I-methylene blue ngesifo se-Lyme: okutholwe elabhorethri nobufakazi basemtholampilo

Isitsha sokukhulisa amagciwane asisona isiguli. Lowo mehluko uchaza cishe zonke izimangalo nge-methylene blue nesifo se-Lyme.

Ake sithi abafundi ababili babona umusho ofanayo: abacwaningi “baqeda nya” amagciwane e-Lyme ngenhlanganisela yemithi. Omunye umfundi ukuqonda ngokuthi isitsha sengilazi sahlala singenawo amagciwane amasonto amabili. Omunye ukuqonda ngokuthi iziguli ezazikhathele zalulama. Zombili lezi zincazelo zizwakala zinengqondo. Eyokuqala kuphela ehambisana nalokho okwakukalwa ukuhlola kwaselabhorethri.

Lesi sihloko sigcina le mibono emibili ihlukene. Sibuyekeza lokho i-methylene blue eyakwenza ku-Borrelia burgdorferi eyayikhuliswe elabhorethri, okwenzeka lapho isetshenziswa ezinhlelweni eziyinkimbinkimbi zokwelapha iziguli, nokuthi kungani kungekho miphumela kule emibili ephendula ukuthi kufanele ithathwe isikhathi esingakanani i-methylene blue nge-Lyme.

I-Lyme ibangelwa amagciwane, ngakho ubufakazi ngezilokazane abudluliseki kuyo

Isifo se-Lyme sibangelwa yi-Borrelia burgdorferi, igciwane elinesimo esisongene elidluliselwa imikhaza. Ukwelashwa okujwayelekile kusebenzisa imithi elwa namagciwane efana ne-doxycycline, i-amoxicillin, noma i-cefuroxime, njengoba kuchazwe esiqondisweni se-Lyme sango-2020 se-IDSA, i-AAN, ne-ACR.

Ukuthi lokhu kubangelwa igciwane kubalulekile ngoba i-methylene blue inomlando ohlukile wokusetshenziswa ngokumelene nezilokazane. Yacwaningwa ngokumelene nezilokazane zikamalaleveva futhi ngezinye izikhathi kuxoxwa ngayo nge-Babesia, isilokazane esidluliselwa imikhaza esingaba khona kanye ne-Lyme. Umphumela ngokumelene nesilokazane awufakazeli indlela efanayo yokusebenza ngokumelene ne-Borrelia. Lezi zidalwa ziyahlukahluka ngokwakheka, ukushintshana kwezinto emzimbeni, izindawo eziqondwa yimithi, kanye nengxenye yomzimba eziyithelelayo. Ukubuka kwethu konke ukuthi i-methylene blue isebenza kanjani emangqamuzaneni kuveza iphuzu elifanayo ngokujwayelekile: ukusebenza kwe-redox kubanzi, kodwa umphumela wezinto eziphilayo usancike esidalweni nasezimweni.

Ngakho gcina imibuzo emibili ihlukene. Okokuqala, i-methylene blue yenzani ku-Borrelia ekhuliswa ngaphansi kwezimo ezilawulwayo. Okwesibili, kwenzekani kubantu abanesifo se-Lyme. Okusele kulesi sihloko kulandela lolo hlelo.

Amangqamuzana aphikelelayo ayisimo, hhayi uhlobo olunamandla kakhulu

Imithi elwa namagciwane ivame ukubulala iningi le-Borrelia ngokushesha bese ishiya iqembu elincane elikwazi ukubekezelela le mithi. Lapho abacwaningi bephinda bekhulisa lawo asindile, amangqamuzana aphuma kuwo ngokuvamile ayesephinde ezwela kule mithi. Lelo phethini likhomba isimo sokusebenza kwamangqamuzana esingaguquleka kunokumelana nemithi okuzuzwa ngofuzo. Ubufakazi obucacile buvela emsebenzini ka-Sharma nozakwabo ngokubulawa kwezigaba ezimbili nokuphinda kukhule kwamangqamuzana aphikelelayo.

Empeleni, amagciwane asanda kukhuliswa asesigabeni sokukhula ngesivinini aqukethe ikakhulu ama-spirochete anyakazayo futhi asabela kalula emithini ejwayelekile. Amagciwane asekhule isikhathi eside asesigabeni sokuma kokukhula aqukethe amangqamuzana amaningi ayindilinga namaqoqo amancane ahlangene, futhi abekezelela kangcono yona leyo mithi. Lawo magama achaza izimo zamangqamuzana nezimo zokukhula esitsheni. Awubona ubufakazi bokuthi lezo zimo ezifanayo zichaza izimpawu ezihlala zikhona ngemva kokwelashwa kwesifo se-Lyme.

