{"id":1774,"date":"2019-11-04T13:10:26","date_gmt":"2019-11-04T12:10:26","guid":{"rendered":"https:\/\/www.newslab.sk\/?p=1774"},"modified":"2019-11-04T13:59:45","modified_gmt":"2019-11-04T12:59:45","slug":"accidental-capture-of-the-toxic-strain-corynebacterium-diphteriae","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/accidental-capture-of-the-toxic-strain-corynebacterium-diphteriae\/","title":{"rendered":"Accidental capture of the toxic strain Corynebacterium diphteriae"},"content":{"rendered":"

*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf attachment at the end of the paper.<\/strong><\/span><\/p>\n

 <\/p>\n

\u00davod<\/strong><\/p>\n

Epidemiol\u00f3gia<\/em><\/strong><\/p>\n

V predvakcina\u010dnej \u00e9re bola dift\u00e9ria jednou z naj\u010dastej\u0161ie sa vyskytuj\u00facich infek\u010dn\u00fdch ochoren\u00ed u det\u00ed s vysokou \u00famrtnos\u0165ou. Po vytvoren\u00ed toxoidovej vakc\u00edny v r. 1923 a n\u00e1sledne po zaveden\u00ed povinn\u00e9ho o\u010dkovania v roku 1946 sa toto ochorenie podarilo prakticky celosvetovo eliminova\u0165(1). Av\u0161ak na konci 80. rokov vypukla vo ve\u013ek\u00fdch mest\u00e1ch v Rusku rozsiahla epid\u00e9mia, ktor\u00e1 sa do roku 1995 roz\u0161\u00edrila do v\u0161etk\u00fdch postsovietskych kraj\u00edn. Celkovo bolo zaznamenan\u00fdch 157 000 pr\u00edpadov s 5 000 \u00famrtiami. Pr\u00ed\u010dinami boli jednak environment\u00e1lne faktory, ako migr\u00e1cia obyvate\u013estva a pokles socioekonomick\u00fdch podmienok, ale aj chyby v o\u010dkovacom programe a v z\u00e1sobovan\u00ed o\u010dkovac\u00edmi l\u00e1tkami(2). V\u00e4\u010d\u0161ina z nakazen\u00fdch pacientov dosiahla vek viac ako 15 rokov. K\u013e\u00fa\u010dov\u00e9 bolo spojenie dvoch faktorov, a to ve\u013ek\u00fd po\u010det neimunizovan\u00fdch dospel\u00fdch a nedostato\u010dn\u00e1 vakcin\u00e1cia u det\u00ed. Medzi pacientov s \u0165a\u017ek\u00fdm priebehom patrili dospel\u00ed vo veku 40 a\u017e 49 rokov, u ktor\u00fdch sa v ich detskom veku vakcin\u00e1cia DTP (diphteria \u2013 tetanus \u2013 pertussis) e\u0161te len zav\u00e1dzala. U mlad\u0161\u00edch pacientov sa predpoklad\u00e1, \u017ee zlyhala tzv. imunologick\u00e1 pam\u00e4\u0165, k \u010domu prispel aj vekov\u00fd posun preo\u010dkovania, zo 6 na 9 rokov. Po celoplo\u0161nej imuniz\u00e1cii obyvate\u013eov s odli\u0161n\u00fdm re\u017eimom aplik\u00e1cie vakc\u00edny sa dosiahlo zn\u00ed\u017eenie v\u00fdskytu ochorenia koncom roka 2001 na 12 % a n\u00e1sledne na 0,2 % koncom roka 2015(3). V s\u00fa\u010dasnosti sa \u00famrtnos\u0165 na dift\u00e9riu napriek adekv\u00e1tnej lie\u010dbe pohybuje medzi 5 \u2013 10 % u det\u00ed mlad\u0161\u00edch ako 5 rokov a u os\u00f4b nad 40 rokov dosahuje a\u017e 20 %. U nelie\u010den\u00fdch pacientov je \u00famrtnos\u0165 a\u017e u polovice pr\u00edpadov(2). Odhaduje sa, \u017ee celosvetovo sa ro\u010dne vyskytuje pribli\u017ene 5 000 pr\u00edpadov ochoren\u00ed(3). Na Slovensku bol posledn\u00fd pr\u00edpad ochorenia zaznamenan\u00fd v roku 1980(4).<\/p>\n

