Cardiovascular Journal of Africa: Vol 30 No 6 (November/December 2019)

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 30, No 6, November/December 2019 314 AFRICA
patients and a decrease in the proportion of days at risk in the
whole cohort in the maintenance phase. ARF recurrence rates
however did not differ between study sites during the intensive
phase and the whole jurisdiction, showing that the strategy did
not improve adherence to RHD secondary prophylaxis within
the study time frame.6
Within the health services, fear of major adverse events related
to the drug, including severe anaphylactic reactions also needs to
addressed. In Zambia, concern by health workers about allergic
events following the administration of BPG was addressed
through an educational and access-to-medicine programme,
resulting in increased usage of the drug.7 Understanding the
determinants and mechanisms of non-allergic deaths will also
help to overcome this fear.
Recently,Marantelli and colleagues8 assessed adverse reactions
to BPG by circulating a questionnaire through professional
networks, soliciting retrospective reports of adverse events
from treating physicians, and using the Brighton Collaboration
case definition to identity potential anaphylaxis. Ten cases with
clinical or echocardiogram-obtained evidence of valvular disease
were reported from various locations, with patients ranging from
early teens to adults; 80% had received BPG prior to the event
with no previous adverse reaction. In eight cases, the reaction
was fatal, but only three cases met criteria consistent with
anaphylaxis. The authors suggest that major allergic reactions
are not the main cause of adverse reactions to BPG. Moreover,
they proposed sudden death in people with severe RHD as
an alternative mechanism, opening up the possibility of risk
stratification of patients to help in identifying those who may not
be suitable for injectable BPG.
While primary and secondary prophylaxis significantly
improves outcomes and is recognised to be the standard of care,
with intra-muscular BPG being recommended as the preferred
agent by many technical experts, progress in tools to describe
BPG pharmacokinetics has been slow and inconvenient in the
context of endemic regions, considering the need for repeated
venous blood collection, the young age of the patients, the high
prevalence of anaemia in the endemic communities, and the
scarcity of laboratories with capacity for blood preservation
and testing of BPG blood levels. The recent development and
validation of point-of-care dried blood spot (DBS) assays would
facilitate pharmacokinetic studies in situations where frequent
venous blood sampling is logistically difficult or clinically
unacceptable. Interestingly, the limit of quantification for
penicillin G in DBS, using samples from adult patients receiving
penicillin as part of an infection-management plan was 0.005
mg/l, and plasma and DBS penicillin G concentrations for
patients receiving BPG and penicillin G given via bolus doses
correlated well and had comparable time–concentration profiles.9
These results open new possibilities for research into novel
formulations and delivery systems for BPG.
Owing to the early disease onset in Africa, the current
prophylactic treatment should last for 15 to 25 years, representing
a high burden to the patient, the family and the health system.
Biodegradable polymer matrices have been investigated, trying
to reduce the frequency of BPG administration to improve
adherence. The results show that some are not suitable for
development of sustained-release BPG treatments, while others
provide favourable release behaviour, but the total size of the
implant still presents a hurdle. Taking into account the mass
of polymer tested and the total dose of drug calculated from
the literature on pharmacokinetic parameters for penicillin G,
an implant size of over 7 g would still be required, precluding
clinical deployment of polymer matrix-type delivery system for
this indication in children and adolescents.10
In conclusion, research using modern tools is needed to
address the unmet needs for RF prophylaxis. While awaiting
new advances in all components of the complex issue of using
BPG for RHD prevention, health system strengthening and
innovative strategies to improve delivery platforms for secondary
prophylaxis are needed to reach and retain those in need in
Africa.
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