Prof. P. Krishnam Raju CARE Hospitals & CARE Foundation Hyderabad Acute Rheumatic Fever - Natural...

Prof. P. Krishnam RajuCARE Hospitals & CARE Foundation

Hyderabadwww.carehospitals.comwww.carefoundation.org.in

Acute Rheumatic Fever - Natural History- Indian Scenario

Historical Vignettes

• Vieussens-autopsy of valvar lesions – 1715

• RHEUMATISM – Baillie – 1797

• Pitcain – Rheumatism & heart disease

• Peter latham---Rh:pericarditis, endocarditis.

• Boulland-hallmark article-father of rheumatic heart disease.

• Scolt – RHD in India. [ 1938]

RF

Natural History

• Provides insights into pathophysiology of the disease

• Permits better recognition of the disease and sequelae

• Clues for more effective intervention strategies

UNIVERSITY OF DISEASE

Sequence of events

Leading to onset of RF

RF disease/ course

/complications

RHD

Demographic

Socioeconomic/Housing

Genetic /Ethnic

Host Factors

Rheumatogenicity of STR

RF

• 19th and Early 20th century RF – leading cause of death

(5 to 20 yrs group)

• Second leading cause of death in the age group 20 to 30 Y

• Mortality - due to carditis

• 60% of all ARF deaths in the first 5 yrs

(carditis / chronic RhVHD / IE )

20th Century

• Pre penicillin era – mortality from AC carditis – 8 to 30%

• Decline evident by 1930s – 1 yr mortality – 4%

• There after steady decline.

Rheumatic Heart Disease

Not gone

But

Almost Forgotten

World congress of Cardiology 2006

Barcelona

RF

• Major problem in developing Nations

• Children and young adults – Victims

• 60% of CVD in young / children – RHD

• Affects upto 20 m people World wide

• 2 million children are affected / World wide

• 500000 deaths / Annually / World wide

• Undermines National Productivity

“ Most solvable cardiac probem affecting the developing world”

“Cardiac surgery for RHD “ Chews up” funds”

Introduction

• Acute rheumatic fever: inflammatory disease with devastating sequelae• Link to pharyngeal infection with group A beta

hemolytic streptococci* Continues to be a problem worldwide:

Sporadic outbreaks in developed countriesFrequent occurrences in developing

countries• Still gaining understanding of etiology andLink between genetic predisposition and clinical

manifestations Best prevention still-- correct use of antibiotics

Epidemiology (continued)

• Usually occurs in people between 5 and

18 years old

• Males and females equally affected

• Overcrowding, poverty, lack of access to

medical care contributes to transmission

• Virulence of strain important

• In tropics/subtropics: year-round incidence

with peak in colder months

Pathogenesis

• Group A strep pharyngeal infection precedes clinical

manifestations of ARF by 2 - 6 weeks

• Antibodies made against group A strep cross-react

with human tissue

heart valve and brain share common antigenic

sequences with GAS bacteria

theory of molecular mimicry

• Host immune responses may play a role in determining who

gets ARF following infection

• Virulent strains: rheumatogenic serotypes

The Epidemiologic Triad of Rheumatic Fever

RHEUMATIC FEVER

Incidence : Strep. Infection

Sporadic : 0.3%

Epidemic : 3.0%

(closed communities)

Why do others escape?

? Genetic susceptibility

ARF and RHD

• Major health problem in developing countries including India

• Approximately 2 million cases have RHD and 50,000 new

episodes of RF occur/year

• RHD prevalence 1 – 5.4 / 1000 school children

• ARF incidence 0.3 – 0.5 / 1000 school children

Padmavathi et al. 1995

Epidemiology – WHO

• 15.6 million people – RHD

• 300 000 of about 0.5 million individuals who acquire ARF every year go on to develop RHD

• 233 000 deaths annually are directly attributable to ARF or RHD.

Epidemiology

• ARF is a rare disease in the very young

• Only 5% of first episodes – children younger than

age 5 years.

• Almost unheard of in those younger than 2 years.

