imunitn\u00e9ho syst\u00e9mu, hoci klinick\u00e9 prejavy nemusia by\u0165 zjavn\u00e9). Inkuba\u010dn\u00e1 lehota oby\u010dajne trv\u00e1 v rozmedz\u00ed 9 \u2013 60 dn\u00ed (4).<\/p>\n<p>Ako pri prim\u00e1rnej, tak i pri ka\u017edej reaktiv\u00e1cii sa viri\u00f3nov\u00e9 \u010dastice vylu\u010duj\u00fa z tela r\u00f4znymi telesn\u00fdmi sekr\u00e9tmi, hlavne mo\u010dom a slinami, ale aj matersk\u00fdm mliekom, cervik\u00e1lnym sekr\u00e9tom, ejakul\u00e1tom alebo slzami. K prenosu infekcie m\u00f4\u017ee d\u00f4js\u0165 i iatrog\u00e9nne (krvou \u010di transplantovan\u00fdm org\u00e1nom) \u00a0(1, 5). Vylu\u010dovanie \u00a0v\u00edrusu m\u00f4\u017ee \u00a0by\u0165 intermitentn\u00e9 \u00a0alebo kontinu\u00e1lne a be\u017ene trv\u00e1 u dospel\u00fdch nieko\u013eko dn\u00ed a\u017e t\u00fd\u017ed\u0148ov, u mal\u00fdch det\u00ed sk\u00f4r nieko\u013eko mesiacov a\u017e rokov (6, 7, 8, 9). Pre tehotn\u00e9 \u00a0\u017eeny je oby\u010dajne pr\u00ed\u010dinou infekcie pr\u00e1ve kontakt s de\u0165mi, \u010dasto vlastn\u00fdmi (5, 10).<\/p>\n<p>Vylu\u010dovanie CMV matersk\u00fdm mliekom je jeden z najv\u00fdznamnej\u0161\u00edch rizikov\u00fdch faktorov postnat\u00e1lnej \u00a0infekcie (60 \u2013 80 % pravdepodobnos\u0165 transmisie) \u00a0(11). Naj\u010dastej\u0161ie \u00a0sa v\u00edrus vylu\u010duje \u00a02. a\u017e 3. t\u00fd\u017ede\u0148 \u00a0po p\u00f4rode (12). Obdobie vylu\u010dovania \u00a0i mno\u017estvo vylu\u010dovan\u00e9ho v\u00edrusu s\u00fa r\u00f4zne.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Kli<\/strong><strong>ni<\/strong><strong>c<\/strong><strong>k<\/strong><strong>\u00fd obraz<\/strong><\/p>\n<p>Prim\u00e1rna infekcia prebieha v\u00e4\u010d\u0161inou v detstve a spravidla inaparentne. Niekedy sa m\u00f4\u017ee vyskytn\u00fa\u0165 ochorenie \u00a0bez \u0161pecifick\u00fdch pr\u00edznakov (hor\u00fa\u010dka, zduren\u00e9 uzliny, \u00fanava, slabos\u0165, boles\u0165 svalov\/k\u013abov, nechutenstvo), respekt\u00edve syndr\u00f3m infek\u010dnej mononukle\u00f3zy (IM), ktor\u00fd je klinicky neodl\u00ed\u0161ite\u013en\u00fd od IM sp\u00f4sobenej \u00a0v\u00edrusom Epsteina-Barrovej (EBV) (4).<\/p>\n<p>Vz\u00e1cnej\u0161ie m\u00f4\u017ee CMV infekcia \u00a0vyvola\u0165 \u00a0napr\u00edklad \u00a0kolit\u00eddu, Guillain-Barr\u00e9ho syndr\u00f3m, meningoencefalit\u00eddu, trombocytop\u00e9niu, hemolytick\u00fa an\u00e9miu, anikterick\u00fa \u010di mierne ikterick\u00fa hepatopatiu (hepatosplenomeg\u00e1lia a lymfocyt\u00f3za), pneum\u00f3niu, \u00a0perikardit\u00eddu, myokardit\u00eddu, vaskul\u00e1rnu tromb\u00f3zu, uveit\u00eddu (4). Viacer\u00e9 hl\u00e1sen\u00e9 pr\u00edpady CMV ochoren\u00ed \u00a0u imuno- kompetentn\u00fdch pacientov boli asociovan\u00e9 s komorbiditami, ako napr\u00edklad diabetes mellitus a ren\u00e1lne zlyhanie. Predpoklad\u00e1 sa, \u017ee mierna dysfunkcia imunitn\u00e9ho syst\u00e9mu m\u00f4\u017ee predstavova\u0165 v s\u00fa\u010dasnosti zatia\u013e prehliadan\u00e9 riziko rozvoja CMV ochorenia \u00a0(13, 14, 15, 16).<\/p>\n<p><em>K<\/em><em>o<\/em><em>ngenit\u00e1lne <\/em><em>CMV <\/em>infekcie s\u00fa relat\u00edvne \u010dast\u00e9 (0,6 \u2013 0,7 % \u017eivonaroden\u00fdch det\u00ed), pri\u010dom \u00a0stupe\u0148 \u00a0klinick\u00e9ho prejavu je z\u00e1visl\u00fd od infek\u010dnej d\u00e1vky. Infekcia tehotn\u00fdch \u00a0\u017eien m\u00f4\u017ee vies\u0165 k transplacent\u00e1rnemu prenosu v\u00edrusu na plod\u00a0 alebo\u00a0 k perinat\u00e1lnej n\u00e1kaze novorodenca. Kongenit\u00e1lna infekcia nasleduje hlavne po prim\u00e1rnej infekcii gravidnej matky (20 \u2013 40 % pr\u00edpadov), av\u0161ak aj reinfekcia in\u00fdm \u00a0kme\u0148om \u00a0CMV alebo reaktiv\u00e1cia latentn\u00e9ho v\u00edrusu (latentne perzistuj\u00faceho kme\u0148a v hostite\u013eovi po prekonanej prim\u00e1rnej CMV infekcii v minulosti) m\u00f4\u017ee sp\u00f4sobi\u0165 infekciu plodu, hoci v podstatne men\u0161ej \u00a0miere (0,2 \u2013 2 % incidencia) \u00a0(5, 7, 10, 17, 18). Asi 10 % kongenit\u00e1lne infikovan\u00fdch det\u00ed je pri p\u00f4rode symptomatic- k\u00fdch. Symptomatick\u00e1 \u00a0kongenit\u00e1lna infekcia sa m\u00f4\u017ee manifestova\u0165 ako perinat\u00e1lna sepsa, hepatit\u00edda, hepatosplenomeg\u00e1lia, lymfocyt\u00f3za, trombocytop\u00e9nia, petechie, pneum\u00f3nia alebo chorioretinit\u00edda (18). \u00damrtnos\u0165 b\u00fdva v rozmedz\u00ed 2 \u2013 30 %. D\u00f4sledkom teratog\u00e9nneho \u00fa\u010dinku CMV m\u00f4\u017eu ma\u0165 novorodenci r\u00f4zne vroden\u00e9 chyby, \u010dasto so z\u00e1va\u017en\u00fdmi trval\u00fdmi n\u00e1sledkami. Pribli\u017ene u 5 \u2013 15 % kongenit\u00e1lne infikovan\u00fdch det\u00ed, ktor\u00e9 s\u00fa pri p\u00f4rode asymptomatick\u00e9, sa rozvin\u00fa sympt\u00f3my v priebehu nieko\u013ek\u00fdch mesiacov a\u017e rokov. Naj\u010dastej\u0161ie ide o po\u0161kodenie sluchov\u00e9ho nervu (10, 18).<\/p>\n<p>Perinat\u00e1lne infekcie a skor\u00e9 infekcie po naroden\u00ed u nedonosen\u00fdch det\u00ed m\u00f4\u017eu ma\u0165 podobn\u00e9 \u00a0klinick\u00e9 prejavy ako infekcie <em>i<\/em><em>n utero, <\/em>av\u0161ak e\u0161te doned\u00e1vna sa predpokladalo, \u017ee neb\u00fdvaj\u00fa spojen\u00e9 s trval\u00fdmi n\u00e1sledkami (19). Niektor\u00e9 nov\u0161ie \u0161t\u00fadie v\u0161ak pri dlhodobom sledovan\u00ed pred\u010dasne naroden\u00fdch det\u00ed s postnat\u00e1lnou CMV infekciou zistili ur\u010dit\u00e9 mierne kognit\u00edvne rozdiely u tejto skupiny det\u00ed v porovnan\u00ed s kontrolnou skupinou jedincov bez v\u010dasnej postnat\u00e1lnej CMV infekcie (20).