Bousema T, Okell L, Felger I, Drakeley C, 2014. Asymptomatic malaria infections: detectability, transmissibility and public health relevance. Nat Rev Microbiol 12 :833–840.
Bruce MC, Donnelly CA, Packer M, Lagog M, Gibson N, Narara A, Walliker D, Alpers MP, Dar KP, 2000. Age- and species-specific duration of infection in asymptomatic malaria infections in Papua New Guinea. Parasitology 121 :247–256.
Felger I, Maire M, Bretscher MT, Falk N, Tiaden A, Sama W, Beck H-P, Owusu-Agyei S, Smith TA, 2012. The dynamics of natural Plasmodium falciparum infections. PLoS One 7 :e45542.
Anderson TJ et al.., 2000. Microsatellite markers reveal a spectrum of population structures in the malaria parasite Plasmodium falciparum. Mol Biol Evol 17 :1467–1482.
Yalcindag E et al.., 2012. Multiple independent introductions of Plasmodium falciparum in South America. Proc Natl Acad Sci USA 109 :511–516.
Schultz L et al.., 2010. Multilocus haplotypes reveal variable levels of diversity and population structure of Plasmodium falciparum in Papua New Guinea, a region of intense perennial transmission. Malar J 9 :336.
Mobegi VA, Loua KM, Ahouidi AD, Satoguina J, Nwakanma DC, Amambua-Ngwa A, Conway DJ, 2012. Population genetic structure of Plasmodium falciparum across a region of diverse endemicity in West Africa. Malar J 11 :223.
Leclerc MC, Durand P, De Meeûs T, Robert V, Renaud F, 2002. Genetic diversity and population structure of Plasmodium falciparum isolates from Dakar, Senegal, investigated from microsatellite and antigen determinant loci. Microbes Infect 4 :685–692.
Durand P, Michalakis Y, Cestier S, Oury B, Leclerc MC, Tibayrenc M, Renaud F, 2003. Significant linkage disequilibrium and high genetic diversity in a population of Plasmodium falciparum from an area (Republic of the Congo) highly endemic for malaria. Am J Trop Med Hyg 68 :345–349.
Tiedje KE, Oduro A, Agongo G, Anyorigiya T, Azongo D, Awine T, Ghansah A, Pascual M, Koram K, Day KP, 2017. Seasonal variation in the epidemiology of asymptomatic Plasmodium falciparum infections across two catchment areas in Bongo District, Ghana. Am J Trop Med Hyg. 97 :199–212
WHO, 2010. Basic Malaria Microscopy. Geneva, Switzerland: World Health Organization.
Snounou G, Zhu X, 1999. Biased distribution of msp1 and msp2 allelic variants in Plasmodium falciparum populations in Thailand. Trans R Soc Trop Med Hyg 93: 369–374.
Anderson TJ, Su XZ, Bockarie M, Lagog M, Day KP, 1999. Twelve microsatellite markers for characterization of Plasmodium falciparum from finger-prick blood samples. Parasitology 119: 113–125.
Matschiner M, Salzburger W, 2009. TANDEM: integrating automated allele binning into genetics and genomics workflows. Bioinformatics 25 :1982–1983.
Glaubitz JC, 2004. CONVERT: a user-friendly program to reformat diploid genotypic data for commonly used population genetic software packages. Mol Ecol Notes 4 :309–310.
Antao T, Lopes A, Lopes RJ, Beja-Pereira A, Luikart G, 2008. LOSITAN: a workbench to detect molecular adaptation based on a F st -outlier method. BMC Bioinformatics 9 :1–5.
Excoffier L, Lischer HEL, 2010. Arlequin suite ver 3.5: a new series of programs to perform population genetics analyses under Linux and Windows. Mol Ecol Resour 10 :564–567.
Goudet J, 1995. FSTAT (Version 1.2): a computer program to calculate F-statistics. J Hered 86: 485–486.
Haubold B, Hudson RR, 2000. LIAN 3.0: detecting linkage disequilibrium in multilocus data. Linkage Analysis. Bioinformatics 16 :847–848.
Gerlach G, Jueterbock A, Kraemer P, Deppermann J, Harmand P, 2010. Calculations of population differentiation based on GST and D: forget GST but not all of statistics. Mol Ecol 19 :3845–3852.
Francisco AP, Vaz C, Monteiro PT, Melo-Cristino J, Ramirez M, Carriço JA, 2012. PHYLOViZ: phylogenetic inference and data visualization for sequence based typing methods. BMC Bioinformatics 13 :87.
Rogier C, Commences D, Trape JF, 1996. Evidence for an age-dependent pyrogenic threshold of Plasmodium falciparum parasitemia in highly endemic populations. Am J Trop Med Hyg 54 :613–619.