• First episodes of ARF are most common just

before adolescence

• Rare in adults older than age 35 years

Organism – GAS

• RHEUMATOGENECITY – strains 1,3,6 and 18- M Serotypes

• Infrequently found in several communities with high burdens of

ARF and RHD, where newly identified serotypes or those most

often associated with skin infections have been linked with

disease.

“Diagnostic criteria must be subject to change as knowledge and experience increases”

T Duckett Jones 1944

- Original Jones Criteria 1944

- Modified Jones Criteria 1956 (Modified in 1951

for use in a trial)

- Revised Jones Criteria 1965, 1984 (Reference to Echo)

- Jones Criteria update 1992 (discussed the Role of Echo)

Undergone remarkably few changes

- Compulsory evidence of Preceding strep infection.

- Applicability only for the initial attack of RF

- Recurrent episodes (1 major or 2 or more minor criteria)

T. Duckett Jones Criteria – Evolution

The Original Jones Criteria – 1944*Major Manifestations Minor Manifestations

1. Carditis 1. Fever

2. Arthralgia 2. Abdominal pain

3. Chorea 3. Precordial pain

4. Subcutaneous 4. Rashes (erythema

nodules marginatum)

5. History of previous 5. Epistaxis

definite rheumatic 6. Pulmonary findings

fever or rheumatic 7. Laboratory findings

heart disease a. Electrocardiographic

abnormalities

b. Microcytic anemia

c. Elevated total leukocyte

count

d. Elevated erythrocyte sedimentation rate

I

T. Duckett Jones Criteria – Evolution

The Modified Jones Criteria – 1956*

Major Manifestations Minor Manifestations

1. Carditis 1. Fever2. Polyarthritis 2. Arthralgia3. Chorea 3. Prolonged PR interval4. Subcutaneous nodules 4. Increased erythrocyte

sedimention rate, presence of C-reactive protein or leukocytosis

5.Erythema Marginatum 5. Previous history of rheumatic fever or the presence of inactive rheumatic heart disease6. Evidence of preceding betahemolytic streptococcal infection

II

T. Duckett Jones Criteria – EvolutionThe Revised Jones Criteria – 1965*


1. Carditis 1. Fever2. Polyarthritis 2. Arthralgia3. Chorea 3. Previous rheumatic fever or

rheumatic heart disease.4.Erythema marginatum 4. Elevated erythrocyte sedi-

mentation rate, positive C- reactive protein, leukocytosis

5.Subcutaneous nodules 5. Prolonged PR interval

Plus supporting evidence of preceding streptococcal infection : history of recent scarlet fever; positive throat culture for group A streptococcus; increased ASO titer or other streptococcal antibodies:

III

T. Duckett Jones Criteria – EvolutionThe Jones Criteria Update – 1992*


1. Carditis 1. Clinical findings2. Polyarthritis 2. Arthralgia3. Chorea 3. Fever4. Erythema marginatum 4. Laboratory findings 5. Subcutaneous nodules Elevated acute phase

reactants, erythrocyte sedimentation rate, C-reactive protein 5. Prolonged PR interval

Supporting Evidence of Antecedent Group A Streptococcal InfectionPositive throat culture or rapid streptococcal antigen test Elevated or rising streptococcal antibody titer

IF supported by evidence of preceding group A streptococcal infection, the presence of two major manifestations of one major and two minor manifestations indicates a high probability of acute rheumatic fever.

IV

Evolution of Laboratory tests in Diagnosis of Acute Rheumatic Fever

Laboratory Test

Year of Revision

1944 1955 1965 1984 1992

Evidence of preceding streptococal infection

Acute phase reactants

(ESR,CRP) leukocytosis and electrocardiiographic criteria

-

MC

MC*

MC§

EC**

MC

EC†

MC

EC‡

MC

* MC indicates minor criteria; EC essential criteria; ESR. Erythrocyte sedimentation rate. CRP, C-reactive protein.

** Evidence of preceding streptococcal infection was not considered mandatory for the diagnosis of indolent carditis and Sydenham’s chorea.

† History of sore throat is no longer considered adequate as evidence of a preceding streptococcal infection.

