AN7IMALARIAL RSIS7ANC

NoedI H et aI. vdence o/

Artemsnn resstance n Western
Camboda.N[M 2008,860(24).2610
'R'IW MALARIA
DINI7IN 7RMS IN MALARIAL
RSIS7ANC
PHARMACL AR7MISININ
WH MALARIAL 7RA7MN7
&IDLINS 2010
R'IW [&RNAL
AC7S RM 7HR [&RNALS
CNCL&SIN
PSngIe most mortant arastc n/estaton
o/ man
PCaused by Iasmodum ss, aded by the
vector anoheIne mosquto
PAbout 8 bIIon eoIe are at rsk n
endemc regons
PAbout 800-600 mIIon new cases anuaIIy
P1-8 mIIon deaths occur annuaIIy
PDrug resstance has aIways been a
robIem
P1
st
descrton o/ CQ resstance was n
BraaI n 1010.
PCQ resstance was /rst reorted n South
Amerca & South ast Asa n 1060
PKenya and 7anaana documented CQ
resstance n 1078.
PNgera documented CQ resstance n
1087, In Zara, t was n 1080.
PResstance aIso reorted /or other
antmaIaraIs such SP, Amodaqune,
Me/Ioqune, Qunne, HaIo/antrne and
recentIy Artemsnns.
Zones CQ
(2003)
SP
(2003)
ART/LUM
(2004)
AT/AMQ
(2004)
SE 3.7% 14.9% 100% 100%
SS 9.1% 8.5% 87% 82.5
NC 52.2% 82.7% 100% 96%
NW 77.3% 94.2% 100% 100%
SW 40.9% 75.6% -- --
NE 50.8% 64.8% -- --
P IocaI atudy in zaria (may 2004)ahowed efficacy of 90 and
97 to chIoroquine and 8P reapectiveIy.
"
Slide 6
DDO1 local study in zaria (may 2004)showed efficacy of 88.7 and 37 to chloroquine and SP respectively.
r. . "oina, 8//2006
PCombnaton 7heray-Combnaton o/ 2 or
more d//erent cIasses o/ antmaIara
medcnes wth unreIated mxsms o/ acton
PAC7- Combnaton o/ artemsnn or one o/
ts dervatves wth an antmaIaraI o/ a
d//erent cIass
PCure-Imnaton o/ symtoms and
asexuaI bIood stages o/ maIara arastes
PRecurrence-occurrence o/ asexuaI
arastema a/ter Rx
recrudescence,reIase,or new n/ecton
PRecrudescence-occurrence o/ asexuaI
arastema a/ter Rx o/ n/ecton wth the
same n/ecton that cause the orgnaI
IIness
PReIase-recurrence o/ asexuaI araste o/
P.vvax, P.ovaIe dervng /rom the ersstent
Iver stages
PDrug resstance-abIty o/ a araste stran to
survve or muItIy deste the admnstraton
and absorton o/ a drug gven ndoses equaI
to or hgher than those usuaIIy recommended
but wthn toIerabIe Imt o/ the subject,
rovded the drug exosure at the ste o/
acton s adequate.
P7reatment aIure-nabIty to cIear maIaraI
arastema or resoIve cIncaI symtoms
deste admnstraton o/ an antmaIaraI
medcne
PIn generaI, /our basc methods have been
routneIy used to study or measure
antmaIaraI drug resstance.
Pn vvo,
Pn vtro,
PanmaI modeI studes, and
PmoIecuIar characteraaton.
P 7radtonaIIy, drug resstance was categoraed
ureIy on arastoIogcaI grounds as Senstve,
RI, RII, and RIII
P However, the occurrence o/ asymtomatc
arastaemc eoIe n A/rca has necesstated
mod/catons
P WH now recommends the use o/ cIncaI and
Iaboratory crtera n determnng treatment
/aIuretheraeutc e//cacy .
P&ses study o/ arastema 4 28days, /Ims
done on day 2, 7 and 28 days
PSenstve(S)-asexuaI araste count reduce
to 26% reRx IeveI n 48 hrs and comIete
cIearance a/ter 7 days wtout
recrudescence
PR1(deIayed resstance)-AsexuaI araste
reduce to < 26% o/ reRx IeveI n 48hrs,
but reaears wthn2-4 wks
PR1(earIy recrudescence)-reaerance s
earIer
PR11-marked reducton n asexuaI
arastema(26-76%) o/ reRX IeveI n
48hrs, wthout comIete cIearance
PR111-mnmaI reducton or ncrease n
arastema a/ter 48hrs
3 Categotles
ParIy treatment /aIure (7)
PLate treatment /aIure (L7)
N Late cIncaI /aIure
N Late arastoIogcaI /aIure
P Adequate cIncaI and arastoIogcaI
resonse (ACPR)
PDeveIoment o/ danger sgns o/ severe
maIara on Days 1, 2 or D8, n the
resence o/ arastaema.
