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Determination of the processes driving the acquisition of immunity to malaria using a mathematical transmission model.

Filipe JA, Riley EM, Drakeley CJ, Sutherland CJ, Ghani AC - PLoS Comput. Biol. (2007)

Bottom Line: The results were compared to age patterns of parasite prevalence and clinical disease in endemic settings in northeastern Tanzania and The Gambia.Two types of immune function were required to reproduce the epidemiological age-prevalence curves seen in the empirical data; a form of clinical immunity that reduces susceptibility to clinical disease and develops with age and exposure (with half-life of the order of five years or more) and a form of anti-parasite immunity which results in more rapid clearance of parasitaemia, is acquired later in life and is longer lasting (half-life of >20 y).The development of anti-parasite immunity better reproduced observed epidemiological patterns if it was dominated by age-dependent physiological processes rather than by the magnitude of exposure (provided some exposure occurs).

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.

ABSTRACT
Acquisition of partially protective immunity is a dominant feature of the epidemiology of malaria among exposed individuals. The processes that determine the acquisition of immunity to clinical disease and to asymptomatic carriage of malaria parasites are poorly understood, in part because of a lack of validated immunological markers of protection. Using mathematical models, we seek to better understand the processes that determine observed epidemiological patterns. We have developed an age-structured mathematical model of malaria transmission in which acquired immunity can act in three ways ("immunity functions"): reducing the probability of clinical disease, speeding the clearance of parasites, and increasing tolerance to subpatent infections. Each immunity function was allowed to vary in efficacy depending on both age and malaria transmission intensity. The results were compared to age patterns of parasite prevalence and clinical disease in endemic settings in northeastern Tanzania and The Gambia. Two types of immune function were required to reproduce the epidemiological age-prevalence curves seen in the empirical data; a form of clinical immunity that reduces susceptibility to clinical disease and develops with age and exposure (with half-life of the order of five years or more) and a form of anti-parasite immunity which results in more rapid clearance of parasitaemia, is acquired later in life and is longer lasting (half-life of >20 y). The development of anti-parasite immunity better reproduced observed epidemiological patterns if it was dominated by age-dependent physiological processes rather than by the magnitude of exposure (provided some exposure occurs). Tolerance to subpatent infections was not required to explain the empirical data. The model comprising immunity to clinical disease which develops early in life and is exposure-dependent, and anti-parasite immunity which develops later in life and is not dependent on the magnitude of exposure, appears to best reproduce the pattern of parasite prevalence and clinical disease by age in different malaria transmission settings. Understanding the effector mechanisms underlying these two immune functions will assist in the design of transmission-reducing interventions against malaria.

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Immunity Functions That Act on: (A,B) the Susceptibility to Developing Clinical Disease; (C,D) the Clearance of Detectable Parasites, and (E,F) the Clearance of Subpatent Infection(A,C,E) Show schematically how each model assumes that immunity is developed (through exposure and/or age) and lost.(B,D,F) Show the resulting effect of these immunity levels on (B) susceptibility to clinical disease, (D) the rate of clearance of detectable parasites, and (F) the clearance of subpatent infection as people age and for five different transmission settings (identified by the EIR in ibppy). Further mathematical details are given in Protocol S1.
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pcbi-0030255-g007: Immunity Functions That Act on: (A,B) the Susceptibility to Developing Clinical Disease; (C,D) the Clearance of Detectable Parasites, and (E,F) the Clearance of Subpatent Infection(A,C,E) Show schematically how each model assumes that immunity is developed (through exposure and/or age) and lost.(B,D,F) Show the resulting effect of these immunity levels on (B) susceptibility to clinical disease, (D) the rate of clearance of detectable parasites, and (F) the clearance of subpatent infection as people age and for five different transmission settings (identified by the EIR in ibppy). Further mathematical details are given in Protocol S1.

Mentions: 1. Susceptibility to symptomatic disease, φ (immunity function 1). We assume that individuals are born with maternally acquired immunity which is determined by the endemic level of disease and decays with a half-life dM. Following birth, clinical immunity accumulates due to exposure at a rate dependent on the force of infection in the population, Λ. This acquired immunity decays with a half-life dS. The schematic for this model is shown in Figure 7A. Susceptibility to symptomatic disease is then assumed to decrease in a nonlinear way as levels of clinical immunity increase. The overall dependence of susceptibility φ on age and EIR resulting from this model is shown in Figure 7B.


