African Pharmacogenomics Consortium: Consolidating pharmacogenomics knowledge, capacity development and translation in Africa

Abstract

The African Pharmacogenomics Consortium (APC) was formally launched on the 6th September 2018. This white paper outlines its vision, and objectives towards addressing challenges of conducting and applying pharmacogenomics in Africa and identifies opportunities for advancement of individualized drugs use on the continent. Africa, especially south of the Sahara, is beset with a huge burden of infectious diseases with much co-morbidity whose multiplicity and intersection are major challenges in achieving the sustainable development goals (SDG), SDG3, on health and wellness. The profile of drugs commonly used in African populations lead to a different spectrum of adverse drug reactions (ADRs) when compared to other parts of the world. Coupled with the genetic diversity among Africans, the APC is established to promote pharmacogenomics research and its clinical implementation for safe and effective use of medicine in the continent. Variation in the way patients respond to treatment is mainly due to differences in activity of enzymes and transporters involved in pathways associated with each drug’s disposition. Knowledge of pharmacogenomics, therefore, helps in identifying genetic variants in these proteins and their functional effects. Africa needs to consolidate its pharmacogenomics expertise and technological platforms to bring pharmacogenomics to use.

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OPENLETTER
African Pharmacogenomics Consortium: Consolidating
pharmacogenomics knowledge, capacity development and
translation in Africa [version 1; peer review: awaiting peer
review]
ColletDandara ,   CollenMasimirembwa , YosrZ.Haffani , BernhardsOgutu ,
  JennifferMabuka , EleniAklillu , OluseyeBolaji , H3Africa
Pathology&InstituteofInfectiousDiseasesandMolecularMedicine,UniversityofCapeTown,CapeTown,7925,SouthAfrica
AfricanInstituteofBiomedicalScienceandTechnology,Harare,Zimbabwe
HigherInstituteofBiotechnologySidiThabet,ManoubaUniversity,Ariana,LR17ES03,Tunisia
CentreforResearchinTherapeuticSciences,StrathmoreUniversity,Nairobi,Kenya
Secretariat,TheAfricanAcademyofSciences(AAS),Nairobi,Kenya
DepartmentofLaboratoryMedicine,KarolinskaInstitutet,Stockholm,Sweden
DepartmentofPharmaceuticalChemistry,ObafemiAwolowoUniversity,Ile-Ife,Nigeria
Abstract
TheAfricanPharmacogenomicsConsortium(APC)wasformallylaunched
onthe6thSeptember2018.Thiswhitepaperoutlinesitsvision,and
objectivestowardsaddressingchallengesofconductingandapplying
pharmacogenomicsinAfricaandidentifiesopportunitiesforadvancement
ofindividualizeddrugsuseonthecontinent.Africa,especiallysouthofthe
Sahara,isbesetwithahugeburdenofinfectiousdiseaseswithmuch
co-morbiditywhosemultiplicityandintersectionaremajorchallengesin
achievingthesustainabledevelopmentgoals(SDG),SDG3,onhealthand
wellness.TheprofileofdrugscommonlyusedinAfricanpopulationsleadto
adifferentspectrumofadversedrugreactions(ADRs)whencomparedto
otherpartsoftheworld.CoupledwiththegeneticdiversityamongAfricans,
theAPCisestablishedtopromotepharmacogenomicsresearchandits
clinicalimplementationforsafeandeffectiveuseofmedicineinthe
continent.Variationinthewaypatientsrespondtotreatmentismainlydue
todifferencesinactivityofenzymesandtransportersinvolvedinpathways
associatedwitheachdrug’sdisposition.Knowledgeof
pharmacogenomics,therefore,helpsinidentifyinggeneticvariantsinthese
proteinsandtheirfunctionaleffects.Africaneedstoconsolidateits
pharmacogenomicsexpertiseandtechnologicalplatformstobring
pharmacogenomicstouse.
