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Study Reveals Genomic Effects of Enhanced Malaria Control Efforts in Senegal

NEW YORK (GenomeWeb) – A study appearing online this week in the Proceedings of the National Academy of Sciences revealed the rapid genetic changes that can occur in malaria-causing Plasmodium falciparum parasites in the wake of increased control efforts.

Using a barcode of 24 unlinked SNPs, researchers from the US, Senegal, and Malawi genotyped more than 1,000 P. falciparum parasites collected in Senegal in the eight years following the introduction of revamped malaria interventions in the region that began in 2006.

From these genotypes, along with whole-genome sequences for 164 of the isolates, the team found detectable genomic effects on P. falciparum populations, which appeared to coincide with epidemiological patterns described in the region during the same time frame.

"These findings imply that intensive intervention to control malaria results in rapid and dramatic changes in parasite population genomics," senior authors Dyann Wirth and Daniel Hartl, immunology and infectious diseases researchers at Harvard University, and their colleagues wrote.

Consequently, the group argued that "genomics combined with epidemiological modeling may afford prompt, continuous, and cost-effective tracking of progress toward malaria elimination."

Malaria cases in parts of Senegal took a nosedive between 2006 and 2009 after the National Malaria Control Program was redesigned, the team explained. The efforts ranged from rapid diagnostic testing and combination treatments involving artemisinin to treated bed nets and indoor spraying for mosquito vectors.

To take a peek at the genomic effects, if any, on local Plasmodium parasite populations, the authors looked back at samples collected each year from 2006 until 2013 in Thiès, Senegal.

"Genetic changes would be expected to include bottlenecks in the parasite population size, increased random genetic drift, reduced genetic variation, greater self-fertilization during transmission, and increased allele sharing and identity by descent," they wrote.

If such predictions fit and occur relatively rapidly, they explained, it might be possible to use parasite genotypes in models assessing the success of newly introduced malaria control efforts.

Based on genotyping information gleaned from a 24-SNP barcode in 1,007 P. falciparum isolates that turned up in Thiès between 2006 and 2013, for example, the team found that almost one-third of the parasites tested in the years after enhanced malaria control shared the same barcodes.

The team found that allele frequencies fluctuated from one year to the next in unison with shifts in parasite population sizes, falling into networks of related parasites that reflected transmission patterns documented during the same time frame.

Whole-genome sequences generated for 164 of the P. falciparum parasites with Illumina HiSeq instruments underscored the increasing similarity between isolates after 2006, pointing to between-parasite allele sharing and increased genomic identity that mirrored the epidemiological effects of malaria interventions.

While P. falciparum transmission dipped between 2006 and 2010, though, the team also noticed genomic features in more recent samples that reflected a parasite population resurgence that took place in 2012 and 2013.

The study's authors emphasized that "[m]ore complex models will require more detailed data to constrain the parameterization, but as sample sizes grow and the resolution of patient meta-data increases, our ability to resolve features of malaria transmission vulnerable to intervention strategies will improve."