‡ Anti-DNase B and antihyaluronidase tests introduced as newer diagnostic tools.

§ In 1955, the hematologic and electrocardiographic criteria (prolonged PR interval) were split into separate minor criteria each of which could contribute to the diagnosis of acute rheumatic fever.

WHO Criteria…

• WHO criteria ( 2002-03)

• Chorea and indolent carditis do not require

evidence of antecedent group A streptococcus

infection

• First episode – As per Jones criteria

Arthritis

• Most common feature: present in 80% of

patients

• Painful, migratory, short duration, excellent

response of salicylates

• Usually >5 joints affected and large joints

preferred

Knees, ankles, wrists, elbows, shoulders

• Small joints and cervical spine less commonly

involved

Natural history of rheumatic arthritis

• Usually resolves in 3 weeks even when untreated.

• Usually no chronic sequale

• Jaccoud’s arthritis – periarticular fibrosis of

metacarpophalaqngeal joints – in those with

multiple recurrence.

Subcutaneous Nodules

• Usually 0.5 - 2 cm long

Firm, non-tender, isolated or in clusters

• Most common: along extensor surfaces of joint

Knees, elbows, wrists

• Also: on bony prominences, tendons, dorsi of feet, occiput or cervical spine

• Last a few days only

• Occur in 9 - 20% of cases

• Often associated with carditis

Erythema Marginatum

• Present in 7% of patients

• Highly specific to ARF

• Cutaneous lesion:

• Reddish pink border

• Pale center

• Round or irregular shape

• Often on trunk, abdomen, inner arms, or thighs

• Highly suggestive of carditis

Rh Chorea

Natural History

• Isolated chorea in 10% with RF

• Female Propensity

• Subsides in > 75% in 6 months

• Recurs in 1/3rd

• No Long term neuro sequelae

• Concomitant carditis – 3 to 73% (various reports)

• Chronic RHD on follow up in Isolated Chorea

(20-34%)

Jaccoud’s Arthritis

Prevalence Studies

• Pioneer study in India – berry et al [1972]– chandigarh population based study.

• Total No : 3396

• Male – 1.23%

• Female – 2.07%

ICMR Studies

• Prevalence in 1000 school children

• Agra - 5.3

• Delhi - 11.0

• Hyderabad - 6.7

• Alappuzha - 2.2

• Bombay -1.8

RF / RHD in India

• PADMAVATHI et al 1995

• Prevalence - 1-5.4/1000

• ARF incidence - 0.3-0.5/1000

• Koshey et al - 4.9/1000

• Newdelhi study - 9.0/1000

• K.S. Reddy, Delhi - 1.8/1000

Studies…

• According to a conservative estimate

[ vijaykumar et al] approximately 1 million people

have RHD in India and there are 50000 new

episodes of RF per year.

RF PREVALANCE

ICMR 1970 1.8 -11 /1000

KANPUR 2000 4.5 /1000

HOSPITAL DATA

SAT NEW RF 1998 - 79

1999 - 76

2000 - 97

Rheumatic Fever

Burden in India

Population 1.2 Billion.

Adults with RHD (1/1000) 12 million

Children 5 to 15 yrs (25%) 30 million

RF / RHD at 1/1000 3 million

0.5/1000 1.5 million.

RHEUMATIC FEVER

Problems in India

• Juvenile sympt. RHD common

• 25% present with severe valvar lesions below

20 yrs.

• Majority symptomatic in II / III decade of life

• Repeated hospitalisation

• Expensive surgical management

• Loss of productive manpower

RHEUMATIC FEVER

Carditis : frequency

Padmawati (1966 / 74) 14%

Sanyal (1974) 33.3%

Roy (1960) 46%

Aggarwal (1986) 51%

Vaishnava (1960) 90%

SAT, Trivandrum Study

• 66 patients

• 3 years follow up, 58% had clinical & 71.2%

had echo evidence of rhd.

Natural History….

• As high as 70% of MR in the initial attack can disappear clinically over a period of time.

• JUVENILE MS – in young people [<20 years]

• In India 23% and in the west 5%

• The latent period in west 5-10 years, in India as short as 1-3 years.