<\/p>\n<p><em>Infekcie <\/em><em>u imunodeficitn\u00fdch \u00a0pacientov. \u00a0<\/em>Rizikov\u00fa skupinu tvoria najm\u00e4 pacienti po transplant\u00e1cii kostnej drene, sol\u00eddnych org\u00e1nov a pacienti s AIDS, u ktor\u00fdch m\u00f4\u017ee CMV infekcia vyvola\u0165 z\u00e1va\u017en\u00e9 syst\u00e9mov\u00e9 ochorenie (21, 22, 23, 24).<\/p>\n<p>U imunosuprimovan\u00fdch \u00a0s\u00e9ronegat\u00edvnych pacientov doch\u00e1dza k infekcii prostredn\u00edctvom transplantovan\u00fdch org\u00e1nov\/\u0161tepu od s\u00e9ropozit\u00edvnych darcov; u s\u00e9ropozit\u00edvnych pr\u00edjemcov m\u00f4\u017ee \u00eds\u0165 o reaktiv\u00e1ciu endog\u00e9nnej latentnej infekcie alebo reinfekciu in\u00fdm kme\u0148om CMV poch\u00e1dzaj\u00facim od darcu (25). CMV infekcia m\u00f4\u017ee \u00a0ma\u0165 potom \u00a0priame\u00a0 a nepriame d\u00f4sledky. Medzi priame d\u00f4sledky patr\u00ed napr\u00edklad supresia kostnej drene, pneum\u00f3nia, myokardit\u00edda, ochorenie gastrointestin\u00e1lneho \u00a0traktu, hepatit\u00edda, pankreatit\u00edda, nefrit\u00edda, retinit\u00edda, encefalit\u00edda; medzi nepriame d\u00f4sledky ak\u00fatna alebo chronick\u00e1 rejekcia \u0161tepu, akcelerovan\u00e1 ateroskler\u00f3za (transplant\u00e1cia srdca), sekund\u00e1rne v\u00edrusov\u00e9 infekcie (napr\u00edklad EBV-sociovan\u00e9 posttransplanta\u010dn\u00e9 lymfoproliferat\u00edvne ochorenie, infekcie herpesv\u00edrusmi \u013eud\u00ed 6, 7, denov\u00edrusmi), bakteri\u00e1lne (napr\u00edklad enterokoky, <em>St<\/em><em>ap<\/em><em>h<\/em><em>y<\/em><em>l<\/em><em>o<\/em><em>c<\/em><em>o<\/em><em>c<\/em><em>c<\/em><em>u<\/em><em>s <\/em><em>au<\/em><em>r<\/em><em>eus, <\/em>aer\u00f3bne a fakultat\u00edvne anaer\u00f3bne gramnegat\u00edvne pali\u010dky) a mykotick\u00e9 infekcie <em>(C<\/em><em>andida <\/em>spp., <em>A<\/em><em>s<\/em><em>p<\/em><em>ergillus <\/em>spp., <em>P<\/em><em>neumocystis jiroveci), <\/em>zn\u00ed\u017een\u00e1 odolnos\u0165 \u0161tepu a celkov\u00e9 pre\u017e\u00edvanie pacienta \u00a0(24, 26, 27, 28).<\/p>\n<p>&nbsp;<\/p>\n<p><strong>L<\/strong><strong>a<\/strong><strong>b<\/strong><strong>o<\/strong><strong>ra<\/strong><strong>t\u00f3<\/strong><strong>r<\/strong><strong>n<\/strong><strong>a diagnostika<\/strong><\/p>\n<p>Na diagnostiku CMV infekci\u00ed u imunokompetentn\u00fdch jedincov je vo v\u00e4\u010d\u0161ine pr\u00edpadov posta\u010duj\u00faca \u00a0s\u00e9rologick\u00e1 diagnostika \u2013 stanovenie \u0161pecifick\u00fdch IgM (pr\u00edpadne i IgA) a IgG (u s\u00e9ropozit\u00edvnych gravidn\u00fdch \u017eien doplnen\u00e1 \u00a0i o stanovenie avidity anti-CMV IgG). Molekul\u00e1rno-biologick\u00e9 met\u00f3dy (najm\u00e4 PCR) s\u00fa vhodn\u00e9 predov\u0161etk\u00fdm pre \u0165a\u017eko imunodeficitn\u00fdch pacientov, novorodencov, pri diferenci\u00e1lnej diagnostike kongenit\u00e1lnych infekci\u00ed, neurologick\u00fdch\/o\u010dn\u00fdch infekci\u00ed a in\u00fdch z\u00e1va\u017en\u00fdch stavov.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Stanovenie \u0161pecifick\u00fdch protil\u00e1tok proti CMV<\/strong><\/p>\n<p>Z nepriamych met\u00f3d sa v s\u00fa\u010dasnosti vyu\u017e\u00edvaj\u00fa najm\u00e4 met\u00f3dy enz\u00fdmovej alebo chemiluminiscen\u010dnej imunoanal\u00fdzy (ELISA, CLIA). Stanovuj\u00fa sa protil\u00e1tky triedy IgG (kvantitat\u00edvne) a IgM (semikvantitat\u00edvne), v ojedinel\u00fdch pr\u00edpadoch i IgA (semikvantitat\u00edvne). Algoritmus s\u00e9rologick\u00fdch testov v s\u00fa\u010dasnosti v mnoh\u00fdch pr\u00edpadoch umo\u017e\u0148uje interpret\u00e1ciu v\u00fdsledku\u00a0a ur\u010denie \u0161t\u00e1dia infekcie z vy\u0161etrenia jednej vzorky. Ak je potrebn\u00e9 \u00a0pos\u00fadi\u0165 signifikantn\u00e9 zmeny v protil\u00e1tkovej\u00a0 aktivite, vy\u0161etrenie \u00a0druhej \u00a0vzorky je vhodn\u00e9 cca o 7 \u2013 14 dn\u00ed.<\/p>\n<p>Anti-CMV IgM a IgA protil\u00e1tky sa tvoria len prechodne \u00a0v s\u00favislosti s akt\u00edvnou CMV infekciou (hlavne prim\u00e1rnou, ale i rekurentnou). V priebehu prim\u00e1rnej infekcie oby\u010dajne po 2 \u2013 3 mesiacoch r\u00fdchlo klesaj\u00fa, mo\u017en\u00e1 \u00a0je v\u0161ak aj dlhodob\u00e1 perzistencia \u00a0IgM (29). Stanovenie samotn\u00fdch anti-CMV IgM nesta\u010d\u00ed na d\u00f4kaz akt\u00edvnej infekcie, mo\u017en\u00e1 je aj heterotypick\u00e1 imunitn\u00e1 odpove\u010f \u00a0vplyvom inej prebiehaj\u00facej infekcie (napr\u00edklad Toxoplasma gondii, Legionella pneumophila, chlam\u00fddie, v\u00edrus parotit\u00eddy, EBV) (5, 30).