Rodrigo Cavallazzi, MD - Webber Training · Dr. Rodrigo Cavallazzi, University of Louisville A...

Influenza and Viral PneumoniaDr.RodrigoCavallazzi, University of Louisville

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InfluenzaandViralPneumonia

RodrigoCavallazzi,MDUniversityofLouisville

Hostedby Paul [email protected]

www.webbertraining.com March21,2019


• Conflictsofinterest

• Siteinvestigatorforaclinicaltrialinvestigatinganewantiviralforadultswithrespiratorysyncytial virusinfection(Gilead)

• Siteinvestigatorforaclinicaltrialinvestigatinganewdrugforinfluenza(GlaxoSmithKline)

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• Objectives

• Reviewtheepidemiologyofthemainrespiratoryviruses• Highlightthedifficultytorecognizeaviralinfectiononclinical

grounds• Layoutatreatmentstrategyforpatientswithpneumoniaand

respiratoryviralinfection• Pointfuturedirections

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• Outline• Cases• Epidemiology• Clinicalmanifestations• Treatment• Futuredirections

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• Case1• A65-year-oldladypresentstotheERinJanuarywiththe

suddenonsetofhightemperatures,pleuritic chestpainandshortnessofbreathoverthelast24hours.Shealsohasrunnynoseandmalaise.Sheadmittedhavingahouseholdcontactrecentlydiagnosedwithinfluenza.Onphysicalexamination,thepatientappearsillandhasatemperatureof39.9°C.Achestradiographshowsinfiltrateintherightmiddlelobe.Youdiagnosethepatientwithcommunity-acquiredpneumoniaanddecidetoadmitheronthebasisofvitalsignsandco-morbidities.Youobtainbloodandsputumcultures.Arapidinfluenzaimmunoassaysentbythetriagestaffmemberreturnsnegative.Whatactionsdoyoutake?

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• Case1

A. Starttreatmentforcommunityacquiredbacterialpneumoniawithazithromycin only

B. Starttreatmentforcommunityacquiredbacterialpneumoniawithceftiaxone andazithromycin

C.Starttreatmentforcommunityacquiredbacterialpneumoniawithantibioticsandforinfluenzawithoseltamivir

D.Starttreatmentforcommunityacquiredbacterialpneumoniawithantibioticsandforinfluenzawithamantadine

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• Case1

A. Starttreatmentforcommunityacquiredbacterialpneumoniawithazithromycin only

B. Starttreatmentforcommunityacquiredbacterialpneumoniawithceftiaxone andazithromycin

C.Starttreatmentforcommunityacquiredbacterialpneumoniawithantibioticsandforinfluenzawithoseltamivir

D.Starttreatmentforcommunityacquiredbacterialpneumoniawithantibioticsandforinfluenzawithamantadine

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• 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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• Case2

a)Klebsiella pneumoniaeb)Moraxella catarrhalisc)Pseudomonasaeruginosad)Acinetobacter baumanniie)Staphylococcusaureus

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• Case2

a)Klebsiella pneumoniaeb)Moraxella catarrhalisc)Pseudomonasaeruginosad)Acinetobacter baumanniie)Staphylococcusaureus

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Epidemiology

• Respiratoryviralinfectionsareprevalent• Affectvulnerable,suchaschildren,elderly,andpeopleliving

indevelopingareas• Moleculartechniques• Pandemicsandoutbreaks

Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.

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EpidemiologyPandemicsandOutbreaks

• 1918to1919Spanishinfluenzapandemic• 1957H2N2Asianinfluenzapandemic• 1968H3N2HongKonginfluenzapandemic• 1977H1N1Russianinfluenzapandemic• 2009H1N1pandemic

– 201,200respiratorydeaths– 83,000cardiovasculardeaths– Mostofthesedeathsoccurredinpatientsyoungerthan65yearsold


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• February282013– Hospitalcontactedthe Hanoioffice oftheWHO• Patientpresentedwithunusualinfluenza-likevirus

Reilley Betal.NEngl JMed.2003May15;348(20):1951-2.

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•Dr.CarloUrbani answeredthecall•Heworkedonthehospital,documentedfindings,arrangedforsamplestobetested


Reilley Betal.NEngl JMed.2003May15;348(20):1951-2.14



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• Ofthefirst60patientswiththeillness,morethanhalfwerehealthcareworkers

• Manyofthestaffmembersmadethedifficultdecisiontoquarantinethemselves

• Somehealthcareworkers decidedtosleepinthehospital




• OnMarch92013Dr.Urbani hadameetingwiththeViceMinisterofHealthofVietnam

• 4four-hourdiscussion– thehospitalwasquarantined• March11,hebegantohavesymptomsduringaflightto

Bangkok




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• 2003:Severeacuterespiratorysyndrome– Urbani strainofsevereacuterespiratorysyndrome–associatedcoronavirus

• 2012:MiddleEastrespiratorysyndrome—coronavirus


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Immunocompetent vs immunosuppressed

Communityrespiratoryviruses

Epidemiology

EndogenousreactivationCommunity-acquiredrespiratoryviruses


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Proportionofviral infection

Community-acquiredpneumonia 24.5%

Hospital-acquiredpneumonia

Non-immunocompromised 11.2%

Immunocompromised 36.1%

Epidemiology


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Epidemiology

Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721. 20



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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



EpidemiologyCharacteristicsoftheviruses


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EpidemiologyInfluenza

Availableat:https://en.wikipedia.org/wiki/Discovery_and_development_of_neuraminidase_inhibitors

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• RNAvirus• TypesA,B,andCbasedonitsnucleoproteinandmatrix

protein• InfluenzaA

– H1N1,H1N2,andH3N2basedonhemagglutinin andneuraminidase

• InfluenzaB– B/YamagataandtheB/Victorialineages



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• Antigenicdrift:genemutationthatinfluenzaundergoeseveryyear

