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.
