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The effect of antibody-dependent enhancement on the transmission dynamics and persistence of multiple-strain
N Ferguson1, R Anderson, S Gupta
1The Wellcome Trust Centre for the Epidemiology of Infectious Disease, Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, United Kingdom.
Abstract:
Cross-reactive antibodies produced by a mammalian host during infection by a particular microparasitic strain usually have the effect of reducing the probability of the host being infected by a different, but closely related, pathogen strain. Such cross-reactive immunological responses thereby induce between-strain competition within the pathogen population. However, in some cases such as dengue virus, evidence suggests that cross-reactive antibodies act to enhance rather than restrict the severity of a subsequent infection by another strain. This cooperative mechanism is thought to explain why pre-existing immunity to dengue virus is an important risk factor for the development of severe disease (i.e., dengue shock syndrome and dengue hemorrhagic fever). In this paper, we explore the effect of antibody-dependent enhancement on the transmission dynamics of multistrain pathogen populations. We show that enhancement frequently may generate complex and persistent cyclical or chaotic epidemic behavior. Furthermore, enhancement acts to permit the coexistence of all strains where in its absence only one or a subset would persist.
Insights
Antibody-dependent enhancement (ADE) can worsen subsequent infections, unlike typical cross-reactive immunity. This study reveals ADE can cause complex epidemics and allow multiple pathogen strains to coexist.
Area of Science:
- Immunology
- Epidemiology
- Mathematical Biology
Background:
- Cross-reactive antibodies usually limit pathogen spread by inducing competition between strains.
- However, antibody-dependent enhancement (ADE) can paradoxically increase disease severity, as seen in dengue virus infections.
Purpose of the Study:
- To investigate the impact of ADE on the transmission dynamics of multi-strain pathogen populations.
- To understand how ADE influences epidemic behavior and pathogen strain coexistence.
Main Methods:
- Mathematical modeling of pathogen transmission dynamics.
- Analysis of multi-strain pathogen populations under varying immunological responses.
Main Results:
- Antibody-dependent enhancement can lead to complex, persistent cyclical, or chaotic epidemic patterns.
- ADE facilitates the coexistence of multiple pathogen strains, which would otherwise be outcompeted.
Conclusions:
- Antibody-dependent enhancement significantly alters pathogen transmission dynamics, promoting complex epidemics.
- ADE plays a crucial role in enabling the persistence of diverse pathogen strains within a host population.