Early complicated schistosomiasis in a returning traveller: key contribution of new molecular diagnostic methods

HAL Id: hal-03209498

https://hal.archives-ouvertes.fr/hal-03209498

Submitted on 27 Apr 2021

HAL is a multi-disciplinary open access archive for the deposit and dissemination of sci- entific research documents, whether they are pub- lished or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.

L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Early complicated schistosomiasis in a returning traveller: key contribution of new molecular diagnostic

methods

S. Bonnefond, L. Cnops, Alexandre Duvignaud, E. Bottieau, Thierry Pistone, J. Clerinx, Denis Malvy

To cite this version:

S. Bonnefond, L. Cnops, Alexandre Duvignaud, E. Bottieau, Thierry Pistone, et al.. Early compli- cated schistosomiasis in a returning traveller: key contribution of new molecular diagnostic methods.

International Journal of Infectious Diseases, Elsevier, 2019, 79, pp.72-74. �10.1016/j.ijid.2018.11.018�.

�hal-03209498�

Case Report

Early complicated schistosomiasis in a returning traveller: Key contribution of new molecular diagnostic methods

Simon Bonnefond

**, Lieselotte Cnops

, Alexandre Duvignaud

, Emmanuel Bottieau

, Thierry Pistone

, Jan Clerinx

, Denis Malvy

*

aDivisionofClinicalTropicalMedicine,DepartmentforInfectiousandTropicalDiseases,BordeauxUniversityHospital,Bordeaux,France

bDepartmentofClinicalSciences,InstituteofTropicalMedicine,Antwerp,Belgium

ARTICLE INFO

Articlehistory:

Received9September2018

Receivedinrevisedform22November2018 Accepted22November2018

CorrespondingEditor:EskildPetersen,Aar- hus,Denmark

Keywords:

Earlyschistosomiasis Neuroschistosomiasis PCR

Traveller

ABSTRACT

Early schistosomiasis poses a serious diagnostic challenge, because current standard diagnostic techniquesbasedonserologyandeggmicroscopylacksensitivityattheinitialpresentation.Wereport spinalcordneuroschistosomiasisinatravellerdeveloping6weeksafterexposure.Thediagnosiswas confirmedbySchistosomamansoni-targetedreal-timePCRinbloodandcerebrospinalfluid,beforethe resultsofconventionalmethodsbecamepositive.Molecularassaysrepresentaparadigmshiftforthe difficultdiagnosisofearlyschistosomiasisandrelatedcomplications.

©2018TheAuthors.PublishedbyElsevierLtdonbehalfofInternationalSocietyforInfectiousDiseases.

ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by- nc-nd/4.0/).

Introduction

Neuroschistosomiasis is a rare, life-threatening or incapaci- tatingconditionthatusuallyoccursasalong-termcomplication followingtheresolutionoftheacuteinvasivedisease.However, more rarely it may occur early, overlapping or immediately followingthe acute phase of thedisease (Clerinx et al., 2006;

Ahmed et al., 2008). Early schistosomiasis poses a serious diagnosticchallenge,becausecurrentstandarddiagnostictech- niquesbasedonserologyandeggmicroscopylacksensitivityat the initial presentation. More accurate diagnosis is essential, since the prompt treatment of neuroschistosomiasis with corticosteroidscanpreventdebilitatingoutcomes.Morereliable tests includingmolecular methodsare needed toimprove the diagnosis of earlyschistosomiasis and to minimize the risk of complications.

Theobjectiveofthisstudywastoreporttheutilityofmolecular diagnosisinclinicalpracticefortheearlydetectionofschistoso- miasisandrelatedcomplications.

Casereport

In April 2012, a 63-year-old French male spent 1 month travellingintheIvoryCoast,wherehewentswimminginalakein theManRegiononMay1.AfterreturningtoFrance,hedevelopeda feveronday25afterthissinglefreshwaterexposure,followedby anelevationineosinophilcountonday29(0.8710⁹/l).When seenattheoutpatientclinicoftheUniversityHospitalofBordeaux onday36,hepresentedwithfebrileeosinophilia.Apartfromthe elevatedtemperatureof38.4C,thepatientwasasymptomaticand theclinicalexaminationwasnormal.Hisbloodeosinophilcount was elevated at 1.4110⁹/l (19.1%), while both ELISA (ELISA Bordier)andanindirecthaemagglutinationinhibitionassay(IHI) (Kit H.A.PFumouze) for Schistosomaantibodies werenegative.

Stooland urine microscopywas negativeforSchistosomaeggs.

Figure1depictstheclinicalcourse.

Despitetheonsetofamildright-sidedlowerlimbparesthesia on day39, the patienttravelled to Cameroon against medical advice.Fromday47,saddlehypoesthesiaandurinaryretention appeared, followed by bilateral lower limb paresthesia and rapidly progressive paraplegia. The patient wasrepatriated on day59.

