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I-compound nitisidone, ekwiklasi ye-β-triketones, inako ukubulala iingcongconi ezimelana neentsholongwane ngokufunxa kwi-epidermis.

   Isibulali-zinambuzaneUkuxhathisa kwii-arthropods ezithwala izifo, ezibalulekileyo kwezolimo, kwisayensi yezilwanyana, nakwimpilo yoluntu, kusongela kakhulu iinkqubo zokulawula ii-vector zehlabathi. Izifundo zangaphambili zibonise ukuba ii-arthropod vectors ezifunxa igazi zifa kakhulu xa zitya igazi eline-4-hydroxyphenylpyruvate dioxygenase (HPPD, i-enzyme yesibini kwindlela ye-tyrosine metabolic). Olu phononongo luhlolisise ukusebenza kakuhle kwee-HPPD inhibitors kwi-β-triketone herbicides ngokuchasene neentlobo ezintathu eziphambili zeengcongconi vector, kuquka ezo zidlulisela izifo zemveli ezifana nemalariya, izifo ezisulelayo ezivelayo ezifana ne-dengue fever kunye ne-Zika virus, kunye nezoyikiso zentsholongwane ezivelayo ezifana ne-oropuche virus kunye ne-ursutu virus.Ezi ntlobo zaziquka zombini iingcongconi ezikwaziyo ukumelana ne-pyrethroid kunye ne-pyrethroid.

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Yi-nitisidone kuphela (hayi i-mesotrione, i-sulfadiazine, okanye i-thiamethoxam) ebonakalise umsebenzi omkhulu wokulawula iingcongconi xa iingcongconi ezifunxa igazi zidibana neendawo ezinyangiweyo. Akukho mahluko mkhulu ekufumanekeni kwe-nitisidone phakathi kwe-Anopheles gambiae mosquitoes ezibuthathaka kwizinambuzane kunye neentlobo zeengcongconi ezineendlela ezininzi zokuxhathisa. Le compound ibonakalise ukusebenza ngokuqhubekayo kuzo zonke iintlobo ezintathu zeengcongconi ezivavanyiweyo, nto leyo ebonisa umsebenzi obanzi ngokuchasene nezifo ezinkulu.
Olu phononongo lubonisa ukuba i-nitisidone inendlela entsha yokusebenza, eyahlukileyo kwiindidi zeKomiti ye-Insecticide Resistance Action Committee (IRAC) ezikhoyo, ejolise kwinkqubo yokugaya igazi. Ukusebenza kwe-Nitisidone ngokuchasene neentlobo ezinganyangekiyo kunye nokukwazi kwayo ukudibana namanyathelo okulawula ii-vector akhoyo, njengeenethi zomngxunya ezinyangiweyo kunye nokutshiza izinambuzane zangaphakathi, kuyenza ibe yeyona ndlela ifanelekileyo yokwandisa amaqhinga okuthintela nokulawula i-malaria, umkhuhlane we-dengue, isifo se-Zika virus, kunye nezinye izifo ezisasazekayo zentsholongwane.
Okubangel’ umdla kukuba, ii-bioassays ze-World Health Organisation ezisemgangathweni zisebenzisa kuphela iingcongconi ezitya iswekile ukuvavanya ubuninzi bezinambuzane ezinokuthi zingabulali iingcongconi ezifunxa igazi.[38] Oku kugxininisa ukubaluleka kokuqwalasela umahluko onokubakho kwiidosi ezisebenzayo phakathi kweingcongconi ezifunxa igazi nezifunxa igazi, ezinokuchaphazela ukusebenza kakuhle okuseleyo kunye nophuhliso lokuxhathisa. Nangona iidosi ezifunxayo (ii-DD) zihlala zimiselwa ngokusekelwe kumaxabiso e-LD99 kwiingcongconi ezifunxa igazi, umahluko kwi-physiology yezinambuzane unokuchaphazela ukuthambekela kwazo, kwaye ke ngoko ukuvavanya kuphela iingcongconi ezifunxa igazi akunakubonisa ngokupheleleyo uluhlu lwamanqanaba okuxhathisa.
