Tinenge tese takanzwa kana kuverenga nhau nezve coronavirus iri kupararira. Sezvimwe nechimwe chirwere, kuongororwa kwekutanga kwakakosha mukurwisa hutachiona hutsva. Nekudaro, havazi vese vanhu vane hutachiona vanoratidza zviratidzo zvakafanana, uye kunyange ma scanner epa airport akagadzirirwa kuona zviratidzo zvehutachiona haawanzo zivisa murwere pakati pemhomho yevafambi. Mubvunzo unomuka: sei hutachiona humwe huchizviratidza zvakasiyana muvanhu vakasiyana? Sezvingatarisirwa, mhinduro yekutanga immunity. Zvisinei, iyi haisi iyo chete yakakosha parameter inokonzera kusiyana kwezviratidzo uye kuoma kwechirwere. Masayendisiti kubva kuYunivhesiti yeCalifornia neArizona (USA) vakaona kuti simba rekudzivirira kune utachiona hunoenderana kwete chete nemhando ipi yefuruwenza iyo munhu ave nayo muhupenyu hwake hwose, asiwo pakutevedzana kwavo. Chii chaizvo chakaonekwa nemasayendisiti, nzira dzipi dzakashandiswa muchidzidzo ichi, uye basa iri ringabatsira sei mukurwisa zvirwere? Tichawana mhinduro dzemibvunzo iyi mumushumo weboka retsvakurudzo. Enda.
Hwaro hwechidzidzo
Sezvatinoziva, furuwenza inozviratidza zvakasiyana muvanhu vakasiyana. Mukuwedzera kune chinhu chevanhu (immune system, kutora antiviral zvinodhaka, matanho ekudzivirira, nezvimwewo), chinhu chakakosha hutachiona pachahwo, kana kuti subtype yayo, iyo inotapukira mumwe murwere. Imwe neimwe subtype ine hunhu hwayo, kusanganisira huwandu hwekukanganiswa kwemapoka akasiyana. Masayendisiti anocherechedza kuti H1N1 ("flue flu") uye H3N2 (Hong Kong flu) mavhairasi, ayo anyanya kuitika panguva ino, anobata vanhu vezera rakasiyana zvakasiyana: H3N2 inokonzera zvirwere zvakanyanya zvechirwere kune vakwegura, uye zvakare inonzi inokonzerwa nehuwandu hwevakafa; H1N1 haina kuuraya zvakanyanya asi kazhinji inobata vanhu vezera repakati uye vechidiki.
Misiyano yakadaro inogona kunge iri nekuda kwezvose mutsauko wehuwandu hwekushanduka kwehutachiona pachahwo uye mutsauko mukati immune imprinting* muvana.
Immune imprinting* - rudzi rwekurangarira kwenguva refu kwesimba rekudzivirira, rakaumbwa pahwaro hweruzivo rwehutachiona hwekurwisa muviri uye maitiro ayo kwavari.
Muchidzidzo ichi, vaongorori vakaongorora epidemiological dhata kuti vaone kana kudhindisa kwehudiki kuchikanganisa epidemiology yemwaka furuwenza uye, kana zvakadaro, ingave ichiita zvakanyanya kuburikidza. homosubtypic* immune memory kana kuburikidza nehupamhi heterosubtypic* ndangariro.
Homosubtypic immunity* - kutapukirwa nemwaka wefuruwenza A mavhairasi anosimudzira kuvandudzwa kwekudzivirira kwekudzivirira kubva kune chaiyo subtype yehutachiona.
Heterosubtypic immunity* - kutapukirwa nemwaka wefluenza A viruses kunokurudzira kuvandudzwa kwekudzivirirwa kwekudzivirira kubva kune sub-strains isingaenderane nehutachiona uhu.
Mune mamwe mazwi, kusadzivirirwa kwemwana uye zvese zvaanosangana nazvo zvinosiya mucherechedzo pakudzivirira kwehupenyu hwehupenyu. Zvidzidzo zvakapfuura zvakaratidza kuti vanhu vakuru vane dziviriro yakasimba kurwisa mhando dzehutachiona hwavakatapukirwa nadzo vachiri vana. Imprinting ichangobva kuratidzwa kudzivirira kubva kune itsva avian influenza virus subtypes yeiyo yakafanana hemagglutinin phylogenetic boka.hemagglutinin, HA), sezvinoitwa nehutachiona hwekutanga muhuduku.
