LOW MULTIPLICATION RATES OF AFRICAN PLASMODIUM FALCIPARUM ISOLATES AND LACK OF ASSOCIATION OF MULTIPLICATION RATE AND RED BLOOD CELL SELECTIVITY WITH MALARIA VIRULENCE

ANNE-MARIE DEANS Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom; Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Malaria Research and Training Center, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Centre for Geographic Medicine Research Coast/Wellcome Trust Collaborative Program, Kenya Medical Research Institute, Kilifi, Kenya

Search for other papers by ANNE-MARIE DEANS in
Current site
Google Scholar
PubMed
Close
,
KIRSTEN E. LYKE Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom; Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Malaria Research and Training Center, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Centre for Geographic Medicine Research Coast/Wellcome Trust Collaborative Program, Kenya Medical Research Institute, Kilifi, Kenya

Search for other papers by KIRSTEN E. LYKE in
Current site
Google Scholar
PubMed
Close
,
MAHAMADOU A. THERA Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom; Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Malaria Research and Training Center, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Centre for Geographic Medicine Research Coast/Wellcome Trust Collaborative Program, Kenya Medical Research Institute, Kilifi, Kenya

Search for other papers by MAHAMADOU A. THERA in
Current site
Google Scholar
PubMed
Close
,
CHRISTOPHER V. PLOWE Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom; Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Malaria Research and Training Center, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Centre for Geographic Medicine Research Coast/Wellcome Trust Collaborative Program, Kenya Medical Research Institute, Kilifi, Kenya

Search for other papers by CHRISTOPHER V. PLOWE in
Current site
Google Scholar
PubMed
Close
,
ABDOULAYE KONÉ Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom; Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Malaria Research and Training Center, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Centre for Geographic Medicine Research Coast/Wellcome Trust Collaborative Program, Kenya Medical Research Institute, Kilifi, Kenya

Search for other papers by ABDOULAYE KONÉ in
Current site
Google Scholar
PubMed
Close
,
OGOBARA K. DOUMBO Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom; Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Malaria Research and Training Center, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Centre for Geographic Medicine Research Coast/Wellcome Trust Collaborative Program, Kenya Medical Research Institute, Kilifi, Kenya

Search for other papers by OGOBARA K. DOUMBO in
Current site
Google Scholar
PubMed
Close
,
OSCAR KAI Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom; Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Malaria Research and Training Center, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Centre for Geographic Medicine Research Coast/Wellcome Trust Collaborative Program, Kenya Medical Research Institute, Kilifi, Kenya

Search for other papers by OSCAR KAI in
Current site
Google Scholar
PubMed
Close
,
KEVIN MARSH Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom; Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Malaria Research and Training Center, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Centre for Geographic Medicine Research Coast/Wellcome Trust Collaborative Program, Kenya Medical Research Institute, Kilifi, Kenya

Search for other papers by KEVIN MARSH in
Current site
Google Scholar
PubMed
Close
,
MARGARET J. MACKINNON Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom; Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Malaria Research and Training Center, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Centre for Geographic Medicine Research Coast/Wellcome Trust Collaborative Program, Kenya Medical Research Institute, Kilifi, Kenya

Search for other papers by MARGARET J. MACKINNON in
Current site
Google Scholar
PubMed
Close
,
AHMED RAZA Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom; Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Malaria Research and Training Center, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Centre for Geographic Medicine Research Coast/Wellcome Trust Collaborative Program, Kenya Medical Research Institute, Kilifi, Kenya

Search for other papers by AHMED RAZA in
Current site
Google Scholar
PubMed
Close
, and
J. ALEXANDRA ROWE Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom; Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Malaria Research and Training Center, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Centre for Geographic Medicine Research Coast/Wellcome Trust Collaborative Program, Kenya Medical Research Institute, Kilifi, Kenya

Search for other papers by J. ALEXANDRA ROWE in
Current site
Google Scholar
PubMed
Close
Restricted access

