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Kako se općenito prenose ljudski rotavirusi?

Kako se općenito prenose ljudski rotavirusi?


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Znam da su rotavirusi dvolančani RNA virusi i pitam se je li ljudski prijenos sličan načinima veterinarskog prijenosa.


Fekalno-oralni prijenos. Ref sa https://en.wikipedia.org/wiki/Rotavirus


Kako se ljudski rotavirusi općenito prenose? - Biologija

Mehanizmi infekcije i širenja virusa kroz tijelo

(stranice 595-614 u vašoj knjizi)

Patogeneza virusa = cijeli proces kojim virusi uzrokuju bolest

Virulencija = patogenost = sposobnost virusa da izazove bolest

  • Velike čestice (10 µm i više) se filtriraju na mukocilijarnom sloju nazalnih turbina. Zatim je spušten u jednjak
  • Intermedijarne čestice (5-10 µm) obično su zarobljene na mukocilijarnom sloju traheje i bronhiola. Odatle se odvode u jednjak.
  • Manje čestice često dopiru do alveola pluća gdje mogu izazvati infekciju ili ih uništiti alveolarni makrofagi.
  • pluća i drugo tkivo sluznice mjesta su sekretornog imunoglobulina (IgA) koji će olakšati ubijanje virusa
  • debeli sloj jednjaka
  • sekretorna antitela (IgA)
  • kemikalije - žuč, želučana kiselina, proteaze

C. Koža, genitalni trakt i konjunktiva

koža: Čvrsti vanjski sloj gotovo je neprobojan - ulazak je kroz posjekotine, ogrebotine, ugrize (insekt ili životinja), jatrogen (ljudska intervencija - igle)

Neki virusi proizvode lokaliziranu infekciju na koži (papiloma), ali većina se kreće kroz kožu u dublje slojeve i na kraju u krvotok (viremija).

Genitalni trakt: genitalni trakt je put ulaska važnih patogena poput HSV -a, papiloma, HIV -a, HTLV -a, hepatitisa B i C. Seksualna aktivnost može uzrokovati sitne suze u vagini i uretri kroz koje virus može ući. Neki variraju i ostaju lokalni (papiloma virus), drugi se sistemski šire (HIV, HepB i C, HTLV)

Oči: Konjunktiva ima zaštitne mehanizme (lizozim u suzama, pranje, brisanje kapaka, itd.) i obično nije put infekcije. Međutim, ovdje se može zaraziti nekoliko virusa. Obično se infekcija odvija kroz malu rascjepu u konjunktivi, a čak i tada infekcija se obično pokreće direktnom inokulacijom (fizičkim dodirom nečega na čemu je virus).

O. Virusi imaju izbor postavljanja infekcije na mjestu ulaska u tijelo ili ulaska u krvotok i postavljanja infekcije na drugom mjestu.

Usmjerenost pupanja je vrlo važna za način na koji se virus širi. Ako se proširi na apikalnoj površini, obično se oslobađa u lumen gdje se može brzo proširiti na lumenalnu epitelnu površinu, ili se čak izliti na vanjsku stranu domaćina. Ako pukne bazolateralno, naići će na sporo kretanje i bezbroj odbrana domaćina. U mnogim slučajevima pupanje diktira vrstu infekcije koja se postavlja.

B. Lokalno širenje na epitelnim površinama

To se ne dešava mnogo na koži jer se virus teško prenosi bez pomoći vode. Papiloma virusi inficiraju bazalni sloj epidermisa, ali virusi ne sazrijevaju sve dok se stanice ne pomaknu prema vanjskoj površini kože i postanu keratanizirane. U ovom trenutku virus sazrijeva i proizvodi bradavice. Neki virusi boginja, kao što su molluscum contagiosum, orf i tanapox ostaju lokalizirani u koži, šire se od stanice do stanice i uzrokuju kvržice (točke infekcije) na koži. Drugi poksvirusi, poput malih boginja, ulaze u limfni sistem i šire se po cijelom tijelu.

U unutrašnjem epitelu površina je prekrivena vodom i to znatno olakšava širenje. Stoga ove infekcije obično imaju kraće vrijeme inkubacije. U slučaju paramiksovirusa, virusa gripe i rotavirusa, epitelno tkivo je inficirano, ali nema invazije izvan ovog sloja -- vjerovatno zbog nedostatka ćelijskih receptora u dubljim slojevima tkiva, ili moguće zbog viših temperatura u dubljim ćelijskim tkivima . Međutim, oni i dalje mogu biti prilično ozbiljni.

C. Subepitelna invas ion i limfni namaz

Limfni sistem je sistem kanala, sudova i žlijezda koji se nalazi neposredno ispod bazalne membrane kože. Glavna svrha imunološkog nadzora - otkrivanje i uklanjanje stranih napadača. Mnoge imunološke stanice mogu se naći u limfnim čvorovima i limfnoj tekućini. Makrofagi su vjerovatno primarni branitelji. Oni jedu viruse i koriste proteinske dijelove da aktiviraju imunološki odgovor.

Virusi izbjegavaju limfni sistem na dva primarna načina. Oni mogu direktno zaraziti imunološke stanice (koje na kraju nađu svoj put u krvotok), ili mogu brzo proći kroz limfni sistem (izbjegavajući makrofage) i u krvotok.

D. Primarna i sekundarna viremija

Prvi ulazak virusa u krvotok je primarna viremija (može biti aktivna ili pasivna). Ova viremija može biti subklinička i put je kojim virusi dopiru do mjesta infekcije. Nakon infekcije može doći do sekundarne viremije zbog izbacivanja virusa iz zaraženog organa. Ova sekundarna viremija tada može biti uzrok infekcije na još jednom mjestu u tijelu.

Virusi mogu slobodno cirkulirati u krvi (hepadnavirusi, togavirusi, flavivirusi i enterovirusi), ili se mogu povezati s leukocitima (WBC), trombocitima ili eritrocitima i oni ih mogu hraniti (HIV, groznica Rift Valley, koloradska krpelja). Potonje virusne infekcije je teže očistiti i imaju tendenciju da budu trajnije infekcije.

Makrofagi imaju mnogo veze s vrstom infekcije koja može biti uzrokovana nakon primarne viremije. Faktori koji su bitni su područje tijela u kojem se infekcija javlja (različite vrste makrofaga u različitim dijelovima tijela), osjetljivost makrofaga na infekciju, stanje njihove aktivacije, te starost i genetika host. U većini slučajeva, makrofagi su efikasni uništavači virusa, ali u nekim slučajevima, poput denga groznice, mogu poslužiti kao domaćin i prenijeti virus u različite dijelove tijela.

Infekcija na mjestu nakon primarne viremije ima mnogo veze s prirodom vaskularnih endotelnih stanica na tom mjestu i količinom protoka krvi kroz to mjesto. Virioni se bolje vežu u područjima gdje je protok krvi sporiji. Virusi mogu proći kroz endotelne ćelije stiskanjem između stanica ili izravnom infekcijom i prelaskom iz ćelije u ćeliju.

Budući da se vaš imunološki sistem konstantno bori protiv virusa u krvotoku, mora postojati neka vrsta mehanizma za stalno izbacivanje virusa kako bi se održala viremija. Ovo je posebno važno u širenju na određene dijelove tijela, poput centralnog nervnog sistema, gdje je potrebna stalna viremija da bi virus mogao proći krvno -moždanu barijeru. Viremija se obično održava ili direktnom infekcijom krvnih stanica (obično leukociti) ili infekcijom drugog organa koji neprestano ispušta virus u krvotok.

E. Sekundarna mjesta infekcije.

Koža - ovo obično rezultira nekom vrstom osipa koji se sastoji od makula, papula, vezikula ili pustula.

CNS – širenje je obično iz krvnih sudova u moždanim ovojnicama i horoidnim pleksusom i infekcijom neurona u likvoru, ili direktno iz krvnih sudova mozga i kičmene moždine. Širenje je obično ili infekcijom endotelnih ćelija ili transportom direktno kroz endotelni sloj. Rijetko se inficirani leukociti useljavaju u mozak.

Drugi važan put je putovanje virusa do neurona (bjesnilo, varičela, herpes simplex)

Meningitis je infekcija sluznice mozga i CNS-a (meninge)

Encefalitis je infekcija mozga

Ostali organi - jetra (hepatitis), srce (karditis), pluća (pneumonija), pljuvačne žlezde (zauške), testisi (orhitis)

Fetus - 1) teratogeni efekti (CMV i rubeola) kao što su gluhoća, sljepoća, urođene srčane i moždane mane, 2) fetalna smrt (male boginje, parvovirus 19)

Osnova za tropizam

  • ćelijski receptori
  • transkripcijski faktori - neki pojačivački elementi djeluju samo na specifične ćelijske transkripcijske faktore (hep B u jetri, papiloma 11 u keratinocitima)
  • stanične proteaze - prisutnost stanične proteaze potrebne za cijepanje virusnih proteina za stvaranje zrelog virusa - gripa HA i triptaza Clara

Mjesto ulaska često diktira način širenja i težinu bolesti – bjesnilo.

