Phantse sonke sivile okanye safunda iindaba malunga nokusasazeka kwe-coronavirus. Njengaso nasiphi na esinye isifo, ukuxilongwa kwangoko kubalulekile kumlo ochasene nentsholongwane entsha. Nangona kunjalo, ayingabo bonke abantu abosulelekileyo ababonisa iimpawu ezifanayo, kwaye nezixhobo zokuskena zesikhululo seenqwelomoya ezenzelwe ukubona iimpawu zosulelo azisoloko zisichaza isigulana ngempumelelo phakathi kwesihlwele sabakhweli. Umbuzo uvela: kutheni intsholongwane enye izibonakalisa ngokwahlukileyo kubantu abahlukeneyo? Ngokwemvelo, impendulo yokuqala i-immunity. Nangona kunjalo, oku akukuphela kweparameter ebalulekileyo echaphazela ukuguquguquka kweempawu kunye nobukhulu besifo. Iingcali zenzululwazi ezivela kwiYunivesithi yaseCalifornia naseArizona (e-USA) ziye zafumanisa ukuba amandla okumelana neentsholongwane akuxhomeki nje kuphela kwiintlobo ze-subtypes zomkhuhlane umntu abe nazo ebomini bakhe bonke, kodwa kunye nokulandelelana kwazo. Yintoni kanye kanye eyafunyaniswa zizazinzulu, zeziphi iindlela ezisetyenzisiweyo kolu phando, kwaye lo msebenzi unokunceda njani ekulweni nobhubhane? Siza kufumana iimpendulo kule mibuzo kwingxelo yeqela lophando. Hamba.
Isiseko sophando
Njengoko sisazi, umkhuhlane uzibonakalisa ngokwahlukileyo kubantu abohlukeneyo. Ukongeza kwinkalo yomntu (i-immune system, ukuthatha amachiza e-antiviral, amanyathelo okuthintela, njl.), inkalo ebalulekileyo yintsholongwane ngokwayo, okanye kunoko i-subtype yayo, echaphazela isigulane esithile. I-subtype nganye ineempawu zayo, kubandakanywa ubungakanani bamaqela ahlukeneyo abantu abachaphazelekayo. Iingcali zenzululwazi ziqaphela ukuba i-H1N1 ("umkhuhlane wehagu") kunye ne-H3N2 (i-Hong Kong flu) iintsholongwane, eziye zezona zixhaphakileyo okwangoku, zichaphazela abantu beminyaka eyahlukeneyo ngokwahlukileyo: I-H3N2 ibangela iimeko ezinzima kakhulu zesifo kubantu abadala, kwaye kubalelwa kuninzi lokufa; I-H1N1 ayibulali kangako kodwa idla ngokuchaphazela abantu abakubudala obuphakathi kunye nolutsha.
Umahluko onjalo usenokuba ngenxa yokubini umahluko kwisantya sokuzivelela kweentsholongwane ngokwazo kunye nomahluko phakathi imprinting yomzimba * ebantwaneni.
Ushicilelo lwamajoni omzimba* - uhlobo lwenkumbulo yexesha elide lwe-immune system, eyenziwe ngesiseko sokuhlaselwa kwentsholongwane enamava emzimbeni kunye neempendulo zayo kubo.
Kolu phononongo, abaphandi bahlalutya idatha ye-epidemiological ukufumanisa ukuba ukuprintwa kwabantwana kunempembelelo kwi-epidemiology yomkhuhlane wonyaka kwaye, ukuba kunjalo, ingaba isebenza ngokuyintloko i-homosubtypic* inkumbulo yomzimba okanye ngobubanzi heterosubtypic* inkumbulo.
I-homosubtypic immunity* - ukusuleleka ngentsholongwane ye-influenza yonyaka A ikhuthaza ukuphuhliswa kokhuselo lomzimba ngokuchasene nohlobo oluthile lwentsholongwane.
I-Heterosubtypic immunity* - ukosuleleka ngentsholongwane ye-influenza ye-seasonal A ikhuthaza uphuhliso lokhuselo lomzimba ngokuchasene ne-sub-strains engahambelani nale ntsholongwane.