Keywords
pharmacogenomics,pharmacogenetics,Africa,adversedrugresponse
(ADR),genotype,phenotype
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Reviewer Status AWAITING PEER REVIEW
04Jun2019, :19(First published: 2
)https://doi.org/10.12688/aasopenres.12965.1
04Jun2019, :19(Latest published: 2
)https://doi.org/10.12688/aasopenres.12965.1
v1
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AAS Open Research 2019, 2:19 Last updated: 04 JUN 2019

AAS Open Research
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ThisarticleisincludedintheAfricanSocietyof
gateway.HumanGenetics
ColletDandara( )Corresponding author: collet.dandara@uct.ac.za
 :Conceptualization,Writing–OriginalDraftPreparation,Writing–Review&Editing; :Author roles: Dandara C Masimirembwa C
Conceptualization,Resources,Writing–OriginalDraftPreparation,Writing–Review&Editing; :Conceptualization,Writing–Review&Haffani YZ
Editing; :Conceptualization,ProjectAdministration,Writing–Review&Editing; :Writing–Review&Editing; :Ogutu B Mabuka J Aklillu E
Conceptualization,Writing–Review&Editing; :Conceptualization,Writing–Review&Editing;Bolaji O
Nocompetinginterestsweredisclosed.Competing interests:
H3ABioNetissupportedbytheNationalInstitutesofHealthCommonFund[2U24HG006941-06].H3ABioNetisaninitiativeofGrant information:
theHumanHealthandHeredityinAfricaConsortium(H3Africa)programmeoftheAfricanAcademyofSciences(AAS).
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
©2019DandaraC .Thisisanopenaccessarticledistributedunderthetermsofthe ,whichCopyright: et al CreativeCommonsAttributionLicence
permitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.
DandaraC,MasimirembwaC,HaffaniYZ How to cite this article: et al. African Pharmacogenomics Consortium: Consolidating
AASpharmacogenomics knowledge, capacity development and translation in Africa [version 1; peer review: awaiting peer review]
OpenResearch2019, :19( )2https://doi.org/10.12688/aasopenres.12965.1
04Jun2019, :19( )First published: 2 https://doi.org/10.12688/aasopenres.12965.1
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Disclaimer
The views expressed in this article are those of the authors. Pub-
lication in AAS Open Research does not imply endorsement
by the AAS.
The problem to be addressed by the African
pharmacogenomics consortium
Traditionally, disease patterns are characterised with infectious
diseases (malaria, TB, HIV, cholera, neglected tropical diseases)
being the major cause of morbidity and mortality in develop-
ing countries in Africa, Asia and South America (Srivastava
et al., 2018). On the other hand, non-communicable diseases
such as cancer, cardiovascular disease, and neuropsychiatric
disorders have been associated with developed countries of
Europe, North America and Japan (Guthold et al., 2018).
However, changes in life style in developing countries have
resulted in what is termed the ‘epidemiological transition’ where
these countries now bear the double burden of infectious and non-
communicable diseases (Juma et al., 2018; Keates et al., 2017).
This has increased the disease burden in these countries where
Africa, which has 10% of the world population, now carries 25%
of the global disease burden (See AfricaRenewal, 2016–2017;
Crisp, 2011). This has in turn increased the need for treat-
ment interventions to reduce morbidity and mortality. Whilst
the use of medicines has been associated with huge reductions
in mortality thereby increasing life expectancy, some medicines
such as anti-retroviral drugs (ARVs) have been associated with a
huge surge in adverse drug reactions (ADRs) where up to 80% of
ADRs in some sub-Saharan Africa are now due to ARVs (Ampadu
et al., 2016; Appiah, 2012; Nemaura et al., 2012; Rajman et al.,
2017; Sarfo et al., 2014a). On the other hand, efforts to combat
non-communicable disease have shown a widespread lack of
efficacy of some medicines used in treating hypertension
(Fontana et al., 2014) and breast cancer (Li et al., 2017). The
burden of ADRs and poor efficacy translates to disability, death
and huge costs to the already constrained healthcare systems of
Africa. It is this burden of poor safety and lack of efficacy of
medicines in African populations that the African Pharmacog-
enomics Consortium seeks to address. This will be done by
quantifying the disease burden, understanding the underlaying
biomedical mechanisms, evaluating costs to the healthcare sys-
tems and finding interventions for improved treatment outcomes
using a responsible innovation (RI) approach.
ADRs are unwanted drug effects and have considerable
economic as well as clinical costs as they often lead to hospital
admissions and prolongation of hospital stay which increases
pressure on health care systems that are often overstretched
(Sultana et al., 2013). Estimates from USA and Canada show
that ADRs account for 4–30% and 6–35% hospital admissions
and hospitalization, respectively, while France reports at least,
100,000 patients presenting with ADRs per annum. The
Food and Drug Administration (FDA) of the United States of
America reports 58,000-106,000 annual deaths due to ADRs
(Sultana et al., 2013). ADRs add to the healthcare cost as illus-
trated by Watanabe et al. (2018) in a study where they report on
an estimated cost of prescription drug-related morbidity and
mortality resulting from non-optimal medication therapy of at
least $500 billion for 2016. This is equivalent to nearly 15% of
total US healthcare expenditure and way above most GDPs in
African countries. Another study from the United Kingdom,
reported that ADRs increased the mean hospital stay from an
average of 8 days in patients without ADRs to 20 days in patients
with ADRs (Davies et al., 2009) which was accompanied by
an increased risk of mortality in patients who experienced ADRs.