Neophodan za održavanje infekcije u populaciji.

A. Respiratorne i orofaringealne sekrecije

sluz ili slina zbog kašljanja, kihanja i razgovora - ospice. boginje, rubeola. direktan prijenos sline ili sluzi - herpesvirusi, CMV, EBV

B. Feces

enterični virusi - često mogu trajati duže vrijeme (bez razvoja)

C. Koža

Za prijenos je potreban direktan kontakt - zarazni mekušac, bradavice, genitalni herpes, poksvirusi.

D. Urin

Virurija je glavni način širenja kod arenavirusnih infekcija glodara. Virus zaušnjaka i CMV kod ljudi

E. Mlijeko

CMV u majčinom mlijeku

F. Genitalni sekret

HIV, HSV I, HSV II, papilomavirusi, hepatitis B i C, HTLV

G. Krv i tjelesne tečnosti

Heptitis B, C, D, HIV, HTLV. Srećom, neke od smrtonosnijih hemoragičnih groznica mogu se prenijeti samo na ovaj način.

H. Bez prolijevanja - priča o Kuruu


Rotavirus prepušta vanjske ćelijske proteine ​​CK1-alpha za okupljanje tvornica virusa

Transmisioni elektronski mikrosnimak intaktnih čestica rotavirusa, dvostruke ljuske. Kredit: CDC

Rotavirusi se, poput svih virusa, razmnožavaju unutar živih stanica. Stvaranje novih virusa zahtijeva sastavljanje tvornica replikacije putem složenog, malo poznatog procesa koji uključuje i virusne i stanične komponente. Izveštaj u Zbornik radova Nacionalne akademije nauka od strane multidisciplinarnog tima predvođenog istraživačima na Baylor College of Medicine otkriva da formiranje fabrika rotavirusa ovisi o ćelijskom proteinu zvanom CK1α, koji kemijski modificira virusnu komponentu NSP2, čime pokreće njenu lokalizaciju i sklapanje u tvornicu virusa, što je bitan korak u stvaranje novih virusa.

"Jedan od interesa naših laboratorija je bolje razumijevanje procesa sastavljanja tvornica rotavirusa", rekla je prva koautorica dr. Jeanette M. Criglar, stručnjakinja za molekularnu virologiju i mikrobiologiju na Medicinskom fakultetu Baylor i diplomirana studentica programa .

U procesu istraživanja ovoga, Criglar i njene kolege otkrile su da je ćelijski protein nazvan CK1α neophodan za sastavljanje fabrika rotavirusa. "Kad smo ušutkali CK1α u stanicama prije infekcije rotavirusom, oborili smo replikaciju virusa za više od 90 posto, što ukazuje na to da CK1α uvelike kontrolira stvaranje tvornica rotavirusa", rekao je Criglar.

CK1α je enzim sa sposobnošću da kemijski modificira druge proteine ​​i njihove funkcije dodavanjem fosfatnih grupa u njih. Istraživači su otkrili da CK1α posreduje svoj učinak na stvaranje tvornica replikacije rotavirusa dodavanjem fosfatne grupe u rotavirusni protein nazvan NSP2. Ova modifikacija fosfata pokreće sklapanje NSP2 oktamernih jedinica u strukturu nalik kristalu i čini se da je potrebna za formiranje fabrika rotavirusa.

"CK1α obično vodi brigu o poslovima održavanja unutar ćelije. Rotavirus iskorištava aktivnost ovog proteina, prepuštajući ga vanjskim kompanijama za okupljanje tvornica virusa", rekla je dopisna autorica dr. Mary K. Estes, Katedra za ljudske i molekularne zadužbine Cullen Foundation Virologija na Medicinskom fakultetu Baylor i direktor emeritus osnivač Centra za probavne bolesti Teksaškog medicinskog centra.

Osim toga, tim je otkrio da rotavirusni protein NSP2 može sebi dodati fosfatne grupe, mijenjajući tako njegovu aktivnost i utječući na druge proteine ​​uključene u sastavljanje virusa. Ovo je iznenađujući nalaz, objašnjava Estes, jer ova funkcija prije nije bila opisana za ovaj virusni protein.

"Uzeti zajedno, naši nalazi sugeriraju da je kaskada kemijskih modifikacija fosfata, koja je dijelom posredovana CK1α i NSP2, neophodna za formiranje fabrika rotavirusa", rekao je koautor dr. BV Venkataram Prasad, profesor i predsjedavajući Alvina Romanskyja. biokemije i molekularne biologije, te član Sveobuhvatnog centra za rak Dan L Duncan u Bayloru. "Ovi nalazi pružaju nove uvide koji bi mogli dovesti do ranije neslućenih načina za borbu protiv bolesti u budućnosti." "Moguće je da naši nalazi mogu također baciti svjetlo na sklapanje tvornica virusa za druge viruse koji također zahtijevaju CK1α, kao što je hepatitis C, ili koji također formiraju tvornice citoplazmatskih virusa poput Zapadnog Nila i virusa denga", rekao je Criglar. "Ako možemo razumjeti kako drugi virusi okupljaju svoje tvornice, možda koristeći slične mehanizme za rotavirus, mogli bismo unaprijediti razumijevanje i tih bolesti."


Dijagnoza i testovi

Kako se dijagnosticira rotavirus?

Ako vaše dijete ima znakove rotavirusa, obratite se svom ljekaru. Pružaoci usluga često mogu dijagnosticirati rotavirus na osnovu simptoma i fizičkog pregleda. U nekim slučajevima mogu uzeti uzorak stolice (izmete) kako bi ga testirali na rotavirus. Međutim, ovaj korak obično nije potreban.

Ako ipak trebate uzeti uzorak stolice, vaš će vam liječnik dati sterilnu posudu (bez klica). Sakupljate dio stolice vašeg djeteta u kontejner. Laboratorija analizira stolicu na rotavirus.


Sadržaj

Enterovirusi su članovi porodice pikornavirusa, velike i raznolike grupe malih RNK ​​virusa koju karakteriše jedna genomska RNK sa jednim lancem. Svi enterovirusi sadrže genom od približno 7.500 baza i poznato je da imaju visoku stopu mutacija zbog replikacije niske vjernosti i česte rekombinacije. [4] [5] Nakon infekcije ćelije domaćina, genom se prevodi na način nezavisan od kape u jedan poliprotein, koji se potom obrađuje proteazama kodiranih virusom u strukturne kapsidne proteine ​​i nestrukturne proteine, koji su uglavnom uključeni u replikaciju virusa. [6]

Čini se da je rekombinacija RNK glavna pokretačka snaga u evoluciji enterovirusa, kao i u oblikovanju njihove genetske arhitekture. [7] [5] Mehanizam rekombinacije genoma RNA vjerovatno uključuje promjenu lanca šablona tokom replikacije RNA, proces poznat kao rekombinacija izbora kopije. [7] Smatra se da je RNA rekombinacija adaptacija za bavljenje oštećenjem genoma RNK i izvor genetske raznolikosti. [8] To je također izvor zabrinutosti za strategije cijepljenja, jer se živi atenuirani/mutirani sojevi koji se koriste za cijepljenje mogu potencijalno rekombinirati sa sojevima divljeg tipa, kao što je to bio slučaj sa cirkulirajućim poliovirusima polimeriziranim vakcinama (cVDPD) [9] [ 10]. Kapsidna regija, a posebno VP1, je rekombinacijska hladna točka, [5] i to je jedan od glavnih razloga za korištenje ove regije za genotipizaciju [2]. Međutim, 5'UTR - kapsidni spoj i početak P2 Uočeno je da se rekombinacije vrlo često rekombinuju, iako se rekombinacije dešavaju iu ostatku genoma. [5] Zanimljivo je da enterovirusne vrste EV-A, EV-B, EV-C, EV-D do sada nisu primijećene da razmjenjuju genomske regije među njima, s izuzetkom 5'UTR. [5] [11] [12] Umjesto toga, genomski regioni ORF-a se razmjenjuju između različitih genotipova iste vrste, sa određenim genotipovima kao što su EV71 i CVA6 iz EV-A, E30 i E6 iz EV-B, PV1 i PV2 iz EV-C igra ključnu ulogu kao čvorišta rekombinacije. [5] Osim toga, rekombinacija analize

