STREPTOCOCCUS STREPTOCOCCUS • General Features: - Gram positive cocci in pairs and chains - Catalase negative History - Billroth coined the term ‘streptococci’ (streptos meaning twisted or coiled), - Ogston differentiated them from staphylococci - Rosenbach coined the species S. pyogenes Classification of Streptococcus STREPTOCOCCUS PYOGENES VIRULENCE FACTORS.. Cell wall antigens • • - Lipoteichoic acid – adhesion M protein Opsonization Strep. Toxic Shock Syndrome Ig to class 1 M protein Rheumatic fever VIRULENCE FACTORS.. Toxins Streptolysin-O (SL-O) Oxygen labile , Heat labile Hemolysis only in deep colonies (pour plate) Cytotoxic for neutrophils, platelets and cardiac tissue. Strongly antigenic Antistreptolysin-O antibodies (ASO) -for retrospective diagnosis of streptococcal infections Streptolysin-S (SL-S) Oxygen stable, Serum soluble Hemolysis on surface of blood agar Leucocidal Not antigenic Not useful for serological diagnosis of streptococcal infections. VIRULENCE FATCORS.. Toxins Haemolysins • Streptolysin-O is structurally and functionally similar to• Tetanolysin of Clostridium tetani • Pneumolysin of S.pneumoniae • Theta toxin of Clostridium perfringens • Listeriolysin O of Listeria • Cereolysin of Bacillus cereus Streptococcal pyrogenic exotoxin (SPE) • Causes - scarlet fever, necrotizing fasciitis & streptococcal toxic shock syndrome. • Antigenic subtypes- SPE-A,B and C • SPE-A and C are bacteriophage coded, superantigens • SPE-B is chromosomally mediated. • Dick test-SPE was previously called as erythrogenic or scarlet fever toxin because its intradermal injection in susceptible children produced local erythema indicating susceptible to scarlet fever. VIRULENCE FATCORS.. Enzymes • Streptokinase (fibrinolysin)• Activates plasminogen to plasmin  breaks down the fibrin barrier  spread of infection. • Antibodies to streptokinase - retrospective diagnosis • Therapeutic use- myocardial infarction and other thromboembolic disorders. VIRULENCE FATCORS.. Enzymes • Streptodornase (DNase)• Liquefying the thick pus - responsible for the serous nature of streptococcal exudates • Therapeutic use- to liquefy the thick exudates in empyema cases. • Subtypes -B is most antigenic • Diagnostic use- Anti-DNase B antibodies - retrospective diagnosis of skin infections (pyoderma) and acute glomerulonephritis where ASO titre is low VIRULENCE FATCORS.. Enzymes • Hyaluronidase (spreading factor)- breaks down the hyaluronic acid of the tissues- spread of infection • NADase- antigenic and leucotoxic. • Serum opacity factor- Lipoproteinase - opacity when applied on agar gel containing serum. • SpyCEP- Serine protease - inactivates interleukin 8 (neutrophil chemoattractant) • C5a peptidase- Serine protease -Cleaves C5a (neutrophil ials of Medi chemoattrEsseantct ant) Streptococcal Suppurative Infections • Pharyngitis - GAS is MC cause in children - Erythema and swelling of pharyngeal mucosa with purulent exudate - Complications due to contiguous spread, through blood and lymph • - Scarlet fever SPE A, B & C Rash with sandpaper feel Rash in skin folds Strawberry tongue Streptococcal Suppurative Infections • Impetigo - superficial infection of the skin – face & legs - Children, tropical climates, poor hygiene, colonization of group A Streptococcus and trauma - Painless & No fever Red papules vesicles  pustular lesions  thin papery honeycomb-like crusts Streptococcal Suppurative Infections • Erysipelas: - Form of cellulitis - Tender, bright red, swollen and indurated peau d'orange texture of involved skin Superficial blebs or bullae - Fever and chills - Malar area of the face & legs - Recurrences involving the same site. Streptococcal Suppurative Infections • Necrotizing Fasciitis - Aka- hemolytic streptococcal gangrene - GAS - MC cause (60%) – Flesh eating bacteria - Pyrogenic exotoxins • Dusky Skin or mottled • Source of the infection erythema and anesthetized extensive necrosis of - Trauma & GIT breach subcutaneous tissue, fascia • Invasion of Fascia &Muscles Streptococcal Non-Suppurative Lesions • Acute rheumatic fever • Post-streptococcal glomerulonephritis (PSGN) • Guttate psoriasis • R eactive arthritis • Pediatric Autoimmune Neuropsychiatric Disorders • Associated with Streptococcus pyogenes (PANDAS) Streptococcal Ag Mammalian Ag Cell wall M protein Myocardium Cell wall C carbohydrate Cardiac valves Cytoplasmic membrane Glomerular vascular intima Peptidoglycan Skin antigens Hyaluronic acid Synovial fluid Streptococcal Non-Suppurative Lesions • Acute Rheumatic Fever • Previous streptococcal pharyngitis • Pathogenesis - Autoimmune theory: Antibody cross reaction & - Cytotoxicity theory • Clinical manifestations - Affects heart, joints, and skin. Modified Jones criteria • Repeated attacks common – Long-term penicillin prophylaxis Revised Jones Criteria.. Criteria Manifestations Major manifestations Subcutaneous nodules Pancarditis (SPACE) Arthritis (migrating polyarthritis) Chorea (CNS manifestation) Erythema marginatum (skin lesion) Minor manifestations Clinical: fever, arthralgia Laboratory: elevated ESR and C-reactive protein ECG: Prolonged P-R interval Revised Jones Criteria.. Criteria Supporting evidence (of previous streptococcal infection) Manifestations Elevated ASO, or A positive throat