Maƙala
Methylene blue da zazzabin cizon sauro: amfani a tarihi da gwaje-gwajen zamani
A 1891 an yi wa marasa lafiya biyu masu zazzabin cizon sauro magani da wani shuɗin rinin masana'anta. Paul Guttmann da Paul Ehrlich sun lura cewa methylene blue yana rina ƙwayoyin zazzabin cizon sauro musamman, kuma suka yi tunanin cewa rinin da zai iya zaɓar ƙwayar cutar ya nuna ta, wataƙila zai iya zaɓarta ya cutar da ita. Duk marasa lafiyan biyu sun warke. Wannan gwajin ya sa methylene blue ya zama maganin zazzabin cizon sauro na farko da aka ƙera ta hanyar haɗa sinadarai, shekaru da dama kafin samuwar chloroquine.
Daga nan, rinin ya shafe mafi yawan ƙarni na ashirin yana rasa matsayinsa. Magungunan da aka ƙera ta haɗa sinadarai waɗanda marasa lafiya suka fi iya jurewa sun maye gurbinsa, kuma zuwa zamanin yanzu an fi amfani da shi ne a matsayin sinadarin gwajin dakin bincike, rinin gano cuta, da maganin gaggawa na wata cutar jini daban. Saboda haka, komawarsa cikin binciken zazzabin cizon sauro a Burkina Faso da Mali ba wai don kewar tsohon zamani ba ne. Masu bincike suna da takamaiman hasashe: irin mu'amalar sinadaran redox da ke sa wannan sinadari ya zama rini na iya kawo cikas ga kariyar redox ta ƙwayar cutar kanta, kuma tasirinsa a matakin ƙwayar cutar da ke ba da damar yaɗuwa na iya yin abin da magungunan da aka saba amfani da su ba sa yi sosai. Gwada wannan hasashe ya buƙaci a bayyana haɗin magungunan, nau'in ƙwayar cutar, da ma'aunin sakamako a kowane lokaci, domin canza ko ɗaya daga cikinsu yana canza abin da za a kammala da shi.
An bayyana bambancin da ya fi faɗi tsakanin magungunan da aka amince da su da amfanin da ake kan bincike a kansu a methylene blue a aikin likitanci. Amfaninsa wajen zazzabin cizon sauro yana ɓangaren bincike: yana da tasiri a kan ƙwayoyin cutar, an gwada shi cikin haɗin magunguna, amma ba magani ne da ƙa'idojin jinya suka ɗauka a matsayin na yau da kullum ba.
Dalilin da ya sa rinin Ehrlich ya yi aiki da dalilin da ya sa aka daina amfani da shi
Bayanan farko suna zama misali na yadda za a karanta shaidar da ta gabaci hanyoyin bincike na zamani. Wani bita na 1904 kan rahotannin marasa lafiya 425 ya kiyasta samun amsa ga magani a kusan kashi 85 cikin ɗari, amma waɗannan rahotanni sun gabaci raba mahalarta bazuwar zuwa rukunonin gwaji, daidaita ma'aunan sakamako, tabbatar da nau'in ƙwayar cuta, da sa ido kan juriya ga magani. Sun tabbatar cewa sinadarin yana da tasirin yaƙar zazzabin cizon sauro da ya cancanci ƙarin bincike, ba cewa yana da ƙimar warkarwa da za a iya kwatanta da ta gwajin zamani ba.
An daina amfani da shi saboda matsalolin amfani a aikace, ba saboda an karyata tasirinsa ba. Methylene blue yana mayar da fitsari shuɗi ko kore, yana rina kyallen jiki, kuma yana haifar da matsalolin tsarin narkewar abinci da fitsari, ciki har da amai da jin zafi yayin fitsari, a adadin da ake amfani da shi a lokacin. Sabbin magunguna suna kawar da ƙwayoyin cutar ba tare da rina jikin mara lafiya ba. Bitar tarihi da ke bin tafiyar methylene blue zuwa chloroquine ta ba da labarin wannan maye gurbi, yayin da bitar magungunan phenothiazinium na zazzabin cizon sauro ta tattara hasashen hanyoyin aikinsu waɗanda suka sa masu bincike suka ci gaba da sha'awa bayan amfani da su wajen jinya ya ragu.
