Genetic Mutations Encourage Resistance Against Key Malaria Preventive Drug

Genetic Mutations Encourage Resistance Against Key Malaria Preventive Drug

Posted by Valerie Walters on Jan 4, 2021 7:01 am

Malaria causes 435,000 deaths per year in Sub-Saharan Africa. Children under the age of five years have been reported to suffer from the highest fatality rates. The growing threat of Plasmodium falciparum is jeopardizing global efforts to control malaria. Scientists have recently found that this malaria parasite’s populations in Africa and Southeast Asia have been growing resistant to a currently available antimalarial drug.

Genetic mutations that fuel resistance to a drug intended to prevent malaria in pregnant women and children are common in countries that are fighting the disease, according to a PLOS Genetics analysis. Taane Clark and colleagues at the London School of Hygiene and Tropical Medicine (LSHTM) report that new mutations that enhance resistance to sulfadoxine/pyrimethamine (SP) used to prevent malaria in pregnant women and children are already common in countries fighting the disease.

structure of sulfadoxine

 

Sulfadoxine-pyrimethamine (SP), for example, was once a first-line anti-malarial treatment, but now primarily is used to prevent infection in pregnant women and children because the parasite Plasmodium falciparum has become resistant to it, the researchers said. Mutations in two genes in the parasite Plasmodium falciparum offer resistance to SP, but recently, mutations related to resistance were discovered in a third gene, pfgch1. To understand the extent and spread of these new mutations, Clark and colleagues analyzed genome sequences from 4,134 blood samples collected from 29 countries where malaria is endemic. They observed that there are at least 10 different pfgch1 structural variants existing in the presence of pfdhfr and pfdhps mutations. That could result in children and pregnant women in some African and Southeast Asian populations having zero protection from malaria.

structure of pyrimethamine

The growth in the number of malaria parasites with pfgch1 mutations is concerning because the mutations enhance resistance to SP and may encourage the evolution of new resistant strains. With the identification of these pfgch1 mutations through the new study, however, scientists can monitor their presence in parasite populations, to understand where SP can be used effectively, and where rates of drug-resistance are already too high.

In the study, the researchers concluded, “The selection of P. falciparum with pfgch1 amplifications may enhance the fitness of parasites with pfdhfr and pfdhps substitutions, intensifying the persistence of SP resistance, and potentially threatening the efficacy of this regimen for prevention of malaria in vulnerable groups. Our work has revealed new forms of pfgch1 amplification, which can be used for surveillance activities.” The growth in these mutations could threaten efforts to use sulfadoxine-pyrimethamine to prevent malaria in communities at high-risk for severe disease, the researchers said.

 

Sulfadoxine, pyrimethamine and other related compounds for research use

Compound More information
Sulfadoxine https://www.vulcanchem.com/product/inhibitors/VC1088227
Pyrimethamine https://www.vulcanchem.com/product/inhibitors/VC1081467
Sulfathiazole https://www.vulcanchem.com/product/inhibitors/VC1088275
Sulfamoxole https://www.vulcanchem.com/product/inhibitors/VC1088255
Sulfadiazine https://www.vulcanchem.com/product/inhibitors/VC1088223
Sulfoxone https://www.vulcanchem.com/product/main-products/144-76-3
Sulfadoxine https://www.vulcanchem.com/product/inhibitors/VC1088227
Sulfalene https://www.vulcanchem.com/product/inhibitors/VC1088231
Proguanil https://www.vulcanchem.com/product/impurities/VC388073
Pyrimethamine https://www.vulcanchem.com/product/inhibitors/VC1081467
Pemetrexed https://www.vulcanchem.com/product/inhibitors/VC1077867
Methotrexate https://www.vulcanchem.com/product/inhibitors/VC1070267
Trimetrexate https://www.vulcanchem.com/product/inhibitors/VC1091809

 

Want to reply?

You must be signed in to MyRSC to respond to forum posts. If you're not currently a member, you can register for free.