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

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

Single low dose primaquine to block the transmission of Plasmodium falciparum-proposed stand-alone and ACT-adapted regimens. (PubMed, BMC Med) - "These regimens offer flexibility for malaria control programmes and guidance for drug manufacturers wishing to co-blister SLDPQ with ACTs. The WHO should reinstate the 3.75 mg tablet for prequalification and determine which regimens should be incorporated into their treatment guidelines to advance malaria elimination."

Journal • Hematological Disorders • Infectious Disease • Malaria • Metabolic Disorders

Spectrum of movement disorders in Malaria: a systematic review of case reports, case series, and cohort studies. (PubMed, Neurol Sci) - "Movement disorders in malaria are rare but clinically significant. They may occur during acute illness or weeks later, often linked to Plasmodium falciparum or antimalarial drugs. Early identification and supportive care usually lead to favorable outcomes."

Journal • Review • Ataxia • CNS Disorders • Dystonia • Infectious Disease • Malaria • Movement Disorders

Antimalarial compounds exhibit variant- and cell-type-specific activity against SARS-CoV-2 isolated in Panama. (PubMed, Front Pharmacol) - "In Calu-3 cells, a wider variety of compounds, including chloroquine (CQ), amodiaquine (AQ), artesunate (AS), lumefantrine (LUM), and hydroxychloroquine (HCQ), were found to be effective against the Delta variant...Time-of-addition experiments suggested that CQ and primaquine (PQ) were ineffective during the viral adsorption phase but showed a dose-dependent antiviral effect against the A2.5 variant in the early replication phase, whereas the Delta variant showed resistance. This study underscores the critical role of selecting appropriate cell models for SARS-CoV-2 research, as drug efficacy varies between viral variants and host cell types."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A LC-MS/MS Assay for Quantification of Amodiaquine and Desethylamodiaquine in Dried Blood Spots on Filter Paper. (PubMed, Int J Anal Chem) - "Artesunate-amodiaquine (ARS-AQ) is a first-line antimalarial treatment recommended by the World Health Organization. The developed method was demonstrated to be reliable and accurate. This assay may be particularly useful in the context of resource limited settings and in pediatric field studies."

Journal • Infectious Disease • Malaria • Pediatrics

Plasmodium falciparum multidrug resistance 1 gene polymorphisms associated with outcomes after anti-malarial treatment. (PubMed, Malar J) - "These results support prior studies that suggested: (1) patients given AL and infected with parasites carrying N86 were more likely to experience a recurrent infection; (2) patients given ASAQ and infected with parasites carrying 86Y were more likely to experience a recurrent infection. These findings suggest that ACT and Pfmdr1 genotype may influence outcome after Plasmodium falciparum infection."

Journal • Infectious Disease • Malaria • ABCB1

Slowing the spread of treatment failure to artemisinin-based combination therapies in Uganda. (PubMed, medRxiv) - "We assume that artemether-lumefantrine (AL) will continue to be used in the private sector. A change of first-line therapy from AL to artesunate-amodiaquine (ASAQ) is projected to reduce treatment failures by 34.7% to 38.3% (90% range of simulation outcomes) over six years, while a change to dihydroartemisinin-piperaquine (DHA-PPQ) is projected to reduce treatment failures over the same period by 10.0% to 12.9%...With continued AL use in the private sector, ASAQ and DHA-PPQ deployment in the public sector creates a public-private MFT mix of antimalarial use. DHA-PPQ deployment should be accompanied by real-time molecular surveillance for piperaquine-resistant genotypes."

Journal • Infectious Disease • Malaria

OPTIMAH: OPTImizing Malaria And HIV Treatment in a Shifting Landscape in Africa (clinicaltrials.gov) - P4 | N=380 | Not yet recruiting | Sponsor: Yale University

New P4 trial • Human Immunodeficiency Virus • Infectious Disease • Malaria

Kidney Toxicity Studies in Mice (BALB/C) Recurrently Infected with Plasmodium berghei and Treated With either Artemether plus Lumefantrine (AL) or Artesunate plus Amodiaquine (AA). (PubMed, Arch Razi Inst) - "However, there was also evidence of elevated levels of GPx, SOD, and CAT activity in the kidneys, which may have protected against lipid peroxidation and preserved renal function. Nevertheless, the observed antioxidant activity proved to be insufficient for the prevention of glomerular edema."

