Amanethi okulala aqukethe i-pyrethroid clofenpyr (CFP) kanye ne-pyrethroid piperonyl butoxide (PBO) ayakhuthazwa emazweni atholakala kalula ukuze kuthuthukiswe ukulawulwa komalaleveva odluliselwa omiyane abamelana ne-pyrethroid. I-CFP iyi-proinsecticide edinga ukusebenza yi-mosquito cytochrome P450 monooxygenase (P450), kanti i-PBO ithuthukisa ukusebenza kwe-pyrethroid ngokuvimbela ukusebenza kwala ma-enzyme komiyane abamelana ne-pyrethroid. Ngakho-ke, ukuvinjelwa kwe-P450 yi-PBO kunganciphisa ukusebenza kwamanethi e-pyrethroid-CFP uma esetshenziswa ekhaya elifanayo namanethi e-pyrethroid-PBO.
Kwenziwe izivivinyo ezimbili zokuhlola i-cockpit ukuze kuhlolwe izinhlobo ezimbili ezahlukene ze-pyrethroid-CFP ITN (Interceptor® G2, PermaNet® Dual) zodwa futhi zihlanganiswe ne-pyrethroid-PBO ITN (DuraNet® Plus, PermaNet® 3.0). Imiphumela ye-entomological yokusetshenziswa kwe-Pyrethroid resistance Vector populations eningizimu yeBenin. Kuzo zombili izifundo, zonke izinhlobo ze-mesh zahlolwa ekwelashweni kwe-single kanye ne-double mesh. Ukuhlolwa kwe-bioassays kwenziwa futhi ukuze kuhlolwe ukumelana nemithi kwe-vector populations e-hut kanye nokutadisha ukusebenzisana phakathi kwe-CFP ne-PBO.
Inani labantu abathwala izifo lalizwela kakhulu ku-CFP kodwa labonisa amazinga aphezulu okumelana nama-pyrethroid, kodwa lokhu kumelana kwanqotshwa ukuchayeka ngaphambi kwe-PBO. Ukufa kwama-vector kwehle kakhulu ezindlini ezisebenzisa inhlanganisela yamanethi e-pyrethroid-CFP kanye namanethi e-pyrethroid-PBO uma kuqhathaniswa nezindlu ezisebenzisa amanethi amabili e-pyrethroid-CFP (74% we-Interceptor® G2 vs. 85%, i-PermaNet® Dual 57% vs. 83 %), p < 0.001). Ukuchayeka ngaphambi kwe-PBO kunciphisa ubuthi be-CFP ekuhlolweni kwe-bioassay kwamabhodlela, okuphakamisa ukuthi lo mphumela ungase ubangelwe ngokwengxenye ukuphikisana phakathi kwe-CFP ne-PBO. Ukufa kwama-vector kwakuphezulu ezindlini ezisebenzisa inhlanganisela yamanethi aqukethe amanethi e-pyrethroid-CFP uma kuqhathaniswa nezindlu ezingenamanethi e-pyrethroid-CFP, futhi lapho amanethi e-pyrethroid-CFP esetshenziswa wodwa njengamanethi amabili. Uma kusetshenziswa ndawonye, ukufa kuphakeme kakhulu (83-85%).
Lolu cwaningo lubonise ukuthi ukusebenza kahle kwama-meshe e-pyrethroid-CFP kwehlisiwe uma kusetshenziswa kanye ne-pyrethroid-PBO ITN uma kuqhathaniswa nokusetshenziswa kodwa, kanti ukusebenza kahle kwezinhlanganisela zama-mesh eziqukethe ama-meshe e-pyrethroid-CFP kwakuphakeme. Le miphumela iphakamisa ukuthi ukubeka phambili ukusatshalaliswa kwamanethiwekhi e-pyrethroid-CFP kunezinye izinhlobo zamanethiwekhi kuzokhulisa imiphumela yokulawula ama-vector ezimweni ezifanayo.
