Inqaku
Imethylene blue nemalariya: ukusetyenziswa kwembali neemvavanyo zangoku
Ngo-1891 izigulana ezimbini ezazinemalariya zanyangwa ngedayi eluhlaza okwesibhakabhaka yamalaphu. UPaul Guttmann noPaul Ehrlich babeqaphele ukuba imethylene blue yayifaka umbala ngokukhethekileyo kwizifunxi-gazi zemalariya, baza baqiqa ngelithi idayi ekwazi ukukhetha ngokwaneleyo ukuze ibonise isifunxi-gazi inokukhetha ngokwaneleyo ukuze isonzakalise. Zombini izigulana zaphila. Olo vavanyo lwenza imethylene blue yaba liyeza lokuqala elenziwe ngokwenziwa lokulwa nemalariya, kumashumi eminyaka ngaphambi kokuba kubekho ichloroquine.
Le dayi yathi ke yachitha ixesha elininzi lenkulungwane yamashumi amabini iphulukana nendawo yayo. Amayeza enziwe ngokwenziwa anyamezeleka ngcono athatha indawo yayo, yaye ekufikeni kwexesha langoku yayisele isetyenziswa ikakhulu njengesixhobo semichiza selabhoratri, idayi yokunceda ekuxilongeni, neyeza likaxakeka lesinye isigulo segazi. Ngoko ukubuyela kwayo kuphando lwemalariya eBurkina Faso naseMali kwakungengomdla wokukhumbula okwakudala. Abaphandi babenengcinga ethile ababezama ukuyivavanya: kwaloo khemistri ye-redox eyenza le dayi ikwazi ukufaka umbala inokuphazamisa ukhuseleko lwe-redox lwesifunxi-gazi ngokwaso, kwaye impembelelo yayo kwinqanaba lesifunxi-gazi elidluliselwa kwabanye inokwenza into engenziwa kakuhle ngamayeza aqhelekileyo. Ukuvavanya loo ngcinga kwakufuna ukuchaza indibaniselwano yamayeza, uhlobo lwesifunxi-gazi, nesiphumo esilinganisiweyo rhoqo, kuba ukutshintsha nokuba yenye kuzo kutshintsha nesigqibo.
Umahluko obanzi phakathi kwamayeza agunyazisiweyo nokusetyenziswa okusaphandwayo uchazwe kwinqaku elithi imethylene blue kwezonyango. Ukusetyenziswa kwimalariya kukwicala elisaphandwayo: iyasebenza ngokwebhayoloji, kwaye ivavanyiwe kwiindibaniselwano zamayeza, kodwa ayilonyango oluqhelekileyo ngokwezikhokelo.
Kutheni idayi kaEhrlich yasebenza nokuba kutheni yayekwa
Ingxelo yamandulo ingumzekelo wendlela yokufunda ubungqina bexesha langaphambi kweendlela zangoku. Uphononongo lwango-1904 lweemeko ezingama-425 ezixeliweyo lwaqikelela ukuba malunga nama-85 ekhulwini asabela kunyango, kodwa ezo meko zazikho ngaphambi kokwabiwa ngokungakhethiyo kumaqela, ukulinganiswa kweziphumo ngendlela emiselweyo, ukuqinisekiswa kohlobo lwesifunxi-gazi, nokubekwa esweni kokunganyangeki ngamayeza. Zibonisa ukuba le khompawundi yayinesenzo sokulwa nemalariya esasifanele ukuphandwa ngakumbi, kungekhona izinga lokuphiliswa elinokuthelekiswa novavanyo lwangoku.
Ukuyekwa kwayo kwakubangelwa ziingxaki zokusetyenziswa kunokuba bubungqina bokuba ayisebenzi. Imethylene blue yenza umchamo ube luhlaza okwesibhakabhaka okanye luhlaza, ifake umbala kwizicubu, ize ibangele iingxaki zesisu namathumbu nezokuchama, kuquka ukugabha nokuchama okubuhlungu, kwiidosi ezazisetyenziswa ngelo xesha. Amayeza amatsha ayesusa izifunxi-gazi ngaphandle kokufaka umbala kwisigulana. Uphononongo lwembali olulandela indlela esuka kwimethylene blue iye kwichloroquine lubalisa indlela eyathatyathelwa ngayo indawo, ngoxa uphononongo lwamayeza ephenothiazinium okulwa nemalariya luqokelela iingcinga ngeendlela zokusebenza ezagcina umdla wabaphandi emva kokuncipha kokusetyenziswa kwayo kunyango.
