Coarsucam (artesunate/amodiaquine) / Sanofi, DNDi - LARVOL DELTA

Polymeric microarray patches for transdermal delivery of amodiaquine and artesunate: A novel strategy against Plasmodium falciparum. (PubMed, Mater Today Bio) - "In a Plasmodium berghei-infected murine model, the combined MAP treatment reduced parasitaemia by 99.5 % within seven days, showing comparable efficacy to oral administration. These findings demonstrate that dissolving MAPs offer a minimally invasive, needle-free strategy for ACT delivery, with potential to enhance treatment adherence, reduce gastrointestinal side effects, and combat drug resistance, particularly in resource-limited malaria-endemic settings."

Journal • Infectious Disease • Malaria

Comparative effects of antimalarial drugs on oxidative phosphorylation, mitochondrial dynamics and mitophagy in Plasmodium berghei-infected mice. (PubMed, Toxicol Rep) - "Thirty-five Swiss-mice (18 ± 3 g) were infected intraperitoneally with chloroquine resistant (ANKA) strain of Plasmodium berghei and treated orally and once daily with (10 mg/kg) dose of Amodiaquine artesunate (AA), Artemether-Lemefantrine (AL), Sulfadoxine- pyrimethamine (SP) and Artesunate (ART), On day 6, animals were sacrificed and livers were removed. Significant down-regulation in the expressions of PINK 1 by SP, FUNDC1 by AA and AL, DNM1L by ART, PGC-1α by AA, AL, and ART, and prohibitins 1 and 2 by AA and AL similar to the infected control were observed. This study showed that host mitochondria respond differently to antimalarial drugs."

Journal • Preclinical • Infectious Disease • MFN2

Efficacy and safety of artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum in Eritrea in 2022 (ANZCTR) - P4 | N=352 | Completed | Sponsor: Ministry of Health

New P4 trial • Infectious Disease • Malaria

Spatio-temporal trends of artemisinin-based combination therapy efficacy from 2010 to 2024 in sub-Saharan Africa: a systematic review and meta-analysis. (PubMed, BMC Infect Dis) - "While AS-AQ, DHA-PPQ, and AS-PY have maintained high efficacy over time in sub-Saharan Africa, there is a concern about the declining efficacy of AL in some West and East African countries. Our findings suggest that AS-PY could be a promising candidate for inclusion in first-line malaria treatments to address the declining efficacy of AL. Continuous monitoring of ACT efficacy, innovative and efficient control strategies are crucial to prevent the spread of antimalarial drug resistance."

Journal • Retrospective data • Review • Infectious Disease • Malaria

FD-TACT: A Study to Find Out if a Combination of 3 Medicines for the Treatment of Malaria Works as Well and is as Safe and Tolerable as Combinations of 2 Medicines (clinicaltrials.gov) - P3 | N=1680 | Recruiting | Sponsor: University of Oxford | Not yet recruiting ➔ Recruiting | Trial completion date: May 2025 ➔ Jul 2026 | Trial primary completion date: Nov 2024 ➔ Jul 2026

Enrollment open • Head-to-Head • Trial completion date • Trial primary completion date • Infectious Disease • Malaria

Effect of malaria chemoprevention for school-age children across transmission archetypes: a modelling study. (PubMed, Lancet Glob Health) - "Our model suggests that adding IPT of school-age children to current control tools could decrease malaria burden in this group and reduce P falciparum transmission."

Journal • Hematological Disorders • Infectious Disease • Malaria • FPR2

Efficacy and Safety of Artesunate + Amodiaquine and Artemether + Lumefantrine for the Treatment of Uncomplicated Plasmodium falciparum Malaria in Madagascar, 2020. (PubMed, Am J Trop Med Hyg) - "Of 727 samples successfully analyzed for pfK13, no mutation associated with artemisinin resistance was observed. The study results reveal that ASAQ and AL remain safe and efficacious for treating uncomplicated P. falciparum malaria in Madagascar."

