Upper Respiratory Infections: Focus on Group A Streptococcus, Pertussis and Diphtheria

Pharyngitis

Acute Pharyngitis Etiology –Viral >90% Adenovirus Herpes simplex virus Coxsackievirus –Bacterial Group A beta-hemolytic streptococci (S. pyogenes) Mycoplasma pneumoniae Arcanobacterium hemolyticum Neisseria gonorrhea Chlamydia pneumonia

Group A Streptococcal Pharyngitis Gram positive cocci in pairs or chains Classified on the basis of hemolysis ( , , or  ) on blood agar plate Classified into groups on the basis of chemical composition of cell-wall polysaccharide (Lancefield classification)

Group A Streptococcus

Group A Beta Hemolytic Streptococcus

Group A Streptococci The streptococcus most commonly associated with human disease Cellular structure is important –Cell wall has 3 major components Peptidoglycan: rigidity Carbohydrate: serologic group specificity Proteins (M protein most important) –Capsule made of hyaluronic acid

Streptococcal M Protein Cell surface antigen Major virulence factor Allows the organism to resist phagocytosis and intracellular killing by PMNs Immunity to group A strep infections is M-type specific

Structure of Group A Streptococcus

Extracellular Products of Group A Streptococcus Hemolysins (2) –Streptolysin S and Streptolysin O –Measurement of antibody against Streptolysin O (ASO) useful for retrospective diagnosis of streptococcal pharyngeal infection Streptococcal pyrogenic exotoxin –Causes rash of scarlet fever

Extracellular Products of Group A Streptococcus Deoxyribonucleases –DNAse B antibody to this is a marker of prior infection Streptokinase –Prevents formation of fibrin clots, promotes spread of infection Hyaluronidase –Promotes spread of the organism

Pharyngitis: Streptococcal Clinical Features –Fever, sore throat, headache –Pharyngeal/tonsillar inflammation (often exudates) Doughnut lesions- raised red or hemorrhagic with yellow centers –Tender anterior cervical adenopathy –Scarlatiniform rash –Absence of viral symptoms (rhinorrhea, cough, hoarseness)

Suppurative Complications of Group A Streptococcal Pharyngitis Otitis media Sinusitis Peritonsillar and retropharyngeal abscesses Suppurative cervical adenitis

Streptococcal Cervical Adenitis

Epidemiology of Streptococcal Pharyngitis Spread by contact with respiratory secretions Peaks in winter and spring School age child (5-15 yo) Communicability highest during acute infection Patient no longer contagious after 24 hours of antibiotics If hospitalized, droplet precautions needed until no longer contagious

Nonsuppurative Complications of Group A Streptococcus Acute rheumatic fever –follows only streptococcal pharyngitis (not group A strep skin infections) Acute glomerulonephritis –May follow pharyngitis or skin infection (pyoderma) –Nephritogenic strains

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

Treatment of Streptococcal Pharyngitis Objective of therapy –Eliminate streptococci from the pharynx –Prevent rheumatic fever –Prevent suppurative complications –Hasten clinical recovery

Treatment of Streptococcal Pharyngitis Penicillin - drug of choice –One intramuscular injection of long acting penicillin (benzathine) or oral therapy for 10 days –No significant penicillin resistance Erythromycin - if penicillin allergic

Scarlet Fever Occurs most commonly in association with pharyngitis –Raspberry or strawberry tongue –Rash Generalized fine, sandpapery scarlet erythema with accentuation in skin folds (Pastia’s lines) Circumoral pallor Palms and soles spared –Treatment same as strep pharyngitis

Strawberry Tongue in Scarlet Fever

Rash of Scarlet Fever

Acute Rheumatic Fever Immune mediated - ?humoral Diagnosis by Jones criteria –5 major criteria Carditis Polyarthritis (migratory) Sydenham’s chorea –muscular spasms, incoordination, weakness Subcutaneous nodules –painless, firm, near bony prominences Erythema marginatum

Erythema Marginatum

Acute Rheumatic Fever Minor manifestations –Clinical Findings arthralgia fever –Laboratory Findings Elevated acute phase reactants –erythrocyte sedimentation rate –C-reactive protein Prolonged P-R interval on EKG

Acute Rheumatic Fever Supporting evidence of antecedent group A streptococcal infection –Positive throat culture or rapid streptococcal antigen test –Elevated or rising streptococcal antibody titer antistreptolysin O (ASO), antiDNAse B If evidence of prior group A streptococcal infection, 2 major or one major and 2 minor manifestations indicates high probability of ARF

Acute Rheumatic Fever Therapy –Goal: decrease inflammation, fever and toxicity and control heart failure –Treatment may include anti-inflammatory agents and steroids depending on severity of illness

