Scientists pinpoint malaria parasite hotspots with new technique
In a groundbreaking study, an international team of scientists has created a novel tool to identify hotspots of malaria parasite evolution, and to quickly and efficiently track the increase of malarial drug resistance. The findings are presented in the journal Nature.
Led by the Wellcome Trust Sanger Institute in the United Kingdom, the researchers used new sequencing technologies and informatics methods to evaluate malaria genomes from 227 patient blood samples in six countries. They identified a number of differences in how malaria develops in Africa, Asia and Oceania.
Mosquitoes spread the parasite Plasmodium falciparum, which is responsible for severe forms of malaria infection. More than 200 million people suffer from malaria, and around 600 000 die from this disease each year. Children living in sub-Saharan Africa, aged five and under, are affected most.
'One of the most striking features of P. falciparum is its ability to evolve, and overcome anti-malarial drugs,' said Professor Dominic Kwiatkowski of the Wellcome Trust Sanger Institute and Oxford University in the United Kingdom, senior author of the study.
'Chloroquine has become ineffective against malaria, and resistance to the other frontline drugs is emerging. If we want to control resistance, we first need to be able to monitor the genetic diversity of P. falciparum and identify hotspots of potential resistance as they occur. Rapid sequencing of parasite genomes from the blood of infected people is a powerful way of detecting changes in the parasite population, and potentially an important new surveillance tool in the armamentarium for controlling malaria.'
The tool developed by the team enables the parasite deoxyribonucleic acid (DNA) to be extracted from blood. The researchers can also remove as much human DNA from the sample as possible. Thanks to this technique, researchers do not have to grow the parasite in a blood culture before sequencing. So not only does the process become shorter, but replication errors are diminished as well.
According to the team, the task to sequence P. falciparum genomes is complex, because they must sequence the DNA repeatedly, unlike with human DNA. So the reconstruction of whole parasite genome DNA sequences is slow, costly and prone to errors using current DNA sequencing methods. Thanks to the sequence data used to generate list of single DNA letter changes, known as single-nucleotide polymorphisms (SNPs), the researchers identified and measured variability in natural parasite populations.
'We catalogued approximately 86 000 SNPs in the parasite genome that allow us to pinpoint differences between parasites around the world, a starting point for understanding how these populations adapt to changes in their environment,' said Dr Magnus Manske, co-first author from the Wellcome Trust Sanger Institute.
For his part, Dr Olivo Miotto, also from the Wellcome Trust Sanger Institute and Oxford University, and a co-first author, said: 'Many malaria patients, especially in Africa, are continually infected by malaria parasites, and we have created a new tool for studying the genetic diversity within a single patient, and compare it to the diversity in their environment.'
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Data Source Provider: Nature; Wellcome Trust Sanger Institute
Document Reference: Manske, M., et al., 'Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing', Nature, 2012. doi:10.1038/nature11174
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