UPPER RESPIRATORY TRACT INFECTION · • The upper respiratory tract: – Nasal cavity, sinuses, pharynx, and larynx – Infections are fairly common. – Usually nothing more than

UPPERRESPIRATORYTRACTINFECTION

OVERVIEW

• TolearntheepidemiologyandvariousclinicalpresentationofURT

• Toidentifythecommonetiologicalagentscausingthesesyndromes

• Tostudythelaboratorydiagnosisofthesesyndromes

• Todeterminetheantibioticofchoicefortreatment

WHYISTHISIMPORTANT?

• Therespiratorysystemisthemostcommonlyinfectedsystem.

• Healthcareproviderswillseemorerespiratoryinfectionsthananyothertype.

• Doctorswillprescribemoreantibioticsfortheseinfectionsthanforanyothertype.

THERESPIRATORYSYSTEM

• Amajorportalofentryforinfectiousorganisms

• Itisdividedintotwotracts– upperandlower.– Thedivisionisbasedonstructuresandfunctionsineachpart.

• Thetwopartshavedifferenttypesofinfection.

THERESPIRATORYSYSTEM

• Theupperrespiratorytract:– Nasalcavity,sinuses,pharynx,andlarynx– Infectionsarefairlycommon.– Usuallynothingmorethananirritation

• Thelowerrespiratorytract:– Lungsandbronchi– Infectionsaremoredangerous.– Canbeverydifficulttotreat

DEFENSESOFTHERESPIRATORYSYSTEM

• Thebodyhasavarietyofhostdefensemechanisms.– Innateimmuneresponse- thecellsandmechanismsthatdefendthehostfrominfectionbyotherorganisms,inanon-specificmanner

– Adaptiveimmunity- thebody'simmunesystempreparesitselfforfuturechallenges

• Therespiratorysystemhassignificantdefenses.– Theupperrespiratorytracthas:

• Mucociliaryescalator.• Coughing.

– Thelowerrespiratorytracthas:• Alveolarmacrophages.

PATHOGENSOFTHERESPIRATORYSYSTEM

§ Respiratorypathogensareeasilytransmittedfromhumantohuman.ú Theycirculatewithinacommunity.ú Infectionsspreadeasily.

§ Somerespiratorypathogensexistaspartofthenormalflora.

§ Othersareacquiredfromanimalsource,water,air,etc.§ Fungiarealsoasourceofrespiratoryinfection.

ú Usuallyinimmunocompromisedpatientsú MostdangerousareAspergillusand Pneumocystis.

PATHOGENSOFTHERESPIRATORYSYSTEM

• Somepathogensarerestrictedtocertainsites.

– Legionellaonlyinfectsthelung.

• Otherpathogenscauseinfectioninmultiplesites.

– Streptococcuscancause:

• Middleearinfections.

• Sinusitis.

• Pneumonia.

INFECTIONSOFTHEUPPERRESPIRATORYTRACT

• Laryngitis&Epiglottitis

• Otitismedia,mastoiditis,andsinusitis

• Pharyngitis

• Scarletfever

• Diphtheria

• Pertussis

LARYNGITIS• Laryngitis isswellingandirritation(inflammation)ofthevoicebox(larynx)thatisusuallyassociatedwithhoarsenessorlossofvoice– Rhinoviruses– Parainfluenzaviruses– Respiratorysyncytialvirus– Adenoviruses– Influenzaviruses– Measlesvirus– Mumpsvirus– Bordetellapertussis– Varicella-zostervirus.

EPIGLOTTITIS• Usuallyyoungunimmunizedchildrenpresentedwithdysphagia,andrespiratorydistress

• H.influenzae (++)• H.parainfluenzae• S.pneumoniae• StreptococcusgroupA• Viral

AntibioticTreatment:-Ceftriaxone/Cefotaxime- Amoxi/clav

OTITISOtitis media - general term for infection or inflammation of the ear - fluid/exudates/pus in the middle ear

ACUTEOTITISMEDIA• S.pneumoniae• H.influenzae• Streptococcuspyogenes• S.aureus• Moraxellacatarrhalis• Viralandfungal• Tympanocentesis incertaincircumstances:• Neonates<6weeks• FailureofTx• Immunosuppressed

ACUTEOTITISMEDIAAntibiotictreatment

• Antibioticisnotalwaysnecessary(symptomatictreatment).

