Rhematic Fever

• Delayed nonsuppurative sequalae of group A streptococcus pharyngeal infection

Pathophysiology:

• Need:
  • GAS Pharyngitis
    • Only 20-40% of pharyngitis episodes are associated with GAS infection
    • The remainder are caused by viruses or bacteria for which antibiotic treatment is not recommended
  • Genetic susceptibility
• Mechanism:
  • Molecular mimicry
  • GAStrep Pharyngitis induces a Type 3 hypersensitivity reaction
• Immune Response:
  • Antibodies against M protein of certain strains cross-react with glycoprotein antigens in the heart, joints, nerves, and other tissues
  • Only a minority of infected patients develop Rheumatic Fever (RF)
• Consequences of Recurrence:
  • Carditis:
    • Worsens with each recurrence; damage is cumulative
  • Embolization:
    • From mural thrombi
  • Infective Endocarditis:
    • Risk increases on deformed valves
  • Chronic Rheumatic Heart Disease:
    • Murmurs
    • Hypertrophy
    • Dilation
    • Heart failure
    • Arrhythmias

• Delay in Onset:
  • There is typically a 2-4 week delay between the initial streptococcal infection and the onset of RF due to the time required for the immune response to cause tissue damage.

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High-Risk Groups for Acute Rheumatic Fever (ARF) and Rheumatic Heart Disease (RHD)

• Aboriginal and Torres Strait Islander Peoples
  • Especially those living in rural or remote communities.
  • Disproportionately affected due to healthcare access barriers, household crowding, and environmental risk factors.
• Children and Adolescents
  • Highest incidence: 5–14 years.
  • Recurrent ARF can occur well into early adulthood (up to 40s).

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Epidemiology

Indicator	Statistic
ARF incidence (age 5–14)	>30 per 100,000 per year
RHD all-age prevalence	>2 per 1,000
Peak incidence	Ages 5–15 years
Burden of disease	Concentrated in low-resource, high-burden populations

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Risk Factors for ARF and RHD

A. Age-Related Risk

• Children aged 5–15 years:
  • Immature immune systems.
  • Higher susceptibility to Group A Streptococcus (GAS) pharyngitis.
  • More likely to develop abnormal autoimmune responses to GAS.

B. Geographic and Environmental Risk

• Endemic regions (e.g. Northern Australia, Pacific Islands, Sub-Saharan Africa):
  • Poor infrastructure for early diagnosis and treatment.
  • Climate factors may promote bacterial spread.
• Remote communities:
  • Limited access to healthcare professionals and antibiotics.
  • Inadequate follow-up for secondary prophylaxis.

C. Socioeconomic Determinants

• Poverty and Overcrowding:
  • Close contact increases GAS transmission.
  • Delayed health-seeking behaviour due to cost/logistics.
• Poor nutrition:
  • Impaired immune responses.

D. Past Medical History

• Previous ARF episode:
  • High risk of recurrence.
  • Autoimmune memory primes the host for exaggerated response.
• Inadequate Secondary Prophylaxis:
  • Missed or irregular benzathine penicillin injections lead to increased recurrence risk.

E. Family and Genetic Predisposition

• Family history of ARF/RHD:
  • May reflect genetic susceptibility to aberrant immune responses.
  • Shared exposure to untreated GAS infections in households.

F. Hygiene and Health Access

• Poor hygiene/sanitation:
  • Increased GAS carriage and transmission.
• Limited access to healthcare:
  • Underdiagnosis of strep pharyngitis.
  • Delays in initiating appropriate antibiotic treatment.
  • Gaps in school or community-based screening and prophylaxis programs.

G. Systemic and Structural Health Barriers

• Healthcare system deficits:
  • Inadequate public health surveillance.
  • Shortages of long-acting penicillin in remote clinics.
• Cultural and language barriers:
  • Mistrust or lack of culturally safe care may deter engagement in preventive programs.