Through global coordinated efforts, medicine supply includ-
ing new drugs to treat poverty related diseases is increasing but
this effort is not matched well with local capacity to monitor
patient safety in indigenous African populations. The impact of
the burden of ADRs in Africa with respect to people affected,
drugs involved and cost to the healthcare system is poorly
characterized. Available data on ADRs in Africa is scarce
except for a few studies from Kenya (Aminkeng et al., 2014),
Ethiopia (Petros et al., 2017a; Yimer et al., 2012), Ghana (Sarfo
et al., 2014), South Africa (Aminkeng et al., 2014), Zimbabwe
(Nemaura et al., 2012) and in a few other African countries
of which most are single hospital studies. This is reflected by
low participation in pharmacovigilance programs where, by
2016, only 35 countries were participating in the WHO Program
for International Drug Monitoring (PIDM) which involves
reporting of individual safety case report (ICSR). Africa con-
tributes a mere 0.88% ICSR to this VigiBaseR, with South Africa
being the most active (Ampadu et al., 2016). Despite this low
reporting for many drugs, data shows that ADRs from ARVs
and some antibiotics are 5–10% higher in Africans compared
to the rest of the world (Ampadu et al., 2016). Whereas, in
most developed countries, ADRs have also been characterized
(e.g., for drugs such as Nonsteroidal anti-inflammatory drugs
(NSAIDs), coumarins, antibiotics, anticancer, and beta-blockers),
facilitating their recognition and prevention; ADRs in African
populations are mainly on the backbone of antiretroviral
(Ampadu et al., 2016; Mouton et al., 2016; Rajman et al., 2017)
accounting for at least 30% of ICSRs, followed by anti-
tuberculosis and antimalarial therapy, respectively (Ampadu
et al., 2016; Birbal et al., 2016; Mouton et al., 2016).
To our knowledge, there is no published data on the burden of
ADRs with respect to mortality at national or regional level
in Africa, there are very few studies that have evaluated the
economic impact of ADRs. A recent study conducted by
Management Sciences for Health, a Virginia–based international
nonprofit organization, showed that 6.3% of hospital admis-
sions in Sub-Saharan Africa were direct consequences of an
ADRs, while between 6.3% and 49.5% of hospitalized patients
developed ADRs (Appiah, 2012). A study in South Africa
showed that 1 in 12 admissions was because of an ADR, and
that ADRs were associated with drugs mostly used for the
treatment of HIV and TB (Mouton et al., 2016). There is also a
distinct complex disease-disease, and drug-disease as well as
drug-drug interaction profiles emerging in sub-Saharan Africa
where HIV patients have been shown to have a high risk for
cardiovascular diseases (Keates et al., 2017) and where some
ARVs have been shown to increase the risk for metabolic dis-
orders in these patients (Keates et al., 2017). For example, at
least 40% of HIV/AIDS patients on combination antiretroviral
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therapy (cART) in South Africa present with hypertension
(Nlooto, 2017). Most drugs used for the treatment of non-
communicable diseases were developed after clinical trials car-
ried out in Caucasian and Asian populations with a poor or
no representation of African populations, except in trials on
HIV/AIDS (GBD 2016 and HALE collaborators, 2017;
Kharsany & Karim, 2016). This has led to reports of ADRs in
African patients with drugs that sometimes have not shown any
such effects in Caucasian populations (Taylor, 2018). Moreover,
some drugs that have proven efficacious in Caucasian populations
have not shown similar action in African populations (Fontana
et al., 2014; Li et al., 2017). In particular, the massive use of
cART for HIV/AIDS has led to many people living with HIV
for longer periods of time, allowing ADRs associated with long
term cART use to manifest (Ghosn et al., 2018; Kharsany et al.,
2018; Montjane et al., 2018; Soko et al., 2018). A distinct popu-
lation specific drug interaction profile between rifampicin and
efavirenz in black African and Caucasian populations, has neces-
sitated different efavirenz dose modification strategies during
rifampicin co-treatment (Habtewold et al., 2015; Habtewold
et al., 2017). The impact of rifampicin enzyme induction in
reducing efavirenz plasma exposure observed in Caucasian or
Asians was not replicated in black Africans, partly due to phar-
macogenetic variations (Mukonzo et al., 2014a; Ngaimisi et al.,
2011). Recent studies recommended pharmacogenetic-based
EFV dose modification during rifampicin based anti-tuberculosis
co-treatment for sub Saharan African population (Mukonzo
et al., 2016; Mukonzo et al., 2014b).
