Chinyorwa
Methylene blue nemarariya: kushandiswa kare nemiedzo yemazuva ano
Muna 1891 varwere vaviri vemarariya vakarapwa nedhayi yebhuruu yaishandiswa pamachira. Paul Guttmann naPaul Ehrlich vakanga vaona kuti methylene blue yaiisa ruvara pazvipembenene zvinokonzera marariya ichizvisarudza, uye vakafunga kuti dhayi yaikwanisa kusarudza chipembenene zvakadaro ingangokwanisawo kuchikuvadza. Varwere vose vari vaviri vakapora. Muedzo iwoyo wakaita kuti methylene blue ive mushonga wekutanga wemarariya wakagadzirwa nemakemikari, makumi emakore chloroquine isati yavapo.
Dhayi iyi yakabva yapedza chikamu chikuru chezana remakore rechimakumi maviri ichirasikirwa nenzvimbo yayo. Mishonga yakagadzirwa nemakemikari yaigamuchirwa zviri nani nemuviri yakaitora nzvimbo, uye pakazosvika nguva yemazuva ano yakanga yasara ichinyanya kushandiswa sekemikari yemurabhoritari, dhayi yekubatsira kuongorora, uye mushonga wekukurumidzira wechimwe chirwere cheropa. Saka kudzoka kwayo mutsvakurudzo yemarariya muBurkina Faso neMali kwakanga kusiri kungoshuva zvekare. Vatsvakurudzi vaiva nepfungwa chaiyo yavaida kuedza: mashandiro emakemikari e-redox anoita kuti dhayi iyi iise ruvara angakanganisa nzira dzechipembenene dzekuzvidzivirira mu-redox, uye kushanda kwayo pachikamu chechipembenene chinotapuriranwa kungaita chimwe chinhu chisingaitwi zvakanaka nemishonga inowanzoshandiswa. Kuedza pfungwa iyi kwaida kuti nguva dzose pataurwe mishonga yakabatanidzwa, rudzi rwechipembenene, uye chiyero chemhedzisiro, nokuti kuchinja chimwe chete chezvinhu izvi kunochinja mhedziso.
Musiyano wakakura pakati pemishonga yakatenderwa uye kushandiswa kuchiri kutsvakurudzwa unotsanangurwa mumethylene blue mukurapa. Marariya iri kudivi rekushandiswa kuchiri kutsvakurudzwa: methylene blue inoshanda pazvipembenene, yakaedzwa mumiedzo yakabatanidzwa nemimwe mishonga, asi haisi kurapa kunowanzokurudzirwa nemirayiridzo yekurapa.
Nei dhayi yaEhrlich yakashanda uye nei yakasiyiwa
Zvinyorwa zvekutanga zvinopa muenzaniso wemaverengerwo anofanira kuitwa uchapupu hwekurapa kusati kwava nemaitiro emazuva ano. Ongororo ya1904 yezviitiko 425 zvakashumwa yakafungidzira kuti kurapa kwakabatsira vanenge 85 muzana, asi zviitiko izvozvo zvakaitika kusati kwava nekugoverwa kwevarwere mumapoka zvisina kurongwa, zviyero zvemhedzisiro zvakafanana, kusimbiswa kwerudzi rwechipembenene, uye kutariswa kwekuramba kwemishonga. Zvinoratidza kuti kemikari iyi yaishanda pakurwisa marariya zvakakodzera kuenderera mberi netsvakurudzo, kwete kuti yaiva nemwero wekuporesa unogona kuenzaniswa newemuedzo wemazuva ano.
Kusiyiwa kwayo kwakabva pamatambudziko ekushandisa, kwete pakuratidzwa kuti yaisashanda. Methylene blue inoita weti yebhuruu kana yegirini, inoisa ruvara munyama dzemuviri, uye inokonzera matambudziko emudumbu neenzira yeweti, kusanganisira kurutsa uye kurwadziwa pakuita weti pamiyero yaishandiswa panguva iyoyo. Mishonga mitsva yaibvisa zvipembenene isingaisi ruvara pamuviri wemurwere. Ongororo yenhoroondo inotevera methylene blue kusvika kuchloroquine inotsanangura kutorwa kwenzvimbo yayo, ukuwo ongororo yemishonga yemarariya yerudzi rwephenothiazinium ichiunganidza pfungwa pamusoro pemashandiro ayo dzakaita kuti vatsvakurudzi varambe vachiifarira kunyange kushandiswa kwayo pakurapa kwakanga kwaderera.