• Amoxicillin isthefirstchoiceofantibiotictherapy;ifamoxicilliniscontraindicated,azithromycin istheappropriatefirst-linetherapy.

• ForAOMthatisunresponsivetoamoxicillinafter72hoursoftherapy,administeramoxicillin-clavulanateorazithromycin.

• Patientswithsignificant,persistentsymptomsonhigh-doseamoxicillin-clavulanateorazithromycinmayrespondtointramuscularceftriaxone.

SINUSITIS

SINUSITIS• Acutesinusitis

– Viral(+++)– S.pneumoniae– H.influenzae– M.catarrhalis– S.aureus(sphenoid)

• Chronicsinusitis– S.pneumoniae– H.influenzae– M.catarrhalis– Oralanaerobes– Fungus

Acutebacterialsinusitis.AxialCTscan(A)showsanair-fluidlevelintherightantrum.Theattenuationofthisfluidislessthanthatofmuscleandtypicallyiswaterysinussecretions.Thiscouldrepresentanacutelyobstructedsinus,asinuswithpoordrainageinachronicallysupine(unconscious)patient,orapatientwhohadarecentantralwashingforsinusitis.CoronalCTscan(B)showsatypicalair-fluidlevelintheleftantrumwithminimalmucosalthickeningandobstructionoftheostiomeatal unit.Somemucosaldiseaseisalsopresentintheleftethmoidandrightmaxillarysinuses.Clinically,thispatienthadacutesinusitis.(FromSomPM,CurtinHD:Headandneckimaging,ed5,Philadelphia,2011,Elsevier,2011,p174,Fig.3-10.)

Non-NeoplasticLesionsoftheSinonasalTractWenig,BruceM.,MD,AtlasofHeadandNeckPathology,Chapter2,9-80.e9Copyright©2016Copyright©2016byElsevier,Inc.Allrightsreserved.

Acutebacterialsinusitis.Axialcontrast-enhancedCTscansofthreedifferentpatients.A,Enhancementoftheinflamedmucosawithintheleftmaxillarysinus.Thereisazoneofwaterattenuationseparatingthismucosafromthebonywallofthesinus.Thiszoneissubmucosaledema.Therearealsowaterattenuationsecretionswithinthesinuscavitythatrepresentincreasedsurfacesecretionsfromtheinflamedmucosa.Thisisthetypicalpictureofsinusinflammation.(FromSomPM,CurtinHD:Headandneckimaging,ed5,Philadelphia,2011,Elsevier,2011,p168,Fig.3-2.)

Non-NeoplasticLesionsoftheSinonasalTractWenig,BruceM.,MD,AtlasofHeadandNeckPathology,Chapter2,9-80.e9Copyright©2016Copyright©2016byElsevier,Inc.Allrightsreserved.

SINUSITIS

• Acutesinusitis(durationrange,1–33days)usuallyiscausedbyaviralinfectionassociatedwiththecommoncold;symptomsincludenasalcongestion,purulentnasaldischarge,maxillarytoothpain,facialpain,fever,andearpain.

• Acutebacterialsinusitiscandevelopsecondarytoaviralupperrespiratoryinfection(URI);however,fewerthan2%ofviralURIsarecomplicatedbybacterialrhinosinusitis.

SINUSITIS

• Giventhesimilarradiographicappearanceofviralsinusitisandbacterialsinusitis,imagingisnothelpful.

• Antibioticsshouldbereservedforpatientswhosesymptomspersistfor>10days,aresevere(i.e.,fever>39°C,purulentnasaldischarge,facialpainfor>3consecutivedays),ordeteriorateafterinitialimprovement.