<\/p>\n<p>Nako\u013eko anti-CMV IgG s\u00fa pr\u00edtomn\u00e9 u\u017e v ak\u00fatnej f\u00e1ze infekcie a po jej odznen\u00ed pretrv\u00e1vaj\u00fa cel\u00fd \u017eivot, diagnostick\u00fd v\u00fdznam m\u00e1 d\u00f4kaz s\u00e9rokonverzie alebo signifikantn\u00e9ho vzostupu t\u00fdchto protil\u00e1tok v p\u00e1rov\u00fdch vzork\u00e1ch s\u00e9ra. Vzostup protil\u00e1tkovej aktivity m\u00f4\u017ee by\u0165 sp\u00f4soben\u00fd aj heterol\u00f3gnou imunitnou odpove\u010fou v d\u00f4sledku \u00a0inej infekcie \u00a0(napr\u00edklad HSV). D\u00f4kaz v\u00edrusovo \u0161pecifick\u00fdch protil\u00e1tok m\u00e1 dobr\u00fa v\u00fdpovedn\u00fa hodnotu, hlavne pri diagnostike prim\u00e1rnych infekci\u00ed. Vzh\u013eadom na nasleduj\u00face \u00a0celo\u017eivotn\u00e9 nosi\u010dstvo v\u00edrusu je hostite\u013esk\u00fd organizmus opakovane stimulovan\u00fd v\u00edrusov\u00fdmi antig\u00e9nmi. D\u00f4sledkom toho m\u00e1 dlhodobo vysok\u00fa hladinu protil\u00e1tok, ktor\u00e1 pri reaktiv\u00e1ci\u00e1ch nemus\u00ed \u00a0vykazova\u0165 signifikantn\u00e9 zmeny. Preto je diagnostick\u00fd v\u00fdznam s\u00e9rologick\u00fdch met\u00f3d pri reaktiv\u00e1ci\u00e1ch a reinfekci\u00e1ch n\u00edzky. U dospel\u00fdch pacientov je interpret\u00e1cia s\u00e9rologick\u00e9ho n\u00e1lezu \u010dasto komplikovan\u00e1 a nejednozna\u010dn\u00e1: dospel\u00fd organizmus \u00a0je u\u017e infikovan\u00fd viacer\u00fdmi druhmi herpetick\u00fdch \u00a0v\u00edrusov, ktor\u00e9 sa m\u00f4\u017eu v r\u00f4znych klinick\u00fdch situ\u00e1ci\u00e1ch sekund\u00e1rne reaktivova\u0165 a vyvola\u0165 tvorbu druhovo \u0161pecifick\u00fdch i skr\u00ed\u017eene reaguj\u00facich \u00a0protil\u00e1tok. Typick\u00fdm \u00a0pr\u00edkladom \u00a0je sekund\u00e1rna reaktiv\u00e1cia CMV a HHV-6 pri infek\u010dnej mononukle\u00f3ze vyvolanej EBV (6, 30).<\/p>\n<p>V\u00fdsledok s\u00e9rologick\u00e9ho \u00a0vy\u0161etrenia mus\u00ed by\u0165 hodnoten\u00fd v s\u00favislosti s klinick\u00fdm stavom pacienta a s v\u00fdsledkami in\u00fdch laborat\u00f3rnych vy\u0161etren\u00ed. Plo\u0161n\u00fd s\u00e9rologick\u00fd skr\u00edning \u017eien pred graviditou (na selekciu a \u010fal\u0161ie sledovanie s\u00e9ronegat\u00edvnych os\u00f4b) sa vzh\u013eadom na vysok\u00fa prevalenciu CMV v popul\u00e1cii a relat\u00edvne n\u00edzke percenta symptomatick\u00fdch kongenit\u00e1lnych infekci\u00ed pau\u0161\u00e1lne nerob\u00ed (29).<\/p>\n<p>U imunodeficitn\u00fdch \u00a0pacientov \u00a0i novorodencov \u00a0je s\u00e9rologick\u00e1 diagnostika nedostato\u010dn\u00e1 \u00a0a je potrebn\u00e9 \u00a0ju doplni\u0165 met\u00f3dami \u00a0priameho d\u00f4kazu CMV (21).<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Stanovenie avidity (v\u00e4zobnej schopnosti) IgG protil\u00e1tok<\/strong><\/p>\n<p>Stanovenie avidity IgG protil\u00e1tok je ve\u013emi d\u00f4le\u017eit\u00e9 na diagnostiku CMV infekcie u gravidn\u00fdch \u017eien. Vyu\u017e\u00edva sa na odl\u00ed\u0161enie prim\u00e1rnej infekcie, ke\u010f je riziko transplacent\u00e1rneho prenosu v\u00edrusu najvy\u0161\u0161ie, od reinfekcie\/ reaktiv\u00e1cie v\u00edrusu (31). Pri prim\u00e1rnej infekcii sa tvoria n\u00edzkoavidn\u00e9 protil\u00e1tky, ktor\u00e9 s\u00fa po\u010das 2 \u2013 4 mesiacov rekonvalescencie postupne nahr\u00e1dzan\u00e9 protil\u00e1tkami s vysokou aviditou (<em>cu<\/em><em>t<\/em><em>&#8211;<\/em><em>off <\/em>pre n\u00edzku aviditu sa v z\u00e1vislosti od pou\u017eitej diagnostickej s\u00fapravy oby\u010dajne ud\u00e1va od 35 % do 50 %; pre vysok\u00fa aviditu v rozmedz\u00ed od 50 % do 65 %). Vysok\u00e1 avidita anti-CMV IgG v 1. trimestri vylu\u010duje \u00a0prim\u00e1rnu \u00a0infekciu po\u010das \u00a0gravidity a indikuje n\u00edzke riziko intrauterinnej transmisie v\u00edrusu. Naproti tomu, interpret\u00e1cia s\u00e9rologick\u00e9ho v\u00fdsledku so stredne vysokou, respekt\u00edve vysokou aviditou stanovenou v 2. alebo 3. trimestri je ob\u0165a\u017en\u00e1, nako\u013eko nie je mo\u017en\u00e9 jednozna\u010dne vyl\u00fa\u010di\u0165 prim\u00e1rnu \u00a0infekciu po\u010das \u00a0tehotenstva \u00a0(18, 30, 32).<\/p>\n<p>Diagnostika prim\u00e1rnych infekci\u00ed sa m\u00f4\u017ee v niektor\u00fdch pr\u00edpadoch doplni\u0165 o \u010fal\u0161ie testy, ako napr\u00edklad d\u00f4kaz anti-CMV glykoprote\u00ednu \u00a0B (synt\u00e9za 50 a\u017e 100 dn\u00ed po infekcii) (33).<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Stanovenie \u0161pecifickej bunkovej imunitnej odpovede<\/strong><\/p>\n<p>U imunosuprimovan\u00fdch \u00a0pacientov po transplant\u00e1cii \u00a0je reaktiv\u00e1cia\/ reinfekcia, respekt\u00edve prim\u00e1rna infekcia CMV relat\u00edvne \u010dast\u00fdm rizikov\u00fdm faktorom rozvoja ochorenia. Profylaktick\u00e1\/v\u010dasn\u00e1 preempt\u00edvna \u00a0terapia \u0161pecifick\u00fdmi antiv\u00edrusov\u00fdmi \u00a0l\u00e1tkami je \u0165a\u017eiskov\u00e1 na zn\u00ed\u017eenie morbidity a mortality u tejto skupiny pacientov \u00a0(21, 22, 24). Vzh\u013eadom \u00a0na vysok\u00fa toxicitu prepar\u00e1tov a \u010fal\u0161ie nev\u00fdhody \u00a0(napr\u00edklad neskor\u00fd n\u00e1stup CMV ochorenia \u00a0pri profylaktickej terapii a \u0165a\u017ekosti s ur\u010den\u00edm <em>cu<\/em><em>t<\/em><em>&#8211;<\/em><em>off <\/em>hran\u00edc v\u00edrusovej n\u00e1lo\u017ee na za\u010datie preempt\u00edvnej terapie) sa u\u017e nieko\u013eko rokov h\u013ead\u00e1 n\u00e1stroj na odl\u00ed\u0161enie asymptomatickej aktiv\u00e1cie CMV od aktiv\u00e1cie s rizikom rozvoja CMV ochorenia. V rutinnej praxi sa zvykne sledova\u0165 dynamika n\u00e1lo\u017ee CMV DNA pomocou kvantitat\u00edvnej PCR, av\u0161ak v posledn\u00fdch rokoch sa \u010doraz \u010dastej\u0161ie zd\u00f4raz\u0148uje potreba sledovania rekon\u0161tit\u00facie bunkovej zlo\u017eky adapt\u00edvnej imunity (napr\u00edklad pomocou \u00a0ELISPOT alebo cytok\u00ednovej prietokovej cytometrie), konkr\u00e9tne anti-CMV \u0161pecifick\u00fdch CD4+ a CD8+ T-lymfocytov a ich produktov, ktor\u00e9 s\u00fa k\u013e\u00fa\u010dov\u00e9 na dosiahnutie dlhodobej protektivity proti reaktiv\u00e1cii v\u00edrusu a rozvoju ochorenia \u00a0(25, 34, 35, 36, 37).