Natural History

• AR

• Overall incidence : 50%

• Isolated : < 10%.– rare

• It has no latent period

• It can also disappear with time, but rare.

Natural History…

• AS-if AS is present with MV involvement rheumatic.

• As below 20 years – 12% rheumatic

• Isolated As below 12 years is almost always congenital.

•TV : rare, organic TR/TS can be found in 5-8%

• PV: involvemnt is very rare: < 1%

Natural History of ASO

• Appears at diagnostic titre by 7-10 days,

peaks by 2-3 weeks.

• 70-80% positive > 240 in adults,> 320 in

children.

• Rh: Chorea – 20-40%

• The ASO elevation at diagnostic titres can

remain up to 3-6 months.

ASO…

• Aso response is affected by antibiotic usage,

steroid administration.

• Anti DNA ase B: second most useful antibody test.

positive in 80% ARF may be positive in ARF even if

ASO is negative.

• Titer: > 120 in adults, > 240 in children.

RHEUMATIC FEVER

School surveys for RF/RHD (ICMR) Age 5-14 yrs

• 1972 – 75 (40,000 / centre)Agra, Alleppy, Bombay, Delhi, Hyderabad.

• 1984-87 (20,000 / centre).Delhi, Varanasi, Vellore.

• 2002-2005 (25,000 / Centre)Kochi, Vellore, Chandigarh, Indore.

RHEUMATIC FEVER

RF / RHD : School Surveys

• 1972 – 75 (133,000)0.8 to 11/1000; overall 5.3/1000.

• 1984-87 (52, 793).1.0 to 5.7 / 1000 overall 2.97 / 1000.

• 2002-2005 (100,269)0.43 – 1.47 / 1000 overall 0.9 / 1000

Carditis

Bland & Jones (20 yr. F.U.-1951) 80%

Recent U.S. epidemics 91%

New Zealand 76%

RHEUMATIC FEVERRHEUMATIC FEVER

The Prevalence of Rheumatic Fever Worldwide

Area No

Screened

Prevalence (RF+RHD/

1000)

Range of Prevalence

Africa 173,408 4.7 3.4-2.6

E.Mediterranean 409,933 4.4 0.9-10.2

Americas 23,328 1.5 0.1-7.9

W.Pacific 631,899 0.7 06-1.4

S.E. Asia 195,142 0.1 0.1-1.3

Frequency of Carditis in Acute Rheumatic Fever

Country (Ref) Carditis in All Attacks Country (Ref) Carditis in First Attacks (%) (%)

Iran 83 India 30Philippines 73 Chile 40Pakistan 75 Iraq 40Egypt 80 Kuwait 40Thailand 99 USA 40Nigeria 99 USA 70

India 90 USA 50

Yearly Estimates of New Rheumatic Fever Cases in Developing Countries

Population (millions)

Worldwide 5298

Low income countries 3013

Children below 15 years age 904

(estimated at approximately 30% of the population)

No. of sore throats per year (estimated at 1 per child/year) 904

No. of strep sore throats per year (estimated at 10% of all sore

throats per year) 90.4

No. of new rheumatic fever cases per year (estimate at 0.3-3%

of strep sore throat infections) 0.27-2.71

* Data taken from references 133,219, and 23.

Clinical Presentation of Rheumatic Fever in the first attack

Presentation All Patients (%)** Severe Carditis (%) RHD and

USA India USA India Follow-up (%)†

Chorea 4 16 0 - 22

Arthritis 76 67 3 5 26

No Chorea/ 11 7 55 71 81

Arthritis

• From references 24 and 53 .

• Numbers do not add up to 100 percent since more than one presentation is possible. Excludes arthralgias and other presentations of rheumatic fever.

• † Data from the Indian series for all patients.

Frequency of Major Manifestations in Initial Attacks of Rheumatic Fever in Prospective Studies*

Manifestation Kuwait India UK USA

Carditis 46 34 55 42

Polyarthritis 79 67 85 76

Chorea 8 20 13 8

Nodules 0.5 3 - 1

Erythema marginatum 0.5 2 - 4

*Adapted from: Markowitz M, Evolution and critique of changes in the Jones criteria for the diagnosis of rheumatic fever. N Engl J Med 1988: 101:392-4.

