Centenary Review Article

7/27/2019 Centenary Review Article

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Rheumatic fever & rheumatic heart disease: The ast 50 years

R. Krishna Kumar & R. Tandon*

Division of Pediatric Cardiology, Amrita Institute of Medical Sciences & Research Centre,

Kochi & *Sitaram Bhartia Institute of Science & Research, New Delhi, India

Received December 19, 2012

Rheumatic fever (RF) and rheumatic heart disease (RHD) continue to be a major health hazard in

most developing countries as well as sporadically in developed economies. Despite reservations about

the utility, echocardiographic and Doppler (E&D) studies have identied a massive burden of RHD

suggesting the inadequacy of the Jones criteria updated by the American Heart Association in 1992.

Subclinical carditis has been recognized by E&D in patients with acute RF without clinical carditis as

well as by follow up of RHD patients presenting as isolated chorea or those without clinical evidence of

carditis. Over the years, the medical management of RF has not changed. Paediatric and juvenile mitral

stenosis (MS), upto the age of 12 and 20 yr respectively, severe enough to require operative treatement

was documented. These negate the belief that patients of RHD become symptomatic 20 years after RF

as well as the fact that congestive cardiac failure in childhood indicates active carditis and RF. Non-

surgical balloon mitral valvotomy for MS has been initiated. Mitral and/or aortic valve replacement

during active RF in patients not responding to medical treatment has been found to be life saving as

well as conrming that congestive heart failure in acute RF is due to an acute haemodynamic overload.

Pathogenesis as well as susceptibility to RF continue to be elusive. Prevention of RF morbidity depends

on secondary prophylaxis which cannot reduce the burden of diseases. Primary prophylaxis is not

feasible in the absence of a suitable vaccine. Attempts to design an antistreptococcal vaccine utilizing

the M-protein has not succeeded in the last 40 years. Besides pathogenesis many other questions remain

unanswered.

Key words Antistreptococca vaccine - heart disease - myocarditis - rheumatic fever - rheumatic heart disease - streptococca infections -

subcinica carditis

Centenary Review Article

Indian J Med Res 137, Apri 2013, pp 643-658

643

Rheumatic heart disease (RHD) foows rheumaticfever (RF), as a non-suppurative manifestation of groupA beta haemoytic streptococca (GAS) pharyngitis.RF is widey accepted as an immunoogica disorderfoowing GAS infection. Athough the burden hascome down in deveoped countries, RHD continues

to be a prominent cause of morbidity and mortaityin deveoping countries of the word. This review

highights the changes that have occurred in the area ofRF and RHD in the ast 50 years.

Historical perspective

About 100 years back RF/RHD was beieved to bea disease of temperate cimate. In 1835, Macomsonobserved that rheumatism was prevaent among

sepoys1 and in 1870 Moore2 reported numerous cases


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of rheumatism in Rajasthan. Rogers3 indicated absenceof RF in India as except one possibe case he did notnd RHD in 4800 postmortem records in 37 years inCacutta (Kokata) inspite of 25 cases of mitra stenosiswhich he abeed as non rheumatic. Megaw4 reported

RHD from pains of India but fet that it was esscommon than seen in coder cimates. Cark5 reportedabsence of haemoytic streptococca infections andow prevaence of RF/RHD in tropics. Keats6 did notnd a single case of RHD in 600 autopsies in Amritsar.Drury7 found mitra vave disease in 62 per cent andmitra stenosis in 10 per cent in an anaysis of 319cinicay diagnosed cases of heart disease admittedto the Medica Coege Hospita in Cacutta (Kokata).Basu8 found 8.3 per cent cases of rheumatic carditis andpericarditis in 446 patients of acquired heart disease.Hughes and Yusuf9 referred to mitra stenosis in an

artice on heart disease in Punjab9. Hodge reported onrheumatism and indicated that it was not rare in India.

The rst clinical evidence of RF came from Punjabby Wig in 193511 and on rheumatism in chidhoodand adoescence by Kutumbiah in 194012. This wasfoowed by a arge number of hospita-based surveysfor the reativey new disease accounting for 20 to 50per cent admissions in hospitas in various parts of thecountry (Tabe I). With the resuts, rheumatic fever wasabeed as severe or maignant in India with mutivaveinvovement and congestive cardiac faiure even in theinitia attack of RF21. Roy deineated the features of RF

and compared with features seen in Boston (USA)22.The presence of RF/RHD was not ony estabished butaso considered to be the commonest heart disease inthe country by mid 1950s.

Burden of the disease in India

The information regarding the burden of diseasecomes from hospita data, popuation based studies andschoo surveys. Hospita based data between 1945 and1963 indicated that anywhere from 20 to 50 per centhospita admissions for cardiac patients were for RHD(Tabe I). Since the hospita-based data do not represent

the popuation of the region, there is a bias towardsthe worst affected and those seeking admission forprocedures. Additiona bias may be introduced throughchanges in the popuation served by the hospita overmany years. With increasing marginaization of thepoorer sections of the society some hospitas may noonger be serving those who are worst affected withRHD. Perhaps the most important source of bias is inthe preference of the admitting units. With emergence

of the epidemic of coronary artery disease (CAD),

hospita admissions are argey represented by CADpatients in most hospitas.

Popuation based surveys for prevaence arevery few and scattered. (Tabe II). In a study in ruraHaryana prevaence of RHD was found to be 2.2/1000in 5 to 30 year od subjects23. Mathur in a study of theurban popuation of Agra found RHD in 1.8/1000 in thesame age group24. Berry25 studied the urban popuationof Chandigarh and found RHD in 1.23/1000 mae and2.07/1000 in the femae popuation of a age groups.A recent Indian Counci of Medica Research (ICMR)

study (between 2000 and 2010) in 10 different, mostyurban, ocations of the country found the prevaenceto range from 0.2 to 1.1/1000 for RHD and 0.0007 to0.2 /1000 for RF26. The data were based on registration

of a cases in one miion popuation by approachinghospitas, private practitioners and extensive advertisingfor estabishing a registry of a known cases. Therecent registry data suggests decine but registries areabe to coect about 50 to 70 per cent cases. Hence,

overa decine is debatabe.

ICMR has conducted three schoo-based surveys inchidren 5 to 14 yr in age over a 40-year period between1970 and 2010. The rst survey from 1972 to 1975was in schoos at Agra, Aeppy, Bombay (Mumbai),Dehi and Hyderabad. The second from 1984 to 1987

incuded schoos at Dehi, Varanasi and Veore.

