Malaria science advances amid eradication pessimism

Friday August 23rd, 2019

British scientists have unveiled major discoveries about malaria – as the World Health Organisation warned the disease would not be eradicated in the near future.

The genetic features of the malaria parasite Plasmodium falciparum, which inhabit different regions of Africa, have been uncovered for the first time, it was announced last night (22 August 2019).

The Plasmodium Diversity Network Africa (PDNA), the first network of African scientists, say their findings, which include the genetic factors that result in resistance to anti-malarial drugs, sheds new light on the way that drug resistance is emerging in different locations.

The research, published last night (22 August 2019) in Science, was undertaken with the Wellcome Sanger Institute and focused on the genetic diversity of P. falciparum populations that endemic to several countries in sub-Saharan Africa, including Ethiopia and Ghana.

Although the population of P. falciparum parasites in sub-Saharan Africa is genetically diverse, previous research suggested this diversity was relatively similar across the continent. It was also thought the flow of genetic material tended to be from east to west, with resistance to antimalarial drugs believed to originate in South East Asia.

However, this study, which involved the collection of samples of P. falciparum from 15 African countries as part of the MalariaGEN data-sharing network, has indicated that P. falciparum parasites are genetically distinct according to which African region they are found.

Professor Abdoulaye Djimdé, Wellcome international fellow at the Wellcome Sanger Institute, said: “Contrary to previous studies, we identified distinct Western, Central and Eastern populations of P. falciparum, as well as a highly-divergent Ethiopian population.

“Genetic material originating from all directions was shared by all populations, indicating that the flow of genes is multi-directional, as opposed to unidirectional from east to west as previously thought. This is crucial information for understanding how resistance to malaria drugs is developing in Africa.”

The Ethiopian parasite population was found to be highly differentiated from those in the rest of Africa, which suggested the ancestry of malaria parasites may have been influenced by human migration. The human population in Ethiopia also has a distinct ancestry to others in Africa, which suggests the lack of colonisation of the country might explain its outlier status.

The findings confirmed that populations of P. falciparum have shared genetic information over time, particularly genes associated with resistance to antimalarial drugs.

First author Dr Alfred Amambua-Ngwa, Wellcome international fellow at the Wellcome Sanger Institute, said: “Whatever the historic factors affecting the flow of genes between the distinct P. falciparum populations, the multi-directional flow we’ve identified raises the prospect of continental spread of resistance to artemisinin-based combination therapies, which could arise from anywhere in Africa.”

* Scientists also reported mapping, for the first time, the behaviour of individual malaria parasites across each stage of their complicated life cycle, which could eventually help in the development of new drugs.

The Malaria Cell Atlas was created by researchers at the Wellcome Sanger Institute and collaborators, who used advanced single-cell technology to isolate individual parasites and measure their gene activity.

The map, which is reported in today’s edition of Science, provides the highest resolution view of malaria parasite gene expression to date and monitors how individual parasites change as they develop in both the mosquito and human host.

The research team have also been able to pinpoint the stages in the life cycle where each malaria parasite gene is likely to play a key role in parasite development.

This could be important for developing much-needed antimalarial drugs, vaccines, and transmission blocking strategies.

Joint first author Dr Virginia Howick, of the Wellcome Sanger Institute, said: “The malaria parasite’s life cycle is key to research into this disease and the Malaria Cell Atlas will help us truly understand the parasite in order to effectively control malaria.”

The team isolated and measured the gene activity of 1,787 individual malaria parasites from 10 stages across the complete life cycle, spanning both the human and the mosquito. They then measured which genes were active in individual parasites across the entire life cycle.

Joint first author Andrew Russell from the Wellcome Sanger Institute said: “Using the Malaria Cell Atlas, we’ve inferred the roles of parasite genes that until now were entirely unknown. We do this through ‘guilt-by-association’: by looking at functions of previously studied genes, we can predict roles of unknown genes if they show similar activity patterns to known genes. This provides a new opportunity to find novel drug targets.”

The Malaria Cell Atlas was expanded after using another single-cell technology to examine a further 16,000 individual parasites from the blood stages of malaria that infect mice, monkeys and humans. This showed similar gene activity behaviour across the three malaria parasite species.

Researchers also collected parasites in the blood of three Kenyan people who were infected with malaria and used the Malaria Cell Atlas to examine individual “wild” parasites from two different human malaria parasite species for the first time.

Dr Mara Lawniczak, lead author from the Wellcome Sanger Institute, said: “To defeat malaria we need to understand all the tricks the parasite uses throughout its life cycle. The Malaria Cell Atlas is the first detailed map that gives us insight into how different one parasite is from another, even when they are genetically identical.

“We face the problem of malaria becoming more resistant to current malaria drugs, and as new drugs are introduced, we hope the Malaria Cell Atlas will act as a reference to understand how parasites change their behaviours in response to our efforts to control them. Knowing this will help reveal how to corner the parasites and ultimately eliminate them.”

* The World Health Organisation said yesterday it was technically feasible to eradicate malaria – but this was unlikely to be achieved in the near future.

WHO warned of obstacles in Africa to successful eradication programmes – but said it remained committed to the target.

Amambua-Ngwa A et al. Major sub-populations of Plasmodium falciparum in sub-Saharan Africa. Science 22 August 2019; https://science.sciencemag.org/cgi/doi/10.1126/science.aav5427

Howick V, Russell A et al. The Malaria Cell Atlas: single parasite transcriptomes across the complete Plasmodium life cycle. Science 22 August 2019. DOI: 10.1126/science.aaw2619

Tags: Africa | Genetics | UK News | World Health

Printer friendly page