I

Circulation, Volume XLIX, January 1974

SUMMARY

A prospective study was done to determine the clinical profile of first attacks of acute rheumatic fever in

children in North India. Unlike other reports, the clinical profile described here closely resembles the

spectrum prevalent in the West. Arthritis, the most common manifestation, was seen in 66.6% of the 102

patients, chorea in 20.7%, and carditis in 33.7%. Carditis was considered mild in 22 patients and severe in

12; a persistent elevation of sleeping pulse rate and mitral regurgitation was noted in each case. Patients

with severe carditis also had significant cardiomegaly and apical mid-diastolic murmur. Two patients with

severe carditis developed congestive heart failure; one of them had pericarditis as well. Murmur of aortic

origin was not noted in this series. One patient with severe carditis died from the disease. Erythema

marginatum was noted in two, both of whom had severe carditis. There were two instances of

subcutaneous nodules, one with and one without carditis. The close similarity of these results with those in

the West is attributed to the prospective design of the study, analysis of first attacks only and survey of a

general pediatric population for all manifestations suggestive of the disease.

III


IV


Arthritis Carditis

V

Chorea Congestive Heart Failure

62-85%

76%

66.66%

40-51%41.8%

33.3%

20.5%

15%

7.6% 5-10% 5.6%1-9%0

20

40

60

80

100


Markowitz et al

Feinstein et alOurs

I

SUMMARY :

We determined the outcome of acute rheumatic fever in 85 children from North India who had received regular antistreptococcal prophylaxis after their first attack. By the end of the 5-year follow-up, 33 patients had rheumatic heart disease. Mitral insufficiency, the most common valvular lesion, appeared in 91% of the patients, whereas mitral stenosis developed in only 18%. Initial carditis, congestive heart failure, cardiomegaly or moderate-to-severe mitral insufficiency significantly increased the risk of rheumatic heart disease (p < 0.001). The recurrence rate of acute rheumatic fever in children who received continuous prophylaxis was 0.006 per patient-year. Most recurrences (92%) mimicked the first attack and produced further cardiac damage in five patients with carditis and in one patient with chorea. Cardiac status during the first attack of rheumatic fever and the continuity of prophylaxis were the major determinants of outcome. Statistical comparisons disclosed that with continuous prophylaxis, the prevalence rate, evolution and clinical spectrum of the sequelae of acute rheumatic fever in children from India do not differ significantly from those in the West.

Circulation 65, No.2, 1982

II


III


IV


NATIONAL MORTALITY DUE TO R F (USA) NEJM 1988

Evolution of Chronic Valve Disease after Rheumatic Fever (Overall Rates Pooling Cases with and without Carditis)

Author (ref) Year Number Average Number

of RF Follow with RHD(%)

Patients up (yrs)

I. Studies in the Prepenicillin Era

Wilson (139) 1928 416 - 331 (80)

Findlay (51) 1932 644 - 428 (66)

Kaiser (73) 1934 1240 - 794 (64)

Schlesinger

(115) 1938 1000 - 742 (74)

Ash (10) 1948 537 10 334 (62)

Bland and Jones

(24) 1951 1000 10 677 (67.7) 1951 1000 20 671

(67.1)

Thomas (126) 1961 125 5 66 (53)

Perry (106)† 1969 938 12 528 (57)

I

Evolution of Chronic Valve Disease after Rheumatic Fever (Overall Rates Polling Cases with and without Carditis)



Patients up (yrs)

II. Data from the Early Penicillin Era (1950s and 1960s)

Feinstein (48) 1964 441 7.8 147 (33.3)‡

US-UK trial

(100) 1965 347 10 130 (38)

Perry (106) 1969 68 12 6 (9)

II

Evolution of Chronic Valve Disease after Rheumatic Fever (Overall Rates Polling Cases with and without Carditis)



Patients up (yrs)

