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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 30, No 6, November/December 2019
AFRICA
313
The challenges of improving benzathine penicillin usage
for prevention of rheumatic fever in Africa
Ana Olga Mocumbi
Rheumatic heart disease (RHD) is arguably the most preventable
of all cardiovascular diseases, but remains an important global
health challenge. While acute rheumatic fever (ARF) frequently
causes death, chronic rheumatic heart disease is an important
cause of chronic heart failure
1
and associated premature
mortality in low- and middle-income countries (LMIC).
2
The World Health Organisation (WHO) recommends
administration of benzathine penicillin G (BPG) every two
to four weeks to prevent recurrent episodes of ARF and/or
progression to RHD. The regimens may vary according to the
severity of the first ARF attack, the presence of carditis, and
the estimated risk of recurrence depending on age and socio-
economic environment. It is accepted that for patients who have
had ARF, there is a need for long-term prophylaxis but the
duration of the prevention takes into account the occurrence of
ARF and the severity of the cardiac lesions. It is established that
optimal delivery of regular BPG injections is vital to preventing
disease morbidity and cardiac sequelae in affected paediatric and
young adult populations, and even low adherence rates reduce
the recurrence of ARF and the risk of all-cause mortality.
3
BPG administration has been a challenge in Africa. In
their article on page 369, Ali
et al
.
4
describe BPG availability
and administration for the prevention of rheumatic fever
(RF), as assessed through an online survey targeting 30 health
workers from 14 countries on the continent. The study reports
concerning levels of unavailability of BPG, lack of guidelines
for administration, excessive use of skin testing, unavailability
of emergency kits to respond to anaphylactic reactions, and
health practitioners not being confident to manage BPG allergy.
The authors conclude that shortage of BPG supply is a concern
that needs to be urgently addressed by governments, and that
clinicians must be trained to use BPG and to deal with its major
adverse events.
Despite the obvious limitations of the study methodology, this
work from the Working Group on Penicillin from the Taskforce
on Rheumatic Heart Disease of the Pan-African Society of
Cardiology helps us to understand the barriers and practices
regarding usage of BPG in Africa, where RHD is endemic.
Among the barriers for implementation of RF/RHD prevention
programmes in this region, erratic penicillin supply, deficient
service delivery, resistance from health workers to administer
injectable BPG, low access to health facilities, and individual
issues related to cost and loss of working time are the most
commonly discussed. Pain caused by intramuscular injection
of BPG contributes to low adherence. With the dissemination
of echocardiography for screening, large cohorts of young
people with confirmed asymptomatic disease have increased the
number of people who need BPG. Therefore, adequate supply
of high-quality BPG at an affordable cost and skilled health
professionals to administer it are needed.
Unfortunately, the BPGmarket worldwide has been hampered
by insufficient stocks of penicillin, with a dramatic reduction of
producers worldwide in the last decades. A study carried out
by Health Reproductive Programme, the Special Programme
of Research, Development and Research Training in Human
Reproduction in the WHO’s Department of Reproductive
Health and Research and the Clinton Health Access Initiative
(CHAI) used a combination of data-collection methods to
obtain data on BPG availability globally. The motivation for this
study was BPG use to prevent mother-to-child transmission of
syphilis.
Of the 114 countries approached, 95 had valuable information;
of these, 39 (41%) reported a BPG shortage and 10 indicated the
use of alternative treatments, including ceftriaxone, amoxicillin
and erythromycin.
5
Because it is an off-patent medication, BPG
is currently sold at a very low price, estimated at US$0.11 for
a 1.2-million international unit (IU) dose and US$0.20 for a
2.4-million IU dose in LMICs. This is in clear contrast to the
significant financial investment in specialised manufacturing
infrastructure that is needed to manufacture injectable BPG,
therefore reducing the enthusiasm for commercial manufacturers
to enter or even continue in the BPG market. Moreover, none of
the three current active pharmaceutical ingredient manufacturers
of BPG has market authorisation from a global regulatory
authority, and two have experienced quality issues in the past
few years, further disrupting supply. In addition, issues such
as underestimating need, inflexible purchasing cycles, lack of
funding, and limited BPG product registrations contribute to
low availability of BPG.
5
Poor uptake of secondary prophylaxis for RF/RHD remains a
problem globally, related to patient demographics, clinical, socio-
cultural and healthcare service-delivery factors. New knowledge
is needed to support the necessary changes within the health
systems and delivery platforms. In northern Australia a stepped-
wedge, randomised trial of five pairs of indigenous community
clinics provided a multicomponent intervention to support
activities to improve penicillin delivery, aligned with a chronic-
care model and continuous quality-improvement feedback on
adherence.
6
Over 30 to 39 months of implementation, there
was a modest improvement in adherence among high-adhering
Instituto Nacional de Saúde; Vila de Marracuene, Estrada
Nacional No 1, Parcela No 3943, Provincia de Maputo,
Mozambique
Ana Olga Mocumbi, MD, PhD,
amocumbi@gmail.comEditorials