P Parastaema on D2 greater than D0
count rresectve o/ axIIary
temerature.
PParastaema on D8 wth axIIary
temerature > 87.6
0
C
PParastaema on D8 > 26% count on D0.
a) Late CIlnlcaI FalIute
P DeveIoment o/ danger sgns or severe maIara a/ter Day 8
n the resence o/ arastaema, wthout revousIy
meetng any o/ the crtera o/ earIy treatment /aIure.
P Presence o/ arastaema and axIIary temerature > 87
0
C
n the on any day /rom Day 4 to D 14 wthout revousIy
meetng any o/ the crtera o/ earIy treatment /aIure.
-)Late PatasltoIoglcaI FalIute
P Presence o/ arastaema on D14 and axIIary
temerature < 87.6
0
C, wthout revousIy meetng any
o/ the crtera o/ earIy treatment /aIure.
PAbsence o/ arastaema on D 14 and
axIIary temerature wthout revousIy
meetng any o/ the crtera o/ earIy
treatment /aIure or Iate cIncaI /aIure or
Iate arastoIogcaI /aIure
PA sesquterene Iactone extracted
/romArtemsa annua(sweetwormwood) or
qnghao.
P&sed atIeast 2000 yrs ago
PIn 1072, actve ngredent was ur/ed and
name qnghaosu(essence o/ qnghao) but
Iater named artemsnn
P&nreaIabIe 'knetc ro/Ie Ied to
semsynthetc dervatves
PAct quckIy and eImnated quckIy
PRad araste cIearance rate
PDervatves are artesunate, artemether,
arteether, dhydroartemsnn
PPotent nducer o/ CP enaymes CP
2B6,CP8A4,CP2A6
PHaI/ I/e s short-2-6 hrs (artemsnn),
artesunate <1 hr,arthemeter 2-4hrs
PMetaboItes are conjugated n the Iver and
excreted n bIe
PReeated dosng Iead to decrease serum
con(autonducton)
PRC7
P04 aduIts /rom Camboda(Battambang
Provnce)
PRandomsed n a rato 2.1
P&ncomIcated maIara,100-100,000
arastesuL
PHgh dose artesunate 4mgkg oraIIy /or
7days(60ts)
PQunne 80mgkg + tetracycIne 26mgkg n
a sIt dose 8hrIy /or 7 days(84).
PAdmtted 4 28 days to ruIe out re-n/ecton
Putcome-cIncaI outcome, Iasma drug
conc, nvtro susc testng, moIecuIar resstance
text. Resstance-arastema a/ter 7 days,re-
emergence a/ter 28 days, adeq Iasma conc
o/ dhydroartemsnn, roIong araste
cIearance tme,Decrease nvtro susc to
dhydro
PRS&L7.
P4 o/ 60-reemergence btw 21-28
days{kaIer-Meer rob o/ cure at 28days
08.6%[84.7-07.7]
P2 o/ the atents were cIass/ed as havng
artemsnn resstance[araste cIearance
tme o/ 188 and 08 hrs, as comared to the
medan o/ 62.2 hrs.
PSAQ&AMA7 study gr
Pen IabeI RC7 n BangIedesh,Inda,
Indonesa, Myanmar
PI' artesunate 2.4mgkg boIus at 0,12, 24
hrs and daIy(780) R I' qunne 20mgkg
saIt Ioadng dose over 4 hrs and 10mhkg
8hrIy(781)
PraI medcaton substtuted when ossbIe
PRS&L7S-rm endont-mortaIty
PArtesunate 16%[107 o/ 780], qunne
22%[164 o/ 781]
PAbsoIute reducton o/ 84.7%[18.6-47.6%,
-0.0002]
PArtesunate weII toIerated, wheras qunne
assoc wth hyogIycema, RR=8.2[1.8-8.7,
=0.000]
PMeta-anaIyss. Artesunate's Qunne n
severe maIara[ sncIar D et aI]
P8 traIs[1664-aduIts, 6766-chIdren]
PArtesunate decrease death n both aduIt
and chIdren.
PRR 0.61[0.60-0.76] aduIts[1644,6 traIs],
RR=0.76[0.66-0.00] chIdren[6766,4
traIs{2011 revew}.
PCNCL&SIN