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Risk Factors for ARF/RHD

Category	Risk Factor	Impact
Demographics	Age 5–15 years	Peak incidence window
Ethnicity	Aboriginal and Torres Strait Islander peoples	Higher burden, especially remote/rural
Socioeconomic	Poverty, overcrowding	↑ GAS exposure, ↓ access to timely care
Past history	Previous ARF	High recurrence risk without secondary prophylaxis
Family history	Genetic predisposition, shared environments	↑ Risk of immune-mediated complications
Hygiene and healthcare	Poor hygiene, limited medical access	↑ GAS spread and untreated infections
Systemic	Weak public health infrastructure	↓ Screening, diagnosis, and preventive antibiotic programs

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History and Examination

Preceding Illness:

1. Symptoms:
   • Typically follows streptococcal pharyngeal infection.
   • Symptoms develop 2-4 weeks after infection.
2. Cultures:
   • Throat cultures may be taken to identify group A streptococcus.
3. Timing:
   • Symptoms appear 2-4 weeks post-infection.

Vital Signs:

1. Fever:
   • Low-grade fever.

Cardiovascular System (CVS):

1. Symptoms:
   • Chest pain or discomfort.
   • Dyspnea.
2. Signs:
   • New onset mitral regurgitation (MR) or other murmurs.
   • Pericardial rub.
   • Palpitations.
   • Heart failure.

Rheumatological:

1. Symptoms:
   • Pain more than clinical inflammation.
   • Migratory arthritis involving large joints, usually starting in the legs.
   • Each joint affected for < 1 week but often overlap.

Rash:

1. Erythema Marginatum:
   • Non-pruritic rash with pale centers on the trunk and proximal limbs.

Central Nervous System (CNS) – Sydenham Chorea:

1. Symptoms:
   • Abrupt, purposeless, nonrhythmic involuntary movements, worse on one side.
   • Muscular weakness (milking sign).
   • Emotional instability.

Dermatology:

1. Subcutaneous Nodules:
   • <2 cm, firm, painless nodules over bony surfaces or near tendons.
2. Erythema Annulare:
   • Non-pruritic rash with pale centers on the trunk and proximal limbs.

Differentials

• Septic arthritis (including gonococcal arthritis)/   osteomyelitis
• Reactive arthritis
• Viral arthritis (CMV, EBV, rubella vaccination, hepatitis)
• Rheumatic fever
• Juvenile idiopathic arthritis
• Rheumatoid arthritis, IBD, SLE, vasculitis,  sarcoidosis
• Haemarthrosis
• MSK injury/ trauma/ fall (perthes,  SUFE)
• Gout/ pseudogout
• Non-­accidental injury

Diagnosis & Investigations

Currently, there is no specific laboratory test to definitively diagnose Acute Rheumatic Fever (ARF). As such, diagnosis is a clinical decision, guided by the recognition of major and minor criteria as defined by the Jones Criteria.

Confirming Diagnosis Using the Jones Criteria

Definite Initial Episode of ARF requires one of the following:

• Two major criteria, or
• One major criterion plus two minor criteria,
  with evidence of a preceding Group A Streptococcal (GAS) infection.

Definite Recurrent Episode of ARF in patients with a history of ARF or Rheumatic Heart Disease (RHD) requires:

• Two major criteria, or
• One major criterion and one minor criterion, or
• Three minor criteria,
  with evidence of a preceding GAS infection.

Major Criteria:

1. Carditis
2. Arthritis
   • High-Risk Groups: Aseptic monoarthritis
   • Low-Risk Groups: Polyarthritis
3. Chorea
4. Erythema marginatum
5. Subcutaneous nodules

Minor Criteria:

1. Arthritis
   • High-Risk Groups: Monoarthralgia
   • Low-Risk Groups: Polyarthralgia or aseptic monoarthritis
2. Fever
3. Elevated Erythrocyte Sedimentation Rate (ESR) or C-reactive Protein (CRP)
4. Prolonged PR interval on an electrocardiogram (ECG)

Evidence of Preceding Streptococcal Infection:

• Positive throat culture for Group A β-haemolytic streptococcus
• Positive rapid streptococcal antigen test
• Elevated or rising streptococcal antibody titres (most commonly antistreptolysin O; others include anti-DNAse B, streptokinase, antihyaluronidase)

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Investigations:

• Evidence of preceding streptococcal infection:
• All suspected cases of ARF (except those with chorea or low-grade subacute carditis) should have elevated serum streptococcal serology:
  • ASOT (Antistreptolysin O titer) + anti-DNase B titres
    • if available (repeat 10–14 days later if first test not confirmatory)
    • The false negatives rate is 20-30%, reduce false negative with anti-DNase B titre 
    • False positives can result from liver disease and tuberculosis.