Olu phononongo lugxile ekusebenzeni kakuhle kweentlobo ezintathu zeengcongconi—i-Anopheles gambiae, i-Aedes aegypti, kunye ne-Culex quinquefasciatus—kuvavanyo lokufunxa igazi, olulinganisa ukufika kweengcongconi eludongeni kwaye lusebenza njengethagethi yonyango lwangaphakathi ngee-insecticide ezihlala ixesha elide (IRS). Zonke iingcongconi ezingamabhinqa zabulawa xa zidibana neendawo ezigqunywe yi-nitisidone, kodwa azizange zibulawe nezinye ii-HPPD β-triketone inhibitors. Ukusebenzisa imilenze yeengcongconi ukufunxwa kwee-HPPD inhibitors kubonisa icebo elithembisayo lokoyisa ukuxhathisa ii-insecticide kunye nokuphucula ulawulo lwe-vector. Olu phononongo luxhasa imfuneko yophando olongezelelweyo kunye nophuhliso lwe-nitisidone yonyango lwangaphakathi ngee-insecticide ezihlala ixesha elide njengendlela eyahlukileyo kwii-sprays ezikhoyo zokubulala izinambuzane.
Iindlela ezintathu zokuvavanya ukusebenza kwe-nitisidone njengesibulali-zinambuzane sangaphandle zithelekisiwe. Umahluko uhlalutywe phakathi kovavanyo olusebenzisa ukufakwa kwesikhumba, ukufakwa kwemilenze yezinambuzane, kunye nokufakwa kwebhotile, kunye nendlela yokufaka, indlela yokuhambisa izinambuzane, kunye nexesha lokuvezwa.
Nangona kunjalo, nangona kukho umahluko kwizinga lokufa phakathi kweNew Orleans neMukhza kwidosi ephezulu, zonke ezinye iindawo ezixinzelelweyo bezisebenza ngakumbi eNew Orleans (zinokuchaphazeleka) kunakwiMukhza (zinganyangeki) emva kweeyure ezingama-24.
Ukuphonononga amaqhinga okulawula iivektha ezintsha, indlela ethembisayo yokufumana iikhompawundi ezintsha zokubulala izinambuzane kukwandisa uphando ngaphaya kweenjongo zemveli zenkqubo yemithambo-luvo kunye ne-genes yokukhupha ityhefu ukuze kuqukwe neendlela zokufunxa igazi kwizinambuzane. Izifundo zangaphambili zibonise ukuba i-nitisidone inetyhefu emva kokuginywa zizinambuzane ezifunxa igazi okanye emva kokufunxwa kwe-epidermal emva kokusetyenziswa endaweni ethile (kusetyenziswa isinyibilikisi).
Ukudibanisa idatha evela kwiindlela ezininzi zokufumanisa kunokuphucula ukuthembeka kovavanyo lokusebenza kakuhle kwezinambuzane. Nangona kunjalo, kufuneka kuqatshelwe ukuba kwiindlela ezintathu eziqwalaselweyo, indlela yokusebenzisa phezulu yeyona incinci kakhulu kwiimeko zokwenyani zentsimi. Ukusetyenziswa ngokuthe ngqo kwezinambuzane esifubeni seengcongconi kusetyenziswa isisombululo samanzi akulinganisi ukuvezwa okuqhelekileyo kwi-Anopheles gambiae sl. [47], nangona inokubonelela ngesalathiso esiqikelelweyo sokuba i-Anopheles isengozini yokufumana i-compound ethile. Nangona zombini iindlela zeglasi kunye nebhotile zilinganisa ukusebenza kwe-bioactivity ngokudibana nemilenze, iziphumo zazo azifani ngokuthe ngqo. Umahluko kwixesha lokuvezwa kunye nokugqunywa komphezulu unokuchaphazela kakhulu ukufa okubonwayo kwindlela nganye yokufumanisa; ke ngoko, ukukhetha indlela efanelekileyo yokufumanisa kubalulekile ekuhloleni ngokuchanekileyo ukusebenza kakuhle kwezinambuzane.
