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BOYTO VI NSOTIT-KGSINHTRUNG-CONTRUNGTRUNGUONG BAOCAOKITQUANGHIENC N DCTAICAPVIEN Téndét‹ii.- NGHIENCL/UANHHLIONGCUATHUOCSOTRET PHOIHCIP DIHYDROARTEMISININ- PIPERAQUIN DOVIETNAMSANXUATDENMOTSOCHIICNANG TIMMACHVATHANKINHTRUNGLfO NGCUA Chu nhiin d é téi.ThS.NguyenTh]M i n h Thu Cdquanchutridétéi.VienSétrét-KST -CTTLf Cdpqi/dn/.Vin Sétrét-KST-CTTU HANOI-2007 BAOCAOKITQUANGHIENC N DCTAICAPVI N Téndétiii.NGHIENC N ANHHUONGCUATHUOCSOTRETPHOIHOPDI HYDROARTEMISININPIPERAQUINDOVIETxAMsixXUATDENMOTSOCHUCNANG TIMMACHVATHANKINHTRUNGUONGCUADONGVATTH CNGH IE M Cliiinhiémdétai.-ThS.NguyenTh)MinhThu Thotgranthu:chién.-1ndm(5/2006-4/2007) NHLfNGNGLf Vi(nSotrét- KST-CTTU ITHIC H I E N DaihocYHaNoi,BtimonDn‹icly CACCHUVIETTAT ACT:AntimalarialCombinationTreatmentALT:Ala nineaminotransferase ART:artemisinin AS:artesunate “ ‹ AST:Aspartateaminotransferase BN:b(nhnh:In BNSR:benh nh6nsotre’t CQ:chloroquifie CL:dfithanhth:ii(clearance)Cs: congsu CT:cfintiring DHA: dihydroartemisinin DVTN:d0ngv(itthucnghii n ECG:die:nthindo(electrocardiogram) G6PD:glucose6-phosphatedehydrogenase lC50:nongdoticché507‹s8sinhv)tthinghiem(inhibitoryc o n c e n t r a t i o n ) KII&CNVN:KhoahocvicfingngheViétNam KST:kysinhtiling KSTSR:kysinhtinngsfitrét LD50:liéuglychit509csosinhvétthi nghii n (lethaldose)NST:nhiémsa.c the PQ:p i p e r a q i i i n e PQP:pipei‘aquinep h o s p h a t e R:kh:ing(resistance) SP:sulfadoxine-pyrimethamine SR:sotrét SRAT:s6trét:ictinhIp: thoigianbanth:iiTU:tr unguong VSDT:vsinhdichID XNDPTUI:Xinghi(pDucicph6mtrunguongI WHO: chiic thfigi6i(WorldHealthOrganization) N0id u n g Trang PHANA:TOMTATCACKETQUANOIBATCUADETAI Donggopcuadétavén0idungnghiénemu , d ‘ • Hi u quavé a’ota o ’‹ Hie‘uquav6kinhté 4.Hiéuquav6x5hQi 5.Apdungvao thuctién sanxu:Itvadcii PHANB:NOI’DUNGBAOCAOCHITIETKETQUANGHIENC LfU Témtiit D:itv:indé Ttingquan 2.1 Tinhhinhnghiénciiringoainucrc 2.2 Tinhhinhnghiénelmtrongnucrc Doi tiipng,vatlieuvaphiiongph:ipnghiénemu 3.1 Diadiem, t hc ii giannghiénc i i u 3.2 Dongv i t nghiéne m u 3.3 Thuocv a h o : i c h i t nghiénc i i u 3.4 C:icdungcuvathietbiditngtrongnghiéncilu 3.5 Phirongph:ipnghienciiu 3.6 C‹acchitiéud:inhgi:i 3.7 Xiilysoliéu Kétqu:i 4.1 Anhhuéngciiathuocph0ihppdénhuyét:ipchfi 4.2 Anhhuéngcuathu6cphoihppdéntimSchcoljp 4.3.Anhh u é ngc i ia t h u c p h o i hpp dénphanx a t i m t h trca n me cuac h u t n h‹att r a n g 5.Banlutin 5.1.Anhhuéin ciia thuocphoihppdénhuyét:ipchfivatiméch cfiljp 5.2.A nh h u é n g c u a t h u o c p h o i h p p dé n p h a n x a t i m t h i i c a n t r o n g m é l o cuachutnhattr½g Kétluanvad é xuat 6.1 Kétlun 6.2.Déxu:It CACBAIBAOKHOAHOCDACONGBO CIJ CUADETAI UICAMON TAILIEUTHAMKHAO 2 3 5 11 1I II II 1l 12 15 15 16 16 18 19 21 2I 2I 23 23 23 VEK E T QUAN G H I E N 24 