Ngamanye amazwi, ukukhuseleka komntwana kunye nayo yonke into ayifumanayo ishiya uphawu lwayo kukhuselo lomzimba ebomini. Uphononongo lwangaphambili lubonise ukuba abantu abadala banokhuselo olunamandla ngokuchasene neentlobo zeentsholongwane ezosulelwe zizo besengabantwana. Ukuprintwa kutsha nje kubonakaliswe ukukhusela kwintsholongwane entsha ye-avian influenza virus subtypes yeqela elifanayo le-hemagglutinin phylogenetic.hemagglutinin, HA), njengosulelo lokuqala ebuntwaneni.
Ukuza kuthi ga ngoku, ukhuselo olunqamlezileyo olunqamlezileyo olukhethekileyo kwiintlobo ezahlukeneyo ze-HA subtype yayithathwa njengeyona ndlela iphambili yokhuseleko kumkhuhlane wonyaka. Nangona kunjalo, kukho ubungqina obutsha obubonisa ukuba ukubunjwa kwe-immunity kunokuphenjelelwa yinkumbulo yezinye ii-antigens zomkhuhlane (umzekelo, i-neuraminidase, i-NA). Ukususela ngo-1918, iintlobo ezintathu ze-AN ziye zachongwa ebantwini: i-H1, i-H2 kunye ne-H3. Ngaphezu koko, i-H1 kunye ne-H2 yeqela le-phylogenetic 1, kunye ne-H3 kwiqela lesi-2.
Ngenxa yenyani yokuba ushicilelo lunokubangela utshintsho oluninzi kwinkumbulo yomzimba, kunokucingelwa ukuba olu tshintsho lunolawulo oluthile.
Iingcali zenzululwazi ziqaphela ukuba ukususela ngo-1977, iintlobo ezimbini ze-influenza A-H1N1 kunye ne-H3N2-ziye zajikeleza ngexesha elithile phakathi kwabemi. Kwangaxeshanye, iyantlukwano kwinani labantu bosulelo kunye neempawu zazicace gca, kodwa zingafundwanga kakuhle. Lo mahluko usenokuba ngenxa yokushicilelwa kwabantwana: abantu abadala baphantse bavezwa kwi-H1N1 njengabantwana (ukususela ngo-1918 ukuya ku-1975 yayikuphela kohlobo oluncinane olujikeleza ebantwini). Ngenxa yoko, aba bantu ngoku bakhuselwe ngcono kwiintlobo ezahlukeneyo zamaxesha onyaka ale ntsholongwane yolu hlobo. Ngokunjalo, phakathi kwabantu abadala abasebatsha, awona mathuba aphezulu okuprintwa komntwana ngowe-H3N2 yamva nje (umfanekiso #1), ohambelana nenani eliphantsi ngokwentelekiso leemeko ezixelwe ekliniki ze-H3N2 kolu luhlu lwabantu.
Umfanekiso weNombolo ye-1: iimodeli ezihlukeneyo zokuxhomekeka kwe-immunity kwi-imprinting ebuntwaneni kunye ne-factor of viral evolution.
Kwelinye icala, lo mahluko unokunxulunyaniswa nokuvela kweentsholongwane ezisezantsi ngokwazo. Ngaloo ndlela, i-H3N2 ibonisa ngokukhawuleza ukukhukuliseka* phenotype yayo antigenic kune H1N1.
Ukukhukuliseka kweAntigen* - utshintsho kwimiba ye-immune-forming surface yeentsholongwane.
Ngesi sizathu, i-H3N2 inokukwazi ngcono ukuphepha ukhuseleko olusele lukhona kubantu abadala abanamava, ngelixa i-H1N1 inokulinganiselwa kwiziphumo zayo kuphela kubantwana abangenayo i-immunologically.
Ukuvavanya zonke iingqikelelo ezibambekayo, izazinzulu zahlalutya idatha ye-epidemiological ngokudala imisebenzi enokwenzeka yokwahluka kwemodeli nganye yezibalo, ezithelekiswe kusetyenziswa i-Akaike Information Criterion (AIC).