The underlying mechanisms of high frequency of ADRs and
poor efficacy of some medicines in African populations remain
largely unknown. Studies in European populations have shown
that most ADRs are concentration dependent. A high concen-
tration of the parent drug and/or its metabolites can result in
exaggerated primary pharmacological effects and/or appearance
of new and undesirable secondary pharmacological effects. The
high concentrations could be due to the physicians’ deliberate
effort to increase therapeutic effect or errors in prescription. A
large percentage of ADRs due to high drug exposures have been
attributed to reduced metabolic activity of enzymes responsible
for the metabolism and excretion of the drug of interest. For
instance, the CYP3A enzyme activity is significantly lower in
Tanzanians than Swedes or Koreans (Diczfalusy et al., 2008;
Mirghani et al., 2006). Factors that affect drug metabolism and
disposition (drug metabolising enzymes and transporters) have
therefore been extensively studied as the mechanism behind
most observed ADRs. Two major mechanisms have been demon-
strated to be responsible for variable drug exposures; enzyme or
transport inhibition or induction, and genetic variation in genes
coding for drug metabolising enzymes or drug transporters asso-
ciated with reduced or increased function. A study in about a
thousand patients showed that interactions associated with risk
for ADRs involved 50% due to drug-drug interactions, 34%
drug-gene interactions and 19% of drug-drug-gene interactions
(Verbeurgt et al., 2014).
The possible contribution of these mechanism to the ADRs
observed in African populations are poorly understood due to
several reasons including, lack of knowledge on the extent of
pharmacogenetic variation in African populations (Rajman et al.,
2017), lack of clinical pharmacogenetic studies to evaluate the
role of the known genetic variants in observed ADRs, and lack of
known enzymes and transporters involved in the disposition of
many drugs commonly used in African populations such as anti-
parasitic drugs. There is therefore a great need to investigate the
role of drug-drug, drug-gene and drug-drug-gene interactions
as risk factors for ADRs in African populations. The African
Pharmacogenomics Consortium (APC) has therefore identi-
fied genomic factors as important factor in understanding ADRs
in African populations and intends to come up with interven-
tions for improved treatment outcome. In a contribution to
domestication of precision medicine, the consortium will foster
development of robust electronic health records for patients and
decision support systems to translate, share and communicate
pharmacogenomics results to healthcare providers and patients,
and to provide evidence-based recommendation for policy makers
to revise treatment guidelines relevant for African populations.
Pharmacogenomics as the solution
Pharmacogenomics utilizes a person’s genome (or genetic
makeup), to identify drugs and drug doses that are likely to work
best for that particular person, or drugs that are likely to cause
ADRs. In Africa, there have been several initiatives filling the gaps
that will eventually inform new ways of improving health, two
of these include MalariaGen and H3Africa (see Table 1). How-
ever, the focus of most of these initiatives has been primarily on
the genomics of disease susceptibility with little or no pharma-
cogenomics. African health care systems are complex, involving
contemporary and herbal medicines. Thus, pharmacogenomics
could enable a better understanding of the basis of both west-
ern and traditional medicine leading to better integration
(Thomford et al., 2018; Xin et al., 2019).
Pharmacogenomics in drugs and diagnostics
discovery, development and deployment
The two most important concerns for new drug development
are efficacy and safety. Generally, the process of drug discov-
ery starts with the identification of a potential target at which
the drug can act. The target can be an enzyme in a vital path-
way, a receptor, a transporter, a protein in signal transduction
or any protein important in disease manifestation. Currently,
about 300 targets of the potentially 5000 drug targets are being
exploited for drug discovery. These are mostly proteins (e.g.
enzymes and receptors) that are coded for by genes that
exhibit genetic polymorphisms. Knowledge of pharmacog-
enomics at this level has helped in the development of anti-
cancer drugs that work in patients of specific genotypes and
thus informed the development of companion diagnostic
tools to identify such responders in the clinical setting (see
Pharmacogenomics Knowledge Database).
The pharmaceutical industry has reported that up to 60% of
compounds in their discovery and development pipelines have
a pharmacogenomics component (Zhang et al., 2012) neces-
sitating the need of a pharmacogenomic strategy in the whole
discovery and development value chain. There is an Industry
Pharmacogenetics working group that provides the relevant stra-
tegic input on this matter for its membership. Genetic studies in
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conjunction with gene expression, proteomic, and metabonomic
analyses provide a powerful tool to identify molecular subtypes
of disease. Using these molecular data, pharmacogenomics has
the potential to impact on the drug discovery and develop-
ment process at many stages of the pipeline, contributing to both
target identification and increased confidence in the therapeutic
rationale.
