Recent technological advances have enabled next-generation genomic and transcriptomic analysis of Plasmodium falciparum from parasitized whole blood samples without the need for culturing. High-density genotyping of parasites obtained directly from patients with malaria has improved our understanding of population structure and genomic and transcriptional variation [1, 2]. Highly parallel sequencing is currently being used to identify the genetic determinants of clinically relevant phenotypes including drug resistance, vaccine escape and disease severity. Importantly, genomic characterization of parasite populations in patients captures intra-host diversity and prevents the potential loss of sequence data from phenotype-conferring parasite isolates during their culture adaptation.
The performance of highly parallel sequencing platforms, such as Illumina, is greatly enhanced in sample preparations with a high parasite-to-human nucleic acid ratio . Such high ratios can be achieved by either selectively capturing parasite nucleic acids or by removing human material from the sample. Hybrid selection  using RNA 'baits' complementary to the P. falciparum genome can achieve over 40-fold enrichment of parasite DNA and can be performed at any time following DNA extraction ; however, at $250 USD per sample, this technique may be prohibitively costly for epidemiological or population-level studies.
The alternative, leukocyte depletion, must be performed in field sites soon after blood collection and before transport and storage. Commercially available magnetic columns have been used to rapidly isolate parasitized red blood cells (RBCs) from uninfected RBCs and leukocytes . However, magnetic purification depends on short-term culturing of patient blood to transform ring-stage parasites to haemozoin-rich trophozoites and schizonts, which requires equipment for in vitro parasite cultivation. Furthermore, parasites obtained directly from patients mature at different rates in culture, resulting in inconvenient time-points for purification. The current standard for leukocyte depletion of parasitized blood for P. falciparum nucleotide sequencing is a two-step process: centrifugation using Lymphoprep or another sucrose density gradient solution, followed by filtration using Plasmodipur filters . This 'LP' method is effective but difficult to scale-up in field settings because it requires extensive handling and transfer of blood, training to perform sensitive steps, and costly commercial reagents and materials.
Filtration with hand-made columns has been used as an inexpensive and less time-consuming alternative for leukocyte depletion of Plasmodium-infected blood for decades [7, 8]. Recently, non-woven fabric filters  and plastic syringes filled with CF11 cellulose powder (Whatman)  were shown to effectively remove leukocytes and platelets from Plasmodium vivax-infected blood, where their phagocytic and degranulating activities may interfere with some ex vivo studies. CF11 filtration has also been used to improve microarray-based transcriptome analysis of P. vivax-infected blood [2, 11]. CF11 cellulose is thought to work by trapping leukocytes by size exclusion and/or interactions between cellulose hydroxyl groups and leukocyte surface molecules. In this study, laboratory-adapted P. falciparum clones were used to adapt CF11 columns to remove human DNA from P. falciparum-infected blood for genomic studies, compare CF11 filtration to the established LP method, and validate a centrifuge-free option for CF11 filtration. Both methods were also compared in a field setting using P. falciparum isolates obtained directly from patients with malaria. Furthermore, routine CF11 filtration of parasitized blood collected from patients in a second field site with minimal facilities was successfully implemented.