culture, or Rapid antigen test for GAS, or Recent scarlet fever Rheumatic fever is diagnosed if: Two major manifestations or one major and two minor manifestations plus evidence of previous streptococcal infection Streptococcal Non-Suppurative Lesions • Post-streptococcal Glomerulonephritis (PSGN) - 2–3 weeks following pyoderma - (M types–49, 53-55 and 59-61) or rarely pharyngitis (M-types 1 and 12) • Antigen antibody complex deposition on the glomerular basement membrane complement activation urine retention and renal insufficiency edema, hypertension, hematuria and proteinuria Rheumatic Fever v/s Acute Glomerulonephritis Feature Prior history of infection with ARF Pharyngitis strains Serotype Most strains of GAS Immune response Marked Complement level Unaltered Essentials of PSGN Mainly pyoderma, or rarely pharyngitis strains Pyodermal strains49,53-55, 59-61& Pharyngitis strains1,12 Moderate Low (due to depositionin glomeruli) Rheumatic Fever v/s Acute Glomerulonephritis Feature Genetic susceptibility Repeated attack Penicillin prophylaxis Course Prognosis Hypersensitivity reaction ARF Present PSGN Absent Common Indicated Progressive Uncommon Not indicated Spontaneous resolution Good Type III Variable Type II Lab Diagnosis... • Specimens: - Throat swab, pus swab, exudates and blood - Pike’s transport media • Microscopy - Pram positive cocci in chains Lab Diagnosis... Culture • Aerobe & Fastidious • Blood Agar – Beta hemolytic pinpoint colonies • Liquid medium – Granular turbidity • Selective Medium - Crystal violet blood agar - PNF medium Biochemical reactions • Catalase – positive • Bacitracin - sensitive Serologic Classification • Lancefield Grouping - Based on C-antigen - Lancefield’s acid extraction - Fuller’s method - Rantz and Randall method - Maxted’s method • Griffith Typing - Based on M protein - 100 serotypes - Emm Typing – based on gene coding for M protein SEROLOGY • ASO (Anti-streptolysin O) antibodies - Titer >200 Todd unit/ml in most of the streptococcal infections except pyoderma and PSGN. - detected by latex agglutination test. • Anti-DNase-B antibodies – - Titre >300-350 units/ml is diagnostic of PSGN and pyoderma • Anti-hyaluronidase antibodies • Anti-streptokinase antibodies TREATMENT Conditions Treatment recommended Pharyngitis Necrotizing fasciitis Benzathine penicillin G, IM single dose; or Oral penicillin V for 10 days Mild- Procaine penicillin Severe- Penicillin G Surgical debridement (most crucial) + Penicillin G + Clindamycin Pneumonia & empyema Penicillin G + drainage of empyema Streptococcal TSS Penicillin G + Clindamycin + immunoglobulin (to SPE) Erysipelas/Cellulitis Rheumatic fever Benzathine penicillin G, IM single dose; or Oral Penicillin V for 10 days Long term maintenance therapy- with penicillin G monthly • 5 yr or until 21 yr of age, (without carditis), • 10 yrs (with carditis), OTHER BETA HEMOLYTIC STREPTOCOCCI S.agalactiae • • • • • Group B Streptococcus Carriage in vagina and rectum in 30% women Neonatal sepsis & meningitis Pregnancy  peripartum fever Cellulitis and soft tissue infections urinary tract infection, pneumonia, and endocarditis – in diabetics, cancer patients Early v/s Late GBS Disease Characteristics Early-onset disease Late-onset disease Age of onset 0–6 days of birth 7–90 days of birth Increased risk following obstetric complications Mode of transmission to the baby Not associated Common serotypes Prematurity and prolonged labor During or before birth from the colonized maternal genital tract Pneumonia and/or respiratory distress syndrome followed by meningitis Ia, III, V, II, Ib Case fatality rate 4.7% 2.8% Common clinical manifestations Contact with a colonized mother and nursing personnel Bacteremia&meningitis (most common) III predominates S.agalactiae • Lab Diagnosis • CAMP positive: CAMP factor (named after the discoverers: Christie, Atkins-Munch-Petersen) S.agalactiae • Other Tests: - Hippurate hydrolysis test positive - Bacitracin resistant - PYRtest negative - Orange pigment - Islam’s medium - Mucoid β haemolytic colonies • Treatment - Penicillin or higher penicillins • Prevention - Screening at 35-37 wks of pregnancy - Ampicillin or penicillin to carrier mothers GROUP C STREPTOCOCCI • Common animal pathogen. Human infections rare • S.equi, S.equisimilis, S.dysgalactiae, S.zooepidermicus • S.equisimilis - pharyngitis especially epidemic food-borne pharyngitis after ingestion of contaminated products (milk) • Others- skin and soft tissue infections, osteomyelitis, pneumonitis, infective endocarditis, bacteremia and septicemia, meningitis, epiglottitis, pericarditis, urinary tract infections, and puerperal sepsis. • S.equisimilis - source of streptokinase GROUP F STREPTOCOCCI • Minute streptococci, Grow poorly on blood agar occasionally cause suppurative infection. Antibodies to Streptococcus MG for diagnosis of primary atypical pneumonia (caused by Mycoplasma pneumoniae) Other β Hemolytic Streptococci • GROUP G STREPTOCOCCI • Throat commensals • Occasionally causing puerperal sepsis, neonatal infection, skin and soft tissue infections, tonsillitis, and endocarditis. • • GROUP D STREPTOCOCCI • common group D lipoteichoic acid antigen • Group D streptococci comprises of enterococci & nonenterococci (S.bovis and S.equinus)