Table I. Percentage of RHD patients in hospita admission

Author Pace Year (%)

Kutumbiah13 Madras (Chennai) 1941 39.5

Bannerjea14 Cacutta (Kokata) 1965 44.6

Sanjeevi15 Madras (Chennai) 1946 46.8

Vaki16 Bombay (Mumbai) 1954 24.7

Padmawati17 Dehi 1958 39.1

Devichand18 Shima 1959 50.6

Mathur19 Agra 1960 35.1

Mahotra20 Punjab 1963 27.6

Table II. Prevalence of RHD in population surveys

Age group (yr) N Prevalence/1000

Roy23 5-30 4847 2.2

Mathuret al24 5-30 7953 1.8

Berry25 5-30 19768 1.87

All ages 33361 1.55

644 INDIAN J MED RES, APRIl 2013


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The third study incuded chidren from 10 centres inthe country ocated at Shima, Jammu, Chandigarh,Jodhpur, Indore, Kochi, Wayanad, Mumbai, Veoreand Dibrugarh. It has a wider coverage but not of thewhole country. In the rst study (1972-1975), 1,33,000

chidren were evauated and the prevaence of RHDvaried from 0.8 to 11/1000, overa 5.3/1000. Thesecond study (1984-1987) incuded 53,786 chidrenand the prevaence ranged from 1.0 to 5.6/1000 overa

2.9/1000. The third and the argest study incuded1,76,904 schoo chidren with a prevaence varyingfrom 0.13 to 1.5/1000 (overa 0.9/1000) in the 5 to 14yr age range26. The data suggest a progressive decinein RHD from 5.3 to 2.9 to beow 1.0/1000 between1970 to 2010. In the ast study echocardiographicevauation was performed in a chidren cinicaydiagnosed to have a heart murmur and chidren with

congenita heart disease coud be excuded. In a studyon 1,18,212 schoo chidren 4-18 yr in age a heartmurmur was found in 389 norma chidren. Echoevaluation identied 61 children with RHD giving aprevaence of 0.5/1000 chidren in Uttar Pradesh27.Studies from Punjab, Gujarat, Rajasthan, Uttar Pradeshand Tami Nadu have found the prevaence to rangefrom 0.67 to 4.54/1000 children (Table III). The guresare variabe but suggest a decine in the prevaence of

RHD over time, however, whether they identify a rea

decline in prevalence is a difcult question to answer.At the same time, addition of echocardiographic RHDsurveys of norma chidren have introduced a newdimension to the assessment of disease burden. Mostavaiabe echocardiographic evauation studies for the

presence of RHD in schoo chidren suggest more than10 to 20 times higher prevaence of cinicay sientRHD (Tabe IV). The reiabiity or acceptabiity of theprevaence data based on cinica evauation aone is

not known with certainty. Further, echocardiographicdiagnosis has faacies and foow up studies of thecinicay sient or subcinica (SC) RHD are required toestablish the signicance of disease identied throughechocardiography aone. Is this subcinica vavedisease reay sient RHD? A ong-term foow up ofthe patients is required to estabish the natura historyof disease identied through echocardiography alone.

An anaysis of the shortcomings associated with theestimation of the prevaence of RF/RHD in our countryhas been discussed earier38. The overa prevaenceestimated to be about 1.5-2/1000 in a age groups, inIndia (tota popuation about 1.3 biion) suggests thatthere are about 2.0 to 2.5 miion patients of RHD inthe country.

Global and Asian burden of RF/RHD

The burden of RF/ RHD has been described in detaiby Carapetis and coeagues39,40. Excuding deveopedeconomies, the goba burden of RHD in the 5 to 14 yr

od chidren was estimated to be 0.8 - 5.7/1000 with amedian of 1.3/1000. The estimated number of chidrenwoud be about 2.4 miion (Tabe V). Subsequentdata from studies in Asia suggested that the number ofchidren with RHD in Asia coud be between 1.96 to2.21 million. The ndings were extrapolated to includea ages and estimated that gobay there were 15.6 -19.6 miion patients. In the study of Asian countries theburden of RHD was estimated to be 10.8 - 15.9 miionpatients. The estimates of RHD in Asian countries

Table III. Prevaence of rheumatic heart disease (RHD) inschoo surveys

Pace Year Age (yr) Prevaence/1000

Punjab28 1988-91 5-15 2.1

Gujarat29 1986 8-18 2.03

Punjab30 1987 6-16 1.3

Uttar Pradesh31 2000 7-15 4.54

Tami Nadu32 2001-2 5-18 0.68

Rajasthan33 2006 5-14 0.67

Table IV. Prevaence of subcinica carditis in echo studies of schoo chidren

Pace n Cinica Echo Subcinica

Nicaragua34 3150 13 (4) 150 (48) 137 (44)

Tonga35 5053 78 (15.4) 169 (33.4) 91 (18)

Cambodia36 3677 8 (2.2) 79 (21.5) 71 (19.3)

Mozambique36 2170 5 (2.3) 66 (30.4) 61 (28.1)

India37 6270 5 (0.8) 128 (20.4) 123 (19.6)

Tonga auscultation positive 46% silent 54 % (gures calculated)

Figures in parenthesis are per 1000

KRISHNA KUMAR & TANDON: RHEUMATIC FEVER & HEART DISEASE 645


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indicate that the global burden is signicantly higherthan the earier estimates for chidren as we as a agegroups.

On the basis of 1.5 per cent mortaity per year,goba deaths from RHD were estimated to be 233,000- 294,000/year. The mortaity in Asian countries wascacuated on the basis of a study showing 3.3 per

cent per year mortaity41. As such the mortaity in Asiaaccounts for 356,000 to 524,000 deaths/year suggestingthat the goba mortaity must be higher.

For acute RF a goba estimate in the 5-14 yrage group suggested 336000 new cases per year.Extrapoating to a ages it indicated that about 471,000/year get RF. Cacuating on the basis of 60 per centpatients of RF getting carditis, about 282,000 new casesof RF are added each year with the remaining 40 percent or 189,000/year having a potentia for subcinica

RHD (Tabe V). A review of the incidence of acute RF,in popuation based studies in the word has estimatedthat the overa incidence varies from 5 to 51/100,000popuation with a mean of 19/100, 00042.

These estimates do not take into account subcinicacarditis identied on the basis of echocardiographyand Dopper studies in surveys of schoo chidren

(Table IV). Although the exact signicance of thesubcinica carditis in terms of morbidity has not beenestabished, it cannot be disregarded. Studies suggestthat subcinica RHD can progress to cinica RHD. At

the same time it is we known that recurrences of RHDhave mimetic features and the subcinica disease maybecome a cinicay obvious disease in recurrences inthe absence of secondary prophyaxis43. The magnitudeof subcinica carditis, 10 to 20 times higher than

manifest RHD, indicates the difculties regardingsecondary prophyaxis. Secondary prophyaxis isethicay mandatory in this age group. Can we identifychidren with subcinica carditis and not put them onsecondary prophyaxis ?