\u00a0<\/em><\/strong><\/p>\n

P\u00f4vodca ochorenia a jeho klinick\u00e9 prejavy<\/em><\/strong><\/p>\n

P\u00f4vodcom n\u00e1kazy je v\u00fdlu\u010dne \u013eudsk\u00fd patog\u00e9n Corynebacterium diphtheriae<\/em>, grampozit\u00edvna fakultat\u00edvne anaer\u00f3bna, pleomorfn\u00e1 bakt\u00e9ria (obr\u00e1zok 1)<\/em><\/strong>. Mikroskopicky je charakteristick\u00e1 palis\u00e1dovit\u00fdm usporiadan\u00edm s\u00a0metachromatick\u00fdmi granulami v cytoplazme, ktor\u00e9 mo\u017eno dok\u00e1za\u0165 farben\u00edm pod\u013ea Alberta alebo Neissera. Rastie na be\u017en\u00fdch p\u00f4dach s\u00a0pr\u00edmesou krvi alebo s\u00e9ra s tvorbou hemol\u00fdzy (obr\u00e1zok 2)<\/em><\/strong>. Pod\u013ea vzh\u013eadu kol\u00f3ni\u00ed rozli\u0161ujeme \u0161tyri biotypy: gravis, mitis, intermedius a belfanti(5). <\/em>Na selekt\u00edvno-diagnostick\u00fdch p\u00f4dach so so\u013eami tel\u00faru tvor\u00ed v d\u00f4sledku jeho redukcie \u010diernohned\u00e9 kol\u00f3nie so sivou z\u00f3nou (obr\u00e1zok 3)<\/em><\/strong>.<\/p>\n

Nosi\u010dstvo tejto bakt\u00e9rie v nosohltane alebo na ko\u017ei sa vyskytuje pribli\u017ene u 3 \u2013 5 % \u013eud\u00ed, av\u0161ak v popul\u00e1cii s\u00a0dostato\u010dnou hygienou a postvakcina\u010dnou imunitou zriedkavo vyvol\u00e1va ochorenie. Bakt\u00e9ria m\u00f4\u017ee pre\u017e\u00edva\u0165 t\u00fd\u017edne v\u00a0prachu a na kontaminovan\u00fdch predmetoch. Zdrojom n\u00e1kazy je chor\u00fd \u010dlovek, ktor\u00fd sa infikuje vdychovan\u00edm kontaminovan\u00e9ho vzduchu. Ochorenie s inkuba\u010dnou dobou 2 a\u017e 5 dn\u00ed m\u00f4\u017ee postihova\u0165 v\u0161etky muk\u00f3zne sliznice, av\u0161ak Corynebacterium diphteriae <\/em>preva\u017ene infikuje respira\u010dn\u00fd trakt a \u010dast\u00e1 je i ko\u017en\u00e1 forma(5). Klinick\u00fd obraz z\u00e1vis\u00ed od stavu imunity hostite\u013ea a miesta vstupu infekcie. M\u00f4\u017ee prebieha\u0165 od asymptomatickej koloniz\u00e1cie cez mierne respira\u010dn\u00e9 ochorenie a\u017e po fulminantn\u00fa dift\u00e9riu s rozvojom myokardit\u00eddy, polyneurit\u00eddy a toxickej nefrit\u00eddy(6). Naj\u010dastej\u0161\u00edm miestom vstupu bakt\u00e9rie do organizmu s\u00fa horn\u00e9 d\u00fdchacie cesty, kde sa tvoria typick\u00e9 pseudomembr\u00e1ny z fibr\u00ednu, nekrotick\u00fdch buniek a leukocytov\u00a0(obr\u00e1zok 4)<\/em><\/strong>. Pseudomembr\u00e1ny vznikaj\u00face na sliznici d\u00fdchac\u00edch ciest sa m\u00f4\u017eu uvo\u013eni\u0165 so vznikom mechanickej ob\u0161trukcie s n\u00e1sledn\u00fdm dusen\u00edm a zakrv\u00e1can\u00edm. Ochorenie je sprev\u00e1dzan\u00e9 v\u00fdrazn\u00fdm zduren\u00edm lymfatick\u00fdch uzl\u00edn a vysokou teplotou. Ko\u017en\u00e1 forma dift\u00e9rie sa vyskytuje preva\u017ene v tropick\u00fdch krajin\u00e1ch, pri\u010dom klinick\u00fd obraz var\u00edruje od ko\u017en\u00fdch eflorescenci\u00ed a\u017e po chronick\u00e9 nehojace sa vredy. Bakt\u00e9rie sa postupne uvo\u013e\u0148uj\u00fa z l\u00e9zi\u00ed, ktor\u00e9 sl\u00fa\u017eia ako rezervo\u00e1r pri \u0161\u00edren\u00ed infekcie. Infekciozita pacienta s ko\u017enou formou trv\u00e1 dlh\u0161ie ako pri respira\u010dnej forme. T\u00e1to forma dift\u00e9rie postihuje preva\u017ene \u013eud\u00ed s ni\u017e\u0161\u00edm socioekonomick\u00fdm statusom. Hlavn\u00fdm faktorom patogenity je difterick\u00fd tox\u00edn, k\u00f3dovan\u00fd tox <\/em>g\u00e9nom, ktor\u00fd sa \u0161\u00edri prostredn\u00edctvom beta-bakteriof\u00e1gu(7). Na molekulovej \u00farovni je tox\u00edn zlo\u017een\u00fd z dvoch podjednotiek (polypeptid A a B). Polypeptid B sa via\u017ee na cytoplazmatick\u00fa membr\u00e1nu bunky a umo\u017e\u0148uje polypeptidu A prechod do cytoplazmy s n\u00e1slednou blok\u00e1dou proteosynt\u00e9zy na riboz\u00f3moch(5). Produkcia tox\u00ednu sa in vitro <\/em>dokazuje precipita\u010dnou reakciou s protil\u00e1tkami, tzv. Elekov\u00fdm testom a in vivo <\/em>na mor\u010dat\u00e1ch. PCR test sl\u00fa\u017ei len na d\u00f4kaz pr\u00edtomnosti g\u00e9nu, nie v\u0161ak tvorby tox\u00ednu(2).<\/p>\n

