Malaria parasites resistant to artemisinin now prevalent in Africa

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For the last 15 years, malaria episodes caused by Plasmodium falciparum have been treated with artemisinin-based combination therapies (ACTs), now, research has shown the recent spread of malaria parasites that can resist artemisinin antimalarials.

A collaborative group of researchers from the Institut Pasteur (Paris, France), the National Malaria Control Program in Rwanda (Rwanda Biomedical Center), the World Health Organization (WHO), Cochin Hospital (Paris, France) and Columbia University (New York, NY, USA) have published a paper in Nature Medicine detailing the emergence of artemisinin-resistant malaria parasites in Rwanda.

Artemisinin-resistant parasites have been increasingly prevalent in South-East Asia and the presence in Africa causes concern of spreading through Sub-Saharan Africa where over 90% of the continent is affected by malaria.

The resistance to the drug causes a delay in the clearing of the parasites from the bloodstream of those patients who have received ACT.

Scientists have been monitoring the geographical distribution of artemisinin-resistant malaria parasites by mapping the occurrence of parasites with a mutation in the Kelch13 gene. This gene is thought to play a role in the degradation of hemoglobin in infected red blood cells. In Africa, this mutation has so far been rare, with less than 5% of samples from Africa showing the mutation, meaning ACTs are still considered very effective. However, the Institut Pasteur, as part of a project supported by the WHO on molecular monitoring of such resistance in Africa, have detected what they believe to be the early signs of artemisinin-resistant Kelch13 mutant parasites surfacing in Africa.

Results published in the manuscript describe significant proportions of parasites carrying the R561H mutation in two locations – Masaka and Rukara – at 100km apart (with a prevalence of 7.4% and 0.7% respectively). Whole-genome sequencing of these parasites was carried out and indicated that the R561H mutants were selected from Rwandan parasite populations and had not spread from Asian parasites as expected.

“These unexpected results contrast with previous scenarios in which the emergence of chloroquine- or pyrimethamine-resistant parasites in Africa was caused by the spread of resistant parasites from South-East Asia. It was thought that a similar scenario would apply for the emergence of artemisinin-resistant parasites in Africa,” explained Didier Ménard of Institut Pasteur.

As the cases occurred so far away from each other it suggests that this resistant strain has the ability to spread throughout Rwanda and therefore, could have major public health implications. Without effective measures to curb the spread, including to neighboring countries, there is a risk that over time the parasites will grow resistant to the drugs used in partnership with ACTs. This could lead to the available treatments becoming redundant, as has been seen in South-East Asia. Models predict that inefficacy of ACTs in Africa could be responsible for 78 million additional cases and lead to 116,000 additional deaths over a five-year period.

Sources: Uwimana A, Legrand E, Stokes BH et al. Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda. Nat. Med. doi:org/10.1038/s41591-020-1005-2 (2020) (Epub ahead of print); www.pasteur.fr/en/home/press-area/press-documents/malaria-parasite-resistance-artemisinin-derivatives-now-affecting-africa

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