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The dynamics of naturally acquired immunity to Plasmodium falciparum infection.

Pinkevych M, Petravic J, Chelimo K, Kazura JW, Moormann AM, Davenport MP - PLoS Comput. Biol. (2012)

Bottom Line: Here we analyse the dynamics of Plasmodium falciparum malaria infection after treatment in a cohort of 197 healthy study participants of different ages in order to model naturally acquired immunity.We find that both delayed time-to-infection and reductions in asymptomatic parasitaemias in older age groups can be explained by immunity that reduces the growth of blood stage as opposed to liver stage parasites.We found that this mechanism would require at least two components - a rapidly acting strain-specific component, as well as a slowly acquired cross-reactive or general immunity to all strains.

View Article: PubMed Central - PubMed

Affiliation: Centre for Vascular Research, University of New South Wales, Sydney, New South Wales, Australia.

ABSTRACT
Severe malaria occurs predominantly in young children and immunity to clinical disease is associated with cumulative exposure in holoendemic settings. The relative contribution of immunity against various stages of the parasite life cycle that results in controlling infection and limiting disease is not well understood. Here we analyse the dynamics of Plasmodium falciparum malaria infection after treatment in a cohort of 197 healthy study participants of different ages in order to model naturally acquired immunity. We find that both delayed time-to-infection and reductions in asymptomatic parasitaemias in older age groups can be explained by immunity that reduces the growth of blood stage as opposed to liver stage parasites. We found that this mechanism would require at least two components - a rapidly acting strain-specific component, as well as a slowly acquired cross-reactive or general immunity to all strains. Analysis and modelling of malaria infection dynamics and naturally acquired immunity with age provides important insights into what mechanisms of immune control may be harnessed by malaria vaccine strategists.

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The impact of immunity on reinfection curves.The effects of liver stage immunity blocking a proportion of infected bites (A), or blood stage immunity decreasing the growth of parasites (decreased PMR) (B) is shown. Liver stage immunity alone decreases the rate of new infections, producing a family of exponential curves. Slower growth produces a family of curves shifted due to an increasing delay in detection. The same biting rate is used for all age groups. Blue triangle and blue line- C1, green diamond and green line - C2, orange square and orange line - C3, red circle and red line - A.
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pcbi-1002729-g002: The impact of immunity on reinfection curves.The effects of liver stage immunity blocking a proportion of infected bites (A), or blood stage immunity decreasing the growth of parasites (decreased PMR) (B) is shown. Liver stage immunity alone decreases the rate of new infections, producing a family of exponential curves. Slower growth produces a family of curves shifted due to an increasing delay in detection. The same biting rate is used for all age groups. Blue triangle and blue line- C1, green diamond and green line - C2, orange square and orange line - C3, red circle and red line - A.

Mentions: From a modeling perspective, anything that reduces the initiation of successful blood stage infection has the same effect – it simply decreases the slope of our reinfection curve (which remains in exponential form). Fig. 2.A. illustrates the predicted effects of decreasing the rate of initiation of blood stage infection and shows the best fits of a model that incorporates this change to the cohort data. The fits are essentially a family of curves commencing at the same time, and decreasing at different rates. The best fit parameters and goodness of fit statistics are in the [Text S4], (model 1). This is quite different from the observed infection rates in two respects: (a) it does not capture the greater delay until infection is observed in older children and adults, and (b) it does not capture the convex part of the adults' and older children's infection curve.


The dynamics of naturally acquired immunity to Plasmodium falciparum infection.

Pinkevych M, Petravic J, Chelimo K, Kazura JW, Moormann AM, Davenport MP - PLoS Comput. Biol. (2012)

The impact of immunity on reinfection curves.The effects of liver stage immunity blocking a proportion of infected bites (A), or blood stage immunity decreasing the growth of parasites (decreased PMR) (B) is shown. Liver stage immunity alone decreases the rate of new infections, producing a family of exponential curves. Slower growth produces a family of curves shifted due to an increasing delay in detection. The same biting rate is used for all age groups. Blue triangle and blue line- C1, green diamond and green line - C2, orange square and orange line - C3, red circle and red line - A.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475668&req=5

pcbi-1002729-g002: The impact of immunity on reinfection curves.The effects of liver stage immunity blocking a proportion of infected bites (A), or blood stage immunity decreasing the growth of parasites (decreased PMR) (B) is shown. Liver stage immunity alone decreases the rate of new infections, producing a family of exponential curves. Slower growth produces a family of curves shifted due to an increasing delay in detection. The same biting rate is used for all age groups. Blue triangle and blue line- C1, green diamond and green line - C2, orange square and orange line - C3, red circle and red line - A.
Mentions: From a modeling perspective, anything that reduces the initiation of successful blood stage infection has the same effect – it simply decreases the slope of our reinfection curve (which remains in exponential form). Fig. 2.A. illustrates the predicted effects of decreasing the rate of initiation of blood stage infection and shows the best fits of a model that incorporates this change to the cohort data. The fits are essentially a family of curves commencing at the same time, and decreasing at different rates. The best fit parameters and goodness of fit statistics are in the [Text S4], (model 1). This is quite different from the observed infection rates in two respects: (a) it does not capture the greater delay until infection is observed in older children and adults, and (b) it does not capture the convex part of the adults' and older children's infection curve.

Bottom Line: Here we analyse the dynamics of Plasmodium falciparum malaria infection after treatment in a cohort of 197 healthy study participants of different ages in order to model naturally acquired immunity.We find that both delayed time-to-infection and reductions in asymptomatic parasitaemias in older age groups can be explained by immunity that reduces the growth of blood stage as opposed to liver stage parasites.We found that this mechanism would require at least two components - a rapidly acting strain-specific component, as well as a slowly acquired cross-reactive or general immunity to all strains.

View Article: PubMed Central - PubMed

Affiliation: Centre for Vascular Research, University of New South Wales, Sydney, New South Wales, Australia.

ABSTRACT
Severe malaria occurs predominantly in young children and immunity to clinical disease is associated with cumulative exposure in holoendemic settings. The relative contribution of immunity against various stages of the parasite life cycle that results in controlling infection and limiting disease is not well understood. Here we analyse the dynamics of Plasmodium falciparum malaria infection after treatment in a cohort of 197 healthy study participants of different ages in order to model naturally acquired immunity. We find that both delayed time-to-infection and reductions in asymptomatic parasitaemias in older age groups can be explained by immunity that reduces the growth of blood stage as opposed to liver stage parasites. We found that this mechanism would require at least two components - a rapidly acting strain-specific component, as well as a slowly acquired cross-reactive or general immunity to all strains. Analysis and modelling of malaria infection dynamics and naturally acquired immunity with age provides important insights into what mechanisms of immune control may be harnessed by malaria vaccine strategists.

Show MeSH
Related in: MedlinePlus