Dangane da yadda yake aiki, ya fi dacewa a bayyana rinin a matsayin sinadari mai aikin redox maimakon wanda ke kai hari ga manufa guda. Yana hana aikin glutathione reductase na ƙwayar cutar a bututun gwaji, sannan a lokaci guda yana zagayar da electrons ta hanyoyin da ke cinye ƙarfin reduction da ƙwayar cutar ke buƙata, yana kuma haifar da damuwar oxidation; an kuma yi hasashen cewa yana kawo cikas ga kawar da gubar heme. Har yanzu ba a tabbatar da wanne daga cikin waɗannan ya fi rinjaye a jikin mara lafiya ba. Muhimmin sakamakon ba takamaiman abin da yake kai wa hari ba ne, sai dai bambancin tasirinsa bisa matakin rayuwar ƙwayar cutar: methylene blue yana da tasiri na musamman a kan gametocytes, matakin jinsi da dole sauro ya haɗiye domin yaɗuwar cutar ta ci gaba. Haɗin magungunan artemisinin da aka saba amfani da su yana kawar da ƙwayoyin cutar masu hayayyafa ba tare da saduwar jinsi ba waɗanda ke sa mara lafiya rashin lafiya, amma yana iya barin gametocytes da suka balaga. Maganin da ke rage tsawon lokacin ɗauke da gametocytes ko ya hana su iya yaɗa cuta yana kai hari ga yaɗuwar cutar kanta.
Abin da gwaje-gwajen zamani suka gwada
Kowane sakamakon zamani da ke ƙasa sakamakon haɗin magunguna ne. Adadin magani, maganin da aka haɗa da shi, nau'in ƙwayar cuta, da ma'aunin sakamako duk suna cikin abin da aka gano.
| Gwaji da rukunin mahalarta | Tsarin magani | Ma'aunin sakamako da abin da aka samu | Iyaka |
|---|---|---|---|
| Burkina Faso 2005, yara 226 masu watanni 6 zuwa 59, zazzabin cizon sauro na falciparum | Chloroquine tare da methylene blue 4 mg/kg/day na kwanaki 3 idan aka kwatanta da chloroquine kaɗai | Amsa mai gamsarwa a rana ta 14 kusan kashi 56 idan aka kwatanta da 46 cikin ɗari; babu wata fa'ida bayyananniya | Ƙaramin adadin rini a yanayin da ƙwayoyin cuta ke da juriya ga chloroquine; bai zama gwaji mai kyau na tsarin magani na zamani ba |
| Zoungrana 2008, mataki na 2, yara 180 masu shekaru 6 zuwa 10, zazzabin cizon sauro na falciparum | Methylene blue tare da artesunate, tare da amodiaquine, ko haɗin artesunate-amodiaquine da aka saba amfani da shi; rini 20 mg/kg/day na kwanaki 3 | Warkarwa bayan gyaran ƙididdiga a rana ta 28 kashi 62, 95, da 82 cikin ɗari bi da bi; kawar da ƙwayoyin cuta mafi sauri tare da haɗin artesunate; duka rukunonin rinin sun rage ɗauke da gametocytes a ranakun 3, 7, da 14 | Gwaji marar ɓoye nau'in magani tare da ƙananan rukunoni; ƙarancin warkarwa a haɗin artesunate ya nuna cewa maganin da aka haɗa da shi ne ke ƙayyade sakamakon |
| Coulibaly 2015, mataki na IIb, yara 193 a rukunin tantance tasiri, zazzabin cizon sauro na falciparum | Artesunate-amodiaquine tare da rini 15 mg/kg/day na kwanaki 3 idan aka kwatanta da wannan haɗin kaɗai | Gametocytes da aka gani da na'urar hangen ƙwayoyin halitta a rana ta 7 kashi 1.2 idan aka kwatanta da 8.9 cikin ɗari; kawar da ƙwayoyin cuta masu hayayyafa ba tare da saduwar jinsi ba ya ɗan fi sauri; warkarwa bayan gyaran ƙididdiga ta yi kama, kusan kashi 80 idan aka kwatanta da 85 cikin ɗari | Rage yawan masu gametocytes, ba warkarwa ba, shi ne babban abin da aka samu; ƙarin amai da raguwar hemoglobin na ɗan lokaci tare da rini |