<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Priame met\u00f3dy<\/strong><\/p>\n<p>V minulosti bola na d\u00f4kaz CMV infekcie \u0161tandardn\u00fdm postupom kultiv\u00e1cia v\u00edrusu <em>i<\/em><em>n vitro <\/em>na bunkov\u00fdch kult\u00farach (napr\u00edklad \u013eudsk\u00e9 fibroblastov\u00e9 bunky). Vznik typick\u00e9ho cytopatick\u00e9ho efektu bolo mo\u017en\u00e9 pozorova\u0165 po 2 \u2013 21 d\u0148och, t. j. \u017ee na vydanie negat\u00edvneho v\u00fdsledku bolo nutn\u00e9 vzorku kultivova\u0165 minim\u00e1lne 3 \u2013 4 t\u00fd\u017edne. Zr\u00fdchlen\u00fd \u00a0variant kultiv\u00e1cie (tzv. shell vial assay) pomocou \u00a0centrifug\u00e1cie vzorky na monovrstvu fibroblastov\u00fdch buniek pomohol v\u00fdrazne zr\u00fdchli\u0165 detekciu v\u00edrusu (38).<\/p>\n<p>V\u00edrusov\u00e9 antig\u00e9ny (najm\u00e4 IE = immediate-early; t. j. ve\u013emi skor\u00e9 antig\u00e9ny, produkovan\u00e9 na za\u010diatku replik\u00e1cie v\u00edrusu) m\u00f4\u017eu by\u0165 tie\u017e detegovan\u00e9 pomocou fluorescen\u010dne zna\u010den\u00fdch monoklonov\u00fdch protil\u00e1tok, a to u\u017e po 16 hodin\u00e1ch inkub\u00e1cie vzorky (mikroskopicky alebo v mikrotitra\u010dn\u00fdch platni\u010dk\u00e1ch) (38).<\/p>\n<p>Na diagnostiku CMV infekcie je pou\u017eite\u013en\u00e1 i met\u00f3da antigen\u00e9mie pp65 (imunofluorescen\u010dn\u00e9 \u00a0mikroskopick\u00e9 stanovenie antig\u00e9nu pp65, tegumentov\u00e9ho fosfoprote\u00ednu CMV, v perif\u00e9rnych polymorfonukle\u00e1roch a mononukle\u00e1roch), hybridiz\u00e1cia <em>i<\/em><em>n situ<\/em>, imunohistochemick\u00e9 \u00a0vy\u0161etrenie vzoriek tkan\u00edv alebo tekut\u00e9ho biologick\u00e9ho materi\u00e1lu (pomocou fluorescen\u010dn\u00fdch alebo enz\u00fdmovo zna\u010den\u00fdch monoklonov\u00fdch\/polyklonov\u00fdch protil\u00e1tok proti skor\u00fdm CMV antig\u00e9nom), met\u00f3da \u201ehybrid capture\u201c (detekcia CMV DNA pomocou RNA zna\u010den\u00fdch sond) alebo d\u00f4kaz IE mRNA (ve\u013emi skor\u00fd transkript CMV proteosynt\u00e9zy) met\u00f3dou \u00a0NASBA (nucleic acid sequence-based \u00a0amplification) \u00a0(21, 22, 30, 38, 39, 40).<\/p>\n<p>Je potrebn\u00e9 zd\u00f4razni\u0165, \u017ee hoci vy\u0161\u0161ie spomenut\u00e9 met\u00f3dy sa v priebehu nieko\u013ek\u00fdch posledn\u00fdch desiatok rokov postupne vyv\u00edjali a pou\u017e\u00edvali \u010di u\u017e diagnosticky, alebo na z\u00edskanie nov\u00fdch poznatkov o CMV a jeho interakcii s hostite\u013eom, vzh\u013eadom na \u010dasov\u00fa n\u00e1ro\u010dnos\u0165, pr\u00e1cnos\u0165, po\u017eiadavky na erudovan\u00fa sp\u00f4sobilos\u0165 pri hodnoten\u00ed niektor\u00fdch testov a v neposlednom rade i ni\u017e\u0161iu citlivos\u0165 (okrem NASBA) sa v s\u00fa\u010dasnosti v rutinn\u00fdch laborat\u00f3ri\u00e1ch u\u017e skoro v\u00f4bec nepou\u017e\u00edvaj\u00fa.<\/p>\n<p>Amplifika\u010dn\u00e9 met\u00f3dy (najm\u00e4 PCR na kvantitat\u00edvne stanovenie v\u00edrusovej nukleovej kyseliny) v\u010faka r\u00fdchlosti, vysokej citlivosti, \u0161pecifickosti a relat\u00edvne dobrej aplikovate\u013enosti st\u00e1le viac nahr\u00e1dzaj\u00fa ostatn\u00e9 met\u00f3dy priameho \u00a0d\u00f4kazu v\u00edrusov (21, 22).<\/p>\n<p>Pri vy\u0161etren\u00ed \u00a0vzoriek pomocou PCR, ktor\u00e9 je realizovan\u00e9 \u00a0na \u00fa\u010dely diferenci\u00e1lnej diagnostiky, je vhodn\u00e9 odobera\u0165 materi\u00e1l zodpovedaj\u00faci postihnut\u00fdm org\u00e1nom: napr\u00edklad cerebrospin\u00e1lny \u00a0mok pri ochoren\u00ed nervov\u00e9ho \u00a0syst\u00e9mu, bronchoalveol\u00e1rnu \u00a0lav\u00e1\u017e (BAL) alebo sp\u00fatum pri postihnut\u00ed doln\u00fdch d\u00fdchac\u00edch ciest, v\u00fdter zo spojovkov\u00e9ho \u00a0vaku pri keratokonjuktivit\u00eddach, o\u010dn\u00fa \u00a0tekutinu pri retinit\u00edde, biopsiu pri gastroenterit\u00edde, perif\u00e9rnu nezrazen\u00fa \u00a0krv pri ak\u00fatnych hor\u00fa\u010dkov\u00fdch \u00a0ochoreniach \u010di uzlinov\u00fdch syndr\u00f3moch (30), plodov\u00fa vodu pri prenat\u00e1lnej diagnostike a mo\u010d, sliny, krv, pr\u00edpadne \u00a0i in\u00fd materi\u00e1l pri postnat\u00e1lnej \u00a0diagnostike \u00a0kon- genit\u00e1lnych \u00a0CMV infekci\u00ed (29, 38, 40).<\/p>\n<p>Na z\u00e1klade d\u00f4kazu v\u00edrusovej DNA nie je mo\u017en\u00e9 odl\u00ed\u0161i\u0165 latentn\u00fd v\u00edrus od replikuj\u00faceho. V\u00fdsledky kvalitat\u00edvneho vy\u0161etrenia PCR m\u00f4\u017eu by\u0165 pozit\u00edvne ako v ak\u00fatnej f\u00e1ze infekcie, tak i v prodrom\u00e1lnom asymptomatickom \u0161t\u00e1diu, \u010di vo v\u010dasnej f\u00e1ze rekonvalescencie (30). S\u00fa to ve\u013emi citliv\u00e9 met\u00f3dy, schopn\u00e9 \u00a0zachyti\u0165 i mal\u00e9 \u00a0mno\u017estvo \u00a0v\u00edrusu (napr\u00edklad 100 \u2013 1 000 k\u00f3pi\u00ed v\u00edrusov\u00e9ho gen\u00f3mu\/1 \u00a0ml). Tieto met\u00f3dy \u00a0m\u00f4\u017eu detegova\u0165 \u00a0i bezpr\u00edznakov\u00fa alebo lok\u00e1lnu aktiv\u00e1ciu CMV. Rozl\u00ed\u0161i\u0165 tieto \u0161t\u00e1di\u00e1 je \u010dasto mo\u017en\u00e9 len pomocou kvantitat\u00edvnej PCR (real time PCR).