Pakutsanangura mashandiro ayo, dhayi iyi inonyatsotsanangurwa sechinhu chinoshanda mu-redox, kwete sechinonangana nechinhu chimwe chete. Murabhoritari, inodzivisa enzyme yechipembenene inonzi glutathione reductase uye panguva imwe chete inotenderedza maerekitironi nenzira dzinopedza simba rekudzikisa oxidation rinodiwa nechipembenene uye dzinokonzera kushushikana kunokonzerwa neoxidation; kukanganiswa kwekubviswa kwehuturu hweheme kwakataurwawo seimwe nzira yainogona kushanda nayo. Hazvisati zvanyatsojeka kuti ndeipi yenzira idzi inonyanya kushanda mukati memurwere. Chinokosha pamhedzisiro yacho hachisi chinhu chaicho chainonangana nacho, asi kusarudza chikamu chehupenyu hwechipembenene: methylene blue inoshanda zvakanyanya kupfuura zvakajairika pama-gametocyte, chikamu chine chekuita nekuberekana chinofanira kumedzwa neumhutu kuti kutapurirana kuenderere mberi. Mishonga inowanzoshandiswa yakabatanidzwa neartemisinin inobvisa zvipembenene zvisiri pachikamu chekuberekana zvinoita kuti murwere arware, asi inogona kusiya ma-gametocyte akura. Mushonga unopfupisa nguva yekuvapo kwema-gametocyte kana kuaita kuti asakwanise kutapurira unorwisa kutapurirana pachako.
Zvakayedzwa nemiedzo yemazuva ano
Mhedzisiro yose yemazuva ano iri pasi apa ndeyemishonga yakabatanidzwa. Muyero, mushonga unoperekedza, rudzi rwechipembenene, uye chiyero chemhedzisiro zvose chikamu chezvakawanikwa.
| Muedzo nevanhu vakaongororwa | Kurongeka kwemishonga | Chiyero chemhedzisiro nezvakawanikwa | Muganho |
|---|---|---|---|
| Burkina Faso 2005, vana 226 vane mwedzi 6 kusvika 59, marariya yefalciparum | Chloroquine pamwe ne4 mg/kg/day yemethylene blue kwemazuva 3 zvichienzaniswa nechloroquine yoga | Kupindura kwakakwana pakurapa paZuva-14 kwaiva vanenge 56 zvichienzaniswa ne46 muzana; hapana mukana wakajeka wakaonekwa | Muyero wakaderera wedhayi pachinhu chaiva nekuramba chloroquine; muedzo usina kunyatsokodzera kuongorora kurongeka kwemishonga kwemazuva ano |
| Zoungrana 2008, chikamu 2, vana 180 vane makore 6 kusvika 10, marariya yefalciparum | Methylene blue pamwe neartesunate, pamwe neamodiaquine, kana artesunate-amodiaquine inowanzoshandiswa; dhayi 20 mg/kg/day kwemazuva 3 | Mwero wekupora wakagadziridzwa paZuva-28 waiva 62, 95, ne82 muzana zvichitevedzana; kubviswa kwezvipembenene kwakakurumidza zvikuru pakabatanidzwa artesunate; mapoka ose ari maviri edhayi akaderedza kuvapo kwema-gametocyte pamazuva 3, 7, ne14 | Mushonga waipiwa waizivikanwa uye mapoka aiva madiki; mwero wakaderera wekupora pakabatanidzwa artesunate unoratidza kuti mushonga unoperekedza ndiwo unosarudza mhedzisiro |
| Coulibaly 2015, chikamu IIb, vana 193 muboka rekuongorora kushanda kwemushonga, marariya yefalciparum | Artesunate-amodiaquine pamwe ne15 mg/kg/day yedhayi kwemazuva 3 zvichienzaniswa nemishonga yakabatanidzwa iyoyo yoga | Ma-gametocyte akaonekwa nemakorosikopu paZuva-7 aiva 1.2 zvichienzaniswa ne8.9 muzana; kubviswa kwezvipembenene zvisiri pachikamu chekuberekana kwakakurumidza zvishoma; mwero wekupora wakagadziridzwa waiva wakafanana, panenge 80 zvichienzaniswa ne85 muzana | Kuderedzwa kwekuvapo kwema-gametocyte, kwete kupora, ndiko kwaiva kubudirira kukuru; kurutsa kwakawanda uye hemoglobin yakaderera kwenguva pfupi pakushandisa dhayi |
