Bottleneck effects on vaccine-candidate antigen diversity of malaria parasites in Thailand

Jongwutiwes, Somchai; Putaporntip, Chaturong; Hughes, Austin L.

doi:10.1016/j.vaccine.2010.02.062

Cited by 32 publications

(37 citation statements)

References 28 publications

(49 reference statements)

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“…This evidence suggests that more recent selective forces have shaped population structure in this species. Previous studies also suggest that P. falciparum infections in Southeast Asia were more multiclonal two decades ago, again suggesting that recent forces have constrained its genetic diversification (75)(76)(77). This evidence is consistent with our findings that P. falciparum in Cambodia has undergone large demographic shifts much more recently than P. vivax.…”

Section: Discussionsupporting

confidence: 92%

Selective sweep suggests transcriptional regulation may underlie Plasmodium vivax resilience to malaria control measures in Cambodia

Parobek

Lin

Saunders

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Cambodia, in which both Plasmodium vivax and Plasmodium falciparum are endemic, has been the focus of numerous malaria-control interventions, resulting in a marked decline in overall malaria incidence. Despite this decline, the number of P. vivax cases has actually increased. To understand better the factors underlying this resilience, we compared the genetic responses of the two species to recent selective pressures. We sequenced and studied the genomes of 70 P. vivax and 80 P. falciparum isolates collected between 2009 and 2013. We found that although P. falciparum has undergone population fracturing, the coendemic P. vivax population has grown undisrupted, resulting in a larger effective population size, no discernable population structure, and frequent multiclonal infections. Signatures of selection suggest recent, species-specific evolutionary differences. Particularly, in contrast to P. falciparum, P. vivax transcription factors, chromatin modifiers, and histone deacetylases have undergone strong directional selection, including a particularly strong selective sweep at an AP2 transcription factor. Together, our findings point to different population-level adaptive mechanisms used by P. vivax and P. falciparum parasites. Although population substructuring in P. falciparum has resulted in clonal outgrowths of resistant parasites, P. vivax may use a nuanced transcriptional regulatory approach to population maintenance, enabling it to preserve a larger, more diverse population better suited to facing selective threats. We conclude that transcriptional control may underlie P. vivax's resilience to malaria control measures. Novel strategies to target such processes are likely required to eradicate P. vivax and achieve malaria elimination.D uring the last decade, western Cambodia has been the focus of numerous and multimodal interventions to control the spread of artemisinin-resistant Plasmodium falciparum (1, 2). Such interventions, including increased vector control, increased surveillance, and improved access to quality artemisinin-combination therapy (ACT), would be expected to curtail coendemic Plasmodium vivax as well. However, even as P. falciparum infections in Cambodia decreased by 81% between 2009 and 2013, P. vivax cases have increased, making it the predominant species in the Mekong region (3-6). This scenario, repeated in Brazil and other areas of coendemicity, has led to growing awareness that P. vivax, although infecting the same populations and transmitted by the same mosquito vectors, will likely be the more challenging species to eradicate (6-9). In this study, we use population genomics to gain insight into the evolutionary factors underlying P. vivax's resilience to malaria control measures.Population genetic studies have previously hinted at the resilience of P. vivax populations in comparison with P. falciparum. Studies of microsatellites and highly variable antigens of sympatric P. vivax and P. falciparum populations in Southeast Asia and the Southwest Pacific have consistently shown P. viv...

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Section: Discussionsupporting

confidence: 92%

Selective sweep suggests transcriptional regulation may underlie Plasmodium vivax resilience to malaria control measures in Cambodia

Parobek

Lin

Saunders

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Moreover, they were also identical at neutral microsatellite loci (mean H e at 8 neutral loci of 0.05 Ϯ 0.03; n ϭ 30). This observation is consistent with results from recent studies that also indicated a population bottleneck in the Yala population, leading to a reduction in genetic diversity (24,38). Pumpaibool et al (38) previously analyzed the genetic diversity at 12 neutral microsatellite markers in parasites from seven Thai provinces (Mae Hong Son, Tak, Kanchanaburi, and Ranong on the Burma border and Trat, Ubonratchathani, and Yala on the Cambodia, Laos, and Malaysia borders, respectively) and found a significant level of genetic differentiation between the Yala population and the populations from Thailand-Burma (fixation index [F ST ] ϭ 0.1321) and Thailand-Cambodia (F ST ϭ 0.1199) borders (38).…”

Section: Figsupporting

confidence: 93%

Tracking Origins and Spread of Sulfadoxine-Resistant Plasmodium falciparum dhps Alleles in Thailand