Journal • Infectious Disease • Malaria • Pain

OPTIMAH: OPTImizing Malaria And HIV Treatment in a Shifting Landscape in Africa (clinicaltrials.gov) - P4 | N=380 | Not yet recruiting | Sponsor: Yale University | Trial completion date: Sep 2027 ➔ Dec 2027 | Initiation date: Sep 2025 ➔ Dec 2025 | Trial primary completion date: Sep 2027 ➔ Dec 2027

Trial completion date • Trial initiation date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • Malaria

Evidence from Genomic Surveillance Shows Imported Drug-Resistant Strains Threatening Malaria Elimination in São Tomé and Príncipe (ASTMH 2025) - "To evaluate if antimalarial drug resistance undermines eradication efforts in STP, we analyzed temporal trends (2010-2016) of resistance mutations in Plasmodium falciparum parasites to sulfadoxine-pyrimethamine (SP), artesunate-amodiaquine (AS-AQ), and artesunate-lumefantrine (AL). However, declining AL sensitivity, despite limited local use, combined with genetic similarity of STP parasite samples to those from Central and West Africa, strongly suggests imported resistant parasite strains. These findings underscore the critical need for robust traveler monitoring and surveillance to prevent the introduction and dissemination of drug-resistant malaria, protecting and sustaining elimination efforts."

Late-breaking abstract • Infectious Disease • Malaria

Therapeutic Efficacy of Artemether-Lumefantrine combination in the treatment of uncomplicated malaria in ten sentinel sites across Ghana (ASTMH 2025) - "In 2008, Artemether-Lumefantrine (AL) combination was added to Amodiaquine-Artesunate (ASAQ) combination as a second first-line artemisinin-based combination therapy (ACT) for uncomplicated malaria in Ghana. None of the patients enrolled was parasitemic on Day-3. We conclude that AL remains efficacious in the treatment of uncomplicated malaria in Ghana."

Clinical • Late-breaking abstract • Infectious Disease • Malaria

The Role of Plasmodium falciparum Gametocytogenesis in the Spread of Resistance to Artemisinin-Based Combination Therapies (ASTMH 2025) - "In response, several countries replace current artemisinin combination therapies (ACTs), often artemether-lumefantrine (AL), with triple ACTs, or introduce alternative treatments, to sustain drug efficacy. A late-stage gametocytocidal effect contains the spread of resistance only if it is sustained beyond the clearance of asexual parasites. These findings challenge current attempts to introduce artesunate-amodiaquine (ASAQ) or dihydroartemisinin-piperaquine (DHAPPQ) as alternatives to AL, unless combined with 8-aminiquinolines, which target both early- and late-stage gametocytes, since these treatments are associated with higher gametocytemia."

Combination therapy • Infectious Disease • Malaria

Emerging signals of artemisinin partial resistance in Equatorial Guinea: Analysis of parasite clearance rates and molecular markers from therapeutic efficacy studies (ASTMH 2025) - "Standard WHO TES protocols were followed with 28-day monitoring, evaluating both Artemether+Lumefantrine and Artesunate+Amodiaquine treatments. While overall efficacy of ACTs remains acceptable, these early warning signs necessitate enhanced surveillance, improved treatment adherence monitoring, and consideration of resistance containment strategies. We will present comprehensive clearance rate analyses and discuss implications for national treatment policy in the context of regional artemisinin partial resistance concerns."

Biomarker • Clinical • Infectious Disease • Malaria

Polyparasitism among school aged children living near source and irrigated rice fields in Ankililoaka in the subarid south-western part of Madagascar in 2023 (ASTMH 2025) - "All STH infections were treated with albendazole 500 mg. All malaria cases were treated with artesunate + amodiaquine...Given the increasing rainfall following the cyclones in early 2025, we believe that an integrated intervention is needed. Malaria chemoprevention using ACTs and repeated mass drug administration of praziquantel and mebendazole expanded to the adults (not limited to children) would be the better strategy to fight these parasitic diseases in the area."