Diagnosis of RF

The criteria for the diagnosis enunciated by DrT. Duckett Jones have been modied, revised andupdated by the American Heart Association (AHA)44.The diagnostic criteria consist of major manifestationscarditis, arthritis, subcutaneous nodues, erythema

marginatum and chorea. Rheumatic carditis resutingin a more or ess permanent damage to the heart is themain viruent manifestation of RF.

The minor manifestations consist of fever,arthragia, eevated sedimentation rate, C-reactiveprotein (CRP) and proonged PR interva in theeectrocardiogram. Presence of two major or onemajor and two minor manifestations with an evidencefor recent GAS infection (essentia criterion) indicateacute RF. Evidence for recent GAS infection can bein the form of a positive throat cuture, eevated anti-streptococca, antibodies or presence of features for

recent scaret fever, rare in our country.

The components of major, minor and essentiacriteria for the diagnosis remain more or ess as beforein AHA guideines44. The updated criteria emphasizethe vaue of indoent carditis and chorea to be acceptedas evidence of RF and have removed previous RF orpresence of RHD as a minor manifestation to simpifythe diagnosis of rst attack of RF. In the presence ofprevious history of RF/RHD one major or more thanone minor criterion is acceptabe for the diagnosisof recurrent RF. Additionay echocardiogram baseddiagnosis of carditis has been questioned in the absenceof clinical ndings to indicate cardiac involvement.The cinica manifestations of RF, except for minordifferences in frequency, is the same a over the word.In our country erythema marginatum is not recognizedpossiby because of the darker skin compexion (TabeVI)22,45-48.

It needs to be emphasized that the diagnosticcriteria are guideines that help in the identicationof RF. However, physicians have a right to make a

Table V. Goba and Asian magnitude of RF/RHD (Excuding

deveoped economies)

RHD Age (yr) No. of patients

(Miion)

Goba 5-14 2.4Asia 5-14 01.96 - 2.2

Goba a ages 15.6 - 19.6

Asia a ages 10.8 - 15.9

Acute RF n / year

Goba 5-14 336000

A ages 471000

If 282 60% have RHD

188.4 40% potential RHD

282000 new cases

189000

Estimated deathsRate/year

(%)

n / year

Goba 1.5 233000 - 294000

Asia 3.3 356000 - 524000

Source: Refs 39, 40



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diagnosis of RF on the basis of cinica judgment even

if the updated criteria are not satised. This may be

due to (i) absence of history suggestive of RF in amost50 per cent patients of RHD, and (ii) identicationof subcinica carditis by echocardiographic studies,

indicating inadequacy of cinica diagnosis.

Identication of RF

RHD can occur ony after a patient has had RF.Evauation of data indicates that about 65 per centpatients get cinicay recognizabe RHD foowingRF. In the global estimate a conservative gure of

60 per cent carditis has been used for cacuating theburden of RHD39. This suggests that at east 40 per cent

patients who have had RF coud be potentiay patientsof subcinica carditis. On the basis of Utah study, 27per cent patients had subcinica carditis49. Hence, theactua estimated burden coud be much more thanthe actual burden. Secondly, most prevalence gures

indicate that the prevaence of RF in surveys is aboutone tenth or even ess than that of RHD (0.1/1000 vs1/1000)26. The inference coud be that the diagnosisof RF is being missed more often than desirabe or

acceptabe. less than haf of a RHD patients givehistory of past RF. Unfortunatey, diagnosis of past RFis not possibe uness patients give history of arthritis,arthragia, chorea or have estabished RHD. Hence,

retrospective diagnosis or identication of past RF ismissed or not avaiabe in amost 50 per cent patientswith RHD.

Foow up of patients with pure chorea withoutRHD or of patients who have had RF but no cinicaevidence of carditis indicates that RHD can deveop

over a period of time. Band50 in a 20 year foow up ofpatients with isoated chorea found 23 per cent patientswithout cinica carditis to deveop RHD predominanty

mitra vave obstruction (MS). Simiary, Aron et al51in a 30-year foow up of 50 patients of pure chorea

ended up with RHD, predominanty MS, in 34 per centpatients. Roy et al52 drew attention towards the onsetof symptomatic severe MS beow the age of 20 yr anddesignated it as juvenie MS in India. In our evauationof chidren beow 12 yr of age who have been operatedfor MS 57 per cent gave history consistent with RF,haemodynamic studies in 29 and operation in 35 of the42 patients indicated moderatey severe to severe MSrequiring operative treatment beow the age of 12 yr53.The assessment of the exact time of RF and the intervabetween RF and onset of symptoms of MS coud befaacious since it was dependent entirey on the pasthistory of arthritis and arthragia. Nine patients becamesymptomatic, within a year and ve within two years,a beow 12 yr in age. The youngest patient was sixyears od at the time of operation without a historysuggestive of RF53. In a subsequent evauation of 125chidren beow of the age of 12 yr with isoated mitrastenosis, past history of rheumatic fever was avaiabein 54 (51%)54.

These studies indicate that MS can occur veryquicky foowing RF. Secondy 43-50 per centdeveloped signicant mitral obstruction without ahistory to suggest RF indicating that acute RF is notbeing recognized, possiby because RF is occurringwith subcinica carditis but without arthritis, arthragia,subcutaneous nodues, and chorea. Missing a cinicadiagnosis of acute RF in chidren ess than 12 yr of ageis most disturbing since the time avaiabe to forget themanifestation of acute RF is very short if we acceptthat RF must have occurred beyond the age of 2 to 3 yrin most.

Presence of subcinica carditis diagnosed usingechocardiography in surveys of 5-14 yr od chidren


Table VI. Major manifestations of acute RF

Roy22 Padmawati &

Arora45Sanya et al46 Agarwa &

Agarwa47Vaishnava et al48

Dehi Boston Dehi Dehi Aahabad Veore

N 113 490 - 102 100 166

Carditis 46 53 14 33 51 97

Arthritis 32 58 36 67 68 2.4

Chorea 5 19 4 21 16 5.4

SC nod 3 12 1 2 5 1.2

E. marg 0 11 0 2 0 0

Figures indicate percentage of patients

SC nod, subcutaneous nodues; E. marg, erythema marginatum


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when combined with the ndings of the childrenwith MS suggests that RF is being missed more oftenthan desirabe. Some patients have ony one cinicamanifestation - fever with vavuitis during the episode

of RF and the diagnosis of RF is being missed since

the carditis is asymptomatic, mid and not associatedwith any murmurs (subclinical). The ndings suggestthat the diagnosis of RF based on the 1992 guideines

of AHA are necessary but insufcient in identifying RFin a fairy arge number of patients44.