Ngokwendlela yokusebenza, le dayi ichazwa ngcono njengento esebenzayo kwi-redox kunokuba ibe nento enye kuphela ejolise kuyo. Ithintela iglutathione reductase yesifunxi-gazi kwityhubhu yovavanyo, yaye kwangaxeshanye ijikelezisa ii-electron ngeendlela ezisebenzisa amandla okunciphisa ioksideshini afunwa sisifunxi-gazi nezibangela uxinzelelo lweoksideshini; kukwacetyiswe ukuba iyaphazamisa inkqubo yokuphelisa ubuthi beheme. Akukaqinisekiswa ukuba yeyiphi kwezi ndlela elawula ngaphakathi kwisigulana. Isiphumo esibalulekileyo asiyonto kanye ejoliswe kuyo, kodwa kukusebenza kwayo kwinqanaba elithile: imethylene blue isebenza ngamandla angaqhelekanga kwiigametocyte, inqanaba lokuzala ngesondo ekufuneka ingcongconi iliginye ukuze usulelo luqhubeke. Iindibaniselwano eziqhelekileyo zeartemisinin zisusa izifunxi-gazi ezizala ngaphandle kwesondo ezibangela ukuba isigulana sigule, kodwa zinokushiya iigametocyte ezivuthiweyo. Iyeza elinciphisa ixesha lokuthwalwa kweegametocyte okanye elenza iigametocyte zingakwazi ukosulela lijolisa ekudluliselweni kosulelo ngokwako.
Oko kwavavanywa ziimvavanyo zangoku
Zonke iziphumo zangoku ezingezantsi ziziphumo zendibaniselwano yamayeza. Idosi, iyeza elidityanisiweyo, uhlobo lwesifunxi-gazi, nesiphumo esilinganisiweyo ziyinxalenye yoko kufunyenweyo.
| Uvavanyo nabantu ababandakanyiweyo | Inkqubo yonyango | Into eyalinganiswayo nesiphumo | Umda |
|---|---|---|---|
| Burkina Faso 2005, abantwana abangama-226 abaneenyanga ezi-6 ukuya kwezingama-59, imalariya yefalciparum | Ichloroquine kunye nemethylene blue eyi-4 mg/kg/day kangangeentsuku ezi-3 xa kuthelekiswa nechloroquine kuphela | Ukusabela okwaneleyo ngosuku lwe-14 kwakumalunga nama-56 xa kuthelekiswa nama-46 ekhulwini; akukho nzuzo icacileyo | Idosi ephantsi yedayi kwimeko yokunganyangeki ngechloroquine; uvavanyo olungomelelanga lwenkqubo yonyango yale mihla |
| Zoungrana 2008, isigaba 2, abantwana abali-180 abaneminyaka emi-6 ukuya kweli-10, imalariya yefalciparum | Imethylene blue kunye neartesunate, okanye kunye neamodiaquine, okanye iartesunate-amodiaquine eqhelekileyo; idayi eyi-20 mg/kg/day kangangeentsuku ezi-3 | Izinga lokuphiliswa elilungisiweyo ngosuku lwe-28 lalingama-62, 95, nama-82 ekhulwini ngokulandelelana; ukususwa kwezifunxi-gazi kwakukhawuleza kakhulu kwindibaniselwano year tesunate; omabini amaqela edayi anciphisa ukuthwalwa kweegametocyte ngeentsuku ezi-3, 7, ne-14 | Uvavanyo olungafihlwanga olunamaqela amancinane; izinga eliphantsi lokuphiliswa kwindibaniselwano year tesunate libonisa ukuba iyeza elidityanisiweyo lilo elimisela isiphumo |
| Coulibaly 2015, isigaba IIb, abantwana abali-193 kwiqela lokuhlalutya ukusebenza, imalariya yefalciparum | Iartesunate-amodiaquine kunye nedayi eyi-15 mg/kg/day kangangeentsuku ezi-3 xa kuthelekiswa naloo ndibaniselwano kuphela | Iigametocyte ngosuku lwe-7 ezifunyenwe ngemikroskopu zazili-1.2 xa kuthelekiswa ne-8.9 ekhulwini; ukususwa kwezifunxi-gazi ezizala ngaphandle kwesondo kwakukhawuleza kancinane; izinga lokuphiliswa elilungisiweyo lalifana, limalunga nama-80 xa kuthelekiswa nama-85 ekhulwini | Ukuncipha kobukho beegametocyte, kungekhona ukuphiliswa, yayiyeyona nzuzo iphambili; ukugabha okungakumbi nehemoglobin ephantsi okwethutyana xa kusetyenziswa idayi |