• Rapid antigen test
  • Turnaround time of 1-3 hours
  • sensitivity of 86% and specificity of 96%
  •  cost only $5-$10 compared with $30 for throat cultures
  • But unfortunately DOES NOT attract an MBS rebate.
• Bloods – ESR/CRP, FBC (chronic anaemia)
• ECG (heart block)
• U/A (GN for CTD)
• Imaging:
  • Serial CXR (cardiomegaly due to carditis, monitor course)
  • Echo (acute carditis, valvular regurgitation/stenosis, chamber size and function, pericardial effusion)
• Tests for alternative diagnoses, depending on clinical features
  • Repeated blood cultures, if possible endocarditis
  • Joint aspirate (microscopy and culture) for possible septic arthritis
  • Copper, ceruloplasmin, antinuclear antibody, drug screen for choreiform movements
  • Serology and autoimmune markers for arboviral, autoimmune or reactive arthritis

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Immediate Management

Goals: Goals: symptomatic relief + eradication of GAS + prophylaxis

Symptomatic Relief

• Aspirin:
  • Children: 80-100 mg/kg/day
  • Adults: 4-8 g/day
  • Continue until symptoms resolve and ESR/CRP levels normalize.
• Antihistamines: For rash relief.
• Cardiac Involvement:
  • Severe carditis may cause cardiomegaly, congestive heart failure (CHF), or 3rd-degree heart block.
  • Management follows acute pulmonary oedema (APO) protocols (e.g., Frusemide, ACE inhibitors).
  • Prednisone: 2 mg/kg/day orally for 1-2 weeks, then tapered over 2 weeks for severe carditis.
  • Valve Surgery: Considered for heart failure due to refractory regurgitant lesions, with valve repair preferred over replacement.
• Chorea (if present):
  • Usually self-limiting and may not require treatment.
  • If needed:
    • Carbamazepine: 7-20 mg/kg/day, typically given three times daily (tds).
    • Valproic Acid: 15-20 mg/kg/day, may be increased to 30 mg/kg/day, given tds.

Antibiotic Therapy

• All Cases:
  • IM Benzathine Penicillin G (preferred):
    • ≥20 kg: 900 mg (1,200,000 units)
    • <20 kg: 450 mg (600,000 units)
  • Alternative (if IM injection not possible): Oral Phenoxymethylpenicillin (Penicillin V) for 10 days:
    • Children: 250 mg twice daily (bd)
    • Adolescents and Adults: 500 mg bd
  • Penicillin Allergy: Use Erythromycin:
    • Children: 20 mg/kg up to 800 mg bd for 10 days
    • Adults: 800 mg bd for 10 days

Management for Family Contacts

• Throat swab for GAS culture.
• If positive, initiate appropriate penicillin therapy.

General Care Recommendations

• Rest: Strict bed rest is often unnecessary; include planned rest periods.
• Age-Appropriate Activities: Encourage suitable activities based on age.
• Family Involvement: Educate family members on the condition and engage them in care.
• School Notification: Inform teachers about the patient’s care requirements.

Discharge Planning

• Plan for transfer to a primary care facility with scheduled follow-up appointments.

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Drugs used for rheumatic fever