• Antigenicshift:newhemagglutinin orneuraminidasesubtypesareacquired



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• Inoldersubjects,theburdenofRSVinfectionissimilartothatofinfluenza

• RSV–associatedhospitalizationrateper100,000person-years– age50to64years:12.8– >65years:86.1

• Cohortofhospitalizedpatients>65yearswithRSV:– 31%hadaninfiltrateonchestradiograph– 15%requiredICUadmission– 13%requiredmechanicalventilation– 8%died

EpidemiologyRespiratorySyncytial Virus



• Mostcommoncauseofcommoncold(2to4timesperyearinadults)

• Sneezing,nasaldischarge,sorethroat,andlow-gradefever• Rhinovirustendstooccurmoreoftenintheearlyfallorspring• Mostcommonlyidentifiedpathogeninalargecohortofadult

patientshospitalizedwithcommunity-acquiredpneumoniaconductedintheUnitedStates

EpidemiologyRhinovirus


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• Winterandfollowsseasonalpatternsimilartoinfluenza• HCoV-229E,HCoV-NL63,HCoV-OC43,andHCoV-HKU1are

commoncauseofcommoncold• Adulthospitalizedpatientswithcoronavirus infectionare

oftenimmunocompromised,andpneumoniaisacommon• Severeacuterespiratorysyndromecoronavirus andMiddle

Eastrespiratorysyndromecoronavirus

EpidemiologyCoronavirus


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• Commoncauseofupperrespiratorytractsymptomsandconjunctivitis

• Adultpatientswithadenoviruspneumoniaarerelativelyyoung

• Causesseriousinfectioninimmunocompromised patients• Outbreaks

EpidemiologyAdenovirus


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• Mostinfectionsarecausedbyparainfluenza 1and3• Influenzalike symptomsareacommonmanifestationof

parainfluenza• Inchildren,commonpresentationsarecroupandbronchiolitis• Inhospitalizedpatients,ageranged61.5to77.5years• Ofthoseinfectedbyparainfluenza-3,59%hadaninfiltrateon

chestradiograph

EpidemiologyParainfluenza


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• 4.5%ofacuterespiratoryillnessesofadultsprospectivelyfollowedasoutpatients

• 4%ofpatientswithcommunity-acquiredpneumonia• MeanageinCAPandmetapneumovirus infection:62years

EpidemiologyMetapneumovirus


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• Morecommoninchildren• Morecommoninthewinter• Commonclinicalpresentationsincludeupperrespiratorytract

symptoms,bronchiolitis,andpneumonia• Detectedinacuterespiratoryillnessofadultswith

immunosuppression andchroniclungdisease

EpidemiologyHumanbocavirus


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• Cough• Fever• Fatigue• Myalgia• Runnynose• Wheezing• Dyspnea

ClinicalManifestationsInfluenza


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• Symptomsorclinicalimpressionarenotenoughtoruleinorruleoutinfluenza

• Cliniciansfailedtoclinicallydiagnoseinfluenzainapproximatelytwo-thirdsofinfluenza-confirmedpatients

• Surveillancedata• Contactwithpersonswithacutefebrileillness• Recenttravel



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• Wheezing• Clinical-radiologicaldissociation• Cough(97%)• Dyspnea (95%)• Wheezing(73%)• Physicalexamination

– Wheezing(82%)– Temp>39°C(13%)

ClinicalManifestationsRespiratorySyncytial Virus


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• Nospecificclinicalmanifestations• Diagnosisofviralinfectioninpatientswithpneumoniarelies

ontherecognitionthatrespiratoryvirusesareacommonetiology

ClinicalManifestationsOtherViruses


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RadiologicalManifestations






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Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.41

Empiricaltreatmentforinfluenza

• Point-of-carePCRavailable• Influenzaseason

TreatmentApproachtothepatientwithcommunity-acquiredpneumonia



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• Immunocompetent vs Immunosuppressed• Riskfactors(e.g.pregnancy)• Severityofillness

TreatmentViralpathogen-directedtherapy



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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


Influenza





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• Hospitalized• Severe,complicated,orprogressivedisease• Higherriskforinfluenzacomplications

• Benefitgreatestwhenitisstartedearly• Survivalbenefithasbeendemonstratedwithtreatmentupto

5daysaftersymptominitiation


Influenza


Cavallazzi R,RamirezJA.Clin ChestMed.2018Dec;39(4):703-721.47

DiscontinuationofAntibiotics

• Clinicalpathway– Viralmicrobiologytestingplusprocalcitonin



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Corticosteroidtherapy


Siemieniuk RAetal.AnnInternMed.2015Oct6;163(7):519-28.49

CorticosteroidTherapy


RodrigoCetal.JInfectDis.2015Jul 15;212(2):183-94.

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CorticosteroidTherapy


Annane Detal.IntensiveCareMed.2012Jan;38(1):29-39.51


• Clinicalpathwaysusingpoint-of-caretests• Newantivirals

– FusioninhibitorforRSV– InhibitionofmRNAsynthesisforinfluenza

• Combinationtherapyforinfluenzaandotherviruses

FutureResearch

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• Respiratoryviralinfectionsarecommon• 25%ofpatientswithcommunity-acquiredpneumonia• Alsocommoninhospital-acquiredpneumonia• Outbreaksandpandemics• Immunocompetent vs Immunosuppressed• Itisdifficulttodiagnoseinfluenzaorotherviralinfectionon

clinicalgrounds

Take-homepoints


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• PCRbasedtests• Pathogendirectedtherapy

– Immunestatus– Riskfactors– Severityofillness

Take-homepoints


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THANKYOU

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