Rev. Bras. Hematol. Hemoter. vol.36 número6

rev bras hematol hemoter. 2014;36(6):385–387

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

w w w . r b h h . o r g

Scientific

comment

We

need

to

talk

more

about

transfusion-transmitted

malaria

in

Plasmodium

vivax

endemic

areas

夽

Marcus

Vinícius

Guimarães

Lacerda

,

Wuelton

Marcelo

Monteiro

,

Márcia

Almeida

Araújo

Alexandre

,

Regina

Rebouc¸as

Mendes

Alho

,

Dagmar

Kiesslich

,

Nelson

Abrahim

Fraiji

a_{UniversidadedoEstadodoAmazonas(UEA),Manaus,AM,Brazil}

b_{Fundac¸ãodeMedicinaTropicalDr.HeitorVieiraDourado,Manaus,AM,Brazil}

c_{Fundac¸ãoHospitalardeHematologiaeHemoterapiadoAmazonas(HEMOAM),Manaus,AM,Brazil}

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Availableonline16September2014

Malariaisthemostwidespreadandrelevantparasiticdisease

worldwide;itisprimarilytransmittedbybitesofAnophelessp.,

butcanalsobetransmittedcongenitallyorthroughinfected

bloodtransfusions.Themajorspeciesinfectinghumansare

PlasmodiumfalciparumandP.vivax.Evenconsideringthatboth

speciesleadtoseveredisease,thefirsthasbeentraditionally

associatedtomoredeaths,mostlyintheAfricancontinent.

Novaccineisavailablesofarandthemajorcontroltoolsare

basedonearlydiagnosisandtreatment,andvectorcontrol.

In Brazil,after the eradication campaign started in the

1950s,malariabecamerestrictedtotheAmazonRegion,which

despiterepresenting50% ofthenational territoryholdsno

morethan10%ofthepopulation.Afterthe1990s,duetobetter

controlofP.falciparum,P.vivaxbecamethemainspecies,andis

responsibleforalmost85%ofthereportedcases,paralleling

thedecreaseintheoverallfatalityrate,themostsuccessful

goaloftheBrazilianMalariaControlProgram.1_However,this

parasiteisabletodevelopdormantstages(hypnozoites) in

DOIoforiginalarticle:http://dx.doi.org/10.1016/j.bjhh.2014.09.002.

夽

SeepaperbyFreitas&Duarteonpages394–402.

∗ _{Correspondingauthorat:Fundac¸ãodeMedicinaTropicalDr.HeitorVieiraDourado,Av.PedroTeixeira,25,DomPedro,69040-000Manaus,}

AM,Brazil.

E-mailaddress:marcuslacerda.br@gmail.com(M.V.G.Lacerda).

the liverleading tofrequentrelapses,therebyconfounding

officiallyreporteddata,sinceitisnotpossibletodistinguish

newinfectionsfromrelapse.Withrenewedinterestinmalaria

eradicationin2007,P.vivaxbecameasignificantchallengeas

nogoodtoolsareavailabletotacklehypnozoitesandtherefore,

relapse.2 _{In this context,uncommon waysoftransmission}

regain attention, such as transfusion-transmitted malaria,

whichiscapableofreintroducingtheparasiteinanarea

mov-ingtowarditselimination.

Itis doubtless that transfusion-transmittedP. falciparum

malaria is a real danger to a patient, who may develop

severediseaseanddie.However,inareassuchastheAmazon

region,whereP.vivaxpredominates,thereisageneral

con-sensus,duetothemisleadinginformationthatvivaxmalaria

ismorebenign, thattransfusion-transmittedmalaria isnot

soproblematicandthereforenotmuchpublichealth

atten-tionisgiventothisscenario.Recentdataconclusivelyshow

thatP.vivaxisactuallyassociatedtoseveredisease,3_namely

http://dx.doi.org/10.1016/j.bjhh.2014.09.005

1516-8484/©2014Associac¸ãoBrasileiradeHematologia,HemoterapiaeTerapiaCelular.PublishedbyElsevierEditoraLtda.Allrights

386

amongstpatientswithcomorbidities,whichfitspreciselythe

characteristicsofbloodtransfusionrecipients.Takingthisinto

account,itispossiblethatbothvivaxandfalciparumendemic

areasdeservesimilarattentionregardingthecontrolofthis

healthcareassociatedinfection.

