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Mechanistic Deep Dive
Molecular Mimicry
- M protein on Strep cross-reacts with myosin (heart), tropomyosin, neural antigens
- Triggers Type II hypersensitivity
- Genetic susceptibility (HLA-DR7, HLA-DR4)
- âStreptococcal antibodiesâ against host tissues
Sydenham Chorea Pathophysiology
- Anti-basal ganglia antibodies
- Anti-D2 dopamine receptor antibodies
- Carbonic anhydrase III
- PANDAS / PANS (similar concept in children)
Recent Trials & Updates
Subclinical Carditis (2015 Jones Modification)
- Echocardiographic screening in high-risk populations
- Reveals more cases
- Treatment decisions individualized
RHEUMATIC (2024) â RHD Vaccine
- Multi-antigen vaccine candidates in trial
- StreptAnova phase II
- Hope for primary prevention
Penicillin Adherence Strategies
- Implantable formulations in development
- 6-12 month formulations being trialed
- â Compliance + â ARF recurrence
Endemic Country Strategies
- Australia: Aboriginal communities high burden
- Pacific: similar
- New Zealand: BPG availability
- WHO RHD Action Plan 2024-2030
High-Yield Specialist Points
Carditis Severity Grading
- Mild: subclinical or trivial murmur
- Moderate: clear murmur + LV function preserved
- Severe: HF, LV dysfunction
Anti-Inflammatory Choice
- ASA still standard for arthritis (high-dose)
- Naproxen also used
- Steroids for HF, severe carditis (debated for valve protection)
Surgery + Pregnancy
- Pregnancy + severe MS: PMBV during pregnancy
- Pregnancy mWHO 2-4 for RHD
- Anticoagulation considerations (warfarin teratogenic; LMWH for mechanical valve)
Newer Diagnostic Modalities
- Handheld echocardiography
- AI-assisted screening
- Smartphone-based devices
- Increasing access globally
Global Health Initiative
- Penicillin G global access challenges
- Generic shortages
- Storage requirements
- Workforce training for IM administration
Migration Health
- Travelers / immigrants from endemic areas
- Screening with echo
- Continue prophylaxis
Vaccine Development
- StreptAnova (multi-valent M protein)
- C5a peptidase
- Polysaccharide conjugates
- Phase I-II trials
- Decades-long effort
Pearls
- ARF: 2-4 wk post-GAS pharyngitis; Jones criteria + GAS evidence
- 5 major manifestations: carditis, migratory polyarthritis, Sydenham chorea, erythema marginatum, subcutaneous nodules
- GAS pharyngitis: penicillin V or BPG; prevents ARF
- Secondary prevention: BPG IM q3-4 wk; duration varies
- RHD: MS most common; MR, AR, AS may coexist
- 2015 Jones: subclinical carditis accepted for moderate/high-risk populations
- 2024 RHD Action Plan: echo screening + penicillin access + vaccine R&D
- Global burden: 33 million RHD prevalent; 470,000 new ARF/yr