Kusvika nguva pfupi yadarika, yakamanikana-yekudzivirira yekudzivirira yekudzivirira yakanangana nekusiyana kweiyo HA subtype yaionekwa senzira huru yekudzivirira kubva mumwaka furuwenza. Zvisinei, kune humbowo hutsva hunoratidza kuti kuumbwa kwekudzivirira muviri kunogonawo kukanganiswa nekuyeuka mamwe maantigen efuruwenza (semuenzaniso, neuraminidase, NA). Kubva 1918, matatu subtypes eAN akaonekwa muvanhu: H1, H2 uye H3. Uyezve, H1 uye H2 ndeye phylogenetic boka 1, uye H3 kuboka 2.
Tichifunga nezve chokwadi chekuti kudhinda kunonyanya kukonzera shanduko dzakawanda mundangariro dzekudzivirira, zvinogona kufungidzirwa kuti shanduko idzi dzine humwe hutongi.
Masayendisiti anocherekedza kuti kubvira 1977, maviri subtypes efuruwenza A-H1N1 uye H3N2-akatenderera mwaka pakati pehuwandu. Panguva imwecheteyo, kusiyana kwehuwandu hwehutachiona uye muzviratidzo zvaive pachena, asi zvisina kunyatsodzidza. Misiyano iyi inogona kunge yakakonzerwa nekunyorwa kwehudiki: vanhu vakura vaive vanyatso kuoneswa H1N1 vachiri vana (kubvira 1918 kusvika 1975 ndiyo yega subtype yaitenderera muvanhu). Nekuda kweizvozvo, vanhu ava vadzivirirwa zvirinani kubva kumhando dzemazuva ano dzehutachiona hweiyi subtype. Saizvozvovo, pakati pevadiki vechidiki, mukana wepamusoro wekudhindwa kwehudiki ndeweH3N2 ichangoburwa (mufananidzo #1), iyo inofambirana nenhamba yakaderera yezviitiko zvakashumwa zveH3N2 muhuwandu hwevanhu.
Mufananidzo Nhamba 1: mhando dzakasiyana dzekutsamira kwekudzivirira pakudhinda muhuduku uye chikonzero chehutachiona hwehutachiona.
Nekune rumwe rutivi, misiyano iyi inogona kuve yakabatana nekushanduka kwehutachiona subtypes pachavo. Saka, H3N2 inoratidza nekukurumidza kukukurwa* its antigenic phenotype pane H1N1.
Antigen Drift * - shanduko mukudzivirira-kuumba pamusoro pezvinhu zvevhairasi.
Nechikonzero ichi, H3N2 inogona kunge ichikwanisa kunzvenga kusadzivirirwa kwagara kuripo muvanhu vakuru vane ruzivo rwekuziva, nepo H1N1 inogona kushomeka mumhedzisiro yayo chete pavana vasina immunologically naΓ―ve.
Kuti vaedze fungidziro dzese dzinogoneka, masayendisiti akaongorora dhata rechirwere nekugadzira zvingangoita mabasa ega ega emhando dzenhamba, dzakafananidzwa uchishandisa Akaike Information Criterion (AIC).
Ongororo yekuwedzera yakaitwawo pane iyo hypothesis umo misiyano isiri nekuda kwekudhindisa mukushanduka kwehutachiona.
Kugadzirira kudzidza
Hypothesis modeling yakashandisa data kubva kuArizona Department of Health Services (ADHS) ye9510 statewide seasonal H1N1 uye H3N2 kesi. Inenge 76% yenyaya dzakataurwa dzakarekodhwa muzvipatara nemarabhoritari, nyaya dzakasara hadzina kutaurwa mumarabhoritari. Zvinozivikanwa zvakare kuti inosvika hafu yezviitiko zvakaongororwa murabhoritari zvaive zvakakomba zvekuti zvakakonzera kuchipatara.
Iyo data yakashandiswa muchidzidzo ichi inosanganisira makore makumi maviri nemaviri kubva mumwaka wefuruwenza wa22-1993 kusvika mumwaka wa1994-2014. Zvakakosha kucherechedza kuti saizi dzemuenzaniso dzakawedzera zvakanyanya mushure medenda ra2015, saka nguva iyi haina kuverengerwa kubva kumuenzaniso (Tafura 2009).
Tafura Nhamba 1: epidemiological data kubva ku1993 kusvika ku2015 maererano nezvinyorwa zvakanyorwa zveH1N1 uye H3N2 viruses.