OtherspecificcharacteristicsofP.vivaxwhichmakecontrol

oftransfusion-transmitted malaria even morecomplicated

are: (1) faster acquisition of immunity, leading to more

asymptomaticcasesthatcannotbedetectedduring

epidemi-ologicalscreeninginbloodbanks;(2)asP.vivaxinfectsonly

reticulocytes,parasitemiaisusuallylowand therefore,less

likelytobedetectedbytheroutinethickbloodsmear

exami-nation;(3)frequentmultiplerelapsesaredetectedessentially

throughactivecase searchesbecauseclone-specific

immu-nityleadstoasymptomaticrelapse;(4)chloroquineresistance

(includingreportsfromtheBrazilianAmazon)isabletoextend

periods of asymptomatic low parasitemia after beginning

treatment.2_{Thus,donorsimplicatedinthiskindof}

transmis-sionareoftensemi-immune,andwithparasitelevelsbelow

thedetectionthresholdofcurrentlyavailableassaysatblood

banks.Furthermore,inmanyendemicareasinLatinAmerica,

malariaisbecomingadiseaseofperi-urbanareas,wherethe

populationhasbeenconcentrated(ruralexodus).4_This

epi-demiologicaltransitiontakesPlasmodiumcarrierscloserto

theurbanbloodbanks,enablingmoreandmoredonationsof

contaminatedblood.

Thedichotomyofthis issuefocuseseitheronthe

infec-tionofthebloodrecipientifalesssensitivemethodisused

forPlasmodiumscreening,oroninsufficientbloodstocksif

a morerigid approach isadopted. Ingeneral,

transfusion-transmittedmalariadoes notcalltheattention ofnational

authorities.Since2002,officialdatafromBrazilreportedonly

fourcases.Whethertheverylownumberofcasesisdueto

under-reportingornot,isanissuethatneedstobeaddressed.

Thereisnoclearpolicyonthefollowingupofbloodrecipients

intheAmazon,andsincemostofthemalreadyliveinendemic

areas, new infections may not necessarily be reported as

transfusional.Nomatterwhatstrategyisadoptedtoprevent

transfusion-transmittedmalaria,itislikelythatthiskindof

transmissionmaystilloccur,andsomalariamustalwaysbe

consideredinanypatientwithapost-transfusionfebrile

ill-ness.

Inthenon-AmazonareaofBrazil,thepolicyisclear:no

patientcomingfromanendemicareaisacceptedasadonor.

However,recentdatapointtotheoccurrenceofPlasmodium

positivebloodinbloodbanksfromtheBrazilianSoutheast.5_If

thesesamplescomefromtravelersorfrompatientsincontact

withtheAtlanticForest,whereautochthonousPlasmodiumis

occasionallyfound,isstillamatterofdebate.

IntheAmazonarea,epidemiologicalscreeningof

poten-tialdonorshasbeentraditionallyadopted.Patientsreportinga

confirmedmalariainfectioninthepastsixmonthshavetheir

donationdeclined,aswellaspatientscomingfrom

munic-ipalitieswithanannualparasiteindex(API)higherthan49

cases/10,000inhabitants.6,7 _{Moreover,sinceno quantitative}

buffycoattest(QBC),amoresensitive techniquebasedon

thesearchofparasitesstainedwithafluorescentdyeinthe

concentratedbuffycoat,isavailable,somecenters perform

theroutine thickblood smearmicroscopy evaluationinall

samples.Themajorproblemswiththisscreeningstrategyis

thatasymptomaticP.vivaxrelapsesmayoccurevenaftersix

monthsoftheprimaryinfection;2_{API,despitebeingreliable}

inBrazil,isnotuniformthroughoutthewholemunicipality

andchangesconsiderablyfromoneyeartothenext(on-line

updatedofficialdata are notavailabletoblood banks); the

thickbloodsmearisnotassensitiveastoallowaproper

detec-tionoflowparasitemiainasymptomaticpatients,andtheuse

ofrapiddiagnostictestsisnotdifferent.