| Mali 2018, isigaba 2, abantu abangamadoda abangama-80 abane-G6PD eqhelekileyo, abanosulelo lwefalciparum oluneegametocyte kodwa olungenazimpawu | Idihydroartemisinin-piperaquine kunye nedayi eyi-15 mg/kg/day kangangeentsuku ezi-3 xa kuthelekiswa neyeza lokulwa nemalariya kuphela | Kubathathi-nxaxheba ababekwazi ukosulela ekuqaleni, ixabiso eliphakathi lokuncipha kokukwazi ukosulela iingcongconi lalingama-100 ekhulwini ngedayi, xa kuthelekiswa nokungabikho phantse kokuncipha ngaphandle kwayo ngosuku lwe-2, kwaye oko kwaqhubeka ngosuku lwe-7 | Babali-11 kuphela abafumana idayi nababekwazi ukosulela kuthelekiso oluphambili; ngamadoda kuphela, abane-G6PD eqhelekileyo kuphela, abathwali abangenazimpawu; isiphumo sokudluliselwa kosulelo, hayi uvavanyo lokuphiliswa |
| Burkina Faso 2019, abantwana abali-100, imalariya yefalciparum | Iartesunate-amodiaquine kunye nedayi xa kuthelekiswa nale ndibaniselwano kunye nedosi enye yeprimaquine | Izinga lokuphiliswa elilungisiweyo lalimalunga nama-96 ekhulwini kuwo omabini amaqela; ukususwa kwezifunxi-gazi ngosuku lwe-1 kwakukhawuleza ngedayi; iigametocyte ngosuku lwe-2 zazikho kuma-4 xa kuthelekiswa nama-31 ekhulwini, nangona iprimaquine ingazange inikwe de kube lusuku lwe-2 | Uvavanyo oluncinane nolungafihlwanga; ixesha lokunikwa kwamayeza lenza uthelekiso lwangaphambili lweegametocyte lungalingani; eyona nto yayijoliswe kuyo yayilukhuseleko olunxulumene negazi |
Zimbini iipateni ezihlala zibonakala kwezi zifundo. Okokuqala, le dayi iyasebenza ngokwenene kwiPlasmodium falciparum, kodwa xa isetyenziswa yodwa isusa izifunxi-gazi ngokucotha kakhulu yaye ivumela usulelo ukuba lubuye kuba lungaphelanga ngokupheleleyo; isifundo esincinane sabantu abadala sagqiba kwelokuba kufuneka idityaniswe neyeza elisebenza ngokukhawuleza. Okwesibini, eyona nzuzo yayo yongezelelweyo iphinda ibonakale ngokuthembekileyo, xa yongezwa kwindibaniselwano yangoku ekhethwe ngokuchanekileyo, ikwiziphumo zeegametocyte nezokudluliselwa kosulelo kunokuba ibe kukwanda okukhulu kokuphiliswa okuqhelekileyo. Isifundo saseMali sokondla iingcongconi ngegazi ngenwebu ngokuthe ngqo sesona sibonisa ngokucacileyo loo ngxelo yesibini, kuba amathuba okuba iingcongconi ezazondliwa ngegazi labathathi-nxaxheba zosuleleke ancipha kakhulu.
Imida yeentlobo ibaluleke ngokulinganayo nemida yeendibaniselwano zamayeza. Phantse bonke ubungqina obuqinisekisayo bezonyango bale mihla bumalunga nemalariya yefalciparum. Kwimalariya yevivax, ingxelo yezonyango iquka ukuqwalaselwa kwembali kunye nomsebenzi wale mihla kwityhubhu yovavanyo nowokondla iingcongconi, kuquka ukuba izifunxi-gazi ezahlulwe kwiisampulu zaseThailand naseMyanmar zichaphazeleka yidayi kumaqondo aphantsi eenanomolar, kunye nokuthintelwa ngamandla kokudluliselwa kosulelo kwisifundo sokondla sango-2024. Akukho nanye kwezo zinto eqinisekisa ukuphiliswa kwizigulana kwamanqanaba evivax asegazini, yaye akukho nanye ejongana neehypnozoite ezisesibindini ezibangela ukubuyela kwemalariya yevivax, ezifuna izigqibo zazo zonyango ezijoliswe kolu hlobo. Ukwandisa isiphumo sokudluliselwa kwefalciparum usenze ibango ngazo zonke izifunxi-gazi kuphinda eyona mpazamo indala kolu phando. Ithala lophando ligcina iziphumo zeemvavanyo ebantwini nezophando lokulinga kwiikholamu ezahlukeneyo kanye ngenxa yesi sizathu.
Ukhuseleko luhamba nenkqubo yonyango
Imingcipheko emithathu kufuneka ijongwe ngokucacileyo kuba imisela ukuba ngoobani ekungafanele balinge.
