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1 Pearce, R.. 2006. When the rivers run dry: water - the defining crisis of the twenty-first century. Boston, MA, USA: Beacon Press. 324p.
(Location: IWMI HQ Call no: 333.91 G000 PEA Record No: H041912)
(0.06 MB)
2 Schousboe, M. L.; Rajakaruna, R. S.; Amerasinghe, Priyanie.; Konradsen, F.; Ord, R.; Pearce, R.; Bygbjerg, C.; Roper, C.; Alifrangis, M. 2011. Analysis of polymorphisms in the merozoite surface protein-3a gene and two microsatellite loci in Sri Lankan Plasmodium vivax: evidence of population substructure in Sri Lanka. American Journal of Tropical Medicine and Hygiene, 85(6):994-1001. [doi: https://doi.org/10.4269/ajtmh.2011.11-0338]
(Location: IWMI HQ Call no: e-copy only Record No: H044603)
(0.59 MB)
The geographical distribution of genetic variation in Plasmodium vivax samples ( N = 386) from nine districts across Sri Lanka is described using three markers; the P. vivax merozoite surface protein -3a ( Pvmsp -3a) gene, and the two microsatellites m1501 and m3502. At Pvmsp -3a, 11 alleles were found with an expected heterozygosity (H e ) of 0.81, whereas at m1501 and m3502, 24 alleles (H e = 0.85) and 8 alleles (H e = 0.74) were detected, respectively. Overall, 95 unique three locus genotypes were detected among the 279 samples positive at all three loci (H e = 0.95). Calculating the pairwise fixation index ( F ST ) revealed statistically significant population structure. The presence of identical 2-loci microsatellite genotypes in a significant proportion of samples revealed local clusters of closely related isolates contributing to strong linkage disequilibrium between marker alleles. The results show evidence of high genetic diversity and possible population substructure of P. vivax populations in Sri Lanka.
3 Schousboe, M. L.; Ranjitkar, S.; Rajakaruna, R. S.; Amerasinghe, Priyanie; Konradsen, F.; Morales, F.; Ord, R.; Pearce, R.; Leslie, T.; Rowland, M.; Gadalla, N; Bygbjerg, C.; Alifrangis, M.; Roper, C. 2014. Global and local genetic diversity at two microsatellite loci in Plasmodium vivax parasites from Asia, Africa and South America. Malaria Journal, 13:1-9. [doi: https://doi.org/10.1186/1475-2875-13-392]
(Location: IWMI HQ Call no: e-copy only Record No: H047016)
(0.34 MB) (349 KB)
Background: Even though Plasmodium vivax has the widest worldwide distribution of the human malaria species and imposes a serious impact on global public health, the investigation of genetic diversity in this species has been limited in comparison to Plasmodium falciparum. Markers of genetic diversity are vital to the evaluation of drug and vaccine efficacy, tracking of P. vivax outbreaks, and assessing geographical differentiation between parasite populations.
Methods: The genetic diversity of eight P. vivax populations (n = 543) was investigated by using two microsatellites (MS), m1501 and m3502, chosen because of their seven and eight base-pair (bp) repeat lengths, respectively. These were compared with published data of the same loci from six other P. vivax populations.
Results: In total, 1,440 P. vivax samples from 14 countries on three continents were compared. There was highest heterozygosity within Asian populations, where expected heterozygosity (He) was 0.92-0.98, and alleles with a high repeat number were more common. Pairwise FST revealed significant differentiation between most P. vivax populations, with the highest divergence found between Asian and South American populations, yet the majority of the diversity (~89%) was found to exist within rather than between populations.
Conclusions: The MS markers used were informative in both global and local P. vivax population comparisons and their seven and eight bp repeat length facilitated population comparison using data from independent studies. A complex spatial pattern of MS polymorphisms among global P. vivax populations was observed which has potential utility in future epidemiological studies of the P. vivax parasite.
4 Schousboe, M. L.; Ranjitkar, S.; Rajakaruna, R. S.; Amerasinghe, Priyanie H.; Morales, F.; Pearce, R.; Ord, R.; Leslie, T.; Rowland, M.; Gadalla, N. B.; Konradsen, F.; Bygbjerg, C.; Roper, C.; Alifrangis, M. 2015. Multiple origins of mutations in the mdr1 gene—a putative marker of chloroquine resistance in P. vivax. PLoS Neglected Tropical Diseases, 9(11):1-17. [doi: https://doi.org/10.1371/journal.pntd.0004196]
(Location: IWMI HQ Call no: e-copy only Record No: H047288)
(1.19 MB) (1.19 MB)
Background
Chloroquine combined with primaquine has been the ecommended antimalarial treatment of Plasmodium vivax malaria infections for six decades but the efficacy of this treatment regimen is threatened by chloroquine resistance (CQR). Single nucleotide polymorphisms (SNPs) in the multidrug resistance gene, Pvmdr1 are putative determinants of CQR but the extent of their emergence at population level remains to be explored.
Objective
In this study we describe the prevalence of SNPs in the Pvmdr1 among samples collected in seven P. vivax endemic countries and we looked for molecular evidence of drug selection by characterising polymorphism at microsatellite (MS) loci flanking the Pvmdr1 gene.
Methods
We examined the prevalence of SNPs in the Pvmdr1 gene among 267 samples collected from Pakistan, Afghanistan, Sri Lanka, Nepal, Sudan, Sao Tome and Ecuador. We measured and diversity in four microsatellite (MS) markers flanking the Pvmdr1 gene to look evidence of selection on mutant alleles.
Results
SNP polymorphism in the Pvmdr1 gene was largely confined to codons T958M, Y976F and F1076L. Only 2.4% of samples were wildtype at all three codons (TYF, n = 5), 13.3% (n =28) of the samples were single mutant MYF, 63.0% of samples (n = 133) were double mutant MYL, and 21.3%(n = 45) were triple mutant MFL. Clear geographic differences in the prevalence of these Pvmdr mutation combinations were observed. Significant linkage disequilibrium (LD) between Pvmdr1 and MS alleles was found in populations sampled in Ecuador, Nepal and Sri Lanka, while significant LD between Pvmdr1 and the combined 4 MS locus haplotype was only seen in Ecuador and Sri Lanka. When combining the 5 loci, high level diversity, measured as expected heterozygosity (He), was seen in the complete sample set (He = 0.99), while He estimates for individual loci ranged from 0.00–0.93. Although Pvmdr1 haplotypes were not consistently associated with specific flanking MS alleles, there was significant differentiation between geographic sites which could indicate directional selection through local drug pressure.
Conclusions
Our observations suggest that Pvmdr1 mutations emerged independently on multiple occasions even within the same population. In Sri Lanka population analysis at multiple sites showed evidence of local selection and geographical dispersal of Pvmdr1 mutations between sites.
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