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    Ganesan Karthikeyan and Bongani M. MayosiHeart Disease in Africa?

    Is Primary Prevention of Rheumatic Fever the Missing Link in the Control of Rheumatic

    Print ISSN: 0009-7322. Online ISSN: 1524-4539Copyright 2009 American Heart Association, Inc. All rights reserved.is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231

    Circulation

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    Is Primary Prevention of Rheumatic Fever the Missing Linkin the Control of Rheumatic Heart Disease in Africa?

    Ganesan Karthikeyan, MBBS, MD, DM; Bongani M. Mayosi, MBChB, DPhil

    AbstractRheumatic fever and rheumatic heart disease continue to be major public health problems in the developing

    world, particularly in the countries of sub-Saharan Africa. Because of its cost effectiveness, secondary prophylaxis is

    advocated as the principal means of disease prevention and control. However, in developing countries, valvular damage,

    due to earlier, unrecognized episodes of rheumatic fever, has already occurred by the time secondary prophylaxis is

    instituted. Secondary prophylaxis cannot reduce the incidence of new cases of rheumatic fever and has not been shown

    to alter the natural history of rheumatic valvular disease. Experience from several regions of the world suggests that

    incorporation of a strategy of primary antibiotic prophylaxis into a comprehensive program for disease control can

    reduce the incidence of rheumatic fever and rheumatic heart disease. In this article, we argue that a strategy of primary

    antibiotic prophylaxis, with appropriate modifications, can be successfully implemented in resource-poor settings across

    the world and should be a key component of any rheumatic heart disease control program. This, we believe, is essential

    for reducing the global burden of rheumatic heart disease. (Circulation. 2009;120:709-713.)

    Key Words:rheumatic heart disease prevention epidemiology

    Worldwide, nearly 16 million people suffer from rheu-matic heart disease (RHD), and more than 200,000deaths occur due to the disease and its sequelae.1 The vastmajority of this burden is borne by less developed countries,

    particularly those in the African continent. The highest

    prevalence of RHD in the world is found in sub-SaharanAfrica (5.7 per 1000 school children), and it is estimated that

    more than 1 million children between the ages of 5 and 14years are affected by the disease.1,2 This might well be an

    underestimate, given that recent cross-sectional studies usingechocardiographic screening have found a much higher prev-alence.3 Although the developed world is for the large part

    free of RHD, there has been an unexplained resurgence and

    persistence in some areas.4

    Despite the existence of proven preventive strategies for

    more than 50 years,5,6 prevalence rates in sub-Saharan Africa

    have not shown any significant decline.2,3,7 An importantreason for this is the lack of improvement in living conditions

    in most countries and the slow pace of improvement in others.

    This may also be because current approaches to control ofRHD rely almost entirely on secondary prophylaxis, as

    recommended by the World Health Organization (WHO) and

    several national bodies.8 In this article, we present argumentsas to why a strategy that relies exclusively on secondaryprevention is unlikely to reduce the burden of RHD in the

    developing world and highlight the importance of incorpo-

    rating primary prevention strategies, suitably modified tolocal conditions, for the success of any RHD control program.

    Prevention of Rheumatic Fever and RHD:Rationale and Strategies

    Rheumatic fever (RF) occurs in 0.3% to 3% of patients whohave pharyngitis due to group A streptococcal (GAS) infec-tion, as an autoimmune response to the infecting agent.9

    Involvement of heart valves during an acute episode of RF(carditis) leads to valve damage and chronic RHD. In studiesfrom developing countries in the postpenicillin era, 50% to

    80% of patients who have carditis develop chronic RHD at

    long-term follow-up.1012 Patients who have had carditis inthe past are more likely to develop carditis during recurrencesand, presumably, suffer cumulative valve damage.

    There are no proven treatments that alter the natural historyof RF.5,13 Therefore, prevention is the key to reducing theburden of disease in the community. Given our understandingof the pathogenesis of RHD, 2 broad strategies for preventionare applicable. Primary prevention involves the detection ofsymptomatic GAS sore throats in susceptible individuals inthe community (mainly children) and treatment with a courseof oral or parenteral penicillin.6 Secondary prophylaxis is

    achieved by periodic administration of penicillin to individ-uals who have had previous episodes of RF or have RHD,

    with the aim of preventing recurrent GAS sore throat.5

    Secondary prevention reduces the risk of recurrences ofrheumatic fever, but it has not been shown to reduce thedevelopment of chronic RHD or mortality due to RHD.5,14

    Several arguments have been made against adopting pri-mary antibiotic prophylaxis for the prevention of RF and

    From the Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada (G.K.); Department of Cardiology, All India Instituteof Medical Sciences, New Delhi, India (G.K.); and Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, SouthAfrica (B.M.M.).