Determination of the processes driving the acquisition of immunity to malaria using a mathematical transmission model.

Filipe JA, Riley EM, Drakeley CJ, Sutherland CJ, Ghani AC - PLoS Comput. Biol. (2007)

Immunity Functions That Act on: (A,B) the Susceptibility to Developing Clinical Disease; (C,D) the Clearance of Detectable Parasites, and (E,F) the Clearance of Subpatent Infection(A,C,E) Show schematically how each model assumes that immunity is developed (through exposure and/or age) and lost.(B,D,F) Show the resulting effect of these immunity levels on (B) susceptibility to clinical disease, (D) the rate of clearance of detectable parasites, and (F) the clearance of subpatent infection as people age and for five different transmission settings (identified by the EIR in ibppy). Further mathematical details are given in Protocol S1.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2230683&req=5

pcbi-0030255-g007: Immunity Functions That Act on: (A,B) the Susceptibility to Developing Clinical Disease; (C,D) the Clearance of Detectable Parasites, and (E,F) the Clearance of Subpatent Infection(A,C,E) Show schematically how each model assumes that immunity is developed (through exposure and/or age) and lost.(B,D,F) Show the resulting effect of these immunity levels on (B) susceptibility to clinical disease, (D) the rate of clearance of detectable parasites, and (F) the clearance of subpatent infection as people age and for five different transmission settings (identified by the EIR in ibppy). Further mathematical details are given in Protocol S1.
Mentions: 1. Susceptibility to symptomatic disease, φ (immunity function 1). We assume that individuals are born with maternally acquired immunity which is determined by the endemic level of disease and decays with a half-life dM. Following birth, clinical immunity accumulates due to exposure at a rate dependent on the force of infection in the population, Λ. This acquired immunity decays with a half-life dS. The schematic for this model is shown in Figure 7A. Susceptibility to symptomatic disease is then assumed to decrease in a nonlinear way as levels of clinical immunity increase. The overall dependence of susceptibility φ on age and EIR resulting from this model is shown in Figure 7B.

Bottom Line: The results were compared to age patterns of parasite prevalence and clinical disease in endemic settings in northeastern Tanzania and The Gambia.Two types of immune function were required to reproduce the epidemiological age-prevalence curves seen in the empirical data; a form of clinical immunity that reduces susceptibility to clinical disease and develops with age and exposure (with half-life of the order of five years or more) and a form of anti-parasite immunity which results in more rapid clearance of parasitaemia, is acquired later in life and is longer lasting (half-life of >20 y).The development of anti-parasite immunity better reproduced observed epidemiological patterns if it was dominated by age-dependent physiological processes rather than by the magnitude of exposure (provided some exposure occurs).

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.

ABSTRACT
Acquisition of partially protective immunity is a dominant feature of the epidemiology of malaria among exposed individuals. The processes that determine the acquisition of immunity to clinical disease and to asymptomatic carriage of malaria parasites are poorly understood, in part because of a lack of validated immunological markers of protection. Using mathematical models, we seek to better understand the processes that determine observed epidemiological patterns. We have developed an age-structured mathematical model of malaria transmission in which acquired immunity can act in three ways ("immunity functions"): reducing the probability of clinical disease, speeding the clearance of parasites, and increasing tolerance to subpatent infections. Each immunity function was allowed to vary in efficacy depending on both age and malaria transmission intensity. The results were compared to age patterns of parasite prevalence and clinical disease in endemic settings in northeastern Tanzania and The Gambia. Two types of immune function were required to reproduce the epidemiological age-prevalence curves seen in the empirical data; a form of clinical immunity that reduces susceptibility to clinical disease and develops with age and exposure (with half-life of the order of five years or more) and a form of anti-parasite immunity which results in more rapid clearance of parasitaemia, is acquired later in life and is longer lasting (half-life of >20 y). The development of anti-parasite immunity better reproduced observed epidemiological patterns if it was dominated by age-dependent physiological processes rather than by the magnitude of exposure (provided some exposure occurs). Tolerance to subpatent infections was not required to explain the empirical data. The model comprising immunity to clinical disease which develops early in life and is exposure-dependent, and anti-parasite immunity which develops later in life and is not dependent on the magnitude of exposure, appears to best reproduce the pattern of parasite prevalence and clinical disease by age in different malaria transmission settings. Understanding the effector mechanisms underlying these two immune functions will assist in the design of transmission-reducing interventions against malaria.

Show MeSH
Related in: MedlinePlus