• Amoxicillin-clavulanateisthepreferredagentifantibioticsarenecessary

PHARYNGITIS

• Latefall,winter,earlyspring

• 5to15years(++)• erythema,edema,and/orexudates

• Tender,enlarged>1cmlymphnodes

• Fever>38.4ºC

PHARYNGITIS• Etiology• Viral isthemostcommon

• Enterovirus,HSV,EBV,HIV,Respiratoryviruses

• Bacterial• GroupAStreptococcus• Neisseriagonorrhoeae• Anaerobicbacteria(e.g.

Lemierre's syndrome)• Corynebacterium

diphtheriae

PHARYNGITIS• Pharyngitismostoftenisviral;aviraletiologyismorelikelyin

patientswithassociatedcough,nasalcongestion,conjunctivitis,ororalulcersorvesicles.

• PatientswithfewerthanthreeCentorcriteria(i.e.,feverbyhistory,tonsillarexudates,tenderanteriorcervicaladenopathy,absenceofcough)havealowprobabilityofgroupAstreptococcalinfectionanddonotrequirefurthertesting.

• Antibiotics(e.g.,penicillin,amoxicillin)shouldbeprescribedonlyifgroupAstreptococcalpharyngitisisconfirmed.

PHARYNGITIS

ú Treatment  Firstline

  PenicillinGBenzathine  1.2millionunitsIMx1(adults)

  Amoxicillin

  Alternatives  Firstgenerationoralcephalosporin  Macrolide(?)

  10daysoftreatment(?)

PERTUSSIS(WHOOPINGCOUGH)

PERTUSSIS

• CausedbyBordetellapertussis– Gram-negativecoccobacillus– Doesnotsurviveintheenvironment– Reservoirishumans.

• Symptomscanbesimilartothoseofacold.– Infectedadultsoftenspreadtheinfectiontoschoolsandnurseries.

PERTUSSIS

• Spreadbyairbornedropletsfrompatientsintheearlystages.

• Highlycontagious– Infects80-100%ofexposedsusceptibleindividuals.

– Spreadsrapidlyinschools,hospitals,offices,andhomes– justaboutanywhere.

PERTUSSIS• Mortalityishighestininfantsandchildrenunder

1yearold.• Immunizationagainstpertussisstartedinthe

1940s,andinthe60sinPortugal– ContinuestodayaspartofDTaP vaccination

• Pertussisappearstobemakingacomeback.– Epidemicsareoccurringevery3-5years.– Greatestnumbersofinfectionsareamong10-20

year-olds.– Peoplewhowerenotimmunized– Showsarelationshipbetweenlackofvaccination

andinfection

PERTUSSIS: Pathogenesis

• Bordetellapertussishasanaffinityforciliatedbronchialepithelium.

• Afterattaching,itproducesatrachealtoxin.– Immobilizesandprogressivelydestroystheciliated

cells.– Causespersistentcoughing

• Causedbytheinabilitytomovethemucusthatbuildsup

• Pertussisdoesnotinvadecellsoftherespiratorytractordeepertissues.

• Incubationperiodis7to10days.

PERTUSSIS:Pathogenesis

• Infectionhasthreestages:– CatarrhalStage1-2weeks

• Persistentperfuseandmucoidrhinorrhea(runnynose)

• Mayhavesneezing,malaise,andanorexia

• Mostcommunicableduringthisstage

– ParoxysmalStage1-6weeks

– ConvalescentStage3-6weeks

• Complicationofpertussiscanleadtosuperinfectionwith

Streptococcuspneumonia.

PERTUSSIS:Diagnosis

• Aconfirmedcaseisdefinedasoneofthefollowing:– AnycoughillnessinwhichB.pertussis isisolatedandcultured

– Acaseconsistentwiththeclinicalcasedefinitionconfirmedbypolymerasechainreaction(PCR)assayfindings

– Serologic antibodytitertestingisavailable,butoftenneedstobecomparedwithresults1-2weekslaterandthusisnotcommonlyhelpful

PERTUSSIS:Treatment

• Antibioticscanbeusedintheearlystages.

