Malaria: Parasite resistance to artemisinin derivatives now affecting Africa

August 04, 2020

Resistance to artemisinin, the main component of the current antimalarial treatments recommended by WHO, is already widespread in South-East Asia, but it had not previously been described in Africa. Scientists from the Institut Pasteur, in collaboration with the National Malaria Control Program in Rwanda (Rwanda Biomedical Center), the World Health Organization (WHO), Cochin Hospital and Columbia University (New York, USA), recently detected the emergence and spread of malaria parasites capable of resisting artemisinin derivatives for the first time in Rwanda. The results of the research were published on August 3, 2020 in Nature Medicine.

Malaria, caused by parasites of the genus Plasmodium, represents a major public health problem. Almost 3.2 billion people (virtually half the world's population) in 89 countries are at risk of contracting the disease, for which there is currently no vaccine. Every year, over 200 million cases and over 400,000 deaths are recorded.

For more than 15 years, treatment of malaria episodes (typical cycles of the disease alternating between fever, shivering and chills, and severe sweating) caused by Plasmodium falciparum has depended on artemisinin-based combination therapies (ACTs), which combine a fast-acting artemisinin derivative and a partner drug with a long half-life. Since 2008, parasites capable of resisting artemisinin derivatives in South-East Asia (Cambodia, Thailand, Vietnam, Myanmar and Laos) have become increasingly prevalent. This resistance, which leads to a delay in the clearance of parasites from the bloodstream of individuals treated with an ACT, is currently a serious threat that may hinder efforts to tackle the disease. A major concern is that these resistant parasites will spread through Sub-Saharan Africa, the continent most affected by malaria (>90% of cases), as was the case with previous generations of antimalarial treatments (chloroquine and folic acid antagonists). In the 1980s, the reduced efficacy of chloroquine is thought to have contributed to several million additional deaths from malaria in young African children.

Since 2014, the geographical distribution of artemisinin resistance has been monitored based on the detection of mutations in the Kelch13 gene in parasites. These mutations are believed to reduce the function of the Kelch13 protein, thought to be involved in hemoglobin degradation in infected red blood cells. Currently, the most widespread resistant parasites in South-East Asia have the C580Y mutation. Recently, C580Y mutant parasites have also been detected in Guyana and Papua New Guinea. In Africa, where ACTs remain very effective, Kelch13 mutant parasites have remained rare. For instance, the KARMA study, the first global map of artemisinin resistance, showed that less than 5% of African samples had mutations and that more than 50% of the mutants detected had only been observed once. Scientists also demonstrated that the most frequently observed mutation in Africa (A578S) did not confer artemisinin resistance to gene-edited Asian parasites.

Scientists from the Institut Pasteur, involved in a WHO-supported project on molecular monitoring of resistance in Africa, recently identified the first signs of emergence of artemisinin-resistant Kelch13 mutant parasites in Africa. The results describe significant proportions of parasites carrying the R561H mutation in two locations 100km apart (prevalences of 7.4% in Masaka and 0.7% in Rukara, respectively). Whole-genome sequencing of these parasites indicates that the R561H mutants were selected from Rwandan parasite populations and that they had not spread from Asian parasites (from Thailand or Myanmar, where the R561H mutation has previously been observed). "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," explains Didier Ménard, Head of the Malaria Genetics and Resistance Unit at the Institut Pasteur. The fact that this resistant strain has spread between several places in Rwanda and its ability to resist artemisinin in vitro have major public health implications. In the absence of effective measures to contain the spread of resistant parasites in Rwanda and neighboring countries, there is a risk that over time they will acquire the ability to resist the partner drugs used in ACTs. This would mean that the only available treatments would become ineffective, as has occurred in South-East Asia. A model of this scenario, in which no measures are taken, recently predicted that the inefficacy of ACTs in Africa could be responsible for 78 million additional cases and 116,000 additional deaths over a five-year period.
This research was supported by the Institut Pasteur, the World Health Organization, the World Bank (via the East African Public Health Laboratory Networking Project), the Bill & Melinda Gates Foundation (Grant OPP1140599), the United States Department of Defense (W81XWH-19-1-0086) and the National Institutes of Health (R01 AI109023).

Institut Pasteur

Related Malaria Articles from Brightsurf:

Clocking in with malaria parasites
Discovery of a malaria parasite's internal clock could lead to new treatment strategies.

Breakthrough in malaria research
An international scientific consortium led by the cell biologists Volker Heussler from the University of Bern and Oliver Billker from the UmeƄ University in Sweden has for the first time systematically investigated the genome of the malaria parasite Plasmodium throughout its life cycle in a large-scale experiment.

Scientists close in on malaria vaccine
Scientists have taken another big step forward towards developing a vaccine that's effective against the most severe forms of malaria.

New tool in fight against malaria
Modifying a class of molecules originally developed to treat the skin disease psoriasis could lead to a new malaria drug that is effective against malaria parasites resistant to currently available drugs.

Malaria expert warns of need for malaria drug to treat severe cases in US
The US each year sees more than 1,500 cases of malaria, and currently there is limited access to an intravenously administered (IV) drug needed for the more serious cases.

Monkey malaria breakthrough offers cure for relapsing malaria
A breakthrough in monkey malaria research by two University of Otago scientists could help scientists diagnose and treat a relapsing form of human malaria.

Getting to zero malaria cases in zanzibar
New research led by the Johns Hopkins Center for Communication Programs, Ifakara Health Institute and the Zanzibar Malaria Elimination Program suggests that a better understanding of human behavior at night -- when malaria mosquitoes are biting -- could be key to preventing lingering cases.

Widely used malaria treatment to prevent malaria in pregnant women
A global team of researchers, led by a research team at the Liverpool School of Tropical Medicine (LSTM), are calling for a review of drug-based strategies used to prevent malaria infections in pregnant women, in areas where there is widespread resistance to existing antimalarial medicines.

Protection against Malaria: A matter of balance
A balanced production of pro and anti-inflammatory cytokines at two years of age protects against clinical malaria in early childhood, according to a study led by ISGlobal, an institution supported by ''la Caixa'' Foundation.

The math of malaria
A new mathematical model for malaria shows how competition between parasite strains within a human host reduces the odds of drug resistance developing in a high-transmission setting.

Read More: Malaria News and Malaria Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to