Long term neurologic sequelae in a Mexican rocky mountain spotted fever case

brazjinfectdis2019;23(2):121–123

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

Long

term

neurologic

sequelae

in

a

Mexican

rocky

mountain

spotted

fever

case

Karla

Rossanet

Dzul-Rosado

_,

_Cesar

_{Lugo-Caballero}

_,

_Alejandra

_{Salcedo-Parra}

_,

Raymundo

Daniel

López-Soto

_,

_Álvaro

_A.

_{Faccini-Martínez}

a_{UniversidadAutónomadeYucatán,EmergingandRe-emergingDiseasesLaboratoryofRegionalResearchCenter“Dr.HideyoNoguchi”,}

Yucatán,Mexico

b_{UniversidadAutonomadeYucatán,GraduateandResearchUnit,NursingFaculty,Yucatán,Mexico} c_{IMSSCampeche,ServiciodeNeurologíaHospitalGeneral,Campeche,Mexico}

d_{UniversidadeFederaldoEspíritoSanto,HealthScienceCenter,PostgraduatePrograminInfectiousDiseases,Vitória,ES,Brazil}

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Articlehistory: Received4March2019 Accepted10April2019 Availableonline16May2019

Keywords:

Rockymountainspottedfever Rickettsiarickettsii

Neurologicmanifestations

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Duringthesecondhalfofthetwentiethcentury,neurologicsequelaeassociatedwith cen-tral nervous system impairmentcaused by Rickettsia rickettsiiwerestudied widely and exclusivelyintheUnitedStates.WepresentthecaseofaMexicanpediatricpatientwith neurologicsequelae10yearsafteranacuteinfectionbyR.rickettsii.

©2019SociedadeBrasileiradeInfectologia.PublishedbyElsevierEspa ˜na,S.L.U.Thisis anopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/ licenses/by-nc-nd/4.0/).

Rocky mountain spotted fever (RMSF), caused by Rickettsia rickettsii,isahighly lethaltick-borneinfectious disease.Its distributionislimitedtotheAmericas,wheredifferenttick speciessuchasDermacentor,RhipicephalusandAmblyommaare recognizedascompetentvectors.1

InMexico,casesofRMSFhavebeendescribedsince1940; theRhipicephalussanguineustickbeingthe mostresponsible foritstransmission.Aftermultipledecadesofinactivity,the diseaseagainemergedinthenorthernMexicanstatesatthe beginningofthetwentiethcentury,andcasesinYucatanin thelastdecade.2–4

Althoughtheseverityoftheinfectioniswellrecognized, thereareregionalvariationsoflethalitythatfluctuatefrom 5 to 10% in the United States, to approximately 30% in Mexico. Inappropriate medical management of the cases, differentialdiagnosisbetweenotherlesslethalrickettsioses,

∗ _{Correspondingauthor.}

E-mailaddress:karla.dzul@correo.uady.mx(K.R.Dzul-Rosado).

anddifferencesinvirulenceoftheR.rickettsiistrainswould explainthesevariations.1,2,5

Symptoms may include fever, headache, photophobia, general discomfort, myalgias, and petechial eruption that beginsinthewristsandanklesandextendstothetrunk.The rashmaynotbepresentin<15%ofpatientsandtheclassic triadoffever,headacheand rashisquite suggestiveofthe disease. Severe cases include meningoencephalitis, acute renalfailure,acuterespiratorydistresssyndrome,cutaneous necrosis,shock,andarrhythmias.6_{Severeneurologicsignsof}

RMSFincludefocalneurologicdeficitsasupperorlowermotor neuron lesions, hearing loss,neuragenic bladder,delirium, comaandgeneralizedtonic–clonicseizures.7

The characteristics and neurologic sequelae caused by RMSFwere widelystudied inthe secondhalf ofthe twen-tieth century in the United States. Although the illness is

https://doi.org/10.1016/j.bjid.2019.04.006

1413-8670/©2019SociedadeBrasileiradeInfectologia.PublishedbyElsevierEspa ˜na,S.L.U.ThisisanopenaccessarticleundertheCC BY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).

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also endemic in other countries of the Americas such as Mexico,CostaRica,Panama,Colombia,Brazil,andArgentina, neurologicinvolvementhavenotbeendocumentedinthese countries.ThisstudypresentsthecaseofaMexicanfemale withpersistentlanguageandpsychomotorneurologic seque-lae10yearsafterRickettsiarickettsiiacuteinfection.