Diagnostic tests in RF/RHD

The diagnostic tests can be considered as thosemeant for(i) diagnosis of RF, (ii) presence of active vs.inactive RF in recurrences, and (iii) identication of

carditis and vave damage in RHD.

Diagnosis of RF:

(1) The diagnosis of RF is dependent on someaboratory tests incuded as minor criteria andconsist of the foowing:

(i) Acute phase reactants (eukocytosis, eevatedsedimentation rate and presence of C reactiveprotein CRP).

(ii) Proonged PR interva in the eectrocardiogram.

(2) The diagnosis requires presence of essentia criteriain the form of evidence for recent GAS infection

and consists of:

(i) eevated antistreptococca antibodies,

(ii) positive throat cuture for GAS, and

(iii) evidence for recent scaret fever- rare in India.

Eevated erythrocyte sedimentation rate (ESR)is a nonspecic evidence for an active disease. It iseevated in acute RF but can be norma if the patienthas congestive faiure and can be high in the presence

of anaemia. Norma CRP is against the diagnosis ofactive RF. Proonged PR interva can be seen in theeectrocardiograms in patients with active RF. Proonged

PR interval is a non specic nding and does not indicatethe presence of myocarditis. Eevated antistreptococcaantibodies identify recent streptococca infection. Afair amount of confusion exists about the exact eveof antibodies to be considered as high. Generay

antistreptoysin O (ASlO) is the commonest antibodymeasured. It appears in about 7 to 10 days and peaks in2 to 3 wk55. It is considered high if the gure is morethan the baseine vaue present in the community. In

endemic areas the baseine ASlO coud be 250 Todd

units or more whereas in non-endemic areas it coudbe as ow as 50 Todd units. Increasing titres indicaterecent GAS infection. Using two antibody titres, thatis, ASlO combined with deoxyribonucease B titresincreases the specicity of diagnosis to 90 per cent56.

Presence of GAS in throat cuture with ow vauesof ASlO suggests a carrier state. As such a positive

throat cuture for GAS cannot be taken as recentinfection uness the antibody titres are eevated.

Presence of active vs. inactive RF in recurrences: Twoinvestigations have been tried to assess the presenceor absence of active RF in patients with recurrencesbesides ESR, CRP and evidence for recent GASinfection.

(i) Induced subcutaneous nodules (SCN): Masse etal57 tried inducing SCN by injecting ve dl autologousbood drawn from a vein and injecting over theoecranon process of one ebow and saine in the otherebow. Frictiona pressure was appied to the injectedsites. Appearance of a SCN in 5 to 10 days wasaccepted as indicating active RF. Vasan modied this

test and used concentrated eukocyte injection insteadof whoe bood with 86 per cent sensitivity and 94 percent specically to identify active RF. The test offersthe advantage of being cheap and easiy avaiabeeverywhere. The potentia utiity of the test ies inidentifying active RF. However, additiona vaidationstudies are perhaps needed.

(ii) Myocardial biopsy: A study of myocardia histoogyto identify active vs. inactive RF was utiized inpatients of RF59. Myocardia biopsies were performedin 89 patients of active RF and chronic RHD to identifyactive carditis Myocardia biopsies faied to improve oncinicay assessed presence of active RF. Myocardiabiopsy was fet to be insensitive for identifying presenceof active carditis58.

Rheumatic carditis and valve damage

The viruence of RF is reated to its capacity tocause cardiac damage. Cinicay carditis has beenreported by severa investigators in the initia attackin India (Tabe VI)22,45-48. Rheumatic carditis has been

considered to be a pancarditis causing pericardia,myocardia and endocardia disease.

Pericarditis occurs in about 15 per cent cases. It isidentied by the presence of a pericardial friction ruband may be associated with precordia chest pain. Itcan be evanescent and may appear for a brief period.An echocardiogram can identify the effusion, which



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never resuts in tamponade and subsides without anysequeae.

Studies strongy suggest that RF does not causemyocarditis. Absence of myocarditis has been

documented by (i) absence of increase in markers ofmyocardia damage - MB fraction of creatinine kinase(CK-MB), troponin I & T and myogobin60-62, (ii)norma eft ventricuar systoic function and myocardiacontractiity by echocardiographic studies62,63, (iii)radionucide studies using technetium pyrophosphatescanning and indiumIII abeed anticardiac myocinFab (FAB) do not indicate presence of myocardiadamage64,65, (iv) myocardia biopsy studies have notbeen abe to identify the presence of myocarditis59,(v) normaization of heart size and disappearance ofcongestive faiure foowing surgica mitra and/or aorticvave repacement in patients deteriorating in spite ofaggressive medica management66, (vi) histopathoogyof the eft ventricuar myocardium showing absenceof myocardia or inter-myocardia connective tissuedamage67 and (vii) immunopathoogy of Ashoff nodue(AN), the diagnostic marker of rheumatic pathoogy,being derived from mesenchyma ces, competeabsence of ces of myocardia origin in AN and absenceof actin, myosin and desmin (of myocardia origin) inthe AN indicating that AN is not of myocardia origin68.Hence, congestive cardiac faiure in acute RF is dueto an acute voume overoad from mitra and/or aorticregurgitation but not due to myocarditisper se.

Rheumatic endocarditis represented by cardiacvave invovement resuts in the ony permanentdamage from RF. Pathoogica evauation of the vavesof patients dying from acute RF indicates microscopicdisease in each of the four cardiac vaves69. However,cinicay mitra vave invovement occurs in 90 to 95per cent of whom in 20 to 25 per cent, it is associatedwith aortic vave disease as we. Cinicay isoatedaortic vave invovement has been reported in essthan ve to eight per cent cases70,71. Tricuspid vaveinvovement in acute RF is uncommon and thepumonary vave invovement very rare. Tricuspidvave disease has been found to occur in up to 30 to50 per cent in necropsy studies72. Since pericarditissubsides without sequeae and myocarditis does notoccur, the morbidity and mortaity of RF is determinedby vavuitis the cause of permanent cardiac damage inRF.

In an evaluation of patients with RF the naldiagnosis regarding the presence or absence of carditisis determined by clinical ndings reated to the mitra

and aortic vave disease. Cinicay carditis has been

found in anywhere between 14 to 97 per cent patients(Table VI). The commonest clinical nding is thepresence of mitra regurgitation with or without aorticregurgitation.

