Antimalarial resistance surveillance and mechanisms in African malaria parasites

Malaria continues to be one of the most important public health problems in Africa. Children and pregnant women are disproportionately affected. There are recent fears that the disease is resurging, despite the increased deployment of insecticide and antimalarial drugs.

The malaria parasites in some regions of the world such as South East Asia have developed resistance to old and new drugs, while resistance to the drugs used for prophylaxis in women and children is also highly prevalent in Africa. If resistance to the new Artemisinin Combination drugs were to emerge or spread to Africa, this will worsen the patterns of increasing prevalence currently being reported in areas where the parasite was previously reported to be declining.

Two studies carried out by the MRC Unit The Gambia at LSHTM, in collaboration with the University of Ghana and the Wellcome Trust Sanger Institute (UK), are developing sensitive assays and surveying for drug resistant phenotypes and genotypes of the most common malaria parasite in Africa (Plasmodium falciparum). New antimalarial drugs are also being tested against parasite isolates from across Africa, to determine their potency. This is in collaboration with the Medicine for Malaria Venture.

It is expected that these new analyses will provide information on how parasites develop resistance to antimalarials, leading us to develop new approaches to combat them. A total of 1,500 malaria parasite isolates have been tested against 10 common antimalarials.

Results have shown that malaria parasite isolates from The Gambia and Senegal are gaining new genetic mutations that are helping them tolerate the partner drugs in Artemisinin Combination Therapies. Specifically, there is increased tolerance of lumefantrine, and this builds upon resistance to older antimalarials such as chloroquine and sulphadoxinepyrimethamine. There is a risk of multidrug resistance in malaria in Africa.

Molecular markers and benchtop cellular assays that would quickly inform resistance to drugs in infected individuals and communities will, therefore, help to guide control. We continue to employ NextGeneration sequencing and genomic manipulation approaches to understand this phenomenon and help to identify and develop markers.