Indlela ewusizo yokukuqonda ilula. Ukukhula okusebenzayo kuveza izindawo eziqondwa yimithi, njengokwakhiwa kodonga lwengqamuzana. Ukukhula okuhamba kancane noma okushintshile kufihla lezo zindawo. Isakhi samakhemikhali esisiza esimweni sesibili singase singabaluleki kwesokuqala, futhi okuphambene nakho kuyiqiniso.

Lokho ucwaningo lokuhlola lwango-2015 olukutholile ngempela

Umthombo ocashunwa kakhulu ngalesi sihloko ukuhlolwa kweqoqo lemithi ye-FDA kwango-2015 okwenziwa ngu-Feng nozakwabo. Lwahlola izakhi zamakhemikhali ku-Borrelia eyayikhuliswe izinsuku eziyisikhombisa yasesigabeni sokuma kokukhula, lwakwenza ezinye izinsuku eziyisikhombisa, isakhi ngasinye esihlolwayo sisezingeni elingu-50 micromolar.

I-methylene blue yasebenza ngokwanele ukuba idonse ukunakwa, kodwa ayizange iqede zonke izinto eziphilayo. Ngokuhlolwa ngesibonakhulu, cishe amaphesenti angu-40 amangqamuzana ayesaphila ngemva kwe-methylene blue, uma kuqhathaniswa namaphesenti angu-93 eqenjini lokuqhathanisa elingazange lelashwe, angu-75 ngemva kwe-doxycycline, angu-76 ngemva kwe-amoxicillin, angu-49 ngemva kwe-cefuroxime, nangu-35 ngemva kwe-daptomycin eyasetshenziswa njengesiqhathaniso. Umphumela womshini wokufunda amapuleti nge-methylene blue awukwazanga ukusetshenziswa ngoba umbala wayo ogqamile waphazamisa ukuhlolwa nge-fluorescence, ngakho isiphetho sancika ekuhlolweni okuqondile ngesibonakhulu.

Lokho kuwuphawu olutholwe ekuhloleni, hhayi ukuqedwa nya. Akuzange kuboniswe ukuthi amagciwane ayechayeke ku-methylene blue ahlala engekho lapho ephinde efakwa endaweni entsha engenamithi isikhathi eside. Ababhali baphakamisa ukuthi kamuva kwenziwe ucwaningo lwenhlanganisela kanye nolwezilwane, okuyindlela efanele yokuqonda ukuhlolwa kweqoqo lemithi.

Kungani kulula ukungaqondi kahle imiphumela yenhlanganisela

Ucwaningo oluhlobene nalo lwango-2015 luvame ukuhlanganiswa nesimangalo esifanayo. Ocwaningweni luka-Feng, u-Auwaerter, no-Zhang ngenhlanganisela yemithi ngokumelene ne-Borrelia esigabeni sokuma kokukhula, umphumela oqine kakhulu waselabhorethri wavela ku-daptomycin kanye ne-doxycycline kanye ne-cefoperazone, ngayinye iku-10 micrograms per milliliter izinsuku eziyisikhombisa. Ngemva kokwelashwa, imithi yahlanjululwa ngokufakwa endaweni entsha yokukhulisa amagciwane, kwase kuqashwa ukuthi amagciwane aphinde akhule yini.

Yileyo nhlanganisela yemithi emithathu kuphela eyahlala ingenazo izinto eziphilayo ezitholakalayo ngemva kwezinsuku ezingu-15 zokuphinda ikhuliswe. Umkhawulo wokutholwa ngesibonakhulu owabikwa wawungaphansi kwezinto eziphilayo ezingu-100,000, ngakho “ukuqedwa nya” kwakusho ukuthi akukho kuphinda kukhule okwakutholakala ngesibonakhulu ngaphansi kwaleyo ndlela yokuhlola. Kwakungasho ukuthi kufakazelwe ukungabikho ngisho kwesidalwa esisodwa, ukungena komuthi ezicutshini zesilwane, noma ukwelapheka komuntu. Iphepha ngokwalo laxwayisa ngokusebenzisa le miphumela ngokuqondile ekwelapheni.

