HIGH COMPLEXITY OF PLASMODIUM VIVAX INFECTIONS IN PAPUA NEW GUINEAN CHILDREN

JENNIFER L. COLE-TOBIAN Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio; Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea

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MOSES BIASOR Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio; Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea

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CHRISTOPHER L. KING Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio; Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea

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Although genetically distinct malaria parasites have been shown to simultaneously infect an individual, the total number of unique parasites has not been systematically studied. We examined multiple clones (8–38) from individual blood samples collected from Papua New Guinean children for polymorphisms in the Plasmodium vivax Duffy binding protein (dbpII) and the merozoite surface protein 3α (msp3α). We found a median of 4 (range = 2–6) and 12 (range = 2–23) unique genotypes based on dbpII and msp3α, respectively, per person at one time point and at least 12–33 unique genotypes per person over a four-month period. Control polymerase chain reactions (PCRs) detected 0–31% of clones with haplotypes that arose from PCR artifacts, indicating that caution must be taken when using PCR-based analysis to examine complex infections. To reduce artifacts from clones, analysis was based on haplotypes unlikely to have been generated by PCR artifacts or had been previously identified. Plasmodium vivax infections can be highly complex in disease-endemic areas, suggesting continual genetic mixing that could have significant implications for the use of antimalarial drugs and malaria vaccines.

Author Notes

Reprint requests: Christopher L. King, Center for Global Health and Disease, Case Western Reserve University, Wolstein Research Building 4-132, 2103 Cornell Rd., Cleveland, OH 44106.
  • 1

    Mendis K, Sina BJ, Marchesini P, Carter R, 2001. The neglected burden of Plasmodium vivax malaria. Am J Trop Med Hyg 64 :97–106.

  • 2

    Cui L, Escalante AA, Imwong M, Snounou G, 2003. The genetic diversity of Plasmodium vivax populations. Trends Parasitol 19 :220–226.

  • 3

    Conway DJ, McBride JS, 1991. Genetic evidence for the importance of interrupted feeding by mosquitoes in the transmission of malaria. Trans R Soc Trop Med Hyg 85 :454–456.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Burkot TR, Graves PM, Paru R, Lagog M, 1988. Mixed blood feeding by the malaria vectors in the Anopheles punctulatus complex (Diptera: Culicidae). J Med Entomol 25 :205–213.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Rosenberg R, Wirtz RA, Schneider I, Burge R, 1990. An estimation of the number of malaria sporozoites ejected by a feeding mosquito. Trans R Soc Trop Med Hyg 84 :209–212.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    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 :257–272.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    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 :1709–1711.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Babiker HA, 1998. Unstable malaria in Sudan: the influence of the dry season. Plasmodium falciparum population in the unstable malaria area of eastern Sudan is stable and genetically complex. Trans R Soc Trop Med Hyg 92 :585–589.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Engelbrecht F, Togel E, Beck HP, Enwezor F, Oettli A, Felger I, 2000. Analysis of Plasmodium falciparum infections in a village community in northern Nigeria: determination of msp2 genotypes and parasite-specific IgG responses. Acta Trop 74 :63–71.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Magesa SM, Mdira KY, Babiker HA, Alifrangis M, Farnert A, Simonsen PE, Bygbjerg IC, Walliker D, Jakobsen PH, 2002. Diversity of Plasmodium falciparum clones infecting children living in a holoendemic area in north-eastern Tanzania. Acta Trop 84 :83–92.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Babiker HA, Ranford-Cartwright LC, Walliker D, 1999. Genetic structure and dynamics of Plasmodium falciparum infections in the Kilombero region of Tanzania. Trans R Soc Trop Med Hyg 93 (Suppl 1):11–14.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Konate L, Zwetyenga J, Rogier C, Bischoff E, Fontenille D, Tall A, Spiegel A, Trape JF, Mercereau-Puijalon O, 1999. Variation of Plasmodium falciparum msp1 block 2 and msp2 allele prevalence and of infection complexity in two neighbouring Senegalese villages with different transmission conditions. Trans R Soc Trop Med Hyg 93 (Suppl 1):21–28.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Owusu-Agyei S, Smith T, Beck HP, Amenga-Etego L, Felger I, 2002. Molecular epidemiology of Plasmodium falciparum infections among asymptomatic inhabitants of a holoendemic malarious area in northern Ghana. Trop Med Int Health 7 :421–428.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Contamin H, Fandeur T, Bonnefoy S, Skouri F, Ntoumi F, Mercereau-Puijalon O, 1995. PCR typing of field isolates of Plasmodium falciparum.J Clin Microbiol 33 :944–951.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Farnert A, Arez AP, Babiker HA, Beck HP, Benito A, Bjorkman A, Bruce MC, Conway DJ, Day KP, Henning L, Mercereau-Puijalon O, Ranford-Cartwright LC, Rubio JM, Snounou G, Walliker D, Zwetyenga J, do Rosario VE, 2001. Genotyping of Plasmodium falciparum infections by PCR: a comparative multicentre study. Trans R Soc Trop Med Hyg 95 :225–232.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Suwanabun N, Sattabongkot J, Wirtz RA, Rosenberg R, 1994. The epidemiology of Plasmodium vivax circumsporozoite protein polymorphs in Thailand. Am J Trop Med Hyg 50 :460–464.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Cui L, Mascorro CN, Fan Q, Rzomp KA, Khuntirat B, Zhou G, Chen H, Yan G, Sattabongkot J, 2003. Genetic diversity and multiple infections of Plasmodium vivax malaria in western Thailand. Am J Trop Med Hyg 68 :613–619.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Joshi H, Subbarao SK, Adak T, Nanda N, Ghosh SK, Carter R, Sharma VA, 1997. Genetic structure of Plasmodium vivax isolates in India. Trans R Soc Trop Med Hyg 91 :231–235.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Cole-Tobian J, Cortes A, Baisor M, Kastens W, Xainli J, Bockarie M, Adams J, King C, 2002. Age-acquired immunity to a Plasmodium vivax invasion ligand, the Duffy binding protein. J Infect Dis 186 :531–539.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Kolakovich KA, Ssengoba A, Wojcik K, Tsuboi T, Al-Yaman F, Alpers M, Adams JH, 1996. Plasmodium vivax: favored gene frequencies of the merozoite surface protein-1 and the multiplicity of infection in a malaria endemic region. Exp Parasitol 83 :11–18.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    McKenzie FE, Jeffery GM, Collins WE, 2002. Plasmodium vivax blood-stage dynamics. J Parasitol 88 :521–535.