Journal • Preclinical • Infectious Disease • Malaria • CAT

MEFI_IV: In Vivo Efficacy of Artemether-Lumefantrine, Amodiaquine-Artesunate, Dihydroartemisinin-Piperaquine, and Pironaridine-Artesunate in Mozambique (clinicaltrials.gov) - P4 | N=870 | Active, not recruiting | Sponsor: Centro de Investigacao em Saude de Manhica | Trial completion date: Jul 2024 ➔ Jul 2025

Trial completion date • Infectious Disease • Malaria

Cambodian Plasmodium vivax parasites with reduced hemoglobin digestion display delayed clearance upon artesunate treatment. (PubMed, medRxiv) - "Evidence before this study: The WHO treatment guidelines recommend artemisinin-combination therapy (ACT) for treatment of blood-stage infections caused by Plasmodium vivax in all areas (with chloroquine recommended only in areas where P. vivax are still chloroquine-sensitive)...We searched Pubmed for studies containing the terms "vivax" AND "clearance" AND ("artesunate" OR "dihydroartemisinin" OR "artemether" OR "artemisinin") published between 1990 and February 2025, with no language restrictions...While all these studies concluded that artemisinin derivatives provided rapid clearance of P. vivax parasites, two studies reported a low frequency of day 3 positivity following artesunate-amodiaquine treatment (2.6% in Brazil) or dihydroartemisinin-piperaquine (0.6% in Indonesia)...Gene expression analyses suggest that metabolic variations may underlie slow clearance. Increased monitoring of treatment efficacy and..."

Journal • Infectious Disease • Malaria

Decreased dihydroartemisinin-piperaquine protection against recurrent malaria associated with Plasmodium falciparum plasmepsin 3 copy number variation in Africa. (PubMed, Nat Commun) - "Here, we retrospectively analyzed data from a randomized clinical trial, where patients received either DHA-PPQ or artesunate-amodiaquine for recurrent malaria episodes over two years...This was driven by shorter average times to reinfection and coincided with an increased frequency of infections comprising pfpm3 multi-copy parasites. The decline in post-treatment protection of DHA-PPQ upon repeated use in a high transmission setting raises concerns for its wider use for chemopreventive strategies in Africa."

Clinical • Journal • Retrospective data • Infectious Disease • Malaria

The impact of intermittent preventive treatment in school aged children with dihydroartemisinin piperaquine and artesunate amodiaquine on IgG response against six blood stage Plasmodium falciparum antigens. (PubMed, PLoS One) - "In the DP group, however, during the intervention period IPTsc did not impair antibody against MSP1, MSP3, CIDRa1.1, CIDRa1.4 and CIDRa1.5, but it did impair against GLURP-R2. The current study has shown that effective IPTsc with DP or ASAQ does not interfere with the development of antibodies against malaria antigens of the blood stages, suggesting that the advancement of naturally acquired immunity to malaria is not impeded by IPTsc interventions."

Journal • Infectious Disease • Malaria

Efficacy and safety of praziquantel plus artemisinin-based combinations versus praziquantel in the treatment of Kenyan children with Schistosoma mansoni infection: open-label, randomized, head-to-head, non-inferiority trial. (PubMed, Antimicrob Agents Chemother) - "Participants were randomly assigned (1:1:1:1:1) via a computer-generated block randomization procedure to receive a single oral dose of praziquantel (PZQ) (40 mg/kg/day) alone or in combination with a 3-day course (4 mg/kg of artesunate) of artesunate plus sulfalene-pyrimethamine (As + SP), artesunate plus amodiaquine (As + AQ), artesunate plus mefloquine (As + MQ) or dihydroartemisinin-piperaquine (DHAP). Alternatives to praziquantel should include praziquantel plus artesunate-mefloquine or praziquantel plus dihydroartemisinin-piperaquine. However, further multicentre trials are needed in different epidemiological settings and population groups to confirm these findings.CLINICAL TRIALSThis study is registered with the Pan-African Clinical Trials Registry under PACTR202001919442161."