Alam

Vinayak

Congpuong

et al. 2011

Antimicrob Agents Chemother

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The emergence and spread of drug-resistant Plasmodium falciparum have been a major impediment for the control of malaria worldwide. Earlier studies have shown that similar to chloroquine (CQ) resistance, high levels of pyrimethamine resistance in P. falciparum originated independently 4 to 5 times globally, including one origin at the Thailand-Cambodia border. In this study we describe the origins and spread of sulfadoxineresistance-conferring dihydropteroate synthase (dhps) alleles in Thailand. The dhps mutations and flanking microsatellite loci were genotyped for P. falciparum isolates collected from 11 Thai provinces along the Burma, Cambodia, and Malaysia borders. Results indicated that resistant dhps alleles were fixed in Thailand, predominantly being the SGEGA, AGEAA, and SGNGA triple mutants and the AGKAA double mutant (mutated codons are underlined). These alleles had different geographical distributions. The SGEGA alleles were found mostly at the Burma border, while the SGNGA alleles occurred mainly at the Cambodia border and nearby provinces. Microsatellite data suggested that there were two major genetic lineages of the triple mutants in Thailand, one common for SGEGA/SGNGA alleles and another one independent for AGEAA. Importantly, the newly reported SGNGA alleles possibly originated at the Thailand-Cambodia border. All parasites in the Yala province (Malaysia border) had AGKAA alleles with almost identical flanking microsatellites haplotypes. They were also identical at putatively neutral loci on chromosomes 2 and 3, suggesting a clonal nature of the parasite population in Yala. In summary, this study suggests multiple and independent origins of resistant dhps alleles in Thailand.

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“…The Thai P. vivax populations collected from three regions (northwestern, eastern and southern) from 1996 and 2007 also showed significant population subdivision [48], which may be due to temporal and spatial separations among these populations. Later studies confirmed that the southern Thai population had experienced a genetic bottleneck with significantly reduced genetic diversity [9, 10]. Yet, very little genetic differentiation was observed between the combined Thai parasite population and the China-Myanmar border population, despite that our parasite samples were acquired more recently.…”

Section: Discussionmentioning

confidence: 70%

“…While it is expected that genetic diversity diminishes following the reduction in malaria incidence, the relationship between the two aspects is complex and could vary according to many epidemiological parameters. In Thailand, for example, P. vivax population in the western border was highly diverse as compared to being almost clonal in the southern border [9, 10]. It remains to be determined whether these differences were due to different histories of malaria control efforts and levels of parasite introduction from neighboring highly endemic areas.…”

Section: Discussionmentioning

confidence: 99%

“…In these border regions, cross-border human migration as a major source of malaria introduction presents a significant challenge to the malaria elimination course [7, 8]. Since control efforts are expected to have great impacts on the genetic diversity of the parasite populations [9, 10], tracking their spatial and temporal dynamics may provide timely measurement of the progress of regional malaria elimination.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Analysis of Pvama1 genes from China-Myanmar border reveals little regional genetic differentiation of Plasmodium vivax populations

et al. 2016

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BackgroundWith the premise of diminishing parasite genetic diversity following the reduction of malaria incidence, the analysis of polymorphic antigenic markers may provide important information about the impact of malaria control on local parasite populations. Here we evaluated the genetic diversity of Plasmodium vivax apical membrane antigen 1 (Pvama1) gene in a parasite population from the China-Myanmar border and compared it with global P. vivax populations.MethodsWe performed evolutionary analysis to examine the genetic diversity, natural selection, and population differentiation of 73 Pvama1 sequences acquired from the China-Myanmar border as well as 615 publically available Pvama1 sequences from seven global P. vivax populations.ResultsA total of 308 Pvama1 haplotypes were identified among the global P. vivax isolates. The overall nucleotide diversity of Pvama1 gene among the 73 China-Myanmar border parasite isolates was 0.008 with 41 haplotypes being identified (Hd = 0.958). Domain I (DI) harbored the majority (26/33) of the polymorphic sites. The McDonald Kreitman test showed a significant positive selection across the ectodomain and the DI of Pvama1. The fixation index (F ST) estimation between the China-Myanmar border, Thailand (0.01) and Myanmar (0.10) showed only slight geographical genetic differentiation. Notably, the Sal-I haplotype was not detected in any of the analyzed global isolates, whereas the Belem strain was restricted to the Thai population. The detected mutations are mapped outside the overlapped region of the predicted B-cell epitopes and intrinsically unstructured/disordered regions.ConclusionsThis study revealed high levels of genetic diversity of Pvama1 in the P. vivax parasite population from the China-Myanmar border with DI displaying stronger diversifying selection than other domains. There were low levels of population subdivision among parasite populations from the Greater Mekong Subregion.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1899-1) contains supplementary material, which is available to authorized users.

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Bottleneck effects on vaccine-candidate antigen diversity of malaria parasites in Thailand

Cited by 32 publications

References 28 publications

Selective sweep suggests transcriptional regulation may underlie Plasmodium vivax resilience to malaria control measures in Cambodia

Selective sweep suggests transcriptional regulation may underlie Plasmodium vivax resilience to malaria control measures in Cambodia

Tracking Origins and Spread of Sulfadoxine-Resistant Plasmodium falciparum dhps Alleles in Thailand

Analysis of Pvama1 genes from China-Myanmar border reveals little regional genetic differentiation of Plasmodium vivax populations

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