Indication	Drug options listed in order of preference	Comment
Eradication of inciting streptococcal infection	1. Benzathine benzylpenicillin G 1,200,000 units child <20 kg: 600,000 units ≥20 kg: 1,200,000 units intramuscularly, single dose OR	Streptococcal infection may not be evident by the time acute rheumatic fever manifests (e.g. cultures often negative), but eradication therapy for possible persisting streptococci is recommended. Intramuscular penicillin is preferred as streptococcal eradication therapy due to better adherence and its subsequent ongoing use in secondary prophylaxis.
	2. Phenoxymethylpenicillin 500 mg child: 15 mg/kg up to500 mg orally, every 12 hours for 10 days OR
	3. For patients with penicillin hypersensitivity (non-severe): cefalexin 1 g child: 25 mg/kg up to 1 g orally, every12 hours for 10 days OR	Between 3% and 30% of group A streptococcus isolates internationally are resistant to macrolide antibiotics (e.g., azithromycin).
	4. For patients with immediate penicillin hypersensitivity: azithromycin 500 mg (child: 12 mg/kg up to 500 mg) orally, daily for 5 days
Initial analgesia while awaiting diagnostic confirmation:mild to moderate painsevere pain	Paracetamol 1000 mg (in children: 15 mg/kg) orally, every four hours as needed up to a maximum of 60 mg/kg/day or 4000 mg/day	Initial analgesia is preferred during diagnostic uncertainty to avoid the masking effect that anti-inflammatory use can have on migratory joint symptoms, fever and concentrations of inflammatory markers.
	Tramadol immediate-release 50–100 mg (in children: 1–2 mg/kg) orally, every four hours as needed up to a maximum of 400 mg/day	Tramadol (or codeine) is usually avoided in children<12 years of age due to variable metabolism. Use only when strong analgesia is essential and cautious monitoring is available.
Symptomatic management of arthritis/arthralgia after confirmation of acute rheumatic fever diagnosis	1. Naproxen immediate-release 250–500 mg (in children: 10–20 mg/kg/day) orally twice daily, up to a maximum of 1250 mg dailyOR	Naproxen may be safer than aspirin and convenient due to twice-daily dosing and the availability of oral suspension. Ibuprofen is well tolerated and readily available, but there are less data and experience with its use for acute rheumatic fever than those associated with naproxen. The dose of NSAIDs needed for acute rheumatic fever is generally higher than the dose recommended for other conditions; therefore, it may be appropriate to start at the higher dose range. Due to the rare possibility of Reye’s syndrome in children, aspirin may need to be discontinue during intercurrent acute viral illness; thus, influenza vaccination is strongly recommended to reduce the likelihood of this case.
	2. Ibuprofen 200–400 mg (in children: 5–10 mg/kg) orally three times daily, up to a maximum of 2400 mg dailyOR
	3. Aspirin 50–60 mg/kg/day orally, in 4–5 divided doses in adults and children. Dose can be escalated up to a maximum of 80–100 mg/kg/day in 4–5 divided doses
Symptomatic management of moderate to severe chorea	1. Carbamazepine 3.5–10 mg/kg per dose orally twice daily	Treatment of Sydenham chorea should be considered if movements interfere substantially with normal activities.
	2. Sodium valproate 7.5–10 mg/kg per dose orally twice daily
Symptomatic management of very severe chorea or chorea paralytica	In addition to an anticonvulsant drug, consider adding a corticosteroid:· = Prednisolone 1–2 mg/kg up to a maximum of 80 mg orally once daily
Symptomatic management of carditis	Paediatric dosing:· Furosemide (frusemide) 1–2 mg/kg orally as a single dose, then 0.5–1 mg/kg (to a maximum of 6 mg/kg) orally every 6–24 hours Spironolactone 1–3 mg/kg (initially) up to 100 mg orally in 1–3 divided doses daily. Round dose to a multiple of6.25 mg (a quarter of a 25-mg tablet)	Treatment of heart failure may be required for severe, acute carditis. Seek advice from a specialist cardiologist.
	Enalapril 0.1 mg/kg orally in 1 or 2 divided doses daily, increased gradually over 2 weeks to a maximum of1 mg/kg orally in 1 or 2 divided doses daily. Alternative ACE inhibitors: captopril, lisinopril	The choice of ACE inhibitor will vary depending on the clinical situation. Seek advice from a specialist cardiologist.
	Adult dosing:· Furosemide (frusemide) 20–40 mg orally or intravenously as a single dose followed by 20–40 mg orally or intravenously every 8–12 hours. Ongoing dose adjustment is based on clinical progression and renal function.· Spironolactone may be added for patients with limited or no response to loop diuretic; 12.5–200 mg orally once daily with dose escalation based on clinical and electrolyte responses.· Nitrate therapy may be added for patients with limited or no response to diuretic therapy and systolic blood pressure greater than 90 mmHg. Intravenous or topical glyceryl trinitrate may be used. ACE inhibitor therapy with perindopril or ramipril is recommended in patients with moderate or severe left ventricular systolic dysfunction, unless contraindicated.	The management of acute carditis follows the same principles as those for the management of acute heart failure. This table provides a guide to the initial management of acute heart failure due to acute carditis in adults. Seeking advice from a specialist cardiologist early is strongly recommended.
	Digoxin 15 micrograms/kg orally as a single dose, then5 micrograms/kg after 6 hours, then 3–5 micrograms/kg (in adults: – 125–250 micrograms) orally, daily	Digoxin is rarely used for the treatment of acute carditis. Seek advice from a specialist cardiologist.
Disease-modifying (immunomodulatory) treatments	Prednisolone 1–2 mg/kg up to a maximum of 80 mg orally, once daily	Considered for use in selected cases of severe carditis, despite meta-analyses in which the overall benefit was not evident.
Secondary prophylaxis	1. Benzathine benzylpenicillin G by deep intramuscular injection 1,200,000 units (≥20 kg) or 600,000 units (<20 kg) *OR2. Phenoxymethylpenicillin (penicillin V) 250 mg orally twice dailyOR3. For patients with penicillin hypersensitivity (non-severe) or immediate penicillin hypersensitivity: – erythromycin 250 mg orally twice daily	Every 28 days. †Every 21 days for selected groups. ‡Intramuscular penicillin is preferred due to greater effectiveness in head-to-head trial and better adherence.