Uhlalutyo olongezelelweyo luye lwenziwa kwi-hypothesis apho ulwahlulo alukho ngenxa yokuprinta ekuziphendukeleni kweentsholongwane.
Ukulungiselela isifundo
I-hypothesis modeling isetyenzisiweyo idatha evela kwiSebe leeNkonzo zezeMpilo zase-Arizona (ADHS) ze-9510 zelizwe lonke ze-H1N1 kunye neemeko ze-H3N2. Malunga ne-76% yeemeko ezixeliweyo zarekhodwa kwizibhedlele nakwiilabhoratri, iimeko eziseleyo azichazwanga kwiilebhu. Kukwayaziwa ukuba malunga nesiqingatha seemeko eziye zafunyaniswa elabhoratri zazinobuzaza kangangokuba zikhokelela esibhedlele.
Idatha esetyenzisiweyo kwisifundo ihlanganisa ixesha le-22 iminyaka ukusuka kwixesha lomkhuhlane we-1993-1994 ukuya kwixesha le-2014-2015. Kuyafaneleka ukuba uqaphele ukuba ubungakanani besampulu bonyuke ngokukhawuleza emva kobhubhane ka-2009, ngoko eli xesha lalingabandakanyi kwisampulu (Itheyibhile 1).
Itheyibhile ye-1: idatha ye-epidemiological ukusuka kwi-1993 ukuya kwi-2015 malunga neemeko ezirekhodiweyo ze-H1N1 kunye ne-H3N2 iintsholongwane.
Kwakhona kubalulekile ukuqwalasela ukuba ukususela ngo-2004, iilebhu zorhwebo e-United States ziye zafuneka ukuba zidlulisele yonke idatha malunga nokusuleleka kwintsholongwane yezigulane kumagunya ezempilo karhulumente. Nangona kunjalo, uninzi lwamatyala ahlalutyiweyo (9150/9451) avela kwisizini ye-2004-2005, emva kokuba umthetho usebenze.
Kuzo zonke iimeko ze-9510, i-58 yayingabandakanywanga ngenxa yokuba yayingabantu abanonyaka wokuzalwa ngaphambi kwe-1918 (imeko yabo yokuprinta ayinakucaciswa ngokucacileyo), kunye nenye imeko ye-1 ngenxa yokuba unyaka wokuzalwa wawuchazwe ngokungachanekanga. Ngaloo ndlela, iimeko ze-9541 ββzifakwe kumzekelo wokuhlalutya.
Kwinqanaba lokuqala lomzekelo, amathuba okuprintwa kwi-H1N1, i-H2N2 okanye i-H3N2 iintsholongwane, ngokuthe ngqo kunyaka wokuzalwa, zinqunywe. Oku nokwenzeka kubonisa indlela yokuchanabeka kumkhuhlane A ebantwaneni kunye nokuxhaphaka kwawo ngonyaka.
Uninzi lwabantu abazalwa phakathi kwe-1918 kunye ne-1957 bhubhane baqala ukusuleleka nge-H1N1 subtype. Abantu abazalwa phakathi kwe-1957 kunye ne-1968 bhubhane phantse bonke bosulelwa yi-H2N2 subtype (1A). Kwaye ukususela ngo-1968, i-subtype eyongameleyo yentsholongwane yayiyi-H3N2, eyaba ngunobangela wosulelo lwabantu abaninzi beqela elincinane labantu.
Ngaphandle kokuxhaphaka kwe-H3N2, i-H1N1 isasasazwa ngamaxesha athile onyaka kubemi ukusukela ngo-1977, ibangela ukuba kushicilelwe inani labantu abazalwe ukusukela phakathi koo-1970.1A).
Ukuba ushicilelo kwinqanaba lohlobo olusezantsi lwe-AN lubumba ukubakho kosulelo ngexesha lomkhuhlane wonyaka, emva koko ukuvezwa kwe-H1 okanye i-H3 AN subtypes ebuntwaneni kufuneka kubonelele ngokhuseleko lobomi bonke kwiiyantlukwano zamva nje zohlobo olusezantsi lwe-AN. Ukuba i-imprinting immunity isebenza kumlinganiselo omkhulu ngokuchasene neentlobo ezithile ze-NA (neuraminidase), ngoko ukhuseleko lobomi bonke luya kuba luphawu lwe-N1 okanye i-N2.1B).
