Transmission of dengue virus from deceased donors to solid organ transplant recipients: case report and literature review

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w w w . e l s e v i e r . c o m / l o c a t e / b j i d

The

Brazilian

Journal

of

INFECTIOUS

DISEASES

Case

report

Transmission

of

dengue

virus

from

deceased

donors

to

solid

organ

transplant

recipients:

case

report

and

literature

review

Fernando

Rosso

a,b,c,∗

_,

_Juan

_C.

_Pineda

b

_,

_Ana

_M.

_Sanz

c

_,

_Jorge

_A.

_Cedano

c

_,

Luis

A. Caicedo

d

a_Fundación_Valle_del_Lili,_Departamento_de_Medicina_Interna_–_Enfermedades_Infecciosas,_Cali,_Colombia b_Universidad_Icesi,_Facultad_de_Ciencias_de_la_Salud,_Cali,_Colombia

c_Fundación_Valle_del_Lili,_Centro_de_{Investigaciones}_Clínicas,_Cali,_Colombia d_Fundación_Valle_del_Lili,_División_de_Cirugía_de_Trasplante,_Cali,_Colombia

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received27October2017

Accepted1January2018

Availableonline19January2018

Keywords:

Denguevirus

Transmission

Solidorgantransplantation

Screening

a

b

s

t

r

a

c

t

Denguefeverisavector-transmittedviralinfection.Non-vectorialformsoftransmission

can occur through organ transplantation.We reviewed medicalrecords ofdonors and

recipientswithsuspecteddengueintheﬁrstpost-transplantweek.Weusedserologicand

molecularanalysistoconﬁrmtheinfection.Herein,wedescribefourcasesofdenguevirus

transmissionthroughsolidorgantransplantation.Therecipientshadpositiveserologyand

RT-PCR.Infectionindonorswasdetectedthroughserology.Allcasespresentedwithfever

withintheﬁrstweekaftertransplantation.Therewerenofatalcases.Afterthesecases,

weimplementeddenguescreeningwithNS1antigendetectionindonorsduringdengue

outbreaks,andnonewcasesweredetected.Intheliteraturereview,additionalcaseshad

beenpublishedthroughAugust2017.TransmissionofDengueviruscanoccurthroughorgan

donation.Inendemicregions,itisimportanttosuspectandscreenfordengueinfebrileand

thrombocytopenicrecipientsinthepostoperativeperiod.

openaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/

by-nc-nd/4.0/).

Background

Themost common mechanism of transmission ofdengue

virusisviaAedesaegyptimosquitoes.Thereare fewreports

ofotherroutesoftransmissionsuchaspercutaneous

trans-∗ _{Corresponding}_author.

E-mailaddress:frosso07@gmail.com(F.Rosso).

mission,bloodtransfusion1_or_bone_marrow_and_solid_organ

transplantation.2,3

Theriskofvirustransmissionbydonatingbloodororgans

isrelatedtothepresenceofasymptomaticcarriersandthe

shortincubationperiodthatprecedesviremia.Thereis

insuf-ﬁcientdatatoallowanaccurateestimationoftheincidenceof

denguetransmissionthroughtransplantedorgansin

develop-ingtropicalcountries,asdiagnostictestsfordetectinginfected

donorsisnotroutinelyperformed.

https://doi.org/10.1016/j.bjid.2018.01.001

(2)

This article describes four cases of solid organ

recipi-ents with signs and symptoms of dengue infection in the

postoperativeperiodfollowingtransplantation,inwhomthe

probabletransmissionmechanismwasthegraft.

Materials

and

methods

Thisisadescriptionofdenguevirusinfectioninfour

recip-ientsof solidorgan grafts takenfrom donors withdengue

infection.All casesreceivedcareatFundaciónValledelLili

(FVL)inCali,Colombia.TheInstitutionalCommitteeofEthics

inBiomedicalResearchapprovedthisstudy.

The diagnosis of dengue in donors and recipients was

made by detecting IgM and IgG antibodies and

antigene-mia(NS1).4 _In_recipients, _Reverse_{Transcriptase}_Polymerase

ChainReaction(RT-PCR)5_for_dengue_was_also_carried_out,_in

theMicrobiologyLaboratoryoftheUniversidadDelValle.In

2007, arapid chromatographic immunoassaywas used for

thequalitative detectionofIgGand IgMantibodies against

denguevirusinhumanblood(ACON®).In2010,NS1Ag+ABSD

BIOLINE(StandardDiagnostic®)immunochromatographytest

wasusedtodetectthevirusNS1antigenandantibodies(IgM

andIgG)inserum.Areviewoftheliteratureonnon-vectorial

transmissionduetoorgantransplantation,usingMeshterms

ispresented.

