Methylene Blue ndi Malungo: Mbiri ndi Umboni wa Mayesero

Mu 1891 odwala malungo awiri anachiritsidwa ndi utoto wabuluu wa nsalu. Paul Guttmann ndi Paul Ehrlich anaona kuti methylene blue inkadetsa mwapadera tizilombo ta malungo, ndipo anaganiza kuti utoto wokhoza kusiyanitsa tizilombozo kuti utionetse ungathenso kutisiyanitsa kuti utiwononge. Odwala onse awiri anachira. Kuyesera kumeneko kunapangitsa methylene blue kukhala mankhwala oyamba opangidwa ndi anthu olimbana ndi malungo, zaka makumi angapo chloroquine isanakhalepo.

Kenako utotowo unakhala ukukankhidwa pambali kwa zaka zambiri za m'ma 1900. Mankhwala ena opangidwa ndi anthu omwe odwala ankatha kuwapirira bwino analowa m'malo mwake, ndipo pofika nthawi yamakono unali kugwiritsidwa ntchito makamaka ngati chinthu choyesera mu labotale, utoto wothandiza pozindikira matenda, ndi mankhwala a mwadzidzidzi a vuto lina la magazi. Choncho kubwerera kwake mu kafukufuku wa malungo ku Burkina Faso ndi Mali sikunali kungolakalaka zakale. Ochita kafukufuku anali ndi lingaliro lenileni loti ayese: njira za redox, kutanthauza kusinthana kwa maelekitironi, zomwe zimapangitsa utotowo kudetsa zinthu zingasokoneze chitetezo cha redox cha tizilombo ta malungo, ndipo mmene umakhudzira gawo la tizilombo lomwe limatha kufalikira ungachite zomwe mankhwala omwe amagwiritsidwa ntchito nthawi zonse sachita bwino. Kuyesa lingaliro limenelo kunafuna kutchula mankhwala ophatikizidwa, mtundu wa tizilombo, ndi chotsatira chomwe chikuyesedwa nthawi iliyonse, chifukwa kusintha chilichonse mwa zimenezi kumasintha mfundo yomwe ingatsimikizidwe.

Kusiyana kwakukulu pakati pa mankhwala ovomerezeka ndi ntchito zomwe zikufufuzidwabe kwafotokozedwa mu methylene blue m'zachipatala. Kugwiritsa ntchito pa malungo kuli kumbali ya kafukufuku: imagwira ntchito pa tizilombo, yayesedwa itaphatikizidwa ndi mankhwala ena, koma si mankhwala ovomerezedwa monga oyenera kutsatiridwa m'malangizo achipatala.

Chifukwa chake utoto wa Ehrlich unagwira ntchito ndi chifukwa chake unasiyidwa

Zolemba zoyambirira ndi chitsanzo cha mmene tiyenera kuwerengera umboni wa nthawi isanakwane njira zamakono. Kuwunika kwa mu 1904 kwa milandu 425 yolembedwa kunayerekezera kuti pafupifupi 85 peresenti anasonyeza kuyankha ku mankhwalawo, koma milanduyi inachitika asanayambe kugawa odwala m'magulu mwachisawawa, kugwiritsa ntchito miyezo yofanana ya zotsatira, kutsimikizira mitundu ya tizilombo, ndi kuyang'anira kusamva mankhwala. Imatsimikizira kuti chinthucho chinali ndi mphamvu yolimbana ndi malungo yoyenera kufufuzidwa, osati kuchuluka kwa ochira kofanana ndi komwe kumapezeka mu mayesero amakono.

Kusiyidwa kwake kunasonyeza mavuto a kugwiritsa ntchito, osati kutsutsa kuti sichigwira ntchito. Methylene blue imasandutsa mkodzo kukhala wabuluu kapena wobiriwira, imadetsa minofu ya m'thupi, ndipo imayambitsa mavuto a m'mimba ndi a pokodza, kuphatikizapo kusanza ndi kupweteka pokodza pa milingo yomwe inkagwiritsidwa ntchito panthawiyo. Mankhwala atsopano ankachotsa tizilombo popanda kupaka wodwalayo utoto. Kuwunika mbiri kuyambira pa methylene blue mpaka pa chloroquine kumafotokoza nkhani ya kulowedwa m'malo imeneyo, pamene kuwunika mankhwala a phenothiazinium olimbana ndi malungo kumasonkhanitsa malingaliro a mmene amagwirira ntchito omwe anachititsa ochita kafukufuku kupitiriza kukhala ndi chidwi atasiya kugwiritsidwa ntchito kwambiri m'chipatala.

