Pharmacokinetics of Ganaplacide and Lumefantrine in Adults, Adolescents, and Children with Plasmodium falciparum Malaria Treated with Ganaplacide Plus Lumefantrine Solid Dispersion Formulation: Analysis of Data from a Multinational Phase 2 Study. The novel antimalarial ganaplacide combined with lumefantrine solid dispersion formulation (LUM-SDF) was effective and well tolerated in the treatment of ganaplacide 200 mg plus LUM-SDF 960 mg assessed potential pharmacokinetic (PK) interactions between ganaplacide and lumefantrine; in Part A, adult/adolescent patients received one of the six ganaplacide-LUM-SDF regimens or artemether-lumefantrine; and in Part B, three dose regimens identified in Part A, and artemether-lumefantrine, were assessed in children aged 2 to <12 years, with body weight ≥10 kg
Day 3 parasitemia and Plasmodium falciparum Kelch 13 mutations among uncomplicated malaria patients treated with artemether-lumefantrine in Adjumani district, Uganda. Artemisinin resistance threatens malaria control and elimination efforts globally. Recent studies have reported the emergence of Plasmodium falciparum parasites tolerant to artemisinin agents in sub-Saharan Africa, including Uganda . The current study assessed the day 3 parasite clearance and its correlation with P. falciparum K13 propeller gene (pfkelch13) mutations in P. falciparum parasites isolated from patients with uncomplicated malaria under artemether-lumefantrine (AL) treatment. This study enrolled 100 P. falciparum-positive patients to whom AL was prescribed between 09/September/2022 and 06/November/2022. Blood samples were
Increased sensitivity of malaria parasites to common antimalaria drugs after the introduction of artemether-lumefantrine: Implication of policy change and implementation of more effective drugs in fight against malaria. Single nucleotide polymorphisms (SNPs) in the Plasmodium falciparum multi-drug resistance protein 1 (Pfmrp1) gene have previously been reported to confer resistance to Artemisinin -based Combination Therapies (ACTs) in Southeast Asia. A total of 300 samples collected from six sites between 2008 and 2019 under an ongoing malaria drug sensitivity patterns in Kenya study were evaluated for the presence of SNPs at Pfmrp1 gene codons: H191Y, S437A, I876V, and F1390I using the Agena MassARRAY® platform. Each isolate was further tested against artemisinin (ART), lumefantrine (LU
Recurrent Plasmodium falciparum Malaria in U.S. Travelers Treated with Artemether-Lumefantrine. We report two cases of recurrent malaria in U.S. travelers returning from Africa (Ghana and Central African Republic) despite a full course of artemether-lumefantrine (AL). Both patients presented to New York City hospitals, received AL treatment, and clinically improved. Within 2 weeks, they presented
Artemether-lumefantrine-amodiaquine or artesunate-amodiaquine combined with single low-dose primaquine to reduce Plasmodium falciparum malaria transmission in Ouélessébougou, Mali: a five-arm, phase 2, single-blind, randomised controlled trial. Triple artemisinin-based combination therapies (TACTs) can delay the spread of antimalarial drug resistance. Artesunate-amodiaquine is widely used for uncomplicated Plasmodium falciparum malaria. We therefore aimed to determine the safety and efficacy of artemether-lumefantrine-amodiaquine and artesunate-amodiaquine with and without single low-dose primaquine for reducing gametocyte carriage and transmission to mosquitoes. We did a five-arm, single-blind, phase 2 randomised controlled trial at the Ouélessébougou Clinical Research Unit of the Malaria
Increasing day three parasitaemia is observed after treatment of patients with artemether-lumefantrine and single dose of primaquine for uncomplicated Plasmodium falciparum malaria in Arbaminch Zuria district, Southwest Ethiopia. Since 2017, the first-line treatment for uncomplicated Plasmodium falciparum infection in Ethiopia has been artemether-lumefantrine (AL), plus a single dose
Therapeutic efficacy of artemether-lumefantrine in North-Eastern states of India and prevalence of drug resistance-associated molecular markers. Plasmodium falciparum is the main cause of malaria in North-Eastern (NE) states of India. Artemether-lumefantrine (AL) was introduced as first-line therapy against uncomplicated P. falciparum cases in 2013 after the emergence of resistance
