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Halofantrine and Primaquine for Radical Cure of Malaria in Irian Jaya, Indonesia D University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Public Health Resources Public Health Resources 1997 Halofantrine and primaquine for radical cure of malaria in Irian Jaya, Indonesia D. J. Fryauff U.S. NAMRU-2 (Jakarta), Box 3, APO AP 96520-8132, U.S.A. J. Kevin Baird U.S. NAMRU-2 (Jakarta), Box 3, APO AP 96520-8132, U.S.A., [email protected] H. Basri U.S. NAMRU-2 (Jakarta), Box 3, APO AP 96520-8132, U.S.A. I. Wiady U.S. NAMRU-2 (Jakarta), Box 3, APO AP 96520-8132, U.S.A. U.S. NAMRU-2 (Jakarta), Box 3, APO AP 96520-8132, U.S.A. See next page for additional authors Follow this and additional works at: http://digitalcommons.unl.edu/publichealthresources Fryauff, D. J.; Baird, J. Kevin; Basri, H.; Wiady, I.; U.S. NAMRU-2 (Jakarta), Box 3, APO AP 96520-8132, U.S.A.; Bangs, M. J.; Subianto, B.; Harjosuwarno, S.; Tjitra, E.; Richie, T. L.; and Hoffman, S. L., "Halofantrine and primaquine for radical cure of malaria in Irian Jaya, Indonesia" (1997). Public Health Resources. 376. http://digitalcommons.unl.edu/publichealthresources/376 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 D. J. Fryauff; J. Kevin Baird; H. Basri; I. Wiady; U.S. NAMRU-2 (Jakarta), Box 3, APO AP 96520-8132, U.S.A.; M. J. Bangs; B. Subianto; S. Harjosuwarno; E. Tjitra; T. L. Richie; and S. L. Hoffman This article is available at DigitalCommons@University of Nebraska - Lincoln: http://digitalcommons.unl.edu/ publichealthresources/376 Annals ofTropical Medicine &Parasitology, Vol. 91, No. 1, 7±16 (1997) Halofantrineandprimaquineforradicalcure ofmalaria inI rianJaya,Indonesia BY D.J. FRYAUFF*, J. K.BAIRD,H.BASRI, I. WIADY,PURNOMO,M.J. BANGS U.S.NAMRU-2 (Jakarta), Box3, APOAP 96520-8132,U.S.A. B.SUBIANTO,S.HARJOSUWARNO KANWILO f® ce, ProvincialHealth Service, Jayapura, IrianJaya, Indonesia E. TJITRA P3M,Kompleks LITBANGKES/P2MPLP,Ministry ofH ealth,Jakarta,Indonesia T. L. RICHIE U.S.NAMRU-2 (Jakarta), Box3, APOAP 96520-8132,U.S.A. AND S.L.HOFFMAN Naval MedicalResearchInstitute,Bethesda,Maryland, U.S.A. Received 30July19 96,Revised 29Au gust 1996, Accepted 2September 1996 Thecombinationof halofantrineandprim aquinetherapies wasevaluatedasaregimen forachievingradical cure offalciparumorvivaxm alariain Irian Jaya,Ind onesia, andcomparedw ith combined chloroquineand primaquine therapies. Thepatientsw hov olunteered forthestu dy{ adult, male, Indonesianim migrants withno prev iousexp osureto en demic malaria, normal glucose-6-phosphatedehy drogenase(G 6PD) activity,uncomplicated malariaillness, noprioruse ofantimalarials, andparasitaemiasof0.001%±1.0%} were randomized toreceive either halofantrine (24m gbase/kgbodyweight, in three equal dosesov er 12h) orchloroquine (25m gbase/kgbodyweightover 48h,in dosesof 10 ,10a nd5 mgbase/kgat 24 -h intervals). Eachp atientalso receive dconcurrentdaily primaquine (0.5m gbase/kgbodyweight)fo r14days followed byth esamedoseo nalternate daysto day 28 .Arecurrentparasitaemia duringthe28 d aysof follow-upconstituted drugfailure.Ofthe4 0cases offalciparummalaria and26cases ofvivaxmalaria treatedwithhalofa ntrine-primaquine, nonehad a recurrentparasitaemia (100%ef® cacy). In contrast,20 of30pa tientswithfalcip arumm alaria andthree of27 w ith vivaxm alariahad recurr entparasitaemiasafter chloroquine-primaquine, givingef® cacies of33%an d89%,respectively. Halofantrine-primaquinewas signi® cantlym oreeffecti veth anchloro quine-primaquine againstfalcip arumm alaria( P , 0.001)butwas similarly ef® caciousaga instv ivaxm alaria( P 5 0.23).O naverage,feverassoci atedw ithfalcip arumo rvivax malaria cleared 17hfasterw ithhalo fantrine-primaquine ( P , 0.01)alth oughthere were nosigni® cant differences ( P . 0.4)in parasite-clearance times between thetw oregimens. Thehalofantrine-primaquine regimen wasalsoassocia tedw itha morerap id andsigni® cantdeclinein malaria-related physical complaints. Radical cureo fmalaria, theelim inationof relapsing malaria is endemic. Instu diesthat both theb loodandtissuestages ofthepara- measureattack rates of malaria, with orwith- sitesbychemotherapeutic agents, is desirable out chemoprophylactic intervention,radical forprevention ofrecurrenceof infection after cure is also necessary to eliminate interference returningfrom worko rtravel in places where andconfoundingb yrelapsingorrecrudescing parasitaemias. Thereis currently nosingle *E-mail: [email protected]; fax: 1 6221 424 drugw ith suf® cientsafety anddualbloodand 4507. tissueschizonticidal propertiesto achieveth is 0003-4983/97/010007-10$9.00 Ó 1997Liverpoo lSchool ofTropical Medicine CarfaxPublishing Company 8 FRYAUFF ET AL. sterilizingcure. Most ofourstudies