Treatment of Plasmodium falciparum malaria in the Democratic Republic of the Congo

Thesis

Despite international efforts, the malaria burden remains high worldwide with half of all malaria-attributable deaths occurring in the Democratic Republic of Congo and Nigeria. Children under five and pregnant women bear the heaviest burden. New treatment options for falciparum malaria are urgently needed due to potential wide spreading plasmodium resistance to artemisinin derivatives.

In the first study, amodiaquine-artesunate, artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PQ) were assessed in 684 Congolese children under 5. The efficacy was good and comparable for all combinations. The short parasitaemia clearance half-life suggested that the local parasite populations are still susceptible to the artemisinin derivatives. DHA-PQ provided the greatest prophylactic effect making it a good candidate for Intermittent Preventive Treatment in pregnancy. Plasma level of piperaquine and lumefantrine in small children at day 7 was however suboptimal indicating the necessity of adjusting the current dosage.

Artemether-lumefantrine is the most recommended ACT for malaria treatment in pregnancy although its pharmacokinetics properties are altered in this group. In the second study, the PK, efficacy, safety and tolerability of a 5 days regimen of AL were tested in a group of 48 pregnant women and a control group of 48 non-pregnant women with uncomplicated falciparum malaria versus the standard 3 day regimen. The day 42 PCR corrected efficacy was 100% in both treatment arms. Pregnancy was associated with reduced exposure to both lumefantrine and dihydroartemisinin. The extended regimen improved the exposure to lumefantrine, artemether and DHA in pregnancy. The QTc duration remained normal, but transient hematological or biochemical changes were observed in both groups. Babies born from the women treated in the study displayed a normal physical and neurological development in the first 12 months of life. At delivery 38% of women had placental malaria. The extended AL regimen is a promising option for those areas with emerging artemisinin resistance.

Authors: Onyamboko, M

• DOI: 10.5287/ora-rjgm6dpde
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford