Species Interactions and Immunity to

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16 Νοε 2013 (πριν από 3 χρόνια και 8 μήνες)

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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


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

P. falciparum

Genotyping

EthBr

ICI

FC27

EthBr

ICI

FC27

EthBr

ICI

FC27

m 0 3 6 9 12 15 18 24 27 33 36 42 51 60 m

m 0 3 9 12 15 18 24 27 33 36 42 m

m 0 6 9 12 15 18 21 24 27 30 33 36 39 42 51 54 57 60 m

HB3

HB3

3D7+HB3

3D7

m

P. vivax
Genotyping

child
day

Hha
I

Alu
I

PCR/RFLP analysis at the polymeric
Msp3


locus

Correlation of Multiplicity and
Prevalence

P. vivax
genotype

P. falciparum
genotype

proportion of samples
P. vivax
smear
positive

proportion of samples
P. falciparum
smear positive



4 yrs



5
-
9 yrs



10
-
14 yrs

total density
(parasites/

I
)

10000

1000

100

10

1

proportion of
each species
making total
density

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60

P. falciparum
genotypes

P. vivax
genotypes

total density
(parasites/

I
)

10000

1000

100

10

1

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

P. vivax
genotypes

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60

Stability of Parasite Density



total parasite density



P. falciparum



P. vivax



P. malariae

proportion

proportion

parasites/

I

proportion

proportion

parasites/

I

parasites/

I

parasites/

I

Regulation of Multiple Malaria
Populations

parasite density
(parasites/

I
)

10000

1000

100

10

days

suppression

antigenic
variation

threshold

detection
limit

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

Mechanisms Underlying Density
Dependent Regulation


competition


antigenic variation


antibody
-
dependent cellular immunity
(ADCI)


fever


innate immune mechanisms


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

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)


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

time

slide detection
level

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

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