28/05/2024
HIGHLIGHTS
- What: This study assessed the trends of molecular markers of artemisinin and/or reduced susceptibility to lumefantrine using samples collected in TES conducted in Mainland from 2016 to 2021. Study site This study was based on the analysis of samples that were collected by the TWG of NMCP during TESs, which were conducted to assess the efficacy and safety of AL. For the pfmrd1 gene, the analysis focused on the three SNPs (N86Y, Y184F, and D1246Y) and their corresponding haplotypes, which have been associated with reduced susceptibility to lumefantrine. This study reported less than 2.5% of non-synonymous mutations in k13 gene, and only one sample had validated k13 mutation (R622I) from Morogoro in 2020.
- Who: Catherine Bakari from the National Institute for Medical Research NMCP have published the research: Trends of Plasmodium falciparum molecular markers associated with resistance to artemisinins and reduced susceptibility to lumefantrine in Mainland Tanzania from 2016 to, in the Journal: (JOURNAL)
SUMMARY
Anti-malarial drugs, particularly artemisinin-based combinations, are recommended and widely used for effective case management, but drug resistance is a major threat that has impacted their effectiveness for malaria control and elimination. According to the WHO, analysis of molecular markers associated with anti-malarial resistance should also be done within TES to capture the emergence and track the spread of resistant parasites to artemisinins and partner drugs. Polymorphisms in different parasite genes, including Plasmodium falciparum kelch 13 (k13), P. falciparum chloroquine resistance transporter (pfcrt), P. falciparum dihydrofolate reductase (pfdhfr), P. falciparum dihydropteroate synthase (pfdhps), and P. falciparum multidrug resistance 1 (pfmdr1), have been identified and are commonly used as key molecular markers for tracking anti-malarial resistance to the respective drugs. For commonly used artemisinin-based combinations, such as artemetherlumefantrine (AL), mutations in k13 have been linked to ART-R while mutations in pfmdr1 are associated with tolerance or reduced sensitivity to lumefantrine and/or resistance to other drugs such as CQ and amodiaquine (AQ). Currently, the WHO recommends monitoring any of the 13 validated non-synonymous mutations in k13 as markers of ART-R (A675V, R622I, C580Y, P574L, R561H, P553L, I543T, R539T, Y493H, M476I, C469Y, N458Y, and M476I), while eight mutations are considered to be candidate markers (P441L, G449A, C469F, A481V, R515K, P527H, G538V, and V568G). Reports have also come from East African countries like: Rwanda, where ART-R was associated with R561H mutation; Tanzania, with R561H and 675 mutations and_(3) Uganda, where C469Y and A675V mutations have been reported. Despite the reports of ART-R in Rwanda and Uganda, this study did not report any other validated mutations in these study sites in Tanzania apart from R622I. @@
LAY DEFINITIONS
- Amodiaquine: A 4-aminoquinoline compound with anti-inflammatory properties.
- lumefantrine: A fluorene derivative that is used in combination with ARTEMETHER for the treatment of MALARIA (see ARTEMETHER-LUMEFANTRINE DRUG COMBINATION).
- Molecular markers: A molecular marker is a molecule contained within a sample taken from an organism (biological markers) or other matter. It can be used to reveal certain characteristics about the respective source
- Tanzania: A republic in eastern Africa, south of UGANDA and north of MOZAMBIQUE. Its capital is Dar es Salaam
- World health organization: A specialized agency of the United Nations designed as a coordinating authority on international health work; its aim is to promote the attainment of the highest possible level of health by all peoples.
- Chloroquine: Chloroquine is a medication primarily used to prevent and treat malaria in areas where malaria remains sensitive to its effects. Certain types of malaria, resistant strains, and complicated cases typically require different or additional medication
- Artemetherlumefantrine: Drug combination of artemether and lumefantrine that is used to treat PLASMODIUM FALCIPARUM MALARIA.
- Malaria: Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches
- Plasmodium falciparum: Plasmodium falciparum is a protozoan parasite, one of the species of Plasmodium that cause malaria in humans. It is transmitted by the female Anopheles mosquito
- artemisinins: Sesquiterpenes are a class of terpenes that consist of three isoprene units and often have the molecular formula C15H24. Like monoterpenes, sesquiterpenes may be cyclic or contain rings, including many unique combinations
Licence: cc-by
Site reference: https://malariajournal.biomedcentral.com/counter/pdf/10.1186/s12936-024-04896-0
DOI reference: https://www.doi.org/10.1186/s12936-024-04896-0
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