Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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InfluenzaandViralPneumonia
RodrigoCavallazzi,MDUniversityofLouisville
Hostedby Paul [email protected]
www.webbertraining.com March21,2019
InfluenzaandViralPneumonia
• Conflictsofinterest
• Siteinvestigatorforaclinicaltrialinvestigatinganewantiviralforadultswithrespiratorysyncytial virusinfection(Gilead)
• Siteinvestigatorforaclinicaltrialinvestigatinganewdrugforinfluenza(GlaxoSmithKline)
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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InfluenzaandViralPneumonia
• Objectives
• Reviewtheepidemiologyofthemainrespiratoryviruses• Highlightthedifficultytorecognizeaviralinfectiononclinical
grounds• Layoutatreatmentstrategyforpatientswithpneumoniaand
respiratoryviralinfection• Pointfuturedirections
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InfluenzaandViralPneumonia
• Outline• Cases• Epidemiology• Clinicalmanifestations• Treatment• Futuredirections
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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InfluenzaandViralPneumonia
• Case1• A65-year-oldladypresentstotheERinJanuarywiththe
suddenonsetofhightemperatures,pleuritic chestpainandshortnessofbreathoverthelast24hours.Shealsohasrunnynoseandmalaise.Sheadmittedhavingahouseholdcontactrecentlydiagnosedwithinfluenza.Onphysicalexamination,thepatientappearsillandhasatemperatureof39.9°C.Achestradiographshowsinfiltrateintherightmiddlelobe.Youdiagnosethepatientwithcommunity-acquiredpneumoniaanddecidetoadmitheronthebasisofvitalsignsandco-morbidities.Youobtainbloodandsputumcultures.Arapidinfluenzaimmunoassaysentbythetriagestaffmemberreturnsnegative.Whatactionsdoyoutake?
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InfluenzaandViralPneumonia
• Case1
A. Starttreatmentforcommunityacquiredbacterialpneumoniawithazithromycin only
B. Starttreatmentforcommunityacquiredbacterialpneumoniawithceftiaxone andazithromycin
C.Starttreatmentforcommunityacquiredbacterialpneumoniawithantibioticsandforinfluenzawithoseltamivir
D.Starttreatmentforcommunityacquiredbacterialpneumoniawithantibioticsandforinfluenzawithamantadine
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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InfluenzaandViralPneumonia
• Case1
A. Starttreatmentforcommunityacquiredbacterialpneumoniawithazithromycin only
B. Starttreatmentforcommunityacquiredbacterialpneumoniawithceftiaxone andazithromycin
C.Starttreatmentforcommunityacquiredbacterialpneumoniawithantibioticsandforinfluenzawithoseltamivir
D.Starttreatmentforcommunityacquiredbacterialpneumoniawithantibioticsandforinfluenzawithamantadine
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InfluenzaandViralPneumonia
• Case2• A41year-oldgentlemanpresentstotheERwithcough,
sputumproduction,pleuritic chestpain,andshortnessofbreathoverthelast2days.Hehadbeendiagnosedwithinfluenzainfection3weeksagoandreceivedatreatmentcoursewithoseltamivir.Onphysicalexamination,histemperatureis39°C,respiratoryrateis28breaths/min,bloodpressureis110/60mmHg,andheartrateis115beats/min.Onlungauscultationtherearecracklesontherightbase.TheCXRrevealsaninfiltrateintherightlowerlobe.InadditiontoStreptococcuspneumoniae,whichotherpathogenwouldbeofparticularconcerninthisscenario:
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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InfluenzaandViralPneumonia
• Case2
a)Klebsiella pneumoniaeb)Moraxella catarrhalisc)Pseudomonasaeruginosad)Acinetobacter baumanniie)Staphylococcusaureus
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InfluenzaandViralPneumonia
• Case2
a)Klebsiella pneumoniaeb)Moraxella catarrhalisc)Pseudomonasaeruginosad)Acinetobacter baumanniie)Staphylococcusaureus
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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InfluenzaandViralPneumonia
Epidemiology
• Respiratoryviralinfectionsareprevalent• Affectvulnerable,suchaschildren,elderly,andpeopleliving
indevelopingareas• Moleculartechniques• Pandemicsandoutbreaks
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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InfluenzaandViralPneumonia
EpidemiologyPandemicsandOutbreaks
• 1918to1919Spanishinfluenzapandemic• 1957H2N2Asianinfluenzapandemic• 1968H3N2HongKonginfluenzapandemic• 1977H1N1Russianinfluenzapandemic• 2009H1N1pandemic
– 201,200respiratorydeaths– 83,000cardiovasculardeaths– Mostofthesedeathsoccurredinpatientsyoungerthan65yearsold
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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InfluenzaandViralPneumonia
EpidemiologyPandemicsandOutbreaks
• February282013– Hospitalcontactedthe Hanoioffice oftheWHO• Patientpresentedwithunusualinfluenza-likevirus
Reilley Betal.NEngl JMed.2003May15;348(20):1951-2.
