Ubururu bwa metilene na malariya: amateka n’ibimenyetso byo mu magerageza

Mu 1891 abarwayi babiri ba malariya bavuwe hakoreshejwe irangi ry’ubururu ry’imyenda. Paul Guttmann na Paul Ehrlich bari babonye ko ubururu bwa metilene busiga ibara ku dukoko dutera malariya mu buryo bwihariye, maze batekereza ko irangi rifite umwihariko uhagije wo kugaragaza ako gakoko rishobora no kugira umwihariko uhagije wo kukangiza. Abo barwayi bombi barakize. Iryo gerageza ryatumye ubururu bwa metilene buba umuti wa mbere wa malariya wakozwe mu buryo bwa shimi, imyaka ibarirwa muri za mirongo mbere y’uko chloroquine ibaho.

Nyuma yaho, mu gice kinini cy’ikinyejana cya makumyabiri, iryo rangi ryagiye ritakaza umwanya. Imiti mishya yakozwe mu buryo bwa shimi, umubiri wihanganiraga neza kurushaho, yararisimbuye. Mu bihe bya none, ryari risigaye rikoreshwa ahanini nk’ikinyabutabire cyo muri laboratwari, irangi rifasha mu gusuzuma, n’umuti w’ubutabazi ku yindi ndwara y’amaraso. Bityo rero, kongera kurikoresha mu bushakashatsi kuri malariya muri Burkina Faso na Mali ntibyari ugukumbura ibya kera. Abashakashatsi bari bafite igitekerezo cyihariye cyo kugenzura: ibikorwa bya shimi bya redox bituma riba irangi bishobora kubangamira uburyo ako gakoko kirinda impinduka za redox, kandi ingaruka rigira ku gakoko kari mu cyiciro gishobora kwanduzwa zishobora gukora ibyo imiti isanzwe idakora neza. Kugenzura icyo gitekerezo byasabaga kuvuga buri gihe imiti ivanze yakoreshejwe, ubwoko bw’agakoko, n’igipimo cy’ibyavuye mu igerageza, kuko guhindura kimwe muri ibyo bihindura umwanzuro.

Itandukaniro rusange hagati y’imiti yemerewe gukoreshwa n’imikoreshereze ikiri gukorwaho ubushakashatsi risobanurwa mu ngingo ubururu bwa metilene mu buvuzi. Malariya iri ku ruhande rw’imikoreshereze ikiri gukorwaho ubushakashatsi: ubururu bwa metilene bugira igikorwa ku dukoko, bwageragejwe buvanze n’indi miti, ariko si uburyo busanzwe bwo kuvura bwemejwe mu mabwiriza.

Impamvu irangi rya Ehrlich ryakoraga n’impamvu ryaretswe

Ibyanditswe bya mbere ni urugero rufasha kumenya uko ibimenyetso byo mu bihe bya kera bigomba gusomwa. Isesengura ryo mu 1904 ry’inkuru z’abarwayi 425 ryagereranyije ko hafi 85 ku ijana bagaragaje kwitabira ubuvuzi, ariko izo nkuru zanditswe mbere y’uko habaho kugabanya abitabiriye amagerageza mu matsinda ku buryo bwa tombola, ibipimo bimwe byo gusuzuma ibyavuye mu buvuzi, kwemeza ubwoko bw’agakoko, no gukurikirana ukudakangwa n’imiti. Zigaragaza ko icyo kinyabutabire cyagiraga igikorwa kuri malariya cyari gikwiye gukomeza gukorwaho ubushakashatsi, ariko ntizitanga igipimo cyo gukira cyagereranywa n’icy’igerageza rya none.

Kureka kugikoresha byatewe n’ingorane z’imikoreshereze aho guterwa no guhakana ko cyakoraga. Ubururu bwa metilene butuma inkari ziba ubururu cyangwa icyatsi, busiga ibara mu ngingo z’umubiri, kandi ku bipimo byakoreshwaga icyo gihe bwatezaga ibibazo by’igogora n’inzira z’inkari, birimo kuruka no kubabara mu gihe cyo kwihagarika. Imiti mishya yakuragaho udukoko idahinduye umurwayi ibara. Isesengura ry’amateka akurikirana kuva ku bururu bwa metilene kugera kuri chloroquine rivuga uko iryo rangi ryasimbuwe, naho isesengura ry’imiti ya malariya yo mu muryango wa phenothiazinium rikusanya ibitekerezo ku buryo ikora byatumye abashakashatsi bakomeza kuyitaho nubwo imikoreshereze yayo mu buvuzi yagabanukaga.