Ponena za mmene umagwirira ntchito, utotowo umafotokozedwa bwino ngati wogwira ntchito pa redox osati wongolunjika pa chinthu chimodzi. Umalepheretsa glutathione reductase ya tizilombo mu mayesero a m'labotale ndipo nthawi yomweyo umasinthanitsa maelekitironi m'njira zomwe zimawononga mphamvu yochepetsera okosideshoni yomwe tizilombo timafunikira ndi kuyambitsa kupanikizika chifukwa cha okosideshoni; akuganiziranso kuti umasokoneza kuchotsa poizoni wa heme. Sizikudziwikabe kuti ndi njira iti yomwe imagwira ntchito kwambiri m'thupi la wodwala. Chofunika si chinthu chenicheni chomwe umalunjika nacho, koma kusiyana kwa mphamvu yake pa magawo a moyo wa tizilombo: methylene blue imagwira ntchito kwambiri kuposa momwe zimakhalira nthawi zambiri polimbana ndi magametocyte, gawo la kuberekana pogonana lomwe udzudzu uyenera kuyamwa kuti kufalikira kupitirire. Mankhwala ophatikizidwa a artemisinin omwe amagwiritsidwa ntchito nthawi zonse amachotsa tizilombo ta gawo losaberekana pogonana lomwe limadwalitsa munthu, koma angasiye magametocyte okhwima. Mankhwala omwe amafupikitsa nthawi imene munthu amakhala ndi magametocyte kapena kuwapangitsa kusatha kupatsira matenda amalimbana ndi kufalikira komweko.

Zomwe mayesero amakono anayesa

Zotsatira zonse zamakono pansipa ndi za mankhwala ophatikizidwa. Mlingo, mankhwala omwe anaphatikizidwa nawo, mtundu wa tizilombo, ndi chotsatira chomwe chinayesedwa ndi mbali za zomwe anapeza.

Mayesero ndi anthu omwe anayesedwa	Ndondomeko ya mankhwala	Chotsatira chomwe chinayesedwa ndi zomwe anapeza	Malire
Burkina Faso 2005, ana 226 a miyezi 6 mpaka 59, malungo a falciparum	Chloroquine ndi methylene blue 4 mg/kg/day kwa masiku 3 poyerekeza ndi chloroquine yokha	Kuyankha kokwanira pa tsiku-14 kunali pafupifupi 56 poyerekeza ndi 46 peresenti; panalibe ubwino womveka bwino	Mlingo wochepa wa utoto pamene tizilombo tinali kusamva chloroquine; sikunali kuyesa kwabwino kwa ndondomeko yamakono ya mankhwala
Zoungrana 2008, gawo 2, ana 180 a zaka 6 mpaka 10, malungo a falciparum	Methylene blue ndi artesunate, kapena ndi amodiaquine, kapena artesunate-amodiaquine yomwe imagwiritsidwa ntchito nthawi zonse; utoto 20 mg/kg/day kwa masiku 3	Kuchira pa tsiku-28 pambuyo pokonza kuwerengera kunali 62, 95, ndi 82 peresenti motsatira ndondomekozo; kuchotsa tizilombo kunali kofulumira kwambiri ndi kuphatikiza kwa artesunate; magulu onse awiri a utoto anachepetsa kukhala ndi magametocyte pa masiku 3, 7, ndi 14	Aliyense ankadziwa mankhwala omwe anaperekedwa ndipo magulu anali ang'onoang'ono; kuchira kochepa ndi kuphatikiza kwa artesunate kumasonyeza kuti mankhwala ophatikizidwa nawo ndi amene amatsimikizira zotsatira
Coulibaly 2015, gawo IIb, ana 193 m'gulu loyesa mphamvu ya mankhwala, malungo a falciparum	Artesunate-amodiaquine ndi utoto 15 mg/kg/day kwa masiku 3 poyerekeza ndi kuphatikiza komweko kokha	Magametocyte ooneka ndi maikulosikopu pa tsiku-7 anali 1.2 poyerekeza ndi 8.9 peresenti; kuchotsa tizilombo ta gawo losaberekana pogonana kunali kofulumira pang'ono; kuchira pambuyo pokonza kuwerengera kunali kofanana, pafupifupi 80 poyerekeza ndi 85 peresenti	Kuchepetsa kuchuluka kwa anthu okhala ndi magametocyte, osati kuchira, ndiko kunali phindu lalikulu; kusanza kunachuluka ndipo hemoglobin inatsika kwakanthawi ndi utoto
Mali 2018, gawo 2, amuna 80 okhala ndi G6PD yabwinobwino ndi matenda a falciparum opanda zizindikiro koma okhala ndi magametocyte	Dihydroartemisinin-piperaquine ndi utoto 15 mg/kg/day kwa masiku 3 poyerekeza ndi mankhwala a malungo okha	Mwa anthu omwe ankatha kupatsira udzudzu matenda pachiyambi, kuchepa kwapakati kwa kuthekera kopatsira udzudzu kunali 100 peresenti ndi utoto poyerekeza ndi pafupifupi kusachepa konse popanda utoto pa tsiku 2, ndipo kunapitirira mpaka tsiku 7	Anthu 11 okha omwe ankatha kupatsira matenda ndi kulandira utoto ndi amene anali mu kufananitsa kwakukulu; amuna okha, okhala ndi G6PD yabwinobwino okha, onyamula tizilombo opanda zizindikiro; chotsatira chinali cha kufalikira, osati mayesero a kuchira
Burkina Faso 2019, ana 100, malungo a falciparum	Artesunate-amodiaquine ndi utoto poyerekeza ndi kuphatikiza komweko ndi primaquine yoperekedwa kamodzi	Kuchira pambuyo pokonza kuwerengera kunali pafupifupi 96 peresenti m'magulu onse awiri; kuchotsa tizilombo pofika tsiku 1 kunali kofulumira ndi utoto; magametocyte pa tsiku-2 anali 4 poyerekeza ndi 31 peresenti, ngakhale primaquine sinaperekedwe mpaka tsiku 2	Mayesero anali ang'onoang'ono ndipo aliyense ankadziwa mankhwala omwe anaperekedwa; nthawi yopereka mankhwala imapangitsa kufananitsa koyambirira kwa magametocyte kukhala kosalingana; cholinga chachikulu chinali chitetezo cha magazi

