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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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