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InfluenzaandViralPneumonia
•Dr.CarloUrbani answeredthecall•Heworkedonthehospital,documentedfindings,arrangedforsamplestobetested
EpidemiologyPandemicsandOutbreaks
Reilley Betal.NEngl JMed.2003May15;348(20):1951-2.14
Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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InfluenzaandViralPneumonia
EpidemiologyPandemicsandOutbreaks
• Ofthefirst60patientswiththeillness,morethanhalfwerehealthcareworkers
• Manyofthestaffmembersmadethedifficultdecisiontoquarantinethemselves
• Somehealthcareworkers decidedtosleepinthehospital
Reilley Betal.NEngl JMed.2003May15;348(20):1951-2.15
InfluenzaandViralPneumonia
EpidemiologyPandemicsandOutbreaks
• OnMarch92013Dr.Urbani hadameetingwiththeViceMinisterofHealthofVietnam
• 4four-hourdiscussion– thehospitalwasquarantined• March11,hebegantohavesymptomsduringaflightto
Bangkok
Reilley Betal.NEngl JMed.2003May15;348(20):1951-2.16
Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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InfluenzaandViralPneumonia
EpidemiologyPandemicsandOutbreaks
• 2003:Severeacuterespiratorysyndrome– Urbani strainofsevereacuterespiratorysyndrome–associatedcoronavirus
• 2012:MiddleEastrespiratorysyndrome—coronavirus
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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InfluenzaandViralPneumonia
Immunocompetent vs immunosuppressed
Communityrespiratoryviruses
Epidemiology
EndogenousreactivationCommunity-acquiredrespiratoryviruses
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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InfluenzaandViralPneumonia
Proportionofviral infection
Community-acquiredpneumonia 24.5%
Hospital-acquiredpneumonia
Non-immunocompromised 11.2%
Immunocompromised 36.1%
Epidemiology
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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InfluenzaandViralPneumonia
Epidemiology
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721. 20
Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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InfluenzaandViralPneumonia
Virus is a “bystander” and does not have a pathogenic effect.
Although uncommon in adults, asymptomatic carriage of respiratory viruses occurs.
Virus has a pathogenic effect and is causing pneumonia in isolation.
Potential mechanisms include dysregulation of cytokines and chemokines, infection of epithelial cells in the lungs, and apoptosis.
Virus has a pathogenic effect and is causing pneumonia along with a bacterial pathogen
A study showed that the mortality for patients with community-acquired pneumonia and bacterial and viral co-infection is higher.
Virus caused a recent infection that prompted a secondary bacterial infection.
This occurs particularly with Streptococcus pneumoniae or Staphylococcus aureus infection following influenza infection.Lag time of 2 to 4 weeks between the viral and bacterial infection.Polymerase chain reaction test may remain positive for up to 5 weeks after a viral infection.