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Terapia a prevencia dift\u00e9rie<\/em><\/strong><\/p>\n

V priebehu dvadsiatych rokov 19. storo\u010dia bola dift\u00e9ria klinicky vy\u010dlenen\u00e1 od in\u00fdch foriem ang\u00edny. V roku 1883 Klebs dok\u00e1zal, \u017ee Corynebacterium diphteriae <\/em>je vyvol\u00e1vate\u013eom dift\u00e9rie, o rok nesk\u00f4r ju L\u04e7effler vykultivoval z\u00a0nazofarynge\u00e1lnej dutiny. V roku 1888 Roux a Yersin dok\u00e1zali, \u017ee hlavn\u00fdm faktorom patogenity je difterick\u00fd exotox\u00edn(7). V roku 1923 bola vyn\u00e1jden\u00e1 vakc\u00edna proti z\u00e1\u0161krtu, ktor\u00e1 sa vo ve\u013ekom za\u010dala pou\u017e\u00edva\u0165 v USA a ostatn\u00fdch industrializovan\u00fdch krajin\u00e1ch(3). Lie\u010dbou ak\u00fatnej infekcie je podanie antitox\u00ednu a\u00a0antibiotick\u00e1 lie\u010dba. Antitox\u00edn neutralizuje vo\u013en\u00fd cirkuluj\u00faci tox\u00edn, av\u0161ak nep\u00f4sob\u00ed na tox\u00edn naviazan\u00fd na bunky(3). Antibiotick\u00e1 lie\u010dba eliminuje bakt\u00e9rie, a t\u00fdm zabra\u0148uje \u010fal\u0161ej produkcii tox\u00ednu.<\/p>\n

Liekmi vo\u013eby s\u00fa penicil\u00edn a erytromyc\u00edn(9). U pacientov s alergiou na penicil\u00edn alebo netoleruj\u00facich erytromyc\u00edn sa odpor\u00fa\u010da rifampic\u00edn a klindamyc\u00edn. Po 48 hodin\u00e1ch antibiotickej terapie sa pacient u\u017e nepova\u017euje za infek\u010dn\u00e9ho(10). Imunitu mo\u017eno z\u00edska\u0165 o\u010dkovan\u00edm alebo prekonan\u00edm ochorenia sp\u00f4soben\u00e9ho toxick\u00fdm kme\u0148om. O\u010dkovanie nechr\u00e1ni pred os\u00eddlen\u00edm samotnou bakt\u00e9riou, ale br\u00e1ni vzniku a rozvoju ochorenia. Pod\u013ea \u0161tatist\u00edk v\u00fdraznej\u0161\u00ed \u00fastup ochrany po o\u010dkovan\u00ed nast\u00e1va po \u0161tyridsiatke, najohrozenej\u0161\u00ed s\u00fa p\u00e4\u0165desiatnici(11). O\u010dkuje sa difterick\u00fdm toxoidom, \u010do je tox\u00edn upraven\u00fd formal\u00ednom, pri ktorom doch\u00e1dza k strate toxicity a\u00a0zachovaniu imunogenity. Toxoid vyvol\u00e1va tvorbu neutralizuj\u00facich protil\u00e1tok. Hladiny neutraliza\u010dn\u00fdch protil\u00e1tok mo\u017eno stanovi\u0165 z perif\u00e9rnej krvi. V minulosti sa pou\u017e\u00edval ko\u017en\u00fd Shickov test, pri ktorom sa intraderm\u00e1lne pod\u00e1valo mal\u00e9 mno\u017estvo difterick\u00e9ho toxoidu so sledovan\u00edm eryt\u00e9mu a zdurenia v\u00a0mieste vpichu.<\/p>\n