25 PHANA:TOMTATCACSETQUANO BATCUADETAI Nghiéne m u n a y , c i initmii c d nhltd i n h , d a d a n h g i : i d u o c a n h hi ri ng c i i a thu8cs t r ét ph8ih p p dihydroartemisinin - piperaquin( D H A P Q P , n g u y é n l i u d o Vie’tNams a n xu6t)denmdts c h i i c uangt i m machvah o a t d cingt h a n k i n h t r u n g nonci i a d o n g vjtt h u c n g h i e’m.Kéiquang hi 0n m i n c i i a d é Hib o s u n g chohos o thiinghiemtiénthinsang ciiaint thuficsotiéthiendangiatdunequanthinvoikhauangc h n g kh:ing.c:to,hiéuq u a diéutrt t tv f i a n toankhi s it dung.C‹ a c k c : tquanghiénc i i u nay‹iidonggopdunemots8 loiichnhvsau: Donggopciiadetiiivenoidungnghienciru Gopph:Innghiénemuvédéctinhcuathu‹5csotre’tph6ih ppDHAPQPvoinguyeri1i(uPQP1:iiidautie‘ndnacsxu 4tthanhc‹5ngciVietNam(mathitrirciiignguyénlieun ayttrtrirfict6inay‘ n TrungQuficd6cquye‘n).Két quachoth:iy- diemba n d é u , ciingi i h u Hi(uq u a véd a o tao Nghiéne m u g o p p h t t n b o s u n g cacd f i liu c h o 1u(n‹ a n t i é n chuyénng‹anhDirocly Hiéuqu:ivékinhté iDuochoc Nghiénc i i u n a y d b8s u n g c:icdfili2uv é dietf nhc u a t h u f i c s o t rétphoih p p DHAP Q P , v o i n g u y n i ( u PQPl n dttu t i é n d u n e s a n x ud t t a i V i IN a m, t o p p h a n ph att r i m i n tt h u c s t r é t v c i i n g u y é n l i é u s a n x u d tt r o n g n u é i c , k h f i ngp h a i n hapkhttu 4.H i e n q u : i véxfihol • ’ ’ _ ' ThuocphfiihppDHA-PQPhennayda duocdwav‹“nodanhmuct h u 0csfitiét thiéty é u tiongc h u o n g t i i n h p h o n g c h o n g s o t r é t q u o c g i a c t i a V i e t N a m Ct ack i t quanghiénc t i u nayg o p phbos u n g chovicdanhgi:it i n h a n to? ancuathuoc,l a m tighiéuquasirdungthu0ctrongcQngdong,hanchec:icI:iedung phu Apdungvaothiictiénsfin xu:ftvadcisongxah‹ii Thiiocp h c i ih p p D H A - P Q P a n t o a n v c i c h i l c n /angt i m m a c h v ? ah o a t d o n g thank i n h t i r i n g u o n g c i i a d findv ) t t h i nghiemc i liéut v o n g d u o n g v o i l i e u c l i é c t i iti‘6nn g t t o i Vcii lieuc a o , t h u o c gtyt i c c h é h e t h 'tnk i n h tiringv e n t V i v a y,v o i n h i i r i g ngucr iv5nhanhmaymochoacdithuxephaith‹antion khidungqufalieu PHANB:NO DUNGBAOCAOCHITIETKETQUANGHIENCN Tomt:It: N ghiéncuucinhhuéng rétphoihop40mgcliliyJrociric•misiiiiii (DHA]vé320mgpiperaquinphosphat(PQP) ,vernguyinliétiPQPl‹iii cliumin clitocscinxuéttciiViétNamdénhuyétidpviitimcol‹ipciiuclon$v‹il tliitcii3liim ‹luoctié’nhunhlciiBomérD u p c I),T r i r gDefh o c YH‹iNoi,thcing3v?titili‹iii,q 7-8 huangciiathuo“cphoihopDHA-P QP‹litipli‹inxutimthitc‹in in22000066 Anh téit i c lt sovéiléclii’iii¿(P>0,05) Ofilm2 mglLglu g‹ivx5iigév,Id c i , llmo‹’f›lioili‹ipD B A -PQPtermicii;• Dohi6nt u p n g kh:ingt h u c c i i a kys i n h trii ng(KST ) ngayc i n