Ukutshiza i-residual-effect inambuzane (RIA) kusebenzisa indlela iingcongconi eziphumla ngayo emva kokuncancisa, okubangela ukuba zitye i-insecticide xa zidibana neendawo ezinyangiweyo. Ukonakala kwe-insecticide, ukugquma okungaphelelanga kwe-spray, kunye nokuphathwa kweendawo ezinyangiweyo (umz., ukuhlamba iindonga emva konyango) kunokunciphisa kakhulu ukusebenza kwe-RIA. Ezi ngxaki zikhokelela kwiingxaki ezimbini: (1) iingcongconi zinokusinda ekuchatshazelweni kwi-doses ezingezizo ezibulalayo; kwaye (2) nangona ukuchasana kubangelwa kakhulu kukukhethwa okubulalayo, ukuchasana okuphindaphindiweyo kwi-doses ezingaphantsi kwe-subfal kunokukhuthaza ukuvela kokuchasana ngokuvumela abanye abantu abachasayo ukuba baphile kwaye bagcine ii-alleles ezinxulumene nokuncipha kokuchaneka [54]. Ngenxa yokuba sisebenzise iingcongconi ezitya igazi endaweni ye-insecticides ezitya iswekile ezisemgangathweni weshishini, ukuthelekiswa ngokuthe ngqo nedatha epapashwe ngaphambili bekungenakwenzeka. Nangona kunjalo, uthelekiso lwe-discriminant dose (DD) kunye ne-dose-response curve shape ye-nitisidone kunye nedatha yezinye ii-compounds [47] kuyakhuthaza. I-discriminant dose idibanisa ixesha elimiselweyo lokuvezwa kunye nenani le-insecticide esetyenziswa kwi-vial, kunye nenani le-compound efakwe kwi-adsorbed ngokuxhomekeke kwixesha lokwenyani lokudibana kwi-paw. Ngokusekelwe kwezi ziphumo, i-nitisidone inamandla ngakumbi kune-thiamethoxam, i-spinosad, i-mefenoxam, kunye ne-dinotefuran [47], nto leyo eyenza ukuba ibe yeyona ndlela ifanelekileyo yokwenza i-insecticide entsha yangaphakathi efuna ukuphuculwa ngakumbi. Ukuqwalasela ukuthambeka kwe-dose-response curve (eyaqikelelwa ngokubala i-LC95 kunye ne-LC50 slopes kuMfanekiso 3), i-nitisidone yayine-steep curve, nto leyo ebonisa ukusebenza kwayo okuphezulu. Oku kuhambelana nezifundo zangaphambili ze-nitisidone ekondleni igazi kunye novavanyo lwangaphandle kwenye i-dipteran vector, i-tsetse fly (Glossina morsitans morsitans) [26]. Sivavanye kancinci ukusebenza kwe-nitisidone (sisebenzisa uvavanyo lweglasi) ngokutyhila iingcongconi zaseKissou (Umfanekiso S1A) okanye iingcongconi zaseNew Orleans (Umfanekiso S1B) kwi-nitisidone ngaphambi kokuba zityise. I-Nitisidone yahlala isebenza emilenzeni, ilinganisa imeko yeengcongconi eziwela eludongeni ezinyangwe nge-nitisidone ngaphambi kokuba zityise, nto leyo efuna uphando olongezelelweyo. Ukusebenza kakuhle kwe-nitisidone (kunye nezinye izithinteli ze-HPPD) emilenzeni kunokuphuculwa ngokudityaniswa nezincedisi ezifana ne-rapeseed methyl ester (RME), njengoko kuchaziwe kwezinye izibulali-zinambuzane [44, 55]. Ngokuvavanya imiphumo ye-RME kwi-*Gnaphalium affine* ngaphambi kokuba ityise (Umfanekiso S2), sifumanise ukuba kuxinzelelo lwe-5 mg/m², ukudityaniswa nezincedisi ezifana ne-RME kwandisa kakhulu ukufa kweengcongconi.