Results

Cases1and2

In 2007, cases 1 and 2 received a heart and liver

trans-plant,respectively,fromthesamedeceaseddonor,whodied

ofanintracranial hemorrhagesecondary toahypertensive

emergency inMedellin,Colombia. Afterthetransplant, the

institutionthatrescuedtheorgansnotiﬁedourhospitalthat

thedonorhadconsultedaweekbeforehisdeathwithfever

andmildthrombocytopenia.Duetotheepidemicseasonof

dengue,wetestedthedonorsamplesandwere positivefor

dengueIgMandIgG.

Recipient1

A 41-year-old male, was a recipient of a heart

trans-plant due to dilated cardiomyopathy (Table 1). After

transplantation, he was put on immunosuppression with

methylprednisolone, cyclosporine, and mycophenolate. On

the thirdpostoperativeday,the patientdevelopedmyalgia,

arthralgia, and general discomfort associated with

throm-bocytopenia, and lymphopenia, which did not improve by

decreasing thedoseofmycophenolate.Subsequently,there

was an elevation of transaminases, bilirubin, and

alka-line phosphatase. Positive IgM for dengue was detected

(Fig. 1) and RT-PCR was positive for DEN 3. On the

six-teenth day after surgery, the patient developed dengue

shock syndrome (DSS), severe thrombocytopenia, and a

transesophagealechocardiogramshowedacardiac

tampon-ade. A pericardiocentesis drained 1530mL of hemorrhagic

ﬂuid. Endomyocardial biopsies showed no rejection. The

bacterial cultures of the pericardial ﬂuid were negative.

Three weeks after the start of these symptoms,

lym-phopenia, and thrombocytopenia improved, the dose of

mycophenolate was increased, and the patient was

dis-charged.

Table1–Clinicalcharacteristicsoftransplantedpatientswithdenguevirusinfection.

Patient Donor Age(yr)/gender Clinicalmanifestations Organ Daysofonset Mortality Testresults Recipient1 A 41/male Myalgia,arthralgia.

Thrombocytopenia, lymphopenia DSS

Heart 8 Alive IgG−

IgM+

RT-PCR+(DEN3) Recipient2 53/male Fever,transient

encephalopathy. Thrombocytopenia, lymphopenia, anemia. Hepatitis.

Liver 2 Alive IgG−IgM+ RT-PCR+(DEN3)

Recipient3 B 31/female Fever,vomiting, diarrhea,jaundice. Thrombocytopenia, lymphopenia. Hepatitis.

Kidney 8 Alive IgG+IgM+

NS1+RT-PCR+(DEN4)

Recipient4 48/female Fever Kidney 4 Alive IgG−IgM+ NS1−PCR− DonorA – 40/male Mildfever,

thrombocytopenia, lymphopenia – – Deathintracranial hemorrhage IgM+ IgG+ DonorB – 32/male Asymptomatic – – Deathtraumatic

braininjuries

IgG− IgM− NS1+ +,Positiveresult;−,Negativeresult;CRD,chronickidneydisease;DSS,dengueshocksyndrome.

(3)

Transplant

Transplant Liver biopsy: Hepatitis

Liver doppler

ultrasonography: Normal Onset of symptoms

Onset of symptoms, fever, delirium, IgM + RT-PCR + (DEN 3) Pericardial effusion shock pericardiocentesis IgM + IgM, IgG (–) RT – PCR + Patient 1 Patient 2 Platelets patient 1 Platelets patient 2 400 350 300 250 200 150 100 50 0 0 2 4 6 8 10 Post-transplant days Platelet count 10 ^3/uL 12 14 16 18 20 22 24 26 28 30 32

Fig.1–Clinicalcourseofdengueinfectioninrecipients1and2.

