C OCCUSHusni SamadinDept. of Microbiology

Selected Bacterial InfectionsPharyngitisGroup A Strep - Streptococcus pyogenes(Many viruses also cause this)Pneumonia - Streptococcus pneumoniaeDiphtheria - Corynebacterium diphtheriae Tuberculosis - Mycobacterium tuberculosisWhooping cough - Bordetella pertussis

Streptococcus pyogenesGram positive streptococciCarried and transmitted from the throatIn Respiratory secretions

Streptococcus pneumoniaePneumococcusEncapsulatedOften secondary infection following influenza virus

Bacterial PneumoniaStreptococcus pneumoniae 2/3 of all pneumonia Risk Factors- old age, season, underlying viral infection, diabetes, alcohol and narcotic use Variable capsular antigen Purified component (capsule) vaccineOthers that cause pneumonia:Mycoplasma pneumoniaeLegionella pneumophila

Pharyngitis

Acute PharyngitisEtiologyViral >90% AdenovirusHerpes simplex virusCoxsackievirusBacterialGroup A beta-hemolytic streptococci (S. pyogenes)Mycoplasma pneumoniaeArcanobacterium hemolyticumNeisseria gonorrheaChlamydia pneumonia

Group A Streptococcal PharyngitisGram positive cocci in pairs or chainsClassified on the basis of hemolysis (, , or ) on blood agar plateClassified into groups on the basis of chemical composition of cell-wall polysaccharide (Lancefield classification)

Group A StrepCapsule -resistant to phagocytosisEnzymes damage host cells M protein adhesinThe M protein has many antigenic varietiesand thus, different strain of S.pyogenes cause repeat infections

Group A Streptococcus

Group A Beta Hemolytic Streptococcus

Group A StreptococciThe streptococcus most commonly associated with human diseaseCellular structure is importantCell wall has 3 major componentsPeptidoglycan: rigidityCarbohydrate: serologic group specificityProteins (M protein most important)Capsule made of hyaluronic acid

Streptococcal M ProteinCell surface antigen Major virulence factorAllows the organism to resist phagocytosis and intracellular killing by PMNsImmunity to group A strep infections is M-type specific

Structure of Group A Streptococcus

Extracellular Products of Group A StreptococcusHemolysins (2)Streptolysin S and Streptolysin OMeasurement of antibody against Streptolysin O (ASO) useful for retrospective diagnosis of streptococcal pharyngeal infectionStreptococcal pyrogenic exotoxinCauses rash of scarlet fever

Extracellular Products of Group A StreptococcusDeoxyribonucleasesDNAse Bantibody to this is a marker of prior infectionStreptokinasePrevents formation of fibrin clots, promotes spread of infectionHyaluronidasePromotes spread of the organism

Pharyngitis: StreptococcalClinical FeaturesFever, sore throat, headachePharyngeal/tonsillar inflammation (often exudates)Doughnut lesions- raised red or hemorrhagic with yellow centersTender anterior cervical adenopathyScarlatiniform rashAbsence of viral symptoms (rhinorrhea, cough, hoarseness)

Suppurative Complications of Group A Streptococcal PharyngitisOtitis mediaSinusitisPeritonsillar and retropharyngeal abscessesSuppurative cervical adenitis

Streptococcal Cervical Adenitis

Epidemiology of Streptococcal PharyngitisSpread by contact with respiratory secretionsPeaks in winter and springSchool age child (5-15 yo)Communicability highest during acute infectionPatient no longer contagious after 24 hours of antibioticsIf hospitalized, droplet precautions needed until no longer contagious

Nonsuppurative Complications of Group A StreptococcusAcute rheumatic feverfollows only streptococcal pharyngitis (not group A strep skin infections)Acute glomerulonephritisMay follow pharyngitis or skin infection (pyoderma)Nephritogenic strains

Group A Streptococcal Pharyngitis: DiagnosisRapid screening test: latex agglutination or ELISASpecificity high: usually >98%Sensitivity variable: 68-95% Gold standard: culture of swab of tonsils and posterior pharynx

Pneumococcal pneumonia(Streptococcus pneumoniae) Gram-positive diplococcusEncapsulated (>80 serotypes)

Susceptible populationElderlyPreviously illPhagocytic dysfunction (e.g., asplenic, sickle cell)Also cause meningitis, otitis mediaSensitive to optichin; autolysis by bile

Stages of pathogenesisEncounter - humans only, by respiratory dropletEntry - colonization of the oropharynx, aspiration into lung (pneumonia)Spread (extracellular)Pneumonia - blood culture can be positiveMeningitis - penetration of mucous membraneOtitis media- eustachian tube to middle earMultiplication Grows well in serous fluid in alveoli spaceEvade defensesCapsule--antiphagocyticsIgA protease

S. pneumoniaeDamageInflammation (peptidoglycan)Pneumolysin (binds cholesterol in the host cell membrane, lyse ciliated epithelial cells)Spread to new hosts - droplet/salivaVaccine23-valent polysaccharides (1983)adults at high risk7-valent polysaccharide conjugated vaccine (2000)Conjugated to a nontoxic diphtheria toxinChildren younger than 2 yr13-valent (Phase III trial-2008)

Stages of pathogenesisEncounter - respiratory dropletEntry - direct inhalation into LRT (ID=10)SPREAD - alveoli, but can spread throughout body seeding many tissuesMultiplicationGrows in phagosome of macrophageStrict aerobeVery slow in culture (24 hr doubling time)Evade defenses Inhibits phagolysosomal fusion

Scarlet FeverOccurs most commonly in association with pharyngitisRaspberry or strawberry tongueRashGeneralized fine, sandpapery scarlet erythema with accentuation in skin folds (Pastias lines)Circumoral pallorPalms and soles sparedTreatment same as strep pharyngitis