IIIData from the Later Penicillin Era (1970s and later)

Tompkins 1972 115 9.3 30 (26)

(130)

Sanyal (114) 1982 85 5 33 (39)

Majeed 1986 126 6 38 (30)

(85,88) 1992 64 12.3 13 (20)

III

0

20

40

60

80

100

1921 1930 1940 1950

% o

f P

atie

nts

with

Rhe

umat

ic F

ever

0

20

40

60

80

100

Pre 1939 1939-1946 1947-1954 1955-1962

= Incidence of Carditis

= Incidence of severe carditis

= Return of heart size to normal after attack of carditis

Evolution of Chronic Valve Disease after Rheumatic Fever (with Carditis)


of RF Duration Follow with RHD(%)

Patients up (yrs)


Ash (10) 1948 318 10 288 (91)

Bland and 1951 653 10 577 (89)

Jones (24) 653 20 545 (84)

Thomas (126) 1961 84 5 51 (61)

Wilson (135) 1962 757 40 449 (59)

Perry (106)† 1969 701 12 584 (70)

I




Patients up (yrs)

II Data from the Early Penicillin Era (1950s and 1960s)

Feinstein (48) 1964 216 7.8 143 (66.2)

US-UK trial

(100) 1965 267 10 127 (47.5)

II




Patients up (yrs)

III. Data from the Later Penicillin Era (1970s and later)

Tompkins 1972 80 9.3 28(35)

(126)

Lue (84)‡ 1978 539 5.4 428 (79)

Sanyal (114) 1982 45 5 30 (66)

Majeed 1986 61 6 34 (56)

(85,88) 1992 29 12.3 13 (45)

III

Severity of Rheumatic Carditis and Rates of Disappearance of Murmurs (Data From the Penicillin Era)

Author, Yr No. of

Patients

Follow-up

(years)

No Cardiac

Enlargement

Cardiac

Enlargement

Overall

US-UK Trail, 1965 (100)

188 10 70 32 62

Feinstein, 1964 (48)*† 25 7.8 61 25 44

Tompkins, 1972 (130)* 79 9.3 84 36 74

Regression of Murmurs (%)

• Data shown in this table for these series is only for regression of mitral regurgitation.

† Data on initial attack of rheumatic carditis.

Incidence of Bacterial Endocarditis Among Patients with Rheumatic Heart Disease

Author, year No. of Duration Bacterial(Reference) Patients of FollowEndocarditis

Up(yrs) (%)I. Studies in the Prepenicillin Era Grant, 1933 (59) 668 10 5.5 Ash, 1948 (10) 318 10 3.7Bland and Jones 653 10 2.31951 (24) 475 20 4.4Perry, 1969 (106)* 560 15 5.0

II. Data from the Penicilin Era Feinstein, 1964 (49) 441 7.8 0.01 Doyle, 1967 (39) 1762 5.3 2.3

*Includes a few patients in the penicillin era.

Evolution of Chronic Valve Disease after Rheumatic Fever in Patients without Carditis in the Initial Attack


of RF Follow with RHD(%)**

Patients up (yrs)


Boone and Levine

(25)1938 225 5 9(4)

Ash (10) 1948 219 10 51(23)

Bland and 1951 347 10 83 (24)

Jones (24) 1951 347 20 154 (44)

Thomas (126) 1961 22 5 0 (0)

Perry (106)† 1969 274 12 50 (18)

I




Patients up (yrs)

II. Data from the Early Penicillin Era (1950s and 1960s)

Kuttner (76)† 1963 50 9 6 (12)

Feinstein (48) 1964 181 7.8 0(0)

US-UK trial 1965 80 10 5 (6)

(100)

Aron (9)‡ 1965 50 29 15 (30)

Leonard and

Wenger (79) 1966 265 5 1/265

II




Patients up (yrs)

III. Data from the Later Penicillin Era (1970s and later)

Tompkins (130) 1972 35 9.3 0

Sanyal (114) 1982 40 5 3(8)

Majeed 1986 65 6 4 (6)

(85,88) 1992 35 12.3 0?