Recipient2

A53-year-oldmale,hadundergonelivertransplantation

with-out complications. We initiated immunosuppression with

methylprednisolone,cyclosporine,andmycophenolateafter

surgery. Two days post-transplant the patient presented

fever, anemia, lymphopenia, thrombocytopenia, and

alter-ation of liver function tests. Subsequently, he developed

transientencephalopathy. Theinitialtestsfordenguewere

positive forIgM and negativeIgG. RT-PCR was positive for

serotypeDEN3.Duringhospitalization,thetransaminase

lev-elsfell,butthebilirubinandalkalinephosphataseincreased

until day 14, and the platelet count showed a tendency

to increase on day 10 (Fig. 1). Blood and urine cultures

werenegative.Graftthrombosisandobstructionofthebile

duct were ruled out using Doppler ultrasound and

endo-scopicretrogradecholangiopancreatographyrespectively.The

liver biopsy found lymphoplasmacytic inﬂammatory

inﬁl-trate,neutrophils,andcholestasis.Thediagnosiswasofacute

hepatitisdue todengue. The immunosuppressionregimen

wasnotchanged.Thepatientwasdischargedatday14

post-transplant.

Cases3and4

Cases 3 and 4 were recipients of a kidney transplant in

May2010,fromthesamedeceaseddonor,whopassedaway

due toa severe traumaticbraininjury. Due tothe

diagno-sis of dengue in recipient 3, serum from the donor was

tested post-transplant,detectingapositive dengueantigen

NS1.

Recipient3

A 31-year-old female, with chronic renal failure, received

a kidney transplant with no complications (Table 1). We

startedimmunosuppressionwithprednisolone,cyclosporine,

andmycophenolatesodiumaftertransplantation.Thepatient

wasdischargedontheﬁfthpost-transplantday.Ontheeighth

daypost-transplant,shewasreadmittedwithfever,vomiting,

diarrhea,andjaundice.Thepatientpresentedpainintheright

iliacfossa,anemia,andthrombocytopenia.Anultrasoundat

day15aftertransplantationshowedaperirenalhematomaof

1300mL,whichwasdrained.Laboratorytestsshowed

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Transplant

Transplant Patient 3

Patient 4

48 hours after onset of symptoms,

IgM +, IgG +, NS1 + Abdominal pain/ Peritenal hematoma/

Laparotomy Abdominal closure

RBCs and platelets transfusion

Fever (38.3 °C)/Positive urocultive: E. Coli/ Ciprofloxacin VO RT – PCR + (DEN 4) Elevated AST/ALT Platelet count 10 ^3/uL Post-transplant days 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 400 350 300 250 200 150 100 50 0 IgM + /IgG – / NS1 – /RT – PCR – Platelets patient 3 Platelets patient 4 Fig.2–Clinicalcourseofdengueinfectioninrecipients3and4.

oftransaminases,bilirubin,andLDH,withnoalterationsin

renalfunction.Thepatientrequiredtransfusionofredblood

cells, platelets, and fresh frozen plasma. The serology for

cytomegalovirusand toxoplasma antibodies were negative.

IgG,IgM,andthedengueNS1antigenwerepositive,and

sub-sequentlyRT-PCR(serotypeDEN4)wasalsopositive.Severe

denguewas diagnosed, duetohepatitisand major

hemor-rhagicmanifestations.Thepatientwas dischargedafter25

days and continued outpatient follow-up with satisfactory

evolution(Fig.2).

Recipient4

A48-year-oldfemalewhoreceivedakidneytransplantwith

no complications. She was started on immunosuppressive

treatment via prednisolone, cyclosporine,and

mycopheno-latesodium.Onthefourthdaypost-transplant,shedeveloped

fever, associated with mild anemia but with no other

hematologicalalteration.Bacterialcultureofbloodand

per-itoneal ﬂuid were negative. Escherichia coli was isolated in

a urine culture, and the patient received treatment with

oralciproﬂoxacin.Atday23post-transplant,thepatientwas

asymptomatic,withanelevationoftransaminases.Duetothe

historyofdengueinrecipient3,whohadalsoreceiveda

kid-neyfrom thesamedonor,diagnostic testswere performed,

whichwere positiveforIgMand negativeforIgG,NS1,and

RT-PCR(Fig.2).Duringtheoutpatientfollow-up,thepatient

becameasymptomatic,withadequatefunctioningofthegraft

andnormalizationoftheliverproﬁle.

Discussion

Hereinwereportedaseriesofhighlyprobabledonor

trans-mission ofdengueinfoursolidorgantransplantrecipients.

Dengueinfection inanearly postoperativeperiodcouldbe

amajorchallengeforinfectiousdiseases physiciansdueto

thepossiblevectorialandnon-vectorialtransmission.Wewill

brieﬂydiscussthisdifferentiation.