InthetimelypaperpublishedbyFreitas&Duarteinthis

issueoftheRevistaBrasileiradeHematologiaeHemoterapia,8

the first extensive evaluation of nine blood banks from

the Brazilian Amazon pointto non-uniform and imprecise

adoptedpractices.Thestandardizationofnationalpoliciesis

urgentandtheevaluatedimpactofthesepoliciesneedstobe

sharedwithsimilarendemicareasthroughouttheworld.

Maybe this is the right time to address more

aggres-sivemeasuresintheeliminationoftransfusion-transmitted

malaria,aspartofajointstrategytoeliminatemalariafrom

endemicareas.9_{Thefirstandmostimportantthingtodoisto}

estimatetherealburdenoftransfusion-transmittedmalaria.

Therefore,bettersurveillanceisurgentlyneeded,bothinthe

manymalariadiagnosticpostsspreadthroughoutthe

Ama-zonregionandinbloodbanks.Screeningforarecentblood

donationisrecommendedinmalariaservices.Inbloodbanks,

thickbloodsmearsareprobablynotthebestdiagnostictool

forasymptomatic donorsevenif thenumber ofread fields

inmicroscopyisincreased,becauseitistime-consumingand

presentslowsensitivityforthispurpose.Manystudieshave

suggestedpolymerasechainreaction(PCR)asamore

sensi-tivetooltodetectsmallconcentrationsofparasiteDNA.10_New

techniquessuchasreal-timePCRandloopmediated

isother-malamplification(LAMP),withcoststhathavedecreasedin

thelastfewyears,wouldbeidealinbloodbanks.11_Increasing

thevolumeofbloodforDNAextraction,andPCRperformed

in blood sample pools12 _{are interesting strategies as well,}

however,thesensitivityofthesetechniquesneedsadditional

evaluation. Serological markershave been abandoned asa

screening tool because of the low specificity, especially in

endemicareas.However,newepitopesarebeingdiscovered

as reasonably good markers of the asymptomatic

popula-tion intheAmazon.13 _{Thesemorespecificmarkersneedto}

be addressed inblood banks, because of their lower costs

comparedtoPCRandbecausetheyarecompatiblewith

simi-larserologiesalreadyperformedforotherinfectiousdiseases

inthesesettings.Furthermore,newmethodsare neededto

ensuretransfusionsafetywithoutrejectingpotentialdonors,

which would ensure safetransfusion without harming the

bloodsupply.14_{Notalongtimeago,gentianvioletwasadded}

tothebloodtocontroltransfusion-transmittedChagas’

dis-ease.TheactionagainstPlasmodiumseemstobesimilar,15

but gentianviolethasneverbeenstudiedforthispurpose.

Theeffectsofgentianviolet(withactionagainstother

para-sitessuchasToxoplasma,Trypanosomaand Leishmaniaor

evenawidespectrum)andthesafetyofantimalarialdrugson

bloodcomponentsneedtoberevisited.

MalariaisundercontrolinmostofLatinAmerica,however,

a new challenging goal is its elimination. Thus, all

possi-ble transmission routes need to be interrupted. In theory,

not many private blood banks exist inthe Brazilian

revbrashematolhemoter.2014;36(6):385–387

387

strategiesintermsofeffectivenessandefficiency.Thatwould

substantiallyaddinformationtoaneglectedprobleminmost

P.vivaxendemicareas.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

r

e

f

e

r

e

n

c

e

s

1. Oliveira-FerreiraJ,LacerdaMV,BrasilP,LadislauJL,TauilPL, Daniel-RibeiroCT.MalariainBrazil:anoverview.MalarJ. 2010;9:115.