3000 genoma enterovirusa identificiralo je mnoge rekombinacijske događaje u kojima jedan od partnera rekombinacije još nije sekvenciran, otkrivajući tako da postoji veliki, ali još neotkriveni genetski rezervoar enterovirusa koji može dovesti do novih rekombinacijskih događaja i pojave novih sojeva, genotipova i patogena. [5]

Enterovirus A - L Edit

Enterovirusi su grupa sveprisutnih virusa koji uzrokuju brojne infekcije koje su obično blage. Rod pikornavirusa uključuje enteroviruse i rinoviruse. Enterovirus A uključuje koksakivirus A2, A3, A4, A5, A6, A7, A8, A10, A12, A14, A16 i enterovirus A71, A76 A89, A89, A90, A91, A92, A144, A119, A120, A121, A122 ( majmunski virus 19), A123 (virus majmuna 43), A124 (virus majmuna 46), A125 (babunski enterovirus A13). [13] Utvrđeno je da su neki virusi koji su u početku prijavljeni kao novi pogrešno identificirani. Dakle, koksakivirus A23 je isti serotip kao i ehovirus 9, a koksakivirus A15 je isti serotip kao koksakivirus A11, a koksakivirus A18 je isti serotip kao koksakivirus A13.

Coxsackie A16 virus uzrokuje bolesti šaka, stopala i usta kod ljudi.

Enterovirus B uključuje koksakivirus B1,2,3,4,5,6 koksakivirus A9 ehovirus 1-33 i enterovirus B69-113. [13] Coxsackie B virusi se nalaze širom svijeta i mogu uzrokovati miokarditis (upala srca), perikarditis (upala vrećice koja okružuje srce), meningitis (upala membrana koje oblažu mozak i kičmenu moždinu) i pankreatitis (upala pankreas). Virusi Coxsackie B također uzrokuju spastičnu paralizu zbog degeneracije neuronskog tkiva i ozljede mišića. Infekcije se obično javljaju tokom toplih ljetnih mjeseci sa simptomima uključujući egzantem, pleurodiniju, bolest nalik gripi koja se sastoji od groznice, umora, malaksalosti, mijalgije, mučnine, bolova u trbuhu i povraćanja. [14] Ehovirusi su uzročnici mnogih nespecifičnih virusnih infekcija koje mogu varirati od lakših bolesti do teških, potencijalno fatalnih stanja kao što su aseptični meningitis, encefalitis, paraliza i miokarditis. [15] Uglavnom se nalazi u crijevima i može uzrokovati nervne poremećaje. [16] Enterovirusi tipa B odgovorni su za veliki broj blagih i akutnih infekcija. Prijavljeno je da ostaju u tijelu uzrokujući trajne infekcije koje doprinose kroničnim bolestima kao što je dijabetes tipa I. [17]

Enterovirus C čine poliovirusi 1,2 i 3 koksaki virusa A1, A11, A13, A18, A17, 20, A21, A22, A24 i enterovirus C95, C96, C99, C102, C104, C105, C109, C113, C118. Sva tri serotipa poliovirusa, PV-1, PV-2 i PV-3 imaju nešto drugačiji kapsidni protein. Kapsidni proteini definiraju specifičnost staničnih receptora i antigenost virusa. PV-1 je najčešći tip koji izaziva infekciju kod ljudi, međutim, sva tri oblika su izuzetno zarazna i šire se kontaktom s osobe na osobu. Poliovirus uzrokuje dječju paralizu ili poliomijelitis, koji je onesposobljavajuća i po život opasna bolest koja uzrokuje paresteziju, meningitis i trajnu paralizu. [18] Simptomi mogu uključivati ​​upalu grla, groznicu, umor, mučninu, glavobolju i bol u stomaku, iako 72% onih koji se zaraze neće pokazati vidljive simptome. [18] Postoje dvije vrste vakcina koje su dostupne za prevenciju dječje paralize: inaktivirana poliovirusna vakcina koja se daje kao injekcija u nogu (IPV) ili cjepivo za ruke i oralna poliovirusna vakcina (OPV). Vakcina protiv poliomijelitisa je vrlo efikasna i štiti 99 od 100 vakcinisane djece. [18]

Necitolitički (necitopatski) enterovirus Edit

Enterovirusi su obično sposobni izazvati samo akutne infekcije koje se brzo uklanjaju adaptivnim imunološkim odgovorom. [19] [20] Međutim, mutacije genoma, koje enterovirus B serotipovi mogu steći u domaćinu tijekom akutne faze, mogu transformirati te viruse u necitolitički oblik (poznat i kao necitopatski ili defektni enterovirus). Ovo je mutirana kvazivrsta [19] enterovirusa, koja može uzrokovati trajnu infekciju u ljudskim srčanim tkivima, posebno kod nekih pacijenata s miokarditisom ili dilatiranom kardiomiopatijom. [21] [19] U upornim infekcijama virusna RNA prisutna je samo na vrlo niskim razinama i ne vjeruje se da doprinosi bilo kojoj tekućoj bolesti miokarda koja je blijedeći ostatak nedavne akutne infekcije [20] iako neki naučnici misle drugačije. [22]

Enterovirus D68 Edit

EV-D68 je prvi put identificiran u Kaliforniji 1962. U usporedbi s drugim enterovirusima, rijetko je prijavljen u SAD-u u posljednjih 40 godina. Većina ljudi koji se zaraze su novorođenčad, djeca i tinejdžeri. EV-D68 obično uzrokuje blage do teške respiratorne bolesti, međutim, cijeli spektar bolesti EV-D68 nije dobro definiran. Većina počinje sa simptomima uobičajene prehlade kao što su curenje iz nosa i kašalj. Neki, ali ne svi, mogu imati i temperaturu. U težim slučajevima može doći do otežanog disanja, piskanja ili problema s dahom. Od 4. oktobra 2014. godine, u New Jerseyu je bila jedna smrt koja je direktno povezana sa EV-D68, [23] kao i jedna smrt na Rhode Islandu [ potreban citat ] pripisuje kombinaciji EV-D68 i sepse uzrokovane infekcijom stafilokoka aureusa. [24] [25]

Enterovirus A71 Edit

Enterovirus A71 (EV-A71) je značajan kao jedan od glavnih uzročnika bolesti šaka, stopala i usta (HFMD), a ponekad je povezan s teškim oboljenjima centralnog nervnog sistema. [26] EV-A71 je prvi put izoliran i okarakteriziran iz slučajeva neurološke bolesti u Kaliforniji 1969. [27] [28] Do danas se malo zna o molekularnim mehanizmima odgovora domaćina na infekciju EV-A71, ali se povećava u uključeni su nivoi mRNA koji kodiraju hemokine, proteine ​​uključene u razgradnju proteina, proteine ​​komplementa i proteine ​​proapoptotisa. [29]

Poliovirus Edit

Postoje tri serotipa poliovirusa, PV-1, PV-2, i PV-3 svaki sa nešto drugačijim kapsidnim proteinom. Kapsidni proteini određuju specifičnost ćelijskog receptora i antigenost virusa. PV-1 je najčešći oblik u prirodi, međutim, sva tri oblika su izuzetno zarazna. [30] Poliovirus može utjecati na kičmenu moždinu i uzrokovati poliomijelitis.