– Limitsthespreadofinfection

– Azithromycin isthechoiceforallages

• Oncetheparoxysmalstageisreached,therapy

isonlysupportive.

• Vaccinationisthebestoption.

VIRALINFECTIONSOFTHEUPPERRESPIRATORYTRACT

• RHINOVIRUSINFECTION-Thereareseveralhundredserotypesofrhinovirus.– Fewerthanhalfhavebeencharacterized.– 50%thathaveareallpicornaviruses.– Extremelysmall,non-enveloped,single-strandedRNAviruses

• Optimumtemperatureforpicornavirusgrowthis33˚C.– Thetemperatureinthenasopharynx

VIRALINFECTIONSOFTHEUPPERRESPIRATORYTRACT

• PARAINFLUENZA:Therearefourtypesofparainfluenzavirus.– Allbelongtotheparamyxovirusgroup.– Single-strandedenvelopedRNAviruses– Containhemagglutininandneuraminidase

• Transmissionandpathologysimilartoinfluenzavirus,buttherearedifferences.– Parainfluenzavirusreplicatesinthecytoplasm.– Influenzavirusreplicatesinthenucleus.

VIRALINFECTIONSOFTHEUPPERRESPIRATORYTRACT

• Parainfluenzaisgeneticallymorestablethaninfluenza.– Verylittlemutation– Littleantigenicdrift– Noantigenicshift

• Parainfluenza isaseriousproblemininfantsandsmallchildren.– Onlyatransitoryimmunitytoreinfection– Infectionbecomesmilderasthechildages.

Epstein-BarrVirus

38

Infectious mononucleosis and Epstein-Barr virus

• EBVisagammaherpesvirus– TwodistincttypesofEBV:

• type1(typeA):moreprevalentworldwide• type2(typeB):morecommoninAfrica

• Indevelopingcountries,subclinicalinfectioninchildhoodisvirtuallyuniversal.

• Indevelopedcountries,primaryinfectionmaybedelayeduntilearlyadultlife.

• Thevirusisacquiredfromasymptomaticexcretersviasaliva,bydropletinfection,orbykissing.

• EBVisnothighlycontagious,isolationisunnecessary.

DISEASEASSOCIATION1.InfectiousMononucleosis2.Burkitt'slymphoma3.Nasopharyngealcarcinoma4.Lymphoproliferativediseaseandlymphomaintheimmunosuppressed.

5.X-linkedlymphoproliferativesyndrome6.Chronicinfectiousmononucleosis7.OralleukoplakiainAIDSpatients8.ChronicinterstitialpneumonitisinAIDSpatients.

40

INFECTIOUSMONONUCLEOSIS• PrimaryEBVinfectionisusuallysubclinicalinchildhood.

Howeverinadolescentsandadults,thereisa50%chancethatthesyndromeofinfectiousmononucleosis(IM)willdevelop.

• IMisusuallyaself-limiteddiseasewhichconsistsoffever,lymphadenopathyandsplenomegaly.Insomepatientsjaundicemaybeseenwhichisduetohepatitis.Atypicallymphocytesarepresentintheblood.

• Complicationsoccurrarelybutmaybeseriouse.g.splenicrupture,meningoencephalitis,andpharyngealobstruction.

• Insomepatients,chronicIMmayoccurwhereeventuallythepatientdiesoflymphoproliferativediseaseorlymphoma.

41

INFECTIOUSMONONUCLEOSIS

Exudative pharyngotonsillitis42

INFECTIOUS MONONUCLEOSIS

• Whereas~90%ofcasesofIMareduetoEBV,5–10%ofcasesareduetoCytomegalovirus(CMV).

• CMVisthemostcommoncauseofheterophile-negativemononucleosis.