Case

report

In 2007, a Mayan 9-year-old female from the indigenous community of Tahdziú, Yucatan, Mexico, living in highly unsanitaryconditions and constantly incontact with tick-infected undomesticated animals, seeks medical attention atthelocalhealthcenter ofhercommunitywithfever for oneday, receiving antipyretic treatmentatthat time. Over thefollowingthreedays,sheadditionallyexperienced asthe-nia,adynamia,headache,abdominalcolic,nausea,vomiting, anorexia,polyarthritisandpolymyositis.Onthesixthdayafter febrileonset,shebeganwithphotophobia,dysphagia, obtun-dation;andlater,generalizedtonic–clonicseizures,forwhich shewastransferredtotheGeneralHospitalAgostínO’Horan inMerida.Hereshewasadmittedtothepediatricservicewith probablediagnosisofneuroinfection.

Uponadmission to the hospital, the patient was found lethargic with a Glasgow coma scale of 8, showing vesti-bular signs, nucal rigidity positive Brudzinski and Kernig signs, hyperesthesia, ataxia, persistent fever above 39◦C (102.2◦F), anasarca, pulmonary edema, hepatomegaly, and maculopapularrashonthefaceandextremities.

Initial laboratory studies revealed leukocytosis, transaminitis and coagulopathy. Lumbar puncture showed no signs of neuroinfection (abundant red erythrocytes, decreased leukocytes, proteins at 137mg/dL). Serology for Dengue, Leptospira,and West NileVirus were negative.On the tenth day offebrile illness, IgM anti-Rickettsia rickettsii ImmunofluorescenceAssay(IFA)wasperformedandturned outpositivewithatiterof1:1024,aswellasamplificationand sequencingoftherickettsialgenefragment17kDathrough bloodsample,resulting98%homologoustoRickettsiarickettsii. Givengeneralworseningofthepatient’sstatus,shewas transferredtothe Pediatric IntensiveCareUnit, whereshe stayedforfivedaysincriticalcondition,duringwhichtime intravenous chloramphenicol was initiated with dosing at 50mg/kg/day,giveneveryfourhoursforfivedays.

Twenty-threedayslatersheisdischargedfromthe hospi-talwithneuromotordeficitsincludingdistalupperandlower extremity spasticity, as well as motor aphasia. With poor functional prognosis, she is prescribed Phenytoin as anti-convulsanttherapy, Citicolineforneuroprotection, physical therapy,andareferraltoneurologyforfollow-up.

In2017,10yearsafterherinitialclinical presentation,a homevisitismadebytheteamofresearchersaccompanied by a physician. The patient, now aged 19, is found con-scious,reactive,cooperative,withsardonicfacies,sialorrhea, globalaphasia,ataxicgait,lowerextremitymuscularatrophy, andupperextremityspasticityatgrade3onAshworthScale (Fig.1).

Themotherstatesthatthepatientdidnothave appropri-ateneurologicfollowupnorphysicaltherapyduetolimited

resourcesaswellaslongtravelrequiredtothehospitalwhere shewasreceivingcare.Shehadnothadanotherneurologic eventsinceherinitialhospitalization.Theneurologic seque-laeofthepatientlimitherabilitytoparticipateandbesocially accepted.

Discussion

Theclinicalpresentationinthispatientaresimilarintypeand frequencytothosedescribedintheliterature.1,2,6_The

neuro-logicalcomplicationsoccurinlessthan40%ofthepatients and include altered mentalstate, meningism, convulsions, neuralgias, confusion, photophobia, and psychosis. In the presentcase,allofthesewerepresentexceptpsychosis.

Itisworthmentioningthattheneurologicmanifestations aremostfrequentlyobservedinpatientswithprolonged hos-pitalcourse.8_{Thispatientwashospitalizedformorethan20}

days,fiveofwhichwereinthePediatricIntensiveCareUnit. Thepatientpresentedwithmultipleclinicaland epidemi-ologicalsignswarrantinghighsuspicionofthediagnosisof RMSF.Nonetheless,thiswasnotestablisheduntilthetenth dayofillness,whichcauseddelayintreatment,andas conse-quence,rapidclinicaldeterioration.

Doxycycline isthe treatment ofchoiceforchildren and adults of all ages with suspicion of RMSF and is effective inpreventionofmoreseveresequelaeofthisdiseasewhen administeredwithinthefirstfivedaysofsymptoms. Chloram-phenicolistheonlyalternativepharmacologictreatmentthat hasbeenusedtotreatRMSF.Nonetheless,theepidemiological studiessuggestthatpatientswithRMSFtreatedwith chloram-phenicolhavehigherriskofdeaththanpersonswhoreceived atetracycline.6 _{Chloramphenicolisassociatedwithadverse}

hematologiceffects,andclosemonitoringofbloodlevelsis requiredwithuseofthismedication9

Thelong-termreevaluationofthispatientrevealeddiffuse neurologic damage:cortex damageinvolving language and psychomotor components, which was significantly dimin-ished incomparisonwith herstatebeforeinfection.Motor sequelaewerenotedregardingspasticityinallfour extrem-itiesaswellasgaitreflectedspasticpattern.