Poliovirusi ranije su bile klasificirane kao vrsta koja pripada rodu Enterovirus u porodici Picornaviridae. Vrsta poliovirusa eliminisana je iz roda Enterovirusa. Sljedeći serotipovi, humani poliovirus 1, humani poliovirus 2 i humani poliovirus 3, pripisani su vrsti humanog enterovirusa C, iz roda enterovirus iz porodice Picornaviridae. Tipska vrsta roda Enterovirus promijenjena je iz Poliovirusa u Human enterovirus C. Ovo je ratificirano u aprilu 2008. [31] 39. Izvršni komitet (EC39) Međunarodnog komiteta za taksonomiju virusa (ICTV) sastao se u Kanadi tokom juna 2007. s novim taksonomskim prijedlozima. [32]

Dva prijedloga s tri izmjene su:

  • Šifra 2005.261V.04: Za uklanjanje sljedeće vrste poliovirusa iz postojećeg roda Enterovirus u porodici Picornaviridae.
  • Šifra 2005.262V.04: Dodijeliti viruse PV-1, PV-2, PV-3 postojećoj vrsti Humani enterovirus C iz roda Enterovirus iz porodice Picornaviridae. [33]
  • Šifra 2005.263V.04: Za promjenu tipa vrste Poliovirus iz postojećeg roda Enterovirus u porodici Picornaviridae u tipsku vrstu Human enterovirus C. [34]

Prijedlozi odobreni na (EC39) sastanku 2007. godine, poslani su članovima ICTV -a putem e -pošte na ratifikaciju i postali su službena taksonomija. Bilo je ukupno 215 taksonomskih prijedloga, koji su odobreni i ratificirani od 8. ICTV izvještaja 2005. [35]

Proces ratifikacije je obavljen putem elektronske pošte. Prijedlozi su poslani elektroničkom poštom putem e-pošte 18. marta 2008. članovima ICTV-a sa zahtjevom za glasanje o tome hoće li ratifikovati taksonomske prijedloge, sa rokom od mjesec dana. U nastavku su dva taksonomska prijedloga s tri izmjene koje su članovi ICTV -a ratificirali u travnju 2008 .:

  • 2005.261V.04: Ukloniti sljedeće vrste iz postojećeg roda Enterovirus u porodici Picornaviridae: Poliovirus. (Napomena: Poliovirus ovim gubi status vrste virusa.)
  • 2005.262V.04: Dodijeliti sljedeće viruse vrsti Human enterovirus C u postojećem rodu Enterovirus u porodici Picornaviridae: Humani poliovirus 1, Human poliovirus 2, Human poliovirus 3. (Ovo nije striktno neophodno kao taksonomski prijedlog jer tiče entiteta ispod nivoa vrste, ali ostavljeno je da se pojasni ova reorganizacija Picornaviridae.)
  • 2005.263V.04: Za promjenu vrste roda Enterovirus u porodici Picornaviridae, iz poliovirusa u humani enterovirus C. [31]

Enterovirusi uzrokuju širok raspon simptoma, i iako bi ih duga lista znakova i simptoma trebala staviti na popis diferencijalne dijagnoze mnogih bolesti, često ostaju nezapaženi. Enterovirusi mogu uzrokovati bilo šta, od osipa kod male djece, preko ljetnih prehlada, do encefalitisa, do zamagljenog vida, do perikarditisa. Enterovirusne infekcije imaju veliki raspon u prezentaciji i ozbiljnosti. Enterovirusi bez poliomijelitisa uzrokuju 10–15 miliona infekcija i desetine hiljada hospitalizacija u SAD -u svake godine. [37] Enterovirusi se mogu identificirati putem ćelijske kulture ili PCR analize, prikupljene iz fekalnih ili respiratornih uzoraka. [38] Ispod su uobičajene bolesti povezane s enterovirusom, uključujući poliomijelitis.

    prvenstveno fekalno-oralnim putem koji se nalazi kod djece koja su pozitivna na enterovirus 68. [39] [40]
  • Nespecifična febrilna bolest najčešća je manifestacija enterovirusne infekcije. Osim temperature, simptomi uključuju bol u mišićima, grlobolju, gastrointestinalne tegobe/nelagodu u trbuhu i glavobolju. [41] Međutim, kod novorođenčadi slika može biti slika sepse i može biti teška i opasna po život.
  • Enterovirusi su daleko najčešći uzročnici aseptičnog meningitisa kod djece. U Sjedinjenim Državama enterovirusi su odgovorni za 30.000 do 50.000 hospitalizacija meningitisa godišnje kao rezultat 10-15 miliona infekcija. [42] ili epidemijsku pleurodiniju karakterizira teški paroksizmalni bol u grudima i abdomenu, uz groznicu, a ponekad i mučninu, glavobolju i povraćanje. i/ili miokarditis tipično uzrokovani enterovirusima simptomi se sastoje od groznice s dispnejom i bolovima u prsima. Zabilježene su i aritmije, zatajenje srca i infarkt miokarda. mogu biti uzrokovani enterovirusima. je uzrokovan Coxsackie A virusom i uzrokuje vezikularni osip u usnoj šupljini i na ždrijelu, uz visoku temperaturu, upalu grla, malaksalost, a često i disfagiju, gubitak apetita, bolove u leđima i glavobolju. Također je samoograničavajući, sa simptomima koji obično završavaju za 3-4 dana. je dječja bolest koja je najčešće uzrokovana infekcijom virusom Coxsackie A ili EV71. je rijetka manifestacija enterovirusne infekcije kada se pojavi, najčešći enterovirus za koji se utvrdi da ga uzrokuje je ehovirus 9. karakterizira upala miokarda (ćelije srčanog mišića). U posljednjih nekoliko desetljeća identificirani su brojni krivci koji imaju ulogu u patogenezi miokarditisa pored enterovirusa, koji je isprva bio najčešće uključeni virus u ovu patologiju. [43] Jedan od najčešćih enterovirusa za koje se utvrdi da su odgovorni za izazivanje miokarditisa je virus Coxsackie B3. [44]
  • Studija iz 2007. sugerira da akutne respiratorne ili gastrointestinalne infekcije povezane s enterovirusom mogu biti faktor u sindromu kroničnog umora. [45]

Sumnja na bolesti Uredi

Moguće korelacije koje se proučavaju Uredi

Pretpostavlja se da je enterovirus povezan s dijabetesom tipa 1. [47] [48] [49] [50] Predloženo je da je dijabetes tipa 1 autoimuni odgovor izazvan virusom u kojem imunološki sistem napada stanice zaražene virusom zajedno s beta stanicama koje proizvode inzulin u gušterači. [51] Tim koji radi na Univerzitetu u Tampereu u Finskoj identifikovao je tip enterovirusa koji ima moguću vezu sa dijabetesom tipa 1 (koji je autoimuna bolest). [52] [53]

Većina ljudi koji se zaraze enterovirusom imaju blage simptome koji traju oko tjedan dana. Oni s većim rizikom mogu imati više komplikacija, koje ponekad postaju fatalne. [54] Najčešći znak enterovirusa je obična prehlada. Intenzivniji simptomi enterovirusa uključuju hipoksiju, aseptični meningitis, konjunktivitis, bolesti ruku, stopala i usta i paralizu.

Liječenje enterovirusne infekcije uglavnom je podržavajuće. U slučajevima pleurodinije, liječenje se sastoji od analgetika za ublažavanje jake boli koja se javlja kod pacijenata sa bolešću, u nekim teškim slučajevima mogu biti potrebni opijati. Liječenje aseptičnog meningitisa uzrokovanog enterovirusima također je uglavnom simptomatsko. Kod pacijenata s enterovirusnim karditisom, liječenje se sastoji od prevencije i liječenja komplikacija poput aritmija, perikardnog izljeva i zatajenja srca. Drugi tretmani koji su ispitani za enterovirusni karditis uključuju intravenozni imunoglobulin. [55]


Kako se općenito prenose ljudski rotavirusi? - Biologija

U Španiji proljev ostaje glavni uzrok bolesti odojčadi i male djece. Da bi se utvrdila prevalencija genotipova rotavirusa i vremenske i geografske razlike u distribuciji soja, strukturirano nadzorno istraživanje hospitalizirane djece starije od 5 godina s dijarejom je pokrenuto u različitim regijama Španije tokom 2005. Rotavirus je otkriven sam u uzorcima od 362 (55,2% ) uzorcima i kao koinfekcija sa drugim virusima u 41 uzorku (6,3%). Enteropatogeni bakterijski agensi otkriveni su u 4,9% uzoraka astrovirusa, a norovirusa u 3,2% i 12,0% uzoraka, a adenovirusni antigen je otkriven u 1,8% uzoraka. Uključujući mješovite infekcije, najčešći G tip bio je G9 (50,6%), zatim G3 (33,0%) i G1 (20,2%). Infekcija sa više sojeva rotavirusa otkrivena je u> 11,4% uzoraka proučavanih tokom 2005.

Rotavirusi grupe A glavni su uzrok teške proljeva u odojčadi. U zemljama u razvoju, teška dijareja uzrokovana ljudskim rotavirusom dovodi do procijenjenih 500.000 do 608.000 smrtnih slučajeva u djetinjstvu godišnje širom svijeta, što rezultira sa ≈2 miliona hospitalizacija (1,2).