    Correspondence to Dr Bongani M. Mayosi, Department of Medicine, J Floor, Old Main Building, Groote Schuur Hospital, Observatory 7925, CapeTown, South Africa. E-mail [email protected]

    2009 American Heart Association, Inc.Circulationis available at http://circ.ahajournals.org DOI: 10.1161/CIRCULATIONAHA.108.836510

    709

    Special Report

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    In the Cuban province, the additional cost incurred was just

    $2000 per year, which was mainly spent on the educational

    campaign.25 Moreover, with the reduction in RF incidence,

    the direct spending on RF/RHD care decreased progressively

    from a high of $145 000 per year at the beginning of the

    program to $22 000 per year after 10 years.25

    Safety of Primary PreventionThe 2 principal concerns of a primary antibiotic prophylaxis

    program, particularly one where a substantial proportion of

    individuals without streptococcal sore throats may receive

    benzathine penicillin, are (1) the problem of anaphylaxis and

    (2) the emergence of bacterial resistance. Contrary to popular

    belief, serious allergic reactions and anaphylaxis with benza-

    thine penicillin prophylaxis for RHD are rare. The Interna-

    tional Rheumatic Fever Study Group reported that after more

    than 32 000 injections and 2736 patient-years of follow up,

    the incidence of anaphylaxis was 1.2/10 000 injections, and

    the incidence of death was 0.31/10 000 injections (1 death inall).43 During the Costa Rican campaign, no deaths due to

    penicillin were reported, and anaphylaxis was reported only

    sporadically.26 In the same vein, strains of GAS, Streptococ-

    cus pneumoniae, and Hemophilus influenzae isolated at the

    National Childrens Hospital in Costa Rica continued to be

    100% sensitive to penicillin 2 decades after the RHD control

    program was implemented.26 Indeed, despite the widespread

    use of penicillin worldwide, GAS infections have continued

    to remain susceptible to the antibiotic.

    Primary Prevention in AfricaTreatment of sore throat is already part of the Integrated

    Management of Childhood Illness program in Africa, and

    penicillin is on the essential drug list of the WHO. Therefore,

    our call is for the implementation of existing policy within

    existing health systems, which we believe is within the reach

    of most African countries. The Awareness Surveillance

    Advocacy Prevention (ASAP) Program is an ongoing preven-

    tion program being implemented under the auspices of the

    Pan African Society of Cardiology (www.pascar.co.za)44 with

    the support of the national Departments of Health of SouthAfrica, Ghana, and Egypt and the World Heart Federation. In

    addition to the objectives of raising awareness about the

    disease in the community and among physicians, ASAP aims

    to implement primary prevention strategies in tandem with

    secondary prevention within the existing primary healthcare

    system. Pilot programs will be developed at selected sentinel/

    demonstration sites in the participating countries, which will

    ultimately serve as the basis for the establishment of national

    programs for the control of RF/RHD in these countries.45

    ConclusionsWe believe that a preventive program that relies almost

    exclusively on secondary prevention, such as the one advo-

    cated by the WHO, is unlikely to reduce the burden of RF and

    RHD in Africa. A strategy consisting of educating health

    personnel to recognize bacterial sore throat using simple

    clinical algorithms (instead of relying on a bacteriologic

    diagnosis), followed by a single injection of benzathine

    penicillin for the treatment of suspected cases, has been

    shown to be effective. The implementation of such a strategy

    through the existing healthcare infrastructure may be efficient

    and cost-effective and has the potential to reduce the burden

    of RF/RHD. The recently devised ASAP program is the first

    step toward implementing such a comprehensive preventive

    strategy in Africa.44

    The initial effort and expense in integrat-ing primary prevention into national RHD programs can be

    expected to be more than offset by the reduction in the

    number of patients with severe valvular disease who will

    subsequently require expensive tertiary care. Finally, it can-

    not be overemphasized that RF/RHD is a disease of poverty.

    Therefore, over and above the preventive strategies, living

    conditions and access to healthcare must improve substan-

    tially in order to reduce disease burden in sub-Saharan Africa.

    Sources of FundingDr Karthikeyan was a Heart Outcomes Prevention Evaluation(HOPE) Scholar at the Population Health Research Institute at

    McMaster University, Hamilton, Ontario, Canada in 20082009. DrMayosi is funded in part by the Medical Research Council of South

    Figure.Decline of the incidence of rheumatic fever with theintroduction of a comprehensive program that included treat-ment of all clinically suspected streptococcal sore throats. (A)Costa Rica; (B) Cuba. Data are from Nordet et al25 and Argue-das and Mohs.26

    712 Circulation August 25, 2009

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    Africa, National Research Foundation, Medtronic Foundation, andthe Lily and Ernst Hausman Trust.

    DisclosuresNone.

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