Zvakakoshawo kufunga kuti kubva muna 2004, marabhoritari ekutengeserana muUnited States ave achidiwa kuendesa data yese ine chekuita nehutachiona hwevarwere kune zviremera zvehutano zvehurumende. Nekudaro, ruzhinji rwenyaya dzakaongororwa (9150/9451) dzakaitika kubva mumwaka wa2004-2005, mushure mekunge mutemo watanga kushanda.
Pakati pezviitiko zvose zve9510, 58 yakabviswa nokuti vakanga vari vanhu vane gore rokuberekwa pamberi pe1918 (chimiro chavo chekunyora hachigoni kutsanangurwa zvakajeka), uye imwe nyaya ye1 nokuti gore rekuberekwa rakanga risina kutaurwa. Nokudaro, 9541 nyaya dzakabatanidzwa mumuenzaniso wekuongorora.
Panhanho yekutanga yekuenzanisira, mikana yekudhinda kune H1N1, H2N2 kana H3N2 mavhairasi, yakanangana negore rekuzvarwa, yakatemwa. Izvi zvingangoitika zvinoratidza maitiro ekubatwa nefuruwenza A muvana uye kuwanda kwayo pagore.
Vanhu vazhinji vakazvarwa pakati pe1918 na1957 denda vakatanga kutapukirwa neH1N1 subtype. Vanhu vakazvarwa pakati pe1957 na1968 denda vangangove vese vakatapukirwa neH2N2 subtype.1A) Uye kubva muna 1968, hutachiona hwehutachiona hwakanga huri H3N2, iyo yakava chikonzero chetachiona cheruzhinji rwevanhu kubva muboka revechidiki.
Kunyangwe kupararira kweH3N2, H1N1 ichiri kutenderera mwaka muhuwandu kubva 1977, zvichikonzera kudhindwa muchikamu chevanhu vakazvarwa kubva pakati pe1970s.1A).
Kana kudhinda pachikamu cheAN subtype kuchigadzira mukana wekutapukirwa panguva yefuruwenza, saka kuratidzwa kune H1 kana H3 AN subtypes muhudiki kunofanirwa kupa hutachiona hwehupenyu hwese kune zvimwe zvichangobva kuitika zveiyo AN subtype. Kana imprinting immune system ikashanda zvakanyanya kune mamwe marudzi eNA (neuraminidase), ipapo kudzivirira kwehupenyu hwese kuchave hunhu hweN1 kana N2 (1B).
Kana kudhindwa kwakavakirwa pane yakakura NA, i.e. dziviriro kubva kune yakakura siyana ye subtypes inoitika, ipapo vanhu vakadhindwa kubva kuH1 neH2 vanofanirwa kuchengetedzwa kubva kumazuva ano mwaka H1N1. Panguva imwecheteyo, vanhu vakadhindwa kuH3 vanozochengetedzwa chete kubva mumwaka wemazuva ano H3N2 (1B).
Masayendisiti anocherekedza kuti collinearity (kungotaura, kufanana) kwekufanotaura kwemhando dzakasiyana dzekudhindisa (1D-1I) yakanga isingadzivisiki yakapiwa kusiyana kushoma kwefuruwenza antigenic subtypes inotenderera muhuwandu mukati mezana ramakore rapfuura.
Basa rinonyanya kukosha mukusiyanisa pakati pekudhindisa paHA subtype, NA subtype kana HA nhanho yeboka inotambwa nevanhu vepakati-kati vakatanga kutapukirwa neH2N2.1B).
Imwe neimwe yemamodheru akaedzwa akashandisa mutsetse musanganiswa wehutachiona hunoenderana nezera (1Π‘), uye utachiona hunoenderana negore rekuzvarwa (1D-1F), kuwana kugoverwa kweH1N1 kana H3N2 kesi (1G - 1I).
Zvose zvemhando dze4 dzakagadzirwa: iyo yakapfava yaingova nezera rezera, uye mamwe mamodheru akaoma akawedzera zvinhu zvinodhinda paHA subtype level, paNA subtype level, kana paHA group level.
Age factor curve ine chimiro chedanho rekuita umo mukana wekutapukirwa wakaiswa kune 1 muzera 0-4. Pamusoro peboka rezera rekutanga, pakanga painewo zvinotevera: 5β10, 11β17, 18β24, 25β31, 32β38, 39β45, 46β52, 53β59, 60β66; 67β73, 74β80, 81+.
