Aug 7, 2002 - Chloroquine or sulfadoxine-pyrimethamine for the treatment of uncomplicated, Plasmodium falciparurn malaria during an epidemic in Central.
University of Nebraska - Lincoln
DigitalCommons@University of Nebraska - Lincoln Public Health Resources
Public Health Resources
2002
Chloroquine or sulfadoxine-pyrimethamine for the treatment of uncomplicated, Plasmodium falciparurn malaria during an epidemic in Central Java, Indonesia J. D. Maguire U.S. Naval Medical Research Unit #2
M. D. Lacy Flagstaff Medical Center
Purworejo District Health Service (DINKES) P. Sismadi Ministry of Health Institute of Health Research and Development
U.S. Naval Medical Research Unit #2 See next page for additional authors
Follow this and additional works at: http://digitalcommons.unl.edu/publichealthresources Maguire, J. D.; Lacy, M. D.; Purworejo District Health Service (DINKES); Sismadi, P.; U.S. Naval Medical Research Unit #2; Wiady, I.; Laksana, B.; Bangs, M. J.; Masbar, S.; Susanti, I.; Basuki, W.; Barcus, M. J.; Marwoto, H.; Edstein, M. D.; Tjokrosonto, S.; and Baird, J. Kevin, "Chloroquine or sulfadoxine-pyrimethamine for the treatment of uncomplicated, Plasmodium falciparurn malaria during an epidemic in Central Java, Indonesia" (2002). Public Health Resources. Paper 420. http://digitalcommons.unl.edu/publichealthresources/420
This Article is brought to you for free and open access by the Public Health Resources at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Public Health Resources by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln.
Authors
J. D. Maguire, M. D. Lacy, Purworejo District Health Service (DINKES), P. Sismadi, U.S. Naval Medical Research Unit #2, I. Wiady, B. Laksana, M. J. Bangs, S. Masbar, I. Susanti, W. Basuki, M. J. Barcus, H. Marwoto, M. D. Edstein, S. Tjokrosonto, and J. Kevin Baird
This article is available at DigitalCommons@University of Nebraska - Lincoln: http://digitalcommons.unl.edu/ publichealthresources/420
.AI/Ilu/s oj Tro pical M .,did llO: & l'arasiwloKY , Vol. 96 , No. 7, 65 5 -668 (200 2)
Chloroquine or sulfadoxine-pyrimethamine for the treatment of uncomplicated, Plasmodium falciparurn malaria during an epidemic in Central Java, Indonesia ]. D. J\ lAG U IR P , M . D . LACYt, SURURI' , P. SISMADII, KRIS IN* , I. WIADY* , B. LAKSANA* , M. j. BANGS*, s. MASBAW , I. SUSANTI*, W. BASUKI* , M .]. BAR C US* , H . lvlARWOTOI, ,\ \. D . EDSTEIN\ s. T jOKROSONTO* * and j . K . BAIRD* ' U. S. Nava l M edieal Research Unil # 2, U.s. Ernbassyfahorta, Unit 8 132, N A M R U- T IrlO, FPOA P 96520-8132, U.S .A . t Flagstaff M edical Center, 1200 N . Beaver Stre et, Flagstaff, A Z 8600 I, U.S .A . *Put'n1v rejo Dist rict Health S ervice ( DIN K ES), J a/an M ayjeu SUlOj'O No. 17, Puruorejo, Central Ja'va 54114, Indonesia sAlinisto , of H ealth Institute of H ealth Research and Dev elopment, LITBA1VGKES, Jalan Percetak an Ncg ara JVo. 29, fa ka na /0570) Indonesia ~A ustraliall Army M alaria Institute (A }" H) , Gallipoli Barracks, W'eaJ:'V Dunlop Drive, Euoggera, Qu eensland 4052, Australia *-Gadjah M odo Uniuenity, B agian Parasitologi, Sekip, Yogya ka rta 5528 1, Indonesia
Received / 4 Ju ne 2002, Rev ised 7 August 2002, A ccepted 8 A ugust 2002
A recent malaria ep idemic in th e M cn oreh Hills of Ce ntral j ava has increa sed co nce rn abo ut the re-e me rgence of endemic m alaria on j ava, whic h th rea ten s the islan d 's 120 million res ide n ts. A 2R-uay, in-vivo test of the efficacy oftreat me nt of malariu with ant irnalnrial drugs was con du cted amo ng 167 village rs in the .\ \c no reh Hills. 1111." treatment s investiga ted . chloroq uine (e Q) and sulfa do xine- pyrimc thum ine (SP) , co nstit ute, respectively, th e first- and seco nd -line rrcarmcn rs for uncomplicated malaria in Indonesia. 'I111~ prevalenc e of malaria among 1389 resi dents screened prior to enroll men t was 3.l% . Treatm en t o utc o mes were assessed by micros copical di agn oses, p eR-based confi rmation of the di agn oses, me asu reme nt or the whole -blo od co nce nt rations of C Q and descth ylchloroq uine (DC Q) , an d ide ntifica tion of the Plasmodium [alc iparunt genoty pes. The 2 8 ~ 0.
