Hostname: page-component-586b7cd67f-tf8b9 Total loading time: 0 Render date: 2024-11-23T04:03:28.609Z Has data issue: false hasContentIssue false
  • English
  • Français

The Sri Lankan paradox: high genetic diversity in Plasmodium vivax populations despite decreasing levels of malaria transmission

Published online by Cambridge University Press:  14 February 2014

SHARMINI GUNAWARDENA ,
MARCELO U. FERREIRA ,
G. M. G. KAPILANANDA ,
DYANN F. WIRTH  and
NADIRA D. KARUNAWEERA
SHARMINI GUNAWARDENA
Affiliation:
Department of Parasitology, Faculty of Medicine, University of Colombo, Sri Lanka
MARCELO U. FERREIRA
Affiliation:
Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, Brazil
G. M. G. KAPILANANDA
Affiliation:
Department of Parasitology, Faculty of Medicine, University of Colombo, Sri Lanka
DYANN F. WIRTH
Affiliation:
Department of Immunology and Infectious Diseases, Harvard School of Public Health, USA
NADIRA D. KARUNAWEERA*
Affiliation:
Department of Parasitology, Faculty of Medicine, University of Colombo, Sri Lanka
*
*Corresponding author: Department of Parasitology, Faculty of Medicine, University of Colombo, P. O. Box 271, Kynsey Road, Colombo 8, Sri Lanka. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

Here we examined whether the recent dramatic decline in malaria transmission in Sri Lanka led to a major bottleneck in the local Plasmodium vivax population, with a substantial decrease in the effective population size. To this end, we typed 14 highly polymorphic microsatellite markers in 185 P. vivax patient isolates collected from 13 districts in Sri Lanka over a period of 5 years (2003–2007). Overall, we found a high degree of polymorphism, with 184 unique haplotypes (12–46 alleles per locus) and average genetic diversity (expected heterozygosity) of 0·8744. Almost 69% (n = 127) isolates had multiple-clone infections (MCI). Significant spatial and temporal differentiation (FST = 0·04–0·25; P⩽0·0009) between populations was observed. The effective population size was relatively high but showed a decline from 2003–4 to 2006–7 periods (estimated as 45 661 to 22 896 or 10 513 to 7057, depending on the underlying model used). We used three approaches – namely, mode-shift in allele frequency distribution, detection of heterozygote excess and the M-ratio statistics – to test for evidence of a recent population bottleneck but only the low values of M-ratio statistics (ranging between 0·15–0·33, mean 0·26) were suggestive of such a bottleneck. The persistence of high genetic diversity and high proportion of MCI, with little change in effective population size, despite the collapse in demographic population size of P. vivax in Sri Lanka indicates the importance of maintaining stringent control and surveillance measures to prevent resurgence.