Vectorialversusnon-vectorialtransmissionofdengue

DenguevirusisanRNAviruswithfourdescribedserotypes

widely distributed in tropical regions where A. aegypti is

(5)

ahyperendemicareafordengue.Thisinfectionhasan

incu-bationperiodof7–14days,andmostoftheinfectedpatients

havemildsymptoms orare asymptomatic (78%).In

hyper-endemicareas,potentialrecipientscouldgetinfectedbefore

theirtransplant, andthose patientswilldevelopdengue in

anearlystageaftertransplantation.Inthosecases,noother

recipientsofthesamedonorwillgetthisinfection.In

con-trast, inthis hyperendemic regions potentialdonors could

getinfectedpriororganprocurationandcouldtransmitthe

dengue virus tothe recipient. In these cases,other

recipi-entsfromthesamedonorwillmorelikelypresentwithearly

dengueinfection.

Multiplesformsofnon-vectorialtransmissionhavebeen

reported:bloodproducts,solidorgantransplant,bonemarrow,

andnosocomialtransmissionthroughacontaminatedneedle

stick.7–9_Dengue_infection_due_to_blood_products_is_probably

themostreportednon-vectorialinfection,withaclinical

spec-trumsimilar toavectorialtransmission,although,mostof

theseinfectionsareunderreportedeveninendemiccountries

like Brazil and Puerto Rico.7 _Recently, _the _American

Asso-ciationofBloodBanksand theCentersofDiseasesControl

and Prevention haverecommended the screening ofblood

productsfordengue inendemic countries.10 _However,_this

recommendationisnotincludedintheguidelinesfororgan

transplantoftheAmericanSocietyofTransplantation.

Noso-comialtransmissionhasbeenreportedthroughneedlestick

injury from dengue infected patients.11 _Cases _of

vecto-rial transmitteddengue havebeen reported as nosocomial

acquiredinfectionaswell,inendemiccountriessuchasBrazil

andIndia, withsomepapersreporting thepresenceofthe

vectorinsidetheHospital.12,13

Non-vectorial transmission of dengue due to infected

donorshaverarelybeenreported.8_There_have_been_limited

descriptionsofpossiblenon-vectorialtransmissionofdengue

throughsolidorgantransplant(SOT).14_The_majority_of_reports

areclassiﬁedaspossibletransmissionduetolackofviralPCR

conﬁrmationinthedonor.Noneofthesecasesreportedhave

morethanonerecipientinfectedfromthesamedonor.

There-fore,avectorialinfectionpriortransplantcannotberuledout.

AsummaryofallcasesreportedispresentedinTable2.To

ourknowledge,ourreportistheﬁrsttodescribemorethan

onerecipientinfectedfromthesamedonorandisalsothe

largest.A central clue to suspecttransmission through an

infecteddonor,besidesviralPCR5_{conﬁrmation}_in_the_donor,_is

thepresenceofmorethanonerecipientinfectedbythesame

donor.Simultaneouslyvectorialinfection inmorethan one

recipientofthesamedonorwouldbeveryimprobable.

Clinicalcourseofdengueinfectionduetotransplantation

Theclinicalspectrumofvectorialdengueintransplant

recip-ients is broad, withsome studies suggestingthat there is

asimilarity to the non-transplantedpopulation.15,16 _In_the

possibleorgan transmission, moresevere caseshave been

reported.17 _Table ₂ _summarizes _the _most _important

clin-ical manifestations of the cases that have been reported.

All patientsdevelopsymptoms duringthe ﬁrst week

post-transplant. Fever and thrombocytopenia were the most

frequentﬁndings.Fatalcaseshave beenreported, one

kid-neyandonebonemarrowtransplants.Inourseries,non-fatal

caseswerepresented.Tworecipientspresentedsevere

man-ifestations, namely severe postoperative hemorrhage in a

kidney recipient and dengue shock syndrome in a

car-diacrecipient.Regardlessoftheimmunosuppressionstatus,

severe dengue could bemore frequentin acute secondary

infections,whicharemoreprobableintropicalareaswhere

thesepatientsarelikelyexposedtomultipleserotypesofthe

virus.6

There are no reports of graft rejection among dengue

infectedcases. Inourseries, patientswere followed upfor

morethanoneyearwithnohumoralorcellularsigniﬁcant

changesandmaintainedtheimmunosuppressivedose.

Screeningorgandonorsfordengueinfectionin hyperendemicregions

As previously stated, routine screening for dengue is not

recommended by the American Society ofTransplantation

guidelines.Ontheotherhand,ithasbeenjustrecently

recom-mendedbyboththeAmericanAssociationofBloodBanksand

bytheCentersofDiseasesControlandPreventionguidelines.

