Ese methylene blue ivura parazite?

Ikibazo gisa n’aho ari kimwe. Mu by’ukuri ni ibibazo byinshi bitandukanye byambaye isura imwe. Parazite ya malariya iri mu nsoro zitukura z’amaraso, umunyorogoto uri mu mara, n’ikinyabuzima gitera leishmaniasis yo ku ruhu nta byinshi bihuriyeho uretse ijambo parazite. Umuti wangiza imwe nta tegeko na rimwe rifite ko ugomba no kwangiza izindi. Komeza kuzirikana iki gitekerezo muri iri sesengura ryose: ubushobozi bwo kurwanya parazite si umutungo wa molekile yonyine. Ni umutungo wa molekile ifatanyije n’ikinyabuzima runaka, ku cyiciro runaka cy’ubuzima bwacyo, kandi kiri mu gice runaka cy’umubiri.

Iyo utandukanije ibyo binyabuzima, amakuru yerekeye methylene blue kuri parazite ahita agabanyikamo ibice bisobanutse. Hari malariya, aho hari ibigeragezo byakorewe ku bantu. Hanyuma hari ibindi byose: ubushakashatsi bwo mu masahani ya laboratwari, ku mbeba, ubuvuzi bw’uruhu bukoresha urumuri, n’inkuru zimaze imyaka irenga ijana. Nta buryo rusange bwo kuvura parazite bushobora gukomoka kuri ibyo.

Igisubizo kigufi

Methylene blue ni umuti nyakuri w’igerageza urwanya malariya. Isesengura rikusanyije ry’ubushakashatsi 21 bwakorewe ku bantu 1,504 barwaye malariya ryasanze ifite ibikorwa nyabyo ku byiciro bya parazite biri mu maraso, cyane cyane ku cyiciro cya gametocyte gituma ubwandu bushobora kwanduzwa imibu. Hanze ya malariya, ibimenyetso byatangajwe ntibishyigikira gufata methylene blue nk’umuti urwanya parazite nyinshi cyangwa nk’uburyo bwo gusukura parazite zo mu mara. Hafi ya buri gisubizo kitareba malariya kiri ku rwego rwo hasi rw’ibimenyetso: ikora mu isahani ya laboratwari, rimwe na rimwe igakora ku mbeba, ariko hafi na rimwe ntigeragerezwe ku bantu bafite ubwandu.

Malariya: parazite imwe rukumbi ifite ibigeragezo byakorewe ku bantu

Mu 1891, Guttmann na Ehrlich batangaje ko bavuje abarwayi ba malariya bakoresheje methylene blue, bikaba bishobora gufatwa nk’ikoreshwa rya mbere ry’umuti wakozwe mu buryo bwa sintetike mu kuvura indwara y’abantu. Amateka yayo kuva ku ibara kugeza ku kinyabutabire cyabaye intangiriro y’imiti irwanya malariya agera kuri chloroquine, yakomotse ku miterere y’ubutabire yatangiye kwigwa kuri iri bara.