• Lesscommoncauses:rubella,Toxoplasma,HIV,herpesvirus6,hepatitisvirusesanddrugreactions.

COMPLICATIONS OF EPSTEIN–BARR VIRUS INFECTION

INFECTIOUSMONONUCLEOSIS

HepatosplenomegalyCervical lymphadenopathy 45

INFECTIOUSMONONUCLEOSIS

IMwithrashaftertreatmentwithamoxicillinorampicillin

46

Epstein–BarrVirus(MononucleosisandLymphoproliferativeDisorders)Katz,BenZ.,PrinciplesandPracticeofPediatricInfectiousDiseases,208,1059-1065.e6Copyright©2012©2012,ElsevierInc.Allrightsreserved.

MOLECULARBIOLOGY :LATENCY

• LatentlyinfectedBcellsaretheprimaryreservoirofEBVinthebody.

• >100geneproductsmaybeexpressedduringactiveviralreplication,only11areexpressedduringvirallatency.

• Inthisway,theviruslimitscytotoxicT-cellrecognitionofEBV-infectedcells.

48

Inchildrenunder10yearstheillnessismildandshort-lived,butinadultsover30yearsofageitcanbesevereandprolonged.InvestigationsAtypicallymphocytes arecommoninEBVinfectionbutalsooccurinothercausesofIM.Themostcommonlyuseddiagnosticcriteriaisthepresenceof50%lymphocytes(atleast10%atypical).AcuteEBVinfectiondiagnosisisusuallymade

bytheheterophilantibodytestand/ordetectionofanti-EBVVCAIgM.

Atypical lymphocytes.

Enlarged lymphocytes thathave abundantcytoplasm, vacuoles,and indentations ofthe cell membrane .

DIAGNOSIS

INFECTIOUSMONONUCLEOSIS:LAB

• A'heterophile'antibodyispresentduringtheacuteillnessandconvalescence,agglutinateserythrocytesofotherspecies,e.g.sheepandhorse.

• DetectedbytheclassicalPaul-Bunnelltitrationoramoreconvenientslidetestsuchasthe'Monotest'.

INFECTIOUSMONONUCLEOSIS:LAB

• SpecificEBVserology(immunofluorescence)canbeusedtoconfirmthediagnosisifnecessary.– AcuteinfectionischaracterizedbyIgMantibodiesagainsttheviralcapsid,antibodiestoEBVearlyantigenandtheinitialabsenceofantibodiestoEBVnuclearantigen(anti-EBNA).

– Seroconversionofanti-EBNAatapproximately1monthaftertheinitialillnessmayconfirmthediagnosisinretrospect.

• CNSinfectionsmaybediagnosedbydetectionofviralDNAincerebrospinalfluid.

ANTIBODIESINEBVINFECTION

Infection VCA IgG

VCA IgM

EA EBNA

No previous infection

- - - -

Acute infectionRecent infection

+

+

+

+/-

+/-

+/-

-

+/-

Past infection

+ - +/- +

response to viral capsid antigen (VCA) is divided because ofthe significant differences noted according to age of the patient.

Specific EBV antibodies

I.M.- TREATMENT

• Largelysymptomatic• Ifathroatcultureyieldsaβ-haemolyticStreptococcus,acourseofpenicillinshouldNOT beprescribed(colonization,notinfection).– ampicillinoramoxicillininthisconditioncommonlycausesanitchymacularrash,andshouldalsobeavoided.

• Whenpharyngealedemaissevere,ashortcourseofcorticosteroids,e.g.prednisolone30mgdailyfor5days,mayhelp.– Someadviseusingalsometronidazole

• AntiviralsarenotsufficientlyactiveagainstEBV.

I.M.- EVOLUTION

• Returntoworkorschoolisgovernedbythepatient'sphysicalfitness.

• Contactsportsshouldbeavoideduntilsplenomegalyhascompletelyresolvedbecauseofthedangerofsplenicrupture.

• 10%ofpatientswithIMsufferachronicrelapsingsyndrome.