In the drug discovery and development value chain, pharmacog-
enomics can be useful at the following stages:
(1) Drug target identification and validation– characterising the
heterogeneity of drug targets and variable target-chemical inter-
actions with potential pharmacodynamic effects. This can result
in avoiding certain drug targets or developing a companion
diagnostics strategy that will be used to identify responder and
non-responder patient subgroups in the clinical setting. Genetic
variation in the human CD4 cells receptor, CCR5 inspired the
discovery of the cells entry inhibitor, maraviroc (Dorr et al.,
2005; Perry, 2010; Veljkovic et al., 2015) and a companion
diagnostic for its use in patients likely to benefit from the drug
(Kim et al., 2016; Whitcomb et al., 2007). Pharmacogenomics
has already been used in oncology to demonstrate that molecu-
lar data facilitates assessment of disease heterogeneity, and thus
identification of molecular markers of response to drugs such
as imatinib mesylate (Gleevec) and trastuzumab (Herceptin).
Knowledge of genetic variation in a target allows early assess-
ment of the clinical significance of polymorphism through the
appropriate design of preclinical studies.
(2) Lead and candidate drug discovery phase – in vitro char-
acterisation of compounds for metabolism or transport by
proteins that exhibit functionally important variations. This will
result in either molecular design to avoid compounds likely to
have unfavourable pharmacokinetics and pharmacodynamics
in some patient groups or to design phase I clinical studies that
target affected enzymes or transporters. In lead and candidate
drug discovery, assessment of drug metabolising enzyme and
drug transporters pharmacogenetics studies are performed to
inform selection of suitable candidates for first time in man and
the subsequent design of clinical trials (Raymer & Bhattacharya,
2018)
(3) Phase I and II clinical trials – In clinical studies, pharma-
cogenetic tests are used for stratification of patients based on
their genotype, which corresponds to their metabolizing capac-
ity. This prevents the occurrence of severe ADRs and helps in
providing better outcomes from clinical trials. This can also
reduce attrition of drug compounds.
(4) Phase III – identification and validation of the function
of common genetic variants on drug PK and PD, design of
preventive trials based on predisposed PGx biomarkers, develop-
ment of dosage algorithm based on PGx and discovery of ADRs
related PGX biomarkers.
(5) Phase IV clinical trials– identification and validation of the
function of rare genetic variants on drug PK, PD and ADRs,
validation of the PGx biomarkers related to ADRs and design of
prospective study in prevention of ADRs based on PGx biomark-
ers (Wen et al., 2015). In this regard members of the APC have
conducted clinical pharmacogenetic studies on the use of efa-
virenz in HIV patients (Dhoro et al., 2015; Habtewold et al.,
2015; Nemaura et al., 2012; Ngaimisi et al., 2011; Nyakutira
et al., 2008; Olagunju et al., 2015a; Olagunju et al., 2015b; Swart
et al., 2013), antiretroviral and antimalarial drug interactions
(Maganda et al., 2016; Mutagonda et al., 2017), genetic biomarkers
for antiretroviral and anti-tuberculosis drug induced hepatotoxic-
ity (Petros et al., 2017a; Petros et al., 2017b; Petros et al., 2016),
imatinib in the treatment of chronic myelogovenous leukaemia
Table 1. A list of some of the common genomics initiatives in Africa.
INITIATIVE FOCUS ADDRESS/ CONTACT
African Pharmacogenomics
Consortium (APC)
The genetics of drug effectiveness (meetings,
training workshops, conferences, collaborations)
Current initiative (website to be developed)
(bsiddondo@strathmore.edu)
The African Society for Human
Genetics (AfSHG)
Annual conferences/meetings https://www.afshg.org/
African Human Genome
Initiative
Lectures, conferences, discussions www.africagenome.co.za
H3Africa Genomics and environmental determinants of
disease
https://h3africa.org
MalariaGEN Malaria genomic epidemiology Network, focussing
on effects of genetic variation on the biology and
epidemiology of malaria
www.malariagen.net
H3ABioNet pan-African bioinformatics network https://www.h3abionet.org/
the Southern African Human
Genome Project
Understanding of DNA variation among southern
Africans and how this impact on the health of the
people of our country.
https://sahgp.sanbi.ac.za
African Genome Variation
Project
Aims to collect essential information about the
structure of African genomes to provide a basic
framework for genetic disease studies in Africa
https://www.sanger.ac.uk /science/collaboration/
african-genome-variation-project
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(Adeagbo et al., 2016), and the pharmacokinetics of rosuvastatin
in African populations (Soko et al., 2016; Soko et al., 2018) and
showed the potential importance of pharmacogenetic biomarkers in
the optimal use of these drugs in African populations.