Ubushakashatsi bwa none bwongeye kuyisuzuma kubera ko parazite zari zimaze kugira ubudahangarwa ku miti. Mu mikurire yo muri laboratwari, methylene blue ibuza Plasmodium falciparum yitabira chloroquine n’iyihanganiye ku bipimo byo hasi bya nanomolar, kandi hari ubufatanye bwatangajwe hagati yayo n’ibikomoka kuri artemisinin. Iyo yakoreshejwe yonyine ku bantu, yagaragaye ko ikora buhoro: igeragezo rigenzuwe ku bantu bakuru bari bafite ubudahangarwa buke muri Burkina Faso ryabonye igipimo cya 16 percent cyo kunanirwa hakiri kare, kandi abanditsi bemeje ko idakwiriye nk’umuti umwe ukoreshwa mu gihe gito. Kuvanga imiti byatanze umusaruro mwiza kurushaho. Mu igeragezo ryatoranyije ku buryo bwa random abana 180, methylene blue ivanze na amodiaquine yageze kuri 95 percent by’igisubizo cyakosowe ku munsi wa 28, kandi amatsinda yombi yakiriye methylene blue yagabanyije cyane gutwara gametocyte mu isesengura ry’inyongera ryerekeye kwanduza. Igeragezo ry’imiti itatu ivanze ku bana 221 ryaje kwemeza ingaruka kuri gametocyte hifashishijwe microscope n’uburyo bwo kumenya ibinyabuzima ku rwego rwa molekile. Igisubizo cyagaragaye cyane kurusha ibindi cyakoresheje imibu nk’igipimo nyamukuru: mu igeragezo rya phase 2 muri Mali, kongeraho methylene blue mu minsi itatu byatanze igabanuka rya median 100 percent ry’ubushobozi bwo kwanduza imibu ku munsi wa kabiri.

Hari uburyo butatu bushoboka bwo gukora bwaganiriweho kandi ntibukwiye gufatwa nk’uburyo bumwe. Iri bara ribuza enzyme ya parazite glutathione reductase mu kizamini cya laboratwari (Ki hafi ya 6.4 micromolar) kandi rikora redox cycling nk’ikinyabutabire gikoresha reducing equivalents (byagaragajwe kuri reductases z’abantu n’iza parazite). Ariko parazite zahinduwe mu rwego rwa genetike ku buryo zidafite iyo enzyme zigumana ubushobozi bumwe bwo kuyitabira, bityo ntishobora kuba ari yo nkuru yose, kandi igitekerezo cya kera cy’uko ibangamira gukuraho heme (byagaragaye ko bifitanye isano n’imbaraga za nanomolar) ntikirahamya ku barwayi. Incamake iboneye: hari imikorere nyayo ku bantu, nta ntego imwe yemejwe burundu, kandi nta mwanya ifite mu buryo busanzwe bwo kuvura. Amakuru ku buryo bwo kuyikoresha no ku kwanduza ari mu isesengura ryacu rya methylene blue kuri malariya, kandi iyi paji ntirisubiramo ibyo.

Babesia na Toxoplasma: ikomeye muri laboratwari, nta makuru yo mu mavuriro

Babesia, parazite ya hafi ya malariya na yo iba mu nsoro zitukura z’amaraso, yiciwe mu masahani ya laboratwari ku bipimo biri munsi ya micromolar, kandi parazite zari zimaze guhura nayo ntizongeye gukura (Journal of Protozoology Research) kandi isuzuma ryakurikiyeho ryashyize iri bara ku mwanya w’ikintu cyari gikomeye kurusha ibindi byageragejwe, hafi ya 0.2 micromolar (Carvalho na bagenzi be, 2020). Ku mbeba, na 50 mg/kg yatanze kubuza gukura ku rwego ruto gusa, kandi nta bushakashatsi bwakorewe ku bantu bafite babesiosis bubaho.

Toxoplasma na yo igaragaza ishusho imwe. Ubushakashatsi bubiri bwo muri laboratwari bwatandukanijwe n’imyaka myinshi bwabonye ko ibuza tachyzoites zikomeje kwiyongera ku bipimo biri munsi ya micromolar: 0.45 micromolar muri macrophages mu 1989 na hafi ya 0.30 micromolar mu isuzuma ry’imiti irwanya malariya mu 2018. Nta na kimwe cyageze kuri tissue cyst ya bradyzoite yihishe, ari cyo cyiciro kigoye mu buvuzi, kandi nta bushakashatsi bwo kuyivura ku nyamaswa cyangwa ku bantu bwabonetse. Umubare wa tachyzoite wabonetse mu isahani ya laboratwari si ikimenyetso ku bwandu buri mu muntu.