Ukuba ukuprintwa kusekelwe kwi-NA ebanzi, okt. ukukhuselwa kuluhlu olubanzi lwee-subtypes lwenzeka, ngoko ke abantu abashicilelwe kwi-H1 kunye ne-H2 kufuneka bakhuselwe kwi-H1N1 yanamhlanje. Kwangaxeshanye, abantu abashicilelwe kwi-H3 baya kukhuselwa kuphela kwixesha langoku le-H3N2 (1B).
Iingcali zenzululwazi ziqaphela ukuba i-collinearity (ethetha ngokuthe ngqo, i-parallelism) yoqikelelo lweemodeli ezahlukeneyo zokuprinta (1D-1I) bekungenakuphepheka xa kujongwa ulwahlulo olulinganiselweyo lwe-antigenic subtypes yomkhuhlane ejikeleza kubemi kwinkulungwane edlulileyo.
Indima ebaluleke kakhulu ekuhlukaniseni phakathi kokushicilelwa kwi-HA subtype, i-NA subtype okanye inqanaba leqela le-HA lidlalwa ngabantu abaneminyaka ephakathi abaqala ukusuleleka nge-H2N2 (1B).
Imodeli nganye evavanyiweyo isebenzise indibaniselwano yomgca wosulelo olunxulumene nobudala (1C), kunye nosulelo olunxulumene nonyaka wokuzalwa (1D-1F), ukufumana ukuhanjiswa kweemeko ze-H1N1 okanye i-H3N2 (1G - 1I).
Iimodeli ezipheleleyo ze-4 zidalwe: eyona ilula iqulethe kuphela iminyaka yobudala, kwaye imodeli enzima ngakumbi yongeza izinto zokuprinta kwinqanaba le-HA, kwinqanaba le-NA, okanye kwinqanaba leqela le-HA.
I-curve factor curve inesimo somsebenzi wesinyathelo apho umngcipheko wokosuleleka ubekwe kwi-1 kwiqela leminyaka 0-4. Ukongeza kwiqela leminyaka ephambili, kukho kwakhona oku kulandelayo: 5β10, 11β17, 18β24, 25β31, 32β38, 39β45, 46β52, 53β59, 60β66; 67-73, 74-80, 81+.
Kwimifuziselo equka iziphumo zokuprinta, umlinganiselo wabantu kunyaka ngamnye wokuzalwa ngokuprintwa komntwana okhuselweyo kwakucingelwa ukuba ulingana nokwehliswa komngcipheko wosulelo.
Umba wokuziphendukela kwentsholongwane egazini nawo wathathelwa ingqalelo kwimodeli. Ukwenza oku, sasebenzisa idatha echaza inkqubela ye-antigenic yonyaka, echazwe njenge-avareji yomgama we-antigenic phakathi kweentlobo ze-viral lineage (H1N1 ngaphambi kwe-2009, i-H1N1 emva kwe-2009, kunye ne-H3N2). "Umgama we-Antigenic" phakathi kweentlobo ezimbini zomkhuhlane usetyenziswa njengesalathisi sokufana kwi-phenotype ye-antigenic kunye nokukhuselwa kwe-immune cross-protection.
Ukuvavanya impembelelo ye-antigenic evolution kwi-age bhubhane, utshintsho kwi-proportion yamatyala kubantwana bavavanywa ngexesha lonyaka apho utshintsho olunamandla lwe-antigenic lwenzeke.