Fewdengueinfectedorgantransmissionshavebeenreported

asthisarboviruswasnotinthescopeofdonorrelated

infec-tions.However,anincreaseindenguecasesandtheriskof

anotherrecentarbovirus,suchasZikaandChikungunyacould

beasigniﬁcantthreatinorgandonation.Screeningfordengue

couldbeavailablethroughrapidtestdetectingNS1antigen.

Thisantigenishighlypreservedthroughthedifferentdengue

serotypesandcanbedetectedbeforeclinicalmanifestations

develop.Inmosttropicalregions,thisrapidtestisavailablein

combinationwithIgM/IgGantibodies.Thelowcostofthistest

couldfacilitatethescreeningintransplantprograms.ViralPCR

conﬁrmation5isnotavailableonregularbasisinmosttropical

countries.

WorldwidePCRavailabilityforthediagnosisofdengueis

verylow,5_but _some_rapid_tests_are _inexpensive_and_can_be

easilydone. Theturnaroundtime forhavingtheresultsof

NS1AgandIgG/IgMtestsis15–20minwithveryhigh

sensitiv-ityandspeciﬁcityinprimaryinfections.(NS1:Sens92%Spec:

98%;IgG/IgMSens:94%Spec:96%)However,inthesecondary

infectionsthesensitivitycandecreaseto80%.18

Inareaswheredengueisendemic,theabilitytorun

low-cost and high-performance tests, suchas the antigen NS1

test,4,19_during_outbreaks,_could_allow_the_detection_of_organ

donorswho areasymptomatic carriersofthevirus.20 _Early

detection indonorscould preventlate recipientinfections,

and could modifyclinicalmanagement reducing

complica-tions and mortality. Our institution decided to screen all

donorsduringoutbreakseasononlybecauseourcasesoccur

duringthisoutbreakperiods.

Morestudiesarerequiredtoaccuratelyrecommend

rou-tinescreeningorgandonorsfordenguevirusinhyperendemic

regionsduringoutbreaksandtoestablishcost-effectiveness,

sothepoolofdonorsisnotreducedwiththisadditional

test-ing.

Shouldweuseorgansfrominfecteddonors?

Thedecision touse organs from infecteddonorshas been

(6)

Table2–Denguetransmissionthroughtransplantationofaninfectedorgan.

Authors Age Organ Daysof onset

Symptoms Mortality Testrecipient Testdonor

Guptaetal.20 ₄₀ _Liver ₂ _Fever,

thrombocytopenia

Alive NS1+ NS1+

Lankaetal.17 ₅₁ _Bone_Marrow ₃ _Fever,

thrombocytopenia, hematochezia Decease (enterocolitis) IgM/IgG−NS1+PCR (DEN1) IgM/IgG+NS1+ PCR(DEN1)

Tanetal.9 ₂₃ _Kidney ₅ _Fever,

thrombocytopenia, Gibleeding, hematuria

Alive PCR+(DEN1) Notestreported

PresentStudy Case1

41 Heart 8 Fever,

thrombocytopenia, shock

Alive IgM+IgG−PCR

(DEN3) IgM+ IgG+a PresentStudy Case2 53 Liver 2 Fever, thrombocytopenia, anemia,hepatitis

Alive IgM+IgG−PCR

(DEN3) PresentStudy Case3 31 Kidney 8 Fever, thrombocytopenia, diarrhea,hepatitis

Alive IgM+IgG+NS1+

PCR+(DEN4)

IgM−IgG− NS1+b

PresentStudy Case4

48 Kidney 4 Fever Alive IgM+IgG−NS1−

PCR− PCR,polymerasechainreaction;NS1,non-structuralprotein1;DEN,dengueserotype.

a _Donor_of_case_1–2. b _Donor_of_case_3–4.

therisk/beneﬁtratio.Inourreviewofthereportedpossible

donorinfectionsmostauthorsdidnotreachtoanydeﬁnitive

conclusiononthis subject.Someauthorssuggesttoscreen

fordengue infection duringoutbreak periods21 _but _do _not

giveanyrecommendationregardingorganuse.Otherauthors

recommend that organs could be used in individual case

analysis.9

In ourown experience we have excluded patients with

positiveNS1antigenbutnotwithpositiveantibodiesand

neg-ativeantigen.Sincewestartedthisscreeningstrategy,wedid

nothaveany newdengue recipientsinfecteddue toorgan

transplant.Basedonourexperienceandthecasesreported,a

screeningmethodatlowcostcouldbefeasible.Inourreview,

fatalcaseshaveoccurredinlessthan20%ofpatients.