Clinical • Anemia • Hematological Disorders • Infectious Disease • Malaria

Finally - evidence-based regimens for single, low dose primaquine for transmission blocking. How did we do it? (ASTMH 2025) - "The ACTs were dihydroartemisinin piperaquine, artesunate pyronaridine, artesunate amodiaquine (ASAQ), artesunate mefloquine, artemether lumefantrine (AL), and the triple ALAQ. These regimens offer flexibility for malaria control programmes and guidance for drug manufacturers wishing to coblister SLDPQ with ACTs. The WHO should reinstate the 3.75 mg for prequalification and determine which of these regimens should be incorporated into their treatment guidelines to advance malaria elimination."

Infectious Disease • Malaria

Measuring the transmissibility of recurrent parasitemias that arise following artemisinin-based combination therapy (ASTMH 2025) - "Artemisinin combination therapy (ACT) artemether-lumefantrine (AL) is the frontline treatment for malaria in Tanzania, but partial resistance to artemisinins has recently been detected in the country, prompting investigation of triple ACT safety and efficacy. The 3ACT Kibindu study evaluated addition of amodiaquine (AQ) or artesunate-amodiaquine (ASAQ) to the AL treatment regimen...Amplicon sequencing of resistance markers and RT-qPCR gametocyte quantification are ongoing to better understand implications of these results. Overall, this study provides a uniquely comprehensive analysis of ACT efficacy and impact on transmission and emerging resistance in endemic east Africa."

Combination therapy • Infectious Disease • Malaria

Modeling the impact of PfCRT-mediated Piperaquine resistance on antimalarial deployment strategies in Plasmodium falciparum (ASTMH 2025) - "The efficacy of artemisinin-based combination therapies (ACTs) is increasingly compromised by the emergence of drug-resistant Plasmodium falciparum strains, notably those with mutations in the chloroquine resistance transporter (PfCRT) linked to piperaquine resistance...Among cycling strategies, initiating rotation with artemether-lumefantrine (AL), followed by artesunate-amodiaquine (ASAQ), and then DHA-PPQ demonstrates initial advantages over the reverse order, but only in settings where there is no partner-drug resistance...However, the emergence of pfcrt mutations conferring piperaquine resistance challenges this paradigm—particularly when resistance arises during periods of predominant DHA-PPQ use. These results highlight the importance of optimizing both the sequence and duration of therapies use in ACT cycling strategies while awaiting the approval and deployment of more effective interventions."

Infectious Disease

Safety of primaquine for the radical cure of Plasmodium vivax in Ethiopia and Madagascar, results of a large scale cluster randomised intervention study. (ASTMH 2025) - "G6PD enzyme activity is assessed using the STANDARD G6PD Test (SD Biosensor), and all participants with a G6PD enzyme activity above 4.0 U/gram Hb are treated with chloroquine (Ethiopia) or artesunate-amodiaquine (Madagascar) plus primaquine (both countries, 0.5mg/kg for 7 days). The prevalence of genes conferring G6PD deficiency is 7.9% in Madagascar and 0.2% in Ethiopia. We will present the results on the safety of primaquine treatment in our study, with a specific focus on the safety of primaquine in women with intermediate G6PD enzyme activity in both Madagascar and Ethiopia."

Clinical • Hematological Disorders • Infectious Disease • Malaria • Metabolic Disorders

Efficacy of artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria among children aged 2-11 years in the Asante Akim North Municipality, Ghana: a single-arm open trial. (PubMed, Malar J) - "The study confirmed that artesunate (AS) combined with amodiaquine (AQ) remains an effective treatment for uncomplicated Plasmodium falciparum malaria in children aged 2-11 years in Ghana. Additionally, a high prevalence of a haplotype associated with reinfection following artemether-lumefantrine treatment, one of Ghana's first-line antimalarial therapies, was observed."

