41
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Local population structure of Plasmodium: impact on malaria control and elimination

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Regardless of the growing interest in detecting population structures in malarial parasites, there have been limited discussions on how to use this concept in control programmes. In such context, the effects of the parasite population structures will depend on interventions’ spatial or temporal scales. This investigation explores the problem of identifying genetic markers, in this case microsatellites, to unveil Plasmodium genetic structures that could affect decisions in the context of elimination. The study was performed in a low-transmission area, which offers a good proxy to better understand problems associated with surveillance at the final stages of malaria elimination.

          Methods

          Plasmodium vivax samples collected in Tumeremo, Venezuela, between March 2003 and November 2004 were analysed. Since Plasmodium falciparum also circulates in many low endemic areas, P. falciparum samples from the same locality and time period were included for comparison. Plasmodium vivax samples were assayed for an original set of 25 microsatellites and P. falciparum samples were assayed for 12 microsatellites.

          Results

          Not all microsatellite loci assayed offered reliable local data. A complex temporal-cluster dynamics is found in both P. vivax and P. falciparum. Such dynamics affect the numbers and the type of microsatellites required for identifying individual parasites or parasite clusters when performing cross-sectional studies. The minimum number of microsatellites required to differentiate circulating P. vivax clusters differs from the minimum number of hyper-variable microsatellites required to distinguish individuals within these clusters. Regardless the extended number of microsatellites used in P. vivax, it was not possible to separate all individual infections.

          Conclusions

          Molecular surveillance has great potential; however, it requires preliminary local studies in order to properly interpret the emerging patterns in the context of elimination. Clonal expansions and clusters turnovers need to be taken into account when using molecular markers. Those affect the number and type of microsatellite markers, as well as, the expected genetic patterns in the context of operational investigations. By considering the local dynamics, elimination programmes could cost-effectively use molecular markers. However, population level studies need to consider the local limitations of a given set of loci in terms of providing epidemiologically relevant information.

          Related collections

          Most cited references33

          • Record: found
          • Abstract: found
          • Article: not found

          The trouble with isolation by distance.

          The genetic population structure of many species is characterised by a pattern of isolation by distance (IBD): due to limited dispersal, individuals that are geographically close tend to be genetically more similar than individuals that are far apart. Despite the ubiquity of IBD in nature, many commonly used statistical tests are based on a null model that is completely non-spatial, the Island model. Here, I argue that patterns of spatial autocorrelation deriving from IBD present a problem for such tests as it can severely bias their outcome. I use simulated data to illustrate this problem for two widely used types of tests: tests of hierarchical population structure and the detection of loci under selection. My results show that for both types of tests the presence of IBD can indeed lead to a large number of false positives. I therefore argue that all analyses in a study should take the spatial dependence in the data into account, unless it can be shown that there is no spatial autocorrelation in the allele frequency distribution that is under investigation. Thus, it is urgent to develop additional statistical approaches that are based on a spatially explicit null model instead of the non-spatial Island model. © 2012 Blackwell Publishing Ltd.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum.

            Widespread use of antimalarial agents can profoundly influence the evolution of the human malaria parasite Plasmodium falciparum. Recent selective sweeps for drug-resistant genotypes may have restricted the genetic diversity of this parasite, resembling effects attributed in current debates to a historic population bottleneck. Chloroquine-resistant (CQR) parasites were initially reported about 45 years ago from two foci in southeast Asia and South America, but the number of CQR founder mutations and the impact of chlorquine on parasite genomes worldwide have been difficult to evaluate. Using 342 highly polymorphic microsatellite markers from a genetic map, here we show that the level of genetic diversity varies substantially among different regions of the parasite genome, revealing extensive linkage disequilibrium surrounding the key CQR gene pfcrt and at least four CQR founder events. This disequilibrium and its decay rate in the pfcrt-flanking region are consistent with strong directional selective sweeps occurring over only approximately 20-80 sexual generations, especially a single resistant pfcrt haplotype spreading to very high frequencies throughout most of Asia and Africa. The presence of linkage disequilibrium provides a basis for mapping genes under drug selection in P. falciparum.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Efficient genetic markers for population biology.

              Population genetics has come of age. Three important components have come together: efficient techniques to examine informative segments of DNA, statistics to analyse DNA data and the availability of easy-to-use computer packages. Single-locus genetic markers and those that produce gene genealogies yield information that is truly comparable among studies. These markers answer biological questions most efficiently and also contribute to much broader investigations of evolutionary, population and conservation biology. For these reasons, single-locus and genealogical markers should be the focus of the intensive genetic data collection that has begun owing to the power of genetics in population biology.
                Bookmark

                Author and article information

                Journal
                Malar J
                Malar. J
                Malaria Journal
                BioMed Central
                1475-2875
                2012
                11 December 2012
                : 11
                : 412
                Affiliations
                [1 ]School of Life Sciences, Arizona State University, Tempe, AZ, USA
                [2 ]Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, Tempe, AZ, USA
                [3 ]Department MNI, University of Applied Sciences Mittweida, Mittweida, Germany
                [4 ]Department of Mathematics, University of Vienna, Vienna, Austria
                [5 ]Centro de Investigación de Campo Francesco Vitanza, Tumeremo, Bolívar State, Venezuela
                [6 ]ICF International, International Health & Development Division, Calverton, MD, USA
                Article
                1475-2875-11-412
                10.1186/1475-2875-11-412
                3538601
                23232077
                24bbd28d-0a45-4e13-a1ee-fc35c748adee
                Copyright ©2012 Chenet et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 August 2012
                : 5 December 2012
                Categories
                Research

                Infectious disease & Microbiology
                plasmodium,malaria control,population structure,microsatellites,recrudescence,linkage disequilibrium

                Comments

                Comment on this article