Ku birebana n’uburyo rikora, iryo rangi risobanurwa neza nk’ikinyabutabire kigira igikorwa cya redox aho kuba ikigira igikorwa ku kintu kimwe gusa. Mu igerageza ryo muri laboratwari, ribuza gukora kwa glutathione reductase y’agakoko, kandi icyarimwe rigahererekanya elekitoroni mu buryo bukoresha ubushobozi bwo gukora redigisiyo ako gakoko gakeneye, bigateza ihungabana riterwa na okisidasiyo; hanatanzwe igitekerezo cy’uko ribangamira uburyo heme ihindurwa kugira ngo itagira uburozi. Ntiharamenyekana neza igikorwa muri ibyo cyiganje imbere mu mubiri w’umurwayi. Ingaruka y’ingenzi si ukumenya neza ikintu gikorerwaho, ahubwo ni umwihariko w’igikorwa ku cyiciro cy’agakoko: ubururu bwa metilene bugira igikorwa gikomeye bidasanzwe kuri gametocytes, icyiciro cy’imyororokere imibu igomba gufata mu maraso kugira ngo kwanduzanya bikomeze. Imiti isanzwe ivanzemo artemisinin ikuraho udukoko tutari mu cyiciro cy’imyororokere dutuma umurwayi arwara, ariko ishobora gusiga gametocytes zikuze. Umuti ugabanya igihe umuntu amara afite gametocytes cyangwa utuma zidashobora kwanduza uba ugamije kwanduzanya ubwako.

Ibyo amagerageza ya none yagenzuye

Buri gisubizo cya none gikurikira cyavuye ku miti ivanze. Igipimo cy’umuti, umuti uvanze na wo, ubwoko bw’agakoko, n’igipimo cy’ibyavuye mu igerageza byose ni igice cy’ibyagaragajwe.

Igerageza n’abaryitabiriye	Uburyo bwo gutanga imiti	Igipimo cyasuzumwe n’ibyavuyemo	Imbibi
Burkina Faso 2005, abana 226 bafite amezi 6 kugeza kuri 59, malariya ya falciparum	Chloroquine ivanze n’ubururu bwa metilene 4 mg/kg/day mu gihe cy’iminsi 3, ugereranyije na chloroquine yonyine	Ku munsi wa 14, kwitabira ubuvuzi ku rwego ruhagije byari hafi 56 ugereranyije na 46 ku ijana; nta nyungu isobanutse	Igipimo gito cy’irangi mu gihe udukoko tutakangwa na chloroquine; igerageza ridakomeye ry’uburyo bwa none bwo gutanga imiti
Zoungrana 2008, icyiciro cya 2, abana 180 bafite imyaka 6 kugeza kuri 10, malariya ya falciparum	Ubururu bwa metilene buvanze na artesunate, buvanze na amodiaquine, cyangwa imvange isanzwe ya artesunate-amodiaquine; irangi 20 mg/kg/day mu gihe cy’iminsi 3	Ku munsi wa 28, igipimo cyo gukira cyakosowe cyari 62, 95, na 82 ku ijana, muri urwo rutonde; udukoko twavuyeho vuba kurushaho mu mvange ya artesunate; amatsinda yombi yahawe irangi yagabanyije kugira gametocytes ku minsi ya 3, 7, na 14	Abitabiriye n’abashakashatsi bari bazi imiti yatanzwe, kandi amatsinda yari mato; igipimo gito cyo gukira mu mvange ya artesunate kigaragaza ko umuti uvanze n’irangi ari wo ugena ibivamo
Coulibaly 2015, icyiciro cya IIb, abana 193 mu itsinda ryasuzumiwe imikorere y’umuti, malariya ya falciparum	Artesunate-amodiaquine ivanze n’irangi 15 mg/kg/day mu gihe cy’iminsi 3, ugereranyije n’iyo mvange yonyine	Ku munsi wa 7, gametocytes zagaragajwe na mikorosikopi zari kuri 1.2 ugereranyije na 8.9 ku ijana; udukoko tutari mu cyiciro cy’imyororokere twavuyeho vuba ho gato; igipimo cyo gukira cyakosowe cyari hafi kimwe, hafi 80 ugereranyije na 85 ku ijana	Kugabanya umubare w’abafite gametocytes, si ugukira, ni yo nyungu y’ingenzi; irangi ryajyanaga no kuruka kurushaho no kugabanuka kwa hemoglobine kw’igihe gito
Mali 2018, icyiciro cya 2, abantu b’igitsina gabo 80 bafite G6PD isanzwe, bafite ubwandu bwa falciparum burimo gametocytes ariko nta bimenyetso	Dihydroartemisinin-piperaquine ivanze n’irangi 15 mg/kg/day mu gihe cy’iminsi 3, ugereranyije n’umuti wa malariya wonyine	Mu bitabiriye bashoboraga kwanduza ku ntangiriro, agaciro ko hagati k’igabanuka ry’ubushobozi bwo kwanduza imibu kari 100 ku ijana mu bahawe irangi, ugereranyije n’igabanuka risa n’iritariho mu batarihawe ku munsi wa 2, kandi byarakomeje ku munsi wa 7	Mu igereranya ry’ingenzi, 11 gusa mu bahawe irangi ni bo bashoboraga kwanduza; harimo ab’igitsina gabo gusa, abafite G6PD isanzwe gusa, n’abafite ubwandu butagira ibimenyetso; igipimo cyarebaga kwanduzanya, si igerageza ryo gukira
Burkina Faso 2019, abana 100, malariya ya falciparum	Artesunate-amodiaquine ivanze n’irangi, ugereranyije n’iyo mvange yongewemo primaquine itangwa rimwe	Igipimo cyo gukira cyakosowe cyari hafi 96 ku ijana mu matsinda yombi; kugeza ku munsi wa 1, udukoko twavuyeho vuba kurushaho mu bahawe irangi; ku munsi wa 2, abafite gametocytes bari 4 ugereranyije na 31 ku ijana, nubwo primaquine itatanzwe mbere y’umunsi wa 2	Igerageza rito kandi abitabiriye n’abashakashatsi bari bazi imiti yatanzwe; igihe imiti yatangiwe gituma igereranya rya gametocytes ryo mu minsi ya mbere ritaba ku buryo bumwe; intego nyamukuru yari umutekano ku maraso

