Endemic Fungal Infections in HIV - Southeast AIDS Education & … · 2019-12-09 · The vast...

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EndemicMycosisinHIVInfectedIndividuals

Presentedby:

Mesfin Fransua,MD

AssociateProfessorofMedicineMorehouseSchoolofMedicine

PrincipalInvestigator

GeorgiaAIDSEducationandTrainingCenter

LearningObjectives

• Uponcompletionofthisactivity,participantsshouldbeableto:• DescribetheepidemiologyofHistoplasmosisandCoccidioidomycosisintheUSA

• EnumeratetheclinicalmanifestationofHistoplasmosisandCoccidioidomycosisinHIVinfectedpatients

• DiscusslaboratorytestutilizedinthediagnosisofHistoplasmosisandCoccidioidomycosis

• ApplycurrentguidelinestopreventandtreatHistoplasmosisandCoccidioidomycosisinthesettingofHIV

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Thisspeakerhasnosignificantfinancialrelationshipswithcommercialentitiestodisclose.

DisclosureofFinancialRelationships

This slide set has been peer-reviewed to ensure that there areno conflicts of interest represented in the presentation.

Case1

• A35yr oldAAMwithhistoryofAIDSnon-adherenttoARTpresentedwithfever,cough,SOBanddiarrhea.LastCD4countwas85(8%)andHIV-VLlog5.

• OnphysicalexamT38.5,PR112/m,BP90/60,RR20/m.Hehasulcersinthebuccalmucosa,cracklesonlungexamaswellashepatosplenomegaly

• LaboratorytestsincludeWBC3,000/mm3,HgB 7gm,urineandserumHistoplasmaAgwerepositiveandperipheralsmearrevealedbuddingyeastformsconfirmingdisseminatedHistoplasmosis

Whichoneofthefollowingisthepreferredinitialtreatmentforthispatient• A.Fluconazole400mgIVdaily• B.Fluconazole800mgIVdaily• C.Iitraconazole200mgPOTIDfor3daysthen200mgBIDfor12months

• D.AmphotericinBdeoxycholate 0.5mg/kgIVdailyplusFlucytosine• E.LiposomalAmphotericinB3mg/kgdaily

Case1continuation

AftercompletingLiposomalAmphotericininductiontreatmentfortwoweeks,hewasstartedonIitraconazoleformaintenancetreatmentwhichhehasbeentakingforthelast15months.CurrentmedicationsincludeDTG/ABC/3TC1tabdaily,BactrimDSdaily,Iitraconazole200mgBID.SixmonthsafterstartingART,hisCD4countis250(20%)andHIV-VLisundetected.BloodcultureisnegativeforHistoplasmaandurineHistoplama Agisalsonegative.

WhichofthefollowingistheappropriatenextstepregardingIitraconazolemaintenancetherapy?A. DecreasedoseofItraconazole to200mgdailyB. SwitchIitraconazoletoFluconazoletoreduceDDIC. StopItraconazoleD. ContinueItroconazole currentdoseuntilCD4countincreasesto300

Histoplasmosis

Etiology:HistoplasmacapsulatumNaturalreservoir:soil,batandavianhabitatThelungsprovideportalofentrywhensporeormyceliaareinhaledThevastmajorityofprimaryinfections(>90%)gounrecognizedmedically.Extentofexposureandhostimmunitydeterminesdiseaseprogression.

Epidemiology

Distribution-worldwideItisthemostprevalentendemicmycosisintheUnitedStatesMostendemicregionisfoundintheOhioandMississippiRivervalleys.Upto50millionpeopleintheUnitedStateshavebeeninfectedandupto500,000newinfectionseveryyear

DistributionofHistoplasmosisintheUSA

Clinicalfeatures

Varybasedonhostimmunityandthedegreeofexposuretothefungus.Acuteinfection

• Flulikesymptomswithpulmonarycomplaints,bronchopneumoniaoraninterstitialpneumonitis

Progressivedisseminatedhistoplasmosis

Progressivedisseminatedhistoplasmosisoccursintwoforms:AcutePDHmostlyseenininfantsandheavilyimmunocompromisedhosts.Patientspresentwithfever,fatigue,hepatosplenomegaly,pancytopenia.AIDSpatientsandorthosereceivingimmunosuppressivemedicationscanpresentwithoverwhelminginfectionmanifestedbyshock,respiratorydistress,hepaticandrenalfailure,obtundation, andcoagulopathy.ThemortalityinspiteofamphotericinBtreatmentapproaches50%insuchcasesChronicPDHisnotedmostlyinelderlypatientsandinmenmoreoften.Patientspresentwithpancytopenia,hepatosplenomegaly,elevatedliverenzymes,oropharyngealorGIulcers.Othersitesincludeskin,brainandadrenalglands