Never-theless,supportmeasurementscanbeeffectiveinreducing

denguemortalityandcomplications.

Acknowledgments

Dr.BeatrizParra,chiefoftheVirologyLaboratory,Department

ofMicrobiology,UniversidaddelValle,Cali,Colombia.

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1. WiwanitkitV.Nonvector-bornetransmissionmodesof dengue.JInfectDevCtries.2010;4:051–54.

2. TanFL-S,LohDLSK,PrabhakaranK,TambyahPA,YapH-K. Denguehemorrhagicfeverafterlivingdonorrenal transplantation.NephrolDialTransplant.2005; 20:1281.

3.TangnararatchakitK,TirapanichW,Tapaneya-OlarnW,etal. Severenonfebriledengueinfectioninanadolescentafter postoperativekidneytransplantation:acasereport. TransplantProc[Internet].2012;44:303–6.

4.GanVC,TanLK,LyeDC,etal.Diagnosingdengueatthe point-of-care:utilityofarapidcombineddiagnostickitin singapore.PLoSONE.2014;9:1–6.

5.WorldHealthOrganization(WHO)RegionalOfﬁcefor South-EastAsia.EstablishmentofPCRlaboratoryin developingcountries.2nded.WorldHealthOrganization (WHO)RegionalOfﬁceforSouth-EastAsia,editor;2016. 6.SimmonsCP,FarrarJJ,VinhN,WillsB.Currentconcepts

Dengue.NEnglJMed.2012;366:1423–32.

7.LanteriM,BuschM.Dengueinthecontextof“safeblood”and globalepidemiology:toscreenornottoscreen?NIH. 2012;52:1634–9.

8.WagnerD,deWithK,HuzlyD,etal.Nosocomialacquisition ofdengue.EmergInfectDis.2004;10:1872–3.

9.LankaS,AltuntaF,CamposRDM,etal.Denguevirus transmissionbycelldonoraftertraveltoSriLanka;Germany, 2013.EmergInfectDis.2014;20:1366–9.

10.AshshiAM.Theprevalenceofdenguevirusserotypesin asymptomaticblooddonorsrevealstheemergenceof serotype4inSaudiArabia.VirolJ.2017;14:107. 11.WazieresB,GilH,VuittonD,DupondJ-L.Nosocomial

transmissionofdenguefromaneedlestickinjury.Lancet. 1998;351:498.

12.HalsteadSB.Correspondencenosocomialdenguein health-careworkers.Lancet.2008:299.

13.Almeida-NunesJ,MarcilioI,OliveiraMS,etal. Hospital-acquiredvector-transmitteddenguefever:an overlookedproblem?InfectControlHospEpidemiol. 2016;37:1387–9.

14.Wilder-SmithA,ChenLH,MassadE,WilsonME.Threatof denguetobloodsafetyindengue-endemiccountries.Emerg InfectDis.2009;15:8–11.

(7)

15.GuptaRK,GuptaG,ChorasiyaVK,etal.Denguevirus transmissionfromlivingdonortorecipientinliver transplantation:acasereport.JClinExpHepatol. 2016;6:59–61.

16.daSilvaGB,JacintoCN,MartinianoLVM,etal.Denguefever amongrenaltransplantrecipients:aseriesof10casesina tropicalcountry.AmJTropMedHyg.2015;93:394–6. 17.WeerakkodyRM,PatrickJA,SheriffMHR.Denguefeverin

renaltransplantpatients:asystematicreviewofliterature. BMCNephrol.2017;18:15.

18.GuzmanMG,JaenischT,GaczkowskiR,etal.Multi-country evaluationofthesensitivityandspeciﬁcityoftwo

commercially-availableNS1ELISAassaysfordengue diagnosis.PLoSNeglTropDis.2010;4:2–11.

19.GreenwaldMA,KuehnertMJ,FishmanJA.Infectiousdisease transmissionduringorganandtissuetransplantation.Emerg InfectDis.2012;18:e1.

20.MachadoCM,LeviJE.Transplant-associatedandblood transfusion-associatedtropicalandparasiticinfections. InfectDisClinNorthAm.2012;26:225–41.

21.MaiaSHF,BrasilIRC,EsmeraldoRDM,PonteDaCN,Costa RCS,LiraRA.Severedengueintheearlypostoperativeperiod afterkidneytransplantation:twocasereportsfromHospital GeraldeFortaleza.RevSocBrasMedTrop.2015;48:783–5.