Ibintu bibiri bigaragara mu buryo buhoraho muri ubu bushakashatsi. Icya mbere, irangi rigira koko igikorwa kuri Plasmodium falciparum, ariko iyo rikoreshejwe ryonyine rikuraho udukoko buhoro cyane kandi rikemerera ubwandu kongera kugaragara; ubushakashatsi buto ku bantu bakuru bwanzuye ko rigomba kuvangwa n’umuti ukora vuba. Icya kabiri, inyungu yaryo y’inyongera igaragara mu buryo bushobora gusubirwamo kurusha izindi, iyo ryongewe ku mvange ya none yatoranyijwe neza, ireba ibipimo bya gametocytes n’ikwirakwira aho kuba ukwiyongera gukomeye kw’igipimo gisanzwe cyo gukira. Ubushakashatsi bwo muri Mali bwo kugaburira imibu amaraso binyuze mu gahu ni bwo bugaragaza neza icyo cya kabiri, kuko imibu yagaburiwe amaraso y’abitabiriye yagize amahirwe make cyane yo kwandura.

Imbibi z’ubwoko bw’udukoko zifite akamaro kangana n’iz’imiti ivanze. Hafi ibimenyetso byose bya none byemeza imikorere ku barwayi bireba malariya ya falciparum. Kuri malariya ya vivax, ibyanditswe ku barwayi bigizwe n’ibyabonetse kera, byiyongeraho ubushakashatsi bwa none bwo muri laboratwari no kugaburira imibu amaraso, harimo kuba udukoko twakuwe mu karere ka Tayilande na Myanmar twitabira irangi ku gipimo gito cyo ku rwego rwa nanomolar, no kubuza cyane ikwirakwira mu bushakashatsi bwo kugaburira imibu bwo mu 2024. Nta na kimwe muri ibyo cyemeza ugukira mu buvuzi kw’ibyiciro bya vivax biri mu maraso, kandi nta na kimwe gisubiza ikibazo cya hypnozoites zo mu mwijima zituma malariya ya vivax igaruka, zisaba ibyemezo by’ubuvuzi byihariye kuri ubwo bwoko. Gufata ibyavuye ku kwanduzanya kwa falciparum ukabigira ikirego kireba udukoko twose ni ugusubiramo ikosa rya kera kurusha ayandi muri izi nyandiko. Ububiko bw’ubushakashatsi bushyira ibyavuye mu magerageza ku bantu n’ibyavuye mu bushakashatsi bwo mu igerageza mu nkingi zitandukanye kubera iyo mpamvu nyine.

Umutekano ujyana n’uburyo bwo gutanga imiti

Ibyago bitatu bigomba kwitabwaho mu buryo bweruye kuko ari byo bigena abagomba kutagerageza kwivura.