Mumienzaniso yaisanganisira kudhindisa mhedzisiro, chiyero chevanhu mugore rega rega rekuzvarwa nekudzivirira kwehudiki imprinting yaifungidzirwa kuti yakaenzana nekuderedzwa kwenjodzi yekutapukirwa.
Chinhu chekushanduka kwehutachiwana chakatorwawo munhoroondo mukuenzanisa. Kuti tiite izvi, takashandisa data inotsanangura kufambira mberi kweantigenic pagore, iyo yakatsanangurwa seavhareji antigenic kureba pakati pemhando dzeimwe mutsara wehutachiona (H1N1 pamberi pa2009, H1N1 mushure me2009, uye H3N2). "Antigenic distance" pakati pemhando mbiri dzefuruwenza inoshandiswa sechiratidzo chekufanana mune antigenic phenotype uye inogona kudzivirira immune cross-protection.
Kuongorora kukanganiswa kweantigenic evolution pazera rekupararira, shanduko muchikamu chezviitiko muvana zvakaedzwa mumwaka umo shanduko yakasimba yeantigenic yakaitika.
Kana chiyero che antigenic drift chiri chinhu chakakosha muhutano hunoenderana nezera rehutachiwana, saka chikamu chezviitiko zvinoonekwa muvana zvinofanira kunge zvakashata zvakabatanidzwa nekufambira mberi kwegore negore kwe antigenic. Mune mamwe mazwi, matambudziko asina kuita shanduko dzakakosha dzeantigenic kubva mumwaka wapfuura anofanirwa kutadza kupukunyuka kudzivirirwa kwagara kuripo muvanhu vakuru vane ruzivo. Matambudziko akadaro achanyanya kushanda pakati pevanhu vasina ruzivo rwekudzivirira zvirwere, kureva, pakati pevana.
Mhedzisiro yekutsvaga
Ongororo yedata gore negore yakaratidza kuti mwaka H3N2 ndiyo yaive honzeri yekutapukira pakati pevanhu vakura, nepo H1N1 ichikanganisa vezera repakati uye vechidiki (mufananidzo #2).
Mufananidzo Nhamba 2: Kugoverwa kweH1N1 neH3N2 furuwenza nezera munguva dzakasiyana-siyana.
Iyi pateni yaivepo mune data risati rasvika denda ra2009 uye shure kwaro.
Iyo data yakaratidza kuti kudhinda paNA subtype level inotungamira pamusoro pekudhindisa paHA subtype level (ΞAIC = 34.54). Panguva imwecheteyo, pakanga pane kunenge kusina kukwana kwekudhindwa pamwero weHA boka (ΞAIC = 249.06), pamwe nekusavapo kwakakwana kwekudhindwa (ΞAIC = 385.42).
Mufananidzo #3: Kuongorora kukwana kwemamodheru kune data rekutsvagisa.
Kuona kuongororwa kwemuenzaniso wakakodzera (3C ΠΈ 3D) akasimbisa kuti mamodheru ane imprinting effects pamitsetse yakamanikana yeNA kana HA subtypes yakapa yakanakisa kudhidha yakashandiswa muchidzidzo. Icho chokwadi chekuti iyo muenzaniso iyo imprinting isipo haigone kutsigirwa nedata inoratidza kuti imprinting chinhu chakanyanya kukosha chekuvandudza kusadzivirirwa muhuwandu hwevanhu vakuru maererano nemwaka furuwenza subtypes. Nekudaro, kudhinda kunoshanda mune yakamanikana nyanzvi, ndiko kuti, inoshanda chete pane chaiyo subtype, uye kwete pane yese spectrum yefuruwenza subtypes.
Tafura Nhamba 2: kuongororwa kwekukodzera kwemamodhi kune data rekutsvaga.
Mushure mekudzora kugoverwa kwezera rehuwandu, njodzi inofungidzirwa inoenderana nezera yaive yakanyanya muvana nevakuru vakuru, zvinoenderana nekuunganidzwa kwendangariro dzemuviri muhuduku uye kudzikira simba rekudzivirira muviri muvakuru vakuru (pa 3A inofungidzirwa curve kubva kune yakanakisa modhi inoratidzwa). Imprinting parameter fungidziro yaive isingasviki imwe, zvichiratidza kuderera kushoma mungozi yehukama (Table 2). Mumuenzaniso wakanakisisa, iyo inofungidzirwa kuderedzwa kwengozi kubva pauduku yakadhindwa yakanga yakakura kune H1N1 (0.34, 95% CI 0.29β0.42) pane yeH3N2 (0.71, 95% CI 0.62-0.82).