Rogier C, 2000. Natural history of Plasmodium falciparum malaria and determining factors of the acquisition of antimalaria immunity in two endemic areas, Dielmo and Ndiop (Senegal). Bull Mem Acad R Med Belg 155 :218–226.
Chenet SM, Schneider KA, Villegas L, Escalante AA, 2012. Local population structure of Plasmodium : impact on malaria control and elimination. Malar J 11 :1.
Smith JM, Smith NH, O’Rourke M, Spratt BG, 1993. How clonal are bacteria? Proc Natl Acad Sci USA 90 :4384–4388.
Razakandrainibe FG, Durand P, Koella JC, De Meeüs T, Rousset F, Ayala FJ, Renaud F, 2005. “Clonal” population structure of the malaria agent Plasmodium falciparum in high-infection regions. Proc Natl Acad Sci USA 102 :17388–17393.
Anderson TJ, Day KP, 2000. Geographical structure and sequence evolution as inferred from the Plasmodium falciparum S-antigen locus. Mol Biochem Parasitol 106 :321–326.
Gunawardena S, Ferreira MU, Kapilananda GMG, Wirth DF, Karunaweera ND, 2014. The Sri Lankan paradox: high genetic diversity in Plasmodium vivax populations despite decreasing levels of malaria transmission. Parasitology 2014 :880–890.
Hedrick PW, 1980. Hitchhiking: a comparison of linkage and partial selfing. Genetics 94 :791–808.
Alam MT et al.., 2011. Selective sweeps and genetic lineages of Plasmodium falciparum drug -resistant alleles in Ghana. J Infect Dis 203 :220–227.
Waltmann A et al.., 2017. Increasingly inbred and fragmented populations of Plasmodium vivax with declining transmission. BioRxiv, doi:10.1101/100610.
Jennison C et al.., 2015. Plasmodium vivax populations are more genetically diverse and less structured than sympatric Plasmodium falciparum populations. PLoS Negl Trop Dis 9 :1–20.
Batista CL, Barbosa S, Silva Bastos M, Viana SAS, Ferreira MU, 2015. Genetic diversity of Plasmodium vivax over time and space: a community-based study in rural Amazonia. Parasitology 2014 :1–11.
Escalante AA et al.., 2015. Malaria molecular epidemiology: lessons from the International Centers of Excellence for Malaria Research Network. Am J Trop Med Hyg 93 (Suppl): 79–86.
|Past two years||Past Year||Past 30 Days|
|Full Text Views||457||136||3|
Malaria control in West Africa is impeded by the large reservoir of chronic asymptomatic Plasmodium falciparum infections in the human population. This study aimed to assess the extent of diversity in the P. falciparum reservoir in Bongo District (BD), Ghana, at the end of the dry season, the lowest point in malaria transmission over the course of the year. Analysis of the variation in 12 microsatellite loci was completed for 200 P. falciparum isolates collected from a cross-sectional survey of residents of all ages from two catchment areas in BD. Analysis of the multilocus haplotypes showed high levels of genetic diversity (He = 0.74), no population differentiation yet significant linkage disequilibrium (LD) (ISA = 0.0127, P = 0.006) in BD. Multilocus LD was significant between and within catchment areas even though every haplotype in the population was unique and the majority of individuals (84.0%) harbored multiple-clone infections. The linkage structure among multilocus haplotypes was not associated with sampling location. These data provide the first study with deep sampling of the P. falciparum reservoir in an area of seasonal malaria transmission in West Africa. The co-occurrence of high multiplicity of infection (multiple-clone infections) with significant multilocus LD is surprising given the likelihood of high recombination rates in BD. The results suggest that the linkage structure among multilocus haplotypes has not been shaped by geographic separation of parasite populations. Furthermore, the observed LD levels provide a baseline population genetic metric with putatively neutral markers to evaluate the effects of seasonality and malaria control efforts in BD.
Financial support: This research was supported by the Fogarty International Center at National Institutes of Health (Program on the Ecology and Evolution of Infectious Diseases [EEID], Grant number: R01-TW009670).
Authors’ addresses: Shazia Ruybal-Pesántez, Kathryn E. Tiedje, and Karen P. Day, School of BioSciences, Bio21 Institute/The University of Melbourne, Melbourne, Australia, E-mails: firstname.lastname@example.org, email@example.com, and firstname.lastname@example.org. Mary M. Rorick, Department of Ecology and Evolution, University of Chicago, Chicago, IL, E-mail: email@example.com. Lucas Amenga-Etengo and Abraham R. Oduro, Navrongo Health Research Center, Navrongo, Ghana, E-mails: firstname.lastname@example.org and email@example.com. Anita Ghansah and Kwadwo A. Koram, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana, E-mails: firstname.lastname@example.org and email@example.com.