Prv\u00e1 d\u00e1vka o\u010dkovacej l\u00e1tky sa pod\u00e1va de\u0165om v\u00a0kombin\u00e1cii s o\u010dkovacou l\u00e1tkou proti \u010fal\u0161\u00edm piatim ochoreniam (tetanus, \u010dierny ka\u0161e\u013e, v\u00edrusov\u00e1 hepatit\u00edda B, hemofilov\u00e9 invaz\u00edvne infekcie, detsk\u00e1 obrna). Z\u00e1kladn\u00e9 o\u010dkovanie sa sklad\u00e1 z\u00a0troch d\u00e1vok vakc\u00edny, podan\u00fdch v 3., 5. a 11. mesiaci veku die\u0165a\u0165a. Na dosiahnutie ochrannej hladiny protil\u00e1tok a\u017e do dospelosti je potrebn\u00e9 preo\u010dkovanie det\u00ed v 6. a 13. roku \u017eivota. Dvojkombin\u00e1ciou o\u010dkovacej l\u00e1tky proti tetanu a z\u00e1\u0161krtu sa preo\u010dkov\u00e1vaj\u00fa dospel\u00e9 osoby ka\u017ed\u00fdch 15 rokov(12).<\/p>\n

\u00a0<\/strong><\/p>\n

Kazuistika<\/strong><\/p>\n

Pri kultiva\u010dnom vy\u0161etren\u00ed materi\u00e1lu z horn\u00fdch d\u00fdchac\u00edch ciest (v\u00fdter z nosa) u 14-ro\u010dn\u00e9ho pacienta s diagn\u00f3zou ak\u00fatnej s\u00ednusit\u00eddy bol za\u010diatkom decembra v roku 2018 zachyten\u00fd a identifikovan\u00fd met\u00f3dou hmotnostnej spektrometrie (MALDI-TOF, Bruker, Nemecko) kme\u0148 Corynebacterium diphteriae.<\/em><\/p>\n

Pre verifik\u00e1ciu identifik\u00e1cie a zistenie produkcie tox\u00ednu bol kme\u0148 d\u0148a 11. 12. 2018 zaslan\u00fd do N\u00e1rodn\u00e9ho referen\u010dn\u00e9ho centra pre dift\u00e9riu (NRC) v Ko\u0161iciach. Toxicita kme\u0148a bola testovan\u00e1 na bunkovej l\u00ednii Vero, \u010do s\u00fa bunkov\u00e9 l\u00ednie z\u00edskan\u00e9 z epiteli\u00e1lnych buniek obli\u010diek op\u00edc druhu makak. S v\u00fdsledkom kultiva\u010dn\u00e9ho vy\u0161etrenia bol obozn\u00e1men\u00fd obvodn\u00fd pediater a region\u00e1lny epidemiol\u00f3g. Vy\u0161etren\u00edm kvalitat\u00edvnej antibiotickej (ATB) citlivosti dif\u00faznym diskov\u00fdm testom (obr\u00e1zok 5) <\/em><\/strong>sa zistila citlivos\u0165 kme\u0148a na sledovan\u00e9 antibiotik\u00e1, t. j. penicil\u00edn, klindamyc\u00edn, ciprofloxac\u00edn, gentamic\u00edn, tetracykl\u00edn a linezolid (tabu\u013eka 1)<\/em><\/strong>.<\/p>\n

