HIGH FREQUENCY OF RECOMBINATION-DRIVEN ALLELIC DIVERSITY AND TEMPORAL VARIATION OF PLASMODIUM FALCIPARUM MSP1 IN TANZANIA

KAZUYUKI TANABE Laboratory of Malariology, International Research Center of Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; Nyamisati Malaria Research Unit, Dar es Salaam, Tanzania; Unit of Infectious Diseases, Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden

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NAOKO SAKIHAMA Laboratory of Malariology, International Research Center of Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; Nyamisati Malaria Research Unit, Dar es Salaam, Tanzania; Unit of Infectious Diseases, Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden

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INGEGERD ROOTH Laboratory of Malariology, International Research Center of Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; Nyamisati Malaria Research Unit, Dar es Salaam, Tanzania; Unit of Infectious Diseases, Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden

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ANDERS BJÖRKMAN Laboratory of Malariology, International Research Center of Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; Nyamisati Malaria Research Unit, Dar es Salaam, Tanzania; Unit of Infectious Diseases, Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden

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ANNA FÄRNERT Laboratory of Malariology, International Research Center of Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; Nyamisati Malaria Research Unit, Dar es Salaam, Tanzania; Unit of Infectious Diseases, Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden

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A major mechanism for the generation allelic diversity in the Plasmodium falciparum msp1 gene is meiotic recombination in the Anopheles mosquito. The frequency of recombination events is dependent on the intensity of transmission. Herein we investigate the frequency of recombination-driven allelic diversity and temporal variation of msp1 in Rufiji, eastern coastal Tanzania, where malaria transmission is intense. We identified 5′ recombinant types, 3′ sequence types, and msp1 haplotypes (unique associations of 5′ recombinant types and 3′ sequence types) to measure the extent and temporal variation of msp1 allelic diversity. The results show that msp1 haplotype diversity is higher in Tanzania as compared with areas with lower transmission rates. The frequencies of individual polymorphic regions/sites remained stable during the study period. However, the frequency distribution of msp1 haplotypes varied between 1993 and 1998. These results suggest that frequent recombination events between msp1 alleles intermittently generate novel alleles in high transmission areas.

Author Notes

Reprint requests: Kazuyuki Tanabe, Laboratory of Malariology, International Research Center of Infectious Diseases, Research Institute for Microbial Diseases Osaka University, 3-1, Yamada-Oka, Suita, 565-0871, Japan. Telephone: +81-6-6879-4260, Fax: +81-6-6879-4262, E-mail: kztanabe@biken.osaka-u.ac.jp.
  • 1

    Holder AA, Guevara Patino JA, Uthaipibull C, Syed SE, Ling IT, Scott-Finnigan T, Blackman MJ, 1999. Merozoite surface protein 1, immune evasion, and vaccine against asexual blood stage malaria. Parassitologia 41 :409–414.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Mahanty S, Saul A, Miller LH, 2003. Progress in the development of recombinant and synthetic blood-stage malaria vaccines. J Exp Biol 206 :3781–3788.