Two potential malaria virulence factors, parasite multiplication rate (PMR) and red blood cell selectivity (measured as selectivity index [SI]), were assessed in Plasmodium falciparum clinical isolates from Mali and Kenya. At both sites, PMRs were low (Kenya median = 2.2, n = 33; Mali median = 2.6, n = 61) and did not differ significantly between uncomplicated and severe malaria cases. Malian isolates from hyperparasitemic patients had significantly lower PMRs (median = 1.8, n = 19) than other Malian isolates (uncomplicated malaria median = 3.1, n = 23; severe malaria median = 2.8, n = 19; P = 0.03, by Kruskal-Wallis test). Selective invasion occurred at both sites (Kenya geometric mean SI = 1.9, n = 98; Mali geometric mean SI = 1.6, n = 104), and there was no significant association between the SI and malaria severity. Therefore, in contrast to previous results from Thailand, we found no association of PMR and SI with malaria severity in African children. This raises the possibility of differences in the mechanisms of malaria virulence between sub-Saharan Africa and Asia.

Author Notes

Reprint requests: J. Alexandra Rowe, Institute of Immunology and Infection Research, University of Edinburgh, West Mains Road, Ed-inburgh, EH9 3JT, United Kingdom.
  • 1

    Miller LH, Baruch DI, Marsh K, Doumbo OK, 2002. The pathogenic basis of malaria. Nature 415 :673–679.

  • 2

    James SP, Nicol WD, Shute PG, 1932. A study of induced malignant tertian malaria. Proc R Soc Med 25 :1153–1181.

  • 3

    Anderson RM, May RM, 1982. Coevolution of hosts and parasites. Parasitology 85 :411–426.

  • 4

    Mackinnon MJ, Read AF, 1999. Genetic relationship between parasite virulence and transmission in the rodent malaria Plasmodium chabaudi. Evolution 53 :689–703.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Mackinnon MJ, Read AF, 2003. The effects of host immunity on virulence-transmissibility relationships in the rodent malaria parasite Plasmodium chabaudi. Parasitology 126 :103–112.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Mackinnon MJ, Read AF, 2004. Virulence in malaria: an evolutionary viewpoint. Philos Trans R Soc Lond B Biol Sci 359 :965–986.

  • 7

    Chotivanich K, Udomsangpetch R, Simpson JA, Newton P, Pukrittayakamee S, Looareesuwan S, White NJ, 2000. Parasite multiplication potential and the severity of falciparum malaria. J Infect Dis 181 :1206–1209.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Simpson JA, Silamut K, Chotivanich K, Pukrittayakamee S, White NJ, 1999. Red cell selectivity in malaria: a study of multiple-infected erythrocytes. Trans R Soc Trop Med Hyg 93 :165–168.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Miller LH, David PH, Hudson DE, Hadley TJ, Richards RL, Aikawa M, 1984. Monoclonal antibodies to a 140,000-m.w. protein on Plasmodium knowlesi merozoites inhibit their invasion of rhesus erythrocytes. J Immunol 132 :438–442.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Ramasamy R, Ramasamy M, Yasawardena S, 2001. Antibodies and Plasmodium falciparum merozoites. Trends Parasitol 17 :194–197.

  • 11

    Ramasamy R, Yasawardena S, Kanagaratnam R, Buratti E, Baralle FE, Ramasamy MS, 1999. Antibodies to a merozoite surface protein promote multiple invasion of red blood cells by malaria parasites. Parasite Immunol 21 :397–407.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Lyke KE, Dicko A, Kone A, Coulibaly D, Guindo A, Cissoko Y, Traore K, Plowe CV, Doumbo OK, 2004. Incidence of severe Plasmodium falciparum malaria as a primary endpoint for vaccine efficacy trials in Bandiagara, Mali. Vaccine 22 :3169–3174.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Kinyanjui SM, Mwangi T, Bull PC, Newbold CI, Marsh K, 2004. Protection against clinical malaria by heterologous immunoglobulin G antibodies against malaria-infected erythrocyte variant surface antigens requires interaction with asymptomatic infections. J Infect Dis 190 :1527–1533.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Lyke KE, Diallo DA, Dicko A, Kone A, Coulibaly D, Guindo A, Cissoko Y, Sangare L, Coulibaly S, Dakouo B, Taylor TE, Doumbo OK, Plowe CV, 2003. Association of intraleukocytic Plasmodium falciparum malaria pigment with disease severity, clinical manifestations, and prognosis in severe malaria. Am J Trop Med Hyg 69 :253–259.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    World Health Organization, 2000. Severe falciparum malaria. Trans R Soc Trop Med Hyg 94 (Suppl 1):S1–90.