Amanethi okulala aphathwa ngezibulala-zinambuzane (ama-ITN) aqukethe izibulala-zinambuzane ze-pyrethroid abe yisisekelo sokulawulwa kwe-malaria eminyakeni engamashumi amabili edlule. Kusukela ngo-2004, cishe amanethi okulala aphathwa ngezibulala-zinambuzane ayizigidigidi ezingu-2.5 anikezwe e-Afrika engaphansi kweSahara [1], okwaholela ekwandeni kwenani labantu abalala ngaphansi kwamanethi okulala aphathwa ngezibulala-zinambuzane kusukela ku-4% kuya ku-47% [2]. Umphumela walokhu kuqaliswa wawubalulekile. Kulinganiselwa ukuthi cishe amacala e-malaria ayizigidigidi ezimbili kanye nokufa kwabantu abayizigidi ezingu-6.2 kwagwenywa emhlabeni wonke phakathi kuka-2000 no-2021, kanti ukuhlaziywa komodeli kuphakamisa ukuthi amanethi aphathwa ngezibulala-zinambuzane ayeyimbangela enkulu yale nzuzo [2, 3]. Kodwa-ke, le ntuthuko iza ngentengo: ukuthuthuka okusheshayo kokumelana ne-pyrethroid kubantu abathwala i-malaria. Nakuba amanethi okulala aphathwa ngezibulala-zinambuzane e-pyrethroid angase ahlinzeke ngokuvikelwa komuntu ngamunye ngokumelene ne-malaria ezindaweni lapho i-vectors ibonisa ukumelana ne-pyrethroid [4], izifundo zomodeli zibikezela ukuthi emazingeni aphezulu okumelana, amanethi okulala aphathwa ngezibulala-zinambuzane azonciphisa umthelela we-epidemiological [5]. Ngakho-ke, ukumelana ne-pyrethroid kungenye yezinsongo ezibaluleke kakhulu entuthukweni eqhubekayo ekulawulweni komalaleveva.
Eminyakeni embalwa edlule, isizukulwane esisha samanethi okulala aphathwa ngezibulala-zinambuzane, ahlanganisa ama-pyrethroids nekhemikhali yesibili, sakhiwe ukuthuthukisa ukulawulwa komalaleveva odluliselwa omiyane abamelana ne-pyrethroid. Iklasi elisha lokuqala le-ITN liqukethe i-synergist piperonyl butoxide (PBO), eqinisa ama-pyrethroids ngokunciphisa ama-enzyme aqeda ubuthi ahlobene nokumelana ne-pyrethroid, ikakhulukazi ukusebenza kahle kwama-cytochrome P450 monooxygenases (P450s) [6]. Amanethi okulala aphathwa nge-fluprone (CFP), isibulala-zinambuzane se-azole esinomshini omusha wokusebenza ohlose ukuphefumula kwamaseli, nawo asanda kutholakala. Ngemva kokubonakaliswa komthelela othuthukisiwe we-entomological ezivivinyweni zokuhlola ze-hut [7, 8], uchungechunge lwezivivinyo ezilawulwa ngokungahleliwe zeqembu (cRCT) lwenziwa ukuze kuhlolwe izinzuzo zezempilo zomphakathi zala manethi uma kuqhathaniswa namanethi aphathwa ngezibulala-zinambuzane asebenzisa ama-pyrethroids kuphela futhi kunikezwe ubufakazi obudingekayo ukuze kunikezwe izincomo zenqubomgomo ezivela kwi-World Health Organisation (WHO) [9]. Ngokusekelwe ebufakazini bokuthi umthelela we-epidemiological othuthukisiwe ovela kuma-CRCT e-Uganda [11] naseTanzania [12], i-WHO ivume amanethi okulala aphathwe nge-pyrethroid-PBO zinambuzane [10]. I-pyrethroid-CFP ITN nayo ishicilelwe muva nje ngemuva kokuthi ama-RCT afanayo eBenin [13] naseTanzania [14] abonise ukuthi i-prototype ITN (Interceptor® G2) inciphise ukwanda kwe-malaria yezingane ngo-46% no-44%, ngokulandelana. 10].
