Frequency-Dependent Competition Between Strains Imparts Persistence to Perturbations in a Model of Plasmodium falciparum Malaria Transmission
In high-transmission endemic regions, local populations of Plasmodium falciparum exhibit vast diversity of the var genes encoding its major surface antigen, with each parasite comprising multiple copies from this diverse gene pool. This strategy to evade the immune system through large combinatorial...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Ecology and Evolution |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fevo.2021.633263/full |
| _version_ | 1818490617931497472 |
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| author | Qixin He Shai Pilosof Kathryn E. Tiedje Karen P. Day Mercedes Pascual Mercedes Pascual |
| author_facet | Qixin He Shai Pilosof Kathryn E. Tiedje Karen P. Day Mercedes Pascual Mercedes Pascual |
| author_sort | Qixin He |
| collection | DOAJ |
| description | In high-transmission endemic regions, local populations of Plasmodium falciparum exhibit vast diversity of the var genes encoding its major surface antigen, with each parasite comprising multiple copies from this diverse gene pool. This strategy to evade the immune system through large combinatorial antigenic diversity is common to other hyperdiverse pathogens. It underlies a series of fundamental epidemiological characteristics, including large reservoirs of transmission from high prevalence of asymptomatics and long-lasting infections. Previous theory has shown that negative frequency-dependent selection (NFDS) mediated by the acquisition of specific immunity by hosts structures the diversity of var gene repertoires, or strains, in a pattern of limiting similarity that is both non-random and non-neutral. A combination of stochastic agent-based models and network analyses has enabled the development and testing of theory in these complex adaptive systems, where assembly of local parasite diversity occurs under frequency-dependent selection and large pools of variation. We show here the application of these approaches to theory comparing the response of the malaria transmission system to intervention when strain diversity is assembled under (competition-based) selection vs. a form of neutrality, where immunity depends only on the number but not the genetic identity of previous infections. The transmission system is considerably more persistent under NFDS, exhibiting a lower extinction probability despite comparable prevalence during intervention. We explain this pattern on the basis of the structure of strain diversity, in particular the more pronounced fraction of highly dissimilar parasites. For simulations that survive intervention, prevalence under specific immunity is lower than under neutrality, because the recovery of diversity is considerably slower than that of prevalence and decreased var gene diversity reduces parasite transmission. A Principal Component Analysis of network features describing parasite similarity reveals that despite lower overall diversity, NFDS is quickly restored after intervention constraining strain structure and maintaining patterns of limiting similarity important to parasite persistence. Given the described enhanced persistence under perturbation, intervention efforts will likely require longer times than the usual practice to eliminate P. falciparum populations. We discuss implications of our findings and potential analogies for ecological communities with non-neutral assembly processes involving frequency-dependence. |
| first_indexed | 2024-12-10T17:19:24Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2296-701X |
| language | English |
| last_indexed | 2024-12-10T17:19:24Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Ecology and Evolution |
| spelling | doaj.art-4d6af3ee1d594cd3ab662dc2880009972022-12-22T01:40:02ZengFrontiers Media S.A.Frontiers in Ecology and Evolution2296-701X2021-05-01910.3389/fevo.2021.633263633263Frequency-Dependent Competition Between Strains Imparts Persistence to Perturbations in a Model of Plasmodium falciparum Malaria TransmissionQixin He0Shai Pilosof1Kathryn E. Tiedje2Karen P. Day3Mercedes Pascual4Mercedes Pascual5Department of Biological Sciences, Purdue University, West Lafayette, IN, United StatesDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, IsraelDepartment of Microbiology and Immunology, Bio21 Institute, The University of Melbourne, Melbourne, VIC, AustraliaDepartment of Microbiology and Immunology, Bio21 Institute, The University of Melbourne, Melbourne, VIC, AustraliaDepartment of Ecology and Evolution, University of Chicago, Chicago, IL, United StatesSanta Fe Institute, Santa Fe, NM, United StatesIn high-transmission endemic regions, local populations of Plasmodium falciparum exhibit vast diversity of the var genes encoding its major surface antigen, with each parasite comprising multiple copies from this diverse gene pool. This strategy to evade the immune system through large combinatorial antigenic diversity is common to other hyperdiverse pathogens. It underlies a series of fundamental epidemiological characteristics, including large reservoirs of transmission from high prevalence of asymptomatics and long-lasting infections. Previous theory has shown that negative frequency-dependent selection (NFDS) mediated by the acquisition of specific immunity by hosts structures the diversity of var gene repertoires, or strains, in a pattern of limiting similarity that is both non-random and non-neutral. A combination of stochastic agent-based models and network analyses has enabled the development and testing of theory in these complex adaptive systems, where assembly of local parasite diversity occurs under frequency-dependent selection and large pools of variation. We show here the application of these approaches to theory comparing the response of the malaria transmission system to intervention when strain diversity is assembled under (competition-based) selection vs. a form of neutrality, where immunity depends only on the number but not the genetic identity of previous infections. The transmission system is considerably more persistent under NFDS, exhibiting a lower extinction probability despite comparable prevalence during intervention. We explain this pattern on the basis of the structure of strain diversity, in particular the more pronounced fraction of highly dissimilar parasites. For simulations that survive intervention, prevalence under specific immunity is lower than under neutrality, because the recovery of diversity is considerably slower than that of prevalence and decreased var gene diversity reduces parasite transmission. A Principal Component Analysis of network features describing parasite similarity reveals that despite lower overall diversity, NFDS is quickly restored after intervention constraining strain structure and maintaining patterns of limiting similarity important to parasite persistence. Given the described enhanced persistence under perturbation, intervention efforts will likely require longer times than the usual practice to eliminate P. falciparum populations. We discuss implications of our findings and potential analogies for ecological communities with non-neutral assembly processes involving frequency-dependence.https://www.frontiersin.org/articles/10.3389/fevo.2021.633263/fullstrain diversitystabilizing competitionstochastic assemblypersistencemalaria and antigenic diversitynegative frequency-dependent selection |
| spellingShingle | Qixin He Shai Pilosof Kathryn E. Tiedje Karen P. Day Mercedes Pascual Mercedes Pascual Frequency-Dependent Competition Between Strains Imparts Persistence to Perturbations in a Model of Plasmodium falciparum Malaria Transmission Frontiers in Ecology and Evolution strain diversity stabilizing competition stochastic assembly persistence malaria and antigenic diversity negative frequency-dependent selection |
| title | Frequency-Dependent Competition Between Strains Imparts Persistence to Perturbations in a Model of Plasmodium falciparum Malaria Transmission |
| title_full | Frequency-Dependent Competition Between Strains Imparts Persistence to Perturbations in a Model of Plasmodium falciparum Malaria Transmission |
| title_fullStr | Frequency-Dependent Competition Between Strains Imparts Persistence to Perturbations in a Model of Plasmodium falciparum Malaria Transmission |
| title_full_unstemmed | Frequency-Dependent Competition Between Strains Imparts Persistence to Perturbations in a Model of Plasmodium falciparum Malaria Transmission |
| title_short | Frequency-Dependent Competition Between Strains Imparts Persistence to Perturbations in a Model of Plasmodium falciparum Malaria Transmission |
| title_sort | frequency dependent competition between strains imparts persistence to perturbations in a model of plasmodium falciparum malaria transmission |
| topic | strain diversity stabilizing competition stochastic assembly persistence malaria and antigenic diversity negative frequency-dependent selection |
| url | https://www.frontiersin.org/articles/10.3389/fevo.2021.633263/full |
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