<\/p>\n<p>Pri interpret\u00e1cii n\u00e1lezu je potrebn\u00e9 zoh\u013eadni\u0165, z ak\u00e9ho materi\u00e1lu bolo vy\u0161etrenie realizovan\u00e9. Najlep\u0161ie na pos\u00fadenie akt\u00edvnej CMV infekcie je vy\u0161etrenie \u00a0perif\u00e9rnej \u00a0krvi s kvantitat\u00edvnym vyjadren\u00edm \u00a0v\u00edrusovej n\u00e1lo\u017ee. D\u00f4kaz DNA v slin\u00e1ch, mo\u010di alebo vagin\u00e1lnom sekr\u00e9te m\u00f4\u017ee znamena\u0165 ako prim\u00e1rnu infekciu, tak i reinfekciu, \u010di reaktiv\u00e1ciu. Pri n\u00e1leze CMV DNA v BAL je potrebn\u00e9 zoh\u013eadni\u0165 mo\u017en\u00fa kontamin\u00e1ciu vplyvom asymptomatick\u00e9ho vylu\u010dovania v\u00edrusu do nazofarynge\u00e1lneho sekr\u00e9tu. Na vyl\u00fa\u010denie mo\u017enej\u00a0\u201emylnej\u201c pozitivity BAL je vhodn\u00e9 opakovan\u00e9 alebo paraleln\u00e9 vy\u0161etrenie BAL a perif\u00e9rnej krvi (30).<\/p>\n<p>V diagnostike kongenit\u00e1lnych \u00a0infekci\u00ed je z\u00e1kladom d\u00f4kaz prim\u00e1rnej infekcie, respekt\u00edve reinfekcie\/reaktiv\u00e1cie CMV u matky v gravidite. Ak sa akt\u00edvna infekcia u matky potvrd\u00ed, respekt\u00edve je ve\u013emi suspektn\u00e1 (s\u00e9rokonverzia v triede IgG, v\u00fdrazne vysok\u00e9 hladiny anti-CMV IgM\/IgG alebo signifikantn\u00fd vzostup \u00a0hladiny \u0161pecifick\u00fdch \u00a0protil\u00e1tok, n\u00edzka avidita \u0161pecifick\u00fdch \u00a0IgG, detekcia \u00a0CMV DNA v krvi, mo\u010di alebo slin\u00e1ch matky, abnorm\u00e1lny ultrasonografick\u00fd obraz plodu), je mo\u017en\u00e9 urobi\u0165 laborat\u00f3rne vy\u0161etrenia amniotickej tekutiny (met\u00f3dou PCR). V tomto pr\u00edpade m\u00e1 PCR met\u00f3da vysok\u00fa negat\u00edvnu aj pozit\u00edvnu \u00a0predikt\u00edvnu hodnotu, v\u00fdsledok je v\u0161ak nutn\u00e9 \u00a0interpretova\u0165 v z\u00e1vislosti od gesta\u010dn\u00e9ho \u00a0t\u00fd\u017ed\u0148a (testovanie amniotickej tekutiny pred 21. t\u00fd\u017ed\u0148om gest\u00e1cie m\u00e1 len asi 30 \u2013 45 % senzitivitu) (41). Pozit\u00edvny v\u00fdsledok testu indikuje, \u017ee do\u0161lo k prenosu infek\u010dn\u00e9ho agensa na plod.<\/p>\n<p>Na diferenci\u00e1lnu diagnostiku kongenit\u00e1lnych CMV infekci\u00ed u novorodencov a najm\u00e4 na odl\u00ed\u0161enie od peri\/postnat\u00e1lnych infekci\u00ed je najvhodnej\u0161\u00edm materi\u00e1lom mo\u010d, respekt\u00edve sliny odobrat\u00e9 do cca 2 t\u00fd\u017ed\u0148ov po naroden\u00ed die\u0165a\u0165a (38). Pozitivita potvrd\u00ed infekciu, ktor\u00e1 m\u00f4\u017ee by\u0165 symptomatick\u00e1 alebo asymptomatick\u00e1. Pri lie\u010dbe \u00a0symptomatick\u00fdch \u00a0infekci\u00ed sa zvykne monitorova\u0165 mno\u017estvo \u00a0DNA v\u00edrusu v perif\u00e9rnej \u00a0krvi, pr\u00edpadne paralelne \u00a0i v inom biologickom \u00a0materi\u00e1li (napr\u00edklad mo\u010d, BAL, ascites) kvantitat\u00edvnou PCR met\u00f3dou (30, 38).<\/p>\n<p>Probl\u00e9mom \u00a0je retrospekt\u00edvny d\u00f4kaz kongenit\u00e1lnej \u00a0infekcie u det\u00ed, u ktor\u00fdch sa klinick\u00e9 pr\u00edznaky prejavia oneskorene a pr\u00edtomnos\u0165 akt\u00edvnej CMV infekcie sa u\u017e ned\u00e1 dok\u00e1za\u0165. Na retrospekt\u00edvne stanovenie infekcie CMV sa m\u00f4\u017ee pou\u017ei\u0165 detekcia CMV DNA z vysu\u0161en\u00fdch \u00a0vzoriek krvi aplikovan\u00fdch hne\u010f po p\u00f4rode na tzv. perinat\u00e1lne \u00a0karty (Guthrie \u00a0cards) (42, 43, 44). Perif\u00e9rna nezrazen\u00e1 krv je vhodn\u00fdm \u00a0materi\u00e1lom \u00a0pri monitorovan\u00ed infekcie na \u00fa\u010dely v\u010dasn\u00e9ho z\u00e1chytu aktiv\u00e1cie v\u00edrusu u vysoko rizikov\u00fdch pacientov (napr\u00edklad pacienti po transplant\u00e1cii, pacienti s AIDS, nedonosen\u00ed novorodenci v riziku perinat\u00e1lnej infekcie) pomocou kvalitat\u00edvnej PCR a pri monitorovan\u00ed \u00faspe\u0161nosti terapie sledovan\u00edm v\u00edrusovej n\u00e1lo\u017ee pomocou kvantitat\u00edvnej molekul\u00e1rno-biologickej \u00a0met\u00f3dy (21, 22, 23, 24, 45, 46).<\/p>\n<p>Rezistencia CMV vo\u010di antiv\u00edrusov\u00fdm l\u00e1tkam sa st\u00e1va st\u00e1le v\u00e4\u010d\u0161\u00edm klinick\u00fdm probl\u00e9mom, najm\u00e4 pri lie\u010dbe pacientov po transplant\u00e1cii a HIV pozit\u00edvnych pacientov. Na diagnostiku rezistenci\u00ed je najviac vyu\u017e\u00edvan\u00e1 sekven\u00e1cia gen\u00f3mu CMV a sledovanie mut\u00e1ci\u00ed v \u00fasekoch k\u00f3duj\u00facich <em>U<\/em><em>L<\/em><em>97 <\/em>(g\u00e9n pre fosfotransfer\u00e1zu) alebo <em>U<\/em><em>L<\/em><em>5<\/em><em>4 <\/em>(g\u00e9n pre v\u00edrusov\u00fa DNA polymer\u00e1zu). Diagnostika \u00a0je v\u0161ak ve\u013emi n\u00e1kladn\u00e1, ned\u00e1va \u00a0kvantitat\u00edvny \u00a0v\u00fdsledok \u00a0(t. j. nevieme ko\u013eko % v\u00edrusovej popul\u00e1cie dan\u00fa mut\u00e1ciu obsahuje), a tie\u017e je n\u00e1ro\u010dn\u00e1 na interpret\u00e1ciu (m\u00f4\u017eu by\u0165 detegovan\u00e9 \u00a0i n\u00e1hodn\u00e9, irelevantn\u00e9 mut\u00e1cie), preto neb\u00fdva dostupn\u00e1 v rutinn\u00fdch laborat\u00f3ri\u00e1ch (47).<\/p>\n<p>&nbsp;<\/p>\n<p><strong>T<\/strong><strong>e<\/strong><strong>r<\/strong><strong>a<\/strong><strong>pi<\/strong><strong>a a profylaxia<\/strong><\/p>\n<p>Lie\u010dba prim\u00e1rnej, nekomplikovanej CMV infekcie u imunokompetentn\u00fdch os\u00f4b je oby\u010dajne symptomatick\u00e1 (podporn\u00e1 \u00a0terapia, pe\u010de\u0148ov\u00e1 \u00a0di\u00e9ta, obmedzenie \u00a0fyzicky n\u00e1ro\u010dn\u00fdch aktiv\u00edt). \u0160pecifick\u00e1 antiv\u00edrusov\u00e1 terapia sa pod\u00e1va len vo v\u00fdnimo\u010dn\u00fdch pr\u00edpadoch, napr\u00edklad pri meningoencefalit\u00edde, o\u010dn\u00fdch komplik\u00e1ci\u00e1ch alebo \u0165a\u017ekej pneum\u00f3nii vyvolanej CMV infekciou\/ aktiv\u00e1ciou (16).