Ukunqongophala kweglucose-6-phosphate dehydrogenase kubangela umngcipheko wehemolysis. Uhlalutyo oludityanisiweyo lwezifundo ezine zabantwana zaseBurkina Faso ezibandakanya abantwana abali-1,005 lwafumanisa ukuhla okukhulu kancinane kwehemoglobin emva kokufumana idayi kubathathi-nxaxheba ababenokunqongophala okupheleleyo, kunye neziganeko ezimbini zehemolysis kubantwana ababenokunqongophala okanye ababeheterozygous abanyangwa ngedayi. Inkcazelo esemthethweni yaseUnited States yemethylene blue etofwayo iyakwalela ukusetyenziswa kwayo kubantu abanokunqongophala kwe-G6PD kuba kunokwenzeka ihemolysis enzima. Iinkqubo zonyango lwemalariya ngamayeza aselwa ngomlomo zahlukile kwidosi kaxakeka efakwa emthanjeni, ngoko inkcazelo esemthethweni ayinakuguqulelwa ngokwamanani ibe ngumda wedosi yemalariya, kodwa umngcipheko ngokwebhayoloji uyafana. Ukuhlolwa nokubekwa esweni kufuneka kube yinxalenye yako nakuphi na ukusetyenziswa okucwangciswe ngenyameko.
Ukudibana namayeza achaphazela iserotonin kufuneka kujongwe kunye naloo mngcipheko. Imethylene blue esebenza emzimbeni wonke ithintela imonoamine oxidase kwaye inokubangela iserotonin syndrome xa idibene namayeza athintela ngokukhethekileyo ukuphinda kufunxwe iserotonin, amayeza athintela ukuphinda kufunxwe iserotonin nenorepinephrine, amayeza athintela imonoamine oxidase, kunye nezinye iiopioid namayeza okukhohlela; kuye kwaxelwa iimeko ezibangele ukufa. Ukudibana kwamayeza, iimeko apho kungavumelekanga ukuwasebenzisa, nokubekwa esweni kuchazwe ngokweenkcukacha kwinqaku elithi iziphumo ebezingalindelekanga, iimeko ezingavumeli ukusetyenziswa, nokhuseleko.
Ukunyamezeleka kungumqobo ongabonakali kakhulu. Umchamo oluhlaza okwesibhakabhaka nohlaza ulindelekile yaye awunabungozi, kodwa ubonakala ngokwaneleyo ukuba uchaphazele ukwamkeleka ukusukela kwiminyaka yoo-1890. Ukugabha kuxhomekeke kwidosi nakwindlela iyeza elilungiselelwe ngayo, kwaye kwabangela ukurhoxa kwiimvavanyo zabantwana, kufikelela kuma-40 ekhulwini abafumana idayi xa kuthelekiswa ne-14 ekhulwini abafumana iprimaquine kolunye uthelekiso lwamva. Iyeza eligabhwayo ngabantwana liyeza elisebenza ephepheni kuphela kwabo bantwana.
Kutheni obu bungqina bungakuxhasi ukuzinyanga
Izikhokelo zangoku zemalariya zifuna ukuqinisekiswa kwesifunxi-gazi kwaye zikhetha unyango ngokohlobo, ubunzima besigulo, indawo nokunganyangeki ngamayeza kuyo, ubudala nobunzima bomzimba, ukukhulelwa, nesimo se-G6PD, kusetyenziswa iindibaniselwano zeartemisinin njengonyango oluqhelekileyo lwesifo sef alciparum. Akukho nto kuphando ngale dayi ithatha indawo yale ndlela yokwenza izigqibo. Ukusetyenziswa kwechiza elinye kucotha kakhulu, ukhetho lweyeza elidityanisiweyo lumisela ukuphiliswa, iihypnozoite zevivax zifuna unyango olwahlukileyo, isimo se-G6PD sibeka imida ekusetyenzisweni, kwaye amayeza achaphazela iserotonin asetyenziswa ngaxeshanye abangela ukudibana okuyingozi. Unyango olungachanekanga lunokushiya usulelo lwefalciparum olubuyayo kuba lungaphelanga ngokupheleleyo, lungakuqapheli ukubuyela kwevivax, lubangele ihemolysis, kwaye lubeke uxinzelelo olubuthathaka lwamayeza olukhuthaza ukunganyangeki ngamayeza.
Isishwankathelo esithembekileyo sinomda ocutheneyo ngakumbi kunoko kukhethwa ngabaxhasi okanye abagxeki. Idayi yenkulungwane yeshumi elinesithoba inesenzo sokwenene samayeza kwinkulungwane yamashumi amabini ananye, kwaye elona galelo layo licacileyo lale mihla kukuthintela ukudluliselwa kwefalciparum xa yongezwa kwindibaniselwano efanelekileyo phantsi kokubekwa esweni kovavanyo. Oko kufunyenweyo kumalunga nokuphazamisa ukusasazeka kubantu abaphononongiweyo, kungekhona umyalelo wokuzinyanga.