D\u0148a 27. 12. 2018 bol doru\u010den\u00fd v\u00fdsledok vy\u0161etrenia z\u00a0NRC pre dift\u00e9riu s potvrdenou identifik\u00e1ciou: Corynebacterium<\/em> diphteriae <\/em>biotyp gravis, <\/em>s produkciou tox\u00ednu<\/strong>. Od obvodn\u00e9ho pediatra a epidemiol\u00f3ga bola doplnen\u00e1 soci\u00e1lna, rodinn\u00e1 a cestovate\u013esk\u00e1 anamn\u00e9za. Ide o 14-ro\u010dn\u00e9ho chlapca r\u00f3mskeho p\u00f4vodu s r\u00e1z\u0161tepom podnebia, u\u00a0ktor\u00e9ho doch\u00e1dza k \u010dast\u00fdm recid\u00edvam ak\u00fatnej s\u00ednusit\u00eddy. V\u00a0na\u0161om laborat\u00f3riu boli u tohto pacienta opakovane kultiva\u010dne identifikovan\u00e9 Streptococcus pyogenes <\/em>a Moraxella catharralis<\/em> s dobrou citlivos\u0165ou na testovan\u00e9 antibiotik\u00e1. Na z\u00e1klade poskytnut\u00fdch inform\u00e1ci\u00ed od pediatra je pacient riadne o\u010dkovan\u00fd pod\u013ea o\u010dkovacieho kalend\u00e1ra, \u010domu zodpoved\u00e1 aj plne ochrann\u00e1 hladina protil\u00e1tok doplnen\u00e1 vy\u0161etren\u00edm v NRC pre dift\u00e9riu s hodnotou 0,65536 IU\/ml. Pacient b\u00fdva v obci Brekov (okres Humenn\u00e9) s dvoma sestrami, rodi\u010dmi a so starou matkou v dobr\u00fdch soci\u00e1lnych podmienkach. Do Humenn\u00e9ho doch\u00e1dza k svojmu obvodn\u00e9mu pediatrovi. Kontakt s migrantmi epidemiol\u00f3g nepova\u017euje za mo\u017en\u00fd zdroj infekcie, ke\u010f\u017ee pacient nepoch\u00e1dza priamo z Humenn\u00e9ho a cesta na stanicu sa nenach\u00e1dza v bl\u00edzkosti azylov\u00e9ho centra. Kontakty v \u0161kole v Str\u00e1\u017eskom epidemiol\u00f3g nepre\u0161etroval vzh\u013eadom na ch\u00fdbaj\u00face klinick\u00e9 sympt\u00f3my typick\u00e9 pre dift\u00e9riu, ktor\u00e9 sa nezistili ani pri otorinolaryngologickom a neurologickom vy\u0161etren\u00ed. V cestovate\u013eskej anamn\u00e9ze pacient neud\u00e1va pobyt na Ukrajine, uv\u00e1dza v\u0161ak vycestovanie s rodinou do Spojen\u00e9ho kr\u00e1\u013eovstva pred \u0161tyrmi rokmi. Kultiva\u010dn\u00e9 vy\u0161etrenia ostatn\u00fdch \u010dlenov rodiny boli negat\u00edvne. Matka a star\u00e1 matka sa nepodrobili vy\u0161etreniu z d\u00f4vodu nespolupr\u00e1ce. Napriek tomu, \u017ee kultiva\u010dn\u00e9 vy\u0161etrenie sestier pacienta bolo negat\u00edvne, epidemiol\u00f3govia predpokladaj\u00fa, \u017ee ide o nosi\u010dsk\u00fd kme\u0148 z\u00edskan\u00fd v \u0161kolskom prostred\u00ed. Kontroln\u00e9 kultiva\u010dn\u00e9 vy\u0161etrenia pacienta po prelie\u010den\u00ed antibiotikami boli opakovane negat\u00edvne.<\/p>\n

\u00a0<\/strong><\/p>\n

Diskusia<\/strong><\/p>\n

U viacer\u00fdch n\u00e1chyln\u00fdch os\u00f4b sa vyvinie sk\u00f4r prechodn\u00e9 nosi\u010dstvo v nazofaryngu ako samotn\u00e9 ochorenie, o\u00a0\u010dom sved\u010d\u00ed opisovan\u00fd pr\u00edpad. Bez p\u00f4sobenia antibiot\u00edk pre\u017e\u00edva v\u00e4\u010d\u0161ina mikroorganizmov v nosohltane pribli\u017ene dva t\u00fd\u017edne, pri\u010dom chronick\u00ed nosi\u010di m\u00f4\u017eu vylu\u010dova\u0165 Corynebacterium sp.<\/em> a\u017e 6 mesiacov. Asymptomatick\u00e9 nazofarynge\u00e1lne nosi\u010dstvo je pravdepodobne vzh\u013eadom na lep\u0161\u00ed skr\u00edningov\u00fd program viac zdokumentovan\u00e9 v endemick\u00fdch regi\u00f3noch ako v oblastiach, kde sa dift\u00e9ria vyskytuje len sporadicky. Av\u0161ak aj pri podozren\u00ed na dift\u00e9riu m\u00f4\u017ee by\u0165 laborat\u00f3rna diagnostika obtia\u017ena. Je to zapr\u00ed\u010dinen\u00e9 t\u00fdm, \u017ee Corynebacterium diphteriae<\/em> je \u0165a\u017eko rozpoznate\u013en\u00e1 na be\u017enom krvnom \u010di \u010dokol\u00e1dovom agare. Navy\u0161e v\u00fdtery z d\u00fdchac\u00edch ciest od asymptomatick\u00fdch nosi\u010dov m\u00f4\u017eu obsahova\u0165 len mal\u00e9 mno\u017estvo bakt\u00e9ri\u00ed, ktor\u00e9 s\u00fa po kultiv\u00e1cii prekryt\u00e9 be\u017enou bakteri\u00e1lnou fl\u00f3rou horn\u00fdch d\u00fdchac\u00edch ciest(14). Preto sa t\u00e1to bakt\u00e9ria be\u017ene nezachyt\u00e1va, \u010do m\u00f4\u017ee skres\u013eova\u0165 re\u00e1lny epidemiologick\u00fd stav na Slovensku. <\/strong>Imunita indukovan\u00e1 vakc\u00ednou v priebehu \u017eivota kles\u00e1 a\u00a0pri nedostato\u010dnom preo\u010dkovan\u00ed po\u010det vn\u00edmav\u00fdch os\u00f4b st\u00fapa.<\/p>\n