<\/p>\n<p>Na lie\u010dbu pacientov so z\u00e1va\u017en\u00fdm priebehom CMV infekcie sa oby\u010dajne pou\u017e\u00edva gancyklovir, foskarnet alebo cidofovir. Tieto lieky v\u0161ak maj\u00fa ve\u013ea ne\u017eiaducich \u00a0ved\u013eaj\u0161\u00edch \u00fa\u010dinkov, pri ktor\u00fdch medzi \u00a0najz\u00e1va\u017enej\u0161ie patr\u00ed myelotoxicita a nefrotoxicita \u00a0(48, 49). Nov\u0161ie \u00a0prepar\u00e1ty, ako napr\u00edklad brincidofovir, maribavir, leflunomid, maj\u00fa viacer\u00e9 v\u00fdhody (men\u0161ia toxicita, lep\u0161ia biologick\u00e1 \u00a0dostupnos\u0165, \u00a0vy\u0161\u0161ia \u00fa\u010dinnos\u0165 \u00a0lieku), no s\u00fa ekonomicky n\u00e1kladnej\u0161ie (50, 52, 53). Ka\u017ed\u00e9 transplanta\u010dn\u00e9 \u00a0centrum \u00a0m\u00e1 svoje algoritmy na mana\u017ement pacienta v z\u00e1vislosti od typu transplant\u00e1cie, biologick\u00fdch parametrov donora a recipienta a in\u00fdch rizikov\u00fdch faktorov. Profylaktick\u00e1 terapia sa vol\u00ed najm\u00e4 u s\u00e9ronegat\u00edvnych pr\u00edjemcov, ktor\u00fdm sa transplantuje \u0161tep\/org\u00e1n od s\u00e9ropozit\u00edvneho darcu. Preempt\u00edvna terapia sa zvykne voli\u0165 u menej \u00a0rizikov\u00fdch pacientov \u00a0(21, 22, 24). Pod\u013ea typu\u00a0 transplant\u00e1cie a \u010fal\u0161\u00edch \u00a0rizikov\u00fdch faktorov sa nastav\u00ed tzv. <em>cu<\/em><em>t<\/em><em>&#8211;<\/em><em>off <\/em>hladina v\u00edrusovej n\u00e1lo\u017ee, po prekro\u010den\u00ed \u00a0ktorej sa pod\u00e1va \u0161pecifick\u00e1 antiv\u00edrusov\u00e1 l\u00e1tka. \u010eal\u0161ou mo\u017enos\u0165ou \u00a0pri aktiv\u00e1cii CMV je redukcia imunosupresie, pod\u00e1vanie intraven\u00f3zneho imunoglobul\u00ednu \u00a0alebo transfer <em>e<\/em><em>x vivo <\/em>upraven\u00fdch klonov cytotoxick\u00fdch T-lymfocytov \u0161pecifick\u00fdch proti CMV, izolovan\u00fdch od darcu transplant\u00e1tu \u00a0(25, 36, 54).<\/p>\n<p>\u0160pecifick\u00e1 antiv\u00edrusov\u00e1 terapia nie je vhodn\u00e1 na aplik\u00e1ciu v gravidite. Kladn\u00fd efekt zabr\u00e1nenia \u0165a\u017ek\u00e9ho po\u0161kodenia plodu sa pozoroval napr\u00edklad podan\u00edm hyperim\u00fanneho imunoglobul\u00ednu matke intraven\u00f3zne (raz mesa\u010dne a\u017e do p\u00f4rodu), respekt\u00edve intraamniotickou inf\u00faziou alebo inf\u00faziou do pupo\u010dn\u00edkovej \u017eily (55, 56). Pri laborat\u00f3rne \u00a0potvrdenej kongenit\u00e1lnej \u00a0CMV infekcii s\u00fa symptomatick\u00ed novorodenci oby\u010dajne lie\u010den\u00ed gancyklovirom\/valgancyklovirom (57, 58). Na profylaktick\u00fa terapiu asymptomatick\u00fdch \u00a0novorodencov \u00a0nie je jednotn\u00fd \u00a0n\u00e1zor. Zatia\u013e nie je mo\u017en\u00e9 definova\u0165, u ktor\u00fdch z nich sa v priebehu \u00a0rokov prejavia neskor\u00e9 n\u00e1sledky kongenit\u00e1lnej \u00a0infekcie, ako napr\u00edklad strata sluchu, aby boli cielene lie\u010den\u00ed len t\u00edto pacienti. Vzh\u013eadom na toxicitu prepar\u00e1tu a mo\u017en\u00e9 riziko vzniku an\u00e9mie v d\u00f4sledku pod\u00e1vania antiv\u00edrusovej l\u00e1tky sa v s\u00fa\u010dasnosti sk\u00f4r odpor\u00fa\u010da \u00a0pravideln\u00e9 monitorovanie die\u0165a\u0165a v \u0161pecializovan\u00fdch ambulanci\u00e1ch (napr\u00edklad ORL, o\u010dn\u00e9 oddelenie) po\u010das \u00a0nieko\u013ek\u00fdch rokov po naroden\u00ed pre v\u010dasn\u00fa intervenciu v pr\u00edpade rozvoja senzorineur\u00e1lnej poruchy \u00a0(podanie \u00a0gancykloviru, logopedick\u00e9 cvi\u010denia, kochle\u00e1rny \u00a0implant\u00e1t) \u00a0(59, 60). \u010eal\u0161\u00edm probl\u00e9mom z h\u013eadiska ekonomick\u00fdch \u00a0n\u00e1kladov sa jav\u00ed ot\u00e1zka zavedenia \u00a0plo\u0161n\u00e9ho \u00a0skr\u00edningu novorodencov na selekciu det\u00ed s asymptomatickou kongenit\u00e1lnou CMV infekciou, ktor\u00e9 by dan\u00e9mu monitoringu malo predch\u00e1dza\u0165.<\/p>\n<p>Pri postnat\u00e1lnych \u00a0infekci\u00e1ch b\u00fdva lie\u010dba antivirotikami indikovan\u00e1 v z\u00e1vislosti od klinick\u00e9ho stavu die\u0165a\u0165a. V r\u00e1mci prevencie proti postnat\u00e1lnej CMV infekcii u nedonosencov sa odpor\u00fa\u010da pod\u00e1va\u0165 matersk\u00e9 mlieko po \u0161etrnej tepelnej inaktiv\u00e1cii (\u00fadajne je optim\u00e1lne \u00a0zahriatie 5 min\u00fat na 72 \u00baC) (61).<\/p>\n<p>Mo\u017enosti prevencie kongenit\u00e1lnej CMV infekcie a prevencie alebo aspo\u0148 zmiernenia CMV ochoren\u00ed u imunosuprimovan\u00fdch \u00a0pacientov pomocou vakcin\u00e1cie s\u00fa zatia\u013e v \u0161t\u00e1diu v\u00fdskumu. Viacer\u00e9 vakc\u00edny u\u017e boli testovan\u00e9 na vybran\u00fdch skupin\u00e1ch pacientov: \u017eiv\u00e1 atenuovan\u00e1 \u00a0vakc\u00edna, rekombinantn\u00e9 vakc\u00edny, DNA vakc\u00edna alebo subjednotkov\u00e1 \u00a0vakc\u00edna (obsahuj\u00faca \u00a0glykoprote\u00edn \u00a0B) (25, 29, 62).<\/p>\n<p>&nbsp;<\/p>\n<p><strong>L<\/strong><strong>it<\/strong><strong>e<\/strong><strong>ra<\/strong><strong>t<\/strong><strong>\u00fa<\/strong><strong>ra<\/strong><\/p>\n<ol>\n<li>Raj\u010d\u00e1ni J, \u010ciampor F. <em>L<\/em><em>e<\/em><em>k\u00e1rska virol\u00f3gia. <\/em>Bratislava: Veda; 2006: 574.<\/li>\n<li>Klein M, Schoppel K, Amvrossiadis N, et al. Strain-Specific Neutralization \u00a0of Human \u00a0Cytomegalovirus Isolates by Human \u00a0Sera. <em>J Virol. <\/em>1999;73(2):878\u201388<\/li>\n<li>Boeckh M, Leisenring W, Riddell SR, et al. 