NSAID non-steroidal anti-inflammatory drug

* For children weighing less than 10 kg, a dose of 600,000 units is still generally recommended, but seek paediatric advice for careful planning of the secondary prophylaxis regimen.

† Patients on 28-day regimens can be recalled from 21 days to help ensure that injections are given by day 28.

‡ Benzathine benzylpenicillin G given every 21 days may be considered for:

  • patients who have breakthrough acute rheumatic fever despite complete adherence to a 28-day regimen

  • patients who are at a high risk of adverse consequences if acute rheumatic fever occurs (have severe rheumatic heart disease or a history of heart valve surgery).

Source: modified from reference 2 with permission

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Long-Term Management

Complications of ARF

• Rheumatic Heart Disease (RHD):
  • Progression: Carditis worsens over time with cumulative valve damage, typically developing 10-20 years after initial ARF.
  • Valve Involvement:
    • Mitral Valve: Most commonly affected.
    • Aortic Valve: Less common.
    • Mitral Stenosis (MS): A key chronic finding requiring surgical intervention in some cases (e.g., balloon valvuloplasty).
  • Complications:
    • Embolization: Due to mural thrombi.
    • Infective Endocarditis: Increased risk on deformed valves.
  • Chronic RHD Manifestations: Murmurs, hypertrophy, dilation, heart failure, arrhythmias.

Education and Long-Term Secondary Prophylaxis

• Understanding ARF: Educate patients and families about ARF’s causes and the importance of early treatment for sore throats and skin infections.
• Risk Awareness: Inform family members of their increased risk compared to the general population.
• Long-Term Prophylaxis: Emphasize the importance of adherence to secondary prophylaxis to prevent ARF recurrences and associated cardiac damage.
  • Benzathine Penicillin G: 1.2 million units IM every 3-4 weeks.
  • Oral Phenoxymethylpenicillin: If IM route is unsuitable.
• Duration of Prophylaxis: Minimum 10 years after the last ARF episode or until age 21, whichever is longer.

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Primary Prophylaxis

• Target Population: Individuals at risk of ARF following a GAS infection.
• Treatment of Streptococcal Pharyngitis:
  • Timing: Initiate treatment within 9 days of symptom onset.
  • Benzathine Penicillin G (IM Single Dose):
    • Children:
      • ≥20 kg: 900 mg
      • 15-20 kg: 675 mg
      • 10-15 kg: 450 mg
      • 6-10 kg: 337.5 mg
      • 3-6 kg: 225 mg
    • Adults: 900 mg
  • Alternative (Oral Phenoxymethylpenicillin):
    • Children: 10 mg/kg up to 500 mg, bd for 10 days.
    • Adults: 500 mg, bd for 10 days.
  • Penicillin Allergy: Use Erythromycin Ethyl Succinate.

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Secondary Prophylaxis for Rheumatic Fever

Purpose

• Prevent recurrent ARF episodes and limit progression of valve damage in patients with or at risk of Rheumatic Heart Disease (RHD).

Pathophysiology Rationale

• ARF is an autoimmune sequela of new Group A Streptococcal (GAS) pharyngitis or skin infection.
• Antibodies produced in ARF are pathogenic, not protective.
• Immunity is M-protein (emm-type) specific → new GAS serotype can trigger a relapse.
• Each recurrence increases the risk of progressive valve scarring, leading to permanent RHD.
• Risk of recurrence is highest within 5 years post initial episode.

