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

  • SHARMINI GUNAWARDENA (a1), MARCELO U. FERREIRA (a2), G. M. G. KAPILANANDA (a1), DYANN F. WIRTH (a3) and NADIRA D. KARUNAWEERA (a1)...
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 (F ST  = 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.

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Corresponding author
* Corresponding author: Department of Parasitology, Faculty of Medicine, University of Colombo, P. O. Box 271, Kynsey Road, Colombo 8, Sri Lanka. E-mail: nadira@parasit.cmb.ac.lk
References
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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.
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, 113125.
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, 14671482.
Anti Malaria Campaign. Ministry of Health, Sri Lanka. http://www.malariacampaign.gov.lk.
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, 757763.
Cooper, G., Amos, W., Hoffman, D. and Rubinsztein, D. C. (1996). Network analysis of human Y microsatellite haplotypes. Human Molecular Genetics 5, 17591766.
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, 10431049.
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.
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, 339350.
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, 4750.
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, 15181530.
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, 763767.
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, 12181226.
Frankham, R. (1996). Relationship of genetic variation to population size in wildlife. Conservation Biology 10, 15001508.
Frankham, R., Ballou, J. D. and Briscoe, D. A. (2003). Introduction to Conservation Genetics. Cambridge University Press, Cambridge, UK.
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, 761768.
Garza, J. C. and Williamson, E. G. (2001). Detection of reduction in population size using data from microsatellite loci. Molecular Ecology 10, 305318.
Global Malaria Action Plan (2011). Elimination and Eradication: Achieving Zero Transmission. World Health Organization, Geneva, Switzerland.
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.
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, 235242.
Haubold, B. and Hudson, R. R. (2000). LIAN 3.0: detecting linkage disequilibrium in multilocus data. Linkage analysis. Bioinformatics 16, 847848.
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, 6773.
Havryliuk, T., Orjuela-Sanchez, P. and Ferreira, M. U. (2008). Plasmodium vivax: microsatellite analysis of multiple-clone infections. Experimental Parasitology 120, 330336.
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, 221224.
Hudson, R. R. (1994). Analytical results concerning linkage disequilibrium in models with genetic transformation and recombination. Journal of Evolutionary Biology 7, 535548.
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, 10131022.
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, 927933.
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, 172175.
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, 105112.
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.
Levinson, G. and Gutman, G. A. (1987). Slipped-strand mispairing: a major mechanism for DNA sequence evolution. Molecular Biology and Evolution 4, 203221.
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, 238247.
Luikart, G., Cornuet, J. M. and Allendorf, F. W. (1999). Temporal changes in allele frequencies provide estimates of population bottlenecks size. Conservation Biology 13, 523530.
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, 802809.
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, 10461052.
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, 273285.
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.
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, 34283447.
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, 502503.
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.
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, 16861694.
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, 9941001.
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.
World Health Organization (2008). Global Malaria Control and Elimination: Report of a Technical Review. Geneva, Switzerland.
World Health Organization (2008). Malaria Situation in South-East Asia Region: Country Reports. http://www.searo.who.int/LinkFiles/Malaria_wmd10_Sri_Lanka.pdf.
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.
World Malaria Report (2010). WHO Global Malaria Programme. http://www.who.int/malaria/publications/country-profiles/2010/mal2010_lka.pdf.
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