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Prenatal diagnosis of congenital \u00a0cytomegalovirus infection: prospective study of 237 pregnancies at risk. <em>O<\/em><em>bstet. \u00a0<\/em><em>G<\/em><em>y<\/em><em>ne<\/em><em>c<\/em><em>o<\/em><em>l<\/em>. 2000;95:881\u2013888.<\/li>\n<\/ol>\n<ol start=\"42\">\n<li>Boppana SB, Ross SA, Novak Z, et al. for the National Institute on Deafness and Other Communication \u00a0Disorders CMV and Hearing Multicenter Screening (CHIMES) Study: Dried blood spot real-time polymerase chain reaction assays to screen newborns\u00a0 for congenital cytomegalovirus infection. <em>J<\/em><em>AM<\/em><em>A<\/em><em>. <\/em>2010;303(14):1375\u20131382.<\/li>\n<\/ol>\n<ol start=\"43\">\n<li>Misono S, Sie KCY, Weiss NS, et al. Congenital Cytomegalovirus Infection in Pediatric Hea- ring Loss. <em>A<\/em><em>r<\/em><em>ch Otolaryngol Head Neck Surg. <\/em>2011;137(1):47\u201353.<\/li>\n<li>Scanga L, Chaing S, Powell C, et al. Diagnosis of human congenital cytomegalovirus infection by amplification of viral DNA from dried blood spots on perinatal cards. <em>J Mol Diagnost.\u00a0<\/em>2006;8(2):240\u2013245.<\/li>\n<\/ol>\n<ol start=\"45\">\n<li>Hu\u010dkov\u00e1 D, Koll\u00e1rov\u00e1 K, Jan\u010dovi\u010dov\u00e1 K, et al. Monitoring CMV ochorenia \u00a0u pacienta po transplant\u00e1cii obli\u010dky a u pacienta po TKB pomocou \u00a0real-time PCR. <em>K<\/em><em>MI<\/em><em>L<\/em><em>. <\/em>2005;11(5):176\u2013181.<\/li>\n<li>Razonable RR, Haydenb RT. Clinical \u00a0Utility of Viral Load in Management \u00a0of Cytomegalovirus Infection after Solid Organ Transplantation. <em>Clin Microbiol Rev. <\/em>2013;26(4):703\u2013727.<\/li>\n<\/ol>\n<ol start=\"47\">\n<li>Drew WL. Cytomegalovirus Resistance Testing: Pitfalls and Problems for the Clinician.\u00a0<em>Clin Infect Dis. <\/em>2010;50(5):733\u2013736.<\/li>\n<\/ol>\n<ol start=\"48\">\n<li>Deray G, Martinez F, Katlama C, et al. Foscarnet \u00a0nephrotoxicity: mechanism, incidence and prevention. <em>A<\/em><em>m J Nephrol. <\/em>1989;9:316\u2013321.<\/li>\n<li>Sommadosi JP, Carlisle R. Toxicity of 3\u00b4-azido-3\u00b4-deoxythymidine and 9-(1,3-dihydroxymethyl) guanine for normal human hematopoietic progenitor cells in vitro. <em>A<\/em><em>n<\/em><em>timicrob <\/em><em>Agents\u00a0<\/em><em>Chemother. <\/em>1987;31:452\u2013454.<\/li>\n<\/ol>\n<ol start=\"50\">\n<li>Alain S, Revest M, Veyer D, et al. Maribavir use in practice for cytomegalovirus infection in French transplantation centers. <em>T<\/em><em>r<\/em><em>a<\/em><em>n<\/em><em>splant Proc. <\/em>2013;45(4):1603\u20131607.<\/li>\n<li>Chong AS, Zeng H, Knight DA, et al. Concurrent antiviral and immunosuppressive activities of leflunomide \u00a0in vivo. <em>A<\/em><em>m J Transplant. <\/em>2006;6:69\u201375.<\/li>\n<\/ol>\n<ol start=\"52\">\n<li>McGregor A, Yeon Choi \u00a0K. Cytomegalovirus \u00a0Antivirals and Development \u00a0of Improved Animal Models. <em>E<\/em><em>x<\/em><em>p<\/em><em>e<\/em><em>r<\/em><em>t Opin Drug Metab Toxicol. <\/em>2011;7(10):1245\u20131265.<\/li>\n<li>Marcelin JR, Beam E, Razonable RR. Cytomegalovirus \u00a0infection in liver transplant recipients:\u00a0Updates on clinical management. <em>W<\/em><em>orl<\/em><em>d Journal of Gastroenterology. <\/em>2014;20(31):10658\u201310667.<\/li>\n<\/ol>\n<ol start=\"54\">\n<li>Sokos DR, Berger M,Lazarus HM.Intravenous immunoglobulin:\u00a0appropriate indications and uses in hematopoietic stem cell transplantation. <em>Biol Blood Marrow Transplant. <\/em>2002;8(3):117\u2013130.<\/li>\n<\/ol>\n<ol start=\"55\">\n<li>Nigro G, Adler SP, Parruti G, et al. Immunoglobulin Therapy of Fetal Cytomegalovirus In- fection Occurring in the First Half of Pregnancy \u2013 A Case-Control Study of the Outcome in Children. <em>J Infect Dis. <\/em>2012;205(2):215\u2013227.<\/li>\n<li>Nigro G, Adler SP, La Torre R, et al. for the Congenital Cytomegalovirus Collaborating Group: Passive Immunization during Pregnancy for Congenital Cytomegalovirus Infection. <em>N Engl J Med. <\/em>2005;353:1350\u20131362.<\/li>\n<li>Morton CC, Nance WE. Newborn hearing screening \u2013 a silent revolution. <em><em>N Engl J Med.<\/em><\/em><\/li>\n<li>Lackner A, Acham A, Alborno T, et al. Effect on hearing of ganciclovir therapy for asymptomatic congenital cytomegalovirus infection: four to 10 year follow up. <em><em>J Laryngol Otol.\u00a0<span style=\"font-size: inherit;\">2009;123(4):391\u2013396.\u00a0<\/span><span style=\"font-size: inherit;\">2006;354(20):2151\u20132164.<\/span><\/em><\/em><\/li>\n<li>Amir J, Wolf DG, Levy I. Treatment of symptomatic congenital\u00a0 cytomegalovirus \u00a0infection with intravenous ganciclovir followed by long-term \u00a0oral valganciclovir. <em>E<\/em><em>u<\/em><em><em>r J Pediatr.\u00a02010;169(9):1061\u20137.<\/em><\/em><\/li>\n<li>Nassetta L, Kimberlin D, Whitley \u00a0R. Treatment of congenital cytomegalovirus infection:implications for future therapeutic strategies. <em>J Antimicrob Chemother. <\/em>2009;63(5):862\u2013867.<\/li>\n<li>Hamprecht K, Maschmann J, M\u00fcller D, et al. Cytomegalovirus (CMV) inactivation in breast milk: reassessment of pasteurization \u00a0and freeze-thawing. <em>P<\/em><em>e<\/em><em>diat<\/em><em>r Res. <\/em>2004;56(4):529\u201335.