Keywords

genotypingdiversitymicrosatellitesbottleneckPlasmodium vivaxSri Lanka
Type
Research Article
Information
Parasitology , Volume 141 , Issue 7 , June 2014 , pp. 880 - 890
Check for updates
Copyright
Copyright © Cambridge University Press 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Abeyasinghe, R. R., Galappaththy, G. N. L., Smith Gueye, C., Kahn, J. G. and Feachem, R. G. A. (2012). Malaria control and elimination in Sri Lanka: documenting progress and success factors in a conflict setting. Plos ONE 7, e43162. doi: 10.1371/journal.pone.0043162.CrossRefGoogle Scholar
Anderson, T. J., Su, X. Z., Bockarie, M., Lagog, M. and Day, K. P. (1999). Twelve microsatellite markers for characterization of Plasmodium falciparum from finger-prick blood samples. Parasitology 119, 113–125.Google Scholar
Anderson, T. J., Haubold, B., Williams, J. T., Estrada-Franco, J. G., Richardson, L., Mollinedo, R., Bockarie, M., Mokili, J., Mharakurwa, S., French, N., Whitworth, J., Velez, I. D., Brockman, A. H., Nosten, F., Ferreira, M. U. and Day, K. P. (2000). Microsatellite markers reveal a spectrum of population structures in the malaria parasite P. falciparum . Molecular Biology and Evolution 17, 1467–1482.Google Scholar
Anti Malaria Campaign. Ministry of Health, Sri Lanka. http://www.malariacampaign.gov.lk.Google Scholar
Carlton, J. M., Adams, J. H., Silva, J. C., Bidwell, S. L., Lorenzi, H., Caler, E., Crabtree, J., Angiuoli, S. V., Merino, E. F., Amedeo, P., Cheng, Q., Coulson, R. M., Crabb, B. S., Del Portillo, H. A., Essien, K., Feldblyum, T. V., Fernandez-Becerra, C., Gilson, P. R., Gueye, A. H., Guo, X., Kang'a, S., Kooij, T. W., Korsinczky, M., Meyer, E. V., Nene, V., Paulsen, I., White, O., Ralph, S. A., Ren, Q., Sargeant, T. J., Salzberg, S. L., Stoeckert, C. J., Sullivan, S. A., Yamamoto, M. M., Hoffman, S. L., Wortman, J. R., Gardner, M. J., Galinski, M. R., Barnwell, J. W. and Fraser-Liggett, C. M. (2008). Comparative genomics of the neglected human malaria parasite Plasmodium vivax . Nature 455, 757–763.Google Scholar
Cooper, G., Amos, W., Hoffman, D. and Rubinsztein, D. C. (1996). Network analysis of human Y microsatellite haplotypes. Human Molecular Genetics 5, 1759–1766.CrossRefGoogle ScholarPubMed
Cristescu, R., Sherwin, W. B., Handasyde, K., Cahill, V. and Cooper, D. W. (2010). Detecting bottlenecks using BOTTLENECK 1.2.02 in wild populations: the importance of the microsatellite structure. Conservation Genetics 11, 1043–1049.Google Scholar
Daniels, R., Chang, H. H., Sene, P. D., Park, D. C., Neafsey, D. E., Schaffner, S. F., Hamilton, E. J., Lukens, A. K., Van Tyne, D., Mboup, S., Sabeti, P. C., Ndiaye, D., Wirth, D. F., Hartl, D. L. and Volkman, S. K. (2013). Genetic surveillance detects both clonal and epidemic transmission of malaria following enhanced intervention in Senegal. Plos ONE 8, e60780. doi: 10.1371/journal.pone.0060780.CrossRefGoogle ScholarPubMed
Dorken, M. E. and Eckert, C. G. (2001). Severely reduced sexual reproduction in northern populations of a clonal plant, Decoden verticillatus (Lythraceae). Journal of Ecology 89, 339–350.CrossRefGoogle Scholar
Excoffier, L., Laval, G. and Schneider, S. (2006). Arlequin (version 3.1): an integrated software package for population genetics data analysis. Evolution of Bioinformatics Online 1, 47–50.Google Scholar
Feil, E. J., Li, B. C., Aanensen, D. M., Hanage, W. P. and Spratt, B. G. (2004). eBURST: inferring patterns of evolutionary descent among clusters of related bacterial genotypes from multilocus sequence typing data. Journal of Bacteriology 186, 1518–1530.CrossRefGoogle ScholarPubMed
Fernando, S. D., Abeyasinghe, R. R., Galappaththy, G. N. L. and Rajapaksa, L. C. (2009). Absence of asymptomatic malaria infections in previously high endemic areas of Sri Lanka. American Journal of Tropical Medicine and Hygiene 81, 763–767.CrossRefGoogle ScholarPubMed
Ferreira, M. U., Karunaweera, N. D., Silva-Nunes, M., Da Silva, N. S., Wirth, D. F. and Hartl, D. L. (2007). Population structure and transmission dynamics of Plasmodium vivax in rural Amazonia. Journal of Infectious Diseases 195, 1218–1226.Google Scholar