Onreadmission,hepresentedflaccidparaplegiawithsensory levellossuptoL1, analhypotonia,andabsenceofdeeptendon reflexes in the lower limbs. Cerebrospinal fluid (CSF) analysis showed an elevated protein content (2.90g/l) and pleocytosis (79cells/mm³)withlymphocyticpredominance(94%).Spinalcord

*Correspondingauthorat:DivisionofClinicalTropicalMedicine,Departmentfor InfectiousandTropicalDiseases,PlaceAmélie-RabaLéon,F-33075BordeauxCedex, France.

**Correspondingauthor.

E-mailaddresses:simon.bonnefond@u-bordeaux.fr(S.Bonnefond), denis.malvy@chu-bordeaux.fr(D.Malvy).

https://doi.org/10.1016/j.ijid.2018.11.018

1201-9712/©2018TheAuthors.PublishedbyElsevierLtdonbehalfofInternationalSocietyforInfectiousDiseases.ThisisanopenaccessarticleundertheCCBY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).

InternationalJournalofInfectiousDiseases79(2019)72–74

ContentslistsavailableatScienceDirect

International Journal of Infectious Diseases

j o u r n a lh o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / i j i d

magneticresonanceimaging(MRI)revealedahyperintensesignal at levels from Th2 to Th8, in T2-weighted sequences, with a heterogeneousdiffusegranularenhancementfollowinggadolini- uminjection,aswellasalinearradicularcontrastenhancement (Supplementary material, Figure S1). At this stage, the serum schistosomeantibodyELISAassaywaspositive,but theschisto- someIHIantibodytestremainednegative.Again,noSchistosoma eggswererecoveredfromstoolorurine(Supplementarymaterial, TableS1).

Thepatientwaspromptlytreatedwithhigh-dosecorticoste- roids(methylprednisolone10mg/kg,threebolusinfusionsover 5days(days67,69,and71),followedbyprednisone2mg/kgdaily for8weeks).After2weeksofsteroids,praziquantel(60mg/kgin three fractioned doses over 1day) was given on day 74 to eliminate the matured schistosomes. After a second round of praziquanteland steroidstapered over 4months, neurological function had not improved despite intense hospital-based rehabilitation.MRI showedacomplete resolutionofthe spinal cordandradicularlesions.Whenlastseen5years later,hehad sufferedfrommultiplecomorbiditiesduetocompleteparaplegia sequelae, includingseveral hospitalizations for Fournier’sgan- grene,necroticcolitisrequiringcolostomy,andrecurrenturinary tract infections due to extended-spectrum beta-lactamase- producingbacterialstrains.

Prior to hospitalization, the patient was regularly screened forsexually transmittedinfections. Thus, storedserum samples

collectedprior toas well asduring thecourseof diseasewere analyzed retrospectively at the Institute of Tropical Medicine, Antwerp,Belgium.Sm1-7PCRtargetingthe121-bptandemrepeat sequence sensitive for Schistosoma mansoni complex group described by Wichmann et al. (2009), yielded a consistently positive signalfrom day21onwards.A Dra1-PCR targetingthe Dra1 tandem repeat sequence specific for Schistosoma haema- tobiumcomplexgroupremainednegativethroughout(Cnopsetal., 2013)(Figure1).ThissuggeststhatS.mansoniwastheinfective speciesinvolved.

Discussion

=Thepresenceoffebrileeosinophiliainnon-immunereturning travellerswitharecenthistoryoffreshwatercontactshouldalert physicians to the possibility of a schistosomal infection. Acute symptomsofschistosomiasistypicallyappear14to60daysafter primaryinfection(FerrariandMoreira,2011).Asillustratedinthis case,theprincipalchallengeistoconfirmthediagnosisofacute schistosomiasisatatimewhenstandarddiagnostictests,namely serologyandfaeces/urinemicroscopy,areoftenstillnegative.Ina prospectiveEuropean-widemulticenterstudyon38patientswith acuteschistosomiasis,S.mansoni-specificreal-timePCRinserum wasmoresensitive(92%)thanserology(70%)(Wichmannetal., 2013). A S. haematobium-specific real-time PCR in serum has shownpromisingresultsforconfirmingthediagnosisofurogenital Figure1.Timelinesofsymptoms,eosinophilia,serology,andgeneticmaterialdetection.ThistimelinehighlightstheperformanceofthePCRtechniquefordetecting neuroschistosomiasisassociatedwithanearlyectopiclesion.Eosinophilsdenotestheeosinophilcount(numberpercubicmillimetre);ELISA:enzyme-linkedimmunosorbent assay;IHI:indirecthaemagglutinationinhibitionassay;PCR:polymerasechainreaction;Sm1-7PCRtargetstheSm1-7geneofSchistosomamansonicomplexspecies;WB:

WesternblotIgG(LDBIODiagnostics).