Rotavirusi pripadaju Reoviridae porodica. Virusne čestice su bez ovojnice, a troslojni proteinski kapsidi obuhvataju genom od 11 segmenata dsRNA. Glavni protein u središnjem sloju virusne kapside je VP6, koji određuje 7 različitih grupa rotavirusa (A-G). Vanjski sloj virusnog kapsida sastoji se od 2 strukturna proteina, VP4 (kodiran genom 4) i VP7 (kodiran genom 7, 8 ili 9, ovisno o soju) (3). Ova 2 proteina nose glavne antigene determinante, koje izazivaju neutralizirajuća antitijela i za koje se smatra da su specifični za tip. Rotavirusi grupe A rasprostranjeni su kod ljudi i životinja i podijeljeni su na različite genotipove, G i P (4). Epidemiološke studije rotavirusnih infekcija sve više pokazuju da veliki broj sojeva rotavirusa kocikulira u ljudskoj populaciji širom svijeta. Najčešći genotipovi rotavirusa grupe A (≈90%), koji uzrokuju dehidrirajući gastroenteritis kod odojčadi i male djece širom svijeta, bili su G1P [8], G2P [4], G3P [8] i G4P [8] G1P [8] najrasprostranjeniji je u svijetu (5). Međutim, drugi G genotipovi su epidemiološki važni, kao što je G5 u Brazilu (6,7), G9 i G10 u Indiji (8,9), i G8 u Malaviju (10).

U Španjolskoj je proljev i dalje važan uzrok bolesti odojčadi i male djece. Studija sprovedena od 1998. do 2002. godine otkrila je rotavirus u 1.155 (31%) od 3.760 testiranih uzoraka. G1 je bio dominantni detektovani genotip (53%), zatim G4 (24%), G2 (14%), G9 (6%) i G3 (2%) (11). The distribution of genotypes indicated a genotypic shift over time: G4 strains predominated (57%) from 1998 through 2000, whereas G1 gradually increased to account for 75% from 2000 through 2002 (11). Similar studies conducted in other regions of Spain indicated similar shifts in the prevalence of rotavirus genotypes (12,13).

We conducted structured surveillance among children with diarrhea who were hospitalized in 6 hospitals in Spain our primary goals were to determine the prevalence of rotavirus diarrhea in hospitalized children, the G and P types among infecting rotavirus strains, and the temporal and geographic differences in strain distribution throughout the regions.

Materijali i metode

Hospitals and Patients

Stool samples were collected from children attending 6 public hospitals located in different healthcare areas throughout Spain. These hospitals intentionally represented the geographic, climatic, and ethnic diversity of Spain. Their respective catchment areas are shown in Table 1. The study was conducted between January 2005 and January 2006 and included children <5years of age who were hospitalized with acute gastroenteritis and from whom a stool sample was obtained.

Acute gastroenteritis was defined as >3 looser-than-normal stools within a 24-hour period or an episode of forceful vomiting and any loose stool. To enable reporting of test results to hospitals, stool specimens were labeled with the date of collection and a unique surveillance identification number. Permission for enrollment in the study was obtained from children's legal guardians, and ethical approval was obtained from the institutional review board of the Hospital de La Ribera.

Specimen Collection and Testing

Whole stool specimens were collected and transported immediately to hospital laboratories and stored at 4°C until processing. All fecal samples were screened for enteropathogenic bacterial agents by conventional culture methods previously described (14).

Each month, specimens were sent to the reference laboratory (Viral Gastroenteritis Unit, National Center for Microbiology, Instituto de Salud Carlos III, Madrid, Spain). A 10% suspension in 0.1 mol/L phosphate-buffered saline (pH 7.2) was prepared and tested by reverse transcription (RT)-PCR for rotavirus, astrovirus, norovirus, and sapovirus (11,15,16) and by an immunochromatographic method for enteric adenoviruses (14).

Nucleic Acid Extraction and G/P Rotavirus Typing

Viral RNA was extracted from 250 μL of the 10% fecal suspension by using the guanidine isothiocyanate method and the Rnaid Spin Kit (BIO 101, Anachem Bioscience, Bedfordshire, UK) according to the manufacturer's instructions, with slight modifications (16). RNA was eluted in 50 μL of RNase-free distilled water and stored at –20°C. To determine the G/P type patterns present in children hospitalized from 2005 through 2006, a total of 98 rotavirus strains were P typed. G and P rotavirus genotyping were performed by using RT-PCR methods as previously reported (11,17).

DNA Sequencing and Analysis

Rotavirus amplicons were genetically characterized by nucleotide sequencing of both strands of the amplified PCR products. These products were purified by using QIAquick PCR Purification kit (Qiagen, Valencia, CA, USA) and then sequenced using an ABI PRISM BigDye Terminator Cycle Sequencing Ready Reaction Kit (Applied Biosystems, Foster City, CA, USA) on an ABI automated sequencer (Applied Biosystems, model 3700). Data analysis was performed by using Clustal for multiple alignments and neighbor-joining and maximum parsimony methods for phylogenetic analysis (Bionumerics, Kortrijk, Belgium). Spanish strains were submitted to GenBank under accession numbers DQ440613 through DQ440624.

Rezultati

Mikrobiologija

A total of 656 hospitalized children were enrolled. Enteropathogenic bacterial strains were detected in 5.0% of samples (Table 2). Astrovirus and norovirus RNA was detected in 3.2% and 12.0% samples, respectively, and adenovirus antigen in 1.8% samples.

A total of 403 rotavirus strains were detected. Rotavirus was found alone in 362 (55.2%) samples but was found in another 41 samples (6.3%) as a coinfection with other viruses. The percentage of children with gastroenteritis caused by rotavirus as unique agent ranged from 36.7% in Leon to 68.2% in Valencia (Table 2).

Rotavirus Characterization

G typing RT-PCR for rotavirus alone was performed on 362 samples positive for rotavirus but could not be determined in 10 (2.8%) samples. The G types detected, including mixed infections with multiple rotavirus strains, are shown in Table 3. Briefly, the most predominant G type was G9 (50.6%), followed by G3 (33.0%), G1 (20.2%), and G2 (7.1%) the least common G type was G4 (0.6%). G1, previously reported as the most common G type in Spain, was found in only 20.2% of rotavirus infections. With the exceptions of Valencia and Albacete, where G1 and G3, respectively, were the predominant G types, the results from all other regions showed a predominance of G9. However, even in these 2 areas, G9 was the second most common strain detected when cases with coinfection were added (26.7% and 31.6%, respectively).

Common G/P combinations, infrequent patterns, and mixed-infection combinations were all detected (Table 4). G9P[8] (40%) and G3P[8] (31%) were the most common combinations detected, but G types in combination with P[6] and P[9] were also detected.

Using DNA sequencing and phylogenetic analysis of partial sequences of the gene encoding VP7, we compared 2 G3 strains from this study with 9 G3 strains isolated previously in Spain. All G3 strains from Spain shared >99.0% homology and were more closely related to each other than to strains isolated in Italy, United Kingdom, India, and China.

Diskusija

Genetically and antigenically diverse rotavirus strains cocirculate in humans. The prevalence of rotavirus genotypes varies according to location and time. Throughout the world, genotyping and serotyping studies have identified common cocirculating rotavirus types, and G1P[8], G2P[4], G3P[8], and G4P[8] are the predominant strains. However, from time to time, other less common genotypes, such as G9P[8], G5P[8], and G8P[6], have been predominant in various countries (5).

In Spain, previous studies have identified G1P[8] and G4P[8] as the predominant cocirculating strains from 1996 through 2004 (11,17,18) (Table 5). However, in our study, conducted in 2005 and 2006, a major shift in the predominant strains was detected. G9P[8] and G3P[8] have become the predominant genotypes cocirculating in several regions of Spain, and infection with multiple rotavirus strains was detected in 11.4% of the cases studied.

Since its widespread introduction into the human population in 1995, G9P[8] has become one of the predominant viruses worldwide. In 2 separate studies conducted in Thailand (19,20), this genotype has been reported as the predominant virus circulating from 2000 through 2002 and in Brazil from 1999 through 2002 (21). G3P[8] has recently been reported as the predominant strain circulating in the Japanese population (22).

Less common G- and P-type combinations were also detected in this study. This finding may suggest either an earlier reassortment between animal and human strains, resulting in the emergence of strains such as G2P[6] and G3P[9], or zoonotic transmission to humans of an animal strain, as possibly occurred with G9P[6]. The VP4-genotypes P[6] and P[9] are reported to be associated with infection in pigs and cats, respectively. Although animal rotavirus strains replicate poorly in humans and person-to-person transmission is rare, the relatively high frequency of multiple infections detected in this study suggests that the opportunity for dual infection of a cell, and therefore reassortments, exists (23).

The main limitations of this study are having only 1 year of data, the minimal variations in the sampling schemes in each institution (frequency of sampling, test procedures, motivations of investigators), and the small sample size collected. Although the sampling strategy enabled monitoring for rotavirus in a large number of children, future studies with hospital-based surveillance should be initiated in different areas of Spain, and even Europe, with larger samples.

