DIAGNOSIS AND TREATMENT BY HYDROXYUREA OF CHILDREN WITH SICKLE CELL ANEMIA IN THE DEMOCRATIC REPUBLIC OF CONGO.

Sickle cell anemia (SCA) is the most common severe genetic disorder worldwide and is considered by the World Health Organization as the 4th public health priority after AIDS, malaria, and tuberculosis. This autosomal recessive disorder constitutes a genuine public health concern in Africa, especially in the Democratic Republic of Congo (DRC) where the incidence at birth of homozygotes is around 2% and leads to severe morbidity and early mortality, especially in children below the age of five years. However, due to several factors, accurate diagnosis remains a major issue in DRC, especially in a rural area, where the diagnosis relies currently on different techniques, such as the sickling test (Emmel test), and in the most well-equipped hospitals, hemoglobin electrophoresis (HE) and hemoglobin IsoElectrofocusing (IEF). Besides reaching an early and correct diagnosis, effective drug treatment with Hydroxyurea (HU) also remains challenging. This PhD aimed to improve the diagnosis and treatment of sickle cell anemia in DRC, especially in children living in a rural area. Specifically, this PhD envisioned determining the value of DNA-based tests for the diagnosis of SCA in children in a rural area, to assess the clinical and biological profile of childhood SCA and evaluate the use of Hydroxyurea treating these children. The introduction of this thesis, gave an overview of the definition of SCA, the epidemiology in DRC, the physiopathology of the disease, the clinical features, and the disease severity, the biological features, the diagnosis of the disease and prevention and treatment. This chapter highlights the challenges for the diagnosis and treatment occurring in a rural area in Central Africa and offers eventual solutions to overcome all these challenges. The objectives of the research which aimed mainly to improve the diagnosis of SCA and treatment with Hydroxyurea in Children in a rural area of Central Africa. This thesis includes studies we performed which are presented in 3 chapters. In chapter 1, we determined the value of DNA-based testing for diagnosing SCA in children in a rural area. This study revealed a high rate of wrongly diagnosed SCA patients in a rural environment in Central Africa. Therefore, it underscored the importance of a DNA-based test in addition to hemoglobin electrophoresis to clarify the diagnosis of SCA in some cases. In chapter 2 we determined the clinical and biological profile of SCA children living in a rural area of Central Africa. This section showed the variability of disease severity, which depends on factors such as age, gender and the baseline level of HbF. Moreover, it confirmed that fetal hemoglobin is the main modulator of disease severity. In chapter 3, we describe a clinical trial with HU. This study confirmed that the HU is actually an effective drug treatment for SCA and demonstrated the possibility of its use in a rural setting of Central Africa despite a high proportion of drop-outs. This PhD revealed the value of DNA-based tests of diagnosing SCA in low-income countries, especially in rural areas of DRC. In addition, we have shown the possibility to use an effective drug treatment in SCA children living in a rural area of DRC without noticeable side effects. We emphasize the need to conduct awareness campaigns to raise the knowledge on SCA in the population, in order to improve early diagnosis and increase compliance to HU treatment.

Jaar van publicatie:2023

Toegankelijkheid:Open