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 50 -

100% 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 10-14 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