Head-to-Head • Journal • Infectious Disease • Pain

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. (PubMed, Lancet Microbe) - P2 | "Our findings support the effectiveness of artemether-lumefantrine alone or as part of TACT for preventing nearly all human-mosquito malaria parasite transmission within 48 h. By contrast, substantial transmission was observed following treatment with artesunate-amodiaquine. The addition of a single low dose of primaquine blocks transmission to mosquitoes rapidly regardless of schizonticide."

Journal • P2 data • CNS Disorders • Infectious Disease • Malaria • Psychiatry • Schizophrenia

3ACT: Triple Artemisinin-based Combination Therapy for Delaying Drug Resistance Development - a Randomized Clinical Trial (clinicaltrials.gov) - P2/3 | N=384 | Recruiting | Sponsor: Muhimbili University of Health and Allied Sciences | Not yet recruiting ➔ Recruiting | Trial completion date: Jan 2024 ➔ Dec 2024 | Trial primary completion date: Sep 2023 ➔ Dec 2024

Combination therapy • Enrollment open • Trial completion date • Trial primary completion date • Infectious Disease • Malaria • ABCB1 • SLC27A6

The spread of molecular markers of artemisinin partial resistance and diagnostic evasion in Eritrea: a retrospective molecular epidemiology study. (PubMed, Lancet Microbe) - "The geographical spread of the pfk13 Arg622Ile mutation might have initially resulted from the clonal expansion and spread of pfhrp2/3 deletions under the test-and-treat policy using HRP2-detecting RDTs. Subsequently, selective pressure from artemisinin combination therapy could have further facilitated the spread of both pfk13 Arg622Ile and pfhrp2/3 deletions. Continuous monitoring of trends in pfk13 and pfhrp2/3 variants is needed to inform effective malaria control and elimination strategies in Eritrea and other African countries."

Biomarker • Journal • Retrospective data • Infectious Disease • Malaria

InSMART-school: Effectiveness and Safety of Intermittent Preventive Treatment for Malaria Using Either Dihydroartemisinin-piperaquine or Artesunate-amodiaquine in Reducing Malaria Related Morbidities and Improving Cognitive Ability in School-aged Children in Tanzania (clinicaltrials.gov) - P3 | N=1555 | Completed | Sponsor: National Institute for Medical Research, Tanzania | Unknown status ➔ Completed

Trial completion • Anemia • Hematological Disorders • Infectious Disease • Malaria

Therapeutic Efficacy of Artesunate-Pyronaridine and Dihydroartemisinin-Piperaquine combinations in the treatment of uncomplicated malaria in Ghana (ASTMH 2024) - "The other first-line medicines for treating uncomplicated malaria are Artesunate-Amodiaquine (ASAQ) and Artemether-Lumefantrine (AL) combinations. These children were aparasitemic on Day-7 and remained aparasitemic from Day-14 to Day-42. We conclude that AP and DHAP are highly efficacious in the treatment of uncomplicated malaria in Ghana."

Clinical • Late-breaking abstract • Infectious Disease • Malaria

Increasing lumefantrine resistance markers in a malaria longitudinal study in Kinshasa Province, Democratic Republic of Congo (ASTMH 2024) - "In 2018, artemether-lumefantrine was introduced as a first-line ACT in 2018 at our study sites where artesunate-amodiaquine was the only ACT used...No chloroquine resistance transporter SVMNT haplotype associated with amodiaquine resistance and no pfkelch13 mutations associated with artemisinin resistance were observed. Sulfadoxine-pyrimethamine resistance markers in dihydrofolate reductase and dihydropteroate synthase were highly prevalent in both 2015 and 2021, with prevalence above 85% for all the markers. Our initial finding of increasing partner-drug resistance along with new evidence of artemisinin partial resistance in neighboring countries confirm the need for ongoing antimalarial drug resistance surveillance in the DRC. Ongoing analyses of all falciparum infections will provide a better understanding of changes in resistance markers in the setting of evolving drug policy and identify key factors that may be targeted to preserve ACTs efficacy."