Mfundo ziwiri zimakhalabe zoona m'maphunziro onsewa. Choyamba, utotowo umagwiradi ntchito polimbana ndi Plasmodium falciparum, koma pawokha umachotsa tizilombo pang'onopang'ono kwambiri ndipo umalola matendawa kubwereranso chifukwa cha tizilombo totsala; kafukufuku wochepa wa akuluakulu unatsimikiza kuti uyenera kuphatikizidwa ndi mankhwala ogwira ntchito mofulumira. Chachiwiri, phindu lowonjezera lomwe limapezeka mobwerezabwereza akauwonjezera ku mankhwala amakono ophatikizidwa osankhidwa moyenera limakhala pa zotsatira za magametocyte ndi kufalikira, osati kuwonjezeka kwakukulu kwa kuchira komwe kumayesedwa nthawi zonse. Kafukufuku wa ku Mali wodyetsa udzudzu magazi mwachindunji kudzera pa nembanemba ndi umboni womveka bwino kwambiri wa mfundo yachiwiriyi, chifukwa udzudzu womwe unayamwa magazi a anthu omwe anali mu kafukufukuyo unakhala ndi mwayi wochepa kwambiri wotenga matenda.

Malire a mitundu ya tizilombo ndi ofunika mofanana ndi malire a kuphatikiza mankhwala. Pafupifupi umboni wonse wokhutiritsa wa mayesero amakono a anthu ukukhudza malungo a falciparum. Pa malungo a vivax, zolemba za odwala zimaphatikiza zomwe zinaonedwa kale ndi ntchito zamakono za m'labotale ndi zodyetsa udzudzu magazi, kuphatikizapo kuti tizilombo totengedwa kumalire a Thailand ndi Myanmar timakhudzidwa ndi utoto pa mlingo wochepa wa nanomolar, komanso kuletsa kufalikira mwamphamvu mu kafukufuku wodyetsa udzudzu wa mu 2024. Palibe mwa zimenezi chomwe chimatsimikizira kuchiritsa odwala ku tizilombo ta vivax ta m'magazi, ndipo palibe chomwe chimakhudza ma hypnozoite a m'chiwindi omwe amachititsa malungo a vivax kuyambiranso, omwe amafunikira zisankho zawozawo za mankhwala zogwirizana ndi mtundu wa tizilombo. Kutenga zotsatira za kufalikira kwa falciparum ndi kunena kuti zikukhudza tizilombo tonse n'kubwereza cholakwa chakale kwambiri m'zolemba zimenezi. Laibulale ya kafukufuku imaika zotsatira za mayesero a anthu ndi zotsatira za kuyesera m'mizati yosiyana pachifukwa chimenechi.

Chitetezo chimayendera limodzi ndi ndondomeko ya mankhwala

Zoopsa zitatu ziyenera kusamaliridwa momveka bwino chifukwa zimatsimikizira kuti ndani sayenera kudziyesera.