  • 16

    Marsh K, Forster D, Waruiru C, Mwangi I, Winstanley M, Marsh V, Newton C, Winstanley P, Warn P, Peshu N, Pasvol G, Snow R, 1995. Indicators of life-threatening malaria in African children. N Engl J Med 332 :1399–1404.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Lyke KE, Burges R, Cissoko Y, Sangare L, Dao M, Diarra I, Kone A, Harley R, Plowe CV, Doumbo OK, Sztein MB, 2004. Serum levels of the proinflammatory cytokines interleukin-1 beta (IL-1beta), IL-6, IL-8, IL-10, tumor necrosis factor alpha, and IL-12(p70) in Malian children with severe Plasmodium falciparum malaria and matched uncomplicated malaria or healthy controls. Infect Immun 72 :5630–5637.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Rowe JA, Obiero J, Marsh K, Raza A, 2002. Correlation between rosetting and parasitaemia in Plasmodium falciparum clinical isolates. Am J Trop Med Hyg 66 :458–460.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Rowe A, Obeiro J, Newbold CI, Marsh K, 1995. Plasmodium falciparum rosetting is associated with malaria severity in Kenya. Infect Immun 63 :2323–2326.

  • 20

    Clough B, Atilola FA, Pasvol G, 1998. The role of rosetting in the multiplication of Plasmodium falciparum: rosette formation neither enhances nor targets parasite invasion into uninfected red cells. Br J Haematol 100 :99–104.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Lawrence G, Cheng QQ, Reed C, Taylor D, Stowers A, Cloonan N, Rzepczyk C, Smillie A, Anderson K, Pombo D, Allworth A, Eisen D, Anders R, Saul A, 2000. Effect of vaccination with 3 recombinant asexual-stage malaria antigens on initial growth rates of Plasmodium falciparum in non-immune volunteers. Vaccine 18 :1925–1931.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Cheng Q, Lawrence G, Reed C, Stowers A, Ranford-Cartwright L, Creasey A, Carter R, Saul A, 1997. Measurement of Plasmodium falciparum growth rates in vivo: a test of malaria vaccines. Am J Trop Med Hyg 57 :495–500.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Bejon P, Andrews L, Andersen RF, Dunachie S, Webster D, Walther M, Gilbert SC, Peto T, Hill AV, 2005. Calculation of liver-to-blood inocula, parasite growth rates, and preerythrocytic vaccine efficacy, from serial quantitative polymerase chain reaction studies of volunteers challenged with malaria sporozoites. J Infect Dis 191 :619–626.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Simpson JA, Aarons L, Collins WE, Jeffery GM, White NJ, 2002. Population dynamics of untreated Plasmodium falciparum malaria within the adult human host during the expansion phase of the infection. Parasitology 124 :247–263.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Gravenor MB, McLean AR, Kwiatkowski D, 1995. The regulation of malaria parasitaemia: parameter estimates for a population model. Parasitology 110 :115–122.

