Mechanistic within-host models of the asexual Plasmodium falciparum infection: a review and analytical assessment
Abstract Background Malaria blood-stage infection length and intensity are important drivers of disease and transmission; however, the underlying mechanisms of parasite growth and the host’s immune response during infection remain largely unknown. Over the last 30 years, several mechanistic mathemat...
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ftdoajarticles:oai:doaj.org/article:eba80c56afd94f5281dc9d94fcaea061 2023-05-15T15:15:46+02:00 Mechanistic within-host models of the asexual Plasmodium falciparum infection: a review and analytical assessment Flavia Camponovo Tamsin E. Lee Jonathan R. Russell Lydia Burgert Jaline Gerardin Melissa A. Penny 2021-07-01T00:00:00Z https://doi.org/10.1186/s12936-021-03813-z https://doaj.org/article/eba80c56afd94f5281dc9d94fcaea061 EN eng BMC https://doi.org/10.1186/s12936-021-03813-z https://doaj.org/toc/1475-2875 doi:10.1186/s12936-021-03813-z 1475-2875 https://doaj.org/article/eba80c56afd94f5281dc9d94fcaea061 Malaria Journal, Vol 20, Iss 1, Pp 1-22 (2021) Plasmodium falciparum Within-host mathematical models Asexual parasite dynamics Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2021 ftdoajarticles https://doi.org/10.1186/s12936-021-03813-z 2022-12-31T07:06:53Z Abstract Background Malaria blood-stage infection length and intensity are important drivers of disease and transmission; however, the underlying mechanisms of parasite growth and the host’s immune response during infection remain largely unknown. Over the last 30 years, several mechanistic mathematical models of malaria parasite within-host dynamics have been published and used in malaria transmission models. Methods Mechanistic within-host models of parasite dynamics were identified through a review of published literature. For a subset of these, model code was reproduced and descriptive statistics compared between the models using fitted data. Through simulation and model analysis, key features of the models were compared, including assumptions on growth, immune response components, variant switching mechanisms, and inter-individual variability. Results The assessed within-host malaria models generally replicate infection dynamics in malaria-naïve individuals. However, there are substantial differences between the model dynamics after disease onset, and models do not always reproduce late infection parasitaemia data used for calibration of the within host infections. Models have attempted to capture the considerable variability in parasite dynamics between individuals by including stochastic parasite multiplication rates; variant switching dynamics leading to immune escape; variable effects of the host immune responses; or via probabilistic events. For models that capture realistic length of infections, model representations of innate immunity explain early peaks in infection density that cause clinical symptoms, and model representations of antibody immune responses control the length of infection. Models differed in their assumptions concerning variant switching dynamics, reflecting uncertainty in the underlying mechanisms of variant switching revealed by recent clinical data during early infection. Overall, given the scarce availability of the biological evidence there is limited support for complex ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 20 1 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Plasmodium falciparum Within-host mathematical models Asexual parasite dynamics Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Plasmodium falciparum Within-host mathematical models Asexual parasite dynamics Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Flavia Camponovo Tamsin E. Lee Jonathan R. Russell Lydia Burgert Jaline Gerardin Melissa A. Penny Mechanistic within-host models of the asexual Plasmodium falciparum infection: a review and analytical assessment |
topic_facet |
Plasmodium falciparum Within-host mathematical models Asexual parasite dynamics Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Malaria blood-stage infection length and intensity are important drivers of disease and transmission; however, the underlying mechanisms of parasite growth and the host’s immune response during infection remain largely unknown. Over the last 30 years, several mechanistic mathematical models of malaria parasite within-host dynamics have been published and used in malaria transmission models. Methods Mechanistic within-host models of parasite dynamics were identified through a review of published literature. For a subset of these, model code was reproduced and descriptive statistics compared between the models using fitted data. Through simulation and model analysis, key features of the models were compared, including assumptions on growth, immune response components, variant switching mechanisms, and inter-individual variability. Results The assessed within-host malaria models generally replicate infection dynamics in malaria-naïve individuals. However, there are substantial differences between the model dynamics after disease onset, and models do not always reproduce late infection parasitaemia data used for calibration of the within host infections. Models have attempted to capture the considerable variability in parasite dynamics between individuals by including stochastic parasite multiplication rates; variant switching dynamics leading to immune escape; variable effects of the host immune responses; or via probabilistic events. For models that capture realistic length of infections, model representations of innate immunity explain early peaks in infection density that cause clinical symptoms, and model representations of antibody immune responses control the length of infection. Models differed in their assumptions concerning variant switching dynamics, reflecting uncertainty in the underlying mechanisms of variant switching revealed by recent clinical data during early infection. Overall, given the scarce availability of the biological evidence there is limited support for complex ... |
format |
Article in Journal/Newspaper |
author |
Flavia Camponovo Tamsin E. Lee Jonathan R. Russell Lydia Burgert Jaline Gerardin Melissa A. Penny |
author_facet |
Flavia Camponovo Tamsin E. Lee Jonathan R. Russell Lydia Burgert Jaline Gerardin Melissa A. Penny |
author_sort |
Flavia Camponovo |
title |
Mechanistic within-host models of the asexual Plasmodium falciparum infection: a review and analytical assessment |
title_short |
Mechanistic within-host models of the asexual Plasmodium falciparum infection: a review and analytical assessment |
title_full |
Mechanistic within-host models of the asexual Plasmodium falciparum infection: a review and analytical assessment |
title_fullStr |
Mechanistic within-host models of the asexual Plasmodium falciparum infection: a review and analytical assessment |
title_full_unstemmed |
Mechanistic within-host models of the asexual Plasmodium falciparum infection: a review and analytical assessment |
title_sort |
mechanistic within-host models of the asexual plasmodium falciparum infection: a review and analytical assessment |
publisher |
BMC |
publishDate |
2021 |
url |
https://doi.org/10.1186/s12936-021-03813-z https://doaj.org/article/eba80c56afd94f5281dc9d94fcaea061 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 20, Iss 1, Pp 1-22 (2021) |
op_relation |
https://doi.org/10.1186/s12936-021-03813-z https://doaj.org/toc/1475-2875 doi:10.1186/s12936-021-03813-z 1475-2875 https://doaj.org/article/eba80c56afd94f5281dc9d94fcaea061 |
op_doi |
https://doi.org/10.1186/s12936-021-03813-z |
container_title |
Malaria Journal |
container_volume |
20 |
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1 |
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1766346112357105664 |