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Species Interactions and Immunity to Malaria Parasites

Species Interactions and Immunity to Malaria Parasites. Marian Bruce, Christl Donnelly, Michael Alpers, Mary Galinski, John Barnwell, David Walker, Karen Day. Study Design. Village of Gonoa, Madang Province, Papua New Guinea 34 asymptomatic children

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Species Interactions and Immunity to Malaria Parasites

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  1. Species Interactions and Immunity to Malaria Parasites Marian Bruce, Christl Donnelly, Michael Alpers, Mary Galinski, John Barnwell, David Walker, Karen Day

  2. Study Design • Village of Gonoa, Madang Province, Papua New Guinea • 34 asymptomatic children • Parasite sampling from fingerpricks at 3 day intervals for 60 days • Dynamics of P. falciparum, P. vivax and P. malariae from blood smears • Dynamics of P. falciparum and P. vivax genotypes

  3. P. falciparum Genotyping 3D7+HB3 HB3 HB3 3D7 m m 0 3 9 12 15 18 24 27 33 36 42 m m 0 3 6 9 12 15 18 24 27 33 36 42 51 60 m EthBr ICI FC27 EthBr ICI FC27 m 0 6 9 12 15 18 21 24 27 30 33 36 39 42 51 54 57 60 m EthBr ICI FC27

  4. P. vivax Genotyping PCR/RFLP analysis at the polymeric Msp3 locus child day HhaI AluI

  5. Correlation of Multiplicity and Prevalence P. falciparum genotype P. vivax genotype proportion of samples P. vivax smear positive proportion of samples P. falciparum smear positive • 4 yrs • 5-9 yrs • 10-14 yrs

  6. 10000 1000 100 10 1 total density (parasites/I) 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 proportion of each species making total density P. falciparum genotypes 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 P. vivax genotypes

  7. 10000 1000 100 10 1 total density (parasites/I) 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 proportion of each species making total density P. falciparum genotypes 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 P. vivax genotypes

  8. Stability of Parasite Density parasites/I parasites/I proportion proportion parasites/I parasites/I proportion proportion • P. malariae • P. vivax • total parasite density • P. falciparum

  9. Regulation of Multiple Malaria Populations 10000 1000 100 10 threshold parasite density (parasites/I) detection limit suppression antigenic variation days

  10. Bulmer’s Test children with >50% smears positive no autocorrelation in total density data n = 19 16/19 data conforms with model of density-dependence 9/13 significance reduced or abolished applied to data from each species

  11. Mechanisms Underlying Density Dependent Regulation • competition • antigenic variation • antibody-dependent cellular immunity (ADCI) • fever • innate immune mechanisms

  12. Species Interactions Evidence for parasite interactions Deficit of mixed species infections in cross-sectional surveys - associated with children - associated with high transmission rates Reciprocal seasonality in the prevalence of species - associated with the dominance of P. falciparum

  13. Pattern of Infection with Multiple Species Longitudinal number of infections with each species as expressed from prevalence of each (Chi-square=1.60 p=0.449) Cross-sectional deficit of mixed infections (Chi-square=9.06 p=0.028) Peaks of episodes peaks did not coincide as often as expected by chance (Chi-square=6.56 p=0.01)

  14. Sequential Episodes of Infection • sequential pattern of infection is a result of density dependent regulation • during cross-sectional sampling this appears as a deficit of mixed infections density slide detection level time

  15. Conclusions • density dependent regulation of parasite density is species- and genotype-transcending • acts to enhance sequential nature of infection with each species • sequential pattern of infection underlies parasite ‘interaction’ observed as mixed infection deficits

  16. Acknowledgements The people of Gonoa Mike Packer PNG Institute of Medical Research Moses Lagog Georges Snounou Imperial College Wellcome Trust European Commission British Medical Research Council

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