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Sequencing Study Points to Malaria Parasite Diversity in Colombia

NEW YORK (GenomeWeb) – Populations of the malaria-causing parasite Plasmodium vivax appear to be relatively genetically robust in Colombia, a new study suggests, contrary to the low diversity detected in other parts of the Americas.

Researchers from the US and Colombia did whole-genome sequencing on eight P. vivax isolates obtained from a malaria-endemic region of Colombia called Cordóba. Their analyses of these isolates, published online this week in PLOS Neglected Tropical Diseases, uncovered thousands more single nucleotide variants in the Colombian population than described in P. vivax samples from Peru.

Based on these and other results, the study's authors argued that their findings "differ substantially from the perception that South American P. vivax populations have low diversity as a result of a simple evolutionary history."

"A comprehensive population genomic study of South America would be required to understand the extent of such genetic polymorphism and the process involved in its maintenance," wrote the researchers, who were led by co-senior authors and Arizona State University researchers Reed Cartwright and Ananias Escalante. "Nevertheless, our results demonstrate that South American P. vivax populations do not universally have low genetic diversity."

The team used the Illumina HiSeq 2000 to generate genome sequence data for eight P. vivax isolates obtained from individuals treated for malaria in the Cordóba region between 2011 and 2013. After generating as many as 36 million paired-end reads per sample, the group tossed out as many human DNA sequences as possible before mapping the malaria parasite sequences to an existing reference genome.

From the genome sequences, which varied in their mean depth from just under one-fold coverage to more than 42-fold coverage, the researchers identified 34 single nucleotide changes relative to the P. vivax reference genome, along with nearly 34,000 non-reference SNVs and 789 potential microsatellite markers.

Meanwhile, comparisons with data for previously sequenced and/or genotyped P. vivax populations from Peru, Madagascar, and Cambodia suggested that isolates from South America are missing thousands of alleles described in isolates from both Madagascar and Cambodia.

On the other hand, the newly sequenced samples from Colombia contained more than 7,300 of the almost 11,000 SNVs described in P. vivax samples from Peru.

Their results suggest that each of the individuals tested was infected by parasites from a single P. vivax lineage, contrary to the notion that apparent genetic diversity was boosted as a consequence of multiple parasite lineages in each person.

But while genetic diversity appeared to be somewhat higher overall in the Colombian samples than in those from other parts of the Americas, the team saw regions of low diversity in and around an enzyme gene variant implicated in resistance to sulfadoxine drugs.

"The evolution of [sulfadoxine] resistance … demonstrates that this P. vivax population has been subject to drug pressure from [sulfadoxine]," the study's authors noted, "a drug that has not been part of the approved treatment for uncomplicated P. vivax malaria in Colombia."

"[Sulfadoxine] has been used to treat P. falciparum infections in Colombia," they continued, "so it is possible this selective pressure has arisen from misdiagnosis of P. vivax infections or the use of [sulfadoxine] to treat mixed P. vivax-P. falciparum infections."