If the emerging genomic diversity of African populations is
also observed in clinically significant pharmacogenes, that diver-
sity will therefore present an opportunity for Africa to actively
participate in the drug discovery and development process. This
can be done through several ways including (i) opportunities to
discover disease receptor subtypes that can help provide proof
of concept through validation of the selected target as suitable
for drug discovery, (ii) having higher frequency of important
PGx variants not commonly found in other world popula-
tions, thus making it strategically and economically attractive to
conduct phase I clinical studies in African populations, and
(iii) biomarker discovery for ADRs will be more productive in
a population that shows a wide genetic diversity of involved
gene(s). Africa and the rest of the world is currently not taking
full advantage of this opportunity despite leading world scientists
in the field such as Rotimi (See Newsweek interview) and
Tishkoff (See Scientifc American blog) highlighting the perils
of excluding African genomics in the advancement of medical
research. The APC will therefore build a case for the exploita-
tion of this opportunity through engaging biopharmaceutical
companies and biotechnology companies for joint ventures in
drugs and diagnostics discovery and innovation.
Vision of African pharmacogenomics consortium
The vision of the APC is to explore the diverse African genome
for better health in the continent. The consortium aims to char-
acterise the genomes of African populations to unravel crucial
pharmacogenes for the improvement of quality of life of African
patients. This vision will be achieved through consolidation of
pharmacogenomics research and its implementation in Africa
through strategic collaborations of Africans based in Africa
leveraging expertise from international partners.
Historical perspective on APC
The vision of the consortium is built through multiple func-
tional interactions and partnership of the network members
which is supported by a strong history. Formation of the APC
can be traced to August 2003, when African scientific experts
focussing on pharmacogenomics met in Nairobi, Kenya, with
the aim of strengthening pharmacogenomics research in Africa,
through collaborations and postgraduate students training. The
need of this collaboration was raised following the incorporation
of some pharmacogenomic tests and clinical decision making,
developed on Caucasian and Asian populations, which have proved
not to be fully transferable to African populations through algo-
rithms because of the extent of genetic diversity in these popu-
lations. Thus, pharmacogenomic characterisation of African
populations needs to be carried out as such knowledge has the
potential to save lives and reduce healthcare costs through reduc-
tion in hospital admissions, mortality thereby freeing resources
for use in other healthcare areas. Adoption of pharmacogenomics
in Africans can, thus, lead to improved drug effectiveness, and
prevent morbidity and mortality (Ashley et al., 2010; Mallal
et al., 2008; Squassina et al., 2010).
Objectives of African pharmacogenomics
consortium
A. Awareness of pharmacogenomics among Africans
APC will create awareness in pharmacogenomics through
training by offering short courses and degree programmes in
partnership with accredited universities. In addition, dissemina-
tion of pharmacogenomics knowledge will form part of aware-
ness and this will be achieved through publications (policy
briefs, opeds, etc). The consortium will organise workshops and
demonstrations to train stakeholders on the use of the delivered
technologies regarding pharmacogenomics. Special emphasis
will be conducted on “train the trainer” outreach so that the
information will be disseminated to the greatest extent possi-
ble. It will coordinate and manage publications of the project
findings in pharmacogenomics, biological and medicinal trade
magazines and scientific journals. It will also establish an online
consultation platform ’Consult Expert’, implement, manage,
maintain and further grow databases of contacts and links that
can be used by the consortium to specifically target messages to
stakeholder’s groups and actors (hospitals, clinics, schools,
national educational authorities, training centres, SMEs, associa-
tions, social media and forums and others). Lastly, APC will carry
out public engagements for pharmacogenomics through the
media (print, digital, audio visual), publish scientific knowledge
into popular messages, including multi-lingual concepts target-
ing the different languages in Africa, and also develop a non-
verbal communication tool based on symbols.