III

Occurrence of Carditis during Recurrences in Patients without Carditis in the Initial Attack of Rheumatic Fever

Author (ref) Year No.of No withPatients Carditis in

Recurrences (%)

Roth (112) 1937 149 51 (34) Feinstein (46)* 1960 71 10 (14) Kuttner (76) 1963 50 13 (26) Feinstein (47)† 1967 34 4 (12) Perry (106) 1969 55 27 (50) Sanyal (114) 1982 14 1 (7) Majeed (87) 1984 26 2 (8)

Factors Affecting the Incidence and Detection of Carditis

• First attacks versus recurrences

• Community versus hospital-based patient population

• Criteria used, e.g. changing murmurs, cardiac enlargment, pericarditis, etc.

• Methods used for detection, e.g. echocardiography versus clinical recognition

• Effectiveness of prophylaxis

Hospital Admissions for Rheumatic Heart Disease

Country Admissions as Percentage of All Cardiac Admissions

ASIABangladesh 34.0Burma 30.0

India 16.5-50.6Mongolia 30.0Pakistan 23.0Thailand 34.0

AFRICAEthiopia 34.8Ghana 20.6Malawi 23.0Nigeria 18.1-23.0South Africa 25.0Tanzania 9.7Uganda 24.7Zambia 18.2

Beta-Hemolytic Streptococcal Carriage rate in Asymptomatic Children*

Country Carriage DistributionArea Rate (%) of Groups (%)

A C or G

Egypt 50 30 70

South India 49 14 67Kuwait 47 22 74Liberia 49 20 65Netherlands 51 61 28Nigeria 8 21 77USA 11-28 63 31

*Adapted from the World Health Organization Special Study Group. Control of rheumatic fever and rheumatic heart disease. Technical Report Series, no. 764, World Health Organization, Geneva, 1988

Rheumatic Heart Disease in school-age children of developing countries

Region Population (Millions) Prevalence of Total No. of

Total <15 Years RHD (per 1,000) Patients with

RHD

(in millions)

Africa 662 298 9.9-15.5 2.95-4.62

Latin America 430 146 1.0-17.0 1.46-2.48

Asia 3171 1043 0.4-21.0 0.42-21.9

Pacific 2 7 7 4.7-18.6 0.03-0.13

* Adaapted from the 1991 World Health Statistics Annual, WHO (1992), Geneva, and reference 166.

Recurrence rates in patients with rheumatic fever in the preprophylaxis era

Author Year No.

Patients

Follow up

(years)

Recurrence (%)

All group of Patients

Roth et al.

Bland and Jones

Stollerman

Wilson et al.

Ash et al.

Macue and Gavin

Patients without Carditis

Boone and Levine

Bland and Jones

1937

1939

1944

1944

1948

1948

1937

1939

488

1000

239

499**

345

537

225

166

314

8

10

7

7.9

4.98

10

3

9.6

10

68

66

77

69

13

63

61

41

58

Relation of type of streptococcal infection to the recurrence rates in Rheumatic Fever

Subset Streptococcal Recurrence

Infection (n) (%)

Positive throat culture 45 0

Throat culture and pharyngitis 13 0

Culture and pharyngitis and 55 24

ASO

ASO alone 58 21

ASO and throat culture 85 15

ASO and pharyngitis 29 31

Risk factors for Rheumatic Fever Recurrences in Multivariate Analyses

Associated Not Associated

Presence of heart disease Ethnic group

Time since last attack Overcrowding

Number of previous attacks Family income

Age of patient Family history

Severity of symptoms

Oral rather than injectable prophylaxis

Natural History

• Without secondary prophylaxis recurrence is

maximum in the first five years and minimal

beyond 15 years.

• < 5 years - 20% • 5-10 -10% • 10-15 - 5% • >15 years-2%

Natural History..

• In post penicillin era, the recurrence rate is

around 0.004-0.006.

• ic 1/250 patient years[With…benzathine

prophylaxis].

• the efficacy is approximately 10 times less

when sulfonamide/oral penicillin is used.