More recent studies on patients with acute RFutiizing echocardiography have brought out the

shortcomings of auscutation in identifying vavedisease which does not resut in haemodynamicabnormaities consisting of regurgitant systoic (mitra)or diastoic (aortic) murmurs. This has resuted in theidentication of sub-clinical carditis (SC). Data for SCare now avaiabe from a number of studies. However,follow up data are insufcient. Subclinical carditishas been assessed by echocardiographic and Dopper(E&D) studies in (i) patients with acute RF, (ii) foow

up of patients with past RF who were cinicay judgednot to have carditis (NHD), and (iii) evauation ofnorma chidren. SC has been found in 5 to 29 per cent

patients of acute RF (Tabe VII)73-76 by E&D studies. Inthe Utah epidemic of acute RF clinically identiablecarditis was present in 64 per cent whereas SCdiagnosed by E&D was found in 27 per cent resutingin an overa prevaence of 91 per cent49. Athough theAmerican Heart Association (AHA) has not accepted

E&D studies for the identication of carditis, manycinicians fee that E&D studies are necessary for thecare of patients with acute RF since SC cannot bedisregarded. Foow up data on patients of acute RF withSC are unsatisfactory. Avaiabe foow up E&D studiesindicate that the SC can worsen to become cinicay

obvious RHD, improve or remain unchanged. lanna etal73 reported an 8-year foow up on 40 patients of RF.

Initiay they found two patients with SC but after eightyears six ost cinica evidence of mitra regurgitationresuting in eight patients (20%) having SC. Araujo etal76 foowed 462 patients for 2 to 23 yr (mean 13.6 yr).Initia evauation indicated that 258 (56%) had carditisand 204 without cinica evidence for heart disease.E&D studies identied 72 (16%) with SC. At the endof foow up (13.6 yr) the number with cinica carditis

Table VII. Frequency of subcinica (SC) carditis in acute RF

Studies N RHD SC (%) Carditis (%)

lanna et al72 40 28 02 (5) 30 (75)

Hiario et al73 22 08 05 (22.7) 13 (59)

Figuero et al74 35 15 10 (28.6) 25 (71)

Araujo et al75 462 258 72 (15.6) 330 (71)

SC, subcinica carditis



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went up to 298 (65 from 56%)76. The E&D studies thusindicate that patients identied as SC could improveand ose features of SC or become worse and deveopcinica carditis (RHD).

A review of SC invoving more than 1700 patientsfound overa prevaence to be 16.8 per cent77. WHOcriteria for the identication of SC by E&D weresatised by 10 studies which gave a prevalence of 18.1per cent. Of the 99 patients whose foow up of up to 2years was avaiabe, 48 per cent showed improvementand 52 per cent either no change or became worseindicating variabe course of SC77.

In one of the argest study of 1000 patients of acuteRF with a 100 per cent 20 year foow up, 154 (15%)patients deveoped RHD out of 347 (35%) patientsinitiay diagnosed as NHD (abeed as potentia

RHD), indicating the presence of SC in retrospect78.In the same study 32 (20%) of the 157 chidren withpure chorea (NHD) deveoped RHD, predominantymitra stenosis in 20 years identifying the presence ofSC. Band and Jones78 in their study made two cruciastatements whie detaiing the deayed appearance ofRHD. Both statements are sharp cinica judgments(in 1951) in the absence of investigative faciities foridentication of carditis.

It may be that minimay scarred vaves (initiaysient as far as physica signs are concerned) providea ocus for ------------------- deformed and stenotic

orice78.

In an occasiona instance a bowing diastoicmurmur (sight aortic regurgitation) of grade 1to 2intensity has been observed to disappear. We suspectthat minima scarring persists in spite of the absence ofmurmurs or enargement. Postmortem examination inone instance foowing accidenta death supports thissuspicion, as we as the insidious appearance of mitrastenosis in a few patients 10 to 20 years ater78.

A arge amount of data is now accumuating andidentifying SC by E&D studies of norma chidren

(Table IV). The exact signicance of SC identiedin apparenty norma schoo chidren needs to beestabished. The criteria for identifying SC by E&Dstudies need careful denition. Presently WHOand Word Heart Federation (WHF) guideines areavaiabe79,80. WHO has used ony Dopper basedguideines identifying the presence and severity ofvave regurgitation. WHF has used changes in vavemorphoogy as we as Dopper estimation of vaveregurgitation. At east one study has aready indicated

that WHO guidelines are insufcient81. logicaydiagnosis of SC shoud be based on changes of vave

damage as we as the haemodynamic consequences of

vave damage. We beieve that morphoogica changes

indicating vave damage shoud be considered more

important and essentia rather than the presence ofvave regurgitation aone, since it is the rheumatic vavedamage which is responsibe for the haemodynamic

changes in RHD.

At present we need to (i) estabish E&D guideines

for identication of SC, (ii) identify the magnitude of

SC in apparenty heathy chidren, and (iii) foow

up studies of SC in apparenty heathy chidren to

decide the ine of management. If foow up studies

indicate that SC can deteriorate to RHD in the absence

of secondary prophylaxis those identied as having SC

wi have to be put on secondary prophyaxis. In theabsence of ong term foow up it is desirabe to evauate

adults 20 to 35 yr in age to nd out the prevalence of

SC. This should help in dening the course of SC to

some extent. The study from Nicaragua of 376 aduts

identifying 23/1000 with SC is usefu but too sma for

any concusion34.

Pathogenesis of RF

It is we estabished that RF causes permanentdamage ony to the cardiac vaves. Cinicay the mitra

aortic, tricuspid and pumonary vaves are invoved in

order of frequency. Mitra vave invovement is the

commonest and the pumonary vave invovement is

rare. However, pathoogica evauation of vaves from

patients dying of acute RF indicates that microscopic

invovement of tricuspid and pumonary vaves occursin amost 100 per cent cases69. The cardiac vave damage

is the basic reason why RF needs to be controed to

reduce the morbidity and mortaity reated to RF.

Cardiac vaves are derived from the ventricuar

myocardium by a process of undermining. The vaves

are composed of a centra core of connective tissue

covered on both sides by endotheium. The centra core

of connective tissue is derived from the ventricuarmyocardium - musce and inter-myocardia connectivetissue. Histopathoogy indicates absence of myocardia

and connective tissue damage in carditis due to acute

RF. Immuno-histopathoogy excudes myocardia

damage in RF. Hence, the site of damage in the vaves

derived from the ventricuar myocardium has to be

the vave endotheium82. Endotheium per se consistsof two components the endotheia ces and the

basement membrane to which the ces are attached. By



9/16

excusion the ndings suggest that the valve damage isreated to the vave endotheium- the endotheia ces,the basement membrane and the substance bindingthese together82.