I)v
1)1' 17'57 (RO·-H2 , -lUO)
32 ( '5- 6 5) ·12.5 ( 11-68)
11.7 lOll
66q Otl -2l), 520)
GEO MHfUC :-.tEAS t'AKA!\IfAFMIA A1\:U ( ItAS l iE) (as exu al p ara " i te ~ lp l )
:'l1'1.I:::-':U.\lf.(jAI,Y (':.~ ,) . Amo ng all sub jects Amon g sub jects aged < 10 years
r ~EVAl.ESCE tW
I I ( 15)
" (3 6) 15 (00)
3 1 (47)
7 (1 0)
0 (0 )
27
-, ,-
Pu re 1'\"
15 5
lC, (6 - 60)
t"~'
Chloroq uine th erapy
3
25 II 11
I:fllllp
Pure Pf
trl.'i1f ll/mr
d"",ogruphll', chnico! < md /'I.lrasulltOj(ic,d churactvriaics of
M ale.. Fe m ales Aged < 10 years With < 10 9 haemoglcbi n/d l Wit h fever 37.; · C) Symptomat ic M ean age and (range) (y ea rs) M ean weight and (range) (kg)
AO
SO . ANI>
~·lIrllflm~·tlt
by f arw'ire .{p~'dc.\ and
1'11.:
spt'('i~s, srrut~/;.:d
TABLE I .
il~rcai"'H
830 (8 0 - 2-.t. 4 ( 0 )
132 ( 12 0-7-l.1O)
100
-
S 31 ( 40- 23 . 200)
55 . 1 100
38.8 (I8-bO) '53. 3
38 .·l ( 1 1- 60)
28 (7 - 70)
18 (37)
12 (2 5)
25 3
2 ·~
·10
Pure Pf
Q
-
An
roo
l OU
23
220 (MO- 16 AO)
'590 (200 -2H-10)
60
1'5..1 (2U- ·IH)
3 (60) 29 (1 1-65 )
I (20)
0 (0)
2 ( 10)
o (0)
n
5 I I
Pf + I'v
I 0 (0 )
(l
I I
Pure Pv
Sulf ad oxin c-pyrirnctbumine therap y
fiJilli Pla ..rn odium Ialc ipuru m ( Pi J, P. vivux (1"1.,) or ""th
34 (6 l ) 2K (7 - 70)
15 7 8 I 3 (20) 3 (20) 8 (5 3)
Pf + Pv
subjcas who had
...:...
..,'"
~
C
o
;i:
:.-
o
00-
CQ OR SP FOR MALARIA ON JAVA (4 8%) co m plained of symptoms. In ge neral, the P. [ alciparum parasite densities were greater than th ose of P. vivax; the o nly excep tion was in the mixed infection s in those treated with CQ , w he re the P. viuax parasite densities were g reater than the P. fal ciparum .