Morbidity rates worldwide and morbidity and mortality rates caused by diarrhea in developing countries remain high despite efforts to improve sanitary conditions, water quality, and the healthcare infrastructure. These high rates have driven efforts to develop a safe and effective rotavirus vaccine, and the World Health Organization has recognized that developing a vaccine is a priority for reducing infant deaths in developing countries. The level and type of protection in rotavirus disease is poorly understood, although neutralizing antibody responses are thought to be type specific. Because these responses are associated with VP7 and VP4 viral proteins, establishing the G and P genotypes of strains circulating in the human population is important. Currently, 2 candidate rotavirus vaccines are undergoing clinical trials. A multivalent vaccine directed against G1, G2, G3, G4, and P[8] and a monovalent vaccine to G1P[8] have been developed (24,25). Homotypic protection has been demonstrated for both vaccines, but the degree to which they cross-protect against less common G- and P-type combinations not included in the vaccine formulations has yet to be established, and the importance of genotype-specific protection against rotavirus disease is still under discussion (26,27). Considering that G9 rotavirus type has emerged as one of the most common rotavirus genotypes in humans around the world, and it is becoming very prevalent in some countries, future rotavirus vaccine candidates will need to provide adequate protection against disease caused by G9 viruses. Therefore, surveillance of regional networks must be maintained to document rotavirus strain distribution and prevent the appearance of new strains or new variants that could escape immune protection induced by an outdated vaccine.

Dr Sánchez-Fauquier is the head of the Viral Gastroenteritis Unit, National Center for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid. Her primary research interests are the epidemiology, immunology, pathogenesis, and molecular biology of viral gastroenteritis. She also is coordinator of the Spanish Viral Gastroenteritis Network (VIGESS-Net).


Upravljanje

Regardless of the infecting agent, children presenting with diarrhoea are assessed for dehydration and treated accordingly. A mild case of rotavirus disease, where the child is active, shows no signs of dehydration, has had between zero and two vomiting episodes within 12 hours, has had a few loose or low output watery stools per day and has no fever or a low-grade fever, requires only observation. Symptoms can last for 1–5 days, but if they last for >1 week, medical consultation should be sought. Increasing and/or intense vomiting and repeated episodes of watery diarrhoea (for example, >1 episode per hour, especially if abundant) are the main features that indicate the need for specific treatment. In low-income countries, the goal of treatment is avoiding or rapidly treating severe dehydration and maintaining protein–calorie intake to prevent death or worsening malnutrition, whereas in middle-income and high-income countries, reducing hospitalization and the duration of diarrhoea are the main goals. Key treatment concepts including fluid and electrolyte management (including ORS and intravenous rehydration), dietary management and the use of probiotics, anti-emetics, antisecretory drugs and antiviral drugs are discussed below comprehensive reviews of acute diarrhoea management can be found elsewhere 135,136 .

Fluid and electrolyte management

One of the most important medical advancements in the past 50 years that has saved millions of infant lives was that administration of ORS resulted in glucose-coupled sodium and water absorption in the small intestine 137 . Oral rehydration therapy has been used safely and successfully to prevent and treat dehydration due to diarrhoeal pathogens, including rotavirus, in infants and young children 138 . Clinical scales that consider the presence of signs and symptoms are available to assess for dehydration 139,140 , and a thirsty, restless or fatigued child with a dry mouth should alert caretakers to ongoing dehydration. Prompt replacement of fluids and electrolytes, spoon by spoon if necessary, with hypo-osmolar ORS (containing 60–75 mmol per litre of sodium in addition to glucose, potassium, chloride and citrate) 141 is the cornerstone of treatment for children without dehydration but with intense and repeated vomiting and/or diarrhoea episodes and for children with mild to moderate dehydration. If ORS is not available, homemade solutions can be prepared using water, sugar and salt. Plain water, soda, chicken broth and apple juice should be avoided in children with dehydration, especially in infants, as they are hyperosmolar solutions and do not sufficiently restore potassium, bicarbonate and sodium levels 142 . Intravenous fluids can be used in cases of severe dehydration, hyperemesis, oral rehydration therapy failure or severe electrolyte imbalances. Importantly, most children, even those with severe dehydration, can be managed effectively with ORS to prevent severe complications, including death.

Dietary management

Dietary management is an important factor in the care of children with acute diarrhoea 143 . Breastfeeding should be encouraged and is never contraindicated. In patients with dehydration, food withdrawal is advised for only 4–6 hours after initiating rehydration therapy 136,144 . The administration of repetitive, small portions of regular undiluted milk formulas is recommended for infants and children >6 months of age. The administration of lactose-free formulas might reduce the duration of treatment and the risk of treatment failure 143 and can be considered for selected children, such as those requiring hospitalization 136 . Importantly, the maintenance of adequate protein–calorie intake during the diarrhoea episode using home-available, age-appropriate foods should be encouraged, especially in low-income settings 143 . In addition, zinc supplementation can improve the outcome of acute diarrhoea in low-income regions, in which malnutrition is common. Although the mechanisms of the efficacy of zinc supplementation are unclear, data from animal studies suggest zinc has anti-inflammatory properties 145 and antisecretory effects 146 , among others. Zinc deficiency is common in low-income countries and can occur in children with acute gastroenteritis due to intestinal fluid loss. For children living in low-income regions, the WHO recommends daily zinc supplementation for infants and children for 10–14 days, starting as soon as the diarrhoea episode has been diagnosed 147 . However, zinc supplementation can increase vomiting after the initial dose 148 .

Probiotics

Commonly used probiotics for the treatment of acute diarrhoea are lactic acid-producing bacteria, such as Lactobacillus rhamnosus, Lactobacillus plantarum, several strains of Bifidobakterije i Enterococcus faecium (the SF68 strain), and yeast, such as Saccharomyces boulardii 149 . Most meta-analyses suggest a modest benefit of probiotics in reducing the duration of diarrhoea by ∼ 1 day and up to 2 days for rotavirus-induced diarrhoea, although studies have been performed largely in middle-income and high-income countries 3 , and some studies did not report a clear benefit 150,151 . The mechanisms underlying this have been postulated to include the activation of antigen-presenting cells, a reduction in the levels of pro-inflammatory cytokines, the modulation of effector T cell and regulatory T cell immune responses, innate immune signalling (through interactions with several TLRs) and the promotion of enterocyte proliferation and/or migration 152 . In low-income regions, treatment with probiotics has a positive immunomodulatory effect (that is, an increased anti-rotavirus IgG response in individuals who received treatment compared with individuals who received placebo), improves intestinal function in children with rotavirus infection and might decrease repeat episodes of rotavirus diarrhoea 153,154 . However, probiotics are not included in the standard of care for children with rotavirus diarrhoea globally.

Other drugs

Antiviral therapy for rotavirus infection has been studied but remains mostly in preclinical stages. One exception is nitazoxanide, a broad-spectrum antiviral drug 155 that has been reported to reduce the duration of diarrhoea and the duration of hospitalization of children with acute rotavirus diarrhoea 155–157 . Nitazoxanide inhibits the replication of rotavirus by interfering with viral morphogenesis 158 . One study in hospitalized children 5 months to 7 years of age reported a significant reduction in the median time to the resolution of all rotavirus-associated gastrointestinal symptoms from 75 hours in children who received placebo treatment to 31 hours in children who received a 3-day course of nitazoxanide treatment 156 .

Recommendations for the use of anti-emetics (such as metoclopramide, dimenhydrinate and ondansetron) for children with rotavirus disease have progressed from ‘not recommended’ to ‘possibly recommended’ owing to their effects of reducing the number of vomiting episodes and reducing the need for intravenous rehydration and hospitalization 150,159 . Indeed, one dose of ondansetron reduces the likelihood of needing intravenous rehydration, although this can increase diarrhoea output. Importantly, repeated doses do not provide an additional benefit over one dose. The largest benefit can be gained when ondansetron is used early in the clinical course of children with rotavirus infection and intense vomiting.

Other potential therapies for rotavirus gastroenteritis include racecadotril and smectite. Racecadotril (an intestinal enkephalinase inhibitor that reduces the secretion of water and electrolytes into the gut 160 ) has been shown to significantly decrease diarrhoea output at 48 hours after treatment and did not increase the frequency of adverse effects 161 . However, treatment with racecadotril did not reduce the proportion of patients with diarrhoea 5 days after treatment 161 . In addition, one meta-analysis of seven clinical trials reported that racecadotril treatment is more effective than placebo or no intervention at reducing the duration of illness and stool output in children with acute diarrhoea 162 . However, in Kenya, racecadotril did not alter the number of stools after 48 hours, the duration of hospital stay or the duration of diarrhoea in children with severe gastroenteritis who received ORS and zinc 163 and was not effective in Indian children with acute diarrhoea and vomiting 164 . Thus, racecadotril can be considered for the management of children with severe secretory diarrhoea, but the efficacy is variable. Smectite (a natural adsorbent that binds to endotoxins, exotoxins, bacteria and viral particles) has been reported to decrease the duration of acute diarrhoea by 18–29% in a meta-analysis of mostly open-label trials in children with acute diarrhoea. In addition, smectite has been shown to increase the cure rate at day 5, without any increase in the risk of adverse events and accordingly could be beneficial in some individuals with rotavirus disease 165,166 .