It is we estabished that RF foows GAS infectionof the tonsiopharynx and does not foow skininfection. Mesotheium and endotheium are derivedfrom mesenchyma ces. Mesotheia ces covertonsiopharyngea region whereas ectoderma ces,which are competey different in composition frommesotheia ces, cover skin. Why shoud RF foowpharyngea infection but not derma infection? Is itbecause the GAS infection affecting the pharyngeamesotheia ces sensitizes the ces in a way whichater manifests as endotheia ce damage of the vavetissue and mesotheia ce damage esewhere (arthritis,etc.) ater on ?

Pathogenesis of RF is not known. Research toeucidate the pathogenesis has been directed amostexcusivey toward myocarditis and myosin for the astmore than 60 years without any breakthrough83,84. Anaternative approach with endotheium as the targetof rheumatic damage as we as guideines for furtherresearch have been suggested in the hope that these mayhep in identifying the GAS antigen (s) responsibe forRF82.

Acute RF: duration of disease

A combination of some cinica manifestationsand aboratory tests put together by Jones, revised andmodied from time to time by the AHA, identify thesyndrome of RF. Elevated ESR and CRP are nonspecicand identify the presence of an active inammatorydisease. Eevated anti-streptococca antibodies indicatestreptococcal infection. Thus there is no specicinvestigation, which is diagnostic for RF. Of thecinica manifestations arthritis, erythema marginatumand carditis suggest acute and active RF. Subcutaneousnodues and chorea are ate manifestations and indicatepast RF not active RF.

The inference that RF asts 10 to 12 wk in about 80per cent patients was dependent on the eevated ESRand CRP. As of today we do not know the duration ofactive rheumatic process per se. Arthritis suggestsactive RF, however, if the rheumatic process is activewhy shoud arthritis subside without treatment? Thecentra nervous system (CNS) damage occurs withacute RF. At the time patients present with chorea theESR and CRP may be norma indicating absence of anactive disease process. Is the rheumatic inammation

active or inactive at the time a patient presents as

chorea? Hence high or norma ESR and CRP do not

identify active or inactive rheumatic process. Why

shoud chorea occur three to six months after the CNS

damage that occurs during acute RF? What is the

duration of active rheumatic inammation in RF? The

damage resuting from active rheumatic process has

to be separated from the residua effect of the damage

caused by the rheumatic disease. The duration of the

disease in acute gomeruonephritis, the other non-

suppurative manifestation of GAS infection, is ess than

seven to ten days85. Majority of patients recover within

that time. Urinaysis continues to show microscopic

haematuria for severa months in spite of cinica

recovery. Unfortunatey there are no investigations,

which can identify active rheumatic disease process

itsef.

Management

There has been no signicant change in the

management of acute RF in the ast 50 years. Patients

need peniciin to eradicate GAS present in throat. Anti

inammatory agents - aspirin or steroids - are used to

contro rheumatic activity. Aspirin or steroids do not

cure RF. These suppress the inammatory response

which asts for about 12 wk in more than 80 per cent

patients. Hence, the standard dose of aspirin (90-120

mg/kg/day) is given for ten weeks and tapered in the

next two weeks. The dose of prednisone 60 mg/day

above 20 kg and 40 mg /day beow 20 kg in weightis given for three weeks and tapered in the next nine

weeks. The standard 12 week course can be reduced to

four to eight weeks depending on the patients response.

Patients without carditis can have weeky foow up of

ESR and CRP. If they normaize, the course can be

reduced to a shorter period. Aspirin is preferred over

steroids as ong as the carditis is mid and the patient is

not in congestive faiure. However, with severe carditis

and congestive faiure steroid is the drug of choice

because of the more potent suppressive effect.

Non-steroidal anti-inammatory drugs (NSAIDs)have not been systematicay utiized to estabish their

usefuness. Immunosuppressive agents ike azathioprine

and cycosporine A have aso been considered for acute

rheumatic fever. Despite of the concerns of side effects,

toxicity and ate onset of ymphomas with the use of

these immunosuppressive it is possibe to argue that a

short course of 6 to 8 wk may result in a greater benet

than harm. However, most ethics committees wi

hesitate to permit systematic testing of these agents.



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It is now we accepted that rheumatic endocarditisinvoving heart vaves is the main cause of morbidityand mortaity in RF. Surgica management consistingof mitra and /or aortic vave repacement in patientswhose congestive faiure cannot be controed by

aggressive medica treatment during acute RF, is ifesaving. It the congestive faiure cannot be controedwith maxima medica therapy and the patient isdeteriorating due to mitra regurgitation, mitra vaverepacement during active RF is indicated. In spite ofcinica evidence for active RF, the heart size returns tonormal and congestive failure disappears, conrmingthat rheumatic myocarditis pays itte or no roe in themortaity of RF66.

Management of chorea: It has a sef imiting course,hence parents need reassurance. The chidren coud betreated with sedatives ike phenobarbitone 30 mg thricedaiy. chorpromazine, vaium, diphendydramine orpromethazine can be used as sedatives. Haoperido 5 to10 mg twice daiy has been used effectivey. Athoughaspirin and steroids are not supposed to have a pacein the treatment of chorea, some patients have showndramatic response to steroids, if they do not showadequate response to sedatives86,87. Since, ong termfollow up of chorea patients have identied subclinicalcarditis in 20 to 30 per cent patients, peniciinprophyaxis is essentia and shoud be continued on aong term basis50,51.

Rheumatic heart disease: Surgica managementof vave disease was the standard approach tibaoon mitra vavotomy was introduced in 1985.Mitra stenosis coud be corrected surgicay eitherby cosed vavotomy, open commissurotomy or byvalve replacement if the valve was calcied. Balloonvavotomy provides resuts as good as surgicavavotomy and has become the treatment of choice inspite of being more expensive. For mitra regurgitationthe choice of treatment woud be vave repair especiayin younger patients to avoid ong-term anti-coaguanttherapy. Most patients with mitra or aortic vaveregurgitation end up with vave repacement. Hence,athough surgica hep is very usefu it is expensiveand requires proonged care with anticoaguant therapywith the associated compications of vave thrombosisand systemic emboic disasters especiay in the ow-income popuation of the country. Over a ong foow upperiod reativey few patients remain free of events.