B. Research and training on pharmacogenomics in Africa
APC will work towards building integrated capacities for
pharmacogenomics in terms of bioanalysis, bioinformatic, clini-
cal trials and biobanking/ genomic analysis. This will enable
African researchers to generate relevant research questions which
they have capacity to answer. As far as world trends are con-
cerned, Africa’s current contribution is insignificant (Adedokun
et al., 2016), yet the continent is a “gold-mine” with respect to
the wide genetic diversity of the human genome as well as its
co-evolution with some of the problematic pathogens such as
tuberculosis bacteria, which could provide answers to some of
the currently elusive genetic markers of susceptibility, response
and co-evolution. Some of the major reasons for this low
research capacity are poor infrastructure for research at public
research institutions such as universities, and lack of a research
and innovation-based biopharmaceutical and biotechnology
industry to invest in genomic research. This has also meant that
the few skilled genomics scientists have been trained abroad as
there is no local capacity for such training. Governments and the
private sector in Africa need to invest in infrastructure, technol-
ogy and skilled manpower to enable Africa to participate in the
genomics driven development in life sciences.
C. Implementation of pharmacogenomics in Africa
In translating African pharmacogenomics knowledge, opti-
mization of available pharmaceuticals is a major priority as
these drugs are already in use. The conduct of bridging studies
is, thus, most relevant in African populations. This is supported
by observations in China and Japan for drugs in which their
populations have not been part of during clinical trials, are not
allowed for use in their populations without first carrying out
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AAS Open Research 2019, 2:19 Last updated: 04 JUN 2019

relevant bridging studies. The next challenge in improving
human health is being tackled through precision medicine, thus,
APC seeks to ensure domestication of precision medicine in
the African health system. African populations are unique in
that they use a diverse health care system; thus, APC seeks to
target health system strengthening of medicinal products use
(traditional and conventional). Coding and sharing of best practices
in African pharmacogenomics will be at the core of its implemen-
tation strategies. In order to support the health care system, APC
will develop and regularly update pharmacogenomics implemen-
tation guidelines for African populations and these should benefit
from seamless link with the pharmacovigilance and clinical trials
platforms in Africa. APC will harness the genomic diversity
Africans in drugs and diagnostics discovery/commercialisation
in partnership with local and international biotechnology and
biopharmaceutical companies. To increase uptake of pharmacog-
enomics, APC will partner in the development of curricula for
training in pharmacogenomics. To retain and equip practitioners
of pharmacogenomics APC will create regional hubs of excel-
lence in pharmacogenomics. The consortium will regularly develop
matrices/models for pharmacogenomics implementation impact
assessment. It seeks to be the “African voice” on pharmacog-
enomics and affiliate with appropriate international bodies
including but not limited to genomic societies.
Recommendations by the African
pharmacogenomics consortium/network (APC)
(i) Capacity development for pharmacogenomics in Africa
APC aims to develop research leadership impactful of research
on Africa and led by Africans. Currently most research in
genomics is led or coordinated by researchers in Europe or
America in which African researchers have acted as sample
collectors (Dandara et al., 2014; H3Africa sustainability). It is,
therefore, not surprising to come across genomics research on
Africans published without acknowledgement of African
authors, and in the few cases where African researchers are
involved they are ‘middle-of-the-pack’ insignificant co-authors.
Although Africa has seen some leap in the development of human
capital resources for genomics research, there has not been much
focus on pharmacogenomics. It is our intention that APC should
develop an infrastructure and programs that support harmo-
nisation of participant recruitment and phenotype recording.
There are very few centres in Africa that are equipped for
pharmacogenomics phenotype analysis as well as genome
characterisations. This will be associated with the establishment of
biobanks/biorepositories to support pharmacogenomics research
and linked to local capacity for laboratory drug and genomic
analysis. We would like to strengthen these centres and make
them core-facilities where students and researchers can get access
on a short-term basis to resolve issues/challenges they would
be facing in their research at any particular moment, through
training and analysis of their samples.
(ii) Education/training support and ethical, legal, and social
issues (ELSi)
APC seeks to take stock of the number of researchers working
on pharmacogenomics in Africa, increase this number with train-
ing of MSc/PhD graduates and incorporating ethical, legal and
social issues (ELSi) that are sensitive to African populations.
This will reduce cases of ethics dumping. Currently, alignment
of ELSi on African genomics is led by researchers from outside
Africa, as can be viewed through published literature. While
acknowledging the Western view on ethics, it is our view that, the
African voice should find space and lead in the discourse, if
we are going to have ethics that respond to African values.
Moreover, the continent has varied local ethics regulations which
require harmonisation for across country initiatives such as the
APC. This could be achieved through influencing policy at the
level of continental institutions/bodies such as the African Union
Development Agency (AUDA), a technical arm of the African
Union (AU).
There are no programs that capture pharmacogenomics in
African universities, thus, there is a need to develop innova-
tive courses for training MSc/PhD students in these universities,
leveraging expertise from APC hubs of excellence, and APC
network of experts. In addition, the APC would endeavour to
carry out community engagements by domesticating pharma-
cogenomics through presentation of the topics and issues in the
context of people’s social and cultural experiences. This will
include qualitative engagements on safety and efficacy of
medicines through focus-group discussions and interviews.
