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 modalities23. Effective and accessible treatment globally is based on use of blood transfusions, antibiotics, analgesics and hydroxyurea in the context of a comprehensive approach to care45. 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 countries16. 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 women78. 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 interventions249.
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 countries11121314As 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 therapy192021,22. 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 response51923,24. 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 Nigeria192627have 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 stroke2829. 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.