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PA-728 Exploring the disposition of select artemisinin combination therapies in the treatment of malaria and malaria parasite kinetics in children with sickle cell disease in Kenya
  1. Godfrey Allan Otieno,
  2. Bernhards Ragama Ogutu
  1. CREATES-Strathmore University, Kenya


Background Children with Sickle Cell Disease (SCD) have decreased spleen function which is responsible for increased susceptibility of SCD patients to malaria and other infections. There is evidence that hemoglobinopathies such as SCD may influence the activity of artemisinin derivatives by altering their accumulation and binding to target molecules within the parasitized erythrocyte. If hemoglobinopathies alter the efficacy of Artemisinin-based Combination Therapies (ACTs) through an attenuated effect of the artemisinin component, further research into dose optimization would be justified. Currently there is no data on the disposition of ACTs and malaria parasite kinetics in children with sickle cell disease in Kenya.

Methods A proposed five-arm open-label, prospective, randomized, clinical trial will be conducted at the KEMRI Kondele Children Hospital in Kisumu, Kenya. Children less than 18 years with SCD and co-infected with P. falciparum will be enrolled based on the set inclusion and exclusion criteria with up to 20 participants in each of the of the five (5) arms. The aim is to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), Dihydroartemisinin-piperaquine(DHA-PPQ), artesunate-mefloquine and artesunate-pyronaridine (AP) fixed-dose combinations in children with uncomplicated falciparum malaria and sickle cell disease. Samples for PK/PD analysis and malaria will be taken at specified time points. Mathematical modelling based on the following set criteria will be conducted: phenotype- percentage of haemoglobin F, makers of splenic dysfunction, previous exposure to prophylactic antimalaria drug- chlorproguanil and malaria parasite kinetics.

Results The results of this proposed study will bridge the gap of knowledge on the disposition of ACTs in children with SCD as well as help in formulating new or review current treatment for malaria in children with SCD.

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