High Levels of Genetic Diversity of Plasmodium falciparum Populations in Papua New Guinea despite Variable Infection Prevalence

Alyssa E. Barry Centre for Population Health, Burnet Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne, Australia; Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Australia; Swiss Tropical and Public Health Institute, Basel, Switzerland; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; Barcelona Centre for International Health Research (CRESIB), Barcelona, Spain; School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia

Search for other papers by Alyssa E. Barry in
Current site
Google Scholar
PubMed
Close
,
Lee Schultz Centre for Population Health, Burnet Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne, Australia; Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Australia; Swiss Tropical and Public Health Institute, Basel, Switzerland; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; Barcelona Centre for International Health Research (CRESIB), Barcelona, Spain; School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia

Search for other papers by Lee Schultz in
Current site
Google Scholar
PubMed
Close
,
Nicholas Senn Centre for Population Health, Burnet Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne, Australia; Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Australia; Swiss Tropical and Public Health Institute, Basel, Switzerland; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; Barcelona Centre for International Health Research (CRESIB), Barcelona, Spain; School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia

Search for other papers by Nicholas Senn in
Current site
Google Scholar
PubMed
Close
,
Joe Nale Centre for Population Health, Burnet Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne, Australia; Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Australia; Swiss Tropical and Public Health Institute, Basel, Switzerland; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; Barcelona Centre for International Health Research (CRESIB), Barcelona, Spain; School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia

Search for other papers by Joe Nale in
Current site
Google Scholar
PubMed
Close
,
Benson Kiniboro Centre for Population Health, Burnet Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne, Australia; Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Australia; Swiss Tropical and Public Health Institute, Basel, Switzerland; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; Barcelona Centre for International Health Research (CRESIB), Barcelona, Spain; School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia

Search for other papers by Benson Kiniboro in
Current site
Google Scholar
PubMed
Close
,
Peter M. Siba Centre for Population Health, Burnet Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne, Australia; Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Australia; Swiss Tropical and Public Health Institute, Basel, Switzerland; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; Barcelona Centre for International Health Research (CRESIB), Barcelona, Spain; School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia

Search for other papers by Peter M. Siba in
Current site
Google Scholar
PubMed
Close
,
Ivo Mueller Centre for Population Health, Burnet Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne, Australia; Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Australia; Swiss Tropical and Public Health Institute, Basel, Switzerland; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; Barcelona Centre for International Health Research (CRESIB), Barcelona, Spain; School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia

Search for other papers by Ivo Mueller in
Current site
Google Scholar
PubMed
Close
, and
John C. Reeder Centre for Population Health, Burnet Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne, Australia; Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Australia; Swiss Tropical and Public Health Institute, Basel, Switzerland; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; Barcelona Centre for International Health Research (CRESIB), Barcelona, Spain; School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia

Search for other papers by John C. Reeder in
Current site
Google Scholar
PubMed
Close
Restricted access

High levels of genetic diversity in Plasmodium falciparum populations are an obstacle to malaria control. Here, we investigate the relationship between local variation in malaria epidemiology and parasite genetic diversity in Papua New Guinea (PNG). Cross-sectional malaria surveys were performed in 14 villages spanning four distinct malaria-endemic areas on the north coast, including one area that was sampled during the dry season. High-resolution msp2 genotyping of 2,147 blood samples identified 761 P. falciparum infections containing a total of 1,392 clones whose genotypes were used to measure genetic diversity. Considerable variability in infection prevalence and mean multiplicity of infection was observed at all of the study sites, with the area sampled during the dry season showing particularly striking local variability. Genetic diversity was strongly associated with multiplicity of infection but not with infection prevalence. In highly endemic areas, differences in infection prevalence may not translate into a decrease in parasite population diversity.

Author Notes

* Address correspondence to Alyssa E. Barry, Division of Infection and Immunity, Walter and Eliza Hall Institute for Medical Research, 1G Royal Parade, Parkville, Victoria, Australia, 3052. E-mail: barry@wehi.edu.au

Financial support: The samples used in the study were collected during a study of Intermittent Preventive Treatment in infants (IPTi) for malaria in Papua New Guinea supported by the Bill & Melinda Gates Foundation. This work was made possible with the support of the National Health and Medical Research Council (NHMRC) of Australia through project grant 488221 and a Research Fellowship awarded to JCR, the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS.

Authors' addresses: Alyssa E. Barry, Division of Infection and Immunity, Walter and Eliza Hall Institute for Medical Research, Victoria, Australia, E-mail: barry@wehi.edu.au. Lee Schultz, BioSciences Research Division, Department of Primary Industries, Victoria, Australia, E-mail: Lee.Schultz@dpi.vic.gov.au. Nicolas Senn, Swiss Tropical and Public Health Institute, Basel, Switzerland, E-mail: Nicolas.senn@gmail.com. Joe Nale, Benson Kiniboro, and Peter M. Siba, Papua New Guinea Institute of Medical Research, Papua New Guinea, E-mails: jnalejr@gmail.com, benson.kiniboro@pngimr.org.pg, and Peter.Siba@pngimr.org.pg. Ivo Mueller, Division of Infection and Immunity, Walter and Eliza Hall Institute for Medical Research, Victoria, Australia, E-mail: mueller@wehi.edu.au. John C. Reeder, Centre for Population Health, Burnet Institute, Victoria, Australia, E-mail: jreeder@burnet.edu.au.

  • 1.

    Feachem RG, Phillips AA, Targett GA, Snow RW, 2010. Call to action: priorities for malaria elimination. Lancet 376: 15171521.

  • 2.

    Anderson TJ, Haubold B, Williams JT, Estrada-Franco JG, Richardson L, Mollinedo R, Bockarie M, Mokili J, Mharakurwa S, French N, Whitworth J, Velez ID, Brockman AH, Nosten F, Ferreira MU, Day KP, 2000. Microsatellite markers reveal a spectrum of population structures in the malaria parasite Plasmodium falciparum. Mol Biol Evol 17: 14671482.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    DHaFer R, 2003. Correlation between fitness and genetic diversity. Conservation Ecology 17: 231237.

  • 4.

    Tanabe K, Mita T, Jombart T, Eriksson A, Horibe S, Palacpac N, Ranford-Cartwright L, Sawai H, Sakihama N, Ohmae H, Nakamura M, Ferreira MU, Escalante AA, Prugnolle F, Bjorkman A, Farnert A, Kaneko A, Horii T, Manica A, Kishino H, Balloux F, 2010. Plasmodium falciparum accompanied the human expansion out of Africa. Curr Biol 20: 12831289.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Mu J, Awadalla P, Duan J, McGee KM, Joy DA, McVean GA, Su XZ, 2005. Recombination hotspots and population structure in Plasmodium falciparum. PLoS Biol 3: e335.

  • 6.

    Joy DA, Feng X, Mu J, Furuya T, Chotivanich K, Krettli AU, Ho M, Wang A, White NJ, Suh E, Beerli P, Su XZ, 2003. Early origin and recent expansion of Plasmodium falciparum. Science 300: 318321.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Anthony TG, Conway DJ, Cox-Singh J, Matusop A, Ratnam S, Shamsul S, Singh B, 2005. Fragmented population structure of Plasmodium falciparum in a region of declining endemicity. J Infect Dis 191: 15581564.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Bogreau H, Renaud F, Bouchiba H, Durand P, Assi SB, Henry MC, Garnotel E, Pradines B, Fusai T, Wade B, Adehossi E, Parola P, Kamil MA, Puijalon O, Rogier C, 2006. Genetic diversity and structure of African Plasmodium falciparum populations in urban and rural areas. Am J Trop Med Hyg 74: 953959.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    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: 345349.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Leclerc MC, Durand P, de Meeus 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: 685692.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Tsumori Y, Ndounga M, Sunahara T, Hayashida N, Inoue M, Nakazawa S, Casimiro P, Isozumi R, Uemura H, Tanabe K, Kaneko O, Culleton R, 2011. Plasmodium falciparum: differential selection of drug resistance alleles in contiguous urban and peri-urban areas of Brazzaville, Republic of Congo. PLoS ONE 6: e23430.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Takala SL, Plowe CV, 2009. Genetic diversity and malaria vaccine design, testing and efficacy: preventing and overcoming ‘vaccine resistant malaria’. Parasite Immunol 31: 560573.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Mehlotra RK, Fujioka H, Roepe PD, Janneh O, Ursos LM, Jacobs-Lorena V, McNamara DT, Bockarie MJ, Kazura JW, Kyle DE, Fidock DA, Zimmerman PA, 2001. Evolution of a unique Plasmodium falciparum chloroquine-resistance phenotype in association with pfcrt polymorphism in Papua New Guinea and South America. Proc Natl Acad Sci USA 98: 1268912694.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Hetzel MW, 2009. An integrated approach to malaria control in Papua New Guinea. P N G Med J 52: 17.

  • 15.