Journal • Infectious Disease • Malaria • ABCB1

Pyronaridine-artesunate for treating uncomplicated Plasmodium falciparum malaria. (PubMed, Cochrane Database Syst Rev) - "Pyronaridine-artesunate was efficacious against uncomplicated P falciparum malaria; achieved a PCR-adjusted treatment failure rate of less than 8% at days 28 and 42; and may be at least as good as artesunate-amodiaquine and artesunate-mefloquine (based on 1 RCT per drug) and may be at least as good as, or better than, artemether-lumefantrine. Pyronaridine-artesunate increases the risk of episodes of abnormally raised ALT and AST compared to other studied therapeutics."

Clinical • Journal • Review • Hepatology • Infectious Disease • Liver Failure • Malaria

Health system challenges and facilitators associated with adaptive cycling deployment of multiple first-line treatment for uncomplicated malaria: a pilot study in a malaria-endemic region of Kenya. (PubMed, Malar J) - "Adaptive cycling MFT implementation is feasible in Kenya with adequate planning and addressing health systems challenges. Stakeholder engagement and continuous training were critical for success. Policy implications and regional cooperation potential warrant exploration in other sub-Saharan African countries with different deployment contexts."

Journal • Infectious Disease • Malaria

Efficacy and safety of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) for the treatment of uncomplicated Plasmodium falciparum malaria in Liberia, 2022-2023. (PubMed, Malar J) - "The PCR-corrected ACPR efficacy greater than the 90% WHO threshold, and day 3 slide positivity rate demonstrate that AL and ASAQ are both effective treatments for uncomplicated malaria in Liberia."

Journal • Infectious Disease • Malaria

MEFI_IV: In Vivo Efficacy of Artemether-Lumefantrine, Amodiaquine-Artesunate, Dihydroartemisinin-Piperaquine, and Pironaridine-Artesunate in Mozambique (clinicaltrials.gov) - P4 | N=870 | Completed | Sponsor: Centro de Investigacao em Saude de Manhica | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Malaria

Trajectory of Plasmodium falciparum Molecular Markers of Amodiaquine Resistance in São Tomé and Príncipe. (PubMed, Open Forum Infect Dis) - "Artesunate-amodiaquine has been the first-line treatment for uncomplicated malaria in São Tomé and Príncipe since 2005, following many decades of chloroquine usage. The results suggest that the introduction of artesunate-amodiaquine led to a trajectory of single nucleotide polymorphism (SNP) successive accretion in a pre-existing environment of pfcrt 76T near fixation, leading to the emergence of a dominant 86Y/Y184/1246Y haplotype. Our data support increased vigilance of artesunate-amodiaquine performance in São Tomé and Príncipe."

Biomarker • Journal • Infectious Disease • Malaria • ABCB1

Malaria-malnutrition interaction: prevalence, risk factors, and the impact of intermittent preventive therapy for malaria on nutritional status of school-age children in Muheza, Tanga, Tanzania - A cross-sectional survey and a randomized controlled open-label trial. (PubMed, BMC Public Health) - P3 | "Although substantial efforts to control malaria are ongoing in the study setting, the dual burden of malaria and malnutrition remains significant. Anti-malaria use for preventive purpose may not be sufficient to improve nutritional status, reinforcing that integrated interventions are required to address both malaria and malnutrition. Public health efforts should combine malaria control with nutrition programs, including community-driven strategies to enhance sustainable nutrition education and access to adequate food at home and school. Protocol for the parent study that generated these data was registered with ClinicalTrials.gov (NCT03640403) on Aug 21, 2018."

Journal • Infectious Disease • Malaria

Efficacy of artemether-lumefantrine, artesunate-amodiaquine, dihydroartemisinin-piperaquine and artesunate-pyronaridine for the treatment of uncomplicated Plasmodium falciparum malaria in Mozambique, 2022. (PubMed, Malar J) - P4 | "AL and AS-AQ remain effective, as their efficacy remained above the 90% WHO-recommended cut-off. DP and AS-PY also showed therapeutic efficacy above the WHO-acceptable cut-off and could be used as first-line treatments when needed. All four artemisinin-based combinations were well tolerated, with minimal safety concerns."

Journal • Infectious Disease • Malaria