Ukuba inqanaba le-antigenic drift liyinto ebalulekileyo kwingozi enxulumene neminyaka yokusuleleka, ngoko ke umlinganiselo wamatyala abonwa kubantwana kufuneka udibaniswe kakubi nenkqubela phambili ye-antigenic yonyaka. Ngamanye amazwi, iintlobo ezingazange zenzeke utshintsho olubalulekileyo lwe-antigenic kwixesha elidlulileyo kufuneka zingakwazi ukubalekela i-immunity ekhoyo kubantu abadala abanamava e-immunologically. Iintlobo ezinjalo ziya kusebenza ngakumbi phakathi kwabemi abangenawo amava e-immunoloji, oko kukuthi, phakathi kwabantwana.
Iziphumo zophando
Uhlalutyo lwedatha ngonyaka lubonise ukuba i-H3N2 yexesha lonyaka yayiyeyona nto ibangela usulelo phakathi kwabantu abadala, ngelixa i-H1N1 ichaphazele abantu abaphakathi kunye nabaselula (umfanekiso #2).
Umfanekiso we-2: Ukusasazwa kwe-H1N1 kunye ne-H3N2 umkhuhlane ngeminyaka yobudala ngamaxesha ahlukeneyo.
Le pateni yayikhona kwidatha phambi kobhubhani ka-2009 nasemva kwawo.
Idatha ibonise ukuba ukuprintwa kwinqanaba le-NA le-subtype lihamba phambili ngaphezu kokushicilela kwinqanaba le-HA subtype (ΞAIC = 34.54). Ngelo xesha, kwakukho phantse ukungabikho okupheleleyo kokuprintwa kwinqanaba leqela le-HA (ΞAIC = 249.06), kunye nokungabikho ngokupheleleyo kokushicilela (ΞAIC = 385.42).
Umfanekiso #3: Ukuvavanya ukufaneleka kweemodeli kwidatha yophando.
Uvavanyo olubonakalayo lwemodeli efanelekileyo (3C ΠΈ 3D) iqinisekisile ukuba iimodeli eziqulethe iziphumo zokuprinta kumanqanaba amancinci e-NA okanye e-HA subtypes anikezela ngokufanelekileyo kwidatha esetyenziswe kwisifundo. Inyaniso yokuba imodeli apho imprinting ingekho ayikwazi ukuxhaswa ngedatha ibonisa ukuba ukuprintwa kuyinkalo ebaluleke kakhulu yokuphuhliswa kokugonywa kwabantu abadala ngokumalunga nee-subtypes zomkhuhlane wonyaka. Nangona kunjalo, ukushicilela kusebenza kwi-specialization emxinwa kakhulu, oko kukuthi, kusebenza ngokukodwa kwi-subtype ethile, kwaye kungekhona kwi-spectrum yonke ye-influenza subtypes.
Itheyibhile yesi-2: uvavanyo lokufaneleka kweemodeli kwidatha yophando.
Emva kokulawula ukuhanjiswa kweminyaka yobudala, umngcipheko onxulumene neminyaka wawuphezulu ebantwaneni nakubantu abadala, ngokuhambelana nokuqokelelwa kwememori yokuzikhusela ebuntwaneni kunye nokuncipha kokusebenza komzimba kubantu abadala 3A ijika eliqikelelweyo elisuka kweyona modeli ilungileyo ibonisiwe). Uqikelelo lweparameter yokuprinta lwalungaphantsi kwesinye, lubonisa ukunciphisa okuncinci kumngcipheko ohambelanayo (Itheyibhile 2). Kwimodeli engcono kakhulu, ukuncitshiswa komngcipheko oqikelelwayo ukusuka ekuprintweni komntwana kwakukhulu kwi-H1N1 (0.34, 95% CI 0.29-0.42) kune-H3N2 (0.71, 95% CI 0.62-0.82).
Ukuvavanya impembelelo yentsholongwane kwintsholongwane kwiminyaka yobudala yomngcipheko wosulelo, abaphandi bajonge ukuhla kwenani losulelo phakathi kwabantwana ngamaxesha ahambelana notshintsho lwe-antigenic, xa iintlobo ezine-antigenic drift ephezulu zisebenza ngakumbi ekosuleleni abantu abadala abanamava.
Uhlalutyo lwedatha lubonise umbutho omncinci ongalunganga kodwa ongabalulekanga phakathi kokunyuka konyaka kumsebenzi we-antigenic kunye nomlinganiselo wamatyala e-H3N2 abonwa kubantwana (4A).