Leishmania na trypanosomes: witondere urumuri, witondere imbeba

Inyandiko nyinshi kuri Leishmania mu by’ukuri zivuga photodynamic therapy, igitekerezo gitandukanye no kunywa irangi. Gukoresha urumuri byagabanyije inhibitory concentration kuri Leishmania amazonensis kuva hafi ya 100 ikagera kuri 20 micromolar, kandi ibimenyetso byose byo ku bantu bigarukira ku murwayi umwe wavuwe ibisebe na antimony, aho kimwe muri byo cyongeye kuvurwa n’irangi ryakoreshejwe hamwe n’urumuri. Ubushakashatsi ku hamster bwabonye ko ubuvuzi bwo ku ruhu bukoresha irangi n’urumuri bwafashije, mu gihe irangi ryatewe mu ruhu ritafashije (Sbeghen na bagenzi be, 2015). Irangi rishyirwa ahantu hamwe ku ruhu rikajyanishwa n’urumuri rutukura si ubuvuzi bw’umubiri wose.

Amakuru kuri trypanosome arimo igisubizo kibi gifite akamaro kurusha ibindi muri iri sesengura: methylene blue yishe Trypanosoma brucei in vitro ariko inanirwa gukiza imbeba zanduye kuri 300 mg/kg zahawe mu kanwa cyangwa 200 mg/kg zatewe. Ku ndwara ya Chagas, ibimenyetso ni ibya biochemical, binyuze kuri enzyme yihariye ya parazite yitwa trypanothione reductase (Buchholz na bagenzi be, 2008), hiyongereyeho kwica parazite in vitro kongerwa n’urumuri (Barbosa na bagenzi be, 2020). Guhumanura plasma yashyizwemo parazite mu bigega by’amaraso (Gironés na bagenzi be, 2006) bireba ibikomoka ku maraso, si abarwayi. Abasomyi bageze hano kubera indwara zanduzwa n’udukoko nka ticks bakwiye kumenya ko Lyme disease ari indwara ya bacteria, atari iya parazite; ibimenyetso byayo byasesenguwe mu isesengura ryacu rya methylene blue kuri Lyme disease.

Inyo, flukes, n’ikirego cyo gusukura amara

Schistosoma mansoni ni urugero rukomeye kurusha izindi ku nyo, ariko na rwo ntiruhagije: irangi ryishe schistosomula munsi ya 10 micromolar n’inkuru kuri 10 kugeza kuri 30 micromolar, ariko imbeba zanduye zagaragaje igabanuka ry’umutwaro wa parazite rya hafi ya 60 percent kandi nta zakize burundu. Igeragezo rito ry’abantu ryavuzwe muri iyo nyandiko ryarebaga urundi ruvange rw’imiti, bityo ntirishobora gufatwa nk’igeragezo ry’irangi ku bantu. Kuri larvae n’inkuru za Strongyloides, inhibitory concentrations hafi ya 4 kugeza kuri 6 micromolar zahuye n’ubushobozi bw’irangi bwo kwinjira mu munyorogoto, ariko imbeba zahawe umuti mu kanwa zagaragaje ko ubwandu butagenzuwe ku buryo bufatika. Kuri scabies na lice, nta bimenyetso by’ubuvuzi ku bantu byabonetse.

Nta geragezo rya none, urukurikirane rw’abarwayi, cyangwa raporo yizewe y’umurwayi umwe igaragaza ko methylene blue inyowe ikuraho Giardia, Entamoeba, Strongyloides, cyangwa intestinal helminths mu bantu. Icyegereye cyane mu nyandiko zashyizwe mu bubiko ni raporo yo mu 1956 kuri giardiasis yo mu gallbladder idafite dose iboneka cyangwa gukira bishobora kugenzurwa. Inyandiko ebyiri za none kuri Giardia zoroshye gusoma nabi: muri imwe, irangi rya 1 percent ni ryo ryakoreshwaga mu gutuma trophozoites zigaragara, naho mu yindi, irangi rivanze ku gipimo gito ryakoreshwaga nk’ikimenyetso cyo gusoma ibisubizo nyuma y’imiti isanzwe. Irangi rituma parazite igaragara munsi ya microscope si umuti uyica mu mara. Kuri Trichomonas, ubushakashatsi bumwe rukumbi ku nyamaswa na bwo ni photodynamic: irangi rishyirwa mu nda ibyara hamwe n’urumuri ku mbeba zanduye (Fonseca na bagenzi be, 2019), si uburyo bwo gusukura umubiri bunyobwa.