Ngemva kwemizamo evuselelwe yi-Global Fund kanye nabanye abanikeli abakhulu be-malaria yokubhekana nokumelana nezinambuzane ngokusheshisa ukwethulwa kwamanethi amasha ombhede [15], amanethi ombhede e-pyrethroid-PBO kanye ne-pyrethroid-CFP asevele esetshenziswa ezindaweni ezivamile. Ithatha indawo yamanethi ombhede aphathwayo asebenzisa ama-pyrethroid kuphela. Phakathi kuka-2019 no-2022, inani lamanethi omiyane e-PBO pyrethroid anikezwa e-Afrika engaphansi kweSahara likhuphuke lisuka ku-8% laya ku-51% [1], kuyilapho amanethi omiyane e-PBO pyrethroid, okuhlanganisa namanethi omiyane e-CFP pyrethroid, amanethi omiyane “asebenza kabili” kulindeleke ukuthi afake u-56% wokuthunyelwa. Ngena emakethe yase-Afrika ngo-2025[16]. Njengobufakazi bokusebenza kahle kwamanethi omiyane e-pyrethroid-PBO kanye ne-pyrethroid-CFP ayaqhubeka nokukhula, la manethi kulindeleke ukuthi atholakale kabanzi eminyakeni ezayo. Ngakho-ke, kunesidingo esikhulayo sokugcwalisa izikhala zolwazi mayelana nokusetshenziswa okuhle kwamanethi ombhede aphathwe ngezibulala-zinambuzane esizukulwaneni esisha ukuze kufezwe umphumela omkhulu uma kwandiswa ukusetshenziswa okugcwele.
Njengoba kubhekwe ukwanda ngasikhathi sinye kwamanethi omiyane e-pyrethroid CFP kanye ne-pyrethroid PBO, i-National Malaria Control Program (NMCP) inombuzo owodwa wocwaningo olusebenzayo: Ingabe ukusebenza kwayo kuzoncishiswa - i-PBO ITN? Isizathu salokhu kukhathazeka ukuthi i-PBO isebenza ngokuvimbela ama-enzyme e-mosquito P450 [6], kanti i-CFP iyi-proinsecticide edinga ukusebenza nge-P450s [17]. Ngakho-ke, kucatshangwa ukuthi lapho i-pyrethroid-CFP ITN kanye ne-pyrethroid-CFP ITN kusetshenziswa ekhaya elifanayo, umphumela wokuvimbela we-PBO ku-P450 unganciphisa ukusebenza kwe-pyrethroid-CFP ITN. Izifundo eziningana zelebhu zibonise ukuthi ukuvezwa kusengaphambili ku-PBO kunciphisa ubuthi obukhulu be-CFP kuma-vector omiyane ekuhlolweni okuqondile kwe-bioassays [18,19,20,21,22]. Kodwa-ke, lapho kwenziwa izifundo phakathi kwamanethiwekhi ahlukene ensimini, ukusebenzisana phakathi kwala makhemikhali kuzoba nzima kakhulu. Izifundo ezingashicilelwanga zihlole imiphumela yokusebenzisa izinhlobo ezahlukene zamanethi aphathwe ngezinambuzane ndawonye. Ngakho-ke, izifundo zasensimini ezihlola umthelela wokusebenzisa inhlanganisela yamanethi ombhede e-pyrethroid-CFP kanye ne-pyrethroid-PBO aphathwe ngezibulala-zinambuzane endlini efanayo zizosiza ekunqumeni ukuthi ukuphikisana okungenzeka phakathi kwalezi zinhlobo zamanethi kudala inkinga yokusebenza futhi kusize ekunqumeni ukusetshenziswa kwesu okungcono kakhulu.
Isikhathi sokuthunyelwe: Septhemba-21-2023