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AFRICA
S53
CVJAFRICA • Volume 26, No 2, H3Africa Supplement, March/April 2015
Integrating outcomes of genetics research
into new-born screening and interventions to
reduce childhood mortality and survival in SCD
Major benefits in the health and survival of children with SCD
have been attained through the implementation of a few simple,
evidence-based interventions. The most striking achievements
have resulted from early diagnosis of SCD through new-born
screening and the subsequent enrolment of these patients into
comprehensive care programmes. These programmes provide
interventions that include prophylaxis against pneumococcal
infection using penicillin, and early detection and treatment of
acute clinical events such as anaemia, septicaemia, stroke and
acute chest syndrome. These interventions have been introduced
in a limited manner in Africa, despite the fact that they have been
shown to be highly effective in developed countries.
Hydroxyurea, an important therapeutic intervention for SCD
in high-income settings, is beginning to be usedmore frequently in
several African countries.
50-53
There is no doubt that hydroxyurea
will have a large public health impact in Africa.
54
However
there are questions regarding the effectiveness of hydroxyurea
in some individuals possessing characteristics associated with
poor response to treatment. This includes SCD populations with
low levels of haemolysis,
55
low HbF level and Central African
Republic (CAR) haplotype,
56
as well as children under five years
of age with SCD, even though some data indicate that efficacy
is just as good or better in younger children.
57
These questions
should not delay the use of hydroxyurea in Africa, but it is
strongly recommended that research trials should be conducted
to monitor and evaluate effectiveness in this setting.
The second challenge regarding use of hydroxyurea in SCD in
Africa is access due to limited supply and high cost. It has also
been suggested that patients and families may resist adherence
with this treatment. In Cameroon, only 3.4% of SCD patients
had access to hydroxyurea.
58
Sociological data on the barriers
associated with prescription of and adherence with hydroxyurea
is needed in order to plan effective strategies to address these
issues in Africa.
Despite the limited access to hydroxyurea and other care
and therapies, about 3% of the 700 studied Cameroonian
patients with SCD lived longer than 40 years.
14
Specific survivor
SCD populations in sub-Saharan Africa can offer new research
opportunities to uncover possible variation that could improve the
life of SCD patients. With more and more genomic data available,
it is anticipated that new-born screening could also allow early
identification of genetic factors (e.g. HbF-promoting SNPs or
stroke-associated SNPs) to potentially assess each individual
patient’s risks and plan appropriate anticipatory guidance.
Perspectives: H3Africa and opportunity for
genomic research of cardiovascular diseases
in SCD
Currently, H3Africa extends across African countries, comprising
23 grants. It is anticipated that, together, H3Africa projects will
analyse samples from 50 000 to 75 000 participants. Specifically,
three projects have the objective to study stroke, kidney disease
and other cardiovascular diseases (rheumatic heart disease) in
various African countries where SCD is also prevalent
59
(e.g.
Cameroon, Tanzania, Nigeria, Ghana, Mali, Uganda). These
projects offer the opportunity to extend the existing network
of researchers in Cameroon, Ghana, Nigeria, South Africa and
Tanzania, which have been assembled to conduct multicentre,
Africa-based studies on the genetics and genomics of SCD.
To strengthen the case for genomic studies in Africa, several
genetic variations have been discovered throughmolecular studies
on the African continent.
60
There is enough evidence, including
whole-genome data from African populations, that emphasises
the high levels of genomic variation and the heterogeneity of
African populations.
61,62
Some of the tremendous genetic variation in Africa is
responsible for problems in clinical management of SCD, such
as red blood cell transfusion, red blood cell Rh D polymorphism
and allo-immunisation,
63
and response to medications
(cytochrome P450 polymorphisms and codeine/other opioids for
pain therapy).
64
Polymorphisms in ribonucleotide reductase, the
target enzyme for hydroxyurea, may have variable effects on SCD
patient response and deserves further investigation in Africa.
One SCD project currently funded under the H3Africa
umbrella is focused on research in Cameroon, Ghana and
Tanzania (FOA: RM12-005, 1 U01 HG007459-01). The project
aims to: (1) explore perspectives and attitudes regarding genomic
research and its implementation and implications in Africa,
and (2) assess perceptions about public health interventions to
increase awareness, early detection and prevention of SCD-related
complications. Beyond this project, the investigators are building
on biological materials, preliminary clinical and genomics data
from Cameroon, Tanzania, Nigeria and Ghana, and extending
the experience to other African countries, with the goal to
improve infrastructure for research and training. The ultimate
goal is to conduct research to understand the relationship
between genes, the environment and disease, in order to translate
genome-based knowledge into health benefits for SCD patients
and their families in Africa.
Role of the funding source: This report was funded by the National Institute
of Health (NIH, NHLBI), USA, grant number 1U01HG007459–01.
Key messages
•
SCD is characterised by marked clinical variability, with
genetic factors playing key modulating roles. Studies in
Tanzania and Cameroon have reported that SNPs in the
BCL11A
loci and
HBS1L-MYB
region (
HMIP
), and
co-inheritance of alpha-thalassaemia impact on HbF
level and clinical severity.
•
There are several cardiovascular phenotypes in SCD,
such as stroke, heart failure, pulmonary hypertension
and renal disease that contribute to its morbidity and
mortality.
•
The prevalence of overt stroke among SCD patients in
Cameroon (6.7%) and Nigeria (8.7%) suggests a higher
burden than in high-income countries.
•
The genetics of stroke, kidney disease and pulmonary
hypertension have seldom been investigated in SCD in
Africa.
•
Several H3Africa projects are focused on cardiovascu-
lar phenotypes, which creates a major opportunity to
build on existing SCD work in Africa, a genome-based
research on key cardiovascular phenotypes to transform
the health benefits of SCD patients.