Na z\u00e1klade s\u00e9rologickej \u0161t\u00fadie bolo zisten\u00e9, \u017ee 20 \u2013 60 % svetovej popul\u00e1cie m\u00e1 protil\u00e1tky proti dift\u00e9rii pod minim\u00e1lnou ochrannou hladinou(15). V pr\u00edpade, \u017ee d\u00f4jde k n\u00e1rastu po\u010dtu takto n\u00e1chyln\u00fdch obyvate\u013eov, existuje re\u00e1lne nebezpe\u010denstvo vypuknutia epid\u00e9mie. Aby sa tomu zabr\u00e1nilo, je nevyhnutn\u00e1 dobr\u00e1 a r\u00fdchla spolupr\u00e1ca klinick\u00fdch lek\u00e1rov, epidemiol\u00f3gov a soci\u00e1lnych pracovn\u00edkov. T\u00ed by mali kooperova\u0165 v r\u00fdchlej diagnostike a mana\u017emente jednotliv\u00fdch pr\u00edpadov ochorenia, vo vy\u0161etren\u00ed os\u00f4b, ktor\u00e9 boli v kontakte s\u00a0pacientom a imuniz\u00e1cii vybran\u00fdch skup\u00edn obyvate\u013estva s\u00a0cie\u013eom pred\u00eds\u0165 sekund\u00e1rnym n\u00e1kaz\u00e1m(16). Hrozbou pre zdravie popul\u00e1cie okrem toxick\u00fdch kme\u0148ov s\u00fa kmene, ktor\u00e9 nes\u00fa tox <\/em>g\u00e9n, av\u0161ak neprodukuj\u00fa tox\u00edn. K expresii tohto g\u00e9nu nedoch\u00e1dza v d\u00f4sledku del\u00e9cie alebo inzercie nukleotidu na A podjednotke(17). Za ur\u010dit\u00fdch okolnost\u00ed m\u00f4\u017ee by\u0165 bakteriof\u00e1g neakt\u00edvny (vysok\u00e1 koncentr\u00e1cia \u017eeleza), respekt\u00edve nemus\u00ed d\u00f4js\u0165 k expresii tox <\/em>g\u00e9nu (inzercia bakteri\u00e1lnej DNA v g\u00e9ne difterick\u00e9ho tox\u00ednu). Po expoz\u00edcii lyz\u00e1tu dvoch in\u00fdch netoxig\u00e9nnych kme\u0148ov sa m\u00f4\u017ee sta\u0165 tak\u00fdto kme\u0148 toxig\u00e9nnym v d\u00f4sledku rekombin\u00e1cie jeho DNA. To znamen\u00e1, \u017ee pr\u00edtomnos\u0165 netoxig\u00e9nnych kme\u0148ov v\u00a0popul\u00e1cii predstavuje re\u00e1lne nebezpe\u010denstvo pre ich mo\u017en\u00fa konverziu na toxig\u00e9nne kmene(18). \u010eal\u0161\u00edm zdrojom nebezpe\u010dnej infekcie m\u00f4\u017eu by\u0165 druhovo pr\u00edbuzn\u00e9 patog\u00e9ny zvierat, ak\u00fdmi s\u00fa Corynebacterium pseudotuberculosis <\/em>a Corynebacterium ulcerans<\/em>. Oba druhy m\u00f4\u017eu obsahova\u0165 beta-bakteriof\u00e1g s tox <\/em>g\u00e9nom, ktor\u00fd je schopn\u00fd lyzova\u0165 v\u0161etky tri druhy a n\u00e1sledne infikova\u0165 netoxick\u00e9 kmene Corynebacterium diphteriae.<\/em><\/p>\n