Frankham, R. (1996). Relationship of genetic variation to population size in wildlife. Conservation Biology 10, 1500–1508.Google Scholar
Frankham, R., Ballou, J. D. and Briscoe, D. A. (2003). Introduction to Conservation Genetics. Cambridge University Press, Cambridge, UK.Google Scholar
Galappaththy, G. N. L., Fernando, S. D. and Abeyasinghe, R. R. (2013). Imported malaria: a possible threat to the elimination of malaria from Sri Lanka? Tropical Medicine and International Health 18, 761–768.Google Scholar
Garza, J. C. and Williamson, E. G. (2001). Detection of reduction in population size using data from microsatellite loci. Molecular Ecology 10, 305–318.CrossRefGoogle ScholarPubMed
Global Malaria Action Plan (2011). Elimination and Eradication: Achieving Zero Transmission. World Health Organization, Geneva, Switzerland.Google Scholar
Gunawardena, D. M. (1998). A micro-epidemiological study of malaria in southern Sri Lanka, including aspects of clinical disease and immunity. Ph.D. thesis. University of Colombo, Sri Lanka.Google Scholar
Gunawardena, S., Karunaweera, N. D., Ferreira, M. U., Phone-Kyaw, M., Pollack, R. J., Alifrangis, M., Rajakaruna, R. S., Konradsen, F., Amerasinghe, P. H., Schousboe, M. L., Galappaththy, G. N. L., Abeyasinghe, R. R., Hartl, D. L. and Wirth, D. F. (2010). Geographic structure of Plasmodium vivax: microsatellite analysis of parasite populations from Sri Lanka, Myanmar and Ethiopia. American Journal of Tropical Medicine and Hygiene 82, 235–242.CrossRefGoogle ScholarPubMed
Haubold, B. and Hudson, R. R. (2000). LIAN 3.0: detecting linkage disequilibrium in multilocus data. Linkage analysis. Bioinformatics 16, 847–848.CrossRefGoogle ScholarPubMed
Havryliuk, T. and Ferreira, M. U. (2009). A closer look at multiple-clone Plasmodium vivax infections: detection methods, prevalence and consequences. Memorias do Instituto Oswaldo Cruz 104, 67–73.Google Scholar
Havryliuk, T., Orjuela-Sanchez, P. and Ferreira, M. U. (2008). Plasmodium vivax: microsatellite analysis of multiple-clone infections. Experimental Parasitology 120, 330–336.CrossRefGoogle ScholarPubMed
Hedrick, P. W. (2004). Estimation of relative fitnesses from relative risk data and the predicted future of hemoglobin alleles S and C. Journal of Evolutionary Biology 17, 221–224.Google Scholar
Hudson, R. R. (1994). Analytical results concerning linkage disequilibrium in models with genetic transformation and recombination. Journal of Evolutionary Biology 7, 535–548.CrossRefGoogle Scholar
Imwong, M., Nair, S., Pukrittayakamee, S., Sudimack, D., Williams, J. T., Mayxay, M., Newton, P., Kim, J. R., Nandy, A., Osorio, L., Carlton, J. M., White, N. J., Day, N. P. J. and Anderson, T. J. C. (2007 a). Contrasting genetic structure in Plasmodium vivax populations from Asia and South America. International Journal for Parasitology 37, 1013–1022.Google Scholar
Imwong, M., Snounou, G., Pukrittayakamee, S., Tanomsing, N., Kim, J. R., Nandy, A., Guthmann, J. P., Nosten, F., Carlton, J. M., Looareesuwan, S., Nair, S., Sudimack, D., Day, N. P. J., Anderson, T. J. C. and White, N. J. (2007 b). Relapses of Plasmodium vivax infection usually result from activation of heterologous hypnozoites. Journal of Infectious Diseases 195, 927–933.CrossRefGoogle ScholarPubMed
Karunaweera, N. D., Ferreira, M. U., Hartl, D. L. and Wirth, D. F. (2007). Fourteen polymorphic microsatellite DNA markers for the human malaria parasite Plasmodium vivax . Molecular Ecology Notes 7, 172–175.Google Scholar
Karunaweera, N. D., Ferreira, M. U., Munasinghe, A., Barnwell, J. W., Collins, W. E., King, C. L., Kawamoto, F., Hartl, D. L. and Wirth, D. F. (2008). Extensive microsatellite diversity in the human malaria parasite Plasmodium vivax . Gene 410, 105–112.Google Scholar
Kodisinghe, H. M. (1991). An analysis of the distribution of symptomatic and asymptomatic malaria in the Kurunegala district. M. Sc thesis. University of Colombo, Colombo, Sri Lanka.Google Scholar
Levinson, G. and Gutman, G. A. (1987). Slipped-strand mispairing: a major mechanism for DNA sequence evolution. Molecular Biology and Evolution 4, 203–221.Google Scholar
Luikart, G., Allendorf, F. W., Cornuet, J. M. and Sherwin, W. B. (1998). Distortion of allele frequency distributions provides a test for recent population bottlenecks. Journal of Heredity 89, 238–247.Google Scholar