| Mali 2018, mataki na 2, maza 80 masu G6PD na al'ada da kamuwa da falciparum mai gametocytes ba tare da alamomin cuta ba | Dihydroartemisinin-piperaquine tare da rini 15 mg/kg/day na kwanaki 3 idan aka kwatanta da maganin zazzabin cizon sauro kaɗai | A cikin mahalartan da suka iya yaɗa cuta a farkon gwaji, ƙimar tsakiya ta raguwar iya harba sauro da cuta ta kasance kashi 100 cikin ɗari tare da rini, idan aka kwatanta da kusan babu raguwa ba tare da shi ba a rana ta 2, kuma hakan ya dore a rana ta 7 | Mutane 11 kawai masu iya yaɗa cuta da suka karɓi rini a babban kwatancen; maza kaɗai, masu G6PD na al'ada kaɗai, masu ɗauke da cuta ba tare da alamomi ba; ma'aunin yaɗuwa ne, ba gwajin warkarwa ba |
| Burkina Faso 2019, yara 100, zazzabin cizon sauro na falciparum | Artesunate-amodiaquine tare da rini idan aka kwatanta da wannan haɗin tare da primaquine da aka ba sau ɗaya | Warkarwa bayan gyaran ƙididdiga kusan kashi 96 cikin ɗari a rukunonin biyu; kawar da ƙwayoyin cuta zuwa rana ta 1 ya fi sauri tare da rini; gametocytes a rana ta 2 kashi 4 idan aka kwatanta da 31 cikin ɗari, duk da cewa ba a ba da primaquine ba sai rana ta 2 | Ƙaramin gwaji marar ɓoye nau'in magani; lokacin ba da magani ya sa kwatancen farko na gametocytes bai daidaita ba; babban abin da aka fi mayar da hankali a kai shi ne amincin jini |
Abubuwa biyu sun fito a duk waɗannan binciken. Na farko, rinin yana da tasiri na gaske a kan Plasmodium falciparum, amma idan aka yi amfani da shi shi kaɗai, yana kawar da ƙwayoyin cutar a hankali sosai kuma yana ba su damar sake yawaita; wani ƙaramin bincike a manya ya kammala cewa ya kamata a haɗa shi da magani mai saurin aiki. Na biyu, ƙarin fa'idarsa da aka fi samun maimaituwarta idan aka ƙara shi ga haɗin magunguna na zamani da aka zaɓa daidai tana cikin ma'aunan gametocytes da yaɗuwa, maimakon babban ƙaruwa a warkarwa ta ma'aunan da aka saba amfani da su. Binciken ciyar da sauro jini kai tsaye ta membrane a Mali shi ne ya fi nuna wannan magana ta biyu a sarari, domin yiwuwar kamuwar sauro da cuta bayan ya sha jinin mahalarta ta ragu sosai.
Iyakokin nau'in ƙwayar cuta suna da muhimmanci kamar iyakokin haɗin magunguna. Kusan duk shaidar zamani mai ƙarfi daga gwaje-gwajen jinya ta shafi zazzabin cizon sauro na falciparum. Ga zazzabin cizon sauro na vivax, bayanan jinya sun ƙunshi lura ta tarihi tare da aikin zamani a bututun gwaji da ciyar da sauro, ciki har da tasirin ƙananan matakan nanomolar na rinin a kan ƙwayoyin da aka ware a iyakar Thailand da Myanmar, da ƙarfi wajen hana yaɗuwa a wani binciken ciyar da sauro na 2024. Babu ɗaya daga cikin waɗannan da ya tabbatar da warkar da matakan vivax da ke cikin jini a jikin marasa lafiya, kuma babu ɗaya da ya shafi hypnozoites na hanta da ke haifar da dawowar vivax, waɗanda ke buƙatar nasu shawarar magani ta musamman ga wannan nau'in. Faɗaɗa sakamakon yaɗuwar falciparum zuwa ikirari game da duk ƙwayoyin cuta yana maimaita kuskure mafi daɗewa a waɗannan rubuce-rubucen bincike. Ɗakin tattara bincike yana ware sakamakon gwaje-gwajen mutane da na sauran gwaje-gwajen bincike a ginshiƙai daban saboda wannan dalili.
Aminci yana tafiya tare da tsarin magani
Haɗurra uku suna buƙatar kulawa a sarari domin su ne ke ƙayyade waɗanda bai kamata su gwada amfani ba.