g giat•angné nhi(nnayTO chilcYtéthégiéii(WHO) dangkhuy8nc : t o ph:itt ri én c: i e cfingthiic I! u e phoih p p D i m h i n h lac : i c t h u c cot h a n h phlnccb i i n lad a n x u a t ciiaa rtemisininvcri initthuockhdccothoigianbiinthaidaihon Méiid:ty,t h u f i c A i l e k i n v oi t ( i : i n h phln c o p banl a piperaquin( g o m : m g plperaquin v a 40mgdihydroart emi si ni n, d o TrungQuocs a n xudt)dadunes i r dungvacho k6tqu‹adieutris0trétt8t(thoigiansachKSTnhanh,tyl‹:die:uti’ikhfiicac95969‹) [23].Chodénddunam2004,trénthégioimcrichicoTiringQuoclanuocduyn h d ts a n xul t d u n e P Q P vax u l t k h a u s a n g V i e t N a m C f i n g namd f i , c:i e n h a khoah o c c i i a V i c:nH o hoc,V i c:nKhoah o c v ?ac o n g n g h c : V i ( t N a m d s a n x u ½ t a‹ thanhc f in g piperaqinp h o s p h a t ( P Q P ) Dola ccsédCs/ anxu6tthuocs o t rétphoih ppdihydioai’temisinin-pipei’aquin(DHAPQP)tirnguyénlintiongnircic[9].PQPdfid eacV i n S o t iét- KSTCTTUsobfit h i r t :i c d u n g trénKST SR,kétqudc h o thym d uP Q P c i i a V i é n H o a h o c t u o n g t i r n h u m d un h ) p c i i aT i r i n g Q u o c v é t/ acd u n g ti6nKST[ ] Thuocp h o i hppDHAPQP( n g u y é n l i i i doViétN a m s a n x i i t)daiagduocnghiénc i i u t h i r nhiémt i e n l m s a ng val l m s in g tain i r o c t a De:gopphanv a o viecn g h i é n c i l u motthuoc S R c f i kh‹a n i n g choia g k h /an,hieu qii dieutiic a o , itd o c , a n t o a n , d v o c b a o c h é t i r c : i e n g u y é n lietis a i i x u d tt i a o i i • nucrc,ctét ‹ainayd u o c t i é n h‹anhn m nghié nc i i u a n h hiringc i i a thriocs o t iét phoi hppd i h y d i ‘ o a i ‘ t e m i s i n i n p ip e i‘aquinde n h u y é t d p,t i m c o 1a(pw mots f i chicu a n g hoatd n g t h i n kinht i u n g u o n g c i i a donv ; i tt h u c n g h i m M!²º²²: Dénhgiéc l n h hu:kge t a thuo’cpho‘ihppDHL-PQPd é n huyétépvatimcé lépciiadongvétthitcn gh ié m Dénhgiéi i n h huéngciiathucicphoih o p DHA-PQPd é n p h a n x a ti m thii:c ’iiIronm é ’ if i t trfiri TONGQ U A N 2.1 Tinhhinhnghiénemungoai niroc: Artemisinin(ART)v a c : i c d i n xu:ftc o t : i e d u n g ; c t s o t v a t h i n s a c h K S T nhanhnh6ttrongtdtcac:icIu c SRhi(nco.HieulucdieutiiP.fcilcipcirumd akh:ingt h u f i c , k h a n a n g t a i n c h i n h i( n t u o n g kh;ingt h u o c k h i d i i n g p h o i h o p d i n d/ anxu at A R T dupec h imgminhl a dungnaprlt161tiongcacthiinghiemla.msang(Hien andWhite,1993).Chicoit t:iedungphud‹angkedviacghinh.anfihon2ti‘ie'' c6n sit(cs),1999).Ai‘temetheivfiai’teethei‘lacdc diéuti‘i3 BNSRdoP.falciparumt f i n g lieula480mgDHAtiong5 ngaydattylkhfiibenh97Wo Th‹aiLan,Looareesuwandieutii52BNSRdoP.falripciriimph:icdfinhutiendattyI(khfii909o[18] Pipeiaquinla motb i s q u i n o l i n e d u n e t o n g h p p d