RF in very young / adults

Natural History Very young (< 3 yrs) • < 1% in children < 3 years • Mortality in Pre penicillin era - 50%

Penicillin era - < 5% • High incidence of carditis / CHF • > 70% develop chronic RHD Adults • Arthritis dominant • Symmetrical, lower limbs, large joints • Profound tenosynovitis• Cardiac involvement – less severe • Valve sequelae – less often • Mortality is rare (RF / carditis)

Natural history in adults

• ‘Rheumatic fever bites the heart and licks the joints in

children, but licks the heart and bites the joints in adults’.

• Arthritis resemble those in children.

• Additive pattern – unlike the classic migratory pattern – is

symmetrical with a lower extremity, large joint predominace,

‘profoundly symptomatic tenosynovitis.

• Cardiac involvement less severe. mortality –rare

Initial Attack of A.R.Fclinical And

Echocardiographic Study

Dr.S.V. Prashanthi, MDDr. P. Krishnam Raju,MD

Dr. K. Laxmana Rao, DM (Card) Dr. S. Manohar, MD

Osmania General Hospital, Hyderabad

Jones Criteria, Updated 1992: Echocardiography

“At present there is insufficient information to allow

the use of echocardiography, including Doppler to

document valvular regurgitation without

accompanying auscultatory findings as the sole

criterion for valvulitis in acute rheumatic fever”.

ACUTE RHEUMATIC FEVER

Carditis in Study (40 patients)

• ECHO Evidence - 90%

• Clinical Carditis - 55%

• Subclinical Carditis - 35%

• No Carditis - 10%

RHEUMATIC FEVER

Carditis : ECHO (Vasan)

108 patients of Acute RF; 80 with carditis

• Focal nodular thickening 25%• Restricted mobility 37%• MV prolapse 16% (AoV. uncommon)• Annular dilation 21%• Normal : No clinical carditis

Echo : Carditis

Vasan et al – 1996

Echo / Doppler did not detect valvar regurg. in

any of 28 patients with Ac RF who did not

have clinical findings.

RHEUMATIC FEVER

Global Research Priorities in Rheumatic Fever and Rheumatic Heart Disease

Challenge 1: Translating what we know already into practical RHD Control.

o Improving uptake of proven RHD control strategies around the world.

o New approaches to integrating centralized control programmes with

primary care and with overall chronic disease care.

o Using RHD registers to understand disease outcomes.

o How to improve delivery of secondary prophylaxis.

* Understanding determinants of adherence.

* Trials of new strategies to improve adherence

* Developing ways to monitor quality of benzathine pencillin G

* Implantable penicillin

ANNALS OF PAED CARD 2012

1


Challenge 1: How to identify people with RHD earlier, so that preventive measures have a higher chance of success

o Standardization of echocardiographic screening for RHD

o Evidence based diagnostic criteria for RHD

o Determining the significance of subclinical carditis

o Determining the cost effectiveness of screening, and making it

practical and affordable.


2


Challenge 3 : Better understanding of disease

pathogenesis, with a view to

improved diagnosis and treatment of

ARF and RHD.

o Immunology of ARF and RHD o Genetics of ARF / RHD



Challenge 4 : Finding an effective approach

TO PRIMARY PREVENTIONo A vaccine for rheumatic fever o The role of primary prophylaxis of STREPTOCOCCAL SORE THROAT

the role of controlling skin infection

ANNALS OF PAED CARDIOLOGY JAN 2011

RF / RHD

ASAP

AwarenessSurveillanceAdvocacy Prevention

CONCLUSIONS

• ONLY Carditis is associated with long term sequelae

• Nat. HX changed during 20th century

• Decline in sev of carditis by 1930s more decline in the 2nd

half of 20th century.

• Lesser cardiac disability and lower mortality.

• Improvement in socioeconomic conditions

• Availability of Penicillin/ changing virulence of streptococcus.

• Pre Penicillin era - 2/3rd of all RF → RHD

Penicillin era - 1/3rd of RF develop RHD

Prof. P. Krishnam Raju CARE Hospitals & CARE Foundation Hyderabad Acute Rheumatic Fever - Natural...

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