Endemic Fungal Infections in HIV - Southeast AIDS Education & … · 2019-12-09 · The vast...
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1 Endemic Mycosis in HIV Infected Individuals Presented by: Mesfin Fransua, MD Associate Professor of Medicine Morehouse School of Medicine Principal Investigator Georgia AIDS Education and Training Center
Transcript of 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