Ibura rya glucose-6-phosphate dehydrogenase ritera ibyago byo gusenyuka kw’insoro zitukura. Isesengura ryahurije hamwe ubushakashatsi bune bwo muri Burkina Faso ku bana 1,005 ryasanze hemoglobine yaragabanutse ho gato kurushaho mu bitabiriye bafite iryo bura ryuzuye bahawe irangi, kandi habaye ibihe bibiri byo gusenyuka kw’insoro zitukura mu bana bahawe irangi bari bafite iryo bura cyangwa bafite alele ebyiri zitandukanye. Amabwiriza yo muri Leta Zunze Ubumwe za Amerika y’ubururu bwa metilene butangwa mu nshinge abuza kubukoresha ku bafite ibura rya G6PD, kuko hashobora kubaho gusenyuka gukomeye kw’insoro zitukura. Uburyo bwo gutanga imiti ya malariya inyuzwa mu kanwa buratandukanye n’igipimo cy’ubutabazi gitangwa mu mutsi, bityo imibare yo muri ayo mabwiriza ntishobora guhindurwa ngo ibe igipimo ntarengwa cy’umuti wa malariya, ariko icyerekezo cy’ingaruka ku mubiri ni kimwe. Gusuzuma no kugenzura umurwayi bigomba kujyana n’imikoreshereze yose ikozwe mu buryo bwitondewe.

Imikoranire n’imiti igira igikorwa kuri serotonine na yo igomba kwitabwaho. Ubururu bwa metilene bugera mu mubiri hose bubuza monoamine oxidase gukora, kandi bushobora gutera sindorome ya serotonine iyo bukoreshejwe hamwe n’imiti ibuza kongera kwinjizwa kwa serotonine mu buryo bwihariye, imiti ibuza kongera kwinjizwa kwa serotonine na norepinephrine, imiti ibuza monoamine oxidase gukora, na zimwe muri opioids n’imiti y’inkorora; hari n’impfu zavuzwe. Iyo mikoranire, ibibuza imikoreshereze, n’ikurikiranwa bisobanurwa birambuye mu ngingo ingaruka mbi, ibibuza imikoreshereze, n’umutekano.

Ubushobozi bw’umubiri bwo kwihanganira umuti ni inzitizi itavugwa cyane. Inkari z’ubururu buvanze n’icyatsi ni ikintu giteganyijwe kandi kidateza ikibazo, ariko ziragaragara cyane ku buryo zagabanyije uko abantu bemera uyu muti kuva mu myaka ya 1890. Kuruka guterwa n’igipimo cy’umuti n’uburyo uteguwe, kandi kwatumye bamwe bava mu magerageza ku bana. Mu igereranya rimwe ryakozwe nyuma, kuruka kwageze kuri 40 ku ijana by’abahawe irangi, ugereranyije na 14 ku ijana by’abahawe primaquine. Ku bana baruka umuti, imikorere yawo kuri abo bana iba iri ku mpapuro gusa.

Impamvu ibi bimenyetso bidashyigikira kwivura

Amabwiriza ya none ya malariya asaba kwemeza ko udukoko duhari, kandi agahitamo ubuvuzi hashingiwe ku bwoko bw’agakoko, ubukana bw’indwara, aho udukoko tudakangwa n’imiti, imyaka n’ibiro, gutwita, n’imiterere ya G6PD, imiti ivanzemo artemisinin ikaba ari yo isanzwe ikoreshwa kuri malariya ya falciparum. Nta kintu na kimwe mu nyandiko zerekeye irangi gisimbura ubwo buryo bwo gufata ibyemezo. Gukoresha umuti umwe gusa biratinda cyane, guhitamo umuti uvangwa na wo ni byo bigena ugukira, hypnozoites za vivax zikeneye ubuvuzi bwihariye, imiterere ya G6PD igena imbibi z’imikoreshereze, kandi gukoresha icyarimwe imiti igira igikorwa kuri serotonine bitera imikoranire iteje akaga. Ubuvuzi butari bwo bushobora gusiga ubwandu bwa falciparum bwongera kugaragara, ntibwite ku kugaruka kwa vivax, bugatera gusenyuka kw’insoro zitukura, kandi bugashyira ku dukoko igitutu cy’umuti kidahagije gituma ukudakangwa n’imiti kwiyongera.

Incamake ivugisha ukuri iragufi kurusha uko abashyigikiye cyane uyu muti cyangwa abawuhakana babyifuza. Irangi ryo mu kinyejana cya cumi n’icyenda rifite koko igikorwa cy’umuti cyo mu kinyejana cya makumyabiri na kimwe, kandi umusanzu waryo wa none ugaragara neza kurusha indi ni ukubuza ikwirakwira rya falciparum iyo ryongewe ku mvange ikwiye, rikoreshwa rikurikiranwa mu igerageza. Ibyo ni ibyagaragajwe ku guhagarika ikwirakwira mu matsinda yakorewe ubushakashatsi, si amabwiriza yo kwivura.