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Quantification of anti-parasite and anti-disease immunity to malaria as a function of age and exposure

View ORCID ProfileIsabel Rodriguez-Barraquer, Emmanuel Arinaitwe, Prasanna Jagannathan, Moses R Kamya, Philip J. Rosenthal, John Rek, Grant Dorsey, Joaniter Nankabirwa, Sarah G. Staedke, Maxwell Kilama, View ORCID ProfileChris Drakeley, Isaac Ssewanyana, View ORCID ProfileDavid L Smith, Bryan Greenhouse
doi: https://doi.org/10.1101/191197
Isabel Rodriguez-Barraquer
1Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA, USA
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Emmanuel Arinaitwe
2Infectious Diseases Research Collaboration, Kampala, Uganda
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Prasanna Jagannathan
3Department of Medicine, Stanford University, Stanford, CA, USA
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Moses R Kamya
4Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
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Philip J. Rosenthal
1Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA, USA
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John Rek
2Infectious Diseases Research Collaboration, Kampala, Uganda
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Grant Dorsey
1Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA, USA
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Joaniter Nankabirwa
2Infectious Diseases Research Collaboration, Kampala, Uganda
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Sarah G. Staedke
5London School of Hygiene and Tropical Medicine, London, United Kingdom
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Maxwell Kilama
2Infectious Diseases Research Collaboration, Kampala, Uganda
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Chris Drakeley
5London School of Hygiene and Tropical Medicine, London, United Kingdom
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Isaac Ssewanyana
2Infectious Diseases Research Collaboration, Kampala, Uganda
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David L Smith
6Institute of Health Metrics and Evaluation, University of Washington, Seattle, WA
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Bryan Greenhouse
1Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA, USA
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Abstract

Malaria immunity is complex and multi-faceted, and fundamental gaps remain in our understanding of how it develops. Here, we use detailed clinical and entomological data from three parallel cohort studies conducted across the malaria transmission spectrum in Uganda to quantify the development of immunity against symptomatic Plasmodium falciparum as a function of age and transmission intensity. We focus on: anti-parasite immunity (i.e; ability to control parasite densities) and anti-disease immunity (i.e; ability to tolerate higher parasite densities without fever). Our findings suggest a strong effect of age on both types of immunity, that remains significant after adjusting for cumulative exposure. They also show a non-linear effect of transmission intensity, where children experiencing the lowest transmission appear to develop immunity faster than those experiencing higher transmission. These findings illustrate how anti-parasite and anti-disease immunity develop in parallel, reducing the probability of experiencing symptomatic malaria upon each subsequent P. falciparum infection.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted September 20, 2017.
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Quantification of anti-parasite and anti-disease immunity to malaria as a function of age and exposure
Isabel Rodriguez-Barraquer, Emmanuel Arinaitwe, Prasanna Jagannathan, Moses R Kamya, Philip J. Rosenthal, John Rek, Grant Dorsey, Joaniter Nankabirwa, Sarah G. Staedke, Maxwell Kilama, Chris Drakeley, Isaac Ssewanyana, David L Smith, Bryan Greenhouse
bioRxiv 191197; doi: https://doi.org/10.1101/191197
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Quantification of anti-parasite and anti-disease immunity to malaria as a function of age and exposure
Isabel Rodriguez-Barraquer, Emmanuel Arinaitwe, Prasanna Jagannathan, Moses R Kamya, Philip J. Rosenthal, John Rek, Grant Dorsey, Joaniter Nankabirwa, Sarah G. Staedke, Maxwell Kilama, Chris Drakeley, Isaac Ssewanyana, David L Smith, Bryan Greenhouse
bioRxiv 191197; doi: https://doi.org/10.1101/191197

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