Luikart, G., Cornuet, J. M. and Allendorf, F. W. (1999). Temporal changes in allele frequencies provide estimates of population bottlenecks size. Conservation Biology 13, 523–530.Google Scholar
Mendis, K., Rietveld, A., Warsame, M., Bosman, A., Greenwood, B. and Wernsdorfer, W. H. (2009). From malaria control to eradication: the WHO perspective. Tropical Medicine and International Health 14, 802–809.Google Scholar
Neafsey, D. E., Galinsky, K., Jiang, R. H. Y., Young, L., Sykes, S. M., Saif, S., Gujja, S., Goldberg, J. M., Young, S., Zeng, Q., Chapman, S. B., Dash, A. P., Anvikar, A. R., Sutton, P. L., Birren, B. W., Escalante, A. A., Barnwell, J. W. and Carlton, J. M. (2012). The malaria parasite Plasmodium vivax exhibits greater genetic diversity than Plasmodium falciparum . Nature Genetics 44, 1046–1052.Google Scholar
Nkhoma, S. C., Nair, S., Al-Saai, S., Ashley, E., McGready, R., Phyo, A. P., Nosten, F. and Anderson, T. J. C. (2012). Population genetic correlates of declining transmission in a human pathogen. Molecular Ecology 22, 273–285.Google Scholar
Orjuela-Sanchez, P., Karunaweera, N. D., da Silva-Nunes, M., da Silva, N. S., Scopel, K. K. G., Goncalves, R. M., Amaratunga, C., Sa, J. M., Socheat, D., Fairhurst, R. M., Gunawardena, S., Thavakodirasah, T., Galapaththy, G., Abeysinghe, R., Kawamoto, F., Wirth, D. F. and Ferreira, M. U. (2010). Single-nucleotide polymorphism, linkage disequilibrium and geographic structure in the malaria parasite Plasmodium vivax: prospects for genome-wide association studies. BMC Genetics 11, 65.CrossRefGoogle ScholarPubMed
Palstra, F. P. and Ruzzante, D. E. (2008). Genetic estimates of contemporary effective population size: what can they tell us about the importance of genetic stochasticity for wild population persistence? Molecular Ecology 17, 3428–3447.Google Scholar
Piry, S., Luikart, G. and Cornuet, J. M. (1999). BOTTLENECK: a program for detecting recent effective population size reductions from allele data frequencies. Journal of Heredity 90, 502–503.Google Scholar
Rajakaruna, R. S., Alifrangis, M., Amerasinghe, P. H. and Konradsen, F. (2010). Pre-elimination stage of malaria in Sri Lanka: assessing the level of hidden parasites in the population. Malaria Journal 9, 25.Google Scholar
Rebaudet, S., Bogreau, H., Silaï, R., Lepère, J. F., Bertaux, L., Pradines, B., Delmont, J., Gautret, P., Parola, P. and Rogier, C. (2010). Genetic structure of Plasmodium falciparum and elimination of malaria, Comoros Archipelago. Emerging Infectious Diseases 16, 1686–1694.Google Scholar
Schousboe, M. L., Rajakaruna, R. S., Amerasinghe, P. H., Konradsen, F., Ord, R., Pearce, R., Bygbjerg, I. C., Roper, C. and Alifrangis, M. (2011). Analysis of polymorphisms in the Merozoite Surface Protein-3α gene and two microsatellite loci in Sri Lankan Plasmodium vivax: evidence of substructure in Sri Lanka. American Journal of Tropical Medicine and Hygiene 85, 994–1001.Google Scholar
Wickramage, K., Premaratne, R. G., Peiris, S. L. and Mosca, D. (2013). High attack rate for malaria through irregular migration routes to a country on verge of elimination. Malaria Journal 12, 276.Google Scholar
World Health Organization (2008). Global Malaria Control and Elimination: Report of a Technical Review. Geneva, Switzerland.Google Scholar
World Health Organization (2008). Malaria Situation in South-East Asia Region: Country Reports. http://www.searo.who.int/LinkFiles/Malaria_wmd10_Sri_Lanka.pdf.Google Scholar
World Health Organization (2012). Eliminating Malaria. Case study 3. Progress towards Elimination in Sri Lanka. WHO, Geneva, Switzerland. http://www.who.int/malaria/publications/atoz/9789241504454/en/index.html.Google Scholar
World Malaria Report (2010). WHO Global Malaria Programme. http://www.who.int/malaria/publications/country-profiles/2010/mal2010_lka.pdf.Google Scholar
Supplementary material: File

Gunawardena Supplementary Material

Table 1

Download Gunawardena Supplementary Material(File)
File 91.1 KB
Supplementary material: File

Gunawardena Supplementary Material

Table 2

Download Gunawardena Supplementary Material(File)
File 105 KB