HistoplasmosisSkinlesions

HistoplasmosisSkinlesions

RISKFACTORSFORPROGRESSIVEDISSEMINATEDHISTOPLASMOSIS

HIV/AIDSandotherimmunosuppressivedisorders

Immunosuppressivemedications:steroids,methotrexate,TNF-blockingtherapies,otherimmunosuppressant

Extremesofage

IdiopathicCD4lymphocytopenia

APatientwithAIDSandDisseminatedHistoplasmosis

Diagnosis

Samples:sputum,tissue,bonemarrow,CSF,blood(lysescentrifugation)Directexamination:Geimisa/Wrightstainintra/extracellularyeastcellsCulture:moldat25º cconversiontoyeastinenrichedmediumat37ºcSerology:CF,IDandHistoplasmaantigenfrombloodandurine

PeripheralbloodsmearDisseminatedHisto

Histoplasmosis

EstimatedSensitivityofDiagnosticTestsforDisseminatedHistoplasmosisinpatientswithAIDS

TreatmentofLesssevereDisease

TreatmentofDisseminatedHistoplasmosis

TreatingHistoplasmaMeningitis

MonitoringResponse

AntigenconcentrationsfallwitheffectivetherapyandincreaseatthetimeofrelapseAntigenconcentrationsinurineorserumrisebyatleast2unitsin90percentofpatientsatthetimeofrelapse

DiscontinuingLong-TermSuppressiveTherapy

• Secondaryprophylaxiscanbediscontinuedwhenthepatientmeetsthefollowingcriteria:

• Receivedazoletherapyforlongerthan1year,and• Hasnegativefungalbloodcultures,and• Serum Histoplasma antigenislessthan2ng/mL,and• CD4counthasbeenhigherthan150cells/mm3 foratleast6monthsduetoantiretroviraltherapy.

Histoplasmosis

• RestartingLong-TermSuppressiveTherapy• Long-termsuppressivetherapyshouldberestartedifthepatient'sCD4countdecreasestoless150cells/mm

• TimingofInitiatingAntiretroviralTherapy• Patientsdiagnosedwithhistoplasmosisshouldbestartedonantiretroviraltherapyassoonaspossibleafterstartingantifungaltreatmentforhistoplasmosis

Case2

• 35y/omalewithAIDSandarecentCD4countof100cells/mm3presentswithcoughanddyspnea.HewaslosttofollowupanddidnottakeHIVmedicationsforfiveyears.HeisfromMexicobuthedeniestravellingoutsideGAsincehecame10yearsago.Physicalexaminationshowsatemperatureof38.6°C,cracklesinthelungfields,axillaryandinguinallymphadenopathy,hepatosplenomegaly,anda2by3cmulceratedlesiononhisface.

Case2continue

• Labs:CD4100(5%),HIV-VLlog6,WBC10K/mm3,neutrophils50%,Eosinophils10%,CXRDiffusebilateralinfiltrates,serumCryptococcusAgneg,askinbiopsyofthefaciallesiondemonstratesnumerousspherules(10to80micronsindiameter),manyofwhichcontainmultiplesmallerendospores(daughtercysts).

• BALculturestainalsoshowedspherulesconfirmingdiagnosisofsevereCoccidioidomycoisis.

• Whatisthepreferredinitialtreatmentforthispatient?• A.Itraconazole 200mgPOTIDfor3daysfollowedby200mgBID• B.Fluconazole800mgIVdaily• C.AmphotericinB• D.AmphotericinBandFlucysoine

Case2cont..

• ThepatienthasbeentakingFluconazoleformaintenancetreatmentforthepastsixmonths.HeisalsoonDTGplusTAF/FTCforabout5mothsandcurrentlyhisCD4is250/mm3(16%)andHIV-VLisundetectedbutCFABispositive.HeisfeelinggreatandwouldliketoknowifhestillneedstobeonFluconazole.