  • 3

    Conway DJ, Cavanagh DR, Tanabe K, Roper C, Mikes ZS, Sakihama N, Bojang KA, Oduola AMJ, Kremsner PG, Arnot DE, Greenwood BM, McBride JS, 2000. A principal target of human immunity to malaria identified by molecular population genetic and immunological analyses. Nat Med 6 :689–692.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Blackman MJ, Ling IT, Nicholls SC, Holder AA, 1991. Proteolytic processing of the Plasmodium falciparum merozoite surface protein-1 produces a membrane-bound fragment containing two epidermal growth factor-like domains. Mol Biochem Parasitol 49 :29–34.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Chang SP, Gibson HL, Lee-Ng CT, Barr PJ, Hui GS, 1992. A carboxyl-terminal fragment of Plasmodium falciparum gp195 expressed by a recombinant baculovirus induces antibodies that completely inhibit parasite growth. J Immunol 149 :548–555.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Kumar S, Yadava A, Keister DB, Tian JH, Ohl M, Perdue-Greenfield KA, Miller LH, Kaslow DC, 1995. Immunogenicity and in vivo efficacy of recombinant Plasmodium falciparum merozoite surface protein-1 in Aotus monkeys. Mol Med 1 :325–333.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Egan AF, Morris J, Barnish G, Allen S, Greenwood BM, Kaslow DC, Holder AA, Riley EM, 1996. Clinical immunity to Plasmodium falciparum malaria is associated with serum antibodies to the 19-kDa C-terminal fragment of the merozoite surface antigen, PfMSP-1. J Inf Dis 173 :765–769.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Nwuba R, Sodeinde O, Anumudu C, Omosum Y, Odaibo A, Holder A, Nwagwu M, 2002. The human immune response to Plasmodium falciparum includes both antibodies that inhibit merozoite surface protein 1 secondary processing and blocking antibodies. Infect Immun 70 :5328–5331.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    O’Donnel RA, de Koning-Ward TF, Burr RA, Bockarie M, Reeder JC, Cowman A, Crabb B, 2001. Antibodies against merozoite surface protein (MSP)-119 are a major component of the invasion-inhibitory response in individuals immune to malaria. J Exp Med 193 :1403–1412.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Tanabe K, Mackay M, Goman M, Scaife JG, 1987. Allelic dimorphism in a surface antigen gene of the malaria parasite Plasmodium falciparum.J Mol Biol 195 :273–287.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Miller LH, Roberts T, Shahabuddin M, McCutchan TF, 1993. Analysis of genetic diversity in the Plasmodium falciparum merozoite surface protein-1 (MSP1). Mol Biochem Parasitol 59 :1–14.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Martinelli A, Cheesman S, Hunt P, Culleton R, Raza A, Mackinnon M, Carter R, 2005. A genetic approach to the de novo identification of targets of strain specific immunity in malaria parasites. Proc Natl Acad Sci USA 102 :814–819.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Cheesman S, Raza A, Carter R, 2006. Mixed strain infections and strain-specific protective immunity in the rodent malaria parasite Plasmodium chabaudi chabaudi in mice. Infect Immun 74 :2996–3001.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Tanabe K, Sakihama N, Kaneko A, 2004. Stable SNPs in malaria antigen genes in isolated populations. Science 303 :493.

  • 15

    Polley SD, Weedal GD, Thomas AW, Golightly LM, Conway DJ, 2005. Orthologous gene sequences of merozoite surface protein 1 (MSP1) from Plasmodium reichenowi and P. gallinaceum confirm an ancient divergence of P. falciparum alleles. Mol Biochem Parasitol 142 :25–31.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Ferreira MU, Ribeiro WL, Tonon AP, Kawamoto F, Rich SM, 2003. Sequence diversity and evolution of the malaria vaccine candidate merozoite surface protein-1 (MSP1) of Plasmodium falciparum.Gene 304 :65–75.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Snounou G, Zhu X, Siripoon N, Jarra W, Thaithong S, Brown KN, Viriyakosol S, 1999. Biased distribution of msp1 and msp2 allelic variants in Plasmodium falciparum populations in Thailand. Trans R Soc Trop Med Hyg 93 :369–374.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Rooth I, Björkman A, 1992. Fever episodes in a holoendemic area of Tanzania: parasitological and clinical findings and diagnostic aspects related to malaria. Trans R Soc Trop Med Hyg 86 :479–482.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Hay SI, Rogers DJ, Toomer JF, Snow RW, 2000. Annual Plasmodium falciparum entomological inoculation rates (EIR) across Africa: literature survey, internet access and review. Trans R Soc Trop Med Hyg 94 :113–127.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Sakihama N, Ohmae H, Bakote B, Kawabata M, Hirayama K, Tanabe K, 2006. Limited allelic diversity of Plasmodium falciparum msp1 from populations in The Solomon Islands, a highly endemic area. Am J Trop Med Hyg 74 :31–40.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Sakihama N, Kimura M, Hirayama K, Kanda T, Na-Bangchang K, Jongwutiwes S, Conway D, Tanabe K, 1999. Allelic recombination and linkage disequilibrium within Msp1 of Plasmodium falciparum, the malignant human malaria parasite. Gene 230 :47–54.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Tanabe K, Sakihama N, Färnert A, Rooth I, Björkman 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
  • 23