V s\u00fa\u010dasnosti okrem toxick\u00fdch kme\u0148ov, ktor\u00e9 m\u00f4\u017eu by\u0165 do na\u0161ej krajiny zavle\u010den\u00e9 z endemick\u00fdch regi\u00f3nov vr\u00e1tane kraj\u00edn v\u00fdchodnej Eur\u00f3py, narast\u00e1 v\u00fdskyt netoxick\u00fdch, ale invaz\u00edvnych kme\u0148ov napriek vysokej zao\u010dkovanosti. Tak\u00e9to kmene s\u00fa schopn\u00e9 vyvola\u0165 endokardit\u00eddu, artrit\u00eddu, bakteri\u00e9miu \u010di osteomyelit\u00eddu. Na rozdiel od toxick\u00fdch kme\u0148ov za vy\u0161\u0161iu invazivitu netoxick\u00fdch kme\u0148ov nie s\u00fa zodpovedn\u00e9 bakteriof\u00e1gy nes\u00face g\u00e9n, ale g\u00e9nov\u00e9 lokusy na chromoz\u00f3me bakt\u00e9rie. Preto je potrebn\u00e9 sledovanie molekulov\u00fdch zmien v cirkuluj\u00facich kme\u0148och, v ktor\u00fdch m\u00f4\u017ee narasta\u0165 invazivita a patogenita. Na z\u00e1klade t\u00fdchto poznatkov by bolo mo\u017en\u00e9 n\u00e1sledne vyvin\u00fa\u0165 nov\u00fa vakc\u00ednu proti netoxick\u00fdm, av\u0161ak invaz\u00edvnym kme\u0148om(19).<\/p>\n

\u00a0<\/strong><\/p>\n

Z\u00e1ver<\/strong><\/p>\n

Zachyten\u00fd kme\u0148 Corynebacterium diphteriae <\/em>izolovan\u00fd z nazofaryngu malolet\u00e9ho pacienta bol identifikovan\u00fd NRC pre dift\u00e9riu ako toxick\u00fd. Na z\u00e1klade diagn\u00f3zy a\u00a0epidemiologickej anal\u00fdzy bol tento pr\u00edpad vyhodnoten\u00fd ako v\u00fdskyt asymptomatick\u00e9ho nosi\u010dstva. Vzh\u013eadom na to, \u017ee ide o\u00a0rizikov\u00e9ho pacienta s r\u00e1z\u0161tepom podnebia, s\u00a0pravdepodobn\u00fdm kontaktom s osobami z endemick\u00fdch oblast\u00ed a mo\u017enou klesaj\u00facou postvakcina\u010dnou imunitou, je vhodn\u00e9 sledova\u0165 tohto pacienta aj v bud\u00facnosti.<\/p>\n

\u00a0<\/strong><\/p>\n

LITERAT\u00daRA<\/strong><\/p>\n

    \n
  1. Karzon DT, Edwards KM. Diphtheria outbreaks in immunized population, N Engl J Med 1988; 318: 41-43.<\/li>\n
  2. Tejpratap SP T. Diphteria, Hunter\u2019s Tropical Medicine and Emerging Infectious Disease (Ninth Edition) 2013; 402-406.<\/li>\n
  3. https:\/\/www.who.int\/immunization\/sage\/meetings\/2017\/april\/1_<\/a> Final_report_Clarke_april3.pdf<\/li>\n
  4. http:\/\/www.uvzsr.sk\/en\/index.php\/documents\/12-importance-<\/a> of-vaccination<\/li>\n
  5. Forbes BA. \u201eDid I Hear You Correctly? The Organism Identified Was Corynebacterium diphtheriae?\u201c Clinical Microbiology Newsletter 2017; 39(5): 35-41.<\/li>\n
  6. Hadfield TL, McEvoy P, Polotsky Y, et al. The pathology of diphtheria. J Infect Dis 2000; 181(1): 116-120.<\/li>\n
  7. Sangal V, Burkovski A, Hunt AC, et al. A lack of genetic basis for biovar differentiation in clinically important Corynebacterium diphtheriae from whole genome sequencing, Infection, Genetics and Evolution 2014; 21: 54-57.<\/li>\n
  8. Murphy JR. Corynebacterium diphtheriae. In: Baron EJ. Medical microbiology. Galveston, TX: University of Texas Medical Branch at Galveston 1996: 1-13.<\/li>\n
  9. American Academy of Pediatrics. Diphtheria. In: Pickering LK, Baker CJ, Long SS, McMillan JA, eds. Red Book: 2009 Report of the Committee on Infectious Diseases, 28th edn. Elk Grove Village: American Academy of Pediatrics; 2009: 280-283.<\/li>\n
  10. Weinbaum C. Diphtheria. In: Hamborsky J, Kroger A, Wolfe C, editors. Epidemiology and prevention of vaccine-preventable diseases. 13th ed. Washington DC: Public Health Foundation; 2015. 10717p.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    *All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf attachment at the end of the paper.   \u00davod Epidemiol\u00f3gia V predvakcina\u010dnej \u00e9re bola dift\u00e9ria jednou z naj\u010dastej\u0161ie sa vyskytuj\u00facich infek\u010dn\u00fdch ochoren\u00ed u det\u00ed s vysokou \u00famrtnos\u0165ou. Po vytvoren\u00ed toxoidovej vakc\u00edny v r. 1923 a n\u00e1sledne po<\/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":[1236,1240,1241,1242],"class_list":["post-1774","post","type-post","status-publish","format-standard","hentry","category-microbiology","tag-corynebacterium-diphteriae-en","tag-diphtheria","tag-toxic-strain","tag-vaccination","typ_clanku-casuistry"],"acf":{"abstrakt":"

