Streptococcal Infections: The Case of Acute Rheumatic Fever / Rheumatic Heart Disease

Streptococcal Infections: The Case of Acute Rheumatic Fever / Rheumatic Heart Disease

Ahmed MandilProf of Epidemiology

Family & Community Medicine DeptKing Saud University

Headlines

Streptococcal Infections Sore throat (streptococcal

versus viral) Acute rheumatic fever Rheumatic heart disease Prevention and control

April 20, 2023 2ARF/RHD

Types of Streptococcal Infections

According to reaction on blood-agar plates: Αlpha-hemolytic group (Streptococcus

viridans): produces hemolysis circled by a greenish ring surrounding the central colony

Βeta-hemolytic group (Streptococcus pyogenes): produces a completely clear zone around the central colony

April 20, 2023 ARF/RHD 3

Upper respiratory infections (sore throat): acute pharyngitis or acute tonsillitis Skin infections: impetigo, pyoderma Other acute infections: scarlet fever, puerperal sepsis, septicemia, erysipelas,

cellulitis, mastoiditis, otitis media, pneumonia, rarely: toxic shock syndrome Non-suppurative complications: acute rheumatic fever (within 19 days on the

average), acute glomerulo-nephritis (within 1-5 weeks on the average), rheumatic heart disease (days-weeks)

Group A β-Hemolytic Streptococci: Clinical presentations


Group A β-Hemolytic Streptococci could be a precursor of two serious non-suppurative sequlae, namely:

• Post streptococcal glomerulonephritis• Acute rheumatic fever and rheumatic

heart disease

Public Health Importance:


What are the clinical What are the clinical features of strep sore features of strep sore throat?throat?

Hallmarks of STREP sore Hallmarks of STREP sore throatthroat

Close contact with infected person Tender lymph nodes Excoriated nares (crusted lesions) in infants Tonsillar exudates in older children Scarlet fever rash Abdominal pain GOLD STANDARD: POSITIVE THROAT

CULTURE


Hallmarks of VIRAL sore Hallmarks of VIRAL sore throatthroat

Other family member with COLD symptoms; evidence of other viral infection

Coryza: runny nose or mouth ulcers Itchy watery eyes Hoarseness and cough: non-specific Fever: not specific Red Throat: not specific


What are the treatment What are the treatment regimens of streptococcal regimens of streptococcal sore throat?sore throat?

Primary Prevention of Primary Prevention of Rheumatic Fever by treating Rheumatic Fever by treating sore throatsore throat

Oral penicillin is less efficacious than Penicillin IMIAnaphylaxis is extremely unusual


Is it cost-effective to administer Is it cost-effective to administer penicillin for all cases of penicillin for all cases of suspected strep sore throat?suspected strep sore throat?

An overall protective effect for the use of penicillin against acute rheumatic fever of 80% with an NNT of 60 children per year to prevent 1 episode of rheumatic fever.

Mild hypertension: have to treat 800 people per year to prevent 1 episode of stroke


Is it cost-effective to administer Is it cost-effective to administer penicillin for all cases of penicillin for all cases of suspected strep sore throat?suspected strep sore throat?

The estimated cost of preventing one case of rheumatic fever by a single intramuscular injection of penicillin is US$46

Valve replacement surgery for 1 case of RHD is at least US$15, 000

Cardiac surgery in African nations: available in Egypt, South Africa, and Ghana


Acute Rheumatic Fever

Occurrence

Children: 3-18 years, more in developing nations compared to developed

Equal gender distribution Risk factors include: poor socio-economic

conditions and access to healthcare Peak in colder months 2-6 weeks

following GA-β hemolytic strep infection Sudden onset of fever, pallor, malaise


Incidence of ARF: Incidence of ARF: Population-based StudiesPopulation-based Studies

40

35

30

25

20

15

10

5

0

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/1

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0 p

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1 2 3 4

USA (all ages)Martinique (<20yrs)New Zealand (<30yrs)Kuwait (5-14yrs)Iran (all ages

11

5 6 7 8 9 10Time (years)

Figure 5: Trend in I ncidence of First Attack of Acute Rheumatic Fever Over Time


General FeaturesGeneral Features

Autoimmune consequence of infection with Group A streptococcal infection

Results in a generalised inflammatory response affecting brains, joints, skin, subcutaneous tissues and the heart.