    Qari SH, Shi YP, Goldman IF, Nahlen BL, Tibayrenc M, Lal AA, 1998. Predicted and observed alleles of Plasmodium falciparum merozoite surface protein-1 (MSP-1), a potential malaria vaccine antigen. Mol Biochem Parasitol 92 :241–252.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Tanabe K, Sakihama N, Nakamura Y, Kaneko O, Kimura M, Ferreira MU, Hirayama K, 2000. Selection and genetic drift of polymorphisms within the merozoite surface protein-1 gene of Plasmodium falciparum.Gene 241 :325–331.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Ferreira MU, Liu Q, Kimura M, Tanabe K, Kawamoto F, 1998. Allelic diversity in the merozoite surface protein-1 and epidemiology of multiple-clone Plasmodium falciparum infections in northern Tanzania. J Parasitol 84 :1286–1289.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Babiker H, Walliker D, 1997. Current views on the population structure of Plasmodium falciparum: implications for control. Parasitol Today 13 :262–267.

  • 27

    Mu J, Awadalla P, Duan J, McGee KM, Joy DA, McVean GAT, Su AZ, 2005. Recombination hot spots and population structure in Plasmodium falciparum.PLoS Biol 3 :1734–1741.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Conway DJ, Roper C, Oduola AM, Arnot DE, Kremsner PG, Grobusch MP, Curtis CF, Greenwood BM, 1999. High recombination rate in natural populations of Plasmodium falciparum.Proc Natl Acad Sci USA 96 :4506–4511.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Silva NS, Silveira LA, Machado RL, Povoa MM, Ferreira MU, 2000. Temporal and spatial distribution of the variants of merozoite surface protein-1 (MSP-1) in Plasmodium falciparum populations in Brazil. Ann Trop Med Parasitol 94 :675–688.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Beck HP, Felger I, Huber W, Steiger S, Smith T, Weiss N, Alonso P, Tanner M, 1997. Analysis of multiple Plasmodium falciparum infections in Tanzanian children during the phase III trials of the malaria vaccine SPf66. J Inf Dis 175 :921–926.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Contamin H, Fandeur T, Rogier C, Bonnefoy S, Trape JF, Mercereau-Puijalon O, 1996. Different genetic characteristics of Plasmodium falciparum isolates collected during successive clinical malaria episodes in Senegalese children. Am J Trop Med Hyg 54 :632–643.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Färnert A, Rooth I, Svensson A, Snounou G, Bjorkman A, 1999. Complexity of Plasmodium falciparum infections is consistent over time and protects against clinical disease in Tanzanian children. J Infect Dis 179 :989–995.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Woehlbier U, Epp C, Kauth CW, Lutz R, Long CA, Coulibaly B, Kouyaté B, Arevalo-Herrera M, Herrera S, Bujard H, 2006. Analysis of antibodies directed against merozoite surface protein 1 of the human malaria parasite Plasmodium falciparum.Infect Immun 74 :1313–1322.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34

    Ekaka MT, Jouin H, Lekoulou F, Issifou S, Mercereau-Puijalon O, Ntoumi F, 2002. Plasmodium falciparum merozoite surface protein 1 (MSP1) genotyping and humoral responses to allele-specific variants. Acta Trop 81 :33–46.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35

    Fraser-Hurt N, Felger I, Edoh D, Steiger S, Mashaka M, Masanja H, Smith T, Mbena F, Beck HP, 1999. Effect of insecticide-treated bed nets on haemoglobin values, prevalence and multiplicity of infection with Plasmodium falciparum in a randomized controlled trial in Tanzania. Trans R Soc Trop Med Hyg 93 (Suppl 1):47–51.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36

    Bereczky S, Liljander A, Rooth I, Faraja L, Montgomery SM, Färnert A, 2007. Multiclonal asymptomatic Plasmodium falciparum infections predict a reduced risk of malaria disease in a Tanzanian population. Microbes Infect 9 :103–110.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37

    Conway DJ, Greenwood BM, McBride JS, 1992. Longitudinal study of Plasmodium falciparum polymorphic antigens in a malaria-endemic population. Infect Immun 60 :1122–1127.

    • PubMed
    • Search Google Scholar
    • Export Citation
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