Imininingwane yenhlanganisela ye-methylene blue eyavela kamuva yayivela ezingeni lobufakazi elihlukile nelibuthakathaka kakhulu. Umbhalo wocwaningo lweziqu ze-masters ka-Megan Weitner wase-Johns Hopkins wango-2016 wahlola i-methylene blue iku-4 micrograms per milliliter, izinga elakhethwa kubhekwa ukuchayeka ku-plasma yegazi, kanye nemithi efana ne-cefuroxime, i-doxycycline, i-azithromycin, i-rifabutin, i-rifaximin, i-nitrofurantoin, ne-pyrimethamine. Amagciwane akhulisiwe achayekwa izinsuku eziyisikhombisa futhi ahlolwa ngokufakwa umbala nangesibonakhulu. Izinhlanganisela ezazinenani lokuphila okusele elilungiselwe esilinganisweni elingaphansi kuka-0.90 zabizwa ngokuthi ziyasebenza. Ngokwesibonelo, i-methylene blue kanye ne-azithromycin zafinyelela ku-0.88, kwathuthuka kwaba ngu-0.64 lapho kwengezwa i-cefuroxime, kanti ezinye izinhlanganisela zemithi emithathu zafinyelela cishe ku-0.69 kuya ku-0.82.

Lokho kuwukuncipha kwesignali yokufakwa umbala, hhayi ukuqedwa kwazo zonke izinto eziphilayo ekukhulisweni kwamagciwane. Umbhalo wocwaningo awuzange ubonise ukuthi izinhlanganisela ze-methylene blue zigcina amagciwane engatholakali isikhathi eside ngendlela efana nomphumela wenhlanganisela yemithi emithathu eyayine-daptomycin. Futhi ungumbhalo wocwaningo lweziqu, hhayi iphepha lejenali elibuyekezwe abanye ochwepheshe. Ungaveza imibono edinga ukuhlolwa. Awukwazi ukuba nesisindo esifanayo nobufakazi basemtholampilo obuvela ocwaningweni olulawulwayo.

Yingakho “uhlelo lokwelapha i-Lyme nge-methylene blue” lungeke luthathwe kulawa maphepha. Ukuchayeka kwaselabhorethri okucwilisa izinto eziphilayo ngokuqhubekayo izinsuku eziyisikhombisa akuchazi umthamo womuntu, indlela yokuwufaka emzimbeni, ubude besikhathi, izinga lomuthi ezicutshini, noma ubuthi obamukelekayo. Futhi akuhloli i-methylene blue iyodwa ngemiphumela yasemtholampilo ebalulekile ezigulini, njengobuhlungu, ukukhathala, ukuvuvukala kwamalunga, izimpawu zesimiso sezinzwa, noma ukubuya kwesifo. Ukuze uthole usizo lokuhlukanisa la mazinga obufakazi, bheka umhlahlandlela wethu wokufunda izimangalo zocwaningo lwe-methylene blue.

Kusukela ezitsheni kuya ezigulini: isinyathelo sasemtholampilo esingekho

Ngesikhathi kubhalwa lokhu, akukho sivivinyo esihlela ababambiqhaza ngokungahleliwe noma ucwaningo olulawulwayo olulandelela iziguli kusukela ekuqaleni olubonisa ukuthi i-methylene blue yelapha isifo se-Lyme. Okukhona kubantu yimibiko engalawulwanga lapho i-methylene blue yayiyingxenye eyodwa yohlelo lokwelapha ngemithi eminingi.

Isibonelo esicace kakhulu ucwaningo olubheka emuva ekwelapheni ngenhlanganisela ye-dapsone olwenziwa ngu-Horowitz, u-Fallon, nozakwabo, kuhlanganise nombiko wango-2023 ngeziguli ezingu-25 ezazithole ukwelashwa okuningi ngaphambili. Kwabikwa ukuthi ezingu-8 kwezingu-25 zaphelelwa yizimpawu ze-Lyme ezazikhona okungenani izinyanga ezintathu. Kodwa iziguli zaphinde zathola i-dapsone, ama-tetracycline, i-rifampin noma i-rifabutin, ama-macrolide, futhi ngezinye izikhathi eminye imithi. Kwakungekho qembu elathola i-methylene blue kuphela futhi kungekho qembu lokuqhathanisa elakhethwa ngokungahleliwe. Imibiko emincane yeziguli eyavela kamuva inohlelo olufanayo.