Kusowa kwa glucose-6-phosphate dehydrogenase kumapangitsa ngozi ya hemolysis, kutanthauza kuwonongeka kwa maselo ofiira a magazi. Kuwunika kophatikiza maphunziro anayi a ana ku Burkina Faso okhudza ana 1,005 kunapeza kuti hemoglobin inatsika mochulukirapo pang'ono mwa omwe anali osowa enzyme imeneyi kwathunthu atalandira utoto, ndipo panali zochitika ziwiri za hemolysis mwa ana osowa enzyme kapena a heterozygous omwe analandira utoto. Zolemba za mankhwala a methylene blue obayidwa ku United States zimaletsa kugwiritsa ntchito mwa anthu osowa G6PD chifukwa hemolysis yoopsa ingachitike. Ndondomeko ya mankhwala a malungo omwedwa imasiyana ndi mlingo wa mwadzidzidzi woperekedwa mumtsempha, choncho zolembazo sizingasinthidwe ndi kuwerengera kuti zikhale malire a mlingo wa malungo, koma mmene zimakhudzira thupi ndi komweko. Kuyezetsa ndi kuyang'aniridwa kuyenera kukhala mbali ya kugwiritsa ntchito kulikonse kosamalitsa.

Kuyanjana ndi mankhwala okhudza serotonin kuyeneranso kuganiziridwa limodzi ndi zimenezi. Methylene blue yomwe imafalikira m'thupi imalepheretsa monoamine oxidase ndipo ingayambitse serotonin syndrome ikagwiritsidwa ntchito ndi mankhwala oletsa kubwezeretsedwa kwa serotonin mosankha, oletsa kubwezeretsedwa kwa serotonin ndi norepinephrine, oletsa monoamine oxidase, komanso ena mwa mankhwala a opioid ndi a chifuwa; imfa zalembedwa chifukwa cha zimenezi. Kuyanjana kumeneku, zinthu zomwe zimaletsa kugwiritsa ntchito, ndi kuyang'anira zafotokozedwa mwatsatanetsatane mu zotsatira zosafunika, zinthu zomwe zimaletsa kugwiritsa ntchito, ndi chitetezo.

Kutha kupirira mankhwalawo ndi chopinga chosamveka kwambiri. Mkodzo wabuluu wobiriwira umayembekezeredwa ndipo si woopsa, koma umaonekera kwambiri moti wakhala ukuchepetsa kuvomerezeka kwa mankhwalawo kuyambira m'ma 1890. Kusanza kumadalira mlingo ndi kapangidwe ka mankhwalawo ndipo kunachititsa ena kusiya nawo mayesero a ana; mu kufananitsa kwina komwe kunachitika pambuyo pake kunafika pa 40 peresenti ya omwe analandira utoto poyerekeza ndi 14 peresenti ya omwe analandira primaquine. Mankhwala omwe ana amasanza ndi mankhwala omwe mphamvu yake kwa anawo imangokhala papepala.

Chifukwa chake umboniwu sukuthandiza kudzichiritsa

Malangizo amakono a malungo amafuna kutsimikizira kuti pali tizilombo ndipo amasankha mankhwala potengera mtundu wa tizilombo, kuopsa kwa matenda, madera omwe tizilombo sitimva mankhwala, msinkhu ndi kulemera, kukhala ndi pakati, ndi momwe G6PD ilili, ndipo mankhwala ophatikizidwa a artemisinin ndi omwe amagwiritsidwa ntchito nthawi zonse pa matenda a falciparum. Palibe m'zolemba za utotowu chomwe chimalowa m'malo mwa njira imeneyi yosankhira chithandizo. Kugwiritsa ntchito mankhwalawo okha kumagwira ntchito pang'onopang'ono kwambiri, kusankha mankhwala ophatikizidwa nawo kumatsimikizira kuchira, ma hypnozoite a vivax amafunikira mankhwala osiyana, momwe G6PD ilili kumachepetsa omwe angawagwiritse ntchito, ndipo mankhwala ena okhudza serotonin omwe akugwiritsidwa ntchito nthawi yomweyo amayambitsa kuyanjana koopsa. Chithandizo cholakwika chingasiye matenda a falciparum omwe amabwereranso chifukwa cha tizilombo totsala, kulephera kuthana ndi kuyambiranso kwa vivax, kuyambitsa hemolysis, ndi kuyika tizilombo pa mphamvu yochepa ya mankhwala yomwe imathandiza kukula kwa kusamva mankhwala.

Chidule choona chili ndi malire ochepa kuposa momwe okonda mankhwalawa kapena owakana angafunire. Utoto wa m'zaka za m'ma 1800 uli ndi ntchito yeniyeni ya mankhwala m'zaka za m'ma 2000, ndipo thandizo lake lomveka bwino kwambiri masiku ano ndi kuletsa kufalikira kwa falciparum ukawonjezeredwa ku mankhwala ophatikizidwa oyenera moyang'aniridwa mu mayesero. Izi ndi zomwe zapezeka pa kusokoneza kufalikira mwa anthu omwe aphunziridwa, osati malangizo oti munthu adzichiritse yekha.