  • 22

    Farnert A, Snounou G, Rooth I, Bjorkman A, 1997. Daily dynamics of Plasmodium falciparum subpopulations in asymptomatic children in a holoendemic area. Am J Trop Med Hyg 56 :538–547.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Hall TA, 1999. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser 41 :95–98.

  • 24

    Bruce MC, Galinski MR, Barnwell JW, Snounou G, Day KP, 1999. Polymorphism at the merozoite surface protein-3alpha locus of Plasmodium vivax: global and local diversity. Am J Trop Med Hyg 61 :518–525.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    VanBuskirk KM, Cole-Tobian JL, Baisor M, Sevova ES, Bockarie M, King CL, Adams JH, 2004. Antigenic drift in the ligand domain of Plasmodium vivax Duffy binding protein confers resistance to inhibitory antibodies. J Infect Dis 190 :1556–1562.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Tanabe K, Sakihama N, Farnert A, Rooth I, Bjorkman A, Walliker D, Ranford-Cartwright L, 2002. In vitro recombination during PCR of Plasmodium falciparum DNA: a potential pitfall in molecular population genetic analysis. Mol Biochem Parasitol 122 :211–216.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Qiu X, Wu L, Huang H, McDonel PE, Palumbo AV, Tiedje JM, Zhou J, 2001. Evaluation of PCR-generated chimeras, mutations, and heteroduplexes with 16S rRNA gene-based cloning. Appl Environ Microbiol 67 :880–887.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Krotoski WA, 1989. The hypnozoite and malarial relapse. Prog Clin Parasitol 1 :1–19.

  • 29

    Ntoumi F, Contamin H, Rogier C, Bonnefoy S, Trape, JF, Mercerau-Puijalon O, 1995. Age-dependent carriage of multiple Plasmodium falciparum merozoite surface antigen-2 alleles in asymptomatic malaria infections. Am J Trop Med Hyg 51 :81–88.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Owusu-Agyei S, Fryauff DJ, Chandramohan D, Koram KA, Binka FN, Nkrumah FK, Utz GC, Hoffman SL, 2002. Characteristics of severe anemia and its association with malaria in young children of the Kassena-Nankana District of northern Ghana. Am J Trop Med Hyg 67 :371–377.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Imwong M, Pukrittakayamee S, Looareesuwan S, Poirriez J, Pasvol G, White NJ, Snounou G, 2001. Plasmodium vivax: polymerase chain reaction amplification artifacts limit the suitability of pvgam1 as a genetic marker. Exp Parasitol 99 :175–179.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Cline J, Braman JC, Hogrefe HH, 1996. PCR fidelity of pfu DNA polymerase and other thermostable DNA polymerases. Nucleic Acids Res 24 :3546–3551.

  • 33

    Jensen MA, Straus N, 1993. Effect of PCR conditions on the formation of heteroduplex and single-stranded DNA products in the amplification of bacterial ribosomal DNA spacer regions. PCR Methods Appl 3 :186–194.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34

    Carraway M, Marinus MG, 1993. Repair of heteroduplex DNA molecules with multibase loops in Escherichia coli.J Bacteriol 175 :3972–3980.

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