Artemether-Lumefantrine treatment selects Plasmodium falciparum multidrug resistance 1 (pfmdr1) increased copy number among African malaria infections. Decreased efficacy of artemether-lumefantrine, the globally most used antimalarial, has recently emerged in Africa. An efficacy trial based on directly observed artemether-lumefantrine therapy at Bengo, Northern Angola. 100 Plasmodium falciparum uncomplicated malaria patients (2-10 year-old) were enrolled, hospitalized for the treatment period, and followed up for 42 days. PCR correction was performed with pfmsp1/2 + glurp, with analysis considering 2 or 3 coincident markers. Infections were tested by qPCR for pfmdr1 copy number (pfmdr1xN), a potential Plasmodium falciparum marker of lumefantrine resistance previously identified in the region
Extended Treatment Duration of Artemether-Lumefantrine in Ugandan Children with HIV on Efavirenz-Based Antiretroviral Therapy: A Randomized Controlled Pharmacokinetic and Pharmacodynamic Trial. Malaria and HIV co-infection are prevalent in sub-Saharan Africa causing significant drug interactions with co-treatment. We previously reported a 30%-70% reduction in exposure to the standard 3-day (6 -dose) artemether-lumefantrine (AL) treatment for malaria when given with efavirenz-based HIV therapy, impacting malaria reinfection risk. We conducted a prospective, randomized study comparing the 3-day regimen to an extended 5-day (10-dose) regimen with pharmacokinetic sampling for artemether, dihydroartemisinin, lumefantrine, and desbutyl-lumefantrine (DBL) over 42 days. The primary outcome
Comparison of lumefantrine, mefloquine, and piperaquine concentrations between capillary plasma and venous plasma samples in pregnant women with uncomplicated falciparum and vivax malaria. Capillary samples offer practical benefits compared with venous samples for the measurement of drug concentrations, but the relationship between the two measures varies between different drugs. We measured the concentrations of lumefantrine, mefloquine, piperaquine in 270 pairs of venous plasma and concurrent capillary plasma samples collected from 270 pregnant women with uncomplicated falciparum or vivax malaria. The median and range of venous plasma concentrations included in this study were 447.5 ng/mL (8.81-3,370) for lumefantrine (day 7, = 76, median total dose received 96.0 mg/kg), 17.9 ng/mL (1.72-181
Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in mainland Tanzania, 2019. Artemisinin-based combination therapy (ACT) has been a major contributor to the substantial reductions in global malaria morbidity and mortality over the last decade. In Tanzania, artemether-lumefantrine (AL) was introduced as the first-line treatment for uncomplicated
Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in mainland Tanzania, 2018. The use of artemisinin-based combination therapy (ACT) is recommended by the World Health Organization for the treatment of uncomplicated falciparum malaria. Artemether-lumefantrine (AL) is the most widely adopted first-line ACT for uncomplicated malaria in sub-Saharan
Effectiveness of artemether-lumefantrine for treating uncomplicated malaria in low- and high-transmission areas of Ghana. Artemisinin-based combination therapy (ACT) has been effective in the supervised treatment of uncomplicated malaria in Ghana. Since ACT usage is primarily unsupervised, this study aimed to determine the effectiveness of artemether-lumefantrine (AL) for treating malaria
Trends of Plasmodium falciparum molecular markers associated with resistance to artemisinins and reduced susceptibility to lumefantrine in Mainland Tanzania from 2016 to 2021. Therapeutic efficacy studies (TESs) and detection of molecular markers of drug resistance are recommended by the World Health Organization (WHO) to monitor the efficacy of artemisinin-based combination therapy (ACT ). This study assessed the trends of molecular markers of artemisinin resistance and/or reduced susceptibility to lumefantrine using samples collected in TES conducted in Mainland Tanzania from 2016 to 2021. A total of 2,015 samples were collected during TES of artemether-lumefantrine at eight sentinel sites (in Kigoma, Mbeya, Morogoro, Mtwara, Mwanza, Pwani, Tabora, and Tanga regions) between 2016 and 2021
