• 1

    Smith T, Vounatsou P, 2003. Estimation of infection and recovery rates for highly polymorphic parasites when detectability is imperfect, using hidden Markov models. Stat Med 22 :1709–1724.

    • Search Google Scholar
    • Export Citation
  • 2

    Ntoumi F, Contamin H, Rogier C, Bonnefoy S, Trape JF, Mercereau-Puijalon O, 1995. Age-dependent carriage of multiple Plasmodium falciparum merozoite surface antigen-2 alleles in asymptomatic malaria infections. Am J Trop Med Hyg 52 :81–88.

    • Search Google Scholar
    • Export Citation
  • 3

    Felger I, Irion A, Steiger S, Beck HP, 1999. Genotypes of merozoite surface protein 2 of Plasmodium falciparum in Tanzania. Trans R Soc Trop Med Hyg 93 (suppl 1):3–9.

    • Search Google Scholar
    • Export Citation
  • 4

    Smith T, Felger I, Tanner M, Beck HP, 1999. Premunition in Plasmodium falciparum infection: insights from the epidemiology of multiple infections. Trans R Soc Trop Med Hyg 93 (suppl 1):59–64.

    • Search Google Scholar
    • Export Citation
  • 5

    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.

    • Search Google Scholar
    • Export Citation
  • 6

    Bruce MC, Donnelly CA, Packer M, Lagog M, Gibson N, Narara A, Walliker D, Alpers MP, Day KP, 2000. Age- and species-specific duration of infection in asymptomatic malaria infections in Papua New Guinea. Parasitology 121 :247–256.

    • Search Google Scholar
    • Export Citation
  • 7

    Smith T, Felger I, Fraser-Hurt N, Beck HP, 1999. Effect of insecticide-treated bed nets on the dynamics of multiple Plasmodium falciparum infections. Trans R Soc Trop Med Hyg 93 (suppl 1):53–57.

    • Search Google Scholar
    • Export Citation
  • 8

    Sama W, Owusu-Agyei S, Felger I, Vounatsou P, Smith T, 2005. An immigration-death model to estimate the duration of malaria infection when detectability of the parasite is imperfect. Stat Med 24: 3269–3288.

    • Search Google Scholar
    • Export Citation
  • 9

    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 :106–116.

    • Search Google Scholar
    • Export Citation
  • 10

    Binka FN, Morris SS, Ross DA, Arthur P, Aryeetey ME, 1994. Patterns of malaria morbidity and mortality in children in northern Ghana. Trans R Soc Trop Med Hyg 88 :381–385.

    • Search Google Scholar
    • Export Citation
  • 11

    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.

    • Search Google Scholar
    • Export Citation
  • 12

    Felger I, Beck HP, 2002. Genotyping of Plasmodium falciparum. PCR-RFLP analysis. Methods Mol Med 72 :117–129.

  • 13

    Brownstein MJ, Carpten JD, Smith JR, 1996. Modulation of non-templated nucleotide addition by Taq DNA polymerase: primer modifications that facilitate genotyping. Biotechniques 20 :1004–1006.

    • Search Google Scholar
    • Export Citation
  • 14

    Beck HP, 2002. Extraction and purification of Plasmodium parasite DNA. Methods Mol Med 72 :159–163.

  • 15

    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 :820–827.

    • Search Google Scholar
    • Export Citation
  • 16

    Felger I, Smith T, Edoh D, Kitua A, Alonso P, Tanner M, Beck HP, 1999. Multiple Plasmodium falciparum infections in Tanzanian infants. Trans R Soc Trop Med Hyg 93 (suppl 1):29–34.

    • Search Google Scholar
    • Export Citation
  • 17

    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.

    • Search Google Scholar
    • Export Citation
  • 18

    Irion A, Felger I, Abdulla S, Smith T, Mull R, Tanner M, Hatz C, Beck HP, 1998. Distinction of recrudescences from new infections by PCR-RFLP analysis in a comparative trial of CGP 56 697 and chloroquine in Tanzanian children. Trop Med Int Health 3 :490–497.

    • Search Google Scholar
    • Export Citation
  • 19

    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 Thai-land. Trans R Soc Trop Med Hyg 93 :369–374.

    • Search Google Scholar
    • Export Citation
  • 20

    Ranford-Cartwright LC, Balfe P, Carter R, Walliker D, 1993. Frequency of cross-fertilization in the human malaria parasite Plasmodium falciparum. Parasitology 107 :11–18.

    • Search Google Scholar
    • Export Citation
  • 21

    Hill WG, Babiker HA, 1995. Estimation of numbers of malaria clones in blood samples. Proc Biol Sci 262 :249–257.

  • 22

    Jafari S, Le Bras J, Bouchaud O, Durand R, 2004. Plasmodium falciparum clonal population dynamics during malaria treatment. J Infect Dis 189 :195–203.

    • Search Google Scholar
    • Export Citation
  • 23

    Felger I, Genton B, Smith T, Tanner M, Beck HP, 2003. Molecular monitoring in malaria vaccine trials. Trends Parasitol 19 :60–63.

  • 24

    Bojang KA, Milligan PJ, Pinder M, Vigneron L, Alloueche A, Kester KE, Ballou WR, Conway DJ, Reece WH, Gothard P, Yamuah L, Delchambre M, Voss G, Greenwood BM, Hill A, McAdam KP, Tornieporth N, Cohen JD, Doherty T, 2001. Malaria Vaccine Trial Team. Efficacy of RTS,S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomized trial. Lancet 358 :1927–1934.

    • Search Google Scholar
    • Export Citation
 
 
 

 

 

 

 

 

 

COMPARISON OF PCR-RFLP AND GENESCAN–BASED GENOTYPING FOR ANALYZING INFECTION DYNAMICS OF PLASMODIUM FALCIPARUM

View More View Less
  • 1 Swiss Tropical Institute, Basel, Switzerland; Navrongo Health Research Center, Navrongo, Ghana

Parameters describing the infection dynamics of Plasmodium falciparum are important determinants of the potential impact of interventions and are potential outcome measurements for malaria intervention trials. Low parasite densities, periodic sequestration of parasites, and the presence of multiple concurrent infections make it essential to use molecular techniques to estimate the force of infection and duration of infections in endemic areas. We now compare two approaches for tracking individual genotypes of the highly polymorphic merozoite surface protein 2: 1) fluorescence-labeled polymerase chain reaction (PCR) and GeneScan-sizing and 2) restriction fragment length polymorphism (RFLP). We analyze samples from a longitudinal field study in Ghana and use statistical approaches that allow for imperfect detectability. The two methods gave broadly similar estimates of parasite dynamics, but GeneScan is more precise and can achieve a higher throughput. The analysis of parasite dynamics indicated an average duration of infection of 210 days by GeneScan versus 152 days by PCR-RFLP in the study population in Kassena-Nankana, Northern Ghana. This reflects the good performance of GeneScan-based genotyping for studies of parasite infection dynamics.

Save