Combination trials evaluating the simultaneous use of several treatments are lacking 99 . Indeed, improvements in treatment strategies are needed, especially in regions where rotavirus-associated deaths occur and where vaccines are underutilized.


Rotavirus Infection

Rotavirus is a virus that infects the bowels, causing severe inflammation of the stomach and bowels (known as gastroenteritis). Rotavirus is the most common cause of severe diarrhea among infants and children throughout the world and causes the death of about 500,000 children worldwide annually. The name rotavirus comes from the characteristic wheel-like appearance of the virus when viewed by electron microscopy (the name rotavirus comes from the Latin rota, meaning "wheel").

Since 2006, vaccines have been available for rotavirus infection. Before the availability of a rotavirus vaccine, rotavirus infected almost all children by their third birthday. Repeat infections with different viral strains are possible, and most children had several episodes of rotavirus infection in the first years of life. After several infections with different strains of the virus, children acquire immunity to rotavirus. Babies and toddlers between 6-24 months of age are at the greatest risk for developing severe disease from rotavirus infection. Adults sometimes become infected, but the resulting illness is usually mild.

Worldwide, rotavirus infection is still a significant cause of death in infants and children. Rotavirus affects populations in all socioeconomic groups and is equally prevalent in industrialized and developing countries, so differences in sanitation practices or water supply are not likely to affect the incidence of the infection.

In the U.S., rotavirus infections usually peak in the fall months in the Southwest and spread to the Northeast by spring, so infections are most common during the winter months from November to May. However, infection with rotavirus can occur at any time of the year.

Rotavirus Infection

Childhood Illnesses Every Parent Should Know Slideshow

Rotavirus infection is responsible for significant morbidity and mortality in children in less developed countries where access to the rotavirus vaccine is limited. The infection causes significant fever, vomiting, and diarrhea in children. This can often lead to serious problems with dehydration, especially in very young children and infants.

What are rotavirus infection symptoms and signs?

Symptoms of the disease include fever, vomiting, and watery diarrhea. Abdominal pain may also occur, and infected children may have profuse watery diarrhea up to several times per day. Symptoms generally persist for three to nine days. Immunity from repeated infection is incomplete after a rotavirus infection, but repeated infections tend to be less severe than the original infection.

Rotavirus infection can be associated with severe dehydration in infants and children. Severe dehydration can lead to death in rare cases, so it is important to recognize and treat this complication of rotavirus infection. In addition to the symptoms of rotavirus infection discussed above, parents should be aware of the symptoms of dehydration that can occur with rotavirus infection or with other serious conditions.

Symptoms of dehydration include

  • lethargy,
  • dry, cool skin,
  • absence of tears when crying,
  • dry or sticky mouth,
  • sunken eyes or sunken fontanel (the soft spot on the head of infants), and
  • extreme thirst.

Šta causes rotavirus infections?

The rotavirus is a member of the Reoviridae family of viruses and contains double-stranded RNA enclosed by a double-shelled outer layer (capsid). Infection with different strains of the virus is possible, so it is common to have several separate rotavirus infections in childhood. Adults may also become infected, but the resulting illness is usually less severe than that in infants and young children.

Rotavirus vs. norovirus

Norovirus is the most common cause of gastroenteritis in the U.S. Noroviruses cause about 50%-70% of cases of gastroenteritis in adults, whereas rotavirus most typically affects young children. Like rotavirus, norovirus is highly contagious and spreads rapidly. Contaminated food and liquids can transmit noroviruses, as can touching objects contaminated with norovirus and then placing the hands or fingers in the mouth, direct contact with an infected individual, and contact with infected individuals and objects in day care centers and nursing homes.

What are risk factors for rotavirus infection?

Rotavirus most commonly infects infants and children. Since rotavirus infection is highly contagious, those who are around infected people are at high risk of infection. For this reason, children in group day care settings are at risk. However, rotavirus infects most children by 3 years of age.

Can adults get a rotavirus infection?

Yes, it is possible for anyone to develop a rotavirus infection. However, most adults who become infected have only minor symptoms, or may not have symptoms at all. Since neither vaccination nor previous infection provides full immunity, it is possible to get rotavirus infection more than once. The first infection tends to produce more severe symptoms than subsequent infections, and vaccination is very effective in infants in preventing severe symptoms (see below).

SLIDESHOW

Is rotavirus contagious? How long is rotavirus contagious?

Rotavirus infection is highly contagious. Contamination of hands or surfaces with the stool of an infected person and then touching the mouth is the main method of spread. Rotavirus infection is contagious (can be spread to other people) from the time before diarrhea develops until up to 10 days after symptoms have disappeared.

How does rotavirus spread?

The primary mode of transmission of rotavirus is the passage of the virus in stool to the mouth of another child, known as a fecal-oral route of transmission. Children can transmit the virus when they forget to wash their hands before eating or after using the toilet. Touching a surface contaminated with rotavirus and then touching the mouth area can result in infection.

There also have been cases of low levels of rotavirus in respiratory-tract secretions and other body fluids. Because the virus is stable (remains infective) in the environment, transmission can occur through ingestion of contaminated water or food and contact with contaminated surfaces. Rotavirus can survive for days on hard and dry surfaces, and it can live for hours on human hands.

What is the incubation period for rotavirus?

The time from initial infection to symptoms (incubation period) for rotavirus disease is typically around two days, but varies from one to three days.


How are human rotaviruses generally transmitted? - Biologija

Infection with a rare G3P[19] rotavirus A strain was identified in an immunosuppressed patient in Italy. The strain showed a P[19] viral protein 4 gene and a complete AU-1–like genomic constellation. Phylogenetic analyses showed high nucleotide identity between this strain and G3P[19] rotavirus A strains from Asia, indicating possible reassortment events.

Group A rotavirus (RVA) is the leading cause of acute gastroenteritis in children <5 years of age worldwide, causing ≈450,000 deaths annually. The RVA genome is composed of 11 double-stranded RNA segments, encoding 6 structural viral (VP) and 5 nonstructural (NS) proteins (1). The outer capsid proteins, VP7 and VP4, elicit neutralizing antibodies. The genes encoding these proteins specify at least 27 G and 37 P genotypes, which are used for RVA binary classification.

Most RVA human infections worldwide are related to 5 major genotypes: G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8] (2). Genome segment reassortment between human strains or human and animal strains during co-infections can generate viruses with novel genotype combinations, possibly influencing the virus phenotype (2). Some human and animal RVA strains possess unusual genotype combinations (3,4), and some strains might partially escape vaccine-induced immune protection (5).

Since 2007, the RVA surveillance network RotaNet-Italy has confirmed circulation of common RVA genotypes among children in Italy, despite sporadic uncommon, exotic, or zoonotic genotypes (6,7). We describe infection with a rare G3P[19] RVA strain in an immunosuppressed adult patient in Italy who had severe diarrhea.

Studija

In 2012, a 35-year-old woman who was hospitalized in the Hematology Unit of Rome University Hospital “Agostino Gemelli” in Rome, Italy she experienced acute gastroenteritis after a bone marrow allotransplant. Stool samples were collected and tested for classic bacterial, viral, and parasitic enteropathogens. The study was performed in compliance with informed consent guidelines in Italy.

Viral RNA was extracted by using the Viral RNeasy MiniKit (QIAGEN/Westburg, Milan, Italy) and stored at −80°C until use. Rotavirus G- and P-genotyping were performed by reverse transcription nested PCR by using VP7 or VP4 primer mixtures described previously (8,9). Nucleotide sequencing was performed by Macrogen, Inc. (Seoul, South Korea) by using the PCR primers. After analysis in Chromas Pro 2.23 (http://www.technelysium.com.au), consensus sequences were obtained by using SeqMan II (http://www.dnastar.com/t-seqmanpro.aspx). Multiple sequence alignments were carried out, and phylogenetic trees were created by using MEGA5 software (http://www.megasoftware.net) (10), using the maximum-likelihood method and Kimura 2- (NS 4–5) or Tamura 3- (all other genes) parameter tests. Strain sequences from this study were deposited in GenBank (accession nos. KF729023–729032).