Kuti uedze pesvedzero yehutachiona hwekushanduka-shanduka pazera rekugovaniswa kwenjodzi yehutachiona, vaongorori vakatsvaga kudzikira kwechikamu chehutachiona pakati pevana panguva dzine chekuita nekuchinja kweantigenic, apo madhiri ane antigenic drift akanyanya kushanda mukutapurira vanhu vakuru vane ruzivo.
Kuongororwa kwemashoko kwakaratidza kushamwaridzana kuduku kusina kunaka asi kusingakoshi pakati pekuwedzera kwegore negore kwekuita antigenic uye chikamu chezviitiko zveH3N2 zvakaonekwa muvana (4A).
Mufananidzo Nhamba 4: simba rekushanduka kwehutachiwana pazera rezera rengozi yehutachiona.
Zvisinei, hapana hukama hwakajeka hwakawanikwa pakati pekuchinja kweantigenic uye chikamu chezviitiko zvakaonekwa muvana vanopfuura makore gumi uye kune vanhu vakuru. Kana kushanduka kwehutachiwana kwakabata basa guru mukuparadzirwa uku, mhedzisiro yaizova humbowo hwakajeka hwesimba rekushanduka-shanduka pakati pevakuru, kwete chete kana tichienzanisa vakuru nevana vari pasi pemakore gumi.
Uyezve, kana dhigirii rekushanduka kwehutachiwana rakanyanya kune subtype-chaiwo misiyano mukuparadzirwa kwezera redenda, zvino kana H1N1 neH3N2 subtypes dzichiratidza mwero wakafanana wekupararira kweantigen pagore, kugoverwa kwezera ravo kwehutachiona kunofanirwa kutaridzika zvakafanana.
Kuti uwane rumwe ruzivo rwakadzama rwema nuances echidzidzo, ini ndinokurudzira kutarisa .
Epilogue
Mubasa iri, masayendisiti akaongorora epidemiological data pazviitiko zvehutachiona neH1N1, H3N2 uye H2N2. Kuongororwa kwedata kwakaratidza hukama hwakajeka pakati pekudhindisa muhuduku uye njodzi yehutachiona mukukura. Mune mamwe mazwi, kana mwana ari mumakore makumi mashanu akatapukirwa apo H50N1 yakanga ichitenderera uye H1N3 yakanga isipo, ipapo muhukuru mukana wekutapukirwa neH2N3 uchava mukuru kudarika mukana wekubata H2N1.
Mhedziso huru yechidzidzo ichi ndeyokuti inokosha kwete chete izvo munhu akatambura kubva muhuduku, asiwo mune zvakarongeka. Immune ndangariro, inokura muhupenyu hwese, inoshingairira "inonyora" data kubva kuhutachiona hwekutanga hwehutachiona, hunoita kuti pave nekurwisa kunobudirira kwavari mukukura.
Masayendisiti anotarisira kuti basa ravo richaita kuti zvikwanisike kufanotaura zviri nani kuti ndeapi mapoka ezera anonyanya kubatwa nemhedzisiro yemhando dzipi dzefuruwenza. Ruzivo urwu runogona kubatsira kudzivirira kupararira kwedenda, kunyanya kana nhamba shoma yemishonga yekudzivirira ichida kugoverwa kuvanhu.
Tsvagiridzo iyi haina kunangana nekutsvaga mishonga yepamusoro kune chero rudzi rwefuruu, kunyangwe izvo zvingave zvakanaka. Inotarirwa kune izvo zvakanyanya chaizvo uye zvakakosha panguva ino - kudzivirira kupararira kwehutachiona. Kana isu tisingakwanise kubvisa hutachiona ipapo ipapo, saka tinofanira kunge tine zvese zvinogoneka zvekushandisa kuti tive nazvo. Imwe yevabatsiri vakatendeseka vedenda ripi neripi ipfungwa yekusangwarira pairi zvese kudivi renyika mune zvese uye munhu wega wega. Kuvhunduka, hongu, hazvidiwi, nekuti zvinogona kungoita kuti zvinhu zvinyanye kushata, asi kudzivirira hakumbokuvadze.
Ndatenda nekuverenga, gara uchida kuziva, zvichengete iwe nevadikanwi vako uye uve nekupera kwevhiki kwakanaka vakomana! π
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Source: www.habr.com