2. MuellerI,GalinskiMR,BairdJK,CarltonJM,KocharDK, AlonsoPL,etal.KeygapsintheknowledgeofPlasmodium vivax,aneglectedhumanmalariaparasite.LancetInfectDis. 2009;9(9):555–66.

3. LacerdaMV,FragosoSC,AlecrimMG,AlexandreMA, MagalhãesBM,SiqueiraAM,etal.Postmortem characterizationofpatientswithclinicaldiagnosisof Plasmodiumvivaxmalaria:towhatextentdoesthisparasite kill?ClinInfectDis.2012;55(8):e67–74.

4. SaraivaMG,AmorimRD,MouraMA,Martinez-EspinosaFE, BarbosaMG.Urbanexpansionandspatialdistributionof malariainthemunicipalityofManausStateofAmazonas. RevSocBrasMedTrop.2009;42(5):515–22.

5. MaselliLM,LevyD,LaportaGZ,MonteiroAM,FukuyaLA, Ferreira-da-CruzMF,etal.DetectionofPlasmodium falciparumandPlasmodiumvivaxsubclinicalinfectionin non-endemicregion:implicationsforbloodtransfusionand malariaepidemiology.MalarJ.2014;13:224.

6. KiesslichD,AraújoMA,YurtseverSV,TorresK.Controleda maláriapós-transfusionalnaAmazôniaBrasileira:proposta demodificac¸ãodasnormastécnicas.InfEpidemiolSus. 1999;8(2):53–7.

7.MinistériodaSaúde.Portarian◦_{2.712/2013.Redefineo}

regulamentotécnicodeprocedimentoshemoterápicos.

DiárioOficialdaUnião2013;14nov.

8.FreitasDR,DuarteEC.Normativeevaluationofbloodbanksin theBrazilianAmazonregioninrespecttothepreventionof transfusion-transmittedmalaria.RevBrasHematolHemoter. 2014;36(6):394–402.

9.WorldHealthOrganization.WHOproceduresforcertification ofmalariaelimination.WklyEpidemiolRec.

2014;89(29):321–5.

10.TorresKL,FigueiredoDV,ZalisMG,Daniel-RibeiroCT,Alecrim W,Ferreira-da-CruzMF.Standardizationofaveryspecificand sensitivesinglePCRfordetectionofPlasmodiumvivaxinlow parasitizedindividualsanditsusefulnessforscreeningblood donors.ParasitolRes.2006;98(6):519–24.

11.SurabattulaR,VejandlaMP,MallepaddiPC,FaulstichK, PolavarapuR.Simple,rapid,inexpensiveplatformforthe diagnosisofmalariabyloopmediatedisothermal amplification(LAMP).ExpParasitol.2013;134(3):333–40.

12.FreitasDR,GomesLT,FontesCJ,TauilPL,PangLW,DuarteEC. Sensitivityofnested-PCRforPlasmodiumdetectioninpooled wholebloodsamplesanditsusefulnesstoblooddonor screeninginendemicareas.TransfusApherSci. 2014;50(2):242–6.

13.VersianiFG,AlmeidaME,MeloGC,VersianiFO,OrlandiPP, MariúbaLA,etal.HighlevelsofIgG3antiICB2-5in

Plasmodiumvivax-infectedindividualswhodidnotdevelop symptoms.MalarJ.2013;12:294.

14.TorresKL,MorescoMNS,SalesLR,AbranchesJS,Alexandre MAA,MalheiroA.Transfusion-transmittedmalariain endemiczone:epidemiologicalprofileofblooddonorsatthe Fundac¸ãoHEMOAManduseofrapiddiagnostictestsfor malariascreeninginManaus.RevBrasHematolHemoter. 2014;36(4):269–74.