Members in the APC will leverage their rich history of train-
ing students across Africa to accomplish this task. It is expected
that this initiative should further empower such trained individu-
als to compete for grant funding thereby putting into use knowl-
edge acquired. APC will build on existing platforms to leverage
on their support and endeavour that projects running under its
banner meet the ethical, legal, and socially appropriate standards
for research. APC will also seek the harmonisation of participant
recruitment and engagements for pharmacogenomics research
and implementation in Africa.
(iii) Resource development and utilization
APC will work towards building integrated capacities for
pharmacogenomics. African entities such as New Partnership
for Africa’s Development (NEPAD) and the African Academy
of Sciences (AAS) could be used as sounding boards for across
the board implementation, resource mobilisation and utili-
zation. APC will work for recognition from WHO, which is
respected by African governments, making it easier for adoption
of its recommendations. It is noteworthy that the WHO developed
a position paper on pharmacogenomics (WHO Drug Information
Vol 19. No. 1, 2005). Though now old, it is aligned to the now
well-developed guidelines for pharmacogenomics by European
Medicines Agency (EMA) (EMA February, 2018) and a series
of pharmacogenomics guidelines by the FDA and by industry
working group on pharmacogenomics (Patterson et al., 2011).
It is thus imperative that the APC spearheads the development
of a position on pharmacogenomics for Africa.
(iv) Database for clinical pharmacogenomics
implementation guidelines for African populations
The biggest resource that African populations have is the genomic
diversity. This diversity probably holds the keys to unlocking the
identification of genomic determinants of susceptibility to com-
plex diseases such as diabetes and determinants of differential
response to drug treatments. However, for the effective use
Page 7 of 10
AAS Open Research 2019, 2:19 Last updated: 04 JUN 2019

of African genomes, baseline frequencies of pharmacogene
variants need to be developed. After pharmacokinetic and phar-
macodynamic studies, the APC should be in a position to come
up with recommendations for priority pharmacogenomics for
different drug/disease combinations in African patients. APC
will lead the developing and updating of recommendations for
implementation of pharmacogenomics in African populations.
(v) Building sustainable governance in pharmacogenomics
in Africa
The consortium will aim to put into place ethical and sustain-
able structures in the area of pharmacogenomics research with
respect to sample/data collection and storage, data sharing and
release, and student training exchange. This will be achieved
through structured governance. For any project that the consortium
will embark on, a principal applicant (project coordinator) and
co-applicants will be chosen from participating countries to
form a steering committee (SC) as the decision-making organ.
The SC will provide general direction and scientific guid-
ance to the proposed work. The project coordinator will act
as the communications liaison person for such an application
and will play a coordinating role for all the proposed research
activities.
Conclusions
The WHO urged the implementation of pharmacovigilance cen-
tres in Africa to raise the awareness of ADRs (US Agency for
International Development). A recent report on the action taken
regarding regulatory authorities in African nations showed that
it “requires the necessary infrastructure and resources includ-
ing laws, systems and structures, human resources (in terms of
numbers, knowledge and skills) and financial resources to
execute their mandate” including pharmacovigilance to monitor
drug safety (see report from the Africa Pharmacovigilance
Meeting 2012). In this, the APC will be implementing hubs of
excellence in African countries to promote pharmacogenomics
and pharmacovigilance according to the regional needs of the
continent. Interestingly, the APC support the wise words of the
South African revolutionary, political leader, and philanthropist
Nelson Mandela, ‘We must face the matter squarely, that where
there is something wrong in how we govern ourselves, it must be
said that the fault is not in the stars, but in ourselves. We know
that we have it in ourselves as Africans to change all this. We
must assert our will to do so; we must say there is no obstacle
(large) enough to stop us bringing about an African renaissance’1
(Herbert & Gruzd, 2017).
Data availability
Underlying data
No data are associated with this article
Grant information
H3ABioNet is supported by the National Institutes of Health
Common Fund [2U24HG006941-06]. H3ABioNet is an ini-
tiative of the Human Health and Heredity in Africa Consortium
(H3Africa) programme of the African Academy of Sciences
(AAS).
The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
1 Mandela N, Statement of the President of the Republic of South Africa,
at the Organization of African Unity (OAU) Meeting of Heads of State and
Government, Tunis, Tunisia, 13 June 1994.
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AAS Open Research 2019, 2:19 Last updated: 04 JUN 2019