Lolo hlobo locwaningo lungachaza imiphumela. Alukwazi ukusho ukuthi i-methylene blue yiyona eyabangela leyo miphumela. Ukuthuthuka kungase kubangelwe omunye umuthi, inhlanganisela, ukuhamba kwemvelo kwesimo, imiphumela ye-placebo, ukuqashwa eduze, noma ukukhethwa kweziguli ezinamathuba amakhulu okuthuthuka. Ithebula lenza leli gebe licace.

Ngakho iphethini iwukuhlolwa kokuqala kanye nezinhlanganisela ezisembhalweni wocwaningo lweziqu kanye nemibiko engalawulwanga yokwelashwa ngemithi eminingi. Lokho kulandelana kubuthakathaka kunomphumela wokwelapha oboniswe esivivinyweni sasemtholampilo.

Awukho umbuzo ophendulwa ubufakazi wokuthi ithathwe isikhathi esingakanani

Intshisekelo yokusesha ukuthi “ithathwe isikhathi esingakanani i-methylene blue nge-Lyme” iyaqondakala. Izimpawu eziqhubekayo zidala ingcindezi yokwenza okuthile. Kodwa ubude besikhathi buthathela ekutheni sekukhona umthamo osebenzayo osuqinisekisiwe, futhi akukho sivivinyo esiqinisekise owodwa nge-Lyme.

I-methylene blue ngumuthi osebenza emzimbeni wonke onemikhawulo yangempela. Ilebula yomuthi kadokotela yase-U.S. ye-methemoglobinemia etholakala kamuva ichaza u-1 mg per kg ofakwa emthanjeni phakathi kwemizuzu engu-5 kuya kwengu-30, okuyisifo, indlela yokuwufaka emzimbeni, nenhloso ehlukile, okungeke kuguqulwe kube umthamo we-Lyme. Ilebula inesexwayiso esifakwe ebhokisini nge-serotonin syndrome lapho i-methylene blue ihlanganiswa nemithi esebenza ku-serotonin, ikakhulukazi ama-SSRI, ama-SNRI, nemithi evimbela i-MAO, futhi iyakwenqabela ukusetshenziswa uma kunokuntuleka kwe-G6PD ngenxa yengozi ye-hemolytic anemia. Noma ubani ocabanga ukuyisebenzisa udinga ukuthi uchwepheshe wezokwelapha abuyekeze imithi ayithathayo, isimo se-G6PD, ukukhulelwa, ukusebenza kwezinso, nokusebenzisana kwemithi. Isifinyezo sethu sokuphepha nokuphathwa sichaza ukuthi kungani ubumsulwa nokuqashwa kwezokwelapha kubalulekile ngaphambi kwanoma yikuphi ukusetshenziswa okuthinta umzimba wonke.

Ngezimpawu eziqhubekayo ngemva kokwelashwa kwe-Lyme okunconyiwe ngaphandle kobufakazi obuqondile bokuphinda kutheleleke noma ukwehluleka kokwelashwa, isiqondiso se-IDSA sincoma ukuthi kunganikezwa okunye ukwelashwa ngemithi elwa namagciwane futhi sithi akukho bufakazi basemtholampilo obusekela izinhlelo eziqondiswe ngqo emangqamuzaneni aphikelelayo noma ezimweni zamangqamuzana ezinokwakheka okuhlukile. Lokho akuphiki ukuthi amangqamuzana abekezelela imithi akhona ezitsheni. Kusho ukuthi ibhuloho eliya ekwelapheni iziguli alikakhiwa.

Indlela ewusizo yokufunda isimangalo esilandelayo ohlangana naso iwukubuza imibuzo emithathu. Ingabe umphumela wawusekukhulisweni kwamagciwane oketshezini olunomsoco, esilwaneni, noma ezigulini. Ingabe i-methylene blue yahlolwa iyodwa noma yayihlolwa kuphela ngaphakathi kwengxube yemithi eminingi. Ingabe umphumela okalwayo wawukala ukuphinda kukhule esitsheni noma ukululama kwabantu. Uma izimpendulo ziyisitsha, ingxube, nokuphinda kukhule, khona-ke ucwaningo luveza imibono edinga ukuhlolwa. Alulona uhlelo lokwelapha.