Fig 1.
Spatial and temporal distribution of Plasmodium falciparum samples in Guyana.
a) Epidemiological zones (n = 20) delimited using an informed approach following access using roads and rivers. Administrative Regions are indicated in purple. b) temporal distribution of samples (n = 1,409 monoclonal infections) colored by patient travel history. Three sampling periods could be observed 2016–2017 (n = 773), 2018/2019 where samples were collected as part of a therapeutic efficacy study (TES) (n = 174) with no information on patient travel history, and 2020–2021 (n = 531). Samples with no travel history information are represented in black. Map was created using Basemap v1.4.1. plotted using Guyana—Subnational Administrative Boundaries acquired from [75].
Fig 2.
The mean pairwise identity-by-descent (IBD) between samples highlighting highly related clusters (IBD ≥ 0.4).
Different sampling years are indicated as well as the presence/absence of pfcrt C350R.
Fig 3.
Clonal temporal dynamics between 2016 and 2021.
Clone C#1 in highly related cluster 1 was the largest clone present in the dataset (n = 73 samples). C#268 is the clonal background harboring pfk13 C580Y, while C#321 carried the pfk13 G718S. All clones highlighted on the figure are referenced in the text.
Table 1.
Change in highly related cluster frequencies between 2016–2017 and 2020–2021.
Fig 4.
Clone persistence and clonal abundance for nonsynonymous (NSY) mutation with similar (± 0.05) MAF (a-b) pfk13 C580Y (minor allele frequency (MAF) = 0.007 ± 0.05 n = 2,360), c-d) pfcrt C350R (MAF = 0.46 ± 0.05 n = 683) and (e-f) Eleven NSY (nine genes) on chromosome 9 which increased in frequency (in 99th percentile: ΔFREQUENCY ≥ 28.4%—MAF = 0.29 ± 0.05 n = 853). Vertical black lines represent the mean of the distribution, red vertical lines are the mutations observed, and the dashed line is 95th percentile at the particular MAF.
Fig 5.
Clone persistence and the number of epidemiological zones reached (> 1 sample and at least one spatial location, n = 130, mean = 287 days).
Clones are coloured by highly related clusters. C#268 carrying the pfk13 C580Y mutation is highlighted right on the persistence 80th percentile (vertical line). The horizontal and vertical dashed lines represent the 95th percentiles. The density plot illustrates the maximum number of epidemiological zones reached by the clone. All clones labeled on the figure (C#1, C#134, C#137, C#268) are referenced in the text.
Fig 6.
pfcrt C350R and plasmepsin amplification (xpfpm2/3) in the different clones (> 1 sample) from 2020–2021.
Copy number in plasmepsin appears not consistent among clones (p < 0.0349) and recurrent mutational events of pfcrt C350R were observed in four clones (C#116, C#45, C#4, C#160). Wildtype (WT) and pfcrt C350R mutation are indicated in blue and red respectively. The term xpfpm2/3 to designate the amplification of pfpm2 or pfpm3 and 1pfpm2/3 to denote one copy of both genes1pfpm2/3 refer to having one copy of pfpm2/3.
Fig 7.
Selection signals from isoRelate in long-lasting clones (sampled over three months) and short-lived clones sampled over two study periods (a-b) 2016–2017 and (c-d) 2020–2021.
Dashed lines represent the threshold for the different selection signals investigated using a false discovery rate of 0.01.