Sickle Cell Anaemia

Sickle cell anaemia is the most common and severe inherited disease in humans. Around 550,000 children are born with the condition every year, with approximately 80% of cases occurring in sub-Saharan Africa. Sickle cell anaemia results in multiple complications that result from acute and chronic organ damage caused by the “sickling” of red blood cells. Complications include severe pain, a vulnerability to infections, and an increased risk of stroke, all of which result in chronic ill health and early death.  

Malaria 

Carriers of the sickle gene are very strongly protected against death from malaria. Sickle cell anaemia is also protective against malaria, but when children do become infected, they are at high risk of severe and sometimes fatal complications that include catastrophic episodes of severe anaemia. Imperial scientists are leading a range of research studies and clinical trials in this area. 

The REACH Trial  

REACH (Realizing Effectiveness Across Continents with Hydroxyurea) is a multicentre clinical trial that is investigating the safety and efficacy of hydroxyurea treatment. Hydroxyurea is a drug taken once daily by mouth that works to reduce the complications of sickle cell anaemia by encouraging the body to produce more fetal haemoglobin, the form of haemoglobin normally made by babies in the womb that stops red blood cells from sickling.  The treatment is being tested in children and young adults at four sites in Africa: Kilifi in Kenya, Mbale in Uganda, Kinshasa in the Democratic Republic of Congo, and Luanda in Angola. REACH has been running for more than 10 years and has already shown that hydroxyurea therapy is both safe and highly effective when used under strictly monitored conditions in Africa.1 It has also shown that higher doses of the drug are more effective than lower doses2 but questions remain about how safe it would be to use it in low resource settings.  

H-PRIME  

The H-PRIME (Hydroxyurea-Pragmatic Reduction in Mortality and Economic burden) trial3 follows on from the REACH trial by investigating the use of hydroxyurea in low resource health facilities that lack specialist staff and sophisticated laboratories. H-PRIME is the largest therapeutic trial ever conducted in patients with SCA and involves 1800 children recruited from four sites in Eastern Uganda. H-PRIME is also investigating how best to prevent malaria and bacterial diseases based on two further randomized interventions. H-PRIME is due to complete in January 2028.  

Malaria parasites and sickle cell 

Through a Wellcome funded discovery award, “Epidemiological and functional dissection of the co-evolution between Plasmodium falciparum parasites and sickle haemoglobin”, Imperial scientists are leading a multidisciplinary team from Kenya, Cambridge, Oxford and Edinburgh to investigate the mechanisms by which the sickle mutation result in protection from clinical malaria. The work started in 2025, and  will continue until 2032. 

 

  1. Tshilolo L, Tomlinson G, Williams TN, et al. Hydroxyurea for Children with Sickle Cell Anemia in Sub-Saharan Africa. N Engl J Med 2019; 380(2): 121–31.
  2. Aygun B, Lane A, Smart LR, et al. Hydroxyurea dose optimisation for children with sickle cell anaemia in sub-Saharan Africa (REACH): extended follow-up of a multicentre, open-label, phase 1/2 trial. The Lancet Haematology 2024; 11(6): e425–e35.
  3. Olupot-Olupot P, Amorut D, Ongodia P, et al. Hydroxyurea - Pragmatic Reduction In Mortality and Economic burden (H-PRIME): A 2x2x2 factorial randomised open-label trial investigating practical approaches to the treatment of sickle cell disease at four sites in Eastern Uganda. Wellcome Open 2025.