Target Populations

All patients with:

• Definite, probable, or possible ARF (per Jones Criteria).
• Echo-proven RHD.

Priority groups:

• Children aged 5–20 years.
• Aboriginal and Torres Strait Islander peoples.
• Pacific Islander or migrant populations from high-burden countries.
• Women of childbearing age with RHD.

First-Line Prophylaxis

Benzathine benzylpenicillin G (BPG) IM:

• povides sustained therapeutic penicillin levels for ~3–4 weeks, sufficient to prevent colonisation or infection with Group A Streptococcus (GAS).

• ≥20 kg: 1.2 million units
• <20 kg: 600,000 units
• <10 kg: Consult paediatric guidelines

Interval:

• Every 4 weeks
• Every 3 weeks if:
  • Breakthrough ARF despite 4-weekly dosing
  • Very high-risk groups

Oral Alternatives (if BPG unsuitable)

Drug	Dose	Indication
Phenoxymethylpenicillin V	250 mg BD PO	Non-allergic, BPG-intolerant
Erythromycin	250 mg BD PO	Non-severe penicillin allergy
Sulfadiazine	0.5–1 g daily PO	Severe penicillin anaphylaxis

Note: Ensure local program support and patient adherence for oral options.

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Duration of Prophylaxis

Clinical Scenario	Duration
No carditis	5 years post last ARF or until age 21 (whichever longer)
Mild carditis/RHD	10 years post last ARF or until age 35
Moderate RHD	10 years post last ARF or until age 40
Severe RHD / valve surgery	Lifelong (or as per cardiology advice)

Pathophysiological Rationale

Factor	What Changes Over Time?	Impact on Recurrence Risk
Frequency of GAS pharyngitis	Peaks in primary-school years, falls sharply after late adolescence	Fewer triggers for ARF in adults
Host immune response	Immunological “priming” wanes with age; cross-reactive antibody titres fall	Auto-immune flare after GAS becomes less likely in adulthood
Cardiac substrate	Mild/no valve damage may stabilise once skeletal growth stops	Further ARF episodes add little incremental damage if first episode fully healed

Take-home: In a child with normal valves, the twin drivers for recurrence (strep exposure + hyper-responsive immunity) both fall after the early 20s—hence prophylaxis can safely stop once that window has passed.

Risk–Benefit Framework Used by Guidelines

Risk Stratum	Determinants	Guideline Duration	Key Arguments
Low	· Single ARF episode · No carditis on follow-up echo · Living in region with moderate GAS burden	≥ 5 years or until age 21 (whichever longer)	• By ~5 y the recurrence curve flattens (most repeat ARF occurs earlier). • Adherence fatigue & injection-site complications start to outweigh benefit.
Moderate	· ARF with carditis but valves have returned to normal size/function	≥ 10 years or until age 21	• Even subclinical carditis signals a more “reactive” immune profile. • Another ARF within first decade jeopardises otherwise normal valves.
High	· Persistent structural RHD (mild/moderate) · Residence in high-exposure community	Continue until age 35–40	• Valve damage is permanent; any recurrence accelerates stenosis/regurgitation. • GAS exposure often remains high into early adult working life.
Very High	· Severe RHD, prosthetic valve, valve repair, pulmonary hypertension · Ongoing high GAS exposure where timely treatment of pharyngitis is unreliable	Lifelong	• Catastrophic consequences of even one more ARF episode (heart failure, redo surgery). • GAS is endemic; complete elimination of exposure unrealistic. • Monthly BPG injections have proven net mortality benefit.

Evidence Base

1. Natural-history cohorts
   • 80 % of all ARF recurrences occur within 5 years of the index attack.
   • Reinfection risk plateaus after early adulthood in settings where GAS exposure falls.
2. Penicillin-versus-placebo trials (1950s) and modern observational data
   • IM BPG every 28 days reduces recurrence by > 60 %; benefit greatest in first decade post-ARF.
3. Valve-outcome studies
   • Each recurrence adds incremental scarring; a third episode roughly doubles the chance of needing valve surgery.
4. Cost-effectiveness and harms
   • Injection reactions, anaphylaxis, and adherence burden climb with length of therapy.
   • Beyond age 35, NNT to prevent a single recurrence in mild RHD rises steeply (> 1 000 in low-exposure settings).

