Long term persistence of clonal malaria parasite Plasmodium falciparum lineages in the Colombian Pacific region

Abstract

BackgroundResistance to chloroquine and antifolate drugs has evolved independently in South America, suggesting that genotype - phenotype studies aimed at understanding the genetic basis of resistance to these and other drugs should be conducted in this continent. This research was conducted to better understand the population structure of Colombian Plasmodium falciparum in preparation for such studies.ResultsA set of 384 SNPs were genotyped in blood spot DNA samples from 447 P. falciparum infected subjects collected over a ten year period from four provinces of the Colombian Pacific coast to evaluate clonality, population structure and linkage disequilibrium (LD). Most infections (81%) contained a single predominant clone. These clustered into 136 multilocus genotypes (MLGs), with 32% of MLGs recovered from multiple (2 – 28) independent subjects. We observed extremely low genotypic richness (R = 0.42) and long persistence of MLGs through time (median = 537 days, range = 1 – 2,997 days). There was a high probability (>5%) of sampling parasites from the same MLG in different subjects within 28 days, suggesting caution is needed when using genotyping methods to assess treatment success in clinical drug trials. Panmixia was rejected as four well differentiated subpopulations (FST = 0.084 - 0.279) were identified. These occurred sympatrically but varied in frequency within the four provinces. Linkage disequilibrium (LD) decayed more rapidly (r2 = 0.17 for markers <10 kb apart) than observed previously in South American samples.ConclusionsWe conclude that Colombian populations have several advantages for association studies, because multiple clone infections are uncommon and LD decays over the scale of one or a few genes. However, the extensive population structure and low genotype richness will need to be accounted for when designing and analyzing association studies.

K13 Propeller Alleles, mdr1 Polymorphism, and Drug Effectiveness at Day 3 after Artemether-Lumefantrine Treatment for Plasmodium falciparum Malaria in Colombia, 2014-2015

“…Moreover, we identified only 4 D3-positive patients (all of which had an initial parasite density of Ͻ10,000 parasites/l) and therefore could not investigate parasite correlates of D3 positivity. Finally, we did not genotype our parasite isolates to investigate whether we have repeatedly sampled persistent, clonal parasite populations that may be circulating in Colombia (33). If they are, and if some mutations are genetically fixed within them, this could partly explain the very high prevalence of double and triple mdr1 mutants, for example, or the absence of K13 propeller polymorphism (unlike in Africa) in our study.…”

“…These data differ moderately from those of a previous study (32), which found the NFSDD and NFSDY haplotypes in 40.0% and 53.3% of samples, respectively, from the Colombian Pacific Coast 16 years ago. Since there is a high probability of finding clonal P. falciparum infections in regions of malaria endemicity in Colombia (33), it is possible that we have repeatedly sampled the same clone in our study. No clear associations between these common mdr1 SNPs and treatment failures have been found in South America.…”

Malaria Genomics in the Era of Eradication

“…Several groups have explored the use of socalled SNP "barcodes" to distinguish unique versus clonal parasite lineages and track changes in disease transmission over time (Campino et al 2011;Daniels et al 2013Daniels et al , 2008Daniels et al , 2015Echeverry et al 2013;Nkhoma et al 2013). Other groups have used amplification of highly polymorphic regions of the parasite genome to create haplotypes, which is the basis of merozoite surface protein type 1 (MSP) typing strate-gies used to distinguish parasite reinfection (Tanabe et al 1998).…”

The utility of genomic data forPlasmodium vivaxpopulation surveillance

“…49,50 A major differentiating biological feature between P. vivax and P. falciparum is relapse of vivax parasites, which can contribute to elevated COIs not associated with new infections. Indeed, a study of P. vivax in Sri Lanka reported a puzzling persistence of genetic diversity and a high proportion of complex infections even as prevalence dramatically declined due to control efforts.…”