Sickle Cell Anaemia (SCA) is one of the most common inherited disorders in the world. The disorder causes complications and substantial morbidity and death in children under five in sub-Saharan Africa. Malaria remains widespread and is a major cause of morbidity and mortality. Children with SCA have higher mortality compared to those without SCA when infected with malaria, making prevention of malaria important.
Standard prevention of malaria among children with SCA is either difficult to administer due to requirements of daily dosing (progruanil), or is no longer effective due to high levels of parasite resistance (sulphadoxine-pyrimethamine (SP)). Evidence suggests that dihydroartemisinin-piperaquine (DP) might be a better alternative than the drugs presently recommended. .
The main objective of this project is to evaluate whether it is safe and more efficacious to give monthly DP compared to monthly SP in preventing malaria among children with SCA in eastern and southern Africa. We will also consider if DP is feasible, acceptable and cost effective.
Children with SCA will be recruited from health centres in Uganda and Malawi and randomized to either DP or SP. We hope that this project will generate evidence to support policy change toward a more effective treatment in preventing malaria in a vulnerable population and thereby reduce morbidity and mortality.
The multidisciplinary team, led by Dr. Idro Richard (Makerere University, Uganda), has an exceptional publication record in this field, and includes senior researchers from University of Malawi, Makerere University (Uganda), Kenya Medical Research Institute and Liverpool School of Tropical Medicine. This is the same team that recently successfully completed a major multi-centre project on the use of DP in the post-discharge chemoprevention of malaria in children discharged from hospital with severe anaemia. The project is hosted at the University of Bergen, with Prof. Bjarne Robberstad as project manager.
The project has undergone ethical approvals in Uganda, Malawi, England and Norway. The Covid-19 situation has caused national lock-downs in Uganda and Malawi with subesequent project delays, but despite this we recruitment of patients is already well underway.
This project is funded by GLOBVAC and is part of the EDCTP2-Program supported by the European Union.
Sickle Cell Anaemia (SCA) is one of the most common inherited disorders in the world: annually, 300,000 children are born with this disorder. Patients suffer repeated ill health and early mortality most often due to severe complications related to hypoxia often precipitated by febrile illnesses. In particular, children with SCA suffer severe complications and much higher mortality if hospitalised with malaria. Thus, in malaria endemic areas, all are prescribed malaria chemoprevention. However, current chemoprevention regimes are either difficult to adhere to or have sub-optimal efficacy. Dihydroartemisinin-piperaquine (DP) is showing promise to become the malaria chemoprevention agent of choice for children and pregnant women. However, DP lack the antimicrobial and antiflammatory Properties of SP, and there is some concern that other sick visits than malaria may increase if SP is replaced.
We propose a multicentre randomised trial to determine the efficacy, safety, cost-effectiveness, and uptake of weekly courses of DP compared to the current standard of care regime in most of eastern and southern Africa, monthly sulphadoxine-pyrimethamine (SP).
Participants will be 552 children 6 months – 15 years with a diagnosis of SCA on haemoglobin electrophoresis, recruited from clinics in Jinja and Soroti Regional Referral hospitals in Uganda and from Queen Elizabeth and Kamuzu Central hospitals in Malawi.
With the minimum incidence rate of clinical malaria in SCA patients receiving monthly SP estimated at 0.2 events per year, and an effect size of 50% if DP is used (i.e. a 50% reduction in the rate if DP is used as in Bigira et al(19)), will give us a hypothesised incidence rate of 0.1 events per person per year in the DP group. At a power of 0.9 and 0.05 level of significance, we will need 438 individuals to be followed up for 18 months. Allowing for 20% losses to follow up, we shall need 548 participants (274 in each group) to be followed for 18 months. With one interim analysis this number will need to be inflated to 552 participants (276 in either arm) followed up for an average of 18 months to answer the primary question
In addition, we will assess the acceptability and uptake of the intervention, the effect on SCA related disease outcomes, the risk of toxicity from cumulative dosing, the development of markers of resistance to DP and Health related quality of life and costs to determine cost-effectiveness.
At the end of the study, we shall have available comprehensive evidence on the efficacy, safety, acceptability and cost-effectiveness of the two regimes and which will guide regional policy and national guidelines for preventing malaria in children with SCA.