Artemether-lumefantrine with or without single-dose primaquine and sulfadoxine-pyrimethamine plus amodiaquine with or without single-dose tafenoquine to reduce Plasmodium falciparum transmission: a phase 2, single-blind, randomised clinical trial in Ouel Artemether-lumefantrine is widely used for uncomplicated Plasmodium falciparum malaria; sulfadoxine-pyrimethamine plus amodiaquine is used for seasonal malaria chemoprevention. We aimed to determine the efficacy of artemether-lumefantrine with and without primaquine and sulfadoxine-pyrimethamine plus amodiaquine with and without tafenoquine for reducing gametocyte carriage and transmission to mosquitoes. In this phase 2, single-blind, randomised clinical trial conducted in Ouelessebougou, Mali, asymptomatic individuals aged 10-50 years with P
Efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine and prevalence of molecular markers of anti-malarial drug resistance in children in Togo in 2021. Artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) are the currently recommended first- and second-line therapies for uncomplicated Plasmodium falciparum infections in Togo. This study assessed the efficacy
In vitro evaluation of ganaplacide/lumefantrine combination against Plasmodium falciparum in a context of artemisinin resistance. Ganaplacide, also known as KAF156, is among the new antimalarial drug candidates that have successfully reached Phase III clinical trials, and is proposed in combination with lumefantrine. This combination could replace the current front-line artemisinin-based to evaluate the risk of cross-resistance between artemisinins and KAF156 alone, and in combination with lumefantrine, using a panel of artemisinin-resistant strains carrying different pfk13 mutations and markers of other antiplasmodial drug resistances; secondly to explore in vitro the relevance of combining KAF156 and lumefantrine with artemisinins, based on the model of triple ACTs. Our results
Efficacy and safety of artemether-lumefantrine against uncomplicated falciparum malaria infection in Tanzania, 2022, a single arm clinical trial. Artemether-lumefantrine (AL) is the first line anti-malarial drug for the treatment of uncomplicated malaria in Tanzania. The World Health Organization (WHO) recommends regular efficacy monitoring of anti-malarial drugs to inform case management policy -lumefantrine remains highly efficacious in three regions of Tanzania but the PCR-corrected efficacy in Pwani fell below the WHO-defined 90% threshold at which policy change is recommended. Implementing strategies to diversify ACTs to ensure effective case management in Tanzania is critical.
Therapeutic efficacy and safety of artemether-lumefantrine combination therapy for the treatment of uncomplicated Plasmodium falciparum malaria at Teda Health Centre, Northwest Ethiopia, 2022/23. The emergence of Plasmodium falciparum drug resistance against artemisinin-based combination therapy has threatened malaria control efforts. Since malaria control and elimination plans are dependent on these drugs, they must remain efficacious. However, resistance to these drugs was detected in low-transmission settings and is predicted to emerge in high-transmission settings, including in unspecified areas of Ethiopia. Therefore, this study aimed to assess the therapeutic efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated P. falciparum malaria. A single-arm prospective
Assessing the therapeutic efficacy of artemether-lumefantrine for uncomplicated malaria in Lagos, Nigeria: a comprehensive study on treatment response and resistance markers. The burden of malaria persists in sub-Saharan Africa and the emergence of artemisinin resistance has introduced complexity to control efforts. Monitoring the efficacy of artemisinin-based treatment for malaria is crucial to address this challenge. This study assessed treatment efficacy of artemether-lumefantrine (AL) and genetic diversity of Plasmodium falciparum isolates in a Nigerian population. Participants presenting with clinical symptoms of uncomplicated malaria at a health centre in Lagos, Nigeria, were screened for P. falciparum. Enrolled participants were treated with AL and monitored through scheduled check-up