Practical Modifiers That Can Shorten or Extend Therapy

Extends Duration	May Shorten Duration
• Residence in high-burden Aboriginal communities or Pacific Island nations	• Migration to low-GAS, high-access health-care environment
• Crowded housing, childcare work, frequent GAS carriage	• Documented excellent adherence + three consecutive normal echocardiograms
• Prior non-adherence or >2 recurrences	• Documented GAS culture and serology negative for 5 years

Clinical Pearls

Shared decision-making matters. Explain the rationale so that patients tolerate years of injections—adherence collapses if they believe “the heart is fixed”.

Never stop prophylaxis on echo findings alone. Always integrate age, exposure, and adherence history.

Valve surgery ≠ cure. Patients with valve replacement remain lifelong high-risk; endocardial injury amplifies the autoimmune response.

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Adherence Strategies

• Injection recall systems (e.g., 21-day alerts for 28-day cycle).
• Local RHD register enrolment.
• Use of lignocaine with BPG to reduce pain.
• Patient and family education.
• Involvement of schools and community health workers.

Why Prophylaxis is Still Required Despite Antibodies

Mechanism	Explanation
Antibody type	ARF antibodies are pathogenic, not protective – they cross-react with human tissue (molecular mimicry).
Type-specific immunity	Immunity to GAS is type-specific, meaning it’s determined by the specific emm (M-protein) type of the bacteria.  There are over 250 different emm types, and a new infection with a different emm type will trigger a new immune response
T-cell memory	Re-exposure activates autoreactive memory T/B cells → faster, more destructive inflammation.
Penicillin role	Eliminates GAS colonisation → removes antigenic trigger → prevents ARF reactivation.

Why This Does NOT Apply to Post-Streptococcal Glomerulonephritis (PSGN)

Feature	ARF/RHD	PSGN
Immunopathology	Type II hypersensitivity (cross-reactive antibodies/T-cells)	Type III hypersensitivity (immune complex-mediated)
GAS Strains	Multiple rheumatogenic strains; recurrence common	Limited nephritogenic strains; recurrence rare
Natural History	Progressive cardiac morbidity with each recurrence	Usually self-limited; rare long-term renal damage
Penicillin efficacy	Long-term penicillin reduces recurrence by >80%	No benefit from long-term penicillin prophylaxis
Guideline stance	Long-term secondary prophylaxis is mandatory	Not recommended; manage acute infection and outbreak control only

Sources: australianprescriber.tg.org.au, wacountry.health.wa.gov.au, cdc.gov

Clinical Take-Home Points

• Start BPG before hospital discharge after ARF diagnosis.
• Enrol in RHD register and arrange long-term follow-up.
• Do not cease prophylaxis early – reassess only when guideline duration is completed, with echocardiographic review.
• Educate families: “Penicillin protects the heart by preventing the strep infections that re-trigger the disease.”
• For PSGN:
  • Treat index case with single-dose BPG.
  • No secondary prophylaxis unless in an outbreak.
  • Focus on hygiene education and renal monitoring.

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Improving Adherence to Secondary Prophylaxis for ARF and RHD

Challenges to Adherence

Adherence to regular benzathine penicillin G (BPG) injections remains a significant barrier to effective secondary prevention of Acute Rheumatic Fever (ARF) and Rheumatic Heart Disease (RHD), particularly in high-risk populations.

1. Sociocultural and Systemic Barriers

• Limited availability and accessibility of health services in remote Aboriginal and Torres Strait Islander (ATSI) communities.
• Acceptability of care is reduced due to past negative experiences, systemic racism, and mistrust of healthcare institutions.

2. Individual Factors (relatively smaller role)

• Fear or refusal of injections
• Pain associated with BPG injections
• Limited health literacy regarding ARF/RHD causes and consequences

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Strategies to Improve Adherence

1. Culturally Safe, Person-Centred Care

• Foster a sense of belonging within the clinic through culturally safe care and respectful relationships.
• Utilise Aboriginal Health Workers (AHWs) for language interpretation, cultural navigation, and community trust-building.

2. Enhanced Recall and Reminder Systems

• Implement automated (SMS) or manual (phone, letter) reminders for appointments and injections.
• Use recall systems that transcend community boundaries, ensuring continuity during travel or relocation.