    In the past diphtheria belonged to one of the main causes of childhood morbidity and mortality. Toxigenic strains of Corynebacterium diphteriae <\/em>are still present worldwide, including Europe, North and South America, India, Africa, South Asia and the Eastern Mediterranean. After the introduction of vaccination, worldwide cases of the disease have been reduced. However, the loss of immunity after vaccination, deterioration of socio-economic conditions and a decrease in vaccination rate or \u201eanti-vaccination\u201c trend can also have an impact on disease development.<\/p>\n

    Nowadays, the clinicians should consider the possibility of spreading toxigenic strains from areas with endemic prevalence, especially from developing countries with a higher percentage of asymptomatic carriage in the population and its connection with migration and refugees. Due to the increase of migration and tourism, it is necessary to maintain a high vaccination rate and to monitor diphtheria consistently.<\/p>\n

    Keywords: <\/strong>Corynebacterium diphteriae<\/em>, diphtheria, toxic strain, vaccination<\/p>\n

    \u00a0<\/em><\/strong><\/p>\n","casopis":[{"ID":1883,"post_author":"7","post_date":"2019-10-28 13:35:57","post_date_gmt":"2019-10-28 12:35:57","post_content":"

      \r\n \t
    • Detection and validation of subchromosomal aberrations detected as additional findings in routine noninvasive prenatal testing for common trisomies<\/li>\r\n \t
    • Finding of a marker chromosome in a child with Cat-eye syndrome (case study)<\/li>\r\n \t
    • Experimental therapy with stem cells is promissing in the treatment of chronic diabetic ulcer \u2013 a case study<\/li>\r\n \t
    • Colonic mucosal Schwann cell hamartoma with tactile corpuscle-like bodies: a case report<\/li>\r\n \t
    • Accidental capture of the toxic strain Corynebacterium diphteriae<\/li>\r\n<\/ul>","post_title":"newsLab","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"newslab-004","to_ping":"","pinged":"","post_modified":"2019-11-04 13:53:35","post_modified_gmt":"2019-11-04 12:53:35","post_content_filtered":"","post_parent":0,"guid":"https:\/\/www.newslab.sk\/casopis\/newslab-4\/","menu_order":0,"post_type":"casopis","post_mime_type":"","comment_count":"0","filter":"raw"}],"strana":"102","upload_clanok":{"ID":1772,"id":1772,"title":"NEWSLAB_2-2019_Dobr\u00edkov\u00e1","filename":"NEWSLAB_2-2019_Dobr\u00edkov\u00e1.pdf","filesize":267271,"url":"https:\/\/www.newslab.sk\/wp-content\/uploads\/2019\/10\/NEWSLAB_2-2019_Dobr\u00edkov\u00e1.pdf","link":"https:\/\/www.newslab.sk\/en\/accidental-capture-of-the-toxic-strain-corynebacterium-diphteriae\/newslab_2-2019_dobrikova-2\/","alt":"","author":"7","description":"","caption":"","name":"newslab_2-2019_dobrikova-2","status":"inherit","uploaded_to":1774,"date":"2019-10-28 12:30:35","modified":"2019-10-28 12:30:35","menu_order":0,"mime_type":"application\/pdf","type":"application","subtype":"pdf","icon":"https:\/\/www.newslab.sk\/wp-includes\/images\/media\/document.png"}},"_links":{"self":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1774","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=1774"}],"version-history":[{"count":0,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1774\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/media?parent=1774"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/categories?post=1774"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/tags?post=1774"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}