Currently the modified Duckett-Jones criteria form the basis of the diagnosis of the condition.


Carapetis. Lancet 2005;366:155


Jones’ Criteria

Major criteria: arthritis; carditis; Sydenham’s chorea; erythema marginatum; subcutaneous nodules

Minor criteria: fever; arthralgia; elevated C-reactive protein; Rising Erythrocyte Sedimentation Rate; prolonged PR-interval (on ECG examination)


Rheumatic Heart Disease

Overview - 1Overview - 1

Rheumatic Heart Disease is the permanent heart valve damage resulting from one or more attacks of ARF.

It is estimated that 40-60% of patients with ARF will go on to developing RHD

The commonest affected valves are the mitral and aortic, in that order. However all four valves could be affected.



Sadly, RHD can go undetected with the result that patients present with debilitating heart failure.

At this stage surgery is the only possible treatment option.



Patients living in poor countries have limited or no access to expensive heart surgery.

Prosthetic valves themselves are costly and associated with a not insignificant morbidity and mortality.


In the Pacific Islander population of New Zealand the incidence rate of ARF is 80-100 per 100 000 compared to non-indigenous new Zealanders <10 per 100 000.

In a recent systematic review of the incidence of first attack of rheumatic fever, a Maori community in New Zealand has a disturbingly high incidence of >80/100,000 per year.


What is the incidence of acute What is the incidence of acute rheumatic fever and rheumatic rheumatic fever and rheumatic heart disease?heart disease?

Incidence of newly Incidence of newly diagnosed RHDdiagnosed RHD

A prospective clinical registry captured data from new presentation of structural and functional valvular heart disease presenting to the department of cardiology in 2006/7.

Of the 4005 de novo cases, 344 (8.6%) were diagnosed as having RHD. A significant proportion presented with complications and 22% subsequently underwent surgery.


What is the prevalence of What is the prevalence of rheumatic heart disease?rheumatic heart disease?


Prevention & Control

Basic principles 1 In some developing countries, remarkable

progress has been made in terms of decreasing incidence of ARF

In 1986 a comprehensive 10-year prevention programme was conducted in a Cuban province.

This programme relied on comprehensive primary and secondary prevention of RF/RHD as well as awareness and education programmes


Basic principles 2 The main content of the activities focused

around early detection and treatment of sore throats and streptococcal pharyngitis

The project also included primary and secondary prevention of RF/RHD, training of personnel, health education, dissemination of information, community involvement and epidemiological surveillance.


Basic principles 3 There was a progressive decline in the occurrence

and severity of acute RF and RHD, with a marked decrease in the prevalence of RHD in school children.

A marked and progressive decline was also seen in the incidence and severity of ARF

There was an even more marked reduction in recurrent attacks of RF as well as in the number and severity of patients requiring hospitalisation and surgical care.


RHEUMATIC FEVER IS RHEUMATIC FEVER IS PREVENTABLEPREVENTABLE

Costa Rica

CubaApril 20, 2023 39ARF/RHD

Primary Prevention of Primary Prevention of Rheumatic Fever by treating Rheumatic Fever by treating sore throatsore throat

Oral penicillin is less efficacious than Penicillin IMIAnaphylaxis is extremely unusual


Rheumatic Heart Disease:Rheumatic Heart Disease:SECONDARY PREVENTIONSECONDARY PREVENTION

PICTURE TAKEN OUT FOR SPACE ISSUES

THIS IS TOO THIS IS TOO LATELATE


Secondary Prevention Secondary Prevention Stops sore throat, prevents Stops sore throat, prevents recurrences of ARF and aids in recurrences of ARF and aids in regression of RHD regression of RHD

Oral penicillin has been shown to be less effective than Penicillin IMIAnaphylaxis is extremely unusual


Review: Penicillin for secondary prevention of rheumatic feverComparison: 02 Two-weekly versus 4-weekly penicillin injectionsOutcome: 02 Streptococcal throat infections

Study 2-weekly injections 4-weekly injections RR (fixed) Weight RR (fixed)or sub-category n / N n / N 95% CI % 95% CI

Kassem 1996 38 / 190 57 / 170 100.00 0.60 [0.42, 0.85]