    Mueller I, Widmer S, Daniela M, Maraga S, McNamara DT, Kiniboro B, Sie A, Smith TA, Zimmerman PA, 2009. High sensitivity detection of Plasmodium species reveals positive correlations between infections of different species, shifts in age distribution and reduced local variation in Papua New Guinea. Malar J 8: 4155.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Bruce MC, Galinski MR, Barnwell JW, Donnelly CA, Walmsley M, Alpers MP, Walliker D, Day KP, 2000. Genetic diversity and dynamics of Plasmodium falciparum and P. vivax populations in multiply infected children with asymptomatic malaria infections in Papua New Guinea. Parasitology 121: 257272.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Cortes A, Felger I, Beck HP, 2003. Molecular parasitology of malaria in Papua New Guinea. Trends Parasitol 19: 246249.

  • 18.

    Schultz L, Wapling J, Mueller I, Ntsuke PO, Senn N, Nale J, Kiniboro B, Buckee CO, Tavul L, Siba PM, Reeder JC, Barry AE, 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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Falk N, Maire N, Sama W, Owusu-Agyei S, Smith T, Beck HP, Felger I, 2006. Comparison of PCR-RFLP and Genescan-based genotyping for analyzing infection dynamics of Plasmodium falciparum. Am J Trop Med Hyg 74: 944950.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Schoepflin S, Valsangiacomo F, Lin E, Kiniboro B, Mueller I, Felger I, 2009. Comparison of Plasmodium falciparum allelic frequency distribution in different endemic settings by high-resolution genotyping. Malar J 8: 250.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Burkot TR, Graves PM, Paru R, Wirtz RA, Heywood PF, 1988. Human malaria transmission studies in the Anopheles punctulatus complex in Papua New Guinea: sporozoite rates, inoculation rates, and sporozoite densities. Am J Trop Med Hyg 39: 135144.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Michon P, Cole-Tobian JL, Dabod E, Schoepflin S, Igu J, Susapu M, Tarongka N, Zimmerman PA, Reeder JC, Beeson JG, Schofield L, King CL, Mueller I, 2007. The risk of malarial infections and disease in Papua New Guinean children. Am J Trop Med Hyg 76: 9971008.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Paul RE, Packer MJ, Walmsley M, Lagog M, Ranford-Cartwright LC, Paru R, Day KP, 1995. Mating patterns in malaria parasite populations of Papua New Guinea. Science 269: 17091711.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Genton B, al-Yaman F, Beck HP, Hii J, Mellor S, Narara A, Gibson N, Smith T, Alpers MP, 1995. The epidemiology of malaria in the Wosera area, East Sepik Province, Papua New Guinea, in preparation for vaccine trials. I. Malariometric indices and immunity. Ann Trop Med Parasitol 89: 359376.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Genton B, al-Yaman F, Beck HP, Hii J, Mellor S, Rare L, Ginny M, Smith T, Alpers MP, 1995. The epidemiology of malaria in the Wosera area, East Sepik Province, Papua New Guinea, in preparation for vaccine trials. II. Mortality and morbidity. Ann Trop Med Parasitol 89: 377390.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Hii JL, Smith T, Mai A, Ibam E, Alpers MP, 2000. Comparison between anopheline mosquitoes (Diptera: Culicidae) caught using different methods in a malaria endemic area of Papua New Guinea. Bull Entomol Res 90: 211219.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Bockarie MJ, Alexander N, Bockarie F, Ibam E, Barnish G, Alpers M, 1996. The late biting habit of parous Anopheles mosquitoes and pre-bedtime exposure of humans to infective female mosquitoes. Trans R Soc Trop Med Hyg 90: 2325.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Hii JL, Smith T, Vounatsou P, Alexander N, Mai A, Ibam E, Alpers MP, 2001. Area effects of bednet use in a malaria-endemic area in Papua New Guinea. Trans R Soc Trop Med Hyg 95: 713.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Kasehagen LJ, Mueller I, McNamara DT, Bockarie MJ, Kiniboro B, Rare L, Lorry K, Kastens W, Reeder JC, Kazura JW, Zimmerman PA, 2006. Changing patterns of Plasmodium blood-stage infections in the Wosera region of Papua New Guinea monitored by light microscopy and high throughput PCR diagnosis. Am J Trop Med Hyg 75: 588596.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Senn N, Rarau P, Stanisic DI, Robinson L, Barnadas C, Manong D, Salib M, Iga J, Tarongka N, Ley S, Rosanas-Urgell A, Aponte JJ, Zimmerman PA, Beeson JG, Schofield L, Siba P, Rogerson SJ, Reeder JC, Mueller I, 2012. Intermittent preventive treatment for malaria in Papua New Guinean infants exposed to Plasmodium falciparum and P. vivax: a randomized controlled trial. PLoS Med 9: e1001195.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Lin E, Kiniboro B, Gray L, Dobbie S, Robinson L, Laumaea A, Schopflin S, Stanisic D, Betuela I, Blood-Zikursh M, Siba P, Felger I, Schofield L, Zimmerman P, Mueller I, 2010. Differential patterns of infection and disease with P. falciparum and P. vivax in young Papua New Guinean children. PLoS ONE 5: e9047.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Smith DL, Guerra CA, Snow RW, Hay SI, 2007. Standardizing estimates of the Plasmodium falciparum parasite rate. Malar J 6: 131.