Baoon mitra vavotomy has been utiized in thepaediatric patients beow 12 yr in age with acceptabe

resuts. It has been extended to patients of mitra stenosis

with acute RF, without additiona risk and acceptabe

resuts. In the presence of acute RF restenosis rate was,

however, 40 per cent compared to 10 per cent in those

without active RF88,89.

Prevention of RF and RHD

A disease which foows a bacteria infection

shoud, theoreticay, be preventabe if the organism

does not become resistant to antibiotics. GAS have

remained sensitive to peniciin and shoud have

been eradicated. Unfortunatey despite a decine in

prevaence, RF continues to occur in socioeconomicay

disadvantaged popuations and even deveoped

countries have witnessed resurgences in ocaized

areas49,90. Steps in the deveopment of RF consist

of GAS pharyngitis, which shoud be symptomatic

enough to require medica attention, throat cuture

to conrm the diagnosis and ensuring that the course

of peniciin treatment has been competed. The ast

epidemic of RF in Utah area in USA occurred in we

to do midde cass famiies, absence of overcrowding

and with access to good medical care. The ndings of

the epidemic indicated that the preceding pharyngitis

was asymptomatic in 78 per cent, 18 per cent obtained

medica hep and the 10 day course of ora peniciin

was not competed by patients49,90.

Prevaence of RF/RHD has been attributed to

overcrowding and unhygienic iving reated to ow

socio-economic status. Unhygienic iving resuts inpersistent GAS in the environment. Since GAS spreads

by dropet dissemination, overcrowding causes cross

infection from person to person. low socio-economic

status may undermine nutrition and seriousy imit

access to medica treatment. Poor nutritiona status is

beieved to contribute to a decreased immune response.

The resut is not ony endemic RF but aso a more

severe or viruent disease (Fig. 1).

It is possibe at the same time that the initia

attack of RF is mid and resuts in mid carditis, which

remains subcinica, undiagnosed, and as such the

patient does not get prophyaxis to prevent recurrences.

In ow socio-economic settings, recurrences causing

further cardiac damage resut in symptomatic RHD

with mutivave invovement and congestive faiure

identied as the rst attack of severe (malignant) RF

(Fig. 2). The high prevaence of subcinica carditis

found by echocardiographic studies suggests that the

initia attack of RF is probaby reativey mid and in the

absence of secondary prophyaxis it is the recurrences,



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which are responsibe for patients presenting withsevere disease being labelled as the rst attack of RF.

The strategies for prevention consist of primordiaprevention, primary prevention and secondary

prevention.

Primordial prevention: It requires, preventing thedeveopment of risk factors in the community toprevent the disease in the popuation and thus protect

individuas. Requirements for primordia prevention inreation with RF and RHD consist of(i) improvement insocio-economic status, (ii) prevention of overcrowding,

(iii) improving nutritiona status, (iv) avaiabiity ofprompt medica care, and (v) pubic education regarding

the risk of RF from sore throat speciay beow the age

of 15 yr.

Improvement in nutrition improves immune

response and the capacity of individuas to resist and

ght infection. Public education is the most importantcomponent for primordia prevention. Uness parents

know that a sore throat can cause RF and RHD, it is

most unikey to be seen by a physician and treated.

Improvement in socio-economic status and preventing

overcrowding cannot be reied upon to reduce the

burden of RHD.

Primary prevention: Primary prevention is theoreticay

feasible but practically extremely difcult to achieve.

Primary prevention requires identication of (GAS)sore throat and use of peniciin to eradicate the

streptococci. The requirement for primary prevention

consist of (i) pubic awareness regarding danger ofRF from sore throat (ii) identication of sore throat as

being due to GAS infection, and (iii) use of injectabe

peniciin to cure the infection.

It is important to know that ora peniciin may not

be effective in preventing RF. RF occurred in 15 to 48per cent chidren given ora peniciin for 10 days in an

earier epidemic in USA90. Compiance of a 10 day ora

treatment even in educated famiies is not certain. It

is, therefore, essentia that injectabe peniciin is used

to prevent RF. The recommended dose of peniciin

is 400,000 units of procaine peniciin twice daiy for

ten days. Athough recommended, one injection of 1.2mega units of benzathine peniciin may not be enough

to eradicate GAS infection especiay in endemic

areas91. Since GAS infection spreads through dropets

from person to person, eradication of GAS even in one

individua wi reduce the tota burden of the organism

in the community. The inabiity to utiize primary

prevention at the community eve is due to the argenumber of sore throats requiring treatment to prevent a

singe episode of RF.

Community eve management requires a

sedgehammer approach, that is, each sore throat mustbe treated. At present, bacterioogica faciities required

to identify GAS sore throat at the community eve for

the whoe country, woud be expensive, do not exist

and are not ikey in the near future. Hence, each sorethroat wi need to be treated to reduce the cost. Treating

each sore throat is ogisticay not feasibe. Anywhere

from 3 to 20 per cent of sore throats can be due to GAS

infection, the rest being vira infections, which do not

require treatment. About 0.3 per cent of streptococca

Low socio-economic status

GAS GAS

Fig. 1. Reationship of ow socio-economic status to rheumatic

fever (RF).

Fig. 2. Possibe mechanism to expain why RF appears to be severe

in the initia attack.



12/16

sore throats resut in RF92. Recent data suggest thatamost 90 per cent of those who get RF deveop RHD49.

Hence if 10,000 sore throats were treated by the

sedgehammer approach, anywhere between 300-2000

GAS sore throats woud be treated (assuming 3 to 20%

are due to GAS). This woud resut in preventing RF inone to six chidren (0.3% GAS throats cause RF), andRHD in either ve or six children. Therefore, 10,000

sore throats need to be treated to prevent RHD in ve

to six chidren. A community eve primary prevention

by sedge-hammer approach is not feasibe.

Another probem in sedgehammer approach is the

identication of sore throat and its treatment. The data

from resurgence of RF in USA indicate that as much as

78 per cent of GAS sore throats may be asymptomatic,

ten day ora peniciin treatment was not foowed by

we educated famiies and 48 per cent of those givenora peniciin deveoped RF49,90. Uness a sore throat

is symptomatic, it woud not be treated and coud sti

resut in RF. Even an individua patient cannot be

protected if the preceding sore throat is asymptomatic.

This makes primary prevention based on the diagnosis

of GAS sore throat and use of ora peniciin inadequateto reduce the burden of RHD in the country. The amount

of peniciin required for sedgehammer approach is

not avaiabe in the country.

As of today there are no markers that can be used

to identify susceptibiity to RF. Studies on HlA and the

B-ymphocyte antigen, D8/17 have not given resutswhich can be used to identify the susceptibe peope in

the popuation to practice primary prevention92.

