Streptococcus — Classification, Lancefield Grouping, Rheumatic Fever and Post-Streptococcal Glomerulonephritis

Streptococci are gram-positive, catalase-negative cocci arranged in pairs or chains. StatPearls divides them first by haemolysis on blood agar: beta (complete lysis, clear zone), alpha (partial lysis, green discolouration) and gamma (no haemolysis). Among the beta-haemolytic organisms, group A is Streptococcus pyogenes and group B is Streptococcus agalactiae.

The second system is Lancefield grouping, a serological scheme based on the cell-wall carbohydrate antigen. For group A the carbohydrate is N-acetylglucosamine on a rhamnose backbone. Within group A, the surface M protein defines more than 80 serotypes. Group B carries its own group-specific carbohydrate, and its capsular polysaccharide divides it into types Ia, Ib, II to IX.

S. pyogenes is a facultative anaerobe that forms pinpoint colonies on blood agar. It is spread by respiratory droplets and by contact with infected skin or nasal discharge, and crowding (schools, camps) favours outbreaks.

Clinical syndromes. Pharyngitis: sudden fever, malaise, tonsillar exudate and tender cervical nodes. Impetigo: honey-coloured crusted lesions on the face and legs, non-bullous (bullous impetigo is S. aureus). Scarlet fever: sore throat, strawberry tongue, a blanching rash with desquamation. Necrotising fasciitis and toxic shock are the invasive forms.

For GAS pharyngitis, a rapid antigen detection test (RADT) is the first-line test. Its sensitivity can be below 90 percent, so a negative RADT in a child should be backed up by throat culture, which remains the gold standard. A PYR test separates S. pyogenes from other beta-haemolytic streptococci, and throat-swab work-ups also use bacitracin susceptibility before confirming the Lancefield group.

Serology for sequelae. ARF and PSGN appear weeks after the infection, so culture is often already negative. Antibodies to streptolysin O (ASO) and anti-DNase B are used instead. Titres rise about 2 to 3 weeks after infection; a two-fold rise between paired samples is positive. In a Nepali review, positive ASO went with preceding throat infection and positive anti-DNase B with skin infection.

Both follow group A streptococcal infection and both are immune-mediated, but the targets and triggers differ. In the classical scheme, class I M-protein strains cause rheumatic fever and class II strains cause acute glomerulonephritis.

ARF is a clinical diagnosis. The revised Jones criteria split patients into low-risk populations (ARF incidence up to 2 per 100,000 school-aged children) and moderate/high-risk populations (above 2 per 100,000). An initial episode needs 2 major criteria, or 1 major plus 2 minor, with evidence of preceding GAS infection.

A recurrent episode can be diagnosed with 2 major, or 1 major plus 2 minor, or 3 minor criteria. Sydenham chorea or indolent carditis presenting months after infection can be diagnosed without the full criteria. Carditis is the most serious feature: pancarditis with mitral regurgitation as the earliest valve lesion, and the PR interval is the commonest ECG change.

• Migratory polyarthritis of large joints (knee, ankle, wrist) is usually the earliest manifestation, in about 60 to 80 percent.
• Subcutaneous nodules (under 10 percent) are firm, painless, on extensor surfaces and tend to occur with severe carditis.
• Erythema marginatum (under 6 percent) is a fleeting, pink, non-itchy ring-shaped rash on the trunk and limbs, not the face.
• Sydenham chorea (10 to 30 percent) is late; the milkmaid's sign is a grip that cannot be sustained.

Histology. Antibodies to GAS antigens bind heart valves and raise vascular cell adhesion molecule 1, letting T cells settle in the endocardium. They form Aschoff bodies: granulomatous lesions with fibrinoid necrosis, lymphocytes, plasma cells and Anitschkow cells (enlarged macrophages whose ribbon-like chromatin looks like a caterpillar).

Eradication. Penicillin is the drug of choice: oral penicillin V for 10 days or a single intramuscular benzathine penicillin G dose (600,000 units if under 27 kg, 1.2 million units if over 27 kg). In penicillin allergy without anaphylaxis, use a first-generation cephalosporin; with anaphylaxis, a macrolide (resistance is rising) or clindamycin. Every patient diagnosed with ARF receives an eradication course even if the throat culture is negative.

Symptomatic treatment. Arthritis responds to aspirin (60 to 100 mg/kg/day, historically) or, in newer practice, NSAIDs such as naproxen. Neither steroids nor IVIG proved better than aspirin for carditis; corticosteroids are kept for severe carditis (significant MR or persistent AV block). Sydenham chorea is self-limited; carbamazepine or valproate are options when it disrupts daily life.

The standard agent is IM benzathine penicillin G every 28 days; in higher-incidence populations it is given every 21 days. Oral penicillin V twice daily is less reliable because of poor adherence. Patients with Sydenham chorea alone also need prophylaxis.

PSGN is the classic nephritic syndrome of childhood, caused by nephritogenic strains of group A beta-haemolytic streptococci. The commonest antigens implicated are the nephritis-associated plasmin receptor and streptococcal pyrogenic exotoxin B. They activate the alternative complement pathway, so serum C3 falls.

• Presentation: haematuria (cola-coloured urine), oedema, hypertension, oliguria and rising urea and creatinine, 1 to 2 weeks after a sore throat or about 6 weeks after impetigo.
• Serology: raised ASO, anti-DNase B (anti-hyaluronidase also used); low C3 that normalises in about 6 to 8 weeks.
• Biopsy is not needed unless the course is atypical: rapidly progressive GN, normal complement, or no rise in antistreptococcal antibodies.
• Light microscopy: diffuse endocapillary proliferation with neutrophils. IF: coarse granular IgG and C3 ('starry sky', garland, mesangial patterns). EM: large subepithelial hump-shaped deposits.
• Epidemiology: the commonest cause of glomerulonephritis in children worldwide, mainly in developing countries.

Group B streptococcus (GBS) colonises the maternal genital and gastro-intestinal tracts. Neonatal disease is early-onset (first 6 days, acquired in labour) or late-onset (days 7 to 89). Third-trimester screening plus intrapartum antibiotic prophylaxis cut early-onset disease from about 1.7 per 1,000 live births in the early 1990s to about 0.22, but late-onset disease did not change. Its sialic-acid-rich capsule helps it evade newborn immunity.

*Streptococcus pneumoniae* is a lancet-shaped, capsulated organism; the capsular polysaccharide defines its serotypes (97 isolated by 2022) and is the target of pneumococcal vaccines. Risk groups include children under 2 years, adults over 65, and people with asplenia.

Viridans streptococci are normal oral, gut and genital flora in five phenotypic groups: sanguinis, mitis, mutans, anginosus and salivarius. They are the classic cause of subacute infective endocarditis on damaged valves, and also of abscesses and bacteraemia. Enterococci carry the group D antigen, are intrinsically resistant to cephalosporins, and E. faecium is far more often vancomycin-resistant than E. faecalis.