Strawberry Tongue in Scarlet Fever

Rash of Scarlet Fever

Acute Rheumatic FeverImmune mediated - ?humoralDiagnosis by Jones criteria5 major criteriaCarditisPolyarthritis (migratory)Sydenhams choreamuscular spasms, incoordination, weaknessSubcutaneous nodulespainless, firm, near bony prominencesErythema marginatum

Erythema Marginatum

Acute Rheumatic FeverMinor manifestationsClinical FindingsarthralgiafeverLaboratory FindingsElevated acute phase reactantserythrocyte sedimentation rateC-reactive proteinProlonged P-R interval on EKG

Acute Rheumatic FeverSupporting evidence of antecedent group A streptococcal infectionPositive throat culture or rapid streptococcal antigen testElevated or rising streptococcal antibody titer antistreptolysin O (ASO), antiDNAse BIf evidence of prior group A streptococcal infection, 2 major or one major and 2 minor manifestations indicates high probability of ARF

Acute Rheumatic FeverTherapyGoal: decrease inflammation, fever and toxicity and control heart failureTreatment may include anti-inflammatory agents and steroids depending on severity of illness

Poststreptococcal GlomerulonephritisDevelops about 10 days after pharyngitisImmune mediated damage to the kidney that results in renal dysfunctionNephritogenic strain of S. pyogenes

Poststreptococcal GlomerulonephritisClinical PresentationEdema, hypertension, and smoky or rusty colored urinePallor, lethargy, malaise, weakness, anorexia, headache and dull back painFever not prominentLaboratory FindingsAnemia, hematuria, proteinuriaUrinalysis with RBCs, WBCs and casts

Poststreptococcal GlomerulonephritisDiagnosisClinical history, physical findings, and confirmatory evidence of antecedent streptococcal infection (ASO or anti-DNAse B)TherapyPenicillin to eradicate the nephritogenic streptococci (erythromycin if allergic)Supportive care of complications

DiphtheriaEtiologic agent: Corynebacterium diphtheriagram positive rod (Chinese figures)nonspore formingstrains may be toxigenic or nontoxigenicexotoxin required for disease

Corynebacterium Diphtheriae

DiphtheriaEpidemiologyHumans are the only reserviorSpread by respiratory secretionsInfectivity lasts 2-6 weeks if untreatedIf treated, communicability usually lasts less than 4 daysEpidemic in former Soviet UnionIf hospitalized, droplet precautions

DiphtheriaClinical manifestationsFever of 100-102 FSore throatWeaknessDysphagia, headache, change of voice < 50%Bull neck, difficulty breathing < 10%

Bull Neck of Diphtheria

DiphtheriaPseudomembrane developmentUnlike exudate in Strep pharyngitis, extends beyond tonsilsDislodging causes bleeding

Pseudomembrane in Diptheria

DiphtheriaComplicationsObstruction of respiratory tract by pseudomembraneMyocarditisPolyneuritis (bulbar and peripheral)Mortality 10-30% usually due to cardiac damage

Predictors of Poor OutcomeExtent of pseudomembrane formationDelay between onset of local disease and treatmentDeath highest in first week of illnessBull-neck diphtheriaMyocarditis with severe arrhythmiasBulbar paralysisExtremes of age

Diphtheria: DiagnosisLaboratoryGram stain and cultureSpecimen from under membrane or membrane itselfTell lab suspect diphtheriaLofflers or tellurite selective media (Tindales agar)Test strains for toxigenicity

Diphtheria: TreatmentTreatment Equine antitoxin + penicillin G (erythromycin if PCN allergy)PreventionImmunization with formalin inactivated toxin

Diphtheria Public Health ConcernsShould report to public health immediatelyExposed persons at risk for infectionEpidemiologic studies will determine need for monitoring, booster immunization, antibiotics, etc to prevent secondary cases

PertussisEtiologic agent: Bordatella pertussisminute, gram negative coccobacillary organismssingles or pairsColonization of tracheal epithelial cells by B. pertussis

PertussisEpidemiologyHumans are the only known hostsTransmission by respiratory secretionsHighly contagious with an attack rate of 50 - 100% depending on nature of exposureChanges since vaccine introductionMore infections in adults and children < 1 year

PertussisClinical Manifestations (Classic)Catarrhal phase - mild URI symptomsmost contagiousParoxysmal phasedry, nonproductive coughseries of short expiratory bursts, followed by inspiratory gasp - whoopmay cause cyanosis and classically end in vomitingfever absent or minimalConvalescent phase

Paroxysm of Coughing in Pertussis

PertussisAtypical infection common in adults and others with partial immunityCatarrhal phase may be brief or unrecognized and the whoop and leukocytosis absentLeads to spread of unrecognized infectionSuspect this diagnosis in an adult with a cough > or = 2 weeks duration

PertussisComplications of infectionApneaSeizuresPneumoniaEncephalopathyDeathPremature infants at greatest risk for severe complications

PertussisDiagnosisGold standard: isolation of B. pertussis by culture in the setting of clinical illnessRequires special media: Bordet and Gengou (BG) mediumObtain by nasopharyngeal swab (calcium alginate) or nasal aspirationSlow growing (10-14 days)Antibody detection

PertussisTreatmentSupportive careErythromycin or Trimethoprim-sulfamethoxazole may shorten illness if given during catarrhal phase

PertussisPreventionBy vaccinationImmunity lasts about 12 yearsReportable diseaseProphylaxis for household and childcare contacts = erythromycin for 10-14 daysRecommended irrespective of age or immunization status

SummaryDiagnosis and management of Streptococcal pharyngitisComplication of group A strep infectionsDiagnosis and management of diphtheriaDiagnosis and management of pertussis