  • 26

    Luxemburger C, Ricci F, Nosten F, Raimond D, Bathet S, White NJ, 1997. The epidemiology of severe malaria in an area of low transmission in Thailand. Trans R Soc Trop Med Hyg 91 :256–262.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Carlson J, Helmby H, Hill AV, Brewster D, Greenwood BM, Wahlgren M, 1990. Human cerebral malaria: association with erythrocyte rosetting and lack of anti-rosetting antibodies. Lancet 336 :1457–1460.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Kun JF, Schmidt-Ott RJ, Lehman LG, Lell B, Luckner D, Greve B, Matousek P, Kremsner PG, 1998. Merozoite surface antigen 1 and 2 genotypes and rosetting of Plasmodium falciparum in severe and mild malaria in Lambarene, Gabon. Trans R Soc Trop Med Hyg 92 :110–114.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Ho M, Davis TM, Silamut K, Bunnag D, White NJ, 1991. Rosette formation of Plasmodium falciparum-infected erythrocytes from patients with acute malaria. Infect Immun 59 :2135–2139.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Angkasekwinai P, Looareesuwan S, Chaiyaroj SC, 1998. Lack of significant association between rosette formation and parasitized erythrocyte adherence to purified CD36. Southeast Asian J Trop Med Public Health 29 :41–45.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Tyler KM, Higgs PG, Matthews KR, Gull K, 2001. Limitation of Trypanosoma brucei parasitaemia results from density-dependent parasite differentiation and parasite killing by the host immune response. Proc R Soc Lond B Biol Sci 268 :2235–2243.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Reuner B, Vassella E, Yutzy B, Boshart M, 1997. Cell density triggers slender to stumpy differentiation of Trypanosoma brucei bloodstream forms in culture. Mol Biochem Parasitol 90 :269–280.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Bruce MC, Donnelly CA, Alpers MP, Galinski MR, Barnwell JW, Walliker D, Day KP, 2000. Cross-species interactions between malaria parasites in humans. Science 287 :845–848.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34

    Bruce MC, Day KP, 2003. Cross-species regulation of Plasmodium parasitemia in semi-immune children from Papua New Guinea. Trends Parasitol 19 :271–277.

  • 35

    Dolan SA, Miller LH, Wellems TE, 1990. Evidence for a switching mechanism in the invasion of erythrocytes by Plasmodium falciparum. J Clin Invest 86 :618–624.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36

    Soubes SC, Wellems TE, Miller LH, 1997. Plasmodium falciparum: a high proportion of parasites from a population of the Dd2 strain are able to invade erythrocytes by an alternative pathway. Exp Parasitol 86 :79–83.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37

    Reed MB, Caruana SR, Batchelor AH, Thompson JK, Crabb BS, Cowman AF, 2000. Targeted disruption of an erythrocyte binding antigen in Plasmodium falciparum is associated with a switch toward a sialic acid-independent pathway of invasion. Proc Natl Acad Sci USA 97 :7509–7514.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38

    Cowman AF, Baldi DL, Healer J, Mills KE, O’Donnell RA, Reed MB, Triglia T, Wickham ME, Crabb BS, 2000. Functional analysis of proteins involved in Plasmodium falciparum merozoite invasion of red blood cells. FEBS Lett 476 :84–88.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39

    Gaur D, Mayer DC, Miller LH, 2004. Parasite ligand-host receptor interactions during invasion of erythrocytes by Plasmodium merozoites. Int J Parasitol 34 :1413–1429.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40

    Baum J, Pinder M, Conway DJ, 2003. Erythrocyte invasion phenotypes of Plasmodium falciparum in The Gambia. Infect Immun 71 :1856–1863.

  • 41

    Walliker D, Sanderson A, Yoeli M, Hargreaves BJ, 1976. A genetic investigation of virulence in a rodent malaria parasite. Parasitology 72 :183–194.

  • 42

    Swardson-Olver CJ, Dawson TC, Burnett RC, Peiper SC, Maeda N, Avery AC, 2002. Plasmodium yoelii uses the murine Duffy antigen receptor for chemokines as a receptor for normocyte invasion and an alternative receptor for reticulocyte invasion. Blood 99 :2677–2684.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43

    Pain A, Ferguson DJ, Kai O, Urban BC, Lowe B, Marsh K, Roberts DJ, 2001. Platelet-mediated clumping of Plasmodium falciparum-infected erythrocytes is a common adhesive phenotype and is associated with severe malaria. Proc Natl Acad Sci USA 98 :1805–1810.

    • PubMed
    • Search Google Scholar
    • Export Citation
Past two years Past Year Past 30 Days
Abstract Views 1295 1134 103
Full Text Views 289 4 1
PDF Downloads 41 3 1
 
 
 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save