Rashin glucose-6-phosphate dehydrogenase yana haifar da haɗarin rushewar jajayen ƙwayoyin jini. Wani nazarin haɗa bayanai daga bincike huɗu na yara a Burkina Faso, wanda ya ƙunshi yara 1,005, ya gano raguwar hemoglobin da ta ɗan fi yawa bayan amfani da rini a mahalartan da ke da cikakken rashin wannan enzyme, tare da aukuwar rushewar jajayen ƙwayoyin jini sau biyu a yaran da aka ba rini waɗanda ke da rashin enzyme ko bambancin gado na heterozygous. Bayanin maganin methylene blue na allura a Amurka ya hana amfani da shi ga masu rashin G6PD saboda tsananin rushewar jajayen ƙwayoyin jini na iya faruwa. Tsarin ba da maganin zazzabin cizon sauro ta baki ya bambanta da adadin gaggawa da ake ba ta jijiya, don haka ba za a iya sauya bayanin maganin zuwa iyakar adadin maganin zazzabin cizon sauro ta hanyar lissafi ba, amma yanayin haɗarin a jiki iri ɗaya ne. Duk wani amfani da aka ɗauka da muhimmanci yana buƙatar tantancewa da kulawar ƙwararru.
Mu'amala da magungunan da ke shafar serotonin tana da muhimmanci haka nan. Methylene blue da ya shiga tsarin jiki yana hana aikin monoamine oxidase kuma yana iya tayar da matsalar serotonin syndrome idan aka haɗa shi da masu hana sake ɗaukar serotonin na zaɓaɓɓen nau'i, masu hana sake ɗaukar serotonin da norepinephrine, masu hana monoamine oxidase, da wasu opioids da magungunan tari; an bayar da rahotannin mace-mace. An yi bayani dalla-dalla kan wannan mu'amala, yanayin da ya hana amfani, da sa ido a illolin gefe, yanayin da ya hana amfani, da aminci.
Iya jure maganin shi ne shingen da ba ya yawan ɗaukar hankali. Ana sa ran fitsari mai shuɗi-kore kuma ba shi da illa, amma yana bayyana sosai har ya rage karɓuwar maganin tun shekarun 1890s. Amai ya danganta da adadin magani da yadda aka tsara shi, kuma ya sa aka janye wasu yara daga gwaje-gwaje, inda ya kai kashi 40 cikin ɗari na masu karɓar rini idan aka kwatanta da kashi 14 cikin ɗari tare da primaquine a wani kwatancen da aka yi daga baya. Maganin da yara suke amayarwa, tasirinsa ga waɗannan yaran yana kasancewa a takarda kawai.
Dalilin da ya sa wannan shaida ba ta goyi bayan yin magani da kai ba
Jagororin zazzabin cizon sauro na yanzu suna buƙatar tabbatar da ƙwayar cuta, sannan a zaɓi magani bisa nau'inta, tsananin cutar, yanayin juriya ga magani a yankin, shekaru da nauyi, ciki, da matsayin G6PD, tare da haɗin magungunan artemisinin a matsayin tsarin da aka saba amfani da shi ga cutar falciparum. Babu wani abu a rubuce-rubucen binciken rinin da ya maye gurbin wannan tsarin yanke shawara. Amfani da magani guda yana aiki a hankali sosai, zaɓin maganin da za a haɗa da shi yana ƙayyade warkarwa, hypnozoites na vivax suna buƙatar magani dabam, matsayin G6PD yana iyakance amfani, kuma amfani da magungunan da ke shafar serotonin a lokaci guda yana haifar da mu'amala mai haɗari. Maganin da bai dace ba na iya barin ƙwayoyin falciparum su sake yawaita, ya kasa magance dawowar vivax, ya tayar da rushewar jajayen ƙwayoyin jini, kuma ya fallasa ƙwayoyin cuta ga tasirin magani mai rauni wanda ke ƙarfafa juriya.
Taƙaitawa ta gaskiya tana da iyaka fiye da yadda masu goyon baya ko masu watsi da shi suke so. Wani rini na ƙarni na goma sha tara yana da tasirin magani na gaske a ƙarni na ashirin da ɗaya, kuma gudummawarsa ta zamani da ta fi bayyana ita ce hana yaɗuwar falciparum idan aka ƙara shi cikin haɗin magunguna da ya dace ƙarƙashin kulawar gwaji. Wannan sakamako ne game da katse yaɗuwar cuta a rukunonin da aka yi bincike a kansu, ba umarnin yin magani da kai ba.