The patient had Down syndrome, acute lymphatic leukemia, and blood type A Rh+ CCDeekk phenotype a transcranial Doppler scane did not show any abnormalities . She had received a stem cell allotransplant, followed by immunosuppressive treatment. Acute gastroenteritis began 2 days after immunosuppression, on day 10 after admission to the Hematology Unit. Diarrhea was nonbloody and watery, not accompanied by vomiting and fever, and lasted 3 days, during which rehydration therapy was administered. The patient was released from the hospital in stable condition she died of systemic complications 3 months later.

Stool samples were collected at diarrhea onset and tested for bacterial and viral enteric pathogens. Results were negative for Salmonella, Shigella, Campylobacter, Yersinia, Escherichia coli, staphylococci, Giardia, norovirus, and adenovirus. Only rotavirus and Klebsiella pneumoniae were detected because the patient did not exhibit chronic/bloody diarrhea or other systemic pathologies typically related to K. pneumoniae infection, this pathogen was not investigated further.

Figure 1. Phylogenetic trees of rotavirus A (RVA) isolates based on the open reading frames of genes coding for the viral protein (VP) regions. A) VP1 (nt 73–390) B) VP2 (nt 1–425) C).

Figure 2. Phylogenetic trees of rotavirus A (RVA) isolates based on the open reading frames of genes coding for the nonstructural protein (NS) regions. A) NS1 (nt 67–1087), B) NS2 (nt 47–1012), C).

The rotavirus strain, RVA/human-wt/ITA/ROMA116/2012/G3P[19] (ROMA116), was characterized by analyzing its 11 genomic RNA segment sequences in RotaC Tool (http://rotac.regatools.be/). The strain showed the genotype constellation of G3-P[19]-I3-R3-C3-M3-A3-N3-T3-E3-H3. Phylogenetic analyses confirmed a full AU-1–like genomic constellation, associated with the P[19] VP4 gene (Figures 1, 2). The strain clustered strictly with RVA/human-tc/CHN/L621/2006/G3P[9] from China (11), sharing 98%–99% nucleotide identities for most genes except VP1 (identity 91%), and the VP4 and NS5 genes, which belonged to different genotypes (Figures 1, 2). ROMA116 also showed high nucleotide identities (98%–99%) in VP2, VP6–7, and NS1–4 genes with strain RVA/human-wt/THA/CU365-KK/2008/G3P[9] from Thailand (12).

The VP7 tree (Figure 1, panel D) revealed strict clustering of ROMA116 with G3 strains from China, Thailand, and Hong Kong, all associated with P[9] VP4. However, other G3 RVA strains from Italy reported in humans or cats grouped in the same cluster. The VP4 tree (Figure 1, panel E) shows the correlation of the ROMA116 P[19] sequence with P[19] sequences detected in human and swine strains from 1994–2010, suggesting possible human-pig reassortment at the origin of ROMA116 VP4. Further evidence of reassortment resulted from both VP1 and NS5 tree analyses. In VP1, ROMA116 showed the highest nucleotide identity (95%) with simian strain TUCH (Figure 1, panel A) in NS5, the uncommon H3 genotype of ROMA116 clustered with strains detected in or derived from animals (Figure 2, panel E).

The phylogenetic trees show the divergence of ROMA116 from the constellation 3 putative ancestor AU-1 (13), characterized during the 1980s. ROMA116 shared relatively high nucleotide sequence conservation of only the NS1 gene with AU-1, but all other genes analyzed clustered more closely with RVA strains detected in Asia. This mixed genomic pattern probably was generated by previous reassortment events between strains circulating in that area. Analysis of the VP1, VP4, and NS5 gene trees together indicates that ROMA116 may have evolved through multiple reassortment events involving RVA strains of different animal origins.

Zaključci

The G3P[19] RVA strain we identified represents a single sporadic detection among >7,000 human RVA strains investigated in Italy during a 7-year period, which suggests either a recent introduction or a low ability of this strain to spread among humans. However, the phylogenetic analysis shows that the overall genome of ROMA116 is more similar to those reported for human strains than for animal strains, suggesting that the strain has a lower fitness for replicating in animal hosts than in humans. A study in Thailand (14) reported an outbreak of diarrhea in piglets caused by G3P[19] RVA, but no information was available for the other genes of that strain.

The possible importation of an apparently exotic rotavirus strain such as ROMA116 into Italy is not surprising the country’s geographic position favors massive migratory flows of persons from developing countries. Although rare, similar events have been suggested previously (7). The source of this infection was not identified no additional case was reported among hospital ward patients and personnel or in the patient’s family. The patient’s parents had been cleared to assist their daughter daily after the transplant, but strict control measures for opportunistic infectious agents were otherwise enforced. The patient’s family lived in a rural area where swine, bovine, and ovine farming activities occur in close proximity to human residential settlements, which may favor the circulation and zoonotic transmission of viruses from domestic animals to a higher extent than is possible inside urban settings such as Rome. The G3P[19] RVA strain may have been transmitted by an asymptomatic but infected relative, or the patient may have been harboring the strain in the gut before hospital admission, with active viral replication and disease occurring after immunosuppressive treatment.

Because no other enteropathogens were detected among the large panel of bacteria, viruses, and parasites investigated, it is likely that rotavirus was directly involved in causing illness in the patient, whose clinical symptoms were compatible with acute watery rotavirus diarrhea. It is possible that this RVA genotype may not cause disease in immunocompetent persons and that the compromised immune status of this patient played a critical role. Even if G3P[19] RVA, as with other uncommon viral strains, does not present a direct risk for public health in Italy, it could nonetheless be a donor of atypical RVA genes that might reassort into novel epidemic strains that could escape existing herd immunity in humans. In this view, RVA surveillance of both farmed and pet animals could be of valuable support to human surveillance of severe cases in hospitals (15), particularly in the postvaccine globalized world.

Dr Ianiro works as a postdoctoral researcher in the National Center for Immunobiologicals Research and Evaluation and the Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome. His main research areas are molecular biology and epidemiology of human and animal rotaviruses.


Zaključak

Efforts to help alleviate the burden of rotavirus disease in sub-Saharan Africa and other developing countries have increased significantly in recent years. In this study, we evaluated the possibility of producing rotavirus VLPs using a plant expression system to produce a vaccine specifically adapted to the sub-Saharan African regions. We had partial success in demonstrating the capacity of the transient plant expression system to express specific rotavirus proteins. Despite the fact that no VLPs were observed for our fusion proteins, expression was detected for all chimeric proteins engineered, illustrating the versatility of plant-based systems. While this work is preliminary, we believe that it will serve as a solid basis for future studies on plant-made rotavirus vaccines for Africa.


Characterization of a Novel P[25],G11 Human Group A Rotavirus

Sl. 1. Neighbor-joining phylogenetic tree based on nucleotide sequences of the VP7 encoding genes (nt 49-1026) for Dhaka6 and other established rotavirus G types. BO, bovine HU, human PO, porcine EQ, equine AV, avian. The VP7 sequences were obtained from published reports and the GenBank database. The GenBank accession numbers of the following strains are given in parentheses: Wa (KO2033), HU5 (A01028), SA11 (K02028), ST3 (X13603), OSU (X04613), NCDV (M12394), PA151 (L20881), Se584 (AJ311740), Ch2 (X56784), B37 (J04334), B223 (X57852), YM (M23194), L26 (M58290), L333 (D13549), FI23 (M61876), and Hg18 (AF237666). The VP7 sequence of WI61 was obtained from Green et al. (16). Sl. 2. Comparison of the amino acid sequences of antigenic regions of Dhaka6 and other rotavirus G types. Dots indicate amino acids identical to the respective amino acids of Dhaka6. Sl. 3 . Neighbor-joining phylogenetic tree based on the nucleotide sequences (nt 44-762) of the VP8* fragments of the VP4 genes for Dhaka6 and other established rotavirus P types. BO, bovine HU, human PO, porcine EQ, equine SI, simian OV, ovine MU, murine RH, rhesus LA, lupine. The VP4 sequences and their GenBank accession numbers are as follows: A5 (D13395), SA11 (X14204), HCR3 (L19712), RV5 (M32559), UK ST3 (L33895), OSU (X13190), Wa (L34161), AU1 (D10970), 69 M (M60600), 116E (L94072), H2 (L04638), MDR13 (L07886), Mc35 (D14032), Lp14 (L11599), Eb (L18992), 993/83 (D16352), L338 (D13399), 4F (L10359), EHP (U08424), Hg18 (AF237665) 160/01 (AF528202), A34 (L35059), and TUCH (AY596179).


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