  • 33.

    Malaria Atlas Project, 2011. Available at: http://www.map.ox.ac.uk.

  • 34.

    Goudet J, 1995. FSTAT (Version 1.2): a computer program to calculate F-statistics. J Hered 86: 485486.

  • 35.

    Hurlbert SH, 1971. The non-concept of species diversity: a critique and alternative parameters. Ecology 52: 577586.

  • 36.

    Liljander A, Wiklund L, Falk N, Kweku M, Martensson A, Felger I, Farnert A, 2009. Optimization and validation of multi-colored capillary electrophoresis for genotyping of Plasmodium falciparum merozoite surface proteins (msp1 and 2). Malar J 8: 78.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Cattani JA, Tulloch JL, Vrbova H, Jolley D, Gibson FD, Moir JS, Heywood PF, Alpers MP, Stevenson A, Clancy R, 1986. The epidemiology of malaria in a population surrounding Madang, Papua New Guinea. Am J Trop Med Hyg 35: 315.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Genton B, Betuela I, Felger I, Al-Yaman F, Anders RF, Saul A, Rare L, Baisor M, Lorry K, Brown GV, Pye D, Irving DO, Smith TA, Beck HP, Alpers MP, 2002. A recombinant blood-stage malaria vaccine reduces Plasmodium falciparum density and exerts selective pressure on parasite populations in a phase 1-2b trial in Papua New Guinea. J Infect Dis 185: 820827.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Felger I, Tavul L, Kabintik S, Marshall V, Genton B, Alpers M, Beck HP, 1994. Plasmodium falciparum: extensive polymorphism in merozoite surface antigen 2 alleles in an area with endemic malaria in Papua New Guinea. Exp Parasitol 79: 106116.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40.

    Hartl DL, Clark AG, 1997. Principles of Population Genetics. Sunderland, MD: Sinauer Associates.

  • 41.

    Sanders PR, Gilson PR, Cantin GT, Greenbaum DC, Nebl T, Carucci DJ, McConville MJ, Schofield L, Hodder AN, Yates JR 3rd, Crabb BS, 2005. Distinct protein classes including novel merozoite surface antigens in Raft-like membranes of Plasmodium falciparum. J Biol Chem 280: 4016940176.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42.

    al-Yaman F, Genton B, Anders R, Taraika J, Ginny M, Mellor S, Alpers MP, 1995. Assessment of the role of the humoral response to Plasmodium falciparum MSP2 compared to RESA and SPf66 in protecting Papua New Guinean children from clinical malaria. Parasite Immunol 17: 493501.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43.

    Stanisic DI, Richards JS, McCallum FJ, Michon P, King CL, Schoepflin S, Gilson PR, Murphy VJ, Anders RF, Mueller I, Beeson JG, 2009. Immunoglobulin G subclass-specific responses against Plasmodium falciparum merozoite antigens are associated with control of parasitemia and protection from symptomatic illness. Infect Immun 77: 11651174.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44.

    Babiker HA, Ranford-Cartwright LC, Currie D, Charlwood JD, Billingsley P, Teuscher T, Walliker D, 1994. Random mating in a natural population of the malaria parasite Plasmodium falciparum. Parasitology 109: 413421.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45.

    Gatei W, Kariuki S, Hawley W, ter Kuile F, Terlouw D, Phillips-Howard P, Nahlen B, Gimnig J, Lindblade K, Walker E, Hamel M, Crawford S, Williamson J, Slutsker L, Shi YP, 2010. Effects of transmission reduction by insecticide-treated bed nets (ITNs) on parasite genetics population structure: I. The genetic diversity of Plasmodium falciparum parasites by microsatellite markers in western Kenya. Malar J 9: 353.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 46.

    Sutton PL, Torres LP, Branch OH, 2011. Sexual recombination is a signature of a persisting malaria epidemic in Peru. Malar J 10: 329.

Past two years Past Year Past 30 Days
Abstract Views 92 92 11
Full Text Views 459 21 0
PDF Downloads 153 16 0
 
Membership Banner
 
 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save