I-kinetics yokubulawa kweengcongconi yi-nitisidone engadalwanga kwiintlobo ezahlukeneyo ezichaseneyo inomdla. Ukufa okucothayo kohlobo lwe-VK7 2014 kusenokuba ngenxa ye-epidermis etyebileyo, ukuncipha kokusetyenziswa kwegazi, okanye ukugaywa kwegazi okukhawulezileyo—izinto esingazange siziphande. I-Nitisidone ibonakalise ubuthi obuphantsi kohlobo lwe-Culex muheza oluchaseneyo, nto leyo ebonisa isidingo sophando olongezelelweyo kumanqanaba aphezulu (25 ukuya kwi-125 mg/m²). Ngaphezu koko, njenge-Culex, ii-Aedes mosquitoes azinangxaki kangako ne-nitisidone kune-Anopheles, nto leyo enokubonisa umahluko we-physiological phakathi kwezi ntlobo zimbini ngokubhekiselele ekusetyenzisweni kwegazi kunye nesantya sokugaya [27]. Olu mahluko lubonisa ukubaluleka kokuqonda iimpawu ezithile zeentlobo xa kuvavanywa izibulali-zinambuzane ezisebenza egazini. Nangona ixhomekeke egazini kwaye ilibazisekile, i-nitisidone inokuba nexabiso elisebenzayo kuba inokusebenza ngaphambi kokuba iingcongconi zibeke amaqanda okanye zinciphise ukuzala kwazo ngokubanzi. Ngenxa yendlela yayo eyahlukileyo yokusebenza, ijolise kwindlela yokuwohloka kwe-tyrosine ngokuthintela i-4-hydroxyphenylpyruvate dioxygenase (HPPD), i-nitisidone inesithembiso njengenxalenye yesicwangciso esibanzi sokulawula i-vector. Nangona kunjalo, kufuneka kuqwalaselwe ukuba kunokwenzeka ukuba kubekho ukuxhathisa amayeza ngenxa yotshintsho kwindawo ekujoliswe kuyo okanye uhlengahlengiso lwe-metabolic, kwaye uphando olongezelelweyo luyaqhubeka okwangoku ukuze kuhlolwe ezi ndlela.
Iziphumo zethu zibonisa ukuba i-nitisidone ibulala iingcongconi ezifunxa igazi ngokudibana nemilenze, indlela engabonwanga nge-mesotrione, i-sulfadiazine, kunye ne-thiamethoxam. Le mpembelelo yokubulala ayikhethi phakathi kweentlobo zeengcongconi ezibuthathaka okanye ezichasayo kakhulu kwezinye iindidi zee-insecticide, kubandakanya i-pyrethroids, i-organochlorides, kunye ne-carbamates ezinokubakho. Ngaphezu koko, ukusebenza kakuhle kwe-nitisidone kwi-epidermal akupheleli kwiintlobo ze-Anopheles; oku kuqinisekiswa kukusebenza kwayo ngokuchasene ne-Culex pipiens pallens kunye ne-Aedes aegypti. Idatha yethu ixhasa isidingo sophando olongezelelweyo lokuphucula ukufunxa kwe-nitisidone, umzekelo, ngokunyusa ukufunxa kwe-epidermal ngamakhemikhali okanye ukusebenzisa ii-adjuvants. Ngendlela yayo eyahlukileyo yokusebenza, i-nitisidone isebenzisa ngempumelelo indlela yokufunxa igazi yeengcongconi ezibhinqileyo. Oku kuyenza ibe ngumviwa ofanelekileyo we-sprays ezintsha zokubulala izinambuzane zangaphakathi kunye ne-mother net enesenzo sokubulala izinambuzane esihlala ixesha elide, ngakumbi kwiindawo apho iindlela zemveli zokulawula iingcongconi zibuthathaka ngenxa yokusasazeka ngokukhawuleza kokumelana ne-pyrethroid.


Ixesha leposi: Disemba-23-2025