Primary prevention is possibe if an anti-streptococca vaccine becomes avaiabe.

Secondary prevention: Secondary preventionrequires identication of those with RF or RHD and

maintenance of a registry. Once identied, the patient

needs injections of benzathine peniciin, given once

in two to three weeks, depending on age, body size

and musce mass. Benzathine peniciin is painfu, may

resut in fever and very rarey in anaphyactic reactions.Most physicians are very reuctant to give peniciininjections. The necessity of peniciin prophyaxis is

due to the fact that RF has a tendency for recurrences

in those who have had RF in the past. Each new attack

causes further damage to the vave tissue making the

disease worse than before43. Secondary prevention can

reduce the damage of recurrences but cannot preventthe initia damage. Further, secondary prevention

cannot reduce the burden of RHD in the community.

Secondary prevention has been found to hep indisappearance of clinical ndings of RHD. However,disappearance of murmurs does not indicate that theheart disease has disappeared. Recurrence of RF resutsnot ony in appearance of murmurs but aso the vave

damage is worse than before.

Anti-streptococcal vaccine

Avaiabiity of a vaccine, which coud preventstreptococca infection, is essentia for primaryprevention of RF. It is at present not avaiabe. GASinfection resuts in suppurative and non-suppurativemanifestations. Suppurative diseases ike toxic shocksyndrome and necrotizing fasciitis coud be etha. Thetwo non-suppurative manifestations are acute RF andacute gomeruonephritis (GN). Severa GAS proteinand poysaccharide components have been considered

in deveoping a vaccine. Most work has been in reationwith the M- protein, considered to be the viruencefactor of the GAS83,84. Other components of GAS beingtried for preparing a vaccine are GAS C5a peptidase,a major surface virulence factor; bronectin bindingprotein sfb1, and the chimeric peptide J8 from theconserved region of the M- protein93.

M- protein has been found to be strain-specic,that is, each strain has its specic characteristics andprotective against ony that particuar strain. Sincemore than 250 different strains have been identied, itis essentia that the vaccine must be poyvaent, that is,

incorporate a the strains present in the community94.GAS has a strong tendency for mutation and thevaccine may not be effective if the infection is due to anorganism, which has mutated after being incorporatedin the vaccine95. Viruent GAS infection causingdeath from toxic shock syndrome is now known notto express M-protein96. Hence, M-protein cannot bethe chief viruence factor of GAS. Vaccine based onM-protein is unikey to succeed because:

On the basis of emm typing of M-protein more than250 strains of GAS can cause infection and provide onystrain-specic immunity. Hence, the anti GAS vaccine

has to incude a the strains in the community94.

Heterogeneous distribution of strains variesfrom pace to pace and keeps changing even withina cosed community in a short period. Vaccine basedon M-protein made in Dehi may not be effective inChandigarh, Chennai or Mumbai or even in Dehi aftera few months97.

GAS mutation aters the emm gene sequence of

the M-protein. Mutation can occur in a few weeks.



13/16

The vaccine may not be effective against infection by

a strain that has mutated after being incorporated in the

vaccine even in a very short time95.

GAS infection has resuted in etha toxic shock

syndrome without expressing M-protein, eectronmicroscopy failing to identify M-protein brils on the

surface of the organism and the isoate faiing to resist

phagocytosis, suggesting the absence of functiona

M-protein96.

M-protein has been excuded as the antigen

responsibe for acute GN the other non suppurative

manifestation of GAS infection85.

The surface M-protein of GAS was designated

as the viruence factor of GAS. The simiarity in the

structure of M-protein and the human tropomyosin

has resuted in accepting, without proof, that it isresponsibe for RF. There is no evidence to indicate

that M-protein is the antigen responsibe for RF.There

is no information regarding the roe M-protein pays in

the suppurative diseases due to GAS infection.

Toxic shock syndrome occurred in the absence of

functiona M-protein and the paediatric nephroogists

have excuded M-protein as being responsibe for

acute GN. Therefore, there is evidence that at east

two, one suppurative and one non-suppurative of the

various GAS reated manifestations are unikey to

be prevented by a vaccine based on M-protein The

vaccine if and when avaiabe is expected to preventGAS infection. This wi prevent GAS infection reated

diseases - necrotizing fasciitis, toxic shock syndrome,

acute gomeruonephritis, rheumatic fever, pyoderma

and septic arthritis, etc.

Unfortunatey in spite of extensive evauation

and efforts it has not been possibe to formuate a

M-protein based vaccine in the ast 40 years. We need

to consider as to why it is necessary to start from RF

and its reation with GAS M-protein to make a vaccine.

Why are we not ooking for the viruent epitope of GAS

from infections causing septic shock, pyoderma orseptic arthritis for its suitabiity for anti GAS vaccine,

since the interest is in preventing GAS infection? It is

we known that GAS infection precedes rheumatic

fever but which epitope of GAS resuts in rheumatic

fever is not known. The interest is in preventing GAS

infection by a suitabe vaccine, which shoud prevent

a GAS infection reated manifestations. Prevention of

rheumatic fever, pyoderma or gomeruonephritis wi

be specic benets of such a vaccine.

The answer to the question Is it possibe toprevent rheumatic fever? has to be No, for primaryprevention at the community eve. Primary preventionwi have to wait ti a safe and effective GAS vaccinebecomes avaiabe.

In our country the heath of the chid generayremains a priority responsibiity of the parents evenwhen the chid becomes an adut. Hence, preventionof RF and RHD is possibe to a arge extent if wecan provide the message, in oca anguages, to thepopuation (parents) that sore throats shoud notbe negected; that sore throats shoud be shown to adoctor for treatment to prevent RF and RHD. Radioand teevision are avaiabe for reaching each cornerof the country and shoud be utiized for this purpose.If education can be made compusory ti the age of15 yr, schoo heath education and schoo heath carefaciities can be utiized to contro RF.

RF and RHD continue to be an undesirabe burden.RF occurring at a young age resuts in morbidity aswe as mortaity in adoescents and young aduts, andaso becomes one of the major causes of oss of themost productive years of ife in our country. With the

identication of subclinical carditis in normal children,the tota burden of RHD is much higher than thatestimated in various studies. Athough the disease (RF)foows a bacteria (GAS) infection, the pathogenesishas not been worked out in more than 60 years. Duration

of the disease, specic medical treatment to control orprevent cardiac damage and primary prevention ofRF continue to be eusive. Primary prevention has to

depend on designing a vaccine to prevent GAS infectionreated suppurative as we as non-suppurative diseasemanifestations.

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