Umfanekiso weNombolo ye-4: impembelelo ye-viral evolution kwi-age-related risk factor for infection.
Nangona kunjalo, akukho budlelwane obucacileyo bufunyenwe phakathi kweenguqu ze-antigenic kunye nomlinganiselo wamatyala abonwa kubantwana abangaphezu kweminyaka eyi-10 kunye nabantu abadala. Ukuba i-viral evolution idlala indima enkulu kolu lwabiwo, umphumo uya kuba bubungqina obucacileyo bempembelelo ye-evolution phakathi kwabantu abadala, kungekhona nje xa kuthelekiswa nabantu abadala kunye nabantwana abangaphantsi kweminyaka eyi-10 ubudala.
Ngaphezu koko, ukuba iqondo lentsholongwane yenguquko yentsholongwane lilawula i-subtype-specific iyantlukwano kwi-epidemic age distribution, ngoko xa i-H1N1 kunye ne-H3N2 subtypes zibonisa amazinga afanayo okusasazeka kwe-antigen yonyaka, ukuhanjiswa kwabo kweminyaka yosulelo kufuneka kubonakale kufana ngakumbi.
Ukuze ufumane ulwazi oluthe kratya malunga nee-nuances zophononongo, ndincoma ukujonga .
Ipilo
Kulo msebenzi, izazinzulu zihlalutye idatha ye-epidemiological kwiimeko zokusuleleka nge-H1N1, i-H3N2 kunye ne-H2N2. Uhlalutyo lwedatha lubonise ubudlelwane obucacileyo phakathi kokushicilela ebuntwaneni kunye nomngcipheko wosulelo kubuntu obudala. Ngamanye amazwi, ukuba umntwana oneminyaka engama-50 wayenosulelo xa i-H1N1 yayijikeleza kwaye i-H3N2 yayingekho, ngoko xa umntu ekhulile amathuba okusuleleka nge-H3N2 kuya kuba mkhulu kunokuba kunokwenzeka ukubamba i-H1N1.
Isiphelo esiphambili solu cwaningo kukuba akubalulekanga nje kuphela oko umntu ahlupheke kuyo ebuntwaneni, kodwa kwanaluphi na umyalelo. Inkumbulo yamajoni omzimba, ekhula kubo bonke ubomi, ngokukhutheleyo "irekhodi" idatha evela kwintsholongwane yokuqala yentsholongwane, enegalelo ekuchaseni okusebenzayo kubo xa bebadala.
Izazinzulu zinethemba lokuba umsebenzi wazo uyakwenza ukuba kube lula ukuqikelela ukuba ngawaphi na amaqela obudala anokuchaphazeleka ngakumbi ukuba zeziphi iindidi zomkhuhlane. Olu lwazi lunokunceda ukuthintela ukusasazeka kwezifo ezibulalayo, ngakumbi ukuba inani eliqingqiweyo lezitofu zokugonya kufuneka lisasazwe kubemi.
Olu phando alujolisanga ekufumaneni unyango olukhulu lwalo naluphi na uhlobo lomkhuhlane, nangona oko kuya kuba kuhle. Ijolise kwinto eyinyani ngakumbi kwaye ibalulekile okwangoku - ukuthintela ukusasazeka kosulelo. Ukuba asikwazi ukuyisusa kwangoko intsholongwane, kufuneka sibe nazo zonke izixhobo zokuyiqulatha. Omnye wawona mahlakani athembekileyo kuwo nawuphi na ubhubhani sisimo sengqondo sokungakhathali ngakuwo zombini kwicala likarhulumente ngokubanzi kunye nomntu ngamnye ngokukodwa. Uloyiko, ngokuqinisekileyo, aluyomfuneko, kuba lunokwenza izinto zibe mbi ngakumbi, kodwa izilumkiso azize zibuhlungu.
Enkosi ngokufunda, hlala unomdla, zinakekele kunye nabo ubathandayo kwaye ube nempelaveki emnandi bafana! π
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