Drug C o n ce n trati o ns Table 2 su m m arizes the CQ + D C Q co ncentrations in the blood samples collected , from the subjects treated with CQ, on day o ( pre-treatm ent) , da y 2 and the day of recurrent para sitaernia. •Mixed infections are included in bo th the P. falciparum and P. ,(liv ax co lumns. Pre-treatment samples were avai lab le for 38 and day-2 sa mples for 37 of the 40 sub jects in fected with P. falciparum and treated with CQ. Pre-treatment and day-2 samples were available fo r 76 and 75, respectively, of the 87 indi viduals with P. v ivax who we re treated with CQ . CQ + DCQ co ncentrations we re dete rmined for all 44 subjects w ith rec urrent par asitaernia during follow-up. Among those tre ated with CQ, 4 2% ( 16/38) of the subjects with P. fatcipanon and 37 % (28176) of those with P. oicax had d etectable C Q + DCQ co ncentratio ns prior to enrollment, indicating self-ad m inistered CQ. The ove ra ll me an (s.n.) day-2 CQ + D CQ co ncentration for all those treated with C Q (regard less o f parasit e species) was 667 (36 2) ngim l. Although two of th e sub jects infect ed with P. [u lcipannn and five of those infected with P. uiuax had day-2 concentrations far bel ow norma l, only one of these seve n subjects (who had a P. vivax infection) developed a recurrent parasita ernia and was there fore excluded from the estima tio n of therapeutic efficacy, o n the presumption of inadequate C Q ab sorption. Am ong th e 54 su bjects treated for 1'. [a lcipannn with SP, only 22 da y-O ( pretreatment ) plasma samples \v·ere available for measurement o f sulfad oxine and pyrimethamine concentrations. Six (2 70/0) of these 22 had det ectable sulfadoxine and
66 1
pyrimethamine co nce ntrations, indica ting recent use of SP prior to enrollment. Plasma samp les from th e day of rec urrent parasitacrnia we re available from six of the nine subjects who experienced SP therapeutic failu re (T able 3) . With th e except ion o f o ne subject with und etectable pyrimethamine co nce ntrations, all six subjects had d etectab le concentrations of bo th drugs on the day of recu rren ce, with mean co ncen tratio ns of 28 ug sulfad oxine and 48 ng pyrimethamine/ ml, respectively . Post-therapeutic C li n ic a l Course of P. fa lciparurn Malaria Clinical co urse did nor differ between treatment groups. M ost of th e physical complai nts reported at enrollme nt had resolved by d ay 4 , whether those affected had been treat ed with C Q o r SP. The numbers of co m plain ts o n da y 4 were o nly 3 1% (C Q) and 38 % (SP) of th ose observed on d ay o. Differences in the resolut ion o f specific co mplaints between the two main treatme nt groups (i.e. C Q t'. SP) were not statistically significant, with P-values between 0.2 and 0.98 (d ata no t shown) . F ever ( i.e. an axillary temperature > 37.5"C) resolved by day 2 among those treated with C Q but not until da y 3 am ong those treated with SP ( P> 0.05).
Outcomes of th e In-vivo Tests Of the 40 subjec ts treat ed with CQ for P. falcipanun, two were lost to follow-up after day 0 or d ay I of the rapy. Of 22 recurrent, same-species infection s, four we re exclu ded from analysis because the day-of-recurrence P. fa lciparum DNA co uld not be amp lified for M SP-2 genoryping , leavin g 34 eva luable infections. T hi rteen (38%) of these 34 co mpleted the test with ou t recurrent parasitaernia, three (9%) developed intercurren t P. 'l:i'l'ux during the post -therapeutic course, and the rem aining 18 (5 3%) developed recurrent P. fakiparum infections during follow-up . Based on MSP-2 genoryping, most (14) of the recurrent P. [alcipannn infections we re identified as recrudescences
n" /wl~'- Ml1 l,i
'WI c~· "'tll tl~ "lI
ilf ,·It/,m'qui",'
No. uf subiccts "
~
2110 - tnu hut < J05
In
[)GW ill
53 (11- 8 35)
l'v
-j-
rtIWS for both species .
·19 (0 - 3 8 5)
7
i ·l
3
18 17
70
"7
le,
"
l"
22
~ I OO
con ccn truno n (nJ.:, ml ) of:
» u but
+ DCQ
·10
o
Assayed \l;' ilh C:Q
:-;(1, Of M,,\U'I.f.s ·
PI
(ef)
Day 0
plli~ "~·)
Tt\ 01..E2.
2
o
75
"7
P"
til
7 3 10 21 11 2 (O- h I O)
22
22
p \,
p'lr:l su lfadoxinc + pyrimethamine ) in human plasm a by two high-pcrforrnaucc liq uid chromatographic met hods. Th erapeutic J)m g ,\ J,' nil Ol'i ll/:, l .l , l ·l6 -1 51 . Felger, 1., T uvul, L. & Heck , II. (Jqq}). Plasmodiusn [alcip anun: a ra p id te chnique fo r gcnotvping the m ero zoite surface pr ot ein 2 . E X!,t'n'm t'lIltl l P,.1... Looa rces uwen, S, & '\X'hi te, N . J. (200 1). Id en tification of cryptic coin fccu on with Plamwdiwll ja/cip.mlJlI in pa tients present in g wi th vivax ma laria, Amaiam JOIln/al f,r Tropi.'al .\lcdidn e and lJy!:icIJe, 65 , '58S-'592 . Ohn, Mi rabd li-P rimd ah l, L , Kam asuta, C .• C ha nra kulkij, S. & K:.lin , K . C . (1997), D istinguish ing P!aHl/odium jo/cipar/l1l/ treatment failures from rein fect ion s by restri cti on fragment length polymorphism and po lymerase chain reac tion genotyping. Amm'call Jtl/lnl111 oj Tropic,,! Alt'd ici" .' (JII(/ f( Vgit'1lt',
s..
c..