3. Organisational and System-Level Interventions

• Maintain a comprehensive RHD patient register to track prophylaxis schedules and missed doses.
• Assign dedicated staff (e.g. chronic disease nurses or AHWs) to coordinate injection delivery and follow-up.

4. Proactive Care Planning

• Conduct routine reviews and structured care plans, including echocardiographic assessment and education updates.
• Tailor individualised prophylaxis plans, particularly for mobile or socially complex patients.

5. Health Professional Education and Workforce Stability

• Provide ongoing staff training on ARF/RHD management, cultural safety, and pain minimisation techniques.
• Address high staff turnover through improved recruitment, retention, and support mechanisms in remote areas.

6. Minimising Injection Discomfort

Ensure skilled, empathetic technique when administering injections, especially for children.

Use lignocaine with BPG to reduce pain.

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Procedures Requiring Endocarditis Prophylaxis for Patients with Rheumatic Heart Disease (RHD):

Dental, Oral, and Respiratory Tract Procedures:

1. Dental extractions
2. Periodontal procedures
3. Dental implant placement
4. Gingival surgery
5. Initial placement of orthodontic appliances
6. Surgical drainage of dental abscess
7. Maxillary or mandibular osteotomies
8. Endodontic surgery and instrumentation
9. Placement of orthodontic bands
10. Intraligamentary local anaesthetic injections
11. Surgical repair or fixation of a fractured jaw
12. Tonsillectomy/adenoidectomy
13. Rigid bronchoscopy
14. Surgery involving the bronchial mucosa
15. Sclerotherapy of oesophageal varices
16. Dilatation of oesophageal stricture

Genitourinary and gastrointestinal procedures

1. Surgery of the intestinal mucosa or biliary tract (except for endoscopy, biopsy and percutaneous endoscopic gastrostomy)
2. Endoscopic retrograde cholangiography
3. Prostate surgery
4. Cystoscopy and urethral dilatation
5. Vaginal delivery in the presence of infection, or prolonged labour or prolonged rupture of membranes
6. Surgical procedures of the genitourinary tract in the presence of infection (e.g. urethral catheterisation, uterine dilatation and curettage, abortion, sterilisation and placement or removal of intrauterine contraceptive devices)

ADDITIONAL INFORMATION

Symptoms in detail:

Arthritis

• Several large joints in quick succession: knees, ankles, elbows, wrists
  • Legs first
  • Each for short time (< 1 week) but overlap 🡪 migratory
• Earliest symptomatic manifestation
• Symptoms – pain > inflammation
• Investigations
  • Xray – may show effusion
  • Joint aspirate – sterile inflammatory fluid
• Treatment
  • Aspirin or NSAIDs

Carditis

• Pancarditis – pericardium, epicardium, myocardium, endocardium
• Symptoms:
  • Chest discomfort, pleuritic chest pain, pericardial rub
  • Exam –
    • Murmurs – new/changing, MR most common
• If severe valve damage + myocarditis causing myocardial dysfunction
  • Can 🡪 heart failure
  • Most life-treathening clinical syndrome
  • Treat as APO
• Investigations
  • ECG – heart block (all degrees)
  • CXR – cardiomegaly
  • Echo – acute carditis, valvular regurgitation/stenosis, chamber size and function, pericardial effusion
  • Antimyosin scintigraphy – 80% sensitive for carditis (any cause)

Chorea

• Sydneyham, chorea minor, “St Vitus dance”
• Abrupt, purposeless, nonrhythmic involuntary movements + muscular weakness + emotional disturbance

• Clinical signs: 
  • More marked on one side
  • Cease during sleep
  • Weakness revealed when ask to squeeze emaminer’s hands 🡪 milking sign
  • Emotional – inappropriate, crying, restless, psychosis
  • Neurological – no sensory changes, diffuse hypotonia
  • Can take to up 8 months to manifest

Subcutaneous nodules

• Firm and painless, overlying skin not attached or inflamed
• < 2cm wide
• Over bony surface or prominence or near tendons
•  Present for < 4 weeks
• Usually only in patients with carditis

Erythema Marginatum/annulare

• Evanscent non-pruritic rash
• Pink/faintly red
• Trunk, sometimes proximal limbs
• Extends outwards while skin in centre return to normal