| Mali 2018, chikamu 2, vanhu vechirume 80 vane G6PD yakajairika, vaiva nehutachiona hwefalciparum hune ma-gametocyte asi vasina zviratidzo | Dihydroartemisinin-piperaquine pamwe ne15 mg/kg/day yedhayi kwemazuva 3 zvichienzaniswa nemushonga wemarariya yoga | Pakati pevatori vechikamu vaikwanisa kutapurira pakutanga, kukosha kwepakati kwekuderera kwekutapurira kuumhutu kwaiva 100 muzana nedhayi zvichienzaniswa nekusava nekuderera kunooneka pasina iyo pazuva 2, uye izvi zvakaramba zvakadaro pazuva 7 | Vanhu 11 chete vaikwanisa kutapurira vakapiwa dhayi ndivo vaiva mukuenzanisa kukuru; vechirume chete, vane G6PD yakajairika chete, vatakuri vasina zviratidzo; chiyero chekutapurirana, kwete muedzo wekupora |
| Burkina Faso 2019, vana 100, marariya yefalciparum | Artesunate-amodiaquine pamwe nedhayi zvichienzaniswa nemishonga yakabatanidzwa iyi pamwe nemuyero mumwe chete weprimaquine | Mwero wekupora wakagadziridzwa waiva vanenge 96 muzana mumapoka ose ari maviri; kubviswa kwezvipembenene pakazosvika zuva 1 kwakakurumidza nedhayi; ma-gametocyte pazuva-2 aiva 4 zvichienzaniswa ne31 muzana, kunyange primaquine yakanga isina kupiwa kusvikira pazuva 2 | Muedzo mudiki uye mushonga waipiwa waizivikanwa; nguva yekupiwa kwemishonga inoita kuti kuenzanisa ma-gametocyte pakutanga kusave pachiyero chimwe; chinangwa chikuru chaiva kuchengeteka kweropa |
Pane zvinhu zviviri zvinoramba zvichionekwa muzvidzidzo izvi. Chekutanga, dhayi inoshanda zvechokwadi pakurwisa Plasmodium falciparum, asi kana iri yoga inobvisa zvipembenene zvishoma nezvishoma uye inobvumira hutachiona hwakasara kuti hudzoke; chidzidzo chidiki chevanhu vakuru chakagumisa kuti inofanira kubatanidzwa nemushonga unoshanda nekukurumidza. Chechipiri, kukosha kwayo kwekuwedzera kunonyanya kudzokororwa kana ichienzaniswa nemishonga yemazuva ano yakabatanidzwa yakasarudzwa zvakanaka kuri muzviyero zvema-gametocyte nekutapurirana, kwete mukuwedzera kukuru kwemwero wekupora kunowanzoyerwa. Chidzidzo cheMali chekudyisa umhutu ropa zvakananga kuburikidza nemembrane ndicho chinoratidza zvakajeka pfungwa yechipiri iyi, nokuti umhutu hwakadyiswa ropa revatori vechikamu hwakanga hwava nemukana wakaderera zvikuru wekutapukirwa.
Miganhu yemarudzi ezvipembenene inokosha sezvinoita miganhu yemishonga yakabatanidzwa. Zvinenge zvose zviri muuchapupu hunogutsa hwemazuva ano hwekurapa vanhu zvine chekuita nemarariya yefalciparum. Pamarariya yevivax, zvinyorwa zvekurapa zvinosanganisira zvakacherechedzwa kare pamwe nebasa remazuva ano remurabhoritari nerekudyisa umhutu, kusanganisira kuti zvipembenene zvakatorwa kuThai-Myanmar zvaikanganiswa nedhayi pahuwandu hwakaderera hwenanomolar uye kuti kutapurirana kwakavharirwa zvakasimba muchidzidzo chekudyisa umhutu cha2024. Hapana pane izvozvo chinosimbisa kuporeswa kwevivax iri pachikamu cheropa muvarwere, uye hapana chinoongorora ma-hypnozoite ari muchiropa anokonzera kudzoka kwevivax, ayo anoda sarudzo dzawo dzekurapa dzakanangana nerudzi urwu. Kushandura mhedzisiro yekutapurirana kwefalciparum kuita chirevo pamusoro pezvipembenene zvose kunodzokorora kukanganisa kwekare zvikuru muzvinyorwa izvi. Raibhurari yetsvakurudzo inoisa zvakawanikwa mumiedzo yevanhu nezvakawanikwa mukuedza kwemurabhoritari mumakoramu akasiyana nokuda kwechikonzero ichi chaicho.
Kuchengeteka kunofambidzana nekurongeka kwemishonga
Njodzi nhatu dzinofanira kubatwa zvakajeka nokuti ndidzo dzinosarudza kuti ndiani asingafaniri kuedza.