Kugereranya

Ibyahindura iki gisubizo

Ibyuho bihari birasobanutse ku buryo byavugwa mu buryo bwihariye. Kugeza muri September 2026, nta geragezo ry’ubuvuzi ryanditswe ku bantu rya methylene blue kuri parazite iyo ari yo yose itari iya malariya ryabonetse, bityo icy’ibanze kibura ni ubushakashatsi ubwo ari bwo bwose bugenzuwe ku bantu hanze ya Plasmodium. Icya kabiri, concentrations zo mu masahani ya laboratwari zigumishwa iminsi myinshi zagiye zinanirwa ku nyamaswa kenshi kubera ko umuti ukurwaho vuba cyangwa ukagera mu bice bitari byo by’umubiri, nk’uko kunanirwa ku mbeba kuri trypanosome na Strongyloides kubigaragaza. Icya gatatu, ibisubizo bya photodynamic ntibikwiye gukomeza gutangwa nk’ibimenyetso bya systemic; irangi rifatanije na dose y’urumuri yapimwe ni uburyo bwo guhumanura ahantu hamwe kandi rifite ikibazo cyaryo cyo kugeza ubuvuzi aho bugomba kugera. Icya kane, ibivugwa ku mara bisaba parasitological endpoints, bivuze kwemeza ko parazite zavuye mu mwanda cyangwa mu tissue mu matsinda agenzuwe, aho gushingira ku buryo umuntu yumva ameze mu gihe akoresha cleanse irimo ibintu byinshi.

Hari ibintu bibiri by’umutekano bigabanya kugerageza ku giti cyawe. Irangi ntirigomba gukoreshwa ku bantu bafite glucose-6-phosphate dehydrogenase deficiency kubera ibyago bya hemolysis, kandi isesengura rihuriza hamwe ibigeragezo bine bya malariya ku bana ryabonye igabanuka rinini rya hemoglobin ku bana bafite deficiency yuzuye ku bipimo byo kurwanya parazite hafi ya 15 mg/kg per day. Ni na potent reversible monoamine oxidase A inhibitor (uburyo butera serotonin toxicity), kandi ibi biri ku nyandiko z’ubu z’umuti nk’umuburo ukomeye, kandi inkari z’ubururu zishobora kubangamira automated urine testing. Ibibazo bya dosing, purity, n’imikoranire y’imiti biri mu mabwiriza yacu afatika ku ikoreshwa rya methylene blue.

Methylene blue yabonye izina ryayo ryo kurwanya parazite mu buryo bufite ishingiro, kuri malariya, mu bigeragezo bya random byakoresheje ibipimo by’imibu. Ibirenze ibyo byose ni ugukoresha ububasha bw’ibimenyetso bitareba ibyo bindi binyabuzima. Kugeza igihe ubushakashatsi bugenzuwe ku bantu bugaragaje ibitandukanye ku kinyabuzima runaka cyavuzwe izina, umwanya ushobora gushyigikirwa n’ibimenyetso ugomba kuguma ari muto: ni umuti nyakuri urwanya malariya kandi ubuza kwanduza ugikorerwaho ubushakashatsi, naho ahandi hose ni igisubizo cya laboratwari kigitegereje gihamya ko gikomeza gukora iyo gihuye n’ikinyabuzima kizima.