Late-breaking abstract • Longitudinal study • Observational data • Infectious Disease • Malaria • ABCB1 • DHFR

Efficacy and Safety of Artemether + Lumefantrine and Artesunate + Amodiaquine for uncomplicated Malaria in Equatorial Guinea (ASTMH 2024) - "Drug safety evaluations will focus on the incidence and nature of adverse events associated with these treatments. Results will provide an evidence base for malaria drug policy in EG, hopefully supporting AL as the first line treatment and evaluating the role of ASAQ as a second-line therapy, ensuring optimal care for malaria patients in Equatorial Guinea."

Clinical • Infectious Disease • Malaria

Therapeutic efficacy and safety of Artemether lumefantrine (AL) and Artesunate amodiaquine (ASAQ) for the treatment of uncomplicated falciparum malaria in Kagera region, Tanzania 2023 (ASTMH 2024) - "With high day 3 parasitemia, low uncorrected efficacy, and regional findings of APR in neighboring Rwanda and Uganda, which both use AL as first-line, a switch from AL to an alternate first-line ACT (ASAQ, Dihydroartemisinin Piperaquine) in Tanzania treatment guidelines should be considered as per WHO guidance. ASAQ’s 100% efficacy and antagonistic selective resistance mechanism make it a strong replacement candidate for AL."

Clinical • Infectious Disease • Malaria

Model-guided Strategies for Mitigating Antimalarial Drug Resistance: Benefits of Early Adoption of Triple Artemisinin-based Combination Therapies in Uganda and Tanzania (ASTMH 2024) - "We compared the outcomes of continuing with artemether-lumefantrine (AL) as the first-line therapy, switching to the triple ACT artemether-lumefantrine-amodiaquine (ALAQ) at different timepoints, temporarily adopting artesunate-amodiaquine (ASAQ) as an interim measure, and other available drugs (e.g. DHAPPQ, extended doses for AL to 5 days) deployments in Uganda and Tanzania. Our model predicts that an immediate switch from AL to ALAQ would result in the lowest number of treatment failures over the next five years (2024-2029). Delaying the transition to ALAQ by four years could double or even triple the number of treatment failures. Furthermore, the earlier the adoption of ALAQ, the more effective it would be in delaying the spread of the kelch13 variants, with predicted frequencies of 0.35 (immediate deployment) and 0.5 to 0.65 (4-year delay) in Tanzania for 2029."

Combination therapy • Infectious Disease • Malaria

Amplicon Deep Sequencing of Pfkelch13 gene in patients with Plasmodium falciparum malaria during the therapeutic efficacy study trials from 2020 to 2022 in Senegal (ASTMH 2024) - "Therapeutic Efficacy Studies (TES) demonstrate that ACTs including artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) remain efficacious in Senegal. While new PfK13 mutations need to be phenotypically tested for partial ART resistance, the appearance of DF infections may also result from partner drug resistance. Ongoing molecular surveillance for known and emerging malaria drug resistance mutations is important for detection of emerging risk and to identify novel mutations that may contribute to ART resistance in different genomic backgrounds."

Clinical • Infectious Disease • Malaria

Drug phenotype assessment to validate drug resistance markers changing among natural Senegalese Plasmodium falciparum isolates (ASTMH 2024) - "Senegal has implemented multiple antimalarial drug-based strategies over the past two decades, including intermittent preventive treatment for pregnant women, artemisinin-based combination therapies as artemether-lumefantrine, artesunate-amodiaquine (AS-AQ) for case management and seasonal malaria chemoprevention (SMC) using SP-AQ...Of note was a decrease in the Pfcrt K76T allele frequency between 2003 and 2014, declining from 76% to 26% coincident with chloroquine (CQ) withdrawal as a primary first line drug...Phenotypic assessment and genetic validation using gene editing in a Senegalese background will be done to assess the impact of Pfcrt K76T mutation on MD-AQ susceptibility. However, these findings raise the question of the duration of AQ efficacy and suggest a need for ongoing monitoring using molecular surveillance and genetic validation to guide drug policy."

Infectious Disease • Malaria • ABCB1