New mutations in malaria parasites stimulate resistance to a major immune drug

In the ongoing armed race between humans and the malaria-causing parasite, Taane Clark and colleagues at the London School of Hygiene and Tropical Medicine (LSHTM) report new mutations that increase resistance to drugs used to prevent put on malaria in pregnant women and children. already common in countries fighting the disease. The new results are published December 31 in Genetics PLOS.

Malaria causes approximately 435,000 deaths each year, mainly in young children in sub-Saharan Africa. Despite a long-term global response, efforts to control the disease are hampered by the proliferation of drug-resistant strains of malaria-causing parasite strains. Sulfadoxine-pyrimethamine (SP), for example, was once an anti-malaria treatment at first line, but is now mainly used to prevent infection in pregnant women. child and children. Mutations in two genes in the parish Plasmodium falciparum offers resistance to SP, but recently, stress-related mutations have been found in a third gene, pfgch1. To understand the extent and distribution of these new mutations, Clark and colleagues analyzed genome sequences from 4,134 blood samples collected from 29 countries where malaria is endemic. They found at least ten different versions of pfgch1, which appear in about a quarter of the samples from Southeast Asia and in a third of the samples from Africa, where carrying rays could mutations to be growing.

The growth in the number of malaria parasites with pfgch1 mutations is worrying, as the mutations strengthen the fight against SP and may stimulate the evolution of new types of immunity. As a result, their growth could threaten efforts to use SP to prevent malaria in vulnerable groups. By identifying these pfgch1 mutations during the new study, however, scientists can monitor their presence in parasite populations, to understand where SP can be used effectively, and where levels of drug attack are already too high.

“We need to understand how these mutations work and monitor them as part of malaria screening programs,” says Clark.

Colin Sutherland, author and co – director of the LSHTM Malaria Center, says, “SP is an established drug for the prevention and treatment of malaria in vulnerable groups such as pregnant women and children. -assess its vulnerability to parasites, such as. display new data. “

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Peer review; Simulation / modeling

In your cover use this URL to access the article which is freely available in Genetics PLOS: http: // magazines.plos.org /plosgenetics /article? id =10.1371 /iris.pgen.1009268

Citation: Turkiewicz A, Manko E, Sutherland CJ, Diez Benavente E, Campino S, Clark TG (2020) Genetic diversity Plasmodium falciparum The genes GTP-cyclohydrolase 1, dihydrofolate reductase and dihydropteroate synthetase reveal new perspectives on the resistance of sulfadoxine-pyrimethamine antimalarial drugs. PLoS Genet 16 (12): e1009268. https: //doi.org /10.1371 /iris.pgen.1009268

Funding: TGC is funded by the UK Medical Examination Council (Grant number MR / M01360X / 1, MR / N010469 / 1, MR / R025576 / 1, and MR / R020973 / 1) and BBSRC (Grant number BB / R013063 / 1). SC is funded by BloomsburySET, UK Medical Examination Council grants (MR / M01360X / 1, MR / R025576 / 1, and MR / R020973 / 1) and BBSRC UK (BB / R013063 / 1) grants. The funders were not involved in the research design, data collection and analysis, publication decision, or preparation of the manuscript.

Competing interests: The authors have stated that there are no competing interests.