Cardiovascular Journal of Africa: Vol 26 No 2 Supplement (March/April 2015)

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CVJAFRICA • Volume 26, No 2, H3Africa Supplement, March/April 2015 AFRICA S21
Review Articles
Rheumatic heart disease in Africa: is there a role for
genetic studies?
Ana Olga Mocumbi
Abstract
Rheumatic heart disease (RHD) constitutes a leading cause
of premature death and incapacity in Africa, where it is
encountered in younger people, and shows a much faster
and more malignant course than that seen in Europe or
North America. While it is well established that RHD is a
consequence of recurrent, untreated group A β-haemolytic
streptococcal infections (GAS), the pathogenesis is incom-
pletely understood, and the variation in natural history and
phenotypes are not fully explained. In Africa patients are
rarely diagnosed with acute rheumatic fever (ARF). They
usually present in the late stages of RHD, with the severe and
virulent forms occurring at early ages, therefore leading to
high morbidity and mortality in young patients.
Evidence suggests that genetic factors may be involved
in determining susceptibility to ARF as well as the severity
and outcomes of RHD. However, the results of genetic stud-
ies have been inconsistent, and conflicting results have been
found in series from Africa when compared to other parts of
the globe. Genetic studies in the African context are therefore
justified to understand the genomic and epigenetic driv-
ers of heterogeneity in individual responses to GAS infec-
tions and progression to RHD. Platforms such as the global
registry of RHD represent an opportunity for adequately
powered genome-wide association studies. The discovery of
all genetic susceptibility loci through whole-genome scanning
may provide a clinically useful genetic risk-prediction tool
that will potentially allow echocardiographic screening and
secondary prophylaxis for moderate lesions to be directed
to those at higher risk, therefore reducing the burden of the
disease to the health system, the work health force and the
communities of this resource-strained continent.
Keywords: rheumatic fever, rheumatic heart disease, genetic
susceptibility
Cardiovasc J Afr 2015; 26: S21–S26
DOI: -2015-037
Epidemiology of ARF and RHD
The global burden of disease caused by rheumatic fever (RF) and
rheumatic heart disease (RHD) currently falls disproportionately
on children living in the developing world and in marginalised
communities where poverty is widespread. Acute rheumatic fever
(ARF) follows in 0.4 to 3.0% of cases of group A β -haemolytic
streptococcal pharyngitis (GAS) in children. It is thought that
as many as 39% of patients with acute rheumatic fever may
develop varying degrees of pancarditis with associated valve
regurgitation and heart failure and in some cases death. RHD is
the only long-term consequence of ARF, and the most serious.1
Progression to chronic RHD is determined by several factors,
among which, repeated episodes of rheumatic fever seem to be
the most important.
The World Health Organisation (WHO) reported trends
in the incidence and prevalence of ARF and RHD for each
continent,2 based on literature from 100 countries around the
world between 1970 and 2009. These studies on ARF incidence
and RHD prevalence used population-based screening, national
health registries, prospective disease surveillance, surgical series,
autopsy series, and retrospective reviews of hospital admissions
or discharges for ARF or RHD. However, data from Africa are
scarce and do not capture the entire timeframe. According to this
study, the reported incidence of ARF is decreasing in all WHO
regions, except for the Americas and the western Pacific, where it
appears to be increasing. The prevalence of RHD is increasing in
all regions except for Europe, where it appears to be decreasing.2
A systematic review and meta-analysis of population-based
studies published between January 1993 and June 2014 recently
reported on the prevalence of RHD among children and
adolescents assessed in 37 populations, six of which were from
Africa.3 It revealed a prevalence of RHD detected by cardiac
auscultation at 2.9 per 1 000 individuals and by echocardiography
at 12.9 per 1 000 people, with substantial heterogeneity between
individual reports for both screening modalities. Prevalence of
clinically silent RHD in this study (21.1 per 1 000) was about
seven to eight times higher than that of manifest disease (2.7 per
1 000). Prevalence progressively increased with advancing age,
from 4.7 per 1 000 at age five years to 21.0 per 1 000 people at 16
years. There was no gender-related differences in prevalence; an
association was found between social inequality expressed by the
Gini coefficient and prevalence of RHD (p = 0.0002).3
The exact incidence and prevalence of RHD in Africa are
unclear because of the recognised differences in epidemiology
between countries, availability of diagnostic approaches,
differences between rural and urban environment, age groups
included in the study, and more importantly, lack of knowledge
Instituto Nacional de Saúde and Universidade Edurado
Mondlane, Maputo, Moçambique
Ana Olga Mocumbi, MD, PhD,