S.Bonnefondetal./InternationalJournalofInfectiousDiseases79(2019)72–74 73

schistosomiasis, but there is a lack of data regarding S.

haematobiumacuteschistosomiasis(Cnopsetal.,2013).

Thispatientdevelopedfeverandeosinophilia,thehallmarkof earlyinvasiveinfection(‘Katayamafever’),soonafterexposure,but owingtonegativeserology,thediagnosiswasoverlookedatthat time; hence a debilitating neurological condition ensued. In contrast,PCRwasalreadypositiveonday21followingexposure, evenbeforetheonsetoffever(day25)andbeforetheeosinophil counthad startedtorise(day29),and wellbeforeschistosome serumantibodiescouldbedetected byELISAand Western blot testing(day60).Thisillustratestheexcellentdiagnosticpotential ofPCRintheveryearlystageofinfectionanditsclearsuperiority overserologyandschistosomeeggmicroscopy,bothintermsof sensitivityandforearlydiagnosticconfirmation(Wichmannetal., 2009,2013;Cnopsetal.,2012,2013).

Ofnote,thispatientlikelydevelopedspinalcordlesionsshortly afterschistosomematurationintoadultwormsand subsequent eggproduction.Indeed,MRIofthespinalcordshowedmultiple intramedullarylesionswithagranularpatternhighlysuggestiveof an inflammatory granulomatous reaction triggered by eggs embeddedinthespinalcordtissueandreleasedbyanectopically migrating pair of adult schistosomes, rather than a vasculitis process. Such a cell-mediated reaction producing peri-ovular granulomasisusuallyseenduringthechronicdiseasephase.Cases ofneuroschistosomiasisappearingduringtheacuteinfectionstage havebeenreportedonlyoccasionally(Clerinxetal.,2006;Ahmed etal.,2008).Theearlyappearanceofspinalcordschistosomiasis offersanargumentagainstdeferringanti-schistosomaltreatment fortoolongafterprimaryinfection.

Duetothecurrentstateofknowledgeonschistosomiasisand theemergenceof newreliable molecularmethods, S.mansoni- specificreal-timePCRassaysshouldhenceforwardbeconsidered as thecurrent gold standard for patientswith suspected early symptomaticschistosomiasis.Inparticular,moleculardiagnostic methods may considerably reduce the time lapse between infection and diagnostic confirmation, and strengthen post- exposuremanagement of non-symptomatic returning travellers witharecenthistoryoffreshwatercontact.

Financialsupport

Nofinancialsupporttodeclare.

Ethicalapproval

Approvalwasnotrequired.

Conflictofinterest

All authors report no conflict of interest. All authors have submittedtheICMJEFormforDisclosureofPotentialConflictsof Interest.Conflictsthattheeditorsconsiderrelevanttothecontent ofthemanuscripthavebeendisclosed.

AppendixA.Supplementarydata

Supplementarydataassociatedwiththisarticlecanbefound,in theonlineversion,athttps://doi.org/10.1016/j.ijid.2018.11.018.

References

Ahmed AF, Idris AS, KareemAM, Dawoud TA. Acutetoxemicschistosomiasis complicatedbyacuteflaccidparaplegiaduetoschistosomalmyeloradiculop- athyinSudan.SaudiMedJ2008;29(May(5)):770–3.

Clerinx J, van Gompel A, Lynen L, Ceulemans B. Early neuroschistosomiasis complicating Katayama syndrome. Emerg Infect Dis 2006;12(September (9)):1465–6.

CnopsL,TannichE,PolmanK,ClerinxJ,VanEsbroeckM.Schistosomareal-timePCR asdiagnostictoolforinternationaltravellersandmigrants.TropMedIntHealth 2012;17(October(10)):1208–16.

CnopsL,SoentjensP,ClerinxJ,VanEsbroeckM.ASchistosomahaematobium-specific real-timePCRfordiagnosisofurogenitalschistosomiasisinserumsamplesof internationaltravelersandmigrants.PLoSNeglTropDis2013;7(8):e2413.

FerrariTCA,MoreiraPRR.Neuroschistosomiasis:clinicalsymptomsandpathogen- esis.LancetNeurol2011;10(September(9)):853–64.

WichmannD,PanningM,QuackT,KrammeS,BurchardG-D,GreveldingC,etal.

Diagnosingschistosomiasisbydetectionofcell-freeparasiteDNAinhuman plasma.PLoSNeglTropDis2009;3(4):e422.

WichmannD,PoppertS,VonThienH,ClerinxJ,DieckmannS,JenseniusM,etal.

ProspectiveEuropean-widemulticentrestudyonabloodbasedreal-timePCR for thediagnosisof acuteschistosomiasis. BMC InfectDis2013;13(Janu- ary):55.

74 S.Bonnefondetal./InternationalJournalofInfectiousDiseases79(2019)72–74