Epidemiology
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721. 21
InfluenzaandViralPneumonia
EpidemiologyCharacteristicsoftheviruses
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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InfluenzaandViralPneumonia
EpidemiologyInfluenza
Availableat:https://en.wikipedia.org/wiki/Discovery_and_development_of_neuraminidase_inhibitors
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InfluenzaandViralPneumonia
• RNAvirus• TypesA,B,andCbasedonitsnucleoproteinandmatrix
protein• InfluenzaA
– H1N1,H1N2,andH3N2basedonhemagglutinin andneuraminidase
• InfluenzaB– B/YamagataandtheB/Victorialineages
EpidemiologyInfluenza
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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InfluenzaandViralPneumonia
• Antigenicdrift:genemutationthatinfluenzaundergoeseveryyear
• Antigenicshift:newhemagglutinin orneuraminidasesubtypesareacquired
EpidemiologyInfluenza
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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InfluenzaandViralPneumonia
EpidemiologyInfluenza
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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InfluenzaandViralPneumonia
• Inoldersubjects,theburdenofRSVinfectionissimilartothatofinfluenza
• RSV–associatedhospitalizationrateper100,000person-years– age50to64years:12.8– >65years:86.1
• Cohortofhospitalizedpatients>65yearswithRSV:– 31%hadaninfiltrateonchestradiograph– 15%requiredICUadmission– 13%requiredmechanicalventilation– 8%died
EpidemiologyRespiratorySyncytial Virus
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721. 27
InfluenzaandViralPneumonia
• Mostcommoncauseofcommoncold(2to4timesperyearinadults)
• Sneezing,nasaldischarge,sorethroat,andlow-gradefever• Rhinovirustendstooccurmoreoftenintheearlyfallorspring• Mostcommonlyidentifiedpathogeninalargecohortofadult
patientshospitalizedwithcommunity-acquiredpneumoniaconductedintheUnitedStates
EpidemiologyRhinovirus
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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InfluenzaandViralPneumonia
• Winterandfollowsseasonalpatternsimilartoinfluenza• HCoV-229E,HCoV-NL63,HCoV-OC43,andHCoV-HKU1are
commoncauseofcommoncold• Adulthospitalizedpatientswithcoronavirus infectionare
oftenimmunocompromised,andpneumoniaisacommon• Severeacuterespiratorysyndromecoronavirus andMiddle
Eastrespiratorysyndromecoronavirus
EpidemiologyCoronavirus
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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InfluenzaandViralPneumonia
• Commoncauseofupperrespiratorytractsymptomsandconjunctivitis
• Adultpatientswithadenoviruspneumoniaarerelativelyyoung
• Causesseriousinfectioninimmunocompromised patients• Outbreaks
EpidemiologyAdenovirus
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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InfluenzaandViralPneumonia
• Mostinfectionsarecausedbyparainfluenza 1and3• Influenzalike symptomsareacommonmanifestationof
parainfluenza• Inchildren,commonpresentationsarecroupandbronchiolitis• Inhospitalizedpatients,ageranged61.5to77.5years• Ofthoseinfectedbyparainfluenza-3,59%hadaninfiltrateon
chestradiograph
EpidemiologyParainfluenza
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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InfluenzaandViralPneumonia
• 4.5%ofacuterespiratoryillnessesofadultsprospectivelyfollowedasoutpatients
• 4%ofpatientswithcommunity-acquiredpneumonia• MeanageinCAPandmetapneumovirus infection:62years
EpidemiologyMetapneumovirus
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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InfluenzaandViralPneumonia
• Morecommoninchildren• Morecommoninthewinter• Commonclinicalpresentationsincludeupperrespiratorytract
symptoms,bronchiolitis,andpneumonia• Detectedinacuterespiratoryillnessofadultswith
immunosuppression andchroniclungdisease
EpidemiologyHumanbocavirus
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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InfluenzaandViralPneumonia
• Cough• Fever• Fatigue• Myalgia• Runnynose• Wheezing• Dyspnea
ClinicalManifestationsInfluenza
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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InfluenzaandViralPneumonia
ClinicalManifestationsInfluenza
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721. 35
InfluenzaandViralPneumonia
• Symptomsorclinicalimpressionarenotenoughtoruleinorruleoutinfluenza
• Cliniciansfailedtoclinicallydiagnoseinfluenzainapproximatelytwo-thirdsofinfluenza-confirmedpatients