• Whatisyourrecommendationatthistime?• A.YesheneedstocontinuemaintenancetreatmentuntilhisCD4countis>500for6months

• B.HecanstopFluconazolenow• C.HecanstopFluconazoleaftersixmonthsifheremainsasymptomaticandserumCFAbisnegative

• D.HeshouldcontinuemaintenancetreatmentwithFluconazoleindefinitelybecauserelapseiscommon.

Coccidioidomycosis

Etiology:coccidioidesimmitisLocation:EndemictosouthernArizona,centralCalifornia,southwesternNewMexico,andwestTexas,Mexico,Central,andSouthAmericaMicro:tissue37º cspherulesfilledwithendospores,25º chyphae,arthroconidia

Coccidioidomycosis

• Coccidioidomycosisiscausedbyasoil-dwellingfungus, Coccidioidesimmitis,andencompassesawidespectrumofclinicaldiseasesamongindividualswithHIVinfection.

• Theincidenceofcoccidioidomycosis hasdecreasedintheeraofpotentantiretroviraltherapy,butwheninfectiondoesoccur,alowerCD4count(<250/mm3)predictsmoreseveredisease

Coccidioidomycosis

ClinicalManifestation PrimaryInfection

MostinfectionsareasymptomaticCoccidialPneumonia(fever,coughandchestpain)HemoptysisoccursmainlyinpatientswithapulmonarycavityArthralgias,Erythemanodosum

Desertbumps

HOSTRISKFACTORSFORCOMPLICATIONSANDDISEASESEVERITY

Majorsuppressionofcellularimmunity(HIV,organtransplant,steroids,Chemotherapyanti- TNF)DiabetesmellitusPregnancy(especiallythirdtrimester)

IndividualsofAfricanorPhilippinedescentmayalsohaveanincreasedriskofextrapulmonarycomplications.

CLINICALMANIFESTATIONS

• InthesettingofHIVinfection,theriskofdevelopingsymptomaticcoccidioidomycosis issignificantlyincreasedinthosewhohaveaCD4countlessthan250cells/mm3 andlive(orpreviouslylived)inaregionendemicforcoccidioidomycosis.

• PersonsathigherriskofacquiringdisseminateddiseaseincludeblackandFilipinomen,NativeAmericans,andpregnantwomenintheirsecondorthirdtrimester.

• PatientswithCD4cellcountgreaterthan250cells/mm3 typicallypresentwithlocalizedpulmonaryinfectionthatmimicscommunity-acquiredpneumonia.PatientswithlowerCD4countsmaydevelopdiffusepneumoniawithinfiltrates(thatmayresemble Pneumocystis pneumonia)ordisseminatedextrapulmonary infectionthatmayincludecutaneous,lymphnode,hepatic,orcentralnervoussystemmanifestations

Cavitary lungdiseaseCoccidioidomycosis

DIAGNOSIS

• Thediagnosisofcoccidioidomycosis canbeconfirmedbyidentifyingthecharacteristicspherulesthatcontainmultipleendosporesonawetmount,potassiumhydroxide(KOH)preparation,culture,oronahistopathologyspecimen.

• Apositiveserologytest(usuallyusingcomplementfixation)suggestsandsupportsthediagnosisofcoccidioidomycosis,thoughserologytestingislessreliableinimmunosuppressedpatients.

Coccidioidomycosisspherules

Coccidioidesimmitis arthroconidiaandhyphae

Serologictests

ImmunodiffusionkitthatmeasuresIgMandIgGantibodiesdirectedagainsttheorganismisthemostcommontestorderedcurrentlyCFgenerallyreservedforspecimensotherthanserum,especiallycerebrospinalfluidEIAhighlysensitivebutfalsepositiveresultscanbeseen.

Serologictests

Veryspecificbuttheyarerelativelyinsensitive,especiallyearlyinaninitialinfection.Mostpatientsloseserologicreactivitywithinmonthsofaninfectionunlessresiduallesionsareevidentorinfectionisactive.Repeatingtests,ifafirstserologictestisnegative,willimprovediagnosticsensitivity

TREATMENTOFMILDINFECTIONS

TreatingSevere,Non-MeningealInfection

TreatmentofMeningealInfection

DurationofMaintenanceTherapyforCoccidioidomycosis

References

• Uptodate.Com• NationalHIVcurriculumhttps://www.hiv.uw.edu• WWW.cdc.gov/fungal