Trial reportPloS one2014
Polymorphisms in K13 and falcipain-2 associated with artemisinin resistance are not prevalent in Plasmodium falciparum isolated from Ugandan children.
Trial report in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
87 citing papers in PubMed, 4 syntheses or guidelines pooled it, 130 citations in OpenAlex.
- Persistence of chloroquine resistance alleles in malaria endemic countries: a systematic review of burden and risk factors.Malaria journal · 2019Pooled it
- K13-propeller gene polymorphisms in Plasmodium falciparum parasite population in malaria affected countries: a systematic review of prevalence and risk factors.Malaria journal · 2019Pooled it
- Pooled it
- Pooled it
- Artesunate/Amodiaquine Versus Artemether/Lumefantrine for the Treatment of Uncomplicated Malaria in Uganda: A Randomized Trial.The Journal of infectious diseases · 2016Trial
- Emerging threat of artemisinin partial resistance markers (pfk13 mutations) in Plasmodium falciparum parasite populations in multiple geographical locations in high transmission regions of Uganda.Malaria journal · 2024Article
- The emergence of artemisinin partial resistance in Africa: how do we respond?The Lancet. Infectious diseases · 2024Review
- Emergence, transmission dynamics and mechanisms of artemisinin partial resistance in malaria parasites in Africa.Nature reviews. Microbiology · 2024Review
- Increase ofJournal of parasitic diseases : official organ of the Indian Society for Parasitology · 2024Article
- Putative molecular markers ofFrontiers in epidemiology · 2024Article
- Distribution of Plasmodium falciparum K13 gene polymorphisms across transmission settings in Ghana.BMC infectious diseases · 2023Article
- Evolution of Partial Resistance to Artemisinins in Malaria Parasites in Uganda.The New England journal of medicine · 2023Article
- Different In Vitro Drug Susceptibility Profile ofTropical medicine and infectious disease · 2022Article
- East Africa International Center of Excellence for Malaria Research: Summary of Key Research Findings.The American journal of tropical medicine and hygiene · 2022Article
- Molecular profiling of the artemisinin resistance Kelch 13 gene in Plasmodium falciparum from Nigeria.PloS one · 2022Article
- Temporal evolution of the resistance genotypes of Plasmodium falciparum in isolates from Equatorial Guinea during 20 years (1999 to 2019).Malaria journal · 2021Article
- Absence of Plasmodium falciparum artemisinin resistance gene mutations eleven years after the adoption of artemisinin-based combination therapy in Nigeria.Malaria journal · 2021Article
- Kelch13 mutations in Plasmodium falciparum and risk of spreading in Amazon basin countries.The Journal of antimicrobial chemotherapy · 2021Article
- Plasmodium falciparum resistance to ACTs: Emergence, mechanisms, and outlook.International journal for parasitology. Drugs and drug resistance · 2021Article
- Molecular surveillance of drug resistance: Plasmodium falciparum artemisinin resistance single nucleotide polymorphisms in Kelch protein propeller (K13) domain from Southern Pakistan.Malaria journal · 2021Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The emergence of resistance to artemisinin derivatives in Southeast Asia, manifested as delayed clearance of Plasmodium falciparum following treatment with artemisinins, is a major concern. Recently, the artemisinin resistance phenotype was attributed to mutations in portions of a P. falciparum gene (PF3D7_1343700) encoding kelch (K13) propeller domains, providing a molecular marker to monitor the spread of resistance. The P. falciparum cysteine protease falcipain-2 (FP2; PF3D7_1115700) has been shown to contribute to artemisinin action, as hemoglobin degradation is required for potent drug activity, and a stop mutation in the FP2 gene was identified in parasites selected for artemisinin resistance. Although delayed parasite clearance after artemisinin-based combination therapy (ACT) has not yet been noted in Uganda and ACTs remain highly efficacious, characterizing the diversity of these genes is important to assess the potential for resistance selection and to provide a baseline for future surveillance. We therefore sequenced the K13-propeller domain and FP2 gene in P. falciparum isolates from children previously treated with ACT in Uganda, including samples from 2006-7 (n = 49) and from 2010-12 (n = 175). Using 3D7 as the reference genome, we identified 5 non-synonymous polymorphisms in the K13-propeller domain (133 isolates) and 35 in FP2 (160 isolates); these did not include the polymorphisms recently associated with resistance after in vitro selection or identified in isolates from Asia. The prevalence of K13-propeller and FP2 polymorphisms did not increase over time, and was not associated with either time since prior receipt of an ACT or the persistence of parasites ≥2 days following treatment with an ACT. Thus, the K13-propeller and FP2 polymorphisms associated with artemisinin resistance are not prevalent in Uganda, and we did not see evidence for selection of polymorphisms in these genes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.