Kushomeka kweglucose-6-phosphate dehydrogenase kunounza njodzi yekuparara kwemasero matsvuku eropa, kunonzi hemolysis. Ongororo yakabatanidza zvidzidzo zvina zvevana muBurkina Faso, zvaisanganisira vana 1,005, yakawana kuderera kwehemoglobin kwakati kurei pakushandisa dhayi muvatori vechikamu vaiva nekushomeka kwakazara, paine zviitiko zviviri zvehemolysis muvana vakarapwa nedhayi vaiva nekushomeka kana kuti heterozygous. Mashoko epamutemo emushonga wejekiseni wemethylene blue muUnited States anorambidza kushandiswa kune vane kushomeka kweG6PD nokuti hemolysis yakakomba inogona kuitika. Kurongeka kwemishonga yemarariya inonwiwa kwakasiyana nemuyero wekukurumidzira unopiwa mutsinga, saka mashoko acho haagoni kushandurwa nenhamba kuita muganho wemuyero wemarariya, asi maitiro emuviri ari kunongedzwa akafanana. Kuongororwa nekutarisirwa nevane ruzivo zvinofanira kuvapo pakushandiswa kupi nokupi kwakanyatsorongwa.
Kudyidzana nemishonga ine chekuita neserotonin kunofanirawo kutariswa pamwe chete nazvo. Methylene blue inosvika mumuviri wose inodzivisa monoamine oxidase uye inogona kukonzera serotonin syndrome kana ikashandiswa pamwe nemishonga inosarudza kudzivisa kudzorerwa kweserotonin mumasero, inodzivisa kudzorerwa kweserotonin nenorepinephrine, inodzivisa monoamine oxidase, uye mimwe mishonga yeopioid neyechikosoro; pane zviitiko zvinouraya zvakashumwa. Kudyidzana uku, mamiriro anorambidza kushandiswa, uye kutarisirwa zvinotsanangurwa mumigumisiro isingadiwi, mamiriro anorambidza kushandiswa, nekuchengeteka.
Kugamuchirwa kwemushonga nemuviri ndicho chipingamupinyi chisinganyanyi kutaurwa. Weti yebhuruu-girini inotarisirwa uye haikuvadzi, asi inooneka zvekuti yakaderedza kugamuchirwa kwemushonga kubva kuma1890s. Kurutsa kunoenderana nemuyero uye magadzirirwo emushonga, uye kwakaita kuti vamwe vabude mumiedzo yevana, kuchisvika 40 muzana yevakapiwa dhayi zvichienzaniswa ne14 muzana nevakapiwa primaquine mune kumwe kuenzanisa kwakaitwa gare gare. Mushonga unorutswa nevana mushonga une kushanda kunongovapo pabepa kuvana ivavo.
Nei uchapupu uhu husingatsigiri kuzvirapa
Mirayiridzo yemarariya iripo iye zvino inoda kusimbiswa kwekuvapo kwechipembenene uye inosarudza kurapa maererano nerudzi rwacho, kukomba kwechirwere, nzvimbo inoratidza kuramba kwemishonga, zera neuremu, pamuviri, uye mamiriro eG6PD, mishonga yakabatanidzwa ine artemisinin iri ndiyo inowanzoshandiswa pachirwere chefalciparum. Hapana muzvinyorwa zvedhayi chinotsiva nzira iyoyo yekuita sarudzo. Kushandisa mushonga mumwe chete kunononoka zvikuru, kusarudzwa kwemushonga unoperekedza ndiko kunosarudza kupora, ma-hypnozoite evivax anoda kurapa kwawo kwakasiyana, mamiriro eG6PD anoisa miganhu pakushandisa, uye kushandiswa panguva imwe chete kwemishonga ine chekuita neserotonin kunounza kudyidzana kune njodzi. Kurapa kusina kururama kunogona kusiya hutachiona hwefalciparum hunozodzoka, kusatambira kudzoka kwevivax, kukonzera hemolysis, uye kuisa kudzvinyirira kusina kusimba kwemushonga pazvipembenene kunokurudzira kuramba mishonga.
Pfupiso yakatendeseka ine miganhu yakamanikana kupfuura inodiwa nevanotsigira zvikuru kana nevanoramba zvachose. Dhayi yezana remakore rechigumi nepfumbamwe ine mashandiro chaiwo emushonga muzana remakore rechimakumi maviri nerimwe, uye kubatsira kwayo kwemazuva ano kwakajeka zvikuru kuri mukuvharira kutapurirana kwefalciparum kana yawedzerwa kumishonga yakabatanidzwa yakakodzera pasi pekutarisirwa kwemuedzo. Icho chinhu chakawanikwa pamusoro pekumisa kupararira mumapoka evanhu akaongororwa, kwete murayiridzo wekuzvirapa.