Poststreptococcal Glomerulonephritis Develops about 10 days after pharyngitis Immune mediated damage to the kidney that results in renal dysfunction Nephritogenic strain of S. pyogenes

Poststreptococcal Glomerulonephritis Clinical Presentation –Edema, hypertension, and smoky or rusty colored urine –Pallor, lethargy, malaise, weakness, anorexia, headache and dull back pain –Fever not prominent Laboratory Findings –Anemia, hematuria, proteinuria –Urinalysis with RBCs, WBCs and casts

Poststreptococcal Glomerulonephritis Diagnosis –Clinical history, physical findings, and confirmatory evidence of antecedent streptococcal infection (ASO or anti-DNAse B) Therapy –Penicillin to eradicate the nephritogenic streptococci (erythromycin if allergic) –Supportive care of complications

Diphtheria Etiologic agent: Corynebacterium diphtheria –gram positive rod (Chinese figures) –nonspore forming –strains may be toxigenic or nontoxigenic exotoxin required for disease

Corynebacterium Diphtheriae

Diphtheria Epidemiology –Humans are the only reservior –Spread by respiratory secretions –Infectivity lasts 2-6 weeks if untreated –If treated, communicability usually lasts less than 4 days –Epidemic in former Soviet Union –If hospitalized, droplet precautions

Diphtheria Clinical manifestations –Fever of 100°-102° F –Sore throat –Weakness –Dysphagia, headache, change of voice < 50% –Bull neck, difficulty breathing < 10%

Bull Neck of Diphtheria

Diphtheria Pseudomembrane development –Unlike exudate in Strep pharyngitis, extends beyond tonsils –Dislodging causes bleeding

Pseudomembrane in Diptheria

Diphtheria Complications –Obstruction of respiratory tract by pseudomembrane –Myocarditis –Polyneuritis (bulbar and peripheral) –Mortality 10-30% usually due to cardiac damage

Predictors of Poor Outcome Extent of pseudomembrane formation Delay between onset of local disease and treatment Death highest in first week of illness Bull-neck diphtheria Myocarditis with severe arrhythmias Bulbar paralysis Extremes of age

Diphtheria: Diagnosis Laboratory –Gram stain and culture Specimen from under membrane or membrane itself Tell lab suspect diphtheria –Loffler’s or tellurite selective media (Tindale’s agar) –Test strains for toxigenicity

Diphtheria: Treatment Treatment –Equine antitoxin + penicillin G (erythromycin if PCN allergy) Prevention –Immunization with formalin inactivated toxin

Diphtheria Public Health Concerns Should report to public health immediately Exposed persons at risk for infection Epidemiologic studies will determine need for monitoring, booster immunization, antibiotics, etc to prevent secondary cases

Pertussis Etiologic agent: Bordatella pertussis –minute, gram negative coccobacillary organisms –singles or pairs Colonization of tracheal epithelial cells by B. pertussis

Pertussis Epidemiology –Humans are the only known hosts –Transmission by respiratory secretions –Highly contagious with an attack rate of % depending on nature of exposure –Changes since vaccine introduction More infections in adults and children < 1 year

Pertussis Clinical Manifestations (Classic) –Catarrhal phase - mild URI symptoms most contagious –Paroxysmal phase dry, nonproductive cough –series of short expiratory bursts, followed by inspiratory gasp - whoop –may cause cyanosis and classically end in vomiting –fever absent or minimal –Convalescent phase

Paroxysm of Coughing in Pertussis

Pertussis Atypical infection common in adults and others with partial immunity Catarrhal phase may be brief or unrecognized and the whoop and leukocytosis absent Leads to spread of unrecognized infection Suspect this diagnosis in an adult with a cough > or = 2 weeks duration

Pertussis Complications of infection –Apnea –Seizures –Pneumonia –Encephalopathy –Death Premature infants at greatest risk for severe complications

Pertussis Diagnosis –Gold standard: isolation of B. pertussis by culture in the setting of clinical illness Requires special media: Bordet and Gengou (BG) medium Obtain by nasopharyngeal swab (calcium alginate) or nasal aspiration Slow growing (10-14 days) –Antibody detection

Pertussis Treatment –Supportive care –Erythromycin or Trimethoprim- sulfamethoxazole may shorten illness if given during catarrhal phase

Pertussis Prevention –By vaccination Immunity lasts about 12 years –Reportable disease Prophylaxis for household and childcare contacts = erythromycin for days Recommended irrespective of age or immunization status

Summary Diagnosis and management of Streptococcal pharyngitis Complication of group A strep infections Diagnosis and management of diphtheria Diagnosis and management of pertussis