haveused fantrineandp rimaquineth erapies. A`control’ acombination ofthreedrugs, quinine,doxy- group, givensim ultaneouschloroquineand cyclineandp rimaquine, to achieveradical primaquinetherapies, wasincludedin orderto cures(Jones et al., 1994; Fryauff et al., 1995; estimate properly theeffect ofprimaquineon C.J.Church,T.L.Richie,C.Ohrt, E.Tjitra, patencyof parasitaemia after chloroquine B.Subianto,B.Sandjaya, E.Gomez,J. K. therapeutic failure. Baird,D.J. Fryauff andA .L.Richards, unpubl. obs.; C.K.Ohrt, T.Richie, H.Wid- jaja, G.D.Shanks, D.J.Fryauff, E.Tjitra, B. Sandjaja, H.Basri, W.Widjaja, C.Church PATIENTSANDMETHODS andG.Watt, unpubl. obs.). Thefrequ ent, prolongeddo sing of quinineandtheundesir- StudySite andP atients ableside effects of this drugcompoundth e Thestudywas conductedin then ew,trans- problemof full compliancewith therapy.The migrant villages ofArso XandX Iin north- drug-relatedillness whichfrequently occurs in eastern Irian Jaya, Indonesia (Baird et al., otherwise healthysubjects discouragestheir 1995b; Fryauff et al.,1995)betweenJanuary voluntary participation and, evenamong andJuly 1993. Most of theapproximately symptomatic cases, rigid supervisionand in- 2000village rshadm ovedfromJava,where the centives are required to achievecompletionof risk ofmalaria infectionhas beenab out1 therapy.Thedoxycyclineco mponentisgener- case/1000 0person-years since19 65(B aird et ally well-tolerated as longas it is nottakeno n al., 1995c). Pointprevalencesofmalaria atthe ane mpty stomachbut, dueto its effecton timeofenrolmentwere2 4%in Arso Xand bonegro wth andtoothd evelopment, useof 38%in Arso XI, despite theprovision of this drugis contra-indicatedin childrenu nder bednets to all householdsandtheavailability theageo f8years andin females during offree chloroquineat thevillag ehealth clinics. pregnancyan dnursing (Anon., 1995). Despite theeffectiveness ofthecurrent, quinine-based radical cure, there is interestin developinga Enrolment morebroad ly acceptable drugreg imenfor Overall, 123Javaneseor Balinesem ales aged radical cure of chloroquine-resistantmalaria. 15y ears, with uncomplicatedmalaria and Halofantrine is aneffe ctivean dgenerally parasitaemias of 0.001%±1.0%,quali® edfor well-tolerated bloodschizonticideforuse enrolment. Informedconsent, aphysical against chloroquine-resistant Plasmodium falci- examinationanda negativeq ualitativetest for parum in areas where me¯oqu ineresistan ce glucose-6-phosphate dehydrogenase(N ADPH has notalso developed(H ortonandParr, spot test; Sigma) precededth eir randomas- 1989). Trials havealso demonstratedthis drug signmentto oneo ftwotreatmentgroups: to behighly effectiveagainst P. vivax, includ- halofantrine-primaquine(H F-PQ)or ingthech loroquine-resistant strainsoccurring chloroquine-primaquine(CQ-PQ). in Irian Jaya,Indonesia (Parkinson et al., 1989; Baird et al., 1995a). Theuse ofhalofantrineas analtern ativecomponentfor achievingrad ical TreatmentandFollow-up cureo fmalaria wasthereforeex plored;theuse Patients in theHF-PQgroupre ceivedh alo- ofthree, well tolerateddosesof halofantrine fantrine(a total of24mgbase/kgbo dyweight, over12hmayb esubstantially betterthan in threeeq ual doses over 12h)andpri- treatmentwith 12poorly tolerateddoses of maquine(0.5 mgbase/kgbodyweightdaily for quinineover 4daysgivencon currently with 14days andthereafter onaltern ate daysuntil 20dosesofdoxycyclineover10days.Theaim day28 ). Those in theC Q-PQgroupwere ofthepresent studyw as to seeif falciparum givench loroquine(a total of 25mgbase/kg andvivaxm alaria acquiredin Irian Jaya could bodyweightin threeun equal doses over 48h: becuredradic ally byu sing combinedhalo- 10mg/kgonD ay0 ;10mg/kgonD ay1 ;and HALOFANTRINE-PRIMAQUINECURE FORMALARIA 9 5mg/kgonDay2 )andp rimaquine(as variancew as usedto compare age,w eight, above). Threedrugformulations wereused : density ofparasitaemia, PCT,frequencyof HalfanÒ (halofantrine;250mgbase hydrochlo- fever andFCTbetweenth etwotreatment ridesalt in uncoatedtab lets, kindly provided groups. Thein cidencedensity (ID)of physi- byDrJ. Horton ofSmithKline Beecham, calco mplaints not associatedw ith para- Brentford,U.K.); primaquine(1 5mgbase as sitaemia was calculatedfrom thenumber of diphosphate salt in coatedtab lets; Sano®- complaints reportedp er person-month of ob- Winthrop,NewY ork, NY); andR esochin Ò servation after discountingday-0co mplaints (chloroquine;150mgbase as phosphate salt in andthoseasso ciatedw ith unremittingor re- uncoatedtablets; P.T.Bayer Indonesia, current parasitaemias. Thedeclineof all Jakarta). Everydo se was supervisedby a physical complaints, includingthose associ- memberoftheresearchteam.Dry biscuits atedw ith theinitial
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