i u t i é i i v a o n h tiiipna mc u a vadiéutr]SR20namti6psaudfi.M8tnhfimc:ienhakhoahocTiengQuocd5d‹anchtm gt a n g P Q P dung n a p t t h o n c h l o r o q u i n ( C Q ) v a c o h i e u l u c d’i éut i is o t iét( SR)doP.falcipariimv“aP.viv‹zxitnhdtlatifongInCQ.Vi(cph‹attrienc:iechiing P.falciparumkh:ingP Q P vas u xulthin ciiac:iedinxuJtAR T dEkhiénc h o PQP itdunesitdung cuathjpky1980[24].D8nhayinvitrocuaPQPva int s8cacthuocSRkh:iedadunecacnhakhoahocTrunkQu6cnghie‘nchino tinhYunnan.Kétquachoth£ymiicdfikh:ingcaociiaP.fulcij:remitsvéiCQvaPQP[25][28] [34].DdnhayiiivivociiaPQP)r6nP.fcilciparumc l i n g daduocdénhginciLinShuivaBaisha ,t i n h Hainan,TrungQuocn‹am1 Vcritongl ieu , g danhbasetiong3 ngayd i é u ti‘i,thciig i a n hets t l:i36I20,7g i c r , t héi giantiring b i n h s a c h KSTth6vdtinhla6 9,7:1:20,9gici TyIeI:iiph‹atcrng‹ay1 via28lia7/47cachothy miicdfikh:ingR IvoiPQP[301 C:icnghiénctiud6utiéntiénnn o t ciiaPQPd‘aduoctienhanht i r nhfingn‹am ciiathapky19 70 , thuocdaduocdieutiichohangna n benhnh‹anngucilérnvatiéem.P Q P d c h f m g t f i h i u l u c d i e u t r i v i k h a n ‹andungn a p t o t , k h f i ngc f i h i e n tuongk h ? angchéovciiC Q GuoXB.v ‹ a c s ( ) s o sanhh i e u qtiad i e u t i ‘ i c u a viéndanA RTvaPQPtrén56b n h n h d n ngirciitinTiringQuocm‹acSRP.fnlcipariimd én h‘anth y : l i e u t i i n h d i e u t i‘i3 ng•ayc i ia A R T danc h o t hc ri g i a n s a c h KST( , I 16,0gicr)n g ‹ a n h o n c u a P Q P ( 0 , +2 , g i d ) n h u r i g t I e t /aip h / ato ngay2 c i i aARTdan( ,29c)c a o honr l t nhiéus o voic i i a P Q P ( 17,/ )[ ] Gu (1988)clingnhjnth a y hieuqu‹aciiadihydi’oaitemisinin(DHA) (calietiti‘iiahclietiti‘i5 va7ngay)d é u t o t honc i i a PQP tiénbenhn h i n S R doP f‹il‹ip‹iir im;t h o i g i a ns a c h KSTv ? at h c r i g i a n hets t ciiahainh fi m d i e u t i‘ibindD H A PQPlanrinhau,tyl e t h a i ph? atk h : i e n h a n k h f i ngc o y n g h i a thongk é [ ] Ga.nd i y , d v o c d c › n g h o c ciiaPQPd advocnghiéne m u trénBNngirciil é i n vati’éemCampuchiai na.cSRdoP fulciparumh o ? c P.vi» ci\‘.NeoHungTY.vac s (2004), P Q l‹at h u o c c o khan ‹an•phoat n n t i t tron l i p i d , P Q P cot h é t i c h p h ?anb o ( V s s / F ) é n,t h c i g r a n b ‹aiit h a i ( t p,)d‹ai(tiringbinh23n‹ a y c inguciil én va1 na y ottéem) ,doth:inhth:ii( C L ) otiéemcaohoné nguoil é n [2 ] TheoLK.BascovaP.Ringwald(2003),PQPcohoattinhcaolit›'iirodoivoic:iechi mgP.falciparump h M ljpc i l a Cameioon(IC50 =38,9nlvI,7,76 78.3nlvl³PQPt h é h i é n khanigt i c c h é m a n h titcac:icp h i i i 1‹apc n i n g dfi 50h o a c 0 nmol/L;c o hoattinh d6ivcric: ic phMl a p nhayva khangCQ.GitiaPQP vaCQcfi’ituo ng quan 0,05).C:iekét quanaygotyin g , vi(cphatti’ienPQP,phoihopvoiDHA,manylai nhiéuhilahenchodieutriSRkh:ingCQ[22]