0.1 0.2 0.5 1 2 5 10

Favours treatment Favours control

Review: Penicillin for secondary prevention of rheumatic feverComparison: 03 Three-weekly versus 4-weekly intramuscular penicillinOutcome: 02 Streptococcal throat infections

Study 3-weekly injections 4-weekly injections RR (fixed) Weight RR (fixed)or sub-category n / N n / N 95% CI % 95% CI

Lue 1996 39 / 124 59 / 125 100.00 0.67 [0.48, 0.92]

0.1 0.2 0.5 1 2 5 10

Favours 3-weekly Favours 4-weekly


During an episode of ARF, valve changes can be minor and are still able to regress.

After recurrent episodes of ARF, thickening of subvalvar apparatus, chordal thickening and shortening and progression to permanent valve damage is evident.


Awareness ♦ Surveillance ♦ Advocacy ♦ Prevention

Secondary Secondary prevention: prevention:

DurationDurationCATEGORY DURATION OF PROPHYLAXISAll persons with ARF with no or mild carditis

MINIMUM 10 years after most recent episode or age 21

All persons with ARF and moderate carditis

MINIMUM 10 years after most recent episode or age 35

All persons with ARF and severe carditis

MINIMUM 10 years after most recent episode or age 35 and then specialist review for need to continue. Post surgical cases definitely lifelong.


Secondary prevention: specificsSecondary prevention: specifics

PENCILLINSecondary prophylaxis also reduces the severity of RHD.It is associated with regression of heart disease in approximately 50-70% of those with good adherence over a decade and reduces mortality.Route:BPG is most effective when given as a deep intramuscular injection.


Secondary prevention: Secondary prevention: AdherenceAdherence

• Use a 23-gauge needle- deeper is better• Local pressure to area for 10 secs• Warm syringe to room temperature• First allow alcohol to dry or use ethylchloride

spray.

How can we reduce the pain associated with IM Penicillin?


Secondary prevention: Secondary prevention: AdherenceAdherence

• Deliver injection very slowly(over 2-3mins)• Distraction techniques• Good rapport with the case, is a significant aid to

injection comfort, compliance and understanding.• Use 0.5-1ml of 1% lignocaine. Reduces pain

significantly and excellent for younger patients.


Ensuring that patients understand their disease, are informed regarding their future and receive secondary prophylaxis

EDUCATIONEDUCATIONHealth education is critical at all levels

Lack of parental awareness of the causes and consequences of ARF/RHD is a key contributor to poor adherence amongst children on long-term prophylaxis.


What is the role of a What is the role of a register-based programme?register-based programme?

Background In 1972, the WHO launched a register-based

programme to combat ARF/RHD By 1990, registers had been established in 16

countries with over a million school-going children involved. However in 2001, the WHO ceased its funding to this global programme.

Experience elsewhere however provides conclusive evidence of registers realising notable successes in reducing RF recurrence.


Purposes Collect data on demographic profiles; Highlight

deficiencies in service deliveryPriority-based guidelines to evaluate and manage patients

A register of cases of RF and RHD can be used to improve treatment adherence in order to prevent recurrent RF and the development of RHD, necessitating surgery.


A.S.A.P. Programme for the A.S.A.P. Programme for the Control of RHD in Africa: Focus Control of RHD in Africa: Focus areas for action areas for action

Awareness raising: public, healthcare workers

Surveillance: incidence, prevalence, temporal trends

Advocacy: appropriate funding of the treatment and prevention programmes

Prevention: application of existing knowledge in primary & secondary prevention


ConclusionConclusion

Rheumatic heart disease is the only truly preventable chronic heart condition

Primary prevention: Penicillin for suspected strep sore

throat Secondary prevention

Penicillin prophylaxis


References Heymann DL. Control of communicable

diseases manual. Washington DC: American Public Health Association, 2008

Zühlke L. The prevention of rheumatic fever and rheumatic heart disease. Cape-Town: Red Cross War Memorial Childrens Hospital.

http://www.who.int/cardiovascular_diseases/resources/trs923/en http://www.pascar.co.za/C_ASAP.asp


Thank you for your kind attention


Streptococcal Infections: The Case of Acute Rheumatic Fever / Rheumatic Heart Disease

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