• Surveillancedata• Contactwithpersonswithacutefebrileillness• Recenttravel
ClinicalManifestationsInfluenza
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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InfluenzaandViralPneumonia
• Wheezing• Clinical-radiologicaldissociation• Cough(97%)• Dyspnea (95%)• Wheezing(73%)• Physicalexamination
– Wheezing(82%)– Temp>39°C(13%)
ClinicalManifestationsRespiratorySyncytial Virus
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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InfluenzaandViralPneumonia
• Nospecificclinicalmanifestations• Diagnosisofviralinfectioninpatientswithpneumoniarelies
ontherecognitionthatrespiratoryvirusesareacommonetiology
ClinicalManifestationsOtherViruses
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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RadiologicalManifestations
InfluenzaandViralPneumonia
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721. 39
RadiologicalManifestations
InfluenzaandViralPneumonia
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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RadiologicalManifestations
InfluenzaandViralPneumonia
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.41
Empiricaltreatmentforinfluenza
• Point-of-carePCRavailable• Influenzaseason
TreatmentApproachtothepatientwithcommunity-acquiredpneumonia
InfluenzaandViralPneumonia
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721. 43
• Immunocompetent vs Immunosuppressed• Riskfactors(e.g.pregnancy)• Severityofillness
TreatmentViralpathogen-directedtherapy
InfluenzaandViralPneumonia
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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TreatmentViralpathogen-directedtherapy
InfluenzaandViralPneumonia
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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Alleviation of symptoms 8 studies 2208 patients oseltamivir1746 patients in placebo
16.8 hours; 95% CI 8.4–25.1 hours
Pneumonia prevention 8 studies 2694 patients oseltamivir1758 in the placebo group
Risk difference of 1% [0.22%–1.49%]
Hospitalization prevention 7 studies 2663 patients oseltamivir1731 in the placebo group
Risk ratio 0.92; 95% CI 0.57–1.5
TreatmentViralpathogen-directedtherapy
Influenza
InfluenzaandViralPneumonia
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721. 46
Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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• Hospitalized• Severe,complicated,orprogressivedisease• Higherriskforinfluenzacomplications
• Benefitgreatestwhenitisstartedearly• Survivalbenefithasbeendemonstratedwithtreatmentupto
5daysaftersymptominitiation
TreatmentViralpathogen-directedtherapy
Influenza
InfluenzaandViralPneumonia
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.47
DiscontinuationofAntibiotics
• Clinicalpathway– Viralmicrobiologytestingplusprocalcitonin
InfluenzaandViralPneumonia
Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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Corticosteroidtherapy
InfluenzaandViralPneumonia
Siemieniuk RAetal.AnnInternMed.2015Oct6;163(7):519-28.49
CorticosteroidTherapy
InfluenzaandViralPneumonia
RodrigoCetal.JInfectDis.2015Jul 15;212(2):183-94.
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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CorticosteroidTherapy
InfluenzaandViralPneumonia
Annane Detal.IntensiveCareMed.2012Jan;38(1):29-39.51
InfluenzaandViralPneumonia
• Clinicalpathwaysusingpoint-of-caretests• Newantivirals
– FusioninhibitorforRSV– InhibitionofmRNAsynthesisforinfluenza
• Combinationtherapyforinfluenzaandotherviruses
FutureResearch
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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• Respiratoryviralinfectionsarecommon• 25%ofpatientswithcommunity-acquiredpneumonia• Alsocommoninhospital-acquiredpneumonia• Outbreaksandpandemics• Immunocompetent vs Immunosuppressed• Itisdifficulttodiagnoseinfluenzaorotherviralinfectionon
clinicalgrounds
Take-homepoints
InfluenzaandViralPneumonia
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• PCRbasedtests• Pathogendirectedtherapy
– Immunestatus– Riskfactors– Severityofillness
Take-homepoints
InfluenzaandViralPneumonia
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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THANKYOU
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Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville
AWebberTrainingTeleclass
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