TheneurologicsequelaereportedintheUnitedStates dur-ingthemiddleofthetwentiethcenturyincludedparaparesis, hearingloss,peripheralneuropathy,urinaryandfecal incon-tinence,cerebellar,vestibularandmotordysfunction,aswell aslanguagedelay.10

The variation in clinical manifestations between those reported and this patient isa productof lackof attention to neurologic sequelae,nutritional state, and other related complications,suchasthespasticparaparesisprogressedto spasticquadriparesis.

NeurologicsequelaerelatedtoRMSFhavebeendescribed, and the treatment forthem includerehabilitationinthree different areas: speech therapy (with aphasia), physical therapy (for paralysis,paraparesis and spasticity), and gait rehabilitation (depending on severity). In the case of this patient, unfortunately, is possible that the socioeconomic statuscausedthelackofneurologicfollowup,rehabilitation and therapy, as well as pharmacologic treatment, which togetherleadtoinadequateneurologicrecuperation.

brazj infect dis.2019;23(2):121–123

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Fig.1–PatientwithneurologicsequelaefromRickettsiarickettsii.(A)9-Year-oldpediatricpatientincriticalconditionduring initialillness(2007).(B)Maculopapularrashwithfacialedema(2007).(C)19-Year-oldpatientwithsardonicfacies(2017).(D) Rigidityandspasticityinupperextremities(2017).

Thetrainingofhealthcareprofessionalsisnecessaryand urgent,asthe suspicionofRMSFtogetherwithappropriate andtimelytreatmentarekeyinavoidingdeathsand unnec-essarycomplicationsofthedisease.

Thepromotionofhealthanddiseasepreventionconstitute thecoreofpublichealth.Onefundamentalelementofhealth promotionisitsanticipatorynature,whichseeksoutnotthe diseasedirectly,butratherthesocialdeterminantsofhealth. Withoutdoubt,povertyandmarginalizationarefactorsthat allowthe vector tofind its idealhostinorder tocontinue reproducingandprevail.Trainingandempoweringthe popu-lationregardingself-carefromdiseasestransmittedbyvectors inendemiczonesisthepathtoeradicatingthisdisease.

Acknowledgements

We thank the researchers Fernando Puerto-Manzano and Travis Gordon fortheir valuable contributions inthis case report.

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1. BiggsHM,BehraveshCB,BradleyKK,etal.Diagnosisand managementoftickbornerickettsialdiseases:rocky mountainspottedfeverandotherspottedfevergroup rickettsiosesehrlichioses,andanaplasmosisUnitedStates. MMWRRecommReports.2016;65:1–44.

2.Álvarez-HernándezG,RoldánJFG,MilanNSH,LashRR, BehraveshCB,PaddockCD.Rockymountainspottedfeverin Mexico:past,present,andfuture.LancetInfectDis. 2017;17:e189–96.

3.Zavala-CastroJE,Dzul-RosadoKR,JoséJ,LeónA,WalkerDH, Zavala-VelázquezJE.Anincreaseinhumancasesofspotted feverrickettsiosisinYucatan,Mexico.AmJTropMedHyg. 2008;79:907–10.

4.Zavala-CastroJE,Zavala-VelázquezJE,WalkerDH,etal.Fatal humaninfectionwithRickettsiarickettsii,Yucatán,Mexico. EmergInfectDis.2006;12:672–4.

5.Delgado-DelaMoraJ,Licona-EnríquezJD,Leyva-GastélumM, etal.AfatalcaseseriesofRockyMountainspottedfeverin Sonora,México.Biomédica.2018;38:69–76.

6.GottliebM,LongB,KoyfmanA.Theevaluationand managementofrockymountainspottedfeverinthe emergencydepartment:areviewoftheliterature.JEmerg Med.2018;55:42–50.

7.HorneyLF,WalkerDH.Meningoencephalitisasamajor manifestationofRockyMountainspottedfever.SouthMedJ. 2019;81:915–8.

8.Álvarez-HernándezG,Candia-PlataMdelC,Delgado-dela MoraJ,Acu ˜na-MeléndrezNH,Vargas-OrtegaAP,

Licona-EnríquezJD.FiebremaculosadelasMonta ˜nasRocosas enni ˜nosyadolescentesmexicanos:cuadroclínicoyfactores demortalidad.SaludPublicaMex.2016:385–92.

9.HolmanRC,PaddockCD,CurnsAT,KrebsJW,McQuistonJH, ChildsJE.Analysisofriskfactorsforfatalrockymountain spottedfever:evidenceforsuperiorityoftetracyclinesfor therapy.JInfectDis.2001;184:1437–44.

10.ArchibaldLK,SextonDJ.Long-termsequelaeofrocky mountainspottedfever.ClinInfectDis.1995;20:1122–5.