Expanding resistance to multiple antimalarials, including chloroquine, in South-East Asia (SEA) urges the development of new therapies. AQ-13, a chloroquine derivative, is a new drug candidate for treating malaria caused by Plasmodium falciparum.
Amodiaquine is a 4-aminoquinoline antimalarial similar to chloroquine that is used extensively for the treatment and prevention of malaria. Data on the cardiovascular effects of amodiaquine are scarce, although transient effects on cardiac electrophysiology (electrocardiographic QT interval prolongation and sinus bradycardia) have been observed. We conducted an individual patient data meta-analysis to characterise the cardiovascular effects of amodiaquine and thereby support development of risk minimisation measures to improve the safety of this important antimalarial.
Atovaquone-proguanil (ATV-PG) plus amodiaquine (AQ) has been considered as a potential replacement for sulfadoxine-pyrimethamine plus AQ for seasonal malaria chemoprevention (SMC) in African children. This randomized, double-blind, placebo-controlled, parallel group study assessed the safety, tolerability, and pharmacokinetics (PK) of ATV-PG plus AQ in healthy adult males and females of Black sub-Saharan African origin.
Artesunate-amodiaquine is a potential therapy for uncomplicated malaria in Cambodia.
In sub-Saharan Africa, artemisinin-containing therapies for malaria treatment are regularly co-administered with ART. Currently, dolutegravir-based regimens are recommended as first-line therapy for HIV across most of Africa.
Accurate measurement of anti-malarial drug concentrations in therapeutic efficacy studies is essential to distinguish between inadequate drug exposure and anti-malarial drug resistance, and to inform optimal anti-malarial dosing in key target population groups.
Previous controlled studies demonstrated seasonal malaria chemoprevention (SMC) reduces malaria morbidity by >80% in children aged 3-59 months. Here, we assessed malaria morbidity after large-scale SMC implementation during a pilot campaign in the health district of Koutiala, Mali.
Artemisinin-based combination therapies (ACTs) are first-line treatments for uncomplicated Plasmodium falciparum malaria. ACT resistance is spreading in Asia but not yet in Africa. Reduced effects of ACT partner drugs have been reported but with little information regarding widely used artesunate/amodiaquine (ASAQ).
Artemisinin-based combination therapy (ACT) partner drugs, currently used in Ghana are lumefantrine, amodiaquine and piperaquine. Plasmodium falciparum isolates with reduced susceptibility to these partner drugs may affect treatment outcome. Mutations in pfmdr1 gene is linked to reduced parasite susceptibility to amodiaquine and lumefantrine. In addition, the potency of the partner drugs in vivo depends on the metabolism by the cytochrome P450 (CYP) enzyme in the host. Mutations in the CYP2C8 and CYP3A4 genes are linked to reduced metabolism of amodiaquine and lumefantrine in vitro, respectively. This study investigated the host and parasite genetic factors affecting the susceptibility of the malaria parasite to ACT partner drugs.
Poor adherence to seasonal malaria chemoprevention (SMC) might affect the protective effectiveness of SMC. Here, we evaluated the population pharmacokinetic properties of amodiaquine and its active metabolite, desethylamodiaquine, in children receiving SMC under directly observed ideal conditions (n = 136), and the adherence of SMC at an implementation phase in children participating in a case‐control study to evaluate SMC effectiveness (n = 869).