<\/li>\n<li>Sung H, Schleiss MR. Update on the current status of cytomegalovirus vaccines<em>. <\/em><em>E<\/em><em>x<\/em><em>p<\/em><em>e<\/em><em>r<\/em><em>t\u00a0<em>R<\/em><em>e<\/em><em>v Vaccines. <\/em>2010;9(11):1303\u20131314.<br \/>\n<\/em><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"<p>*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf\u00a0 attachment at the end of the paper. &nbsp; Cytomegalov\u00edrus Cytomegalov\u00edrus \u013eud\u00ed (CMV, HCMV, \u013eudsk\u00fd herpesv\u00edrus 5, HHV-5) patr\u00ed medzi \u013eudsk\u00e9 herpetick\u00e9 v\u00edrusy; konkr\u00e9tne do pod\u010de\u013eade \u00a0Betaherpesvirinae, do ktorej sa zara\u010fuje spolu s ostatn\u00fdmi cytomegalov\u00edrusmi\u00a0 in\u00fdch cicavcov a<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"footnotes":""},"categories":[292],"tags":[644,645,646,647,564],"class_list":["post-1042","post","type-post","status-publish","format-standard","hentry","category-microbiology","tag-cytomegalovirus","tag-laboratory-diagnosis","tag-primary-infection","tag-secondary-infection","tag-therapy","typ_clanku-review-article"],"acf":{"upload_clanok":{"ID":1043,"id":1043,"title":"Newslab_2_2016_Infekcie vyvolan\u00e9 cytomegalov\u00edrusom_Hu\u010dkov\u00e1_Koll\u00e1rov\u00e1","filename":"Newslab_2_2016_Infekcie-vyvolan\u00e9-cytomegalov\u00edrusom_Hu\u010dkov\u00e1_Koll\u00e1rov\u00e1.pdf","filesize":262144,"url":"https:\/\/www.newslab.sk\/wp-content\/uploads\/2017\/01\/Newslab_2_2016_Infekcie-vyvolan\u00e9-cytomegalov\u00edrusom_Hu\u010dkov\u00e1_Koll\u00e1rov\u00e1.pdf","link":"https:\/\/www.newslab.sk\/en\/infections-caused-by-cytomegalovirus-diagnosis-and-therapy\/newslab_2_2016_infekcie-vyvolane-cytomegalovirusom_huckova_kollarova\/","alt":"","author":"7","description":"","caption":"","name":"newslab_2_2016_infekcie-vyvolane-cytomegalovirusom_huckova_kollarova","status":"inherit","uploaded_to":1042,"date":"2017-02-01 19:43:33","modified":"2017-02-01 19:43:33","menu_order":0,"mime_type":"application\/pdf","type":"application","subtype":"pdf","icon":"https:\/\/www.newslab.sk\/wp-includes\/images\/media\/document.png"},"strana":"78","casopis":[{"ID":991,"post_author":"7","post_date":"2017-02-01 09:43:42","post_date_gmt":"2017-02-01 08:43:42","post_content":"<ul>\r\n \t<li>Pulmonary aspergillosis<\/li>\r\n \t<li>Infections caused by cytomegalovirus \u2013 diagnosis and therapy<\/li>\r\n \t<li>Long-term molecular remission as a precondition for successful pregnancy in patients with chronic myelocyte leukemia<\/li>\r\n \t<li>Chromosome 11 aberrations in a patient with acute myeloid leukemia \u2013 a case study<\/li>\r\n \t<li>New biomarkers in diagnosing IgA nephropathy<\/li>\r\n<\/ul>","post_title":"newslab","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"newslab-2016-02","to_ping":"","pinged":"","post_modified":"2017-08-16 21:36:48","post_modified_gmt":"2017-08-16 19:36:48","post_content_filtered":"","post_parent":0,"guid":"http:\/\/www.newslab.sk\/casopis\/newslab-2016-02\/","menu_order":0,"post_type":"casopis","post_mime_type":"","comment_count":"0","filter":"raw"}],"abstrakt":"<p>As with other human herpesviruses, overcoming of primary cytomegalovirus (CMV) infection is followed by persistent lifelong infection, accompanied by a period of latency and reactivation, which is usually associated with asymptomatic viral shedding in bodily secretions. In immunocompetent individuals, CMV infection and\/or reactivation are usually asymptomatic. In case some clinical symptoms are present, they are usually self-limiting without the need for any specific therapy. The infection is controlled by the host immune system, especially by the cellular immunity.<\/p>\n<p>Primary and secondary CMV infections represent a serious clinical problem in pregnant women (the risk of congenital infections), new-borns and severely immunocompromised individuals (transplant recipients, patients with AIDS, cancer patients).<\/p>\n<p>Laboratory diagnosis of uncomplicated CMV manifestations is based on the determination of specific antibodies. Severe neurological\/ocular CMV complications are complemented by autochthonous antibody production testing and CMV DNA detection in appropriate biological material (cerebrospinal fluid, aqueous\/vitreous humour, whole blood). In pregnant women, the differential diagnosis of CMV congenital infection is usually based on serological testing of anti-CMV IgM\/IgG and avidity of anti-CMV IgG in serum; however, in case that any abnormalities are found in serologic profile of the mother or ultrasound\/MRI testing of the fetus, CMV DNA quantitative real-time PCR of amniotic fluid is recommended. In immunocompromised patients, monitoring of CMV DNA load from a suitable biological material by quantitative molecular-biological method plays a key role in patient management.<\/p>\n<p><strong>Key words:<\/strong> cytomegalovirus, laboratory diagnosis, primary infection, secondary infection, therapy<\/p>\n<p>&nbsp;<\/p>\n"},"_links":{"self":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1042","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/comments?post=1042"}],"version-history":[{"count":0,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1042\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/media?parent=1042"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/categories?post=1042"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/tags?post=1042"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}