INTRODUCTION
Sickle cell disease (SCD) is a chronic debilitating genetic disorder
with significant global public health implications1.
Progress made so far in understanding of the molecular and
clinico-pathological basis of the disorder has not been matched with
corresponding treatment
modalities2’3. Effective and
accessible treatment globally is based on use of blood transfusions,
antibiotics, analgesics and hydroxyurea in the context of a
comprehensive approach to care4’5.
Bone marrow transplant and gene therapy offer tangible hope of cure but
are very expensive and inaccessible to many patients. Comprehensive care
is reported as largely responsible for the improved quality of life and
survival in people with SCD in resource rich
countries1’6. With improved
diagnosis and management, over 98% of children with SCD in resource
-rich countries survive to adulthood with a life-expectancy of 53 years
for men and 58.5 years for women7’8. On the contrary, SCD remains a
huge economic and psychosocial burden in sub-Saharan Africa (SSA) and
for most families in Nigeria, partly because of absence of accessible
quality health care and public health
interventions2’4’9.
In Nigeria, with an estimated disease prevalence of 2% , a carrier rate
of 21%(NDHS 2019) and a projected global increase in annual delivery of
infants with SCD to 400,00010, the scourge of the
disease will increase if interventions are not put in place. The
benefits and safety of hydroxyurea as a disease-modifying agent in the
treatment of SCD in children and adults, is well documented and is in
common use in resource-rich
countries11’12’13’14As part of a comprehensive care for SCD that incorporates early
detection through neonatal screening, penicillin prophylaxis,
immuno-prophylaxis and caregiver education on health maintenance and
splenic palpation, hydroxyurea has been shown to significantly reduce
acute painful episodes, hospitalization, transfusions, and protect
organs with consequent improvement in quality of life and ultimately,
survival12,15,16 . In 2014, the National Heart, Lung
and Blood Institute recommended offering children hydroxyurea from 9
months of age irrespective of their clinical
symptoms17.
Although Nigeria has the highest global burden of the disease with over
150, 000 SCD deliveries annually and 50-90% dying before their fifth
birthday, as reported for most parts of SSA4,18 many
centers still lack the full complement of a comprehensive care that
includes hydroxyurea
therapy19’20’21,22.
Reasons adduced for paucity of use include inadequate knowledge and
experience on the part of healthcare providers, lack of appropriate
treatment guidelines( including paediatric guidelines), lack of data on
the impact and magnitude of SCD in resource-poor settings, concerns
about response to hydroxyurea in children as influenced by issues of
geography, poverty, health literacy, nutrition, infestations, underlying
host disease and immunological
response5’19’23,24.
There are also concerns about affordability (including multiple
laboratory tests and hospital visits) and sustainability of hydroxyurea
within the weak health system that characterizes most health
institutions in Nigeria19,21,22. These issues raise
questions about adopting results of hydroxyurea use in resource-rich
countries to Nigeria or SSA as a whole.
In 2016, the NOHARM clinical trial in Ugandan children with SCD reported
extensively on the safety and effectiveness of hydroxyurea in
malaria-endemic Uganda even though optimum dosing and monitoring
regimens were not explored25. In 2018, a larger
African-based study on hydroxyurea, involving children with SCD in four
countries in SSA (Angola, Democratic Republic of Congo, Kenya and
Uganda) showed that hydroxyurea treatment was feasible, reasonably safe,
and had both laboratory and clinical benefits23.
Some recent studies about hydroxyurea uptake in
Nigeria19’26’27have demonstrated the clinical effects of hydroxyurea that may be
comparable to that observed in resource-rich countries and other African
countries. Lagunju et al, while working on Nigerian children with SCD
reported the benefits of hydroxyurea in primary and secondary prevention
of
stroke28’29.
Focus of research is consequently on increasing HU uptake.
Adeyemo24 and other Nigerian
researchers5,30,31 have reported extensively on
provider-related barriers to HU use but little is, known about user-
related barriers like feasibility (adherence to drug use, regular
hospital visits, laboratory tests and sustainability of affordable
hydroxyurea). As Nigeria and other SSA countries begin to devote more
resources to the care of patients with SCD, survivors would be on the
increase with a corresponding increase in morbidity making it compelling
that hydroxyurea, an affordable and cost-effective treatment option, be
used to boost their quality of life and survival32
This retrospective review deals with issues of acceptability,
availability, monitoring, safety and efficacy of hydroxyurea that
constitute barriers to HU uptake from the user perspective. The study
seeks to answer the following research questions: Can patients comply
with daily use of hydroxyurea? Is monitoring of therapy and dose
escalation possible? Is 15 mg/kg/day a safe starting dose of hydroxyurea
for children? Does HU produce adverse effects? Will daily use of
hydroxyurea produce clinical and laboratory benefits? Are parents
satisfied with the use of hydroxyurea?
The study may identify modifiable
factors that hamper use of hydroxyurea among paediatric sickle cell
population in Nigeria.