Question 3 Answer (WBUHS Style)

(a) What is the current clinical condition?

• Fever (persistent, low-grade in subacute form)
• Anaemia (anaemia of chronic infection/haemolytic anaemia)
• Heart murmur (new or changing murmur due to valvular vegetation and destruction)
• Predisposing structural cardiac disease from previous ARF

• Splinter haemorrhages (subungual)
• Osler's nodes - tender subcutaneous nodules on fingertips and toes (immunologic phenomenon)
• Janeway lesions - non-tender erythematous macules on palms and soles (embolic phenomenon)
• Roth spots - oval haemorrhagic retinal lesions with pale centres
• Clubbing of fingers (in chronic cases)
• Splenomegaly

(b) What was the precipitating event?

• ARF is caused by Group A beta-haemolytic Streptococcus (Streptococcus pyogenes) throat infection
• Molecular mimicry: antibodies against streptococcal M-protein cross-react with cardiac valve antigens (particularly the mitral valve)
• This causes repeated episodes of valvulitis leading to:
  • Valve thickening, fibrosis, and calcification
  • Commissural fusion and regurgitation (most commonly mitral valve stenosis/regurgitation)
• The damaged/deformed valve provides a rough endothelial surface where sterile platelet-fibrin deposits form - this is the nidus for bacterial seeding during transient bacteraemia
• Organisms preferentially adhere to these damaged surfaces, forming vegetations (infected thrombus)

(c) Discuss your approach to laboratory diagnosis

1. Blood Culture (MOST IMPORTANT - CORNERSTONE)

• Collect 3 sets of blood cultures from 3 different venepuncture sites, at least 1 hour apart (or over 24 hours in subacute cases)
• Each set = 1 aerobic + 1 anaerobic bottle (10 mL blood each)
• Collect before starting antibiotics
• In most patients who have not received prior antibiotics, every blood culture is positive (near 100% bacteraemia)
• Incubate for at least 5 days (for HACEK organisms up to 21 days if suspected)
• Sensitivity: ~90-95% in untreated cases

2. Echocardiography

• Transthoracic Echocardiography (TTE): First-line; identifies vegetations (oscillating intracardiac masses), valvular regurgitation, abscesses
• Transesophageal Echocardiography (TEE): More sensitive (~90% vs 65%), preferred for prosthetic valves and when TTE is negative but clinical suspicion remains high

3. Modified Duke Criteria (for definite diagnosis)

• Definite IE: 2 major OR 1 major + 3 minor OR 5 minor criteria
• Possible IE: 1 major + 1 minor OR 3 minor criteria

4. Routine Laboratory Tests

• CBC: Normocytic normochromic anaemia, leukocytosis (acute IE), elevated ESR and CRP
• Urinalysis: Microscopic haematuria and proteinuria (due to immune complex glomerulonephritis)
• Rheumatoid factor: Positive in ~50% of subacute IE (immune complex deposition)
• Serum complement: Low C3, C4 (complement consumption by immune complexes)
• LFT/RFT: Baseline for monitoring

5. Additional/Special Tests (if blood cultures negative)

• Serology: For Coxiella burnetii (Q fever endocarditis) - anti-phase I IgG ≥1:800; Bartonella species
• PCR on blood or excised valve tissue: Detects fastidious organisms
• Histopathology of excised valve: Gold standard - shows colonies of bacteria within fibrinous vegetations
• [18F]-FDG PET/CT: Newer imaging modality; abnormal metabolic activity around prosthetic valves added as major criterion in 2023 Duke criteria

(d) What are the possible etiological agents?

Most Common (Gram-positive organisms):

1. Viridans group Streptococci (S. mutans, S. sanguis, S. mitis, S. salivarius)
   • Most common cause of community-acquired SBE in rheumatic heart disease
   • ~17-50% of cases on damaged/deformed valves
   • Source: oral cavity (dental procedures, minor trauma)
2. Streptococcus bovis (Group D Streptococcus)
   • Associated with colonic polyps/carcinoma
3. Staphylococcus aureus
   • Leading cause worldwide (31% in large cohorts)
   • More often causes acute IE on previously normal valves
   • Healthcare-associated; also in IV drug users
4. Staphylococcus epidermidis (CoNS)
   • Coagulase-negative Staphylococci (~11%)
   • Common in prosthetic valve endocarditis
5. Enterococci (E. faecalis, E. faecium)
   • ~10% of cases; genitourinary/GI source
   • Elderly patients
6. HACEK organisms (Gram-negative fastidious):
   • Haemophilus spp.
   • Aggregatibacter spp. (formerly Actinobacillus)
   • Cardiobacterium hominis
   • Eikenella corrodens
   • Kingella kingae
   • Oral commensals; grow slowly in culture
7. Fungi (rare): Candida spp., Aspergillus - mainly in immunocompromised, IV drug users, prosthetic valves
8. Culture-negative endocarditis (~10%):
   • Coxiella burnetii (Q fever) - needs serology
   • Bartonella spp.
   • Tropheryma whipplei
   • Prior antibiotic therapy most common reason

Key Point for WBUHS: For this particular case (55-year-old with RHD), the most likely agent is viridans group Streptococci entering the bloodstream through a dental or oral source acting on the deformed mitral valve.