57,130 -- 137.
Pu krittayakam ee . S.• Van ijo llonra. S.• Chantra, A " Clemens, R. & W11 ite , N . J. (19(.1.1) . Blond stage
an tim alari al efficacy of primaq uine in Plasmodium vious malaria, JOlll7lal of Inj ectiollS Diseases, 169, 932 -935. Rom bo , L. , Biorkrna n, A. , Segc, E. & Ericsson, O . ( 1986). Wh ole blon d conc en trations o f ch loroquine an d d eseth ylcb lor oq uin e during an d after trea tment of adult patients infec ted with Pll1smodiulII oiu ax, P. ooalc, an d P. maluriac. Tran sactions oj lilt: Rv.val S(1cit·ty vj T ntpit'al Akdici,14' and l (n :im c, SO, 76 3-766. Sarik abu thi , B., Kesch amrus, N ., Noeypauma ncnd . S.• \'(leid eknm m . E., Leimer, R , We m ~d u rfc r , W'. & Kolle, E . U . (1988). P lasm a concentrations of sulfad oxine in healthy and ma lar ia infected Thai subjects. Area Tropics , ~5 , 2 17-224 . Schuerman, C, 1. & Scbuurman-Tcn Bokkel H uin in k, A. ( 1929). Hen rnalaria-vraagsruk aan Java's zuidkust. l\ f>!dcJed inp,J1l va n dl!1I J)J~'lUl dcr l ·olk,t~.'z(mJJl€ ld in S~·derlaJll/sdl - l"di.:, 18. 120- 1-12. Siripoon, 1':., Snounou, G ., Yam ogkul, P., Na-Bangcbang, K. & Thaith ong, S. (200 2) . Cryptic Plastnodium [a lciparunt parasites in clinical P. nioux blood sa mples from Thailand . Tr ansactions oj tile Roy al S Od"H' T ropical Afo!did m: and Hygiene. 96, 70 -71. Smrkovski, L. L. . H offma n, S. L., Pumorno, H ussein, R. P., .\\asbar, S. & Kurniawan. L. (l9t13 ) . Chloroquine-resistant f'!JJl/wdillm j" fcipam m on the island o f Flo res. In donesia. T ransactions of tJIt' R lJ-"uJ ~\'{1ei" fY o] T ropical M .:d/d llt· und Hygiene, 77 , ·159 -462. Swellengrebel, N . H ., Sch uffner. W . & Swellengrebeld e Grauf, J, J\1. I I. ( 19 19) , D e ontvankelii kheid der anophelinen voor malaria-infecties in Ne derla ndschln die. Aledededi,,!:tW v an den Burgcr!ijk"·/1 Genevsk /Illgigell Dienst /11 Xi.'di.'I'!l11/dsch-llldie, 3, 1-62. T akken, w. & Knots, B. G . J. ( 19 90) . At.. taxonomic and bionomic review (If malari a vect or s of In d on esia . lr'U,I!t:l1ill,l,'t'lI A.l.rriwllll r~· Un iuersity Papfm. 90 , 9-62 . Tharn. J. •\\ ., Lee , S. H ., Tan , T . M ., T ing, R. C. & Karn , U. A . ( 199(;1). Detection and spec k s determi na tion of malaria parasites by peR: comparison with microscop y and the ParaSight- 1' and ICT ma laria Pf rests in th e clinical environment . Jo/(nlal 11 CNlIital ,\ Iiaoblltlogy, 3 7, 1 2 b 9~ 1273 . Wddekamm. E., Plozza-N onebrock. H.. Forgo . I. & D ubach, U . C . ( 198 2). Plasm a con cent ralion s of pyrimelhaminc and su lfad\lxine and evaluation of ph annactlkinctic data by computerized curve titting. Hullerill l~f tJu: tV'orid I-lt!alrh O rg,lIl iZar/fI11, 60, 1 15 - 12 2. \'('o rld H ealth Organization ( 19 73 ). Cllmwtlll.'r,lpy vi ,\falan'a 1111J Rt'sL~tl1l1a ttf Aun-mlJ Jana ls: Report oj a if 'HO SCI~·11tI/jC G/'(1JIp. Technical Repo rt Series No. 529. G eneva ; \X'H O . \'('m ld H ealth Organization (20 00) . The .\lu llagemtWt oj So::t't'l"l! .\l,llm i a, .rI P"Oet1l:u! flalldbot'k , 2nd Edn . G eneva : \'''BO .
or
